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Biomedical subjects

J P Olivier

Publications and source records attributed to J P Olivier.

At least 19 recordsLinked to original sources
PubMed2005

[Left auricle myxoma, a rare cause of myocardial infarction].

INTRODUCTION: The association of left auricle myxoma and myocardial infarction is exceptional. Nevertheless, a causal relationship exists between the 2 affections. OBSERVATION: A 54 year-old woman was hospitalised in a rush for myocardial infarction. Sonography revealed a voluminous tumoral formation in the left auricle. The diagnosis of myxoma was confirmed by the anatomopathological examination. DISCUSSION: Although systemic embolism represents the most frequent causal link between left auricle myxoma and myocardial infarction, hypercoagulability is another possible cause. This can be explained by the secretion of interleukins 6 and 8 by the myxoma.

Female↗
PubMed1996

5-Fluorouracil versus 5-fluorouracil plus alpha-interferon as treatment of metastatic colorectal carcinoma. A randomized study.

BACKGROUND: In 1989, S. Wadler reported very promising results (76% response rate) with a combination of 5-fluorouracil (5-FU) plus alpha-2a interferon (IFN) in the treatment of metastatic colorectal carcinoma (MCRC). In vitro, there are several potential explanations for synergism between the two agents. We therefore decided in 1989 to start a randomized study comparing 5-FU alone with 5-FU plus IFN. PATIENTS AND METHODS: 105 non-pretreated patients with measurable metastatic colorectal carcinoma entered into this study. The patients were randomly allocated either in arm A (n = 49) with 5-FU: 750 mg/m2 i.v. CI d1-d5 followed by 750 mg/m2 i.v. bolus once a week, or in arm B (n = 56) with 5-FU as in arm A plus IFN 9 x 10(6) IU sub-cutaneously three times a week. RESULTS: After two months of treatment we observed 1 CR and 2 PR in arm A (response rate 6.1%), 3 CR and 8 PR in arm B (response rate 19.6%), i.e., a significant difference (P = 0.05). Event-free survival was significantly higher in arm B (6 months) than in arm A (2 months) (P < 0.01), while median survival was slightly higher in arm B (12 months) than in arm A (10 months) (P < 0.05). For overall survival the difference was not significant after adjustment on center treatment and baseline Karnofsky status (P = 0.13). Toxicity was also greater in arm B. Sixteen percent of patients in arm A and 36% in arm B experienced certain grade 3-4 side effects (P < 0.05). CONCLUSION: 5-FU plus IFN is more effective than 5-FU alone in terms of response rate, event free survival but not of overall survival. 5-FU plus IFN is more toxic. As IFN has no demonstrated efficacy in MCRC as a single agent, this study suggests that IFN is acting as a 5-FU modulatory agent. The response rate observed (19.6%) is similar to the results obtained elsewhere with 5-FU plus leucovorin.

Adult↗
PubMed1996

[Neuroendocrine primary cutaneous carcinoma. Therapeutic aspects in 13 patients].

INTRODUCTION: Since the description by Toker in 1972, neuroendocrine carcinoma or Merkel cell carcinoma, is a well identified clinical entity although the appropriate treatment is still debated. Wide surgical exeresis is indicated as first line treatment in all cases but the question concerning protocols for adjuvant radiotherapy or chemotherapy remains open. We analyzed retrospectively our series of 13 patients with neuroendocrine carcinoma looking for an association between radiotherapy and surgery. PATIENTS: There were 7 women and 6 men in our study population (age range 43-88 years). Two cancers of the rectum and one prostate cancer were associated. In 6 cases, the tumor was localized on the limbs, in 5 on the face and in 2 on the buttocks. Mean delay to diagnosis was 2.5 months. At diagnosis, only 1 patient had satellite nodes. The pathology examination evidenced intermediary cell type and architecture. Immunohistochemistry tests were positive for NSE, NF, KII and the ultrastructure confirmed the diagnosis. Nine patients were treated with surgical exeresis with wide 1 cm margins and was completed with radiotherapy of the tumoral bed at homogeneous doses of 45 to 60 Gy. Surgery alone was used in 4 patients. RESULTS: Mean follow-up was 27 months (5-98). Among the 13 operated patients, 11 have survived, 1 died due to the neoplasia and in 1 other from another cause. Local and regional recurrence rate after exercise alone was 50 p. 100 (2/4) with concomitant development of metastasis in both cases. When local or locoregional post-operative radiotherapy was given, local or regional recurrence rate was 33 p. 100 (2/6). DISCUSSION: Cutaneous neuroendocrine carcinoma or Merkel cell carcinoma is an uncommon skin tumor. It is difficult to determine the management protocol on the basis of data in the literature. Due to risk of locoregional recurrence, we currently propose post-operative radiotherapy of the tumor bed and drainage nodes in all patients.

