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1.
Pharmacol Res ; 153: 104637, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31935454

RESUMO

The Aidi injection contains multiple active ingredients, including astragaloside (Re, Rb1, and Rg1), ginsenoside, cantharidin, elentheroside E, and syringin, and it is administered with vinorelbine and cisplatin (NP) to treat non-small-cell lung carcinoma (NSCLC). In this study, we performed a systematic review and meta-analysis to determine the clinical efficacy and safety of the Aidi injection with NP, and the optimal threshold and treatment regimen to produce the desired responses. We collected all studies regarding the Aidi injection with NP for NSCLC from Chinese and English databases (up to April 2019). Risk of methodological bias was evaluated for each study. Data for analysis were extracted using a standard data extraction form. Evidence quality was assessed following the Grading of Recommendations Assessment, Development and Evaluation approach. We included 54 trials containing 4,053 patients for analysis. Combining the Aidi injection with NP significantly increased the objective response rate (odds ratio [OR], 1.32; confidence interval [CI], 1.23, 1.42), disease control rate (OR, 1.14; CI, 1.11, 1.18), and quality of life (OR, 1.80; CI, 1.61, 1.98), with decreased risks of myelosuppression, neutropenia, thrombocytopenia, anemia, gastrointestinal reaction, and liver dysfunction. For patients with a Karnofsky Performance Status score of ≥60, the Aidi injection (50 mL/day, two weeks/cycle, with two to three cycles) treatment with vinorelbine (25 mg/m2) and cisplatin (30-35 mg/m2 or 40-50 mg/m2) might be the optimal regimen for producing the desired tumor response and achieving a good safety level. Most results were robust, and their quality was moderate. The results suggest that administration of the Aidi injection and concomitant NP is beneficial to NSCLC, and provide evidence for the optimal threshold and treatment regimen that may improve tumor response with a good safety level.

2.
Biosens Bioelectron ; 150: 111862, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31740256

RESUMO

Salmonella is the leading risk factor in food safety. Rapid, sensitive and accurate detection of Salmonella is a key to prevent and control the outbreaks of foodborne diseases caused by Salmonella. In this study, we reported a colorimetric biosensor for ultrasensitive detection of Salmonella Typhimurium using a magnetic grid separation column to efficiently separate target bacteria from large volume of sample and platinum loaded zeolitic imidazolate framework-8 (Pt@ZIF-8) nanocatalysts to effectively amplify biological signal. The target Salmonella cells in large volume of sample were first separated and concentrated using the magnetic grid separation column with immune magnetic particle chains, then conjugated with the immune Pt@ZIF-8 nanocatalysts to mimic peroxidase for catalysis of hydrogen peroxide-3,3',5,5'-tetramethylbenzidine, and finally determined by measuring the catalysate at characteristic wavelength of 450 nm. This proposed biosensor was able to separate ∼70% of target Salmonella cells from 50 mL of bacterial sample and quantitatively detect Salmonella from 101 to 104 CFU/mL in 2.5 h with the lower detection limit of 11 CFU/mL. The mean recovery for Salmonella in spiked chicken carcass was about 109.8%. This new magnetic grid separation method was first time reported for efficient separation of target bacteria from very large volume of sample to greatly improve the sensitivity of this biosensor and could be used with various biosensing assays for practical applications in routine detection of foodborne pathogens without any bacterial pre-enrichment.

3.
Brain Behav ; 10(2): e01503, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31872978

RESUMO

AIMS: Stroke is a complicated neurological disease and the second leading cause of death in the world. We aimed to investigate the association between CYP24A1 genetic polymorphisms and ischemic stroke risk. METHODS: In this case-control study, four single-nucleotide polymorphisms of CYP24A1 were selected and genotyped by MassARRAY platform in Chinese Han population. Odds ratios and 95% confidence intervals were calculated via logistic regression analysis with adjustment in genetic models. RESULTS: Our results indicated that CYP24A1 variant (rs1570669) was associated with the decreased risk of ischemic stroke (OR = 0.60, p < .001). Stratification analysis showed that the rs6068816 could enhance the ischemic stroke risk by 1.64 times (OR = 1.64, p = .028), while rs1570669 played protective role (OR = 0.63, p = .044) in age >64 years. The rs2762934 had an increased ischemic stroke susceptibility (OR = 1.62, p = .033); however, rs1570669 might reduce stroke risk (OR = 0.61, p = .015) in age ≤64 years. The rs1570669 depressed ischemic stroke susceptibility both in female and male patients (OR = 0.46, p = .002; OR = 0.69, p = .033, respectively), and rs2296241 would weaken the risk in male (OR = 0.63, p = .012). The rs1570669 was associated with decreased risk of ischemic stroke with hypertension (OR = 0.56, p = .042). CONCLUSION: Our study gave the evidences that CYP24A1 genetic polymorphisms were significantly associated with ischemic stroke patients, which would provide useful information of assessment or possible diagnostic markers for ischemic stroke.

