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1.
ACS Chem Biol ; 19(8): 1803-1812, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39069677

RESUMO

Osteosarcoma (OS) is a rare malignant tumor that has predominantly affected children and adolescents in the past 50 years. The genomes of OS tumors exhibit a high degree of complexity, which leads to the great challenge of target identification for anti-OS. To date, no efficient therapeutic target for the treatment of OS has been validated in clinical practice. In our previous drug hunting for the treatment of OS by phenotypic screening, we found that thiazolone derivate (R)-8i was an effective and selective inhibitor against OS in MNNG/HOS cells and in vivo. However, the mechanism of action and specific molecular targets of (R)-8i remain unclear. In this study, we design and synthesize the photo-cross-linking probes based on the lead compound (R)-8i and identify DDX5 as a potential target protein using an activity-based protein profiling strategy. Further experiments including Western blot, shRNA knockdown experiments, cell colony formation, wound healing assays, and cellular thermal shift assays support that (R)-8i binds to DDX5 and induces its degradation, which affect cell proliferation and migration through the PI3K-AKT-mTOR signaling pathway. The research shows that DDX5 is a potential therapeutic target for the treatment of OS.


Assuntos
Proliferação de Células , RNA Helicases DEAD-box , Osteossarcoma , Tiazóis , Humanos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Osteossarcoma/patologia , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Tiazóis/química , Tiazóis/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Movimento Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
2.
Eur J Med Chem ; 266: 116082, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38232462

RESUMO

Chemotherapy combining with surgical treatment has been the main strategy for osteosarcoma treatment in clinical. Due to unclear pathogenesis and unidentified drug targets, significant progress has not been made in the development of targeted drugs for osteosarcoma during the past 50 years. Our previous discovery reported compound R-8i with a high potency for the treatment of osteosarcoma by phenotypic screening. However, both the metabolic stability and bioavailability of R-8i are poor (T1/2 = 5.36 min, mouse liver microsome; and bioavailability in vivo F = 52.1 %, intraperitoneal administration) which limits it use for further drug development. Here, we described an extensive structure-activity relationship study of thiazolidine-4-one sulfone inhibitors from R-8i, which led to the discovery of compound 68. Compound 68 had a potent cellular activity with an IC50 value of 0.217 µM, much higher half-life (T1/2 = 73.8 min, mouse liver microsome) and an excellent pharmacokinetic profile (in vivo bioavailability F = 115 %, intraperitoneal administration). Compound 68 also showed good antitumor effects and low toxicity in a xenograft model (44.6 % inhibition osteosarcoma growth in BALB/c mice). These results suggest that compound 68 is a potential drug candidate for the treatment of osteosarcoma.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Osteossarcoma , Humanos , Camundongos , Animais , Preparações Farmacêuticas , Relação Estrutura-Atividade , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Neoplasias Ósseas/tratamento farmacológico , Proliferação de Células , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral
3.
Mitochondrial DNA B Resour ; 8(5): 629-633, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275397

RESUMO

In the present study, the complete mitochondrial genome of Lepidozona coreanica was sequenced and described. The complete mitogenome sequence of L. coreanica is 16,572 bp long and contains 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and two ribosomal RNA (rRNA) genes. The base composition was AT biased (70.1%). The 13 PCGs of L. coreanica and the other 15 species of Polyplacophora were used for phylogenetic analysis using maximum-likelihood methods. The results showed that L. coreanica, Ischnochiton hakodadensis, and Chaetopleura apiculata are sister groups of the three lineages.