Adult↗
PubMed1995

Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila.

The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of Drosophila. It provides a link between the activated Sev receptor and Sos, a guanine nucleotide release factor that activates Ras1. We have used a combined biochemical and genetic approach to study the interactions between Sev, Drk and Sos. We show that Tyr2546 in the cytoplasmic tail of Sev is required for Drk binding, probably because it provides a recognition site for the Drk SH2 domain. Interestingly, a mutation at this site does not completely block Sev function in vivo. This may suggest that Sev can signal in a Drk-independent, parallel pathway or that Drk can also bind to an intermediate docking protein. Analysis of the Drk-Sos interaction has identified a high affinity binding site for Drk SH3 domains in the Sos tail. We show that the N-terminal Drk SH3 domain is primarily responsible for binding to the tail of Sos in vitro, and for signalling to Ras in vivo.

Amino Acid Sequence↗
PubMed1995

A conserved amino-terminal Shc domain binds to phosphotyrosine motifs in activated receptors and phosphopeptides.

BACKGROUND: Signal transduction by growth factor receptor protein-tyrosine kinases is generally initiated by autophosphorylation on tyrosine residues following ligand binding. Phosphotyrosines within activated receptors form binding sites for the Src homology 2 (SH2) domains of cytoplasmic signalling proteins. One such protein, Shc, is tyrosine phosphorylated in response to a large number of growth factors and cytokines. Phosphorylation of Shc on tyrosine residue Y317 allows binding to the SH2 domain of Grb2, and hence stimulation of the Ras pathway. Shc is therefore implicated as an adaptor protein able to couple normal and oncogenic protein-tyrosine kinases to Ras activation. Shc itself contains an SH2 domain at its carboxyl terminus, but the function of the amino-terminal half of the protein is unknown. RESULTS: We have found that the Shc amino-terminal region binds to a number of tyrosine-phosphorylated proteins in v-src-transformed cells. This domain also bound directly to the activated epidermal growth factor (EGF) receptor. A phosphotyrosine (pY)-containing peptide modeled after the Shc-binding site in polyoma middle T antigen (LLSNPTpYSVMRSK) was able to compete efficiently with the activated EGF receptor for binding to the Shc amino terminus. This competition was dependent on phosphorylation of the tyrosine residue within the peptide, and was abrogated by deletion of the leucine residue at position -5. The Shc amino-terminal domain also bound to the autophosphorylated nerve growth factor receptor (Trk), but bound significantly less well to a mutant receptor in which tyrosine Y490 in the receptor's Shc-binding site had been substituted by phenylalanine. CONCLUSION: These data implicate the amino-terminal region of Shc in binding to activated receptors and other tyrosine-phosphorylated proteins. Binding appears to be specific for phosphorylated tyrosine residues within the sequence NPXpY, which is conserved in many Shc-binding sites. The Shc amino-terminal region bears only very limited sequence identify to known SH2 domains, suggesting that it represents a new class of phosphotyrosine-binding modules. Consistent with this view, the amino-terminal Shc domain is highly conserved in a Drosophila Shc homologue. Binding of Shc to activated receptors through its amino terminus could leave the carboxy-terminal SH2 domain free for other interactions. In this way, Shc may function as an adaptor protein to bring two tyrosine-phosphorylated proteins together.

3T3 Cells↗
PubMed1995

A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase.

Antibodies to the human Shc adaptor protein were used to isolate a cDNA encoding a Drosophila Shc protein (dShc) by screening an expression library. The dshc gene, which maps to position 67B-C on the third chromosome, encodes a 45-kDa protein that is widely expressed throughout the Drosophila life cycle. In flies, the dShc protein physically associates with the activated Drosophila epidermal growth factor receptor homolog (DER) and is inducibly phosphorylated on tyrosine by DER. The 45-kDa dShc protein is closely related both in overall organization and in amino acid sequence (46% identity) to the 52-kDa mammalian Shc isoform. In addition to a C-terminal Src homology 2 (SH2) domain, dShc contains an N-terminal phosphotyrosine-binding (PTB) domain, which associates in vitro with the autophosphorylated DER receptor tyrosine kinase and with phosphopeptides containing an Asn-Pro-X-pTyr motif, where pTyr stands for phosphotyrosine. A potential binding site for the dShc PTB domain is located at Tyr-1228 of DER. These results indicate that the shc gene has been conserved in evolution, as have the binding properties of the Shc PTB and SH2 domains. Despite the close relationship between the Drosophila and mammalian Shc proteins, dShc lacks the high-affinity Grb2-binding site found in mammalian Shc, suggesting that Shc proteins may have functions in addition to regulation of the Ras pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Lenograstim prevents morbidity from intensive induction chemotherapy in the treatment of inflammatory breast cancer.

