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1.
J Thorac Oncol ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38553005

RESUMO

INTRODUCTION: EGFR-mutated NSCLC is characterized by an immunosuppressive microenvironment that confers limited clinical effectiveness to anti-PD-1 or PD-L1 antibodies. Despite the discouraging outcomes of immunotherapy, novel immune checkpoints are constantly emerging, among which the specific vulnerability for therapeutic intervention in the context of EGFR-mutated NSCLC remains unresolved. METHODS: Data sets of patient- and cell line-levels were used for screening and mutual validation of association between EGFR mutation and a panel of immune checkpoint-related genes. Regulatory mechanism was elucidated through in vitro manipulation of EGFR signaling pathway and evaluated by immunoblot analysis, quantitative polymerase chain reaction, flow cytometry, immunofluorescence staining, and chromatin immunoprecipitation. In vivo investigation of different therapeutic strategies were conducted using both immunocompetent and immunodeficient mouse models. RESULTS: Among all screened immune checkpoints, CD47 emerged as the candidate most relevant to EGFR activation. Mechanistically, EGFR mutation constitutively activated downstream ERK and AKT pathways to respectively up-regulate the transcriptional factors c-Myc and NF-κB, both of which structurally bound to the promotor region of CD47 and actively transcribed this "don't eat me" signal. Impaired macrophage phagocytosis was observed on introduction of EGFR-sensitizing mutations in NSCLC cell line models, whereas CD47 blockade restored the phagocytic capacity and augmented tumor cell killing in both in vitro and in vivo models. Remarkably, the combination of anti-CD47 antibody with EGFR tyrosine kinase inhibitor revealed an additive antitumor activity compared with monotherapy of either antitumor agent in both immunocompetent and adaptive immunity-deficient mouse models. CONCLUSIONS: EGFR-sensitizing mutation facilitates NSCLC's escape from innate immune attack through up-regulating CD47. Combination therapy incorporating CD47 blockade holds substantial promise for clinical translation in developing more effective therapeutic approaches against EGFR-mutant NSCLC.

2.
Lung Cancer ; 190: 107528, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38461768

RESUMO

INTRODUCTION: The literature on de novo EGFRT790M-mutant patients diagnosed with lung cancer is limited, and there is currently no consensus concerning the most effective treatment protocols. This study aimed to investigate the genomic characteristics of de novoEGFRT790M-mutant non-small cell lung cancer (NSCLC) and provide insights into its clinical response and resistance mechanism to third-generation EGFR-TKIs. METHODS: Next-generation sequencing was utilized to screen a substantial cohort of 4,228 treatment-naïve patients from the Mygene genomic database to identifythe de novo EGFR-T790M mutation. Meanwhile, we recruited 83 individuals diagnosed with lung cancer who harbored de novo EGFRT790M mutation in the real world. In addition, 166 patients who acquired EGFR-T790M mutation after becoming resistant to first- or second-generation EGFR-TKIs were included as a comparison cohort. RESULTS: De novo EGFRT790M mutation identified by next-generation sequencing is rare (∼1.3 %) in Chinese lung cancer patients. The relative variant allele frequency (VAF) of de novo EGFRT790M mutation was either comparable to or significantly lower than those of EGFR-activating mutations. Patients with de novo-T790M mutations exhibited less favorable clinical outcomes when administered third-generation EGFR-TKIs as first-line therapy thanthose with 19del mutationsdue to a high overlap rate in EGFR p.L858R mutation. In patients with a de novo EGFRT790M mutation, no correlation was observed between T790M clonality and treatment outcomes with third-generation EGFR-TKIs. In contrast, the sub-clonality of the T790M mutation detrimentally affected the third-generation EGFR-TKI treatment efficacy in patients with acquired T790M mutation. Potential resistance mechanisms of third-generation EGFR TKIs in NSCLC patients with de novo or acquired EGFRT790M mutations included EGFR p.C797S in cis or EGFR p.E709X mutation, as well as activation of bypass pathways. CONCLUSIONS: The present study characterized the uncommon but unique de novo EGFRT790M-mutant NSCLC and laid a foundation for designing future clinical trials in the setting of uncommon EGFR mutation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia
4.
Nat Commun ; 14(1): 4674, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37542048

