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1.
Eur J Surg Oncol ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34620508

RESUMO

INTRODUCTION: Despite the heterogeneity among patients with stage IB-IIA non-small cell lung cancer (NSCLC), clinically applicable models to identify patients most suitable for receiving adjuvant chemotherapy (ACT) are limited. We aimed to develop a model for risk stratification and the individualized application of ACT. METHODS: Between January 2008 and March 2018, patients with T2N0M0 NSCLC at Sun Yat-sen University Cancer Center were retrospectively enrolled. Survival curves were estimated by Kaplan-Meier method and compared with log-rank test. Cox regression models were used to identify prognostic factors for disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) was implemented. Subgroup analysis was performed based on clinical risk score (CRS) value and epidermal growth factor receptor (EGFR) mutation status. RESULTS: Of 1063 patients with T2N0 NSCLC enrolled, 272 patients received ACT. Before PSM, patients with high CRS (>1) had a significantly worse OS and DFS outcomes. In the PSM, the baseline characteristics of the 270 pairs of patients were well matched. ACT was associated with improved OS outcomes for patients with a high CRS, while ACT was associated with improved OS and DFS outcomes in patients with wild-type EGFR. The interaction analysis showed an apparent interaction effect between ACT and EGFR-activating mutations as well as chemotherapy regimens and histology. CONCLUSIONS: The CRS can predict the prognosis of patients with stage IB-IIA NSCLC. ACT could improve the outcome of patients with a high CRS. Patients with non-squamous cell histology receiving pemetrexed plus platinum might benefit more, but not those with EGFR-activating mutations.

2.
J Environ Manage ; 301: 113820, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34583281

RESUMO

Soil salinization is a widespread problem affecting global food production. Phytoremediation is emerging as a viable and cost-effective technology to reclaim salt-affected soil. However, its efficiency is not clear due to the uncertainty of plant responses in saline soils. The main objective of this paper is to propose a phytoremediation dynamic model (PDM) for salt-affected soil within the process-based biogeochemical denitrification-decomposition (DNDC) model. The PDM represents two salinity processes of phytoremediation: plant salt uptake and salt-affected biomass growth. The salt-soil-plant interaction is simulated as a coupled mass balance equation of water and salt plant uptake. The salt extraction ability by plant is a combination of salt uptake efficiency (F) and transpiration rate. For water filled pore space (WFPS), the statistical measures RMSE, MAE, and R2 during the calibration period are 2.57, 2.14, and 0.49, and they are 2.67, 2.34, and 0.56 during the validation period, respectively. For soil salinity, RMSE, MAE, and R2 during the calibration period are 0.02, 0.02, and 0.92, and 0.06, 0.04, and 0.68 during the validation period, respectively, which are reasonably good for further scenario analysis. Over the four years, cumulative salt uptake varied based on weather conditions. At the optimal salt uptake efficiency (F = 20), cumulative salt uptake from soil was 16-90% for alfalfa, 11-70% for barley, and 10-80% for spring wheat. While at the lowest salt uptake efficiency (F = 40), cumulative salt uptake was nearly zero for all crops. Although barley has the highest peak transpiration flux, alfalfa and spring wheat have greater cumulative salt uptake because their peak transpiration fluxes occurred more frequently than in barley. For salt-tolerant crops biomass growth depends on their threshold soil salinity which determines their ability to take up salt without affecting biomass growth. In order to phytoremediate salt-affected soil, salt-tolerant crops having longer duration of crop physiological stages should be used, but their phytoremediation effectiveness will depend on weather conditions and the soil environment.

