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1.
An Acad Bras Cienc ; 91(3): e20190068, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508664

RESUMO

To investigate the mechanism of different exercise patterns on neurological function after focal cerebral ischaemia in rats. Rats with focal cerebral cerebral ischaemia were randomly divided into an aerobic exercise group, an exhaustive exercise group and a control group, with 8 rats in each group. A score for nerve function in each group was calculated, and the ultrastructure of nerve cells was observed. Levels of NO and NOS in the brain motor area of the ​​rats were measured in each group. The aerobic exercise group had lower nerve function scores than the exhaustive exercise group and higher scores than the control group (P<0.05). Under transmission electron microscopy, irregular shapes and organs were observed in nerve cells in the control group, while regular cell shapes and organs were observed in the aerobic exercise group. The aerobic exercise group and exhaustive exercise group had higher measures of NO content, NOS activity and eNOS, nNOS and iNOS gene expression than the control group, but eNOS expression in the aerobic exercise group and iNOS expression in the exhaustive exercise group were clearly higher according to RT-PCR (P<0.05). Aerobic exercise can promote the expression of NOS, mainly in eNOS, which can promote nerve repair.


Assuntos
Isquemia Encefálica/fisiopatologia , Regeneração Nervosa/fisiologia , Óxido Nítrico/fisiologia , Condicionamento Físico Animal/métodos , Animais , Isquemia Encefálica/terapia , Modelos Animais de Doenças , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Sprague-Dawley
2.
Braz J Med Biol Res ; 52(9): e8290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482998

RESUMO

Tendon rupture is a very frequent accident involving average people and high-performance athletes. Clinical studies describe tendon recovery as a painful and slow process involving different biochemical and histological events. Ascorbic acid (AA) is a potent antioxidant as well as an important cofactor for collagen synthesis. In the current study, we evaluated if local treatment with AA is able to promote tendon repair in tenotomized rats. Animals were submitted to Achilles tendon rupture followed by surgical suture. Control and AA groups received in loco injection of saline solution (0.9% NaCl) and 30 mM AA, respectively. Histological and functional recovery of Achilles tendon tissue was evaluated at 7, 14, and 21 days post-surgery. Hematoxylin/eosin staining and collagen fluorescence analysis showed intense disarrangement of tendon tissue in the saline group. Tenotomized animals also showed hypercellularity in tendon tissue compared with non-tenotomized animals. The Achilles functional index (AFI) showed a significant decrease of tendon functionality in tenotomized animals at 7, 14, and 21 days post-surgery. AA accelerated tissue organization and the recovery of function of the Achilles tendons. The beneficial effect of AA treatment was also observed in the organization of the collagen network. Data presented in the current work showed that in loco treatment with AA accelerated the recovery of injured Achilles tendon post-surgery.


Assuntos
Tendão do Calcâneo/efeitos dos fármacos , Ácido Ascórbico/administração & dosagem , Colágeno/efeitos dos fármacos , Traumatismos dos Tendões/cirurgia , Tendão do Calcâneo/lesões , Tendão do Calcâneo/patologia , Animais , Colágeno/fisiologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Tenotomia , Cicatrização/efeitos dos fármacos
3.
Biol Res ; 52(1): 49, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492195

RESUMO

BACKGROUND: Psoriasis is a common and intractable skin disease affecting the physical and mental health of patients. The accumulation of ROS is involved in the pathogenesis of psoriasis and antioxidants are believed to be therapeutic. This study aimed to investigate the therapeutic efficacy of astilbin on ROS accumulation in psoriasis. RESULTS: The study showed that 50 µg/ml astilbin could inhibit the growth and reduce the accumulation of ROS in HaCaT cells stimulated by IL-17 and TNF-α. Astilbin could elevate the Nrf2 accumulation in the nuclei, eventually leading to the transcriptional activation of various antioxidant proteins and reducing the expression of VEGF. CONCLUSIONS: Our results collectively suggest that astilbin could induce Nrf2 nucleus translocation, which is contribute to reduce the ROS accumulation and VEGF expression, and inhibit the proliferation of HaCaT cells.