4.
J Vasc Surg Venous Lymphat Disord ; 11(4): 688-691, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36906106

RESUMO

OBJECTIVE: To examine the long-term effectiveness of fluoroscopy-guided foam sclerotherapy for varicose veins in the legs. METHODS: This retrospective cohort study included consecutive patients who underwent fluoroscopy-guided foam sclerotherapy for varicose veins in the legs at the authors' center during a period from August 1, 2011, to May 31, 2016. The last follow-up was conducted by a telephone/WeChat interactive interview in May 2022. Recurrence was defined as the presence of varicose veins regardless of symptoms. RESULTS: The final analysis included 94 patients (58.3 ± 7.8 years of age; 43 men; 119 legs). The median Clinical-Etiology-Anatomy-Pathophysiology (CEAP) clinical class was 3.0 (interquartile range [IQR]: 3.0, 4.0). C5 and C6 accounted for 5.0% (6/119) of the legs. The average total amount of the foam sclerosant used during the procedure was 35 ± 12 mL (range: 10-75 mL). No patients developed stroke, deep vein thrombosis, or pulmonary embolism after the treatment. At the last follow-up, the median CEAP clinical class reduction was 3.0. All 119 legs except for class 5 achieved the CEAP clinical class reduction by at least one grade. The median venous clinical severity score was 2.0 (IQR: 1.0, 5.0) at the last follow-up vs 7.0 (IQR: 5.0, 8.0) at the baseline (P < .001). The recurrence rate was 30.9% (29/94) in the overall analysis, 26.6% (25/94) for the great saphenous vein and 4.3% (4/94) for the small saphenous vein (P < .001). Five patients received subsequent surgical treatment, and the remaining patients opted to receive conservative treatments. Among the two C5 legs at the baseline, ulcer recurred in one leg at 3 months after the treatment and healed after conservative treatments. In the four C6 legs at the baseline, ulcer healed within a month in all patients. The rate of hyperpigmentation was 11.8% (14/119). CONCLUSIONS: Long-term outcomes in patients undergoing fluoroscopy-guided foam sclerotherapy are satisfying, with minimal short-term safety concerns.


Assuntos
Escleroterapia , Varizes , Masculino , Humanos , Escleroterapia/efeitos adversos , Estudos Retrospectivos , Seguimentos , Perna (Membro) , Úlcera/etiologia , Resultado do Tratamento , Varizes/diagnóstico por imagem , Varizes/terapia , Varizes/etiologia , Veia Safena/diagnóstico por imagem , Veia Safena/cirurgia , Fluoroscopia
5.
Comput Biol Med ; 155: 106672, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36805226

RESUMO

The radiogenomics analysis can provide the connections between genomics and radiomics, which can infer the genomic features of tumors from their radiogenomic associations through the low-cost and non-invasiveness screening ultrasonic images. Although there are a number of pioneer approaches exploring the connections between genomic aberrations and ultrasonic features, these studies mainly focus on the relationship between ultrasonic features and only the most popular cancer genes, confronting two difficulties: missing many-to-many relationships as omics-to-omics view, and confounding group-specific associations with whole sample associations. To overcome the difficulty of omics-to-omics view and the issue of tumor heterogeneity, we propose an omics-to-omics joint knowledge association subtensor model. Specifically, the subtensor factorization framework can successfully discover the joint cross-modal module via an omics-to-omics view, while the sparse weight sample indication strategy can mine sample subgroups from the multi-omic data with tumor heterogeneity. The experimental evaluation result shows the jointness of the discovered modules across omics, their association with tumorigenesis contribution, and their relation for cancer related functions. In summary, our proposed omics-to-omics joint knowledge association subtensor model can serve as an efficient tool for radiogenomic knowledge associations, promoting the cross-modal knowledge graph construction of in explainable artificial intelligence cancer diagnosis.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Inteligência Artificial , Ultrassom , Genômica/métodos
7.
Int J Med Robot ; 18(6): e2456, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35996997

