RESUMO
We investigated the effect of selective cerebral ultra-profound hypothermic blood flow occlusion on brain tissue and cell metabolism to ascertain the efficacy and safety of selective deep hypothermic technologies using proton magnetic resonance spectroscopy ((1)H-MRS). The bilateral carotid artery was blocked at room temperature for 10 min. Other neck vessels were then blocked through cold perfusion of the internal carotid artery and reflux of the ipsilateral jugular vein. Thus, selective cerebral extracorporeal circulation was established. Brain temperature was reduced to 15.1° ± 0.9°C. After 60 min, cerebral blood flow recovered naturally. Routine magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and (1)H-MRS examination of the bilateral frontal cortex and basal ganglia were performed prior to surgery and 4, 24, 72 h, 21 days after recovery. The formants and areas under the curve (AUC) of N-acetyl aspartate (NAA), choline (Cho), creatine/phosphocreatine (Cr/Cr2) were analyzed using 1H-MRS. The pre- and postoperative AUC of NAA and Cho at different time points were compared. Conventional MRI and DWI showed no abnormal signal changes in the brain parenchyma or right basal ganglia before and after surgery (P > 0.05). There was no significant difference in the ratio between NAA/(Cr+Cr2) and Cho/(Cr+Cr2) before and after surgery in the bilateral basal ganglia and frontoparietal regions of the cortex (P > 0.05). Quantitative (1)H-MRS showed that selective deep cerebral hypothermia significantly improved the brain's tolerance to ischemia and hypoxia. Our results could provide a better understanding of the efficacy and safety of selective deep hypothermia and blood flow occlusion.
Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Transtornos Cerebrovasculares/patologia , Espectroscopia de Prótons por Ressonância Magnética/métodos , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Estenose das Carótidas , Transtornos Cerebrovasculares/metabolismo , Colina/metabolismo , Parada Circulatória Induzida por Hipotermia Profunda/métodos , Creatina/metabolismo , Feminino , Macaca mulatta , Masculino , RessuscitaçãoRESUMO
We examined the relationships between single-nucleotide polymorphisms (SNPs) in the DNA repair gene XPD751 and the efficacy and time to disease progression (TTP) in colorectal cancer patients after platinum-based chemotherapy. Ninety-eight patients diagnosed with advanced colorectal cancer were subjected to oxaliplatin and 5-fluorouracil combination therapy. DNA was extracted from venous blood before chemotherapy. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to detect XPD751 SNPs. The relationship between genotypes and prognosis was compared. The frequencies of the XPD751 Lys/Lys, Lys/Gln, and Gln/Gln genotypes were 76 (77.55%), 17 (17.35%), and 5 (5.10%), respectively. The efficiency of XPD751 Lys/Lys, Lys/Gln and Gln/Gln genotypes were 50.00, 29.41, and 20%, respectively. The efficiency rate between XPD751 Lys/Lys and Lys/Gln showed a significant difference (c² = 4.04, P < 0.05). After adjusting for gender, age, and metastasis location, chemotherapy failure in patients carrying XPD751 Lys/Gln was 3.404-fold higher than in patients carrying the Lys/Lys genotype. Median TTP was 304 days (10.1 months) and median TTP in patients with XPD751 Lys/Lys and ≥1 Gln genotype was 340 and 87 days. After comparing TTP in patients carrying Lys/Lys and patients carrying ≥1 Gln, the difference was significant. SNPs in the DNA repair gene XPD751 may be associated with oxaliplatin and 5-fluorouracil chemotherapy sensitivity in colorectal cancer patients. These polymorphisms may be associated with TTP in patients with advanced colorectal cancer after first-line chemotherapy of oxaliplatin. XPD751 SNPs may be predictive factors of prognosis in colorectal cancer patients receiving oxaliplatin and 5-fluorouracil chemotherapy.