Assuntos
Flavonóis/administração & dosagem , Queratinócitos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Psoríase/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Interleucina-17/metabolismo , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , Psoríase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
4.
Biol Res ; 52(1): 50, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492196

RESUMO

BACKGROUND: Ureteral obstruction causes injury of the renal tissues and can irreversibly progress to renal fibrosis, with atrophy and apoptosis of tubular cells. The goal of the current study was to examine the effects of rhein on the apoptosis o renal tubular cells as well as renal fibrosis using a rodent model of unilateral ureteral obstruction (UUO). METHODS: UUO was induced through ureteral ligation, then animals received treatments with rhein or vehicle. The control rats only received sham operation. The renal tissue was harvested 1 week after surgery for assessment of kidney fibrosis. RESULTS: The expressions of collagen I and α-smooth muscle actin (α-SMA), as well as the severity of renal tubular apoptosis and fibrosis were time-dependently increased following UUO. Treatments with rhein partially inhibited such responses. Renal interstitial fibrosis was associated with STAT3 (signal transducer and activator of transcription 3) phosphorylation as well as altered expressions of Bax and Bcl2, both apoptosis-related proteins. Treatment with rhein also partly blocked these responses. CONCLUSION: These findings demonstrated that rhein mitigated apoptosis of renal tubular cell as well as renal fibrosis in a UUO rodent model. This curative effect is likely mediated via suppression of STAT3 phosphorylation.


Assuntos
Antraquinonas/administração & dosagem , Apoptose/efeitos dos fármacos , Rim/patologia , Obstrução Ureteral/prevenção & controle , Animais , Modelos Animais de Doenças , Progressão da Doença , Fibrose/metabolismo , Fibrose/patologia , Fibrose/prevenção & controle , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia
5.
Zhonghua Yi Xue Za Zhi ; 99(32): 2536-2541, 2019 Aug 27.
Artigo em Chinês | MEDLINE | ID: mdl-31484283

RESUMO

Objective: To observe the effects of artesunate on airway responsiveness and airway inflammation in asthmatic mice. Methods: Thirty female BALB/c mice aged 6-8 weeks were randomly divided into control group, asthma group and artesunate group. In the asthma group and the artesunate group, the mice were sensitized by intraperitoneal injection of 20 µg of ovalbumin (OVA) and 0.2 ml of aluminum hydroxide suspension (2 mg) on day 0 and 14, respectively, and 1% OVA 10 ml dissolved in sterile phosphate (PBS) buffer was aerosolized for 30 min from the 21st to 28th day. The control group was sensitized with 0.2 ml of 2 mg suspension of aluminum hydroxide on day 0 and 14, and aerosolized by 10 ml of sterile PBS from the 21st to 28th day. Before the challenge, the artesunate group was intraperitoneally injected with 0.2 ml of artesunate. Artesunate was replaced with the same amount of normal saline in the control group and the asthma group. The mice were treated after 24 hours of last stimulation. The airway responsiveness of mice was measured by airway intubation and the changes of airway resistance and compliance were observed. Bronchoalveolar lavage fluid (BALF) was classified by cytology, and pathological changes of left lung tissue were observed and scored. Results: The airway resistance of the three groups increased and the lung compliance decreased with the increase of methacholine (Ach) concentration. The airway resistance and lung compliance of the three groups were different under the same concentration (P<0.05). The airway resistance of the artesunate group at Ach 6.25, 12.5, 25, 50, 100 mg/ml was lower than that of the asthma group at the same concentration [(1.01±0.48) vs (1.30±0.22), (1.06±0.44) vs (1.70±0.31), (1.30±0.64) vs (2.66±0.79), (1.82±0.55) vs (3.38±1.35), (2.49±0.85) vs (4.07±1.34) cmH(2)O·s(-1)·ml(-1)(1 cmH(2)O=0.098 kPa); t=3.862, 7.376, 9.113, 7.051, 6.685, all P<0.05]; the degree of lung compliance decrease at the concentration of Ach 3.125, 6.25, 12.5, 25, 50, 100 mg/ml was lower than that of the asthma group at the same concentration [(3.89±0.55)×10(-2) vs (3.07±0.63)×10(-2), (3.61±0.52)×10(-2) vs (3.04±0.58)×10(-2), (3.48±0.38)×10(-2) vs (2.78±0.57)×10(-2), (3.09±0.52)×10(-2) vs (1.73±0.62)×10(-2), (2.32±0.60)×10(-2) vs (1.29±0.54)×10(-2), (1.87±0.59)×10(-2) vs (1.15±0.44)×10(-2) ml/cmH(2)O; t=-6.295, -4.921, -6.533, -11.135, -8.48, -6.319, all P<0.05]. The proportion of eosinophils in artesunate group in BALF was significantly lower than that in asthma group [(16.63±8.58)% vs (40.44±12.94)%; t=4.336, P<0.05]. In the asthma group, the inflammatory cells infiltration of the bronchi and the perivascular area, the bronchial epithelial edema and degeneration can be observed, and the artesunate could reduce the infiltration of inflammatory cells around the bronchus and blood vessels, and the mucus secretion was also reduced in the artesunate group. Conclusion: Artesunate can improve airway hyperresponsiveness and airway inflammation in asthmatic mice and has a certain therapeutic effect on asthma.


