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1.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298988

RESUMO

This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development.


Assuntos
Implantes Absorvíveis , Materiais Biocompatíveis , Âncoras de Sutura , Alanina Transaminase/sangue , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Fenômenos Biomecânicos , Nitrogênio da Ureia Sanguínea , Fosfatos de Cálcio/química , Fosfatos de Cálcio/toxicidade , Sulfato de Cálcio/administração & dosagem , Sulfato de Cálcio/química , Sulfato de Cálcio/toxicidade , Creatinina/sangue , Desenho de Equipamento , Fêmur/diagnóstico por imagem , Fêmur/ultraestrutura , Ferro , Lasers , Teste de Materiais , Microscopia Eletrônica de Varredura , Estrutura Molecular , Osseointegração , Polímeros/química , Polímeros/toxicidade , Porosidade , Coelhos , Distribuição Aleatória , Resistência à Tração , Vísceras , Microtomografia por Raio-X
2.
Int J Med Sci ; 18(12): 2521-2531, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104083

RESUMO

Developing treatment strategies for triple-negative breast cancer (TNBC) has become an important clinical challenge. Currently, taxane-based chemotherapy is one of the standard treatments for TNBC. However, determining the key factor of taxane-resistance is urgently in need for clinical treatment for breast cancer. We used GEO data to generate paclitaxel resistance in two basal-like TNBC cell lines (SUM149 and MDA-MB-468). Seventy-one common upregulated differentially expressed genes (DEGs) and 11 downregulated DEGs were found to be related to paclitaxel resistance. By constructing protein-protein interactions, 28 hub proteins with a degree cutoff criterion of ≥1 were found. Nine hub genes (COL4A6, COL4A5, IL6, PDGFA, LPAR1, FYB, IL20, IL18R1 and INHBA) are involved in important signaling pathways. We found that upregulated PDGFA and downregulated COL4A6 were significantly associated with an insensitive response to neoadjuvant paclitaxel-based therapy. A Kaplan-Meier plot was created to check the prognostic values of 11 hub DEGs in terms of recurrence-free survival. High expressions of PDGFA and LAMB3 were correlated with poor recurrence-free survival, while low levels of FYB, IL18R1, and RASGRP1 indicated poorer relapse-free survival. Our results suggest that PDGFA, COL4A6, LPAR1, FYB, COL4A5, and RASGRP1 might be candidate target genes for taxane-based therapy in basal-like TNBC.

3.
Biomedicines ; 9(4)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805515

RESUMO

MicroRNAs (miRNAs) function as the post-transcriptional factor that finetunes the gene expression by targeting to the specific candidate. Mis-regulated expression of miRNAs consequently disturbs gene expression profile, which serves as the pivotal mechanism involved in initiation or progression of human malignancy. Cancer-relevant miRNA is potentially considered the therapeutic target or biomarker toward the precise treatment of cancer. Nevertheless, the regulatory mechanism underlying the altered expression of miRNA in cancer is largely uncovered. Detailed knowledge regarding the influence of miRNAs on solid cancer is critical for exploring its potential of clinical application. Herein, we elucidate the regulatory mechanism regarding how miRNA expression is manipulated and its impact on the pathogenesis of distinct solid cancer.

