Search results for "Mammary Neoplasms"
showing 10 items of 30 documents
Tumour-derived and host-derived nitric oxide differentially regulate breast carcinoma metastasis to the lungs.
2004
To study the role of nitric oxide (NO) in lung metastasis of breast carcinoma, we isolated two cell clones (H and J) from the parental EMT-6 murine breast carcinoma cell line, based on their differential NO production. In vitro, EMT-6 J cells, but not EMT-6H cells, constitutively expressed inducible NO synthase (NOS II) and secreted high levels of NO. IL-1beta increased NO production in both clones, and TNF-alpha had a synergistic effect on IL-1beta-induced NO production, but NO production by EMT-6 J cells was always higher than by EMT-6H cells. Proliferation, survival and adhesion to lung-derived endothelial cells of both clones were similar and were not affected by NO. In vivo, both clone…
Tissue gradients of energy metabolites mirror oxygen tension gradients in a rat mammary carcinoma model
2001
Abstract Purpose: It has been shown that oxygen gradients exist in R3230AC tumors grown in window chambers. The fascial surface is better oxygenated than the tumor surface. The purpose of the present study was to determine whether gradients exist for energy metabolites and other end points related to oxygen transport. Methods and Materials: Imaging bioluminescence was used to measure ATP, glucose, and lactate in cryosections of R3230AC tumors. Mean vessel density and hypoxic tissue fraction were assessed using immunohistochemistry. Tumor redox ratio was assessed by redox ratio scanning. Results: Lactate content and hypoxic fraction increased, whereas ATP, glucose, redox ratio, and vessel de…
Chronic exposure to a GSM-like signal (mobile phone) does not stimulate the development of DMBA-induced mammary tumors in rats: results of three cons…
2002
Certain epidemiological and experimental studies raised concerns about the safety of radiofrequency (RF) electromagnetic fields because of a possible increased risk of leukemia and lymphoma. In this study, an RF field used in mobile telecommunication was tested using 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats as a model for human breast cancer. Three experiments were carried out under strictly standardized conditions and were started on the same day of three consecutive years. The field consisted of a GSM-like signal (900 MHz pulsed at 217 Hz, pulse width 577 micros) of relatively low power flux density (100 microW/cm(2) +/- 3 dB) and was appl…
Docosahexaenoic acid inhibits cancer cell growth via p27Kip1, CDK2, ERK1/ERK2, and retinoblastoma phosphorylation
2006
Docosahexaenoic acid (DHA), a PUFA of the n-3 family, inhibited the growth of FM3A mouse mammary cancer cells by arresting their progression from the late-G(1) to the S phase of the cell cycle. DHA upregulated p27(Kip1) levels by inhibiting phosphorylation of mitogen-activated protein (MAP) kinases, i.e., ERK1/ERK2. Indeed, inhibition of ERK1/ERK2 phosphorylation by DHA, U0126 [chemical MAPK extracellularly signal-regulated kinase kinase (MEK) inhibitor], and MEK(SA) (cells expressing dominant negative constructs of MEK) resulted in the accumulation of p27(Kip1). MAP kinase (MAPK) inhibition by DHA did not increase p27(Kip1) mRNA levels. Rather, this fatty acid stabilized p27(Kip1) contents…
S-nitrosylation of the death receptor fas promotes fas ligand-mediated apoptosis in cancer cells.
