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With the rapid development of medical technology and the improvement of people's health awareness, the detection rate of benign gastric tumors and early gastric cancer has increased significantly. Under the premise of ensuring the safety of oncology, challenges for surgeons present is how to adopt precise and reasonable treatment plans according to the characteristics of gastric tumors to minimize surgical trauma and complications, improve postoperative quality of life, and achieve individualized and precise treatment. Laparoscopic surgery and digestive endoscopy are currently the two main methods for treating gastric tumors. However, they both have advantages and shortcomings. The combination of laparoscopy and digestive endoscopy for the treatment of gastric tumors has become a new way to treat gastric tumors. This operation not only fully exploits the advantages of laparoscopy and digestive endoscopy, but also complements the shortcomings of each. This article reviews the surgical technique categories, indications, technical improvements, and perspectives of laparoscopy combined with digestive endoscopy in the treatment of gastric tumors.
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Laparoscopia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Qualidade de Vida , Gastrectomia/métodos , Laparoscopia/métodos , Endoscopia GastrointestinalRESUMO
Objective: To investigate the effect and possible mechanism of Y-box-binding protein 1 (YB-1) on sorafenib resistance in hepatoma cells. Methods: Lentiviral vectors with YB-1 overexpression and knockdown were constructed, respectively, to stimulate human hepatoma cell lines (HepG2 and Huh7) alone or in combination with sorafenib.The overexpression part of the experiment was divided into four groups: overexpression control group (Lv-NC), YB-1 overexpression group (Lv-YB-1), overexpression control combined with sorafenib resistance group (Lv-NC+sorafenib), YB-1 overexpression combined with sorafenib resistance group (Lv-YB-1 + sorafenib). The knockdown part of the experiment was also divided into four groups: knockdown control group (Lv-shNC), YB-1 knockdown group (Lv-shYB-1), knockdown control combined with sorafenib resistance group (Lv-shNC + sorafenib), YB-1 knockdown combined with sorafenib resistance group (Lv-shYB-1 + sorafenib). The occurrence of cell apoptosis was detected by TUNEL. The protein expression levels of phosphorylated (p)-ERK and ERK, key proteins in the extracellular regulatory protein kinase (ERK) signaling pathway, were detected by Western blot and quantified by ImageJ software. Subcutaneous tumorigenesis experiments were performed in nude mice. The effect of YB-1 on the efficacy of sorafenib was verified in vivo. The comparison between the two sets of data was carried out by an independent sample t-test. One-way ANOVA was used for comparisons between the three groups of data above. Results: Sorafenib had accelerated the occurrence of apoptosis in hepatoma cells, while YB-1 overexpression had inhibited cell apoptosis, and at the same time also inhibited the apoptosis-accelerating impact of sorafenib. On the contrary, YB-1 knockdown accelerated cell apoptosis and amplified the induction effect of sorafenib on apoptosis. Furthermore, sorafenib resistance had down-regulated p-ERK levels (HepG2: Lv-NC 0.685 ± 0.143, Lv-NC + sorafenib 0.315 ± 0.168, P < 0.05; Huh7: Lv-NC 0.576 ± 0.078, Lv-NC + sorafenib 0.150 ± 0.131, P < 0.01), whereas YB-1 overexpression had inhibited sorafenib resistance p-ERK reduction (HepG2: Lv-NC + sorafenib 0.315 ± 0.168, Lv-YB-1 + sorafenib 0.688 ± 0.042, P < 0.05; Huh7: Lv-NC + sorafenib 0.150 ± 0.131, Lv-YB-1 + sorafenib 0.553 ± 0.041, P < 0.05). YB-1 knockdown further increased sorafenib-induced p-ERK downregulation (HepG2: Lv-shNC + sorafenib 0.911 ± 0.252, Lv-shYB-1 + sorafenib 0.500 ± 0.201, P < 0.05; Huh7: Lv-shNC + sorafenib 0.577 ± 0.082, Lv-shYB-1 + sorafenib 0.350 ± 0.143, P < 0.05), which was further verified in naked mice (Lv-shNC + sorafenib 0.812 ± 0.279, Lv-shYB-1 + sorafenib 0.352 ± 0.109, P < 0.05). Conclusion: YB-1 mediates the occurrence of sorafenib resistance via the ERK signaling pathway in hepatoma cells.
