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1.
Cancer Lett ; 472: 108-118, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31837443

RESUMO

Despite the common application and considerable efforts to achieve precision radiotherapy (RT) in several types of cancer, RT has not yet entered the era of precision medicine; the ability to predict radiosensitivity and treatment responses in tumors and normal tissues is lacking. Therefore, development of genome-based methods for individual prognosis in radiation oncology is urgently required. Traditional DNA sequencing requires tissue samples collected during invasive operations; therefore, repeated tests are nearly impossible. Intra- and inter-tumoral heterogeneity may undermine the predictive power of a single assay from tumor samples. In contrast, analysis of circulating tumor DNA (ctDNA) allows for non-invasive and near real-time sampling of tumors. By investigating the genetic composition of tumors and monitoring dynamic changes during treatment, ctDNA analysis may potentially be clinically valuable in prediction of treatment responses prior to RT, surveillance of responses during RT, and evaluation of residual disease following RT. As a biomarker for RT response, ctDNA profiling may guide personalized treatments. In this review, we will discuss approaches of tissue DNA sequencing and ctDNA detection and summarize their clinical applications in both traditional RT and in combination with immunotherapy.

2.
PeerJ ; 7: e7522, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565554

RESUMO

Triple-negative breast cancer (TNBC) is a particular subtype of breast malignant tumor with poorer prognosis than other molecular subtypes. Previous studies have demonstrated that some abnormal expression of non-coding RNAs including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were closely related to tumor cell proliferation, apoptosis, invasion, migration and drug sensitivity. However, the role of non-coding RNAs in the pathogenesis of TNBC is still unclear. In order to characterize the molecular mechanism of non-coding RNAs in TNBC, we downloaded RNA data and miRNA data from the cancer genome atlas database. We successfully identified 686 message RNAs (mRNAs), 26 miRNAs and 50 lncRNAs as key molecules for high risk of TNBC. Then, we hypothesized that the lncRNA-miRNA-mRNA regulatory axis positively correlates with TNBC and constructed a competitive endogenous RNA (ceRNA) network of TNBC. Our series of analyses has shown that five molecules (TERT, TRIML2, PHBP4, mir-1-3p, mir-133a-3p) were significantly associated with the prognosis of TNBC, and there is a prognostic ceRNA sub-network between those molecules. We mapped the Kaplan-Meier curve of RNA on the sub-network and also suggested that the expression level of the selected RNA is related to the survival rate of breast cancer. Reverse transcription-quantitative polymerase chain reaction showed that the expression level of TRIML2 in TNBC cells was higher than normal. In general, our findings have implications for predicting metastasis, predicting prognosis and discovering new therapeutic targets for TNBC.

3.
Future Oncol ; 15(28): 3233-3242, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31373223

RESUMO

Aim: To evaluate the value of pretreatment blood biomarkers in predicting pathologic responses to neoadjuvant chemoradiotherapy (neo-CRT) in patients with locally advanced rectal cancer. Materials & methods: We conducted logistic regression analysis and receiver operating characteristic to assess the predictive value of blood biomarkers. The outcome was defined by the pathologic complete response and good response. Results: Carcinoembryonic antigen (CEA) (p < 0.001), neutrophil-to-lymphocyte ratio (p = 0.024), platelet-to-lymphocyte ratio (p = 0.006) and lymphocyte-to-monocyte ratio (LMR) (p < 0.001) were significant predictors of pathologic complete response, with area under the curve of 0.785, 0.794, 0.740 and 0.913, respectively; CEA (p = 0.007) and LMR (p < 0.001) correlated significantly with good response, with area under the curve of 0.743 and 0.771, respectively. Conclusion: Lower LMR and higher CEA, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio before treatment could predict poorer pathologic response to neo-CRT in patients with locally advanced rectal cancer.

