Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to inhibit the chemotaxis and enhance the oxidative burst response of human neutrophils in vitro. The present study describes the effect of recombinant GM-CSF on the neutrophil and monocyte function in patients with lymphoma undergoing GM-CSF treatment. Patients with either Hodgkin's or non-Hodgkin's lymphoma were treated with various dosages (2-16 micrograms kg-1 body weight per day for 5 days) of rhGM-CSF by intravenous or subcutaneous route. Prior to and on day 5 of rhGM-CSF treatment, neutrophil and monocyte chemotaxis and chemiluminescence responses to f-Met-Leu-Phe, zymosan activated serum (ZAS) and opsonized zymosan (OZ) were determined. It was observed that chemotactic response of neutrophils to f-Met-Leu-Phe and ZAS was reduced, whereas the chemiluminescence response of both cell types to f-Met-Leu-Phe and zymosan was enhanced by up to 43-fold. rhGM-CSF treatment did not affect degranulation of the neutrophils as measured by release of vitamin B12 binding protein. Degree of modulation of neutrophil and monocyte function by rhGM-CSF was independent of rhGM-CSF dosages administered. These data suggest that phagocytic defence system may be enhanced by GM-CSF treatment and that this cytokine may be a useful therapeutic adjunct in compromised patients.
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PMID:Modulation of neutrophil and monocyte function by recombinant human granulocyte macrophage colony-stimulating factor in patients with lymphoma. 190 35

Seven patients were studied with positron emission tomography (PET) using 11C-methionine. All had non-Hodgkin's lymphoma but one, who had Hodgkin's disease. By assuming a simple three-compartment model for dynamic data analysis, we used the graphic method proposed by Patlak et al., where Ki (K2K3/(K1+K3)) was compared with DAR (differential absorption ratio). Trichloroacetate was added to each plasma sample, and the activity of the acid-soluble fraction was counted to eliminate the influence of the protein-bound fraction of injected activity. Patlak data plots, using this acid-soluble fraction as an input factor, showed good linearity over the time of data collection. All tumors showed clear 11C-methionine accumulation. Tumor activity reached almost a plateau within 10 min and was kept at the same level for at least 30 min. Ki and DAR were 0.070 +/- 0.035 and 4.64 +/- 1.85 (mean +/- SD), respectively. There was no apparent correlation between histological type and Ki or DAR, while the correlation efficient between Ki and DAR was 0.875. Our conclusion is that DAR will give almost the same result as dynamic data in the analysis of methionine metabolism using PET.
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PMID:[Correlation analysis between patlak plot and DAR using 11C-methionine PET]. 763 54

The positron emission tomography (PET) tracer 2-18F-fluoro-2-deoxy-D-glucose (FDG) is the most widely used tracer in oncology. PET tracer. Another radiotracer, L-methyl-11C-Methionine (11C-methionine), also has been used successfully for PET imaging of brain and lung tumors, non-Hodgkin's lymphoma, breast cancer and head and neck cancer. This study compared FDG and 11C-methionine as tumor-detecting agents in head and neck cancer. Prior to cancer therapy, fourteen patients underwent a PET study with FDG and one with 11C-methionine. Nineteen of 21 malignant lesions that could be evaluated were visible with both tracers. Tracer uptake was measured as standardized uptake values (SUV) and Ki values according to Patlak et al. The mean SUV in FDG studies was 7.7 +/- 4.2 and in 11C-methionine studies 7.7 +/- 2.5, whereas the Ki values in 11C-methionine studies (mean, 0.128 +/- 0.068 min-1) were always higher than in FDG studies (mean, 0.036 +/- 0.023 min-1). A good correlation was found between the SUVs (r = 0.79, p < 0.0001) and the Ki values (r = 0.82, p < 0.001) between the two tracers. Both FDG and 11C-methionine are effective in PET imaging of head and neck cancer, and the uptake rates of the tracers seem to be closely related.
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PMID:Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine in head and neck cancer. 841 Feb 88