4.
Obes Surg ; 31(5): 2153-2160, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33523416

RESUMO

INTRODUCTION: Asian patients with diabetes exhibit different characteristics from Western patients. However, limited large-scale data are available on metabolic surgery procedures in Asia. We compared the short-term efficacies of metabolic surgery procedures for the management of Asian patients with different severities of diabetes. METHODS: We included patients undergoing metabolic surgery in five Asian institutions from January 2008 to December 2015 with at least 1-year postoperative follow-up. Outcomes of weight loss and diabetes control were determined. Diabetes remission rates in different ABCD scores and factors affecting diabetes remission were analyzed. RESULTS: A total of 1016 patients (mean BMI, 39.0 ± 7.2 kg/m2; HbA1c, 8.3% ± 1.7%) underwent metabolic surgery (197, Roux-en-Y gastric bypass [RYGB]; 171, one anastomosis gastric bypass [OAGB]; 437, sleeve gastrectomy [SG]; 130, SG with duodenal-jejunal bypass [SG-DJB]; and 81, single anastomosis duodenal-jejunal bypass with SG [SA-DJBSG]). The OAGB group exhibited significantly higher 1-year total weight loss (30.5%) and type 2 diabetes mellitus (T2DM) remission (78.4%) rates than did the other groups (p < .001). The patients with higher preoperative ABCD scores exhibited higher T2DM remission rates (81.8-100% and 9.5-46.2% in ABCD score subgroups of 9-10 and 1-2, respectively). In multivariate analysis, bypass was found to be an independent predictor of T2DM remission compared with SG (odds ratio of OAGB vs SG, 3.72; RYGB vs SG, 1.96; SG-DJB vs SG, 2.73; SA-DJBSG vs SG, 2.12). CONCLUSION: The metabolic surgeries are highly effective in T2DM treatment. However, SG may not be as effective as gastric bypass and duodenal-jejunum bypass.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Derivação Gástrica , Obesidade Mórbida , Ásia , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia , Humanos , Obesidade Mórbida/cirurgia , Resultado do Tratamento
5.
Artigo em Inglês | MEDLINE | ID: mdl-33610508

RESUMO

BACKGROUND: Tigecycline is an antibiotic that well tolerated for treating complicated infections. It has received attention as an anti-cancer agent and expected to solve two major obstacles, sides effects that accompany chemotherapy and drug resistance, in the breast cancer treatment. However, previous studies reported that the levels in the blood are typically low of tigecycline, so higher doses are needed to treat cancer, that may increase the risk of side effects. To achieve better anti-cancer effects for tigecycline, we need to find a novel adjunct agent. METHODS: In this study, we used different concentration of pyrvinium pamoate combined with tigecycline to treat cell. And assess the effect of two drugs in inhibit cell proliferation, induce cell autophagy, or increase cell apoptosis to evaluate the consequent of combined therapy. RESULTS: We observed that after the combined therapy, the cell cycle arrest at G1/s phase, the level of p21 increased, but decreased the levels of CDK2. Others, two drugs via different mechanisms to inhibit cancer cell proliferation and with selective cytotoxic to different cell lines. That could enhance the effect of breast cancer treatment. CONCLUSION: Combining low dose of tigecycline use with pyrvinium pamoate is a novel approach for breast cancer treatment. Appropriate combined therapy in breast cancer is recommended to improve outcomes. Other problems like drug resistance occur in patients or the microbes surrounding breast tissues would confer susceptibility to cancers then influence the effectiveness of treatment, which could be improved through combined therapy.

6.
Diabetes Obes Metab ; 23(3): 742-753, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33269505

RESUMO

AIM: To assess the outcomes of metabolic surgery in overweight and obese patients in Asia with type 2 diabetes (T2D). MATERIALS AND METHODS: The treatment outcomes of 1999 patients from the Asian Diabetes Surgery Summit database were analysed. The changes in treatment effects across time were assessed with respect to the surgical procedures performed by using generalized estimating equations. RESULTS: The most commonly performed procedure was the single-anastomosis gastric bypass (32.6%). Weight (from 106.2 ± 25.1 to 77.9 ± 18.8 kg), body mass index (BMI; from 38.7 ± 7.9 to 28.5 ± 5.9 kg/m2 ), blood sugar (from 9.3 ± 4.1 to 5.7 ± 1.8 mmol/L) and HbA1c (from 8.4% ± 1.8% to 6.0% ± 1.1%) significantly improved from baseline to 1 year (P < .001) and remained stable at 5 years (weight, 86.3 ± 23.3 kg; BMI, 31.7 ± 7.9 kg/m2 ; blood sugar, 5.8 ± 1.8 mmol/L, and HbA1c, 6.4% ± 1.2%; all P < .001 vs. baseline). Blood pressure and most lipid disorders also improved significantly. Of the treatment procedures, single-anastomosis gastric bypass had the most satisfactory outcomes with statistical significance for most disorders, whereas adjustable gastric banding displayed the least satisfactory outcomes. CONCLUSIONS: Metabolic surgery remarkably improved body weight, T2D and other metabolic disorders in Asian patients. However, the efficacy of individual procedures varied substantially.

