Modulation of TNF-α activity in tumor PC cells using anti-CD45 and anti-CD95 monoclonal antibodies

Colic

Acta Med. (Hradec Kralove, Czech Repub.)

2007

TNF-α is a pleiotropic cytokine that is considered as a primary modifier of inflammatory and immune reaction in response to various inflammatory diseases and tumour. We investigated levels of TNF-α in 43 radicular cysts and 15 odontogenic keratocysts, obtained from patients undergoing surgery, under local anaesthesia, and after aspiration of cystic fluid from non-ruptured cysts. TNF-α is elevated in both cysts’ fluid, but higher values were found in radicular cysts in comparison to keratocysts. The significantly higher concentration of TNF-α was associated with smaller radicular cysts, higher protein concentration, higher presence of inflammatory cells in peri cystic tissues, and the degree of vascularisation and cysts wall thickness (Mann-Whitney U-test, p<0.05). No correlation was found based on these parameters in odontogenic keratocyst, but all cysts have detectable concentrations of TNF-α. We here for the first time present that a difference in the concentration of TNF-α exists between these two cystic types.

Section: Introductionmentioning

confidence: 99%

“…Tumour necrosis factor-α (TNF-α) is a cytokine initially identified as a cause of hemorrhagic necrosis in certain tumors (12,13). It is secreted by macrophages, monocytes and NK cells and many other cell types and it exists in two forms.…”

Section: Introductionmentioning

confidence: 99%

The Inflammatory Radicular Cysts Have Higher Concentration of TNF-α in Comparison to Odontogenic Keratocysts (Odontogenic Tumour)

Colic

Acta Med. (Hradec Kralove, Czech Repub.)

2007

“…A number of these other cytokines, e.g., stem cell factor (c-kit ligand), IL-3, GM-CSF, IFN-g and erythropoietin, have been shown to regulate CD95 (APO-1 or Fas) (51-53), map kinase, AKT, and the JAK-STAT (54) and phosphatidyl inositol-3 kinase (55) pathways, all important mediators of apoptosis and/or proliferation in hematopoietic cells. Moreover, TNF-a has been shown to potentiate apoptosis mediated by anti-CD45 and anti-CD95 antibodies in PC tumor cells in vitro (56). As described in the introduction, there are two receptors for TNF-a (3).…”

Section: Discussionmentioning

confidence: 99%

Myelodysplasia and anemia of chronic disease in human tumor necrosis factor‐α transgenic mice

Capocasale¹,

Makropoulos²,

Achuthanandam³

et al. 2008

Cytometry Pt A

TNF-a is a pleitropic cytokine that expresses both pro-and anti-inflammatory activity and transgenic mice expressing human tumor necrosis factor-a (TNF-a) exhibit a progressive polyarthritis that models rheumatoid arthritis (RA). One of the common comorbidities of RA is anemia of chronic disease (ACD). The purpose of these experiments was to study the changes in the bone marrow and peripheral blood that accompany polyarthritis in TNF-a transgenic mice in an effort to better understand the pathogenesis of myelodysplasia and ACD. Polychromatic cytometry, hematology and serum cytokine analysis were used to study the pathogenesis of ACD in human TNF-a transgenic mice. Our hematological evaluation revealed a mild, compensated, microcytic hypochromic anemia, and monocytosis. In the bone marrow, we observed alterations in cell kinetics, decreased relative expression of transferrin receptor and increased apoptosis and cell death in several late precursor cell populations. Although significant levels of human TNF-a were found in the serum, neither change in serum murine erythropoietin nor any significant difference observed in serum levels of murine IL-b, IL-5, IL-6, IL-10, IL-12(p70), IL-17, TNF-a, IFNg, GM-CSF, MIP-1aJE, MCP-5 was observed. Tg197 mice develop a compensated, microcytic, hypochromic anemia, and a functional iron deficiency by 9 weeks of age. Changes in peripheral blood are reflected in alterations in cell kinetics, transferrin receptor expression and markedly increased apoptosis and cell death in the bone marrow indicating that TNF-a may contribute to myelodysplasia in ACD. Moreover, since human TNF-a can interact only with murine TNFR1, our data suggest that TNFR1 may play an important role in the development of ACD. '

“…Osteolytic bone lesions could be also a consequence of leukemic bone infiltration or focal bone destruction by TNF-α locally released by leukemic cells (7,8). We previously reported that TNF-α can induce apoptosis in leukemic cell lines in vitro (9,14) and can stimulate osteoclast activation with subsequent development of bone degradation. Osteolytic lesions in myelofibrosis have been described but rarely and only in irradiated patients (1,11).…”

Section: Discussionmentioning

confidence: 99%

Diffuse osteolytic lesions in leukemic transformation of myelofibrosis

Jurišić¹,

Čolović²,

Pavlović

et al. 2007

Arch Oncol

Myelofibrosis is a clonal myeloproliferative disorder characterized by splenomegaly, abnormal deposition of reticulin and collagen in the bone marrow, extramedullary hematopoiesis, dacryocytosis and leukoerythroblastic blood smear. Development and sustainment of fibrosis are mediated by complex network of several cytokines. Osteosclerosis is the most frequently observed bone change in myelofibrosis. We present an atypical case of leukemic transformation in myelofibrosis associated with diffuse osteolytic lesions and extremely elevated lactate dehydrogenase in serum, which indicates high bone turnover during leukemic infiltration and bone destruction