Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
Más filtros










Intervalo de año de publicación
1.
PLoS One ; 19(4): e0301379, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38648220

RESUMEN

While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty.


Asunto(s)
Caquexia , Doxorrubicina , Fragilidad , Ratones Endogámicos C57BL , Músculo Esquelético , Sarcopenia , Animales , Doxorrubicina/efectos adversos , Caquexia/inducido químicamente , Caquexia/etiología , Sarcopenia/inducido químicamente , Sarcopenia/patología , Ratones , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Masculino , Fuerza Muscular/efectos de los fármacos , Atrofia Muscular/inducido químicamente , Atrofia Muscular/patología , Pérdida de Peso/efectos de los fármacos , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/toxicidad
2.
Clin. transl. oncol. (Print) ; 24(12): 2366-2378, dec. 2022.
Artículo en Inglés | IBECS | ID: ibc-216083

RESUMEN

Purpose Papillary thyroid carcinoma (PTC) is the most frequent subtype of thyroid cancer; Hashimoto's thyroiditis (HT), autoimmune disease, commonly affects the thyroid gland; there is possibly a correlation between both, but the exact mechanisms that involve this relationship are still under debate. Since oxidative stress (OS) and the inflammatory environment participate in the development of several types of cancer, the objective of the present study was to establish the microenvironment and systemic participation of OS and inflammatory markers in patients with PTC and HT. Methods Blood and tissue samples were collected from 115 patients: BENIGN (n = 63); PTC (n = 27); HT (n = 15) and PTC + HT (n = 10), and sixty-three were samples from healthy individuals (control group). Results Superoxide dismutase, Catalase, reduced Glutathione, markers of lipid peroxidation and inflammation were evaluated in blood. Immunohistochemistry was performed on 3-nitrotyrosine, 4-hydroxynonenal, Ki-67 and VEGF. The results indicate that antioxidant enzymes were more active in groups with thyroid disorders compared to control, while the concentration of Reduced glutathione was reduced in BENIGN and PTC groups. When PTC and PTC + HT groups were analyzed, no significant differences were found in relation to the antioxidant defense and inflammatory markers. The ability to contain the induced lipid peroxidation was lower and a high level of malondialdehyde was observed in the PTC group. All immunohistochemical markers had higher scores in the PTC group compared to PTC + HT. Conclusion There was a more pronounced presence of OS and a greater activity of cell proliferation and angiogenesis markers in PTC than in PTC + HT group (AU)


Asunto(s)
Humanos , Carcinoma Papilar/patología , Enfermedad de Hashimoto/complicaciones , Cáncer Papilar Tiroideo/patología , Antioxidantes , Catalasa , Glutatión , Antígeno Ki-67 , Malondialdehído , Estrés Oxidativo , Superóxido Dismutasa , Microambiente Tumoral , Factor A de Crecimiento Endotelial Vascular/metabolismo
3.
Front Oncol ; 12: 880787, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35847939

RESUMEN

Purpose: Although the role of signal transducers and activators of transcription (STAT3) in cachexia due to the association of circulating IL-6 and muscle wasting has been extensively demonstrated, the effect of resistance training on STAT3 in mediating muscle atrophy in tumor-bearing mice is unknown. The aim of this study is to investigate the effects of resistance exercise training on inflammatory cytokines and oxidative-mediated STAT3 activation and muscle loss prevention in tumor-bearing mice. Methods: Male Swiss mice were inoculated with Ehrlich tumor cells and exposed or not exposed to resistance exercise protocol of ladder climbing. Skeletal muscle STAT3 protein content was measured, compared between groups, and tested for possible association with plasma interleukins and local oxidative stress markers. Components of the ubiquitin-proteasome and autophagy pathways were assessed by real-time PCR or immunoblotting. Results: Resistance training prevented STAT3 excessive activation in skeletal muscle mediated by the overabundance of plasma IL-6 and muscle oxidative stress. These mechanisms contributed to preventing the increased key genes and proteins of ubiquitin-proteasome and autophagy pathways in tumor-bearing mice, such as Atrogin-1, LC3B-II, and Beclin-1. Beyond preventing muscle atrophy, RT also prevented strength loss and impaired locomotor capacity, hallmarks of sarcopenia. Conclusion: Our results suggest that STAT3 inhibition is central in resistance exercise protective effects against cancer-induced muscle atrophy and strength loss.