RESUMO

BACKGROUND: Percutaneous vertebroplasty (PVP) is one of the most effective treatments for patients with vertebral fracture that need surgical treatment, and surgical robotics are promising tools to provide surgeons with improved precision, surgical efficiency and reduce radiation exposure. However, there are currently few robotics that are developed to help assist with PVP. METHODS: A new spinal surgical robotic system 'AOSRV' for autonomous vertebral puncture and bone cement injection was designed and customised in this study. To investigate its practical abilities and the advantages, we performed single-segment/double-segment PVP simulation surgeries on pig spinal specimens manually and using AOSRV. RESULTS: By contrast with the freehand group (FG) in single-segment (SS)/double-segment (DS) surgery, the robotic group (RG) was superior in the operation time (RGSS = 21.14 ± 4.11 min, FGSS = 33.17 ± 6.83 min; RGDS = 42.39 ± 7.31 min, FGDS = 62.86 ± 20.39 min), puncture adjustments (RGSS = 2.30 ± 1.77, FGSS = 14.86 ± 5.46; RGDS = 3.91 ± 1.76, FGDS = 20.00 ± 7.76), intraoperative fluoroscopies (RGSS = 4.10 ± 1.52, FGSS = 20.57 ± 5.44; RGDS = 7.82 ± 1.40, FGDS = 25.91 ± 7.23) and bone cement leakage rate (RGSS = 30%, FGSS = 71.4%; RGDS = 38.6%, FGDS = 83.3%). CONCLUSIONS: AOSRV was successfully developed and had a promising preliminary performance. An innovative attempt was made for the blank space of the autonomous vertebroplasty surgical robotics, and it may shed a light on more promising applications in the future.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Suínos , Animais , Fraturas por Compressão/cirurgia , Cimentos Ósseos , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento
8.
Eur J Med Chem ; 228: 114010, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34861640

RESUMO

Due to unknown pathogenesis and unidentified drug target, no drug for the treatment of osteosarcoma (OS) has been launched to the market. Herein, thiazolidinone 1a was discovered as a hit compound by phenotypic screening with an in-house patrimonial collection of structural diversity. The following SAR (Structure-Activity Relationship) study affords the final water-soluble lead compound (R)-8i as a potential inhibitor for the proliferation of OS cells by the modulation of solubility of the compounds with remarkable cellular potency (IC50 = 21.9 nM for MNNG/HOS cells) and in vivo efficacy (52.9% inhibition OS growth in mice), as well as pharmacokinetic properties. (R)-8i also significantly suppresses OS cell migration in vitro and showed to be well-tolerated. Our preliminary investigation shows that the effects of (R)-8i are not dependent on p53 and myoferlin (MYOF). These results suggest that (R)-8i might be a potential drug candidate for OS treatment.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Piridinas/farmacologia , Tiazolidinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Osteossarcoma/patologia , Piridinas/síntese química , Piridinas/química , Relação Estrutura-Atividade , Tiazolidinas/síntese química , Tiazolidinas/química
9.
Int J Surg ; 82: 95-99, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32805429

RESUMO

BACKGROUND: Laparoscopic pancreaticoduodenectomy is an appealing and minimally invasive method for pancreaticoduodenal tumors. However, an abdominal incision is still required to extract the specimen. We used the natural orifice specimen extraction technique in laparoscopic pancreaticoduodenectomy to accomplish specimen retraction in 8 female patients and summarized the clinical results. MATERIALS AND METHODS: A total of 8 female patients with periampullary carcinoma or duodenal cancer who underwent laparoscopic pancreaticoduodenectomy were enrolled in our study between April 2018 and October 2019. A 4-cm transverse incision was made in the posterior vaginal wall, and the specimen was extracted via the vagina. Age, operative time, intraoperative hemorrhage, pathological data of the tumor, postoperative hospital stay, and postoperative complications were recorded and analyzed. All operations were performed laparoscopically, by the same team of surgeons. RESULTS: The mean age of the patients was 67.5 ± 7.7 years. Mean BMI was 23.7 ± 1.7 kg/m2. The operative time ranged between 312 and 460 min. The intraoperative blood loss ranged from 100 to 600 ml. The average hospital stay of all patients was 9.9 ± 2.2 days; 5 out of 8 patients (62.5%) had postoperative complications, including postoperative pancreatic fistula, delayed gastric emptying, and postpancreatectomy hemorrhage. No patient developed short-term complications due to vaginal extraction of specimens. All patients underwent R0 resection. CONCLUSION: Transvaginal specimen extraction is a practicable method for laparoscopic pancreaticoduodenectomy. By adhering to correct operation specifications and selecting patients with appropriate indications for natural orifice specimen extraction, this technique was safe and beneficial to selected female patients with pancreaticoduodenal tumors.


