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Biomedical subjects

E Tartour

Publications and source records attributed to E Tartour.

67 records · Page 4Linked to original sources
PubMed1993

[Correlation between the serum level of soluble CD16 and the staging of myeloma: study of 214 serums].

Soluble CD16 (sCD16) are soluble part of Fc receptor for IgG which control in mice, proliferation of hybridoma B cells and IgG production. The levels of sCD16 in 165 myeloma patients and 29 patients with MGUS appear significantly different:25a.u./ml versus 144a.u./ml and values of stage I are significantly higher than those of stages II + III.sCD16 might be a prognosis factor in myeloma.

Antibodies↗
PubMed1993

Identification, in mouse macrophages and in serum, of a soluble receptor for the Fc portion of IgG (Fc gamma R) encoded by an alternatively spliced transcript of the Fc gamma RII gene.

Low affinity Fc gamma R are a heterogeneous group of glycoproteins which exist in transmembrane (TM) as well as in soluble forms. Two membrane isoforms of the murine type II Fc gamma R, Fc gamma RIIb1 and Fc gamma RIIb2, have been described. They result from the translation of alternatively spliced pre-mRNA, Fc gamma RIIb2 lacking sequences of the first intracytoplasmic domain (IC1). Soluble forms of Fc gamma R (sFc gamma R) have previously been shown to result from proteolysis of membrane receptors. We report here the identification, in macrophages, of a mRNA derived from the Fc gamma RII gene by splicing exons encoding the TM and IC1 domains, i.e. corresponding to a TM-deleted Fc gamma RIIb2 mRNA. A soluble protein possibly encoded by this mRNA was identified in macrophage supernatants. In accordance with Fc gamma R nomenclature, we propose to name this new Fc gamma RII isoform Fc gamma RIIb3. It is the most abundant sFc gamma R present in serum, as compared with sFc gamma R resulting from cleavage of membrane Fc gamma R.

Alternative Splicing↗
PubMed1993

Soluble Fc gamma receptors.

Soluble Fc gamma receptors have been identified in biological fluids of mice and humans. They are produced either by alternative splicing of the exon encoding the transmembrane region of the receptor (Fc gamma RII) or by proteolytic cleavage at the cell membrane (Fc gamma RII and Fc gamma RIII). They inhibit B cell proliferation and immunoglobulin production. Their concentrations in plasma seem to be modified during the development of certain diseases, as for instance in multiple myeloma, where plasma concentrations of soluble Fc gamma RIII are correlated with the stage of the disease.

Animals↗
PubMed1992

[Neuroendocrine tumor of the trachea of the intermediate type. Value of its individualization].

Tracheobronchial neuroendocrine tumours can be divided into 4 main groups: typical carcinoid; well-differentiated neuroendocrine carcinoma (atypical carcinoid); neuroendocrine carcinoma of the intermediate type, and small-cell carcinoma. Typical and atypical carcinoids are differentiated tumours, whereas intermediate neuroendocrine tumours and small cell carcinomas are little or not differentiated. Morphological or architectural criteria usually suffice to distinguish between carcinoid tumours and small cell carcinomas. In some cases, however, the neuroendocrine nature of poorly differentiated and non-small cell carcinomas is suggested by morphological criteria, but it can be confirmed only by immunohistochemistry and electron microscopy. Tracheobronchial neuroendocrine tumours of the intermediate type have been studied from a first, well-documented clinical case which demonstrated two important points: the prognosis of these tumours seems to be worse than that of carcinoid tumours, and they favourably respond to chemotherapy. In view of the therapeutic consequences, it is necessary to investigate, by the appropriate techniques, the neuroendocrine nature of these poorly differentiated carcinomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Neuroendocrine tumors].

The original classification of neuroendocrine tumours proposed by Pearse was based on a common embryologic origin in the neuroectoderm. This is being replaced by other classifications based on results of modern techniques: secretory granules shown by electron microscopy, neuroendocrine tumour markers (NSE, chromogranin A, NPY ... ) shown by immunocytochemistry and blood measurements. Most endocrine tumours are single and sporadic, but in some patients they are multiple and/or occur as a familial disease such a multiple endocrine neoplasia or other disease, the transmission of which is autosomal dominant. This permits a more reliable classification of tumors, that can be used to determine their prognosis and response to therapy.

Biomarkers, Tumor↗
PubMed1992

Murine soluble Fc gamma receptors/IgG-binding factors (IgG-BF): analysis of the relation to Fc gamma RII and production of milligram quantities of biologically active recombinant IgG-BF.

