RESUMO
Based on the promising development of carbon dots in antibacterial applications, Girard's reagent T-based carbon dots (GRT-CDs) with a mean size of 2.41 nm and excellent antibacterial performance were synthesized through a one-step method. The minimum inhibitory concentration ofGRT-CDswas 200 µg ml-1for bothEscherichia coli (E. coli)andStaphylococcus aureus (S. aureus). The bacterial growth curves showed that the inhibitory effect ofGRT-CDson bacterial multiplication was strongly concentration-dependent. The bactericidal effect ofGRT-CDswas further demonstrated by the large differences in bacterial fluorescence staining plots. Zeta potential measurements and scanning electron microscope images indicated thatGRT-CDsformed complexes with bacteria, which affected the normal physiological activities of bacteria, causing their rupture and death. In addition,GRT-CDsefficiently inhibited biofilm formation and removed mature biofilms. Furthermore,GRT-CDsalso exhibited a remarkable inhibitory activity on MRSA. Cytotoxicity experiments showed thatGRT-CDshad good cytocompatibility and even promoted cell proliferation at low concentrations. Therefore, theGRT-CDsobtained from a one-precursor and one-pot synthesis show good prospects for antibacterial applications.
Assuntos
Carbono , Staphylococcus aureus , Escherichia coli , Antibacterianos/farmacologia , Biofilmes , Bactérias , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Pregnant women with gestational diabetes mellitus (GDM) often have an increased risk of adverse pregnancy outcomes. The purpose of this study was to explore the prevalence and characteristics of GDM in Xi'an from 2015 to 2021 since the implementation of China's "Two-Child policy" and to provide a clinical basis for the management of GDM. METHODS: We analyzed the oral glucose tolerance test (OGTT) results of 152,836 pregnant women who underwent routine prenatal examination at the Northwest Women and Children's Hospital from 2015 to 2021. Additionally, we analyzed the GDM prevalence and characteristics. RESULTS: The prevalence of GDM in the Xi'an urban area was 24.66% and exhibited an increasing trend annually (χ2 for trend = 43.922, p < 0.001) and with age (χ2 for trend = 2527.000, p < 0.001). Consistent with this, the proportion of pregnant women aged 18-25 and 26-30 years decreased significantly with the annual growth (χ2 for trend = 183.279, p < 0.001 and χ2 for trend = 33.192, p < 0.001, respectively). The proportion of pregnant women aged 31-35 and 36-42 years increased gradually annually (χ2 for trend = 134.436, p < 0.001and χ2 for trend = 44.403, p < 0.001, respectively). Of the pregnant women diagnosed with GDM, 71.15% (65.05-74.95%) had abnormal fasting plasma glucose (FPG) values. The highest percentage of patients had a single abnormal OGTT value (68.31%; 65.77-70.61%), followed by two (20.52%; 18.79-22.55%) and three (11.17%; 10.11-11.85%) abnormal values (FPG and 1-h and 2-h plasma glucose (PG). CONCLUSION: The prevalence of GDM among pregnant women in Xi'an region was high, and it had a increasing trend over the period from 2015 to 2021. Notably, the proportion of elder pregnant women, aged 31-42 years, presented a significant rise after the implementation of the universal two-child policy. On the basis of the high incidence of GDM among elder pregnant women and the high rate of abnormal OGTT values (numbe ≥ 2) in pregnant women diagnosed with GDM, the management of GDM should be intensified, and relevant departments should pay more attention to pregnant women of advanced age.
