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Colorectal cancer (CRC) has emerged as the third most prevalent and second deadliest cancer worldwide. Metabolic reprogramming is a key hallmark of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) is over-expressed in multiple cancers, including CRC. Although the role of PHGDH in metabolism has been extensively investigated, its effects on CRC development remains to be elucidated. In the present study, it was demonstrated that PHGDH expression was significantly up-regulated in colorectal cancer. PHGDH expression was positively correlated with that of the aryl hydrocarbon receptor (AhR) and its target genes, CYP1A1 and CYP1B1, in CRC cells. Knockdown of PHGDH reduced AhR levels and activity, as well as the ratio of reduced to oxidized glutathione. The selective AhR antagonist stemregenin 1 induced cell death through reactive oxygen species-dependent autophagy in CRC cells. PHGDH knockdown induced CRC cell sensitivity to stemregenin 1 via the autophagy pathway. Our findings suggest that PHGDH modulates AhR signaling and the redox-dependent autophagy pathway in CRC, and that the combination of inhibition of both PHGDH and AhR may be a novel therapeutic strategy for CRC.
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Neoplasias Colorretais , Receptores de Hidrocarboneto Arílico , Humanos , Autofagia/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Fosfoglicerato Desidrogenase/deficiência , Fosfoglicerato Desidrogenase/genética , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismoRESUMO
Despite recent advances have been made in clinical treatments of breast cancer, the general prognosis of patients remains poor. Therefore, it is imperative to develop a more effective therapeutic strategy. Lysine demethylase 4B (KDM4B) has been reported to participate in breast cancer development recently, but its exact biological role in breast cancer remains unclear. Here, we observed that KDM4B was down-regulated in human primary BRCA tissues and the low levels of KDM4B expression were correlated with poor survival. Gain- and loss-of-function experiments showed that KDM4B inhibited the proliferation and metastasis of breast cancer cells. Besides, knockdown of KDM4B promoted the epithelial-mesenchymal transition (EMT) and cell stemness in breast cancer cells. Mechanistically, KDM4B down-regulates PHGDH by decreasing the enrichment of H3K36me3 on the promoter region of PHGDH. Knockdown of PHGDH could significantly reversed proliferation, migration, EMT, and cell stemness induced by KDM4B silencing in breast cancer cells. Collectively, we propose a model for a KDM4B/PHGDH axis that provides novel insight into breast cancer development, which may serve as a potential factor for predicting prognosis and a therapeutic target for breast cancer.
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Neoplasias da Mama , Humanos , Feminino , Regulação para Cima , Regulação para Baixo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismoRESUMO
Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5+ BMSCs and Tek+ BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5+ TEK+ ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5+ BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition.
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Células Endoteliais , Células-Tronco Mesenquimais , Camundongos , Animais , Medula Óssea , Camundongos TransgênicosRESUMO
Bone regeneration heavily relies on bone marrow mesenchymal stem cells (BMSCs). However, recruiting endogenous BMSCs for in situ bone regeneration remains challenging. In this study, we developed a novel BMSC-aptamer (BMSC-apt) functionalized hydrogel (BMSC-aptgel) and evaluated its functions in recruiting BMSCs and promoting bone regeneration. The functional hydrogels were synthesized between maleimide-terminated 4-arm polyethylene glycols (PEG) and thiol-flanked PEG crosslinker, allowing rapid in situ gel formation. The aldehyde group-modified BMSC-apt was covalently bonded to a thiol-flanked PEG crosslinker to produce high-density aptamer coverage on the hydrogel surface. In vitro and in vivo studies demonstrated that the BMSC-aptgel significantly increased BMSC recruitment, migration, osteogenic differentiation, and biocompatibility. In vivo fluorescence tomography imaging demonstrated that functionalized hydrogels effectively recruited DiR-labeled BMSCs at the fracture site. Consequently, a mouse femur fracture model significantly enhanced new bone formation and mineralization. The aggregated BMSCs stimulated bone regeneration by balancing osteogenic and osteoclastic activities and reduced the local inflammatory response via paracrine effects. This study's findings suggest that the BMSC-aptgel can be a promising and effective strategy for promoting in situ bone regeneration.
