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1.
Int J Clin Oncol ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839664

RESUMO

BACKGROUND: Intrahepatic recurrence is one of the main causes of treatment failure in patients with colorectal cancer liver metastasis (CRLM). Hepatic steatosis was reported to provide fertile soil for metastasis. The effect of irinotecan-inducted hepatic steatosis on the progression of liver metastasis remains to be verified. Therefore, we aim to clarify the effect of hepatic steatosis on postoperative intrahepatic recurrence in CRLM and whether it is relevant to irinotecan-based chemotherapy. METHODS: Data for a total of 284 patients undergoing curative surgical treatment for CRLMs were retrospectively reviewed between March 2007 and June 2018. Hepatic steatosis score (HSS) was established by combining Liver to Spleen CT ratio (LSR) and Uric acid to HDL-cholesterol ratio (UHR) to detect the presence of hepatic steatosis. RESULTS: The evaluation model is consistent with pathological results and has high prediction ability and clinical application value. Patients with HSS high risk (HSS-HR) had significantly worse prognosis than those with HSS low risk (HSS-LR) (3-year intrahepatic RFS: 42.7% vs. 29.4%, P = 0.003; 5-year OS: 45.7% vs. 26.5%, P = 0.002). Univariate and multivariate analysis confirmed its essential role in the prediction of intrahepatic RFS. Besides, patients treated with preoperative irinotecan chemotherapy were more likely to end up with HSS-HR than those with non-irinotecan chemotherapy (63.3% vs. 21.8%, P < 0.001). Furthermore, irinotecan chemotherapy is relevant to worse prognosis in baseline HSS-HR patients. CONCLUSION: In summary, patients with HSS-HR had significantly worse 5-year OS and 3-year intrahepatic RFS. Irinotecan chemotherapy is more likely to lead to HSS-HR and pre-existing hepatic steatosis may be a worse prognostic factor limiting patients underwent IRI-based chemotherapy.

2.
Clin Cosmet Investig Dermatol ; 17: 1083-1092, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765192

RESUMO

Curcumin, derived from Curcuma longa (turmeric), exhibits significant potential in dermatology, addressing conditions like atopic dermatitis, psoriasis, chronic wounds, skin cancer, and infections through its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. This review synthesizes evidence on curcumin's mechanisms, including modulation of immune responses and promotion of wound healing, showcasing its efficacy in reducing inflammation, cytokine levels, and enhancing skin barrier functions. Studies highlight curcumin's ability to selectively target tumor cells, suggesting a multifaceted approach to cancer therapy with minimal side effects. Despite promising therapeutic benefits, challenges remain in bioavailability, potency, and targeted delivery, underscoring the need for further research to optimize dosages, delivery methods, and assess long-term safety. The integration of curcumin into dermatological practice requires a balanced consideration of evidence-based efficacy and safety. Curcumin's comprehensive utility in dermatology, coupled with the necessity for advanced scientific exploration, emphasizes the importance of combining traditional knowledge with contemporary research to improve patient care in dermatology. This approach could significantly enhance outcomes for individuals with skin-related conditions, marking curcumin as a versatile and promising agent in the field.

3.
Int J Surg ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38652147

RESUMO

BACKGROUND: We aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients. METHODS: We performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1). Survival actualization after long-term follow-up was performed in patients analyzed on an intention-to-treat basis. RESULTS: From January 2011 to January 2016, 696 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy and radical surgical resection (n=341) or curative surgical resection alone (n=344). Intraoperative chemotherapy with surgical resection showed no significant survival benefit over surgical resection alone in colorectal cancer patients (3-year DFS: 91.1% vs. 90.0%, P=0.328; 3-year OS: 94.4% vs. 95.9%, P=0.756). However, colon cancer patients benefitted from intraoperative chemotherapy, with a relative 4% reduction in liver and peritoneal metastasis (HR=0.336, 95% CI: 0.148-0.759, P=0.015) and a 6.5% improvement in 3-year DFS (HR=0.579, 95% CI: 0.353-0.949, P=0.032). Meanwhile, patients with colon cancer and abnormal pretreatment CEA levels achieved significant survival benefits from intraoperative chemotherapy (DFS: HR=0.464, 95% CI: 0.233-0.921, P=0.029 and OS: (HR=0.476, 95% CI: 0.223-1.017, P=0.049). CONCLUSIONS: Intraoperative chemotherapy showed no significant extra prognostic benefit in total colorectal cancer patients who underwent radical surgical resection; however, in colon cancer patients with abnormal pretreatment serum CEA levels (> 5 ng/ml), intraoperative chemotherapy could improve long-term survival.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38439666