Assuntos
Diabetes Gestacional , Intolerância à Glucose , Gravidez , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Idoso , Diabetes Gestacional/diagnóstico , Glicemia , Gestantes , Prevalência , Teste de Tolerância a Glucose , Intolerância à Glucose/diagnósticoRESUMO
As sediment is an essential component of rivers, the enrichment of heavy metals in sediment presents a serious threat to the aquatic environment. Many industrial cities are located along the Yellow River, and heavy metal pollution is a prominent problem in these areas. Thus, the study of heavy metal pollution in sediments of the Yellow River basin is of vital significance to the safety of the Yellow River basin ecosystem. In this study, we collected data on the concentrations of heavy metals (Pb, Cd, Cr, As, Zn, Cu, Ni, and Hg) in the sediments of the Yellow River basin from 2000 to 2020. We first analyzed the spatial distribution characteristics of heavy metals based on descriptive statistics and geostatistics and then used the Monte Carlo method to evaluate the probability of the ground accumulation index(Igeo), potential ecological risk, and toxicity units. Finally, the number of pollution sources and their contribution rates were determined by combining the positive definite matrix factor (PMF) decomposition model and Pearson correlation analysis. It was found that the mean values of ω(Pb), ω(As), ω(Zn), ω(Ni), ω(Cu), ω(Hg), ω(Cr), and ω(Cd) in the Yellow River basin sediments were 26.92, 11.78, 87.17, 31.13, 24.96, 0.07, 73.36, and 0.58 mg·kg-1, which exceeded the mean soil background values in the Yellow River basin provinces by 1.27, 1.08, 1.26, 1.05, 1.09, 2.32, 1.14, and 5.95 times, respectively, among which Cd exceeded the standard by the largest factor and should be taken seriously. The Igeo was ranked as Cd>Hg>Cr>Cu>Pb>Zn>As>Ni, and Cd and Hg showed medium-severe pollution. The proportions of heavy ecological risk in sediments in the upper, middle, and lower reaches of the Yellow River basin were 18.6%, 15.7%, and 7.1%, respectively, with a decreasing trend. Heavy metals in the sediments of the Yellow River basin were in a low-toxicity state. The PMF-Pearson correlation analysis showed that the four sources of heavy metals in the Yellow River basin sediments were mining sources (42.2%), natural activities (38.3%), agricultural activities (11.6%), and electroplating wastewater (7.9%). The results of this study can provide a basis for developing relevant pollution prevention and control measures in the Yellow River basin.
Assuntos
Mercúrio , Metais Pesados , Poluentes Químicos da Água , Cádmio/análise , China , Ecossistema , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Chumbo/análise , Mercúrio/análise , Metais Pesados/análise , Método de Monte Carlo , Medição de Risco/métodos , Rios , Poluentes Químicos da Água/análiseRESUMO
Tetracyclines (TCs), a type of antibiotics, are widely used in human therapy and animal husbandry. Public concerns about tetracyclines residues have been raised due to their negative impact on the environment and food, causing bacterias drug resistance and human health concerns. In this work, a luminescent europium MOF (EuUCBA) is constructed via post-synthetic attachment of Eu3+ into a UiO-66 type MOF. The luminescent of EuUCBA exhibits high stability in aqueous media in the pH range of 4-11. Among 36 common veterinary drugs, the synthesized probe is highly selective and sensitive to six tetracyclines with low detection limits of 0.118 µM, 0.228 µM, 0.102 µM, 0.138 µM, 0.206 µM, and 0.078 µM for oxytetracycline (OTC), chlortetracycline (CTC), methylenetetracycline (MTC), minocycline (MOC), tetracycline (TC), and doxycycline (DOXY), respectively. Furthermore, the probe shows good anti-interference ability and fast response. Finally, EuUCBA was successfully to detect DOXY in swine wastewater and pig kidney with good recoveries. This work provides an excellent fluorescent sensor for highly selective and rapid detection of TCs residues in wastewater and complex biological samples.
