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OBJECTIVE: To investigate the effect of Polyetheretherketone (PEEK) rod semi-rigid pedicle screw fixation system in lumbar spine non-fusion surgery. METHODS: A total of 74 patients with tow-level lumbar degenerative diseases who underwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group. In the PEEK rod group, there were 34 patients, including 13 males and 21 females, aged from 51 to 79 years old with an average of (62.4±6.8) years old;There were 1 patient of L1-L3 segments, 7 patients of L2-L4 segments, 20 patients of L3-L5 segments and 6 patients of L4-S1 segments. In the titanium rod group, there were 40 patients, including 17 males and 23 females, aged from 52 to 81 years old with an average of (65.2±7.3) years old;There were 3 patient of L1-L3 segments, 11 patients of L2-L4 segments, 19 patients of L3-L5 segments and 7 patients of L4-S1 segments. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage was recorded. The visual analogue scale (VAS) for low back pain and Oswestry disability index (ODI) were compared in preoperatively and postoperatively(3 months, 12 months and last follow-up) between two groups. The change of range of motion (ROM) was observed by flexion and extension x-ray of lumbar. RESULTS: All patients successfully completed the operation. The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6) months. The operative time (142.2±44.7) min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group [(160.7±57.3) minã(212.8±85.4) ml](P<0.05). There was no significant differences in postoperative drainage between the two groups (P>0.05). At the final follow-up visit, in PEEK group and titanium group VAS of low back pain[(0.8±0.4) points vs (1.0±0.5) points], VAS for leg pain [ (0.7±0.4) points vs (0.8±0.5) points] and ODI [(9.8±1.6)% vs (12.1±1.5)%] were compared with preoperative [ (5.8±1.1) points vs (6.0±1.1)points], [ (7.2±1.7) points vs (7.0±1.6) points], [(68.5±8.9)% vs(66.3±8.2)%] were significantly different(P<0.05). There was no significant difference in VAS scores between the two groups at each postoperative time point (P>0.05). At 3 months after surgery, there was no difference in ODI between the two groups (P>0.05). There were significant differences in ODI between PEEK group and titanium rod group at 12 months [(15.5±2.1)% vs (18.4±2.4)%] and at the last follow-up [(9.8±1.6)% vs (12.1±1.5)%] (P<0.05). The total range of motion (ROM) of lumbar decreased in both groups after surgery. At 12 months after surgery and the last follow-up, the PEEK group compared with the titanium rod group, the total range of motion of lumbar was statistically significant (P<0.05). The range of motion (ROM) of the fixed segments decreased in both groups after surgery. The ROM of the fixed segments in PEEK group decreased from (9.5±4.6)° to (4.1±1.9)° at the last follow-up (P<0.05), which in the titanium rod group was decreased from (9.8±4.3)°to (0.9±0.5)° at the last follow-up (P<0.05). The range of motion (ROM) of upper adjacent segment increased in both groups, there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up, (P<0.05). There was no screw loosening and broken rods in both groups during the follow-up period. CONCLUSION: The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment, showing comparable short-term clinical efficacy to titanium rod fusion. PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degenerative diseases, and its long-term efficacy needs further follow-up observation.
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Benzofenonas , Cetonas , Vértebras Lombares , Parafusos Pediculares , Polietilenoglicóis , Polímeros , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Vértebras Lombares/cirurgia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Leukemia stem cells (LSCs) are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia (AML), as they are protected by the bone marrow microenvironment (BMM) against conventional therapies. Gossypol acetic acid (GAA), which is extracted from the seeds of cotton plants, exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2. AIM: To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism. METHODS: In this study, LSCs were magnetically sorted from AML cell lines and the CD34+CD38- population was obtained. The expression of leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) and forkhead box M1 (FOXM1) was evaluated in LSCs, and the effects of GAA on malignancies and mitochondrial function were measured. RESULTS: LRPPRC was found to be upregulated, and GAA inhibited cell proliferation by degrading LRPPRC. GAA induced LRPPRC degradation and inhibited the activation of interleukin 6 (IL-6)/janus kinase (JAK) 1/signal transducer and activator of transcription (STAT) 3 signaling, enhancing chemosensitivity in LSCs against conventional chemotherapies, including L-Asparaginase, Dexamethasone, and cytarabine. GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC. Furthermore, GAA induced reactive oxygen species accumulation, disturbed mitochondrial homeostasis, and caused mitochondrial dysfunction. By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC, GAA resulted in the elimination of LSCs. Meanwhile, GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage. CONCLUSION: Taken together, the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.
