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1.
Chem Commun (Camb) ; 56(49): 6680-6683, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32412017

RESUMO

A regio- and stereoselective iodolactonization of internal electron-deficient olefinic acids has been reported, which provides a straightforward access to a series of multi-functionalized seven-membered lactones containing two consecutive chiral centers. The ester substituents on the olefins played a key role in achieving high regioselectivity. This result was proved through experiments and DFT calculations.

2.
Mutat Res ; 850-851: 503147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247562

RESUMO

Bulbus Fritillariacirrhosa D. Don (BFC) has been widely used as an herbal medicament for respiratory diseases in China for over 2000 years. The ethnomedicinal effects of BFC have been scientifically verified, nevertheless its toxicity has not been completely studied. Previously, we have reported that the aqueous extract of BFC induces mitotic aberrations and chromosomal instability (CIN) in human colon epithelial NCM460 cells via dysfunctioning the mitotic checkpoint. Here, we extend this study and specifically focus on the influence of BFC on cytokinesis, the final step of cell division. One remarkable change in NCM460 cells following BFC treatment is the high incidence of binucleated cells (BNCs). More detailed investigation of the ana-telophases reveals that furrow ingression, the first stage of cytokinesis, is inhibited by BFC. Asynchronous cultures treatment demonstrates that furrow ingression defects induced by BFCs are highly associated with the formation of BNCs in ensuing interphase, indicating the BNCs phenotype after BFC treatment was resulted from cytokinesis failure. In line with this, the expression of genes involved in the regulation of furrow ingression is significantly de-regulated by BFC (e.g., LATS-1/2 and Aurora-B are upregulated, and YB-1 is downregulated). Furthermore, long-term treatment of BFC elucidates that the BNCs phenotype is transient and the loss of BNCs is associated with increased frequency of micronuclei and nuclear buds, two biomarkers of CIN. In supporting of these findings, the Nin Jiom Pei Pa Koa and Chuanbei Pipa Gao, two commercially available Chinese traditional medicines containing BFC, are able to induce multinucleation and CIN in NCM460 cells. Altogether, these data provide the first in vitro experimental evidence linking BFC to cytokinesis failure and suggest the resultant BNCs may be intermediates to produce CIN progenies.


Assuntos
Instabilidade Cromossômica/efeitos dos fármacos , Citocinese/efeitos dos fármacos , Fritillaria/química , Extratos Vegetais/farmacologia , Aurora Quinase B/genética , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/genética , Instabilidade Cromossômica/genética , Colo/efeitos dos fármacos , Colo/patologia , Citocinese/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mitose/efeitos dos fármacos , Extratos Vegetais/química , Raízes de Plantas/química , Proteínas Serina-Treonina Quinases/genética , Proteína 1 de Ligação a Y-Box/genética
3.
Hum Genet ; 139(4): 421-446, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32020362

RESUMO

Y chromosome (ChrY), the male-specific sex chromosome, has been considered as a genetic wasteland. Aging-related mosaic loss of ChrY (LOY) has been known for more than half a century, but it was constantly considered as a neutral karyotype related to normal aging. These views have been challenged with genome-wide association studies identifying mosaic LOY in human somatic cells is the most commonly acquired mutation in male's genome and is associated with a wide spectrum of human diseases including cancer, Alzheimer's disease, and cardiovascular disease. These previously undescribed clinical significances deeply modify our perception on ChrY and open up a range of new questions. Here, we review the latest advances in our knowledge of the biological origins and clinical consequences of mosaic LOY. We highlight the association of mosaic LOY to pathogenic conditions and evaluate the cause-and-consequence relationships between mosaic LOY and pathogenesis. The known risk factors of mosaic LOY including age, genetic variants, ChrY structural aberrations and environmental stressors are discussed. In light of evidence from pioneering and more recent studies, we propose the micronucleation hypothesis and centromere-dysfunction and telomere-attrition models to explain how mosaic LOY occurs and why ChrY is prone to lose. We believe it is importantly and timely to extend mosaic LOY research from epidemiological associations to mechanistic studies. In this regard, we outline important gaps and assess several future directions from a biological and clinical perspective. An improved understanding of mosaic LOY will open new pathways to modify and increase healthy aging in males.


