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1.
Eur Rev Med Pharmacol Sci ; 24(1): 200-212, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31957833

RESUMO

OBJECTIVE: Tongue cancer is a common malignant tumor in the oral and maxillofacial region, most of which is squamous cell carcinoma. Cisplatin (DDP) is one of the chemotherapy drugs for patients with tongue squamous cell carcinoma (TSCC). However, DDP resistance has become a major obstacle to its clinical application. Our study aimed to investigate the effects of long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) on DDP resistance of tongue cancer and the underlying mechanism. PATIENTS AND METHODS: The levels of KCNQ1OT1, miR-124-3p, and tripartite motif containing 14 (TRIM14) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The maximum size of tumor (MTS) assay was used to detect the cell survival rates. Furthermore, the cell proliferation was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Transwell assay was performed to detect the cell migration and invasion. Western blot assay was used to detect the protein levels of Vimentin, N-cadherin, E-cadherin, and TRIM14. The functional targets of KCNQ1OT1 and miR-124-3p, miR-124-3p and TRIM14 were predicted by starBase 3.0 and TargetScan. The relationship between KCNQ1OT1 and miR-124-3p was confirmed by Dual-Luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull-down. Further, the relationship between miR-124-3p and TRIM14 was verified by Dual-Luciferase reporter assay. Animal experiment revealed the effect of KCNQ1OT1 on DDP resistance of tongue cancer cells in vivo. RESULTS: KCNQ1OT1 was upregulated in DDP-resistant tongue cancer tissues and cells, and mainly expressed in cytoplasm. Functionally, the knockdown of KCNQ1OT1 inhibited the survival rate, proliferation, migration, invasion, and EMT of the DDP-resistant tongue cancer cells. Of note, miR-124-3p acted as a target of KCNQ1OT1 and KCNQ1OT1 could reduce the expression of miR-124-3p. Moreover, miR-124-3p targeted TRIM14 and the downregulation of TRIM14 reduced the DDP resistance of tongue cancer cells. Importantly, KCNQ1OT1 regulated the TRIM14 expression by targeting miR-124-3p. Furthermore, KCNQ1OT1 knockdown reduced the DDP-resistant tumor growth and weight through the miR-124-3p/TRIM14 axis in vivo. CONCLUSIONS: LncRNA KCNQ1OT1 promotes the DDP resistance of tongue cancer by sponging miR-124-3p to regulate TRIM14 expression.

2.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(11): 1147-1151, 2019 Nov 06.
Artigo em Chinês | MEDLINE | ID: mdl-31683403

RESUMO

Objective: To examine the association of pre-pregnancy body mass and weight gain during pregnancy with macrosomia. Methods: From January 2015 to December 2015, a total of 20 477 pregnant women were recruited by probabilistic proportional scale sampling with simple randomization in Sichuan, Yunnan and Guizhou Provinces. Basic information of pregnant women, weight gain during pregnancy and weight of newborn were collected. A multiple logistic regression model was used to assess the association between the pre-pregnancy body mass and gestational weight gain indicators with macrosomia. Results: 20 321 mother-infant were included in the final analysis. 20 321 pregnant women were (30.09±4.10) years old and delivered at (39.20±1.29) weeks, among which 12 341 (60.73%) cases were cesarean delivery. The birth weight of 20 321 infants were (3 292.26±431.67) grams, and 970 (4.77%) were macrosomia. The multiple logistic regression model showed that after adjusting for the age of women, compared to the normal weight group in the pre-pregnancy, the overweight and obesity group elevated the risk of macrosomia, with OR (95%CI) about 1.99 (95%CI: 1.69-2.35) and 4.05 (95%CI: 3.05-5.39), respectively. After adjusting for the age, the pre-pregnancy BMI, delivery weeks, delivery mode and infant's gender, compared to the weight-gain appropriate group, higher weight gain rate in the mid-pregnancy and excessive total gestational weight gain elevated the risk of macrosomia, with OR (95%CI) about 1.99 (95%CI: 1.66-2.39) and 1.80 (95%CI: 1.55-2.08), respectively. Conclusion: The overweight before pregnancy, obesity before pregnancy, the rate of weight gain in the second trimester and the high total weight gain during pregnancy could increase the risk of macrosomia.