RESUMO

Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to different types of cell death. The degree of irreversible myocardial damage is closely related to age, and ferroptosis is involved in cardiomyocyte damage. However, the mechanisms underlying ferroptosis regulation in aging myocardial I/R injury are still unclear. The present study aims to explore the underlying mechanism of piRNA regulation in ferroptosis. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line (H9C2) to construct an aging cardiomyocyte model, we investigate whether ferroptosis occurs after reperfusion injury in vitro and in vivo. This study focuses on the upregulation of piR-000699 after hypoxia/reoxygenation treatment in aging cardiomyocytes by observing hypoxia/reoxygenation (H/R) injury indicators and ferroptosis-related indicators and clarifying the role of piR-000699 in H/R injury caused by ferroptosis in aging cardiomyocytes. Bioinformatics analysis reveals that SLC39A14 is a gene that binds to piR-000699. Our data show that ferroptosis plays an important role in I/R injury both in vivo and in vitro. Furthermore, the results show the potential role of piR-000699 in regulating SLC39A14 in ferroptosis in aging cardiomyocytes under hypoxia/reoxygenation conditions. Together, our results reveal that the mechanism by which piR-000699 binds to SLC39A14 regulates ferroptosis in aging myocardial I/R injury.

5.
Small ; 20(24): e2311174, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38174619

RESUMO

Modulating the coordination configuration of single Fe atom has been an efficient strategy to strengthen the redox dynamics for lithium-sulfur batteries (LSBs) but remains challenging. Herein, the single Fe atom is functioned with nitrogen and carbon atoms in the first shell, and simultaneously, oxidized sulfur (─SOx) in the second shell, which presents a lower antibonding state and well address the redox activity of sulfur cathodes. In the ternary-coordinated single Fe atom catalyst (FeN2C2-SOx-NC), the binary structure of FeN2C2 provides a lower Fe-S bonding strength and d-p orbital hybridization, which obviously optimizes the adsorption and desorption behavior of sulfur species during the reduction and oxidation reaction processes. Simultaneously, the ─SOx redistributes the electron density of the coordinating nitrogen atoms, which possesses high electron-withdrawing ability and develops electrocatalytic activity. As a result, the sulfur cathodes with FeN2C2-SOx-NC present an excellent high-rate cyclic performance, accompanied by a capacity decay rate of 0.08% per cycle for 500 cycles at 4.0 C. This study provides new insights for optimizing the redox dynamics of sulfur cathodes in LSBs at the atomic level.

6.
Nat Commun ; 15(1): 499, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216551

RESUMO

Mutant KRAS (KRASMUT) is often exploited by cancers to shape tumor immunity, but the underlying mechanisms are not fully understood. Here we report that tumor-specific cytotoxic T lymphocytes (CTLs) from KRASMUT cancers are sensitive to activation-induced cell death (AICD). circATXN7, an NF-κB-interacting circular RNA, governs T cell sensitivity to AICD by inactivating NF-κB. Mechanistically, histone lactylation derived from KRASMUT tumor cell-produced lactic acid directly activates transcription of circATXN7, which binds to NF-κB p65 subunit and masks the p65 nuclear localization signal motif, thereby sequestering it in the cytoplasm. Clinically, circATXN7 upregulation in tumor-specific CTLs correlates with adverse clinical outcomes and immunotherapeutic resistance. Genetic ablation of circAtxn7 in CD8+ T cells leads to mutant-selective tumor inhibition, while also increases anti-PD1 efficacy in multiple tumor models in female mice. Furthermore, targeting circATXN7 in adoptively transferred tumor-reactive CTLs improves their antitumor activities. These findings provide insight into how lymphocyte-expressed circRNAs contribute to T-cell fate decisions and anticancer immunotherapies.