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Carcinoma Hepatocelular , Resistencia a Medicamentos Antineoplásicos , Sistema de Sinalização das MAP Quinases , Sorafenibe , Proteína 1 de Ligação a Y-Box , Humanos , Linhagem Celular Tumoral , Sorafenibe/farmacologia , Proteína 1 de Ligação a Y-Box/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Animais , Camundongos , Camundongos NusRESUMO
Objective: To explore the related factors affecting the outcome of treatment free remission (TFR) in patients with chronic myeloid leukemia (CML). Methods: Clinical data of CML patients with automatic discontinuation of tyrosine kinase inhibitor (TKI) from the CML cooperative organization of Henan province between June 2, 2013 to March 27, 2021 and the follow-up time was ≥ 6 months were retrospectively analyzed. Log-rank test was used for univariate analysis and Cox proportional risk regression model was used for multivariate analysis. Results: A total of 135 patients were enrolled, and 69 patients (51.1%) were femal and 66 patients (48.9%)were male. Median age was[M(Q1,Q3)] 49 years (38, 58)at discontinuation.Before discontinuation, 72 patients (53.3%) were on treatment with second-generation TKI, 63 patients (46.7%) were on treatment with IM, 17patients (12.6%) had a history of TKI reduction/withdrawal;median duration of treatment was months 84 (68, 108) for all patients;median time of TKI treatment to DMR was months 12(8, 26);median duration of DMR was months 65 (54, 84), and 9 patients (6.7%) had unsustained DMR.The median follow-up time was months 16(6-96), 35 patients (25.9%) lost MMR at a median months 3(1-22), overall estimated TFR was 74.1%.The univariate analysis results showed that:second-generation TKI was used, the time of TKI treatment to DMR was ≤12 months, DMR duration time ≥48 months, had sustained DMR, without TKI reduction/withdrawal history were favorable factors affecting of TFR in patients with TKI discontinuation (all P<0.05).The TFR rate of the second-generation TKI therapy group was significantly higher than the IM therapy group (81.9% vs 65.1%, P=0.019).The multivariate analysis results showed that second-generation TKI treatment[RR=0.451, 95%CI (0.227-0.896), P=0.023] and had sustained DMR [RR=0.120, 95%CI (0.053-0.271), P<0.001] were the protective factors of TFR in patients with TKI discontinuation. Conclusions: Treated with second-generation TKI and had sustained DMR are the protective factors of TFR in patients with TKI discontinuation.The CML patients who had sustained DMR more≥48 months before TKI discontinuation showed a better TFR.
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Leucemia Mielogênica Crônica BCR-ABL Positiva , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Recent studies have indicated the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) to be a viable adjunctive to alveolar cleft reconstruction owing to its osteoinductive capacity. This study aimed to evaluate the efficacy of rhBMP-2 in the treatment of alveolar cleft with autologous bone grafts by precise volumetric analysis. Twenty-six patients (aged 8-14) with unilateral alveolar clefts were enrolled in this comparative study. Patients were divided into two groups: the iliac crest bone graft (ICBG) was placed at the side of the cleft in the control group (ICBG group), and rhBMP-2 was mixed with the ICBG in the rhBMP-2 group (BMP group). Helical computed tomographic images were obtained preoperatively and 12 months postoperatively. The datasets were reconstructed as three-dimensional (3D) images using Mimics software and processed using Geomagic Wrap. The newly formed bone of the alveolar cleft was segmented by identifying the differences between preoperative and postoperative 3D images. In the ICBG group, the volume of newly formed bone ranged from 0.25 to 0.88 cm3, and the mean (SD) bone formation percentage was 42.01% (15.57%). In the BMP group, the volume of newly formed bone ranged from 0.34 to 1.09 cm3, and the bone formation mean (SD) percentage was 55.79% (11.84%). There was a statistically significant difference between the two groups in terms of the postoperative percentage of bone formation (p = 0.022). Thus, rhBMP-2 combined with an autologous bone graft is a promising technique to improve the results of secondary alveolar bone grafting.