3.
Nat Commun ; 12(1): 5431, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521849

RESUMO

Small cell lung cancer (SCLC) is a highly malignant tumor which is eventually refractory to any treatment. Intratumoral heterogeneity (ITH) may contribute to treatment failure. However, the extent of ITH in SCLC is still largely unknown. Here, we subject 120 tumor samples from 40 stage I-III SCLC patients to multi-regional whole-exome sequencing. The most common mutant genes are TP53 (88%) and RB1 (72%). We observe a medium level of mutational heterogeneity (0.30, range 0.0~0.98) and tumor mutational burden (TMB, 10.2 mutations/Mb, range 1.1~51.7). Our SCLC samples also exhibit somatic copy number variation (CNV) across all patients, with an average CNV ITH of 0.49 (range 0.02~0.99). In terms of mutation distribution, ITH, TMB, mutation clusters, and gene signatures, patients with combined SCLC behave roughly the same way as patients with pure SCLC. This condition also exists in smoking patients and patients with EGFR mutations. A higher TMB per cluster is associated with better disease-free survival while single-nucleotide variant ITH is linked to worse overall survival, and therefore these features may be used as prognostic biomarkers for SCLC. Together, these findings demonstrate the intratumoral genetic heterogeneity of surgically resected SCLC and provide insights into resistance to treatment.


Assuntos
Heterogeneidade Genética , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Proteínas de Ligação a Retinoblastoma/genética , Carcinoma de Pequenas Células do Pulmão/genética , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Variações do Número de Cópias de DNA , Receptores ErbB/genética , Receptores ErbB/metabolismo , Exoma , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Proteínas de Ligação a Retinoblastoma/metabolismo , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/cirurgia , Fumar/fisiopatologia , Análise de Sobrevida , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
4.
J Biomed Nanotechnol ; 17(7): 1380-1391, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446141

RESUMO

Esophageal cancer is one of the most common human malignancies and ranks sixth for global mortality; the major histological type is esophageal squamous cell carcinoma (ESCC). Here we assessed the effect of long non-coding (lnc) RNA OIP5-AS1 on the miR-30a-5p/Forkhead box protein D1 (FOXD1) axis in ESCC and investigated the underlying mechanism involving the ERK1/2 signaling pathway. lnc RNA OIP5-AS1 was highly expressed in human ESCC tissues and cells, targeted miR-30a-5p, and inhibited miR-30a-5p expression. Additionally, in human ESCC tissues, miR-30a-5p was poorly expressed, whereas FOXD1 mRNA and protein were highly expressed, with a negative correlation between miR-30a-5p and FOXD1 expression. miR-30a-5p targeted and inhibited FOXD1 expression. FOXD1 promoted the proliferation and invasion of ESCC and was related to the ERK1/2 signaling pathway; ERK1/2 inhibitors (LY-3214996) reversed the biological function of FOXD1. miR-30a-5p combined with FOXD1 regulated ERK1/2 expression and inhibited tumor growth in vivo. In this study, micro- and nano-particles were used as carriers to construct Nanocapsules carrying miR-30a-5p mimics and miR-30a-5p inhibitor through self-assembly method, so as to realize an efficient Nanocapsules delivery system of miR-30a-5p to esophageal cancer cells. It provides insights into targeted drug therapy and the development of micro- and nano-particles carriers.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , MicroRNAs , RNA Longo não Codificante , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , Transfecção
5.
J Clin Lab Anal ; 35(9): e23895, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34233042

RESUMO

INTRODUCTION: Serum neuron-specific enolase (NSE) is an important tumor marker for small cell lung cancer and neuroblastoma. However, the test of serum NSE compromised by specimen hemolysis is presented as a falsely higher result, which seriously disturbs clinical decision. This study aimed to establish a solution integrated with laboratory information system to clear the bias from hemolysis on serum NSE test. METHODS: The reference range of serum hemolysis index (HI) was first established, and specimen hemolysis rate was compared between HI test and visual observation. NSE concentration in serum pool with normal HI was spiked with serial diluted lysates from red blood cells to deduce individual corrective equation. The agreement between individual corrective equation and original NSE test was assayed by Bland and Altman plots. RESULTS: The high HI existed in 32.6% of specimens from patients. The NSE median of hemolyzed specimens was significant higher than the baseline (p = 0.038), while the corrected NSE median had no difference compared with the baseline (p = 0.757). The mean difference of corrected NSE and initial NSE was 1.92%, the SD of difference was 5.23%, and furthermore, the difference was independent of tendency of HI (Spearman r = -0.069, p = 0.640). The 95% confidence interval of mean difference (from -8.33% to 12.17%) was less than the acceptable bias range (±20%). CONCLUSION: The agreement between individual correction equation and NSE assay was satisfied. Our automated processing algorithm for serum NSE could provide efficient management of posttest data and correct positive bias from specimen hemolysis.