Assuntos
Índice de Massa Corporal , Macrossomia Fetal/epidemiologia , Sobrepeso/epidemiologia , Ganho de Peso , Adulto , Peso ao Nascer , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Obesidade/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Segundo Trimestre da Gravidez , Fatores de Risco
3.
Zhonghua Yi Xue Za Zhi ; 99(4): 260-265, 2019 Jan 22.
Artigo em Chinês | MEDLINE | ID: mdl-30669710

RESUMO

Objective: To investigate the influence factors of carotid endarterectomy(CEA) improving cognitive function in patients with carotid stenosis. Methods: The clinical data of carotid stenosis patients with cognitive impairment who underwent CEA in Nanjing Drum Tower Hospital and the First People's Hospital of Lianyungang from December 2011 to July 2017 were retrospectively analyzed. One week before operation, carotid CT angiography and cranial magnetic resonance imaging were performed, and the cognitive function of patients was evaluated with Montreal Cognitive Scale (MoCA). The magnetic resonance imaging and MoCA were reexamined 4 weeks after the procedure. The patients were divided into improved group (COI+) and un-improved group (COI-) according to whether the cognitive function score was improved or not after operation. The general data, carotid artery occlusiontime, surgical site, preoperative carotid calcification score (CS) and the Fazekas score, pre-operative and post-operative cerebral perfusion parameters, like mean transit time(MTT), time to peak(TTP) and arrivetime (T0), and any new infarcts after operation between the two groups were compared. Results: A total of 70 patients were selected, including 50 patients in group COI+ and 20 patients in group COI-. There were no significant differences in age, gender, hypertension, diabetes mellitus, smoking and drinking habits, as well as in carotid artery occlusiontime and preoperative Fazekas score between the two groups (all P>0.05). The preoperative carotid artery calcification scores of the two groups were 469.75±50.86 and 393.51±77.41, respectively. The changes of pre-and post-operation perfusion parameters between the two groups were statistically significant, with ΔMTT were 7.79±9.51 and 3.03±6.40, ΔTTP were 5.83±8.98 and 1.17±4.77, T0 were 5.89±8.08 and 3.05±5.95, respectively(t=4.844, 2.053, 2.192 and 1.423, respectively, all P<0.05). Proportion of cases with new infarcts after operation(0.38 vs 0.65) or undergoing left CEA (0.66 vs 0.40)between the two groups was statistically different (χ(2)=4.197 and 9.677, respectively, both P<0.05). Conclusion: Higher preoperative CS score, undergoing left CEA, significantly improved cerebral perfusion and without new infarct postoperatively, are independent factors contributing to improving cognitive function through CEA operation.


Assuntos
Disfunção Cognitiva , Endarterectomia das Carótidas , Estenose das Carótidas , Transtornos Cognitivos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
4.
Bull Entomol Res ; 109(2): 248-256, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30514411

RESUMO

Although parasites and microbial pathogens are both detrimental to insects, little information is currently available on the mechanism involved in how parasitized hosts balance their immune responses to defend against microbial infections. We addressed this in the present study by comparing the immune response between unparasitized and parasitized pupae of the chrysomelid beetle, Octodonta nipae (Maulik), to Escherichia coli invasion. In an in vivo survival assay, a markedly reduced number of E. coli colony-forming units per microliter was detected in parasitized pupae at 12 and 24 h post-parasitism, together with decreased phagocytosis and enhanced bactericidal activity at 12 h post-parasitism. The effects that parasitism had on the mRNA expression level of selected antimicrobial peptides (AMPs) of O. nipae pupae showed that nearly all transcripts of AMPs examined were highly upregulated during the early and late parasitism stages except defensin 2B, whose mRNA expression level was downregulated at 24 h post-parasitism. Further elucidation on the main maternal fluids responsible for alteration of the primary immune response against E. coli showed that ovarian fluid increased phagocytosis at 48 h post-injection. These results indicated that the enhanced degradation of E. coli in parasitized pupae resulted mainly from the elevated bactericidal activity without observing the increased transcripts of target AMPs. This study contributes to a better understanding of the mechanisms involved in the immune responses of a parasitized host to bacterial infections.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Besouros/imunologia , Interações Hospedeiro-Parasita , Fagocitose , Vespas/fisiologia , Animais , Besouros/metabolismo , Besouros/parasitologia , Pupa/imunologia , Pupa/metabolismo , Pupa/parasitologia , Venenos de Vespas
5.
Zhonghua Wai Ke Za Zhi ; 56(6): 477-480, 2018 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-29886673

