Background:Translationally controlled tumour protein (TCTP) is an antiapoptotic protein highly conserved through phylogeny. Translationally controlled tumour protein overexpression was detected in several tumour types. Silencing TCTP was shown to induce tumour reversion. There is a reciprocal repression between TCTP and P53. Sertraline interacts with TCTP and decreases its cellular levels.Methods:We evaluate the role of TCTP in melanoma using sertraline and siRNA. Cell viability, migration, and clonogenicity were assessed in human and murine melanoma cells in vitro. Sertraline was evaluated in a murine melanoma model and was compared with dacarbazine, a major chemotherapeutic agent used in melanoma treatment.Results:Inhibition of TCTP levels decreases melanoma cell viability, migration, clonogenicity, and in vivo tumour growth. Human melanoma cells treated with sertraline show diminished migration properties and capacity to form colonies. Sertraline was effective in inhibiting tumour growth in a murine melanoma model; its effect was stronger when compared with dacarbazine.Conclusions:Altogether, these results indicate that sertraline could be effective against melanoma and TCTP can be a target for melanoma therapy.
An experiment was designed to determine the influence of fibre and betaine on the development of the intestine, liver and pancreas of broilers from hatch to 14 d of age. A total of 250-day-old Cobb 500 male broilers were allocated to 16 cages with 15 broilers each. Treatments were arranged in a 2 × 4 factorial design, consisting of 2 feed formulations (low and high fibre diets) and 4 levels of betaine (0, 1, 3 or 5 kg/t). At hatch, 10 birds in total were euthanised, and samples of the liver, pancreas, yolk sac and intestine were collected for reference of the analysed parameters before the start of the trial. On d 4, 9 and 14, 5 birds per cage (10 birds per treatment) were selected, euthanised and treated as the same as the birds at hatch. Villus height and width and crypt depth were determined on the duodenum samples, and absorptive area was calculated. The number of enterocytes in mitosis at the villus was determined by a positive reaction to antibody for Ki67 protein, and fused villus was evaluated visually. The relative weight of the yolk sac reduced ( P < 0.05) as birds aged while the intestine and liver reached a maximum ( P < 0.05) at around d 4 and the pancreas at d 9. Birds fed the high fibre diet had greater feed intake, lower relative weight of the pancreas and higher villus ( P < 0.05) than birds fed the low fibre diet. Villus width increased ( P < 0.05) at 4 d of age, and this was associated with fused villus. Betaine inclusion reduced ( P < 0.05) villus width, increased ( P < 0.05) villus size and absorptive area, and reduced ( P < 0.05) the number of enterocytes with positive reaction for the antibody Ki-67. Betaine inclusion reduced the width and increased the absorptive area and the villus height of the duodenum of birds up to 14 d of age. The higher fibre diet increased feed intake and villus height, yet reduced pancreas relative weight, while not affecting body weight gain. This response was possibly due to a dilution effect of the fibre, reducing nutrient absorption and consequently stimulating villus growth to improve absorption rates.
Altogether these data suggest M1 is an efficient candidate for melanoma therapy to be considered for future clinic studies as this study is the first supporting the idea that melanoma patients may benefit with the treatment. The treatment with M1 provides advantages considering the highly-diluted properties and a cost effective alternative to costly chemotherapeutic approaches with, if any, lower toxicity.
Objectives To evaluate histological and immunohistochemical changes in the great saphenous vein after endovenous laser ablation at two different wavelengths (1470 vs. 1940 nm) and linear endovenous energy density values (50 vs. 100 J/cm). Method Segments were obtained from the conventional eversion removal of great saphenous vein and divided into a control group and four groups for ex vivo irradiation (control group; A: 1470 nm, 50 J/cm; B: 1470 nm, 100 J/cm; C: 1940 nm, 50 J/cm; D: 1940 nm, 100 J/cm). Fifty venous segments ( n = 10/group) were analyzed. Changes were classified into low-temperature changes, moderate-temperature changes, high-temperature changes, and very high-temperature changes. Results In the intima, low-temperature changes + moderate-temperature changes were significantly more prevalent in group A (65.4%) than in D ( p = 0.001). In the media, low-temperature changes + moderate-temperature changes were achieved mostly in groups A and C (77.4% and 75.0%, respectively). In adventitia fragments, 100% of changes in group A were low-temperature changes + moderate-temperature changes. Conclusions The 1940-nm laser wavelength with linear endovenous energy density of 100 J/cm was excessively destructive to the intima and media causing a high rate of high-grade thermal damage. These findings corroborate the possibility of using lower linear endovenous energy densities with 1940-nm devices to achieve effective occlusion with less high grade thermal damage to the intima and media, as well as to prevent damages to the adventitia and perivenous tissues, including venous perforation and its attendant clinical consequences.
A heteropolysaccharide was isolated by cold aqueous extraction from edible mushroom Pleurotus eryngii ("King Oyster") basidiocarps and its biological properties were evaluated. Structural assignments were carried out using mono- and bidimensional NMR spectroscopy, monosaccharide composition, and methylation analyses. A mannogalactan having a main chain of (1→6)-linked α-d-galactopyranosyl and 3-O-methyl-α-d-galactopyranosyl residues, both partially substituted at OH-2 by β-d-Manp (MG-Pe) single-unit was found. Biological effects of mannogalactan from P. eryngii (MG-Pe) were tested against murine melanoma cells. MG-Pe was non-cytotoxic, but reduced in vitro melanoma cells invasion. Also, 50mg/kg MG-Pe administration to melanoma-bearing C57BL/6 mice up to 10days decreased in 60% the tumor volume compared to control. Additionally, no changes were observed when biochemical profile, complete blood cells count (CBC), organs, and body weight were analyzed. Mg-Pe was shown to be a promising anti-melanoma molecule capable of switching melanoma cells to a non-invasive phenotype with no toxicity to melanoma-bearing mice.
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