6.
Sci Rep ; 11(1): 13574, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193903

RESUMO

Groundwater is a vital resource for human welfare. However, due to various factors, groundwater pollution is one of the main environmental concerns. Yet, it is challenging to simulate groundwater quality dynamics due to the insufficient representation of nutrient percolation processes in the soil and Water Assessment Tool model. The objectives of this study were extending the SWAT module to predict groundwater quality. The results proved a linear relationship between observed and calculated groundwater quality with coefficient of determination (R2), Nash-Sutcliffe efficiency (NSE), percent bias (PBIAS) values in the satisfied ranges. While the values of R2, NSE and PBIAS were 0.69, 0.65, and 2.68 during nitrate calibration, they were 0.85, 0.85 and 5.44, respectively during nitrate validation. Whereas the values of R2, NSE and PBIAS were 0.59, 0.37, and - 2.21 during total dissolved solid (TDS) calibration and they were 0.81, 0.80, 7.5 during the validation. The results showed that the nitrate and TDS concentrations in groundwater might change with varying surface water quality. This indicated the requirement for designing adaptive management scenarios. Hence, the extended SWAT model could be a powerful tool for future regional to global scale modelling of nutrient loads and effective surface and groundwater management.

7.
Lancet Oncol ; 22(7): 977-990, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34143971

RESUMO

BACKGROUND: China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2-3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma. METHODS: This randomised, open-label, phase 2-3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab-bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes. FINDINGS: Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab-bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8-46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5-11·7) in the sintilimab-bevacizumab biosimilar group and 10·0 months (8·4-11·7) in the sorafenib group. Patients in the sintilimab-bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1-5·7]) than did patients in the sorafenib group (2·8 months [2·7-3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46-0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab-bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached-not reached] vs 10·4 months [8·5-not reached]; HR 0·57, 95% CI 0·43-0·75; p<0·0001). The most common grade 3-4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab-bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab-bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab-bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause). INTERPRETATION: Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients. FUNDING: Innovent Biologics. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , China , Progressão da Doença , Feminino , Hepatite B/virologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Sorafenibe/efeitos adversos , Fatores de Tempo , Adulto Jovem
8.
Lung Cancer ; 156: 82-90, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33933895

RESUMO

OBJECTIVES: To explore the efficacy and toxicities of split-course hypo-fractionated radiotherapy with concurrent chemotherapy (HFRT-CHT) with intensity modulated radiotherapy (IMRT) technique in non-small cell lung cancer (NSCLC) patients with postoperative locoregional recurrence (LRR). MATERIALS AND METHODS: NSCLC patients were eligible if confirmed as LRR disease without distant metastasis after complete resection. HFRT-CHT using IMRT technique was administered with 51 Gy in 17 fractions or 40 Gy in 10 fractions as the first course followed by a break. Patients with no disease progression and no persistent Grade ≥2 toxicities had the second course of 15 Gy in 5 fractions or 28 Gy in 7 fractions as a boost. The primary endpoint was progression-free survival (PFS). RESULTS: Fifty-eight patients were enrolled and analyzed. With a median follow-up of 23.9 months for all, the 2-year and 3-year PFS rate was 59.7 % and 46.4 %, the 2-year and 3-year OS rate was 72.5 % and 52.2 %, respectively, and a favorable objective response rate of 95.9 % was obtained after the whole courses protocol. Grade 3 acute pneumonitis and esophagitis occurred in 2 (3.4 %) and 7 (12.1 %) patients, and fatal pneumonitis was reported in one case (1.7 %). Exploratory subgroup analysis showed that performance status (PS) (PS 0 vs. 1: 2-year PFS, 88.1 % vs. 46.9 %,P = 0.001; 2-year OS, 100 % vs. 59.4 %, P < 0.001), recurrence site (single vs. multiple: 2-year PFS, 93.8 % vs. 47.4 %, P = 0.008; 2-year OS, 100 % vs. 63.0 %, P = 0.001), and gross tumor volume (GTV) (<50cm3 vs. ≥ 50cm3: 2-year PFS, 70.6 % vs. 46.2 %, P = 0.024; 2-year OS, 85.6 % vs. 57.4 %, P = 0.034) were significantly associated with PFS and OS. CONCLUSION: Split-course HFRT-CHT with IMRT technique achieved promising disease control and satisfactory survival with moderate toxicities in postoperative LRR of NSCLC. Good PS, a single recurrence site and GTV<50cm3 tended to have prolonged PFS and OS. Early detection of LRR may improve the efficacy of HFRT-CHT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fracionamento da Dose de Radiação , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia , Estudos Prospectivos
9.
Curr Oncol ; 28(2): 1424-1436, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33916930

