Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Small ; : e2402474, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38822710

RESUMEN

Although WO3 exhibits both electrochromic and photoelectrochemical (PEC) properties, there is no research conducted to investigate the correlation between them. The study herein reports the electrochromic enhancement of PEC activity on WO3. The electrochromic WO3 (e-WO3) exhibits a significantly enhanced activity for PEC water oxidation compared to raw WO3 (r-WO3), with a limiting photocurrent density three times that of r-WO3. The electrochromic enhancement of PEC activity is universal and independent of the type of cations inserted during electrochromism. Decoloring reduces the PEC activity but a simple re-coloring restores the activity to its maximum value. Electrochromism induces large amounts of oxygen vacancies and surface states, the former improving the electron density of WO3 and the latter facilitating the hole transfer across e-WO3/electrolyte interface. It is proved that the electrochromic enhancement effect is due to the significantly improved electron-hole separation efficiency and the charge transfer efficiency across the WO3/electrolyte interface.

2.
Cancer Lett ; 592: 216909, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38679407

RESUMEN

Natural killer (NK) cells exert an indispensable role in innate immune responses against cancer progression, however NK cell dysfunction has been rarely reported in hepatocellular carcinoma (HCC). This study sought to uncover the immunoregulatory mechanisms of tumor-infiltrating NK cells in HCC. A consensus NK cell-based signature (NKS) was constructed using integrative machine learning algorithms based on multi-omics data of HCC patients. HCC tumors had lower numbers of infiltrating NK cells than para-tumor normal liver tissues. Based on the NK cell-associated genes, the NKS was built for HCC prognostic prediction and clinical utilities. Drug targets and novel compounds were then identified for high-NKS groups. RAC1 was confirmed as the hub gene in the NKS genes. RAC1 was upregulated in HCC tumors and positively correlated with shorter survival time. RAC1 overexpression in NK-92 cells facilitated the cancer-killing capacity by the anticancer cytotoxic effectors and the upregulated NKG2D. The survival time of PDX-bearing mice was also prolonged upon NK-92RAC1 cells. Mechanistically, RAC1 interacted with STAT3 and facilitated its activation, thereby enabling its binding to the promoter region of NKG2D and functioning as a transcriptional regulator in NK-92 via molecular docking, Co-IP assay, CHIP and luciferase experiments. Collectively, our study describes a novel function of RAC1 in potentiating NK cell-mediated cytotoxicity against HCC, highlighting the clinical utilities of NKS score and RAC1high NK cell subset in HCC immunotherapy.


Asunto(s)
Carcinoma Hepatocelular , Células Asesinas Naturales , Neoplasias Hepáticas , Subfamilia K de Receptores Similares a Lectina de Células NK , Factor de Transcripción STAT3 , Proteína de Unión al GTP rac1 , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Proteína de Unión al GTP rac1/genética , Proteína de Unión al GTP rac1/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Animales , Ratones , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Inmunoterapia/métodos , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Masculino , Pronóstico , Ensayos Antitumor por Modelo de Xenoinjerto , Femenino
4.
Cell Signal ; 117: 111072, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38307306

