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)

A number of clinical studies have demonstrated the prognostic significance of angiogenesis and angiogenic growth factors in solid tumours; however, very little is known about the relevance of these parameters in haematological malignancies. We evaluated circulating levels of angiogenic growth factors and endostatin in 36 non-Hodgkin's lymphoma (NHL) patients. Baseline vascular endothelial growth factor (VEGF) levels of patients in complete remission (CR) after a median follow-up of 21 months were significantly lower than those of patients with progressive disease (P = 0.016). Event-free survival (EFS) rate was significantly higher in patients who had baseline VEGF and basic-fibroblast growth factor (b.FGF) levels below the median values of 147 and 19.5 pg/ml (P = 0.018 and 0.039 by log-rank test, respectively). Conversely, the levels of endostatin, angiogenin and leptin were not different in CR patients compared to relapsed patients and did not correlate with EFS. Our data suggest that b-FGF and, particularly, VEGF might be considered prognostic factors in NHL staging and management.
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PMID:Angiogenic growth factors and endostatin in non-Hodgkin's lymphoma. 1084 4

Mast cells are likely to play a role in angiogenesis under pathological conditions. Solid tumor growth is dependent on angiogenesis, but the influence of mast cells on angiogenesis in non-Hodgkin's lymphoma, (NHL) is not clear. We investigated mast cell number and vessel count in 61 cases of NHL. We also evaluated expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), both important cytokines for angiogenesis. The number of mast cells was greater in T-cell lymphomas than in B-cell lymphomas. Of the T-cell lymphomas, the greatest number of mast cells was observed in the angioimmunoblastic T-cell lymphoma (AIL). In all NHLs, significant correlation was found between vessel count and the number of mast cells (p < 0.0001) and between vessel count and the number of VEGF-expressing cells (p < 0.05) but not between vessel count and bFGF-expressing cells. Strong correlation was detected between the number of mast cells and the number of VEGF-expressing cells (p < 0.0001) in all NHLs. Double fluorescence staining of VEGF mRNA and mast cell tryptase revealed that mast cells expressed VEGF mRNA. Our data suggest that mast cells play a very important role in angiogenesis by expressing VEGF in NHL, especially in AIL.
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PMID:Angiogenesis and mast cells in non-Hodgkin's lymphoma: a strong correlation in angioimmunoblastic T-cell lymphoma. 1169 1

Tumor angiogenesis plays a significant role in cancer growth and metastasis. This complex process is influenced by a variety of angiogenic factors. Elevated serum levels or high expression of some of these factors have been shown to correlate with stage and prognosis in certain human malignancies. This has been demonstrated most consistently for vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). We tried to establish, whether pre-treatment serum levels of the angiogenic factors VEGF, bFGF, interleukin 8 (IL-8) and Flt3 ligand (Flt3L) correlate with prognostic variables in 30 patients with primary gastro-intestinal non-Hodgkin's lymphoma. Our results suggest that higher pretreatment serum levels of IL-8 and Flt3L are associated with higher stage (>or= II) and high grade, respectively. Elevated pretreatment serum levels of VEGF and bFGF were not associated with advanced disease characteristics and carried no prognostic information.
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PMID:Interleukin 8 and Flt3 ligand as markers of advanced disease in primary gastrointestinal non-Hodgkin's lymphoma. 1195 21

Therapeutic approaches for non-Hodgkin's lymphoma (NHL) are currently based on the International Prognostic Index (IPI). Research on biological prognostic factors has been actively pursued in recent years, with serum vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) being identified as prognostic factors for NHL. Here, we determined that serum VEGF and IL-6 levels are independent prognostic factors for aggressive lymphoma. Compared with normal controls, serum VEGF and IL-6 levels were significantly higher in patients with aggressive lymphoma or adult T-cell leukemia/lymphoma. Furthermore, overall and disease-free survival rates for patients with high levels of VEGF or IL-6 were significantly poorer than for patients with low levels. In addition, the prognosis for patients with high levels of both serum VEGF and IL-6 was significantly poorer than that for patients with high levels of either VEGF or IL-6 or with low levels of both VEGF and IL-6. Multivariate analyses of a variety of prognostic factors, including the five IPI factors, revealed that serum VEGF and IL-6 were both independent prognostic factors for overall survival of aggressive lymphoma. Therefore, a combination of VEGF and IL-6 represents a useful prognostic factor for aggressive lymphoma.
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PMID:Simultaneous elevation of the serum concentrations of vascular endothelial growth factor and interleukin-6 as independent predictors of prognosis in aggressive non-Hodgkin's lymphoma. 1203 54