RESUMO

BACKGROUND: Recent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma. METHODS: Two hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated. RESULTS: There were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p < 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p < 0.001) for DFS, and EGFR mutation type (p < 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40; p = 0.036; TKIs vs. chemotherapy, HR = 0.38; p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22; p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42; p = 0.034; TKIs vs. chemotherapy, HR = 0.33; p < 0.001) for DFS. No significant difference was found in the incidence of Grade 3-4 toxicities between groups (p = 0.445). CONCLUSIONS: Adjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
10.
J Vasc Interv Radiol ; 32(6): 861-868, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33771712

RESUMO

PURPOSE: To evaluate the efficacy and safety of combined microwave ablation (MWA) and osteoplasty as a palliative therapy for painful bone metastases. MATERIALS AND METHODS: As an extension of a previous limited single-center study, a retrospective review was conducted for 147 patients (77 male, 70 female) with painful bone metastases who underwent MWA combined with osteoplasty. In total, 102 (69.4%), 41 (27.9%), and 4 (2.7%) patients had spinal metastases, extraspinal metastases, and both, respectively. Treatment efficacy was determined by comparing visual analog scale (VAS) scores, daily morphine equivalent opioid consumption, and Oswestry disability index (ODI) scores before treatment and during the follow-up period (mean follow-up, 9.8 months; range 3-16). RESULTS: The mean VAS score significantly declined from 6.4 ± 2.3 before treatment to 3.2 ± 2.1, 1.9 ± 1.6, 1.8 ± 1.6, 1.8 ± 1.6, and 1.9 ± 1.6 at 24 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after treatment, respectively (P < .01). Furthermore, the mean daily morphine equivalent opioid consumption was significantly reduced from 81.5 ± 32.8 mg before treatment to 40.0 ± 20.6, 32.4 ± 10.2, 26.4 ± 10.0, 21.5 ± 8.3, and 19.3 ± 7.4 mg. The mean ODI score also declined after treatment (P < .0001). Major complications occurred in 4 of 147 patients, with 1 pathologic fracture, 1 nerve injury, and 2 mild skin infections. Minor cement leakages were observed at 69 sites (32.8%). CONCLUSIONS: MWA combined with osteoplasty is an effective and safe treatment for painful bone metastases.


Assuntos
Técnicas de Ablação , Neoplasias Ósseas/terapia , Dor do Câncer/terapia , Cementoplastia , Micro-Ondas/uso terapêutico , Cuidados Paliativos , Radiografia Intervencionista , Tomografia Computadorizada por Raios X , Técnicas de Ablação/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/uso terapêutico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Dor do Câncer/diagnóstico , Dor do Câncer/etiologia , Cementoplastia/efeitos adversos , China , Terapia Combinada , Feminino , Humanos , Masculino , Micro-Ondas/efeitos adversos , Pessoa de Meia-Idade , Radiografia Intervencionista/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X/efeitos adversos , Resultado do Tratamento , Adulto Jovem
11.
Dig Dis Sci ; 66(7): 2261-2271, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32740683