Assuntos
Tetraciclinas , Águas Residuárias , Animais , Antibacterianos , Doxiciclina , Rim/química , Estruturas Metalorgânicas , Ácidos Ftálicos , Suínos , Tetraciclinas/análiseRESUMO
The objective of this study is to investigate how the change of hormone receptor (HR) and human epidermal growth factor receptor-2 (Her-2) status is related to patients' clinical features. One hundred ninety-three cases of patients treated at general hospital of PLA from 2000 to 2015 with advanced breast cancer were included. All patients developed recurrence that were re-biopsied and had complete pathological profile both at initial diagnosis and at relapse. HR status before and after relapse were available for all patients, while only 143 cases had Her-2 status at the two stages. The changes of ER, PR, and Her-2 status and their association with clincopathological factors and DFS were analyzed. The discordant rates of ER, PR, and Her-2 status between primary breast cancer and recurrent tumor were 34.2, 38.3, and 16.8 %, respectively. At relapse, the rates of gain of ER and PR positivity were 10.9 and 13.5 %, respectively; the rates of loss of ER and PR positivity were 23.3 and 24.9 %. Loss of positivity was more frequent than gain of positivity (p ER < 0.000, p PR = 0.001). Among patients with Her-2 negative primary tumors, 15.4 % acquired Her-2 positivity at relapse; and among Her-2 positive patients at initial diagnosis, 1.4 % turned to Her-2 negative at relapse; gain of positivity was more frequent than loss of positivity (p < 0.000). Patients with tumor larger than 2 cm in diameter were more likely to experience change of Her-2 status (25.0 vs 5.8 %, p = 0.005). Yet, the change of ER/PR was not significantly associated with the size of primary tumor. Patients with ER positive recurrent disease and PR positive primary tumor had a DFS of more than 40 months. Compared to patients who maintained PR negative, patients who gained PR positivity at relapse had significantly longer DFS by 8.5 % (35.2 vs 26.7 months, p = 0.024). Patients losing ER positivity at relapse had shorter DFS by 7.8 months compared to those with stable ER positive tumors; patients gaining ER positivity experienced longer DFS by 8.3 months; but both differences were not statistically significant. Loss of Her-2 positivity was associated with longer DFS by 13.8 months as opposed to stable Her-2 status, without statistical significance. For patients with Her-2 negative primary tumor, the changes of Her-2 status were not associated with DFS. 34.2, 38.3, and 16.8 % of breast cancer patients had their ER, PR, and Her-2 status changed after recurrence, and these changes of receptor status were associated with DFS to some degree. Gain of PR positivity at relapse was significantly correlated with longer DFS.
Assuntos
Neoplasias da Mama/química , Carcinoma/química , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Biópsia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma/patologia , Carcinoma/secundário , Carcinoma/terapia , Quimioterapia Adjuvante , Gerenciamento Clínico , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Mastectomia , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Trastuzumab/uso terapêutico , Carga Tumoral , Adulto JovemRESUMO
Cancer was viewed to be driven by accumulating genetic abnormalities that generally include chromosomal abnormalities, mutations in tumor-suppressor genes, and oncogenes. The aim of this meta-analysis was to systematically summarize the possible associations between MMP-13 rs2252070 A>G variant and cancer risks. We systematically reviewed studies focusing on MMP-13 polymorphisms with human cancer susceptibility that were published before April 30, 2014. Relevant articles were identified through research of PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases. All analyses were calculated using the Version 12.0 STATA software. Odds ratios (OR) and 95 % confidence interval (95 % CI) were calculated. Eleven independent case-control studies were included in the meta-analysis, which involved 3,465 patients with cancers and 4,073 healthy controls. The results identified a positive association between rs2252070 A>G polymorphism and susceptibility to cancer under five genetic models (all P < 0.05). Ethnicity subgroup analysis implied that significant difference was detected for rs2252070 A>G polymorphism with increased risk of cancers among Asians and Caucasians in majority of the groups. Our findings suggest significant association for MMP-13 rs2252070 A>G to increased susceptibility to human cancer, especially in the progression of lung carcinoma.