2011
International audience; BACKGROUND & AIMS: Fas belongs to the family of tumor necrosis factor receptors which induce apoptosis. Many cancer cells express Fas but do not undergo Fas-mediated apoptosis. Nitric oxide reverses this resistance by increasing levels of Fas at the plasma membrane. We studied the mechanisms by which NO affects Fas function. METHODS: Colon and mammary cancer cell lines were incubated with the NO donor glyceryl trinitrate or lipid A; S-nitrosylation of Fas was monitored using the biotin switch assay. Fas constructs that contained mutations at cysteine residues that prevent S-nitrosylation were used to investigate the involvement of S-nitrosylation in Fas-mediated cell…
Infiltrating mast cell-mediated stimulation of estrogen receptor activity in breast cancer cells promotes the luminal phenotype
2019
Abstract Tumor growth and development is determined by both cancer cell–autonomous and microenvironmental mechanisms, including the contribution of infiltrating immune cells. Because the role of mast cells (MC) in this process is poorly characterized and even controversial, we investigated their part in breast cancer. Crossing C57BL/6 MMTV-PyMT mice, which spontaneously develop mammary carcinomas, with MC-deficient C57BL/6-KitW-sh/W-sh (Wsh) mice, showed that MCs promote tumor growth and prevent the development of basal CK5-positive areas in favor of a luminal gene program. When cocultured with breast cancer cells in vitro, MCs hindered activation of cMET, a master regulator of the basal pr…
PEGylation of HPMA-based block copolymers enhances tumor accumulation in vivo: a quantitative study using radiolabeling and positron emission tomogra…
2013
Abstract This paper reports the body distribution of block copolymers (made by controlled radical polymerization) with N-(2-hydroxypropyl)methacrylamide (HPMA) as hydrophilic block and lauryl methacrylate (LMA) as hydrophobic block. They form micellar aggregates in aqueous solution. For this study the hydrophilic/hydrophobic balance was varied by incorporation of differing amounts of poly(ethylene glycol) (PEG) side chains into the hydrophilic block, while keeping the degree of polymerization of both blocks constant. PEGylation reduced the size of the micellar aggregates (Rh = 113 to 38 nm) and led to a minimum size of 7% PEG side chains. Polymers were labeled with the positron emitter 18F,…
pH distributions in spontaneous and isotransplanted rat tumours.
1988
Spontaneous mammary tumours of the rat with various degrees of malignancy exhibit similar tissue pH distributions. The mean pH (+/- s.d.) of dysplasia is 7.05 +/- 0.20. In benign tumours the mean pH is 6.95 +/- 0.19 and in malignant tumours it is 6.94 +/- 0.19. In contrast, tumours with the same degree of malignancy but different histologies show different pH distributions. Benign tumours with a higher percentage of fibrous tissue exhibit less acidic pH values than those with larger portions of epithelial cells (delta pH = 0.38 pH units). The pH distribution in the benign tumours is independent of the tumour wet weight up to stages of very advanced growth. In the malignant tumours, a trend …
Trastuzumab therapy vs tetracycline controlled ERBB2 downregulation: influence on tumour development in an ERBB2-dependent mouse tumour model
2008
Trastuzumab (Herceptin) has improved therapy of breast cancer. Only patients overexpressing ERBB2 are treated with trastuzumab, whereas its use in tumours without ERBB2 expression is useless. This led to the concept that the subgroup of trastuzumab-sensitive tumours is ‘ERBB2-dependent', meaning that ERBB2 signalling is indispensable for growth of these tumours. We used a mouse model that allows anhydrotetracycline (ATc)-controlled downregulation of ERBB2 in tumour tissue. ERBB2 mRNA and protein expression were downregulated below detection limit leading to a macroscopically complete tumour remission within 14 days. Tumour remission was accompanied by a strong decrease in proliferation, a m…
Oncogene-driven intrinsic inflammation induces leukocyte production of tumor necrosis factor that critically contributes to mammary carcinogenesis.
2010
Abstract Oncogene activation promotes an intrinsic inflammatory pathway that is crucial for cancer development. Here, we have investigated the actual effect of the inflammatory cytokine tumor necrosis factor (TNF) on the natural history of spontaneous mammary cancer in the HER2/neuT (NeuT) transgenic mouse model. Bone marrow transplantation from TNF knockout mice into NeuT recipients significantly impaired tumor growth, indicating that the source of TNF fostering tumor development was of bone marrow origin. We show that the absence of leukocyte-derived TNF disarranged the tumor vasculature, which lacked pericyte coverage and structural integrity, leading to diffuse vascular hemorrhage and s…