RESUMO

Aortic dissection is one of the most common vascular emergent disease. Thoracic endovascular aortic repair (TEVAR) therapy which created the new era of treatment of Stanford type B aortic dissection (TBAD) has gradually replaced the surgical treatment and becomes the gold standard for treatment of TBAD. Aortic remodeling after TEVAR is the key factor to evaluate the mid-term survival rate and successful treatment of the aortic dissection victims. However, there are few studies on aortic remodeling and lack of unified criteria to evaluate it. This article was to summarize the domestic and abroad research advances which focused on the morphological changes, the regularity, and the evaluation criteria of aorta remodeling after TEVAR.


Assuntos
Aneurisma Dissecante , Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma Dissecante/terapia , Aneurisma da Aorta Torácica/terapia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
6.
Zhonghua Yi Xue Za Zhi ; 97(37): 2946-2948, 2017 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-29050168

RESUMO

Objective: To evaluate the efficacy of pleural abrasion in treatment of spontaneous pneumothorax with video-assisted thoracic surgery (VATS) for bullae resection. Methods: The clinical data of 158 patients with initial spontaneous pneumothorax who underwent video-assisted thoracic wedge resections with or without pleural abrasion in Henan Provincial People's Hospital from June 2010 to June 2015 were retrospectively analyzed. The patients were assigned to two equal groups according to whether pleural abrasion was applied or not: experimental group (with pleural abrasion) and control group (without pleural abrasion); and there were 79 patients in each group.There were 62 males and 17 females aged 15-60 years (mean age 34 years) in pleural abrasion group. And there were 70 males and 9 females aged 18-60 years (mean age 38 years) in non-pleural abrasion group.After surgery, all patients were evaluated for postoperative pain, chest tube removal time, hospital stay and other complications.Independent samples t test was used to compare the data between groups. Results: Surgeries for 158 patients were performed successfully.No mortality occurred.There was no conversion to thoracotomy.Postoperative pain, operation time, intraoperative blood loss, chest tube removal time, pleural canals flowand average hospital stay in non-pleural abrasion group was significantly lower for 4.4, 19 minutes, 10 ml, 21 hours, 87 ml and 1.4 days respectively when compared with those in pleural abrasion group (t=32.478, 7.140, 11.093, 7.288, 10.246, 8.070, all P<0.05). There was no missing case with a follow-up of 30 months.No complications, such as pneumothorax, was observed. Conclusions: Postoperative pain, chest tube removal time and hospital stay in non-pleural abrasion group are all lower than those in pleural abrasion group.And there is no significant difference in the recurrence of pneumothorax between the two groups after VATS bullae resection.


Assuntos
Pneumotórax , Cirurgia Torácica Vídeoassistida , Adolescente , Adulto , Vesícula , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
Opt Express ; 25(20): 24400-24409, 2017 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-29041385

RESUMO

Multiplication of the pulse repetition frequency (PRF) of a compact, mode-locked fiber laser by a factor as large as 25 has been achieved with two coupled Fabry-Perot (FP) resonators of low finesse (F = 2). Reducing the FP finesse by at least two orders of magnitude, relative to previous pulse frequency multiplication architectures, has the effect of stabilizing the oscillator with respect to pulse-to-pulse amplitude, dropped pulses, and other effects of cavity detuning. Coupling two Fabry-Perot cavities, each encompassing a 3.3-3.6 cm length of fiber, in a hybrid geometry resembling that of the coupled-cavity laser interferometer has yielded side mode suppressions ≥ 50 dB while simultaneously doubling the laser PRF to 2.87 GHz. Pulses approximately 3.9 ps in duration (FWHM) are emitted at intervals of 27.5 ps, and in groups (bursts) of pulses separated by 350 ps. Thus, the PRF within the pulse bursts is 36 GHz, a factor of 25 greater than the free spectral range for a conventional mode-locked cavity having a length of 6.9 cm. Experimental data are in accord with simulations of the phase coherence and temporal behavior of the mode-locked pulses.