Assuntos
Predisposição Genética para Doença/genética , Metaloproteinase 13 da Matriz/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Humanos , Neoplasias/enzimologia , Fatores de RiscoRESUMO
The transforming growth factor ß1 (TGF-ß1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-ß1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-ß1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-ß1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-ß1 precursor (t-TGF-ß1-pre)-positive patients than in the negative patients in patients without receiving chemotherapy (P=0.053), OS of t-TGF-ß1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-ß1-pre-negative patients. Analysis showed that t-TGF-ß1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-ß1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Precursores de Proteínas/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
Anterior lumbar interbody fusion (ALIF) followed by posterior pedicle screw fixation (PSF) in a second procedure is mostly used to implement lumbar spine fusion. ALIF followed by anterior lumbar screw-plate has a lot of advantages, but its biomechanical stability requires confirmation. This study evaluated the biomechanical stability of a novel anterior lumbar locked screw-plate (ALLSP) by comparison with posterior lumbar PSF. Twelve fresh human cadaveric lumbar specimens (L4-L5) were assigned to four groups: ALIF+PSF group, ALIF+ALLSP (both fixed) group, ALIF group and an untreated control (both non-fixed) group. The first three groups received implantation of a rectangular titanium cage. Tests under axial compression, flexion, extension, lateral bending, or rotation showed that the fixed groups had significantly stronger stability than the non-fixed groups (P=0.000 for all). The ALIF+ALLSP group had significantly greater axial stiffness under applied axial compression and significantly less angular displacement under rotational forces than the ALIF+PSF group. The angular displacement of the ALIF+ALLSP group was less under flexion than that of the ALIF+PSF, and the angular displacement under lateral bending and extension was greater, but these differences were not statistically significant. In summary, the ALLSP conforms to the anterior lumbar spine and has good biomechanical stability. It is a reliable choice for enhancing the stability of ALIF.
RESUMO
Anterior lumbar interbody fusion (ALIF) followed by posterior pedicle screw fixation (PSF) in a second procedure is mostly used to implement lumbar spine fusion. ALIF followed by anterior lumbar screw-plate has a lot of advantages, but its biomechanical stability requires confirmation. This study evaluated the biomechanical stability of a novel anterior lumbar locked screw-plate (ALLSP) by comparison with posterior lumbar PSF. Twelve fresh human cadaveric lumbar specimens (L4-L5) were assigned to four groups: ALIF+PSF group, ALIF+ALLSP (both fixed) group, ALIF group and an untreated control (both non-fixed) group. The first three groups received implantation of a rectangular titanium cage. Tests under axial compression, flexion, extension, lateral bending, or rotation showed that the fixed groups had significantly stronger stability than the non-fixed groups (P=0.000 for all). The ALIF+ALLSP group had significantly greater axial stiffness under applied axial compression and significantly less angular displacement under rotational forces than the ALIF+PSF group. The angular displacement of the ALIF+ALLSP group was less under flexion than that of the ALIF+PSF, and the angular displacement under lateral bending and extension was greater, but these differences were not statistically significant. In summary, the ALLSP conforms to the anterior lumbar spine and has good biomechanical stability. It is a reliable choice for enhancing the stability of ALIF.
