Postoperative radiotherapy for patients at high risk of recurrence of oral cavity squamous cell carcinoma.

Objectives: To evaluate the efficacy of postoperative radiotherapy for oral cavity squamous cell carcinoma (OCSCC) by comparing outcomes of high-risk subgroups.

Study Design: Retrospective review.

Methods: Outcome study of 139 patients with OCSCC treated with gross total resection and postoperative radiotherapy ± chemotherapy and at least one high-risk pathologic finding: positive margin (52%), close (0.

Intrathyroidal parathyroid carcinoma: report of an unusual case and review of the literature.

Intrathyroidal parathyroid carcinoma is an exceedingly rare cause of primary hyperparathyroidism. A 51-year-old African American female presented with goiter, hyperparathyroidism, and symptomatic hypercalcemia. Sestamibi scan revealed diffuse activity within an enlarged thyroid gland with uptake in the right thyroid lobe suggestive of hyperfunctioning parathyroid tissue.

Esthesioneuroblastoma of the nasal cavity.

Objectives: Esthesioneuroblastoma is an uncommon cancer of the nasal cavity. We describe the outcomes for 26 patients treated with curative intent with photon radiotherapy (RT) at the University of Florida.

Methods: Between May 1972 and June 2007, 26 patients received RT for previously untreated esthesioneuroblastoma of the nasal cavity.

The serum- and glucocorticoid-induced protein kinase-1 (Sgk-1) mitochondria connection: identification of the IF-1 inhibitor of the F(1)F(0)-ATPase as a mitochondria-specific binding target and the stress-induced mitochondrial localization of endogenous Sgk-1.

The expression, localization and activity of the serum- and glucocorticoid-induced protein kinase, Sgk-1, are regulated by multiple hormonal and environmental cues including cellular stress. Biochemical fractionation and indirect immunofluorescence demonstrated that sorbitol induced hyperosmotic stress stimulated expression and triggered the localization of endogenous Sgk-1 into the mitochondria of NMuMG mammary epithelial cells. The immunofluorescence pattern of endogenous Sgk-1 was similar to that of a green fluorescent linked fusion protein linked to the N-terminal Sgk-1 fragment that encodes the mitochondrial targeting signal.

Syk-induced phosphatidylinositol-3-kinase activation in Epstein-Barr virus posttransplant lymphoproliferative disorder.

Posttransplant lymphoproliferative disorder (PTLD)-associated Epstein-Barr virus (EBV)+ B cell lymphomas are serious complications of solid organ and bone marrow transplantation. The EBV protein LMP2a, a B cell receptor (BCR) mimic, provides survival signals to virally infected cells through Syk tyrosine kinase. Therefore, we explored whether Syk inhibition is a viable therapeutic strategy for EBV-associated PTLD.

Definitive radiation therapy for squamous cell carcinoma of the pharyngeal wall.

Purpose: To analyze the results of definitive radiation therapy (RT) for squamous cell carcinoma of the pharyngeal wall.

Methods And Materials: Between 1964 and 2009, 170 patients were treated with definitive RT; all living patients had a 1.7-year minimum follow-up.

Locally destructive skull base lesion: IgG4-related sclerosing disease.

A unique case of IgG4(+) sclerosing disease was diagnosed in the sphenoid sinus, a previously unreported location, and was treated in a novel manner. This study describes the clinical presentation and management of IgG4 sclerosing disease in the paranasal sinuses. A retrospective case review and review of the medical literature were performed.

Adenoid cystic carcinoma of the head and neck.

Purpose: To report our experience using radiotherapy alone or combined with surgery to treat adenoid cystic carcinoma of the head and neck.

Materials And Methods: Radiotherapy alone or combined with surgery was used to treat 120 previously untreated patients with adenoid cystic carcinoma (ACC) of the head and neck from August 1966 to March 2008. Patients were treated with curative intent.

Head and neck paragangliomas.

Background: The purpose of this study was to describe the natural history and optimal treatment for head and neck paragangliomas (PGs).

Methods: Our methods were the review of the pertinent literature.

Results: PGs are rare tumors seen most commonly in the head and neck.

