Metastatic undifferentiated nasopharyngeal carcinoma (UCNT) can present as isolated cervical lymphadenopathy.
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Adenocarcinoma↗
Biomedical subjects
J F Côté
Publications and source records attributed to J F Côté.
Efficacy of intraperitoneal chemohyperthermia with oxaliplatin in colorectal peritoneal carcinomatosis. Preliminary results in 24 patients.
BACKGROUND: The complete resection of macroscopic colorectal peritoneal carcinomatosis (PC), followed by intraoperative intraperitoneal chemohyperthermia (IPCH) to treat residual microscopic disease, leads to cure in some patients. We report preliminary results on survival in a phase II study using oxaliplatin (LOHP). PATIENTS AND METHODS: Twenty-four patients with macroscopic colorectal PC underwent complete resection of the PC followed by IPCH with LOHP performed in an open abdominal cavity. The dose of LOHP was 460 mg/m(2) in 2 l/m(2), during 30 min at 43 degrees C, at a flow rate of 2 l/min. During the hour preceding IPCH, they received an intravenous administration of 5-fluorouracil (400 mg/m(2)) and leucovorin (20 mg/m(2)). RESULTS: Mean peritoneal tumoral extension (Sugarbaker's Index) was 16.9 +/- 9.5, median operative duration was 490 min and median blood loss was 965 ml. There were two postoperative deaths (8%) by intracerebral hemorrhage, and morbidity rate was 41.6%. Minimal follow-up was 18 months and median follow-up was 27.4 months (range 18.3-49.6). At 1, 2 and 3 years, overall survival rates were 83%, 74% and 65%, and disease-free survival rates were 70%, 50% and 50%, respectively. Only 32% of the 22 postoperative living patients presented a peritoneal recurrence. A peritoneal index >24 influenced survival, with a 17% recurrence rate at 2 years versus 63% when it was <24 (P = 0.005). CONCLUSION: This new modality of treatment, when feasible, gives encouraging preliminary results, with a promising 3-year survival rate of 65%.
Adult↗
Unusual strong CD34 positivity in a thoracic monophasic fibrous synovial sarcoma.
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Antigens, CD34↗
[Adenomatoid hamartoma of the ethmoid sinus: one case report].
INTRODUCTION: Hamartomas are non-malignant malformations or inborn errors of tissue development. In the head and neck region, especially in the nasal cavity and the ethmoid sinuses, they are relatively rare. PATIENTS AND METHODS: A case of respiratory epithelial adenomatoid hamartoma of the ethmoid sinus and a review of literature are reported in order to describe the diagnostic and therapeutic management of this tumour. RESULTS: A 74-year-old man complaining for unilateral nasal obstruction for years was referred to our institution. Clinical and radiological studies revealed a large intra-nasal tumour, osteolytic in nature, arising from the right ethmoidal sinus. Fifteen months after a complete excision of the tumour using an endoscopic procedure, the nasal cavity was free of tumour. DISCUSSION AND CONCLUSION: Very rare and classified as non-malignant tumours, hamartomas are composed of excessive proliferation of one or more cellular components specific to a given tissue. They can grow out of any part of the body for example the surface epithelium, seromucous glands and vessels. Hamartomas commonly originate from the lung, kidney and intestine. Their localisation in the nasal cavity, especially in the ethmoid sinus, is unusual, but it is really important to be known to distinguish hamartomas from papillomas and adenocarcinomas not to perform useless and destructive surgery.
Adenomatoid Tumor↗
[Is sentinel lymph node mapping relevant for colon cancer?: a feasibility study].
BACKGROUND: Sentinel lymph node (sln) technique using blue injection is controversial for colon cancer. The aim of this study was to evaluate the feasibility and interest of sentinel node detection to identify the ultrastaging rate detecting occult nodal micrometastases missed on routine H&E examination. METHODS: During surgery blue dye was injected subserously around the tumor in 30 patients operated for a colon cancer. The first lymph nodes to turn blue were noted as sln. For each sln three examination levels were performed; if no tumor was detected by H&E examination, a cytokeratine immunohistochemistry study was performed. RESULTS: For each case, one or more sln were found (100%). The median number of lymph nodes examined and of sln found was, respectively, 23 (range 10-55) and 2 (1-4). There were 21 pN0 tumors, among which we found two cases (9%) with a micrometastasis and one case of isolated tumor cells detected, resulting in a 14% (3/21) ultrastaging for pTxN0. The sln was positive in five patients out of nine with a N+ disease. CONCLUSIONS: Sln detection was a successful technique when there was no evident lymph node involvement, no primary large lesion or no associated liver metastasis. Focused examination of the sln identified 10-20% of additional ultrastaging disease for staged pT1, 2, 3N0M0 tumor. This may have an important implication for follow-up and adjuvant treatment in future protocols.