Assuntos
Adulto , Feminino , Humanos , Masculino , Placas Ósseas , Parafusos Ósseos , Vértebras Lombares , Patologia , Teste de MateriaisRESUMO
OBJECTIVE: To assess the efficacy of docetaxel plus capecitabine versus docetaxel plus epirubicin as first-line treatment in women with HER-2 negative advanced breast cancer. METHODS: A paired study was conducted for 92 cases with HER-2 negative advanced breast cancer. They received 3 weekly cycles of either TX (docetaxel 75 mg/m(2), day 1; capecitabine 1000 mg/m(2) orally twice daily, days 1-14) or TE (docetaxel 75 mg/m(2), day 1; epirubicin 75 mg/m(2), day 1). The objective was to compare 6-month non-progression rate, time to progression (TTP) , overall response rate (ORR) and toxicities. RESULTS: The 6-month non-progression rates were 78% with TX versus 70% with TE (P = 0.477). Medium TTP was 10.2 versus 8.7 months (P = 0.128) and ORR was 72% and 63% respectively (P = 0.505) . Severe toxicities included hand-foot syndrome (37% vs 4%, P < 0.001), grade 3-4 neutropenia (30% vs 70%, P < 0.001) and febrile neutropenia (2% vs 11%, P = 0.004) respectively. No relevant differences in other toxicities were observed in two arms. CONCLUSION: Both regimens of TX and TE have similar efficacy and are well-tolerated as the first-line therapy for HER-2 negative advanced breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/patologia , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Taxoides/administração & dosagemRESUMO
OBJECTIVE: This systematic review was conducted to summarize the use of circulating tumour cell (CTC) detection as a prognostic indicator in gastric cancer and hepatocellular carcinoma (HCC). METHODS: Databases (MEDLINE®, EMBASE®, SCOPUS, Web of Science, Conference Proceedings Citation Index-Science, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov) were searched to identify studies that reported the detection of CTCs in patients with gastric cancer or HCC. RESULTS: Fifteen studies in patients with gastric cancer and 10 studies in patients with HCC, with a total of 793 and 577 patients, respectively, met the specific inclusion criteria for further analysis. Heterogeneity and potential bias among the studies prevented any statistical analysis. CONCLUSION: Several methodological techniques have allowed the detection of CTCs in patients with gastric cancer or HCC, but the studies identified in this report generally reported on small cohorts and there was heterogeneity and potential bias in the studies. This highlights the need for large systematic multicentre clinical trials to confirm the potential prognostic benefit of detecting CTCs in patients with cancer.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Células Neoplásicas Circulantes/patologia , Neoplasias Gástricas/diagnóstico , Biomarcadores/análise , Carcinoma/patologia , Carcinoma Hepatocelular/patologia , Ensaios Clínicos como Assunto , Bases de Dados Bibliográficas , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Variações Dependentes do Observador , Prognóstico , Viés de Publicação , Neoplasias Gástricas/patologiaRESUMO
OBJECTIVE: To assess and compare the prognostic role of tumor-infiltrating T lymphocytes in stage 1-3 breast cancer. METHODS: Paraffin sections were retrospectively collected from 130 cases of stage 1-3 breast cancer patients who received surgery between January 2000 and December 2002 in General Hospital of the People's Liberation Army. Immunohistochemistry was used to assess the density of tumor-infiltrating lymphocytes(TILs) that were positive of CD4 and CD8. These variables were evaluated for their association with histopathologic features along with overall survival(OS) , distant disease-free survival(DDFS) and disease-free survival(DFS) . RESULTS: Intraepithelial CD4+lymphocytes infiltration was an independent prognostic factor for DFS(HR=0.248, 95%CI=0.113-0.543, P=0.000) , DDFS(HR=0.361, 95%CI=0.157-0.830, P=0.017) , and OS(HR=0.297, 95%CI=0.119-0.741, P=0.009) in multifactor COX regression model. In hormone receptor negative group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=0.286, 95%CI=0.101-0.807, P=0.018) and DDFS(HR=0.293, 95%CI=0.104-0.825, P=0.020) , respectively. In hormone receptor positive group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=4.854, 95%CI=1.435-16.415, P=0.011) and DDFS(HR=10.493, 95%CI=1.226-89.795, P=0.032) respectively. Further analysis found that OS of hormone receptor positive patients with lower mesenchymal CD8+TILs was significantly proved by adjuvant endocrine therapy. CONCLUSIONS: In the current investigation, intraepithelial CD4+TILs demonstrated independent prognostic significance for survival. CD8+TILs were associated with better survival in hormone receptor negative patients but associated with worse survival in hormone receptor positive patients. The long-term clinical effects of adjuvant endocrine therapy is related with density of mesenchymal CD8+TILs and in turn affected prognostic value of mesenchymal CD8+TILs.
