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2.
Biomater Sci ; 9(22): 7456-7470, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34609385

RESUMO

Severe hypoxia in solid tumors limits the efficacy of oxygen (O2)-dependent photodynamic therapy (PDT). The overexpressed heat shock proteins (HSPs) in tumor cells hamper the effect of photothermal therapy (PTT). Herein, a tumor oxygenation-enhanced and ATP-reduced gelatin nanoreactor (MCGPD ∼ RGD NPs) for PDT/PTT-augmented combination cancer therapy is reported. In this nanosystem, the Arg-Gly-Asp (RGD) peptides of MCGPD ∼ RGD NPs can ensure accurate recognition and sufficient accumulation in the tumor site. After accumulation, doxorubicin (DOX) can be released from MCGPD ∼ RGD NPs in a mild acidic tumor microenvironment (TME) for highly efficient chemotherapy. Upon 808 nm laser irradiation, the overexpressed matrix metalloproteinase-2 (MMP-2) in the TME and the heat produced from the PDA coating trigger Gel NP degradation to expose chlorin e6 (Ce6) and Met from the cavity of MCGPD ∼ RGD NPs. The exposed Met elevates the O2 content and reduces ATP production in tumor sites to spur the successful O2-dependent PDT and HSP-mediated PTT. The heat generated by the PDA coating directly kills the tumor cells to ensure PTT and amplifies the chemotherapeutic effect. In vitro and in vivo assays indicate that MCGPD ∼ RGD NPs have excellent ability to promote cell apoptosis and to inhibit tumor growth. Overall, this smart responsive hydrogel nanosystem with hypoxia-relieving capacity and ATP-decreasing performance provides a promising strategy against cancer.


Assuntos
Metformina , Nanopartículas , Neoplasias , Fotoquimioterapia , Trifosfato de Adenosina , Linhagem Celular Tumoral , Humanos , Hipóxia , Metaloproteinase 2 da Matriz , Nanotecnologia , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente Tumoral
3.
Biomaterials ; 278: 121172, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34653935

RESUMO

Silicon, a highly biocompatible and ubiquitous chemical element in living systems, exhibits great potentials in biomedical applications. However, the silicon-based nanomaterials such as silica and porous silicon have been largely limited to only serving as carriers for delivery systems, due to the lack of intrinsic functionalities of silicon. This work presents the facile construction of a two-dimensional (2D) hydrogen-bonded silicene (H-silicene) nanosystem which is highlighted with tunable bandgap and selective degradability for tumor-specific photodynamic therapy facilely by surface covalent modification of hydrogen atoms. Briefly, the H-silicene nanosheet material is selectively degradable in normal neutral tissues but rather stable in the mildly acidic tumor microenvironment (TME) for achieving efficient photodynamic therapy (PDT). Such a 2D hydrogen-bonded silicene nanosystem featuring the tunable bandgap and tumor-selective degradability provides a new paradigm for the application of multi-functional two-dimensional silicon-based biomaterials towards the diagnosis and treatments of cancer and other diseases.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Hidrogênio , Neoplasias/tratamento farmacológico , Silício , Microambiente Tumoral
4.
J Biomed Nanotechnol ; 17(9): 1788-1797, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34688323

RESUMO

Dengue fever is a classic mosquito viral disease. Dengue virus non-structural protein-1 as a membrane-associated homologous dimer anchored to the surface of infected cells and also secreted into the blood. The nonstructural protein-1 levels are related to disease severity, and the presence of nonstructural protein-1 secreted from cells to the serum of people infected with the dengue virus is an early marker of infection. Paired antibodies are key in the establishment of rapid detection technology. In this study, the prepared recombinant nonstructural protein-1 protein of dengue virus serotype 3 was purified by the prokaryotic expression, and prepared monoclonal antibodies by cell fusion. A method for paired antibody screening was established based on the N-hydroxy succinimide-nanobeads and the prepared monoclonal antibodies. A simple and rapid point-of-care system integrating the paired antibodies and lateral flow assay was established to verify the screened antibody pairs. The results confirmed that the antibody pair screening method based on N-hydroxy succinimide-nanobeads is feasible.


