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Axel Le Cesne

Publications and source records attributed to Axel Le Cesne.

24 records · Page 2Linked to original sources
PubMed2004

Clinicopathologic, phenotypic, and genotypic characteristics of gastrointestinal mesenchymal tumors.

BACKGROUND & AIMS: Variability in the frequency of KIT mutations in gastrointestinal mesenchymal tumors has been reported in the literature, and their prognostic value remains uncertain. This retrospective multicenter study included 276 patients with gastrointestinal mesenchymal tumors. METHODS: We detected c-kit and CD34 protein expression by immunohistochemistry. Mutations in exons 11 and 9 of KIT and exons 12 and 18 of PDGFR were detected by length analysis of polymerase chain reaction products and direct DNA sequencing. RESULTS: Eighty-seven percent of the tumors analyzed were c-kit positive, with gastric tumors expressing CD34 more frequently than other tumors (86% vs. 52%; P < 0.001). KIT exon 11 mutations were detected in 90 of 179 (50.3%) of c-kit-positive and 12% of c-kit-negative tumors. These mutations showed variation in their length and location. Mutations were heterozygous in 94% of cases. Mutations were more frequent in CD34( +) tumors than in CD34( -) tumors ( P < 0.01), and 9% of tumors had a second mutation in exon 11. Mutations in exon 9 of KIT were present in 5.1% of the gastrointestinal stromal tumors, and mutations of the PDGFR were present in 11% of the KIT -nonmutated tumors. Patient's age, the primary location, size, necrosis, and mitotic counts of tumors were associated with metastases in c-kit-positive tumors. However, mitotic activity was the only independent factor identified in multivariate analysis ( P < 0.001). KIT mutations were slightly more frequent in metastatic than in nonmetastatic tumors (61% vs. 46%; P = 0.06). Deletions of codons 562-579 were more strongly associated with metastases than were deletions of codons 550-561 ( P = 0.0001). CONCLUSIONS: Mutations in KIT or PDGFR were detected in 58.4% of the c-kit-positive and also in some c-kit-negative tumors.

Adolescent↗
PubMed2004

Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects.

Mutant isoforms of the KIT or PDGF receptors expressed by gastrointestinal stromal tumors (GISTs) are considered the therapeutic targets for STI571 (imatinib mesylate; Gleevec), a specific inhibitor of these tyrosine kinase receptors. Case reports of clinical efficacy of Gleevec in GISTs lacking the typical receptor mutations prompted a search for an alternate mode of action. Here we show that Gleevec can act on host DCs to promote NK cell activation. DC-mediated NK cell activation was triggered in vitro and in vivo by treatment of DCs with Gleevec as well as by a loss-of-function mutation of KIT. Therefore, tumors that are refractory to the antiproliferative effects of Gleevec in vitro responded to Gleevec in vivo in an NK cell-dependent manner. Longitudinal studies of Gleevec-treated GIST patients revealed a therapy-induced increase in IFN-gamma production by NK cells, correlating with an enhanced antitumor response. These data point to a novel mode of antitumor action for Gleevec.

Animals↗
PubMed2004

[Docetaxel and non-small cell lung cancer].

Docetaxel (Taxotere) is a taxoid used in various tumoral diseases. Its role in metastatic or locally advanced non small cell lung cancer treatment is undeniable. In pretreated patients with metastatic NSCLC, two recent phase III trials have shown an improvement of survival and quality of life for patients receiving docetaxel. In front line treatment, docetaxel administered alone every three weeks or in combination with a platine compound has became a gold standard treatment. Activity of the associations cisplatinium/docetaxel and carboplatin/docetaxel is similar to those reported with previous combinations containing a platine derivative. The weekly schedule of docetaxel and its combination with other well known active drugs in NSCLC such as gemcitabin or vinorelbin deserve further evaluations. Therapeutic options with docetaxel in adjuvant situation in resected NSCLC or in combination with radiation therapy in operable locally advanced NSCLC should be developed in the next future.

Antineoplastic Agents, Phytogenic↗
PubMed2004

[Management of recurrent soft tissue sarcoma of the retroperitoneum].

Local recurrence is the determinant of tumor-related mortality in retroperitoneal sarcomas because death often occurs as a result of local progression mostly without synchronous metastasis. Complete resection of the lesion and surgical margins status are the only therapeutic factors significantly associated with local control. Further outcome improvements need multimodal therapy since prognosis of these recurrences is poor with lower rates of complete resection and higher grade of malignancy than primary. Complete resection of the recurrence often requires removal of adjacent organs to achieve negative margins. External beam radiotherapy (EBRT), eventually associated with a boost of intra-operative electron beam radiotherapy (IORT) could improve the outcome in these patients. Preoperative timing could limit its toxicity. Chemotherapy protocols may enhance local and systemic outcome and can reduce the volume of high grade tumors and therefore allow a higher rate of complete resection. Isolated pelvic perfusion with local high doses chemotherapy is under investigation. Surgical excision of lung metastases should remain the treatment of choice, if preoperative evaluation indicates that complete clearance of the metastases is possible. Intra-operative chemotherapy after cyto-reductive surgery for the treatment of sarcomatosis is disappointing and complete surgery remains the cornerstone of the treatment with best results for low grade sarcomatosis. Adequate management at the time of primary presentation is likely to afford the best chance for long-term survival.

Chemotherapy, Adjuvant↗
PubMed2003

[Gastro-intestinal stromal tumors: news and comments].

Gastrointestinal stromal tumors (GIST) are rare tumors occuring at all levels of the gastrointestinal tract, whose estimated incidence may be close to 2 new cases per 100 000 persons per year. GIST derive from the interstital cells of Cajal (ICC) responsible for the motility of the GI tract, or from a common precursor of ICC and of the smooth muscle cells of the digestive tract. GIST cells express the c-kit protoconcogene under an activated form, either mutated or constitutively activated, as well as the CD34 Ag. Mutations of the KIT gene is an early event in the process of transformation in these tumors. Until recently, GIST were not recognized as a distinct entity among soft tissue sarcoma. It is now clear that conventional chemotherapy is generally inactive in this tumor, surgery being the only efficient therapeutic modality even in patients with advanced disease. Rapidly accruing phase I, II and III trials in the USA and Europe (EORTC) have demonstrated since 2000 that imatinib mesylate (STI571) is an active agent in GIST with an initial response rate of 70 % and 10 % only of primary refractory tumors, yelding an improved overall survival as compared to historical series. Resistance are now being observed however. GIST has become the first model of a solid tumor treated efficiently by a treatment targetting the initial genetic alteration of the disease. Numerous question regarding the integration of this treatment with surgery and the long term outcome of these patients still remain to be answered however.

Age Factors↗