scholarly journals Imatinib Mesylate Alters the Expression of Genes Related to Disease Progression in an Animal Model of Uveal Melanoma

2011 ◽  
Vol 34 (3) ◽  
pp. 123-130 ◽  
Author(s):  
Bruno F. Fernandes ◽  
Sebastian Di Cesare ◽  
Rubens Neto Belfort ◽  
Shawn Maloney ◽  
Claudia Martins ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Treated Group ◽  
Suppressor Gene ◽  
Control Group ◽  
Metastasis Suppressor ◽  
Pcr Array ◽  
Intraocular Tumors ◽  
Expression Of Genes

Imatinib mesylate (IM) is a compound that inhibits both BCR-ABL tyrosine kinase and c-kit receptors. Tyrosine kinases are important in cellular signaling and mediate major cellular processes such as proliferation, differentiation, apoptosis, attachment, and migration. Twenty-six albino rabbits were injected with 1 × 106 human uveal melanoma (UM) cells (92.1) into the suprachoroidal space. Animals were immunosuppressed (cyclosporin A) over the course of the 12-week experiment and divided into two groups (n = 13). The experimental group received IM once daily by gavage while the control group received a placebo. One animal per group was sacrificed every week after the 2nd week. Upon necropsy, organs were harvested for histopathological examination. Cells from the primary tumors were recultured and tested in proliferation and invasion assays. A PCR array was used to investigate the differences in expression of 84 genes related to tumor metastasis. In the treated group, 4 rabbits developed intraocular tumors, with an average largest tumor dimension (LTD) of 2.5 mm and 5 animals reported metastatic disease. Whereas 6 rabbits in the control group developed intraocular tumors, with an average LTD of 5.8 mm and 6 animals reported metastatic disease. The recultured cells from the treated group demonstrated lower proliferation rates and were less invasive (p < 0.001 The PCR array showed differences in expression of genes related to metastasis. Notably, there was 290-fold increase inSERPINB5, a tumor suppressor gene, and a 10-fold higher expression ofKISS1, a metastasis suppressor gene, in the treated group. Proangiogenic genes such asVEGFA,PDGFAandPDGFBwere downregulated in the treated group. To the best of our knowledge, this is the first report detailing the altered expression of specific genes in UM cells after treatment with IM.

scholarly journals Expression of the Metastasis Suppressor KAI1 in Uveal Melanoma

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Shawn C. Maloney ◽  
Bruno F. Fernandes ◽  
Rafaella Cleto Penteado ◽  
Emilia Antecka ◽  
Vasco Bravo-Filho ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Staining Intensity ◽  
Suppressor Gene ◽  
Metastasis Suppressor ◽  
Efficacious Treatment ◽  
Therapeutic Value ◽  
Group 2 ◽  
Group 1

Introduction. Uveal melanoma (UM) is an intraocular tumor that leads to metastatic disease in approximately 50% of afflicted patients. There is no efficacious treatment for metastatic disease in this cancer. Identification of markers that can offer prognostic and therapeutic value is a major focus in this field at present. KAI1 is a metastasis suppressor gene that has been reported to play a role in various human malignancies, although it has not previously been evaluated in UM.Purpose. To investigate the expression of KAI1 in UM and its potential value as a prognostic marker.Materials and Methods. 18 cases of human primary UM were collected and immunostained for KAI1 expression. A pathologist evaluated staining intensity and distribution semiquantitatively. Each case was categorized as group 1 (low staining) or group 2 (high staining).Results. In group 2, two of the 12 cases presented with metastasis. Conversely, in group 1, five out of 6 cases had metastasis. The mean follow-up of patients who did not develop metastasis was 81.81 months (median: 75 months) versus 42.14 months (median: 44 months) for patients with metastasis.Conclusions. KAI1 is a promising candidate marker that may offer prognostic value in UM; it may also represent a therapeutic target in metastatic disease.

scholarly journals Effects of Zeaxanthin on Growth and Invasion of Human Uveal Melanoma in Nude Mouse Model