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Enxerto de Osso Alveolar , Fissura Palatina , Proteína Morfogenética Óssea 2/uso terapêutico , Transplante Ósseo , Fissura Palatina/cirurgia , Computadores , Humanos , Ílio , Proteínas Recombinantes/uso terapêutico , Fator de Crescimento Transformador beta/uso terapêuticoRESUMO
Objective: To examine the effect of pancreaticojejunostomy with pancreatic duct binding external drainage in laparoscopic pancreatoduodenectomy. Methods: The data of 21 patients who underwent laparoscopic pancreaticoduodenectomy in the same treatment group from January 2017 to October 2019 in Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University were analyzed retrospectively.All patients underwent pancreaticojejunostomy with external drainage of pancreatic ducts.There were 12 males and 9 females, aged (63.1±8.1)years old (range: 46 to 77 years old), body mass index (24.8±3.2)kg/m(2)(range: 18.8 to 29.1 kg/m(2)).There were 3 cases of hypertension, 5 cases of diabetes, 3 cases of hypertension and diabetes, 3 cases of liver cirrhosis. Results: Laparoscopic pancreatoduodenectomy was successfully performed in all 21 patients.The operation time was (359.3±71.0)minutes, the pancreaticojejunostomy time was (23.8±7.4)minutes, the diameter of pancreatic duct was(3.3±0.6)mm, the intraoperative blood loss was (247.6±90.1)ml, the postoperative hospital stay was(13.7±4.9)days, the leakage of B-level fistula occurred in 1 case(4.8%), and there was no C-level pancreatic fistula.There were 3 cases of bile leakage, 1 case of incision infection, 2 cases of gastroparesis, 1 case of hydrops abdominis, no death and secondary operation. Conclusion: It is a simple and easy method of pancreatoenterostomy with pancreatic duct binding external drainage, which can reduce the incidence of pancreatic fistula and related complications after laparoscopic pancreatoduodenectomy for patients with high risk pancreatic fistula.
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Drenagem/métodos , Ductos Pancreáticos/cirurgia , Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/métodos , Idoso , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia/efeitos adversos , Pancreaticojejunostomia/efeitos adversos , Estudos RetrospectivosRESUMO
OBJECTIVE: The aim of this study was to explore the effect of microRNA-424-5p on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells, and to investigate its influence on the expression of ITGB1 and potential regulatory mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the level of microRNA-424-5p in 44 paired NSCLC tissues and adjacent tissues. The relation between microRNA-424-5p expression and NSCLC clinical indicators was analyzed. Subsequently, microRNA-424-5p mimics and inhibitors were transfected into NSCLC cells to construct microRNA-424-5p overexpression or knockdown models, respectively. QRT-PCR was used to further verify the transfection efficiency. A series of experiments, including cell counting kit-8 (CCK-8) assay, colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), and flow cytometry were used to analyze the effect of microRNA-424-5p on the biological function of NSCLC A549 and H358 cells. Finally, the potential association between microRNA-424-5p and its downstream gene ITGB1 was explored through luciferase reporter gene assay and cell recovery experiment. RESULTS: QRT-PCR results showed that microRNA-424-5p level was significantly lower in NSCLC tissues than that of adjacent normal tissues. Compared with patients with high expression of microRNA-424-5p, the pathological stage of those with low expression of microRNA-424-5p was significantly higher. In vitro experiments showed that microRNA-424-5p overexpression remarkably decreased cell proliferation and increased cell apoptosis, which were further validated in microRNA-424-5p inhibitor group. Subsequently, ITGB1 expression was found significantly up-regulated in NSCLC cell lines and tissues. Meanwhile, ITGB1 expression was negatively correlated with microRNA-424-5p level. In addition, a recovery experiment indicated that overexpression of ITGB1 could counteract the effect of microRNA-424-5p mimics on the proliferation and apoptosis of NSCLC cells. All these findings revealed that microRNA-424-5p and ITGB1 affected the malignant progression of NSCLC. CONCLUSIONS: MicroRNA-424-5p was closely correlated with the pathological stage and poor prognosis of NSCLC, thereby inhibiting the occurrence and development of NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Integrina beta1/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Estadiamento de Neoplasias , Regulação para CimaRESUMO