Assuntos
Doença de Alzheimer , Doenças Cardiovasculares , Cromossomos Humanos Y , Mosaicismo , Neoplasias , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Cromossomos Humanos Y/genética , Cromossomos Humanos Y/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Masculino , Neoplasias/genética , Neoplasias/metabolismo
4.
Org Lett ; 22(4): 1331-1335, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32009417

RESUMO

Ru(II)-catalyzed direct alkylation of tertiary phosphines via hydroarylation of activated olefins promoted by mono-N-protected amino acid (MPAA) was achieved. This protocol provides a straightforward access to a large library of Buchwald-type bulky alkylated monophosphines from commercially available biaryl phosphine. Moreover, two ruthenacycle intermediates of tertiary phosphines via C-H bond cleavage were isolated to illustrate the mechanism of P(III)-directed C-H activation.

5.
Int J Gynaecol Obstet ; 148(1): 96-101, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31560127

RESUMO

OBJECTIVE: To probe the influence of metabolic syndrome (MS) on the long-term survival of patients with non-endometrioid adenocarcinoma. METHODS: Between January 2003 and December 2012, 139 Chinese patients with non-endometrial adenocarcinoma were analyzed in a retrospective study. Patients who had received any treatment before surgery were excluded. Survival times were compared between patients with and without MS. RESULTS: Overall, 41 (29.5%) patients had MS; the highest incidence of MS was observed in those with uterine serous carcinoma (19/45, 42.2%). For uterine serous carcinoma or adenosquamous carcinoma, MS was an independent predictive factor of morbidity (P=0.023 and 0.016, respectively). For the overall population, those with MS had a significantly lower survival rate than those without MS (P=0.008), and the median overall survival (mOS) was 15 months versus 55 months (P<0.001, hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.29-0.69). Similarly, a lower survival rate (P=0.020) and shorter mOS (19 months vs 55 months, P=0.007, HR 0.41, 95% CI 0.20-0.83) were also found in the uterine serous carcinoma population with MS. Multivariate Cox regression analyses showed that disease stage (P=0.023) and MS (P=0.008) were independent prognostic factors for uterine serous carcinoma. CONCLUSION: The present study suggests that MS is a prognostic factor for non-endometrioid adenocarcinoma, especially uterine serous carcinoma.


Assuntos
Carcinoma Adenoescamoso/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Síndrome Metabólica/complicações , Neoplasias Uterinas/mortalidade , Adulto , Idoso , Carcinoma Adenoescamoso/complicações , Carcinoma Adenoescamoso/patologia , Estudos de Casos e Controles , Cistadenocarcinoma Seroso/complicações , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Uterinas/complicações , Neoplasias Uterinas/patologia
6.
BMC Anesthesiol ; 19(1): 219, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791239

