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1.
BMC Gastroenterol ; 24(1): 240, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075402

RESUMO

PURPOSE: This study aimed to investigate clinical diagnostic values of mSEPT9 combined with NLR, PLR and LMR in CRC. METHODS: 329 subjects composed of 120 CRC patients, 105 polyps patients and 104 healthy participants were prospectively recruited. Clinicopathologic features were collected and analyzed. Plasma samples were collected for mSEPT9, NLR, PLR and LMR test. The sensitivity, specificity and AUC of each biomarker separately or in combination were estimated by the ROC curve. RESULTS: The levels of NLR, PLR and the PDR of mSEPT9 in CRC patients were significantly higher than those in non-CRC subjects, while LMR was the opposite. The PDR of mSEPT9 in CRC patients was significantly correlated with age, tumor size, tumor stage and M stage. ROC curve analysis demonstrated moderate diagnostic values of mSEPT9, NLR, PLR and LMR in CRC patients with AUC of 0.78 (Se = 0.68, and Sp = 0.89), 0.78 (Se = 0.68, and Sp = 0.83), 0.80 (Se = 0.68, and Sp = 0.81), and 0.77 (Se = 0.72, and Sp = 0.73), respectively. Moreover, combination of these four biomarkers dramatically enhanced the diagnostic accuracy of CRC (AUC = 0.92, Se = 0.90, and Sp = 0.87), especially for CRC patients with large tumors (AUC = 0.95) or distal metastasis (AUC = 0.95). CONCLUSION: mSEPT9, NLR, PLR and LMR showed the potential to be reliable biomarkers for the diagnosis of CRC. And the combined application of these biomarkers further improved the diagnostic accuracy of CRC significantly.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Septinas , Humanos , Septinas/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Sensibilidade e Especificidade , Curva ROC , Idoso , Estudos Prospectivos , Contagem de Plaquetas , Metilação de DNA , Adulto , Estudos de Casos e Controles , Neutrófilos , Estadiamento de Neoplasias , Plaquetas
2.
BMC Cancer ; 24(1): 913, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39080593

RESUMO

BACKGROUND: In China, the national cervical cancer screening protocol involves initial testing for high-risk human papillomavirus (hrHPV), followed by cytology for hrHPV-positive cases. This study evaluates the effectiveness of PAX1 methylation (PAX1m) analysis in identifying precancerous or cancerous lesions in cervical samples from Chinese women positive for non-16/18 hrHPV strains. METHODS: Between February 2022 and March 2023, 281 cervical samples from non-16/18 hrHPV-positive women underwent cytological examination and PAX1m analysis. The study assessed the statistical relationship between PAX1m levels and the presence of cervical lesions, comparing the diagnostic performance of PAX1m to conventional cytology. RESULTS: A significant association was found between PAX1 methylation levels and the risk of CIN2 + and CIN3 + lesions, with 47 instances of CIN2 + detected. Odds ratios (ORs) for moderate and high PAX1m levels were 8.86 (95% CI: 2.24-42.17) and 166.32 (95% CI: 47.09-784.97), respectively. The area under the ROC curve for PAX1m in identifying CIN2 + lesions was 0.948 (95% CI: 0.895-0.99). PAX1m demonstrated similar sensitivity and negative predictive value (NPV) to cytology but reduced the colposcopy referral rate from 47.7% with cytology alone to 25.6% with PAX1m, showing superior specificity and positive predictive value across age groups. CONCLUSIONS: PAX1 methylation is a strong indicator of CIN2 + and CIN3 + risk, offering diagnostic performance comparable to cytology with the added benefit of reduced unnecessary colposcopy referrals. These findings support the use of PAX1m analysis as a reliable tool for triaging non-16/18 hrHPV-positive women in outpatient settings.


