Biomedical subjects
J T Parsons
Publications and source records attributed to J T Parsons.
c-Raf-mediated inhibition of epidermal growth factor-stimulated cell migration.
Epidermal growth factor stimulates migration of a number of cell types, yet the signaling pathways that regulate epidermal growth factor-stimulated migration are poorly defined. In this report, we employ a transient transfection migration assay to assess the role of components of the Ras-mitogen-activated protein (MAP) kinase signaling pathway in epidermal growth factor-stimulated chemotaxis of rat embryo fibroblasts. Expression of dominant negative Ras blocks epidermal growth factor-mediated chemotaxis, while constitutively active Ras has no effect on chemokinesis or chemotaxis. PD98059 and U0126, inhibitors of MAP kinase kinase (MEK) activity, decreased epidermal growth factor-stimulated migration, while kinase-defective MEK1, an inhibitor of MAP kinase activation, enhanced migration. To understand the paradoxical effects of these molecules on epidermal growth factor-induced migration, we examined the role of c-Raf on migration. Expression of either wild type c-Raf or the catalytic domain of c-Raf effectively inhibited epidermal growth factor-stimulated cell migration. We suggest that, whereas Ras activity is necessary to promote epidermal growth factor-stimulated migration, sustained activation of c-Raf may be important in down-regulating migratory signaling pathways triggered by epidermal growth factor receptor activation. Further, activation of c-Raf upon inhibition of the MEK-MAP kinase pathway may contribute to the inhibition of cell migration observed with pharmacological MEK inhibitors.
Chicken macrophage stimulating protein is a ligand of the receptor protein-tyrosine kinase Sea.
Affinity chromatography, employing the extracellular domain of the Sea receptor, was used to enrich Sea-binding proteins from chicken serum. One isolated protein bound both a Sea-immunoglobulin fusion protein and an antisera raised against murine macrophage stimulating protein. Amino-terminal sequencing of the dual-reactive protein yielded sequences which were identical to the predicted alpha and beta subunits of chicken macrophage stimulating protein. The partially purified chicken macrophage stimulating protein caused autophosphorylation of the Sea receptor. Previous work showed that recombinant expression of fully activatible human or mouse macrophage stimulating protein required a specific Cys to Ala substitution (Wahl, R. C., Costigan, V. J., Batac, J. P., Chen, K., Cam, L., Courchesne, P. L., Patterson, S. D. Zhang, K., and Pacifici, R. E. (1997) J. Biol. Chem. 272, 1-4). Therefore, we expressed both the wild type and the specific Cys to Ala form of chicken macrophage stimulating protein as recombinant proteins. After proteolytic activation, only conditioned media from COS cells transfected with the C665A chicken macrophage stimulating protein, but not from wild type chicken macrophage-stimulating protein, or control vector, was detected by the Sea-immunoglobulin fusion protein in Western blotting experiments. Conditioned media containing the C665A chicken macrophage-stimulating protein readily caused Sea phosphorylation, while conditioned media containing the wild type chicken macrophage-stimulating protein was only effective at inducing receptor phosphorylation at high concentrations. In addition to receptor phosphorylation, the C665A chicken macrophage-stimulating protein induced phosphorylation of Shc, Erk1, and Erk 2. We conclude that macrophage-stimulating protein is a ligand of the Sea receptor protein-tyrosine kinase.
Pre- and post-radiotherapy computed tomography in laryngeal cancer: imaging-based prediction of local failure.