8.
Opt Express ; 25(17): 20125-20132, 2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-29041696

RESUMO

We identify a new regime where laser pulses represent the dynamics of rectangular-shaped wave packets (RSWPs) in a passively mode-locked Tm3+-doped fiber laser. In this regime the laser consists of a train of mode-locked pulses underneath a rectangular-shaped envelope. The density of pulses within a RSWP can be as high as 2.8 GHz, which is consistent with cavity fundamental repetition rate. The effects of small-signal gain value, pulse repetition rate, and net dispersion on the RSWP performance are analyzed. These results imply that this new regime particularly favors high-repetition-rate ultrafast lasers. We further reproduce the phenomenon from using numerical simulations and understand such behavior by referring to the nonlinear dynamics.

9.
Public Health ; 152: 136-144, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28888618

RESUMO

OBJECTIVES: The doctor-patient relationship (DPR) in China is known to be tense. We tested whether an intervention program providing individualized feedback to doctors by patients could improve patients' satisfaction in an outpatient setting. STUDY DESIGN: A non-randomized controlled prepost intervention study in a tertiary hospital. Six surgery clinics were chosen as the intervention group and eight internal medicine clinics as the control group. METHODS: Before the program started, patients attending each group of clinics were asked to fill in the Short-Form Patient Satisfaction Questionnaire (PSQ-18). In the experimental period, patients attending the intervention clinics were requested to rate their perception of the doctor's quality of care in various domains on an 8-question feedback card immediately after exiting from the examination room and to drop the completed card into the feedback box for the particular doctor. The cards were then collected by the doctor confidentially at the end of each day. There was no feedback in the control clinics. After the experimental period ended, the doctors in both groups of clinics were reassessed by a new series of patients using PSQ-18. The PSQ-18 scores were compared within the same group of clinics over time, and the changes in satisfaction score compared between intervention and control clinics. RESULTS: There were 189 and 190 responders in the intervention group and 190 and 200 in the control group, before and after the intervention period, respectively. Scores in all domains increased significantly (P < 0.001) in the intervention group but not in the control group. Significant improvement in the patient satisfaction scores in the intervention clinics compared with the control clinics was confirmed by mixed-effects linear regression controlling for the effects of gender, age, marital status, education, and household income in the domains of general satisfaction, technical quality, communication, and accessibility and convenience. CONCLUSIONS: Timely feedback to doctors of patients' perception of quality of care received can improve outpatient satisfaction in a Chinese hospital.


Assuntos
Comunicação , Pacientes Ambulatoriais/psicologia , Satisfação do Paciente/estatística & dados numéricos , Relações Médico-Paciente , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Centros de Atenção Terciária , Adulto Jovem
10.
Opt Express ; 24(26): 29882-29895, 2016 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-28059373

RESUMO

With increasing demand on a laser source in the gigahertz pulse repetition rate regime, clarification on the mechanism of instability in high repetition rate fiber lasers - a promising alternative to solid state lasers - is of great importance and can potentially offer guideline for continuous wave (CW) mode locking. Here we present a theoretical approach together with relevant experimental corroboration to analyze the instabilities. By means of appropriate approximations, regimes from Q-switched mode locking, CW mode locking and pulsation are theoretically identified. Meanwhile, a critical curve that characterizes pump level for triggering Q-switched mode locking and pulsation for different repetition rates is given by virtue of both analytical and numerical procedures. In experiment, a passively mode-locked fiber laser with 1.6 GHz fundamental repetition rate is realized. The three regimes and corresponding pump power intervals are revealed, which are in consistence with theoretical prediction. Pulsation, as a relatively exotic phenomenon in GHz fiber laser, is well reproduced by the present model, which further verifies the accuracy of the approach as well as enriches the nonlinear dynamics.