Objective: To investigate the risk factors of postoperative acute kidney injury (AKI) in patients aged between 40 and 50 years old undergoing cardiac valvular surgery and the impact on outcome. Methods: The clinical data of 286 patients aged between 40 and 50 years old undergoing cardiac valve surgery in Guangdong Provincial People's Hospital from January 2012 to December 2016 were analyzed retrospectively. Preoperative coronary angiography was performed in all patients. All patients enrolled were divided into AKI group and non-AKI group according to the existence or not of postoperative AKI. Patients with AKI were further divided into AKI stage 1, stage 2, and stage 3 groups according to KDIGO guideline. Demographic characteristics, preoperative clinical data including serum creatinine, estimated glomerular filtration rate, hemoglobin, uric acid, urinary protein, presence or absence of chronic kidney disease, left ventricular ejection fraction, pulmonary artery pressure, New York Heart Association (NYHA) functional classification, preoperative co-morbidity (hypertension, diabetes, anemia, cerebrovascular disease, peripheral artery disease), preoperative medication(vasoactive drugs, diuretic, renin-angiotensin system inhibitor (RASI), surgical data (contrast dosage in coronary angiography, type of cardiac valve surgery) were recorded and analyzed in this retrospective study. The risk factors for postoperative AKI and its impact on clinical outcomes (mortality, hospitalization expenses and Intensive Care Unit stay duration) were evaluated. Logistic regression analysis was used to determine the risk factors for postoperative AKI and the adjusted variables with P<0.2 were selected for the multivariate logistic regression analysis to define the independent determinants for AKI. Results: AKI was defined in 106 out of 286 enrolled patients, including 96 patients with AKI stage 1, 10 patients with AKI stage 2 and no patients with AKI stage 3. The proportion of coexisting cerebrovascular diseases was higher in AKI group than in non-AKI group (9(8.49%) and 5(2.78%), χ(2)=4.677, P=0.031), while there was no difference among other baseline data between the two groups. Multivariate logistic regression analysis showed that preoperative complications of cerebral vascular disease was an independent risk factor of postoperative AKI (OR=3.578, 95%CI 1.139-11.242, P=0.029). Five out of 106 AKI patients died during hospitalization while there was only 1 patient died among 180 patients without AKI. Patients with AKI after cardiac valve operation experienced higher mortality than patients without AKI (χ(2)=5.625, P=0.028). Further analysis showed that there was no difference in hospitalization mortality between patients with AKI stage 2 and stage (χ(2)=0.686, P=0.408) while the hospitalization mortality in patients with AKI stage 2 was higher than those without AKI (χ(2)=8.113, P=0.004). The hospitalization expenses in patients with AKI were 10.38(8.59,12.54) ×10(4) RMB, significantly higher than that in patients without AKI (9.72(8.03,11.93) ×10(4) RMB)(P=0.043). There was no difference in hospitalization expenses between patients with AKI stage 1 and without AKI (P=0.635). The hospitalization expenses in patients with AKI stage 2 was higher than those without AKI (P=0.023). Intensive Care Unit stay duration in patients with AKI was 3(1,4) days, significantly higher than those without AKI (P=0.044). There was no difference in Intensive Care Unit stay duration in patients with AKI stage 1 and without AKI (P=0.978), while Intensive Care Unit stay duration in patients with AKI stage 2 was significantly longer than those without AKI (P=0.006). Conclusions: Preoperative complications of cerebral vascular disease is an independent risk factor of postoperative AKI. Non-senile patients with AKI after cardiac valvular surgery is associated with a higher proportion of mortality, hospitalization expenses and Intensive Care Unit stay duration as compared patients without postoperative AKI.
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Injúria Renal Aguda , Adulto , Valvas Cardíacas , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de RiscoRESUMO
Objective: To establish a canine model of slow transit constipation (STC), and to test the changes in defecation, gastrointestinal transit time and pathology sections. Methods: Baseline information was measured in 8 beagle dogs, and these dogs were randomly divided into the control group and the model group. The dogs in model group were given a diet of canned meat, as well as a combination of compound diphenoxylate and alosetron hydrochloride for 5 weeks. Dogs in control group were given normal diet with no special intervention. Stool frequency and consistency were observed and recorded daily, and the gastrointestinal transit time (GITT) were measured every week. All animals underwent the midline laparotomy and the colonic tissues were taken from the rectosigmoid colon, then investigated by light microscopy, electron microscopy, and immunohistochemistry to evaluate changes of protein gene product 9.5(PGP9.5), synaptophysin and c-kit between two groups. Results: 8 beagle dogs underwent all experiment items successfully.Both of the stool frequency and scores of stool consistency decreased in model group(F=6.568, P=0.043; F=25.954, P=0.002). GITT delayed in model group(F=42.573, P=0.001). After 5 weeks of intervention, in the model group, the myenteric neurons and interstitial cells of Cajal showed damage such as swelling of mitochondria under electron microscopy, and both of the PGP9.5 and synaptophysin integrated option density of rectosigmoid colon were decreased (t=3.471, P=0.013; t=2.506, P=0.046)under immunohistochemistry. The c-kit integrated option density showed no statistically significant differences between two groups(t=1.709, P=0.138). Conclusions: The canine model of STC which was consistent with clinical symptoms and pathological changes was successfully established, and it can be used to observe and evaluate the therapeutic effect of electrical stimulation, surgery and so on.