Hepatocyte growth factor (HGF)/scatter factor (SF) is the ligand for a tyrosine kinase cell surface receptor encoded by the MET protooncogene (c-MET). HGF/SF can induce proliferation and motility in epithelial cells and promotes invasion of carcinoma cells and NIH3T3 fibroblasts transfected with both HGF/SF and c-MET genes. Our results show that HGF/ SF and c-MET also play a role in adhesion and invasion of human lymphoma cells. c-MET mRNA is expressed in hemopoietic cells, such as hemopoietic progenitor cells (CD34+ cells) in bone marrow (BM) and mobilized peripheral blood, immature B cells in cord blood and BM, and germinal center B-centroblasts. In normal peripheral blood B cells, which are c-MET-, c-MET expression was induced by PMA, ConA, HGF/ SF, and Epstein-Barr virus (EBV) infection. Using immunohistochemistry, we detected c-MET on the cell surface of large activated centroblasts in lymph nodes from patients with B-non-Hodgkin's lymphoma and Hodgkin's disease. In the latter group, c-MET expression correlated well with the presence of EBV. Because HGF/SF and c-MET promote metastasis of carcinoma cells, we studied the effects of c-MET stimulation by HGF/SF of B-lymphoma cells on properties relevant for metastasis, ie, adhesion, migration, and invasion. HGF/SF stimulated adhesion of the c-MET+ B-cell lines to the extracellular matrix molecules fibronectin (FN) and collagen (CN) in a dose dependent manner. However, adhesion to laminin was not affected by HGF/SF. Adhesion to FN was mediated by beta 1-integrins alpha 4 beta 1 (VLA4) and alpha 5 beta 1 (VLA5) since blocking antibodies against beta 1- (CD29), alpha 4-(CD49d), or alpha 5- (CD49e) integrin subunits, completely reversed the effect of HGF/SF. Furthermore, HGF/SF induced adhesion was abrogated by addition of genistein, which blocks protein tyrosine kinases, including c-MET. Addition of HGF/SF resulted in a sixfold increase in migration of c-MET B-lymphoma cells through Matrigel, compared to medium alone. In rat fibroblast cultures, HGF/SF doubled the number of c-MET+ B-lymphoma cells that invaded the fibroblast monolayer. In these adhesion, migration and invasion assays HGF/SF had no effect on c-MET- cell lines. In conclusion, c-MET is expressed or can be induced on immature, activated, and certain malignant B cells. HGF/SF increased adhesion of c-MET+ B-lymphoma cells to FN and CN, mediated via beta 1-integrins alpha 4 beta 1 and alpha 5 beta 1, and furthermore promoted migration and invasion.
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PMID:Hepatocyte growth factor/scatter factor promotes adhesion of lymphoma cells to extracellular matrix molecules via alpha 4 beta 1 and alpha 5 beta 1 integrins. 902 31

The NPM-ALK fusion gene, formed by the t(2;5)(p23;q35) translocation in non-Hodgkin's lymphoma, encodes a 75-kDa hybrid protein that contains the amino-terminal 117 amino acid residues of the nucleolar phosphoprotein nucleophosmin (NPM) joined to the entire cytoplasmic portion of the receptor tyrosine kinase ALK (anaplastic lymphoma kinase). Here, we demonstrate the transforming ability of NPM-ALK and show that oncogenesis by the chimeric protein requires the activation of its kinase function as a result of oligomerization mediated by the NPM segment. Sedimentation gradient experiments revealed that NPM-ALK forms in vivo multimeric complexes of approximately 200 kDa or greater that also contain normal NPM. Cell fractionation studies of the t(2;5) translocation-containing lymphoma cell line SUP-M2 showed NPM-ALK to be localized within both the cytoplasmic and nuclear compartments. Immunostaining performed with both polyclonal and monoclonal anti-ALK antibodies confirmed the dual location of the oncoprotein and also indicated that NPM-ALK is abundant within both the nucleoplasm and the nucleolus. An intact NPM segment is absolutely required for NPM-ALK-mediated oncogenesis, as indicated by our observation that three different NPM-ALK mutant proteins lacking nonoverlapping portions of the NPM segment were each unable to form complexes, lacked kinase activity in vivo, and failed to transform cells. However, NPM could be functionally replaced in the fusion protein with the portion of the unrelated translocated promoter region (TPR) protein that activates the TPR-MET fusion kinase by mediating dimerization through its leucine zipper motif. This engineered TPR-ALK hybrid protein, which transformed cells almost as efficiently as NPM-ALK, was localized solely within the cytoplasm of cells. These data indicate that the nuclear and nucleolar localization of NPM-ALK, which probably occur because of transport via the shuttling activity of NPM, is not required for oncogenesis. Further, the activation of the truncated ALK protein by a completely heterologous oligomerization domain suggests that the functionally important role of the NPM segment of NPM-ALK in transformation is restricted to the formation of kinase-active oligomers and does not involve the alteration of normal NPM functions.
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PMID:Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis. 912 81

