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1.
Biomed Pharmacother ; 178: 117194, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39137647

RESUMEN

Gastric cancer is a remarkably heterogeneous tumor. Despite some advances in the diagnosis and treatment of gastric cancer in recent years, the precise treatment and curative outcomes remain unsatisfactory. Poor prognosis continues to pose a major challenge in gastric cancer. Therefore, it is imperative to identify effective targets to improve the treatment and prognosis of gastric cancer patients. It should be noted that glycosylation, a novel form of posttranslational modification, is a process capable of regulating protein function and influencing cellular activities. Currently, numerous studies have shown that glycosylation plays vital roles in the occurrence and progression of gastric cancer. As crucial enzymes that regulate glycan synthesis in glycosylation processes, glycosyltransferases are potential targets for treating GC. Hence, investigating the regulation of glycosyltransferases and the expression of associated proteins in gastric cancer cells is highly important. In this review, the related glycosyltransferases and their related signaling pathways in gastric cancer, as well as the existing inhibitors of glycosyltransferases, provide more possibilities for targeted therapies for gastric cancer.


Asunto(s)
Glicosiltransferasas , Terapia Molecular Dirigida , Neoplasias Gástricas , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/patología , Humanos , Glicosiltransferasas/metabolismo , Glicosiltransferasas/antagonistas & inhibidores , Animales , Glicosilación , Transducción de Señal , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Inhibidores Enzimáticos/farmacología
2.
J Transl Med ; 22(1): 752, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127679

RESUMEN

Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs characterized by their lack of 5' caps and 3' poly(A) tails. These molecules have garnered substantial attention from the scientific community. A wide range of circRNA types has been found to be expressed in various tissues of the human body, exhibiting unique characteristics such as high abundance, remarkable stability, and tissue-specific expression patterns. These attributes, along with their detectability in liquid biopsy samples such as plasma, position circRNAs an ideal choice as cancer diagnostic and prognostic biomarkers. Additionally, several studies have reported that the functions of circRNAs are associated with tumor proliferation, metastasis, and drug resistance. They achieve this through various mechanisms, including modulation of parental gene expression, regulation of gene transcription, acting as microRNA (miRNA) sponges, and encoding functional proteins. In recent years, a large number of studies have focused on synthesizing circRNAs in vitro and delivering them to tumor tissue to exert its effects in inhibit tumor progression. Herein, we briefly discuss the biogenesis, characteristics, functions, and detection of circRNAs, emphasizing their clinical potential as biomarkers for cancer diagnosis and prognosis. We also provide an overview the recent techniques for synthesizing circRNAs and delivery strategies, and outline the application of engineered circRNAs in clinical cancer therapy.


Asunto(s)
Biomarcadores de Tumor , Neoplasias , ARN Circular , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Neoplasias/genética , Neoplasias/terapia , Neoplasias/diagnóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Animales , Regulación Neoplásica de la Expresión Génica
3.
Int J Surg ; 110(6): 3326-3337, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38729115

RESUMEN

BACKGROUND: Proficient surgical skills are essential for surgeons, making surgical training an important part of surgical education. The development of technology promotes the diversification of surgical training types. This study analyzes the changes in surgical training patterns from the perspective of bibliometrics, and applies the learning curves as a measure to demonstrate their teaching ability. METHOD: Related papers were searched in the Web of Science database using the following formula: TS=[(training OR simulation) AND (learning curve) AND (surgical)]. Two researchers browsed the papers to ensure that the topics of articles were focused on the impact of surgical simulation training on the learning curve. CiteSpace, VOSviewer, and R packages were applied to analyze the publication trends, countries, authors, keywords, and references of selected articles. RESULT: Ultimately, 2461 documents were screened and analyzed. The USA is the most productive and influential country in this field. Surgical endoscopy and other interventional techniques publish the most articles, while surgical endoscopy and other interventional techniques is the most cited journal. Aggarwal Rajesh is the most productive and influential author. Keyword and reference analyses reveal that laparoscopic surgery, robotic surgery, virtue reality, and artificial intelligence were the hotspots in the field. CONCLUSION: This study provided a global overview of the current state and future trend in the surgical education field. The study surmised the applicability of different surgical simulation types by comparing and analyzing the learning curves, which is helpful for the development of this field.