7.
J Orthop Surg Res ; 15(1): 599, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302992

RESUMO

BACKGROUND: Ankle syndesmosis injury is a common condition, and the injury mechanism can be sorted into pure syndesmosis injury, Weber-B, and Weber-C type fractures. This study aims to evaluate the treatment outcomes and stability of suture-button fixation for syndesmosis injury with different injury mechanisms. We hypothesized that injury mechanisms would alter the stability of suture-button fixation. METHODS: We retrospectively reviewed 63 patients with ankle syndesmosis injury who underwent surgery with TightRope (Arthrex, Naples, FL, USA) from April 2014 to February 2019. The stability of suture-button fixation with TightRope was evaluated by comparing the preoperative, postoperative, and final follow-up measurements of tibiofibular clear space (TFCS), tibiofibular overlap (TFO), and medial clear space (MCS). A subgroup analysis for each demographic group and injury type including pure syndesmosis injury, Weber-B, and Weber-C type fractures were performed. RESULTS: Syndesmosis was effectively reduced using TightRope. After the index surgery, the tibiofibular clear space was reduced from 7.73 to 4.04 mm, the tibiofibular overlap was increased from 3.05 to 6.44 mm, and the medial clear space was reduced from 8.12 to 3.54 mm. However, syndesmosis widening was noted at the final follow-up, especially in Weber-C type fractures (TFCS 3.82 to 4.45 mm, p < 0.01 and TFO 6.86 to 6.29 mm, p = 0.04). Though widened, the final follow-up values of tibiofibular clear space and tibiofibular overlap were in the acceptable range. Postoperatively and at the final follow-up, medial clear space was found to be significantly larger in the Weber-C group than in the pure syndesmosis and Weber-B groups (p < 0.05). CONCLUSIONS: Suture-button fixation can offer anatomic reduction and dynamic fixation in syndesmosis injuries. However, when using this modality for Weber-C type fractures, more attention should be focused on the accuracy of reduction, especially of medial clear space, and rediastasis should be carefully monitored. TRIAL REGISTRATION: This trial was retrospectively approved by TMU-JIRB. Registration number N202004122, and the date of approval was May 06, 2020. LEVEL OF EVIDENCE: III.

8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1545-1550, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067952

RESUMO

OBJECTIVE: To investigate the expression and mechanism of histone acetyltransferase 2A (KAT2A) and cyclin D1 dependent kinase 4/6 (CDK4/CDK6) in children with acute leukemia(AL). METHODS: Seventy-one children with leukemia were selected from June 2017 to November 2018 and were enrolled in AL children group. 59 persons of healthy physical examination were selected and enrolled in control group. Real-time fluorescent quantification PCR chip was used to determine the expression of histone-modified genes and the expression levels of CDK4, CDK6 and CDK4/CDK6 mRNA; Western blot was used to validated KAT2A-positive expression; SPSS Pearson correlation analysis software was used to analyze the correlation between KAT2A and CDK4/CDK6 expression in children with acute leukemia. RESULTS: By comprehensive analysis of the existing chip data, the positive expression of KAT2A in the AL children group was 78.87%, which was higher than that in the control group (8.47%) (P<0.05). The expression level of CDK4 and CDK6 mRNA in the AL children group was higher than that in the control group (P<0.05); the expression level of CDK4/CDK6 mRNA in the AL children group was lower than that in the control group (P<0.05). The results of Western blot showed that the expression levels of KAT2A, CDK4 and CDK6 in AL children were higher than those in the control group, while the CDK4/CDK6 expression level in AL children group was lower than that in control group. The results of SPSS Pearson correlation analysis showed that the positive expression rate of KAT2A in AL children group positively correlated with expression level of CDK4 and CDK6 mRNA(r=0.673, r=0.559), and negatively correlated with expression level of CDK4/CDK6 mRNA(r=-0.762). CONCLUSION: The KAT2A is highly expressed in AL children, while the CDK4/CDK6 is lowly expressed in AL children, there is a significant correlation between of them, which is expected to become a new target for the treatment of acute leukemia children.