11.
Neoplasma ; 62(6): 905-14, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26458317

RESUMO

Immunotherapy is a hot issue in cancer research over the years and tumor cell vaccine is one of the increasing number of studies. Although the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. CpG Oligodeoxynucleotides (CpG ODNs), synthetic oligonucleotides containing a cytosine-phosphate-guanine(CpG) motif, was shown to enhance immune responses to a wide variety of antigens. In this study, we generated the radioresistant Lewis lung cancer cell by repeated X-ray radiation and inactivated it as a whole tumor cell vaccine to enhance the immunogenicity of tumor cell vaccine. Mice were subcutaneously immunized with this inactivated vaccine combined with CpG ODN1826 and then inoculated with autologous Lewis lung cancer (LLC) to estimate the antitumor efficacy. The results showed that the radioresistant tumor cell vaccine combined with CpG ODN1826 could significantly inhibit tumor growth, increased survival of the mice and with 20% of the mice surviving tumor free in vivo compared with the unimmunized mice bearing LLC tumor. A significant increase of apoptosis was also observed in the tumor prophylactically immunized with vaccine of inactivated radioresistant tumor cell plus CpG ODN1826. The potent antitumor effect correlated with higher secretion levels of tumor necrosis factor-alpha(TNF-α) and lower levels of interleukin-10(IL-10) concentration in serum. Furthermore, the results suggested that the antitumor mechanism was probably depended on the decreased level of programmed death ligand-1(PD-L1) which plays an important role in the negative regulation of immune response by the inhibition of tumor antigen-specific T cell activation. These findings clearly demonstrated that the radioresistant tumor cell vaccine combined with CpG ODN1826 as an appropriate adjuvant could induce effective antitumor immunity in vivo.

12.
Eur J Vasc Endovasc Surg ; 50(1): 5-12, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25933475

RESUMO

OBJECTIVE: To investigate the influence of carotid endarterectomy (CEA) on cerebral perfusion and cognitive function in patients with internal carotid artery stenosis (ICA). METHODS: Patients were prospectively enrolled in this study. Shunted patients were excluded. Cerebral perfusion was measured by magnetic resonance (MR) perfusion weighted imaging (PWI) and diffusion weighted imaging (DWI) in 46 patients with >65% ICA (31 males, 64.5 ± 6.7 years) 1 week before and 6 weeks after CEA. Cognitive function was assessed using the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) 1 week before and 6 weeks after CEA. RESULTS: After CEA, perfusion parameters from PWI decreased, including mean transit time (MTT) (21.07 ± 7.36 vs. 14.27 ± 6.22, p < .0001), time to peak (TTP) (28.69 ± 8.54 vs. 23.45 ± 4.25, p = .001), arrive time (T0) (19.89 ± 7.32 vs. 15.20 ± 3.51, p = .001), and relative cerebral blood volume (rCBV) (11.48 ± 3.50 vs. 7.53 ± 3.17, p < .0001). A significant improvement was observed in MoCA (20.48 ± 1.70 vs. 22.04 ± 1.48, p = .001). Spearman's rank correlation analysis between TTP and MoCA scores demonstrated a linear relationship with an excellent correlation coefficient (R = -.893, p < .001). Linear regression indicated that diabetes was a risk factor for cognitive improvement in patients with ICA (p = .014). Further analysis showed that patients with DM performed worse in MoCA after the procedure (with-DM 21.15 ± 1.28 vs. non-DM 22.4 ± 1.46, p = .010) while the baselines were similar (non-DM: 20.3 ± 1.8 vs. with-DM: 20.9 ± 1.4, p = .362). CONCLUSION: CEA could improve the cerebral perfusion and the cognitive function in un-shunted ICA patients. Cerebral reperfusion was an important factor for cognitive improvement. Diabetes had a negative effect on cognitive improvement after CEA.


Assuntos
Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/cirurgia , Circulação Cerebrovascular/fisiologia , Cognição/fisiologia , Endarterectomia das Carótidas , Angiografia por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença
13.
J Biol Regul Homeost Agents ; 28(4): 649-57, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25620175

RESUMO

Pentraxin-3 (PTX3), a modulator of tumor-associated inflammation, is known to be positively correlated with tumor grade and severity of malignancies, but the function and molecular underlying mechanisms of PTX3 remain unclear. In the present study, the expression of PTX3 in human lung adenocarcinoma (LAC) was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to explore the effects of lentiviral vector-mediated PTX3 shRNA (Lv-shPTX3) on cell growth and invasive potential in LAC cell lines (A549 and LETPα-2), assessed by MTT and Transwell assays, respectively. We found that the expression of PTX3 protein was significantly increased in LAC tissues compared with that in adjacent non-cancerous tissues (ANCT) (60.42% vs. 29.17%, P=0.004), and positively correlated with lymphatic invasion of the tumor (P=0.006). Furthermore, knockdown of PTX3 suppressed tumor proliferation and invasion of LAC cells, followed by decreased expression of p-AKT, p-NF-kappa B, PCNA, and MMP-9. Taken together, our findings demonstrate that upregulation of PTX3 expression is correlated with tumor metastasis of LAC patients, and knockdown of PTX3 blocks the development of LAC through inhibition of the AKT and NF-kappa B pathways, suggesting that PTX3 may serve as a potential therapeutic target for the treatment of cancer.