RESUMO

Ethylene plays essential roles in rice growth, development and stress adaptation. Translational control of ethylene signaling remains unclear in rice. Here, through analysis of an ethylene-response mutant mhz9, we identified a glycine-tyrosine-phenylalanine (GYF) domain protein MHZ9, which positively regulates ethylene signaling at translational level in rice. MHZ9 is localized in RNA processing bodies. The C-terminal domain of MHZ9 interacts with OsEIN2, a central regulator of rice ethylene signaling, and the N-terminal domain directly binds to the OsEBF1/2 mRNAs for translational inhibition, allowing accumulation of transcription factor OsEIL1 to activate the downstream signaling. RNA-IP seq and CLIP-seq analyses reveal that MHZ9 associates with hundreds of RNAs. Ribo-seq analysis indicates that MHZ9 is required for the regulation of ~ 90% of genes translationally affected by ethylene. Our study identifies a translational regulator MHZ9, which mediates translational regulation of genes in response to ethylene, facilitating stress adaptation and trait improvement in rice.


Assuntos
Oryza , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mutação , Etilenos/metabolismo , RNA/metabolismo , Regulação da Expressão Gênica de Plantas
5.
Int J Cancer ; 152(11): 2338-2350, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36631999

RESUMO

Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and histologically distinctive subtype of nonsmall cell lung cancer (NSCLC). High expression of programmed death ligand 1 (PD-L1) and scarcity of druggable driver mutations raise the potential of immunotherapy for advanced PELEC. However, evidence on the clinical impact of immune-checkpoint inhibitors (ICIs) remained limited and unconvincing. The present study retrospectively enrolled advanced PLELC patients who received ICIs either as up-front or salvage therapy in SYSUCC between March 15, 2017 and March 15, 2022. The comparative efficacy of chemoimmunotherapy vs chemotherapy in the first-line setting and chemoimmunotherapy vs ICIs monotherapy in the ≥2 line setting was investigated. A total of 96 patients were finally enrolled; 49 PLELC patients received immunotherapy plus platinum-based chemotherapy, while 45 patients received platinum-based chemotherapy as first-line treatment. Patients with chemoimmunotherapy significantly obtain more survival benefits than those receiving chemotherapy (median progression-free survival [PFS]: 15.6 vs 8.6 months, P = .0015). Additionally, patients with chemoimmunotherapy obtained more PFS benefits than those with ICIs monotherapy in the ≥2 line of therapy (median PFS: 21.7 months vs 7.8 months, P = .094). A significant correlation was observed between prognostic nutritional index (PNI) and favorable treatment outcomes in patients receiving first-line chemoimmunotherapy (median PFS: 17.8 months vs 7.6 months, P < .0001). Likewise, patients in the monocyte-to-lymphocyte ratio (MLR)-high group had significantly shorter PFS than the MLR-low group (median PFS: 11.2 months vs not reached, P = .0009). Our study elucidated the superior efficacy of ICIs therapy, especially chemoimmunotherapy in advanced PLELC, which may provide new insight into the role of immunotherapy in advanced PLELC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológico , Imunoterapia
6.
BMC Cancer ; 23(1): 72, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36670414