4.
Front Public Health ; 7: 315, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31799230

RESUMO

Background: Cytochrome P450 3A4 (CYP3A4) regulates pharmacokinetic and pharmacodynamic interactions during the process of drug absorption and metabolism, suggesting CYP3A4 plays an important role in drug addiction. However, the association between CYP3A4 polymorphisms and drug addiction risk is still not clear. Methods: This case-control study included 504 drug addicts and 501 healthy controls from Xi'an, China. Four single nucleotide polymorphisms (SNP) in CYP3A4 (rs3735451, rs4646440, rs35564277, and rs4646437) were genotyped by Agena MassARRAY platform. After adjusting by age and gender, we calculated odd ratios (OR) and 95% confidence intervals (CI) by logistic regression to estimate the association between CYP3A4 polymorphisms and drug addiction risk. Results: We found rs4646440 and rs4646437 were associated with decreased risk of drug addiction in codominant (rs4646440: OR = 0.41, 95%CI = 0.19-0.92, p = 0.030; rs4646437: OR = 0.19, 95%CI = 0.04-0.87, p = 0.032) and recessive (rs4646440: OR = 0.41, 95%CI = 0.19-0.91, p = 0.028; rs4646437: OR = 0.20, 95%CI = 0.04-0.90, p = 0.036) models. Rs3735451 and rs4646437 were associated with drug addiction risk in the subgroup of middle-aged people (44 < age ≤ 59) and elderly people (age ≥ 60), individually. For men, rs3735451, rs4646440, and rs4646437 had strong relationship with decreased risk of drug addiction (p < 0.05). The effects of rs3735451 on drug addiction risk were related to drug-using time (p < 0.05). We also observed one block (rs4646440 and rs35564277) in haplotype analysis. Conclusion: CYP3A4 polymorphisms were associated with drug addiction risk among the Chinese Han population.

5.
Theor Biol Med Model ; 16(1): 20, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31865918

RESUMO

Variations of gene expression levels play an important role in tumors. There are numerous methods to identify differentially expressed genes in high-throughput sequencing. Several algorithms endeavor to identify distinctive genetic patterns susceptable to particular diseases. Although these processes have been proved successful, the probability that the number of non-differentially expressed genes measured by false discovery rate (FDR) has a large standard deviation, and the misidentification rate (type I error) grows rapidly when the number of genes to be detected become larger. In this study we developed a new method, Unit Gamma Measurement (UGM), accounting for multiple hypotheses test statistics distribution, which could reduce the dependency problem. Simulated expression profile data and breast cancer RNA-Seq data were utilized to testify the accuracy of UGM. The results show that the number of non-differentially expressed genes identified by the UGM is very close to the real-evidence data, and the UGM also has a smaller standard error, range, quartile range and RMS error. In addition, the UGM can be used to screen many breast cancer-associated genes, such as BRCA1, BRCA2, PTEN, BRIP1, etc., provides better accuracy, robustness and efficiency, the method of identification differentially expressed genes in high-throughput sequencing.

6.
Arch Bronconeumol ; 2019 Nov 21.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31761491

RESUMO

BACKGROUND: High-altitude pulmonary edema (HAPE) is a kind of non-cardiogenic edema with high incidence and life-threatening. This study was designed to explore the association of LINC-PINT and LINC00599 polymorphisms with HAPE susceptibility. METHODS: This study included 244 HAPE patients and 243 age-, sex-matched healthy controls from the Chinese population. The genotypes of polymorphisms were detected using the Agena MassARRAY. The relationship between polymorphisms and HAPE risk was evaluated using a χ2 test with an odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models. RESULTS: We observe a significant association between the rs157928 and decreased HAPE risk in genotype model (OR=0.65, 95% CI=0.43-0.98, p=0.038). The subgroup analysis results indicated that rs2272026 was associated with a decreased risk of HAPE in younger patients with age ≤32 (codominant model: p=0.006; recessive model: p=0.005 additive model: p=0.018; and allele model: p=0.012; rs72625676, codominant model: p=0.038; recessive model: p=0.037). Among patients older than 32 years, there was a significantly increased risk of HAPE associated with the rs2272026 and rs1962430 (rs2272026: genotype model: p=0.049; recessive model: p=0.029; rs1962430: genotype model: p=0.024; recessive model: p=0.020). Nevertheless, rs157928 had relationship with significantly reducing the risk of HAPE in the genotype model (p=0.018). CONCLUSION: Our study suggests that LINC-PINT and LINC00599 polymorphisms are associated with HAPE susceptibility in Chinese population.