Assuntos
Adenocarcinoma/patologia , Proteína C-Reativa/fisiologia , Neoplasias Pulmonares/patologia , NF-kappa B/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Componente Amiloide P Sérico/fisiologia , Transdução de Sinais , Adenocarcinoma de Pulmão , Adulto , Idoso , Proliferação de Células , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Invasividade Neoplásica , Antígeno Nuclear de Célula em Proliferação/análise
14.
Mol Biol (Mosk) ; 42(3): 459-69, 2008.
Artigo em Russo | MEDLINE | ID: mdl-18702304

RESUMO

Hypoxia is a common environmental stress that influences signaling pathways and cells function, which through initiating intracellular signaling pathways and hence leading to the activation of the transcription factor hypoxia-inducible factor-1 (HIF-1). In this study, we initially confirm that hypoxia activates HIF-1alpha protein expression in a time-dependent manner with a maximum reached at 60 min in vitro and 4h in vivo in gastric mucosa epithelial cells. The expression of HIF-1alpha is correlated with the activation of HIF-1 DNA binding and transcriptional activity. Hypoxia dose not affect HIF-1alpha mRNA transcription but regulates HIF-1alpha protein expression through a translation-dependent pathway to regulate protein synthesis. Hypoxia could induce phosphorylation of Akt, MAPK (ERK), and target of p70S6K1. PI3K and MAPK inhibitor, LY294002 and U0126 could inhibit hypoxia-induced HIF-1 and VEGF expression. We also investigated the role of reactive oxygen species (ROS) involved in HIF-1 and VEGF expression Exogenous addition of H2O2 was sufficient to activate Akt and ERK, scavengers of H2O2 significantly inhibited hypoxia-induced Akt and ERK, and subsequent HIF-lax expression and transcriptional activity. In conclusion, our data suggested that hypoxia- PI3K signaling through Akt and ERK kinases regulated ROS-dependent, hypoxia- induced HIF-1 activation and VEGF expression in gastric mucosa epithelial cells.


Assuntos
Células Epiteliais/metabolismo , Mucosa Gástrica/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Hipóxia/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Transformada , Células Epiteliais/patologia , Mucosa Gástrica/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Hipóxia/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Oxidantes/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Quinases S6 Ribossômicas 70-kDa/antagonistas & inibidores , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transcrição Genética/efeitos dos fármacos
15.
J Exp Clin Cancer Res ; 26(2): 261-8, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17725107

RESUMO

Phosphatidylinositol 3-kinase/Akt pathway is an important intracellular pathway that is frequently activated in cancer cells. The role of P-AKT in multidrug resistance of gastric cancer cells and the possible underlying mechanisms are here investigated. Up-regulation of P-AKT expression could confer resistance to both P-glycoprotein-related and P-glycoprotein-non-related drugs on AGS cells, and suppress adriamycin-induced apoptosis, along with decreased accumulation and increased releasing amount of adriamycin. P-AKT could significantly up-regulate the expression of Bcl-2, and down-regulate the expression of Bax, but not alter the expression of PTEN in gastric cancer cells. Inhibition of P-AKT expression could partially reverse P-AKT-mediated multidrug resistance and significantly up-regulate P53 expression, and down-regulate the expression of P-glycoprotein and the transcription of the multidrug resistance gene 1. Further studies of the biological functions of P-AKT may be helpful for understanding the mechanisms of multidrug resistance of gastric cancer and developing possible therapeutical strategies.


