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The small round blue cell tumors of childhood, which include neuroblastoma, rhabdomyosarcoma, non-Hodgkin's lymphoma, and the Ewing's family of tumors, are so called because of their similar appearance on routine histology. Using cDNA microarray gene expression profiles and artificial neural networks (ANNs), we previously identified 93 genes capable of diagnosing these cancers. Using a subset of these, together with some additional genes (total 39), we developed a multiplex polymerase chain reaction (PCR) assay to diagnose these cancer types. Blinded testing of 96 new samples (26 Ewing's family of tumors, 29 rhabdomyosarcomas, 24 neuroblastomas, and 17 lymphomas) using ANNs in a complete leave-one-out analysis demonstrated that all except one sample were accurately diagnosed as their respective category. Moreover, using an ANN-based gene minimization strategy in a separate analysis, we found that the top 31 genes could correctly diagnose all 96 tumors. Our results suggest that this molecular test based on a multiplex PCR reaction may assist the physician in the rapid confirmation of the diagnosis of these cancers.
J Mol Diagn 2007 Feb
PMID:Diagnosis of the small round blue cell tumors using multiplex polymerase chain reaction. 1725 39

We show that prolonged exposure of non-Hodgkin's lymphoma (NHL) cell lines to low doses of the Src family protein tyrosine kinases (SFKs) inhibitor SU6656 caused proliferation abrogation as a result of the formation of cells with single multilobed nuclei and several mitotic spindle poles, features similar to polyploid megakaryocytes. The propensity of the NHL B cells tested to undergo polyploid was unrelated to the presence of p53 mutations in these cells since comparable outcomes were observed in SU6656-exposed cultures of blood B lymphocytes derived from healthy individuals. Thus, in addition to its utility for the study of megakaryocyte polyploidization, our results show that SU6656 can also induce polyploidy in cells of lymphoid origin, revealing a chemotherapeutic potential for this inhibitor to limit tumor propagation of malignant B cell lymphomas, although not without affecting normal B cells as well.
Blood Cells Mol Dis
PMID:Human B lymphocytes and non-Hodgkin's lymphoma cells become polyploid in response to the protein kinase inhibitor SU6656. 1743 68

Favrille Inc is developing FavIld, a patient-specific immunotherapy combining tumor-specific idiotype protein and keyhole limpet hemocyanin, for the potential treatment of lymphoma. A phase III clinical trial in follicular B-cell non-Hodgkin's lymphoma is underway.
Curr Opin Mol Ther 2007 Jun
PMID:Drug evaluation: FavId, a patient-specific idiotypic vaccine for non-Hodgkin's lymphoma. 1760 28

Haploidentical hematopoietic cell transplantation (HHCT) after high dose conditioning with CD34-selected stem cells has been complicated by high regimen related toxicities, slow engraftment and delayed immune reconstitution leading to increased treatment related mortality (TRM). A new regimen using reduced intensity conditioning (RIC) and graft CD3/CD19 depletion with anti-CD3 and anti-CD19 coated microbeads on a CliniMACS device may allow HHCT with lower toxicity and faster engraftment. CD3/CD19 depleted grafts not only contain CD34+ stem cells but also CD34 negative progenitors, natural killer, graft facilitating and dendritic cells. RIC was performed with fludarabine (150-200 mg/m(2)), thiotepa (10 mg/kg), melphalan (120 mg/m(2)) and OKT-3 (5 mg/day, day -5 to +14) and no posttransplant immunosuppression. Twenty nine patients (median age=42 (range, 21-59) years) have been transplanted with this regimen. Diagnosis were AML (n=16), ALL (n=7), NHL (n=3), MM (n=2) and CML (n=1). Patients were "high risk" with refractory disease or relapse after preceding HCT. The CD3/CD19 depleted haploidentical grafts contained a median of 7.6x10(6) (range, 3.4-17x10(6)) CD34+ cells/kg, 4.4x10(4) (range, 0.006-44x10(4)) CD3+ T cells/kg and 7.2x10(7) (range, 0.02-37.3x10(7)) CD56+ cells/kg. Donor-recipient KIR-ligand-mismatch was found in 19 of 29 patients. The regimen was well tolerated with maximum acute toxicity being grade 2-3 mucositis. Because of severe neurotoxicity in 4 patients treated with 200 mg/m(2) fludarabine, the dose was reduced to 150 mg/m(2). Engraftment was rapid with a median time to >500 granulocytes/microL of 12 (range, 10-21) days, >20,000 platelets/microL of 11 (range, 7-38) days and full donor chimerism after 2-4 weeks in all patients. Incidence of grade II-IV degrees GVHD was 48% with grade II degrees =10, III degrees =2 and IV degrees =2. One patient, who received the highest T-cell dose, developed lethal grade IV GVHD. TRM in the first 100 days was 6/29 (20%) with deaths due to idiopathic pneumonia syndrome (n=1), mucormycosis (n=1), pneumonia (n=3) or GVHD (n=1). Overall survival is 9/29 patients (31%) with deaths due to infections (n=7), GVHD (n=1) and relapse (n=12) with a median follow-up of 241 days (range, 112-1271). In conclusion, this regimen is promising in high risk patients lacking a suitable donor, and a prospective phase I/II study is ongoing.
Blood Cells Mol Dis
PMID:Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: an update. 1786 47