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This paper investigates the intervention effect and mechanism of Banxia Xiexin Decoction(BXD) on colitis-associated colorectal cancer(CAC) infected with Fusobacterium nucleatum(Fn). C57BL/6 mice were randomly divided into a control group, Fn group, CAC group [azoxymethane(AOM)/dextran sulfate sodium salt(DSS)](AOM/DSS), model group, and BXD group. Except for the control and AOM/DSS groups, the mice in the other groups were orally administered with Fn suspension twice a week. The AOM/DSS group, model group, and BXD group were also injected with a single dose of 10 mg·kg~(-1) AOM combined with three cycles of 2.5% DSS taken intragastrically. The BXD group received oral administration of BXD starting from the second cycle until the end of the experiment. The general condition and weight changes of the mice were monitored during the experiment, and the disease activity index(DAI) was calculated. At the end of the experiment, the colon length and weight of the mice in each group were compared. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-2, IL-4, and IL-6 inflammatory factors in the serum. Immunohistochemistry(IHC) was used to detect the expression of Ki67, E-cadherin, and ß-catenin in the colon tissue. Western blot was used to detect the protein content of Wnt3a, ß-catenin, E-cadherin, annexin A1, cyclin D1, and glycogen synthase kinase-3ß(GSK-3ß) in the colon tissue. The results showed that compared with the control group, the Fn group had no significant lesions. The mice in the AOM/DSS group and model group had decreased body weight, increased DAI scores, significantly increased colon weight, and significantly shortened colon length, with more significant lesions in the model group. At the same time, the colon histology of the model group showed more severe adenomas, inflammatory infiltration, and cellular dysplasia. The levels of IL-4 and IL-6 in the serum were significantly increased, while the IL-2 content was significantly decreased. The IHC results showed low expression of E-cadherin and high expression of Ki67 and ß-catenin in the model group, with a decreased protein content of E-cadherin and GSK-3ß and an increased protein content of Wnt3a, ß-catenin, annexin A1, and cyclin D1. After intervention with BXD, the body weight of the mice increased; the DAI score decreased; the colon length increased, and the tumor decreased. The histopathology showed reduced tumor proliferation and reduced inflammatory infiltration. The levels of IL-6 and IL-4 in the serum were significantly decreased, while the IL-2 content was increased. Meanwhile, the expression of E-cadherin was upregulated, and that of Ki67 and ß-catenin was downregulated. The protein content of E-cadherin and GSK-3ß increased, while that of Wnt3a, ß-catenin, annexin A1, and cyclin D1 decreased. In conclusion, BXD can inhibit CAC infected with Fn, and its potential mechanism may be related to the inhibition of Fn binding to E-cadherin, the decrease in annexin A1 protein level, and the regulation of the Wnt/ß-catenin pathway.