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most common digestive system diseases and yet lacks effective therapeutic regimen. AIMS: The aim of our present research was to probe the value of hsa_circ_0001017 in GC treatment. METHODS: qRT-PCR and Western blot were performed to detect gene and protein expressions, respectively. CCK-8 assay and clone formation assay were used to ensure the proliferation of GC cell lines. Transwell assay was performed to measure the migration and invasion of GC cell lines. The relationship between hsa_circ_0001017 and miR-197 and that between miR-197 and RHOB 3'-UTR were ensured using the luciferase reporter assay. RESULTS: Decreased hsa_circ_0001017 was discovered in GC, and upregulation of hsa_circ_0001017 notably repressed proliferation, migration, and invasion of GC cell lines. We further certificated that hsa_circ_0001017 served as miR-197 sponge and suppressed the expression of miR-197. Moreover, hsa_circ_0001017 upregulation meaningfully accelerated RHOB expression in both gene and protein levels, and RHOB was a downstream target of miR-197. Overexpression of miR-197 could markedly restrain hsa_circ_0001017-induced RHOB increasing and stifle inhibition of hsa_circ_0001017 to the malignant phenotype of GC cell lines. Next, our results further confirmed that hsa_circ_0001017 increasing notably inhibited tumor growth, impeded miR-197 production, while it enhanced the expression of RHOB in vivo. CONCLUSION: Our data demonstrated that upregulation of hsa_circ_0001017 could notably muffle the proliferation as well as the metastasis of GC cell lines and impede the formation of GC tumor via targeting to miR-197/RHOB signaling pathway. Our results evidenced that hsa_circ_0001017 may act as a rising biomarker for GC treatment.

12.
Ann Surg Oncol ; 28(6): 3025-3033, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33073346

RESUMO

BACKGROUND: The impact of the number of examined lymph nodes (ELNs) on stage correction and prognostication in patients with esophageal squamous cell carcinoma (ESCC) who underwent right transthoracic esophagectomy is still unclear. METHODS: Patients with ESCC who underwent right transthoracic esophagectomy at Sun Yat-sen University Cancer Center between January 1997 and December 2013 were retrospectively enrolled. The Cox proportional hazards regression model was used to determine the effect of ELN count on overall survival. The impact of ELN count on stage correction was evaluated using the hypergeometric distribution and Bayes theorem and ß-binomial distribution estimation, respectively. The threshold of ELNs was determined using the LOWESS smoother and piecewise linear regression. RESULTS: Among the 875 included patients, greater ELNs were associated with a higher rate of nodal metastasis. Significant association between staging bias and the number of ELNs is only observed through the Bayes method. The ELN count did not impact 90-day mortality but significantly impacted long-term survival (adjusted hazard ratio [aHR] 0.986), especially in those patients with node-negative disease (aHR 0.972). In patients with node-negative disease, cut-point analysis showed a threshold ELN count of 21. CONCLUSIONS: A greater number of ELNs is associated with more accurate node staging and better long-term survival in resected ESCC patients. We recommended harvesting at least 21 LNs to acquire accurate staging and long-term survival information for patients with declared node-negative disease using the right thoracic approach.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Teorema de Bayes , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
13.
J Environ Manage ; 280: 111678, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33298392

RESUMO

Soil salinity restricts plant growth, affects soil water balance and nitrous oxide (N2O) fluxes and can contaminate surface and groundwater. In this study, the Denitrification Decomposition (DNDC) model was modified to couple salt and water balance equations (SALT-DNDC) to investigate the effect of salinity on water balance and N2O fluxes. The model was examined against four growing seasons (2008-11) of observed data from Lethbridge, Alberta, Canada. Then, the model was used to simulate water filled pore space (WFPS), salt concentration and the N2O flux from agricultural soils. The results show that the effects of salinity on WFPS vary in different soil layers. Within shallow soil layers (<20 cm from soil surface) the salt concentration does not affect the average WFPS when initial salt concentrations range from 5 to 20 dS/m. However, in deeper soil layers (>20 cm from soil surface), when the initial salt concentration ranges from 5 to 20 dS/m it could indirectly affect the average WFPS due to changes of osmotic potential and transpiration. When AW is greater than 40%, the average growing season N2O emissions increase to a range of 0.6-1.0 g-N/ha/d at initial salt concentrations (5-20 dS/m) from a range of 0.5-0.7 g-N/ha/d when the salt concentrations is 0 dS/m. The newly developed SALT-DNDC model provides a unique tool to help investigate interactive effects among salt, soil, water, vegetation, and weather conditions on N2O fluxes.