7.
Int J Nanomedicine ; 14: 7447-7460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686816

RESUMO

Objective: This study aimed to investigate the interaction between the ion-complementary self-assembling peptide RADA16-I and the hydrophobic drug mangiferin (MA), and the potential of the self-assembling peptide to be exploited as a drug carrier of MA. Methods: The RADA16-I-MA suspension was prepared by magnetic stirring, followed by fluorescence spectrophotometry, particle size determination, rheological properties analysis, and in vitro release assay to characterize the interaction between RADA16-I and MA. Then, the effects of in situ MA-loaded hydrogel on the proliferation of KYSE 30 and DLD-1 tumor cells and the toxic effect of the hydrogel on 293T renal epithelial cells were studied by the Cell Counting Kit 8 method. Results: The RADA16-I-MA suspension was formed in water under magnetic stirring; the in situ hydrogel was formed when the suspension was added to PBS. The particle size in the RADA16-I-MA suspension was around 300-600 nm with an average size of 492 nm. Within 24 h, the cumulative release of MA from the RADA16-I-MA hydrogel was about 80%. The release rate of MA from the hydrogel was dependent on the concentration of RADA16-I and the release can be fitted with a first-order kinetic equation. The results suggested that the self-assembling peptide can stabilize MA in water to form a relatively stable suspension; the results also indicated that controlled release of MA from the RADA16-I-MA in situ hydrogel formed from the RADA16-I-MA suspension can be achieved by adjusting the concentration of the peptide in suspension. The cell viability studies showed that the RADA16-I-MA in situ hydrogel not only can maintain or enhance the intrinsic proliferation inhibition effects of MA on tumor cells, but also can reduce the toxicity of MA to normal cells. Conclusion: The self-assembling peptide RADA16-I can be a potential candidate for constructing a delivery system of the hydrophobic drug MA.


Assuntos
Liberação Controlada de Fármacos , Hidrogéis/química , Peptídeos/química , Xantonas/química , Morte Celular , Linhagem Celular , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Coloides/química , Elasticidade , Humanos , Tamanho da Partícula , Reologia , Espectrometria de Fluorescência , Suspensões , Viscosidade
8.
Artif Cells Nanomed Biotechnol ; 47(1): 3961-3975, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31588802

RESUMO

Ion-complementary self-assembling peptides have potential in delivering hydrophobic drugs. This study involved two self-assembling peptides, RADA16-I and RVDV16-I, of which RVDV16-I was a novel self-assembling peptide with different hydrophobic side chains designed from RADA16-I. The purpose of this study was to observe the interaction between different self-assembling peptides and emodin through fluorescence spectrophotometry, CD, SEM and AFM; to construct a preliminary suspension in-situ hydrogel delivery system for emodin with the self-assembling peptides; and to investigate the drug-loading and drug-releasing properties of the self-assembling peptides on emodin. The results showed that both peptides can interact with emodin and the interaction was dominated by hydrophobic interaction. The aqueous solutions of both self-assembling peptides can form relatively stable suspensions with emodin under mechanical stirring, and the suspension can form in-situ hydrogel under physiological condition. In vitro release of emodin from the hydrogels showed a manner of sustained release to some extent. Cell viability studies showed inherent proliferation inhibiting effects of emodin on tumor cells was maintained or enhanced through the in-situ hydrogels. The self-assembling peptides RADA16-I and RVDV16-I had showed promising drug-loading and drug-releasing performance for hydrophobic drugs. It is reasonable to exploit self-assembling peptides as drug carriers for their great potential to improve delivery of hydrophobic drugs.

