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J T Parsons

Publications and source records attributed to J T Parsons.

At least 91 records · Page 5Linked to original sources
PubMed1997

Inhibition of cell spreading by expression of the C-terminal domain of focal adhesion kinase (FAK) is rescued by coexpression of Src or catalytically inactive FAK: a role for paxillin tyrosine phosphorylation.

pp125FAK is a tyrosine kinase that appears to regulate the assembly of focal adhesions and thereby promotes cell spreading on the extracellular matrix. In some cells, the C terminus of pp125FAK is expressed as a separate protein, pp41/43FRNK. We have previously shown that overexpression of pp41/43FRNK inhibits tyrosine phosphorylation of pp125FAK and paxillin and, in addition, delays cell spreading and focal adhesion assembly. Thus, pp41/43FRNK functions as a negative inhibitor of adhesion signaling and provides a tool to dissect the mechanism by which pp125FAK promotes cell spreading. We report here that the inhibitory effects of pp41/43FRNK expression can be rescued by the co-overexpression of wild-type pp125FAK and partially rescued by catalytically inactive variants of pp125FAK. However, coexpression of an autophosphorylation site mutant of pp125FAK, which fails to bind the SH2 domain of pp60c-Src, or a mutant that fails to bind paxillin did not promote cell spreading. In contrast, expression of pp41/43FRNK and pp60c-Src reconstituted cell spreading and tyrosine phosphorylation of paxillin but did so without inducing tyrosine phosphorylation of pp125FAK. These data provide additional support for a model whereby pp125FAK acts as a "switchable adaptor" that recruits pp60c-Src to phosphorylate paxillin, promoting cell spreading. In addition, these data point to tyrosine phosphorylation of paxillin as being a critical step in focal adhesion assembly.

Animals↗
PubMed1997

Definitive radiotherapy for T3 squamous cell carcinoma of the glottic larynx.

PURPOSE: To report the results of radiotherapy alone for stage T3 squamous cell carcinoma of the true vocal cord and compare these data with those obtained with other treatment modalities. METHODS AND MATERIALS: Seventy-five patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated with curative intent with radiotherapy alone (73 patients) or followed by a planned neck dissection (two patients) at the University of Florida between September 1966 and August 1994. No patient received adjuvant chemotherapy. All patients were monitored for at least 2 years and 85% had a minimum follow-up duration of 5 years. No patient was lost to follow-up evaluation. RESULTS: The 5-year local control and ultimate local control rates were 63% and 86%, respectively. The volume of the primary tumor (which was calculated on pretreatment computed tomographic [CT] scans in 38 patients) was inversely related to local control with larynx preservation: < or = 3.5 cm3, 20 of 23 (87%) versus greater than 3.5 cm3, four of 14 (29%) (P = .0005). There was no apparent relationship between local control after radiotherapy as a function of whether the vocal cord regained mobility or remained fixed during or shortly after completion of treatment. The 5-year absolute and cause-specific survival rates were 54% and 78%, respectively. Multivariate analysis showed that pretreatment tracheostomy was significantly related to diminished cause-specific survival (P = .0345). CONCLUSION: Radiotherapy alone results in long-term local-regional control and survival rates that are comparable to those obtained with surgery. It is unclear whether induction or concomitant chemotherapy is associated with improved local-regional control and survival compared with radiotherapy alone.

Carcinoma, Squamous Cell↗
PubMed1997

Radiotherapy for carcinoma of the supraglottis.

Squamous cell carcinoma of the supraglottic larynx is treated primarily by conservation surgery or radiotherapy for early to moderately advanced lesions, and total laryngectomy, with or without irradiation, for advanced tumors. This article reviews the role of radiotherapy, used alone or in combination with surgery, for squamous cell carcinoma of the supraglottic larynx. Treatment philosophy, techniques, and results from the University of Florida are emphasized.

Carcinoma, Squamous Cell↗
PubMed1996

Integrin-dependent activation of the p70 ribosomal S6 kinase signaling pathway.

