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J T Parsons

Publications and source records attributed to J T Parsons.

At least 145 records · Page 8Linked to original sources
PubMed1993

The protooncogene c-sea encodes a transmembrane protein-tyrosine kinase related to the Met/hepatocyte growth factor/scatter factor receptor.

c-sea is the cellular homologue of the avian erythroblastosis virus S13-encoded oncogene v-sea. We have isolated and determined the nucleotide sequence of overlapping chicken cDNAs that encode the putative c-sea protooncogene product. The predicted reading frame encoded a 1404-aa polypeptide that had the structure of a receptor-like protein-tyrosine kinase and exhibited the highest degree of sequence similarity with the Met/hepatocyte growth factor/scatter factor receptor. Analysis of steady-state RNA expression revealed that c-sea mRNA levels were elevated approximately 5-fold in chicken embryo cells transformed by activated variants of the src nonreceptor protein-tyrosine kinase gene but not in cells transformed by the nuclear oncogenes v-myc or v-rel. A survey of c-sea expression in a variety of chicken tissues indicated that the highest levels of mRNA were located in peripheral white blood cell populations and in the intestine.

Amino Acid Sequence↗
PubMed1993

Radiotherapy alone for squamous cell carcinoma of the nasal vestibule: management of the primary site and regional lymphatics.

PURPOSE: To examine patterns of failures and complications in invasive squamous cell carcinoma of the nasal vestibule treated with radiotherapy alone. METHODS AND MATERIALS: Thirty-nine patients are reported with two-year minimum follow-up. Twenty-nine patients had tumors that were previously untreated; 10 were recurrent after prior surgical resection. Twelve patients received external beam alone, 18 had external beam followed by a radium implant, and nine had radium implant alone. RESULTS: Local control in patients eligible for analysis was as follows: T1, 11 of 13; T2, 6 of 6; and T4, 12 of 17 (1988 AJCC skin cancer staging classification). Previously untreated tumors and tumors recurrent after surgical excision alone had similar local control, stage for stage. Among T4 tumors, local control with radiotherapy was achieved in 11 of 13 lesions measuring < 4 cm in diameter versus 1 of 4 of those measuring > or = 4 cm. Of 37 patients with clinically negative regional nodes at presentation, 32 were managed with observation alone; of those eligible for 1-year minimum follow-up, 4 (15%) of 27 developed disease in the regional lymphatics. All regional node failures have been salvaged. In general, cosmesis was very good and complications were minimal. CONCLUSION: Radiotherapy in this series proved to be an effective and cosmetically favorable alternative to surgery for nasal vestibule carcinoma. Elective treatment of the regional lymphatics is not warranted in early stage, previously untreated patients, but should be considered for selected advanced and recurrent lesions.

Adult↗
PubMed1993

Bladder preservation and durable complete remission of small cell carcinoma of the bladder with systemic chemotherapy and adjuvant radiation therapy.

BACKGROUND: Small cell (oat cell) carcinoma of the bladder is a rare entity characterized clinically by an aggressive behavior with a high incidence of systemic metastases. Radical cystectomy has been the therapeutic focal point for this disease, but systemic relapse is almost universal. RESULTS: The authors report that combination chemotherapy with cisplatin, methotrexate, and vinblastine, followed by external beam irradiation to the bladder, gave a durable continuous complete remission (more than 4.5 years). In addition, this bladder-sparing approach has preserved normal bladder function and an excellent quality of life. CONCLUSION: This experience shows that radical cystectomy may not be necessary for small cell carcinoma of the bladder and that early intervention with systemic chemotherapy offers greater potential for cure.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

T1-T2 squamous cell carcinoma of the glottic larynx treated with radiotherapy: a multivariate analysis of variables potentially influencing local control.

PURPOSE: To examine various parameters that might influence the probability of local control of T1-T2 glottic carcinoma treated with radiotherapy. METHODS AND MATERIALS: Two hundred forty-seven patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx were treated with radiotherapy between May 1977 and December 1989. All patients had a minimum 2-year follow-up. To minimize treatment-related variables, only patients with T1 lesions treated once daily at 225 cGy per fraction and patients with T2 lesions treated once daily at 225 cGy per fraction or twice daily at 120 cGy per fraction were included. Surgical alternative, thickness of the neck at the posterior edge of the lateral fields, vocal cord mobility, anterior commissure involvement, gender, and T stage were evaluated in a multivariate analysis. RESULTS: The 5-year local control rates, calculated by the product-limit method, were T1a, 95%; T1b, 96%; T2a, 87%; and T2b, 76%. The 5-year local control rate for patients with T2 lesions treated with once-daily fractionation was 81% compared with 91% for those who received twice-a-day radiotherapy. For the endpoint of local control with irradiation, the surgical alternative (p = .020) and cord mobility (p = .001) were of independent prognostic significance. CONCLUSION: Of the variables analyzed, only vocal cord mobility and surgical alternative significantly influenced local control. Specifically, anterior commissure involvement and neck thickness did not affect local control.