Assuntos
Óxido Nitroso , Solo , Agricultura , Alberta , Óxido Nitroso/análise , Água
14.
J Environ Qual ; 49(1): 1-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33016361

RESUMO

Nitrous oxide (N2 O) emission from agricultural soils represents a significant source of greenhouse gas to the atmosphere. We evaluated the suitability of a modified Soil and Water Assessment Tool (SWAT) model to estimate the N2 O flux from the application of solid manure at two grassland sites (North Wyke [NW] and Pwllpeiran [PW]) in the United Kingdom. The simulated N2 O emissions were validated against field observations measured in 2011 and 2012 for model calibration and validation, respectively. The SWAT model predicts water-filled pore space (WFPS) very well with Nash-Sutcliffe efficiency (NSE), R2 , RMSE, and percentage bias (PBIAS) values of 0.67, .72, 0.06, and 3.64, respectively, during the calibration period for NW site, whereas it gives 0.68, .69, 0.07, and 3.04, respectively during the validation period. At PW, the model predicted the NSE, R2 , RMSE, and PBIAS of 0.55, .69, 0.04, and -4.5, respectively, during calibration and 0.63, .71, 0.05, and -2.6, respectively, during the validation period. Compared with WFPS, the model resulted in a slightly lower fit for N2 O emissions for NW (NSE = 0.47, R2  = .63 during calibration, and NSE = 0.55, R2  = .58 during validation) and for PW (NSE = 0.54, R2  = .71 for calibration, and NSE = 0.47, R2  = .69 for validation). Results revealed that the SWAT model performed reasonably well in representing the dynamics of N2 O emissions after solid manure application to grassland.


Assuntos
Esterco , Óxido Nitroso/análise , Pradaria , Solo , Reino Unido
15.
World J Surg Oncol ; 18(1): 258, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998771

RESUMO

BACKGROUND: The examination of lymph nodes (LNs) plays an important role in the nodal staging of non-small cell lung cancer (NSCLC). For patients without LN metastasis, the main role of thorough LN examination is accurate staging, which weakens the effect of staging migration. To date, the role of hilar and intrapulmonary (N1) station LNs has not been fully appreciated. In this study, we aimed to confirm the significance of N1 LNs in long-term survival for stage IA-IIA NSCLC patients and to find the minimum number of LN to examine. METHODS: The data of patients who underwent radical lobectomy and were confirmed as having non-metastatic LNs from January 2008 to March 2018 were retrospectively screened. Pathology records were reviewed for the number of LNs examined. The Kaplan-Meier method and Cox regression model were used to identify survival and prognostic factors. RESULTS: The median number of resected N1 LNs was 8. The number of patients with 0-2 N1 LNs, 3-5 N1 LNs, 6-8 N1 LNs, 9-11 N1 LNs, and more than 11 N1 LNs examined was 181, 425, 477, 414, and 531, respectively. Sex (P = 0.004), age (P < 0.001), tumor size (P = 0.004), differentiation degree (P = 0.001), and number of N1 LNs examined (P = 0.008) were independent prognostic factors of overall survival. Gender (P = 0.006), age (P = 0.031), tumor size (P = 0.001), differentiation degree (P = 0.001), vascular invasion (P = 0.034), and number of N1 LNs examined (P = 0.007) were independent prognostic factors of disease-free survival. Compared with patients with 0-5 N1 LNs examined, patients with more than 5 N1 LNs examined had better OS (P = 0.015) and had better DFS (P = 0.015) if only a landmark 5-year follow-up was performed. CONCLUSION: Increasing the number of N1 LN examination might improve the long-term survival of T1-2N0 NSCLC patients. These data indicate that at least 6 N1 nodes examined is an essential part in surgical and pathological management but cannot prove this. This finding should be confirmed in a large, prospective randomized clinical study.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
16.
J Cancer ; 11(20): 6114-6121, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922551