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OBJECTIVE: Nanoparticles (NPs) hold a great promise in combating rheumatoid arthritis, but are often compromised by their toxicities because the currently used NPs are usually synthesized by chemical methods. Our group has previously fabricated Ångstrom-scale silver particles (AgÅPs) and demonstrated the anti-tumor and anti-sepsis efficacy of fructose-coated AgÅPs (F-AgÅPs). This study aimed to uncover the efficacy and mechanisms of F-AgÅPs for arthritis therapy. METHODS: We evaluated the efficacy of F-AgÅPs in collagen-induced arthritis (CIA) mice. We also compared the capacities of F-AgÅPs, the commercial AgNPs, and the clinical drug methotrexate (MTX) in protecting against K/BxN serum-transfer arthritis (STA) mice. Moreover, we evaluated the effects of F-AgÅPs and AgNPs on inflammation, osteoclast formation, synoviocytes migration, and matrix metalloproteinases (MMPs) production in vitro and in vivo. Meanwhile, the toxicities of F-AgÅPs and AgNPs in vitro and in vivo were also tested. RESULTS: F-AgÅPs significantly prevented bone erosion, synovitis, and cartilage damage, attenuated rheumatic pain, and improved the impaired motor function in mouse models of CIA or STA, the anti-rheumatic effects of which were comparable or stronger than AgNPs and MTX. Further studies revealed that F-AgÅPs exhibited similar or greater inhibitory abilities than AgNPs to suppress inflammation, osteoclast formation, synoviocytes migration, and MMPs production. No obvious toxicities were observed in vitro and in vivo after F-AgÅPs treatment. CONCLUSIONS: F-AgÅPs can effectively alleviate arthritis without notable toxicities and their anti-arthritic effects are associated with the inhibition of inflammation, osteoclastogenesis, synoviocytes migration, and MMPs production. Our study suggests the prospect of F-AgÅPs as an efficient and low-toxicity agent for arthritis therapy.
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Artrite Experimental , Artrite Reumatoide , Camundongos , Animais , Prata/uso terapêutico , Osteogênese , Inflamação/tratamento farmacológico , Inflamação/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Colágeno , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Metaloproteinases da MatrizRESUMO
Many studies reported that long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) metastasis and tumorigenesis. However, the underlying mechanisms of lncRNAs in GC remain unexplored to a great extent. LINC01537 expression level was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Its biological roles in GC were then investigated using functional experiments. In order to investigate the underlying mechanism of LINC01537 in GC, RNA pull-down, RNA immunoprecipitation, and ubiquitination assays were performed. LINC01537 was significantly overexpressed in GC tissues and associated with a poor prognosis. Functional experimental results revealed that LINC01537 promoted the proliferation, invasion, and migration of GC cells. The animal experiments revealed that LINC01537 promoted tumorigenesis and metastasis in vivo. Mechanistically, LINC01537 stabilizes RIPK4 by reducing the binding of RIPK4 to TRIM25 and reducing its ubiquitination degradation, thereby promoting the expression of the NF-κB signaling pathway. According to our findings, the LINC01537-RIPK4-NF-κB axis promoted GC metastasis and tumorigenesis.
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The etiology of epilepsy remains undefined in two-thirds of patients. Here, we identified a de novo variant of ATP1A2 (c.2426 T > G, p.Leu809Arg), which encodes the α2 subunit of Na+/K+-ATPase, from a family with idiopathic epilepsy. This variant caused epilepsy with hemiplegic migraine in the study patients. We generated the point variant mouse model Atp1a2L809R, which recapitulated the epilepsy observed in the study patients. In Atp1a2L809R/WT mice, convulsions were observed and cognitive and memory function was impaired. This variant affected the potassium binding function of the protein, disabling its ion transport ability, thereby increasing the frequency of nerve impulses. Valproate (VPA) and Carbamazepine (CBZ) have limited therapeutic efficacy in ameliorating the epileptic syndromes of Atp1a2L809R/WT mice. Our work revealed that ATP1A2L809R variants cause a predisposition to epilepsy. Moreover, we provide a point variant mouse model for epilepsy research and drug screening.
