scholarly journals Chronic Glibenclamide Treatment Attenuates Walker-256 Tumour Growth in Prediabetic Obese Rats

2017 ◽  
Vol 42 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Claudinéia Conationi da Silva Franco ◽  
Carina Previate ◽  
Kátia Gama de Barros Machado ◽  
Silvano Piovan ◽  
Rosiane Aparecida Miranda ◽  
...  
Keyword(s):  
Tumour Growth ◽  
Tumour Cells ◽  
Diabetic Patients ◽  
Adult Rats ◽  
Walker 256 Tumour ◽  
Tumour Growth Inhibition ◽  
Walker 256 ◽  
Growth Methods ◽  
Tumour Weight

Background/Aims: The sulphonylurea glibenclamide (Gli) is widely used in the treatment of type 2 diabetes. In addition to its antidiabetic effects, low incidences of certain types of cancer have been observed in Gli-treated diabetic patients. However, the mechanisms underlying this observation remain unclear. The aim of the present work was to evaluate whether obese adult rats that were chronically treated with an antidiabetic drug, glibenclamide, exhibit resistance to rodent breast carcinoma growth. Methods: Neonatal rats were treated with monosodium L-glutamate (MSG) to induce prediabetes. Control and MSG groups were treated with Gli (2 mg/kg body weight/day) from weaning to 100 days old. After Gli treatment, the control and MSG rats were grafted with Walker-256 tumour cells. After 14 days, grafted rats were euthanized, and tumour weight as well as glucose homeostasis were evaluated. Results: Treatment with Gli normalized tissue insulin sensitivity and glucose tolerance, suppressed fasting hyperinsulinaemia, reduced fat tissue accretion in MSG rats, and attenuated tumour growth by 27% in control and MSG rats. Conclusions: Gli treatment also resulted in a large reduction in the number of PCNA-positive tumour cells. Although treatment did improve the metabolism of pre-diabetic MSG-rats, tumour growth inhibition may be a more direct effect of glibenclamide.

scholarly journals Moderate exercise training since adolescence reduces Walker 256 tumour growth in adult rats

2019 ◽  
Vol 597 (15) ◽  
pp. 3905-3925 ◽  
Author(s):  
Veridiana Mota Moreira ◽  
Douglas Almeida ◽  
Claudinéia Conationi da Silva Franco ◽  
Rodrigo Mello Gomes ◽  
Kesia Palma‐Rigo ◽  
...  
Keyword(s):  
Exercise Training ◽  
Tumour Growth ◽  
Moderate Exercise ◽  
Adult Rats ◽  
Walker 256 Tumour ◽  
Walker 256 ◽  
Moderate Exercise Training

scholarly journals The Fate of Circulating Walker 256 Tumour Cells injected Intravenously in Rats

1963 ◽  
Vol 17 (3) ◽  
pp. 546-557 ◽  
Author(s):  
J D Griffiths ◽  
A J Salsbury
Keyword(s):  
Tumour Cells ◽  
Walker 256 Tumour ◽  
Walker 256

scholarly journals Metformin Impairs Glutamine Metabolism and Autophagy in Tumour Cells

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 49 ◽  
Author(s):  
Serena Saladini ◽  
Michele Aventaggiato ◽  
Federica Barreca ◽  
Emanuela Morgante ◽  
Luigi Sansone ◽  
...  
Keyword(s):  
Apoptotic Cell ◽  
Tumour Cells ◽  
Glutamine Metabolism ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Ammonia Accumulation ◽  
Tumour Cell Lines ◽  
Type 2 Diabetic ◽  
Treated Tumour

Metformin has been shown to inhibit glutaminase (GLS) activity and ammonia accumulation thereby reducing the risk of hepatic encephalopathy in type 2 diabetic patients. Since tumour cells are addicted to glutamine and often show an overexpression of glutaminase, we hypothesize that the antitumoral mechanism of metformin could be ascribed to inhibition of GLS and reduction of ammonia and ammonia-induced autophagy. Our results show that, in different tumour cell lines, micromolar doses of metformin prevent cell growth by reducing glutamate, ammonia accumulation, autophagy markers such as MAP1LC3B-II and GABARAP as well as degradation of long-lived proteins. Reduced autophagy is then accompanied by increased BECN1/BCL2 binding and apoptotic cell death. Interestingly, GLS-silenced cells reproduce the effect of metformin treatment showing reduced MAP1LC3B-II and GABARAP as well as ammonia accumulation. Since metformin is used as adjuvant drug to increase the efficacy of Cisplatin-based neoadjuvant chemotherapy, we co-treated tumour cells with micromolar doses of metformin in the presence of cisplatin observing a marked reduction of MAP1LC3B-II and an increase of caspase 3 cleavage. In conclusion, our work demonstrates that the anti-tumoral action of metformin is due to the inhibition of glutaminase and autophagy and could be used to improve the efficacy of chemotherapy.