RESUMEN

BACKGROUND: Cuproptosis is a novel form of cell death that exhibits close association with mitochondrial respiration and occurs through distinct mechanisms compared to previously characterized forms of cell death. However, the precise impact of cuproptosis-associated genes (CAGs) on prognosis, immune profiles, and treatment efficacy in hepatocellular carcinomas (HCC) remains poorly understood. METHODS: A comprehensive analysis of CAGs in hepatocellular carcinoma (HCC) prognosis was conducted using genomic data from HCC patients. Consensus clustering analysis was performed to determine molecular subtypes related to cuproptosis in HCC. The single-sample gene set enrichment analysis (ssGSEA) algorithm was applied to quantify the infiltration levels of immune cells, while the "ESTIMATE" package was employed to calculate tumor purity, stromal scores, and immune scores in the tumor microenvironment (TME). Principal component analysis (PCA) algorithm was utilized to construct a risk score related to CAGs. Finally, CCK8, wound healing, Transwell migration/invasion, EDU and xenograft model were employed to explore the potential oncogenic role of MTF1. RESULTS: Three distinct patterns of cuproptosis modification were identified, each associated with unique functional enrichments, clinical characteristics, immune cell infiltration, immune checkpoints, tumor microenvironment (TME), and prognosis. A CAGs-related risk score (Cuscore) was developed to predict prognosis in TCGA and validated in GSE76427 and ICGC datasets. Notably, patients with a low Cuscore had better prognoses and were more likely to benefit from immunotherapy.Additionally, the high Cuscore group in HCC also revealed three potential therapeutic targets (TUBA1B, CDC25B, and CSNK2A1) as well as several therapeutic compounds. Moreover, the experiment measured the expression levels of six prognosis-related CAGs, wherein knockdown of MTF1 exhibited suppression of proliferation, invasion, and migration formation in HCC cell lines. CONCLUSION: The findings have enhanced our comprehension of the cuproptosis characteristics in HCC, and stratification based on CuScore may potentially enhance the prediction of patients' prognosis and facilitate the development of effective and innovative treatment strategies.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Algoritmos , Muerte Celular , Línea Celular , Microambiente Tumoral/genética , Apoptosis
5.
Aging (Albany NY) ; 15(14): 7308-7323, 2023 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-37506248

RESUMEN

Pancreatic cancer is one of the most lethal malignancies worldwide. Acquiring infinite proliferation ability is a key hallmark and basis of tumorigenesis. NOP14 is an identified ribosome biogenesis protein that plays potential roles in cell proliferation. However, the function and molecular mechanism of NOP14 remain ambiguous in most human cancers. In this study, we first investigated the subcellular localization and expression of NOP14 by multiple quantitative assays in pancreatic cancer. We confirmed that NOP14 was mainly localized in nucleolus in human pancreatic cancer cells. Then we studied the regulatory effects of this nucleolus protein on tumor cell proliferation in vitro. NOP14 was demonstrated to play a dominant pro-proliferation role in pancreatic cancer. Furthermore, we identified miR17-5p as a downstream target of NOP14. Transfection of miR17-5p mimics or inhibitors rescued the down- or upregulated effect of NOP14 on cell proliferation by regulating expression of P130. In addition, NOP14 induced expression of transcription factor E2F4 independent of miR17-5p/P130 signaling, which simultaneously activated a set of targeted genes, such as CCNE1, PIM1, AKT1 etc., to promote tumor proliferation. These findings might provide novel insights for better understanding the diverse function of NOP14 in human malignancies to develop new strategies for targeted therapy.


Asunto(s)
MicroARNs , Neoplasias Pancreáticas , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Línea Celular Tumoral , Neoplasias Pancreáticas/patología , MicroARNs/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Factor de Transcripción E2F4/genética , Factor de Transcripción E2F4/metabolismo , Neoplasias Pancreáticas
6.
Front Immunol ; 14: 1093716, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37006239

