Verbeek H.H.G.,University of Groningen |
Plukker J.T.M.,University of Groningen |
Koopmans K.P.,Martini Hospital Groningen |
De Groot J.W.B.,Section of Hematology and Medical Oncology |
And 6 more authors.
Journal of Nuclear Medicine | Year: 2012
The transition from stable to progressive disease is unpredictable in patients with biochemical evidence of medullary thyroid carcinoma (MTC). Calcitonin and carcinoembryonic antigen (CEA) doubling times are currently the most reliable markers for progression, but for accurate determination, serial measurements, which need time, are required. We compared 18F-FDG PET and 18F-dihydroxyphenylanaline (18F-DOPA) PET with biochemical parameters and survival to assess whether these imaging modalities could be of value in detecting progressive disease. Methods: We evaluated the outcome of 18F-FDG PET or 18F-DOPA PET with calcitonin and CEA doubling times in 47 MTC patients. A subgroup of patients was included in the whole metabolic burden (WBMTB) analysis, with determination of standardized uptake values and number of lesions. WBMTB of 18F-DOPA PET and 18F-FDG PET was compared with biochemical parameters. Furthermore, survival was compared with 18F-DOPA PET or 18F-FDG PET positivity. Results: Doubling times were available for 38 of 40 patients undergoing 18F-FDG PET. There was a significant correlation with 18F-FDG PET positivity. Doubling times were less than 24 mo in 77% (n = 10/13) of 18F-FDG PET-positive patients, whereas 88% (n = 22/25) of 18F-FDG PET-negative patients had doubling times greater than 24 mo (P < 0.001). Between doubling times and 18F-DOPA PET positivity, no significant correlation existed. 18F-DOPA PET detected significantly more lesions (75%, 56/75) than did 18F-FDG PET (47%, 35/75) in the 21 patients included in WBMTB analysis (P = 0.009). Calcitonin and CEA levels correlated significantly with WBMTB on 18F-DOPA PET, but doubling times did not. 18F-FDG PET positivity was a more important indicator for poor survival in patients for whom both scans were obtained. Conclusion: 18F-FDG PET is superior in detecting patients with biochemical progressive disease and identifying patients with poor survival. Although 18F-DOPA PET has less prognostic value, it can more accurately assess the extent of the disease in patients with residual MTC. Hence, both scans are informative about tumor localization and behavior. On the basis of these results, we designed a clinical flow diagram for general practice in detecting recurrent MTC. COPYRIGHT © 2012 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
Valizadeh N.,Section of Hematology and Medical Oncology |
Musavi J.,Infectious Diseases Specialist |
Nateghi S.H.,Urmia University of Medical Sciences
Shiraz E Medical Journal | Year: 2011
Hemophagocytic syndrome (HPS) is a disorder characterized by benign proliferation of hys-tiocytes and marked hemophagocytosis in bone marrow. Hemaphagocytic syndrome (HPS) is a rare manifestation of brucellosis. Genitiurinary complications of brucellosis are very diverse and include hydrocele, urinary tract infection, pyonephrosis, epididymo-orchitis, infertility and prostatitis. Acute prostatitis is rarely reported as the first manifestation of. This article is introducing a case of brucellosis presented with acute prostatitis and concurrent hemophagocytic syndrome.
Rhodes L.V.,Section of Hematology and Medical Oncology |
Short S.P.,Vanderbilt University |
Neel N.F.,Vanderbilt University |
Salvo V.A.,Section of Hematology and Medical Oncology |
And 26 more authors.
Cancer Research | Year: 2011
Estrogen independence and progression to a metastatic phenotype are hallmarks of therapeutic resistance and mortality in breast cancer patients. Metastasis has been associated with chemokine signaling through the SDF-1-CXCR4 axis. Thus, the development of estrogen independence and endocrine therapy resistance in breast cancer patients may be driven by SDF-1-CXCR4 signaling. Here we report that CXCR4 overexpression is indeed correlated with worse prognosis and decreased patient survival irrespective of the status of the estrogen receptor (ER). Constitutive activation of CXCR4 in poorly metastatic MCF-7 cells led to enhanced tumor growth and metastases that could be reversed by CXCR4 inhibition. CXCR4 overexpression in MCF-7 cells promoted estrogen independence in vivo, whereas exogenous SDF-1 treatment negated the inhibitory effects of treatment with the anti-estrogen ICI 182,780 on CXCR4-mediated tumor growth. The effects of CXCR4 overexpression were correlated with SDF-1-mediated activation of downstream signaling via ERK1/2 and p38 MAPK (mitogen activated protein kinase) and with an enhancement of ER-mediated gene expression. Together, these results show that enhanced CXCR4 signaling is sufficient to drive ER-positive breast cancers to a metastatic and endocrine therapy-resistant phenotype via increased MAPK signaling. Our findings highlight CXCR4 signaling as a rational therapeutic target for the treatment of ER-positive, estrogen-independent breast carcinomas needing improved clinical management. © 2010 American Association for Cancer Research.
Rhodes L.V.,Section of Hematology and Medical Oncology |
Boue S.M.,U.S. Department of Agriculture |
Wang S.,Section of Hematology and Medical Oncology |
Khalili H.,Section of Hematology and Medical Oncology |
And 8 more authors.