Interaction of the cell surface integrin receptors with extracellular matrix proteins results in the activation of intracellular signaling pathways, including activation of the p42/p44 mitogen-activated protein kinases. The protein tyrosine kinase focal adhesion kinase, or FAK, is linked to integrin signaling and interacts with several molecules involved in signal transduction. Here we report that exposure of fibroblast cells to extracellular matrix proteins activates the p70/p85 ribosomal S6 kinase (S6K) pathway in a ligand dependent manner. Treatment of cells with inhibitors of phosphatidylinositol 3-kinase, or FRAP (FKBP 12/rapamycin-associated protein) blocks integrin-mediated activation of S6K. In contrast to the integrin-directed activation of the mitogen-activated protein kinases, cytochalasin D treatment does not inhibit S6K activation. Treatment with the protein tyrosine kinase inhibitors herbimycin A and genistein completely blocks S6K activation, indicating a requirement for tyrosine kinase activity. Overexpression of the COOH-terminal noncatalytic domain of FAK, FRNK (FAK-related non-kinase) in chick embryo cells results in a significant reduction in the integrin-mediated activation of S6K and a concomitant reduction in FAK tyrosine phosphorylation. These results indicate at least a partial requirement for FAK in the S6K activation pathway.

Cell Adhesion Molecules↗
PubMed1996

Quality of life outcomes after primary radiotherapy for squamous cell carcinoma of the base of tongue.

PURPOSE: To determine quality of life functional outcome after primary radiotherapy for carcinoma of the base of tongue. METHODS AND MATERIALS: At the University of Florida, essentially all patients with squamous cell carcinoma of the base of tongue are treated with primary continuous-course, external-beam radiotherapy alone or followed by a neck dissection. Fifty-three patients who remained continuously free of disease at 2 to 23 years were eligible to participate in an assessment of the posttreatment quality of their lives. Three patients could not be located for quality of life assessment, and one patient refused to participate, leaving 49 evaluable patients. Radiotherapy doses were 60 to 75 Gy in once daily fractions, or 74 to 79 Gy in twice daily fractions. The subjective Performance Status Scale for Head and Neck Cancer, which assigns a functional score ranging from 0 to 100, was completed by each of the patients during routine follow-up appointments. The scale measures ability to eat in public, understandability of speech, and normalcy of diet. RESULTS: Patients treated with external-beam radiotherapy alone had excellent results with regard to eating in public though scores showed a decline as T stage increased (average scores were T1: 90.6%; T2: 88.1%; T3: 82.8%; T4: 75.0%). Results for understandability of speech were T1: 93.75%; T2: 100%; T3: 82.8%; and T4: 87.5%. Fixation of the tongue at diagnosis was not a predictor of poor function. Normalcy of diet scores likewise decreased with increasing T stage: T1: 93.8%; T2: 89.5%; T3: 71.3%; T4: 60.0%. The addition of a neck dissection had no impact on the functional outcomes that were evaluated. Functional results did not deteriorate with prolonged follow-up of more than 5 years. Results were compared with those from the literature for patients treated by surgery plus postoperative radiotherapy or external-beam irradiation plus interstitial 192Ir implant. The functional results of high-dose external-beam irradiation alone in the present series were similar to those reported after external plus interstitial irradiation. The functional results after both types of radiation treatment were superior to results for patients who underwent surgery. CONCLUSIONS: Functional outcomes after external-beam radiotherapy were similar to those after external-beam plus 192Ir implant, and were superior to the results of surgical resection. Planned postradiotherapy neck dissection did not affect the analyzed functional endpoints. Function appeared to be stable by 5 years without subsequent change.

Adult↗
PubMed1996

Radiotherapy for local control of aggressive fibromatosis.

PURPOSE: To evaluate local control rates in patients treated with radiotherapy for aggressive fibromatosis. METHODS AND MATERIALS: Fifty-three patients with histologically confirmed aggressive fibromatosis were treated with radiotherapy at the University of Florida between march 1975 and June 1992. The minimum length of follow-up was 2 years; 81% of the patients had follow-up for at least 5 years. The lesions arose in an extremity or limb girdle (39 patients), the trunk (10 patients), or the head and neck area (4 patients). Twenty-four patients were treated for gross disease and 29 for presumed microscopic residual disease after one or more operations. Patients were treated with total doses between 35 and 70 Gy; 83% of patients received 50 to 60 Gy. RESULTS: Local control was achieved in 23 of 29 patients (79%) treated postoperatively for microscopic residual disease and in 21 of 24 patients (88%) treated for gross disease; gross disease was controlled in all 8 patients with previously untreated lesions and in 13 of 16 patients treated postoperatively for gross residual or recurrent disease. Overall, aggressive fibromatosis was locally controlled in 83% of treated patients. All nine treatment failures occurred in patients with extremity lesions 4 to 68 months after initiation of treatment. Three recurrences were in the irradiated field, two were out of the field, and four were at the field margin. Eight patients were salvaged with surgery alone or combined with postoperative radiotherapy. A functional limb was maintained in 38 of 39 patients with extremity or limb girdle lesions. Pathologic fracture occurred in three patients; two patients required rod fixation for treatment. CONCLUSIONS: Radiotherapy is a valuable adjunct to surgery in the management of aggressive fibromatosis and can be used alone in patients with unresectable or inoperable disease.