The production of soluble forms of low-affinity Fc gamma R by cells expressing recombinant or natural membrane Fc gamma RII, and the structural relationships between these soluble receptors and membrane Fc gamma RII are described. We show that 37-40 kD soluble Fc gamma RII, corresponding to the two N-terminal domains of Fc gamma RII and binding to IgG, are spontaneously produced in vitro by cleavage of membrane Fc gamma RII. Moreover, we describe methods to produce and purify to homogeneity large quantities of endotoxin-free recombinant IgG-binding factor (rIgG-BF) from the culture medium of a cell line transfected with a mutated Fc gamma RII cDNA. These methods include the use of bioreactors for culturing transfected fibroblasts and the purification of rIgG-BF by ion-exchange chromatography and hydrophobic-interaction chromatography. By using such procedures, about 2.4 mg of rIgG-BF were purified from 1 liter of culture medium of transfected fibroblasts. Like natural IgG-BF, the 95-99% pure rIgG-BF suppressed, in a dose-dependent manner, secondary in vitro IgG antibody responses to sheep red blood cells.

Amino Acid Sequence↗
PubMed1992

Current status of interleukin-2 therapy in cancer.

In vitro studies and animal experiments showed the existence of a physiological immune response against tumors. Interleukin-2 was the first immunological agent which demonstrated an anti-tumor effect by activating immune effectors. In vitro IL2 may generate Lymphokine Activated Killer (LAK) cells from peripheral blood lymphocytes or Tumor Infiltrating Lymphocytes (TIL) expanded from tumor. In melanoma and renal cell carcinoma, IL2 alone or associated with LAK cells or TIL, mediated clinical responses. However, their clinical efficacy was associated with some toxicity related to a capillary leak syndrome. This implies an improvement in the selection of patients and in the understanding of IL2 action. Future directions in immunotherapy included combination IL2 with other cytokines or monoclonal antibodies or chemotherapy. Lymphokine gene therapy is designed to introduce IL2 or other cytokine genes into tumor infiltrating lymphocytes or directly into tumors to reduce systemic toxicity and to achieve high local cytokine concentration. Animal models and the first human trials make this approach promising.

Animals↗
PubMed1992

Soluble Fc gamma R (sFc gamma R): detection in biological fluids and production of a murine recombinant sFc gamma R biologically active in vitro and in vivo.

Soluble forms of receptors for the Fc portion of IgG (sFc gamma R) were detected in biological fluids from mice and humans. In mouse bearing tumors, circulating amounts of sFc gamma R increased concurrently with tumor growth. Tumors secreting IgG2a, IgG2b or IgG3 led to a 5- to 10-fold increase in serum sFc gamma R levels whereas tumors secreting IgG1, IgGA or other types of tumors (non Ig B cell tumors, T cell lymphoma and a melanoma) increased 2- to 3-fold the levels of circulating sFc gamma R. In the human, sFc gamma R were also detected in whole unstimulated saliva. Levels of sFc gamma RII and of sFc gamma RIII were variable and did not seem to depend on the dental status of the individuals. Finally, a murine recombinant sFc gamma R (rsFc gamma R) composed of the two extracellular domains of Fc gamma RII was produced by culture of transfected L cells in bioreactors. The purified rsFc gamma R was found to inhibit antibody production in vitro in anti-SRBC responses and by cultures of small B cells stimulated by anti-IgM antibodies in the presence of IL-4 and IL-5. Moreover, the i.p. injection of this material into adult mice immunized with SRBC led to a decrease of IgG antibody production by splenocytes, as measured by a hemolytic plaque assay, and in serum, as measured by antigen-specific ELISA.

Animals↗
PubMed1992

Increased levels of soluble low-affinity Fc gamma receptors (IgG-binding factors) in the sera of tumour-bearing mice.

Soluble forms of low affinity Fc gamma receptors (Fc gamma R), also called IgG-binding factors (IgG-BF), have been shown to play a regulatory role in immune responses. By using an immunodot assay with the anti-mouse Fc gamma R MoAb, 2.4G2, the levels of IgG-BF have been measured in the sera of mice bearing syngeneic tumours of lymphoid or non-lymphoid origin or in mice injected with high doses of murine IgG. These sera contained large amounts of IgG-BF as compared with controls. In the case of mice bearing IgG2a- or IgG2b-secreting hybridomas or lymphomas, serum IgG-BF increased progressively with tumour size and serum monoclonal IgG concentration, reaching 4-12 times the normal levels. A less than three-fold increase was found in mice bearing an IgG1-secreting hybridoma or tumours which do not secrete IgG (IgA-secreting hybridoma, non-immunoglobulin-secreting lymphoid tumours or melanoma) or in mice injected with 9 mg of monoclonal IgG2a. The enhancement of serum IgG-BF levels was independent of the expression of Fc gamma R by the tumour cells, suggesting that the majority of IgG-BF secreted in response to tumours was produced by the host rather than by the tumour. The increased production of IgG-BF may participate in the control of tumour growth and in the modulation of the host immune responses in tumour-bearing animals.

Animals↗
PubMedDate not supplied

Gene therapy study of cytokine-transfected xenogeneic cells (Vero-interleukin-2) in patients with metastatic solid tumors.