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Epilepsia , Enxaqueca com Aura , Animais , Modelos Animais de Doenças , Epilepsia/genética , Camundongos , Enxaqueca com Aura/genética , Enxaqueca com Aura/metabolismo , Mutação , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and major cause of cancer death in the world. Ferroptosis is a recently identified type of regulated cell death. Increasing evidence has shown that ferroptosis plays an important regulatory role in the occurrence and development of cancer. This study identified TIGAR as a potential regulator of ferroptosis resistance in the development of CRC. We showed that TIGAR expression in CRC tissues is significantly higher than that in adjacent normal tissues. Knockdown of TIGAR significantly caused an increase in erastin-induced ferroptosis in SW620 and HCT116 cells. Notably, knockdown of TIGAR significantly decreased GSH/GSSG ratio, increased lipid peroxidation production, and facilitated the accumulation of lipid peroxidation product malondialdehyde (MDA), and rendered CRC cells more sensitive to erastin induced ferroptosis. Furthermore, TIGAR inhibition repressed SCD1 expression in a redox and AMPK-dependent manner. Thus, these results suggest that TIGAR induces ferroptosis resistance in CRC cells via the ROS/AMPK/SCD1 signaling pathway.
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Proteínas Reguladoras de Apoptose , Neoplasias Colorretais , Ferroptose , Monoéster Fosfórico Hidrolases , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias Colorretais/metabolismo , Ferroptose/genética , Células HCT116 , Humanos , Monoéster Fosfórico Hidrolases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estearoil-CoA Dessaturase/metabolismoRESUMO
Fracture healing is a complicated process affected by many factors, such as inflammatory responses and angiogenesis. Omentin-1 is an adipokine with anti-inflammatory properties, but whether omentin-1 affects the fracture healing process is still unknown. Here, by using global omentin-1 knockout (omentin-1-/-) mice, we demonstrated that omentin-1 deficiency resulted in delayed fracture healing in mice, accompanied by increased inflammation and osteoclast formation, and decreased production of platelet-derived growth factor-BB (PDGF-BB) and osteogenesis-promoting vessels that are strongly positive for CD31 and Endomucin (CD31hiEmcnhi) in the fracture area. In vitro, omentin-1 treatment suppressed the ability of the tumor necrosis factor-α (TNF-α)-activated macrophages to stimulate multi-nuclear osteoclast formation, resulting in a significant increase in the generation of mono-nuclear preosteoclasts and PDGF-BB, a pro-angiogenic protein that is abundantly secreted by preosteoclasts. PDGF-BB significantly augmented endothelial cell proliferation, tube formation and migration, whereas direct treatment with omentin-1 did not induce obvious effects on angiogenesis activities of endothelial cells. Our study suggests a positive role of omentin-1 in fracture healing, which may be associated with the inhibition of inflammation and stimulation of preosteoclast PDGF-BB-mediated promotion of CD31hiEmcnhi vessel formation.
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Citocinas/genética , Fraturas do Fêmur/genética , Consolidação da Fratura , Proteínas Ligadas por GPI/genética , Lectinas/genética , Sialoglicoproteínas/metabolismo , Animais , Movimento Celular , Modelos Animais de Doenças , Feminino , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/imunologia , Técnicas de Inativação de Genes , Camundongos , Osteoclastos/metabolismo , Osteogênese , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Células RAW 264.7 , Microtomografia por Raio-XRESUMO
Cancer cells can metabolize glutamine to replenish TCA cycle intermediates for cell survival. Glutaminase (GLS1) is over-expressed in multiple cancers, including colorectal cancer (CRC). However, the role of GLS1 in colorectal cancer development has not yet fully elucidated. In this study, we found that GLS1 levels were significantly increased in CRC cells. Knockdown of GLS1 by shRNAs as well as GLS1 inhibitor BPTES decreased DLD1 and SW480 cell proliferation, colony formation and migration. Knockdown of GLS1 as well as BPTES induced reactive oxygen species (ROS) production, down-regulation of GSH/GSSG ratio, an decrease in Nrf2 protein expression and an increase in cytoplasmic Nrf2 protein expression in DLD1 and SW480 cells. Furthermore, Knockdown of GLS1 as well as BPTES inhibited autophagy pathway, antioxidant NAC and Nrf2 activator could reversed inhibition of GLS1-mediated an decrease in autophagic flux in DLD1 and SW480 cells. Depletion of GLS1-induced inhibition of DLD1 and SW480 CRC cell proliferation, colony formation and migration was reversed by autophagy inducer rapamycin. These results suggest that targeting GLS1 might be a new potential therapeutic target for the treatment of CRC.