Asunto(s)
Bibliometría , Curva de Aprendizaje , Entrenamiento Simulado , Humanos , Entrenamiento Simulado/métodos , Procedimientos Quirúrgicos Robotizados/educación , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Competencia Clínica , Laparoscopía/educación , Laparoscopía/estadística & datos numéricos , Cirugía General/educación
4.
Sensors (Basel) ; 24(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38732850

RESUMEN

Standard beams are mainly used for the calibration of strain sensors using their load reconstruction models. However, as an ill-posed inverse problem, the solution to these models often fails to converge, especially when dealing with dynamic loads of different frequencies. To overcome this problem, a piecewise Tikhonov regularization method (PTR) is proposed to reconstruct dynamic loads. The transfer function matrix is built both using the denoised excitations and the corresponding responses. After singular value decomposition (SVD), the singular values are divided into submatrices of different sizes by utilizing a piecewise function. The regularization parameters are solved by optimizing the piecewise submatrices. The experimental result shows that the MREs of the PTR method are 6.20% at 70 Hz and 5.86% at 80 Hz. The traditional Tikhonov regularization method based on GCV exhibits MREs of 28.44% and 29.61% at frequencies of 70 Hz and 80 Hz, respectively, whereas the L-curve-based approach demonstrates MREs of 29.98% and 18.42% at the same frequencies. Furthermore, the PREs of the PTR method are 3.54% at 70 Hz and 3.73% at 80 Hz. The traditional Tikhonov regularization method based on GCV exhibits PREs of 27.01% and 26.88% at frequencies of 70 Hz and 80 Hz, respectively, whereas the L-curve-based approach demonstrates PREs of 29.50% and 15.56% at the same frequencies. All in all, the method proposed in this paper can be extensively applied to load reconstruction across different frequencies.

5.
World J Gastrointest Oncol ; 16(3): 1059-1075, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38577469

RESUMEN

BACKGROUND: Glycosylation, a commonly occurring post-translational modification, is highly expressed in several tumors, specifically in those of the digestive system, and plays a role in various cellular pathophysiological mechanisms. Although the importance and detection methods of glycosylation in digestive system tumors have garnered increasing attention in recent years, bibliometric analysis of this field remains scarce. The present study aims to identify the developmental trends and research hotspots of glycosylation in digestive system tumors. AIM: To find and identify the developmental trends and research hotspots of glycosylation in digestive system tumors. METHODS: We obtained relevant literature from the Web of Science Core Collection and employed VOSviewer 1.6.19 and CiteSpace (version 6.1.R6) to perform bibliometric analysis. RESULTS: A total of 2042 documents spanning from 1978 to the present were analyzed, with the research process divided into three phases: the period of obscurity (1978-1990), continuous development period (1991-2006), and the rapid outbreak period (2007-2023). These documents were authored by researchers from 66 countries or regions, with the United States and China leading in terms of publication output. Reis Celso A had the highest number of publications, while Pinho SS was the most cited author. Co-occurrence analysis revealed the most popular keywords in this field are glycosylation, expression, cancer, colorectal cancer, and pancreatic cancer. Furthermore, the Journal of Proteome Research was the most prolific journal in terms of publications, while the Journal of Biological Chemistry had the most citations. CONCLUSION: The bibliometric analysis shows current research focus is primarily on basic research in this field. However, future research should aim to utilize glycosylation as a target for treating tumor patients.

6.
PeerJ ; 12: e17137, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38529310

RESUMEN

Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P < 0.05). Furthermore, waterlogging hindered the uptake of iron (Fe) and manganese (Mn), as well as the transport of potassium (K). The identified metabolites within the thorns were categorized into 16 distinct groups. Relative to the control soil, fatty acids and derivatives were the most down-regulated metabolites in the waterlogged soil, accounting for 40.58% of the total metabolites, followed by lignans (38.71%), phenolic acids (34.48%), saccharides and alcohols (34.15%), steroids (16.67%), alkaloids (12.24%), flavonoids (9.28%), and glycerophospholipids (7.41%). Conversely, nucleotides and derivatives experienced the greatest up-regulation in the waterlogged soil, accounting for 50.00% of the total metabolites. In conclusion, waterlogging negatively impacted the growth of G. sinensis seedlings and inhibited the accumulation of metabolites. Hence, when considering the accumulation of secondary metabolites such as lignans and phenolic acids, appropriate management of soil moisture levels should be taken into account.