RESUMO

BACKGROUND: Tracheobronchial foreign body aspiration in children is a life-threatening, emergent situation. Currently, the use of fiberoptic bronchoscopy for removing foreign bodies is attracting increasing attention. Oxygen desaturation, body movement, laryngospasm, bronchospasm, and breath-holding are common adverse events during foreign body removal. Dexmedetomidine, as a highly selective α2-adrenergic agonist, produces sedative and analgesic effects, and does not induce respiratory depression. We hypothesized that intranasal dexmedetomidine at 1 µg kg - 1 administered 25 min before anesthesia induction can reduce the incidence of adverse events during fiberoptic bronchoscopy under inhalation general anesthesia with sevoflurane. METHODS: In all, 40 preschool-aged children (6-48 months) with an American Society of Anesthesiologists physical status of I or II were randomly allocated to receive either intranasal dexmedetomidine at 1 µg·kg - 1 or normal saline at 0.01 ml kg- 1 25 min before anesthesia induction. The primary outcome was the incidence of perioperative adverse events. Heart rate, respiratory rate, parent-child separation score, tolerance of the anesthetic mask, agitation score, consumption of sevoflurane, and recovery time were also recorded. RESULTS: Following pre-anesthesia treatment with either intranasal dexmedetomidine or saline, the incidences of laryngospasm (15% vs. 50%), breath-holding (10% vs. 40%), and coughing (5% vs. 30%) were significantly lower in patients given dexmedetomidine than those given saline. Patients who received intranasal dexmedetomidine had a lower parent-child separation score (P = 0.017), more satisfactory tolerance of the anesthetic mask (P = 0.027), and less consumption of sevoflurane (38.18 ± 14.95 vs. 48.03 ± 14.45 ml, P = 0.041). The frequency of postoperative agitation was significantly lower in patients given intranasal dexmedetomidine (P = 0.004), and the recovery time was similar in the two groups. CONCLUSIONS: Intranasal dexmedetomidine 1 µg·kg- 1, with its sedative and analgesic effects, reduced the incidences of laryngospasm, breath-holding, and coughing during fiberoptic bronchoscopy for FB removal. Moreover, it reduced postoperative agitation without a prolonged recovery time. TRAIL REGISTRATION: The study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800017273) on July 20, 2018.

8.
Cancer Manag Res ; 11: 7759-7766, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496818

RESUMO

Objective: The aim of this study was to investigate the potential associations of the sites and the number of specific metastases with survival in patients newly diagnosed with cervical cancer. Methods: Medical records of patients with organ metastases of newly diagnosed cervical cancer at Zhejiang Cancer Hospital from October 2006 to December 2016 were reviewed retrospectively. Survival times were compared using the Kaplan-Meier method. Variables associated with survival were identified using univariate and multivariate Cox proportional hazards models. Results: A total of 99 patients with newly diagnosed organ metastatic cervical cancer were identified. Median follow-up was 11.6 months (range, 0.5-114.7 months). Median overall survival (OS) time was 11.7 months from diagnosis, with 1, 2, and 5-year OS rates of 48.2%, 22.8%, and 12.6%, respectively. The most common site of organ metastasis was bone (36.8%), followed by lung (32.8%) and liver (24%). In univariate analysis, OS rates were better for bone metastasis than visceral metastasis (P=0.013), oligometastasis than non-oligometastasis (P=0.003) and single organ metastasis than multiple organ metastases (P=0.016), while that for liver metastasis was poorer than non-liver metastases (P<0.001). In multivariate analysis, liver metastasis (hazard ratio [HR] =4.02; 95% confidence interval [CI], 1.15-14.05, P=0.029) was significantly and independently related to poor overall survival. Conclusion: Our data revealed the site of metastasis is associated with overall survival of patients with newly diagnosed organ metastatic cervical cancer, with liver metastasis signifying particularly poor overall survival. Individualized treatments should be administered to patients depending on the specific metastatic sites.

9.
J Vis Exp ; (149)2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31380834

RESUMO

Protein-nucleic acid interactions play important roles in biological processes such as transcription, recombination, and RNA metabolism. Experimental methods to study protein-nucleic acid interactions require the use of fluorescent tags, radioactive isotopes, or other labels to detect and analyze specific target molecules. Biotin, a non-radioactive nucleic acid label, is commonly used in electrophoretic mobility shift assays (EMSA) but has not been regularly employed to monitor protein activity during nucleic acid processes. This protocol illustrates the utility of biotin labeling during in vitro enzymatic reactions, demonstrating that this label works well with a range of different biochemical assays. Specifically, in alignment with previous findings using radioisotope 32P-labeled substrates, it is confirmed via biotin-labeled EMSA that MEIOB (a protein specifically involved in the meiotic recombination) is a DNA-binding protein, that MOV10 (an RNA helicase) resolves biotin-labeled RNA duplex structures, and that MEIOB cleaves biotin-labeled single-stranded DNA. This study demonstrates that biotin is capable of substituting 32P in various nucleic acid-related biochemical assays in vitro.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31223331