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Autofagia/genética , Movimento Celular/genética , Neoplasias Colorretais/patologia , Técnicas de Silenciamento de Genes , Glutaminase/deficiência , Glutaminase/genética , Fator 2 Relacionado a NF-E2/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , OxirreduçãoRESUMO
Alzheimer's disease (AD) is currently ranked as the third leading cause of death for eldly people, just behind heart disease and cancer. Autophagy is declined with aging. Our study determined the biphasic changes of miR-331-3p and miR-9-5p associated with AD progression in APPswe/PS1dE9 mouse model and demonstrated inhibiting miR-331-3p and miR-9-5p treatment prevented AD progression by promoting the autophagic clearance of amyloid beta (Aß). Methods: The biphasic changes of microRNAs were obtained from RNA-seq data and verified by qRT-PCR in early-stage (6 months) and late-stage (12 months) APPswe/PS1dE9 mice (hereinafter referred to as AD mice). The AD progression was determined by analyzing Aß levels, neuron numbers (MAP2+) and activated microglia (CD68+IBA1+) in brain tissues using immunohistological and immunofluorescent staining. MRNA and protein levels of autophagic-associated genes (Becn1, Sqstm1, LC3b) were tested to determine the autophagic activity. Morris water maze and object location test were employed to evaluate the memory and learning after antagomirs treatments in AD mice and the Aß in the brain tissues were determined. Results: MiR-331-3p and miR-9-5p are down-regulated in early-stage of AD mice, whereas up-regulated in late-stage of AD mice. We demonstrated that miR-331-3p and miR-9-5p target autophagy receptors Sequestosome 1 (Sqstm1) and Optineurin (Optn), respectively. Overexpression of miR-331-3p and miR-9-5p in SH-SY5Y cell line impaired autophagic activity and promoted amyloid plaques formation. Moreover, AD mice had enhanced Aß clearance, improved cognition and mobility when treated with miR-331-3p and miR-9-5p antagomirs at late-stage. Conclusion: Our study suggests that using miR-331-3p and miR-9-5p, along with autophagic activity and amyloid plaques may distinguish early versus late stage of AD for more accurate and timely diagnosis. Additionally, we further provide a possible new therapeutic strategy for AD patients by inhibiting miR-331-3p and miR-9-5p and enhancing autophagy.
