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Biomedical subjects

Brendan C Stack

Publications and source records attributed to Brendan C Stack.

At least 19 recordsLinked to original sources
PubMed2005

Opioid growth factor enhances tumor growth inhibition and increases the survival of paclitaxel-treated mice with squamous cell carcinoma of the head and neck.

Paclitaxel is used as a single agent, and in combination with other drugs, as a standard of care in the treatment of squamous cell carcinoma of the head and neck (SCCHN). However, the use of paclitaxel for therapy of SCCHN may be accompanied by serious side effects. Paclitaxel is a known cytotoxic inhibitor of cell proliferation that acts by stabilizing microtubules and inducing apoptosis. Opioid growth factor (OGF), [Met(5)]-enkephalin, is an endogenous peptide that has tonically active inhibitory effects on the growth of SCCHN in vitro and in vivo. OGF action is rapid, reversible, mediated by the nuclear-associated OGF receptor (OGFr), and is not cytotoxic (nor apoptotic related). The present study was designed to examine whether a combination of chemotherapy with paclitaxel and biotherapy with OGF is more effective than either agent alone in inhibiting tumor growth. Moreover, focus was placed on whether there are changes in the side effects known to occur with paclitaxel alone, following this combined therapy. Human SCC-1 cells, derived from a well differentiated SCCHN, were transplanted into athymic mice. The mice were randomized to receive intraperitoneal (i.p.) injections of sterile saline (controls), OGF (10 mg/kg, daily), paclitaxel (8 mg/kg, every other day), or both paclitaxel (8 mg/kg, every other day) and OGF (10 mg/kg, daily) beginning on the day of tumor inoculation. OGF, but not paclitaxel, delayed measurable and visible tumor appearance of mice with SCCHN. Treatment with paclitaxel, but not with other agents, had a marked effect on the body weights. Survival only was reduced in the paclitaxel group, with an average life span of 34.3+/-3.1 days recorded, in comparison to the 50-day survival (date of termination) for all other groups. Beginning after week 4 of tumor inoculation and drug treatment, the tumor weight of the paclitaxel/OGF group was significantly reduced from the control, OGF, and paclitaxel-exposed mice. The OGFr number of the SCCHN tumors was 2.1-fold greater in the animals exposed to OGF or paclitaxel, and elevated 38% in the paclitaxel/OGF group; significant differences from the control group were found for the OGF and paclitaxel groups. These data suggest that combined chemotherapy (i.e., paclitaxel) and biotherapy (OGF) provides a valuable alternative to the standard of care for SCCHN patients.

Animals↗
PubMed2005

A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003.

OBJECTIVE: To systematically review the current preoperative diagnostic modalities, surgical treatments, and glandular pathologies associated with primary hyperparathyroidism. STUDY DESIGN: A systematic literature review. RESULTS: Of the 20,225 cases of primary hyperparathyroidism reported, solitary adenomas (SA), multiple gland hyperplasia disease (MGHD), double adenomas (DA), and parathyroid carcinomas (CAR) occurred in 88.90%, 5.74%, 4.14%, and 0.74% of cases respectively. Tc 99m -sestamibi and ultrasound were 88.44% and 78.55% sensitive, respectively, for SA, 44.46% and 34.86% for MGHD, and 29.95% and 16.20% for DA, respectively. Postoperative normocalcemia was achieved in 96.66%, 95.25%, and 97.69% of patients offered minimally invasive radio-guided parathyroidectomy (MIRP), unilateral, and bilateral neck exploration (BNE). Intraoperative PTH assays (IOPTH) were helpful in approximately 60% of bilateral neck exploration conversion (BNEC) surgeries. CONCLUSION: The overall prevalence of multiple gland disease (MGD and DA) was lower than often suggested by conventional wisdom. Furthermore, preoperative imaging was less accurate than it is often perceived for accurately imaging MGD. MIRP and UNE were more successful in achieving normocalcemia than is typically quoted. IOPTH was a helpful but not "fool-proof" adjunct in parathyroid exploration surgery. SIGNIFICANCE: These results support a greater role for the treatment of primary hyperparathyroidism using less invasive approaches. EMB rating: B-3.

Humans↗
PubMed2005

Enhanced growth inhibition of squamous cell carcinoma of the head and neck by combination therapy of paclitaxel and opioid growth factor.