RESUMEN

Background: Programmed cell death protein 1 (PD-1) receptor has two ligands,programmed death-ligand 1 (PD-L1) and PD-L2. When compared with PD-L1, PD-L2 has not received much attention, and its role remains unclear. Methods: The expression profiles of pdcd1lg2 (PD-L2-encoding gene) mRNA and PD-L2 protein were analyzed using TCGA, ICGC, and HPA databases. Kaplan-Meier and Cox regression analyses were used to assess the prognostic significance of PD-L2. We used GSEA, Spearman's correlation analysis and PPI network to explore the biological functions of PD-L2. PD-L2-associated immune cell infiltration was evaluated using the ESTIMATE algorithm and TIMER 2.0. The expressions of PD-L2 in tumor-associated macrophages (TAMs) in human colon cancer samples, and in mice in an immunocompetent syngeneic setting were verified using scRNA-seq datasets, multiplex immunofluorescence staining, and flow cytometry. After fluorescence-activated cell sorting, flow cytometry and qRT-PCR and transwell and colony formation assays were used to evaluate the phenotype and functions of PD-L2+TAMs. Immune checkpoint inhibitors (ICIs) therapy prediction analysis was performed using TIDE and TISMO. Last, a series of targeted small-molecule drugs with promising therapeutic effects were predicted using the GSCA platform. Results: PD-L2 was expressed in all the common human cancer types and deteriorated outcomes in multiple cancers. PPI network and Spearman's correlation analysis revealed that PD-L2 was closely associated with many immune molecules. Moreover, both GSEA results of KEGG pathways and GSEA results for Reactome analysis indicated that PD-L2 expression played an important role in cancer immune response. Further analysis showed that PD-L2 expression was strongly associated with the infiltration of immune cells in tumor tissue in almost all cancer types, among which macrophages were the most positively associated with PD-L2 in colon cancer. According to the results mentioned above, we verified the expression of PD-L2 in TAMs in colon cancer and found that PD-L2+TAMs population was not static. Additionally, PD-L2+TAMs exhibited protumor M2 phenotype and increased the migration, invasion, and proliferative capacity of colon cancer cells. Furthermore, PD-L2 had a substantial predictive value for ICIs therapy cohorts. Conclusion: PD-L2 in the TME, especially expressed on TAMs, could be applied as a potential therapeutic target.


Asunto(s)
Neoplasias del Colon , Animales , Humanos , Ratones , Antígeno B7-H1 , Carcinógenos , Neoplasias del Colon/genética , Pronóstico , Microambiente Tumoral
7.
Front Oncol ; 13: 1067414, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36959789

RESUMEN

Purpose: Total laparoscopic anterior resection (tLAR) has been gradually applied in the treatment of rectal cancer (RC). This study aims to develop a scoring system to predict the surgical difficulty of tLAR. Methods: RC patients treated with tLAR were collected. The blood loss and duration of excision (BLADE) scoring system was built to assess the surgical difficulty by using restricted cubic spline regression. Multivariate logistic regression was used to evaluate the effect of the BLADE score on postoperative complications. The random forest (RF) algorithm was used to establish a preoperative predictive model for the BLADE score. Results: A total of 1,994 RC patients were randomly selected for the training set and the test set, and 325 RC patients were identified as the external validation set. The BLADE score, which was built based on the thresholds of blood loss (60 ml) and duration of surgical excision (165 min), was the most important risk factor for postoperative complications. The areas under the curve of the predictive RF model were 0.786 in the training set, 0.640 in the test set, and 0.665 in the external validation set. Conclusion: This preoperative predictive model for the BLADE score presents clinical feasibility and reliability in identifying the candidates to receive tLAR and in making surgical plans for RC patients.

8.
Langenbecks Arch Surg ; 408(1): 41, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36652004

RESUMEN

BACKGROUND: Laparoscopic total mesorectal excision (LaTME) is a technically challenging for ultralow-lying rectal cancer in obese male patients. Herein, we introduced modified serial techniques "ASTRO" to facilitate LaTME, and the short-term outcomes were presented. METHODS: A prospective study (NCT05067413) was conducted between December 2020 and January 2022. The modified serial surgical techniques "ASTRO" included 5 key steps: (1) Anterior peritoneal reflection (APR) dissection at the highest line along with a "n"-shaped membrane bridge; (2) suspending the APR with a purse-string suture through the bladder peritoneum to enlarge the operating space of the anterior rectal wall; (3) traction and counter-traction continuously of the rectum applied with a cotton tape around the rectum; (4) resection of the pelvic rectum on tripartition, followed by the sequence of "posterior > anterior > lateral" principle; and (5) the trans-anterior Obturator nerve gateway was adapted to transect the distal rectum. The operative data and postoperative short-term outcomes were collected. RESULTS: Twenty-four consecutive patients underwent this procedure successfully. The average body mass index (BMI) was 29.9±1.3. The average of tumor height from anal verge was 4.0 cm (range, 3.0-4.5 cm). The median operating time and blood loss was 217 min (range, 165-420 min) and 50 ml (range, 20-100 ml) respectively. The anterior operation space at the midsagittal plane of the pelvis inlet was increased by 2.0 ± 0.3 cm. The calculated dominant angle was 20 ± 3°. The length of stapling line was 6.8 ± 1.0 cm with 11 cases by one cartridge and 13 cases by 2 cartridges. Eight patients developed postoperative complications including 4 with anastomosis leakage (16.7%), 2 with urinary retention (8.3%), one with anastomotic stenosis (4.2%) and one with ileus (4.2%). All the complications were relatively mild and the patients recovered well. CONCLUSION: Modified serial techniques "ASTRO" could expand the operating space and facilitate LaTME in obese male patients, thereby reducing the risk of conversion to open and transanal dissection.