Adult↗
Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl dephosphorylation.
A search for c-Abl interacting proteins resulted in the recovery of PSTPIP1, originally identified as a binding protein of the PEST-type protein tyrosine phosphatases (PTP). PSTPIP1 was phosphorylated by c-Abl, and growth factor-induced PSTPIP1 phosphorylation was diminished in Abl null fibroblasts. PSTPIP1 was able to bridge c-Abl to the PEST-type PTPs. Several experiments suggest that the PEST-type PTPs negatively regulate c-Abl activity: c-Abl was hyperphosphorylated in PTP-PEST-deficient cells; disruption of the c-Abl-PSTPIP1-PEST-type PTP ternary complex by overexpression of PSTPIP1 mutants increased c-Abl phosphotyrosine content; and PDGF-induced c-Abl kinase activation was prolonged in PTP-PEST-deficient cells. Dephosphorylation of c-Abl by PEST-type PTP represents a novel mechanism by which c-Abl activity is regulated.
Adaptor Proteins, Signal Transducing↗
Intact LIM 3 and LIM 4 domains of paxillin are required for the association to a novel polyproline region (Pro 2) of protein-tyrosine phosphatase-PEST.
The focal adhesion protein p130(Cas) was identified as a substrate for the protein-tyrosine phosphatase (PTP)-PEST, and the specificity of this interaction is mediated by a dual mechanism involving a Src homology 3 domain-mediated binding and PTP domain recognition. Recently, paxillin was also demonstrated to interact with PTP-PEST (Shen, Y., Schneider, G., Cloutier, J. F., Veillette, A., and Schaller, M. D. (1998) J. Biol. Chem. 273, 6474-6481). In the present study, we show that amino acids 344-397 of PTP-PEST are sufficient for the binding to paxillin. We demonstrate that a proline-rich segment of PTP-PEST (Pro 2), 355PPEPHPVPPILTPSPPSAFP374, is essential for this interaction in vivo. Furthermore, mutation of proline residues within the Pro 2 motif reveal that proline 362 is critical for the binding of paxillin. Conversely, using deletion and point mutants of paxillin, LIM 3 and 4 domains were both found to be necessary for binding of PTP-PEST. Finally, using a "substrate trapping" approach, we demonstrate that, unlike p130(Cas), paxillin is not a substrate for PTP-PEST. In conclusion, we show that a novel proline-rich motif found in PTP-PEST serves as a ligand for the LIM domains of paxillin. Interestingly, the focal adhesion targeting of paxillin is mediated by LIM 3. Thus, we propose that PTP-PEST, by a competition with the ligand of paxillin in the focal adhesion complex, could contribute to the removal of paxillin from the adhesion sites and consequently promote focal adhesion turnover.
Adaptor Proteins, Signal Transducing↗
Hic-5, a paxillin homologue, binds to the protein-tyrosine phosphatase PEST (PTP-PEST) through its LIM 3 domain.
The Hic-5 protein is encoded by a transforming growth factor-beta1- and hydrogen peroxide-inducible gene, hic-5, and has striking similarity to paxillin, especially in their C-terminal LIM domains. Like paxillin, Hic-5 is localized in focal adhesion plaques in association with focal adhesion kinase in cultured fibroblasts. We carried out yeast two-hybrid screening to identify cellular factors that form a complex with Hic-5 using its LIM domains as a bait, and we identified a cytoplasmic tyrosine phosphatase (PTP-PEST) as one of the partners of Hic-5. These two proteins are associated in mammalian cells. From in vitro binding experiments using deletion and point mutations, it was demonstrated that the essential domain in Hic-5 for the binding was LIM 3. As for PTP-PEST, one of the five proline-rich sequences found on PTP-PEST, Pro-2, was identified as the binding site for Hic-5 in in vitro binding assays. Paxillin also binds to the Pro-2 domain of PTP-PEST. In conclusion, Hic-5 may participate in the regulation of signaling cascade through its interaction with distinct tyrosine kinases and phosphatases.
Animals↗
Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts.