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Constipação Intestinal , Defecação , Animais , Colo , Cães , Trânsito Gastrointestinal , Células Intersticiais de CajalRESUMO
Objective: To describe the characteristics of the nodular type of pulmonary cryptococcosis (PC) with coexisting lung cancer. Methods: A total of 9 cases of PC with coexisting lung cancer, admitted to Fuzhou Pulmonary Hospital of Fujian from 1st January 2009 to 31th December 2016, and confirmed by pathological examinations, were studied and the related literature were reviewed. Results: The patients consisted of 1 male and 8 females, with a mean age of (53±10) years (range, 38 to 68 years). Four patients (44.4%) had underlying diseases, 3 with diabetes mellitus and 1 with gastric cancer surgery. The main clinical manifestations of most cases were cough and phlegm. The lesions of PC on chest CT were mostly solitary or multiple nodules with a diameter < 1 cm, and the lesions of carcinoma were shown as solitary nodules with a variety of signs suggestive of malignancy. All the patients were confirmed to have concomitant PC and lung adenocarcinoma by pathological examinations. Lung cancer stage was early (Tis and â -â ¡) in 88.9 % (8 cases) of the cases. All the patients received surgery and postoperative medical therapy. The prognosis was relatively good in most of them except 1 case with death due to lung cancer metastasis and 1 case with lung cancer recurrence. Conclusions: Coexistence of PC and lung cancer is rare and the clinical symptoms are not specific. When PC coexists with carcinoma and manifests as pulmonary nodule, it mimics malignant lesions and is extremely easy to be misdiagnosed. Therefore PC must be considered in the differential diagnosis of pulmonary nodules.
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Criptococose/patologia , Neoplasias Pulmonares/patologia , Pulmão/diagnóstico por imagem , Recidiva Local de Neoplasia , Adulto , Idoso , Criptococose/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Down-regulation of miR-138 is observed in a variety of cancers, which suggests that miR-138 may be involved in cancer pathogenesis. Our current work aimed to evaluate the effects of miR-138 in adriamycin (ADM)-resistant human NSCLC cells. MATERIALS AND METHODS: Cell proliferation was determined by MTT assay. Real-time PCR and western blot were performed to detect the mRNA and protein expression levels. The target of miR-138 was validated by luciferase activity assay. RESULTS: Compared with the chemosensitive parental cells, miR-138 was remarkably decreased in A549/ADM and NCI-H23/ADM cells. Ectopic expression of miR-138 sensitized chemoresistant tumor cells to ADM administration. In addition, the epithelial-mesenchymal transition (EMT) related markers E-cadherin or vimentin was up-regulated or down-regulated upon the overexpression of miR-138 in NSCLC cells. Further studies identified zinc finger E-box-binding homeobox 2 (ZEB2) as the target of miR-138 and up-regulation of miR-138 suppressed the mRNA and protein expression of ZEB2. Notably, luciferase reporter assay confirmed that ZEB2 was a direct target of miR-138. CONCLUSIONS: Our study demonstrates that miR-138 sensitizes NSCLC cells to ADM via EMT, suggesting that miR-138 might be a potential therapeutic target for drug-resistant NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas/genética , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Pulmonares/genética , MicroRNAs/fisiologia , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Relação Dose-Resposta a Droga , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
PURPOSE: T cells are dominant in the immune regulation of malignant pleural effusion (MPE). However, it is unclear about the role of IL-17+ T cells, particularly for IL-17+CD8+ Tc17 cells in antitumor immunity. This retrospective study is aimed at evaluating the prognostic significance of IL-17+ T cells in patients with MPE. METHODS: The frequency of IL-17+CD4+ Th17 and IL-17+CD8+ Tc17 cells in peripheral blood (PB), pleural fluids (PF), and tumor tissues in 24 patients undergoing thoracoscopy was determined by flow cytometry, immunohistochemistry, and ELISA. The association among the different measures was analyzed by Spearman's correlation tests. RESULTS: The percentages of PF Th17 and Tc17 cells were significantly higher than those in the PB of MPE patients and healthy controls (p < 0.01). Analysis of Th17 and Tc17 cells in the tumor tissues indicated that the percentages of Th17 and Tc17 cells in the invading tumor edge were significantly higher than those in the non-tumor tissues and intra-tumor regions (p < 0.05). More importantly, the percentages of IL-17+ T cells were associated with prolonged survival of patients with MPE. CONCLUSIONS: Both Th17 and Tc17 cells were involved in the tumor immunity against MPE. Increased frequency of Tc17 cells may serve as a biomarker for the prognosis of patients with MPE.