Assuntos
Neoplasias da Mama/patologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Linfócitos do Interstício Tumoral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Inhibition of angiogenesis can attenuate tumor growth. Hence, mathematical modeling of tumor-induced angiogenesis can be a tool for predicting outcome of angiogenesis inhibitors. We have generated a two-dimensional cornea model of angiogenesis and have tested the effectiveness of the inhibitor through testing representative examples. The effects of thrombospondin and the way it interacts in the cornea with the endothelial cells and tumor angiogenic factors were examined. We were then able to define the inhibitor's role specific to our benchmark model. Finally, a thorough sensitivity analysis was performed to verify baseline values and determine the precise effects of the different parameters. Our findings can be used to design strategies involving manufacturing inhibitors to regulate the angiogenesis process.
Assuntos
Inibidores da Angiogênese/farmacologia , Simulação por Computador , Modelos Biológicos , Neoplasias/tratamento farmacológico , Algoritmos , Proteínas Angiogênicas/fisiologia , Anastomose Arteriovenosa , Córnea/irrigação sanguínea , Humanos , Neoplasias/irrigação sanguíneaRESUMO
AIM: To clarify the specific roles and mechanisms of long interspersed nuclear element-1 ORF-1 protein [human long interspersed nuclear element-1 (LINE-1), ORF-1p] in chemotherapeutic drug resistance and cell proliferation regulation in hepatocellular carcinoma (HCC) cells. METHODS: MTT assays were performed to identify the effect of the chemotherapeutic drug toxicity on HepG2 cells. Cell proliferation inhibition and the IC50 were calculated by the Origin 8.0 software. Western blotting assays were performed to investigate whether LINE-1 ORF-1p modulates the expression of some important genes, including p53, p27, p15, Bcl-2, mdr, and p-gp. To corroborate the proliferation and anchor-independent growth results, the HepG2 cells were analyzed by flow cytometry to investigate the effect of LINE-1 ORF-1p on the apoptosis regulation. RESULTS: LINE-1 ORF-1p contributed to the resistance to several chemotherapeutic drugs (cisplatin and epirubicin) in HepG2 cells. The IC50 of the epirubicin and cisplatin increased from 36.04 nmol/L to 59.11 nmol/L or from 37.94 nmol/L to 119.32 nmol/L. Repression of LINE-1 ORF-1p expression by the siRNA could markedly enhance the response of HepG2 cells to the epirubicin and cisplatin. The IC50 correspondingly decreased from 28.06 nmol/L to 3.83 nmol/L or from 32.04 nmol/L to 2.89 nmol/L. Interestingly, down-regulation of LINE-1 ORF-1p level by siRNA could promote the response of HepG2 cells to the paclitaxel. The IC50 decreased from 35.90 nmol/L to 7.36 nmol/L. However, overexpression of LINE-1 ORF-1p did not modulate the paclitaxel toxicity in HepG2 cells. Further Western blotting revealed that LINE-1 ORF-1p enhanced mdr and p-gp gene expression. As a protein arrested in the nucleus, LINE-1 ORF-1p may function through modulating transcriptional activity of some important transcription factors. Indeed, LINE-1 ORF-1p promoted HepG2 cell proliferation, anchor-independent growth and protected the cells against apoptosis through modulating the expression of p15, p21, p53, and Bcl-2 genes. CONCLUSION: LINE-1 ORF-1p promotes HepG2 cell proliferation and plays an important role in the resistance of chemotherapeutic drugs. By establishing novel roles and defining the mechanisms of LINE-1 ORF-1p in HCC chemotherapeutic drug resistance and cell proliferation regulation, this study indicates that LINE-1 ORF-1p is a potential target for overcoming HCC chemotherapeutic resistance.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/metabolismo , Elementos Nucleotídeos Longos e Dispersos/genética , Ribonucleoproteínas/metabolismo , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Concentração Inibidora 50 , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Interferência de RNA , Ribonucleoproteínas/genética , Fatores de Tempo , TransfecçãoRESUMO