RESUMO

BACKGROUND & OBJECTIVE: "Anti-angiogenetic drugs plus chemotherapy" (anti-angio-chemo) and "immune checkpoint inhibitors plus chemotherapy" (ICI-chemo) are superior to traditional chemotherapy in the first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). However, in the absence of a direct comparison of ICI-chemo with anti-angio-chemo, the superior one between them has not been decided, and the benefit of adding anti-angiogenetic agents to ICI-chemo remains controversial. This study aimed to investigate the role of antiangiogenic agents for advanced NSCLC in the era of immunotherapy. METHODS: Eligible randomized controlled trials (RCTs) comparing chemotherapy versus therapeutic regimens involving ICIs or anti-angiogenetic drugs were included. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and rate of grade 3-4 toxicity assessment. R-4.3.1 was utilized to perform the analysis. RESULTS: A total of 54 studies with a sample size of 25,046 were finally enrolled. "Atezolizumab + Bevacizumab + Chemotherapy" significantly improved the ORR compared with "Atezolizumab + Chemotherapy" (Odds ratio (OR) = 2.73, 95% confidence interval (CI): 1.27-5.87). The trend also favored "Atezolizumab + Bevacizumab + Chemotherapy" in PFS and OS (hazard ratio (HR) = 0.71, 95% CI: 0.39-1.31; HR = 0.94, 95% CI: 0.77-1.16, respectively). In addition, "Pembrolizumab + Chemotherapy" and "Camrelizumab + Chemotherapy" significantly prolonged the PFS compared to "Bevacizumab + Chemotherapy" (HR = 0.65, 95% CI: 0.46-0.92; HR = 0.63, 95% CI: 0.41-0.97; respectively). Meanwhile, "Pembrolizumab + Chemotherapy" and "Sintilimab + Chemotherapy" yielded more OS benefits than "Bevacizumab + Chemotherapy" (HR = 0.69, 95% CI: 0.56-0.83; HR = 0.64, 95%CI: 0.46-0.91; respectively). Scheme between "Atezolizumab + Bevacizumab + Chemotherapy" and "Atezolizumab + Chemotherapy" made no significant difference (OR = 1.18, 95%CI: 0.56-2.42) concerning the rate of grade 3-4 toxicity. It seemed that ICI-chemo yielded more improvement in quality-adjusted life-year (QALY) than "Bevacizumab + Chemotherapy" in cost-effectiveness analysis. CONCLUSION: Our results suggest that ICI-chemo is associated with potentially longer survival, better cost-effectiveness outcomes, and comparable safety profiles than anti-angio-chemo. Also, adding bevacizumab to ICI-chemo seemed to provide additional therapeutic benefits without adding treatment burden. Our findings would supplement the current standard of care and help the design of future clinical trials for the first-line treatment of patients with advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/uso terapêutico , Imunoterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
7.
Plant Cell Environ ; 46(4): 1060-1074, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36397123

RESUMO

Rice is an important food crop in the world and the study of its growth and plasticity has a profound influence on sustainable development. Ethylene modulates multiple agronomic traits of rice as well as abiotic and biotic stresses during its lifecycle. It has diverse roles, depending on the organs, developmental stages and environmental conditions. Compared to Arabidopsis (Arabidopsis thaliana), rice ethylene signalling pathway has its own unique features due to its special semiaquatic living environment and distinct plant structure. Ethylene signalling and responses are part of an intricate network in crosstalk with internal and external factors. This review will summarize the current progress in the mechanisms of ethylene-regulated coleoptile growth in rice, with a special focus on ethylene signaling and interaction with other hormones. Insights into these molecular mechanisms may shed light on ethylene biology and should be beneficial for the genetic improvement of rice and other crops.


Assuntos
Arabidopsis , Oryza , Reguladores de Crescimento de Plantas/metabolismo , Plântula/metabolismo , Oryza/genética , Cotilédone/metabolismo , Etilenos/metabolismo , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas
8.
Cancer ; 128(21): 3804-3814, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36069292