Syk activation of phosphatidylinositol 3-kinase/Akt prevents HtrA2-dependent loss of X-linked inhibitor of apoptosis protein (XIAP) to promote survival of Epstein-Barr virus+ (EBV+) B cell lymphomas.

B cell lymphoma survival requires tonic or ligand-independent signals through activation of Syk by the B cell receptor. The Epstein-Barr virus (EBV) protein latent membrane 2a (LMP2a), a mimic of the B cell receptor, provides constitutive survival signals for latently infected cells through Syk activation; however, the precise downstream mechanisms coordinating this survival response in EBV+ B cell lymphomas remain to be elucidated. Herein, we assess the mechanism of Syk survival signaling in EBV+ B cell lymphomas from post-transplant lymphoproliferative disorder (PTLD) to discover virally controlled therapeutic targets involved in lymphomagenesis and tumor progression.

Tracheocele: an unusual cause of dysphonia.

Educational Objectives: Describe the clinical presentation and management of tracheoceles.

Study Design: Retrospective case review and review of the medical literature.

Results: A 56 year old female patient presented with progressive dysphonia and history of benign thyroid nodules.

Radiotherapy with or without surgery for maxillary sinus squamous cell carcinoma: should the clinical N0 neck be treated?

Objectives: Maxillary sinus squamous cell carcinoma is commonly diagnosed at an advanced stage and treated using radiotherapy, with or without surgical resection.

Methods: Fifty-four patients with maxillary sinus squamous cell carcinoma were treated from 1969 to 2006, using radiotherapy, with or without surgical resection. Fifty-two (96%) patients had American Joint Committee on Cancer stages III to IV disease, and 45 (83%) patients had N0 neck disease.

Head and neck osteosarcoma.

Objective: The objective of the study was to discuss the optimal management and treatment outcomes for patients with head and neck osteosarcomas.

Study Design: Review article.

Methods: Review of the pertinent literature.

Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment.

We have identified a new role for the matrix enzyme lysyl oxidase-like-2 (LOXL2) in the creation and maintenance of the pathologic microenvironment of cancer and fibrotic disease. Our analysis of biopsies from human tumors and fibrotic lung and liver tissues revealed an increase in LOXL2 in disease-associated stroma and limited expression in healthy tissues. Targeting LOXL2 with an inhibitory monoclonal antibody (AB0023) was efficacious in both primary and metastatic xenograft models of cancer, as well as in liver and lung fibrosis models.

Modulation of lysyl oxidase-like 2 enzymatic activity by an allosteric antibody inhibitor.

In this report, we assessed the steady-state enzymatic activity of lysyl oxidase-like 2 (LOXL2) against the substrates 1,5-diaminopentane (DAP), spermine, and fibrillar type I collagen. We find that both DAP and spermine are capable of activating LOXL2 to the same extent and have similar Michaelis constants (K(m) approximately 1 mm) and catalytic rates (k(cat) approximately 0.02 s(-1)).

Elective neck dissection during salvage surgery for locally recurrent head and neck squamous cell carcinoma after radiotherapy with elective nodal irradiation.

Objectives/hypothesis: To define the role of elective neck dissection during salvage surgery for locally recurrent head and neck squamous cell carcinoma (SCCA) initially treated with elective nodal irradiation (ENI).

Study Design: Retrospective chart review.

Methods: We reviewed the medical records of patients treated with ENI at our institution from 1965 to 2006 for T1-4 N0 M0 SCCA of the oropharynx, hypopharynx, or larynx who developed an isolated local recurrence and remained N0.

Altered fractionation and adjuvant chemotherapy for head and neck squamous cell carcinoma.

Background: The aim of this review was to discuss the role of altered fractionation and adjuvant chemotherapy for patients treated with definitive radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC).

Methods: This review explores the pertinent literature and discusses the optimal management of previously untreated patients with stage III-stage IVA and/or -B HNSCCs.

Results: Depending on the schedule, altered fractionation improves locoregional control and survival.

Activation of the JAK/STAT pathway in Epstein Barr virus+-associated posttransplant lymphoproliferative disease: role of interferon-gamma.

