Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential role of histamine in cancer immunotherapy has been a subject of interest for more than a decade. A significant body of research has elucidated the action of histamine in a model system that mimics the tumour microenvironment. In vitro evidence indicates that histamine inhibits the generation and release of reactive oxygen species (ROS) by monocytes/macrophages (MO) during respiratory burst. Since ROS have been shown to abrogate peritumoural and intratumoural cytokine activation of natural killer (NK) and T-cells and induce apoptosis of these cells in vitro, inhibition of ROS may enable cytokines to activate NK and T-cells and restore their antineoplastic, cytotoxic capabilities. Experimental data indicate that histamine and interleukin-2 (IL-2) act synergistically to activate NK cell cytotoxicity (NKCC). Although IL-2, a regulator of immune responses, has been shown to promote NKCC in monotherapy for metastatic melanoma (MM), renal cell carcinoma (RCC) and acute myeloid leukaemia (AML), objective responses occur in a minority of patients and survival is not significantly extended, except for a minority of patients with MM using high-dose regimens which have not been widely adopted. In vitro findings suggest that the addition of histamine to IL-2 therapy might improve response rates and disease-free survival by protecting the cells of the immune system from oxidative stress and inducing natural endogenous immune cytotoxicity. An IL-2/histamine Phase III trial is in progress in a population of AML patients. A recently completed Phase III trial of IL-2 vs. IL-2/histamine in patients with MM demonstrated a trend towards a superior survival benefit from IL-2/histamine for all patients entered, and a statistically significant survival benefit for patients with hepatic metastases.
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PMID:Histamine dihydrochloride: inhibiting oxidants and synergising IL-2-mediated immune activation in the tumour microenvironment. 1172 21

A nondifferentiating mouse myeloid leukemia cell line produces differentiation-inhibiting factors. One of these factors was purified as a homologue of nm23. The nm23 gene was isolated as a metastasis-suppressor gene that exhibits low expression in high-level metastatic cancer cells. The nm23 gene was overexpressed in acute myelogenous leukemia (AML) cells and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML. Multivariate analysis of putative prognostic factors revealed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. The overexpression of nm23-H1 was also observed in various hematological neoplasms. To use nm23 overexpression to determine the prognosis for lymphoma, we established an enzyme-linked immunosorbent assay (ELISA) technique to determine the serum level of nm23-H1 protein. This assay is far simpler than that used to determine nm23 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Using this system, we measured nm23-H1 protein levels in many hematological malignancies. Serum nm23-HI levels were significantly higher in patients with all of the hematological neoplasms tested (AML, chronic myelogenous leukemia, acute lymphoblastic leukemia, (ALL) myelodysplastic syndrome (MDS) and malignant lymphomas) than in normal controls. An elevated serum nm23-H1 protein concentration predicted a poor outcome for AML and non-Hodgkin's lymphoma. Especially in diffuse large B-cell lymphoma (DLBCL), seram nm23-H1 protein levels were an important prognostic factor in planning an appropriate treatment strategy for DLBCL. The serum nm23-H I protein levels probably depend on the total mass of malignant cells overexpressing nm23-H1.
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PMID:Serum nm23-H1 protein as a prognostic factor in hematological malignancies. 1215 76

The nm23 gene was isolated as a metastasis suppressor gene that exhibits low expression in high-level metastatic cancer cells. Its gene is related to the prognosis of acute myelogenous leukemia (AML) and non-Hodgkin's lymphoma (NHL). In this study, we examined the expression of nm23-H1 protein on the lymphoma cell surface of NHL. In 28 of 108 cases (25.9%), we observed > or = 20% of cell surface nm23-H1 protein expression and expression was especially high in peripheral T cell lymphomas and extranodal NK/T cell lymphomas. We also observed a significant correlation between serum nm23-H1 level and cell surface nm23-H1 expression levels. In patients with high levels of cell surface nm23-H1 expression, overall and progression-free survival rates were significantly lower than those in patients with low surface nm23-H1 expression levels. When surface nm23-H1 and serum nm23-H1 were combined, patients with high levels of both exhibited a poorer prognosis than patients with a high level of one or the other. These results indicate that in addition to serum nm23-H1, cell surface nm23-H1 may be used as a prognostic factor in planning a treatment strategy. The nm23-H1 protein appears to be intimately related to biological aggressiveness of lymphoma and, therefore, might be a molecular target of NHL treatment.
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PMID:Clinical significance of nm23-H1 proteins expressed on cell surface in non-Hodgkin's lymphoma. 1252 78