Assuntos
Histonas , Leucemia Mieloide Aguda , Criança , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Histona Acetiltransferases , Humanos , RNA Mensageiro
9.
Int J Mol Sci ; 21(9)2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32370144

RESUMO

Tendons are hypocellular and hypovascular tissues, and thus, their natural healing capacity is low. In this study, we sought to evaluate the efficacy of platelet-rich fibrin (PRF) to serve as a bioactive scaffold in promoting the healing of rabbit Achilles tendon injury. For in vitro study, the essence portion of PRF was determined through bioluminescent assay. Furthermore, we analyzed the time-sequential cytokines-release kinetics of PRF and evaluated their effects on tenocytes proliferation and tenogenic gene expressions. In animal study, the rabbit Achilles tendon defect was left untreated or implanted with normal/heat-denatured PRF scaffolds. Six weeks postoperatively, the specimens were evaluated through sonographic imaging and histological analysis. The results revealed significantly more activated platelets on bottom half of the PRF scaffold. Cytokine concentrations released from PRF could be detected from the first hour to six days. For the in vitro study, PRF enhanced cell viability and collagen I, collagen III, tenomodulin, and tenascin gene expression compared to the standard culture medium. For in vivo study, sonographic images revealed significantly better tendon healing in the PRF group in terms of tissue echogenicity and homogeneity. The histological analysis showed that the healing tissues in the PRF group had more organized collagen fiber, less vascularity, and minimal cartilage formation. In conclusion, bioactive PRF promotes in vitro tenocytes viability and tenogenic phenotypic differentiation. Administration of a PRF scaffold at the tendon defect promotes tissue healing as evidenced by imaging and histological outcomes.


Assuntos
Tendão do Calcâneo/lesões , Citocinas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fibrina Rica em Plaquetas/metabolismo , Traumatismos dos Tendões/cirurgia , Cicatrização , Tendão do Calcâneo/diagnóstico por imagem , Tendão do Calcâneo/patologia , Animais , Diferenciação Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Expressão Gênica , Masculino , Coelhos , Tenascina/genética , Tenascina/metabolismo , Traumatismos dos Tendões/diagnóstico por imagem , Traumatismos dos Tendões/metabolismo , Tenócitos/citologia , Tenócitos/metabolismo , Ultrassonografia/métodos
10.
Int J Mol Sci ; 21(10)2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32455543

RESUMO

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.


Assuntos
Parafusos Ósseos/normas , Osseointegração , Impressão Tridimensional , Tendões/cirurgia , Tíbia/cirurgia , Ligas/química , Animais , Parafusos Ósseos/efeitos adversos , Interface Osso-Implante/cirurgia , Fosfatos de Cálcio/química , Porosidade , Coelhos
11.
Polymers (Basel) ; 12(2)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32069799

RESUMO

Healing of an anterior cruciate ligament graft in bone tunnel yields weaker fibrous scar tissue, which may prolong an already prolonged healing process within the tendon-bone interface. In this study, gelatin molecules were added to thermosensitive chitosan/ß-glycerol phosphate disodium salt hydrogels to form chitosan/gelatin/ß-glycerol phosphate (C/G/GP) hydrogels, which were applied to 0.1 mg/mL collagenase carrier in the tendon-bone junction. New Zealand white rabbit's long digital extensor tendon was detached and translated into a 2.5-mm diameter tibial plateau tunnel. Thirty-six rabbits underwent bilateral surgery and hydrogel injection treatment with and without collagenase. Histological analyses revealed early healing and more bone formation at the tendon-bone interface after collagenase partial digestion. The area of metachromasia significantly increased in both 4-week and 8-week groups after collagenase treatment (p < 0.01). Micro computed tomography showed a significant increase in total bone volume and bone volume/tissue volume in the 8 weeks after collagenase treatment, compared with the control group. Load-to-failure was significantly higher in the treated group at 8 weeks (23.8 ± 8.13 N vs 14.3 ± 3.9 N; p = 0.008). Treatment with collagenase digestion resulted in a 66% increase in pull-out strength. In conclusion, injection of C/G/GP hydrogel with collagenase improves tendon-to-bone healing in a rabbit model.