Walker 256 tumour growth causes marked changes of glutamine metabolism in rat small intestine

2002 ◽  
Vol 20 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Manuela M. Ramos Lima ◽  
Maria Alice R. de Mello ◽  
Rui Curi
Keyword(s):  
Small Intestine ◽  
Tumour Growth ◽  
Glutamine Metabolism ◽  
Rat Small Intestine ◽  
Walker 256 Tumour ◽  
Walker 256

scholarly journals Walker-256 Tumour-Induced Cachexia Altered Liver Metabolomic Profile and Function in Weanling and Adult Rats

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 831
Author(s):  
Natália Angelo da Silva Miyaguti ◽  
Gabriela de Matuoka e Chiocchetti ◽  
Carla de Moraes Salgado ◽  
Leisa Lopes-Aguiar ◽  
Lais Rosa Viana ◽  
...  
Keyword(s):  
Young Adult ◽  
Cancer Cachexia ◽  
Liver Lipid ◽  
Preclinical Model ◽  
Energy Status ◽  
Advanced Cancer Patients ◽  
Adult Rats ◽  
Tumour Bearing ◽  
Walker 256 Tumour ◽  
Walker 256

Cancer cachexia occurs in up to 85% of advanced cancer patients, affecting different tissues and organs, mainly the liver, which plays a central role in body metabolism control. However, liver responses to cancer cachexia progression are still poorly understood. Considering the possible different challenges provided by the rodent’s phase of life and the cachexia progression, we evaluated the liver metabolic alterations affected by Walker-256 tumour growth in weanling and young-adult rats. For this, we applied a metabolomics approach associated with protein and gene expression analyses. Higher amino acid levels and impaired glucose metabolism were important features in tumour-bearing animals’ liver tissue. The weanling hosts had more pronounced cachexia, with higher carcass spoliation, liver lipid metabolism and impaired CII and CIV mitochondrial complexes. The liver alterations in young adult tumour-bearing rats were related to energy status and nucleotide metabolites, such as uridine, NAD+, xanthosine, hypoxanthine and inosine. In conclusion, the Walker-256 tumour-induced cachexia impaired liver metabolism, being more severe in the weanling hosts. Further studies are needed to correlate these changes in the preclinical model, which can be correlated to the clinical features of cancer cachexia, allowing for a translational potential involving the liver function and its responses to potential treatments.

Vitamin D3 supplementation improves glycemic control in type 2 diabetic patients: Results from an Italian clinical trial

2020 ◽  
pp. 1-10
Author(s):  
Giuseppe Derosa ◽  
Angela D’Angelo ◽  
Chiara Martinotti ◽  
Maria Chiara Valentino ◽  
Sergio Di Matteo ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Metabolic Control ◽  
Vitamin D3 ◽  
Therapy Group ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Abstract. Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60 mmol/mol to 7.1% or 54 mmol) at 6 months compared to baseline, and to placebo (p < 0.05 for both). At the end of the study period, we noticed a change in the amount in doses of oral or subcutaneous hypoglycemic agents and insulin, respectively. The use of metformin, acarbose, and pioglitazone was significantly lower (p = 0.037, p = 0.048, and p = 0.042, respectively) than at the beginning of the study in the Vitamin D3 therapy group. The units of Lispro, Aspart, and Glargine insulin were lower in the Vitamin D3 group at the end of the study (p = 0.031, p = 0.037, and p = 0.035, respectively) than in the placebo group. Conclusions: in type 2 diabetic patients with Vitamin D deficiency, the restoration of value in the Vitamin D standard has led not only to an improvement in the glyco-metabolic compensation, but also to a reduced posology of some oral hypoglycemic agents and some types of insulin used.

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