Assuntos
Laparoscopia/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Pancreaticoduodenectomia/métodos , Manejo de Espécimes/métodos , Vagina/cirurgia , Idoso , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Carcinoma/patologia , Carcinoma/cirurgia , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Feminino , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
10.
Gastroenterol Rep (Oxf) ; 8(1): 5-10, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32104581

RESUMO

At present, natural orifice specimen extraction surgery (NOSES) has attracted more and more attention worldwide, because of its great advantages including minimal cutaneous trauma and post-operative pain, fast post-operative recovery, short hospital stay, and positive psychological impact. However, NOSES for the treatment of gastric cancer (GC) is still in its infancy, and there is great potential to improve its theoretical system and clinical practice. Especially, several key points including oncological outcomes, bacteriological concerns, indication selection, and standardized surgical procedures are raised with this innovative technique. Therefore, it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES, which is of great significance for healthy and orderly development of NOSES worldwide.

11.
J Orthop Translat ; 20: 73-79, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31908936

RESUMO

BACKGROUND AND OBJECTIVE: Existing orthopaedic robotic systems are almost restricted to provide guidance for trajectory direction. In the present study, a novel spinal robotic system with automatic drilling power was introduced. The aim of this study is to evaluate the feasibility and safety in pedicle screw â€‹insertion of posterior lumbar interbody fusion assisted by this novel robotic system. METHODS AND MATERIALS: A randomised controlled trial was conducted for 17 participants who were required posterior lumbar interbody fusion process. Seven (3 M/4 F) were randomly assigned to the robot-assisted group (RA group), and the other ten (4 M/6 F) were assigned to the conventional technique group (FH group). A novel robotic system was used in the RA group. All measurements were based on postoperative computed tomography (CT) data. Accuracy of screw insertion was determined using the Gertzbein and Robbins Scale. Precision was measured by the entry point deviation distance and the trajectory rotation. Other variables included operation time, radiation time, length of stay, and screw-related complications. RESULT: A total of 82 pedicle screws were placed in the 17 participants. In the RA group, 90.6% of screws placed were Grade A, and 9.4% were Grade B. In the FH group, 78.0% of screws were Grade A, 20.0% were Grade B, and 2.0% were Grade C. No statistical difference was found in the operation time, radiation time per case, and length of stay between both groups. The radiation time per screw is significantly lower in the RA group. No screw-related complications or revision occurred in the present study. CONCLUSION: The outcome of screw accuracy of this robotic system was comparable with that of experienced surgeons, and no screw-related complication was found in the RA group during hospitalisation. In addition, radiation time per screw in the robotic group was significantly lower than that in the conventional group, which shows the potential to reduce radiation exposure of pedicle screw fixation assisted by this robotic system. TRANSLATIONAL POTENTIAL: Our study shows that pedicle screw fixation assisted by "Orthbot" system is accurate and safe. It is concluded that this novel robotic system offers a new option for internal implantation in spine surgery.

12.
J Vasc Surg Venous Lymphat Disord ; 8(5): 783-788, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917182

RESUMO

OBJECTIVE: In foam sclerotherapy for varicose veins, ultrasound can track the spread of foam in only one direction. We hypothesized that using fluoroscopy in combination with ultrasound can reveal the spread of foam to deep veins through perforator veins and to other varicose veins in different directions. In this study, we examined the safety and effectiveness of ultrasound- and fluoroscopy-guided foam sclerotherapy for lower extremity venous ulcers. METHODS: This retrospective study included all patients receiving ultrasound- and fluoroscopy-guided foam sclerotherapy for varicose ulcers (Clinical, Etiology, Anatomy, and Pathophysiology class 6) of the lower extremities at the Fourth Affiliated Hospital of Jiangsu University (Zhenjiang, China) between May 1, 2016, and April 30, 2018. Polidocanol foam sclerosant was injected through indwelling needles (placed every 20 cm for saphenous veins and every 5-10 cm for others) into the varicose veins. When the contrast medium in the target vessels was replaced by the hypointense foam sclerosant or on signs of foam entry into the perforator veins under fluoroscopy, the injection was stopped and the site was manually pressed. All patients received postprocedure compression with elastic bandages until ulcer healing and compression stockings (30-40 mm Hg) thereafter. RESULTS: A total of 35 patients (42 limbs) were included. The maximal ulcer diameter was 3.6 ± 1.4 cm (range, 1.1-5.8 cm). The number of injection sites ranged from 3 to 10; total foam amount ranged from 4.5 to 35 mL. All 35 patients completed 12-month follow-up. Ulcer healing rate was 100%, and 1-year recurrence rate was 2.9%. The Venous Clinical Severity Score was 12.98 ± 3.91 before treatment, decreasing to 3.02 ± 2.39 at 12 months (P < .01). Superficial thrombophlebitis developed in 21 (50%) limbs. No deep venous thrombosis or pulmonary embolism was observed during follow-up. Among the 33 limbs (27 patients) with ultrasound examination at 12 months, 28 (84.8%) limbs had complete occlusion and the remaining 5 (15.2%) had recanalization. CONCLUSIONS: Ultrasound- and fluoroscopy-guided foam sclerotherapy is safe and effective for the treatment of venous ulcers of the lower extremities.