12.
Life Sci ; 243: 117255, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31923418

RESUMO

BACKGROUND: The occurrence in drug resistance of chronic myeloid leukemia (CML) was accompanied by autophagy activation. Abnormal circular RNAs (circRNAs) participated in this progression. This study attempted to investigate the potential role of circ_0009910 in imatinib resistance of CML cells. METHODS: The expression of circ_0009910 and miR-34a-5p was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The characterization of circ_0009910 was investigated using oligo (dT)18 primers, Actinomycin D and RNase R. Cell viability (IC50 value) and apoptosis were assessed by Cell Counting Kit-8 (CCK8) assay and flow cytometry assay, respectively. The relative protein expression was quantified by western blot. The relationship among miR-34a-5p, circ_0009910 and ULK1 was predicted by online bioinformatics tool, and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). RESULTS: The expression of circ_0009910 was up-regulated in the serum of imatinib-resistance CML patients and K562/R cells, and associated with unfavorable clinicopathologic features. Circ_0009910 in K562 and K562/R cells was mainly localized in the cytoplasm. Circ_0009910 knockdown inhibited cell proliferation and autophagy, but induced apoptosis in K562/R cells. Circ_0009910 targeted miR-34a-5p to regulate ULK1. MiR-34a-5p depression rescued the effects of circ_0009910 knockdown on apoptosis and autophagy in K562/R cells. CONCLUSION: Circ_0009910 accelerated imatinib-resistance in CML cells by modulating ULK1-induced autophagy via targeting miR-34a-5p, providing a potential target in imatinib resistance of CML.


Assuntos
Antineoplásicos/uso terapêutico , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/fisiologia , Autofagia/fisiologia , Mesilato de Imatinib/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , MicroRNAs/genética , Resistencia a Medicamentos Antineoplásicos , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
13.
Sci Rep ; 10(1): 75, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919417

RESUMO

The role of laparoscopic surgery for left-sided colon cancer has been supported by the results of randomized controlled trials. However, its benefits and disadvantages in the real world setting should be further assessed with population-based studies.The hospitalization data of patients undergoing open or laparoscopic surgery for left-sided colon cancer were sourced from the Taiwan National Health Insurance Research Database. Patient and hospital characteristics and perioperative outcomes including length of hospital stay, operation time, opioid use, blood transfusion, intensive care unit (ICU) admission, and use of mechanical ventilation were compared. The overall survival was also assessed. Patients undergoing laparoscopic surgery had shorter hospital stay (p < 0.0001) and less demand for opioid analgesia (p = 0.0005). Further logistic regression revealed that patients undergoing open surgery were 1.70, 2.89, and 3.00 times more likely to have blood transfusion, to be admitted to ICU, and to use mechanical ventilation than patients undergoing laparoscopic surgery. Operations performed in medical centers were also associated with less adverse events. The overall survival was comparable between the 2 groups.With adequate hospital quality and volume, laparoscopic surgery for left-sided colon cancer was associated with improved perioperative outcomes. The long-term survival was not compromised.


Assuntos
Neoplasias do Colo/cirurgia , Laparoscopia , Idoso , Transfusão de Sangue , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Bases de Dados Factuais , Feminino , Humanos , Unidades de Terapia Intensiva , Estimativa de Kaplan-Meier , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
Asian J Surg ; 43(1): 290-296, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31043332

RESUMO

BACKGROUND: Rectal neoplasm is one of the most common malignancies worldwide. Screening programs for rectal neoplasm result in early diagnosis and a decrease in disease-related mortality and morbidity. In selected patients, early rectal cancer may be treated with local excision. Owing to poor exposure during conventional transanal excision, transanal minimally invasive surgery (TAMIS) was developed, and TAMIS is feasible for the local excision of selected rectal neoplasms. However, the limited range of motion is a major disadvantage of this operation. Therefore, robotic TAMIS was developed to resolve this issue. This paper describes the surgical outcomes of robotic TAMIS for selected rectal tumors. METHODS: The eligibility criteria for robotic TAMIS were as follows: benign neoplasms, early malignancy, complete remission after concurrent chemoradiotherapy, lesions located in the middle or lower rectum, and a lesion size of less than 5 cm. To gain access to the anal canal, a transanal access platform was used, and the da Vinci robotic system was mounted for surgery. Patient characteristics and surgical outcomes were recoded. RESULTS: A total of 23 patients were included, and the median tumor size was 2.5 cm (range: 1.1-4.5 cm) on average. The median tumor location was 5 cm (range: 2-8 cm) from the anal verge. The median length of hospital stay was 3 days (range: 1-10 days). No intraoperative complications were reported, and no patient readmission occurred. The median follow-up period was 9.6 months. No recurrent lesion was found in the follow-up period. CONCLUSION: Based on the short-term results, robotic TAMIS is a feasible and safe technique for the local excision of selected rectal neoplasms.