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Linfócitos T CD8-Positivos/imunologia , Interleucina-17/biossíntese , Derrame Pleural Maligno/imunologia , Subpopulações de Linfócitos T/imunologia , Células Th17/imunologia , Idoso , Idoso de 80 Anos ou mais , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes tumorigenesis and metastasis in numerous cell types and is overexpressed in a variety of human tumors. We have demonstrated that PTTG1 expression was up-regulated in both human prostate cancer specimens and prostate cancer cell lines. For a more direct assessment of the function of PTTG1 in prostate tumorigenesis, RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3 human prostate tumor cells. After three weeks of selection, colonies stably transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty vector (the control PC3 cell line) were selected and expanded to investigate the role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3 cell colonies than control colonies after three weeks of growth. In addition, PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence-activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited significantly reduced migration through Matrigel in a transwell assay of invasive potential, and down-regulation of PTTG1 could lead to increased sensitivity of these prostate cancer cells to a commonly used anticancer drug, taxol. Thus, PTTG1 expression is crucial for PC3 cell proliferation and invasion, and could be a promising new target for prostate cancer therapy.
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Humanos , Masculino , Neoplasias da Próstata/metabolismo , Interferência de RNA , Securina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/patologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Securina/genética , Regulação para CimaRESUMO
Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes tumorigenesis and metastasis in numerous cell types and is overexpressed in a variety of human tumors. We have demonstrated that PTTG1 expression was up-regulated in both human prostate cancer specimens and prostate cancer cell lines. For a more direct assessment of the function of PTTG1 in prostate tumorigenesis, RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3 human prostate tumor cells. After three weeks of selection, colonies stably transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty vector (the control PC3 cell line) were selected and expanded to investigate the role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3 cell colonies than control colonies after three weeks of growth. In addition, PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence-activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited significantly reduced migration through Matrigel in a transwell assay of invasive potential, and down-regulation of PTTG1 could lead to increased sensitivity of these prostate cancer cells to a commonly used anticancer drug, taxol. Thus, PTTG1 expression is crucial for PC3 cell proliferation and invasion, and could be a promising new target for prostate cancer therapy.
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Neoplasias da Próstata/metabolismo , Interferência de RNA , Securina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/patologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proto-Oncogene Mas , Securina/genética , Regulação para CimaRESUMO
OBJECTIVE: The aim of this study was to retrospectively evaluate the technical success rates and clinical effectiveness of fluoroscopically guided nose tube drainage of mediastinal abscesses and a nasojejunum feeding tube in post-operative gastro-oesophageal anastomotic leakage (GEAL). METHODS: From January 2006 to June 2011, 18 cases of post-operative GEAL with mediastinal abscesses after oesophagectomy with intrathoracic oesophagogastric anastomotic procedures for oesophageal and cardiac carcinoma were treated by insertion of a nose drainage tube and nasojejunum feeding tube under fluoroscopic guidance. We evaluated the feasibility of two-tube insertion to facilitate leakage site closure and complete resolution of the abscess, and the patients' nutritional benefit was also evaluated by checking the serum albumin level between pre- and post-enteral feeding via the feeding tube. RESULTS: The two tubes were placed successfully under fluoroscopic guidance in 18 patients (100%). The procedure time for two-tube insertion ranged from 20 to 40 min (mean 30 min). 17 patients (94%) achieved leakage site closure after two-tube insertion and had a good tolerance of two tubes in the nasal cavity. The serum albumin level was significant, increased from pre-enteral feeding (2.49 ± 0.42 g dl(-1)) to the post-enteral feeding (3.58 ± 0.47 g dl(-1)) via the feeding tube (p<0.001). The duration of follow-up ranged from 1 to 49 months (mean 19 months). CONCLUSION: The insertion of nose tube drainage and a nasojejunum feeding tube under fluoroscopic guidance is safe, and it provides effective relief from mediastinal abscesses in GEAL after oesophagectomy. Moreover, our findings indicate that two-tube insertion may be used as a selective procedure to treat mediastinal abscesses in post-operative GEAL. Advances in knowledge Directive drainage of mediastinal abscesses in post-operative GEAL may be an effective treatment.