4.
J Biomater Sci Polym Ed ; 30(12): 995-1007, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31084413

RESUMO

A series of injectable in situ dual-crosslinking hydrogels (HA/ALG) based on oxidized sodium alginate (oxi-ALG) and hyaluronic acid modified with thiol and hydrazide (HA-SH/CDH) were prepared via hydrazone bonds and disulfide bonds. The chemical structures, morphologies, rheological properties, gelling time, swelling ratio, degradation rate and drug release behavior of hydrogels were investigated. HA/ALG hydrogels exhibited tunable gelling time, rheological properties, swelling ratio and degradation rate with varying precursor concentrations. The gelling time of HA/ALG hydrogels ranged from 157 s to 955 s, the values of yield stress of HA2/ALG2, HA3/ALG3 and HA4/ALG4 hydrogels were 1724, 4349 and 5306 Pa, and the degradation percentage of HA2/ALG2, HA3/ALG3 and HA4/ALG4 hydrogels were about 64%, 51% and 42% after incubating 35 days, respectively. Bovine serum albumin (BSA) was used as a model drug to investigate the drug controlled release properties, and the in vitro cumulative release percentage of BSA from HA2/ALG2, HA3/ALG3 and HA4/ALG4 drug-loaded hydrogels were about 79%, 72% and 69% after 20 days. The series of injectable in situ dual-crosslinking HA/ALG hydrogels could be an attractive candidate for drug delivery system, tissue engineering and regenerative medicine.

5.
J Biomater Sci Polym Ed ; 29(13): 1643-1655, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29793378

RESUMO

A series of injectable in situ cross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels (HA/CMC) was prepared via disulfide bonds by the oxidation of dissolved oxygen. The results showed that HA/CMC hydrogels exhibited tunable gelling time, appropriate rheology properties, high swelling ratio, good stability, and sustained drug release ability. The gelling time of HA/CMC hydrogels ranged from 1.4 to 7.0 min, and the values of the storage modulus, complex shear modulus, dynamic viscosity, and yield stress of HA3/CMC3 hydrogel were about 5869 Pa, 5870 Pa, 587 Pa·s, and 1969 Pa, respectively. The degradation percentage of HA1/CMC1, HA2/CMC2, and HA3/CMC3 hydrogels were about 60, 49, and 41% after incubating 42 days, and the in vitro cumulative release percentage of BSA from HA1/CMC1, HA2/CMC2, and HA3/CMC3 drug-loaded hydrogels were about 99, 91, and 82% after 30 days. The series of injectable in situ cross-linking HA/CMC hydrogels exhibited good comprehensive performance, signifying that these hydrogels could be potentially used in the fields of short- and medium-term controlled drug release, cell encapsulation, regenerative medicine, and tissue engineering.


Assuntos
Carboximetilcelulose Sódica/química , Reagentes para Ligações Cruzadas/química , Portadores de Fármacos/química , Ácido Hialurônico/química , Hidrogéis/síntese química , Materiais Biocompatíveis/química , Dissulfetos/química , Liberação Controlada de Fármacos , Injeções , Reologia , Fatores de Tempo , Viscosidade
6.
Medicine (Baltimore) ; 96(44): e8490, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29095309

RESUMO

Lymphatic vessel invasion (LVI) is promising in determining prognosis and treatment strategies, but the application of LVI as a histopathological criterion in breast cancer patients especially those of different subgroups is controversial. This research aims to evaluate the prognostic value of LVI assessed by D2-40 not only in patients with early invasive breast cancer but also in lymph node-negative, lymph node-positive, luminal A-like, luminal B-like, HER2-enriched, and triple-negative subgroups.The study cohort included 255 patients with a median follow-up of 101 months. Immunohistochemical staining for D2-40 was performed to identify LVI.LVI was present in 64 (25.1%), 15 (12.1%), 49 (37.4%), 19 (20.9%), 23 (27.7%), 13 (31.7%), and 9 (22.5%), respectively, in the whole cohort, lymph node-negative, lymph node-positive, luminal A-like, luminal B-like, HER2-enriched, and triple-negative patients. LVI was associated with large tumor size (P = .04), high histological grade (P = .004), involved lymph node (P < .001), and high expression of Ki-67 (P = .003). No significant difference was found among patients with different subtypes and LVI status. The presence of LVI was significantly associated with adverse disease-free survival in the whole cohort (P < .001), lymph node-negative (P < .001), lymph node-positive (P < .001), luminal A-like (P < .001), and luminal B-like patients (P < .001) in both of the univariate and multivariate survival analysis.This study indicated that the presence of LVI stained by D2-40 provided independent prognostic information not only in the whole cohort but also in the subgroup of patients with lymph node-negative, lymph node-positive, luminal A-like, and luminal B-like diseases, which may make a case for routine clinical assessment of LVI using D2-40.