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Anexina A1 , Neoplasias Associadas a Colite , Colite , Medicamentos de Ervas Chinesas , Camundongos , Animais , Colite/complicações , Colite/tratamento farmacológico , Colite/genética , beta Catenina/genética , beta Catenina/metabolismo , Ciclina D1/metabolismo , Fusobacterium nucleatum/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Antígeno Ki-67/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Camundongos Endogâmicos C57BL , Caderinas/metabolismo , Peso Corporal , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , AzoximetanoRESUMO
BACKGROUND: Colorectal cancer stem cells (CCSCs) are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer (CRC) patients. CCSCs are generally accepted to be important sources of CRC and are responsible for the progression, metastasis, and therapeutic resistance of CRC. Therefore, targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC. AIM: To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism. METHODS: CCSCs were enriched from CRC cell lines by in conditioned serum-free medium. Western blot, Aldefluor, transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs. The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis, colony formation, sphere formation, flow cytometry, and western blotting assessments in vitro and tumor growth, immunohistochemistry and immunofluorescence assessments in vivo. RESULTS: Compared with parental cells, sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumorigenesis, demonstrating that the CRC sphere cells displayed CSC features. VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells, as indicated by their proliferation, migration and clonality in vitro, and suppressed the tumor of CCSC-derived xenograft tumors in vivo. Besides, VX-509 suppressed the CSC characteristics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition (EMT) signaling in vitro. Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differentially expressed genes and CSC-related database information. VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression. Moreover, VX-509 reversed the dedifferentiation of CCSCs and inhibited the progression of EMT induced by Nodal overexpression. CONCLUSION: VX-509 prevents the EMT process in CCSCs by inhibiting the transcription and protein expression of Nodal, and inhibits the dedifferentiated self-renewal of CCSCs.
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BACKGROUND: Malignant melanoma (MM) has shown an increasing incidence worldwide, and a potential to metastasize to almost any part of the body. Clinically, MM with bone metastasis as the initial manifestation is extremely rare. Spinal metastatic MM can cause spinal cord or nerve root compression, resulting in severe pain and paralysis. Currently, the primary clinical treatments for MM are surgical resection in conjunction with chemotherapy, radiotherapy, and immunotherapy. CASE SUMMARY: Here, we report the case of a 52-year-old male who presented to the clinic with progressive low back pain and limited nerve function. No primary lesion or spinal cord compression was detected from computed tomography and magnetic resonance imaging of the lumbar vertebrae and positron emission tomography scan. A lumbar puncture biopsy confirmed the diagnosis of lumbar spine metastatic MM. Following surgical resection, the patient's quality of life improved, symptoms were relieved, and comprehensive treatment was initiated, which prevented recurrence. CONCLUSION: Spinal metastatic MM is clinically rare, and may cause neurological symptoms, including paraplegia. Currently, the clinical treatment plan consists of surgical resection in combination with chemotherapy, radiotherapy, and immunotherapy.
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BACKGROUND: Previous studies indicated that glucosamine supplements may have a general anticancer effect. This study aimed to assess whether the potential effect differs across different types of cancers in a large prospective cohort study. METHODS: All participants from the UK Biobank who were free of cancers and had complete information on glucosamine use at baseline were included and followed up from 2006 until 2021. Cox proportional hazards models were used to assess the associations between regular glucosamine use and different site-specific cancers. Subgroup analyses were performed to explore potential interactions. Several sensitivity analyses were conducted to assess the robustness of the main findings. RESULTS: A total of 450,207 eligible participants (mean age: 56.2 years; females: 53.3%) were included, of whom 84,895 (18.9%) reported regular glucosamine use at baseline. During a median of 12.5 years follow-up, glucosamine use was significantly associated with an increased risk of overall cancer [HR, 1.04; 95% confidence interval (CI), 1.01-1.06], skin cancer (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.07; 95% CI, 1.01-1.13), and with a reduced risk of lung cancer (HR, 0.88; 95% CI, 0.79-0.97) after adjusting for potential confounders. Statistical interaction was observed for gender, age, and education for the association of glucosamine use with overall cancer risk (all Pinteraction < 0.027). These results remained unchanged in the sensitivity analyses. CONCLUSIONS: Regular glucosamine use was associated with lower risk of lung cancer but higher risk of skin cancer, prostate cancer, and overall cancer. IMPACT: The roles of glucosamine use potentially differ in the development of different site-specific cancers.
