Novel immunogenic HLA-A*0201-restricted epidermal growth factor receptor-specific T-cell epitope in head and neck cancer patients.

Therapeutic targeting of the epidermal growth factor receptor (EGFR), which is highly overexpressed and correlated with poor prognosis in colorectal and head and neck squamous cell carcinoma (SCCHN), has shown clinical efficacy using the blocking mAbs, cetuximab or panitumumab, but only in 10% to 20% of patients. Clinical responsiveness is correlated with certain Fcgamma receptor genotypes, suggesting immune activity may contribute to therapeutic efficacy. In addition, cetuximab-resistant tumor cells exhibit ubiquitination and degradation of EGFR, which would increase its processing as a tumor antigen for cytotoxic T lymphocyte (CTL) lysis.

Management of patients treated with chemoradiotherapy for head and neck cancer without prophylactic feeding tubes: the University of Pittsburgh experience.

Objectives/hypothesis: Mucositis and dysphagia are common complications of chemoradiotherapy (CRT) for head and neck cancer that may necessitate nutritional support with a gastrostomy tube (G-tube).

Methods: We reviewed records of patients who underwent and completed CRT, which included at least one traditional chemotherapeutic, for previously untreated head and neck cancer. G-tubes were placed as needed.

Fractionated stereotactic body radiation therapy in the treatment of previously-irradiated recurrent head and neck carcinoma: updated report of the University of Pittsburgh experience.

Objectives: The aim of this study was to assess the safety and outcome of stereotactic body radiotherapy (SBRT) in patients with recurrent previously irradiated squamous cell carcinoma of the head and neck (rSCCHN).

Methods: We reviewed our experience with 85 patients who received SBRT for rSCCHN between January 2003 and May 2008. The mean dose of SBRT was 35 Gy (range: 15-44 Gy).

Sheddase activity of tumor necrosis factor-alpha converting enzyme is increased and prognostically valuable in head and neck cancer.

Tumor necrosis factor alpha converting enzyme (TACE) is a sheddase overexpressed in cancers that generates cancer cell growth and survival factors, and is implicated in carcinogenesis and tumor growth. This indicates that TACE could be a potentially important cancer biomarker. Unexpectedly, TACE expression in cancer tissues does not correlate with cancer stage or invasiveness.

Current concepts and new horizons in conservation laryngeal surgery: an important part of multidisciplinary care.

Background: New surgical techniques in conservation laryngeal surgery (CLS) have emerged over the past 20 years and now offer a viable "organ-preservation" approach for patients with laryngeal cancer. We review traditional and new CLS procedures and summarize the functional and oncologic outcomes of CLS in both primary and salvage settings.

Methods: We searched the literature by accessing Medline for articles from 1991 to 2007 on primary or salvage surgery (open and transoral) for laryngeal neoplasms.

4,4-Disubstituted cyclohexylamine based CCR5 chemokine receptor antagonists as anti-HIV-1 agents.

A series of 4,4-disubstituted cyclohexylamine based CCR5 antagonists has been designed and synthesized. Their antiviral structure-activity relationship has been extensively explored.

Quantitative expression and immunogenicity of MAGE-3 and -6 in upper aerodigestive tract cancer.

The MAGE antigens are frequently expressed cancer vaccine targets. However, quantitative analysis of MAGE expression in upper aerodigestive tract (UADT) tumor cells and its association with T-cell recognition has not been performed, hindering the selection of appropriate candidates for MAGE-specific immunotherapy. Using quantitative RT-PCR (QRT-PCR), we evaluated the expression of MAGE-3/6 in 65 UADT cancers, 48 normal samples from tumor matched sites and 7 HLA-A*0201+ squamous cell carcinoma of the head and neck (SCCHN) cell lines.

Maturation pathways of dendritic cells determine TAP1 and TAP2 levels and cross-presenting function.

Ability to cross-present exogenous antigens in the human leukocyte antigen class I pathway is key to the antigen presenting function of mature tumor cell-loaded dendritic cells (DC). Conditions of DC maturation have been shown to be important for DCs ability to produce proinflammatory cytokines and induce T cell effector functions. However, it remains unknown if the different pathways of maturation are associated with modulation of the ability of mature DCs to cross-present tumor antigens (TA).