RESUMO

Although deqi, the phenomenon whereby excitation of Qi in the meridians occurs with needling, is critical to the practice of acupuncture and its efficacy, it is poorly understood. So we investigate the influence of the deqi sensation on the analgesic effects of acupuncture in patients who were enrolled in a randomised controlled trial for the treatment of patients with primary dysmenorrhea, a painful and common condition, and cold and dampness stagnation. Two groups were assessed: a deqi group (undergoing deep needling with thick needles and manipulation, n=17) and a non-deqi group (undergoing shallow needling with thin needles and no manipulation, n=51). The Sanyinjiao (SP6) was needled for 30 min in both groups. Pain scores at baseline, upon needle removal, and at 10, 20, and 30 min after needle removal were evaluated by the Visual Analogue Scale for pain. The deqi sensation was evaluated by the Acupuncture Deqi Clinical Assessment Scale. Patients who experienced a genuine deqi sensation (n=39) were selected for further analysis. Compared with patients in the non-deqi group who experienced deqi (n=25), patients who self-reported deqi in the deqi group (n=14) felt a stronger deqi sensation, experienced soreness and fullness more frequently, felt a greater intensity of soreness, fullness, electric sensation, spreading, and radiating, and experienced larger spreading distances. In those who experienced the deqi sensation in the deqi group, the intensity of the sensation, as well as their degree of soreness and fullness, was negatively correlated with pain reduction. In patients who experienced the deqi sensation in the non-deqi group, deqi intensity was positively correlated with pain reduction, while soreness was negatively correlated with pain reduction. The distance of spreading was not correlated with pain reduction in either group. We found, in SP6 needling of patients with primary dysmenorrhea with cold and dampness stagnation, that a moderate deqi response predicted a prolonged analgesic effect better than a strong deqi response.

11.
Mutat Res ; 779: 1-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31097147

RESUMO

Micronuclei (MN), the small nucleus-like bodies separated from the primary nucleus, can exist in cells with numerical and/or structural chromosomal aberrations in apparently normal tissues and more so in tumors in humans. While MN have been observed for over 100 years, they were merely and constantly considered as passive indicators of chromosome instability (CIN) for a long time. Relatively little is known about the molecular origins and biological consequences of MN. Rapid technological advances are helping to close these gaps. Very recent studies provide exciting evidence that MN act as key platform for chromothripsis and a trigger of innate immune response, suggesting that MN could affect cellular functions by both genetic and nongenetic means. These previously unappreciated findings have reawakened widespread interests in MN. In this review, the diverse mechanisms leading to MN generation and the complex fate profiles of MN are discussed, together with the evidence for their contribution to CIN, inflammation, senescence and cell death. Moreover, we put this knowledge together into a speculative perspective on how MN may be responsible for cancer development and how their presence may influence the choice of treatment. We suggest that the heterogeneous responses to MN may function physiological to ensure the arrestment, elimination and immune clearance of damaged cells, but pathologically, may enable the survival and oncogenic transformation of cells bearing CIN. These insights not only underscore the complexity of MN biology, but also raise a host of new questions and provide fertile ground for future research.


Assuntos
Núcleo Celular/genética , Instabilidade Cromossômica/genética , Animais , Aberrações Cromossômicas , Cromotripsia , Humanos , Micronúcleos com Defeito Cromossômico
12.
Radiat Oncol ; 14(1): 82, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109371

