Search results for "toxicity."
showing 10 items of 2180 documents
Analysis of antigens recognized on human melanoma cells by A2-restricted cytolytic t lymphocytes (CTL)
1993
We have pursued our analysis of potential tumor-rejection antigens recognized on human melanoma by autologous cytolytic T lymphocytes (CTL). We reported previously that 3 distinct antigens (A,B,C) were recognized on melanoma cell line SK29-MEL in association with HLA-A2. Selection for melanoma-cell variants resistant to anti-A CTL revealed that antigen A consists of at least 2 determinants (Aa, Ab) which can be lost separately. Genetic linkage between Aa and Ab was suggested by concomitant loss of Aa and Ab in an immunoselected tumor-cell variant. This variant was also resistant to an autologous CTL clone restricted by HLA-B45, indicating that this CTL may also recognize a determinant of an…
Influence of nitric oxide on the generation and repair of oxidative DNA damage in mammalian cells
2002
We have analysed the effects of endogenously and exogenously generated nitric oxide (NO) in cultured mammalian fibroblasts on: (i) the steady-state (background) levels of oxidative DNA base modifications; (ii) the susceptibility of the cells to the induction of additional DNA damage and micronuclei by H(2)O(2); and (iii) the repair kinetics of various types of DNA modifications. Steady-state levels of oxidative DNA base modifications, measured by means of an alkaline elution assay in combination with the repair endonuclease Fpg protein, were similar in NO-overproducing B6 mouse fibroblasts stably transfected with an inducible NO synthase (iNOS) and in control cells. Increased oxidative dama…
Impact of Extracellular Acidity on the Activity of P-glycoprotein and the Cytotoxicity of Chemotherapeutic Drugs
2006
AbstractThe expression and activity of P-glycoprotein (pGP) play a role in the multidrug resistance of tumors. Because solid-growing tumors often show pronounced hypoxia or extracellular acidosis, this study attempted to analyze the impact of an acidic environment on the expression and activity of pGP and on the cytotoxicity of chemotherapeutic agents. For this, prostate carcinoma cells were exposed to an acidic extracellular environment (pH 6.6) for up to 24 hours. pGP activity was more than doubled after 3 to 6 hours of incubation in acidic medium, whereas cellular pGP expression remained constant, indicating that increased transport rate is the result of functional modulation. In paralle…
Highly specific auto-antibodies against claudin-18 isoform 2 induced by a chimeric HBcAg virus-like particle vaccine kill tumor cells and inhibit the…
2011
Abstract Strategies for antibody-mediated cancer immunotherapy, such as active immunization with virus-like particle (VLP)-based vaccines, are gaining increasing attention. We developed chimeric hepatitis B virus core antigen (HBcAg)-VLPs that display a surface epitope of the highly selective tumor-associated cell lineage marker claudin-18 isoform 2 (CLDN18.2) flanked by a mobility-increasing linker. Auto-antibodies elicited by immunization with these chimeric HBcAg-VLPs in 2 relevant species (mouse and rabbit) bind with high precision to native CLDN18.2 at physiologic densities on the surface of living cells but not to the corresponding epitope of the CLDN18.1 splice variant that differs b…
In vivo targeting of human neutralizing antibodies against CD55 and CD59 to lymphoma cells increases the antitumor activity of rituximab.