9.
Oncol Rep ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31524264

RESUMO

Oxaliplatin (OXA) is routinely used as the first­line treatment for colorectal cancer (CRC). The addition of OXA to chemotherapy has significantly improved the prognosis of patients with CRC; however, some cases are resistant to OXA. The present study explored the influence of organic cation transporter 3 (OCT3) expression on the effects of OXA on CRC cell viability, and investigated the direct effects of OCT3 on viability, invasion and migration of CRC cells using MTT assay, wound healing assay, reverse transcription­quantitative polymerase chain reaction, inductively coupled plasma mass spectrometry and lentiviral interference. The results demonstrated that OXA cellular concentration and OXA­induced cytotoxicity were significantly increased in response to high expression of OCT3, whereas OCT3 knockdown directly increased the invasion and migration of colon cancer cells. Furthermore, upregulation of OCT3 expression in colon cancer xenografts via treatment with the DNA methyltransferase inhibitor decitabine increased cellular OXA concentration and improved the curative effect of OXA. These results collectively indicated that OCT3 may enhance the effects of OXA in CRC cells and may directly inhibit their invasion and migration. Therefore, OCT3 may be a therapeutic target in patients with CRC.

10.
Mol Genet Genomic Med ; 7(11): e966, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31487124

RESUMO

BACKGROUND: Kidney cancer is the predominant form of malignancy of the kidney and accounts for approximately 3%-4% of all cancers. Renal cell cancer (RCC) represents more than 85% of kidney cancer. It has been reported that genetic factors may predispose individuals to RCC. This study evaluated the association between Acylphosphatase 2 (ACYP2) gene polymorphisms and RCC risk in the Han Chinese population. METHODS: Twelve single-nucleotide polymorphisms (SNPs) in ACYP2 were genotyped using the Agena MassARRAY platform from 293 RCC patients and 495 controls. The Chi-squared test, genetic models, haplotype, and stratification analyses were used to evaluate the association between SNPs and the risk of RCC. The relative risk was estimated using the odds ratio (OR) and 95% confidence interval (CI). RESULTS: We observed that the rs6713088 allele G (OR = 1.26, 95% CI: 1.03-1.53, p = .023) and rs843711 allele T (OR = 1.29, 95% CI: 1.06-1.57, p = .010) were associated with increased RCC risk. Genetic model analyses found that rs843711 was significantly associated with an increased RCC risk under the recessive model and log-additive model after adjusting for age and gender. Haplotype analysis showed that the haplotype "TTCTCGCC" (OR = 0.67, 95% CI: 0.48-0.94, p = .021) was associated with a decreased risk of RCC in the Han Chinese population. Stratification analysis also found that rs6713088 and rs843711 were significantly associated with increased RCC risk. CONCLUSION: In summary, the results suggested that ACYP2 polymorphisms could be used as a genetic marker for RCC. Additional functional and association studies are required to validate our results.

11.
Mol Genet Genomic Med ; 7(8): e770, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31241240

RESUMO

BACKGROUND: Tuberculosis (TB) is a significant worldwide health problem, and is caused by Mycobacteria tuberculosis. Recent studies have suggested that FOXO3 plays vital roles in the risk of immune-related infectious diseases such as TB. METHODS AND RESULTS: The present study aimed to evaluate FOXO3 genetic variants and TB risk. We recruited 510 TB patients and 508 healthy controls in this study. All subjects were genotyped with the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression adjusted for age and gender. Our result revealed that rs3800229 T/G and rs4946935 G/A genotypes significantly increased the risk of TB (OR = 1.34, 95% CI = 1.04-1.74, p = 0.026; OR = 1.34, 95% CI = 1.03-1.73, p = 0.029, respectively). In stratified analysis according to gender and age, we observed that rs3800229 T/G and rs4946935 G/A genotypes were associated with an increase the risk of TB among males and age ≤41 years, respectively (OR = 1.47, 95% CI = 1.06-2.04, p = 0.022 and OR = 1.45, 95% CI = 1.05-2.02, p = 0.025). CONCLUSIONS: Our study showed that rs3800229 and rs4946935 in FOXO3 were associated with a risk of TB in the Chinese population.