Assuntos
Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neoplasias Retais/patologia , Segurança , Fatores de Tempo , Resultado do Tratamento
15.
Ther Adv Med Oncol ; 11: 1758835919889002, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839809

RESUMO

Background: Stereotactic ablative radiotherapy (SABR) can deliver tumoricidal doses and achieve long-term control in early hepatocellular carcinoma (HCC). However, limited studies have investigated the safety and effectiveness of SABR in patients with advanced diseases that is unsuitable for transarterial chemoembolization (TACE). Methods: In this observational study, we reviewed the medical records of patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease treated with linear accelerator-based SABR between 2008 and 2016. Their tumors were either refractory to TACE or TACE was contraindicated. Overall survival (OS), in-field progression-free survival (IFPFS), and out-field progression-free survival were calculated using Kaplan-Meier analysis. The Cox regression model was used to examine the effects of variables. Treatment-related toxicities were scored according to the Common Terminology Criteria for Adverse Events (version 4.03) and whether patients developed radiation-induced liver disease (RILD) after SABR. Results: This study included 32 patients. The mean maximal tumor diameter and tumor volumes were 4.7 cm and 135.9 ml, respectively. Patients received linear accelerator-based SABR with a median prescribed dose of 48 Gy (30-60 Gy) in three to six fractions. Based on the assessment of treatment response by using the Response Evaluation Criteria in Solid Tumors (version 1.1), 19% of patients achieved a complete response and 53% achieved a partial response. After a median follow-up of 18.1 months (4.0-65.9 months), 10, 19, and 9 patients experienced in-field failure, out-field hepatic recurrence, and extrahepatic metastases, respectively. The estimated 2-year OS and IFPFS rates were 54.4% and 62.7%, respectively. In a multivariate analysis, a pretreatment Cancer of the Liver Italian Program (CLIP) score of ⩾2 (p = 0.01) was a prognostic factor for shorter OS, and a biologically effective dose (BED) of < 85 Gy10 (p = 0.011) and a Child-Pugh score of ⩾6 (p = 0.014) were prognostic factors for inferior IFPFS. In this study five and eight patients developed classic and nonclassic RILD, respectively. Conclusions: SABR can serve as a salvage treatment for patients with HCC with BCLC stage C disease unsuitable for TACE, in particular, in those with a baseline CLIP score of ⩽1. A BED10 of ⩾85 Gy is an appropriate prescribed dose for tumor control. Because out-field relapse is the major cause of treatment failure, SABR in combination with novel systemic modalities should be investigated in future studies.

16.
Biomolecules ; 9(11)2019 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-31684108

RESUMO

Human high-mobility group A2 (HMGA2) encodes for a non-histone chromatin protein which influences a variety of biological processes, including the cell cycle process, apoptosis, the DNA damage repair process, and epithelial-mesenchymal transition. The accumulated evidence suggests that high expression of HMGA2 is related to tumor progression, poor prognosis, and a poor response to therapy. Thus, HMGA2 is an important molecular target for many types of malignancies. Our recent studies revealed the positive connections between heat shock protein 90 (Hsp90) and HMGA2 and that the Hsp90 inhibitor has therapeutic potential to inhibit HMGA2-triggered tumorigenesis. However, 43% of patients suffered visual disturbances in a phase I trial of the second-generation Hsp90 inhibitor, NVP-AUY922. To identify a specific inhibitor to target HMGA2, the Gene Expression Omnibus (GEO) database and the Library of Integrated Network-based Cellular Signatures (LINCS) L1000platform were both analyzed. We identified the approved small-molecule antifungal agent ciclopirox (CPX) as a novel potential inhibitor of HMGA2. In addition, CPX induces cytotoxicity of colorectal cancer (CRC) cells by induction of cell cycle arrest and apoptosis in vitro and in vivo through direct interaction with the AT-hook motif (a small DNA-binding protein motif) of HMGA2. In conclusion, this study is the first to report that CPX is a novel potential inhibitor of HMGA2 using a drug-repurposing approach, which can provide a potential therapeutic intervention in CRC patients.