Adolescent↗
PubMed1996

p130Cas, a substrate associated with v-Src and v-Crk, localizes to focal adhesions and binds to focal adhesion kinase.

p130(Cas) (crk associated substrate) has the structural characteristics of an adapter protein, containing multiple consensus SH2 binding sites, an SH3 domain, and a proline-rich domain. The structure of p130(Cas) suggests that it may act to provide a framework for protein-protein interactions; however, as yet, its functional role in cells is unknown. In this report we show that p130(Cas) is localized to focal adhesions. We demonstrate that p130(Cas) associates both in vitro and in vivo with pp125(FAK) (focal adhesion kinase), a kinase implicated in signaling by the integrin family of cell adhesion receptors. p130(Cas) also associates with pp41/43(FRNK) (pp125(FAK)-related, non-kinase), an autonomously expressed form of pp125(FAK) composed of only the C-terminal noncatalytic domain. We show that the association of p130(Cas) with pp125(Fak) and pp41/43(FRNK) is direct, and is mediated by the binding of the SH3 domain of p130(Cas) to a proline-rich sequence present in both the C terminus of pp125(FAK) and in pp41/43(FRNK). In agreement with recent studies we show that p130(Cas) is tyrosine-phosphorylated upon integrin mediated cell adhesion. The association of p130(Cas) with pp125(FAK), a kinase which is activated upon cell adhesion, is likely to be functionally important in integrin mediated signal transduction.

Animals↗
PubMed1996

The identification of p130cas-binding proteins and their role in cellular transformation.

Adaptor proteins play an important role in signal transduction by regulating the establishment and maintenance of functionally important protein complexes. A recently described member of this group of proteins is p130cas (CAS), which contains numerous sequence motifs predicted to be involved in mediating protein-protein interactions. We propose that adaptor molecules like CAS may help determine the response of a cell to a particular signal by interacting with specific subsets of cellular proteins. To test this hypothesis, we have identified potential binding partners of CAS that may play a rote in cellular transformation by the oncoproteins v-SRC and/or v-CRK. We show that individual domains of CAS associate with specific subsets of proteins in vitro, and that many of these interactions are dependent on the state of tyrosine-phosphorylation of CAS. Sequences necessary for interacting with the focal adhesion kinase pp125FAK (FAK), v-SRC and v-CRK have been mapped to distinct regions of CAS. In addition, the identification of a number of putative CAS-binding partners that are present in crk-transformed cell extracts but undetectable in normal and src-transformed cell extracts supports a model in which unique protein complexes are formed in response to different signals.

Carrier Proteins↗
PubMed1996

Management of minor salivary gland carcinomas.

PURPOSE: To assess the role of radiotherapy alone or in combination with surgery in the treatment of patients with malignant minor salivary gland carcinomas. METHODS AND MATERIALS: Between October 1964 and November 1992, 95 patients with minor salivary gland carcinomas of the head and neck received radiotherapy with curative intent. Eighty-seven patients were previously untreated, and 8 were treated for postsurgical recurrence. Fifty-one patients were treated with radiotherapy alone, and 44 were treated by surgical resection plus radiotherapy. Patients were staged according to the 1983 American Joint Committee on Cancer (AJCC) staging criteria for squamous cell carcinomas. RESULTS: The 20-year actuarial rate of local control was 57% with no significant difference according to histologic type. When tumor stage was taken into consideration, there were no significant differences in local control according to tumor site. The 12-year actuarial probability of distant metastases was 40% (19% as the only site of failure). In multivariate analyses, local control was significantly affected only by tumor stage and treatment type (combined therapy better than radiotherapy alone); tumor stage was a significant predictor of cause-specific survival and freedom from relapse. Freedom-from-relapse rates were higher for patients who received combined treatment (p = 0.068). CONCLUSIONS: Treatment of minor salivary gland carcinomas is usually by combined surgery and radiotherapy, but there are situations where surgery alone or radiotherapy alone may be used. The ability to control these tumors with radiotherapy alone is not widely recognized. In the present series, the tumor was locally controlled in 20 patients with previously untreated primary lesions after radiotherapy alone (2.5 to 21 years) and in 4 other patients who were treated by radiotherapy alone for postsurgical recurrent tumor (3.5 to 14 years after radiotherapy). Contrary to the widely held belief that local recurrence after radiotherapy eventually develops in all patients with adenoid cystic carcinoma, local control has been maintained in 13 patients after radiotherapy alone; 5 of the 13 patients have been observed for 10 to 17 years.