RESUMO

BACKGROUND: The clinical efficacy of definitive pelvic radiotherapy for primary tumors in patients with newly diagnosed organ metastatic cervical cancer is unclear. Therefore, we conducted a retrospective study to evaluate the efficacy of definitive pelvic radiotherapy combined with systemic chemotherapy in patients with organ metastatic cervical cancer. METHODS: We retrospectively analysed medical records from patients with newly diagnosed organ metastatic cervical cancer, all treated with chemotherapy at the Zhejiang Cancer Hospital between October 2006 and December 2016. Survival times were compared using the Kaplan-Meier method. The univariate log-rank method and multivariate Cox proportional hazard models were used to identify associated variables with survival. RESULTS: A total of 48 patients were identified from 11,982 primary cervical cancer patients and divided into two groups according to treatment mode: 36 patients received chemotherapy combined with definitive pelvic radiotherapy (group A), 12 patients underwent chemotherapy with/without palliative pelvic radiotherapy (group B). Median follow-up was 14.4 months (range, 4.6-114.7 months). Median overall survival (OS) for group A and group B was 17.3 and 10 months, respectively. Using the univariate analysis, group A was found to have a better OS than group B (p = 0.002). In multivariate analysis, group A (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15-0.67, p = 0.003) was associated with lower risk of death compared with group B. The main reason for treatment failure was found to be due to the progression of distant metastatic lesions in 36 patients (75%) from the whole cohort. CONCLUSION: In this cohort of organ metastatic cervical cancer patients in good performance status, chemotherapy combined with definitive pelvic radiotherapy was associated with improved survival outcomes when compared with chemotherapy with/without palliative pelvic radiotherapy. Prospective trials evaluating definitive pelvic radiotherapy for newly diagnosed organ metastatic cervical cancer, therefore, are warranted.


Assuntos
Adenocarcinoma/mortalidade , Braquiterapia/mortalidade , Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia/mortalidade , Quimioterapia Adjuvante/mortalidade , Neoplasias Pélvicas/mortalidade , Neoplasias do Colo do Útero/mortalidade , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Adulto , Idoso , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Metástase Linfática , Pessoa de Meia-Idade , Neoplasias Pélvicas/secundário , Neoplasias Pélvicas/terapia , Prognóstico , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
13.
Sci Rep ; 9(1): 6334, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-31004110

RESUMO

Allelic differential expression (ADE) is common in diploid organisms, and is often the key reason for specific phenotype variations. Thus, ADE detection is important for identification of major genes and causal mutations. To date, sensitive and simple methods to detect ADE are still lacking. In this study, we have developed an accurate, simple, and sensitive method, named fluorescence primer PCR-RFLP quantitative method (fPCR-RFLP), for ADE analysis. This method involves two rounds of PCR amplification using a pair of primers, one of which is double-labeled with an overhang 6-FAM. The two alleles are then separated by RFLP and quantified by fluorescence density. fPCR-RFLP could precisely distinguish ADE cross a range of 1- to 32-fold differences. Using this method, we verified PLAG1 and KIT, two candidate genes related to growth rate and immune response traits of pigs, to be ADE both at different developmental stages and in different tissues. Our data demonstrates that fPCR-RFLP is an accurate and sensitive method for detecting ADE on both DNA and RNA level. Therefore, this powerful tool provides a way to analyze mutations that cause ADE.

14.
Mutat Res ; 814: 15-22, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30682723

RESUMO

Patients with type 2 diabetes mellitus (T2DM) are associated with an elevated, but poorly understood baseline of genomic instability (GIN). Expert panels are still debating on whether hyperglycemia is the key element in conferring this high GIN. Since high blood glucose and low blood folate are prevalent in T2DM, we hypothesized that high glucose may work with low folate to induce GIN. Using NCM460, CCD841 and L02 cell lines as in vitro cell models, we investigated the genotoxic effects of high sugars (HS; 1-2% glucose, fructose, galactose or sucrose) alone or in combination with folate deficiency (23 nM, FD) over a course of 7 days by the cytokinesis block micronucleus assay. We found that HS is nongenotoxic to NCM460, CCD841 and L02 cells. However, the combination of HS and FD induced significantly higher levels of micronuclei, nucleoplasmic bridges and nuclear buds. Our in vitro work demonstrates that HS is non-genotoxic under folate repletive condition, but is genotoxic under FD condition. These results provide preclinal proof of concept that concomitant hyperglycemia and low folate may explain, at least in part, the high baseline of GIN in T2DM patients, suggesting that folate levels should be kept under control in order to limit the risk of GIN and carcinogenesis in T2DM.