Deoxycytidine kinase (dCK) is required for the phosphorylation of several deoxyribonucleoside analogues that are widely employed as chemotherapeutic agents. Examples include cytosine arabinoside (Ara-C) and 2-chlorodeoxyadenosine (CdA) in the treatment of acute myeloid leukaemia (AML) and gemcitabine to treat solid tumours. In this study, expression of dCK mRNA was measured by a competitive template reverse transcriptase polymerase chain reaction (CT RT-PCR) in seven cell lines of different histological origin, 16 childhood and adult AML samples, 10 human liver samples and 11 human liver metastases of colorectal cancer origin. The enzyme activity and protein expression levels of dCK in the cell lines were closely related to the mRNA expression levels (r=0.75, P=0.026 and r=0.86, P=0.007). In AML samples, dCK mRNA expression ranged from 1.16 to 35.25 (x10(-3)xdCK/beta-actin). In the cell line panel, the range was 2.97-56.9 (x10(-3)xdCK/beta-actin) of dCK mRNA expression. The enzyme activity in liver metastases was correlated to dCK mRNA expression (r=0.497, P=0.05). In the liver samples, these were not correlated. dCK mRNA expression showed only a 36-fold range in liver while a 150-fold range was observed in the liver metastases. In addition, dCK activity and mean mRNA levels were 2.5-fold higher in the metastases than in the liver samples. Since dCK is associated with the sensitivity to deoxynucleoside analogues and because of the good correlation between the different dCK measurements in malignant cells and tumours, the CT-RT PCR assay will be useful in the selection of patients that can be treated with deoxycytidine analogues.
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PMID:Expression of deoxycytidine kinase in leukaemic cells compared with solid tumour cell lines, liver metastases and normal liver. 1262 50

Three cases of acute renal failure (ARF) requiring renal replacement therapy (RRT) in the course of neoplastic disease were presented. 7.5-yr-old girl admitted with postrenal failure during palliative radiotherapy had metastases in retroperitoneal space. Improvement followed percutaneous placement of nephrostomy catheters. 16-yr-old boy with acute myeloid leukemia was effectively treated with hemodialysis for prerenal and renal ARF mediated by vasomotor, infectious and toxic factors. In 11-yr-old boy ARF was the first clinical presentation of non-Hodgkin's lymphoma. Chemotherapy brought restoration of renal function. As a conclusion we emphasize complex etiology of ARF in such patients as well as the necessity of early introduction of RRT and thorough diagnosis and proper management of the causes of impaired renal function.
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PMID:[Acute renal failure as complication of neoplastic disease in children]. 1266 50

Five patients with primary osteosarcoma who were treated effectively with chemotherapy and resective surgery and in whom a metachronous tumor subsequently developed in another site but who never had evidence of pulmonary metastases are described. The original bone scans of the five patients showed only the primary site as being involved. After diagnosis and treatment of the initial tumor, at intervals ranging from 12 to 78 months (average, 39 months) another osteosarcoma developed in the patients at a distant bony site. After diagnosis and treatment of the second osteosarcoma, followup of these patients for a mean of 77 months (range, 24-96 months) after the appearance of the metachronous tumor and for a mean of 118 months (range, 99-150 months) after the diagnosis of the primary lesion showed that none had pulmonary metastases develop. No recurrences of the local tumors have occurred and four of the patients currently are alive and free of disease. One of the patients had a fatal acute myelogenous leukemia develop 144 months after the discovery of the primary osteosarcoma and 86 months after the appearance of the metachronous disease. At the time of her death, however she had no evidence of osteosarcoma in any site.
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PMID:Metachronous osteosarcoma: a report of five cases. 1278 79

Osteopontin (OPN) is a secreted glycoprotein produced by osteoclasts, macrophages, T cells, hematopoietic cells, and vascular smooth muscle cells. It contributes to macrophage homing and cellular immunity. It also mediates neovascularization, inhibits apoptosis, and plays important roles in extracellular matrix remodeling and angiogenesis. These properties are also characteristics of metastatic cancer cells. Consequently, the OPN gene was found to be upregulated among various metastatic cancer cells. This suggests that OPN is involved in tumor metastasis. How the OPN gene is upregulated in metastatic cancer cells remains to be illustrated. Thus, we investigated the transcriptional activation of the OPN promoter in the human metastatic cancer cell line A2058. We cloned the OPN promoter, and serial deletion analysis of the OPN promoter showed that the region between -170 and -127 may act as an enhancer to control the OPN gene in metastatic tumor cells. This region was found to contain overlapped AML-1 and C/EBP binding site motifs. Gel-mobility-shift assays using the A2058 nuclear extract and AML-1a or C/EBPalpha (CCAAT/enhancer binding protein alpha) recombinant protein indicated that these two transcription factors can bind to the overlapped AML-1 /C/EBP binding site motifs on the OPN regulatory sequence from -147 to -127. Surprisingly, the gel-shift experiments did not show supershift complex formation between AML-1 and C/EBPalpha. Functional analysis showed that the C/EBPalpha was more potent than the complex of AML-1 and its cofactor CBFbeta to upregulate the OPN promoter. In addition, AML-1 and C/EBPalpha did not exhibit transactivation additively or synergistically. Our results suggest that AML-1 and C/EBPalpha play an important role in the upregulation of the OPN gene in metastatic tumor cells.
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PMID:Transcriptional regulation of human osteopontin promoter by C/EBPalpha and AML-1 in metastatic cancer cells. 1471 33