Assuntos
Vírus da Dengue , Dengue , Animais , Anticorpos Antivirais , Dengue/diagnóstico , Ensaio de Imunoadsorção Enzimática , Humanos , Proteínas não Estruturais Virais
6.
Small ; 17(42): e2102113, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34524730

RESUMO

Photodynamic therapy (PDT) has attracted tremendous attention due to its advantages such as high safety and effectiveness compared to traditional radiotherapy and chemotherapy. However, the intratumoral hypoxic microenvironment will inevitably compromise the PDT effect of the highly oxygen-dependent type II photosensitizers, implicating the urgent demand for continuous intratumoral oxygenation. Herein, biocompatible photosynthetic cyanobacteria have been modified with inorganic two-dimensional black phosphorus nanosheets (BPNSs) to be a novel bioreactor termed as Cyan@BPNSs. Upon 660 nm laser irradiation, the photosynthetic cyanobacteria generate oxygen continuously in situ through photosynthesis, followed by the photosensitization of BPNSs for activating oxygen into singlet oxygen (1 O2 ), resulting in a large amount of 1 O2 accumulation at the tumor site and the consequent strong tumor cell killing effect both in vitro and in vivo. This work provides an attractive strategy for efficient and biocompatible PDT, meanwhile extends the scope of microbiotic nanomedicine by hybridizing microorganisms with inorganic nanophotosensitizer.


Assuntos
Cianobactérias , Fotoquimioterapia , Linhagem Celular Tumoral , Fósforo , Fármacos Fotossensibilizantes/uso terapêutico , Fotossíntese
7.
J Am Chem Soc ; 143(38): 15587-15592, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34533932

RESUMO

As a fundamental chemical property, aromaticity guides the synthesis of novel structures and materials. Replacing the carbon moieties of aromatic hydrocarbons with transition metal fragments is a promising strategy to synthesize intriguing organometallic counterparts with a similar aromaticity to their organic parents. However, since antiaromaticity will endow compound instability, it is a great challenge to obtain an antiaromatic organometallic counterpart based on such transition metal replacement in aromatic hydrocarbons. Here, we report an efficient aromaticity transformation on aromatic naphthalene through the bridgehead replacement of an osmium fragment, leading to the unprecedented synthesis of metal-bridgehead naphthalene featuring a highly twisted structure as confirmed by X-ray crystallography characterization. Such a twisted conformation works together with its phosphonium substituents to release the antiaromaticity in the planar conformation of the metal-bridgehead naphthalene. Our findings prove the bridgehead involvement of transition metals in unexpected aromaticity modifications and open an avenue for novel metal-bridgehead complexes.

8.
Proc Natl Acad Sci U S A ; 118(39)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34544859

RESUMO

Electrophilic aromatic substitution (EAS) reactions are widely regarded as characteristic reactions of aromatic species, but no comparable reaction has been reported for molecules with Craig-Möbius aromaticity. Here, we demonstrate successful EAS reactions of Craig-Möbius aromatics, osmapentalenes, and fused osmapentalenes. The highly reactive nature of osmapentalene makes it susceptible to electrophilic attack by halogens, thus osmapentalene, osmafuran-fused osmapentalene, and osmabenzene-fused osmapentalene can undergo typical EAS reactions. In addition, the selective formation of a series of halogen substituted metalla-aromatics via EAS reactions has revealed an unprecedented approach to otherwise elusive compounds such as the unsaturated cyclic chlorirenium ions. Density functional theory calculations were conducted to study the electronic effect on the regioselectivity of the EAS reactions.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34428713

RESUMO

With the increase in farming density and the continuously high summer temperatures against the background of global warming, high temperature stress has become a major challenge in fish farming. In this study, we simulated the high temperature environments (20 °C, 24 °C, and 28 °C) that may occur during turbot culture. High-throughput sequencing was used to investigate the lipid metabolism response patterns in juvenile turbot liver under high temperature stress. A total of 2067 differentially expressed genes (DEGs) were identified. KEGG analysis revealed that the DEGs were mainly associated with glycerophospholipid metabolism, steroid biosynthesis, glycerolipid metabolism, fatty acid metabolic pathways, and the PPAR signaling pathway. A regulatory network was constructed to further elucidate the transcriptional regulation of lipid metabolism. We speculated that high temperature activates PPAR signaling pathway through interaction with ligands such as fatty acids. On the one hand, the HMGCS1 gene in this pathway can inhibit sterol synthesis by down-regulating the expression of key genes in steroid biosynthesis pathway (SQLE, EBP, and DHCR24). On the other hand, the expression of ACSL1 in this pathway is significantly increased under high temperature, which may play an important role in regulating fatty acid metabolism. Moreover, we collected blood and detected changes in serum lipid parameters; the variation patterns were also consistent with our results. These findings reveal that lipid metabolism has an important regulatory role in stress resistance when turbot is exposed to high temperatures.