Asunto(s)
Gleditsia , Lignanos , Plantones , Lignanos/metabolismo , Gleditsia/química , Extractos Vegetales/metabolismo , Raíces de Plantas
7.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 72-81, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38433635

RESUMEN

Circular RNAs(CircRNAs)are a class of non-coding RNAs with a covalently closed-loop structure,high stability,and tissue specificity,with the production mechanisms different from linear RNAs.Recent studies have discovered that some CircRNAs can encode proteins via cap-independent translation mechanisms such as internal ribosome entry site,N6-methyladenosine,and rolling loop translation.The encoded proteins regulate homologous linear proteins or downstream signaling pathways via protein bait or other mechanisms,thereby exerting biological functions.Studies have shown that CircRNAs play a role in various diseases,especially in tumor progression,proliferation,invasion,and metastasis and immune regulation.Therefore,by elucidating the expression and roles of proteins encoded by CircRNAs in tumorigenesis and development,this paper is expected to provide new tumor markers and potential targets for tumor diagnosis and treatment.


Asunto(s)
Neoplasias Gastrointestinales , ARN Circular , Humanos , Neoplasias Gastrointestinales/genética , Adenosina , Biomarcadores de Tumor
8.
Future Oncol ; 20(14): 919-934, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37920954

RESUMEN

Aim: To predict the prognosis of gastric cancer patients with triple-negative tumor markers. Materials & methods: Prognostic factors of the nomogram were identified through univariate and multivariate Cox regression analyses. Calibration and receiver operating characteristic curves were used to assess accuracy. Decision curve analysis and concordance indexes were utilized to compare the nomogram with the pathological tumor, node, metastasis stage. Results: A nomogram incorporating log odds of positive lymph nodes, tumor size and lymphocyte-to-monocyte ratio was constructed. The calibration and receiver operating characteristic curves (area under the curve >0.85) showed high accuracy in predicting overall survival. The concordance indexes (0.832 vs 0.760; p < 0.001) and decision curve analysis demonstrated that the nomogram was superior to the pathological tumor, node, metastasis stage. Conclusion: A prediction and risk stratification nomogram has been developed and validated for gastric cancer patients with triple-negative tumor markers.


Asunto(s)
Neoplasias Gástricas , Humanos , Nomogramas , Biomarcadores de Tumor , Monocitos , Análisis Multivariante , Pronóstico
9.
Heliyon ; 9(9): e19801, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37809417

RESUMEN

Ferroptosis is a form of regulated cell death that was first formally proposed a decade ago. While its role in cancer cell death was initially understudied, it has recently gained considerable interest from researchers. In recent years, a growing number of studies have focused on the role of ferroptosis in cancer progression, with the goal of developing novel ferroptosis-inducing cancer therapies. This study aims to present the developmental trend and hotspots of research on ferroptosis-inducing cancer therapy using bibliometric analysis. A literature search was conducted using the Web of Science Core Collection on October 1st, 2022, to retrieve articles and reviews pertaining to ferroptosis and cancer published from 2012 to 2022. Microsoft Excel 2016, VOSviewer 1.6.18 and CiteSpace (version 6.1. R6) were utilized to conduct the bibliometric analysis of publication trends, authorship, and citation networks, with a focus on identifying countries, institutions, journals, and authors contributing to the field. These analyses were used to predict future trends in this area. A total of 2839 articles were identified and extracted for analysis. The number of publications has increased almost every year, with a sharp increase after 2018. China produced the most publications in this area, followed by the United States. Central South University was the institution that published the most papers. Frontiers in Oncology was the journal with the highest number of publications, while Cell had the greatest impact factor. Daolin Tang was the most productive author and Dixon SJ was the most influential author. Co-occurrence and burst analyses of keywords and references were conducted to identify the developmental trends and hotspots in ferroptosis-inducing cancer therapy research. Main research directions have shifted from investigating the mechanism of ferroptosis to developing novel ferroptosis-targeting cancer therapies. Emerging topicsfocus on the role of ferroptosis in solid tumor therapy. Based on our bibliometric analysis, we predict that research on ferroptosis in cancer therapy will continue to be a hot topic in the future, with a growing number of treatment modalities related to ferroptosis being developed. Our study provides valuable insights into the current state and future trends of research in this field, serving as a useful guide for researchers seeking to make important contributions in this area.