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Abscesso/terapia , Fístula Anastomótica/terapia , Drenagem/métodos , Fluoroscopia/métodos , Intubação Gastrointestinal/métodos , Mediastino , Doenças Torácicas/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
This multicenter study evaluated the mutation spectrum and frequencies of the MLH1 and MSH2 genes and determined the occurrence of large genomic deletions in 93 unrelated Taiwanese families that fulfilled the Amsterdam criteria II by denaturing high-performance liquid chromatography analysis, DNA sequencing for aberrant chromatograms, and multiplex ligation-dependent probe amplification analysis. In total, 38 pathogenic mutations (10 large deletions and 28 point mutations or small deletion/insertions) in the MSH2 or MLH1 gene were identified in 61 of the 93 families (66%). Three of the 10 large deletions and 14 of the 28 point mutations or small insertions/deletions have not been reported elsewhere. Three mutations in the MLH1 gene, the MLH1c.1846_1848delAAG (5 families), deletion exons 11-15 (4 unrelated families), and MLH1c.793C>T (13 unrelated families), accounted for 35% of all cases with pathogenic mutations. Haplotype analysis indicated that mutant c.793C>T alleles were derived from two distinct common founders that might be inherited from a single ancestor of presumably Chinese origin. As a mutation detection strategy for Taiwanese Lynch syndrome patients, we recommend that diagnosis starts with screening for large genomic deletions and continues by screening for common mutations in exons 10 and 16 of the MLH1 gene prior to searching for small mutations in the remaining exons.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Efeito Fundador , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Análise Mutacional de DNA , Saúde da Família , Feminino , Frequência do Gene , Mutação em Linhagem Germinativa , Humanos , Masculino , Proteína 1 Homóloga a MutL , Linhagem , Mutação Puntual , Deleção de Sequência , TaiwanRESUMO
BACKGROUND: The purpose of this study was to evaluate the effects of three different methods of cardioprotection in patients undergoing valve replacement. METHODS: Ninety patients undergoing elective valve replacement were randomly divided into three groups. In group 1 (n=30), the patients received intermittent cold blood cardioplegia. In group 2 (n=30) they received terminal warm cardioplegia and controlled reperfusion, and in group 3 (n=30), the patients received two cycles of ischemia (2 minutes) and reperfusion (3 minutes) before heart arrest induced by cold blood cardioplegia. The parameters of cardiac function, creatine kinase MB, and clinical outcomes were recorded to assess the effects of experiment. RESULTS: The major preoperative and intraoperative variables are comparable within the three groups. The number of patients requiring the support of inotropic agents was 70% (21/30), 33% (11/30) and 40% (12/30) in group 1, 2 and 3, respectively (p<0.05). The doses of inotropic agent in groups 2 and 3, were significantly lower than in group 1 (1.5+/-0.3 and 1.8+/-0.4 versus 4.5+/-0.8 microg x kg x min(-1), p<0.01) during the first 24 hours after operation. Two deaths (30 day-hospital mortality) occurred, one in group 1 and one in group 2. The cardiac index at 2 hours after bypass discontinuing were 2.2+/-0.04, 3.0+/-0.1 and 2.8+/-0.05 L/m(2) in group 1, 2 and 3, respectively (p<0.01). The left ventricular stroke work index were 24.8+/-1.3, 34.5+/-1.6 and 31.6+/-1.2 g/m x m(2) in group 1, 2, 3, respectively (p<0.01). The release of CK-MB in group 2 and 3 were lower than in group 1 (68+/-7, 81+/-9 versus 116+/-10 IU/L, p<0.01). CONCLUSIONS: Terminal warm cardioplegia with controlled aortic root reperfusion and ischemic preconditioning equally improve cardiac function and reduce the requirement of inotropic agents in patients undergoing valve replacement.
Assuntos
Parada Cardíaca Induzida , Implante de Prótese de Valva Cardíaca , Precondicionamento Isquêmico Miocárdico , Adulto , Débito Cardíaco , Feminino , Parada Cardíaca Induzida/métodos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologiaRESUMO
Type II phosphatidylinositol phosphate kinase (PIPKII) is an enzyme responsible for the synthesis of phosphatidylinositol-4,5-bisphosphate (PI-4,5-P(2)) from phosphatidylinositol-5-phosphate (PI-5-P). In this study, we demonstrate the presence of PIPKII alpha in bovine photoreceptor rod outer segments (ROS) and the involvement of tyrosine phosphorylation in the regulation of its activity. PIPKII activity in bovine ROS was verified by the preferential conversion of synthetic dipalmitoyl PI-5-P to PI-4,5-P(2), lack of effect of phosphatidic acid, inhibition by heparin, immunoreaction with an anti-PIPKII alpha antibody on Western blots, and immunocytochemical localization in bovine and rat ROS by anti-PIPKII alpha. Immunoprecipitates of bovine ROS with the anti-PIPKII alpha antibody possessed PIPK enzymatic activity and preferentially used PI-5-P as substrate for PI-4,5-P(2) biosynthesis. The activity of PIPKII was greatly increased under conditions favoring tyrosine phosphorylation in ROS, and PIPKII activity was immunoprecipitated with anti-phosphotyrosine (anti-PY) antibodies from tyrosine phosphorylated ROS. Preincubation of ROS with tyrosine kinase inhibitors almost abolished the kinase activity in the anti-PY immunoprecipitates. Immunoblot analysis showed that PIPKII alpha was present in anti-PY immunoprecipitates from phosphorylated ROS but not from nonphosphorylated controls. We conclude that PIPKII alpha is present in ROS and that its activity is regulated by tyrosine phosphorylation.