Asunto(s)
Laparoscopía , Neoplasias del Recto , Humanos , Masculino , Estudios Prospectivos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Recto/cirugía , Laparoscopía/métodos , Canal Anal/cirugía , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento
9.
Front Oncol ; 12: 933777, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36338709

RESUMEN

Background: Lymphangiomatosis is an extremely rare disease with potential soft tissue, bone, and spleen involvement, which can be characterized by lymphangioma. Only a few cases of colon and mesenteric lymphangiomatosis have been reported. We report a case presenting with fatigue, periumbilical pain, and intermittent bloody stools. This patient underwent a series of examinations. Exploratory laparoscopy, in particular, yielded very valuable images and videos for this disease, which can provide evidence for the diagnosis of this disease. Case summary: The current patient had fatigue, periumbilical pain, and intermittent bloody stools. Colonoscopy indicated numerous variable-sized hyaline cysts in the colon. Submucosal puncture was performed during colonoscopy. The patient was readmitted to the hospital due to periumbilical pain. B-ultrasound and abdominal CT showed multiple hypoechoic nodules in the mesenteric area. Exploratory laparoscopy was performed, and histopathology revealed that D2-40 was positive. Based on auxiliary examination and laparoscopic biopsy, surgeons and pathologists reached the diagnosis of mesenteric lymphangiomatosis. Conclusion: Clinicians need to comprehensively improve their knowledge of lymphangiomatosis, and the combination of clinical symptoms, histological characteristics, and colonoscopy biopsy findings should be considered to improve lymphangiomatosis diagnosis, thereby reducing misdiagnosis. Core tip: Colon and mesenteric lymphangiomatosis is an extremely uncommon benign condition of unknown etiology and pathogenesis in adult patients. We report a case of mesenteric lymphangiomatosis in a 37-year-old woman who presented with fatigue, periumbilical pain, and intermittent bloody stools, as well as lesions in the kidney, spleen, and bones. This case provides new insights into the diagnosis and treatment of this disease.

10.
J Orthop Surg Res ; 15(1): 458, 2020 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-33023628

RESUMEN

BACKGROUND: Microsurgical toe-to-hand transfer is a gold standard when it comes to repairing a thumb defect. Great toenail flap, thumbnail valva flap, free great toe, and second toe transplantation are the common methods in thumb reconstruction. Second toe transplantation achieves good function, but poor esthetics. Great toe transplantation achieves better esthetics, but hindered walking, due to the foot's loss of the great toe and moreover suboptimal thumb function. It is difficult to maintain both functional and esthetic satisfaction in thumb reconstruction. METHODS: We experimented with three different methods of toe to hand transfer. From October 2009 to July 2019, 30 patients with traumatic thumb defects received one of 3 different kinds of thumb reconstruction in our clinic according to their level of amputation. Divided evenly into three groups of ten, group one received a great toe transplantation, group two received a second toe transplantation, and group three received a combined great toenail flap and second toe phalanx transplantation. Each of the patients' thumbs had different levels of amputation at the metatarsophalangeal joint (MPJ) or distal interphalangeal joint (DIPJ). RESULTS: One patient suffered from a partial flap necrosis and received a groin flap to cover the defect. No other thumbs had any complications. The functional and esthetic results of both the donor and the recipient sites were satisfactory. Results show that, for patients with traumatic thumb defects, the combined transfer of flap and second toe phalanx was the best option. CONCLUSIONS: Compared to the great toe or second toe transfer, combined free transfer of the great toenail flap and second toe phalanx achieved a substantially better functional and esthetic result in the thumb reconstruction.