Assuntos
Neoplasias , Proteínas Proto-Oncogênicas p21(ras) , RNA Circular , Evasão Tumoral , Animais , Feminino , Camundongos , Linfócitos T CD8-Positivos , Morte Celular/genética , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , RNA Circular/genética , Evasão Tumoral/genética , Humanos
7.
Autophagy ; 20(1): 114-130, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37615625

RESUMO

Bevacizumab plays an important role in the first and second line treatment for metastatic colorectal cancer (CRC). And induction of hypoxia and the tumors response to it plays an important role in determining the efficacy of antiangiogenic therapy while the connection between them remains unclear. Here, we found that lactate accumulated in the tumor environment of CRC and acted as substrates for histone lactylation, and this process was further induced by cellular enhanced glycolysis in hypoxia. We determined that CRC patients resistant to bevacizumab treatment presented with elevated levels of histone lactylation and inhibition of histone lactylation efficiently suppressed CRC tumorigenesis, progression and survival in hypoxia. Histone lactylation promoted the transcription of RUBCNL/Pacer, facilitating autophagosome maturation through interacting with BECN1 (beclin 1) and mediating the recruitment and function of the class III phosphatidylinositol 3-kinase complex, which had a crucial role in hypoxic cancer cells proliferation and survival. Moreover, combining inhibition of histone lactylation and macroautophagy/autophagy with bevacizumab treatment demonstrated remarkable treatment efficacy in bevacizumab-resistance patients-derived pre-clinical models. These findings delivered a new exploration and important supplement of metabolic reprogramming-epigenetic regulation, and provided a new strategy for improving clinical efficacy of bevacizumab in CRC by inhibition of histone lactylation.Abbreviations: 2-DG: 2-deoxy-D-glucose; BECN1: beclin 1; CQ: chloroquine; CRC: colorectal cancer; DMOG: dimethyloxalylglycine; H3K18la: histone H3 lysine 18 lactylation; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; Nala: sodium lactate; PDO: patient-derived orgnoid; PDX: patient-derived xenograft; RUBCNL/Pacer: rubicon like autophagy enhancer; SQSTM1/p62: sequestosome 1.


Assuntos
Neoplasias Colorretais , Histonas , Humanos , Autofagia/fisiologia , Proteína Beclina-1/metabolismo , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Epigênese Genética , Histonas/metabolismo , Hipóxia , Ácido Láctico , Lisina/metabolismo
8.
Mol Cancer ; 22(1): 202, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38087322

RESUMO

BACKGROUND: Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Emerge evidence suggests that circular RNA (circRNA) is a pivotal player in cancer progression. However, its role in CRC liver metastasis remains largely unknown. METHODS: Circ-YAP expression was detected by qRT-PCR and in situ hybridization. The function of circ-YAP was tested by wound healing, transwell and CCK-8 assays. RNA immunoprecipitation, pull-down, luciferase reporter, chromatin immunoprecipitation assays were used to investigate the mechanism underlying circ-YAP promoting CRC liver metastasis. CRC liver metastasis animal model was established to assess the effect of circ-YAP in vivo. RESULTS: Circ-YAP was notably upregulated in CRC with liver metastasis, which was associated with dismal prognosis. Circ-YAP promoted CRC cell migration and invasion in vitro, and facilitated liver metastasis in patient-derived xenografts (PDX) models in vivo. Mechanistically, circ-YAP encoded a novel truncated protein containing 220 amino acids, termed as YAP-220aa, which competitively bound to LATS1, resulting in YAP dephosphorylation and nuclear translocation, thereby activating a cohort of metastasis-promoting genes. Importantly, N6-methyladenosine (m6A) modification orchestrated efficient initiation of circ-YAP translation, requiring m6A reader YTHDF3 and eIF4G2 translation initiation complex. Intriguingly, circ-YAP was transcriptionally enhanced by YAP/TEAD complex, thus forming a positive regulatory feed-forward loop. CONCLUSIONS: Our findings reveal a previously uncharacterized oncoprotein encoded by circ-YAP, implying a promising biomarker and therapeutic target for CRC patients with liver metastasis.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , MicroRNAs , Animais , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Retroalimentação , RNA/genética , Neoplasias Hepáticas/genética , Neoplasias Colorretais/patologia , Proliferação de Células/genética , MicroRNAs/genética , Regulação Neoplásica da Expressão Gênica
10.
Nutr J ; 22(1): 54, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37899441