Certain aspects of the use of CT, MR imaging and PET were evaluated in patients with non-Hodgkin's lymphoma (NHL) with the aim of determining whether these methods may provide practical guidance for improving the management of these patients. Subjective evaluation of the tumor pattern on CT images, and quantification of tracer uptake using 11C methionine (11C Met) and [18F] fluorodeoxyglucose (18FDG) PET in patients with NHL, were performed to determine their relations to malignancy grade. An inhomogeneous tumor pattern (I) was found on CT in 75% of high-grade tumors, whereas 68% of low-grade tumors were homogeneous (H). Sixteen (94%) of the 17 tumors with a severely inhomogeneous pattern (I) were high-grade NHL, while 22 (72%) of the 29 homogeneous tumors (H) were low-grade. All tumors were clearly visualized with both 11C Met and 18FDG PET. The uptake values for 18FDG were significantly-higher in high- than in low-grade tumors, while no significant differences between the prognostic groups were found for 11C Met. A subjective evaluation of the tumor pattern on CT and on MR images was performed. An inhomogeneity index (IH8) was also used in MR images to make a quantitative assessment of the degree of inhomogeneity to determine their relation to prognosis. Patients with localized NHL, treated with radiotherapy, had an excellent prognosis irrespective of the degree of inhomogeneity, while patients with generalized disease, treated with chemotherapy, had a poor prognosis if the tumors were heterogeneous. Among chemotherapy-treated patients, all 9 patients with high IH8 values (> 2.56) on MR images and 9 out of 11 patients with severe inhomogeneities on CT images died. All patients with gastric NHL except for one patient with low-grade NHL of the MALT type displayed high 18FDG uptake at PET corresponding to the pathological findings at endoscopy and/or CT. 18FDG correctly excluded gastric NHL in a patient with benign gastric ulcer, but was unable to discriminate between gastric NHL and gastric carcinoma. The results suggest that 18FDG PET may demonstrate the extension of NHL in the gastric wall more accurately than CT and endoscopy. The prognostic importance of the size of a residual mass after completion of chemotherapy, and of tumor regression rates during chemotherapy, was evaluated in patients with high-grade NHL. Neither a large tumor size before treatment nor a large residual tumor after treatment correlated with relapse. It appears, however, as if the response rate halfway through the therapy may predict the recurrence rate, although statistical significance was not reached.
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PMID:Computed tomography, magnetic resonance imaging and positron emission tomography in non-Hodgkin's lymphoma. 964 67

The aim of this study was to investigate whether uptake of carbon-11 methionine (MET) is associated with histological grade of malignancy and survival in patients with newly diagnosed or recurrent lymphoma. Thirty-two patients with histologically confirmed lymphoma participated in the study. Twenty-six (81%) were studied before any therapy and six before treatment for recurrent disease. Twenty-eight patients had non-Hodgkin's lymphoma and four had Hodgkin's disease. An ECAT 931/08-12 positron emission tomography (PET) scanner was used for PET imaging. After the transmission scan, a median dose of 293 MBq of MET was injected intravenously and dynamic images were acquired for 40 min. The uptake of MET in tumour was measured as the standardized uptake value (SUV) and influx constant (Ki). The SUV formula was also adjusted to the predicted value of lean body mass (SUVlean) and body surface area (SUVBSA). The PET results were correlated with the clinical follow-up data. The median SUV in 32 malignant lesions was 6.6 (range, 1.9-12.4) and the median Ki was 0. 116 min-1 (range, 0.025-0.201, n=23). The median SUV was 7.0 (range, 5.4-12.4, n=9) in high, 6.2 (range, 1.9-10.4, n=11) in intermediate and 5.7 (range, 3.8-8.3, n=8) in low grade lymphomas. One intermediate grade lymphoma of the skin was visually negative (SUV 1. 9). In Hodgkin's disease the median SUV was 7.0 (range, 3.2-7.9, n=4). The median Ki value was 0.162 min-1 (range, 0.147-0.197, n=7) in high, 0.099 (range, 0.025-0.152, n=10) in intermediate, and 0.078 (range, 0.056-0.152, n=4) in low grade lymphomas and 0.149 (range, 0. 096-0.201, n=2) in Hodgkin's disease. The difference between high and other grade non-Hodgkin's lymphomas was significant when using Ki (P<0.001), but not with SUV, SUVlean or SUVBSA. The final outcome of the patients was not related to MET uptake. Lymphomas with a high Ki value tended to have a high S-phase fraction (r2=0.46, P=0.043). It is concluded that MET PET is highly sensitive for the detection of untreated and recurrent lymphomas. Differentation of high grade lymphomas from lower malignancy grades seems to be possible if graphical analysis is applied to calculate Ki for MET. However, prediction of survival is not possible with MET PET.
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PMID:Use of carbon-11 methionine positron emission tomography to assess malignancy grade and predict survival in patients with lymphomas. 966 95