The aim of the study was to compare the angiogenic status, potential qualitative differences in microvessels and carbonic anhydrase IX expression in bone-marrow (BM) metastases and different haematological tumours at time of diagnosis. The microvessel density (MVD), endothelial-cell proliferation (ECP) and carbonic anhydrase IX (CA IX) immunoreactivity were determined on 210 trephine biopsies from 57 patients with multiple myeloma (MM), 13 with acute myeloid leukaemia (AML), 48 with chronic myeloproliferative syndrome (CMPS), 26 with chronic lymphocytic leukaemia (CLL), 25 with epithelial BM metastases, 18 with monoclonal gammopathy of undetermined significance (MGUS) and from a control group composed of 23 patients without haematological neoplasm. There was an increased MVD and ECP in epithelial BM metastases, MM, AML, CMPS and in a part of CLL. While an ECP greater than 0 was detected in 72% of MM, 75% of CMPS and 92% of AML, it was invariably observed (100%) in the BM metastases. The absence of ECP together with a MVD comparable with the control group in our MGUS cases supports the view that MGUS is a pre-angiogenic condition. Qualitative differences in microvessels were associated with growth patterns in MM and CLL and were observed between the different entities of CMPS. In one-third of the epithelial BM metastases, there was a focal CA IX immunoreactivity, which was never observed in the haematological diseases.
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PMID:Microvessel density, endothelial-cell proliferation and carbonic anhydrase IX expression in haematological malignancies, bone-marrow metastases and monoclonal gammopathy of undetermined significance. 1516 17

We compared the levels of tissue factor (TF) mRNA in leukocytes with plasma TF antigens of patients in hypercoagulable state caused by various diseases. Flow cytometric analysis showed absence of TF antigen expression on neutrophils and monocytes in healthy subjects but strong expression in both cell types of patients with infections.TF mRNA levels in leukocytes were low in healthy subjects but they were significantly elevated in patients with underlying diseases of disseminated intravascular coagulation (DIC), especially in acute myeloid leukaemia (AML) and infections.TF mRNA levels in leukocytes were significantly high in patients with all diseases except those with thrombosis, and plasma TF antigen levels were significantly high in all diseases. TF mRNA in leukocytes and plasma TF antigen levels were significantly high in patients with overt-DIC, and TF mRNA/antigen ratio was significantly high in patients with overt-DIC. In patients with solid cancers, TF mRNA and TF mRNA/antigen ratio were significantly higher in patients with metastases than those without. TF mRNA levels in leukocytes and plasma levels of TF antigen did not correlate in normal subjects and all patients, but they tended to be correlated in patients with AML, infections or overt-DIC. Our analysis suggests that TF expression in leukocytes plays an important role in various diseases but the expression level does not always correlate with plasma levels of TF antigen.
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PMID:Tissue factor messenger RNA levels in leukocytes compared with tissue factor antigens in plasma from patients in hypercoagulable state caused by various diseases. 1521 54

A 21-year-old male presented with right scrotal discomfort. Right high orchiectomy revealed non-seminoma and he was diagnosed with stage I non-seminoma. Since acute myeloid leukemia (AML) was diagnosed incidentally, no adjuvant therapy was given and he received chemotherapy for AML. One year later, he complained of lumbago and general malaise. Complete remission of AML had been achieved and bone marrow puncture revealed no signs of recurrence. Computed tomography showed retroperitoneal lymph node swelling, inferior vena caval embolus distal to the hepatic vein, and multiple lung nodules. Metastasis of testicular neoplasm was suspected and chemotherapy with Bleomycin, Etoposide, and Cisplatin was started. On the fourth day of chemotherapy, the patient complained of sudden dyspnea and acutely went into shock. Pulmonary embolism was diagnosed and an inferior vena cava filter was placed. Chemotherapy was continued for four courses and the tumor showed complete remission. He has been free of disease for 24 months. In rare cases of testicular cancer with inferior vena caval embolus, the physician should be aware of the possibility of causing pulmonary embolism after chemotherapy.
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PMID:[Testicular cancer with inferior vena caval embolus causing pulmonary embolism following chemotherapy: a case report]. 1523 86


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