RESUMO

BACKGROUND: Population-based studies have shown that adequate magnesium intake is associated with a lower risk of stroke and all-cause mortality. Whether adequate magnesium intake is important for reducing all-cause mortality risk after stroke remains unclear. METHODS: We analyzed data from 917 patients with a self-reported history of stroke from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. The total magnesium intake was calculated by summing the magnesium intake from dietary and dietary supplements, and then adjusting for total energy intake according to the nutrient density method. Mortality status was determined using public-use linked mortality files from 2019. Cox regression model and restricted cubic splines were used to explore the relationship between magnesium intake and all-cause mortality. RESULTS: The average total magnesium intake across all patients was 251.0 (184.5-336.5) mg/d, and 321 (70.2%) males and 339 (73.7%) females had insufficient magnesium intake. During a median follow-up period of 5.3 years, 277 deaths occurred. After fully adjusting for confounding factors, total magnesium intake levels were inversely associated with all-cause mortality risk (HR per 1-mg/(100 kcal*d) increase, 0.97; 95% CI, 0.94-1.00; p = 0.017). Participants with the highest quartile of total magnesium intake (≥ 18.5 mg/(100 kcal*d)) had a 40% reduction in all-cause mortality risk compared to those with the lowest quartile (≤ 12.0 mg/(100 kcal*d)) (HR, 0.60; 95% CI, 0.38-0.94; p = 0.024). Stratified analyses showed that this inverse association was statistically significant in those who were older, female, without hypertension, and had smoking, normal renal function, and adequate energy intake. Dietary magnesium intake alone might be not related to all-cause mortality. CONCLUSIONS: Stroke survivors who consumed adequate amounts of magnesium from diet and supplements had a lower risk of all-cause mortality.


Assuntos
Doenças Cardiovasculares , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Estudos de Coortes , Magnésio , Inquéritos Nutricionais
11.
BMC Surg ; 23(1): 271, 2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37689651

RESUMO

BACKGROUND: The pathological tumor burden score (TBS) has been proven to be a better risk stratification tool for liver metastasis of colorectal cancer than the traditional clinical risk score (CRS). The aim of this study was to evaluate the prognostic value of the pathological tumor burden score in patients with or without neoadjuvant chemotherapy (NAC). METHODS: A total of 348 patients with colorectal liver metastases (CRLM) who underwent curative hepatic resection were retrospectively enrolled from September 1999 to December 2016. Univariable and multivariable Cox regression analyses were conducted to identify the independent predictors of prognosis. Kaplan-Meier curves and log-rank tests were used to determine whether TBS has enough discriminatory ability under certain grouping. RESULTS: Patients who received NAC had a higher median TBS than patients who did not receive NAC (4.07 vs. 2.69, P < 0.001). Among patients who did not receive NAC, those with TBS > 3 showed a significantly worse 3-year RFS (41.1% vs. 63.6%, P < 0.001) and 3-year OS rate (73.3% vs. 84.1%, P = 0.003) than those with TBS ≤ 3. Among the patients who received NAC, those with TBS ≤ 3 or TBS > 3 showed comparable 3-year RFS (33.3% vs. 26.4%, P = 0.400) and 3-year OS rates (76.5% vs. 58.2%, P = 0.064) to those who did not. Regardless of the regimen and response to NAC, there was no significant difference about 3-year RFS and 3-year OS rates between the TBS ≤ 3 and TBS > 3 groups. CONCLUSION: Pathological TBS can be applied to predict the RFS and OS of patients suffering from CRLM who did not receive NAC. However, pathological TBS might not be regard as prognosis in patients who did receive NAC.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos , Carga Tumoral , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia
12.
Materials (Basel) ; 16(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37687617