PURPOSE: To determine if pre-radiotherapy (RT) and/or post-radiotherapy computed tomography (CT) can predict local failure in patients with laryngeal carcinoma treated with definitive RT. METHODS AND MATERIALS: The pre- and post-RT CT examinations of 59 patients (T3 glottic carcinoma [n = 30] and T1-T4 supraglottic carcinoma [n = 29]) were reviewed. For each patient, the first post-RT CT study between 1 and 6 months after irradiation was used. All patients were treated with definitive hyperfractionated twice-daily continuous-course irradiation to a total dose of 6,720-7,920 cGy, and followed-up clinically for at least 2 years after completion of RT. Local control was defined as absence of primary tumor recurrence and a functioning larynx. On the pre-treatment CT study, each tumor was assigned a high-or low-risk profile for local failure after RT. The post-RT CT examinations were evaluated for post-treatment changes using a three-point post-RT CT-score: 1 = expected post-RT changes; 2 = focal mass with a maximal diameter of < 1 cm and/or asymmetric obliteration of laryngeal tissue planes; 3 = focal mass with a maximal diameter of > 1 cm, or < 50% estimated tumor volume reduction. RESULTS: The local control rates at 2 years post-RT based on pre-treatment CT evaluation were 88% for low pre-treatment risk profile patients (95% CI: 66-96%) and 34% (95% CI: 19-50%) for high pre-treatment risk profile patients (risk ratio 6.583; 95% CI: 2.265-9.129;p = 0.0001). Based on post-treatment CT, the local control rates at 2 years post-RT were 94% for score 1, 67% for score 2, and 10% for score 3 (risk ratio 4.760; 95% CI: 2.278-9.950 p = 0.0001). Post-RT CT scores added significant information to the pre-treatment risk profiles on prognosis. CONCLUSIONS: Pre-treatment CT risk profiles, as well as post-RT CT evaluation can identify patients, irradiated for laryngeal carcinomas, at high risk for developing local failure. When the post-RT CT score is available, it proves to be an even better prognosticator than the pre-treatment CT-risk profile.
Global ischemia-induced inhibition of the coupling ratio of calcium uptake and ATP hydrolysis by rat whole brain microsomal Mg(2+)/Ca(2+) ATPase.
Ischemia is associated with a loss of cytosolic calcium homeostasis. Intracellular stores, particularly in endoplasmic reticulum, are critical for the maintenance of calcium homeostasis. Recent studies have shown that ischemia significantly inhibited microsomal calcium uptake mediated by Mg(2+)/Ca(2+) ATPase, the major mechanism of endoplasmic reticulum calcium sequestration. This study was initiated to determine whether the decreased calcium uptake caused by ischemia was the result of inhibition of Mg(2+)/Ca(2+) ATPase activity or an uncoupling of calcium uptake from ATP hydrolysis. The microsomal Mg(2+)/Ca(2+) ATPase specific inhibitor thapsigargin partially inhibited ATPase activity and completely inhibited calcium uptake. ATPase inhibited by thapsigargin was considered microsomal Mg(2+)/Ca(2+) ATPase. Ischemia from 5 to 60 min had no significant effect on thapsigargin sensitive ATPase activity. However, under identical conditions, increasing ischemia from 5 to 60 min significantly inhibited microsomal calcium uptake. Comparing calcium uptake to ATP hydrolysis as ischemia increased from 5 to 60 min revealed that the coupling ratio of calcium molecules sequestered to ATP molecules hydrolyzed became significantly decreased. The results demonstrated that the effect of ischemia on microsomal calcium uptake was mediated by an uncoupling of calcium transport from Mg(2+)/Ca(2+) ATPase activity.
Stable association of PYK2 and p130(Cas) in osteoclasts and their co-localization in the sealing zone.
Bone resorption is initiated by osteoclast attachment to the mineralized matrix, cytoskeletal reorganization, cellular polarization, and the formation of the sealing zone. The present study examines the interaction between PYK2 and p130(Cas) (Crk-associated substrate), suggested to be part of the signaling pathway initiated by osteoclast adhesion. Using murine osteoclast-like cells (OCLs) and their mononuclear precursors (pOCs), generated in a co-culture of bone marrow and osteoblastic MB1.8 cells, we show that: 1) p130(Cas) is tyrosine-phosphorylated upon adhesion of pOCs to vitronectin or ligation of beta3 integrins; 2) p130(Cas) colocalizes with PYK2 and the cytoskeletal proteins F-actin, vinculin, and paxillin in the podosomal-rich ring-like structures of OCLs plated on glass and in the sealing zone in actively resorbing OCLs on bone; 3) p130(Cas) and PYK2 form a stable complex in pOCs, independent of tyrosine phosphorylation of either molecule, and this complex is present in Src (-/-) OCLs, in which neither protein is phosphorylated or associated with the osteoclast adhesion structure; 4) the association of p130(Cas) and PYK2 is mediated by the SH3 domain of p130(Cas) and the C-terminal domain of PYK2. These findings suggest that p130(Cas) and its association with PYK2 may play an important role in the adhesion-dependent signaling that leads to cytoskeletal reorganization and formation of the sealing zone during osteoclast activation.
Skin cancer of the head and neck with incidental microscopic perineural invasion.