Assuntos
Resistência a Múltiplos Medicamentos , Proteínas Proto-Oncogênicas c-akt/fisiologia , Neoplasias Gástricas/enzimologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Apoptose , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Regulação para Baixo , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transcrição Genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
16.
Tumour Biol ; 27(2): 84-91, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16582585

RESUMO

Cellular prion protein (PrP(C)), a glycosylphosphatidylinositol-anchored membrane protein, was found in our lab to be widely expressed in gastric cancer cell lines. In order to evaluate its biological significance in human gastric cancer, we investigated its expression in a large series of gastric tissue samples (n = 124) by immuno histochemical staining with the monoclonal antibody 3F4. Compared with normal tissues, gastric adenocarcinoma showed increased PrP(C) expression, correlated with the histopathological differentiation (according to the WHO and Lauren classifications) and tumor progression (as documented by pTNM staging). To better understand the underlying mechanism, we introduced the PrP(C) and two pairs of RNAi into the poorly differentiated gastric cancer cell line AGS and found that PrP(C) suppressed ROS and slowed down apoptosis in transfected cells. Further study proved that the apoptosis-related protein Bcl-2 was upregulated whereas p53 and Bax were downregulated in the PrP(C)-transfected cells. A reverse effect was observed in PrP(C) siRNA-transfected cells. These results strongly suggested that PrP(C) might play a role as an effective antiapoptotic protein through Bcl-2-dependent apoptotic pathways in gastric cancer cells. Further study into the mechanism of these relationships might enrich the knowledge of PrP, better our understanding of the nature of gastric carcinoma, and further develop possible strategies to block or reverse the development of gastric carcinoma.


Assuntos
Apoptose/fisiologia , Regulação Neoplásica da Expressão Gênica , Proteínas PrPC/genética , Proteínas PrPC/fisiologia , Neoplasias Gástricas/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Linhagem Celular Tumoral , Citocromos c/genética , Citocromos c/fisiologia , DNA Complementar , DNA de Neoplasias/genética , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas PrPC/análise , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio , Neoplasias Gástricas/química , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Transfecção , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/fisiologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/fisiologia
17.
Exp Oncol ; 28(4): 258-62, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17285107

RESUMO

Zinc ribbon domain containing 1 (ZNRD1) gene encoding a protein consisting of two zinc ribbon domains was recently cloned from the human HLA locus. So far, ZNRD1 has been found implicated in transcription regulation and might play potential roles in mediating several biological processes, including multidrug resistance, tumorigenesis and cell cycle. This article reviewed these recent findings and provided additional information to support the role of ZNRD1 gene as a novel candidate DNA damage repair related gene.


Assuntos
Ciclo Celular/fisiologia , Transformação Celular Neoplásica/metabolismo , Reparo do DNA/fisiologia , Proteínas de Ligação a DNA/metabolismo , Resistência a Múltiplos Medicamentos/fisiologia , Animais , Humanos
18.
Eur J Vasc Endovasc Surg ; 30(4): 430-6, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16009580

RESUMO

OBJECTIVE: To investigate the pathological and metabolic changes in the gastrocnemius muscle in patients with chronic vein insufficiency (CVI). METHOD: Thirty-six patients with varicose veins were investigated by ambulatory venous pressure (AVP) and duplex ultrasonography. Twelve age and height-matched controls were used for comparison. Patients and controls consented to participate in this study. Twenty-one patients with primary vein varicose (group AI) and 15 patients (group AII) with primary deep venous valve incompetence (DVI) underwent biopsies of the gastrocnemius muscle during operation. Adductor biopsies obtained from the same limbs served as a control group (group B) and specimens from controls subjects without venous disease served as the second control group (group C). All the specimens were investigated by superoxide dismutase (SOD), nitric oxide (NO), Na+-K+-ATPase, Ca2+-ATPase and lactic acid (LD) determinations. Samples were subjected to light and electron microscopy following H & E staining, special ATPase, cytochrome oxidase/succinate dehydrogenase (COX/SDH) stains. RESULTS: Normal muscle architecture was seen following H & E, ATPase and COX/SDH staining and normal cell metabolism was observed in specimens of groups B and C. In group A, pathological changes were encountered in the gastrocnemius muscle including disseminated myofibril atrophy, cell denaturation and necrosis, inflammatory cell infiltration, proliferation and dilation of interfascicular veins. ATPase staining (pH 9.4) demonstrated grouping of atrophic fibres, especially type I myofibril grouping, accompanied by moderate to severe atrophy of type II muscle fibres. However, no patient had selective type I fibre atrophy. Enhanced enzymatic activity in single or multiple myofibrils was demonstrated by COX/SDH staining in approximately half of the specimens in group AII. In group AII, electron microscopy showed swelling, myelin figure denaturation of mitochondria, disruption of the myofibrils and increased lipid droplets in the gastrocnemius muscle. Increased concentration of LD was found in most specimens from group A patients. There were also reductions of SOD, NO, biochemical activity of Na+-K+-ATPase, Ca2+-ATPase with increasing concentration of LD in these patients, most prominently in group AII. We found correlation between AVP assessments and the biochemical measurements as well as morphological appearances of the gastrocnemius muscle. CONCLUSION: Venous hypertension results in pathophysiological changes in the gastrocnemius muscles of patients with DVI, associated with decreased calf pump function.