RESUMO

BACKGROUND: Afatinib is the only currently approved EGFR-tyrosine kinase inhibitors for advanced non-small cell lung cancer (NSCLC) patients with EGFR G719X/L861Q/S768I. However, there are limited real-world data concerning the benefits and resistance mechanisms of afatinib in patients with these nonclassical mutations. To fill this gap, the present study was conducted. METHODS: All NSCLC patients treated with afatinib were screened, and patients with EGFR G719X/L861Q/S768I were enrolled into the analysis. Either tumor tissue or blood specimens were detected by the commercial next-generation sequencing (NGS) panels or amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) to figure out the mutation genotype. RESULTS: A total of 106 advanced NSCLC patients with EGFR G719X/L861Q/S768I received afatinib treatment. The benefits of afatinib exhibited heterogeneity in different mutation genotypes. Notably, at baseline, NGS testing was performed in 59 patients, and TP53 was the most frequently coexisting mutation. Patients with TP53 mutations obtained fewer survival benefits than those with TP53 wild-type. A total of 68 patients ultimately experienced progression, and 27 patients received NGS testing to clarify the potential resistance mechanisms. EGFR-T790M, CDK4 amplification, FGFR1 amplification, PIK3CA, MET amplification, RET fusions, HER2, and BRAF mutations were identified in three (11.1%), three (11.1%), three (11.1%), three (11.1%), three (11.1%), one (3.7%), one (3.7%), and one (3.7%) of the cases, respectively. Five patients underwent ARMS-PCR testing for detecting EGFR-T790M mutation, and only one patient was T790M-positive. CONCLUSIONS: The present study elucidated the differential benefits of afatinib within different mutation genotypes and first revealed the spectrum of potential resistance mechanisms in patients with EGFR G719X/L861Q/S768I. The results of this study may provide practical clinical information that can guide optimal treatment in this setting.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Afatinib/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética
9.
Plant Cell ; 34(11): 4366-4387, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-35972379

RESUMO

Ethylene plays essential roles in adaptive growth of rice (Oryza sativa). Understanding of the crosstalk between ethylene and auxin (Aux) is limited in rice. Here, from an analysis of the root-specific ethylene-insensitive rice mutant mao hu zi 10 (mhz10), we identified the tryptophan aminotransferase (TAR) MHZ10/OsTAR2, which catalyzes the key step in indole-3-pyruvic acid-dependent Aux biosynthesis. Genetically, OsTAR2 acts downstream of ethylene signaling in root ethylene responses. ETHYLENE INSENSITIVE3 like1 (OsEIL1) directly activated OsTAR2 expression. Surprisingly, ethylene induction of OsTAR2 expression still required the Aux pathway. We also show that Os indole-3-acetic acid (IAA)1/9 and OsIAA21/31 physically interact with OsEIL1 and show promotive and repressive effects on OsEIL1-activated OsTAR2 promoter activity, respectively. These effects likely depend on their EAR motif-mediated histone acetylation/deacetylation modification. The special promoting activity of OsIAA1/9 on OsEIL1 may require both the EAR motifs and the flanking sequences for recruitment of histone acetyltransferase. The repressors OsIAA21/31 exhibit earlier degradation upon ethylene treatment than the activators OsIAA1/9 in a TIR1/AFB-dependent manner, allowing OsEIL1 activation by activators OsIAA1/9 for OsTAR2 expression and signal amplification. This study reveals a positive feedback regulation of ethylene signaling by Aux biosynthesis and highlights the crosstalk between ethylene and Aux pathways at a previously underappreciated level for root growth regulation in rice.


Assuntos
Etilenos , Ácidos Indolacéticos , Oryza , Raízes de Plantas , Triptofano Transaminase , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Triptofano Transaminase/genética , Triptofano Transaminase/metabolismo
10.
BMJ Open ; 12(6): e057098, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35697451