PURPOSE: To address outcomes in clinically asymptomatic patients in whom the unexpected finding of microscopic perineural invasion is noted at the time of surgery. METHODS AND MATERIALS: The 35 patients included in this study had skin cancers of the head and neck treated with curative intent between January 1965 and April 1995 at the University of Florida. All patients were without clinical or radiographic evidence of perineural invasion but, at the time of biopsy or surgical excision, had the incidental finding of microscopic perineural invasion. Definitive therapy consisted of radiotherapy alone after lesion biopsy (3 patients) or surgical excision preceded (2 patients) or followed (30 patients) by radiotherapy. All patients had follow-up for at least 1 year, 13 patients (37%) had follow-up for at least 5 years. RESULTS: The 5-year local control rate was 78%. The 5-year local control rate for the few patients treated with radiotherapy alone was statistically similar to that for patients treated with surgery and radiotherapy (100% vs. 77%, p = 0.4). Multivariate analysis for factors affecting local control included sex, histology, age, treatment group, clinical T stage, initial histologic differentiation, and previously untreated vs. recurrent tumors, none of which was found to be significant. CONCLUSIONS: Both surgery plus radiotherapy and radiotherapy alone provide a relatively high rate of local control for patients with incidentally discovered perineural invasion secondary to skin cancer.
Induction chemotherapy and radiation therapy for T4 oropharyngeal carcinoma.
Between 1964 and 1996, 123 patients were treated for T4 oropharyngeal carcinoma; 93 were treated with radiation therapy alone; 30 were treated with induction chemotherapy and radiation therapy. Patients who received induction chemotherapy and radiation therapy were treated between 1985 and 1996; during this time 39 patients were treated with radiation therapy alone. Five-year local control rates for patients undergoing chemotherapy and radiation therapy, radiation therapy alone (all patients), and radiation therapy alone (patients treated since September 1985) were 63%, 38%, and 48%, respectively. The five-year rates of freedom from distant metastasis were 87%, 73%, and 76%, respectively. The five-year actuarial cause-specific survival rates were 58%, 27%, and 37%, respectively, while the five-year absolute survival rates were 42%, 17%, and 23%, respectively. Improvements in local control and freedom from distant metastasis in those receiving chemotherapy were not statistically significant, while the improvements in cause-specific survival and absolute survival were significant at the P < or = 0.05 level. Induction chemotherapy may improve the cure rate for patients with T4 oropharyngeal carcinoma. Although encouraging, these data are nonrandomized and should be interpreted with caution.
Complex formation with focal adhesion kinase: A mechanism to regulate activity and subcellular localization of Src kinases.
Tyrosine phosphorylation of focal adhesion kinase (FAK) creates a high-affinity binding site for the src homology 2 domain of the Src family of tyrosine kinases. Assembly of a complex between FAK and Src kinases may serve to regulate the subcellular localization and the enzymatic activity of members of the Src family of kinases. We show that simultaneous overexpression of FAK and pp60(c-src) or p59(fyn) results in the enhancement of the tyrosine phosphorylation of a limited number of cellular substrates, including paxillin. Under these conditions, tyrosine phosphorylation of paxillin is largely cell adhesion dependent. FAK mutants defective for Src binding or focal adhesion targeting fail to cooperate with pp60(c-src) or p59(fyn) to induce paxillin phosphorylation, whereas catalytically defective FAK mutants can direct paxillin phosphorylation. The negative regulatory site of pp60(c-src) is hypophosphorylated when in complex with FAK, and coexpression with FAK leads to a redistribution of pp60(c-src) from a diffuse cellular location to focal adhesions. A FAK mutant defective for Src binding does not effectively induce the translocation of pp60(c-src) to focal adhesions. These results suggest that association with FAK can alter the localization of Src kinases and that FAK functions to direct phosphorylation of cellular substrates by recruitment of Src kinases.
Regulated expression of focal adhesion kinase-related nonkinase, the autonomously expressed C-terminal domain of focal adhesion kinase.