Assuntos
Perna (Membro)/irrigação sanguínea , Músculo Esquelético/patologia , Insuficiência Venosa/patologia , Adulto , Idoso , Atrofia , ATPases Transportadoras de Cálcio/metabolismo , Estudos de Casos e Controles , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Humanos , Ácido Láctico/metabolismo , Masculino , Microscopia , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/metabolismo , Miofibrilas/patologia , Necrose , Óxido Nítrico/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Succinato Desidrogenase/metabolismo , Superóxido Dismutase/metabolismo , Ultrassonografia Doppler Dupla , Varizes/imunologia , Varizes/patologia , Insuficiência Venosa/imunologia , Pressão Venosa
19.
Int J Clin Pract ; 56(3): 169-72, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12018818

RESUMO

The aim of this study was to ascertain whether MG7Ag is a useful predictor of evolution of gastric dysplasia to carcinoma. A total of 1090 patients with confirmed dysplasia were stained immunohistochemically with MG7 monoclonal antibody by the ABC method. A prospective follow-up study was undertaken on 19 patients with MG7Ag positive staining and 16 with MG7 negative staining over a period of 10-78 months. The expression of MG7Ag was also compared in another two groups by conducting retrospective studies. One group showed an evolution into gastric cancer over 2-4 years, the other did not. Quantitative analysis of MG7Ag expression was carried out on the last two groups. The receiver operating characteristic curve and Youden index were used to assess the best critical value for MG7Ag. MG7Ag was found positive in 456/1090 cases (41.8%) with dysplasia. Prospective follow-up of 35 patients showed that 6/19 patients with MG7Ag positive staining developed gastric cancer, but there were no carcinomatous changes in 16 patients with MG7 negative staining. The results of MG7Ag expression in 72 cases with retrospective follow-up showed there were 24 with positive immunostaining among 34 cancerous cases (70.6%), and only 7 in 38 non-cancerous cases (18.4%) (p<0.01). Image analysis showed that an average MG7Ag density index ++0.19 could be regarded as the critical value for high risk of gastric mucosa with dysplasia evolving to cancer. Positive MG7Ag expression in gastric mucosa of patients with dysplasia, especially in cases with a density index ++0.19, was an indicator of high risk of malignant change.


Assuntos
Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Fragmentos de Imunoglobulinas/imunologia , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Anticorpos Monoclonais/imunologia , Progressão da Doença , Seguimentos , Mucosa Gástrica/química , Mucosa Gástrica/patologia , Humanos , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos , Neoplasias Gástricas/patologia
20.
Curr Biol ; 11(17): 1358-63, 2001 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-11553330

RESUMO

Recent studies have implicated the signaling factor Sonic hedgehog (Shh) as a negative regulator of pancreatic development, but as a positive regulator of pancreas function in amniotes [1-4]. Here, using genetic analysis, we show that specification of the pancreas in the teleost embryo requires the activity of Hh proteins. Zebrafish embryos compromised in Hh signaling exhibit disruption in the expression of the pancreas-specifying homeobox gene pdx-1 and concomitantly show almost complete absence of the endocrine pancreas. Reciprocally, ubiquitous activation of the Hh pathway in wild-type embryos causes ectopic induction of endodermal pdx-1 expression and the differentiation of supernumerary endocrine cells. Our results suggest that Hh proteins influence pancreas specification via inductive interactions from the axial midline rather than through their localized expression in the endodermal cells themselves.


Assuntos
Proteínas de Homeodomínio , Pâncreas/embriologia , Receptores Acoplados a Proteínas-G , Transdução de Sinais/fisiologia , Transativadores/metabolismo , Proteínas de Peixe-Zebra , Animais , Expressão Gênica , Proteínas Hedgehog , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Transdução de Sinais/genética , Receptor Smoothened , Transativadores/genética , Peixe-Zebra/embriologia
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