Clinical and dosimetric factors associated with a prolonged feeding tube requirement in patients treated with chemoradiotherapy (CRT) for head and neck cancers.

Background: Patients treated with chemoradiotherapy (CRT) for head and neck cancers often require feeding tubes (FTs) due to toxicity. We sought to identify factors associated with a prolonged FT requirement.

Patients And Methods: We retrospectively reviewed 80 patients treated with CRT for head and neck cancers.

HGF and c-Met participate in paracrine tumorigenic pathways in head and neck squamous cell cancer.

Purpose: We determined hepatocyte growth factor (HGF) and c-Met expression and signaling in human head and neck squamous cell carcinoma (HNSCC) cells and primary tissues and tested the ability of c-Met tyrosine kinase inhibitors (TKI) to block HGF-induced biological signaling.

Experimental Design: Expression and signaling were determined using immunoblotting, ELISA, and immunohistochemistry. Biological end points included wound healing, cell proliferation, and invasion.

Stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: results of a phase I dose-escalation trial.

Purpose: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) in previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN).

Patients And Methods: In this Phase I dose-escalation clinical trial, 25 patients were treated in five dose tiers up to 44 Gy, administered in 5 fractions over a 2-week course. Response was assessed according to the Response Evaluation Criteria in Solid Tumors and [(18)F]-fluorodeoxyglucose standardized uptake value change on positron emission tomography-computed tomography (PET-CT).

The WHO/PEPFAR collaboration to prepare an operations manual for HIV prevention, care, and treatment at primary health centers in high-prevalence, resource-constrained settings: defining laboratory services.

The expansion of HIV/AIDS care and treatment in resource-constrained countries, especially in sub-Saharan Africa, has generally developed in a top-down manner. Further expansion will involve primary health centers where human and other resources are limited. This article describes the World Health Organization/President's Emergency Plan for AIDS Relief collaboration formed to help scale up HIV services in primary health centers in high-prevalence, resource-constrained settings.

Immunotherapy for head and neck cancer.

Overall survival for patients with squamous cell carcinoma of the head and neck (SCCHN) has not improved appreciably over the past few decades. Novel therapeutic approaches, such as immunotherapy, are under clinical investigation since the standard treatments are toxic and have not successfully controlled this disease with sufficiently high success rates. Cancer immunotherapy describes various techniques to expand and activate the immune system to control tumor growth in vivo, and clinical evaluation has so far demonstrated low toxicity.

PUMA mediates EGFR tyrosine kinase inhibitor-induced apoptosis in head and neck cancer cells.

Overexpression of epidermal growth factor receptor (EGFR) is found in over 80% of head and neck squamous cell carcinomas (HNSCC) and associated with poor clinical outcomes. EFGR selective tyrosine kinase inhibitors (TKIs) or antibodies have recently emerged as promising treatments for solid tumors, including HNSCC, though the response rate to these agents is low. p53 upregulated modulator of apoptosis (PUMA), a BH3-only Bcl-2 family protein, is required for apoptosis induced by p53 and various chemotherapeutic agents.

Management of squamous cell carcinoma of the base of tongue with chemoradiation and brachytherapy.

Background: Treatment of base of tongue (BOT) squamous cell carcinoma (SCC) has traditionally been associated with poor prognosis and significant morbidity. We report a program consisting of concurrent chemoradiation followed by brachytherapy for these patients.

Methods: We reviewed all patients in our institution with previously untreated BOT SCC (1996-2004) who received this treatment program.

Role of polymorphic Fc gamma receptor IIIa and EGFR expression level in cetuximab mediated, NK cell dependent in vitro cytotoxicity of head and neck squamous cell carcinoma cells.

Immunotherapy with the EGFR-specific mAb cetuximab is clinically effective in 10-20% of patients with squamous cell carcinoma of the head and neck (SCCHN). Little information is available about the mechanism(s) underlying patients' differential clinical response to cetuximab-based immunotherapy, although this information may contribute to optimizing the design of cetuximab-based immunotherapy. Our understanding of these mechanisms would benefit from the characterization of the variables which influence the extent of cell dependent-lysis of SCCHN cells incubated with cetuximab in vitro.