RESUMO

OBJECTIVE: This study aimed to compare the efficacy and safety of different platinum adjuvant chemotherapy regimens for early-stage resected non-small-cell lung cancer (NSCLC). DESIGN: Systematic review with network meta-analysis of randomised trials. DATA SOURCES: PubMed, EMBASE, The Cochrane Library, Web of Science and Scopus Google Scholar were searched through 12 March 2021. ELIGIBILITY CRITERIA: Eligible randomised controlled trials (RCTs) comparing the postoperative platinum chemotherapy regimen with the observation-controlled group or comparing two platinum chemotherapy regimens head-to-head were included. DATA EXTRACTION AND SYNTHESIS: The primary outcome was the efficacy of adjuvant chemotherapy regimens including relapse-free survival (RFS), overall survival (OS), 2-year, 3-year, 5-year RFS rate and OS rate. The secondary outcome was the rate of grade 3-4 toxicity assessments. Cochrane Handbook (V.5) was used for the risk of bias assessment. Analyses were performed using R software V.4.3.1. RESULTS: 20 RCTs with a sample size of 5483 were enrolled in meta-analysis. The chemotherapy group had a significant RFS and OS advantage compared with the observation group (HR 0.67; 95% CI 0.56 to 0.81, p<0.0001; HR 0.80; 95% CI, 0.73 to 0.88, p<0.0001, respectively). Compared with the observation arm, only the 'cisplatin_vinorelbine' regimen had a significant RFS and OS advantage (HR 0.63; 95% CI 0.43 to 0.87; HR 0.74; 95% CI 0.63 to 0.87, respectively) while the remaining chemotherapy regimens had no significant difference of efficacy compared with the observation group. In terms of the safety of adjuvant chemotherapy, the incidence of haematological toxicities and nausea/vomiting was not significantly higher in the 'cisplatin_vinorelbine' arm than in other chemotherapy group. CONCLUSION: This study summarised the adjuvant cytotoxicity chemotherapy regimens for patients with early-stage resected NSCLC. Our analysis may provide some guiding significance for the clinicians when determining the optimal chemotherapy regimen.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Metanálise em Rede , Platina/uso terapêutico , Vinorelbina/uso terapêutico
11.
Nat Commun ; 11(1): 518, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980616

RESUMO

Ethylene plays essential roles during adaptive responses to water-saturating environments in rice, but knowledge of its signaling mechanism remains limited. Here, through an analysis of a rice ethylene-response mutant mhz1, we show that MHZ1 positively modulates root ethylene responses. MHZ1 encodes the rice histidine kinase OsHK1. MHZ1/OsHK1 is autophosphorylated at a conserved histidine residue and can transfer the phosphoryl signal to the response regulator OsRR21 via the phosphotransfer proteins OsAHP1/2. This phosphorelay pathway is required for root ethylene responses. Ethylene receptor OsERS2, via its GAF domain, physically interacts with MHZ1/OsHK1 and inhibits its kinase activity. Genetic analyses suggest that MHZ1/OsHK1 acts at the level of ethylene perception and works together with the OsEIN2-mediated pathway to regulate root growth. Our results suggest that MHZ1/OsHK1 mediates the ethylene response partially independently of OsEIN2, and is directly inhibited by ethylene receptors, thus revealing mechanistic details of ethylene signaling for root growth regulation.


Assuntos
Etilenos/metabolismo , Histidina Quinase/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Receptores de Superfície Celular/metabolismo , Epistasia Genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Mutação/genética , Oryza/genética , Fenótipo , Fosforilação , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Ligação Proteica , Transdução de Sinais
12.
Plant Cell ; 29(5): 1053-1072, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28465411