Assuntos
Asma , Animais , Artesunato , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Feminino , Inflamação , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina
6.
Acta Cir Bras ; 34(7): e201900705, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31531527

RESUMO

PURPOSE: The denervation of the intestine with benzalkonium chloride (BAC) reduces mortality and improves weight gain in rats with short bowel syndrome (SBS). Nevertheless, translating these promising findings from bench to bedside is not feasible because BAC promotes peritonitis and irreversible denervation which may be followed by an uncontrolled dilatation of the viscera. The use of botulinum toxin (BT) instead of BAC to achieve the denervation of the remaining small intestine in SBS could be an interesting option because it leads to a mild and transient denervation of the intestine. METHODS: Here we evaluated the effects of the ileal denervation with BT in rats with SBS by verifying the body weight variation and intestinal morphological parameters. Four groups with 6 animals each were submitted to enterectomy with an ileal injection of saline (group E) or BT (group EBT). Control groups were submitted to simulated surgery with an ileal injection of BT (group BT) or saline (group C - control). RESULTS: We observed that the treatment of the remaining ileum with BT completely reversed the weight loss associated to extensive small bowel resection. CONCLUSION: This may provide a new promising approach to the surgical treatment of SBS.


Assuntos
Toxinas Botulínicas/farmacologia , Denervação/métodos , Íleo/inervação , Síndrome do Intestino Curto/cirurgia , Animais , Compostos de Benzalcônio/farmacologia , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Íleo/patologia , Jejuno/inervação , Debilidade Muscular/patologia , Ratos , Ratos Wistar , Síndrome do Intestino Curto/patologia
7.
Acta Cir Bras ; 34(7): e201900707, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31531528

RESUMO

PURPOSE: To evaluate the effects of splenic ischemic preconditioning (sIPC) on oxidative stress induced by hepatic ischemia-reperfusion in rats. METHODS: Fifteen male Wistar rats were equally divided into 3 groups: SHAM, IRI and sIPC. Animals from IRI group were subjected to 45 minutes of partial liver ischemia (70%). In the sIPC group, splenic artery was clamped in 2 cycles of 5 min of ischemia and 5 min of reperfusion (20 min total) prior to hepatic ischemia. SHAM group underwent the same surgical procedures as in the remaining groups, but no liver ischemia or sIPC were induced. After 1h, hepatic and splenic tissue samples were harvested for TBARS, CAT, GPx and GSH-Rd measurement. RESULTS: sIPC treatment significantly decreased both hepatic and splenic levels of TBARS when compared to IRI group (p<0.01). Furthermore, the hepatic and splenic activities of CAT, GPx and GSH- Rd were significantly higher in sIPC group than in IRI group. CONCLUSION: sIPC was able to attenuate hepatic and splenic IRI-induced oxidative stress.


Assuntos
Precondicionamento Isquêmico/métodos , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Estresse Oxidativo/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Fígado/fisiologia , Hepatopatias/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia
8.
Acta Cir Bras ; 34(7): e201900704, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531539