Assuntos
Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Ciclopirox/farmacologia , Neoplasias Colorretais/genética , Proteína HMGA2/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/fisiopatologia , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Humanos , Transcriptoma
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1387-1394, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607288

RESUMO

OBJECTIVE: To investigate the effect of metformin on the proliferation, apoptosis and energy metabolism of acute myeloid leukemia (AML) K562 cells and the possible mechanism. METHODS: Different doses (0, 5, 10, 20 and 30 mmol/L) of metformin was added into the K562 cells, which were cultivated for 24 h, 48 h and 72 h. The inverted optical microscope was used to observe the cell growth, CCK 8 was used to detect the cell vitality. The appropriate metformin doses (0, 10, 20 and 30 mmol/L) and the best time (48 h) were selected for subsequent experiments. The flow cytometer with Annexin V-FITC /PI doulde staining was used to detect apoptosis; the glucose detection kit and lactate detection kit were used to detect glucose consumption and lactate production; fluorescence quantitative PCR was used to detect glycolysis-related gene expression, and Western blot was used to detect protein expression. RESULTS: Metformin inhibited the proliferation of K562 cells in a dose-dependent manner (r=0.92), and the relative survival in the 30 mmol/L group was as low as 19.84% at 72 h. When treated with metformin for 48 h, the apoptosis rates of 0, 10, 20 and 30 mmol/L groups were 5.14%, 12.19%, 26.29% and 35.5%, respectively. Compared with the control group, the glucose consumption and lactate secretion of K562 cells treated with metformin were significantly reduced (P<0.05), and showed a dose-dependent effect(r=0.94,r=0.93,respectively). Metformin inhibited the expression of GLUT1, LDHA, ALDOA, PDK1, and PGK1 genes of K562 cells (P<0.05) showing a dose-dependent manner(r=0.83,r=0.80,r=0.72,r=0.76,r=0.73,respectively). Metformin inhibited the expression of P-Akt, P-S6, GLUT1, LDHA proteins of K562 cells(P<0.05), showing a dose-dependent relationship(r=0.80,r=0.92,r=0.83,r=0.92,respectively). CONCLUSION: Metformin can inhibit the growth and proliferation of K562 cells and promote the apoptosis of K562 cells by inhibiting glycolysis energy metabolism. PI3K/Akt/mTOR signaling pathway may be one of the molecular mechanisms of metformin on k562 cells.


Assuntos
Metformina/farmacologia , Apoptose , Proliferação de Células , Glicólise , Humanos , Células K562 , Fosfatidilinositol 3-Quinases
18.
Asian J Surg ; 42(6): 657-666, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30609955

RESUMO

Controversy still surrounds clinical benefits of robotic-assisted (RS) over laparoscopic surgery (LS) despite its popularity in clinical use in terms of outcomes and complication rates. The study aims to systematically review and provide the evidence concerning the risk of conversion to open laparotomy and oncological outcomes of LS vs RS rectal cancer surgery. The Cochrane Library (including the Cochrane Central Register of Controlled Trials), EMBASE, PubMed, SCOPUS, and Web of Science were searched for randomized controlled trials (RCTs) comparing LS and RS. Eight RCTs including 1305 patients were identified. Pooled conversion rate was reported in 49 (11.89%) of 412 patients who underwent LS and in 23 (5.72%) of 402 patients who underwent RS (95% CI, 1.357 to 3.613; P = .001). However, shorter operative time was noted in LS group than RS group (95% CI, -43.106 to -3.876; P = .019). No significant difference in other outcomes was observed. Finally, in further analysis, the mean age in trial-level was found to be positively associated with operative time (point estimate = 2.598; 95% CI, 1.584 to 3.612; P < .001) and negatively with length of hospital stay. Robot-assisted surgery in rectal cancer showed lower conversion rate in comparison with that of laparoscopic surgery. Secondly, the laparoscopic surgery has shorter operative time compared with robot-assisted approach. The results also showed similar pathological outcomes between these two modalities. Future studies are needed to clarify the relationship between mean age and outcomes of surgery.