10.
Nat Commun ; 14(1): 6523, 2023 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-37863889

RESUMEN

Cuproptosis, caused by excessively high copper concentrations, is urgently exploited as a potential cancer therapeutic. However, the mechanisms underlying the initiation, propagation, and ultimate execution of cuproptosis in tumors remain unknown. Here, we show that copper content is significantly elevated in gastric cancer (GC), especially in malignant tumors. Screening reveals that METTL16, an atypical methyltransferase, is a critical mediator of cuproptosis through the m6A modification on FDX1 mRNA. Furthermore, copper stress promotes METTL16 lactylation at site K229 followed by cuproptosis. The process of METTL16 lactylation is inhibited by SIRT2. Elevated METTL16 lactylation significantly improves the therapeutic efficacy of the copper ionophore- elesclomol. Combining elesclomol with AGK2, a SIRT2-specific inhibitor, induce cuproptosis in gastric tumors in vitro and in vivo. These results reveal the significance of non-histone protein METTL16 lactylation on cuproptosis in tumors. Given the high copper and lactate concentrations in GC, cuproptosis induction becomes a promising therapeutic strategy for GC.


Asunto(s)
Apoptosis , Neoplasias Gástricas , Humanos , Cobre , Ácido Láctico , Metiltransferasas/genética , ARN Mensajero/genética , Sirtuina 2 , Neoplasias Gástricas/genética
11.
Oncogene ; 42(3): 238-252, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36418471

RESUMEN

Tumor hypoxia and circular RNAs (circRNAs) are considered to play key roles in tumor progression and malignancy, respectively. Nevertheless, the biological functions and underlying mechanisms of specific circRNAs exposed to hypoxic microenvironments in colorectal cancer (CRC) remain largely elusive. Herein, a novel circRNA, circTDRD3, which is upregulated under hypoxic conditions, was identified. The expression of circTDRD3 was highly expressed in CRC tissues and positively correlated with overall survival, tumor size, lymph node invasion and clinical stage. CircTDRD3 facilitated CRC cell proliferation, migration and metastasis in vitro and in vivo. Mechanistically, circTDRD3 promoted HIF1α expression by sponging miR-1231, which facilitated CRC progression. Meanwhile, HIF1α directly combined with TDRD3 promoter to increase the expression of TDRD3 pre-mRNA. Then HIF1a-induced PTBP1 accelerated the formation of circTDRD3. Our findings reveal that circTDRD3 facilitates the proliferation and metastasis of CRC through a positive feedback loop mediated by the HIF1α/PTBP1/circTDRD3/miR-1231/HIF1α axis. Therefore, circTDRD3 may serve as a prognostic biomarker and therapeutic target for patients with CRC.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Retroalimentación , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , MicroARNs/genética , Hipoxia/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral , Ribonucleoproteínas Nucleares Heterogéneas/genética , Proteína de Unión al Tracto de Polipirimidina/genética , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Proteínas/genética
12.
Cell Death Discov ; 8(1): 300, 2022 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-35768405

RESUMEN

Accumulating evidence has demonstrated that carbohydrate response element binding protein (CHREBP) has a crucial function in tumor pathology. In this study, we found CHREBP downregulation in gastric cancer (GC) tissues, and CHREBP was determined to be an independent diagnostic marker of GC. The downregulation of CHREBP promoted cell proliferation and inhibited apoptosis. Moreover, the level of cyclin D1 was significantly correlated with CHREBP expression in GC and paracancerous normal samples. In addition, CHREBP transcriptionally inhibited cyclin D1 expression in GC cells. Tumor suppressor activity of CHREBP could be affected by the upregulation of cyclin D1. In summary, CHREBP was found to be an independent diagnostic marker of GC and to influence GC growth and apoptosis via targeting the cyclin D1-Rb-E2F1 pathway.