On the basis of compelling preclinical data in cats and dogs, we initiated a clinical gene therapy study in nine patients with advanced solid tumors using xenogeneic fibroblasts secreting human interleukin (IL)-2 (Vero-IL-2 cells). Cohorts of three successive patients with tumors accessible to computed tomography- or ultrasound-guided injection were treated repeatedly with 5 x 10(5), 5 x 10(6), or 5 x 10(7) Vero-IL-2 cells. The endpoints of the study were feasibility, toxicity, and the clinical and biological effects of this novel approach to immunotherapy of cancer. Histopathological, immunological, and molecular analyses were performed on biopsy specimens of tumors and blood samples before, during, and after treatment. Treatment was well tolerated, and toxicity consisted of transient fever in one patient and short-lived, mild itching and erythema in two others. One patient with soft-tissue sarcoma showed a reduction of >90% and >50% of the volume of two distant, noninjected metastases, lasting for 29+ and 26 months, respectively. Four other patients showed stabilization of their disease for 3-9 months; of these patients, one with melanoma developed marked vitiligo. We conclude that repeated injections of < or =5 x 10(7) Vero-IL-2 cells are feasible and safe in heavily pretreated patients with advanced solid tumors. An additional evaluation of an intratumoral application of Vero-IL-2 seems warranted.

Adult↗
PubMedDate not supplied

Recombinant vaccinia virus encoding human MUC1 and IL2 as immunotherapy in patients with breast cancer.

Polymorphic epithelial mucin, encoded by the MUC1 gene, is present at the apical surface of glandular epithelial cells. It is over-expressed and aberrantly glycosylated in most breast tumors, resulting in an antigenically distinct molecule and a potential target for immunotherapy. This transmembrane protein, when produced by tumor cells, is often cleaved into the circulation, where it is detectable as a tumor marker (CA 15.3) by various antibodies, allowing for early detection of recurrences and evaluation of treatment efficacy. The objective of the current study was to examine the clinical and environmental safety and immunogenicity of a live recombinant vaccinia virus expressing the human MUC1 and IL2 genes (VV TG5058), referred to here as TG1031. The study was an open-label phase 1 and 2 trial in nine patients with advanced inoperable breast cancer recurrences to the chest wall. The patients were vaccinated intramuscularly with a single dose of TG1031; three patients were treated at each of three progressive dose levels ranging from 5x10(5) to 5x10(7) plaque-forming units. A boost injection at their original dose level was administered in patients responding immunologically, clinically, or both. Vaccination resulted in no significant clinical adverse effects, and there was no environmental contamination by live TG1031. All patients had been vaccinated as children, and patients treated at the highest dose level mounted a significant anti-vaccinia antibody response. None of the nine patients had a significant increase in MUC1-specific antibody titers after one single injection, whereas five patients had a detectable increase in vaccinia virus antibody titers. Peripheral blood mononuclear cells of one patient at the intermediate dose level showed a proliferative response to in vitro culture with vaccinia virus, with a stimulation index of 6. A second patient treated at the intermediate dose level had a stimulation index of 7 to MUC1 peptide and of 14 after a boost injection. This patient had a concomitant decrease in carcinoembryonic antigen serum levels and remained clinically stable for 10 weeks. Evidence of MUC1-specific cytotoxic T lymphocytes was detected in two patients. Immunohistochemical analysis revealed an increase in T memory cells (CD45RO) in tumor biopsies after vaccination. The absence of serious adverse events, together with the documentation of immune stimulations in vivo, warrant the further use of TG1031 in immunotherapy trials of breast cancer.

Adult↗
PubMedDate not supplied

Effect of laparoscopy versus laparotomy on circulating tumor cells using isolation by size of epithelial tumor cells.

AIM: To assess the effect of laparoscopy on circulating tumor cell (CTC) detection in case of carcinosis. MATERIAL AND METHODS: We compared laparoscopy versus laparotomy on tumor cell blood release in an animal model of ovarian carcinosis obtained by intraperitoneal inoculation of IGR-OV1 cells in nude rats. Animals were randomly assigned to one of the following groups: CO(2) laparoscopy (L), gasless laparoscopy (GL), midline laparotomy (ML), or general anesthesia as control (C). A 0.5 ml blood sample was taken in each case before and after experiment and tested with a novel assay, ISET (isolation by size of epithelial tumor cells), which isolates CTC by filtration on account of their size. Statistics were performed with the Fisher's and the Chi-square tests. RESULTS: Ten rats were included in each group. We did not find any significant difference in CTC prevalence before and after surgery (2/14 versus 3/19, respectively, P = 1). Similarly, the three surgical accesses were equivalent with one post-experiment detection per group: 1/5 for L, 1/7 for ML, 1/7 for GL, and 1/6 for C (P = 0.9). CONCLUSION: This trial did not show any deleterious effect of laparoscopy on CTC when compared to laparotomy.

Animals↗