Assuntos
Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Segmento Externo da Célula Bastonete/enzimologia , Tirosina/metabolismo , Animais , Bovinos , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Immunoblotting , Imuno-Histoquímica , Antígenos de Histocompatibilidade Menor , Fosfatos de Fosfatidilinositol/metabolismo , Fosforilação , Fosfotransferases (Aceptor do Grupo Álcool)/imunologia , Testes de Precipitina , Proteínas Tirosina Quinases/antagonistas & inibidores , Ratos , Segmento Externo da Célula Bastonete/química , Segmento Externo da Célula Bastonete/metabolismo , Especificidade por Substrato , Tirfostinas/farmacologiaRESUMO
OBJECTIVE: To determine the effect of ischemic preconditioning on isolated lung perfusion (ILP) with chemotherapeutic agents in the treatment of unresectable lung cancer. METHODS: Eight patients with unresectable cancer or metastatic sarcomas in lungs underwent isolated single lung perfusion with doxorubicin. Eight patients were randomly divided into two groups: control group (Group C) and ischemic preconditioning group(Group IP). Group C was only performed isolated lung perfusion with doxorubicin; Group IP was performed isolated lung perfusion with doxorubicin after ischemic preconditioning (in ischemic preconditioning procedure, right or left pulmonary artery was clamped for 10 minutes, then released for 15 minutes). RESULTS: The mean pulmonary artery pressure (MpaP) after ILP in Group IP was much lower than that in Group C (P < 0.05). The PaO2 after ILP in Group IP was much higher than that in Group C(P < 0.01). The lung histologic examination after ILP showed that pulmonary edema, inflammatory cell infiltration, mild focal hemorrhage and alveolar disruption in Group C were significantly serious than those in Group IP, but there was no hospital death in Group C or in Group IP. The complications included hypovolemia shock and acute lung injury. Following up 2 months to 10 months, no death was observed, and the tumours diminished in various degrees or disappeared in the two groups. CONCLUSION: Isolated lung perfusion with chemotherapy can be done safely and effectively in patients with unresectable lung malignancies and metastatic sarcoma in the lung, and ILP can cause lung injury, but lung ischemic preconditioning can reduce the lung injury after isolated lung perfusion.
Assuntos
Antineoplásicos/uso terapêutico , Quimioterapia do Câncer por Perfusão Regional/métodos , Doxorrubicina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Precondicionamento Isquêmico , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate whether there is delayed cardioprotection of captopril pretreatment in open heart surgery. METHODS: Twenty patients with ventricular septal defect (VSD) undergone open heart surgery were randomly divided into captopril group (CAP group) and control group. In the CAP group, patients were pretreated with captopril (1 mg.kg-1, oral) at 48 hours before operation, No special treatment was given at the same time in the control group. Release of creatine phosphokinase-MB (CK-MB) and myocardial adenosine triphosphate (ATP) content was studied. Heart shock protein 70 (HSP70) in myocardum was examined using Western blotting analysis. RESULTS: No statistically significant difference was found in release of CK-MB between control group and CAP group. ATP depletion was (1.40 +/- 0.56) mumol.g-1, (2.06 +/- 0.72) mumol.g-1 in CAP group and control group respectively (P < 0.05). Western blotting analysis showed that both group had HSP70 expression. In CAP group, HSP70 expression was higher than that in control group. CONCLUSION: The results suggest that captopril pretreatment 48 hours before operation could reduce ATP depletion in pediatric patients of VSD during open-heart surgery, and HSP70 might be involved in the delayed cardioprotection induced by captopril.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/uso terapêutico , Procedimentos Cirúrgicos Cardíacos , Cardiotônicos , Comunicação Interventricular/cirurgia , Ponte Cardiopulmonar , Criança , Pré-Escolar , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Masculino , Cuidados Pré-OperatóriosRESUMO
A new cytotoxic polyhydroxysterol, 23,24-dimethylcholest-16(17)-E-en-3beta,5alpha,6beta,2 0(S)-tetraol (2), together with nine known compounds was isolated from the soft coral Sarcophyton trocheliophorum. Their structures were determined by spectroscopic methods. Compound 2 showed potent growth inhibitory activity against human HL60 leukemia, M14 skin melanoma, and MCF7 breast carcinoma cells with EC50 values of 2.8, 4.3, and 4.9 microg/ml, respectively, and exhibited minimal toxicity to normal human peripheral blood lymphocytes.