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Neoplasias Pulmonares , Neoplasias da Próstata , Neoplasias Cutâneas , Masculino , Humanos , Pessoa de Meia-Idade , Glucosamina/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Suplementos Nutricionais , Neoplasias Pulmonares/prevenção & controleRESUMO
Programmed cell death 1 ligand (PD-L1) and its receptor (PD-1) are key molecules for immunoregulation and immunotherapy. PD-L1 binding PD-1 is an effective way to regulate T or B cell immunity in autoimmune diseases such as rheumatoid arthritis (RA). In our study, we overexpressed PD-L1 by constructing a recombinant of PD-L1-lentiviral vector, which was subsequently used to transfect mouse bone marrow mesenchymal stem cells (MBMMSCs) and significantly suppressed the development of collagen-induced arthritis (CIA) in DBA/1j mice. In addition, PD-L1-transfected MBMMSCs (PD-L1-MBMMSCs) ameliorated joint damage, reduced proinflammatory cytokine expression, and inhibited T and B cell activation. Furthermore, PD-L1-MBMMSCs decreased the number of dendritic cells and increased the numbers of regulatory T cells and regulatory B cells in joints of CIA mice. In conclusion, our results provided a potential therapeutic strategy for RA treatment with PD-L1-MBMMSC-targeted therapy.
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Artrite Experimental/terapia , Artrite Reumatoide/terapia , Antígeno B7-H1/administração & dosagem , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Linfócitos T Reguladores/imunologia , Animais , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Células Cultivadas , Modelos Animais de Doenças , Ativação Linfocitária , Masculino , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos DBARESUMO
Although the Mobi-C artificial disc and the ROI-C cervical cage have been widely used in the treatment of cervical degenerative disc diseases (CDDD), few reports addressed the features of combined application of both devices. This study is aimed at comparing the clinical and radiological outcomes of treating contiguous two-level CDDD using Mobi-C and ROI-C combined in a hybrid surgery (HS) with anterior cervical discectomy and fusion (ACDF) using ROI-C. We reviewed ninety-one patients who underwent HS (n = 48) or ACDF (n = 43) surgery for symptomatic contiguous two-level CDDD. >2 years' clinical and radiological outcomes were reviewed and evaluated retrospectively. At the last follow-up, significant improvement in the mean VAS, JOA, and NDI scores was found both in the HS and ACDF groups (p < 0.05), while the differences between groups were not significant (p > 0.05). The global range of motion (ROM) in the HS group was significantly larger than that in the ACDF group (p < 0.05). The local lordosis improved significantly after surgery in all patients (p < 0.05). Bone resorption and heterotopic ossification (HO) were found after surgery. The result showed that, for the selected patients, HS may provide an alternative approach for the treatment of contiguous two-level CDDD. HS also offers the benefit of both greater global ROM and greater ROM at the Mobi-C index level. Some degree of bone resorption may be an integral component in the early stage of bony fusion in the cage index level. Further studies and long-term follow-up are still needed.
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Vértebras Cervicais/cirurgia , Discotomia/métodos , Degeneração do Disco Intervertebral/cirurgia , Fusão Vertebral/métodos , Substituição Total de Disco/métodos , Adulto , Idoso , Vértebras Cervicais/diagnóstico por imagem , Discotomia/normas , Feminino , Seguimentos , Humanos , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Próteses e Implantes/normas , Estudos Retrospectivos , Fusão Vertebral/normas , Fatores de Tempo , Substituição Total de Disco/normas , Resultado do TratamentoRESUMO
BACKGROUND: Seed cells - mesenchymal stem cells (MSCs) - appear to be an attractive tool in the context of tissue engineering. Bone marrow represents the main source of MSCs for both experimental and clinical studies. However, the number limitation of bone marrow MSCs (BMSCs) and decreased function caused by proliferation make the search for adequate alternative sources of these cells for autologous and allogenic transplant necessary. OBJECTIVES: This study was aimed to investigate the roles of cajanine isolated from the extracts of Cajanus cajan L. Millsp. in the proliferation and differentiation of BMSCs, and to discover the mechanism of proliferation of BMSCs promoted by cajanine. MATERIAL AND METHODS: Bone marrow mesenchymal stem cells were cultured in high-glucose Dulbecco's Modified Eagle's Medium (DMEM) and osteogenic differentiation was induced by adding dexamethasone, ascorbic acid and ß-glycerophosphate supplements. Bone marrow MSCs were cultured in medium without cajanine or supplemented with cajanine. The information about the proliferation and osteogenic differentiation of BMSCs was collated. The osteogenic differentiation potential of BMSCs was also assessed at the 3rd passage by Von Kossa staining. To observe cell signal transduction changes of BMSCs after culturing them with cajanine for 24 h, the western blot analysis was performed to detect phosphorylated cell cycle proteins and activated cyclins. RESULTS: After osteogenic induction, the differentiation of BMSCs was accelerated by cajanine treatment. Osteogenesis markers were upregulated by cajanine treatment at both protein and mRNA levels. Cajanine obviously promoted the proliferation of BMSCs. After BMSCs were cultured with cajanine for 24 h, the cell cycle regulator proteins were phosphorylated or upregulated. CONCLUSIONS: Cajanine can promote the expansion efficiency of BMSCs, at the same time keeping their multi-differentiation potential. Cajanine can activate the cell cycle signal transduction pathway, thus inducing cells to enter the G1/S phase and accelerating cells entering the G2/M phase. This study can contribute to the development of cajanine-based drugs in tissue engineering.