The transcription factor CCAAT/enhancer binding protein (C/EBP)alpha is a myeloid-specific transcription factor which is required for normal myeloid differentiation. C/EBPalpha is encoded by an intronless gene that is 2783 bp long and maps to human chromosome 19q13.1. C/EBPalpha is a member of the basic region leucine zipper (bZIP) class of DNA-binding proteins. The loss of function of C/EBPalpha has leukemogenic potential. Four types of polymorphisms and 25 mutations (3 already known mutations and 22 novel mutations) were detected in CEBPA (gene for the transcription factor CCAAT/enhancer binding protein (C/EBP) alpha) in analysed samples from 390 patients with myelodysplastic syndrome (MDS) and hematologic malignancies. CEBPA mutations were found in 14/152 (9.2%) of acute myeloid leukemia (AML) patients' samples, 6/143 (4.2%) of MDS patients' samples, 2/56 (3.6%) of non-Hodgkin's lymphoma (NHL) patients' samples and 2/39 (5.1%) of multiple myeloma (MM) patients' samples. No C/EBPalpha mutations were detected in healthy donors (41 individuals). We discuss how these mutations can affect the cellular function of C/EBPalpha and block the myeloid differentiation.
Blood Cells Mol Dis
PMID:CEBPA polymorphisms and mutations in patients with acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and non-Hodgkin's lymphoma. 1818 75

The Medical Subject Headings (MeSH) thesaurus used by the National Library of Medicine defines logistic regression models as "statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable." Logistic regression models are used to study effects of predictor variables on categorical outcomes and normally the outcome is binary, such as presence or absence of disease (e.g., non-Hodgkin's lymphoma), in which case the model is called a binary logistic model. When there are multiple predictors (e.g., risk factors and treatments) the model is referred to as a multiple or multivariable logistic regression model and is one of the most frequently used statistical model in medical journals. In this chapter, we examine both simple and multiple binary logistic regression models and present related issues, including interaction, categorical predictor variables, continuous predictor variables, and goodness of fit.
Methods Mol Biol 2007
PMID:Logistic regression. 1845 55

Genmab A/S and licensee GlaxoSmithKline plc are developing ofatumumab, an anti-CD20 human mAb, for the potential intravenous treatment of non-Hodgkin's lymphoma and autoimmune diseases, such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Phase I and II clinical trials have been completed in patients with chronic lymphocytic leukemia (CLL), rituximab-refractory follicular lymphoma (FL) and RA. At the time of publication ofatumumab was undergoing a phase II clinical trial in patients with diffuse large B-cell lymphoma and phase III clinical trials in patients with B-cell CLL (B-CLL) in which fludarabine and alemtuzumab treatments have failed and in patients with rituximab-refractory FL. Ofatumumab was also undergoing phase II clinical trials as a combination therapy for previously untreated patients with FL in combination with cyclophosphamide, adriamycin, vincristine, and prednisone and in combination with fludarabine and cyclophosphamide for the treatment of B-CLL. In addition, two phase III clinical trials to assess patients who have an inadequate response to methotrexate and TNFalpha therapy were ongoing for patients with RA, and a phase II clinical trial to investigate the effects of repeated doses of ofatumumab was recruiting patients with RA from a previous trial on ofatumumab. A phase I/II clinical trial of ofatumumab in relapsing-remitting MS was expected to commence in 2008.
Curr Opin Mol Ther 2008 Jun
PMID:Ofatumumab, a human monoclonal antibody for lymphoid malignancies and autoimmune disorders. 1853 37

We report a case of primary hepatic non-Hodgkin's lymphoma in a 67-year-old man with chronic hepatitis C. Laboratory data revealed slightly elevated liver function parameters and positive for hepatitis C virus (HCV) antibody. Abdominal ultrasonography showed hypoechoic lesions approximately 5 mm in diameter in the whole liver. Magnetic resonance imaging showed that the tumors were isointense in relationship to the liver on T(1)-weighted images but were slightly hyperintense on T(2)-weighted images. Under a clinical diagnosis of liver tumor, liver biopsy was performed. Histological examination confirmed a diagnosis of non-Hodgkin's diffuse large B-cell lymphoma, and the immunophenotype was identified to be the germinal cell type.
Med Mol Morphol 2008 Sep
PMID:A case of primary hepatic non-Hodgkin's lymphoma with chronic hepatitis C. 1880 44

Apart from regulating sleep and wakefulness, the circadian system may play an important role in other biological processes, including pathways involved in tumorigenesis. Two genetic association studies recently conducted by our lab have shown that a missense mutation in neuronal PAS domain protein 2 (NPAS2), a core circadian gene and transcriptional regulator, is significantly associated with risk of breast cancer and non-Hodgkin's lymphoma. Our current functional analyses provide the first in vitro evidence further demonstrating that cells with RNA interference-mediated depletion of NPAS2 fail to exhibit the expected cell cycle delay in response to mutagen treatment. DNA repair capacity, as measured by the comet assay, is also impaired. Moreover, a pathway-based PCR expression array of genes important for DNA damage signaling showed that knockdown of NPAS2 significantly represses the expression of several cell cycle and DNA repair genes. Thus, NPAS2 may play a role in tumorigenesis by affecting expression of cancer-related genes and could be considered a novel tumor suppressor.
Mol Cancer Res 2008 Sep
PMID:The circadian gene NPAS2, a putative tumor suppressor, is involved in DNA damage response. 1881 33

Biovest International Inc (a subsidiary of Accentia BioPharmaceuticals Inc), under license from Stanford University, is developing BiovaxID, a personalized therapeutic vaccine against B-cell lymphomas that, in combination with GM-CSF, exclusively targets cancerous B-cells by raising an immune response to tumor-specific immunoglobulin proteins called idiotypes, for the potential treatment of follicular non-Hodgkin's lymphoma (NHL). Phase I and II clinical trials demonstrated the immunogenicity, safety and therapeutic efficacy of BiovaxID. Phase III clinical trials in NHL were ongoing at the time of publication.
Curr Opin Mol Ther 2008 Oct
PMID:BiovaxID, a personalized therapeutic vaccine against B-cell lymphomas. 1883 Sep 28


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