RESUMO

Background: This study aimed to develop a predictive model based on the risk of locoregional recurrence (LRR) in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma after complete resection. Methods: A total of 11,020 patients with lung surgery were screened to determine completely resected EGFR-mutant stage III-pN2 lung adenocarcinoma. Patients were excluded if they received preoperative therapy or postoperative radiation therapy (PORT). The time from surgery to LRR was recorded. Clinicopathological variables with statistical significance predicting LRR in the multivariate Cox regression were incorporated into the competing risk nomogram. Patients were then sub-grouped based on different recurrence risk as a result of the nomogram. Results: Two hundred and eighty-eight patients were enrolled, including 191 (66.3%) with unforeseen N2 (IIIA1-2), 75 (26.0%) with minimal/single station N2 (IIIA3), and 22 (7.6%) with bulky and/or multilevel N2 (IIIA4). The 2-year overall cumulative incidence of LRR was 27.2% (confidence interval [CI], 16.3%-38.0%). IIIA4 disease (hazard ratio, 2.65; CI, 1.15-6.07; P=0.022) and extranodal extension (hazard ratio, 3.33; CI, 1.76-6.30; P<0.001) were independent risk factors for LRR and were incorporated into the nomogram. Based on the nomogram, patients who did not have any risk factor (low-risk) had a significantly lower predicted 2-year incidence of LRR than those with any of the risk factors (high-risk; 4.6% vs 21.9%, P<0.001). Conclusions: Pre-treatment bulky/multilevel N2 and pathological extranodal extension are risk factors for locoregional recurrence in EGFR-mutant stage III-pN2 lung adenocarcinoma. Intensive adjuvant therapies and active follow-up should be considered in patients with any of the risk factors.

17.
Sci Total Environ ; 739: 139092, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32521338

RESUMO

The sustainability of grazing lands lies in the nexus of human consumption behavior, livestock productivity, and environmental footprint. Due to fast growing global food demands, many grazing lands have suffered from overgrazing, leading to soil degradation, air and water pollution, and biodiversity losses. Multidisciplinary efforts are required to understand how these lands can be better assessed and managed to attain predictable outcomes of optimal benefit to society. This paper synthesizes our understanding based on previous work done on modelling the influences of grazing of soil carbon (SC) and greenhouse gas emissions to identify current knowledge gaps and research priorities. We revisit three widely-used process-based models: DeNitrification DeComposition (DNDC), DayCent, and the Pasture Simulation model (PaSim) and two watershed models: The Soil & Water Assessment Tool (SWAT) and Variable Infiltration Capacity Model (VIC), which are widely used to simulate C, nutrient and water cycles. We review their structures and ability as process-based models in representing key feedbacks among grazing management, SOM decomposition and hydrological processes in grazing lands. Then we review some significant advances in the use of models combining biogeochemical and hydrological processes. Finally, we examine challenges of incorporating spatial heterogeneity and temporal variability into modelling C and nutrient cycling in grazing lands and discuss their weakness and strengths. We also highlight key research direction for improving the knowledge base and code structure in modelling C and nutrient cycling in grazing lands, which are essential to conserve grazing lands and maintain their ecosystem goods and services.

18.
Eur J Surg Oncol ; 46(10 Pt A): 1956-1962, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32439262

RESUMO

BACKGROUND: The impact of the number of examined lymph nodes (ELNs) on stage correction and prognostication in patients with oesophageal squamous cell carcinoma (ESCC) who underwent left transthoracic oesophagectomy is still unclear. METHODS: Patients with ESCC who underwent left transthoracic oesophagectomy at Sun Yat-sen University Cancer Center between January 1997 and December 2013 were retrospectively enrolled. The Cox proportional hazards regression model was used to determine the effect of ELN count on overall survival (OS). The association between ELN count and nodal status was investigated through scatter plot and binary logistic regression analyses. The impact of ELN count on stage correction was evaluated using the hypergeometric distribution and Bayes theorem. The threshold of ELNs was determined using the LOWESS smoother and piecewise linear regression. RESULTS: Among the 1826 included patients, greater ELNs were associated with a higher rate of nodal metastasis (adjusted OR = 1.018). When the ELN count increased, the omission rate of positive lymph nodes (LNs) decreased. The ELN count did not impact 90-day mortality but significantly impacted long-term survival (adjusted HR = 0.983), especially in those with node-negative disease (adjust HR = 0.972). In patients with node-negative disease, cut point analysis showed a threshold ELN count of 18. CONCLUSIONS: A greater number of ELNs is associated with more accurate node staging and better long-term survival in resected ESCC patients. We recommended harvesting at least 18 LNs to acquire accurate staging and long-term survival information for patients with declared node-negative disease in the left thoracic approach.