Assuntos
Metilação de DNA , Detecção Precoce de Câncer , Fatores de Transcrição Box Pareados , Infecções por Papillomavirus , Triagem , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/genética , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Adulto , Fatores de Transcrição Box Pareados/genética , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Triagem/métodos , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/genética , China/epidemiologia , Idoso , Curva ROC , Biomarcadores Tumorais/genética , Esfregaço Vaginal
3.
Toxicology ; 506: 153864, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38871208

RESUMO

Mixed lineage kinase domain-like protein (MLKL) is identified as the terminal executor of necroptosis. However, its role in acute alcoholic liver injury remains unclear. This study elucidates that MLKL can contribute to acute alcoholic liver injury independently of necroptosis. Although the expression of MLKL was upregulated, no significant increase in its phosphorylation or membrane translocation was observed in the liver tissues of mice treated with ethanol. This finding confirms that alcohol intake does not induce necroptosis in mouse liver tissue. Additionally, the deletion of Mlkl resulted in the downregulation of NLRP3 expression, which subsequently inhibited the activation of the NLRP3 inflammasome and the ensuing inflammatory response, thereby effectively mitigating liver injury induced by acute alcohol consumption. The knockout of Nlrp3 did not affect the expression of MLKL, further confirming that MLKL acts upstream of NLRP3. Mechanistically, inhibiting the nuclear translocation of MLKL reduced the nuclear entry of p65, the principal transcriptional regulator of NLRP3, thereby limiting the transcription of Nlrp3 mRNA and subsequent NLRP3 expression. Overall, this study unveils a novel mechanism of MLKL regulates the activation of NLRP3 inflammasomes in a necroptosis independent way in acute alcoholic liver injury.


Assuntos
Etanol , Inflamassomos , Hepatopatias Alcoólicas , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas Quinases , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Inflamassomos/metabolismo , Masculino , Camundongos , Etanol/toxicidade , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Fígado/metabolismo , Fígado/patologia , Fígado/efeitos dos fármacos , Necroptose/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo
4.
NPJ Precis Oncol ; 8(1): 100, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740834

RESUMO

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

5.
J Orthop Surg Res ; 19(1): 215, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561771

RESUMO

OBJECTIVE: To study the correlation between achilles tendon rupture (ATR) and hyperuricemia, also verify the known risk factors for ATR. METHODS: A retrospective review of 488 subjects was performed (182 with Achilles tendon rupture, 306 controls with ankle sprains). Demographic variables and risk factors for rupture were tabulated and compared. The baseline data and related indicators were compared, and the risk factors of ATR were analyzed by constructing a binary logistic regression model. RESULTS: Univariate logistic analysis showed that BMI, smoking, and hyperuricemia were risk factors for the development of ATR (OR = 1.65, 95%CI 1.13-2.42, P = 0.01; OR = 1.47, 95%CI 1.00-2.24, P < 0.05; OR = 2.85, 95%CI 1.84-4.42, P < 0.01). Multifactorial analysis showed that BMI ≥ 25 kg/m2, smoking, and hyperuricemia were independent risk factors for the development of ATR (OR = 1.66, 95%CI 1.11-2.49, P = 0.01; OR = 2.15, 95%CI 1.28-3.60, P < 0.01; OR = 3.06, 95%CI 1.92-4.89, P < 0.01). Among the blood biochemical indicators, total cholesterol (TC) and uric acid (UA) were independent risk factors for the occurrence of ATR (OR = 1.54, 95% CI 1.12-2.12, P = 0.01; OR = 1.01, 95% CI 1.01-1.01, P < 0.01). CONCLUSION: Our study confirmed that, as in previous results, higher BMI, smoking, and total cholesterol are risk factors for ATR, Hyperuricemia may contribute to the development of ATR, and adjunctive tests for TC and UA in the blood biochemistry may be helpful in predicting the risk of ATR.