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Doença de Alzheimer/prevenção & controle , Autofagia , Modelos Animais de Doenças , Regulação da Expressão Gênica , MicroRNAs/antagonistas & inibidores , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Animais , Humanos , Masculino , Camundongos , Camundongos Transgênicos , MicroRNAs/genética , Neurônios/metabolismo , Neurônios/patologiaRESUMO
Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified Optn as a critical molecule of cell fate decision for bone marrow mesenchymal stem cells (MSCs), whose expression decreased in aged mice. Aged mice revealed osteoporotic bone loss, elevated senescence of MSCs, decreased osteogenesis, and enhanced adipogenesis, as well as optn-/ - mice. Importantly, restoring Optn by transplanting wild-type MSCs to optn-/ - mice or infecting optn-/ - mice with Optn-containing lentivirus rescued bone loss. The introduction of a loss-of-function mutant of OptnK193R failed to reestablish a bone-fat balance. We further identified FABP3 (fatty acid binding protein 3, muscle and heart) as a novel selective autophagy substrate of OPTN. FABP3 promoted adipogenesis and inhibited osteogenesis of MSCs. Knockdown of FABP3 alleviated bone loss in optn-/ - mice and aged mice. Our study revealed that reduced OPTN expression during aging might lead to OP due to a lack of FABP3 degradation via selective autophagy. FABP3 accumulation impaired osteogenesis of MSCs, leading to the occurrence of OP. Thus, reactivating OPTN or inhibiting FABP3 would open a new avenue to treat senile OP.Abbreviations: ADIPOQ: adiponectin, C1Q and collagen domain containing; ALPL: alkaline phosphatase, liver/bone/kidney; BGLAP/OC/osteocalcin: bone gamma carboxyglutamate protein; BFR/BS: bone formation rate/bone surface; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A/p21: cyclin-dependent kinase inhibitor 1A; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CDKN2B/p15: cyclin dependent kinase inhibitor 2B; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; COL1A1: collagen, type I, alpha 1; Ct. BV/TV: cortical bone volume fraction; Ct. Th: cortical thickness; Es. Pm: endocortical perimeter; FABP4/Ap2: fatty acid binding protein 4, adipocyte; H2AX: H2A.X variant histone; HE: hematoxylin and eosin; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAR: mineral apposition rate; MSCs: bone marrow mesenchymal stem cells; NBR1: NBR1, autophagy cargo receptor; OP: osteoporosis; OPTN: optineurin; PDB: Paget disease of bone; PPARG: peroxisome proliferator activated receptor gamma; Ps. Pm: periosteal perimeter; qRT-PCR: quantitative real-time PCR; γH2AX: Phosphorylation of the Serine residue of H2AX; ROS: reactive oxygen species; RUNX2: runt related transcription factor 2; SA-GLB1: senescence-associated (SA)-GLB1 (galactosidase, beta 1); SP7/Osx/Osterix: Sp7 transcription factor 7; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 (human T cell leukemia virus type I) binding protein 1; Tb. BV/TV: trabecular bone volume fraction; Tb. N: trabecular number; Tb. Sp: trabecular separation; Tb. Th: trabecular thickness; µCT: micro computed tomography.
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Envelhecimento , Autofagia , Proteínas de Ciclo Celular , Proteína 3 Ligante de Ácido Graxo , Proteínas de Membrana Transportadoras , Células-Tronco Mesenquimais , Adipogenia , Animais , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular , Proteína 3 Ligante de Ácido Graxo/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteogênese , Osteoporose , Microtomografia por Raio-XRESUMO
AIM: To compare the short- and long-term outcomes of vascularizing lymph node dissection (VLND) and non-vascularizing lymph node dissection (NVLND) from a single institution. METHODS: Data of 315 patients with advanced gastric cancer who underwent standard D2 lymphadenectomy with curative intent was collected between January 1994 and December 2006. One hundred and fifty-two patients received VLND while 163 patients received NVLND. Short- and long-term clinical outcomes were compared between the two groups. RESULTS: The median followed-up time was 82 mo. The rate of postoperative complications in the VLND group was 13.2%, while that in the NVLND group was 11.7% (P = 0.686). The overall 5-year survival rate was 64% in the VLND group and 59% in the NVLND group (P = 0.047). When subgroup analyses were performed according to Bormann type, type of differentiation and lymph node status, survival benefit was demonstrated in patients with Bormann type III or IV (59% vs 50%, P = 0.032), undifferentiated type (63% vs 49%, P = 0.021) or presence of lymph node metastasis (53% vs 38%, P = 0.010) in the VLND group. CONCLUSION: D2 VLND in advanced gastric cancer treatment allows survival benefit with acceptable morbidity and mortality. VLND for patients with potentially curable advanced gastric cancer is feasible and safe when performed by a well-trained surgical team.