Assuntos
Anticorpos Monoclonais Murinos/análise , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Vasos Linfáticos/patologia , Adulto , Idoso , Biomarcadores Tumorais , China , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Metástase Linfática , Vasos Linfáticos/imunologia , Pessoa de Meia-Idade , Invasividade Neoplásica/imunologia , Prognóstico
7.
Anticancer Res ; 37(10): 5647-5653, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28982882

RESUMO

AIM: To evaluate the efficacy and toxicity of vinorelbine and gemcitabine (NG) versus vinorelbine and cisplatin (NP) in anthracycline- and taxane-pretreated patients with HER2-negative advanced breast cancer. PATIENTS AND METHODS: Patients were randomly assigned on a 1:1 schedule to receive no more than six cycles of NG or NP. Dosing for the NG group was 25 mg/m2 vinorelbine and 1,000 mg/m2 gemcitabine, given on days 1 and 8 every 3 weeks; for the NP group,25 mg/m2 vinorelbine was given on days 1 and 8, and 75 mg/m2 cisplatin was given on day 1 every 3 weeks. The primary endpoint was disease control rate (DCR). The secondary endpoints were the progression-free survival (PFS), overall survival (OS) and safety. RESULTS: The full analysis set comprised of 37 patients receiving NG and 37 receiving NP. The DCR was 70.3% with NG and 64.9% with NP (p=0.619). Median PFS were 7 months (95% CI=5.88-8.12) and 6 months (95% CI=5.29-6.71) respectively in NG and NP group [hazard ratio (HR)=1.696; 95% confidence interval (CI)=0.73-3.93; p=0.217)]. Corresponding median OS was 18 (95% CI=10.35-13.65) months and 12 (95% CI=15.83-20.17) months (HR=1.219; 95% CI=0.67-2.23; p=0.521). For adverse events, neutropenia and nausea/vomiting were milder in the NG group than in the NP group (all p<0.05). CONCLUSION: Although no significant differences were observed in terms of DCR, PFS and OS, with milder toxicity, NG appeared to be a more valuable first-line treatment regimen than NP in anthracycline- and taxane-pretreated patients with HER2-negative advanced breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Receptor ErbB-2/análise , Vimblastina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/enzimologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , China , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vinorelbina
8.
PLoS One ; 12(5): e0177694, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28531218

RESUMO

Epidermal growth factor receptor (EGFR) is over-expressed in about 50% of Triple negative breast cancers (TNBCs), but EGFR inhibitors have not been effective in treating TNBC patients. Increasing evidence supports that autophagy was related to drug resistance at present. However, the role and the mechanism of autophagy to the treatment of TNBC remain unknown. In the current study, we investigated the effect of autophagy inhibitor to gefitinib (Ge) in TNBC cells in vitro and in nude mice vivo. Our study demonstrated that inhibition of autophagy by 3-Methyladenine or bafilomycin A1 improved Ge's sensitivity to MDA-MB-231 and MDA-MB-468 cells, as evidence from stronger inhibition of cell vitality and colony formation, higher level of G0/G1 arrest and DNA damage, and these effects were verified in nude mice vivo. Our data showed that the mitochondrial-dependent apoptosis pathway was activated in favor of promoting apoptosis in the therapy of Ge combined autophagy inhibitor, as the elevation of BAX/Bcl-2, Cytochrome C, and CASP3. These results demonstrated that targeting autophagy should be considered as an effective therapeutic strategy to enhance the sensitivity of EGFR inhibitors on TNBC.


Assuntos
Adenina/análogos & derivados , Macrolídeos/administração & dosagem , Mitocôndrias/efeitos dos fármacos , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adenina/administração & dosagem , Adenina/farmacologia , Animais , Autofagia/efeitos dos fármacos , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Sinergismo Farmacológico , Feminino , Gefitinibe , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Macrolídeos/farmacologia , Camundongos , Camundongos Nus , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Quinazolinas/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
9.
World J Surg Oncol ; 14(1): 183, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27422708

RESUMO

BACKGROUND: The liver is a common site of metastases, followed by the bone and lung in breast cancer. The symptoms of hepatic metastases are similar to intrahepatic cholangiocarcinoma (ICC). ICC is rare, with an overall incidence rate of 0.95 cases per 100,000 adults. The incidence of ICC for patients with breast cancer is very uncommon. Breast cancer patient with ICC is easily misdiagnosed as hepatic metastases. CASE PRESENTATION: We report a breast cancer patient postoperatively who was hospitalized because of having continuous irregular fever for 1 month. Antibiotics were given for 1 week without any significant effect. Her admission bloods revealed elevated levels of carcino-embryonic antigen. Magnetic resonance imaging diagnosis showed multiple liver metastases. We believed that the woman had hepatic metastases until biopsy guided by computed tomography. The liver biopsy pathology analysis considered the possibility of primary intrahepatic cholangiocarcinoma. CONCLUSIONS: Breast cancer patient with space-occupying lesions in the liver is easily considered to be progressed hepatic metastases. Image-guided biopsy is the best diagnostic method for breast cancer with liver mass to avoid misdiagnosis and classify the molecular subtypes to make appropriate treatment.