Carcinoma, Squamous Cell↗
PubMed1993

Squamous cell carcinoma of the head and neck: management after excisional biopsy of a solitary metastatic neck node.

PURPOSE: The judiciousness of open biopsy of lymph node mestastases in the neck is controversial. A retrospective review of treatment results at the University of Florida in patients who underwent excisional biopsy of a solitary metastatic neck node followed by radiotherapy was undertaken to determine whether the approach resulted in increased rates of regional and distant recurrence or wound complications. METHODS AND MATERIALS: Between October 1964 and September 1987, 41 patients were referred for radiotherapy after excisional biopsy of a solitary cervical node containing metastatic squamous cell carcinoma from a known mucosal site (19 patients) or unknown primary (22 patients) in the head and neck. None had known gross residual neck disease. The neck stage (based on N stage before surgery or size of the excised node) was unknown in seven patients, N1 in 15 patients, N2A in 18 patients, and N3A in one patient. All patients received radiotherapy to the neck and two had a planned neck dissection after radiotherapy. Doses to the nodal bed ranged from 5485 cGy to 8100 cGy (median, 6675 cGy). RESULTS: The probability of control of neck disease was 95% at both 5 and 10 years. Five-year probability of disease control above the clavicles was 90%. Distant metastasis occurred in 0 of 36 patients whose disease was controlled above the clavicles vs. 3 of 5 patients who suffered failure above the clavicles. CONCLUSION: Excisional biopsy of a solitary neck node followed by radiotherapy produced excellent regional control and no apparent increased rate of distant metastasis.

Biopsy↗
PubMed1993

Can pretreatment computed tomography findings predict local control in T3 squamous cell carcinoma of the glottic larynx treated with radiotherapy alone?

PURPOSE: To determine if pretreatment computed tomography findings can predict local control in T3 squamous cell carcinoma of the glottic larynx treated with radiotherapy alone. METHODS AND MATERIALS: Twenty-nine patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated for cure with radiotherapy alone; all had a minimum 2-year follow-up. High-quality pretreatment computed tomography scans were retrospectively reviewed by a single head and neck radiologist for tumor involvement of various anatomic subsites within the larynx, and total tumor volumes were calculated for 18 of the most recent patients using a computer digitizer. A tumor score was calculated and assigned to each primary lesion depending on the extent of laryngeal spread. RESULTS: A significant decrease in the local control rate was observed for cancers involving the face of the arytenoid (11 of 20 [55%] vs. 9 of 9 [100%]; p = .02), or the paraglottic space at the false vocal cord level (7 of 16 [44%] vs. 13 of 13 [100%]; p not equal to < .01). Tumors assigned a high tumor score (6, 7, or 8) had a significantly decreased rate of local control with radiation therapy when compared with tumors assigned a low tumor score (< or = 5): 1 of 7 (14%) vs. 19 of 22 (86%) (p = .01). Total tumor volume also significantly correlated with the rate of tumor control. For tumors measuring 3.5 cm3 or less, local control was achieved in 11 of 12 patients (92%), whereas for tumors greater than 3.5 cm3, local control was achieved in 2 of 6 patients (33%) (p = .02). CONCLUSION: Pretreatment computed tomography scans can contribute significantly to the treatment decision for patients with T3 glottic carcinoma and can define a subset of patients with an excellent chance of being cured with preservation of a functional larynx after treatment with radiotherapy alone.

Adult↗
PubMed1993

Radiation therapy for juvenile angiofibroma: evaluation by CT and MRI, analysis of tumor regression, and selection of patients.

PURPOSE: To provide an analysis of nine patients with juvenile angiofibroma treated with radiotherapy between June 1975 and June 1987. METHODS AND MATERIALS: All patients had a minimum 3 years of follow-up; six of the patients had greater than 5 years and four had greater than 10 years of follow-up. Two patients received radiotherapy as primary therapy, and the remaining seven patients were treated with surgery initially, followed by irradiation for recurrent disease. Characteristic computed tomography (CT), magnetic resonance (MR), and angiography findings were identified. All nine patients had nasal cavity or nasopharyngeal involvement. Eight patients had involvement of the base of the skull, and seven had intracranial extension. Tumor regression during and after treatment was estimated clinically and from available imaging studies. RESULTS: Tumor regression during treatment ranged from 25% to 100%, with most patients experiencing between 30% and 50% clinical decrease in the size of the tumor. Seven patients eventually showed complete regression by physical examination, but only two of seven patients evaluated by CT and/or MR showed complete regression. In five patients, follow-up imaging studies showed stable residual changes. Local control was achieved in all patients. No late complications were found. CONCLUSION: The initial treatment of early lesions is surgical. Low dose irradiation appears to be an effective alternative to extensive surgery in treating advanced juvenile angiofibroma. Morbidity has been minimal. Residual changes are seen in subsequent imaging studies but have remained stable with long follow-up.