RESUMO

Elongation of the mesocotyl and coleoptile facilitates the emergence of rice (Oryza sativa) seedlings from soil and is affected by various genetic and environment factors. The regulatory mechanism underlying this process remains largely unclear. Here, we examined the regulation of mesocotyl and coleoptile growth by characterizing a gaoyao1 (gy1) mutant that exhibits a longer mesocotyl and longer coleoptile than its original variety of rice. GY1 was identified through map-based cloning and encodes a PLA1-type phospholipase that localizes in chloroplasts. GY1 functions at the initial step of jasmonic acid (JA) biosynthesis to repress mesocotyl and coleoptile elongation in etiolated rice seedlings. Ethylene inhibits the expression of GY1 and other genes in the JA biosynthesis pathway to reduce JA levels and enhance mesocotyl and coleoptile growth by promoting cell elongation. Genetically, GY1 acts downstream of the OsEIN2-mediated ethylene signaling pathway to regulate mesocotyl/coleoptile growth. Through analysis of the resequencing data from 3000 rice accessions, we identified a single natural variation of the GY1 gene, GY1376T , which contributes to mesocotyl elongation in rice varieties. Our study reveals novel insights into the regulatory mechanism of mesocotyl/coleoptile elongation and should have practical applications in rice breeding programs.


Assuntos
Ciclopentanos/metabolismo , Etilenos/farmacologia , Oryza/efeitos dos fármacos , Oryza/metabolismo , Oxilipinas/metabolismo , Plântula/efeitos dos fármacos , Plântula/metabolismo , Cotilédone/efeitos dos fármacos , Cotilédone/genética , Cotilédone/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/genética , Oryza/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plântula/genética
13.
Zhonghua Yi Xue Za Zhi ; 90(26): 1804-7, 2010 Jul 13.
Artigo em Chinês | MEDLINE | ID: mdl-20979822

RESUMO

OBJECTIVE: To explore the clinical characteristics and the prognostic factors of patients with colorectal cancer. METHODS: The data of 2042 cases of colorectal cancer, pathologically confirmed at our hospital from January 1995 to December 2007, were summarized and analyzed. RESULTS: The median age of all cases with colorectal cancer was 59 years old. The high-risk age ranged from 50 to 70 years old. The ratio of male and female was 1.4:1. The lesions located in rectum accounted for 46.2% and those for 22.0% in sigmoid. Patients under age 40 had a higher percentage of poor differentiation (33.5%) and mucinous carcinoma (16.7%). The cases with confirmed stage I, II, III and IV were 5.8%, 42.9%, 31.0% and 20.3% respectively. For all cases, the 1-, 3-, 5- and 10-year survival rates were 92.3%, 73.9%, 65.1% and 57.5% respectively. The independent risk factors for patient prognosis were age, gross type, differentiation, TNM staging and surgical type. Adjuvant chemotherapy was a protective factor. As compared with phase I (1995 - 2001), phase II (2002 - 2007) had a higher proportions of employing stapler, Dixon operation and adjuvant chemotherapy. The 1-, 3- and 5-year survival rates of phase II were higher than phase I (93.4%, 78.0% and 73.2% vs 90.6%, 69.2% and 58.8%). CONCLUSION: The prognostic factors of patients with colorectal cancer are age, gross type, differentiation, TNM staging, surgical type and adjuvant chemotherapy.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Regressão , Taxa de Sobrevida , Adulto Jovem
14.
Zhonghua Wei Chang Wai Ke Za Zhi ; 12(5): 480-2, 2009 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-19742339

RESUMO

OBJECTIVE: To investigate the effect of GORE-TEX Dual Mesh fixing into peritoneum in sigmoid-colostomy on the prevention of peristomal hernia. METHODS: Sixty patients undergone sigmoid-colostomy from Jan. 2003 to Jan. 2005 in the first affiliated hospital of Sun Yat-sen University were selected and randomly divided into two groups. Patients received papillary sigmoid-colostomy through rectus abdominis and peritoneum in control group and GORE-TEX Dual Mesh fixing into peritoneum during sigmoid-colostomy in observation group. Complications and recurrence rate were recorded in follow-up period. RESULTS: Peristomal hernia occurred in eight patients (8/30) in control group (26.7%), while no hernia happened in observation group (0/30). CONCLUSION: GORE-TEX Dual Mesh fixing into peritoneum in sigmoid-colostomy can prevent peristomal hernia.