4.
Clin Transl Oncol ; 24(12): 2366-2378, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35902455

RESUMEN

PURPOSE: Papillary thyroid carcinoma (PTC) is the most frequent subtype of thyroid cancer; Hashimoto's thyroiditis (HT), autoimmune disease, commonly affects the thyroid gland; there is possibly a correlation between both, but the exact mechanisms that involve this relationship are still under debate. Since oxidative stress (OS) and the inflammatory environment participate in the development of several types of cancer, the objective of the present study was to establish the microenvironment and systemic participation of OS and inflammatory markers in patients with PTC and HT. METHODS: Blood and tissue samples were collected from 115 patients: BENIGN (n = 63); PTC (n = 27); HT (n = 15) and PTC + HT (n = 10), and sixty-three were samples from healthy individuals (control group). RESULTS: Superoxide dismutase, Catalase, reduced Glutathione, markers of lipid peroxidation and inflammation were evaluated in blood. Immunohistochemistry was performed on 3-nitrotyrosine, 4-hydroxynonenal, Ki-67 and VEGF. The results indicate that antioxidant enzymes were more active in groups with thyroid disorders compared to control, while the concentration of Reduced glutathione was reduced in BENIGN and PTC groups. When PTC and PTC + HT groups were analyzed, no significant differences were found in relation to the antioxidant defense and inflammatory markers. The ability to contain the induced lipid peroxidation was lower and a high level of malondialdehyde was observed in the PTC group. All immunohistochemical markers had higher scores in the PTC group compared to PTC + HT. CONCLUSION: There was a more pronounced presence of OS and a greater activity of cell proliferation and angiogenesis markers in PTC than in PTC + HT group.


Asunto(s)
Carcinoma Papilar , Enfermedad de Hashimoto , Neoplasias de la Tiroides , Antioxidantes , Carcinoma Papilar/patología , Catalasa , Glutatión , Enfermedad de Hashimoto/complicaciones , Humanos , Antígeno Ki-67 , Malondialdehído , Estrés Oxidativo , Superóxido Dismutasa , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , Microambiente Tumoral , Factor A de Crecimiento Endotelial Vascular/metabolismo
5.
Bioorg Chem ; 120: 105576, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34979447

RESUMEN

OBJECTIVE: Caffeine has been studied as a potentiating agent in chemotherapy against some types of cancer, but there are few reports on its effects on melanoma. This study aimed to investigate caffeine's ability to enhance the effects of dacarbazine in vitro. MATERIALS AND METHODS: Murine melanoma B16F10 cells were treated 24 h with 1-40 µM caffeine. We evaluated cytotoxicity, DNA damage, apoptosis, and oxidative lesion induced by dacarbazine associated with caffeine. The metabolization of these drugs, as well as immunocytochemical labeling, were also evaluated. CONCLUSIONS: The pre-treatment with caffeine showed to be more effective. Caffeine potentiated dacarbazine-induced cytotoxic effects by increasing dacarbazine biotransformation, apoptosis, DNA damage, and malondialdehyde levels; also, caffeine reduced Ki67 and ERK1/2 nuclear labeling and increased p53 labeling in B16F10 cells. In our experiment, caffeine promoted modifications associated with dacarbazine metabolism by viable cells potentiating this antineoplastic drug. These promising results should be further evaluated in experimental models in vivo.


Asunto(s)
Antineoplásicos , Melanoma , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Cafeína/farmacología , Línea Celular Tumoral , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Melanoma/tratamiento farmacológico , Ratones
6.
Nutr Cancer ; 73(8): 1378-1388, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32691663

RESUMEN

To investigate the effects of caffeine on the proliferation and death of human breast cancer cells MCF-7 and MDA-MB-231. Cells were exposed to 1, 2.5, 5 and 10 mM of caffeine during 24 h, and oxidative stress (OS), cell proliferation and death, metabolic activity and DNA lesions were evaluated in the collected samples. Caffeine was cytotoxic to the cell lines analyzed, reducing cell proliferation and viability by interfering with the cellular metabolism and with lysosomal function. Although the cells presented different behaviors to treatment, in both cell lines, the drug induced OS and predominantly apoptosis. MCF-7 cells responded to OS induction (lipid peroxidation) increasing their antioxidant defenses. However, the OS generated induced oxidative DNA lesions, a finding not observed in MDA-MB-231 cells. The association of different scavengers with caffeine did not result in the recovery of cell viability, which suggests that it is not possible to attribute the caffeine induction of OS to only one of the specific ROS analyzed (superoxide anion, singlet oxygen and peroxyl radical). These results are promising and suggest that caffeine may be a good target for studies to prove its usefulness as an adjuvant in breast cancer treatment.


