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Houston, TX, United States

Adrada B.E.,University of Texas M. D. Anderson Cancer Center | Miranda R.N.,515 Holcombe Blvd. | Rauch G.M.,University of Texas M. D. Anderson Cancer Center | Arribas E.,University of Texas M. D. Anderson Cancer Center | And 12 more authors.
Breast Cancer Research and Treatment

Breast implant-associated anaplastic large cell lymphoma (BIA ALCL) is a newly described clinicopathologic entity. The purpose of this study is to describe the imaging findings of patients with BIA ALCL and determine their sensitivity and specificity in the detection of the presence of an effusion or a mass related to BIA ALCL. A retrospective search was performed of our files as well as of the world literature for patients with pathologically proven BIA ALCL who had been assessed by any imaging study including ultrasound (US), computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT, as well as mammography. The sensitivity and specificity of each imaging modality in the detection of an effusion or a mass around breast implants was determined. We identified 44 patients who had BIA ALCL and imaging studies performed between 1997 and 2013. The sensitivity for detecting an effusion was 84, 55, 82, and 38 %, and for detecting a mass was 46, 50, 50, and 64 %, by US, CT, MRI, and PET, respectively. The sensitivity of mammography in the detection of an abnormality without distinction of effusion or mass was 73 %, and specificity 50 %. Progression-free survival was worse in patients with an implant-associated mass (p = 0.001). Conclusions: Current imaging with US, CT, MR, and PET appears suboptimal in the detection of an imaging abnormality associated with BIA ALCL. This under diagnosis may reflect a lack of awareness of this rare entity suggesting the need for better understanding of the spectrum of imaging findings associated with BIA ALCL by breast imagers. © 2014 Springer Science+Business Media. Source

Williams M.D.,515 Holcombe Blvd. | Esmaeli B.,Section of Ophthalmology | Soheili A.,Section of Ophthalmology | Simantov R.,Curagen Corporation | And 3 more authors.
Melanoma Research

Uveal melanoma is an aggressive disease without effective adjuvant therapy for metastases. Despite genomic differences between cutaneous and uveal melanomas, therapies based on shared biological factors could be effective against both tumor types. High expression of glycoprotein-NMB (GPNMB) in cutaneous melanomas led to the development of CDX-011 (glembatumumab vedotin), a fully human monoclonal antibody against the extracellular domain of GPNMB conjugated to the cytotoxic microtubule toxin monomethylauristatin E. Ongoing phase II trials suggest that CDX-011 has activity against advanced cutaneous melanomas. To determine the potential role of CDX-011 in uveal melanomas, we studied their GPNMB expression. Paraffin-embedded tissues from 22 uveal melanomas treated by enucleation from 2004-2007 at one institution were evaluated immunohistochemically for expression of GPNMB using biotinylated CDX-011 (unconjugated) antibody. Melanoma cells were evaluated for percentage and intensity of expression. Spectral imaging was used in one case with high melanin content. Clinical data were reviewed. Twelve women and 10 men with a median age of 58.7 years (range: 28-83 years) were included. Eighteen of 21 tumors evaluated immunohistochemically (85.7%) expressed GPNMB in 10-90% of tumor cells with variable intensity (5 tumors, 1+; 11, 2+; and 2, 3+). Eleven of 18 tumors (61.1%) expressed GPNMB in≥50% of cells. Spectral imaging showed diffuse CDX-011 (unconjugated) reactivity in the remaining case. Uveal melanoma, like cutaneous melanoma, commonly expresses GPNMB. Ongoing clinical trials of CDX-011 should be extended to patients with metastatic uveal melanoma to determine potential efficacy in this subset of patients with melanoma. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Fokt I.,University of Houston | Skora S.,University of Houston | Conrad C.,515 Holcombe Blvd. | Madden T.,University of Houston | And 2 more authors.
Carbohydrate Research

Altered carbohydrate metabolism in cancer cells was first noted by Otto Warburg more than 80 years ago. Upregulation of genes controlling the glycolytic pathway under normoxia, known as the Warburg effect, clearly differentiates malignant from non-malignant cells. The resurgence of interest in cancer metabolism aims at a better understanding of the metabolic differences between malignant and non-malignant cells and the creation of novel therapeutic and diagnostic agents exploiting these differences. Modified d-glucose and d-mannose analogs were shown to interfere with the metabolism of their respective monosaccharide parent molecules and are potentially clinically useful anticancer and diagnostic agents. One such agent, 2-deoxy-d-glucose (2-DG), has been extensively studied in vitro and in vivo and also clinically evaluated. Studies clearly indicate that 2-DG has a pleiotropic mechanism of action. In addition to effectively inhibiting glycolysis, 2-DG has also been shown to affect protein glycosylation. In order to better understand its molecular mechanism of action, we have designed and synthesized deuterated molecular probes to study 2-DG interference with d-glucose and d-mannose metabolism using mass spectrometry. We present here the synthesis of all desired probes: 2-deutero-d-glucose, 2-deutero-d-mannose, 6-deutero-d-glucose, 6-deutero-d-mannose, and 2-deutero-2-deoxy-d-glucose as well as their complete chemical characterization. © 2012 Elsevier Ltd. All rights reserved. Source

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