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoliang L. Xu ◽  
Dan-Ning Hu ◽  
Codrin Iacob ◽  
Adrienne Jordan ◽  
Sandipkumar Gandhi ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Nude Mice ◽  
Treated Group ◽  
Control Group ◽  
Histopathological Analysis ◽  
Nude Mouse Model ◽  
Promising Agent ◽  
Quantitative Image ◽  
Hematoxylin And Eosin ◽  
Mitotic Figures

Uveal melanoma cells were inoculated into the choroid of nude mice and treated with or without intraocular injection of zeaxanthin. After 21 days, mice were sacrificed and the eyes enucleated. Histopathological analysis was performed in hematoxylin and eosin stained frozen sections. Melanoma developed rapidly in the control group (without treatment of zeaxanthin). Tumor-bearing eye mass and tumor mass in the control group were significantly greater than those in zeaxanthin treated group. Melanoma in the controlled eyes occupied a large part of the eye, was epithelioid in morphology, and was with numerous mitotic figures. Scleral perforation and extraocular extension were observed in half of the eyes. Melanomas in zeaxanthin treated eyes were significantly smaller with many necrosis and apoptosis areas and no extraocular extension could be found. Quantitative image analysis revealed that the tumor size was reduced by 56% in eyes treated with low dosages of zeaxanthin and 92% in eyes treatment with high dosages of zeaxanthin, as compared to the controls. This study demonstrated that zeaxanthin significantly inhibits the growth and invasion of human uveal melanoma in nude mice, suggesting that zeaxanthin may be a promising agent to be explored for the prevention and treatment of uveal melanoma.

Mouse testicular transcriptome after modulation of non-canonical oestrogen receptor activity

2020 ◽  
Vol 32 (10) ◽  
pp. 903
Author(s):  
M. Duliban ◽  
A. Gurgul ◽  
T. Szmatola ◽  
P. Pawlicki ◽  
A. Milon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Oestrogen Receptor ◽  
Protein Modification ◽  
Ring Finger ◽  
Bioinformatic Analysis ◽  
Treated Group ◽  
Receptor Activity ◽  
Control Group ◽  
Genetic Changes ◽  
Expression Of Genes

The aims of this study were to shed light on the role of G-protein-coupled membrane oestrogen receptor (GPER) and oestrogen-related receptor (ERR) in mouse testis function at the gene expression level, as well as the involvement of GPER and ERR in cellular and molecular processes. Male mice were injected (50µg kg−1,s.c.) with the GPER antagonist G-15, the ERRα inverse agonist XCT790 or the ERRβ/ERRγ agonist DY131. Next-generation sequencing (RNA-Seq) was used to evaluate gene expression. Bioinformatic analysis of read abundance revealed that 50, 86 and 171 transcripts were differentially expressed in the G-15-, XCT790- and DY131-treated groups respectively compared with the control group. Annotated genes and their protein products were categorised regarding their associated biological processes and molecular functions. In the XCT790-treated group, genes involved in immunological processes were upregulated. In the DY131-treated group, genes with increased expression were primarily engaged in protein modification (protein folding and small protein conjugation). In addition, the expression of genes recognised as oncogenes, such as BMI1 proto-oncogene, polycomb ring finger (Bmi1) and nucleophosphin 1 (Npm1), was significantly increased in all experimental groups. This study provides detailed information regarding the genetic changes in the testicular transcriptome of the mouse in response to modulation of non-canonical oestrogen receptor activity.

scholarly journals Expression of the metastasis suppressor gene KISS1 in uveal melanoma

Eye ◽  
2008 ◽  
Vol 22 (5) ◽  
pp. 707-711 ◽  
Author(s):  
C M O Martins ◽  
B F Fernandes ◽  
E Antecka ◽  
S Di Cesare ◽  
J J C Mansure ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Suppressor Gene ◽  
Metastasis Suppressor ◽  
Metastasis Suppressor Gene

Tryptophan-Niacin Metabolism in Rat with Puromycin Aminonucleoside-Induced Nephrosis

2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Enzyme Activities ◽  
Treated Group ◽  
Control Group ◽  
Puromycin Aminonucleoside ◽  
Low Level ◽  
Key Enzyme

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.