Asunto(s)
Colgajos Tisulares Libres/trasplante , Microcirugia/métodos , Procedimientos de Cirugía Plástica/métodos , Pulgar/cirugía , Dedos del Pie/cirugía , Dedos del Pie/trasplante , Adolescente , Adulto , Amputación Quirúrgica/métodos , Estética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pulgar/lesiones , Falanges de los Dedos del Pie/cirugía , Falanges de los Dedos del Pie/trasplante , Adulto Joven
11.
Oncotarget ; 11(14): 1203-1217, 2020 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-32292571

RESUMEN

Food-derived plant microRNAs are suggested to control human genes by "cross-kingdom" regulation. We examined microRNAs in sprouts from Brassica rapa sylvestris, known as broccoletti, which are widely used as sulforaphane supplements, and assessed their influence on pancreatic cancer. RNA was isolated from 4-day-old sprouts, followed by deep sequencing and bioinformatic analysis. We identified 2 new and 745 known plant microRNA sequences in the miRbase database and predicted 15,494 human target genes and 76,747 putative 3'-UTR binding sites in these target genes. The most promising candidates were the already known microRNA sequence bra-miR156g-5p and the new sequence Myseq-330, both with predicted human target genes related to apoptosis. The overexpression of the respective oligonucleotides by lipofection did not alter the viability, apoptosis, clonogenicity, migration or associated protein expression patterns in pancreatic cancer cells. These data demonstrate that broccoletti sprouts contain microRNA sequences with putative binding sites in human genes, but the sequences evaluated here did not affect cancer growth. Our database of broccoletti-derived microRNA sequences provides a valuable tool for future analysis.

12.
Clin Exp Pharmacol Physiol ; 47(7): 1311-1319, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32124474

RESUMEN

Cancer stem cells have been identified as the major cause of cancer initiation and progression. To investigate the effects of puerarin 6″-O-xyloside (PXY), derived from Pueraria lobata (Willd.) Ohwi, on lung cancer stem cells, we enriched and identified a subpopulation of lung cancer stem-like cells (LCSLCs) derived from lung adenocarcinoma A549 cells with traits including high self-renewal and invasive capability in vitro, elevated tumourigenicity in vivo, and high expression of stem cell markers CD44, CD133 and aldehyde dehydrogenase 1 (ALDH1). We found that PXY could impair cell viability, suppress self-renewal and invasive capability, and decrease CD133, CD44 and ALDH1 mRNA expression in LCSLCs in a dose-dependent manner. Furthermore, we showed that PXY suppressed the self-renewal and invasive capability of LCSLCs at least in part through suppressing the activation of Akt/c-Myc signalling. In conclusion, PXY can block the traits of LCSLCs, indicating that PXY may be a candidate compound for lung adenocarcinoma therapy via eliminating LCSLCs.


Asunto(s)
Autorrenovación de las Células/efectos de los fármacos , Isoflavonas/farmacología , Neoplasias Pulmonares/patología , Células Madre Neoplásicas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Transducción de Señal/efectos de los fármacos , Células A549 , Humanos , Isoflavonas/química , Invasividad Neoplásica , Células Madre Neoplásicas/patología
13.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(1): 16-20, 2020 Jan 15.
Artículo en Chino | MEDLINE | ID: mdl-31939228

RESUMEN

The 8th World International Symposium on the Diabetic Foot (ISDF) Conference which was sponsored by the International Working Group on Diabetic Foot (IWGDF) was held in the Hague between May 22nd and May 25th, 2019. The conference issued the 2019 IWGDF guidelines on the prevention and management of diabetic foot disease. The update to the 2015 edition of the guidelines involves the following 6 chapters: prevention of foot ulcers in patients with diabetes; offloading foot ulcers in patients with diabetes; diagnosis, prognosis, and management of peripheral arterial disease in patients with a foot ulcer and diabetes; diagnosis and treatment of foot infection in patients with diabetes; interventions to enhance healing of foot ulcers in patients with diabetes; classification of diabetic foot ulcers. This guideline has been changed more than the previous edition. In this paper, the guidelines will be interpreted to provide cutting-edge information for domestic diabetic foot researchers.