This study evaluated the effects of a combination of opioid growth factor (OGF) and paclitaxel on squamous cell carcinoma of the head and neck (SCCHN) using a tissue culture model of human SCCHN. The combination of OGF and paclitaxel was markedly inhibitory to SCCHN proliferation, reducing growth from control levels by 48 to 69% within 48 h. OGF in combination with carboplatin also depressed cell growth. The effect of a combination of OGF and paclitaxel or carboplatin on SCCHN growth was greater than either of the individual compounds. The efficacy of OGF, but not paclitaxel, was mediated by a naloxone-sensitive receptor and completely reversible. OGF, but no other endogenous or exogenous opioid, altered replication of SCCHN. OGF and paclitaxel depressed DNA synthesis, whereas only paclitaxel induced apoptosis. The combination of OGF and paclitaxel also had a supra-additive effect on the growth of another SCCHN, CAL-27, indicating the ubiquity of the combined drug activity. These data suggest that the combination of a biotherapy (OGF) and chemotherapy (paclitaxel and carboplatin) may provide an enhanced antitumor effect with respect to SCCHN.

Aged↗
PubMed2004

Metallopanstimulin as a marker for head and neck cancer.

BACKGROUND: Metallopanstimulin (MPS-1) is a ribosomal protein that is found in elevated amounts in the sera of patients with head and neck squamous cell carcinoma (HNSCC). We used a test, denoted MPS-H, which detects MPS-1 and MPS-1-like proteins, to determine the relationship between MPS-H serum levels and clinical status of patients with, or at risk for, HNSCC. PATIENTS AND METHODS: A total of 125 patients were prospectively enrolled from a university head and neck oncology clinic. Participants included only newly diagnosed HNSCC patients. Two control groups, including 25 non-smokers and 64 smokers, were studied for comparison. A total of 821 serum samples collected over a twenty-four month period were analyzed by the MPS-H radioimmunoassay. RESULTS: HNSCC, non-smokers, and smokers had average MPS-H values of 41.5 ng/mL, 10.2 ng/mL, and 12.8 ng/mL, respectively (p = 0.0001). CONCLUSION: We conclude that MPS-1 and MPS-1-like proteins are elevated in patients with HNSCC, and that MPS-H appears to be a promising marker of presence of disease and response to treatment in HNSCC patients.

Journal Article↗
PubMed2004

Serum protein profiles to identify head and neck cancer.

PURPOSE: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management. The purpose of this study was to determine whether a new proteomic technology could correctly identify protein expression profiles for cancer in patient serum samples. EXPERIMENTAL DESIGN: Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry ProteinChip system was used to screen for differentially expressed proteins in serum from 99 patients with HNSCC and 102 normal controls. Protein peak clustering and classification analyses of the surface-enhanced laser desorption/ionization spectral data were performed using the Biomarker Wizard and Biomarker Patterns software (version 3.0), respectively (Ciphergen Biosystems, Fremont, CA). RESULTS: Several proteins, with masses ranging from 2778 to 20800 Da, were differentially expressed between HNSCC and the healthy controls. The serum protein expression profiles were used to develop and train a classification and regression tree algorithm, which reliably achieved a sensitivity of 83.3% and a specificity of 100% in discriminating HNSCC from normal controls. CONCLUSIONS: We propose that this technique has potential for the development of a screening test for the detection of HNSCC.

Adult↗
PubMed2004

Identification of patients with head and neck cancer using serum protein profiles.

BACKGROUND: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management. OBJECTIVE: To determine if a new proteomic technology can correctly identify protein expression profiles for cancer in patient serum samples as well as detect the presence of a known tumor marker. DESIGN: Direct proteomic analysis and comparison. METHODS: The surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF) ProteinChip system was used to screen for differentially expressed proteins in serum samples from 99 patients with HNSCC, 25 "healthy" smokers, and 102 healthy (normal) controls. Protein peak clustering and classification analyses of the SELDI spectral data were performed. RESULTS: Several proteins, with masses ranging from 2778 to 20,800 Da, were differentially expressed between patients with HNSCC and the normal controls. The serum protein expression profiles were used to develop a classification tree algorithm, which achieved a sensitivity of 83.3% and a specificity of 90% in discriminating HNSCC from normal and healthy smoker controls. The positive and negative predictive values were 80% and 92%, respectively. A peak with an average mass of 10,068 Da was detected in sera from HNSCC patients and identified as the known biomarker metallopanstimulin-1 (MPS-1), based on mass. Peak relative intensity of the 10,068-Da protein correlated consistently with MPS-1 levels detected by radioimmunoassay in serum samples of HNSCC patients and controls. The 10,068-Da peak was provisionally identified as MPS-1 by SELDI immunoassay. CONCLUSION: We propose that this technique may allow for the development of a reliable screening test for the early detection and diagnosis of HNSCC, as well as the potential identification of tumor biomarkers.