10.
Nano Lett ; 21(16): 6764-6772, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34342999

RESUMO

Magnetic-based theranostics feature a high efficiency, excellent tissue penetration, and minimal damage to normal tissues, are noninvasive, and are widely used in the diagnosis and therapy of clinical diseases. Herein, a conceptually novel magnetostrictive-piezoelectric nanocatalytic medicine (MPE-NCM) for tumor therapy is proposed by initiating an intratumoral magneto-driven and piezoelectric-catalyzed reaction using core-shell structured CoFe2O4-BiFeO3 magnetostrictive-piezoelectric nanoparticles (CFO-BFO NPs) under an alternating magnetic field. The CFO-BFO NPs catalyze the generation of cytotoxic reactive oxygen species (ROS): superoxide radicals (•O2-) and hydroxyl radicals (•OH). The simulation calculation demonstrates the highly controllable electric polarization, facilitating the above catalytic reactions under the magnetic stimulation. Both a detailed cell-level assessment and the tumor xenograft evaluation evidence the significant tumor eradication efficacy of MPE-NCM. This study proposes an original and novel magneto-responsive nanocatalytic modality for cancer therapy, which displays promising prospects for the future clinic translation owing to its excellent catalytic dynamic responsiveness, high therapeutic efficacy, and biosafety in vivo.


Assuntos
Peróxido de Hidrogênio , Fototerapia , Catálise , Linhagem Celular Tumoral , Radical Hidroxila
11.
Chemistry ; 27(56): 14017-14024, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34312920

RESUMO

Chiral compounds are known to be important not only because they are the fundamental components of living organisms, but also for their unique chiroptical properties. In recent years, scientists have fabricated several chiral organic supramolecular aggregates by using chiral physical fields, such as vortex flow. Herein, the relationship between dynamic chiroptical properties and rheological nature is discussed, suggesting the shear thinning properties of non-Newtonian fluids might help colloidal particles adopt a chiral arrangement in vortices. Furthermore, the storage modulus of colloids could be increased by adding a linking agent, which successfully kept the dynamic chiroptical properties in the static state. Moreover, the salt effect on the host-guest interaction involved in the colloids was studied, the results suggested a significant enhancement of the transferred dynamic circular dichroism for the achiral guest molecule.


Assuntos
Coloides , Reologia
12.
Exp Ther Med ; 22(2): 860, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34178133

RESUMO

The incidence of lower back pain caused by intervertebral disc degeneration (IDD) is gradually increasing. IDD not only affects the quality of life of the patients, but also poses a major socioeconomic burden. There is currently no optimal method for delaying or reversing IDD, mainly due to its unknown pathogenesis. MicroRNAs (miRNAs/miRs) participate in the development of a number of diseases, including IDD. Abnormal expression of miRNAs in the intervertebral disc is implicated in various pathological processes underlying the development of IDD, including nucleus pulposus (NP) cell (NPC) proliferation, NPC apoptosis, extracellular matrix remodeling, inflammation and cartilaginous endplate changes, among others. The focus of the present review was the advances in research on the involvement of miRNAs in the mechanism underlying IDD. Further research is expected to identify markers for early diagnosis of IDD and new targets for delaying or reversing IDD.

13.
Front Oncol ; 11: 618477, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34026606

RESUMO

Background: There is controversy about the characteristics and prognostic implications of signet ring cell gastric cancers and non-signet ring cell gastric cancers. Objective: This study aims to evaluate clinicopathological characteristics and prognoses of signet ring cell carcinoma (SRCC) and non-signet ring cell carcinoma (NSRCC) of stomach. Methods: Studies compared between SRCC and NSRCC of the stomach after gastrectomy and published before September 1st, 2020, in the PubMed, Cochrane, and Embase databases, were identified systematically. Results: A total of 2,865 studies were screened, and 36 studies were included, with 19,174 patients in the SRCC group and 55,942 patients in the NSRCC group. SRCC patients were younger in age (P < 0.001), less likely to be male patients (P < 0.001), more afflicted with upper third lesions (P < 0.001), and presenting with more Borrmann type IV tumors (P = 0.005) than NSRCC patients. Lymph nodes metastasis was similar between SRCC and NSRCC patients with advanced tumor stage (OR: 0.86, 95% CI: 0.671.10, P = 0.23), but lower in the SRCC than NSRCC patients with early tumor stage (OR: 0.73; 95% CI: 0.560.98, P = 0.02). SRCC patients had comparable survival outcomes with NSRCC patients for early gastric cancers (HR: 1.05, 95% CI: 0.651.68, P < 0.001) but had significantly poor prognosis for patients with advanced tumor stage (HR: 1.50, 95% CI: 1.281.76, P < 0.001). Conclusions: Signet ring cell carcinomas of the stomach are an increasingly common histopathological subtype of gastric cancers. These kinds of patients tend to be younger in age and more often female. Although, signet ring cell gastric cancer is a negative prognostic factor for patients with advanced stage. The difference is that for early stage of signet ring cell gastric cancers, it has low lymph nodes metastasis rate and comparable prognosis with non-signet ring cell cancers.