Assuntos
Neoplasias Colorretais/genética , Progressão da Doença , Prognóstico , Proteína Grupo D do Xeroderma Pigmentoso/genética , Adulto , Idoso , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Reparo do DNA/genética , Feminino , Fluoruracila/administração & dosagem , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Polimorfismo de Nucleotídeo ÚnicoRESUMO
We examined expression differences in breast cancer stem cells (BCSCs) of the doxorubicin-resistant breast cancer cell line MCF-7/ADM and doxorubicin-sensitive cell line MCF-7/S. The effects of Chinese medicine ß-elemene on BCSCs and resistance protein expression were determined. The serum-free cell culture method was used for cell culture, and morphology was observed to determine the rate of cell sphere formation. Reverse transcription-polymerase chain reaction was used to detect breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) gene expression. Flow cytometry was used to determine BCRP- and P-gp-positive cell rates and CD44 + CD24-/low cell ratios. Morphological observation and gene amplification showed that compared with MCF-7/S cells, the serum-free cell sphere-forming rate and P-gp and BCRP gene expression levels were higher in MCF-7/ADM cells. Flow cytometry results showed that P-gp and BCRP protein expression in MCF-7/ADM cells was 77.78 ± 9.55% and 32.33 ± 5.12%, respectively, and the CD44 + CD24-/low cell rate was 64.79 ± 11.78%, which were all significantly higher than those in MCF-7/S cells (3.97 ± 1.51, 14.26 ± 2.51, 18.79 ± 3.28%; P < 0.05). ß-elemene significantly decreased the serum-free cell sphere-forming rate in MCF-7/ADM cells and BCRP and P-gp gene/protein expression (P < 0.01). The proportion of CD44 + CD24-/low cells was reduced. MCF-7/ADM highly expressed the drug-resistant proteins BCRP and P-gp, which can be used for long-term in vitro culture and as a seed cell for studies of BCSCs. ß-elemene can inhibit BCSC and the sphere-forming rate in MCF-7/ADM cells and reduce BCRP expression.
Assuntos
Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Sesquiterpenos/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Meios de Cultura Livres de Soro/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismoRESUMO
This study aimed to establish reference intervals for serum thyroid hormones [serum thyroid-stimulating hormone (TSH), triiodothyronine (TT3), thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4)] in apparently healthy individuals living in Zhengzhou. According to the requirement for laboratory support for the diagnosis and monitoring of thyroid diseases in the National Academy of Clinical Biochemistry (NACB) laboratory medicine practice guidelines, a total of 211 apparently healthy individuals were enrolled (94 men, 117 women, 23-77 years old) from Zhengzhou for measurement of serum levels of TSH, TT3, TT4, FT3, and FT4 by using the Siemens ADVIA Centaur XP analyzer. All markers were analyzed across gender- and age-specific groups by using the t-test and ANOVA. The reference intervals of all markers were determined by P2.5-P97.5. We detected gender-associated statistical significances for TT3, TT4, FT3, and FT4 (t=3.299, 2.141, 5.868, 5.358; P<0.05), but not for TSH (t=-1.776, P>0.05). Correlation analysis showed that all markers were negatively correlated with age (P>0.05). The new reference intervals for TT3, TT4, FT3, FT4, and TSH were established: 0.76-1.38 ng/mL, 5.96-11.27 µg/dL, 3.88-5.59 pM, 11.69-18.84 pM, 0.89-5.93 µIU/mL, respectively. In conclusion, we added a new database of reference intervals of the serum thyroid hormones for the Chinese adult population.
Assuntos
Hormônios Tireóideos/sangue , Adulto , Fatores Etários , Idoso , China , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Fatores Sexuais , Adulto JovemRESUMO
Intracranial aneurysm is a balloon or sac-like dilatation of blood vessels inside the brain. Despite their importance, the biological mechanisms of intracranial aneurysms are not totally understood. We used public genome-wide gene expression profile data to identify potential genes that are involved in intracranial aneurysm in order to construct a regulation network. Some of the transcription factors and target genes that we identified in this network had been identified as related to intracranial aneurysm in previous studies. We found additional transcription factors and target genes that are apparently related to intracranial aneurysm with this method. The confirmation of previously identified genes and transcription factors supports the usefulness of this transcriptome network analysis for the identification of candidate genes involved in intracranial aneurysm.