12.
Anticancer Agents Med Chem ; 19(4): 502-508, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30663574

RESUMO

BACKGROUND: Target therapy has been one of the important strategies in new drug discovery and the resulting drug resistance has also been a serious problem for concern. At the same time, there are several cancer genes or pathways operating within a given cancer. Given these two things, the combination therapy will be needed for optimal therapeutic effect. OBJECTIVE: Camptothecin and norcantharidin were thus chosen to construct a dual anticancer drugs assemblies mainly because CPT was the DNA-topoisomerase I inhibitor and norcantharidin could also suppress the cancer cell growth by inhibiting protein phosphatase. The designed conjugate of camptothecin and norcantharidin linked by alanine was expected to have dual target drug properties. METHODS: EDCI/DMAP was chosen as a coupling agent for the coupling of CPT with substituted norcantharidin derivatives and CCK-8 method was used to test the cytotoxicity and intensity on human hepatoma cell line HepG2. Two kinds of enzymes, Top I and CDC 25B were selected to screen the binding affinity in molecular level. RESULTS: Nine of dual targets camptothecin derivatives were smoothly synthesized by twice coupling in the condition of EDCI/DMAP in moderate yield. All of the synthesized compounds were characterized by 1HNMR and 13CNMR spectrum and exhibited strong potent inhibition against Hep G2, SW480, BGC803, and PANC-1 cell line in vitro. The newly synthesized camptothecin compounds, such as 3j and 3i have strengthened inhibition activity compared to camptothecin and norcantharidin. CONCLUSION: We have successfully synthesized a series of novel camptothecin derivatives constructed from three components of camptothecin, alanine and norcantharidin. These compounds not only preserved strong activity against several cancer cell lines in vitro, but also exhibited potential binding affinity to target Top I and CDC 25B. Therefore, these conjugates linked by alanine could suppress cancer cell growth by inhibiting Top I and protein phosphatase simultaneously, which makes it much valuable as a novel bi-functional target drug candidate to develop in vivo.

13.
J Ethnopharmacol ; 228: 110-122, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30243827

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As an important Chinese herb injection, Aidi injection is composed of the extracts from Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis. Aidi injection plus paclitaxel-based chemotherapy is often used to in the treatment of non-small cell lung cancer (NSCLC) in China. AIM OF THE STUDY: The objective of this study is to further confirm whether Aidi injection can improve the tumor responses and survivals, and reveal its safety, optimal usage and combination with paclitaxel. MATERIALS AND METHODS: A meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All randomized controlled trials (RCTs) concerning the Aidi injection plus paclitaxel-based chemotherapy for NSCLC were selected. Main outcomes were objective response rate (ORR), disease control rate (DCR), survivals, quality of life (QOL) and adverse drug reactions (ADRs). All data were extracted by using a standard data extraction form and synthesized through meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence. RESULTS: Thirty-one RCTs involving 2058 patients were included, and most trials had an unclear methodological bias risk. The risk ratio (RR) and 95% confidence intervals (CI) of ORR, DCR, QOL, neutropenia, thrombocytopenia, gastrointestinal toxicity and liver injury were as following: 1.32 (1.20-1.46), 1.14 (1.09-1.20), 1.89 (1.66-2.16), 0.61 (0.51-0.74), 0.62 (0.45-0.87), 0.59 (0.49-0.72) and 0.52 (0.36-0.75). Compared to chemotherapy alone, all differences were statistically significant. Subgroup analysis showed that only with the TP, Aidi injection could increase the ORR and DCR. Treatment with 100 ml, 80 ml or 50 ml/time, and 14 days/2 cycles or 21 days/2-4 cycles, Aidi injection could increase the ORR and DCR, respectively. Sensitivity analysis showed that the results had good robustness. None of the trials reported the overall survivals (OS), progression free survival (PFS). The quality of evidences was moderate. CONCLUSIONS: Current moderate evidence revealed that Aidi injection plus paclitaxel-based chemotherapy, especially TP can significantly improve the clinical efficacy and QOL for patients with stage III/IV NSCLC. Aidi injection can relieve the risk of hematotoxicity, gastrointestinal toxicity and liver injury in patient with NSCLC receiving paclitaxel-based chemotherapy. The optimal usage may be 50 ml/time and 14 days/2 cycles.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Humanos , Fitoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(4): 546-550, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30378307

RESUMO

OBJECTIVE: To determine the expression of microRNA-221 (miR-221) in endometrial tissues and its impact on the proliferation of ectopic endometrial stromal cells. METHODS: Endometrial stromal cells were isolated, cultured and identified from normal endometrial tissues (taken from patients without endometriosis) and ectopic endometrial tissues (taken from patients with ovarian endometriosis). The expression of microRNA-221 was detected by stem-loop qRT-PCR. Changes in the expression of miR-221-3p in endometrial stromal cells exposed to estraldiol (10-8 mol/L) for 48 h were detected. The effects of miR-221-3p inhibitor on the expressions of miR-221-3p, phosphatase and tensin homology deleted on chromosome ten (PTEN) and cell proliferations were compared with those of the negative control (NC, 10 nmol/L). RESULTS: The expression of miR-221-3p in ectopic endometrial tissues was 4.2 times higher than that in normal endometrial tissues (P=0.039): 2.66 times higher in ectopic endometrial stromal cells compared with normal endometrial stromal cells (P=0.029). But no differences in the expression of miR-221-5p were found (P>0.05). No differences in the change of miR-221-3p expression after exposure to estrogen for 48h were found between normal and ectopic stromal cells. Inhibition of miR-221-3p function was associated with decreased cell proliferation (P=0.018) and increased expression of PTEN gene (P=0.021). CONCLUSION: The expression of microRNA-221 is upregulated in ectopic endometrial tissues and ectopic endometrial stroma cells. Inhibiting the function of miR-221-3p may result in increased PTEN expression and decreased cell proliferation in endometrial stromal cells.