Assuntos
Neoplasias dos Ductos Biliares/complicações , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Colangiocarcinoma/complicações , Erros de Diagnóstico/prevenção & controle , Antibacterianos/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Feminino , Febre/tratamento farmacológico , Febre/etiologia , Humanos , Biópsia Guiada por Imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Imagem por Ressonância Magnética , Mastectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X
10.
Ecotoxicol Environ Saf ; 79: 90-100, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22209111

RESUMO

Metal exposure causes reproductive damage in hermaphrodite nematodes, but effects of metals on male development are unclear. We here investigated the effects of mercury chloride exposure on development of males. Hg exposure severely increased the percentage of abnormal males, disrupted the development of male-specific structures, and caused high reactive oxygen species (ROS) production in male tails. Pre-treatment with antioxidant (vitamin E) protected the nematodes against toxicity from Hg exposure on development of male-specific structures. The ROS production in tails was closely correlated with formation of abnormal male-specific structures in males induced by Hg exposure. Moreover, mutations of clk-1, encoding ortholog of COQ7/CAT5, and daf-2, encoding an insulin/IGF receptor, functioned in two different pathways to suppress the formation of deficits in development of male-specific structures. Thus, three different lines of evidence support our conclusion that HgCl(2) causes male structure-specific teratogenesis via production of oxidative stress.


Assuntos
Poluentes Ambientais/toxicidade , Mercúrio/toxicidade , Nematoides/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Masculino , Nematoides/anatomia & histologia , Nematoides/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Vitamina E/farmacologia
11.
Environ Toxicol Pharmacol ; 32(2): 175-84, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21843797

RESUMO

Here we selected HgCl(2) to investigate the mechanism of Hg toxicity on reproduction in hermaphrodite nematodes. Accompanied with decrease of brood size, Hg exposure caused severe deficits in egg number in uterus, egg laying and reproductive structures, including gonad arms and vulva, and formation of protruding phenotype for vulva. Meanwhile, Hg exposure induced severe stress response and oxidative damage in gonad and vulva. Pre-treatment with vitamin E, a potent antioxidant, at the L2-larval stage prevented the oxidative damage and formation of reproductive deficits in Hg exposed nematodes; however, pre-treatment with paraquat, a regent generating superoxide anions, induced more severe reproductive deficits in Hg exposed nematodes. Moreover, Hg exposure increased expression of clk-2 and isp-1 genes, whose mutations decrease ROS production, and decreased expression of mev-1 and gas-1 genes, whose mutations increase ROS production. Thus, oxidative stress may be essential for the induction of reproductive deficits in Hg exposed hermaphrodite nematodes.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Transtornos do Desenvolvimento Sexual , Mercúrio/toxicidade , Estresse Oxidativo , Reprodução/efeitos dos fármacos , Animais , Animais Geneticamente Modificados , Anti-Infecciosos Locais/toxicidade , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Caenorhabditis elegans/anatomia & histologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Citocromos b , Relação Dose-Resposta a Droga , Complexo III da Cadeia de Transporte de Elétrons/genética , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Gônadas/anatomia & histologia , Gônadas/efeitos dos fármacos , Cloreto de Mercúrio/toxicidade , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismo , Proteínas de Ligação a Telômeros/genética , Proteínas de Ligação a Telômeros/metabolismo , Vitamina E/farmacologia
12.
Neurosci Bull ; 26(2): 104-16, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20332815