RESUMO

PURPOSE: The effects of resveratrol administration on calvarial bone defects with alloplastic graft material was investigated for osteoinductive reaction and bone development in rats. METHODS: Healthy male rats were randomly divided into 3 groups consisting of 10 rats. Groups were as follows: control (defect) group, defect + graft group, and defect + graft + resveratrol group. A calvarial bone defect was created in all groups, alloplastic bone grafts were applied to the defect in the 2nd and 3rd group, resveratrol (5 mg/kg/day) was added to the drinking water of the animals following graft application for 28 days in the 3rd group. RESULTS: Increase in osteoclasts and necrotic changes were observed histopathologically in the control group. In the 2nd group, reduction of inflammation, congestion of blood vessels, increased osteblastic activity, osteoinductive effect, progression of osteocyte development and increased collagen fibers in connective tissue were observed. In the 3rd group, osteoblasts seemed to secrete bone matrix and accelerate osteoinductive effect with increased osteopregenitor activity and positive osteopontin and osteonectin expressions. CONCLUSION: Resveratrol treatment was thought to be an alternative and supportive drug for implant application by inducing new bone formation in the calvaral defect region as a result of short-term treatment.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/administração & dosagem , Transplante Ósseo/métodos , Resveratrol/administração & dosagem , Crânio/cirurgia , Animais , Substitutos Ósseos/uso terapêutico , Modelos Animais de Doenças , Esquema de Medicação , Masculino , Osseointegração/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteonectina/administração & dosagem , Osteopontina/administração & dosagem , Ratos , Crânio/efeitos dos fármacos
9.
Acta Cir Bras ; 34(7): e201900706, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531540

RESUMO

PURPOSE: To investigate the protective roles of pyracantha fortune fruit extract (PFE) on acute renal toxicity induced by cadmium chloride (CdCl2) in rats. METHODS: Rats were pretreated with PFE and consecutively injected with CdCl2 (6.5 mg/kg) for 5 days. RESULTS: The concentration of Cd, kidney weight, malondialdehyde (MDA), and nitric oxide (NO) production were remarkably increased in CdCl2 group as well as the levels of plasma uric acid, urea, and creatinine (P < 0.001). However, the body weight and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione peroxidase (GR) levels were markedly reduced by CdCl2 treatment (P < 0.001). Histological manifestations of renal tissue showed severely adverse changes. Moreover, CdCl2 treatment significantly decreased the B-cell lymphoma-2 (Bcl-2) expression while increased the Bcl-2-Associated X Protein (Bax), tumor necrosis factor-α (TNF-α) expression (P < 0.001). Additionally, the expression of Nrf2/Keap 1 related proteins Keap-1 gained a significant increase (P < 0.001), whereas the Nrf2, HO-1, γ-GCS, GSH-Px and NQO1 expression decreased by CdCl2 treatment (P < 0.05). These rats were pretreated with PFE to improve the changes caused by CdCl2 treatment. CONCLUSION: PFE could protect the kidney against acute renal toxicity induced by CdCl2.


Assuntos
Antioxidantes/farmacologia , Cloreto de Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Rim/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pyracantha/química , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Frutas/química , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo
10.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(3): 285-290, 2019 Jul 26.
Artigo em Chinês | MEDLINE | ID: mdl-31544408

RESUMO

OBJECTIVE: To investigate the pathogenicity of Pneumocystis and its association with the development of chronic obstructive pulmonary disease (COPD). METHODS: The rat model of Pneumocystis pneumonia (PCP) was induced by intraperitoneal injection with dexamethasone, which was confirmed by pathogenic detection. The pathologic changes of rat lung specimens were examined using conventional HE staining, and the expression of inflammatory cells were detected by flow cytometry in bron-choalveolar lavage fluid (BALF) and splenic tissues of the rat model of PCP. In addition, the serum levels of matrix metalloproteinase 8 (MMP-8) and MMP-9 were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Fusion and atrophy of alveolar spaces and hyperplasia of lung tissue were seen in the lung specimens of the rat model of PCP, and foam-like alveolar exudates and infiltration of inflammation cells were observed in the alveolar space, while severe infections exhibited consolidation of lung, which was similar to pathological features of COPD. The counts of CD8+ T lymphocytes (t = -7.920 and -12.514, P < 0.01), macrophages (t = -7.651 and -14.590, P < 0.01) and granulocytes (t = -10.310 and -16.578, P < 0.01) significantly increased and the counts of CD4+ T lymphocytes (t = 6.427 and 18.579, P < 0.01) significantly reduced in the BALF and splenic specimens of the rats with PCP relative to those without PCP. In addition, higher serum MMP-8 (t = -8.689, P < 0.01) and MMP-9 levels (t = -7.041, P < 0.01) were measured in rats with PCP than in those without PCP. CONCLUSIONS: Pneumocystis infection may be associated with the development and progression of COPD.