Assuntos
Endometriose/metabolismo , MicroRNAs/metabolismo , Células Estromais/citologia , Proliferação de Células , Endométrio/citologia , Feminino , Humanos , PTEN Fosfo-Hidrolase/metabolismo , Células Estromais/metabolismo
15.
Oncol Rep ; 40(6): 3694-3704, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30272316

RESUMO

Gastrointestinal cancer (GIC) is a worldwide public health problem with a high mortality rate. Mitochondrial DNA (mtDNA) mutations in the displacement loop (D­loop) region are quite common in various types of primary human cancers; however, their role in the pathogenesis of GIC is controversial. In the present study, tumor and para­tumor tissues were selected from 18 patients with gastric cancer (GC), 21 patients with colon cancer (CC) and 30 patients with rectal cancer (RC). The mtDNA D­loop was analyzed by sequencing and reverse transcription­quantitative polymerase chain reaction. Furthermore, DNA oxidative damage and DNA repair functioning were detected by immunohistochemistry. The results demonstrated that increased mtDNA deletion was not evident in GIC; however, significant DNA oxidative damage was significant in RC by detecting 8­hydroxyguanine expression. In addition, over­activated DNA repair was identified in CC and RC through the detection of 8­oxo­20­deoxyguanosine glycosylase 1 expression. The mtDNA D­loop had a specific mutation hotspot region, and the level of mtDNA D­loop mutations was correlated with the progression of the GIC. The mutations of the mtDNA D­loop were primarily homoplasmic in GIC and often transitioned at pyrimidine sites. Mitochondrial microsatellite instability, including the formation of poly­cytidine stretches, was common in GIC. These results demonstrate the occurrence of mtDNA D­loop mutations in GIC in Chinese patients and support the correlation of these mutations with carcinoma progression. Over­activated DNA repair function possibly repairs the GIC mtDNA lesions.


Assuntos
Reparo do DNA , DNA Mitocondrial/genética , Neoplasias Gastrointestinais/genética , Mitocôndrias/genética , Mutação , Adulto , Idoso , China , Dano ao DNA , DNA Mitocondrial/química , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA/métodos
16.
R Soc Open Sci ; 5(2): 170842, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29515825

RESUMO

A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I. The total yield can reach 71%. This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues. The new synthetic compound I has been shown to exhibit better solubility and similar activity against tumour cell lines.