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Células da Medula Óssea/efeitos dos fármacos , Cajanus/química , Proliferação de Células/efeitos dos fármacos , Dietilestilbestrol/análogos & derivados , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Diferenciação Celular , Células Cultivadas , Dietilestilbestrol/isolamento & purificação , Dietilestilbestrol/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Extratos Vegetais , Plantas Medicinais/químicaRESUMO
Phosphate-solubilizing bacteria (PSB) can promote plant growth by dissolving insoluble phosphate. Therefore, PSB may have the potential to improve the mobility of heavy metals in soils and enhance phytoextraction. This study isolated a few PSB strains that could dissolve CdCO3 and solid Cd in soil. Two typical PSB, namely, high- and low-Cd-mobilizing PSB (Pseudomonas fluorescens gim-3 and Bacillus cereus qh-35, respectively), were selected to analyze the metabolic profiles, metabolic pathways, and mechanisms of mobilization of insoluble Cd. A total of 34 metabolites secreted by the two PSB strains were identified. Gluconic acid was the main contributor to Cd dissolution (42.4%) in high-Cd-mobilizing PSB. By contrast, gluconic acid was not secreted in low-Cd-mobilizing PSB. Metabolic pathway analysis showed that gluconic acid was produced by the peripheral direct oxidation pathway. Hence, PSB with peripheral direct oxidation pathway were likely to have high-Cd-mobilizing capacity.
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Bacillus cereus/fisiologia , Cádmio/química , Gluconatos/química , Pseudomonas fluorescens/fisiologia , Poluentes do Solo/química , Redes e Vias Metabólicas , Fosfatos/química , Solo , Microbiologia do Solo , SolubilidadeRESUMO
Surgery-based multimodality therapies have been used to control the malignant effusion and its recurrence in malignant pleural mesothelioma (MPM). Hyperthermic intrathoracic chemotherapy (HITHOC) has been used in the treatment of malignant pleural mesothelioma, but the results were controversial. The aim of the current study was, therefore, to conduct a systematic review and meta-analysis on the effect of HITHOC on MPM therapy. After thorough searching of online databases, total 21 articles were included into qualitative systematic review and 5 of them were used to conduct qualitative meta-analysis. It was found that most of HITHOC was used in combination of surgical resection including extrapleural pneumonectomy or pleurectomy/decortication. Patients who received HITHOC had significantly longer median survival length compared to the patients without HITHOC (Hedges's g = 0.384 ± 0.105, 95% CI: 0.178â¼0.591, P < 0.001). In addition, HITHOC as palliative therapy was favored (Hedges's g = 0.591 ± 0.201, 95% CI: 0.196â¼0.967, P < 0.001) in terms of recurrence free interval. The findings of the current study suggested that HITHOC is one of the safe and effective therapies in prolonging patients' median survival time and extending recurrence free interval.