Asunto(s)
Neoplasias de la Mama , Cafeína , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Cafeína/farmacología , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Células MCF-7 , Estrés Oxidativo
7.
J Dermatol Sci ; 100(2): 152-155, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33051086
8.
Pathol Res Pract ; 216(11): 153199, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32932214

RESUMEN

The ability to evade apoptosis is an important mechanism of drug resistance and tumor progression in breast cancer. The induction of different pathways of cell death could be an important strategy to limit tumor progression. Metformin, a drug used to treat type two diabetes, has demonstrated promising results in breast cancer experiments. However, little is known about the patterns of cell death induced by this drug. We analyzed the involvement of apoptosis, necroptosis and ferroptosis in the toxicity of metformin in MCF-7 cells, evaluating proliferation, viability and oxidative stress. It was used different inhibitors of cell death: Z-VAD, a pan-caspase inhibitor that blocks apoptosis; Necrostatin-1, which inhibits RIPK1 activity and blocks necroptosis; and the iron chelator, deferoxamine, that chelates iron and prevents ferroptosis. The participation of oxidative stress was analyzed through the evaluation of total thiols, reduced glutathione (GSH) and malondialdehyde (MDA). Our results showed that metformin increased cell death, reduced proliferation, thiol and GSH and increased MDA in cells. After the association between metformin and Z-VAD or Necrostatin-1, the drug toxicity was abolished. Ferroptosis did not significantly enrolled in metformin action against MCF-7 cells. The preservation of cellular antioxidants was found in all situations that cell death was blocked. Together, these results reveals that metformin induces necroptosis and apoptosis in MCF-7 cells and oxidative stress generation play a role in these two pathways of cell death. This information could help future studies to improve strategies to breast cancer treatment.


Asunto(s)
Apoptosis/efectos de los fármacos , Ferroptosis/efectos de los fármacos , Hipoglucemiantes/farmacología , Metformina/farmacología , Necroptosis/efectos de los fármacos , Glutatión/metabolismo , Humanos , Células MCF-7 , Malondialdehído/metabolismo , Oligopéptidos/farmacología , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Sulfhidrilo/metabolismo
9.
Pathol Res Pract ; 216(9): 153098, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32825964

RESUMEN

Thyroid cancer (TC) is the most prevalent malignant neoplasm that affects the endocrine system. Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is the most common autoimmune thyroid disease (AITD) that, together with Graves' disease (GD), represent the main autoimmune diseases that affect the thyroid gland. Some studies suggest a greater risk of AITD and the development of TC, while others, investigate its relationship with TC progression and patient prognosis. In this review, we have analyzed published data on the molecular aspects related to the association between AITD and TC, addressing their influence on TC progression, diagnosis, and prognosis of the patients. MEDLINE database (PubMed) platform was used as a search engine and the original articles related to the topic were selected using the keywords combination "thyroid cancer and Hashimoto thyroiditis" or "thyroid carcinoma and thyroid autoimmune disease". After the selection, we categorized the main findings of the papers into four topics: antitumor immunity, tumor progression, diagnosis, and prognosis. Although most of the studies have pointed out the presence of AITD as a factor that increases the risk of TC, few molecular mechanisms to support this conclusion have been described. Additionally, little information is available to explain, pathophysiologically, the effects of autoimmunity in TC diagnosis, progression, and prognosis.