13.
Sensors (Basel) ; 22(9)2022 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-35591259

RESUMEN

The 3D scanning of a freeform structure relies on the laser probe and the localization system. The localization system, determining the effect of the point cloud reconstruction, will generate positioning errors when the laser probe works in complex paths with a fast speed. To reduce the errors, in this paper, a linear laser scanning measurement method is proposed based on binocular vision calibration. A simple and effective eight-point positioning marker attached to the scanner is proposed to complete the positioning and tracking procedure. Based on this, the method of marked point detection based on image moment and the principle of global coordinate system calibration are introduced in detail. According to the invariance principle of space distance, the corresponding points matching method between different coordinate systems is designed. The experimental results show that the binocular vision system can complete localization under different light intensities and complex environments, and that the repeated translation error of the binocular vision system is less than 0.22 mm, while the rotation error is less than 0.15°. The repeated error of the measurement system is less than 0.36 mm, which can meet the requirements of the 3D shape measurement of the complex workpiece.

14.
Plant Signal Behav ; 17(1): 2005882, 2022 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-34913407

RESUMEN

Seed germination and seedling development in nearly all orchid species rely on a symbiotic relationship with mycorrhizal fungi; however, this is not the case with all mycorrhizal fungi. This study aims to provide an understanding about the important role of mycorrhiza in seed germination and growth of Paphiopedilum barbigerum. Therefore, we isolated and identified endophytic fungi from the roots of wild P. barbigerum. The beneficial mycorrhizal fungi Epulorhiza sp. FQXY019 and Tulasnella calospora FQXY017 were screened by seed symbiotic germination tests and found to promote seed germination. However, only the seeds inoculated with FQXY019 progressed from the seed germination to rooting stage. This shows that mycorrhizal fungi and P. barbigerum have a specific relation at different growth phases. In addition, we selected FQXY019 and inoculated it into MS medium, B5 medium, OMA medium, and PDA medium. The results showed that FQXY019 co-cultured on PDA significantly promoted the increase in seedling fresh weight, leaf length, and root length (p < .01). Furthermore, it significantly promoted the root number and leaf number of seedlings compared with those co-cultured on MS, B5, and OMA media and control (p < .05). Thus, this study demonstrated the promoting effect of Epulorhiza sp. FQXY019 on seed germination and seedling development, making it an alternative method for the artificial propagation of P. barbigerum.


Asunto(s)
Micorrizas , Orchidaceae , Germinación , Orchidaceae/microbiología , Plantones , Semillas , Simbiosis
15.
Cluster Comput ; 25(4): 2585-2599, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34744493

RESUMEN

Blockchain technology is an undeniable ledger technology that stores transactions in high-security chains of blocks. Blockchain can solve security and privacy issues in a variety of domains. With the rapid development of smart environments and complicated contracts between users and intelligent devices, federated learning (FL) is a new paradigm to improve accuracy and precision factors of data mining by supporting information privacy and security. Much sensitive information such as patient health records, safety industrial information, and banking personal information in various domains of the Internet of Things (IoT) including smart city, smart healthcare, and smart industry should be collected and gathered to train and test with high potential privacy and secured manner. Using blockchain technology to the adaption of intelligent learning can influence maintaining and sustaining information security and privacy. Finally, blockchain-based FL mechanisms are very hot topics and cut of scientific edge in data science and artificial intelligence. This research proposes a systematic study on the discussion of privacy and security in the field of blockchain-based FL methodologies on the scientific databases to provide an objective road map of the status of this issue. According to the analytical results of this research, blockchain-based FL has been grown significantly during these 5 years and blockchain technology has been used more to solve problems related to patient healthcare records, image retrieval, cancer datasets, industrial equipment, and economical information in the field of IoT applications and smart environments.