Abnormalities in the cell cycle are responsible for the majority of human neoplasias. Most abnormalities occur due to hyperphosphorylation of the tumor suppressor gene Rb by the key regulators of the cell cycle, the cyclin-dependent kinases (CDKs). Thus, a pharmacological CDK inhibitor may be useful in the prevention and/or treatment of human neoplasms. Flavopiridol is a flavonoid with interesting preclinical properties: (1) potent CDK inhibitory activity; (2) it depletes cyclin D1 and vascular endothelial growth factor mRNA by transcriptional and posttranscriptional mechanisms, respectively; (3) it inhibits positive elongation factor B, leading to transcription "halt"; and (4) it induces apoptosis in several preclinical models. The first phase I trial of a CDK inhibitor, flavopiridol, has been completed. Dose-limiting toxicities included secretory diarrhea and proinflammatory syndrome. Antitumor activity was observed in some patients with non-Hodgkin's lymphoma and renal, colon, and prostate cancers. Concentrations between 300 and 500 n M-necessary to inhibit CDK-were achieved safely. Phase II trials with infusional flavopiridol and phase I infusional trials in combination with standard chemotherapy are being completed with encouraging results. A novel phase I trial of 1-h flavopiridol administration was recently completed. The maximum tolerated doses using flavopiridol daily for 5, 3, and 1 consecutive days are 37.5, 50, and 62.5 mg/m(2) per day. Dose-limiting toxicities include vomiting, neutropenia, proinflammatory syndrome, and diarrhea. Plasma flavopiridol concentrations achieved were in the range 1.5-3.5 MICRO M. Phase II/III trials using this 1-h schedule in several tumor types including non-small-cell lung cancer, chronic lymphocytic leukemia, mantle cell lymphoma, and head and neck cancer are being conducted worldwide. UCN-01, the second CDK modulator that has entered clinical trials, has unique preclinical properties: (1) it inhibits protein kinase C (PKC) activity; (2) it promotes cell-cycle arrest by accumulation in p21/p27; (3) it induces apoptosis in several preclinical models; and (4) it abrogates the G(2) checkpoint by inhibition of chk1. The last of these represents a novel strategy to combine UCN-01 with DNA-damaging agents. In the initial UCN-01 clinical trial (continuous infusion for 72 h), a prolonged half-life of about 600 h (100 times longer than in preclinical models) was observed. The maximum tolerated dose was 42.5 mg/m(2) per day for 3 days. Dose-limiting toxicities were nausea/vomiting, hypoxemia, and symptomatic hyperglycemia. One patient with melanoma achieved a partial response (8 months). Another patient with refractory anaplastic large-cell lymphoma had no evidence of disease at >4 years. Bone marrow and tumor samples obtained from some patients revealed loss in adducin phosphorylation, a substrate of PKC. Phase I trials with shorter infusions are being completed. In summary, the first two CDK modulators have shown encouraging results in early clinical trials. A question that remains unanswered is "Which is the best schedule for combination with standard antitumor agents?" Moreover, it is still unclear which pharmacodynamic endpoint reflects loss of CDK activity in tissue samples from patients in these trials. Despite these caveats, we feel that CDKs are sensible targets for cancer therapy and that there are several small-molecule CDK modulators in clinical trials with encouraging results.
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PMID:Novel direct and indirect cyclin-dependent kinase modulators for the prevention and treatment of human neoplasms. 1281 36

Angiogenesis has a major role in the pathogenesis of malignancies. Studies involving the role of angiogenesis have been most commonly performed in solid tumors. However, studies related to hemapoietic neoplasia and angiogenesis are relatively limited. We investigated the role of angiogenesis in non-Hodgkin's lymphomas (NHLs) and its relation with clinical and histopathologic prognostic indicators. In this respect, angiogenesis markers were evaluated in 71 patients with NHL and these were compared with other prognostic indicators including age, gender, histological grade, stage, extranodal involvement and survival. Microvessel density (MVD) using Factor VIII monoclonal antibody and vascular endothelial growth factor (VEGF) using monoclonal antibody for VEGF expression were studied in paraffin-embedded tissue samples. We did not find a significant relationship between MVD and patient characteristics including age, gender, stage, histological grade, nodal status, international prognostic index (IPI), and response to treatment. MVD was found to be greater in cases with B symptoms compared to those without B symptoms (14.6 +/- 5.7 and 11.4 +/- 5.3, respectively, p = 0.002). No significant relationship was found between VEGF and age, gender, stage, histological grade, IPI, and overall survival. The complete and partial response rate to therapy was significantly higher in VEGF-negative patients than in the VEGF-positive patients (p = 0.003). In conclusion, there appears to be a role for angiogenesis and angiogenic factors in NHLs. The combination of anti-angiogenic drugs with conventional anti-neoplastic treatment will probably be used in the future. Larger series of patients are needed to determine the prognostic value of angiogenesis in NHL.
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PMID:Prognostic significance of microvessel density and vascular endothelial growth factor (VEGF) expression in non-Hodgkin's lymphoma. 1495 52