Asunto(s)
Enfermedades Autoinmunes/genética , Enfermedad de Graves/inmunología , Enfermedad de Hashimoto/inmunología , Neoplasias de la Tiroides/patología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Predisposición Genética a la Enfermedad/genética , Enfermedad de Graves/patología , Enfermedad de Hashimoto/patología , Humanos , Glándula Tiroides/inmunología , Glándula Tiroides/patología , Neoplasias de la Tiroides/inmunología
10.
J Photochem Photobiol B ; 198: 111565, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31374350

RESUMEN

The incidence of skin cancers has increased worldwide, requiring more prevention of this type of cancer. The use of sunscreen and the control of the time of exposure to sunlight are the recognized forms of prevention. However, new substances have been researched in order to develop formulations with more efficient protective activity. Citral is a natural compound with lemon scent that is used in food and cosmetic industries. The present work evaluated the chemoprotective effect of citral during UVB-induced skin carcinogenesis. Male hairless mice HRS/J, 8-12 weeks old, were exposed to UVB irradiation for 24 weeks, with a cumulative radiation dose of 13.875 J/cm2. Citral (0.1, 0.5 and 1%) was applied to the skin at a dosage of 0.1 g/animal, 5 min after UVB exposure. At the end of the experiment, the number of lesion/animal, and size of lesions were measured. The histological sections of the skin were evaluated for the presence and intensity of actinic keratosis and squamous cell carcinoma. TUNEL assay was performed for apoptosis evaluation. Skin samples were used for the measurement of oxidative stress parameters (total radical-trapping antioxidant parameter of skin, glutathione, catalase activity and malondialdehyde), and cytokines levels (IL-1ß, IL-4, IL-10, IL-23, TNF-α, and IFNγ). Citral 1% completely inhibited UVB-induced skin carcinogenesis by reducing levels of oxidative stress and pro-inflammatory cytokines, increasing apoptotic rate in the skin.


Asunto(s)
Carcinoma de Células Escamosas/patología , Monoterpenos/farmacología , Neoplasias Cutáneas/patología , Piel/efectos de los fármacos , Rayos Ultravioleta , Monoterpenos Acíclicos , Animales , Antioxidantes/metabolismo , Carcinoma de Células Escamosas/prevención & control , Catalasa/metabolismo , Citocinas/metabolismo , Glutatión/metabolismo , Queratosis/patología , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Pelados , Monoterpenos/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Piel/metabolismo , Piel/efectos de la radiación , Neoplasias Cutáneas/prevención & control
11.
Nutrition ; 66: 122-130, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31265967

RESUMEN

OBJECTIVE: The aim of this study was to investigate the effects of creatine supplementation on early stages of ethanol-induced hepatic damage. METHODS: Male Swiss mice were divided into three groups (n = 12/group): control (C), ethanol (E), and ethanol supplemented with creatine (EC). The control group received a diet containing 15.8% of total calories from proteins, 46.3% from carbohydrates, and 37.9% from lipids. The ethanol and ethanol and creatine groups received diets containing 15.8% of total calories from proteins, 16.2% from carbohydrates, and 34.5% from lipids; the remaining calories were obtained from the addition of 5% of 95% ethanol. Creatine (1%; weight/vol) was added to the diet of EC mice. After 14 and 28 d, six animals from each group were sacrificed, generating subdivisions in each group: C14 and C28, E14 and E28, EC14 and EC28. After sacrifice, the liver was removed, weighed, and prepared for histologic, biochemical, and molecular analysis, and blood was collected. RESULTS: Ethanol intake induced mild cell degeneration, liver damage, oxidative lesions, and inflammation. Surprisingly, ethanol intake combined with creatine exacerbated cell degeneration and fat accumulation, hepatic expression of genes related to ethanol metabolism, oxidative stress and inflammation, and promoted oxidative stress and elevated plasma alanine aminotransferase (P < 0.05). CONCLUSION: Creatine supplementation associated with ethanol is able to interfere in the alcohol metabolism and oxidative stress and to exacerbate ethanol-induced hepatic damage. These new findings are opposite to those observed in several studies where protective effects of creatine in a wide variety of injury models, including non-alcoholic fatty liver disease, were described.