Multiplex analysis of cytokines as biomarkers that differentiate benign and malignant thyroid diseases.

Thyroid cancer incidence is increasing, and its diagnosis can be challenging. Fine needle biopsy, the principal clinical tool to make a tissue diagnosis, leads to inconclusive diagnoses in up to 30% of the cases, leading to surgery. Advances in proteomics are improving abilities to diagnose malignant conditions using small samples of tissue or body fluids.

[2-(4-Phenyl-4-piperidinyl)ethyl]amine based CCR5 antagonists: derivatizations at the N-terminal of the piperidine ring.

Several series of CCR5 antagonists have been discovered by derivatization at the N-terminal of the piperidine ring of the core template 2. Some derivatives exhibited potent inhibition against HIV-1infection. The pharmacokinetic properties of the lead compounds 11a, 14a, 15b, and 16b have been evaluated in vivo.

Immunotherapy of head and neck cancer using tumor antigen-specific monoclonal antibodies.

Monoclonal antibodies (mAbs) are now commonly used therapeutic agents in cancer patients. Since US Food and Drug Administration approval of cetuximab for head and neck squamous cell carcinoma, it has been used increasingly in this disease. Several other mAbs also are in development or in clinical -trials.

Ocular outcomes after gold weight placement and facial nerve resection.

Objective: To assess the effectiveness of acute gold weight placement after facial nerve resection and to determine the role of concomitant lower eyelid procedures.

Study Design: Retrospective review.

Subjects And Methods: Twenty-two patients who received an upper eyelid gold weight at the time of parotidectomy and facial nerve resection were reviewed to assess ocular outcomes.

The relative activity of "function sparing" HIV-1 entry inhibitors on viral entry and CCR5 internalization: is allosteric functional selectivity a valuable therapeutic property?

Six allosteric HIV-1 entry inhibitor modulators of the chemokine (C-C motif) receptor 5 (CCR5) receptor are compared for their potency as inhibitors of HIV-1 entry [infection of human osteosarcoma (HOS) cells and peripheral blood mononuclear cells (PBMC)] and antagonists of chemokine (C-C motif) ligand 3-like 1 [CCL3L1]-mediated internalization of CCR5. This latter activity has been identified as a beneficial action of CCL3L1 in prolonging survival after HIV-1 infection ( Science 307: 1434-1440, 2005 ). The allosteric nature of these modulators was further confirmed with the finding of a 58-fold (HOS cells) and 282-fold (PBMC) difference in relative potency for blockade of CCL3L1-mediated internalization versus HIV-1 entry.

Reoperative parathyroidectomy.

Reoperative surgery for hyperparathyroidism is associated with increased incidence of complications including vocal cord paralysis, permanent hypoparathyroidism, and persistent hypercalcemia. Surgical re-exploration should consist of symptomatic or low-risk patients. The use of nuclear medicine imaging, ultrasound, and high-resolution CT and MRI may aid in surgical planning.

Role of surgery in limited (T1-2, N0-1) cancers of the oropharynx.

Hypothesis: To define the role of surgical staging in limited (T1-2, N0-1) oropharyngeal squamous cell cancers.

Study Design: Retrospective.

Methods: Forty-nine limited oropharyngeal squamous cell cancers of the tonsil, tongue base, or posterior pharyngeal wall-treated surgically were identified.

Discovery of bioavailable 4,4-disubstituted piperidines as potent ligands of the chemokine receptor 5 and inhibitors of the human immunodeficiency virus-1.

We describe robust chemical approaches toward putative CCR5 scaffolds designed in our laboratories. Evaluation of analogues in the (125)I-[MIP-1beta] binding and Ba-L-HOS antiviral assays resulted in the discovery of 64 and 68 in the 4,4-disubstitited piperidine class H, both potent CCR5 ligands (pIC 50 = 8.30 and 9.

Minimally invasive video-assisted thyroidectomy: expanded indications and oncologic completeness.

Background: Minimally invasive video-assisted thyroidectomy (MIVAT) has received increasing attention as a technique applicable for a subset of thyroid nodules.

Methods: We prospectively assessed 51 MIVAT procedures in 40 patients. Demographic and clinical data were collected, relating to indications, outcome, and oncologic completeness.