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CarreraSilva E.,Yale University | Chan P.,Yale University | Joannas L.,Yale University | Errasti A.,Yale University | And 13 more authors.
Immunity | Year: 2013

Dendritic cell (DC) activation is essential for the induction of immune defense against pathogens, yet needs to be tightly controlled to avoid chronic inflammation and exaggerated immune responses. Here, we identify a mechanism of immune homeostasis by which adaptive immunity, once triggered, tempers DC activation and prevents overreactiveimmune responses. Tcells, once activated, produced Protein S (Pros1) that signaled through TAM receptor tyrosine kinases in DCs to limit the magnitude of DC activation. Genetic ablation of Pros1 in mouse Tcells led to increased expression of costimulatory molecules and cytokines in DCs and enhanced immune responses to Tcell-dependent antigens, as well as increased colitis. Additionally, PROS1 was expressed in activated human Tcells, and its ability to regulate DC activation was conserved. Our results identify a heretofore unrecognized, homeostatic negative feedback mechanism at the interface of adaptive and innate immunity that maintains the physiological magnitude of the immune response. © 2013 Elsevier Inc.

Enzmann D.R.,University of California at Los Angeles | Schomer D.F.,Banner Anderson Cancer Center
Journal of the American College of Radiology | Year: 2013

As health care moves to value orientation, radiology's traditional business model faces challenges to adapt. The authors describe a strategic value framework that radiology practices can use to best position themselves in their environments. This simplified construct encourages practices to define their dominant value propositions. There are 3 main value propositions that form a conceptual triangle, whose vertices represent the low-cost provider, the product leader, and the customer intimacy models. Each vertex has been a valid market position, but each demands specific capabilities and trade-offs. The underlying concepts help practices select value propositions they can successfully deliver in their competitive environments. © 2013 American College of Radiology.

Thompson L.M.,Banner Anderson Cancer Center | Ceja M.E.,University of Houston | Yang S.P.,Norman Regional Health System
American Journal of Health-System Pharmacy | Year: 2012

Purpose. The transplantation of stem cells harvested from bone marrow and cord blood for the treatment of sickle cell disease (SCD) is reviewed. Summary. Current treatment options have lengthened the lifespan of patients with SCD. Hydroxyurea is the standard of care for the management of SCD, but it does not prevent serious complications in all patients. For those patients with severe disease, stem cell transplantation may be an appropriate curative option. However, less than one third of these patients find an appropriate matched related bone marrow donor. Cord blood offers a more readily available source of stem cells for transplantation. Donor morbidity is eliminated, since the cells come from banked cords, and the harvesting process is noninvasive for the donor. Another advantage of cord blood transplantation is the lower occurrence of graft-versus-host disease (GVHD). One disadvantage of transplantation with cord blood includes delayed time to engraftment. Due to the mortality associated with stem cell transplantation, it may be most appropriate to reserve the procedure for patients who have a more severe course of SCD. Conclusion. Although bone marrow, peripheral blood, and cord blood transplantation has been successfully performed in patients with SCD, data remain limited regarding the optimal preparative regimens, the most appropriate stem cell source, and the type of GVHD prophylaxis to be used after transplantation. More data are warranted before this treatment approach can be recommended as a standard of care for SCD. Copyright © 2012, American Society of Health-System Pharmacists, Inc. All rights reserved.

Munoz J.,Banner Anderson Cancer Center | Wheler J.,University of Houston | Kurzrock R.,University of California at San Diego
Cancer and Metastasis Reviews | Year: 2015

Estrogen and progesterone receptors (ERs and PRs) are known for their prognostic as well as treatment predictive value in breast cancer. Although these receptors are differentially expressed in some other malignancies, and likely participate in the biology of those cancer types, the relevance to outcome and therapy is not well established. The use of ER as a highly effective therapeutic target in oncology was pioneered in breast cancer, and the lessons learned from its success could potentially benefit patients with several other malignancies in which hormone receptors are highly expressed. Indeed, there are several potent drugs available that target hormone receptors. These agents show incontrovertible evidence of benefit in patients with hormone receptor-positive breast cancer. It is conceivable that these drugs may have salutary effects in a variety of cancers other than those originating in the breast, based on the overexpression of hormone receptors in some patients, and the preclinical and clinical reports showing responses to these drugs in diverse cancers, albeit in small series or anecdotally. We therefore undertook a literature review in order to summarize the current data regarding the biologic and clinical implications of expression of estrogen and progesterone receptors in various malignancies and the possibilities for deployment of hormone manipulation beyond breast cancer. © 2014, Springer Science+Business Media New York.

Munoz J.,Banner Anderson Cancer Center | Wheler J.J.,University of Houston | Kurzrock R.,University of California at San Diego
Oncotarget | Year: 2015

Androgen receptors (ARs) play a critical role in the development of prostate cancer. Targeting ARs results in important salutary effects in this malignancy. Despite mounting evidence that ARs also participate in the pathogenesis and/or progression of diverse tumors, exploring the impact of hormonal manipulation of these receptors has not been widely pursued beyond prostate cancer. This review describes patterns of AR expression in a spectrum of cancers, and the potential to exploit this knowledge in the clinical therapeutic setting.