Asunto(s)
Creatina/farmacocinética , Suplementos Dietéticos , Etanol/metabolismo , Hepatopatías/metabolismo , Animales , Creatina/administración & dosificación , Modelos Animales de Enfermedad , Etanol/efectos adversos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hepatopatías/etiología , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos
12.
Sci Rep ; 9(1): 5864, 2019 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-30971831

RESUMEN

Metformin was shown to sensitize multidrug resistant breast cancer cells; however, the mechanisms involved in this capacity need to be clarified. We investigated oxidative stress and inflammatory-related pathways during the induction of doxorubicin resistance in MCF-7 and MDA-MB-231 human breast cancer cells (DOX-res group), and evaluated metformin-induced cellular responses that resulted in the prevention of doxorubicin resistance (Met-DOX group). Microarray analysis demonstrated that DOX-res changed the expression of genes involved in oxidative stress (OS) and the TGF- ß1 pathway. The DOX-res group presented increased thiols and reduced lipoperoxidation, increased levels of nitric oxide, nuclear NF-kB and Nrf2, and reduced nuclear p53 labelling. Analysis of the TGF-ß1 signaling pathway by RT-PCR array showed that DOX-res developed adaptive responses, such as resistance against apoptosis and OS. Metformin treatment modified gene expression related to OS and the IFN-α signaling pathway. The Met-DOX group was more sensitive to DOX-induced OS, presented lower levels of nitric oxide, nuclear NF-kB and Nrf2, and increased nuclear p53. Analysis of the IFN-α signaling pathway showed that Met-DOX presented more sensitivity to apoptosis and OS. Our findings indicate that metformin is a promising tool in the prevention of chemoresistance in patients with breast cancer submitted to doxorubicin-based treatments.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , Doxorrubicina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Metformina/farmacología , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Interferón-alfa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Células MCF-7 , Estrés Oxidativo/genética , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo
13.
J Photochem Photobiol B ; 195: 17-26, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31035030

RESUMEN

Cumulative ultraviolet (UV) exposure is associated with squamous skin cell carcinoma. UV radiation induces oxidative modifications in biomolecules of the skin leading to photocarcinogenesis. Indeed, the cyclobutene pyrimidine dimers and other dimers formed by photoaddition between carbon-carbon bonds also have an important role in the initiation process. However, information on the systemic redox status during these processes is scarce. Thus, we investigated the systemic redox profile in UVB-induced squamous cell carcinoma in mice. Female hairless mice were exposed to UVB radiation (cumulative dose = 17.1 J/cm2). The dorsal skin of these mice developed actinic keratosis (AK) and squamous cell carcinoma (SCC) and presented increased levels of oxidative and nitrosative stress biomarkers (4-hydroxy-2-nonenal and 3-nitrotyrosine), and decreased antioxidant defenses. Systemically, we observed the consumption of plasmatic antioxidant defenses and increased levels of advanced oxidized protein products (AOPP), an oxidative stress product derived from systemic inflammatory response. Taken together, our results indicate that UVB chronic irradiation leads not only to adjacent and tumoral oxidative stress in the skin, but it systemically is reflected through the blood. These new findings clarify some aspects of the pathogenesis of SCC and should assist in formulating better chemoprevention strategies, while avoiding additional primary SCC development and metastasis.


Asunto(s)
Carcinoma de Células Escamosas/etiología , Estrés Oxidativo/efectos de la radiación , Neoplasias Cutáneas/etiología , Rayos Ultravioleta , Animales , Catalasa/metabolismo , Femenino , Glutatión/metabolismo , Productos Finales de Glicación Avanzada/sangre , Queratosis/etiología , Malondialdehído/sangre , Ratones , Ratones Pelados , Piel/patología , Piel/efectos de la radiación
14.
Tumour Biol ; 39(3): 1010428317695914, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28351318

RESUMEN

Citral is a natural compound that has shown cytotoxic and antiproliferative effects on breast and hematopoietic cancer cells; however, there are few studies on melanoma cells. Oxidative stress is known to be involved in all stages of melanoma development and is able to modulate intracellular pathways related to cellular proliferation and death. In this study, we hypothesize that citral exerts its cytotoxic effect on melanoma cells by the modulation of cellular oxidative status and/or intracellular signaling. To test this hypothesis, we investigated the antiproliferative and cytotoxic effects of citral on B16F10 murine melanoma cells evaluating its effects on cellular oxidative stress, DNA damage, cell death, and important signaling pathways, as these pathways, namely, extracellular signal-regulated kinases 1/2 (ERK1/2), AKT, and phosphatidylinositol-3 kinase, are involved in cell proliferation and differentiation. The p53 and nuclear factor kappa B were also investigated due to their ability to respond to intracellular stress. We observed that citral exerted antiproliferative and cytotoxic effects in B16F10; induced oxidative stress, DNA lesions, and p53 nuclear translocation; and reduced nitric oxide levels and nuclear factor kappa B, ERK1/2, and AKT. To investigate citral specificity, we used non-neoplastic human and murine cells, HaCaT (human skin keratinocytes) and NIH-3T3 cells (murine fibroblasts), and observed that although citral effects were not specific for cancer cells, non-neoplastic cells were more resistant to citral than B16F10. These findings highlight the potential clinical utility of citral in melanoma, with a mechanism of action involving the oxidative stress generation, nitric oxide depletion, and interference in signaling pathways related to cell proliferation.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Melanoma Experimental/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Monoterpenos/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Monoterpenos Acíclicos , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Humanos , Melanoma/metabolismo , Melanoma/patología , Melanoma Experimental/genética , Melanoma Experimental/patología , Ratones , FN-kappa B/genética , Células 3T3 NIH , Óxido Nítrico/metabolismo , Proteína p53 Supresora de Tumor/genética
15.
J Cancer Surviv ; 11(3): 339-349, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28054255