Adolescent↗
PubMed1993

Focal adhesion kinase: an integrin-linked protein tyrosine kinase.

Recent evidence has shown that binding of integrins to components of the extracellular matrix serves to initiate cellular signals, resulting in changes in cytoskeletal architecture and activation of intracellular signalling pathways. Here we review the evidence that protein tyrosine kinases, including focal-adhesion-associated kinases, play a central role in the generation of some of these molecular signals.

Journal Article↗
PubMed1993

Cortactin, an 80/85-kilodalton pp60src substrate, is a filamentous actin-binding protein enriched in the cell cortex.

Two related cellular proteins, p80 and p85 (cortactin), become phosphorylated on tyrosine in pp60src-transformed cells and in cells stimulated with certain growth factors. The amino-terminal half of cortactin is comprised of multiple copies of an internal, tandem 37-amino acid repeat. The carboxyl-terminal half contains a distal SH3 domain. We report that cortactin is an F-actin-binding protein. The binding to F-actin is specific and saturable. The amino-terminal repeat region appears to be both necessary and sufficient to mediate actin binding, whereas the SH3 domain had no apparent effect on the actin-binding activity. Cortactin, present in several different cell types, is enriched in cortical structures such as membrane ruffles and lamellipodia. The properties of cortactin indicate that it may be important for microfilament-membrane interactions as well as transducing signals from the cell surface to the cytoskeleton. We suggest the name cortactin, reflecting the cortical subcellular localization and its actin-binding activity.

Actins↗
PubMed1993

Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions.

The integrin family of heterodimeric cell surface receptors play critical roles in multiple biological processes by mediating cellular adhesion to the extracellular matrix (ECM). Adhesion triggers intracellular signaling cascades, including tyrosine phosphorylation and elevation of [Ca2+]i. The Focal Adhesion Kinase (FAK or pp125FAK), a protein tyrosine kinase that colocalizes with integrins in cellular focal adhesions, is a prime candidate for a mediator of integrin signaling events. Here we report an analysis of the domain structure of FAK in which we have identified a contiguous stretch of 159 amino acids within the COOH terminus essential for correct subcellular localization. When placed in the context of an unrelated cytosolic protein, this Focal Adhesion Targeting (FAT) sequence functions to efficiently mediate the focal adhesion localization of this fusion protein. Furthermore, this analysis suggests that pp125FAK cannot be activated oncogenically by mutation. This result could be explained if pp125FK either exhibits a narrow substrate specificity or is diametrically opposed by cellular phosphatases or other cellular processes.

Amino Acid Sequence↗
PubMed1993

Identification and sequence analysis of cDNAs encoding a 110-kilodalton actin filament-associated pp60src substrate.

Transformation of chicken embryo cells by oncogenic forms of pp60src (e.g., pp60v-src or pp60527F) is linked with a concomitant increase in the steady-state levels of tyrosine-phosphorylated cellular proteins. Activated forms of the Src protein-tyrosine kinase stably associate with tyrosine-phosphorylated proteins, including a protein of 110 kDa, pp110. Previous reports have established that stable complex formation between pp110 and pp60src requires the structural integrity of the Src SH2 and SH3 domains, whereas tyrosine phosphorylation of pp110 requires only the structural integrity of the SH3 domain. In normal chicken embryo cells, pp110 colocalizes with actin stress filaments, and in Src-transformed cells, pp110 is found associated with podosomes (rosettes). Here, we report the identification and characterization of cDNAs encoding pp110. The predicted open reading frame encodes a polypeptide of 635 amino acids which exhibits little sequence similarity with other protein sequences present in the available sequence data bases. Thus, pp110 is a distinctive cytoskeleton-associated protein. On the basis of its association with actin stress filaments, we propose the term AFAP-110, for actin filament-associated protein of 110 kDa. In vitro analysis of AFAP-110 binding to bacterium-encoded glutathione S-transferase (GST) fusion proteins revealed that AFAP-110 present in normal cell extracts binds efficiently to Src SH3/SH2-containing fusion proteins, less efficiently to Src SH3-containing proteins, and poorly to SH2-containing fusion proteins. In contrast, AFAP-110 in Src-transformed cell extracts bound to GST-SH3/SH2 and GST-SH2 fusion proteins. Analysis of AFAP-110 cDNA sequences revealed the presence of sequence motifs predicted to bind to SH2 and SH3 domains, respectively. We suggest that AFAP-110 may represent a cellular protein capable of interacting with SH3-containing proteins and, upon tyrosine phosphorylation, binds tightly to SH2-containing proteins, such as pp60src or pp59fyn. The potential roles of AFAP-110 as an SH3/SH2 cytoskeletal binding protein are discussed.