Assuntos
Colo Sigmoide/cirurgia , Colostomia/instrumentação , Hérnia/prevenção & controle , Neoplasias Retais/cirurgia , Adulto , Idoso , Materiais Biocompatíveis , Colostomia/métodos , Feminino , Hérnia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Peritônio/cirurgia , Politetrafluoretileno , Telas Cirúrgicas
15.
Chin Med J (Engl) ; 122(18): 2138-41, 2009 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-19781299

RESUMO

BACKGROUND: Mesh reconstruction has been proved to be an effective method in incisional hernia repairment. This study was designed to evaluate the effect of reconstructing the pelvic floor with the high-inlay expanded polytetrafluoroethylene (ePTFE) GORE-TEX Dual Mesh (WLGore And Associates, Flagstuff, USA) in abdominoperineal resection. METHODS: Sixty patients who underwent abdominoperineal resection for rectal cancer were assigned to 2 groups. The pelvic peritoneum was closed by routine sutures in group 1 and reconstructed with ePTFE in group 2. Postoperative complications and related items were evaluated and the patients were followed up. RESULTS: Time of confining to bed, bowel function recovery, fasting, and detaining drainage were significantly different between two groups (P < 0.05). In group 1, three patients developed bowel obstruction (10%), while no bowel obstruction was observed in group 2. CONCLUSION: Reconstruction of the pelvic floor using ePTFE results in quicker postoperative recovery and could decrease the risk of postoperative intestinal obstruction.


Assuntos
Diafragma da Pelve/cirurgia , Politetrafluoretileno/química , Telas Cirúrgicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Resultado do Tratamento
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 12(4): 342-5, 2009 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-19598014

RESUMO

OBJECTIVE: To elucidate an adequate hepatectomy margin for simultaneous liver and colorectal resection in colorectal cancer liver metastasis. METHODS: Clinical data of 39 patients, undergone simultaneous liver and colorectal resection for colorectal cancer liver metastasis from August 1994 to December 2004, were analyzed retrospectively. Two groups were divided according to the width of hepatectomy margin:less than 1 cm in group A, and equal or more than 1 cm in group B. The data were analyzed and compared between the 2 groups using Kaplan-Meier survival analysis and Log-rank test. RESULTS: There were 14 patients in group A and 25 patients in group B. No significant differences in gender, age, primary tumor invasion, lymph node metastasis, the number, distribution and size of liver metastasis, duration and blood lose of surgery were found between two groups. The median survival time was 17 months in group A, and 37 months in group B, and the overall 5-year survival rate in group B was much better than that in group A (19.8% vs 0, P<0.01). CONCLUSION: Simultaneous liver and colorectal resection in colorectal cancer liver metastasis should be performed with a hepatectomy margin equal or more than 1 cm.


Assuntos
Hepatectomia/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Fígado/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Fígado/cirurgia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
17.
Zhonghua Wai Ke Za Zhi ; 47(9): 673-6, 2009 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-19615236

RESUMO

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 Jovem
18.
Zhonghua Wei Chang Wai Ke Za Zhi ; 12(2): 189-92, 2009 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-19296260

RESUMO

OBJECTIVE: To investigate the outcome of repairing pelvic autonomic nerve defects with the tissue-engineered nerve, in order to provide a new method and experimental evidence for solving sexual disturbance induced by pelvic autonomic nerve injury after radical resection of rectal carcinoma. METHODS: Bone marrow stromal cells (BMSCs) were purified with density gradient centrifugation. A 10 mm defect of hypogastric nerve was created in 9 Beagle dogs and the 18 hypogastric nerves were randomly divided into three groups. Group A: nerve defects bridged with copolymer of lactic and glycolic acids (PLGA) tube containing BMSCs and collagen protein sponge. Group B: with PLGA tube only containing collagen protein sponge. Group C: with autologous nerve graft. The effect of nerve recovery was evaluated by morphology, HE staining, neurofilament immunohistochemistry staining, electron microscope scanning and measurement quantity of new axon 12 weeks after the transplantation. RESULTS: Twelve weeks after the transplantation, degradation of PLGA tubes showed in group A and group B. The nerves regenerated through defect area to distal end. The density of regeneration nerve fiber in group A and group C were better than that in group B. The difference was significant between group A or group C and group B (P<0.05), and no significant difference was observed between group A and group C(P>0.05). CONCLUSION: Tissue-engineered nerve, which is constructed by BMSCs mixed with collagen protein sponge and PLGA tube, can be used to bridge and repair the pelvic autonomic nerve defect.