Oncology Letters | Year: 2012
The purpose of this study was to investigate the effects of glyceollins on the suppression of tumorigenesis in triple-negative breast carcinoma cell lines. We further explored the effects of glyceollins on microRNA and protein expression in MDA-MB-231 cells. Triple-negative (ER-, PgR-and Her2/neu-) breast carcinoma cells were used to test the effects of glyceollins on tumorigenesis in vivo. Following this procedure, unbiased microarray analysis of microRNA expression was performed. Additionally, we examined the changes in the proteome induced by glyceollins in the MDA-MB-231 cells. Tumorigenesis studies revealed a modest suppression of MDA-MB-231 and MDA-MB-468 cell tumor growth in vivo. In response to glyceollins we observed a distinct change in microRNA expression profiles and proteomes of the triple-negative breast carcinoma cell line, MDA-MB-231. Our results demonstrated that the glyceollins, previously described as anti-estrogenic agents, also exert antitumor activity in triple-negative breast carcinoma cell systems. This activity correlates with the glyceollin alteration of microRNA and proteomic expression profiles.
Saba N.S.,Section of Hematology and Medical Oncology |
Saba N.S.,Tulane Cancer Center |
Levy L.S.,Tulane Cancer Center |
Levy L.S.,Tulane University
Journal of Investigative Medicine | Year: 2012
Introduction: Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL) constitutes an aggressive variety of lymphomas characterized by increased extranodal involvement, relapse rate, and resistance to chemotherapy. Protein kinase C-beta (PKCA) targeting showed promising results in preclinical and clinical studies involving a wide variety of cancers, but studies describing the role of PKCA in AIDS-NHL are primitive if not lacking. Methods: In the present study, 3 AIDS-NHL cell lines were examined: 2F7 (AIDSYBurkitt lymphoma), BCBL-1 (AIDSYprimary effusion lymphoma), and UMCL01-101 (AIDSYdiffuse large B-cell lymphoma). Results: Immunoblot analysis demonstrated expression of PKCA1 and PKCA2 in 2F7 and UMCL01-101 cells, and PKCA1 alone in BCBL-1 cells. The viability of 2F7 and BCBL-1 cells decreased significantly in the presence of PKCA-selective inhibitor at half-maximal inhibitory concentration of 14 and 15 Kmol/L, respectively, as measured by tetrazolium dye reduction assay. In contrast, UMCL01-101 cells were relatively resistant. As determined using flow cytometric deoxynucleotidyl transferase dUTP nick-end labeling assay with propidium iodide staining, the responsiveness of sensitive cells was associated with apoptotic induction and cell cycle inhibition. Protein kinase C-betaYselective inhibition was observed not to affect AKT phosphorylation but to induce a rapid and sustained reduction in the phosphorylation of glycogen synthase kinase-3 beta, ribosomal protein S6, and mammalian target of rapamycin in sensitive cell lines. Conclusions: The results indicate that PKCA plays an important role in AIDS-related NHL survival and suggest that PKCA targeting should be considered in a broader spectrum of NHL. The observations in BCBL-1 were unexpected in the absence of PKCA2 expression and implicate PKCA1 as a regulator in those cells. © 2012 by The American Federation for Medical Research.
PubMed | University of Massachusetts Boston, Section of Hematology and Medical Oncology, Harvard University and From the Renal Section
Type: Journal Article | Journal: The Journal of biological chemistry | Year: 2015
Wnt signaling plays important roles in both the tumor-induced angiogenesis and tumorigenesis through the transcriptionally active nuclear -catenin. Recently, c-Cbl was identified as a unique E3 ubiquitin ligase targeting the active nuclear -catenin. However, little is known about the molecular mechanisms by which c-Cbl regulates ubiquitination and degradation of active -catenin. Here, we demonstrate that Wnt activation promotes the phosphorylation of c-Cbl at tyrosine 731(Tyr-731), which increases c-Cbl dimerization and binding to -catenin. Tyr-731 phosphorylation and dimerization mediate c-Cbl nuclear translocation and lead to the degradation of nuclearly active -catenin in the Wnt-on phase. c-Cbl activation also inhibits expression of the pro-angiogenic Wnt targets, IL-8 and VEGF. Phospho-Tyr-731-inactive mutant c-Cbl (Y731F) enhances and phosphomimetic mutant c-Cbl (Y731E) suppresses angiogenesis in zebrafish. Taken together, we have identified a novel mechanism for the regulation of active nuclear -catenin by c-Cbl and its critical role in angiogenesis. This mechanism can be further explored to modulate both the pathological angiogenesis and the tumorigenesis.
PubMed | Section of Hematology and Medical Oncology
Type: Journal Article | Journal: Oncology letters | Year: 2012
The purpose of this study was to investigate the effects of glyceollins on the suppression of tumorigenesis in triple-negative breast carcinoma cell lines. We further explored the effects of glyceollins on microRNA and protein expression in MDA-MB-231 cells. Triple-negative (ER-, PgR- and Her2/neu-) breast carcinoma cells were used to test the effects of glyceollins on tumorigenesis in vivo. Following this procedure, unbiased microarray analysis of microRNA expression was performed. Additionally, we examined the changes in the proteome induced by glyceollins in the MDA-MB-231 cells. Tumorigenesis studies revealed a modest suppression of MDA-MB-231 and MDA-MB-468 cell tumor growth in vivo. In response to glyceollins we observed a distinct change in microRNA expression profiles and proteomes of the triple-negative breast carcinoma cell line, MDA-MB-231. Our results demonstrated that the glyceollins, previously described as anti-estrogenic agents, also exert antitumor activity in triple-negative breast carcinoma cell systems. This activity correlates with the glyceollin alteration of microRNA and proteomic expression profiles.