RESUMO

The deterioration process and deterioration mechanism of magnesium oxychloride cement (MOC) in an alkaline environment were studied using a scanning electron microscope (SEM), an X-ray diffractometer (XRD), a Fourier transform infrared spectrometer (FT-IR) and a micro-electro-hydraulic servo pressure testing machine to investigate the effects of soaking time in 10 wt.% NaOH solution on the macro- and micro-morphology, phase composition and compressive strength of MOC samples. The results show that the deterioration of MOC samples under an alkaline environment is mainly caused by the alkaline environment providing more OH- ions, which can react with 5Mg(OH)2·MgCl2·8H2O (P 5) in the sample. The resulting reaction gives rise to a faster decomposition of 5Mg(OH)2·MgCl2·8H2O (P 5) and a substantial reduction in the strength of the sample, and finally leads to a gradual deterioration of MOC samples. Meanwhile, immersion time exhibits a significant effect on MOC samples. The extension of immersion time coincides with more OH- ions entering the sample, and the greater presence of OH ions increases the likelihood that more P 5 will produce a hydrolysis reaction, further resulting in the increased deterioration of the sample. After soaking for 6 h in alkaline media, the main phase composition of the surface layer of an MOC sample changes to MgO and Mg(OH)2, and its microscopic morphology is also dominated by round sheets, giving rise to a sharp decrease in its compressive strength (52.2%). When the immersion time is prolonged to 72 h, OH- ions have already immersed into the inner core of the sample, causing the disappearance of P 5 from the whole sample. At the same time, both the surface and inner core of the sample exhibit a disc-shaped morphology, and chalking phenomena also appear on the surface of the sample. This reduces the compressive strength of the sample to 13.5 MPa, only 20% of its compressive strength in water. The compressive strength of the sample after 120 h of immersion is as low as 8.6 MPa, which is lower than that of the sample dipped in water for 21 days (9.5 MPa). As a result, the MOC samples studied in alkaline environments exhibit a faster deterioration rate, mainly because of a faster hydrolysis reaction by P 5, caused by more OH- ions.

13.
Cancer Med ; 12(19): 19383-19393, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37772478

RESUMO

BACKGROUND AND PURPOSE: Neoadjuvant chemotherapy (NACT) has become an essential component of the comprehensive treatment of cervical squamous cell carcinoma (CSCC). However, not all patients respond to chemotherapy due to individual differences in sensitivity and tolerance to chemotherapy drugs. Therefore, accurately predicting the sensitivity of CSCC patients to NACT was vital for individual chemotherapy. This study aims to construct a machine learning radiomics model based on magnetic resonance imaging (MRI) to assess its efficacy in predicting NACT susceptibility among CSCC patients. METHODS: This study included 234 patients with CSCC from two hospitals, who were divided into a training set (n = 180), a testing set (n = 20), and an external validation set (n = 34). Manual radiomic features were extracted from transverse section MRI images, and feature selection was performed using the recursive feature elimination (RFE) method. A prediction model was then generated using three machine learning algorithms, namely logistic regression, random forest, and support vector machines (SVM), for predicting NACT susceptibility. The model's performance was assessed based on the area under the receiver operating characteristic curve (AUC), accuracy, and sensitivity. RESULTS: The SVM approach achieves the highest scores on both the testing set and the external validation set. In the testing set and external validation set, the AUC of the model was 0.88 and 0.764, and the accuracy was 0.90 and 0.853, the sensitivity was 0.93 and 0.962, respectively. CONCLUSIONS: Machine learning radiomics models based on MRI images have achieved satisfactory performance in predicting the sensitivity of NACT in CSCC patients with high accuracy and robustness, which has great significance for the treatment and personalized medicine of CSCC patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Humanos , Feminino , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/tratamento farmacológico , Terapia Neoadjuvante , Imageamento por Ressonância Magnética , Aprendizado de Máquina , Estudos Retrospectivos
14.
Eur J Radiol ; 165: 110950, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37437437