Adenocarcinoma↗
PubMed1996

Expression and maturation of the cellular sea receptor, a member of the hepatocyte growth factor (HGF) receptor family of protein tyrosine kinases.

The c-sea proto-oncogene is a member of the Met/hepatocyte growth factor/scatter factor family of receptor protein tyrosine kinases. A distinguishing feature of this family, whose other member is the Ron/Stk receptor, is a novel heterodimeric structure. We have previously described cDNA clones encoding the avian Sea receptor. In this report we show that a full length c-sea cDNA directed the synthesis of a single 155 kDa polypeptide chain in vitro, while in vivo two polypeptides of 160 and 180 kDa were observed. We analysed the structure of the Sea receptor using a soluble chimeric protein consisting of the Sea extracellular domain linked to the hinge and constant regions of human IgG gamma 1. These studies indicated that the receptor undergoes proteolytic processing in the extracellular domain yielding an approximate 35 kDa alpha and a 160 kDa beta chain, and thus the Sea receptor appears to display a structure similar to that of the Met and Ron proteins. An examination of embryonic avian tissues using Sea extracellular domain-specific monoclonal antibodies revealed low levels of Sea receptor in a variety of tissues including kidney, intestine, liver, stomach, white blood cells and allantochorion. Elevated levels of expression were observed upon transformation of chicken embyro cells by the Src oncoprotein.

Animals↗
PubMed1996

Oropharyngeal carcinoma treated with radiotherapy: a 30-year experience.

PURPOSE: This study was done to determine the outcome in patients with oropharyngeal carcinoma treated at the University of Florida with radiotherapy alone to the primary site, for comparison with reported results of other types of treatment. METHODS AND MATERIALS: Of a consecutive cohort of 785 patients with biopsy-proven, previously untreated, invasive squamous cell carcinoma of the oropharynx, this report is based on the 490 patients who had continuous-course irradiation with curative intent at the University of Florida between October 1964 and January 1991. All patients had a minimum 2-year follow-up. Forty-eight percent had Stage T3 or T4 disease, and 64% had clinically apparent neck node metastases. The median radiation dose was 68 Gy for once-a-day treatment and 76.8 Gy for twice-a-day treatment. Patients with advanced neck node disease had planned neck dissection(s) after radiotherapy. RESULTS: The overall local control rate after radiotherapy alone was 73%. The ultimate local control rate (including surgical salvage) was 78%. At 5 years, the probability of control of neck disease was 85%; control above the clavicles, 67%; absolute survival, 44%; cause-specific survival, 77%; distant metastasis (as the first or only site of failure), 11%. Thirteen patients (2.6%) experienced severe treatment complications. CONCLUSION: Radiotherapy results in tumor control and survival rates comparable with rates achieved with combined irradiation and surgery, with less morbidity.

Carcinoma, Squamous Cell↗
PubMed1996

The tyrosine kinase receptors Ron and Sea control "scattering" and morphogenesis of liver progenitor cells in vitro.

The mammalian RON and the avian sea genes encode tyrosine kinase receptors of poorly characterized biological functions. We recently identified macrophage-stimulating protein as the ligand for Ron; no ligand has yet been found for Sea. In this work we investigated the biological response to macrophage-stimulating protein in mouse liver progenitor cells expressing Ron. These cells were also transfected with a chimeric cDNA encoding the cytoplasmic domain of Sea, fused to the extracellular domain of Trk (nerve growth factor receptor). In the presence of nanomolar concentrations of the respective ligands, both receptors induced cell "scattering", extracellular matrix invasion, and DNA synthesis. When liver progenitor cells were grown in a tri-dimensional type-I collagen matrix, ligand-induced stimulation of either Ron or Sea induced sprouting of branched cell cords, evolving into ductular-like tubules. The motogenic, mitogenic, and morphogenic responses were also elicited by triggering the structurally related hepatocyte growth factor receptor (Met) but not epidermal growth factor or platelet-derived growth factor receptors. These data show that Ron, Sea, and Met belong to a receptor subfamily that elicits a distinctive biological response in epithelial cells.

Amino Acid Sequence↗
PubMed1996

An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase.

