Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

B-cell lymphoma gene (BCL-6) upregulation contributes to immortalization of mouse embryo fibroblast and primary B cells via upregulation of cyclin D1. As cyclin D1 overexpression is a common phenomenon in different cancers, BCL-6 protein overexpression may not be restricted to lymphomas. In this study, expression of BCL-6 was investigated by immunohistochemistry on paraffin-embedded specimens from 150 breast cancer patients and 10 specimens of normal breast tissue. The results showed BCL-6 overexpression (> or =10% of cells) in 24/150 (16%) breast cancer patients, whereas in normal breast low expression (<1%) of BCL-6 was observed. In linear regression analysis BCL-6 expression was associated with cyclin D1 (r=0.197, P=0.016). Further, in chi2 analyses, BCL-6-positivity was associated with overexpression of p53 (P=0.016), and hypoxia-inducible factor-1alpha (P<0.001). Involvement of BCL-6 in breast carcinogenesis is further underscored by comparative genomic hybridization analysis that showed gains at the BCL-6 locus (3q27) in 14/86 (16%) breast cancer tissues. The cases with amplification in BCL-6 showed an increased (25%) incidence of BCL-6 protein overexpression. Thus, this study is the first to show that BCL-6 oncogene activation plays a role in cancers other than lymphomas.
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PMID:Protein expression of B-cell lymphoma gene 6 (BCL-6) in invasive breast cancer is associated with cyclin D1 and hypoxia-inducible factor-1alpha (HIF-1alpha). 1465 91

Predicted survival probability functions of censored event free survival are improved by bagging survival trees. We suggest a new method to aggregate survival trees in order to obtain better predictions for breast cancer and lymphoma patients. A set of survival trees based on B bootstrap samples is computed. We define the aggregated Kaplan-Meier curve of a new observation by the Kaplan-Meier curve of all observations identified by the B leaves containing the new observation. The integrated Brier score is used for the evaluation of predictive models. We analyse data of a large trial on node positive breast cancer patients conducted by the German Breast Cancer Study Group and a smaller 'pilot' study on diffuse large B-cell lymphoma, where prognostic factors are derived from microarray expression values. In addition, simulation experiments underline the predictive power of our proposal.
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PMID:Bagging survival trees. 1047 58

We hypothesized that the phytosterols beta-sitosterol (BSS), beta-sitosterol glucoside (BSSG), and Moducare (MC; BSS:BSSG = 99:1) could modulate the growth of estrogen-dependent human breast cancer cells in vitro and in vivo. The present study evaluated the estrogenic and antiestrogenic effects of BSS, BSSG, and MC (0.001 to 150 micromol/L) on the proliferation of Michigan Cancer Foundation 7 (MCF-7) cells in vitro. Both BSS (>1 micromol/L) and MC (>50 micromol/L) increased MCF-7 cell proliferation. Treatment with 150 micro mol/L of BSS and MC increased cell growth by 2.4 and 1.5 times, respectively, compared to the negative control (NC) group. However, BSSG had no effect at the concentrations tested. The effects of dietary BSS, BSSG, and MC on the growth of MCF-7 cells implanted in ovariectomized athymic mice were also evaluated. Estrogenic effects of the phytosterols were evaluated in the NC, BSS, BSSG, and MC treatment groups, and antiestrogenic effects were evaluated in the 17 beta-estradiol (E(2)), E(2) + BSS, E(2) + BSSG, and E(2) + MC treatment groups. Mice were treated with dietary BSS (9.8 g/kg AIN93G diet), BSSG (0.2 g/kg diet), or MC (10.0 g/kg diet) for 11 wk. Dietary BSS, BSSG, and MC did not stimulate MCF-7 tumor growth. However, dietary BSS, BSSG, and MC reduced E(2)-induced MCF-7 tumor growth by 38.9% (P < 0.05), 31.6% (P = 0.08), and 42.13% (P < 0.05), respectively. The dietary phytosterols lowered serum E(2) levels by 35.1, 30.2, and 36.5% in the E(2) + BSS, E(2) + BSSG, and E(2) + MC groups, respectively (P < 0.05), compared to that of the E(2) treatment group. Estrogen-responsive pS2 mRNA expression in tumors did not differ among groups, but expression of the antiapoptotic marker B-cell lymphoma/leukemia-2 (bcl-2) in tumors from the E(2) + MC group was downregulated, compared to that of the E(2) treatment group. In summary, BSS and MC stimulated MCF-7 cell growth in vitro. Although BSSG comprises only 1% of MC, BSSG made MC less estrogenic than BSS alone in vitro. However, dietary BSS and MC protected against E(2)-stimulated MCF-7 tumor growth and lowered circulating E(2) levels.
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PMID:beta-Sitosterol, beta-Sitosterol Glucoside, and a Mixture of beta-Sitosterol and beta-Sitosterol Glucoside Modulate the Growth of Estrogen-Responsive Breast Cancer Cells In Vitro and in Ovariectomized Athymic Mice. 1511 61