Assuntos
Polidocanol/administração & dosagem , Radiografia Intervencionista , Soluções Esclerosantes/administração & dosagem , Escleroterapia , Ultrassonografia de Intervenção , Úlcera Varicosa/terapia , Cicatrização , Adulto , Idoso , Bandagens Compressivas , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Úlcera Varicosa/diagnóstico por imagem , Úlcera Varicosa/patologia
13.
BMC Gastroenterol ; 19(1): 224, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864294

RESUMO

BACKGROUND: Various types of medical glues/adhesives/topical coagulants' (referred to as MG hereinafter) have widespread application as surgical adhesives, and have been shown to be safe and effective for a broad range of usage, such as in hemostasis, reinforcement of intestinal anastomoses or sites of potential fluid leakage, adhesion of two surfaces, wound closure, and vascular embolization. However, inappropriate application of MG may sometimes lead to serious complications. Herein, we describe three cases of serious postoperative complications induced by a possible inappropriate use of N-butyl-2-cyanoacrylate MG (NBCA MG). CASE PRESENTATION: Three patients presented with abdominal pain (chronic pain in cases 1 and 2, and acute pain in Case 3), hematochezia (Case 2), and intestinal obstruction (Case 3). All patients had a history of abdominal surgery and intraoperative use of NBCA MG. Abdominal computed tomography and gastroenterological endoscopy revealed foreign bodies (solidified MG in cases 1 and 2) and intestinal obstruction related to a mass of residual non-absorbed MG causing an internal hernia from a dense adhesion (Case 3). All patients underwent exploratory laparotomy, which revealed duodenal perforation, colonic erosion, and an internal hernia, all of which was related to MG use. We undertook removal of the foreign bodies (cases 1 and 2), surgical closure of the site of duodenal erosion (Case 1), partial colectomy (Case 2), and partial enterectomy (Case 3). CONCLUSION: Inappropriate application of MG may induce serious complications. We emphasize the importance of careful evaluation of the indications, dosage, and spraying thickness of MG in clinical practice. Serious complications caused by inappropriate application of MG should be reported to raise awareness in the surgical fraternity.


Assuntos
Dor Abdominal/etiologia , Embucrilato/efeitos adversos , Corpos Estranhos/complicações , Hemorragia Gastrointestinal/etiologia , Obstrução Intestinal/etiologia , Complicações Pós-Operatórias/etiologia , Colo/lesões , Duodeno/lesões , Feminino , Corpos Estranhos/diagnóstico por imagem , Hérnia/diagnóstico por imagem , Hérnia/etiologia , Humanos , Enteropatias/diagnóstico por imagem , Enteropatias/etiologia , Obstrução Intestinal/diagnóstico por imagem , Perfuração Intestinal/diagnóstico por imagem , Perfuração Intestinal/etiologia , Masculino , Pessoa de Meia-Idade
14.
Gastroenterol Rep (Oxf) ; 7(1): 24-31, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30792863