The integrin family of cell surface receptors mediates cell adhesion to components of the extracellular matrix (ECM). Integrin engagement with the ECM initiates signaling cascades that regulate the organization of the actin-cytoskeleton and changes in gene expression. The Rho subfamily of Ras-related low-molecular-weight GTP-binding proteins and several protein tyrosine kinases have been implicated in mediating various aspects of integrin-dependent alterations in cell homeostasis. Focal adhesion kinase (FAK or pp125FAK) is one of the tyrosine kinases predicted to be a critical component of integrin signaling. To elucidate the mechanisms by which FAK participates in integrin-mediated signaling, we have used expression cloning to identify cDNAs that encode potential FAK-binding proteins. We report here the identification of a cDNA that encodes a new member of the GTPase-activating protein (GAP) family of GTPase regulators. This GAP, termed Graf (for GTPase regulator associated with FAK), binds to the C-terminal domain of FAK in an SH3 domain-dependent manner and preferentially stimulates the GTPase activity of the GTP-binding proteins RhoA and Cdc42. Subcellular localization studies using Graf-transfected chicken embryo cells indicates that Graf colocalizes with actin stress fibers, cortical actin structures, and focal adhesions. Graf mRNA is expressed in a variety of avian tissues and is particularly abundant in embryonic brain and liver. Graf represents the first example of a regulator of the Rho family of small GTP-binding proteins that exhibits binding to a protein tyrosine kinase. We suggest that Graf may function to mediate cross talk between the tyrosine kinases such as FAK and the Rho family GTPase that control steps in integrin-initiated signaling events.

Amino Acid Sequence↗
PubMed1996

Occult primary tumors of the head and neck: detection with 2-[F-18] fluoro-2-deoxy-D-glucose SPECT.

PURPOSE: To evaluate 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) single photon emission computed tomography (SPECT) in the detection of clinically occult primary tumors of the upper aerodigestive tract. MATERIALS AND METHODS: Eighteen patients with histologically proved cervical nodal metastasis from squamous cell carcinoma (SCC) underwent FDG SPECT; 17 also underwent computed tomography (CT) and one underwent magnetic resonance (MR) imaging. All 18 patients underwent direct panendoscopy and biopsy. Biopsy and imaging results were correlated. RESULTS: Among 11 histologically proved primary tumors, FDG SPECT depicted nine tumors; CT depicted four lesions. Five patients had abnormal FDG uptake with negative biopsy results. Among five patients with normal SPECT findings, biopsy results were positive in two and negative in three. FDG SPECT at the initial reading had sensitivity of 81%, specificity of 38%, positive predictive value of 64%, and negative predictive value of 60% for detection of occult primary tumors. CONCLUSION: FDG SPECT guidance of endoscopic biopsies in patients with occult primary SCCs of the head and neck has the potential to yield a higher rate of positive biopsy results than that traditionally expected from "blind" endoscopic procedures with "random" or "speculative" biopsy. FDG SPECT and CT are likely to remain complementary studies for the detection of occult primary tumors of the head and neck.

Biopsy↗
PubMed1996

Degradation of aflatoxin by poultry litter.

Two trials were conducted to determine whether deep stacking of contaminated corn with poultry litter destroys aflatoxin. Contaminated corn was ground and mixed with litter to carbon:nitrogen ratios of 30:1. Moistures were adjusted by adding tap water just prior to incubation or stacking. The initial laboratory trial included only broiler litter at 40% moisture, whereas the subsequent field trial involved a 2 x 2 factorial design with litter type (turkey or broiler) and moisture (20 or 40%) as main effects. Aflatoxin assays were reduced in the laboratory trial from 433 and 402 to 54 and 8 ppb in Containers 1 and 2, respectively, after 35 d of incubation at 28 C. In the field trial, aflatoxin disappeared from broiler and turkey litter mixtures with projected moistures of 20% after 10 and 6 wk of storage, respectively, whereas disappearance in mixtures containing projected moistures of 40% required 5 and 3 wk, respectively. Differences in moisture appear to account for differences in the ability of turkey and broiler litter to detoxify aflatoxin. Hence, turkey and broiler litter would appear equal with respect to the ability to detoxify aflatoxin-contaminated corn. Disappearance of aflatoxin during storage with litter could have occurred as a result of ammonia release during storage or microbial detoxification mechanisms. However, nitrogen values suggest that microbial action was responsible for much of the detoxification, as aflatoxin disappeared from mixtures with little apparent ammonia release.

Aflatoxins↗