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Gastrectomia , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , China , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/mortalidade , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of the present study was to inquire into the feasibility, surgical skills required and short-term effect of a laparoscopic resection of the bursa omentalis and lymph node scavenging with radical gastrectomy. In this study, the clinical data of 18 patients who received a laparoscopic resection of the bursa omentalis with radical gastrectomy in the Department of Gastrointestinal Surgery, Guangdong Province Hospital of Traditional Chinese Medicine (Guangzhou, Guangdong, China) during the period between January 2012 and January 2014. A retrospective analysis was performed and the surgical duration, bursa omentalis resection time, amount of bleeding during the surgery, post-operative complications associated with the surgery, length of hospital stay, number of lymph nodes scavenged and short-term follow-up results were assessed. The results indicated that all of these 18 patients successfully received a resection of the bursa omentalis and no one required conversion to open surgery. The mean surgical duration was 289.3±30.3 min, the bursa omentalis resection time was 46.1±18.6 min and the amount of bleeding was recorded as 35.5±6.5 ml in these patients. No patients suffered from post-operative complications, such as pancreatic fistulae, anastomotic fistulae, intestinal obstructions or succumbing to the surgery, and no patients succumbed within a 6-month follow-up period. In conclusion, for advanced gastric carcinoma, laparoscopic resection of the bursa omentalis and lymph node scavenging with radical gastrectomy is feasible. In addition to meeting the requirement that the operator should be skilled and experienced in open bursa omentalis resection, and have well-knit basic skills in using a laparoscope, attention must also be paid to the construction of the surgical team.
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OBJECTIVE: To summarize the experience and short-term clinical outcomes of hand-assisted laparoscopic surgery (HALS) in sphincter-preserving surgery for low and ultralow rectal cancer. METHODS: Data of 49 patients with rectal cancer who underwent HALS for low or ultralow anterior resection between January 2010 and January 2011 were analyzed retrospectively. RESULTS: The proximal resection margin was (14.3±6.9) cm and the distal margin was(4.3±1.9) cm. The mean operative time was(128.3±70.9) min. On postoperative macroscopic evaluation, the mesorectum was intact in 42 cases, nearly intact in 7 cases. The circumferential resection margin was more than 2 mm in 42 cases, and less than 2 mm in 7 cases. Forty-six patients underwent R0 resection, and 3 cases underwent R1 resection. The median retrieved lymph node (LN) was 16.20±9.23, and the median positive LN was 1.12±2.19. Postoperative pathological examination showed TNM stage was I( in 12 patients, II(A in 18, II(B in 1, III(A in 2, III(B in 8, III(C in 5, IIII( in 3. The median postoperative hospital stay was (6.25±3.87) d. There were no anastomotic leakage, ileus, intra-abdominal or anastomotic bleeding. There were two wound infections. CONCLUSION: Low and ultralow anterior resection for rectal cancer using HALS approach is safe and feasible with favorable short-term outcome.
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Laparoscopia Assistida com a Mão/métodos , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: Chronic administration of nicotinic acid (NA), a potent antilipidemic compound, aggravates glycemic control in diabetic patients. It is not known if NA has direct effects on islet ß cells. METHODS: Real-time reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunofluorescence techniques were used to examine the expression of NA receptor PUMA-G, a member of the G protein-coupled receptor (G-PCR) family, in murine islet ß cells. Calcium transient was measured using confocal microscopy, whereas the intracellular cyclic adenosine monophosphate and glucose-stimulated insulin secretion (GSIS) from isolated islets were determined by the enzyme-linked immunosorbent assay. RESULTS: High levels of PUMA-G transcripts and protein were detected in all ß cells, and about 40% of α cells. PUMA-G transcripts increased more than 3-fold in islets incubated with interferon γ. Cyclic adenosine monophosphate accumulation, induced by IBMX/forskolin, was inhibited by NA; however, the inhibition was completely abolished by pretreatment of the culture with pertussis toxin. No calcium transient was detected in islet cells in the presence of NA. Static incubation of islets with NA led to an approximately 30% reduction of GSIS. CONCLUSIONS: The results indicated that PUMA-G stimulation by NA in islet ß cells inhibited GSIS likely via activation of the Gi signaling pathway.