Assuntos
Doença dos Neurônios Motores/cirurgia , Regeneração Nervosa , Pelve/inervação , Engenharia Tecidual , Animais , Órgãos Artificiais , Diferenciação Celular , Células Cultivadas , Cães , Masculino , Transplante de Células-Tronco Mesenquimais , Tecido Nervoso , Engenharia Tecidual/métodos
19.
Proteomics Clin Appl ; 3(12): 1397-406, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21136959

RESUMO

Elucidating the molecular mechanism underlying the development of adenoma, the major precursor lesion of colorectal cancer (CRC), would provide a basis for early detection, prevention as well as treatment of CRC. Using the highly sensitive 2-D DIGE method coupled with MS, we identified 24 differentially expressed proteins in adenoma tissues compared with matched normal colonic mucosa and CRC tissues. Fifteen proteins were downregulated and three proteins were upregulated in adenoma tissues when compared with individual-matched normal colonic mucosa. Five proteins were downregulated, while one protein was upregulated in adenoma tissues when compared with matched CRC tissues. A protein, ß-tropomyosin (TM-ß), recently suggested to be a biomarker of esophageal squamous carcinoma, was downregulated in both adenoma and CRC tissues. Additionally, the reduction in the level of TM-ß in adenoma and CRC tissues was further validated by Western blotting (p<0.05) and RT-PCR (p<0.001). Our findings suggest that downregulation of TM-ß is involved in the early development of CRC and that differentially expressed proteins might serve as potential biomarkers for detection of CRC.

20.
Zhonghua Wei Chang Wai Ke Za Zhi ; 11(4): 322-5, 2008 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-18636351

RESUMO

OBJECTIVE: To investigate the risk factors of local recurrence after radical resection of rectal carcinoma. METHODS: Clinical and follow-up data of 535 patients with rectal carcinoma, received radical resection between August 1994 and July 2004 in our department, were reviewed retrospectively. The association of clinicopathological factors and local recurrence was analyzed using Log-rank test. Cox multiple variate analysis was conducted to determine the independent risk factors. RESULTS: All the 535 rectal carcinoma patients underwent radical resections. Local recurrence occurred in 53 cases (9.9%), and distant metastasis co-occurred in 39 cases (7.3%). The time from the first operation to the recurrence was 4-54 months with a median of 12 months. The Log-rank test showed that the primary tumor site (P<0.01), differentiation(P<0.01), histological type(P=0.038), lymph node metastasis(P=0.023), Dukes staging(P=0.045), blood transfusion(P=0.001), and total mesorectum excision (TME)(P<0.001) were associated with the recurrence, but the operative style(P=0.908), invasive depth of primary tumor(P=0.735), massive pathological type(P=0.562), degree of surgeon(P=0.171) and post-operative chemotherapy (P=0.772) were not associated with the recurrence. Cox multiple variate analysis revealed that blood transfusion, primary tumor site, differentiation, lymph node metastasis, and TME principle were independent prognostic factors affecting local recurrence after radical resection of rectal cancer. CONCLUSIONS: Blood transfusion, low position of tumor, poor differentiation, lymph node metastasis are the risk factors associated with local recurrence in rectal cancer. Application of TME principle is the key point to decrease the local recurrence rate.


Assuntos
Mesentério/cirurgia , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
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