17.
Med Phys ; 44(12): 6504-6514, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28887825

RESUMO

PURPOSE: The purpose of this study was to investigate and characterize the performance of a Multi Leaf Collimator (MLC) designed for Cobalt-60 based MR-guided radiation therapy system in a 0.35 T magnetic field. METHODS: The MLC design and unique assembly features in the ViewRay MRIdian system were first reviewed. The RF cage shielding of MLC motor and cables were evaluated using ACR phantoms with real-time imaging and quantified by signal-to-noise ratio. The dosimetric characterizations, including the leaf transmission, leaf penumbra, tongue-and-groove effect, were investigated using radiosensitive films. The output factor of MLC-defined fields was measured with ionization chambers for both symmetric fields from 2.1 × 2.1 cm2 to 27.3 × 27.3 cm2 and asymmetric fields from 10.5 × 10.5 cm2 to 10.5 × 2.0 cm2 . Multi leaf collimator (MLC) positional accuracy was assessed by delivering either a picket fence (PF) style pattern on radiochromic films with wire-jig phantom or double and triple-rectangular patterns on ArcCheck-MR (Sun Nuclear, Melbourne, FL, USA) with gamma analysis as the pass/fail indicator. Leaf speed tests were performed to assess the capability of full range leaf travel within manufacture's specifications. Multi leaf collimator plan delivery reproducibility was tested by repeatedly delivering both open fields and fields with irregular shaped segments over 1-month period. RESULTS: Comparable SNRs within 4% were observed for MLC moving and stationary plans on vendor-reconstructed images, and the direct k-space reconstructed images showed that the three SNRs are within 1%. The maximum leaf transmission for all three MLCs was less than 0.35% and the average leakage was 0.153 ± 0.006%, 0.151 ± 0.008%, and 0.159 ± 0.015% for head 1, 2, and 3, respectively. Both the leaf edge and leaf end penumbra showed comparable values within 0.05 cm, and the measured values are within 0.1 cm with TPS values. The leaf edge TG effect indicated 10% underdose and the leaf end TG showed a shifted dose distribution with 0.3 cm offset. The leaf positioning test showed a 0.2 cm accuracy in the PF style test, and a gamma passing rate above 96% was observed with a 3%/2 mm criteria when comparing the measured double/triple-rectangular pattern fluence with TPS calculated fluence. The average leaf speed when executing the test plan fell in a range from 1.86 to 1.95 cm/s. The measured and TPS calculated output factors were within 2% for squared fields and within 3% for rectangular fields. The reproducibility test showed the deviation of output factors were well within 2% for square fields and the gamma passing rate within 1.5% for fields with irregular segments. The Monte Carlo predicted output factors were within 2% compared to TPS values. 15 out of the 16 IMRT plans have gamma passing rate more than 98% compared to the TPS fluence with an average passing rate of 99.1 ± 0.6%. CONCLUSION: The MRIdian MLC has a good RF noise shielding design, low radiation leakage, good positioning accuracy, comparable TG effect, and can be modeled by an independent Monte Carlo calculation platform.


Assuntos
Imagem por Ressonância Magnética , Radioterapia Guiada por Imagem/instrumentação , Estudos de Viabilidade , Método de Monte Carlo , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador
18.
Cochrane Database Syst Rev ; 7: CD009881, 2017 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-28742263

RESUMO

BACKGROUND: Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis. OBJECTIVES: To assess the effectiveness and safety of PRMs primarily in terms of pain relief as compared with other treatments or placebo or no treatment in women of reproductive age with endometriosis. SEARCH METHODS: We searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov, and the World Health Organization (WHO) platform, from inception to 28 November 2016. We handsearched reference lists of articles retrieved by the search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects. MAIN RESULTS: We included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants). Mifepristone versus placebo One study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.At three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present. Mifepristone dose comparisons Two studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia. Gestrinone comparisons Ons study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.Evidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n = 222; very low-quality evidence). The gestrinone group had a higher rate of hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to 0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI 0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95% CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).When researchers compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal rating scale (lower score denotes benefit), the mean dysmenorrhoea score was higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n = 55; low-quality evidence), but the mean dyspareunia score was lower in this group (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49; low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92, 95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).Evidence was insufficient to show differences in effectiveness or safety between different doses of gestrinone, if present. Asoprisnil versus placebo One study (n = 130) made this comparison but did not report data suitable for analysis. Ulipristal versus leuprolide acetate One study (n = 38) made this comparison but did not report data suitable for analysis. AUTHORS' CONCLUSIONS: Among women with endometriosis, moderate-quality evidence shows that mifepristone relieves dysmenorrhoea, and low-quality evidence suggests that this agent relieves dyspareunia, although amenorrhoea and hot flushes are common side effects. Data on dosage were inconclusive, although they suggest that the 2.5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.


Assuntos
Endometriose/tratamento farmacológico , Antagonistas de Hormônios/uso terapêutico , Mifepristona/uso terapêutico , Receptores de Progesterona/antagonistas & inibidores , Danazol/uso terapêutico , Dismenorreia/tratamento farmacológico , Dismenorreia/epidemiologia , Dispareunia/tratamento farmacológico , Dispareunia/epidemiologia , Estrenos/uso terapêutico , Feminino , Gestrinone/efeitos adversos , Gestrinone/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/efeitos adversos , Humanos , Leuprolida/efeitos adversos , Leuprolida/uso terapêutico , Mifepristona/administração & dosagem , Mifepristona/efeitos adversos , Norpregnadienos/uso terapêutico , Oximas/uso terapêutico , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Phys Med Biol ; 62(12): 4970-4990, 2017 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-28425920