Biomarkers, Tumor↗
PubMed2004

Significance of primary hyperparathyroidism in the management of osteoporosis.

Primary hyperparathyroidism (HPT) has catabolic effects on cortical bone and anabolic effects on cancellous bone with overall deleterious effects on skeleton. Primary HPT is associated with increased fracture risk both at the cancellous bone-enriched spine and the cortical bone-enriched distal one third of the radius. This risk is reversed by parathyroidectomy.

Bone Density↗
PubMed2004

Minimally invasive radioguided parathyroidectomy using intraoperative sestamibi localization.

This article presents the authors' technique of minimally invasive radio guided parathyroidectomy (MIRP) with intra-operative use of the hand-held gamma probe for primary HPT caused by a solitary adenoma. It points out how this approach varies from that of others who perform MIRP. It also illustrates ways to troubleshoot common problems with the technique in inexperienced hands. The goal is to present an understandable and systematic approach to MIRP for surgeons who do not currently use this technique. This article is not intended to replace formalized training, which is essential to master the technique.

Adenoma↗
PubMed2004

Parathyroid carcinoma.

Parathyroid carcinoma is a relatively rare tumor that is prone to recurrence and poor loco-regional control. This article discusses the epidemiology, presentation, operative findings, pathology,management, genetics, outcome, and other aspects of parathyroid carcinoma.

Carcinoma↗
PubMed2004

Calciphylaxis.

Calciphylaxis is a condition with a generally poor prognosis about which relatively little is known. Possible improvement in prognosis is noted if the diagnosis can be made early to avoid progression of soft tissue lesions and resulting complications. The mainstays of therapy are wound care and therapy aimed at controlling infection and the progression of disease. Parathyroidectomy seems to benefit some patients, but controversy remains as to the extent of overall patient benefit and scenarios for its appropriate use.

Adenoma↗
PubMed2004

Fusaric acid: a novel agent and mechanism to treat HNSCC.

OBJECTIVE: A new class of carboxylic acids has tumoricidal activity for head and neck squamous cell cancer (HNSCC). Fusaric acid (FA) can chelate divalent cations, especially zinc, and inactivate zinc finger proteins involved in DNA repair and protein synthesis. METHODS: 2 squamous carcinoma lines were utilized for in vitro and in vivo portions of this study. Cell counting and flow cytometry were used to analyze cells in culture in treatment and control groups over 96 hours. HNSCC subcutaneous implants were created in treatment and control groups of BALB-c nude mice (N = 30). RESULTS: In vitro studies demonstrated significant changes in cell numbers and cell cycle. In vivo studies of daily intralesional therapy for 1 month also showed reduced onset of growth and overall growth compared to controls. CONCLUSION: FA appears to have a tumoristatic/tumoricidal effect on HNSCC. Further nude mice studies are needed to optimize dosing and administration regimens for FA in anticipation of clinical trials.

Animals↗
PubMed2004

Opioid growth factor inhibition of a human squamous cell carcinoma of the head and neck in nude mice: dependency on the route of administration.

Opioid growth factor (OGF), [Met5]-enkephalin, interacts with the OGF receptor (OGFr) to inhibit the growth of human squamous cell carcinoma of the head and neck (SCCHN) in vitro. Administration of OGF by daily intraperitoneal injection (i.p.) to animals with xenografts of CAL-27, a poorly differentiated SCCHN, is known to repress tumorigenic events. In this study, the ubiquity of OGF action on SCCHN was investigated by examination of OGF activity on SCC-1 tumors; this human cell line is well-differentiated and highly invasive. Mice receiving daily i.p. injections (10 mg/kg) of OGF had more than a 3-day delay in tumor appearance, and decreases in tumor volume ranging from 51 to 64% in comparison to controls throughout the experimental period. Receptor binding analysis for OGFr showed that binding capacity (Bmax) was 2.2-fold greater than control values, but binding affinity (Kd) was comparable. Plasma OGF levels did not vary between OGF and control groups. Mice receiving OGF by continuous infusion using minipumps, or by daily intratumoral injection, had characteristics of tumorigenicity similar to their corresponding control animals, although the OGF levels in mice receiving the OGF by minipump were elevated 18-fold greater than the control group. These data indicate that: i) the inhibitory action of OGF may be ubiquitous for SCCHN, ii) OGF treatment alters the characteristics of the OGF receptor but not of plasma OGF levels, and iii) the magnitude of effects of OGF on SCCHN is dependent on the route of administration.