Haemostatic Clot Formation at Anastomosis of Synthetic Venous Graft in Defibrinogenated Dogs: A Scanning Electron Microscopic Study

1981 ◽  
Vol 45 (03) ◽  
pp. 276-281 ◽  
Author(s):  
S Ishimaru ◽  
E Berglin ◽  
H-A Hansson ◽  
A-C Teger-Nilsson ◽  
G William-Olsson
Keyword(s):  
Vena Cava ◽  
Treated Group ◽  
Control Group ◽  
Electron Microscopic ◽  
Scanning Electron Microscopic Study ◽  
Fibrin Network ◽  
Scanning Electron Microscopic ◽  
Expanded Polytetrafluoroethylene Graft ◽  
Morphological Differences ◽  
Scanning Electron

SummaryA segment of the inferior vena cava was replaced by an expanded polytetrafluoroethylene graft in 13 dogs. Five of them served as a control group, while the other 8 were moderately or severely defibrinogenated with subcutaneous batroxobin. Plasma fibrinogen decreased to extremely low values throughout the experiment in the defibrinogenated dogs except in the moderately treated group in which it temporarily rose to 0.72-0.87 g/1 on the first postoperative day.Scanning electron microscopic observations of the haemostatic clot formed at the anastomoses of the graft revealed no significant morphological differences in platelet adhesion and/or aggregation between the three groups. These findings confirmed that platelets play a key role in primary haemostasis during defibrinogenation.The fibrin network was slightly diminished and only short fibrin filaments could be seen in the moderately and severely defibrinogenated groups respectively. These differences in composition of the clots are discussed in relation to their haemostatic capacity.

Effects of oestradiol benzoate (OeB) and human chorionic gonadotrophin (hCG) on the testes and accessory sex glands of the rat

1981 ◽  
Vol 96 (2) ◽  
pp. 273-280 ◽  
Author(s):  
Mridula Chowdhury ◽  
Robert Tcholakian ◽  
Emil Steinberger
Keyword(s):  
Treated Group ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Control Group ◽  
Intact Male ◽  
Intact Control ◽  
Testosterone Levels ◽  
Oestradiol Benzoate ◽  
Direct Inhibitory Effect

Abstract. It has been suggested that treatment of intact male rats with oestradiol benzoate (OeB) causes an interference with testosterone (T) production by the testes by a direct inhibitory effect on steroidogenesis. To test this hypothesis, different doses (5, 10 or 25 IU) of hCG were administered concomitantly with 50 μg of OeB to adult intact or hypophysectomized male rats. The testicular and plasma testosterone, and serum hCG levels were determined. The sex accessory weights were recorded. In the intact OeB-treated group of animals, hCG stimulated both the secondary sex organs and plasma testosterone levels above the intact control group. However, in hypophysectomized animals, although plasma testosterone levels increased above that of intact controls, their secondary sex organ weights did not. Moreover, inspite of high circulating hCG levels, the testicular testosterone content and concentration remained suppressed in OeB-treated animals. The reason for such dichotomy of hCG action on OeB-treated animals is not clear at present.

Evaluation of anti-psoriatic activity of selected phytochemicals on UV-induced psoriasis in mouse tail model

2020 ◽  
Vol 64 ◽  
pp. 123-128
Author(s):  
Jada Naga Lakshmi ◽  
A. Narendra Babu ◽  
Rama Rao Nadendla
Keyword(s):  
Disease Control ◽  
Ellagic Acid ◽  
Uv Light ◽  
Severity Index ◽  
Treated Group ◽  
Control Group ◽  
Standard Group ◽  
Significant Activity ◽  
Epidermal Thickness ◽  
Psoriasis Severity