Prolactin (PRL) interacts with lymphocyte-signaling molecules and cytokines. Previous work has shown independent and synergistic effects of PRL on the generation of IL-2-driven anti-tumor lymphokine activated killer (LAK) activity by peripheral blood mononuclear cells (PBMC). The potential importance of PRL as a biological immunomodifier, however, is challenged by its ability to influence normal lymphocyte mitogenesis and hence lymphoid tumor growth. Since non-Hodgkin's lymphoma (NHL) cell lines were efficiently killed by LAK generated with native (n) or recombinant (r) human PRL combined with low, per se ineffective doses of IL-2, we have addressed here the question of whether PRL acts as a growth factor for LAK targets. NHL cells were analyzed for: 1. expression of the PRL receptor (PRL-R); 2. responsiveness to nPRL or rPRL; 3. constitutive expression and release of PRL; 4. existence of a PRL autocrine loop. PRL-R, defined by multiple antibodies, was detected in 3 of 12 NHL cell lines. However, nPRL or rPRL, in a wide range of concentrations (0.75-50 ng/ml), were not mitogenic for growth-arrested, PRL-R positive NHL cell lines. PRL mRNA was detected by RT-PCR in 10 of the 12 cell lines examined with a higher frequency among AIDS-related NHL cell lines. PRL protein in the immunoprecipitate of (35)S-methionine-labeled cell lysates and supernatants paralleled mRNA expression, and Western blotting analysis showed the presence of the pituitary/lymphocyte non-glycosylated (23.5 kDa) and glycosylated (25 kDa) isoforms. Experiments with blocking antibodies showed the independence from endogenous PRL for NHL cell growth.
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PMID:Expression of prolactin and prolactin receptors by non-Hodgkin's lymphoma cells. 1058 95

In AIDS, only a few types of tumors (mainly Kaposi's sarcoma and non-Hodgkin's lymphoma) increase in incidence despite global abnormalities in the immune system. In addition, the reason for the higher incidence of these tumors is not immunosuppression but other agents. This shows that the immune system has no absolute role in the prevention of tumors. Consequently, the fact that tumors do not develop in the majority of the population during their lifetime, indicates the existence of other defense system(s). We demonstrated previously that a mixture of 16 substances (selected experimentally out of 89 compounds of the circulatory system using the synergistic tumor cell-killing effect as criteria) had a cytotoxic effect (inducing apoptosis) in vitro and in vivo on tumor cell lines, but not on normal cells in vitro or animals. In our hypothesis these substances (L-tryptophan, L-tyrosine, L-methionine, L(-)malate, L-ascorbate, L-arginine, L-phenylalanine, L-histidine, 2-deoxy-D-ribose, d-biotin, pyridoxine, adenine, riboflavin, D(+)-mannose, orotate, and hippurate) are the active agents of a passive antitumor defense system (PADS). On the basis of the results, a tablet and a cream were developed, and an infusion is in preclinical phase. In this study we demonstrate that the above-mentioned substances can kill tumor cells when the experimental protocols, concentrations, and cell numbers are chosen to be comparable to the physiological conditions that exist in the living system when these substances fight against arising cancer cells. The results of our experiments demonstrate that the PADS really works in the human body.
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PMID:Experimental evidence for the existence of the passive antitumor defense system formed by the synergistic action of certain small substances of the circulatory system. 1496 7

Folate and methionine metabolism is involved in DNA synthesis and methylation processes. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In a case-control study, we evaluated whether four common polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G), and methionine synthase reductase (MTRR A66G) genes may have a role in altering susceptibility to adult acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). We analyzed DNA of 120 adult ALL, 200 NHL, and 257 healthy control subjects. Individual carrying the MTHFR 677TT genotype showed a 3.6-fold decreased ALL risk [odds ratio (OR) 0.28, 95% confidence interval (95% CI) 0.12-0.72] than wild-types. Similarly, MS 2756GG individuals showed a 5.0-fold decreased ALL risk (OR 0.20, 95% CI 0.02-1.45) than wild-types. In combined results, subjects with the MTHFR 677CT/TT and MS 2756AG/GG genotypes revealed a 3.6-fold ALL risk reduction (OR 0.28, 95% CI 0.14-0.58) and those with the MTHFR 677TT and MTRR 66AG genotypes revealed a 4.2-fold ALL risk reduction (OR 0.24, 95% CI 0.06-0.81). Finally, those with the MS 2756AG/GG and MTRR 66AG/GG genotypes revealed a 2.2-fold ALL risk reduction (OR 0.45, 95% CI 0.10-0.85). Single analysis for NHL did not show any significant difference for all the polymorphisms investigated, but in the low-grade NHL subgroup, we found a 2.0-fold risk reduction for the MTRR 66GG homozygous genotype (OR 0.50, 95% CI 0.25-0.99), which was higher (OR 0.37, 95% CI 0.14-0.85) when analyzed in combination with MS 2756AA genotype. These data are in accordance with the hypothesis that polymorphisms in the genes for folate and methionine metabolism might play a greater role in the occurrence of ALL than NHL by influencing DNA synthesis and/or DNA methylation.
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PMID:Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non-Hodgkin's lymphoma in adults. 1515 11


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