Assuntos
Pneumocystis , Pneumonia por Pneumocystis , Doença Pulmonar Obstrutiva Crônica/etiologia , Animais , Líquido da Lavagem Broncoalveolar/microbiologia , Modelos Animais de Doenças , Pulmão/microbiologia , Pneumocystis/patogenicidade , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/microbiologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Ratos , Virulência
11.
Adv Exp Med Biol ; 1161: 133-148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562628

RESUMO

Bioactive lipids, or lipid mediators, are utilized for intercellular communications. They are rapidly produced in response to various stimuli and exported to extracellular spaces followed by binding to cell surface G protein-coupled receptors (GPCRs) or nuclear receptors. Many drugs targeting lipid signaling such as non-steroidal anti-inflammatory drugs (NSAIDs), prostaglandins, and antagonists for lipid GPCRs are in use. For example, the sphingolipid analog, fingolimod (also known as FTY720), was the first oral disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (MS), whose mechanisms of action (MOA) includes sequestration of pathogenic lymphocytes into secondary lymphoid organs, as well as astrocytic modulation, via down-regulation of the sphingosine 1-phosphate (S1P) receptor, S1P1, by in vivo-phosphorylated fingolimod. Though the cause of MS is still under debate, MS is considered to be an autoimmune demyelinating and neurodegenerative disease. This review summarizes the involvement of bioactive lipids (prostaglandins, leukotrienes, platelet-activating factors, lysophosphatidic acid, and S1P) in MS and the animal model, experimental autoimmune encephalomyelitis (EAE). Genetic ablation, along with pharmacological inhibition, of lipid metabolic enzymes and lipid GPCRs revealed that each bioactive lipid has a unique role in regulating immune and neural functions, including helper T cell (TH1 and TH17) differentiation and proliferation, immune cell migration, astrocyte responses, endothelium function, and microglial phagocytosis. A systematic understanding of bioactive lipids in MS and EAE dredges up information about understudied lipid signaling pathways, which should be clarified in the near future to better understand MS pathology and to develop novel DMTs.


Assuntos
Encefalomielite Autoimune Experimental , Metabolismo dos Lipídeos , Lipídeos , Esclerose Múltipla , Doenças Neurodegenerativas , Animais , Modelos Animais de Doenças , Lipídeos/química , Esclerose Múltipla/fisiopatologia , Doenças Neurodegenerativas/enzimologia , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/fisiopatologia
12.
Braz Oral Res ; 33: e037, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508726

RESUMO

Iontophoresis is a noninvasive technique, based on the application of a constant low-intensity electric current to facilitate the release of a variety of drugs, whether ionized or not, through biological membranes. The objective of this research was to evaluate the effect of iontophoresis using different electric current intensities on the uptake of fluoride in dental enamel with artificial caries lesions. In this in vitro operator-blind experiment, bovine enamel blocks (n = 10/group) with caries-like lesions and predetermined surface hardness were randomized into 6 groups: placebo gel without fluoride applied with a current of 0.8 mA (negative control), 2% NaF gel without application of any current, and 2% NaF gel applied with currents of 0.1, 0.2, 0.4 and 0.8 mA. Cathodic iontophoresis was applied for 4 min. The concentration of loosely bound fluoride (calcium fluoride) and firmly bound fluoride (fluorapatite) was determined. The results were analyzed by the nonparametric Kruskal-Wallis and Dunn tests. Iontophoresis at 0.8 mA, combined with the application of fluoridated gel (2% NaF), increased fluoride uptake in enamel with caries-like lesions, as either calcium fluoride or fluorapatite.


Assuntos
Cariostáticos/farmacologia , Cárie Dentária , Esmalte Dentário/efeitos dos fármacos , Fluoretos/farmacologia , Iontoforese/métodos , Animais , Apatitas/análise , Fluoreto de Cálcio/análise , Bovinos , Modelos Animais de Doenças , Eletricidade , Dureza/efeitos dos fármacos , Distribuição Aleatória , Propriedades de Superfície/efeitos dos fármacos , Resultado do Tratamento
13.
Adv Exp Med Biol ; 1167: 1-14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520346

RESUMO

Cancer is a cumulative manifestation of several complicated disease states that affect multiple organs. Over the last few decades, the fruit fly Drosophila melanogaster, has become a successful model for studying human cancers. The genetic simplicity and vast arsenal of genetic tools available in Drosophila provides a unique opportunity to address questions regarding cancer initiation and progression that would be extremely challenging in other model systems. In this chapter we provide a historical overview of Drosophila as a model organism for cancer research, summarize the multitude of genetic tools available, offer a brief comparison between different model organisms and cell culture platforms used in cancer studies and briefly discuss some of the latest models and concepts in recent Drosophila cancer research.