B-cell lymphoma 2 (Bcl-2) is a pivotal regulator of apoptotic cell death and it is overexpressed in many cancers. Consequently, the Bcl-2 protein is an attractive target for drug design, and Bcl-2-specific antisense oligonucleotides or small-molecule Bcl-2 inhibitors have shown broad anticancer activities in preclinical models and are currently in several clinical trials. The clinical application of immunotherapy against cancer is rapidly moving forward in multiple areas, including the adoptive transfer of anti-tumor-reactive T cells and the use of "therapeutic" vaccines. The overexpression of Bcl-2 in cancer and the fact that immune escape by down-regulation or loss of expression of this protein would impair sustained tumor growth makes Bcl-2 a very attractive target for anticancer immunotherapy. Herein, we describe spontaneous T-cell reactivity against Bcl-2 in peripheral blood from patients suffering from unrelated tumor types (ie, pancreatic cancer, breast cancer, acute myeloid leukemia [AML], and chronic lymphocytic leukemia [CLL]). Additionally, we show that these Bcl-2-reactive T cells are indeed peptide-specific, cytotoxic effector cells. Thus, Bcl-2 may serve as an important and widely applicable target for anticancer immunotherapeutic strategies (eg, in the combination with conventional radiotherapy and chemotherapy).
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PMID:Immunogenicity of Bcl-2 in patients with cancer. 1536 32

The B cell, a major component of humoral immunity, is a sensitive target for the immunotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), possibly by rendering cells less responsive to antigenic or mitogenic stimulation. Potential mechanisms of TCDD action on B cells were examined in murine B cell lymphoma cells (CH12.LX) treated with 3 nM TCDD or dimethyl sulfoxide vehicle using sequence-verified cDNA microarrays. One transcript that was significantly induced by TCDD was suppressor of cytokine signaling 2 (Socs2). Changes in Socs2 mRNA levels paralleled that of Cyp1a1 with a maximal 3-fold induction observed at 4 h, as determined by quantitative real-time polymerase chain reaction. Socs2 induction seems B cell-specific, because no induction was observed in TCDD-responsive mouse hepatoma cells or human breast cancer cells. TCDD-mediated induction of Socs2 mRNA was dose-dependent and exhibited the characteristic structure-activity relationships observed for the aryl hydrocarbon receptor (AhR) ligands 3,3',4,4',5-pentachlorobiphenyl (PCB-126), indolo[3,2-b]-carbazole, and beta-naphthoflavone. Experiments with cycloheximide and AhR-deficient B cells indicated that Socs2 mRNA induction is a primary effect that is AhR-dependent. Western blot analysis confirmed that Socs2 and Cyp1a1 protein levels were also induced in CH12.LX cells. Promoter analysis revealed the presence of four dioxin-response elements within 1000 base pairs upstream of the Socs2 transcriptional start site, and a reporter gene regulated by the Socs2 promoter was inducible by TCDD. Promoter activity was also dependent on a functional AhR signaling pathway. These results indicate that Socs2 is a primary TCDD-inducible gene that may represent a novel mechanism by which TCDD elicits its immunosuppressive effects.
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PMID:2,3,7,8-Tetrachlorodibenzo-p-dioxin induces suppressor of cytokine signaling 2 in murine B cells. 1537 57