14.
Immun Inflamm Dis ; 9(3): 1000-1008, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34033704

RESUMO

OBJECTIVE: Previous studies have shown that increased neutrophils, as a manifestation of oxidative stress, may be involved in the progression of kidney disease. To our knowledge, little is known about the relationship between neutrophils and renal impairment in rheumatoid arthritis (RA). Therefore, we aim to investigate whether neutrophil is associated with renal impairment in RA patients. METHODS: We retrospectively investigated the renal function of 602 RA patients in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine by estimated glomerular filtration rate (eGFR) from September 2018 and September 2019. The exposure variable was neutrophils, and the main outcome was eGFR. General data (gender, age, duration, hypertension, diabetes, hobbies, and medication history), whole blood markers, lipid indexes, and inflammatory indexes were collected as much as possible. We used multivariable logistic regression analysis to evaluate the association between neutrophils and renal impairment in RA participants. RESULTS: A total of 89 cases (14.8%) had renal impairment with eGFR < 60 ml/min/1.73 m2 , and 75 cases (84.3%) were female. Subgroup analysis showed that female (odds ratio [OR] = 0.523, 95% confidence interval [CI]: 0.318-0.867, p = .011), neutrophils greater thsn 7.5 × 109 /L (OR = 2.314, 95% CI: 1.310-4.087, p = .004), NLR > 3.53 (OR = 1.757, 95% CI: 1.104-2.799, p = .018), hemoglobin less than 120 g/L (OR = 2.413, 95% CI: 1.418-4.118, p = .001), and UA > 360 µmol/L (OR = 6.052, 95% CI: 3.708-9.878, p < .001) was related to renal damage in RA. Adjusted for several confounders, the multivariable analysis indicated that neutrophils greater than 7.5 × 109 /L (OR = 1.784, 95% CI: 1.164-3.288, p = .031) was independently associated with an increased risk of renal impairment in RA. CONCLUSION: Our study demonstrated that neutrophils greater than 7.5 × 109 /L was associated with a high risk of renal impairment in RA, suggesting that neutrophil may be a biomarker for renal impairment in RA.


Assuntos
Artrite Reumatoide , Neutrófilos , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Estudos Retrospectivos
15.
Ther Adv Hematol ; 12: 2040620720983127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796233

RESUMO

Background and aims: Monoclonal immunoglobulin light chain associated Fanconi syndrome (LC-FS) is a rare disease that involves proximal tubules. As most of the reported cases came from western countries, we aimed to analyze the clinicopathological characteristics of Asian LC-FS and its treatment responses to chemotherapy. Methods: A total of 26 LC-FS patients in a single-center were retrospectively studied. Results: At diagnosis, the mean age of the 26 Asian LC-FS patients was 54.7 ± 14.7 years, with females accounting for 57.7%. They presented with different degrees of proximal tubular dysfunctions with normoglycemic glycosuria (88.0%), hyperphosphaturia (84.2%) and aminoaciduria (84.0%) as the most common features. The mean estimated glomerular filtration rate (eGFR) was (68.0 ± 26.4) ml/min per 1.73 m2. After chemotherapy, renal response was achieved in 58.3% cases, which was accompanied by hematological response, and tubular response was acquired in 66.7% cases. During 3 years of follow-up, the eGFR levels significantly decreased in the monoclonal gammopathy of renal significance patients, few of whom (21.4%) had received chemotherapy. Conclusion: Asian LC-FS patients had mild renal function disorder. The chemotherapy could improve both renal and tubular functions, which may be related to the hematological response.