In this article, we show that, in transfected COS-1 cells, protein tyrosine phosphatase (PTP)-PEST translocates to the membrane periphery following stimulation by the extracellular matrix protein fibronectin. When plated on fibronectin, PTP-PEST (-/-) fibroblasts display a strong defect in motility. 3 h after plating on fibronectin, the number and size of vinculin containing focal adhesions were greatly increased in the homozygous PTP-PEST mutant cells as compared with heterozygous cells. This phenomenon appears to be due in part to a constitutive increase in tyrosine phosphorylation of p130(CAS), a known PTP-PEST substrate, paxillin, which associates with PTP-PEST in vitro, and focal adhesion kinase (FAK). Another effect of this constitutive hyperphosphorylation, consistent with the focal adhesion regulation defect, is that (-/-) cells spread faster than the control cell line when plated on fibronectin. In the PTP-PEST (-/-) cells, an increase in affinity for the SH2 domains of Src and Crk towards p130(CAS) was also observed. In (-/-) cells, we found a significant increase in the level of tyrosine phosphorylation of PSTPIP, a cleavage furrow-associated protein that interacts physically with all PEST family members. An effect of PSTPIP hyperphosphorylation appears to be that some cells remain attached at the site of the cleavage furrow for an extended period of time. In conclusion, our data suggest PTP-PEST plays a dual role in cell cytoskeleton organization, by promoting the turnover of focal adhesions required for cell migration, and by directly or indirectly regulating the proline, serine, threonine phosphatase interacting protein (PSTPIP) tyrosine phosphorylation level which may be involved in regulating cleavage furrow formation or disassembly during normal cell division.
Animals↗
Roles of protein tyrosine phosphatases in cell migration and adhesion.
Signal transduction pathways are often seen as cascades of kinases, whereas phosphatases are relinquished to the housekeeping function of resetting the individual elements to a resting state. However, critical biological processes such as cellular migration require a coordinated and constant remodeling of the actin cytoskeleton as well as a rapid turnover of the cell-substratum linkages that necessitate the concomitant action of antagonistic enzymes. Tyrosine phosphorylation was long known to be involved in adhesion and de-adhesion mediated via the integrin receptors. As the roles of tyrosine kinases such as focal adhesion kinase, c-Src, and Csk in this pathway are being extensively studied, increasing evidence is emerging about the importance of protein tyrosine phosphatases (PTP). In this review we discuss examples of PTPs that were recently shown to play a role in cell adhesion and migration and their mechanism of action.
Animals↗
Combination of gene targeting and substrate trapping to identify substrates of protein tyrosine phosphatases using PTP-PEST as a model.
Identification of physiological substrates of protein tyrosine phosphatases is a key step in understanding the function of these enzymes. We have generated fibroblast cell lines having a gene-targeted PTP-PEST in order to identify potential substrates with the premise that specific substrates of this enzyme would exist in a hyperphosphorylated state. Analysis of the profile of the phosphotyrosine proteins in the PTP-PEST -/- cells revealed the presence of hyperphosphorylated proteins of 180, 130, and 97 kDa when compared to control cells. The p130 was identified as p130(Cas), and direct immunoprecipitates of p130(Cas) demonstrate that this protein is constitutively hyperphosphorylated in cells lacking PTP-PEST. In addition, p130(Cas) was also isolated by the substrate-trapping mutant of PTP-PEST in the PTP-PEST -/- cell lysates. Interestingly, we have demonstrated for the first time that PTP-PEST, through its first proline-rich sequence 332PPKPPR337, interacts with other members of the p130(Cas) family (Hef1 and Sin) via their SH3 domain in vitro. This result suggests that Hef1 and Sin could also be potential substrates of PTP-PEST. In conclusion, we have combined genetic and biochemical strategies to allow the identification of PTP-PEST substrates. This experimental approach could potentially be used to identify substrates of other PTPases. Furthermore, the Cas-like molecules Hef1 and Sin associate via their SH3 domains with a proline-rich motif found on PTP-PEST, suggesting the possibility that PTP-PEST could be a general modulator of the Cas family of proteins.
Adaptor Proteins, Signal Transducing↗
Stereotactic fine-needle aspiration cytology of nonpalpable breast lesions: Institut Curie's experience of 243 histologically correlated cases.