Epstein Barr virus (EBV) is associated with B-cell lymphomas in posttransplant lymphoproliferative disease (PTLD). Latent membrane protein 1 (LMP1), the major oncogenic protein of EBV, promotes tumorigenesis through activation of NF-kappaB, Erk, p38, JNK and Akt. The Jak/STAT signal transduction pathway is also constitutively active in PTLD-associated EBV(+) B-cell lymphomas.

Squamous cell carcinoma of the external auditory canal: long-term clinical outcomes using surgery and external-beam radiotherapy.

Objective: Squamous cell carcinoma (SCCA) of the external auditory canal (EAC) is often treated with a combination of surgery and radiotherapy (RT) to optimize the chance of achieving locoregional control. This retrospective review describes a 27-year experience of treating these tumors at the University of Florida.

Methods: Thirty patients with histologically confirmed SCCA of the EAC received external-beam radiation (RT) alone or combined with surgical resection between 1976 and 2003.

Carcinoma of the nasal cavity and paranasal sinuses.

Objectives/hypothesis: To determine the outcomes after radiotherapy (RT) alone or combined with surgery at the University of Florida for patients with carcinomas of the nasal cavity and paranasal sinuses.

Methods: Between November 1964 and June 2005, 109 patients were treated with curative intent. Patients with maxillary sinus carcinomas were excluded.

Tumor-derived variants of Epstein-Barr virus latent membrane protein 1 induce sustained Erk activation and c-Fos.

Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is a proven oncogene that is essential for transformation of human B cells by the virus. LMP1 induces constitutive activation of several signal transduction pathways involving nuclear factor kappaB, phosphatidylinositol 3-kinase/Akt, and the mitogen-activated protein kinases (MAPK) p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (Erk). Sequencing of LMP1 isolated from a panel of EBV+ B cell lymphomas identified three different variants of LMP1, each distinct from the B95.

Cutaneous squamous cell carcinoma metastatic to parotid-area lymph nodes.

Introduction: Metastatic spread to parotid-area lymph nodes (PALN) occurs in 1% to 3% of patients with cutaneous squamous cell carcinoma of the head and neck. Presented herein is the University of Florida experience using radiation therapy (RT) to treat patients with PALN metastases from a skin primary.

Methods And Materials: From November 1969 to February 2005, 121 parotids in 117 patients received irradiation for nonmelanotic skin carcinoma metastatic to PALN.

Minimally invasive video-assisted thyroidectomy.

Background: Minimally invasive video-assisted thyroidectomy (MIVAT) has been developed and successfully used in Italy to perform thyroidectomy and central node dissection through an incision of 2 to 3 cm.

Objectives: Determine the safety, utility, and complication rates of MIVAT in a university setting within the United States.

Study Design: Single surgeon series of MIVAT performed during an 18-month period.

Rapamycin inhibits proliferation of Epstein-Barr virus-positive B-cell lymphomas through modulation of cell-cycle protein expression.

Background: Posttransplant lymphoproliferative disease (PTLD) is a serious complication of solid organ and bone marrow transplantation and is closely associated with Epstein-Barr virus (EBV) infection. We have previously shown that rapamycin (RAPA) directly inhibits the in vitro and in vivo proliferation of EBV-infected B lymphoblastoid cell lines (SLCL), derived from patients with PTLD, by arresting cells in the G1 phase of the cell cycle. The aim of this study is to elucidate the mechanism by which RAPA causes cell cycle arrest in EBV+ B cells.

Autoantigen arrays for multiplex analysis of antibody isotypes.

We describe here a microarray-based method for multiplexed, antigen-specific assessment of immunoglobulin (Ig) subclasses. We used 1152-feature arrays composed of 140 antigens or antigen fragments to detect isotype-specific mAb, to quantitatively monitor changes in isotype mAb concentration, and to profile antigen-specific antibody isotype production in a murine model of autoimmunity. This platform can be easily adapted to a variety of applications, and has the potential to elucidate mechanisms that govern development and evolution of antibody responses in in vivo and in vitro systems.