16.
Front Microbiol ; 12: 611323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708180

RESUMO

Resveratrol (RSV) is a potential alternative therapy for non-alcoholic fatty liver disease (NAFLD) that has been evaluated in many clinical trials, but the mechanisms of RSV action have not been fully elucidated. Recent studies suggested that the gut microbiota is an important RSV target; therefore, we speculated that the gut microbiota might mediate the beneficial effects of RSV in NAFLD. To verify this hypothesis, we established a high-fat diet (HFD)-induced NAFLD mouse model, which was subjected to RSV gavage to evaluate the therapeutic effects. We observed that RSV reduced liver steatosis and insulin resistance in NAFLD. RSV significantly changed the diversity and composition of the gut microbiota according to 16S rRNA sequencing. Gut microbiota gene function prediction showed that the enrichment of pathways related to lipid and glucose metabolism decreased after RSV treatment. Furthermore, correlation analysis indicated that the improvements in NAFLD metabolic indicators were closely related to the altered gut microbiota. We further fermented RSV with the gut microbiota in vitro to verify that RSV directly affected the gut microbiota. Our data suggested that the gut microbiota might be an important target through which RSV exerts its anti-NAFLD effect.

17.
Cancer Med ; 10(1): 98-108, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33264518

RESUMO

BACKGROUND: Although aberrant expression of N6-methyladenine (m6 A) methylation-related genes contribute to tumorigenesis in many solid tumors, the prognostic value of the m6 A-related genes and their correlation with clinicopathological features in gliomas need advanced study. METHODS: The clinical and sequencing data of 288 patients with glioma were extracted from Chinese Glioma Genome Atlas database. By univariate and multivariable Cox regression analysis, the m6 A-related prognostic genes were identified, and their correlation with clinicopathological features was further analysis. A nomogram was constructed by R software and the performance of it was assessed by calibration and time-dependent receiver operating characteristic curve. RESULTS: Nine m6 A-related genes were identified as independent prognostic factors, which were mostly enriched in RNA splicing, regulation of immune response and vesicle-mediated transport. By expression value and regression coefficient of these genes, we constructed risk score of each patient, which was highly associated with clinicopathological features. Kaplan-Meier curve showed that the prognosis of patients with high-risk scores was significantly worse than that with low-risk scores (HR = 4.30, 95% CI = 3.16-5.85, p < 0.0001). A nomogram was constructed based on the nine m6 A-related genes signature and clinicopathological features with well-fitted calibration curves (c-index = 0.82), showing high specificity and sensitivity (area under the curve for 1-, 3-, and 5-years survival probability = 0.874, 0.918, and 0.934). CONCLUSIONS: A nine m6 A-related genes signature was identified in gliomas. The m6 A-related risk score is a novel prognostic factor for patients with glioma, and is associated with clinicopathological features. Moreover, the nomogram based on the nine m6 A-related genes signature and clinicopathological features had good efficacy in predicting the survival probability.


Assuntos
Adenina/análogos & derivados , Neoplasias Encefálicas/genética , Metilação de DNA , Epigênese Genética , Perfilação da Expressão Gênica , Glioma/genética , Nomogramas , Transcriptoma , Adenina/metabolismo , Adulto , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , China , Bases de Dados de Ácidos Nucleicos , Feminino , Glioma/mortalidade , Glioma/patologia , Glioma/terapia , Humanos , Masculino , Modelos Genéticos , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo
18.
Biomaterials ; 269: 120455, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33162174

RESUMO

The rapid development of nanotechnology has triggered the emerging of tremendous theranostic nanoplatforms for combating cancers. Silicene, as an emerging two-dimensional (2D) material, has been recently explored as therapeutic agent due to their desirable biodegradation and strong photothermal-conversion performance. However, the rational design of silicene-based composites for further exerting multifunctional medical applications is still highly challenging. Herein, we report on the construction of silicene-based silicene@Pt composite nanosheets for computed tomography (CT)/photoacoustic (PA) imaging-guided dual-sensitized radiotherapy combined with photonic tumor hyperthermia, which has been achieved by a seed-growth approach to in situ grow Pt components onto silicene nanosheets' surface. Especially, by functionalization of Pt components, these nanosheets could act as both contrast agents for CT imaging and dual radio-sensitizing agents for radiotherapy, which could deposit Pt-involved radiation energy (sensitized therapeutic process I) and overcome hypoxia-associated radio-resistance by Pt-catalytic O2 generation from overexpressed H2O2 within the tumor microenvironment (sensitized therapeutic process II). The strong photothermal-conversion performance of silicene nanosheets not only endowed silicene@Pt composite nanosheets with photoacoustic imaging property, but also realized the photonic tumor hyperthermia and achieved a combined therapeutic effect with radiotherapy. This work not only broadens the biomedical applications of silicene, but also develops functionalization strategies of silicene for versatile biomedical applications.