Munoz J.,Banner Anderson Cancer Center | Janku F.,University of Houston | Cohen P.R.,University of California at San Diego | Kurzrock R.,University of California at San Diego
Mayo Clinic Proceedings | Year: 2014

Erdheim-Chester disease is a rare CD68+, CD1a- non-Langerhans cell histiocytosis with multiorgan involvement. The etiology of Erdheim-Chester disease is unclear; there are no known associated infectiousor hereditary genetic abnormalities. However, somatic BRAF mutations have recently been identified in these patients. Historically, the literature regarding the management of Erdheim-Chester disease consisted of casereports and small case series with anecdotal therapeutic responses to agents including, but not limited to, cytotoxic chemotherapy, bone marrow transplantation, cladribine, corticosteroids, IFN-α, the BCR-ABL/KIT inhibitor imatinib mesylate, the IL-1 receptor antagonist anakinra, the TNF-inhibitor infliximab, and recently the BRAF inhibitor vemurafenib. We performed a search of the literature using PubMed with the terms Erdheim Chester disease, without date limitations, including case reports, case series, original articles, and previous review articles. In the absence of large-scale studies, experience-based management prevails. The present review details our approach to the management of patients with Erdheim-Chester disease. © 2014 Mayo Foundation for Medical Education and Research.

Shah N.R.,Mayo Clinic Hospital | Craft R.O.,Banner Anderson Cancer Center | Harold K.L.,Mayo Clinic Hospital
Surgical Clinics of North America | Year: 2013

Occurrence of parastomal hernia is considered a near inevitable consequence of stoma formation, making their management a common clinical dilemma. This article reviews the outcomes of different surgical approaches for hernia repair and describes in detail the laparoscopic Sugarbaker technique, which has been shown to have lower recurrence rates than other methods. Also reviewed is the current literature on the impact of prophylactic mesh placement during ostomy formation. © 2013 Elsevier Inc.

Munoz J.,Banner Anderson Cancer Center | Swanton C.,Banner Anderson Cancer Center | Kurzrock R.,Banner Anderson Cancer Center
American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting | Year: 2013

Cancer is one of the leading causes of mortality in the world. Choosing the best treatment is dependent on making the right diagnosis. The diagnostic process has been based on light microscopy and the identification of the organ of tumor origin. Yet we now know that cancer is driven by molecular processes, and that these do not necessarily segregate by organ of origin. Fortunately, revolutionary changes in technology have enabled rapid genomic profiling. It is now apparent that neoplasms classified uniformly (e.g., non-small cell lung cancer) are actually comprised of up to 100 different molecular entities. For instance, tumors bearing ALK alterations make up about 4% of non-small cell lung cancers, and tumors bearing epidermal growth factor receptor (EGFR) mutations, approximately 5% to 10%. Importantly, matching patients to therapies targeted against their driver molecular aberrations has resulted in remarkable response rates. There is now a wealth of evidence supporting a divide-and-conquer strategy. Herein, we provide a concise primer on the current state-of-the-art of molecular profiling in the cancer clinic.

Rivera E.,Banner Anderson Cancer Center | Cianfrocca M.,Banner Anderson Cancer Center
Cancer Chemotherapy and Pharmacology | Year: 2015

Taxanes are an established option in the standard treatment paradigm for patients with metastatic breast cancer (MBC). Neuropathy is a common, dose-limiting side effect of taxane therapy that is often managed by dose reductions and delays. The severity, time to onset, and improvement in neuropathy are important considerations for patient management and vary among currently approved taxanes. The rate of grade ≥3 neuropathy with taxanes has been shown to be dose and schedule dependent; however, time to improvement to grade ≤1 is typically shorter for nab-paclitaxel than for other taxanes in patients with MBC. Many tools for assessing patient-reported neuropathy exist. Because MBC is incurable and patient quality of life must be critically considered when making treatment decisions, there is a need for more prospective trials to assess patient-reported neuropathy. Validated predictors of taxane-related neuropathy may play an important role in treatment decisions in the future. This review will focus on the toxicity profile (i.e., neuropathy) of each of the taxanes used in the treatment of MBC, will provide updates on tools used for the assessment of neuropathy, and will highlight newly discovered predictors of taxane-related neuropathy. © 2015 The Author(s).

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of advanced renal cell carcinoma, pancreatic neuroendocrine tumors, subependymal giant cell astrocytoma associated with tuberous sclerosis complex, renal angiomyolipoma and tuberous sclerosis complex, and, in combination with exemestane, for hormone receptor-positive HER2-negative advanced breast cancer after failure of treatment with letrozole or anastrozole. Results from the phase III BOLERO-2 trial demonstrated that everolimus in combination with exemestane provided significant clinical benefit to patients with advanced hormone receptor-positive breast cancer. Although everolimus is generally well tolerated, as with most therapies administered in an advanced cancer setting, drug-related adverse events (AEs) inevitably occur. Most common AEs observed in the everolimus studies include stomatitis, rash, infection, noninfectious pneumonitis, and hyperglycemia. Clinical awareness and early identification of such AEs by oncology nurses are essential to dosing (interruptions, reduction, and treatment discontinuation); quality of life; and, ultimately, patient outcomes. Because everolimus has already been shown to significantly improve clinical efficacy in patients with advanced breast cancer, a proactive approach to the practical management of AEs associated with this mTOR inhibitor as well as other most common AEs observed in this patient population has been reviewed and outlined here. © 2013 The Author(s).

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