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Leon A.,Bioreference Laboratories | Staropoli J.F.,Massachusetts General Hospital | Hernandez J.M.,University of Salamanca | Longtine J.A.,Harvard University | And 2 more authors.
Leukemia Research | Year: 2011

A cohort of 338 patients diagnosed with myeloproliferative neoplasms was investigated by conventional cytogenetics and evaluated for the presence of the JAK2 V617F mutation. A t(1;9)(p10;q10) in addition to two extra der(1;9)(q10;p10) chromosomes was observed in two patients of essential thrombocythemia that transformed to acute myelogenous leukemia or to myelofibrosis. These findings suggest that the presence of extra derivative chromosomes der(1q;9p) in combination with the JAK2 V617F mutation may play a role in the progression of myeloproliferative neoplasms and supports the use of cytogenetics in the follow-up of the disease. © 2011. Source


Hiemenz M.C.,University of Pennsylvania | Hiemenz M.C.,Bioreference Laboratories | Kadauke S.,University of Pennsylvania | Kadauke S.,Massachusetts General Hospital | And 7 more authors.
PLoS ONE | Year: 2016

Next-generation sequencing (NGS) is a powerful platform for identifying cancer mutations. Routine clinical adoption of NGS requires optimized quality control metrics to ensure accurate results. To assess the robustness of our clinical NGS pipeline, we analyzed the results of 304 solid tumor and hematologic malignancy specimens tested simultaneously by NGS and one or more targeted single-gene tests (EGFR, KRAS, BRAF, NPM1, FLT3, and JAK2). For samples that passed our validated tumor percentage and DNA quality and quantity thresholds, there was perfect concordance between NGS and targeted single-gene tests with the exception of two FLT3 internal tandem duplications that fell below the stringent preestablished reporting threshold but were readily detected by manual inspection. In addition, NGS identified clinically significant mutations not covered by single-gene tests. These findings confirm NGS as a reliable platform for routine clinical use when appropriate quality control metrics, such as tumor percentage and DNA quality cutoffs, are in place. Based on our findings, we suggest a simple workflow that should facilitate adoption of clinical oncologic NGS services at other institutions. © 2016 Hiemenz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source


Vadrevu S.K.,Texas Tech University | Chintala N.K.,Texas Tech University | Sharma S.K.,Texas Tech University | Sharma P.,Texas Tech University | And 8 more authors.
Cancer Research | Year: 2014

The impact of complement on cancer metastasis has not been well studied. In this report, we demonstrate in a preclinical mouse model of breast cancer that the complement anaphylatoxin C5a receptor (C5aR) facilitates metastasis by suppressing effector CD8 and CD4 T-cell responses in the lungs. Mechanisms of this suppression involve recruitment of immature myeloid cells to the lungs and regulation of TGFb and IL10 production in these cells. TGFb and IL10 favored generation of T regulatory cells (Treg) and Th2-oriented responses that rendered CD8 T cells dysfunctional. Importantly, pharmacologic blockade of C5aR or its genetic ablation in C5aRdeficient mice were sufficient to reduce lung metastases. Depletion of CD8 T cells abolished this beneficial effect, suggesting that CD8 T cells were responsible for the effects of C5aR inhibition. In contrast to previous findings, we observed that C5aR signaling promoted Treg generation and suppressed T-cell responses in organs where metastases arose. Overall, our findings indicated that the immunomodulatory functions of C5aR are highly context dependent. Furthermore, they offered proof-of-concept for complement-based immunotherapies to prevent or reduce cancer metastasis. Cancer Res; 74(13); 3454-65. © 2014 American Association for Cancer Research. Source


Ulmer W.D.,Albany Medical Center | Gilbert J.L.,Bioreference Laboratories | De E.J.B.,Albany Medical Center
Current Bladder Dysfunction Reports | Year: 2014

Urethritis is a common condition affecting women in the USA. The symptoms, however, are not specific to a unique cause and are shared among a wide variety of urogenital diseases. This article evaluates the current literature and provides tools to the practicing clinician. Infections, particularly urinary tract infection and vaginitis, are common causes. The sexually transmitted infection Chlamydia trachomatis continues to be one of the most common etiologies for urethritis. Newer research provides evidence for the importance of Ureaplasma and Mycoplasma genitalium. Mechanical trauma, vaginal atrophy, chemical and mechanical exposure, and Skene's gland and other anatomical pathology will also be reviewed. The diagnosis and treatment of urethritis often require the practitioner to treat associated diseases such as chronic pelvic pain syndrome and dyspareunia. Urethritis is intensely symptomatic leading to a pressured office interaction, and it is our intent to provide the tools for a comprehensive approach to female urethritis. © 2014 Springer Science+Business Media New York. Source


Miranda R.N.,University of Houston | Aladily T.N.,University of Jordan | Prince H.M.,University of Melbourne | Kanagal-Shamanna R.,University of Houston | And 31 more authors.
Journal of Clinical Oncology | Year: 2014

Purpose: Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. Patients and Methods: We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. Results: The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Conclusion: Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants. © 2013 by American Society of Clinical Oncology. Source

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