RESUMO

PURPOSE: Total tumor volume (TTV) may play an essential role in the estimation of tumor burden. This study is aimed to investigate the clinical value of the reduction ratio of TTV as a valuable indicator of clinical outcomes in patients with colorectal liver metastases (CRLM). METHODS: A total of 240 initially unresectable CRLM patients who underwent first-line systemic treatment were enrolled in this study. TTV at baseline and at the end of first-line treatment were assessed using a three-dimensional reconstruction system according to CT or MRI images. Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). RESULTS: A total of 212 (88.3%) patients achieved tumor regression with a median reduction ratio of TTV of 86.0%. An increasing reduction ratio of TTV was associated with a gradually ascending successful conversion outcome. Patients with a reduction ratio >86.0% had better survival than those with a reduction ratio 0-86.0% or <0 (5-year overall survival (OS) rates, 64.4% vs. 44.9% vs. 23.5%, P < 0.001; 5-year progression-free survival (PFS) rates, 36.3% vs. 28.2% vs. 6.5%, P < 0.001). Multivariate analysis indicated that the reduction ratio of TTV ≤ 86.0% (OR [95%CI]: 4.956 [2.654-9.253], P < 0.001) was an independent factor for conversion failure outcome. Cox analyses revealed that the reduction ratio of TTV ≤ 86.0% was an independent factor for both unfavorable OS (HR [95%CI]: 2.216 [1.332-3.688], P = 0.002) and PFS (HR [95%CI]: 2.023 [1.376-2.974], P < 0.001). CONCLUSIONS: The reduction ratio of TTV was an effective indicator for conversion outcome and long-term prognosis in patients with initially unresectable CRLM after first-line systemic treatment.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Carga Tumoral , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Estudos Retrospectivos
15.
NPJ Precis Oncol ; 7(1): 50, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37258779

RESUMO

Adjuvant chemotherapy (ACT) is usually used to reduce the risk of disease relapse and improve survival for stage II/III colorectal cancer (CRC). However, only a subset of patients could benefit from ACT. Thus, there is an urgent need to identify improved biomarkers to predict survival and stratify patients to refine the selection of ACT. We used high-throughput proteomics to analyze tumor and adjacent normal tissues of stage II/III CRC patients with /without relapse to identify potential markers for predicting prognosis and benefit from ACT. The machine learning approach was applied to identify relapse-specific markers. Then the artificial intelligence (AI)-assisted multiplex IHC was performed to validate the prognostic value of the relapse-specific markers and construct a proteomic-derived classifier for stage II/III CRC using 3 markers, including FHL3, GGA1, TGFBI. The proteomics profiling-derived signature for stage II/III CRC (PS) not only shows good accuracy to classify patients into high and low risk of relapse and mortality in all three cohorts, but also works independently of clinicopathologic features. ACT was associated with improved disease-free survival (DFS) and overall survival (OS) in stage II (pN0) patients with high PS and pN2 patients with high PS. This study demonstrated the clinical significance of proteomic features, which serve as a valuable source for potential biomarkers. The PS classifier provides prognostic value for identifying patients at high risk of relapse and mortality and optimizes individualized treatment strategy by detecting patients who may benefit from ACT for survival.

16.
Angew Chem Int Ed Engl ; 62(23): e202303506, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37016787

RESUMO

Development of supramolecular adhesives with strong tolerance to extreme conditions has emerged as an important research area. In this study, by balancing supramolecular interactions such as hydrogen bonding interactions, electrostatic interactions, π-π stacking interactions, and cation-π interactions, we designed and prepared a series of two-component supramolecular adhesives derived from small organic molecules. Highly efficient interfacial adhesion with maximum adhesion strength of ≈10.0 MPa was realized on various surfaces in air, organic solvents, or liquid nitrogen. Owing to balanced supramolecular interactions, water participation prolonged and increased the tolerance of the adhesives in extreme environments. We demonstrate that the combination of imidazole-based ionic liquids and phenols can be applied for various interfacial adhesions, thereby aiding the development of next-generation adhesives capable of adapting to various extreme conditions in a controlled manner.