RESUMEN

PURPOSE: Muscle atrophy and strength decline are two of the most prominent characteristics in cancer patients undergoing cancer therapy, leading to decreased functional ability and reduced quality of life. Therefore, the aim is to systematically review research evidence of the effects of resistance exercise (RE) on lower-limb muscular strength, lean body mass (LBM), and body fat (BF) in cancer patients undertaking neoadjuvant or adjuvant therapy. METHODS: This research was conducted using the following online database: Clinical Trial Register, Cochrane Trial Register, PubMed, SPORT Discus, and SciELO, from September 2014 until May 2015. We used the following keywords in various combinations with a systematic search: "Cancer therapy," "Wasting muscle," "Muscle loss," "Muscle function," "Neoadjuvant therapy," "Adjuvant thera-py," "Resistance Training," "Weight training," and "Exercise." After selection of 272 full-text articles, 14 publications were included in this meta-analysis. RESULTS: Resistance exercise (RE) during neoadjuvant or adjuvant therapy increased lower-limb muscular strength (mean: 26.22 kg, 95% CI [16.01, 36.43], heterogeneity: P = <0.01, I 2 = 76%, P = 0.00001) when compared to controls over time. Similarly, lean body mass (LBM) increased (mean 0.8 kg, 95% CI [0.7, 0.9], heterogeneity: P = 0.99, I 2 = 0%, P < 0.00001), and decreased body fat (BF) (mean: -1.3 kg, 95% CI [-1.5, 1.1], heterogeneity: P = 0.93, I2 = 0%, P < 0.00001) compared to controls over time. CONCLUSION: RE is effective to increase lower-limb muscular strength, increase LBM, and decrease BF in cancer patients undergoing neoadjuvant and adjuvant therapy regardless of the kind of treatment. IMPLICATIONS FOR CANCER SURVIVORS: RE increases muscle strength, maintains LBM, and reduces BF in cancer patients undergoing adjuvant and neoadjuvant therapies. Cancer patients and survivors should consider undertaking RE as an effective countermeasure for treatment-related adverse effects to the musculoskeletal system.


Asunto(s)
Composición Corporal/fisiología , Terapia Neoadyuvante/métodos , Neoplasias/terapia , Entrenamiento de Fuerza/métodos , Femenino , Humanos , Masculino , Fuerza Muscular/fisiología
16.
Life Sci ; 162: 47-53, 2016 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-27523048

RESUMEN

AIMS: Well-characterized animal tumor models of cancer cachexia are warranted to elucidate underlying mechanisms and provide a better approach to the human scenario. We aimed to investigate whether solid Ehrlich carcinoma reproduces clinical, functional and biological conditions of tumor-induced cachexia in mice. METHODS: Eight-week old female Swiss mice were subcutaneously inoculated with Ehrlich tumor cells (tumor-bearing, TB group) or vehicle (sham) into the right flank and monitored for 28days. Tumor histopathological features and tumor-host interaction, including tissue weight, muscle structure, strength and biochemical parameters were carried out. KEY FINDINGS: Tumor growth curve demonstrated a linear pattern with no difference in final carcass weight between groups. A well-defined capsule composed by connective tissue infiltrated by inflammatory and neoplastic cells surrounded the tumors. The TB group had reduced handgrip strength, aside from lower cross sectional area (CSA) and critically reduced parametrial fat pads. Plasma parameters of lactate dehydrogenase (LDH), creatine kinase (CK) and tumor necrosis factor-α (TNF-α) were higher in the TB group, suggesting predominance of catabolic and pro-inflammatory activities. Conversely, food intake and tissue weight did not differ between groups. SIGNIFICANCE: Our data elucidated that the solid Ehrlich tumor model is feasible and effective in reproducing some of the relevant issues experienced by cancer patients with cachexia. The solid Ehrlich carcinoma emerges as an alternative tool against more aggressive cancer cachexia models during preclinical research.