Focal adhesion kinase (FAK) has been implicated in cellular processes that control cell adhesion, migration, cell cycle progression, and apoptosis. FRNK (FAK-related nonkinase) is the autonomously expressed, noncatalytic C-terminal portion of FAK. When ectopically expressed in cells, FRNK has been shown to act as a negative regulator of FAK activity, inhibiting cell spreading, migration, and cell cycle progression. The mechanisms that regulate FRNK expression during embryonic development and the functional role of FRNK in normal cell homeostasis remain poorly understood. Herein we show that FRNK expression in chicken cells is directed by an alternative promoter residing within an intron of FAK, positioned 3' of the exon encoding sequences for the catalytic domain and 5' of the exon encoding sequences for the C-terminal domain of FAK (e.g., FRNK). Using probes specific for FRNK, we show that FRNK expression occurs early in chicken embryogenesis, being readily detected at day 3, 6, or 9. Late in embryogenesis, at day 18, FRNK is expressed in a tissue-specific manner, predominately in lung and intestine cells. Western blot analysis of mouse tissues with a FAK-specific antibody revealed the expression of FRNK in the mouse lung. Reverse transcriptase PCR analysis of mouse lung RNA revealed the presence of spliced FRNK mRNAs containing 5' untranslated sequences derived from a positionally conserved exon present in the mouse genome. FAK is the first example of a tyrosine kinase regulated by a domain under the control of an alternative intronic promoter. It is also the first example of a focal adhesion-associated protein regulated by such a mechanism and thus represents a novel means for the modulation of cell adhesion signaling.
Cytoskeletal changes induced by GRAF, the GTPase regulator associated with focal adhesion kinase, are mediated by Rho.
Graf, the GTPase regulator associated with focal adhesion kinase was previously shown to have GAP activity for &Rgr; A and Cdc42 in vitro (Hildebrand et al 1996 Mol. Cell Biol. 16: 3169-3178). In this study we sought to determine whether Graf acted at the level of Cdc42, Rho, or both in vivo and whether Graf was a signal terminator or transducer for these proteins. Microinjection of Graf cDNA into subconfluent Swiss 3T3 cells (in the presence of serum) has marked effects on cell shape and actin localization. Graf expression causes clearing of stress fibers followed by formation of long actin based filopodial-like extensions. Similar phenotypes were observed following injection of the Rho-inhibitor, C3 into these cells. The Graf response was dependent on GAP activity, since injection of Graf cDNA containing point mutations in the GAP domain (R236Q or N351V) which block enzymatic activity, does not confer this phenotype. Injection of Graf into Swiss 3T3 cells in which Rho has been down-regulated by serum starvation has no effect on cell morphology. Using this system, we demonstrate that Graf blocks sphingosine-1-phosphate (SPP) stimulated (Rho-mediated) stress fiber formation. Conversely, Graf expression does not inhibit bradykinin stimulated (Cdc42-mediated) filopodial extensions. These data indicate that Graf is a GAP for Rho in vivo. To further substantiate these results we examined the effect of Graf over-expression on Rho-mediated neurite retraction in nerve growth factor (NGF)-differentiated PC12 cells. In PC12 cells, which express relatively high levels of endogenous Graf, overexpression of Graf (but not Graf containing the R236Q mutation) enhances SPP-induced neurite retraction. These data indicate the possibility that Graf may be an effector for Rho in certain cell types.
Separation of radiolabeled orthophosphate and adenosine 5'-triphosphate by 20% polyacrylamide gel electrophoresis: an assay for brain microsomal Mg2+/Ca2+ ATPase activity.
Measuring orthophosphate is an important tool in biochemical analyses used to study membrane transport ATPases essential for calcium homeostasis. Current techniques involve extraction of radioactive phosphate with organic solvents, a technique that results in large quantities of hazardous radioactive waste. Other colorimetric assays are less sensitive and are complicated by interference of background absorbance from membrane tissue and unutilized ATP. This report describes a unique assay for the detection of inorganic phosphate and its application to the study of rat brain microsomal Mg2+/Ca2+ ATPase from a membrane fraction. The technique involves the separation of radioactive phosphate from unused gamma-radiolabeled ATP by resolution on 20% polyacrylamide gels. Both are visualized with X-ray film and quantitated by liquid scintillation counting after extraction from the gels. The assay can detect as little as 4.1 pmol of radiolabeled ATP and ATPase activity in 3.5 ng/microliter of membrane protein. This method offers the advantage of simultaneous quantitation of radiolabeled ATP and radioactive orthophosphate without the generation of large quantities of radioactive waste. The results demonstrate the development of a novel assay procedure for quantitating orthophosphate that is extremely sensitive, reproducible, and applicable to the study of any phosphate liberating enzyme.
Expression and characterization of splice variants of PYK2, a focal adhesion kinase-related protein.