PURPOSE: To compare the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) versus its inert vehicle in patients with unilateral nonmetastatic inflammatory breast cancer treated with fluorouracil, epirubicin, and cyclophosphamide high-dose (FEC-HD) neoadjuvant chemotherapy. PATIENTS AND METHODS: One hundred twenty patients have been enrolled by nine French centers in this double-blind, parallel-group, vehicle-controlled study to compare at each cycle subcutaneous lenograstim (5 micrograms/kg/d) with placebo given from day 6 to day 15 after the induction chemotherapy (day 1 to day 4, fluorouracil 750 mg/m2 continuous intravenous [IV] infusion; day 2 to day 4, epirubicin 35 mg/m2 and cyclophosphamide 400 mg/m2 both IV push). Four cycles were planned every 3 weeks before locoregional treatment. Patients with febrile neutropenia remained blinded for the subsequent cycles. RESULTS: Lenograstim significantly reduced the duration of neutropenia at less than 0.5 x 10(9)/L and less than 1 x 10(9)/L to a median duration of 2 and 3 days, respectively, as compared with 5 and 7 days in the placebo group. This translated into a statistically significant reduced incidence of microbiologically documented infections, and a decreased need for rehospitalizations for infectious events and antibiotic use. Clinical objective tumor response rate observed after four cycles was 89.6% and 93%, respectively, in the placebo and treated groups. Mild transient bone and injection-site pain, myelemia, and hyperleukocytosis were the most frequently reported adverse events associated with lenograstim. CONCLUSION: Lenograstim is safe and effective to reduce morbidity associated with FEC-HD neoadjuvant chemotherapy in inflammatory breast cancer. Response rate is not affected.

Adenocarcinoma↗
PubMed1994

Backbone 1H and 15N resonance assignments of the N-terminal SH3 domain of drk in folded and unfolded states using enhanced-sensitivity pulsed field gradient NMR techniques.

The backbone 1H and 15N resonances of the N-terminal SH3 domain of the Drosophila signaling adapter protein, drk, have been assigned. This domain is in slow exchange on the NMR timescale between folded and predominantly unfolded states. Data were collected on both states simultaneously, on samples of the SH3 in near physiological buffer exhibiting an approximately 1:1 ratio of the two states. NMR methods which exploit the chemical shift dispersion of the 15N resonances of unfolded states and pulsed field gradient water suppression approaches for avoiding saturation and dephasing of amide protons which rapidly exchange with solvent were utilized for the assignment.

Amino Acid Sequence↗
PubMed1994

[Fixed pigmented erythema caused by levamisole administration].

INTRODUCTION: Description of a case of fixed drug eruption induced by levamisole. OBSERVATION: Fixed toxic erythema with pigmentation was observed in a patient taking levamisole as an adjuvant to 5 fluorouracil chemotherapy for cancer of the colon. The imputability of levamisole was highly likely. Epicutaneous skin tests were negative. DISCUSSION: Several types of skin eruptions have been described after intake of levamisole. It was highly likely that levamisole was implicated here and fixed pigmented erythema should be added to the list.

Adenocarcinoma, Mucinous↗
PubMed1994

Immunolocalization of the Nuk receptor tyrosine kinase suggests roles in segmental patterning of the brain and axonogenesis.

Neural kinase (Nuk) encodes a murine receptor-like tyrosine kinase belonging to the Eph/Elk/Eck family. Protein localization studies indicate that during early embryogenesis Nuk is confined to the developing nervous system, where it marks segments along the axis of the neural tube in the hindbrain (rhombomeres r2, r3 and r5) and specific morphological bulges of the midbrain and forebrain. Subcellular localization of Nuk indicates that this receptor is concentrated at sites of cell-cell contact, often involving migrating neuronal cells or their extensions. Most notably, high levels of Nuk protein are found within initial axon outgrowths and associated nerve fibers. The axonal localization of Nuk is transient and is not detected after migrations have ceased, suggesting a role for this tyrosine kinase during the early pathfinding and/or fasciculation stages of axonogenesis. The subcellular localization of Nuk, as well as the presence of fibronectin type III and immunoglobulin-like adhesive domains on the extracellular region, suggest this receptor tyrosine kinase may function to regulate specific cell-cell interactions during early development of the murine nervous system.

Amino Acid Sequence↗
PubMed1993

A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos.

A Drosophila gene (drk) encodes a widely expressed protein with a single SH2 domain and two flanking SH3 domains, which is homologous to the Sem-5 protein of C. elegans and mammalian GRB2. Genetic analysis suggests that drk function is essential for signaling by the sevenless receptor tyrosine kinase. Drk biological activity correlates with binding of its SH2 domain to activated receptor tyrosine kinases and concomitant localization of drk to the plasma membrane. In vitro, drk also binds directly to the C-terminal tail of Sos, a Ras guanine nucleotide-releasing protein (GNRP), which, like Ras1 and drk, is required for sevenless signaling. These results suggest that drk binds autophosphorylated receptor tyrosine kinases with its SH2 domain and the Sos GNRP through its SH3 domains, thereby coupling receptor tyrosine kinases to Ras activation. The conservation of these signaling proteins during evolution indicates that this is a general mechanism for linking tyrosine kinases to Ras.