Asunto(s)
Caquexia/patología , Carcinoma de Ehrlich/patología , Animales , Femenino , Xenoinjertos , Ratones
17.
Anticancer Res ; 36(8): 3795-802, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27466479

RESUMEN

The WT1 gene encodes a transcription factor involved in regulation of many cellular processes, including proliferation, differentiation, mRNA processing and apoptosis, besides acting as a transcription repressor of growth factors and their receptors' genes. This gene is expressed at high levels in several types of cancers, including acute leukemias. In this regard, many studies have identified WT1 protein as a tumor antigen, considered a target molecule for clinical application in human acute leukemias. Immunotherapy using WT1 antigen has been effective in stimulating immune responses against leukemic cells. Regarding adoptive immunotherapy, the use of dendritic cells (DCs) for the WT1-specific cytotoxic T cells generation proved to be efficient in the development and maintenance of immunologic cells. Therefore, these therapeutic methods, that provided enthusiasm for moving ahead, highlight several opportunities and challenges to be used in clinical practice for managing acute leukemias.


Asunto(s)
Antígenos de Neoplasias/genética , Inmunoterapia , Leucemia/terapia , Proteínas WT1/genética , Antígenos de Neoplasias/inmunología , Apoptosis/genética , Apoptosis/inmunología , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Proliferación Celular/genética , Células Dendríticas/inmunología , Humanos , Leucemia/genética , Leucemia/inmunología , Linfocitos T Citotóxicos/inmunología , Proteínas WT1/inmunología , Proteínas WT1/uso terapéutico
18.
Tumour Biol ; 37(8): 10753-61, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26873487

RESUMEN

TGF-ß1 and oxidative stress are involved in cancer progression, but in melanoma, their role is still controversial. Our aim was to correlate plasma TGF-ß1 levels and systemic oxidative stress biomarkers in patients with melanoma, with or without disease metastasis, to understand their participation in melanoma progression. Thirty patients were recruited for melanoma surveillance, together with 30 healthy volunteers. Patients were divided into two groups: Non-metastasis, comprising patients with tumor removal and no metastatic episode for 3 years; and Metastasis, comprising patients with a metastatic episode. The plasmatic cytokines TGF-ß1, IL-1 ß, and TNF-α were analyzed by ELISA. For oxidative stress, the following assays were performed: malondialdehyde (MDA), advanced oxidation protein products (AOPP) levels, total radical-trapping antioxidant parameter (TRAP) and thiol in plasma, and lipid peroxidation, SOD and catalase activity and GSH in erythrocytes. Patients with a metastatic episode had less circulating TGF-ß1 and increased TRAP, thiol, AOPP and lipid peroxidation levels. MDA was increased in both melanoma groups, while catalase, GSH, and IL-1ß was decreased in Non-metastasis patients. Significant negative correlations were observed between TGF-ß1 levels and systemic MDA, and TGF-ß1 levels and systemic AOPP, while a positive correlation was observed between TGF-ß1 levels and erythrocyte GSH. Lower levels of TGF-ß1 were related to increased oxidative stress in Metastasis patients, reinforcing new evidence that in melanoma TGF-ß1 acts as a tumor suppressor, inhibiting tumor relapse. These findings provide new knowledge concerning this cancer pathophysiology, extending the possibilities of investigating new therapies based on this evidence.