Focal adhesion kinase and the recently identified proline-rich tyrosine kinase 2 (PYK2), also known as cell adhesion kinase &bgr ;, related adhesion focal tyrosine kinase or calcium-dependent protein tyrosine kinase, define a new family of non-receptor protein tyrosine kinases. Activation of PYK2 has been implicated in multiple signaling events, including modulation of ion channels, T- and B-cell receptor signaling and cell death. Mechanisms underlying the functional diversity of PYK2 are unclear. Here, we provide evidence for two novel alternatively expressed isoforms of PYK2. One isoform, designated PYK2s (PYK2 splice form), appears to be a splice variant of PYK2 lacking 42 amino acids within the C-terminal domain. A second isoform, referred to as PRNK (PYK2-related non-kinase), appears to be specified by mRNAs that encode only part of the C-terminal domain of PYK2. Northern blot analysis indicates that the unspliced PYK2 is expressed at high levels in the brain and poorly expressed in the spleen, whereas PYK2s and PRNK are expressed in the spleen. In situ hybridization studies of rat brain demonstrate that the unspliced PYK2 is selectively expressed at high levels in hippocampus, cerebral cortex and olfactory bulb, whereas PYK2s and PRNK are expressed at low levels in all regions of rat brain examined. Immunofluorescence analysis of ectopically expressed PRNK protein shows that PRNK, in contrast to full-length PYK2, is localized to focal adhesions by sequences within the focal adhesion targeting domain. In addition, PYK2, but not PRNK, interacts with p130(cas )and Graf. These results imply that PRNK may selectively regulate PYK2 function in certain cells by binding to some but not all PYK2 binding partners, and the functional diversity mediated by PYK2 may be due in part to complex alternative splicing.
Characterization of graf, the GTPase-activating protein for rho associated with focal adhesion kinase. Phosphorylation and possible regulation by mitogen-activated protein kinase.
Graf is a GTPase-activating protein for Rho that interacts with focal adhesion kinase and co-localizes with the actin cytoskeleton (Hildebrand, J. D., Taylor, J. M. and Parsons, J. T. (1996) Mol. Cell. Biol. 16, 3169-3178). We examined the expression and regulation of Graf as a prelude to understanding the role of Graf in mediating signal transduction in vivo. We demonstrated that Graf is a ubiquitously expressed 95-kDa protein with high levels observed in heart and brain and cells derived from these tissues. Stimulation of PC12 cells with epidermal growth factor or nerve growth factor induced a phosphatase-reversible mobility shift upon gel electrophoresis, indicative of phosphorylation. In vitro, purified mitogen-activated protein (MAP) kinase catalyzed the phosphorylation of Graf on serine 510, suggesting that Graf phosphorylation may be mediated through MAP kinase signaling. In addition, the mutation of serine 510 to alanine inhibited the epidermal growth factor-induced mobility shift of mutant Graf protein in vivo, consistent with serine 510 being the site of in vivo phosphorylation. Based on these data we suggest that phosphorylation of Graf by MAP kinase or related kinases may be a mechanism by which growth factor signaling modulates Rho-mediated cytoskeletal changes in PC12 and perhaps other cells.
T4 laryngeal carcinoma: radiotherapy alone with surgery reserved for salvage.
PURPOSE: To review the results of primary radiation therapy for patients with T4 squamous cell carcinoma of the larynx. METHODS AND MATERIALS: Between October 1964 and October 1994, 43 patients with T4 invasive squamous cell carcinoma of the larynx received radiotherapy with curative intent in the University of Florida Department of Radiation Oncology. All patients had a minimum of 2 years follow-up. There were 26 primary cancers of the supraglottic larynx, 11 of the glottic larynx, and 6 of the subglottic larynx. RESULTS: The 5-year actuarial rate of local control was 52%. By direct calculation, local control was achieved in 8 (38%) of 21 supraglottic carcinomas, 8 (89%) of 9 glottic tumors, and 2 of 6 subglottic tumors. Local control of nonbulky lesions was achieved in 67%, and 38% of bulky lesions were locally controlled. Only 3 (17%) of 18 local recurrences were successfully salvaged by subsequent surgery. There were 2 (5%) severe complications of irradiation. CONCLUSION: From our series, as well as a review of the literature, local control by primary irradiation has been achieved in approximately 50% of patients with T4 laryngeal cancer. Selection factors for choosing irradiation have not been well described: the present series contains a small amount of information suggesting that tumor volume may be a reliable predictor of control, but further substantiation is required.