Assuntos
Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esofagectomia/métodos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Idoso , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Taxa de Sobrevida
19.
Eur Radiol ; 30(5): 2692-2702, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32020400

RESUMO

OBJECTIVES: This prospective trial was performed to verify whether microwave ablation (MWA) in combination with chemotherapy could provide superior survival benefit compared with chemotherapy alone. MATERIALS AND METHODS: From March 1, 2015, to June 20, 2017, treatment-naïve patients with pathologically verified advanced or recurrent non-small cell lung cancer (NSCLC) were randomly assigned to MWA plus chemotherapy group or chemotherapy group. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), time to local progression (TTLP), and objective response rate (ORR). The complications and adverse events were also reported. RESULTS: A total of 293 patients were randomly assigned into the two groups. One hundred forty-eight patients with 117 stage IV tumors were included in the MWA plus chemotherapy group. One hundred forty-five patients with 113 stage IV tumors were included in the chemotherapy group. The median follow-up period was 13.1 months and 12.4 months, respectively. Median PFS was 10.3 months (95% CI 8.0-13.0) in the MWA plus chemotherapy group and 4.9 months (95% CI 4.2-5.7) in the chemotherapy group (HR = 0.44, 95% CI 0.28-0.53; p < 0.0001). Median OS was not reached in the MWA plus chemotherapy group and 12.6 months (95% CI 10.6-14.6) in the chemotherapy group (HR = 0.38, 95% CI 0.27-0.53; p < 0.0001) using Kaplan-Meier analyses with log-rank test. The median TTLP was 24.5 months, and the ORR was 32% in both groups. The adverse event rate was not significantly different in the two groups. CONCLUSIONS: In patients with advanced NSCLC, longer PFS and OS can be achieved with the treatment of combined MWA and chemotherapy than chemotherapy alone. KEY POINTS: • Patients treated with MWA plus chemotherapy had superior PFS and OS over those treated with chemotherapy alone. • The ORR of patients treated with MWA plus chemotherapy was similar to that of those treated with chemotherapy alone. • Complications associated with MWA were common but tolerable and manageable.


Assuntos
Adenocarcinoma de Pulmão/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Micro-Ondas/uso terapêutico , Recidiva Local de Neoplasia/terapia , Ablação por Radiofrequência/métodos , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Compostos Organoplatínicos/administração & dosagem , Paclitaxel/administração & dosagem , Pemetrexede/administração & dosagem , Intervalo Livre de Progressão , Estudos Prospectivos , Resultado do Tratamento , Vinorelbina/administração & dosagem
20.
Biol Reprod ; 102(5): 1122-1133, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-31995151

RESUMO

Gonadotropin-releasing hormone agonists (GnRHa) are used as an alternative to human chorionic gonadotropin (hCG) to trigger ovulation and decrease the risk of ovarian hyperstimulation syndrome. GnRHa is less potent at inducing ovarian vascular endothelial growth factor (VEGF), but may also affect endometrial angiogenesis and early placental development. In this study, we explore the effect of superovulation on endometrial angiogenesis during critical periods of gestation in a mouse model. We assigned female mice to three groups: natural mating or mating following injection with equine chorionic gonadotropin and trigger with GnRHa or hCG trigger. Females were killed prior to implantation (E3.5), post-implantation (E7.5), and at midgestation (E10.5), and maternal serum, uterus, and ovaries were collected. During peri-implantation, endometrial Vegfr1 and Vegfr2 mRNA were significantly increased in the GnRHa trigger group (P < 0.02) relative to the hCG group. Vegfr1 is highly expressed in the endometrial lining and secretory glands immediately prior to implantation. At E7.5, the ectoplacental cone expression of Vegfa and its receptor, Vegfr2, was significantly higher in the hCG trigger group compared to the GnRHa group (P < 0.05). Soluble VEGFR1 and free VEGFA were much higher in the serum of mice exposed to the hCG trigger compared to GnRHa group. At midgestation, there was significantly more local Vegfa expression in the placenta of mice triggered with hCG. GnRHa and hCG triggers differentially disrupt the endometrial expression of key angiogenic factors during critical periods of mouse gestation. These results may have significant implications for placental development and neonatal outcomes following human in vitro fertilization.

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