2007
AbstractAn in vivo model of human CD20+ B-lymphoma was established in severe combined immunodeficiency mice to test the ability of human neutralizing miniantibodies to CD55 and CD59 (MB55 and MB59) to enhance the therapeutic effect of rituximab. The miniantibodies contained single-chain fragment variables and the hinge-CH2-CH3 domains of human IgG1. LCL2 cells were selected for the in vivo study among six B-lymphoma cell lines for their high susceptibility to rituximab-dependent complement-mediated killing enhanced by MB55 and MB59. The cells injected i.p. primarily colonized the liver and spleen, leading to the death of the animals within 30 to 40 days. Thirty percent of mice receiving bio…
Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherap…
2015
The efficacy of antibody-based immunotherapy is due to the activation of apoptosis, the engagement of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (CDC). We developed a novel strategy to enhance CDC using bispecific antibodies (bsAbs) that neutralize the C-regulators CD55 and CD59 to enhance C-mediated functions. Two bsAbs (MB20/55 and MB20/59) were designed to recognize CD20 on one side. The other side neutralizes CD55 or CD59. Analysis of CDC revealed that bsAbs could kill 4-25 times more cells than anti-CD20 recombinant antibody in cell lines or cells isolated from patients with chronic lymphocytic leukemia. The pharmacokinetics of the bsAbs was evaluate…
Impact of Undernutrition on the Pharmacokinetics and Pharmacodynamics of Anticancer Drugs: A Literature Review
2017
The etiology of undernourishment in cancer patients is multifactorial: tumor-related mechanisms (such as obstruction, metabolic abnormalities, and functionality changes) in addition to the influence of anticancer therapies, which can induce or worsen undernutrition. The evident role of undernutrition in cancer treatment outcomes suggests the need of considering nutritional status when evaluating anticancer drugs. In order to merge the available data and offer researchers and clinicians a global view of this phenomenon, the present manuscript reviews on a drug-by-drug basis the undernutrition-related pharmacokinetic and pharmacodynamic aspects of anticancer treatments. This review notes inte…
Acute myeloid leukemia (AML)-reactive cytotoxic T lymphocyte clones rapidly expanded from CD8(+) CD62L((high)+) T cells of healthy donors prevent AML…
2008
Objective Current in vitro techniques for isolating leukemia-reactive cytotoxic T lymphocytes (CTLs) from healthy donors are of relatively low efficiency and yield responder populations with unknown biological significance. This study aimed at the development of a more reliable approach, allowing generation and expansion of acute myeloid leukemia (AML)-reactive CTLs using primary in vitro stimulation. Materials and Methods We established allogeneic mini-mixed lymphocyte-leukemia cultures (mini-MLLCs) by stimulating donor CD8 + T cells with human leukocyte antigen (HLA) class I–matched AML blasts in microtiter plates. Before culture, CD8 + T cells were separated into CD62L (high)+ and CD62L …
Diorganotin(IV) and triorganotin(IV) complexes of meso-tetra(4-sulfonatophenyl) porphine induce apoptosis in A375 human melanoma cells
2006
The cytotoxic effect of several diorganotin(IV) and triorganotin(IV)-meso-tetra(4-sulfonatophenyl)porphine derivatives was tested and only the (Bu(2)Sn)(2)TPPS and the (Bu(3)Sn)(4)TPPS showed cytotoxicity on A375 human melanoma cells. To examine the pathway of (Bu(2)Sn)(2)TPPS or (Bu(3)Sn)(4)TPPS induced A375 cell death, DNA fragmentation analysis, Annexin V binding and PI uptake as well as caspases activation analysis by Western blot were carried out. A375 cells treated exhibited several typical characteristics of apoptosis. Both the (Bu(2)Sn)(2)TPPS and the (Bu(3)Sn)(4)TPPS compounds activate caspase-8 and caspase-9 leading to caspase-3 activation. Thus, we propose that these two porphiri…
Induction of DNA breaks and apoptosis in crosslink-hypersensitive V79 cells by the cytostatic drug beta-D-glucosyl-ifosfamide mustard.
2001
To study molecular aspects of cytotoxicity of the anticancer drug β-D-glucose-ifosfamide mustard we investigated the potential of the agent to induce apoptosis and DNA breakage. Since β-D-glucose-ifosfamide mustard generates DNA interstrand crosslinks, we used as an in vitro model system a pair of isogenic Chinese hamster V79 cells differing in their sensitivity to crosslinking agents. CL-V5B cells are dramatically more sensitive (30-fold based on D10 values) to the cytotoxic effects of β-D-glucose-ifosfamide mustard as compared to parental V79B cells. After 48 h of pulse-treatment with the agent, sensitive cells but not the resistant parental line undergo apoptosis and necrosis, with apopt…