Assuntos
Modelos Animais de Doenças , Drosophila melanogaster , Neoplasias , Animais , Pesquisa Biomédica/tendências , Humanos
14.
Adv Exp Med Biol ; 1167: 15-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520347

RESUMO

The formation, overgrowth and metastasis of tumors comprise a complex series of cellular and molecular events resulting from the combined effects of a variety of aberrant signaling pathways, mutations, and epigenetic alterations. Modeling this complexity in vivo requires multiple genes to be manipulated simultaneously, which is technically challenging. Here, we analyze how Drosophila research can further contribute to identifying pathways and elucidating mechanisms underlying novel cancer driver (risk) genes associated with tumor growth and metastasis in humans.


Assuntos
Drosophila , Neoplasias , Oncogenes , Animais , Modelos Animais de Doenças , Humanos , Mutação , Transdução de Sinais
15.
Adv Exp Med Biol ; 1167: 37-64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520348

RESUMO

Cell competition is an important surveillance mechanism that measures relative fitness between cells in a tissue during development, homeostasis, and disease. Specifically, cells that are "less fit" (losers) are actively eliminated by relatively "more fit" (winners) neighbours, despite the less fit cells otherwise being able to survive in a genetically uniform tissue. Originally described in the epithelial tissues of Drosophila larval imaginal discs, cell competition has since been shown to occur in other epithelial and non-epithelial Drosophila tissues, as well as in mammalian model systems. Many genes and signalling pathways have been identified as playing conserved roles in the mechanisms of cell competition. Among them are genes required for the establishment and maintenance of apico-basal cell polarity: the Crumbs/Stardust/Patj (Crb/Sdt/Patj), Bazooka/Par-6/atypical Protein Kinase C (Baz/Par-6/aPKC), and Scribbled/Discs large 1/Lethal (2) giant larvae (Scrib/Dlg1/L(2)gl) modules. In this chapter, we describe the concepts and mechanisms of cell competition, with emphasis on the relationship between cell polarity proteins and cell competition, particularly the Scrib/Dlg1/L(2)gl module, since this is the best described module in this emerging field.


Assuntos
Polaridade Celular , Transformação Celular Neoplásica , Proteínas de Drosophila , Drosophila , Animais , Modelos Animais de Doenças
16.
Adv Exp Med Biol ; 1167: 113-127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520352

RESUMO

The resurgence of Drosophila as a recognized model for carcinogenesis has contributed greatly to our conceptual advance and mechanistic understanding of tumor growth in vivo. With its powerful genetics, Drosophila has emerged as a prime model organism to study cell biology and physiological functions of autophagy. This has enabled exploration of the contributions of autophagy in several tumor models. Here we review the literature of autophagy related to tumorigenesis in Drosophila. Functional analysis of core autophagy components does not provide proof for a classical tumor suppression role for autophagy alone. Autophagy both serve to suppress or support tumor growth. These effects are context-specific, depending on cell type and oncogenic or tumor suppressive lesion. Future delineation of how autophagy impinges on tumorigenesis will demand to untangle in detail, the regulation and flux of autophagy in the respective tumor models. The downstream tumor-regulative roles of autophagy through organelle homeostasis, metabolism, selective autophagy or alternative mechanisms remain largely unexplored.


Assuntos
Autofagia , Carcinogênese , Drosophila , Animais , Modelos Animais de Doenças
17.
Adv Exp Med Biol ; 1167: 129-155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520353

RESUMO

Multiple large-scale epidemiological studies have identified obesity as an important risk factor for a variety of human cancers, particularly cancers of the uterus, gallbladder, kidney, liver, colon, and ovary, but there is much uncertainty regarding how obesity increases the cancer risks. Given that obesity has been consistently identified as a major risk factor for uterine tumors, the most common malignancies of the female reproductive system, we use uterine tumors as a pathological context to survey the relevant literature and propose a novel hypothesis: chronic downregulation of the cyclin-dependent kinase 8 (CDK8) module, composed of CDK8 (or its paralog CDK19), Cyclin C, MED12 (or MED12L), and MED13 (or MED13L), by elevated insulin or insulin-like growth factor signaling in obese women may increase the chances to dysregulate the activities of transcription factors regulated by the CDK8 module, thereby increasing the risk of uterine tumors. Although we focus on endometrial cancer and uterine leiomyomas (or fibroids), two major forms of uterine tumors, our model may offer additional insights into how obesity increases the risk of other types of cancers and diseases. To illustrate the power of model organisms for studying human diseases, here we place more emphasis on the findings obtained from Drosophila melanogaster.