Asunto(s)
Pie Diabético , Úlcera del Pie , Humanos , Cicatrización de Heridas
14.
Cancer Lett ; 452: 203-212, 2019 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-30910589

RESUMEN

NF-κB contributes to the aggressiveness of pancreatic ductal adenocarcinoma (PDA), which is counteracted by the bioactive agent sulforaphane. We investigated sulforaphane-induced microRNA signaling and its influence on progression features. Using established cell lines, microRNA and gene arrays, we predicted miR-365a as the top candidate for the sulforaphane-induced inhibition of the NF-κB subunit c-Rel. The lipofection of miR-365a-3p mimics inhibited the luciferase activity of a c-Rel 3'-UTR construct, as well as c-Rel expression, NF-κB activity, and tumor viability, migration, and clonogenicity, whereas apoptosis was induced. In vivo, miR-365a-3p reduced the volume of tumor xenografts and the expression of progression markers. In a tissue array, the expression of miR-365a-3p was absent in almost all 91 malignant tissues but not in 5 normal tissues, thus confirming the previous results. Our observations suggest that sulforaphane-induced miR-365a-3p expression inhibits NF-κB activity by downregulating c-Rel, which prevents the progression of PDA.


Asunto(s)
Carcinoma Ductal Pancreático/patología , MicroARNs/genética , Neoplasias Pancreáticas/patología , Proteínas Proto-Oncogénicas c-rel/metabolismo , Factor de Transcripción ReIA/metabolismo , Animales , Anticarcinógenos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Ductal Pancreático/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Embrión de Pollo , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Isotiocianatos/farmacología , MicroARNs/efectos de los fármacos , Neoplasias Pancreáticas/genética , Transducción de Señal , Sulfóxidos , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Cancer Lett ; 426: 14-24, 2018 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-29627496

RESUMEN

Pancreatic ductal adenocarcinoma (PDA) has poor therapeutic options. Recent patient studies indicate that cholesterol-lowering statins have anti-tumor capacities. We examined several established and primary PDA and normal cell lines as well as PDA patient tissues (n = 68). We found that simvastatin inhibited viability, stemness, tumor growth and metastasis and that it enhanced the efficacy of gemcitabine. These changes were associated with modulation of Shh-related gene expression. Overexpression of Shh prevented the anti-cancer effect of simvastatin, and inhibition of Shh mimicked the simvastatin effect. In PDA tissues, expression levels of Shh, downstream mediators of Shh and progression markers, namely, cMet, CxCR4 and Vimentin, were lower when patients were prescribed statin medication prior to surgery. These results suggested that statins are cost effective and well-tolerated drugs for prevention and co-treatment of PDA.


Asunto(s)
Carcinoma Ductal Pancreático/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Proteínas Hedgehog/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Neoplasias Pancreáticas/tratamiento farmacológico , Simvastatina/administración & dosificación , Animales , Carcinoma Ductal Pancreático/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Embrión de Pollo , Desoxicitidina/administración & dosificación , Desoxicitidina/farmacología , Sinergismo Farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Trasplante de Neoplasias , Neoplasias Pancreáticas/metabolismo , Transducción de Señal/efectos de los fármacos , Simvastatina/farmacología , Gemcitabina
16.
Artículo en Chino | MEDLINE | ID: mdl-27062854