BACKGROUND: The early diagnosis of nonpalpable breast lesions is a medical challenge because of the low specificity of different radiologic modalities. Fine-needle aspiration cytology (FNAC) assisted by a stereotactic guidance is an adjunctive diagnostic approach in the management of these lesions. The primary purpose of this article was to assess the diagnostic accuracy of FNAC in patients with nonpalpable breast lesions. METHODS: Three hundred and seventy-one lesions from 357 patients (all female) underwent FNAC using the stereotactically guided technique. Of these cases, 243 lesions from 238 patients subsequently were acquired by surgical excisional biopsies and formed the basis of this study. Statistical analyses of the cytologic and the histologic diagnoses of these cases were performed. RESULTS: Histologically, 107 lesions (44%) were benign and 136 lesions (56%) were malignant. Of the 136 malignant lesions, cytology was concordant in 73 lesions (53.7%), suspicious in 15 lesions (11.0%), false-negative in 12 lesions (8.8%) (benign), and unsatisfactory in 36 lesions (26.5%). Among the 107 benign lesions, cytology was concordant with histology in 75 lesions (70.1%), whereas 4 lesions (3.7%) and 28 lesions (26.2%) were cytologically suspicious and unsatisfactory, respectively. No false-positive cytologies were found in the current series. CONCLUSIONS: The current prospective study indicates that mammography combined with FNAC provides an accurate and practical diagnostic approach for the majority of nonpalpable lesions. Patients with unsatisfactory and false-negative lesions should undergo excisional biopsy.
Adult↗
Ultrasound-guided fine-needle aspiration cytology of nonpalpable breast lesions: Institut Curie's experience with 198 histologically correlated cases.
BACKGROUND: The value of ultrasound-guided fine-needle aspiration cytology (FNAC) in the diagnosis of nonpalpable breast lesions remains a subject of debate. To determine the accuracy of this procedure in these lesions, a comparative analysis with open surgical biopsy in 188 patients was performed. METHODS: Six hundred and fifty-four nonpalpable breast lesions detected by ultrasound in 585 patients were subjected to FNAC. Of these, 198 lesions (30.3%) from 188 patients were surgically excised. RESULTS: Histologically, 105 lesions (53%) were malignant and 93 (47%) were benign. Among carcinomas, 65 cases (61.9%) were concordant, whereas 21 cases (20%) were suspicious, 12 cases (11.4%) were false-negative (benign), and 7 cases (6.7%) were unsatisfactory for diagnosis. Among benign lesions, 80 cases (86%) were concordant, whereas 5 cases (5.4%) were suspicious, and 8 cases (8.6%) were unsatisfactory. No false-positive diagnoses were made. The sensitivity of the FNAC method was 87.8%, the specificity was 94.5%, and the positive predictive value was 94.6%. CONCLUSIONS: These results indicate that, with the exception of random microcalcified lesions, ultrasound-guided FNAC is a valuable and reliable technique in the diagnosis of nonpalpable breast lesions.
Adult↗
Collagenous gastritis revealed by severe anemia in a child.
Collagenous gastritis is a rare histopathological disorder of unknown origin, characterized by a subepithelial collagen deposit greater than 10 microm thick, associated with an inflammatory infiltrate of the gastric mucosa. This report describes a second pediatric case of collagenous gastritis, revealed by severe anemia caused by gastric bleeding, as was the first case. Unlike the adult cases of collagenous gastritis, lesions were limited to the stomach, and remained unchanged on six series of biopsies taken during a 30 month follow-up, despite treatment with omeprazole, sucralfate and corticosteroids. An immunohistochemical study showed signs of local immune activation on all biopsy specimens, including overexpression of HLA-DR by epithelial cells, increased numbers of CD3+ intraepithelial lymphocytes, and CD25+ cells in the lamina propria. Although the cause of the disease remains unclear, our findings suggest that the histopathological lesions of collagenous gastritis may result from a local immune process.
Anemia↗
Nitric oxide synthase in cat brain: cofactors--enzyme-substrate interaction.
Nitric oxide, derived from L-arginine by the enzyme nitric oxide synthase, is an activator of the soluble guanylate cyclase and a cellular messenger. This work demonstrates that, in cat brain, the neuronal constitutive nitric oxide synthase activity is a) NADPH/calcium dependent, b) independent upon exogenous calmodulin in crude brain supernatant, c) significantly enhanced by exogenous FAD and tetrahydrobiopterin (Vmax: 118 instead of 59.4 pmol of citrulline formed .mg of prot.-1 min-1, d) inhibited by calcium chelators and calmodulin antagonist, and e) present in several neuroanatomical structures. Moreover, the Km value for L-arginine was of 11 microM instead of 41 microM in the presence of FAD and tetrahydrobiopterin in the incubation mixture, thus demonstrating that these cofactors are able to stabilize the enzyme-substrate interactions.
Animals↗