Asunto(s)
Melanoma/secundario , Proteínas de Neoplasias/sangre , Factor de Crecimiento Transformador beta1/sangre , Productos Avanzados de Oxidación de Proteínas/sangre , Antioxidantes/análisis , Biomarcadores , Catalasa/sangre , Citocinas/sangre , Progresión de la Enfermedad , Femenino , Disulfuro de Glutatión/sangre , Humanos , Peroxidación de Lípido , Masculino , Malondialdehído/sangre , Melanoma/sangre , Persona de Mediana Edad , Proteínas de Neoplasias/fisiología , Estrés Oxidativo , Compuestos de Sulfhidrilo/sangre , Superóxido Dismutasa/sangre , Factor de Crecimiento Transformador beta1/fisiología
19.
Tumour Biol ; 37(4): 5337-46, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26561471

RESUMEN

The participation of oxidative stress in the mechanism of metformin action in breast cancer remains unclear. We investigated the effects of clinical (6 and 30 µM) and experimental concentrations of metformin (1000 and 5000 µM) in MCF-7 and in MDA-MB-231 cells, verifying cytotoxicity, oxidative stress, DNA damage, and intracellular pathways related to cell growth and survival after 24 h of drug exposure. Clinical concentrations of metformin decreased metabolic activity of MCF-7 cells in the MTT assay, which showed increased oxidative stress and DNA damage, although cell death and impairment in the proliferative capacity were observed only at higher concentrations. The reduction in metabolic activity and proliferation in MDA-MB-231 cells was present only at experimental concentrations after 24 h of drug exposition. Oxidative stress and DNA damage were induced in this cell line at experimental concentrations. The drug decreased cytoplasmic extracellular signal-regulated kinases 1 and 2 (ERK1/2) and AKT and increased nuclear p53 and cytoplasmic transforming growth factor ß1 (TGF-ß1) in both cell lines. These findings suggest that metformin reduces cell survival by increasing reactive oxygen species, which induce DNA damage and apoptosis. A relationship between the increase in TGF-ß1 and p53 levels and the decrease in ERK1/2 and AKT was also observed. These findings suggest the mechanism of action of metformin in both breast cancer cell lineages, whereas cell line specific undergoes redox changes in the cells in which proliferation and survival signaling are modified. Taken together, these results highlight the potential clinical utility of metformin as an adjuvant during the treatment of luminal and triple-negative breast cancer.


Asunto(s)
Metformina/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Factor de Crecimiento Transformador beta1/biosíntesis , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta1/genética , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genética
20.
Cell Tissue Res ; 357(3): 803-14, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24842047

RESUMEN

The role of reactive oxygen species (ROS) in muscle protein hydrolysis and protein oxidation in thyrotoxicosis has not been explored. This study indicates that ROS play a role in skeletal muscle wasting pathways in thyrotoxicosis. Two experimental groups (rats) were treated for 5 days with either 3,3',5-triiodothyronine (HT) or HT with α-tocopherol (HT + αT). Two controls were used, vehicle (Control) and control treated with αT (Control + αT). Serum T3, peritoneal fat, serum glycerol, muscle and body weight, temperature, mitochondrial metabolism (cytochrome c oxidase activity), oxidative stress parameters and proteolytic activities were examined. High body temperature induced by HT returned to normal when animals were treated with αT, although total body and muscle weight did not. An increase in lipolysis was observed in the HT + αT group, as peritoneal fat decreased significantly together with an increase in serum glycerol. GSH, GSSG and total radical-trapping antioxidant parameter (TRAP) decreased and catalase activity increased in the HT group. The glutathione redox ratio was higher in HT + αT than in both HT and Control + αT groups. Carbonyl proteins, AOPP, mitochondrial and chymotrypsin-like proteolytic activities were higher in the HT group than in the Control. HT treatment with αT restored mitochondrial metabolism, TRAP, carbonyl protein, chymotrypsin-like activity and AOPP to the level as that of the Control + αT. Calpain activity was lower in the HT + αT group than in HT and Control + αT and superoxide dismutase (SOD) activity was higher in the HT + αT group than in the Control + αT. Although αT did not reverse muscle loss, ROS was involved in proteolysis to some degree.


Asunto(s)
Músculos/patología , Especies Reactivas de Oxígeno/metabolismo , Tirotoxicosis/patología , Síndrome Debilitante/patología , Animales , Antioxidantes/metabolismo , Peso Corporal/efectos de los fármacos , Calpaína/metabolismo , Citocromos c/metabolismo , Masculino , Malondialdehído/metabolismo , Músculos/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Ratas Wistar , Tirotoxicosis/complicaciones , Triyodotironina/sangre , Triyodotironina/farmacología , Síndrome Debilitante/complicaciones , alfa-Tocoferol/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...