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Long non-coding RNAs (lncRNAs) have been identified as novel biomarkers for the diagnosis, staging and prognosis for gastric cancer. However, various studies have reported a series of significances based on different diagnostic values. Therefore, the current study performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of lncRNAs for gastric cancer, and to discuss lncRNA types and sources of heterogeneity. The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, EMBASE, the Chinese Biomedical Literature Database, the China Academic Journals Full-text Database and the Chinese Scientific Journals Database were systematically searched for potential studies. Studies were included if they were associated with lncRNAs, gastric cancer and reported diagnostic outcomes. Analysis of diagnostic values was used to summarize the overall test performance of lncRNAs. Ten studies were included in this meta-analysis. The ranges of the diagnostic value of lncRNAs for gastric cancer were as follows: Sensitivity was 0.45-0.83, and pooled sensitivity was 0.63; specificity was 0.60-0.93, and pooled specificity was 0.75; positive likelihood ratio was 1.80-6.92, and pooled positive likelihood ratio was 2.51; negative likelihood ratio was 0.23-0.67, and pooled negative likelihood ratio was 0.50; diagnostic odds ratio was 3.33-13.75, and pooled diagnostic odds ratio was 5.47. An overall area under the curve value of the summary receiver operating characteristic curve was 0.7550. LncRNAs did not have a high accuracy for identifying gastric cancer at present, but may be a useful screening tool for diagnosing gastric cancer due to their correlation with gastric cancer biological features. LncRNAs are potential biomarkers for gastric cancer if the screening strategy is altered, or they are combined with other biomarkers to diagnose gastric cancer.
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MicroRNA (miRNA) is a class of noncoding RNA, which targets mRNAs of interest and suppresses its expression by degradation or translational inhibition. miRNA (miR)125a and miR125b were previously demonstrated to translationally and transcriptionally inhibit the expression of p53. The observed downregulation of the protein level of p53 in cisplatintreated patients with nasopharyngeal carcinoma (NPC) indicates the association between cisplatin resistance, miR125a and miR125b. In the present study, through the detection of the expression levels of miR125a and miR125b, a significant upregulation of these miRs was demonstrated in cisplatintreated patients with NPC. As a consequence, the protein expression level of p53 decreased notably. To confirm the induction of miR125a and miR125b by treatment with cisplatin, a cisplatinresistant TW03 cell model (TW03/DDP) was constructed. As expected, in the TW03/DDP cells, the expression levels of miR125a and miR125b were upregulated, and this caused downregulation of p53. Ectopic expression of these miRNAs in the TW03 cell model sensitized TW03 to cisplatin by decreasing the protein expression levels of p53, whereas ectopic expression in the antisense oligos of these microRNAs demonstrated the opposite effect. In addition, the present demonstrated that the cisplatininduced expression of miR125a and miR125b inhibited cisplatininduced apoptosis in the TW03 cells by decreasing the protein expression levels of p53. Taken together, the present study revealed for the first time, to the best of our knowledge, that induction of the expression of miR125a and miR125b by treatment with cisplatin resulted in resistance to the cisplatin drug in the NPC cells.