RESUMEN

OBJECTIVE: To investigate the effect of simulated in vivo physiological environment severed limb fostering system applying remote ischemic conditioning (RIC) perfusion on preserving severed limb. METHODS: Eighteen adult Bama mini pigs (24-30 kg in weight) were randomly divided into 3 groups (n = 6). No ischemic treatment was given in group A as normal control group; the right lower limbs were completely amputated and preserved at room temperature for 3 hours to make ischemic models in groups B and C, and then the severed limbs were put into the simulated in vivo physiological environment severed limb fostering system. Continuous blood perfusion was performed in group B, and continuous blood perfusion was performed after RIC perfusion in group C. After 8 hours of perfusion, the skeletal muscle samples were harvested for the morphology observation by transmission electron microscopy. The protein levels of B-cell lymphoma-2 (Bcl-2) and Caspase-3 were detected by Western blot. The content of cytochrome C in both mitochondria and cytoplasm was determined by ELISA. RESULTS: Transmission electron microscopy results illustrated that the muscle fibers arranged more orderly and the mitochondria swelling was slighter in group C than group B. Western blot analysis showed that the protein levels of Bcl-2 and Caspase-3 were significantly higher in groups B and C than group A (P < 0.05); the protein level of Bcl-2 significantly increased and the protein level of Caspase-3 significantly decreased in group C when compared with those in group B (P < 0.05). ELISA detection implicated that mitochondrial cytochrome C significantly reduced and cytosolic cytochrome C significantly increased in group B when compared with those in groups A and C (P < 0.05), but no significant difference was found between group A and group C (P > 0.05). CONCLUSION: The ischemia/reperfusion-induced injury to skeletal muscle could be considerably inhibited by RIG perfusion. The simulated in vivo physiological environment severed limb fostering system applying RIC perfusion can significantly prolong the severed limb preserving time.


Asunto(s)
Extremidades/fisiopatología , Precondicionamiento Isquémico/métodos , Mitocondrias Musculares/metabolismo , Mitocondrias/metabolismo , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Perfusión/métodos , Animales , Miembro Posterior , Precondicionamiento Isquémico/efectos adversos , Mitocondrias Musculares/patología , Músculo Esquelético/patología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Porcinos , Porcinos Enanos , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
17.
Cancer Lett ; 373(1): 130-137, 2016 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-26828016

RESUMEN

Pancreatic ductal adenocarcinoma (PDA) is among the most lethal malignancies and resistance to chemotherapy prevents the therapeutic outcome. MicroRNAs provide a novel therapeutic strategy. Here, the established and primary human PDA cell lines PANC-1, AsPC-1, MIA-PaCa2, AsanPaCa, BxPC-3 and three gemcitabine-resistant subclones were examined. A gene expression profiling revealed that the ribonucleotide reductase M1 (RRM1) was upregulated in gemcitabine-resistant cells, which was confirmed by qRT-PCR, Western blot analysis and immunostaining. Inhibition of RRM1 by lipotransfection of siRNA reduced its expression and reversed gemcitabine resistance. The expression of RRM1 correlated to gemcitabine resistance in vitro and was higher in malignant patient pancreas tissue compared to non-malignant pancreas tissue. By microRNA expression profiling, we identified microRNA-101-3p as top-downregulated candidate. Lipotransfection of microRNA-101-3p mimics inhibited the expression of RRM1, reduced the luciferase activity of its 3'UTR and sensitized for gemcitabine-induced cytotoxicity. These results underline the relevance of microRNA-101-3p-driven regulation of RRM1 in drug resistance and suggest the co-delivery of microRNA-101-3p and gemcitabine for more effective therapy outcome.


Asunto(s)
Antimetabolitos Antineoplásicos/farmacología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Resistencia a Antineoplásicos , MicroARNs/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Proteínas Supresoras de Tumor/metabolismo , Regiones no Traducidas 3' , Sitios de Unión , Carcinoma Ductal Pancreático/enzimología , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Desoxicitidina/farmacología , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/genética , Perfilación de la Expresión Génica/métodos , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Neoplasias Pancreáticas/enzimología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Interferencia de ARN , Ribonucleósido Difosfato Reductasa , Factores de Tiempo , Transfección , Proteínas Supresoras de Tumor/genética , Regulación hacia Arriba , Gemcitabina
18.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 28(8): 1047-50, 2014 Aug.
Artículo en Chino | MEDLINE | ID: mdl-25417324

