Biomedical subjects

Ivan Théate

Publications and source records attributed to Ivan Théate.

5 recordsLinked to original sources

PubMed2006

Increased protein glycation in fructosamine 3-kinase-deficient mice.

Amines, including those present on proteins, spontaneously react with glucose to form fructosamines in a reaction known as glycation. In the present paper, we have explored, through a targeted gene inactivation approach, the role of FN3K (fructosamine 3-kinase), an intracellular enzyme that phosphorylates free and protein-bound fructose-epsilon-lysines and which is potentially involved in protein repair. Fn3k-/- mice looked healthy and had normal blood glucose and serum fructosamine levels. However, their level of haemoglobin-bound fructosamines was approx. 2.5-fold higher than that of control (Fn3k+/+) or Fn3k+/- mice. Other intracellular proteins were also significantly more glycated in Fn3k-/- mice in erythrocytes (1.8-2.2-fold) and in brain, kidney, liver and skeletal muscle (1.2-1.8-fold), indicating that FN3K removes fructosamines from intracellular proteins in vivo. The urinary excretion of free fructose-epsilon-lysine was 10-20-fold higher in fed mice compared with mice starved for 36 h, and did not differ between fed Fn3k+/+ and Fn3k-/- mice, indicating that food is the main source of urinary fructose-epsilon-lysine in these mice and that FN3K does not participate in the metabolism of food-derived fructose-epsilon-lysine. However, in starved animals, the urinary excretion of fructose-epsilon-lysine was 2.5-fold higher in Fn3k-/- mice compared with Fn3k+/+ or Fn3k+/- mice. Furthermore, a marked increase (5-13-fold) was observed in the concentration of free fructose-epsilon-lysine in tissues of fed Fn3k-/- mice compared with control mice, indicating that FN3K participates in the metabolism of endogenously produced fructose-epsilon-lysine. Taken together, these data indicate that FN3K serves as a protein repair enzyme and also in the metabolism of endogenously produced free fructose-epsilon-lysine.

Animals↗

PubMed2005

Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen.

Melanoma patients have high frequencies of T cells directed against antigens of their tumor. The frequency of these antitumor T cells in the blood is usually well above that of the anti-vaccine T cells observed after vaccination with tumor antigens. In a patient vaccinated with a MAGE-3 antigen presented by HLA-A1, we measured the frequencies of anti-vaccine and antitumor T cells in several metastases to evaluate their respective potential contribution to tumor rejection. The frequency of anti-MAGE-3.A1 T cells was 1.5 x 10(-5) of CD8 T cells in an invaded lymph node, sixfold higher than in the blood. An antitumor cytotoxic T lymphocyte (CTL) recognizing a MAGE-C2 antigen showed a much higher enrichment with a frequency of approximately 10%, 1,000 times higher than its blood frequency. Several other antitumor T clonotypes had frequencies >1%. Similar findings were made on a regressing cutaneous metastasis. Thus, antitumor T cells were approximately 10,000 times more frequent than anti-vaccine T cells inside metastases, representing the majority of T cells present there. This suggests that the anti-vaccine CTLs are not the effectors that kill the bulk of the tumor cells, but that their interaction with the tumor generates conditions enabling the stimulation of large numbers of antitumor CTLs that proceed to destroy the tumor cells. Naive T cells appear to be stimulated in the course of this process as new antitumor clonotypes arise after vaccination.

Antigens, Neoplasm↗

PubMed2005

Activity and safety of combined rituximab with chlorambucil in patients with mantle cell lymphoma.

We evaluated the combination of rituximab with chlorambucil in patients with mantle cell lymphoma (MCL) not eligible for aggressive therapy. Fourteen patients (male/female: 9/5) were included (two newly diagnosed, 12 relapsed/refractory). The toxicities were neutropenia, thrombopenia and infection. Nine (64%) patients responded; five (36%) achieved complete remission and four (29%) achieved partial remission. The median progression-free survival for responders was 26 months (95% CI, 4-48). Marrow polymerase chain reaction negativity was attained in seven responders. These results suggest that this schedule may have notable antitumour activity in patients with MCL, including patients in relapse after autologous stem cell transplantation.

Adult↗

PubMed2004

[A-leukemic caecal myeloid sarcoma: a difficult diagnosis].

Myeloid sarcoma is a malignant neoplasia composed of abnormal myeloid or monocytic cells, often localized in bones, but also rarely in extra-medullary sites such as lymph nodes, skin and soft tissue. We report a case of caecal myeloid sarcoma, diagnosed in a 60 year old woman who complained from abdominal pain and weight loss, in absence of any medullary disorder. Initially misdiagnosed as a B lymphoma because of a weak positivity for CD79a, the diagnosis of primitive caecal myeloid sarcoma was eventually established after further investigations showing a positivity for lysozyme and myeloperoxidase. This report of such a rare clinical and pathological presentation of a myeloid sarcoma underlines a difficult differential diagnosis for which adequate immunohistochemistry, including lysozyme and myeloperoxydase is mandatory.

Abdominal Pain↗

PubMed2003

Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase.

T lymphocytes undergo proliferation arrest when exposed to tryptophan shortage, which can be provoked by indoleamine 2,3-dioxygenase (IDO), an enzyme that is expressed in placenta and catalyzes tryptophan degradation. Here we show that most human tumors constitutively express IDO. We also observed that expression of IDO by immunogenic mouse tumor cells prevents their rejection by preimmunized mice. This effect is accompanied by a lack of accumulation of specific T cells at the tumor site and can be partly reverted by systemic treatment of mice with an inhibitor of IDO, in the absence of noticeable toxicity. These results suggest that the efficacy of therapeutic vaccination of cancer patients might be improved by concomitant administration of an IDO inhibitor.

Animals↗