RESUMO

In recent years, natural orifice specimen extraction surgery (NOSES) in the treatment of colorectal cancer has attracted widespread attention. The potential benefits of NOSES including reduction in postoperative pain and wound complications, less use of postoperative analgesic, faster recovery of bowel function, shorter length of hospital stay, better cosmetic and psychological effect have been described in colorectal surgery. Despite significant decrease in surgical trauma of NOSES have been observed, the potential pitfalls of this technique have been demonstrated. Particularly, several issues including bacteriological concerns, oncological outcomes and patient selection are raised with this new technique. Therefore, it is urgent and necessary to reach a consensus as an industry guideline to standardize the implementation of NOSES in colorectal surgery. After three rounds of discussion by all members of the International Alliance of NOSES, the consensus is finally completed, which is also of great significance to the long-term progress of NOSES worldwide.

15.
Oncol Lett ; 12(5): 4139-4146, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27895783

RESUMO

Curcumin, an active nontoxic ingredient of turmeric, possesses potent anti-inflammatory, antioxidant and anti-cancer properties; however, the molecular mechanisms of curcumin are not fully understood. The transcription factor nuclear factor-κB (NF-κB) is key in cellular processes, and the expression/activation of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9) are crucial for cell invasion. The present study investigated the hypothesis that curcumin inhibits colon cancer cell invasion by modulating NF-κB-mediated expression and activation of uPA and MMP9. Human colon cancer SW480 and LoVo cells were treated with various concentrations of curcumin. Curcumin was demonstrated to dose-dependently inhibit the adhesion and proliferation ability of LoVo and SW480 cells using Transwell and MTT assays, respectively. In addition, curcumin activated 5' AMP-activated protein kinase (AMPK) and suppressed p65 NF-κB phosphorylation, as shown by western blot analysis. Compound C, a potent AMPK inhibitor, abolished curcumin-induced inhibition of NF-κB, uPA and MMP9, suggesting that AMPK activation is responsible for curcumin-mediated NF-κB, uPA and MMP9 inhibition. The binding activity of NF-κB to DNA was examined and western blotting and quantitative polymerase reaction was performed to detect the effect of curcumin on the expression of uPA and MMP9. The present results revealed that curcumin significantly decreased the expression of uPA and MMP9 and NF-κB DNA binding activity. Furthermore, curcumin decreased the level of the p65 subunit of NF-κB binding to the promoter of the gene encoding uPA and MMP9, which suppressed transcriptional activation of uPA and MMP9. Overall, the present data suggest that curcumin inhibits colon cancer cell invasion via AMPK activation and subsequent inhibition of p65 NF-κB, uPA and MMP9. The therapeutic potential of curcumin for colon cancer metastasis required additional study.

16.
Cell Biochem Biophys ; 72(2): 453-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25567655

RESUMO

Sorcin, a soluble resistance-related calcium-binding protein, belongs to the small penta-EF-hand family. Recent study reported that upregulation of sorcin correlated with metastasis and poor prognosis of colorectal cancer (CRC). In the present study, we explored the regulatory role of sorcin in CRC metastasis. To investigate the role of sorcin in CRC metastasis, sorcin overexpressed with empty vector as control in CRC cell line (HCT116). The effect of sorcin overexpression on cell migration and invasion was evaluated via wound healing and transwell assay, respectively. Sorcin-induced changes in EMT process were evaluated by estern blot. Furthermore, the role of PI3K/Akt in the regulatory effect of sorcin on cell migration and invasion, and EMT process was explored by suppressing Akt activity in sorcin-overexpressed HCT116 cells. Sorcin overexpression in HCT116 cells resulted in a significant increase in cell migration and invasion. Sorcin overexpression also markedly promoted the EMT process. More importantly, our results revealed that sorcin stimulated EMT process through activating PI3K/Akt signaling. In summary, this study indicated that the promoting effect of sorcin on CRC metastasis was, at least in part, through PI3K/Akt signaling. The findings in this study highlight the effectiveness and therapeutic potential to utilize sorcin-targeted strategies in the treatment of CRC.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal , Proteínas de Ligação ao Cálcio/genética , Movimento Celular , Células HCT116 , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
17.
World J Gastroenterol ; 19(5): 750-4, 2013 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-23430965