Amino Acid Sequence↗
PubMed1993

Osteosarcoma with calcified regional lymph nodes.

A case of osteosarcoma of osteoblastic type with inguinal calcified lymphadenopathy is described. The primary lesion of the distal left femur was treated with limb-sparing surgery. Chemotherapy was given before and after the surgical procedure. Metachronous calcified lymph node metastases were seen on plain radiography, computed tomography and bone radionuclide scan. The patient is alive and free of disease more than 40 months after lymphadenectomy and radiotherapy of regional node metastases.

Adolescent↗
PubMed1993

Epirubicin and ifosfamide in advanced soft tissue sarcoma: a phase II study.

Thirty patients with previously untreated and measurable or evaluable advanced soft tissue sarcoma entered this phase II study. Median age was 53 years (range: 24-71 years). Starting dose of Epirubicin was 100 mg/m2 IV bolus on day 1 combined with Ifosfamide, 2.5 g/m2, as a 6-hr IV infusion on day 1 and day 2 with uroprotection with Uromitexan, 1.6 g/m2, on day 1 and day 2. This schedule was repeated every 3 weeks. In case of minimal myelosuppression, the dose of Epirubicin was increased by 10 mg/m2 up to 130 mg/m2. Ifosfamide dosage was not increased. Mean cumulative dose of Epirubicin received was 477 +/- 272 mg/m2 (range: 200-1200 mg/m2). Of 27 evaluable patients (WHO criteria), 13 had a partial response (48%), 4 showed no change (15%), and 10 had progressive disease (37%). Median time to progression was 27 weeks. Of 27 patients evaluable for toxicity, hematological toxicity at day 21 was mild. Nonhematological toxicities consisted of nausea and vomiting in 82% of patients (WHO grade 3-4 = 19%), stomatitis in 44.5% (WHO grade 3 = 7.5%), and alopecia in 96% (WHO grade 2-3 = 89%). Appearance of cardiac dysfunction without heart failure during the treatment led to discontinuation of this chemotherapy in 3 patients. The results of this study show that the combination of Epirubicin and Ifosfamide is effective in advanced soft tissue sarcoma with an acceptable toxicity. However, we cannot conclude from this trial whether combination Epirubicin and Ifosfamide is superior to Epirubicin alone.

Adult↗
PubMed1993

Inflammatory breast cancer. Pilot study of intensive induction chemotherapy (FEC-HD) results in a high histologic response rate.

Between July 1988 and May 1990, we treated 45 women with newly diagnosed, unilateral, nonmetastatic, inflammatory breast cancer with an intensive neoadjuvant chemotherapy regimen (FEC-HD) repeated every 21 days, followed by surgery or radiation therapy. Evaluation of efficacy performed 3 to 4 weeks after at least 2 cycles showed disappearance of inflammatory signs in 91% of the patients and improvement in the remaining 9%. With regard to primary tumor and lymph nodes, there were 13 (28.9%) clinical complete responses, 30 (66.6%) partial responses, and 2 (4.5%) without change. No progressive disease was observed. Hematologic toxicity from this regimen was high with grade 4 neutropenia observed at day 14 in 100% of the patients. Retreatment at day 21 was possible in 83% of the cycles. Grade 1 or 2 infections occurred in 102 cycles out of 176 (57.9%). Grade 3 infections were seen in 9 cycles (5%). No septicemia or septic shock occurred. No toxic death occurred. After induction chemotherapy, locoregional treatment consisted of modified radical mastectomy in 39 patients and radiotherapy alone in 6. The mastectomy specimen showed no residual invasive tumor (primary tumor and lymph nodes) in 10 cases (25.6%). Two patients judged as partial responders were in fact histologic complete responders. The clinical and histological response rates observed appeared very promising. For this reason we are currently testing FEC-HD with or without GCSF in a randomized multicenter trial with correction of neutropenia, disease-free survival, and overall survival as main end points.

Adenocarcinoma↗
PubMed1991

[Totally implantable venous access sites. Results of a series of 101 cases].

The authors report their results of the use of 101 totally implanted venous access systems for chemotherapy in 92 patients. They stress the high incidence (19.8%) of complications: thrombosis 6.8% and 6.9% linked to the material. The correct complication rate must be decreased by strict attention paid to the surgical procedure, use and greater education of the nursing staff. The value of this material is to give greater comfort to patients and to assess its widespread use for intensive long-term chemotherapy.

Adult↗