Assuntos
Tendão do Calcâneo , Traumatismos do Tornozelo , Hiperuricemia , Humanos , Masculino , Estudos de Casos e Controles , Hiperuricemia/complicações , Fatores de Risco , Colesterol , Traumatismos do Tornozelo/complicações , Ruptura/etiologia
6.
Cancer Drug Resist ; 7: 9, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510750

RESUMO

Aim: Circular RNAs (circRNAs) have been found to be involved in tumor progression, but their role in colorectal cancer (CRC) immune escape remains to be elucidated. Methods: circRNAs differentially expressed in responsive and resistant CRC tissues to programmed cell death 1 (PD-1) antibody therapy were identified by microarray analysis. The clinical and pathological significance of circNCOA3 was validated in a separate cohort of CRC samples. The function of circNCOA3 was explored experimentally. RNA immunoprecipitation and luciferase activity assays were conducted to identify downstream targets of circNCOA3. Results: The circNCOA3 was markedly overexpressed in CRC samples resistant to PD-1 blockade. circNCOA3 expression was significantly correlated with adverse tumor phenotypes and poor outcomes in CRC patients. Knockdown of circNCOA3 expression markedly suppressed the proliferative and invasive capability of CRC cells. Moreover, knockdown of circNCOA3 increased the proportion of CD8+ T cells while decreasing the proportion of myeloid-derived suppressor cells (MDSCs). Knockdown of circNCOA3 inhibited tumor growth and increased the sensitivity to PD-1 antibody treatment in mouse tumor models. Further studies revealed that circNCOA3 acted as a competing endogenous RNA (ceRNA) for miR-203a-3p.1 to influence the level of CXCL1. Conclusion: Our findings indicate that circNCOA3 might be useful as a potential biomarker to predict the efficacy and prognosis of CRC patients treated with anti-PD-1 therapy.

7.
ACS Appl Mater Interfaces ; 16(7): 8301-8309, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38319249

RESUMO

The precise and effective isolation of living circulating tumor cells (CTCs) from peripheral blood, followed by their real-time monitoring, is crucial for diagnosing cancer patients. In this study, a cell-imprinted double-network (DN) hydrogel modified with circular multi-DNA (CMD), coined the CMD-imprinted hydrogel with fixed cells as templates (CMD-CIDH), was developed. The hydrogel featured a customized surface for proficient capture of viable CTCs and in situ real-time fluorescent detection without subsequent release. The customized surface, constructed using polyacrylamide/chitosan DN hydrogel as the matrix on the cell template, had a dense network structure, thereby ensuring excellent stability and a low degradation rate. Optimal capture efficiencies, recorded at 93 ± 3% for MCF-7 cells and 90 ± 2% for Hela cells, were achieved by grafting the CMD and adjusting the nodule size on the customized surface. The capture efficiency remained significantly high at 67 ± 11% in simulated breast cancer patient experiments even at a minimal concentration of 5 cells mL-1. Furthermore, CMD grafted onto the surface produced a potent fluorescence signature, enabling in situ real-time fluorescent detection of the target cell's growth state even in complex environments. The customized surface is highly efficient for screening CTCs in peripheral blood and has promising potential for setting up the CTCs culture.


Assuntos
Células Neoplásicas Circulantes , Humanos , Células HeLa , Células Neoplásicas Circulantes/patologia , Hidrogéis , Células MCF-7 , DNA , Separação Celular , Linhagem Celular Tumoral
8.
J Hazard Mater ; 463: 132886, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-37913659

RESUMO

Microplastics (MPs) and nanoplastics (NPs) are global pollutants with emerging concerns. Methods to predict and screen their toxicity are crucial. Elemental dyshomeostasis can be used to assess toxicity of environmental pollutants. Non-targeted metallomics, combining synchrotron radiation X-ray fluorescence (SRXRF) and machine learning, has successfully differentiated cancer patients from healthy individuals. The whole idea of this work is to screen the phytotoxicity of nano polyethylene terephthalate (nPET) and micro polyethylene terephthalate (mPET) through non-targeted metallomics with SRXRF and deep learning algorithms. Firstly, Seed germination, seedling growth, photosynthetic changes, and antioxidant activity were used to evaluate the toxicity of mPET and nPET. It was showed that nPET, at 10 mg/L, was more toxic to rice seedlings, inhibiting growth and impairing chlorophyll content, MDA content, and SOD activity compared to mPET. Then, rice seedling leaves exposed to nPET or mPET was examined with SRXRF, and the SRXRF data was differentiated with deep learning algorithms. It was showed that the one-dimensional convolutional neural network (1D-CNN) model achieved 98.99% accuracy without data preprocessing in screening mPET and nPET exposure. In all, non-targeted metallomics with SRXRF and 1D-CNN can effectively screen the exposure and phytotoxicity of nPET/mPET and potentially other emerging pollutants. Further research is needed to assess the phytotoxicity of different types of MPs/NPs using non-targeted metallomics.