Assuntos
Metabolismo dos Carboidratos/efeitos dos fármacos , Dano ao DNA , Deficiência de Ácido Fólico/patologia , Ácido Fólico/farmacologia , Açúcares/farmacologia , Metabolismo dos Carboidratos/genética , Células Cultivadas , Relação Dose-Resposta a Droga , Deficiência de Ácido Fólico/metabolismo , Frutose/farmacologia , Galactose/farmacologia , Instabilidade Genômica/efeitos dos fármacos , Humanos , Testes para Micronúcleos , Testes de Mutagenicidade , Sacarose/farmacologia
15.
Environ Mol Mutagen ; 60(3): 254-268, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30403302

RESUMO

Geraniin has been reported to specifically induce apoptosis in multiple human cancers, but the underlying mechanism is poorly defined. The spindle assembly checkpoint (SAC) is a surveillance system to ensure high-fidelity chromosome segregation during mitosis. Weakening of SAC to enhance chromosome instability (CIN) can be therapeutic because very high levels of CIN are lethal. In this study, we have investigated the effects of geraniin on the SAC of colorectal cancer HCT116 cells and noncancerous colon epithelial CCD841 cells. We find that treatment of HCT116 cells with geraniin leads to dose-dependent decrease of cell proliferation, colony formation, and anchorage-independent growth. Geraniin is found to induce apoptosis in mitotic and postmitotic HCT116 cells. Furthermore, geraniin weakens the SAC function of HCT116 cells by decreasing the transcriptional expression of several SAC kinases (particularly Mad2 and Bub1), which in turn leads to premature anaphase entry, mitotic aberrations, and CIN in HCT116 cells. In contrast, the proliferation of CCD841 cells is slightly inhibited by geraniin. Even more interestingly, geraniin increases the transcriptional expression of several SAC kinases (e.g., Mad1 and BubR1) to strengthen SAC efficiency, which contributes to the reduction of mitotic aberrations and CIN in CCD841 cells. Altogether, our findings reveal that the SAC pathway in human colon cancer and noncancerous cell lineages responses oppositely to geraniin treatment, resulting CIN promotion and suppression, respectively. Specific abrogation of SAC to induce catastrophic CIN in HCT116 cells may account for the selective anticancer action of geraniin.. Environ. Mol. Mutagen. 60:254-268, 2019. © 2018 Wiley Periodicals, Inc.


Assuntos
Antineoplásicos/farmacologia , Instabilidade Cromossômica/efeitos dos fármacos , Neoplasias do Colo/genética , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células HCT116 , Humanos , Phyllanthus emblica/química , Fuso Acromático/metabolismo
16.
J Int Med Res ; : 300060519889741, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31889461

RESUMO

OBJECTIVE: This study aimed to investigate the clinical and histological features affecting the survival of patients with early cervical squamous cell cancer treated with radical hysterectomy. METHODS: We retrospectively analyzed clinical and histological data for patients with stage IB-IIA cervical cancer treated by radical hysterectomy at Zhejiang Cancer Hospital from August 2008 to January 2013. RESULTS: A total of 1435 patients were included in the study. Cox regression analysis identified tumor size >4 cm, lymphovascular space involvement (LVSI), lymph node ratio (LNR), and squamous cell carcinoma antigen (SCC-Ag) >2.65 ng/mL as independent prognostic risk factors. Among 1096 patients without high pathological risk factors, the 5-year local recurrence rates for SCC-Ag ≤2.65 and >2.65 ng/mL were 6.6% and 25.7%, respectively. Among 332 patients with lymph node positivity, the overall survival rates for LNR ≤0.19 and >0.19 were 87.8% and 55.6%, respectively. CONCLUSIONS: LVSI, tumor size >4 cm, LNR >0.19, and SCC-Ag >2.65 ng/mL may predict a poor prognosis in patients with early cervical squamous cell cancer treated with radical hysterectomy. SCC-Ag >2.65 ng/mL may be a useful prognostic factor guiding the use of postoperative radiotherapy in patients without pathologic risk factors.