OBJECTIVE: To evaluate the in vitro cytotoxic effects of cantide or herceptin on human breast cancer SKBR3 cells over-expressing HER2. METHODS: The distribution of HER2 and hTERT protein in SKBR3 cells and the effects of cantide and/or herceptin on the subcellular localization of HER2 and hTERT were observed by indirect immunofluorescent assay. The inhibition rate of herceptin and/or cantide at different concentrations on SKBR3 cells was detected by MTT assay. And the apoptotic rate of cells was evaluated by flow cytometer. RESULTS: (1) The expressions of both HER2 and hTERT proteins in SKBR3 cells were found. HER2 protein was predominant in cell membranes while hTERT protein in nuclei. After the addition of herceptin, the cytoplasmic migration of HER2 was found while there was no distinct location change of cantide. (2) In MTT assay, the single use of cantide or herceptin and the combined use of both produced inhibitory effects on SKBR3 cells while the inhibition rate was higher for combined use. The inhibitory effects became additive in the combined use of 0.4 µmol/L cantide and 0.85 µg/ml herceptin. And there were synergistic effects in the combined use of 0.4 µmol/L cantide and 1.70, 3.40, 6.88 or 13.75 µg/ml herceptin. (3) The apoptotic rate was 25.75% for cantide alone, 11.26% for herceptin alone and 41.41% for their combined use (apoptotic cells predominant in advanced stage). CONCLUSION: Due to different localizations, cantide and herceptin have different action sites in their combined use. When in single use, the inhibition rate is linearly correlated with the concentration of herceptin or cantide. And their combined use produces additive or synergistic antitumor effects on SKBR3 breast cancer cells.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias da Mama/patologia , Oligonucleotídeos Fosforotioatos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Humanos , Receptor ErbB-2/metabolismo , Telomerase/metabolismo , TrastuzumabRESUMO
Expression levels of VEGF and Her-2, levels of T-regulatory (Treg) cells, levels of CD3+ cells, and ratios of Th (CD4+ T cells)/Tr (Treg) cells were compared between stage I, II, III, and IV breast cancer patients (n = 120) prior to chemotherapy and healthy women (n = 30). Cells from peripheral blood were counted by flow cytometry, Her-2 and VEGF expression was detected by pathological examination, and Her-2 was detected by FISH. Breast cancer patients had more Treg cells and a lower ratio of Th/Tr cells than the healthy women. Stage IV breast cancer patients had more Treg cells and a lower ratio of Th/Tr cells than stage I, II, or III breast cancer patients. Patients positive for VEGF had a lower ratio of Th/Tr cells compared with patients negative for VEGF, and those positive for both VEGF and Her-2 also had a lower ratio of Th/Tr cells compared with patients not positive for both VEGF and Her-2. The decreased Th/Tr cells ratio indicates impaired immune function, suggesting that the stage IV breast cancer and the Her-2/VEGF-positive breast cancer patients have lower immune function.
Assuntos
Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Idoso , Feminino , Saúde , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/biossíntese , Receptor ErbB-2/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/imunologia , Adulto JovemRESUMO
OBJECTIVE: To compare the gene expression profiles of nasopharyngeal carcinoma (NPC) cell line 5-8F-EGFP and the liver metastatic 5-8F-H3B-EGFP cells. METHODS: The fluorescence-labeled cDNA were prepared separately from the total RNA extracted from the two cell lines and hybridized with Human_U133A2.0 Genechip (Affymetrix, USA) containing approximately 18 400 known gene. The gene expression profiles were analyzed with special software and cluster analysis. RESULTS: A total of 3767 genes were identified to have significant differential expressions between these two cell lines (P<0.05), among which 281 genes showed twofold or higher differential expressions. Using MILANO software, we found 16 genes with probable close relation with liver metastasis of NPC. CONCLUSION: The 16 genes differentially expressed between the two cell lines can be of importance in the investigation of the molecular mechanism of NPC liver metastasis and identification of molecular markers for prognostic evaluation.
Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Nasofaríngeas/genética , Transcriptoma , Carcinoma , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas/secundário , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Metástase Neoplásica , Análise de Sequência com Séries de OligonucleotídeosRESUMO
OBJECTIVE: To investigate the expressions of human epidermal growth factor receptor 2 (Her-2) and vascular endothelial growth factor (VEGF) in primary and recurrent metastatic breast cancers and explore their relationship. METHODS: The expressions of Her-2 and VEGF in 60 primary and recurrent metastatic breast cancers were detected using immunohistochemical methods. Their relationship was analyzed. RESULTS: The positive rates of Her-2 and VEGF in the recurrent metastatic breast cancer were 40.00% and 53.33%, respectively, which were significantly higher than that in the primary breast cancer (18.33% and 31.67%) (P < 0.05). The total diversify rates of Her-2 and VEGF were 28.33% and 35.00%, respectively. Her-2 and VEGF expressions were significantly correlated between the primary and the recurrent metastatic breast cancers( P < 0.05). CONCLUSIONS: Her-2 and VEGF may play synergic roles in the occurrence and development of breast cancer. Over-expressions of Her-2 and VEGF predict poor prognosis.
Assuntos
Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/metabolismo , PrognósticoRESUMO
OBJECTIVE: To study the clinical and pathological features, diagnosis, therapy and prognosis of primary small intestine malignant tumor. METHODS: A retrospective analysis was performed on the clinical data from the 120 cases of primary small intestine malignant tumor. RESULTS: Abdominal pain, gastrointestinal bleeding, anemia, abdominal mass and jaundice were the main clinical features. The pathology was confirmed by abdominal X-ray, gastrointestinal barium, CT, MRI, endoscopy and surgical exploration. Most tumors originated in the duodenum (54.1%), and adenocarcinoma (55.8%) was the main pathological type. The median survival time of the patients was 19.2 months and the 1-year survival rate was 55.4%. Chemotherapy did not seem to significantly improve the 1-year survival rate of the patients (P=0.842). CONCLUSION: Primary small intestine malignant tumors lack specific clinical manifestations and surgical resection should be performed as early as possible.
Assuntos
Adenocarcinoma , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/cirurgia , Intestino Delgado/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Neoplasias Intestinais/tratamento farmacológico , Intestino Delgado/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To determine the clinical toxicities and antitumor effects of a chemotherapy regimen of FTQ, a compound preparation of tegafur, the drug prototype of 5-furacil (5-FU), gimeracil (CDHP), a decomposition inhibitor of 5-FU, oteracil potassium, phosphorylation inhibitor of 5-FU, and combined with cisplatin in patients with inoperable locally or metastatic advanced gastric cancer. METHODS: 119 patients with inoperable locally or metastatic advanced gastric cancer admitted in 10 hospitals in China were divided into 2 groups: FTQ group (n = 59), undergoing a 3-week regime, i.e. oral use of 80 mg x m(-2) x d(-1) for 14 d and then discontinuance for 1 week and intravenous drip cisplatin 75 mg/m2 on days 1-3; and control group (n = 60) undergoing a 3-week regimen including oral use of tegafur 800 mg x m(-2) x d(-1) tid for 14 d and then discontinuance for 1 week and intravenous drip of cisplatin 75 mg/m2 on days 1-3. The curative was evaluated after at least after 2 regimens. RESULTS: There were 102 patients in the per-protocol population. The overall response rate of the FTQ group was 28. 3% (15/53), significantly higher than that of the control group (4.1%, 2/49, P = 0.004). The clinical improvement of the FTQ group was 50.9%, significantly higher than that of the control group (24.5%, P = 0.006). The main toxicities occurred in bone marrow and the digestive tract. The leucopenia and thrombocytopenia rates of the FTQ group were 47.45% and 32.22% respectively, both similar to those of the control group. There were no differences in the incidence rate of digestive canal side reaction between these 2 groups . CONCLUSION: The regimen of FTQ combined with cisplatin is generally well-tolerated and has substantial antitumor activity.