Assuntos
Drosophila melanogaster , Obesidade/complicações , Neoplasias Uterinas/patologia , Animais , Quinase 8 Dependente de Ciclina/genética , Modelos Animais de Doenças , Proteínas de Drosophila/genética , Feminino , Humanos , Complexo Mediador/genética , Fatores de Risco
18.
Adv Exp Med Biol ; 1167: 157-173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520354

RESUMO

MiRNAs are post-transcriptional regulators of gene expression which have been implicated in virtually all biological processes. MiRNAs are frequently dysregulated in human cancers. However, the functional consequences of aberrant miRNA levels are not well understood. Drosophila is emerging as an important in vivo tumor model, especially in the identification of novel cancer genes. Here, we review Drosophila studies which functionally dissect the roles of miRNAs in tumorigenesis. Ultimately, these advances help to understand the implications of miRNA dysregulation in human cancers.


Assuntos
Drosophila , MicroRNAs/genética , Neoplasias/genética , Animais , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Oncogenes
19.
Adv Exp Med Biol ; 1167: 175-190, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520355

RESUMO

Accumulative studies suggest that a fraction of cells within a tumor, known as cancer stem cells (CSCs) that initiate tumors, show resistance to most of the therapies, and causes tumor recurrence and metastasis. CSCs could be either transformed normal stem cells or reprogrammed differentiated cells. The eventual goal of CSC research is to identify pathways that selectively regulate CSCs and then target these pathways to eradicate CSCs. CSCs and normal stem cells share some common features, such as self-renewal, the production of differentiated progeny, and the expression of stem-cell markers, however, CSCs vary from normal stem cells in forming tumors. Specifically, CSCs are normally resistant to standard therapies. In addition, CSCs and non-CSCs can be mutually convertible in response to different signals or microenvironments. Even though CSCs are involved in human cancers, the biology of CSCs, is still not well understood, there are urgent needs to study CSCs in model organisms. In the last several years, discoveries in Drosophila have greatly contributed to our understanding of human cancer. Stem-cell tumors in Drosophila share various properties with human CSCs and maybe used to understand the biology of CSCs. In this chapter, we first briefly review CSCs in mammalian systems, then discuss stem-cell tumors in the Drosophila posterior midgut and Malpighian tubules (kidney) and their unique properties as revealed by studying oncogenic Ras protein (RasV12)-transformed stem-cell tumors in the Drosophila kidney and dominant-negative Notch (NDN)-transformed stem-cell tumors in the Drosophila intestine. At the end, we will discuss potential approaches to eliminate CSCs and achieve tumor regression. In future, by screening adult Drosophila neoplastic stem-cell tumor models, we hope to identify novel and efficacious compounds for the treatment of human cancers.


Assuntos
Drosophila , Neoplasias/patologia , Células-Tronco Neoplásicas/citologia , Animais , Diferenciação Celular , Modelos Animais de Doenças , Humanos , Microambiente Tumoral
20.
Adv Exp Med Biol ; 1167: 191-205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520356

RESUMO

In humans, cancer-associated cachexia is a complex syndrome that reduces the overall quality of life and survival of cancer patients, particularly for those undergoing chemotherapy. The most easily observable sign of cachexia is organ wasting, the dramatic loss of skeletal muscle and adipose tissue mass. Estimates suggest that 80% of patients in advanced stages of cancer show signs of the syndrome and about 20% of cancer patients die directly of cachexia. Because there is no treatment or drug available to ameliorate organ wasting induced by cancer, cachexia is a relevant clinical problem. However, it is unclear how cachexia is mediated, what factors drive interactions between tumors and host tissues, and which markers of cachexia might be used to allow early detection before the observable signs of organ wasting. In this chapter, we review the current mammalian models of cachexia and the need to use new models of study. We also explain recent developments in Drosophila as a model for studying organ wasting induced by tumors and how fly studies can help unravel important mechanisms that drive cachexia. In particular, we discuss what lessons have been learned from tumor models recently reported to induce systemic organ wasting in Drosophila.


Assuntos
Caquexia/patologia , Drosophila , Neoplasias/patologia , Animais , Modelos Animais de Doenças , Humanos , Músculo Esquelético/patologia , Qualidade de Vida
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