17.
Medicine (Baltimore) ; 97(35): e12144, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30170454

RESUMO

RATIONALE: We herein present a case in which satisfactory analgesia and sedation were provided by the combination of epidural anesthesia with dexmedetomidine for exploratory laparoscopy in a patient who was highly suspected to have tuberculosis. This is an optimal anesthesia method to minimize the risk of nosocomial infection, especially in developing countries that lack sterilizers for anesthesia machines. PATIENT CONCERNS: A 45-year-old woman suspected to have active tuberculosis was scheduled to undergo laparoscopy for definitive diagnosis of a pelvic mass. DIAGNOSES: Tuberculosis was diagnosed by exploratory laparoscopy. INTERVENTIONS: The surgery was performed under general anesthesia to prevent pain and discomfort during the procedure. However, ventilation machine used by patients with tuberculosis may have a potential risk of nosocomial infection and need disinfection by a special sterilizer machine even when using a bacterial/viral filter-heat and moisture exchanger. Therefore, the surgery was performed under continuous epidural anesthesia combined with dexmedetomidine. OUTCOMES: The surgery was successfully completed, and pelvic tubercles were confirmed to be caseous necrotic tissue by pathologic examination. The patient began regular antituberculosis treatment after discharging from the gynecology department. LESSONS: We conclude that administration of dexmedetomidine combined with epidural anesthesia can provide comfortable sedation for short laparoscopic procedures in patients with suspected tuberculosis. This technique can minimize the risk of nosocomial infection.


Assuntos
Anestesia Epidural/métodos , Técnicas de Diagnóstico Obstétrico e Ginecológico , Hipnóticos e Sedativos/administração & dosagem , Laparoscopia/métodos , Tuberculose dos Genitais Femininos/diagnóstico , Carcinoma/diagnóstico , Dexmedetomidina/administração & dosagem , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico
18.
Curr Med Sci ; 38(3): 461-466, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30074213

RESUMO

Filamin A and 14-3-3-σ are closely associated with the development of breast cancer. However, the exact relationship between them is still unknown. The present study aimed to examine the interaction of filamin A with 14-3-3-σ in the invasion and migration of breast cancer. RNA interference technology was employed to silence filamin A in MDA-MB-231 cells. Real-time PCR and Western blotting were used to detect the expression of filamin A and 14-3-3-σ at mRNA and protein levels, respectively. Double immunofluorescence was applied to show their colocalization morphologically. Wound healing assay and Trans-well assay were used to testify the migration and invasion of MDA-MB-231 cells in filamin A-silenced cells. The results showed that silencing filamin A significantly increased the mRNA and protein levels of 14-3-3σ. In addition, double immunofluorescence displayed that filamin A and 14-3-3σ were predominantly colocalized in the cytoplasm of MDA-MB-231 cells. Silencing filamin A led to the enhanced fluorescence of 14-3-3σ. Furthermore, cell functional experiments showed that silencing filamin A inhibited the migration and invasion of MDA-MB-231 cells in vitro. In conclusion, silencing filamin A may inhibit the invasion and migration of breast cancer cells by upregulating 14-3-3σ.