About 75% of breast tumors are positive for the estrogen receptor (ER) or progesterone receptor (PgR) or both, and estrogen is the main stimulant in the development and growth of these tumors. Tamoxifen, an estrogen receptor antagonist has been endocrine treatment for hormone-sensitive breast cancer for more than 20 years. However, the underlying cause of treatment failure in many breast cancer patients receiving tamoxifen is resistance to tamoxifen. The mechanisms of tamoxifen and the molecular events responsible for resistance to tamoxifen are not fully understood. Two ER subtypes, ERalpha and ERbeta, activate the Activator Protein-1 (AP-1) response elements, and through interactions between ERs and the AP-1 transcription factors c-fos and c-jun, these transcription factors regulate the genes involved in many cellular processes, including proliferation, differentiation, cell motility, and apoptosis. Thus, the interaction between ERs and AP-1 could be important clinically and could have bearing on the response to tamoxifen. Tamoxifen acts as an agonist on genes under the control of an AP-1 response elements when ERalpha or ERbeta is expressed. AP-1 blockade suppresses mitogenic signals from multiple different peptide growth factors as well as estrogen, and inhibits the growth of MCF-7 breast cancer cells both in vitro and in vivo. Tamoxifen actually activate the AP-1 transcription factor. Increased AP-1 activity in breast cancer cells can lead to tamoxifen resistance. The proto-oncogene B-cell lymphoma gene 6 (BCL-6) has been characterized as a regulator of B-lymphocyte growth and development. BCL-6 is also expressed in the mammary epithelium in nonpregnant animals and during early pregnancy and is expressed in 68% of histologically high-grade ductal breast carcinomas, which are clinically the most aggressive. BCL-6 is a potent repressor of transcriptional activity mediated by AP-1 factors. We hypothesize that increased BCL-6 in breast cancer cells might block tamoxifen resistance by repressing AP-1, eventually resulting in apoptosis. We also suggest that BCL-6 expression must be analyzed in ER-positive breast cancer patients and the results must be correlated with predictive and prognostic factors and survival.
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PMID:Possible interaction between activator protein-1 and proto-oncogene B-cell lymphoma gene 6 in breast cancer patients resistant to tamoxifen. 1548 54

The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, assays were developed to determine HAGA (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to ''humanize'' MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.
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PMID:A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words. 1564 Jul 88

Determination of the human genome sequence and the development of microarray technologies allowing the rapid measurement of all genes in the genome have generated new perspectives for our current biomedical research. Gene expression analysis will make a major contribution to our insight into the underlying biology of disease and will lead to improved methods for diagnostics, prognosis and treatment. Microarray studies create the possiblity to subclassify patients with diseases such as rheumatoid arthritis, diffuse large B-cell lymphoma and breast cancer, with both prognostic and therapeutic consequences. The simultaneous quantification of the activity of all genes in tissues or cells from patients by microarray technology, linked to the clinical parameters, creates a large number of data points, which cannot be analysed without the aid of the advanced application of bioinformatics. As a result, genomic research has become, in part, a bioinformatics discipline that will be integrated with clinical medicine. The microarray technology makes it possible to develop personalized medicine, with a more accurate diagnosis and prognosis for every patient and subsequently a tailored treatment strategy.
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PMID:[Molecular unraveling of disease by means of DNA-microarrays]. 1581 27

In a 75-year-old woman with a swelling in her left breast, a 39-year-old woman with an anal fissure due to diarrhoea and a 65-year-old woman with chest pain, a mammary tumour was diagnosed that did not originate in mammary tissue. These were a recurrent melanoma, a carcinoma of the thyroid and a B-cell lymphoma, respectively. All patients were treated. The first patient developed new metastases one year later, the second died, partly as a result of the tumour, and the third showed no recurrence of the tumour after two years. Breast cancer is one of the most frequently occurring neoplasms in women. Primary tumours in the breast from other origins and metastatic lesions to the breast from extramammary tumours are rare. Most of these cases concern haematological malignancies and metastases from melanoma and lung cancer. Despite the fact that metastases to the breast are rare, one should always consider the possibility.
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PMID:[A malignant tumour in the breast is not always primary breast cancer]. 1599 99

According to several reports, the 10 year incidence of secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after systemic chemotherapy is approximately 1.5%. The cumulative risk increases by 0.25--1% for the first 8 years after treatment. We have reported only 6 cases of hematological malignancies (0.3%) after breast cancer chemotherapy in our institute. We detected 2 cases of secondary AML and 1 case of MDS, 19, 52 and 12 months, respectively, after systemic chemotherapy for breast cancer. Published data on the occurrence of secondary hematological malignancies other than AML or MDS in this setting are scarce. We encountered diffuse large B-cell lymphoma, angioimmunoblastic lymphoma and mantle cell lymphoma as secondary hematological malignancies after systemic chemotherapy for breast cancer.
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PMID:Secondary hematological malignancies after breast cancer chemotherapy. 1608 60


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