Assuntos
Laparoscopia/métodos , Neoplasias Retais/cirurgia , Reto/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Bases de Dados Bibliográficas , Humanos , Tempo de Internação , Margens de Excisão , Duração da Cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Resultado do Tratamento
19.
Surg Innov ; 26(2): 192-200, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30501567

RESUMO

PURPOSE: Robotic surgery for colorectal cancer is an emerging technique. Potential benefits as compared with the conventional laparoscopic surgery have been demonstrated. However, experience with the previous da Vinci Si robotic system revealed several unsolved problems. The novel features of the new da Vinci Xi increase operational flexibility and maneuverability and are expected to facilitate the performance of multiquadrant surgery. METHODS: Between December 2011 and May 2015, 120 patients with colon or rectal cancer were operated on using the Si robotic system (the Si group). Between May 2015 and October 2017, 60 more patients with colon or rectal cancer were operated on using the Xi robotic system (the Xi group). The clinicopathological characteristics and perioperative outcomes of these 2 groups of patients were compared. RESULTS: The 2 groups of patients were comparable with regard to baseline clinical characteristics, types of resection performed, and the proportion of patients undergoing neoadjuvant chemoradiation therapy. The statuses of resection margin, the numbers of lymph nodes harvested, and the rates of postoperative complications were also similar between the 2 groups. Nevertheless, a lower rate of diverting ileostomy, a shorter operation time, less estimated blood loss, and a faster postoperative recovery was observed in the Xi group. CONCLUSIONS: Colorectal cancer surgery using the Xi robotic system was associated with improved perioperative outcomes. These benefits may be attributed to its improved, more user-friendly design.


Assuntos
Neoplasias Colorretais/cirurgia , Cirurgia Colorretal , Procedimentos Cirúrgicos Robóticos , Adulto , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Neoplasias Colorretais/patologia , Cirurgia Colorretal/efeitos adversos , Cirurgia Colorretal/métodos , Cirurgia Colorretal/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Resultado do Tratamento
20.
Asian J Surg ; 42(1): 172-179, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29454573

RESUMO

OBJECTIVE: Morbidity rates after living donor hepatectomy vary greatly among centers. Donor morbidity in a tertiary center over the past two decades was revisited. METHODS: Clinical data and grading of complications were reviewed by a nontransplant surgeon based on Clavien 5 tier grading. Risk factors were analyzed. RESULTS: In total, 473 consecutive living liver donors from 1997 to 2016 were included for analysis; 305 were right liver donors and 168 left liver donors, and the corresponding morbidity rates were 27.2% and 9.5%. The majority (81/99, 81.2%) of complications were grade I and II. Donors with morbidity compared with those without were significantly younger, nonoverweight body figure (BMI < 25), more as the right liver donors, and longer length of hospital stay. Right liver donation had significantly higher morbidity rates than did left liver donation in earlier periods (before 2011), but not thereafter. Multivariate modeling revealed that right lobe donation and overweight (BMI ≥ 25 kg/m2) were significant factors associated with donor morbidity, with adjusted hazard ratios HR (95% confidence interval) of 3.401 (1.909-6.060) and 0.550 (0.304-0.996), respectively. Further, overweight was a paradoxical risk factor in right donor hepatectomy with HR 0.422 (0.209-0.851), but the effect was nonsignificant in left liver donors. Most complications in overweight donors were grade I and not specific to liver surgery. CONCLUSIONS: The overall complication rate was 20.9%. Overweight might be protective against morbidity in right hepatectomy and warrants further deliberation.


Assuntos
Transplante de Fígado , Doadores Vivos , Sobrepeso , Complicações Pós-Operatórias/epidemiologia , Adulto , Fatores Etários , Feminino , Hepatectomia , Humanos , Tempo de Internação , Masculino , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Fatores de Tempo , Adulto Jovem
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