17.
Chemistry ; 29(23): e202300009, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-36779630

RESUMO

SnO2 is a theoretically excellent transformed anode material with high theoretical capacity for SIBs. However, SnO2 faces serious volume effect and high resistance, which greatly damages its electrochemical performance. Given that, the SnS-SnO2 heterostructures is constructed with special internal electric field, which is beneficial to promote the transfer ability of sodium ions. Besides, the graphene oxide (GO) modification is carried out to isolate the intrinsic materials from direct contact with electrolyte, and alleviate volume expansion of the anode, ultimately promote the electrochemical performance. Furthermore, the structure and the conductivity characteristics of SnS, SnO2 , SnS-SnO2 and SnS-SnO2 @ GO are simulated respectively by first principles and are compared with the correspondence experiment results to verify the accuracy of established models. Owing to the special p-n junction in SnS-SnO2 @GO heterostructures, the resistance of SnS-SnO2 @GO can be reduced to 36.23 Ω, much lower than that of SnO2 (Rct=341.9 Ω). Notably, the combination of GO has effectively alleviated the volume expansion of SnS-SnO2 @GO electrodes, and present excellent capacity higher than 384.7 mAh g-1 after 100 cycles. Thus, the efficient synthesis of SnS-SnO2 @GO heterostructure electrodes with excellent performance for sodium storage is expected to provide valuable direction for SIBs anode materials.

18.
BMC Cancer ; 23(1): 3, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36593480

RESUMO

BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) can indicate poor survival outcomes in colorectal cancer, but few studies have focused on stage III colon cancer. The current study aimed to confirm the prognostic value of LVI and PNI and identify patients who could benefit from a complete duration of adjuvant chemotherapy based on the two pathological factors. METHODS: We enrolled 402 consecutive patients with stage III colon cancer who received colon tumor resection from November 2007 to June 2016 at Sun Yat-sen University Cancer Center. Survival analyses were performed by using Kaplan-Meier method with log-rank tests. Risk factors related to disease-free survival (DFS) and overall survival (OS) were identified through Cox proportional hazards analysis. RESULTS: 141 (35.1%) patients presented with LVI, and 108 (26.9%) patients with PNI. The LVI-positive group was associated with poorer 3-year DFS (86.5% vs. 76.3%, P = 0.001) and OS (96.0% vs. 89.1%, P = 0.003) rates compared with the LVI-negative group. The PNI-positive group showed a worse outcome compared with the PNI-negative group in 3-year DFS rate (72.5% vs. 86.7%, P < 0.001). Moreover, LVI-positive group present better 3-year DFS and OS rate in patients completing 6-8 cycles of adjuvant chemotherapy than those less than 6 cycles (3-year DFS: 80.0% vs. 64.9%, P = 0.019; 3-year OS: 93.2% vs. 76.3%, P = 0.002). CONCLUSIONS: LVI is a superior prognostic factor to PNI in stage III colon cancer patients undergoing curative treatment. PNI status can noly predict the 3-year DFS wihout affecting the 3-year OS. Furthermore, LVI also represents an effective indicator for adjuvant chemotherapy duration.


Assuntos
Neoplasias do Colo , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Intervalo Livre de Doença , Quimioterapia Adjuvante , Invasividade Neoplásica , Estadiamento de Neoplasias
19.
Front Pharmacol ; 13: 950101, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238544