Animals↗
PubMed2004

Sinonasal adenoid cystic carcinoma with widespread symptomatic bony metastasis.

Adenoid cystic carcinoma is a fairly uncommon salivary neoplasm of the head and neck. These lesions often progress insidiously, and they have a propensity for early perineural spread and bony invasion. Distant metastasis to the lungs is fairly common and is usually fatal. We report a rare case of adenoid cystic carcinoma in a patient who on initial evaluation had widespread bony metastasis but no pulmonary involvement.

Adult↗
PubMed2003

Defects in the opioid growth factor receptor in human squamous cell carcinoma of the head and neck.

BACKGROUND: The endogenous opioid peptide, [Met(5)]-enkephalin, termed opioid growth factor (OGF), interacts with its receptor (OGFr) to play a role as a constitutively expressed inhibitory growth factor in the proliferation of epithelial cells. This study compared protein and gene expression of OGFr in surgical specimens of human squamous cell carcinoma of the head and neck (SCCHN) with normal epithelium. METHODS: Tissues from 64 patients with SCCHN and from 49 patients undergoing uvulapalatoplasty or tonsillectomy were utilized. Binding affinity and capacity were assessed by receptor binding assays and the levels of OGFr protein were determined by quantitative Western blot analysis. Immunohistochemistry assessed the presence and distribution of OGFr. Levels of OGFr mRNA were quantitated by Northern blot analysis. Protein and gene expressions of OGFr also were evaluated in the margins of SCCHN. RESULTS: Binding analyses indicated nearly ninefold fewer OGFr binding sites in tumor tissue in comparison with normal samples. The OGFr protein levels were reduced fivefold in tumor tissues relative to normal epithelium. Values of OGFr mRNA were comparable in tumors and normal epithelium. Tumor margins had intermediate levels of protein and binding, but OGFr mRNA values were similar to those of normal specimens. CONCLUSIONS: These data demonstrate that OGFr is defective in SCCHN and that translation/posttranslation of OGFr protein, but not transcriptional levels of the OGFr gene, is involved. In addition, the attenuated levels of OGFr binding capacity may serve as a marker for SCCHN. These subnormal levels of OGFr may be responsible in part for tumor progression, diminishing the interaction of OGF with OGFr that aids in stabilizing cell replication by an inhibitory mechanism. Gene therapy to reinstate OGFr and/or function could provide a useful treatment for inhibiting tumor progression.

Adolescent↗
PubMed2003

Surgical management of amiodarone-induced thyrotoxicosis.

OBJECTIVE: Amiodarone can cause thyroid dysfunction in patients with or without previous thyroid disease. With increased use from its placement in advanced cardiac life support guidelines and cardiac transplant programs, the incidence of amiodarone-induced thyrotoxicosis (AIT) will likely increase. Medical management is complex and nonuniform and frequently fails. This study investigates the role of surgery in AIT and proposes indications for surgical management. STUDY DESIGN AND SETTING: Two AIT case reports at a tertiary care institution and 31 surgical AIT cases in the world literature are reviewed. METHODS: The 2 AIT cases involved patients with cardiomyopathy and resistant arrhythmias. Despite medical therapy, both patients' conditions failed to improve. Thirty-one surgical cases of AIT in the literature are evaluated with respect to symptoms and onset, medical therapy, AIT classification, pathology, perioperative management, and complications. RESULTS: Both patients underwent total thyroidectomy without difficulty or complication, one as an overnight stay and one as an inpatient with an intraaortic balloon pump. One patient received a successful cardiac transplant and the other remains a viable candidate. In the literature, the majority (80%) of surgical cases are AIT type II (less common type) with no underlying thyroid disease. Range and duration of symptoms varied, in addition to type and duration of medical management. Almost all patients underwent total thyroidectomy, and all were successful with no mortality and minimal morbidity. CONCLUSION: AIT can develop in any patient during or after amiodarone therapy. Medical management is extremely difficult due to the absence of a proven therapeutic armamentarium, and surgery offers a safe, viable option. Surgical management should play a larger role in treatment algorithms and should be strongly considered for patients whose conditions necessitate continuation of amiodarone, or with severe symptoms resistant to medical therapy.

Adult↗