Assuntos
Hipertermia Induzida , Neoplasias , Técnicas Fotoacústicas , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio , Hipertermia , Fototerapia , Nanomedicina Teranóstica
19.
Surg Endosc ; 35(3): 1465-1475, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33030588

RESUMO

BACKGROUND: Suprapancreatic lymphadenectomy is the essence of D2 radical gastric cancer surgery. The present study aimed to describe clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area. METHODS: The data from gastric cancer patients who underwent surgical treatment from September 2016 to December 2018 were collected. Patients were divided into clockwise modularized lymphadenectomy (CML) and traditional open gastrectomy (OG) groups according to the surgical treatment strategy. The propensity score matching method was utilized to balance the baseline characteristics between the two groups. RESULTS: Finally, 551 gastric cancer patients were included in the present study. Following propensity score matching, 106 pairs of patients in the CML group and OG group were included in the final analysis. The CML group had more total examined lymph nodes (36, IQR 28-44.74 vs. 29, IQR 29-39.5, p = 0.002) and no. 9 station nodes (2, IQR 1-5 vs. 2, IQR 1-3, p = 0.007) than the OG group. There was less intraoperative blood loss (30, IQR 20-80 ml vs. 80, IQR 50-80 ml, p < 0.001) and a longer surgical duration (262.5 min, IQR 220-303.25 min vs. 232, IQR 220-255 min, p < 0.001) in the CML group than in the OG group. The incidence of postoperative complications (19.8% vs. 16.0%, p = 0.591) and postoperative hospital stay (8, IQR 7-9 days vs. 8, IQR 7-9 days, p = 0.452) were comparable between the CML and OG groups. CONCLUSION: Laparoscopic lymphadenectomy for gastric cancer surgery is technically demanding. Clockwise modularized laparoscopic lymphadenectomy in the suprapancreatic area can attain similar effects as traditional open surgery and without an increase in postoperative adverse events.


Assuntos
Gastrectomia , Laparoscopia , Excisão de Linfonodo , Pâncreas/cirurgia , Pontuação de Propensão , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Complicações Pós-Operatórias/etiologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
20.
Clin Transl Sci ; 14(3): 919-933, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33382906

RESUMO

The efficacy of agents targeting epidermal growth factor receptor (EGFR) in patients with various cancers was well elucidated. However, the safety profile of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has not been systematically investigated. This meta-analysis aimed to evaluate the safety profile of EGFR-TKIs in patients with cancer. A systematic search of PubMed, EMBASE, Cochrane Library databases, ASCO, and ESMO abstracts were conducted. Randomized controlled trials (RCTs) that compared safety profile of EGFR-TKIs with placebo were included. The end points included treatment-related adverse events (AEs), treatment discontinuation, and toxic death. Twenty-eight RCTs containing 17,800 patients were included. The analyses showed that the most frequently observed all-grade AEs in patients treated with EGFR-TKIs were diarrhea (53.7%), rash (48.6%), mucositis (46.5%), alanine aminotransferase (ALT) increased (38.9%), and skin reaction (35.2%). The most common high-grade (grade ≥3) AEs were mucositis (14.8%), pain (8.2%,), metabolism and nutrition disorders (7.4%), diarrhea (6.2%), dyspnea (6.1%), and hypertension (6.1%). The incidence of serious AEs, treatment discontinuation, and toxic death due to AEs were 18.2%, 12.36%, and 3.0%, respectively. Pooled risk ratio (RR) showed that the use of EGFR-TKIs was associated with an increased risk of developing AEs. Subgroup analysis indicated that the risk of AEs varied significantly according to tumor type, generation line, and drug type. Our meta-analysis indicates EGFR-TKIs was associated with a significant increased risk of a series of unique AEs. Early detection and proper management of AEs are important to reduce morbidity, avoid treatment discontinuation, and improve patient quality of life. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? The safety profile of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) varied in different trials, and has not been systemically investigated. WHAT QUESTION DID THIS STUDY ADDRESS? We conducted this meta-analysis of randomized control trials (RCTs) to provide a comprehensive evaluation of adverse event in patients with cancer receiving EGFR-TKIs. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Our meta-analysis indicates EGFR-TKIs was associated with a significant increased risk of a series of unique adverse events (AEs). HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The integrated understanding of safety profile of EGFR-TKIs will help in the future design of new EGFR-TKIs with a better safety profile.

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