Assuntos
Aprendizado Profundo , Poluentes Ambientais , Humanos , Polietilenotereftalatos/toxicidade , Microplásticos , Síncrotrons , Raios X , Plásticos , Fluorescência , Plântula , Polietileno
9.
Heliyon ; 9(12): e22523, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38046149

RESUMO

The application of robotic surgery technologies in neurological surgeries resulted in some advantages compared to traditional surgeries, including higher accuracy and dexterity enhancement. Its success in various surgical fields, especially in urology, cardiology, and gynecology surgeries was reported in previous studies, and similar advantages in neurological surgeries are expected. Surgeries in the central nervous system with the pathology of millimeters through small working channels around vital tissue need especially high precision. Applying robotic surgery is therefore an interesting dilemma for these situations. This article reviews various studies published on the application of brain and spine robotic surgery and discusses the current application of robotic technology in neurological cases.

10.
Heliyon ; 9(11): e21906, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38028013

RESUMO

Background: In this study, we aimed to investigate the performance of GALAD, GALAD-C, and GAAP models in Chinese population in comparison to our newly build statistical model. Methods: In this study, we built the AALP model based on age, α-fetoprotein (AFP), AFP-L3, and prothrombin induced by vitamin K absence-II (PIVKA II) to differentiate between patients with HCC and patients with CLD. We then compared the serum levels of AFP-L3 and PIVKA II in patients with HCC who were defined as remission or progression and showed the prognostic value of combined biomarkers. Results: The AUC value of the AALP model for HCC detection was 0.939 and AALP model exhibited a sensitivity of 81 % and a high specificity of 95 %. AALP model also exhibited good performance in the subgroups of patients with CLD. Furthermore, we demonstrated the consistency between imaging results and serum levels of AFP-L3 and PIVKA II. Conclusions: The AALP model achieved a good diagnostic performance and a high sensitivity for predicting HCC patients. Our research also showed that AFP-L3 and PIVKA II are complementary to each other but irreplaceable in the clinical detection and monitoring of HCC.

11.
Nat Commun ; 14(1): 3776, 2023 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-37355748

RESUMO

Developing highly efficient, selective and low-overpotential electrocatalysts for carbon dioxide (CO2) reduction is crucial. This study reports an efficient Ni single-atom catalyst coordinated with pyrrolic nitrogen and pyridinic nitrogen for CO2 reduction to carbon monoxide (CO). In flow cell experiments, the catalyst achieves a CO partial current density of 20.1 mA cmgeo-2 at -0.15 V vs. reversible hydrogen electrode (VRHE). It exhibits a high turnover frequency of over 274,000 site-1 h-1 at -1.0 VRHE and maintains high Faradaic efficiency of CO (FECO) exceeding 90% within -0.15 to -0.9 VRHE. Operando synchrotron-based infrared and X-ray absorption spectra, and theoretical calculations reveal that mono CO-adsorbed Ni single sites formed during electrochemical processes contribute to the balance between key intermediates formation and CO desorption, providing insights into the catalyst's origin of catalytic activity. Overall, this work presents a Ni single-atom catalyst with good selectivity and activity for CO2 reduction while shedding light on its underlying mechanism.