Evaluation of pretreatment computed tomography as a predictor of local control in T1/T2 pyriform sinus carcinoma treated with definitive radiotherapy.
BACKGROUND: This study was undertaken to determine whether pretreatment computed tomography (CT) findings can predict local control in pyriform sinus carcinoma treated with definitive radiotherapy (RT). METHODS: Twenty-three patients with pyriform sinus carcinoma (T1: n = 5; T2: n = 18) were treated with high-dose RT and followed for a minimum of 2 years. Tumor volumes and extent were determined on pretreatment CT studies. The specific CT parameters assessed were analyzed as predictors of local control. RESULTS: There was a significant decrease in local control rate for tumors over 6.5 mL (1 of 4 [25%]) relative to tumors under 6.5 mL (17 of 19 [89%]; p = .021). Sensitivity and specificity for local control using this cutoff were 94% and 60%, respectively. Tumor score, as a measure of anatomic extent, was also found to be a significant predictor of local control (p = .033). The local control rate was not influenced significantly by the presence of "minimal" apex disease (< 10 mm in greatest dimensions as measured on CT) but decreased significantly when "bulk" apex disease (> OR = 10 mm) was present (p = .027). Laryngeal cartilage sclerosis was not a significant predictor of outcome. CONCLUSION: Computed tomography can stratify pyriform sinus carcinomas into groups more or less likely to be locally controlled with definitive RT.
Carcinoma of the skin metastatic to the parotid area lymph nodes.
BACKGROUND: We performed an analysis of treatment outcome at the University of Florida for 77 patients with previously untreated carcinoma of the skin metastatic to parotid area lymph nodes. METHODS: Seventy-seven patients with 79 parotid node metastases were treated with curative intent between 1966 and 1994. All patients had a minimum 2-year follow-up. Treatment consisted of radiotherapy alone in 18 patients, preoperative radiotherapy in 6 patients (7 parotids), and postoperative radiotherapy in 53 patients (54 parotids). RESULTS: Overall rate of disease control in the parotid area at 5 years was 82%. Parotid area disease control according to treatment group revealed: surgery and postoperative radiotherapy, 43 of 48 (90%); preoperative radiotherapy and surgery, 4 of 5 (80%); and radiotherapy alone, 8 of 15 (53%). Multivariate analysis of parotid disease control revealed the following: treatment method (p = .0037), N stage (p = .0726), cranial nerve involvement (p = .1851), fixation (p = .1820), skin involvement (p = .1771), and sex (p = .5782). Overall 5-year absolute and cause-specific survival rates were 54% and 68%, respectively. The 5-year cause-specific survival rate was 72% after surgery and postoperative radiotherapy and 59% following radiotherapy alone. Multivariate analysis of cause-specific survival revealed the following: skin involvement (p = .0215), cranial nerve involvement (p = .1549), fixation (p = .0347), N stage (p = .4302), sex (p = .6806), and treatment method (p = .9599). CONCLUSIONS: Our current policy is to treat patients with tumor that is initially resectable with surgery followed by radiotherapy, whereas those who have initially unresectable disease undergo preoperative radiotherapy followed by surgical resection if the tumor becomes resectable. If surgery cannot be performed for medical reasons, patients still have better than a 50% chance of being cured with radiotherapy alone.
Radiotherapy in the management of chemodectomas of the carotid body and glomus vagale.
BACKGROUND: Because only limited data are available pertaining to radiotherapy for chemodectomas of the carotid body and glomus vagale, we reviewed our experience. METHODS: Fifteen patients with 23 chemodectomas of either the carotid body or glomus vagale were treated with radiotherapy at the University of Florida between 1981 and 1995. Eighteen lesions were previously untreated. One patient had received prior radiotherapy at another institution and four patients had received prior surgery. RESULTS: The local control rate at 10 years, calculated by the Kaplan-Meier product-limit method, was 96% for the overall group of 23 lesions and 100% for the subset of 22 lesions without prior radiotherapy. The 10-year cause-specific survival rate was 89% for all 15 patients and 100% for the 14 patients who had received no prior radiotherapy. No patient experienced a significant complication secondary to irradiation. CONCLUSIONS: Irradiation offers a high probability of tumor control with relatively minimal risks for patients with chemodectomas of the carotid body and glomus vagale.