16.
Front Oncol ; 11: 709835, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34790565

RESUMEN

BACKGROUND: The overall survival (OS) of patients diagnosed with colon cancer (CC) varied greatly, so did the patients with the same tumor stage. We aimed to design a nomogram that is capable of predicting OS in resected left-sided colon cancers (LSCC) and right-sided colon cancers (RSCC), and thus to stratify patients into different risk groups, respectively. METHODS: Records from a retrospective cohort of 577 patients with complete information were used to construct the nomogram. Univariate and multivariate analyses screened risk factors associated with overall survival. The performance of the nomogram was evaluated with concordance index (c-index), calibration plots, and decision curve analyses for discrimination, accuracy, calibration ability, and clinical net benefits, respectively, which was further compared with the American Joint Committee on Cancer (AJCC) 8th tumor-node-metastasis (TNM) classification. Risk stratification based on nomogram scores was performed with recursive partitioning analysis. RESULTS: The LSCC nomogram incorporated carbohydrate antigen 12-5 (CA12-5), age and log odds of positive lymph nodes (LODDS), and RSCC nomogram enrolled tumor stroma percentage (TSP), age and LODDS. Compared with the TNM classification, the LSCC and RSCC nomograms both had a statistically higher C-index (0.837, 95% CI: 0.827-0.846 and 0.780, 95% CI 0.773-0.787, respectively) and more clinical net benefits, respectively. Calibration plots revealed no deviations from reference lines. All results were reproducible in the validation cohort. CONCLUSIONS: An original predictive nomogram was constructed and validated for OS in patients with CC after surgery, which had facilitated physicians to appraise the individual survival of postoperative patients accurately and to identify high-risk patients who were in need of more aggressive treatment and follow-up strategies.

17.
J Exp Clin Cancer Res ; 40(1): 324, 2021 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-34656159

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is one of the most frequent malignancy and a leading cause of cancer-related deaths. Therefore, further researches are required to identify novel and more effective diagnoses and to identify molecular targets in treatment of CRC. METHODS: C2CD4A expression in CRC tissues and cell lines was detected by qRT-PCR and western blot. The biological functions of C2CD4A were performed both in vitro and in vivo. Western blot, cDNA array, IP-MS, Co-immunoprecipitation assay, and Ubiquitination assay were used to analyze the interaction between C2CD4A and p53. Bioinformatics analysis, FISH, RNA sequencing, luciferase reporter assay, RNA immunoprecipitation, RNA pull-down and rescue experiments, were deployed to detect upstream regulation mechanism of C2CD4A. RESULTS: C2CD4A was elevated in CRC tissues compared with adjacent normal colorectal tissues. C2CD4A knockdown significantly promoted cell apoptosis and with inhibited proliferation in vitro, and tumorigenicity in vivo, whereas C2CD4A overexpression led to opposite effects. Moreover, circSLC6A6 was upregulated and shown to positively regulate C2CD4A expression via sponging miR-1265. Fundamentally, C2CD4A inhibited p53 signaling pathway through interacting with p53 and increasing its ubiquitination and degradation. CONCLUSION: Our results identified that circSLC6A6/miR-1265/C2CD4A axis, which was involved in CRC via the p53 signaling pathway, may serve as a therapeutic target for CRC.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana/metabolismo , MicroARNs/metabolismo , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Células HEK293 , Xenoinjertos , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Proteínas Nucleares/genética , Transducción de Señal , Factores de Transcripción/genética , Regulación hacia Arriba
18.
Transl Oncol ; 14(11): 101190, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34403906

RESUMEN

BACKGROUND: Extranodal extension (ENE) and log odds of positive lymph nodes (LODDS) are associated with the aggressiveness of both colon and rectal cancers. The current study evaluated the clinicopathological significance and the prognostic impact of ENE and LODDS in the colon and rectal patients independently. METHODS: The clinical and histological records of 389 colorectal cancer (CRC) patients who underwent curative surgery were reviewed. RESULTS: For the ENE system, 244 patients were in the ENE1 group and 145 in the ENE2 system. Compared with the ENE1 system, the patients included in the ENE2 system were prone to nerve invasion (P < 0.001) and vessel invasion (P < 0.001) with higher TNM (P = 0.009), higher T category (P = 0.003), higher N category (P < 0.001), advanced differentiation (P = 0.013), more number of positive lymph nodes (NPLN) (P < 0.001), more lymph node ratio (LNR) (P < 0.001), and a higher value of LODDS (P < 0.001). ENE was more frequent in patients with left and rectal than right cancer. For the LODDS system, 280 patients were in the LODDS1 group, and 109 in the LODDS2 group. Compared to the LODDS1 group, the patients included in the LODDS2 group were more prone to nerve invasion (P = 0.0351) and vessel invasion (P < 0.001) with a higher rate of N2 stage, less NDLN (P < 0.001), more NPLN (P < 0.001), more LNR (P < 0.001), and a higher value of ENE (P < 0.001). Based on the results in the univariable analysis, the N, NPLN, LNR, LODDS, and ENE were separately incorporated into five different Cox regression models combined with the same confounders. The multivariable Cox regression analysis demonstrated that all the five staging systems were independent prognostic factors for overall survival. CONCLUSION: The current study confirmed that the LODDS stage is an independent influence on the prognosis of both CRC and CC patients. ENE is an independent influencing factor on the prognosis of both CRC and CC patients, and the prognostic impact of extracapsular lymph node was observed in both CRC and CC. The frequency of ENE increases from the proximal (right) to the distal (left) colon as well as the rectum. Therefore, combining ENE and LODDS into the current TNM system to compensate for the inadequacy of pN staging needs further investigation.