Assuntos
Dióxido de Carbono , Níquel , Monóxido de Carbono , Eletrodos , Nitrogênio
12.
Sci Rep ; 13(1): 8972, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37268697

RESUMO

Posttranslational modifications (PTM) such as acetylation, deubiquitination, and phosphorylation of proteins, play important roles in various kinds of cancer progression. Ubiquitin-specific proteinase 5 (USP5), a unique member of deubiquitinating enzymes (DUBs) which recognizes unanchored polyubiquitin specifically, could regulate the stability of many tumorigenesis-associated proteins to influence cancer initiation and progression. However, the diverse biological significance of USP5 in pan-cancer has not been systematically and comprehensively studied. Here, we explored the role of USP5 in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database, and we also acquired and analyzed data via various software and web platforms such as R, GEPIA2.0, HPA, TISIDB, cBioPortal, UALCAN, TIMER 2.0, CancerSEA and BioGRID. USP5 expression was high in most cancers and differed significantly in different molecular and immune subtypes of cancers. In addition, USP5 had certain diagnostic value in multiple cancers, and high expression of USP5 generally predicted poor prognosis for cancer patients. We also found that the most frequent genetic alterations type of USP5 was mutation, and the DNA methylation level of USP5 decreased in various cancers. Furthermore, USP5 expression correlated with cancer-associated fibroblasts (CAFs), endothelial cells (EC) and genetic markers of immunodulators in cancers. Moreover, the result from single cell sequencing showed that USP5 could regulate several tumor biological behaviors such as apoptosis, DNA damage and metastasis. Gene enrichment analysis indicated "spliceosome" and "RNA splicing" may be the critical mechanism for USP5 to involve in cancer. Taken together, our study elucidates the biological significance of USP5 in the diagnosis, prognosis and immune in human pan-cancer.


Assuntos
Neoplasias , Peptídeo Hidrolases , Humanos , Ubiquitina , Células Endoteliais , Endopeptidases/genética , Neoplasias/genética
13.
Int J Biol Macromol ; 243: 125216, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37301341

RESUMO

Composite films were prepared using a flow casting method, with chitosan and pullulan as film-forming agents and Artemisia annua essential oil as the UV absorber. The utility of the composite films for preserving grape berries was assessed. The effect of the added Artemisia annua essential oil on the physicochemical properties of the composite film was investigated to determine the optimal amount of essential oil that should be added to the composite film. When the Artemisia annua essential oil content was 0.8 %, the elongation at break of the composite film increased to 71.25 ± 2.87 % and the water vapor transmission rate decreased to 0.378 ± 0.007 g‧mm/(m2‧h‧kpa). The transmittance of the composite film was almost 0 % in the UV region (200-280 nm) and <30 % in the visible light region (380-800 nm), reflecting the UV absorption by the composite film. Additionally, the composite film extended the storage time of the grape berries. Therefore, the composite film containing Artemisia annua essential oil may be a promising fruit packaging material.


Assuntos
Artemisia annua , Quitosana , Óleos Voláteis , Vitis , Quitosana/química , Embalagem de Alimentos
14.
Technol Cancer Res Treat ; 22: 15330338231164232, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122229

RESUMO

OBJECTIVE: This study aims to evaluate the diagnostic value of human serum cysteine protease inhibitors (cystatin 4 [CST4]) in colorectal cancer (CRC) patients. METHODS: A total of 291 patients who were admitted to Zhuzhou Central Hospital for colonoscopy from January 2020 to December 2021 and met the inclusion criteria were selected. Serum samples of the patients were collected, and CST4 was detected by double-antibody sandwich enzyme-linked immunosorbent assay. Simultaneously, CEA and CA19-9 were detected, and the patients were divided into the CRC group, benign lesion group, and healthy control group. An attempt was made to construct a CRC prediction model including CST4 and draw a subject working characteristic curve as a diagnostic threshold for CRC prediction, and evaluate the diagnostic efficacy of the above indicators. At the same time, the expression analysis of CST4, CEA, and CA19-9 was verified by combining the data of CRC in the Tumor Genome Atlas (TCGA). RESULTS: In this study, the levels of serum CST4, CEA, and CA19-9 in the CRC group were higher than those in the colorectal benign lesion group and healthy control group, with statistical significance (P < .001). The analysis results of the receiver operating characteristic curve showed that the area under the receiver operator characteristic curve (AUC) of CST4 was 0.7739, which was obviously larger than the AUC of CA19-9 and CEA. CRC data from the TCGA expression database showed that CST4 expression and CEA expression were higher in CRC patients than in normal samples. The combined model based on CST4 was successfully constructed, and the AUC for predicting the occurrence of CRC was 0.7851. CONCLUSION: CST4 is a novel and improved diagnostic marker for CRC. The combined model based on CST4 has a certain potential value in terms of predicting the occurrence of intestinal cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais , Humanos , Biomarcadores Tumorais/genética , Antígeno Carcinoembrionário , Cistatinas Salivares , Inibidores de Cisteína Proteinase , Antígeno CA-19-9 , Neoplasias Colorretais/genética
15.
J Gastroenterol Hepatol ; 38(7): 1181-1191, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37078141