Actins↗
PubMed1993

Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK.

Integrins play a central role in cellular adhesion and anchorage of the cytoskeleton and participate in the generation of intracellular signals, including tyrosine phosphorylation. We have recently isolated a cDNA encoding a unique, focal adhesion-associated protein tyrosine kinase (FAK) that is a component of an integrin-mediated signal transduction pathway. Here we report the isolation of cDNAs encoding the C-terminal, noncatalytic domain of the FAK kinase, termed FRNK (FAK-related nonkinase). Both the FAK- and FRNK-encoded polypeptides, pp125FAK and p41/p43FRNK, are expressed in normal chicken embryo cells. pp125FAK and p41/p43FRNK were localized to focal adhesions, suggesting that pp125FAK is directed to the focal adhesions by sequences within its C-terminal domain. We also show that the fibronectin-dependent increase in tyrosine phosphorylation of pp125FAK is accompanied by a concomitant posttranslational modification of p41FRNK.

Amino Acid Sequence↗
PubMed1993

Tyrosine phosphorylation of the focal adhesion kinase pp125FAK during development: relation to paxillin.

Significant changes in the level of protein tyrosine phosphorylation accompany avian embryonic development. A comparison of different tissues reveals that a similar and remarkably restricted complement of proteins is modified in this manner. In each case the major proteins detected using anti-phosphotyrosine antibodies have molecular masses of approximately 170, 150, 125, 70 and 50 kDa. As a first step in determining the function of this protein modification in embryogenesis we have initiated a study to identify these phosphoproteins. We have previously reported that the 70 kDa band is paxillin, a component of actin-membrane attachment sites associated with regions of cell adhesion (Turner, C. E. (1991) J. Cell Biol. 115, 201-207). We report here that the 125 kDa phosphotyrosine-containing protein is the tyrosine kinase pp125FAK, a protein that co-localizes with paxillin at sites of adhesion (Schaller et al. (1992) Proc. Nat. Acad. Sci. USA 89, 5192-5196). Tyrosine phosphorylation of both pp125FAK and paxillin was detected at low levels as early as embryonic day 3 and increased steadily during the first half of development, reached a maximum between embryonic days eight and twelve, and declined to background levels prior to hatching. Paxillin protein expression also increased during the first half of embryogenesis, suggesting little change in the overall phosphorylation of this protein through embryonic day 8. In contrast, pp125FAK, following an initial increase, is expressed at a constant high level during these early embryonic stages, implying an increase in its overall phosphotyrosine content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Regulation of the cellular src protein tyrosine kinase: interactions of the carboxyl terminal sequences residing between the kinase domain and tyrosine-527.

Negative regulation of the cellular Src tyrosine kinase (pp60c-src) is mediated through the phosphorylation of a C-terminal tyrosine residue, Tyr-527. Current models predict that inhibition of c-Src kinase activity results from an interaction of phosphorylated Tyr-527 with the amino terminal SH2 domain. Tyr-527 is located 11 residues C-terminal from the end of the kinase domain. Insertion or deletion of residues within these 11 residues of pp60c-src activates kinase activity and induces morphological transformation. The resultant variant Src proteins also exhibit a reduced level of phosphorylation of Tyr-527. We have used antibodies to phosphotyrosine, susceptibility to tyrosine phosphatases and binding of mutant Src proteins to peptides mimicking the tyrosine phosphorylated C-terminus of pp60c-src to investigate the tyrosine phosphorylated and unphosphorylated forms of such insertion/deletion variants. The reactivity of variant proteins with phosphotyrosine antibodies and the susceptibility of phosphorylated Tyr-527 to tyrosine phosphatases were similar to that of wild type pp60c-src. In addition, the results of binding experiments performed with a C-terminal peptide containing phosphorylated Tyr-527 indicated that only dephosphorylated forms of variant Src proteins bound phospho-peptide. These data suggest that insertion or deletion mutations within the C-terminal region of pp60c-src do not substantially alter the interaction of phosphorylated Tyr-527 with the SH2 domain. Rather, the data are consistent with the hypothesis that the reduction of phosphorylation of Tyr-527 and the accompanying activation of these variants may be due to the action of a tyrosine phosphatase and the inefficient phosphorylation of Tyr-527 by a regulatory kinase.

Amino Acid Sequence↗