RESUMO

Online adaptive radiation therapy (ART) based on real-time magnetic resonance imaging represents a paradigm-changing treatment scheme. However, conventional quality assurance (QA) methods based on phantom measurements are not feasible with the patient on the treatment couch. The purpose of this work is to develop a fast Monte Carlo system for validating online re-optimized tri-60Co IMRT adaptive plans with both high accuracy and speed. The Monte Carlo system is based on dose planning method (DPM) code with further simplification of electron transport and consideration of external magnetic fields. A vendor-provided head model was incorporated into the code. Both GPU acceleration and variance reduction were implemented. Additionally, to facilitate real-time decision support, a C++ GUI was developed for visualizing 3D dose distributions and performing various analyses in an online adaptive setting. A thoroughly validated Monte Carlo code (gPENELOPE) was used to benchmark the new system, named GPU-accelerated DPM with variance reduction (gDPMvr). The comparison using 15 clinical IMRT plans demonstrated that gDPMvr typically runs 43 times faster with only 0.5% loss in accuracy. Moreover, gDPMvr reached 1% local dose uncertainty within 2.3 min on average, and thus is well-suited for ART QA.


Assuntos
Cabeça/diagnóstico por imagem , Método de Monte Carlo , Neoplasias/radioterapia , Imagens de Fantasmas , Garantia da Qualidade dos Cuidados de Saúde , Planejamento da Radioterapia Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/normas , Humanos , Radiometria , Dosagem Radioterapêutica
20.
Int J Radiat Oncol Biol Phys ; 97(5): 1095-1104, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28332995

RESUMO

PURPOSE: To validate the dosimetric accuracy of a commercially available magnetic resonance guided intensity modulated radiation therapy (MRgIMRT) system using a hybrid approach: 3-dimensional (3D) measurements and Monte Carlo calculations. METHODS AND MATERIALS: We used PRESAGE radiochromic plastic dosimeters with remote optical computed tomography readout to perform 3D high-resolution measurements, following a novel remote dosimetry protocol. We followed the intensity modulated radiation therapy commissioning recommendations of American Association of Physicists in Medicine Task Group 119, adapted to incorporate 3D data. Preliminary tests ("AP" and "3D-Bands") were delivered to 9.5-cm usable diameter cylindrical PRESAGE dosimeters to validate the treatment planning system (TPS) for nonmodulated deliveries; assess the sensitivity, uniformity, and rotational symmetry of the PRESAGE dosimeters; and test the robustness of the remote dosimetry protocol. Following this, 4 clinical MRgIMRT plans ("MultiTarget," "Prostate," "Head/Neck," and "C-Shape") were measured using 13-cm usable diameter PRESAGE dosimeters. For all plans, 3D-γ (3% or 3 mm global, 10% threshold) passing rates were calculated and 3D-γ maps were examined. Point doses were measured with an IBA-CC01 ionization chamber for validation of absolute dose. Finally, by use of an in-house-developed, GPU-accelerated Monte Carlo algorithm (gPENELOPE), we independently calculated dose for all 6 Task Group 119 plans and compared against the TPS. RESULTS: For PRESAGE measurements, 3D-γ analysis yielded passing rates of 98.7%, 99.2%, 98.5%, 98.0%, 99.2%, and 90.7% for AP, 3D-Bands, MultiTarget, Prostate, Head/Neck, and C-Shape, respectively. Ion chamber measurements were within an average of 0.5% (±1.1%) from the TPS dose. Monte Carlo calculations demonstrated good agreement with the TPS, with a mean 3D-γ passing rate of 98.5% ± 1.9% using a stricter 2%/2-mm criterion. CONCLUSIONS: We have validated the dosimetric accuracy of a commercial MRgIMRT system using high-resolution 3D techniques. We have demonstrated for the first time that hybrid 3D remote dosimetry is a comprehensive and feasible approach to commissioning MRgIMRT. This may provide better sensitivity in error detection compared with standard 2-dimensional measurements and could be used when implementing complex new magnetic resonance guided radiation therapy technologies.


Assuntos
Imagem Tridimensional/instrumentação , Imagem por Ressonância Magnética/instrumentação , Neoplasias/radioterapia , Radiometria/instrumentação , Radioterapia Conformacional/instrumentação , Radioterapia Guiada por Imagem/instrumentação , Projeto Auxiliado por Computador , Humanos , Imagem Tridimensional/métodos , Imagem por Ressonância Magnética/métodos , Método de Monte Carlo , Radiometria/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia Guiada por Imagem/métodos , Reprodutibilidade dos Testes , Espalhamento de Radiação , Sensibilidade e Especificidade
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