Objectives: To evaluate anti-psoriatic activity of Phytochemicals on UV-Induced psoriasis in mouse tail model. Materials and Methods: Anti-psoriatic activity of selected phytochemicals on UV-Induced psoriasis in mouse tail model. The animals were dividing into 05 groups and each group contain 5 animals. Disease control group did not receive any treatment only exposure to UV-light, vehicle control treated with simple ointment, standard group treated with salicylic acid (1%w/w) ointment, remaining group are treated 1% and 2% selective phytochemical at two concentrations of ointment to topically on the tail skin. And the data were analysed using one way ANOVA followed by two-way ANOVA (Dunnett’s multiple comparisons test). Results: There was significant decrease in epidermal thickness (P < 0.05) as compared with control group. In 2% phytoconstituents has shown a significant reduction in the total epidermal thickness 8.4****±0.748, 7.6**±0.6781 and 8*±0.8366 in geraniol, glycyrrhizic acid and ellagic acid treated group, when compare to the disease induced animal, there was no lesion of Munro’s microabscess, capillary loop dilation along with elongation of rete ridges in the section of skin of rats. Psoriasis Severity Index was reduced in test treated groups as compared with that of disease control group. It was slowly reduced to 2nd week, totally (55-70%) reduction in PSI is observed at the time of third week of treatment period. Conclusion: The result of the study showed that the 2% of geraniol, ellagic acid, glycyrrhizicacid and hesperidin, exhibited significant activity on UV-induced psoriasis in rodents. The study implies that selected phytoconstituents are a promising research for further investigations to prove its anti-psoriatic activity.

Protective Effect of Moringa Oleifera Leaves Against TramadolInduced Nephrotoxicity in Mice

2017 ◽  
Vol 9 (02) ◽  
Author(s):  
Ashraf Albrakati
Keyword(s):  
Oral Dose ◽  
Moringa Oleifera ◽  
Treated Group ◽  
Control Group ◽  
Serum Urea ◽  
Kidney Function Tests ◽  
Mean Values ◽  
Intraperitoneal Dose ◽  
Moringa Oleifera Leaves ◽  
The Mean

Tramadol, a broadly in recent years, is an effective analgesic agent for the treatment of moderate to acute pain. Its metabolites are excreted by the kidney which may cause nephrotoxicity. Moringa oleifera leaves are commonly used to provide herbal and plant-derived medicinal products especially in developing nations. The present study was carried out to determine the biochemical and histopathological changes in the kidney of tramadol-treated albino mice and to evaluate the possible protective role of Moringa oleifera leaves against tramadol-induced nephrotoxicity. Twenty adult albino mice were divided into four groups. Control group (group i) received daily intraperitoneal injection of normal saline only, group ii received oral dose of Moringa oleifera leaves extract (20 mg/kg/bw) for three weeks, group iii received daily intraperitoneal dose of tramadol (0.3 mg/kg/bw) for the same period, group iv, received daily oral dose of Moringa oleifera leaves extract, (20 mg/kg/bw) three hours before injecting intraperitoneal dose of tramadol (0.3 mg/kg/bw), for the same period. Blood samples were withdrawn at the end of the experiment for kidney function tests and specimens from the kidney were processed for histological study. No significant differences in the mean values of the kidney function tests were noticed between Moringa oleifera group and control group. However, there was highly significant increase in the mean values of serum, urea and creatinine in tramadol-treated group as compared to the control group. Although tramadol + Moringa oleifera group revealed significant difference in the mean values of urea and creatinine when compared with tramadol-treated group. So, Moringa oleifera leaves extract have been shown to attenuate the renal dysfunction, improve the renal architecture, with nearly normalization of serum urea and creatinine levels which indicate improvement of renal function. In conclusion, in the light of biochemical results and histological findings, co-administration of Moringa oleifera leaves lessened the negative effects of tramadol-induced nephrotoxicity; possibly by its antioxidant action. Further investigation of these promising protective effects of Moringa oleifera leaves against tramadol-induced renal injury may have considerable impact on developing an adjunct therapy aiming to improve the therapeutic index of some nephrotoxic drugs.

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