Effect of infliximab on metabolic disorders induced by Walker-256 tumor in rats

Miksza, Daniele Romani; Souza, Camila Oliveira de; Morais, Hely de; Rocha, Aline Franco da; Borba-Murad, Glaucia Regina; Bazotte, Roberto Barbosa; Souza, Helenir Medri de

doi:10.1016/s1734-1140(13)71077-6

Cited by 14 publications

(14 citation statements)

References 47 publications

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“…Although the sedentary rats did not exhibit peripheral resistance to insulin during the tumor growth period in the present study, which has been evidenced in similar cancer models in the literature ( Asp et al, 2010 ; Miksza et al, 2013 ), we pointed out several aspects in the interpretation of results that should be considered, such as animal species, associated insults, inoculated tissue and volume, experimental time, cellular viability, exercise protocol, drug administration, among others. The highly variable biological due these environmental interactions ( Weiss and Harlos, 1979 ) and the lack of pure strains of cells, has been demonstrated long time ago, as a severe handicap to the study of malignant growths, particularly in Walker 256 tumor experimental model ( Earle, 1935 ; Moraes et al, 2000 ).…”

Section: Discussionsupporting

confidence: 65%

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats

et al. 2018

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Aerobic exercise training can improve insulin sensitivity in many tissues; however, the relationship among exercise, insulin, and cancer cell growth is unclear. We tested the hypothesis that aerobic exercise training begun during adolescence can attenuate Walker 256 tumor growth in adult rats and alter insulin secretion. Thirty-day-old male Wistar rats engaged in treadmill running for 8 weeks, 3 days/week, 44 min/day, at 55–65% VO2max until they were 90 days old (TC, Trained Control). An equivalently aged group was kept inactive during the same period (SC, Sedentary Control). Then, half the animals of the SC and TC groups were reserved as the control condition and the other half were inoculated with Walker 256 cancer cells, yielding two additional groups (Sedentary Walker and Trained Walker). Zero mortalities were observed in tumor-bearing rats. Body weight (BW), food intake, plasma glucose, insulin levels, and peripheral insulin sensitivity were analyzed before and after tumor cell inoculation. We also evaluated tumor growth, metastasis and cachexia. Isolated pancreatic islets secretory activity was analyzed. In addition, we evaluated mechanic sensibility. Our results showed improved physical performance according to the final workload and VO2max and reduced BW in trained rats at the end of the running protocol. Chronic adaptation to the aerobic exercise training decreased tumor weight, cachexia and metastasis and were associated with low glucose and insulin levels and high insulin sensitivity before and after tumor cell inoculation. Aerobic exercise started at young age also reduced pancreatic islet insulin content and insulin secretion in response to a glucose stimulus, without impairing islet morphology in trained rats. Walker 256 tumor-bearing sedentary rats also presented reduced pancreatic islet insulin content, without changing insulin secretion through isolated pancreatic islets. The mechanical sensitivity test indicated that aerobic exercise training did not cause injury or trigger inflammatory processes prior to tumor cell inoculation. Taken together, the current study suggests that aerobic exercise training applied during adolescence may mitigate tumor growth and related disorders in Walker 256 tumor-bearing adult rats. Improved insulin sensibility, lower glucose and insulin levels and/or reduced insulin secretion stimulated by glucose may be implicated in this tumor attenuation.

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Section: Discussionsupporting

confidence: 65%

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats

et al. 2018

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“…Walker 256 tumour‐bearing rats and other cancer animal models have tissue insulin resistance, which indicates that more glucose is available for the tumour (Miksza et al . ; Hung et al . ; Porporato, ).…”