Mouse, chimeric, humanized and human monoclonal antibodies (MABs) are all in use for treatment of human cancer. Unconjugated antibodies have a complex mechanism of action, dependent on the nature of the target structure. Antibodies can activate the immune system (antibody-dependent cellular cytotoxicity [ADCC], complement-dependent cytotoxicity [CDC], induction of tumor immunity [idiotype network]). ADCC appears to be one of the most important immune effector functions. Antibodies may also induce apoptosis, cell cycle arrest, inhibition of cell proliferation as well as angiogenesis and metastatic spread. For most antibodies there is no clear dose-response relationship in vivo. The effect of antibodies can be enhanced by combination with chemotherapy and/or by agents which activate the immune system. The best therapeutic effect may be obtained if MABs are used early in the course of the disease. Rituximab (anti-CD20) was the first registered MAB for the therapy of follicular lymphoma. Impressive results have been seen in combination with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone) in follicular and high-grade lymphomas. In other non-Hodgkin's lymphoma subtypes, promising results are also seen in combination with chemotherapy. Trastuzumab (anti-Her2) is a breakthrough in the treatment of breast cancer in combination with chemotherapeutic agents. This antibody is also in clinical testing for adjuvant treatment. Alemtuzumab (anti-CD52) has shown impressive results both in refractory chronic lymphocytic leukemia and as up-front therapy. There are many other antibodies in late stages of testing for registration. Interesting MABs include cetuximab (anti-epidermal growth factor receptor [EGFR]), especially in combination with radiotherapy in head and neck cancer; ABX-EGF (anti-EGFR) in renal carcinoma; bevacizumab (anti-vascular endothelial growth factor) in several solid tumors. Antiepithelial cell adhesion molecule antibodies show promise in combination with chemotherapy in the adjuvant setting of colorectal carcinoma. It is estimated that about 20 antibodies will be in clinical use by the year 2010.
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PMID:Monoclonal antibodies in human cancer. 1498 43

Inflammatory cytokines play important roles in the pathogenesis of lymphomas and may reflect underlying biological processes including tumour-host interactions with prognostic information that is not afforded by conventional clinical parameters. Several lines of evidence suggest that serum levels of interleukin (IL)-6 and vascular endothelial growth factor (VEGF) are independent indicators of long-term outcome in non-Hodgkin's lymphoma (NHL), but the clinical impact of early serial monitoring of these cytokines has not been reported. Serum samples from 64 newly diagnosed patients with aggressive NHL were obtained before the first cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and then weekly until the second cycle was given. Serum IL-6 and VEGF were measured by commercial enzyme-linked immunosorbent assays (ELISA). Pre-treatment serum IL-6 and VEGF levels were significantly correlated to response rate and overall survival. A significant decrease of IL-6 and VEGF levels was observed in the first weeks after CHOP therapy in patients achieving a complete remission after treatment. Multivariate analysis indicated that early changes of IL-6 and VEGF serum levels within the first 3 weeks after initiation of chemotherapy were independent predictors of clinical response even when corrected for the influence of clinical prognostic factors. Only changes in serum IL-6 level had borderline significance for the prediction of overall survival. The data indicate that serial measurements of serum IL-6 and VEGF may be early prognostic indicators and support the hypothesis of a clinical impact by early recognition of poor-risk patients and candidates for new treatment options.
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PMID:Early changes in serum IL-6 and VEGF levels predict clinical outcome following first-line therapy in aggressive non-Hodgkin's lymphoma. 1583 69

Canine non-Hodgkin's lymphoma (NHL) is considered to be a good animal model for its human counterpart; nevertheless, comparative data on neo-angiogenesis are completely lacking. The aim of this study is to investigate the levels of serum vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) 2 and 9 in lymphoma-affected dogs. Circulating levels of VEGF and both MMP 2 and 9 activities significantly correlate with the WHO sub-stage b prognostic factor; moreover, VEGF at admission have an independent influence on the length of the disease free interval. As in humans, serum VEGF concentration and most likely also MMPs plasma activity have prognostic value in canine NHL spontaneous model.
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PMID:Prognostic value of serum vascular endothelial growth factor (VEGF) and plasma activity of matrix metalloproteinase (MMP) 2 and 9 in lymphoma-affected dogs. 1589 73

Angiogenesis plays a major role in the development and progression of haematological malignancies. In our study we measured plasma concentrations of key angiogenic activators vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) using comercially available sandwich enzyme-linked immunosorbent assay (ELISA) in 37 patients with lymphoid malignancies and 20 healthy donors. We found a statistically significant increase in bFGF concentrations in patients with B-cell chronic lymphocytic leukemia (B-CLL, n=18) compared to the control group (median 118.8 vs. 9.3 pg/ml, p<0.001). However, we didn't find any significant difference in VEGF concentrations between B-CLL patients and the control group. There was also no significant increase in bFGF or VEGF in patients with multiple myeloma (n=7) and non-Hodgkin's lymphoma (n=12). Our pilot study shows that measurement of angiogenic activators in plasma is a feasible and reproducible method of angiogenesis assessment. Larger studies are needed for correlation between serum and plasma concentrations and detailed statistical evaluation including the impact on patients' survival.
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PMID:Plasma concentrations of vascular endothelial growth factor and basic fibroblast growth factor in lymphoproliferative disorders. 1608 Mar 87


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