RESUMO

BACKGROUND AND AIM: Tumor progression and distant metastasis are the main causes of deaths in gastric cancer. Growing evidence revealed that circular RNAs (circRNAs) play critical role in the pathology of malignant disease, the role of circRNAs in gastric cancer progression and metastasis is still unknown. METHODS: Differentially expressed circRNAs was identified by circRNA microarray and validated by quantitative reverse transcription polymerase reaction. The biological function of circTNIK was evaluated by in vitro and in vivo experiments after ectopic expression or siRNA mediated knockdown of circTNIK. The interaction between circTNIK and miR-138-5p was determined by luciferase activity assay, RNA immunoprecipitation, and fluorescence in situ hybridization assays. RESULTS: circTNIK rather than linear TINK mRNA was significantly upregulated in gastric cancer tissues, cell lines compared with normal controls. Higher circTNIK expression was correlated with aggressive tumor phenotypes and poor overall survival in gastric cancer patients. Ectopic circTNIK expression promoted cell proliferation, invasion, tumorigenesis, and metastasis in gastric cancer cells whereas knockdown of circTNIK inhibited cell proliferation, invasion, tumorigenesis, and metastasis in gastric cancer cells. Importantly, circTNIK functions as a molecular sponge for miR-138-5p to regulate the expression of ZEB2. CONCLUSIONS: Overall, our study demonstrates how circTNIK regulates gastric cancer progression and metastasis by sponging miR-138-5p to modulate the expression of ZEB2. CircTNIK might be used as a prognostic biomarker in gastric cancer patients.


Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , RNA Circular/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/patologia , Hibridização in Situ Fluorescente , Linhagem Celular Tumoral , Carcinogênese/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Movimento Celular , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo
16.
Front Oncol ; 13: 1019702, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910633

RESUMO

Introduction: Gastric cancer (GC) complicated by bone marrow metastasis (BMM) and disseminated intravascular coagulation (DIC) represents poor prognosis and most of these patients would die in a few months. Active treatment strategies such as chemotherapy are effective in restoring coagulation function and prolonging patients' survival time. Immunotherapy including programmed death protein 1 (PD-1) or programmed death protein ligand 1 (PD-L1) inhibitors has emerged as a first-line treatment of gastric cancer. However, the efficacy of PD-1 inhibitor-based treatment strategies in these patients remains unknown. Case description: Herein, we presented two cases of advanced gastric cancer (AGC) complicated by BMM and DIC, in which two patients received chemotherapy and PD-1 inhibitor as the first-line treatment. Both of them achieved a partial response after treatment, and the coagulation function was restored. The patient who discontinued the PD-1 inhibitor after 6 months experienced DIC relapse, whereas the other patient who maintained the PD-1 inhibitor treatment cycle remained responsive after 10 months. Conclusions: We speculate that PD-1 inhibitor-based treatment strategies are effective and safe in prolonging survival against gastric cancer with BMM and DIC, and the coagulation function is well controlled by the treatment with a combination of immunotherapy and chemotherapy.