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Antineoplásicos/farmacologia , Cisplatino/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Nasofaringe/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Adulto , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Nasofaringe/metabolismo , Nasofaringe/patologia , RNA Mensageiro/genéticaRESUMO
OBJECTIVE: To evaluate the clinical application of intraoperative electrophysiological monitoring in lumbosacral selective posterior rhizotomy for spastic cerebral palsy. METHODS: Total 372 dorsal roots of 89 patients underwent selective posterior rhizotomy at a single medical center. The dorsal roots from L3 to S1 were divided into rootlets and stimulated with a 1-second 50 Hz train. Motor responses were recorded by electromyography. Rootlets were assigned according to the extent of abnormal electrophysiological propagation, and grades of 3+ to 4+ were cut. If no electrical response was observed, the second criterion is the behavioral response (that is, muscle contraction in the legs or toes) assessed by the physical therapist, when rootlets were stimulated at the lowest threshold with a 1-second 50 Hz train. RESULTS: The rootlets of 340 dorsal roots were assigned according to the extent of abnormal electrophysiological propagation, 324 (83.5%) roots were assigned the maximally abnormal response of grade 3+ (76, 22.4%) or 4+ (248, 72.9%) in EMG monitoring and were cut. For no electrical response was observed, according to the second criterion, 48 roots were partially cut. It was also be found that free running EMG occurred earlier than stimulus triggered EMG, and identified "abnormal" rootlets on free running EMG monitoring was more easily and quickly than on stimulus triggered EMG. During the postoperative 2 weeks in hospital, there was a significant decrease in lower-limb spasticity and an increase in range of movement in all patients, and no one case occurred obvious loss of muscle strength, abnormity of sensory, or deterioration of bladder/bowel control. CONCLUSIONS: The spread of electromyography response to the contra lateral limb and/or upper extremity remains a valid criterion to define a "abnormal" posterior nerve rootlet that feeds into a disinhibited spinal circuit involved in uncontrolled spasticity. Intraoperative electrophysiological monitoring is reproducible and reliable for selection of "abnormal" rootlets.
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Paralisia Cerebral/cirurgia , Eletromiografia , Rizotomia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Monitorização Intraoperatória , Raízes Nervosas Espinhais/cirurgiaRESUMO
OBJECTIVE: To evaluate the efficacy and safety of modified FOLFIRI regimen in advanced colorectal cancer (CRC) patients refractory to fluoropyrimidine and oxaliplatin. METHODS: The modified FOLFIRI regimen consisted of intravenous infusion of irinotecan 180 mg/m2 d1 + LV 200 mg/m2 dl + 5-Fu 400 mg/m2 bolus dl plus 46-hour intravenous infusion of 5-Fu 2.4 g/m2, every 2 weeks as one cycle. The main selection criterion for this study was the advanced CRC refractory to fluoropyrimidine and oxaliplatin. RESULTS: Of the 80 evaluable patients for efficacy: 10 (12.5%) had a partial response, 51 (63.7%) stable disease, and 19 (23.8%) progressive disease. The median time to progression was 96 days. Safety analysis was based on the data of 83 evaluable patients. The most frequently observed grade 3 or 4 toxicities were neutropenia (24.1%), nausea/vomiting (8.4%), and diarrhea (2.4%). CONCLUSION: Modified FOLFIRI regimen is effective and well tolerated in patients with advanced colorectal cancer refractory to fluoropyrimidine and oxaliplatin.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Neoplasias do Colo/patologia , Diarreia/induzido quimicamente , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Estudos Prospectivos , Pirimidinas/uso terapêutico , Neoplasias Retais/patologia , Indução de Remissão , Falha de TratamentoRESUMO
OBJECTIVE: To evaluate the cartilage formation ability of allogeneic mesenchymal stem cells implanted into sheep joint cavity without the use of immunosuppressive therapy. METHODS: Allogeneic mesenchymal stem cells (MSCs) loaded onto porous beta-tricalcium phosphate ceramic (beta-TCP) were implanted into normal sheep joint cavity. A complete mismatch between donor stem cells and recipient sheep was confirmed by mixed lymphocyte reaction assays prior to implantation. Eight weeks after implantation, the implants were taken out for histological and immunohistochemical analysis. The histological results were compared with data derived from joint cavity implantation of autologous MSCs-ceramic composites and cell-free ceramics. The systemic immune response was evaluated by the analysis of recipient serum for production of antibodies against allogeneic cells. RESULTS: For implantation with allogeneic MSCs, no sign of adverse immune response was detected. Histologically, few inflammation cells infiltration occurred and no antibodies against allogeneic cells were detected. Neocartilage formation in implants loaded with either allogeneic or autologous mesenchymal stem cells was revealed by histochemical and immunohistochemical analysis. In implants without stem cells, no cartilage formation was detected. CONCLUSIONS: Allogeneic mesenchymal stem cells are capable of forming cartilage under the effect of joint cavity environment. Without the use of immunosuppressive therapy, allogeneic MSCs do not provoke an adverse immune response in vivo.