Section: Discussionmentioning

confidence: 99%

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

Moreira

Almeida

Franco

et al. 2019

The Journal of Physiology

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Key pointsr Cancer growth, cell proliferation and cachexia index can be attenuated by the beneficial programming effect of moderate exercise training, especially if it begins in adolescence.r Walker 256 tumour-bearing rats who started exercise training during adolescence did not revert the basal low glycaemia and insulinaemia observed before tumour cell inoculation.r The moderate exercise training improved glucose tolerance and peripheral insulin sensitivity only in rats exercised early in adolescence.r The chronic effects of our exercise protocol are be beneficial to prevent cancer cachexia and hold clear potential as a nonpharmacological therapy of insulin sensitization.Veridiana Mota Moreira has worked in higher education as an effective member of a research ethics committee, a co-ordinator of physical activity and health research laboratories, an editor and reviewer in major scientific journals, a professor in Physical Education, and in Nursing, Biology and Physiotherapy Degree Courses. She has supervised and co-ordinated monographs and internships in Physical Education. She has participated in a high-performance soccer team as a physiologist. She participates in the Developmental Origins of Health and Disease (DOHaD) research group at the Laboratory of Cellular Biology of Secretion co-ordinated by Paulo Cezar de Freitas Mathias. In the future, she intends to study the application of molecular biology techniques associated with cancer, aiming to understand the multiplicity of cellular networks involved in the response to physical training, providing mechanisms by which the muscular system communicates with other organs, and mediating the beneficial effects of physical exercise related to health at different ages. * These authors contributed equally to this work. AbstractWe tested the hypothesis that moderate exercise training, performed early, starting during adolescence or later in life during adulthood, can inhibit tumour cell growth as a result of changes in biometric and metabolic markers. Male rats that were 30 and 70 days old performed a treadmill running protocol over 8 weeks for 3 days week -1 , 44 min day -1 and at 55-65%V O 2 max . After the end of training, a batch of rats was inoculated with Walker 256 carcinoma cells. At 15 days after carcinoma cell inoculation, the tumour was weighed and certain metabolic parameters were evaluated. The data demonstrated that physical performance was better in rats that started exercise training during adolescence according to the final workload andV O 2 max . Early or later moderate exercise training decreased the cachexia index, cell proliferation and tumour growth; however, the effects were more pronounced in rats that exercised during adolescence. Low glycaemia, insulinaemia and tissue insulin sensitivity was not reverted in Walker 256 tumour-bearing rats who trained during adolescence. Cancer growth can be attenuated by the beneficial programming effect of moderate exercise training, especially if it begins during adolescence. In addition, improvement in glu...

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“…MT-102 (Espindolol), a novel anabolic/catabolic transforming agent, was used to treat subjects with cachexia related to stage III and IV non-small cell lung cancer and colorectal cancer in clinical phase II. Infliximab, anti-TNFα monoclonal antibody, was applied to treat cancer-related cachexia in subjects with pancreatic cancer in clinical phase II ( Wiedenmann et al, 2008 ; Arruda et al, 2010 ; Gueta et al, 2010 ; Miksza et al, 2013 ). Although these agents have entered into clinical evaluation, it is increasingly evident that a single therapy may not be sufficient to prevent or ameliorate cancer cachexia due to the complexity of this syndrome.…”

Section: Introductionmentioning

confidence: 99%

Pyrrolidine Dithiocarbamate (PDTC) Attenuates Cancer Cachexia by Affecting Muscle Atrophy and Fat Lipolysis

Miao

Zhang

et al. 2017

Front. Pharmacol.

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Cancer cachexia is a kind of whole body metabolic disorder syndrome accompanied with severe wasting of muscle and adipose tissue. NF-κB signaling plays an important role during skeletal muscle atrophy and fat lipolysis. As an inhibitor of NF-κB signaling, Pyrrolidine dithiocarbamate (PDTC) was reported to relieve cancer cachexia; however, its mechanism remains largely unknown. In our study, we showed that PDTC attenuated cancer cachexia symptom in C26 tumor bearing mice models in vivo without influencing tumor volume. What’s more, PDTC inhibited muscle atrophy and lipolysis in cells models in vitro induced by TNFα and C26 tumor medium. PDTC suppressed atrophy of myotubes differentiated from C2C12 by reducing MyoD and upregulating MuRF1, and preserving the expression of perilipin as well as blocking the activation of HSL in 3T3-L1 mature adipocytes. Meaningfully, we observed that PDTC also inhibited p38 MAPK signaling besides the NF-κB signaling in cancer cachexia in vitro models. In addition, PDTC also influenced the protein synthesis of skeletal muscle by activating AKT signaling and regulated fat energy metabolism by inhibiting AMPK signaling. Therefore, PDTC primarily influenced different pathways in different tissues. The study not only established a simple and reliable screening drugs model of cancer cachexia in vitro but also provided new theoretical basis for future treatment of cancer cachexia.

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Effect of infliximab on metabolic disorders induced by Walker-256 tumor in rats

Cited by 14 publications

References 47 publications

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats

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

Pyrrolidine Dithiocarbamate (PDTC) Attenuates Cancer Cachexia by Affecting Muscle Atrophy and Fat Lipolysis

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