RESUMO

AIM: To introduce transvaginal or transanal specimen extraction in laparoscopic total mesorectal excision surgery to avoid an abdominal incision. METHODS: Between January 2009 and December 2011, 21 patients with rectal cancer underwent laparoscopic radical resection and the specimen was retrieved by two different ways: transvaginal or transanal rectal removal. Transvaginal specimen extraction approach was strictly limited to elderly post-menopausal women who need hysterectomy. Patients aged between 30 and 80 years, with a body mass index of less than 30 kg/m², underwent elective surgery. The surgical technique and the outcomes related to the specimen extraction, such as duration of surgery, length of hospital stay, and the complications were retrospectively reviewed. RESULTS: Laparoscopic resection using a natural orifice removal approach was successful in all of the 21 patients. Median operating time was 185 min (range, 122-260 min) and the estimated blood loss was 48 mL. The mean length of hospital stay was 7.5 d (range, 2-11 d). One patient developed postoperative ileus and had an extended hospital stay. The patient complained of minimal pain. There were no postoperative complications or surgery-associated death. The mean size of the lesion was 2.8 cm (range, 1.8-6.0 cm), and the mean number of lymph nodes harvested was 18.7 (range, 8-27). At a mean follow-up of 20.6 mo (range, 10-37 mo), there were no functional disorders associated with the transvaginal and transanal specimen extraction. CONCLUSION: Transvaginal or transanal extraction in L-TME is a safe and effective procedure. Natural orifice specimen extraction can avoid the abdominal wall incision and its potential complications.


Assuntos
Laparoscopia , Cirurgia Endoscópica por Orifício Natural , Neoplasias Retais/cirurgia , Feminino , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
Indian J Surg ; 75(Suppl 1): 280-2, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24426591

RESUMO

A male patient with lower-segment rectal carcinoma underwent laparoscopic radical resection and regional lymph node dissection. The extracorporeal rectoanal anastomosis was completed using transanal endoscopic microsurgery (TEMS) without requiring any additional abdominal incision. The pathological examination identified a clean margin. At the postoperative 6-month visit, the patient exhibited generally normal defecation, urination, and sexual function, but no sign of local recurrence or distant metastasis. TEMS integrating laparoscopy is a surgically and oncologically feasible, effective, and safe procedure for lower anterior resection.

19.
Surg Radiol Anat ; 31(3): 191-8, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18923806

RESUMO

The purpose of this study was to describe radiologic anatomy of the left atrium diverticulum. There were 20 patients with 27 left atrium diverticulums in 120 consecutive patients who underwent CT of coronary angiography. The presence probability of left atrium diverticulum was 16.7%, male of it was 13.0%, female was 17.6%. There was no difference on gender (P > 0.05). There were four patients accompanying with variation of pulmonary vein at one time. The diverticulum might be single or multiple, cystiform or tubiform. It could locate anterior wall or posterior wall or superior wall of left atrium. Left atrium diverticulums which was single, cystiform, and located in anterior wall were common. The cervix width of diverticulum was 4.9 +/- 3.2 mm, the body height of them was 5.4 +/- 2.0 mm. The ratio of body height to cervix width was from 0.47 to 4.08 (median 1.16). Ten patients of them undertook cardiac ultrasound examination at same time. There were five patients who left atrial diastolic function decreased, four patients who left ventricular systolic function decreased. Three of them both existed left atrial diastolic function decreasing and left ventricular systolic function decreasing, accompanied with mitral or aortic regurgitation. No patient was found that left atrium pressure or left ventricle diastolic pressure was increasing. The left atrium diverticulums of ten patients were probably congenital because their hemodynamical status cannot lead to diverticulum formation. It can be proved by reexamination after therapy or autopsy at last. In conclusion, multi-detector row computed tomography could provide anatomy details of left atrium diverticulum to help to finish heart and chest surgery successfully.


Assuntos
Divertículo/diagnóstico por imagem , Átrios do Coração/anormalidades , Átrios do Coração/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Distribuição de Qui-Quadrado , Meios de Contraste , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/anormalidades , Veias Pulmonares/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador
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