RESUMO

Background: Several issues on neoadjuvant imatinib therapy remain controversial despite its widespread application for rectal gastrointestinal stromal tumors (GIST). We aimed to describe the clinicopathological characteristics of this specific population, and compare the surgical and oncologic outcomes between patients with or without neoadjuvant imatinib therapy. Patients and methods: A cohort of 58 consecutive locally advanced rectal GIST patients receiving surgical treatment between January 2007 and July 2019 at Sun Yat-sen University Cancer Center and Yunnan Cancer Hospital was retrospectively analyzed. Recurrence-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Results: There were 33 (56.9%) patients who received neoadjuvant imatinib therapy. Among them, 20 (60.6%) patients had partial response (PR) as their best response, 11 (33.3%) patients had stable disease (SD), and 2 (6.1%) patients had progressive disease (PD). The median tumor size reduced from 5.2 to 4.0 cm after treatment (p < 0.001), and an attained "maximal response" was primarily achieved (32/33) on the 12th month after treatment. The most common adverse event was anemia. There were 27 adverse events occurred, most of which were grade 1 (19/27). With respect to intraoperative and postoperative surgical outcomes, no significant difference was found between patients with or without neoadjuvant Imatinib therapy except that patients with neoadjuvant treatment had a significant higher rate of preventive ileostomy (p = 0.004). Patients received neoadjuvant treatment had a superior 2-years RFS outcome than those without, though the difference was no significant (91.7% vs. 78.9%, p = 0.203). There were no significant differences in the 2-years OS rates (95.2% vs. 91.3%, p = 0.441). Conclusion: Neoadjuvant imatinib therapy is an effective and safe treatment for locally advanced rectal GISTs. Further studies are warranted to validate the long-term prognostic benefit for patients with rectal GISTs receiving neoadjuvant imatinib therapy.

20.
Int J Surg ; 106: 106952, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36220519

RESUMO

BACKGROUND: There is little evidence regarding the optimal surgical sequence for colorectal cancer liver metastasis (CRLM) patients undergoing colorectal resection with simultaneous liver metastasis resection. METHODS: CRLM patients from five centers were retrospectively evaluated. The short-term outcomes included intraoperative and postoperative outcomes. Postoperative complications were measured according to the Clavien-Dindo classification. Grade I to II complications were defined as minor postoperative complications. The long-term outcomes were progression-free survival (PFS) and overall survival (OS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to overcome the selection bias between colorectal resection first and liver resection first. RESULTS: A total of 1255 CRLM patients were included. In the multivariable logistic regression analysis, a body mass index (BMI) < 24 kg/m2, primary site in the left hemicolon, non-bilobar distribution of liver metastases and no preoperative chemotherapy were significantly associated with the likelihood of colorectal resection first. After 1:1 PSM, there was no significant difference between the colorectal resection first group and the liver resection first group. Compared with patients with colorectal resection first, patients with liver resection first had a comparable postoperative infection rate (15.0% vs. 16.0%, P = 0.735), a longer operation time (305.0 [231.3-416.0] vs. 300.0 [225.0-374.0], P = 0.033), more intraoperative blood loss (200.0 [150.0-400.0] vs. 100.0 [100.0-300.0], P < 0.001), a higher postoperative minor complication rate (28.7% vs. 20.7%, P = 0.023) and a higher postoperative ICU rate (14.7% vs. 8.7%, P = 0.022). IPTW-adjusted Kaplan-Meier analysis showed that patients who underwent colorectal resection first had a similar PFS (P = 0.702, median: 20.6 months vs. 16.6 months) and unfavourable OS (P = 0.014, median: 48.5 months vs. 67.0 months) compared with patients who underwent liver resection first. In the IPTW-adjusted Cox proportional hazards regression analysis, colorectal resection first was an unfavourable risk factor for OS (hazard ratio [HR] = 1.301, 95% CI 1.048-1.616, P = 0.017) and was not an independent predictor for PFS (HR = 0.986, 95% CI 0.831-1.170, P = 0.874). IPTW-adjusted Cox proportional hazards regression analysis, including postoperative complications, operation time, intraoperative blood loss and postoperative chemotherapy, produced consistent results. CONCLUSION: Although violating the "sterility principle", patients who underwent colorectal resection first did not have an increased postoperative infection rate and had some better short-term outcomes and comparable PFS than those who underwent liver resection first.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Perda Sanguínea Cirúrgica , Neoplasias Colorretais/patologia , Hepatectomia/métodos , Complicações Pós-Operatórias/etiologia
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