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Glucose/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Niacina/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Receptores Nicotínicos/metabolismo , Animais , Cálcio/metabolismo , AMP Cíclico/metabolismo , Imunofluorescência , Hibridização In Situ , Técnicas In Vitro , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Interferon gama/farmacologia , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Receptores Acoplados a Proteínas G/genética , Receptores Nicotínicos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , VasodilatadoresRESUMO
OBJECTIVE: To compare the clinical outcomes of laparoscopic-assisted versus hand-assisted laparoscopic radical operations in colorectal cancer and evaluate the safety and indications of hand-assisted laparoscopic operations. METHODS: A total of 64 consecutive colorectal cancer patients enrolled from November 2009 to December 2011 at our hospital were randomly and prospectively divided into 2 groups: hand-assisted laparoscopic operation (HALS) (n = 32) and laparoscopic-assisted operation (n = 32). And such clinicopathologic features as safety, operative curability and postoperative recovery were compared between two groups. RESULTS: Neither death nor conversion-to-open-surgery was reported among all patients. There were no statistical differences in such clinicopathologic features as age, gender, body mass index, mass size and location (all P > 0.05). There were statistically a shorter operation time [(127 ± 31) min vs (184 ± 71) min, P = 0.022] and a smaller number of Trocar (2.4 vs 5.0, P = 0.015) in the HALS group. However, the laparoscopic-assisted group had a lesser volume of blood loss [(82 ± 31) ml vs (150 ± 42) ml, P = 0.008] and a smaller postoperative 48 h drainage flow [(170 ± 52) ml vs (208 ± 58) ml, P = 0.020]. Moreover, no statistical differences existed in the length of bowel resection [(19 ± 5) cm vs (18 ± 4) cm], amount of lymph nodes dissection (16 ± 4 vs 16 ± 3), postoperative complications [12.5% (4/32) vs 25.0% (8/32)], time of intestinal function recovery [(1.7 ± 0.9) d vs (1.8 ± 0.7) d], time of semifluid tolerance [(2.9 ± 1.3) vs (2.8 ± 1.2) d], hospitalization expenses [(4.8 ± 0.6) 10 000 yuan vs (4.9 ± 0.4) 10 000 yuan] and postoperative hospital stay [(6.7 ± 2.3) d vs (6.6 ± 2.3) d] (all P > 0.05). CONCLUSION: HALS is both safe and efficacious for colorectal cancer patients.
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Colectomia , Laparoscopia Assistida com a Mão , Neoplasias Colorretais/cirurgia , Humanos , Laparoscopia , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate and compare the results of vagina vasorum lymph node dissection (VLND) and non-vagina vasorum lymph node dissection (NVLND) in patients with gastric cancer after radical operation. METHODS: A total of 759 cases of evaluable patients with gastric cancer, operated from June 1994 to April 2005, were retrospectively analyzed. Of which, 627 cases underwent radical gastrectomy: 215 patients received VLND and 412 cases received NVLND. The operation time, intraoperative blood loss, operative complications and survival rate were recorded and compared between the two groups. RESULTS: The 5- and 10-year overall accumulative survival rates of VLND group and NVLND group were 55.4% and 51.2%, 39.1%and 36.8%, respectively (all P < 0.05). No significant differences in intraoperative blood transfusion (loss), operation time, operative complication rate was found between the two groups. The 5- and 10-year accumulative survival in patients with a tumor of phase N0-N2, T2-T4, Ib-IV in VLND groups were all significant higher than those in NVLND group. CONCLUSIONS: VLND is a safe technique in advanced gastric cancer, it dose not prolong operation time or increase operative complications but improves survival.
Assuntos
Excisão de Linfonodo/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Gastrectomia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Z plasty was used in 38 children (male 22, female 16) aged from 0.5 to 6 years with ankyloglossia. There were no infection, dehiscence and tongue adhesion. The wound healed more quickly, and tongue protrusion improved from 13.5 mm preoperatively to 24.6 mm postoperatively. Similarly, tongue elevation improved from 4.8 to 20.6 mm.