Assuntos
Proteínas 14-3-3/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Movimento Celular , Exorribonucleases/genética , Filaminas/metabolismo , Inativação Gênica , Regulação para Cima/genética , Proteínas 14-3-3/metabolismo , Biomarcadores Tumorais/metabolismo , Contagem de Células , Linhagem Celular Tumoral , Citoplasma/metabolismo , Regulação para Baixo/genética , Exorribonucleases/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo
19.
Mutagenesis ; 33(4): 271-281, 2018 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-30085224

RESUMO

Homeostasis of chromosomal instability (CIN) facilitates the origin and evolution of abnormal karyotypes that are critical for the survival and proliferation of cancer cells, but excessive CIN can result in cellular toxicity. Geraniin is a multifunctional ellagitannin found in some species of Geranium and Phyllanthus. We employed the cytokinesis-block micronucleus cytome assay to evaluate the CIN, nuclear division index (NDI) and apoptosis induced by geraniin in human colorectal adenocarcinoma cells (Colo205 and Colo320) and human colon mucosal epithelial cells (NCM460). Cells were exposed to 25, 50 or 100 µg/ml geraniin for 24, 48 or 72 h. 0.05 µg/ml mitomycin C was used as a positive control and media as a negative control. The results showed that, compared to negative controls, geraniin significantly reduced NDI (P < 0.01) and increased CIN (P < 0.01) and apoptosis (P < 0.05) in Colo205 and Colo320 cells in a dose- and time-dependent manner. Conversely, geraniin significantly increased NDI (P < 0.05) and decreased CIN (P < 0.001) and apoptosis (P < 0.01) in NCM460 cells. Moreover, CIN was positively associated with apoptosis (r = 0.437, P < 0.001) and negatively associated with NDI (r = -0.744, P < 0.001) in these cells. Together, our results highlight that the induction of catastrophic CIN may underlie the antitumor potential of geraniin. Our data also suggest that geraniin can decrease the risk of oncogenic transformation via decreasing CIN in normal cells.


Assuntos
Apoptose/efeitos dos fármacos , Instabilidade Cromossômica/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade
20.
Biochem Biophys Res Commun ; 503(2): 697-702, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-29909006

RESUMO

Titanium dioxide nanoparticles (TiO2-NPs) have raised serious attention for their widely use and potential adverse effects on human mainly due to producing ROS. However, the influence of TiO2-NPs on telomere maintaining has not been studied clearly. Shelterin plays core roles in telomere length (TL) regulation. Abnormal TL are associated with chromosome instability (CIN) and high risk of diseases. This study investigated whether TiO2-NPs affect TL to induce CIN through ROS generation and the possible mechanisms. Human hepatocyte L-02 and hepatocarcinoma cells QGY were exposed to TiO2-NPs (0, 40, 80 µg/mL) for 72 h. The intracellular hydrogen dioxide (H2O2) concentration were measured. The TL, Nrf-2, and three core shelterin components (TRF1, TRF2, and POT1) transcription level were determined by quantitative real-time PCR. CIN was measured by cytokinesis-block micronucleus assay. TiO2-NPs exposure increased intracellular H2O2 in both L-02 and QGY cells, and induced Nrf-2, TRF1, TRF2, POT1 downregulated transcription compared with control (P < 0.001) in L-02 but all upregulated (P < 0.05) in QGY. Significant TL shortening (P < 0.001) and CIN increase (P < 0.01) in L-02 cells were observed but not in QGY cells. The differentially responses of the tested components of shelterin and Nrf-2 to oxidative stress induced by TiO2-NPs led to the weakened telomere protection in normal cells and effective telomere maintenance in cancer cells, respectively. The upregulation of Nrf-2 and shelterin could protect TL and chromosome stability against TiO2-NPs exposure.


Assuntos
Hepatócitos/metabolismo , Neoplasias Hepáticas/metabolismo , Nanopartículas/efeitos adversos , Estresse Oxidativo , Proteínas de Ligação a Telômeros/metabolismo , Telômero/metabolismo , Titânio/efeitos adversos , Linhagem Celular , Linhagem Celular Tumoral , Instabilidade Cromossômica , Regulação para Baixo , Hepatócitos/patologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Telômero/patologia , Encurtamento do Telômero , Proteínas de Ligação a Telômeros/genética , Regulação para Cima
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