18.
J Pers Med ; 13(1)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36675776

RESUMO

BACKGROUND: Signet ring cell carcinoma (SRCC) is a specific type of gastric cancer. The clinicopathological and molecular characteristics that can be used to predict the response to anti-PD-1 therapy for these patients are still not clear. METHODS: Patients with advanced SRCC who received first-line anti-PD-1-based treatment were enrolled in this study. The clinicopathological characteristics of these patients were obtained from their medical records. The molecular features of these patients were analyzed by means of a next-generation-sequencing-based panel. The predictive significance of clinicopathological and molecular features for efficacy was analyzed. RESULTS: A total of 71 patients with measurable lesions were included in this study, among which 46 patients had enough tissues for next-generation sequencing. The overall objective response rate (ORR) was 46.4%. ORR was significantly higher in mismatch repair (MMR)-deficient (dMMR) patients than in MMR-proficient (pMMR) patients, in patients with lymph node metastasis only than those with other metastasis sites, and in patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 than with a PS of 1 or 2. The progression-free survival was significantly longer in patients with dMMR, lymph node metastasis only, PD-L1 combined positive score (CPS) ≥ 5, and CDH1 wild type. CONCLUSIONS: Several clinicopathological and molecular features are associated with anti-PD-1 treatment efficacy in SRCC, which might be used to identify patients who can benefit most from these therapies.

19.
Biosens Bioelectron ; 221: 114424, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35691789

RESUMO

Vascular endothelial growth factor (VEGF) plays an important role in atherosclerosis, and the detection of VEGF is critical for the prevention, monitoring, and diagnosis of cardiovascular diseases. Here, a novel "signal on-off-super on" sandwich-type aptamer sensor with a triple signal amplification strategy was developed for the first time. Based on the capture aptamer was labeled with methylene blue (MB) on the internal bases, clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a-coupled voltage enrichment was used to amplify the electrochemical signal. To improve the analytical performance of the aptamer sensor, gold nanoparticles@Ti3C2Tx-Mxene (AuNPs@Ti3C2Tx-Mxene) were synthesized through the electrodeposition of AuNPs on the Ti3C2Tx-Mxene surface, providing active sites for the immobilization of the aptamer and amplifying the electrochemical signals. The excellent trans-cleavage activity of the CRISPR-Cas12a system was harnessed to cleave signal probes. The cleaved signal probes were enriched using an electrochemical signal instead of complicated target amplification steps before detection. Hence, we report a simplified detection process for amplifying electrochemical signals. Under optimal conditions, the aptamer sensor exhibited high sensitivity, acceptable stability, and reproducibility with a wide linear range from 1 pM to 10 µM (R2 = 0.9917) and an ultralow detection limit of 0.33 pM (S/N = 3). Therefore, we propose a novel strategy of CRISPR-Cas12a-based protein detection that opens a new window for the diagnostic applications of various biomarkers.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Ouro/química , Aptâmeros de Nucleotídeos/química , Fator A de Crescimento do Endotélio Vascular/genética , Nanopartículas Metálicas/química , Limite de Detecção , Sistemas CRISPR-Cas/genética , Reprodutibilidade dos Testes
20.
Cancer Lett ; 552: 215978, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36283584

RESUMO

Aberrant glucose metabolism is one of the most striking characteristics of metabolic reprogramming in cancer. Thus, clarifying the regulatory mechanism of glucose metabolism is crucial to understanding tumor progression and developing novel therapeutic strategies for cancer patients. Recent developments in circular RNAs have explained the regulatory mechanism of glucose metabolism from a new dimension. In this review, we briefly summarize the recent advances in circRNA research on cancer glucose metabolism and emphasize the different regulatory mechanisms, including acting as miRNA sponges, interacting with proteins and being translated into proteins. Additionally, we discuss the future research directions of circular RNAs in the field of glucose metabolism.


Assuntos
MicroRNAs , Neoplasias , Humanos , RNA Circular/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Neoplasias/patologia , Glucose
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