RESUMEN

OBJECTIVE: To summarize the research progress of severed limb preservation by perfusion and to analyze difference in effect of severed limb preservation by different perfusate. METHODS: The domestic and foreign related literature about severed limb preservation by perfusion was extensively reviewed and analyzed. RESULTS: Currently the main perfusate includes organ perfusate, free radical scavengers, energy mixture, blood substitutes, and whole blood. They can reduce the skeletal muscle's ischemia-reperfusion injury in different degrees. CONCLUSION: Different perfusate can reduce the skeletal muscle's ischemia-reperfusion injury in different degrees, but the best effect of perfusate and personalized preservation method need further study.


Asunto(s)
Extremidades , Preservación de Órganos/tendencias , Perfusión , Daño por Reperfusión/prevención & control , Criopreservación , Humanos , Músculo Esquelético
19.
Artículo en Chino | MEDLINE | ID: mdl-24171361

RESUMEN

OBJECTIVE: To evaluate the effectiveness of anterolateral thigh and groin conjoined flap in emergent repair of ultra-long complex tissue defects in forearm and hand. METHODS: Between February 2009 and October 2011, 6 patients with complex tissue defect of dorsal forearm and hand were in adminsion. There were 5 male and 1 female with an average age of 38.5 years (range, 32-47 years). Injury reasons included machine injury in 5 cases and traffic accident injury in 1 case. Injury to admission time was from 3 to 16 hours (mean, 6 hours). All case were single limb injury, including right forearm and hand injury in 4 cases and left forearm and hand injury in 2 cases. The wound area was from 36 cm x 9 cm to 48 cm x 12 cm. The type of associated injury included elbow dislocation associated with open injury in 2 cases; fractures of the radial, ulnar, and metacarpal bone in 4 cases; defects of wrist dorsal skin and extensor tendons of fingers and wrist in 5 cases; and defects of ulnar artery and ulnar nerve in 1 case. The anterolateral thigh and groin conjoined free flaps were used to repair defects in the forearm and hand in emergency. The area of flap was from 36 cm x 9 cm to 48 cm x 12 cm. Meanwhile the partial functional reconstruction was performed. The donor site was repaired by skin grafts. RESULTS: The anastomotic embolization of vascular pedicle and arteria interossea dorsalis occurred in 1 case, purulent secretion under the flap in 1 case, which were cured after symptomatic treatment; the skin flaps completely survived, and primary healing of the wounds were obtained in the other cases. The donor skin grafts survived in 2 cases, and partial necrosis of the skin graft of lower abdominal occurred in 4 cases, and healed after changing dressing. All of the 6 patients were followed up 3 to 18 months (mean, 10 months). The appearance and texture of the flaps were good. The protective sensation was recovered in 2 cases followed up for more than 14 months; no sensory recovery was observed in the other cases. At last follow-up, according to the upper extremity functional evaluation standard by Hand Surgery Branch of Chinese Medical Association, the results were excellent in 1 case, good in 4 cases, and poor in 1 case, and the excellent and good rate was 83.3%. CONCLUSION: It could get a good short-term effectiveness to use the anterolateral thigh and groin conjoined flap for emergent repair of the ultra-long and complex tissue defects in forearm and hand.


Asunto(s)
Traumatismos del Antebrazo/cirugía , Traumatismos de la Mano/cirugía , Procedimientos de Cirugía Plástica/métodos , Traumatismos de los Tejidos Blandos/cirugía , Colgajos Quirúrgicos , Adulto , Femenino , Estudios de Seguimiento , Ingle/cirugía , Humanos , Masculino , Persona de Mediana Edad , Fracturas del Radio/cirugía , Recuperación de la Función , Trasplante de Piel/métodos , Colgajos Quirúrgicos/irrigación sanguínea , Transferencia Tendinosa , Muslo/cirugía , Resultado del Tratamiento , Cicatrización de Heridas
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...