RESUMO

OBJECTIVE: To investigate whether genes required for synaptogenesis and synaptic function are also involved in fat storage control in Caenorhabditis elegans. METHODS: Fat storage was examined in mutants of genes affecting the synaptogenesis and synaptic function. In addition, the genetic interactions of SNAREs syntaxin/unc-64 and SNAP-25/ric-4 with daf-2, daf-7, nhr-49, sbp-1 and mdt-15 in regulating fat storage were further investigated. The tissue-specific activities of unc-64 and ric-4 were investigated to study the roles of unc-64 and ric-4 in regulating fat storage in the nervous system and/or the intestine. RESULTS: Mutations of genes required for the formation of presynaptic neurotransmission site did not obviously influence fat storage. However, among the genes required for synaptic function, the plasma membrane-associated SNAREs syntaxin/unc-64 and SNAP-25/ric-4 genes were involved in the fat storage control. Fat storage in the intestinal cells was dramatically increased in unc-64 and ric-4 mutants as revealed by Sudan Black and Nile Red strainings, although the fat droplet size was not significantly changed. Moreover, in both the nervous system and the intestine, expression of unc-64 significantly inhibited the increase in fat storage observed in unc-64 mutant. And expression of ric-4 in the nervous system completely restored fat storage in ric-4 mutant. Genetic interaction assay further indicated that both unc-64 and ric-4 regulated fat storage independently of daf-2 [encoding an insulin-like growth factor-I (IGF-I) receptor], daf-7 [encoding a transforming growth factor-beta (TGF-beta) ligand], and nhr-49 (encoding a nuclear hormone receptor). Besides, mutation of daf-16 did not obviously affect the phenotype of increased fat storage in unc-64 or ric-4 mutant. Furthermore, unc-64 and ric-4 regulated fat storage probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways. In addition, fat storage in unc-64; ric-4 was higher than that in either unc-64 or ric-4 single mutant nematodes, suggesting that unc-64 functions in parallel with ric-4 in regulating fat storage. CONCLUSION: The plasma membrane-associated SNAREs syntaxin/unc-64 and SNAP-25/ric-4 function in parallel in regulating fat storage in C. elegans, probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Gorduras/metabolismo , Mutação/genética , Proteína 25 Associada a Sinaptossoma/genética , Sintaxina 1/genética , Animais , Animais Geneticamente Modificados , Compostos Azo , Caenorhabditis elegans/genética , Sistema Nervoso Central/metabolismo , Genótipo , Insulina/metabolismo , Mucosa Intestinal/metabolismo , Modelos Biológicos , Naftalenos , Oxazinas , Transdução de Sinais/genética , Estatísticas não Paramétricas , Sinapses/genética
13.
Neurosci Bull ; 25(6): 335-42, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19927169

RESUMO

OBJECTIVE: To investigate the role of environmental factor-temperature in the regulation of aging process by unc-13 and sbt-1 in Caenorhabditis elegans. METHODS: The lifespan, the speed of pharynx pumping, and the intestinal autofluorescence of unc-13 and sbt-1 mutants were examined at different temperature conditions. In addition, to exclude the possible influences from other factors in unc-13 and sbt-1 mutants, the dauer formation, the thermotaxis, the brood size and the population percentage of the mutants expressing hsp16.2-gfp were further investigated. RESULTS: Mutations of unc-13 and sbt-1 significantly increased the mean and the maximum lifespans of nematodes cultured at 20 degrees C and 25 degrees C, while no noticeable increase was found at 15 degrees C in either the mean or the maximum lifespan. Investigations on the speed of pharynx pumping and the intestinal autofluorescence suggested that at 20 degrees C and 25 degrees C, mutations of unc-13 and sbt-1 could slow the aging process and delay the accumulation of aging-related cellular damage. Meanwhile, mutations of unc-13 or sbt-1 did not affect the dauer formation or the thermotaxis to different temperatures in nematodes. In contrast, at 20 degrees C and 25 degrees C conditions, mutations of unc-13 and sbt-1 significantly decreased the brood size and the percentage of nematodes expressing hsp16.2-gfp, while no such differences were detected at 15 degrees C. Moreover, the thermotolerance of unc-13 and sbt-1 mutants could be greatly strengthened after the 16-h heat shock at 35 degrees C. CONCLUSION: The regulation of aging by unc-13 and sbt-1 is temperature-dependent. And the alterations in reproduction capability and stress response may be associated with the formation of this temperature-dependent property.


Assuntos
Envelhecimento/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Estresse Fisiológico/fisiologia , Temperatura Ambiente , Envelhecimento/genética , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Proteínas de Transporte , Tamanho da Ninhada/fisiologia , Fluorescência , Proteínas de Choque Térmico/metabolismo , Intestinos/fisiologia , Longevidade/genética , Longevidade/fisiologia , Mutação , Faringe/fisiologia , Estresse Fisiológico/genética
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