19.
Front Oncol ; 11: 606764, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34295803

RESUMEN

Gastric cancer (GC) is one of the digestive tract malignancies with high invasion and mortality rates. Recent studies have reported that non-coding RNAs (ncRNAs) seem to play a crucial part in many tumors. Due to their high stability, ncRNAs may used as novel biomarkers to predict the occurrence and prognosis of GC. Here, we measured miRNA, lncRNA and cirRNA expression profiles of GC patients by using microarray and RNA-sequencing data from tissue samples. The diagnosis prediction model based on the ncRNA signatures and clinical features was evaluated by circulating and tissue validation and ROC analysis. Nine miRNAs and eight lncRNAs were obtained from the microarray analysis. Six miRNAs (miR-550a-5p, miRNA-936, miR-1306-3p, miR-3185, miR-6083, miR-6792-3p) and three lncRNAs (lnc-MB21D1-3:5, lnc-PSCA-4:2 and lnc-ABCC5-2:1) were abnormally expressed in circulating and tissue samples compared with normal control (NC), which was closely related to clinical pathology and survival time of GC patients; circRNA sequencing and qRT-PCR revealed four circRNAs (circASHL2, circCCDC9, circNHSL1 and cirMLLT10) were abnormally expressed in GC tissues and parts of them were negative relationship with their predicted binding miRNAs. These ncRNAs might act as promising molecular markers for the diagnosis and prognosis of gastric cancer.

20.
J Cancer ; 12(15): 4561-4573, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34149920

RESUMEN

Background: Tumor stroma percentage (TSP), as an independent, low-cost prognostic factor, could complement current pathology and act as a more feasible risk factor for prognosis. However, TSP hadn't been applied into TNM staging. Here, the objective of our study was to investigate the prognostic significance of TSP in a robust rapid multi-dynamic approach with the application of MATLAB and threshold Algorithm for Gray Image analysis. Methods: Using a retrospective collection of 1539 CRC patients comprising three independent cohorts; one SGH cohort (N=996) and two validation cohorts (N =106, N= 437) from 2 institutions. We investigated 996 CRC of no special type. According to our established thresholds, 357 cases (35.84%) were classified as TSP-high and 639 cases (64.16%) as TSP-low. We determined the gray image area as the stromal part of the WSI and calculated the stroma percentage with our proposed method on MATLAB software. Results: In both TSP-cad(50%) and TSP-cad(median), multivariate analysis showed the TSP-cad was an independent prognostic factor for the vessel invasion and tumor location. For OS, TSP-manual HR=1.512 (95% CI 1.045-2.187); TSP-cad HR=1.443 (95% CI 0.993-2.097) and TSP-cad(median) HR=1.632 (95% CI 1.105-2.410). Fortunately, TSP-manual and TSP-cad were also found independent prognostic factor in all the cohorts. It was found that TSP-cad had slightly higher HR and wider CI than TSP-manual. Conclusions: Our research showed that TSP was an independent prognostic factor in CRC. Moreover, threshold algorithm for the quantitation of TSP could be established. In conclusion, with this Rapid multi-dynamic threshold Algorithm for Gray Image counting of TSP, which showed a higher accuracy than manual evaluation by pathologists and could be a practical method for CRC to guide clinical decision making.

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