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Oral squamous cell carcinoma (OSCC), a malignancy originating from mucosal epithelial cells. Currently, triggering apoptotic cell death with anticancer drugs is the main way to inhibit OSCC cells. However, the capability to trigger apoptosis in tumors is constrained by the intrinsic resistance of tumor cells to apoptosis, hampering its effectiveness. Thus, utilizing alternative modes of non-apoptotic cell death offers new therapeutic possibilities, such as using a drug combination strategy to simultaneously induce ferroptosis and autophagy has the potential to improve OSCC therapy. In this study, we found the ferroptosis inducer RSL3 has certain inhibitory effects on the proliferation and migration of OSCC cells. Interestingly, our studies showed that RSL3 is also associated with autophagy activation. Based on this finding, we tried to combine RSL3 with the autophagy inducer LYN-1604 to improve the therapeutic effect. The results demonstrated that simultaneous regulation of autophagy and ferroptosis significantly reduced the proliferation and migration of OSCC cells. Taken together, we demonstrated the therapeutic potential of RSL3 in OSCC cells and proposed that simultaneous activation of autophagy and ferroptosis have synergistic effects, which would provide valuable clues for further exploration of targeted therapy for OSCC.
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Carcinoma de Células Escamosas , Ferroptose , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linhagem Celular Tumoral , Neoplasias Bucais/patologia , Apoptose , Autofagia , Proliferação de CélulasRESUMO
Metformin is currently a strong candidate antitumor agent for multiple cancers, and has the potential to inhibit cancer cell viability, growth, and proliferation. Metabolic reprogramming is a critical feature of cancer cells. However, the effects of metformin which targets glucose metabolism on HepG2 cancer cells remain unclear. In this study, to explore the effects of metformin on glucose metabolism in HepG2 cells, we conducted real-time metabolomic monitoring of live HepG2 cells treated with metformin using 13C in-cell NMR spectroscopy. Metabolic tracing with U-13C6-glucose revealed that metformin significantly increased the production of 13C-G3P and 13C-glycerol, which were reported to attenuate liver cancer development, but decreased the production of potential oncogenesis-supportive metabolites, including 13C-lactate, 13C-alanine, 13C-glycine, and 13C-glutamate. Moreover, the expression levels of enzymes associated with the measured metabolites were carried out. The results showed that the levels of ALT1, MCT4, GPD2 and MPC1 were greatly reduced, which were consistent with the changes of measured metabolites in 13C in-cell NMR spectroscopy. Overall, our approach directly provides fundamental insights into the effects of metformin on glucose metabolism in live HepG2 cells, and highlights the potential mechanism of metformin, including the increase in production of G3P and glycerol derived from glucose, as well as the inhibition of glucose incorporation into lactate, alanine, glutamate, and glycine.
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Metformina , Humanos , Metformina/farmacologia , Células Hep G2 , Glicerol , Espectroscopia de Ressonância Magnética , Glucose/metabolismo , Alanina/metabolismo , Ácido Glutâmico , Glicina , LactatosRESUMO
Near-infrared (NIR) fluorescence imaging-guided photodynamic therapy (PDT) technology plays an important role in treating various diseases and still attracts increasing research interests for developing novel photosensitizers (PSs) with outstanding performances. Conventional PSs such as porphyrin and rhodamine derivatives have easy self-aggregation properties in the physiological environment due to their inherent hydrophobic nature caused by their rigid molecular structure that induces strong intermolecular stacking π-π interaction, leading to serious fluorescence quenching and cytotoxic reactive oxygen species (ROS) reduction. Meanwhile, hypoxia is an inherent barrier in the microenvironment of solid tumors, seriously restricting the therapeutic outcome of conventional PDT. Aforementioned disadvantages should be overcome urgently to enhance the therapeutic effect of PSs. Novel NIR fluorescence-guided type I PSs with aggregation-induced emission (AIE), which features the advantages of improving fluorescent intensity and ROS generation efficiency at aggregation as well as outstanding oxygen tolerance, bring hope for resolving aforementioned problems simultaneously. At present, plenty of research works fully demonstrates the advancement of AIE-active PDT based on type I PSs. In this review, cutting-edge advances focusing on AIE-active NIR type I PSs that include the aspects of the photochemical mechanism of type I ROS generation, various molecular structures of reported type I PSs with NIR fluorescence and their design strategies, and typical anticancer applications are summarized. Finally, a brief conclusion is obtained, and the underlying challenges and prospects of AIE-active type I PSs are proposed.
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Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio , Fluorescência , Oxigênio , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
H2 O2 is a widely used eco-friendly oxidant and a potential energy carrier. Photocatalytic H2 O2 production from water and O2 is an ideal approach with the potential to address the current energy crisis and environmental issues. Three zig-zag two-dimensional coordination polymers (2D CPs), named CuX-dptz, were synthesized by a rapid and facile method at room temperature, showing preeminent H2 O2 photoproduction performance under pure water and open air without any additives. CuBr-dptz exhibits a H2 O2 production rate high up to 1874â µmol g-1 h-1 , exceeding most reported photocatalysts under this condition, even comparable to those supported by sacrificial agents and O2 . The coordination environment of Cu can be modulated by halogen atoms (X=Cl, Br, I), which in turn affects the electron transfer process and finally determines the reaction activity. This is the first time that 2D CPs have been used for photocatalytic H2 O2 production in such challenging conditions, which provides a new pathway for the development of portable in situ H2 O2 photosynthesis devices.
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Chimeric antigen receptors (CARs) recognizing tumor-associated antigens (TAAs) effectively target tumor cells without using the major histocompatibility complex (MHC). However, CARs have inaccurate dose determination in clinical practice, and the methods that can solve this problem often produce cytotoxic substances, such as green fluorescent protein (GFP) insertion. Therefore, in this study, we tried to anchor harmless fluorescent labels on CAR-T cell membranes using highly biologically compatible strain-promoted alkyne-azide cycloaddition (SPAAC) without any byproducts. Our conjugated fluorescent label was stable on the CAR-T cell surface for at least two weeks, with excellent light stability and metrology. Also, this method enabled the rapid quantification of the living CAR-T cells without affecting their activity. Thus, this method is a promising reliable strategy for accurately diagnosing and treating cancer.
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Neoplasias , Humanos , Reação de Cicloadição , Antígenos de Neoplasias , Linfócitos TRESUMO
CPS1, the rate-limiting enzyme that controls the first reaction of the urea cycle, is responsible for converting toxic ammonia into non-toxic urea in mammals. While disruption of the functions of CPS1 leads to elevated ammonia and nerve damage in the body, mainly manifested as urea cycle disorder. Moreover, accumulating evidence has recently revealed that CPS1 is involved in a variety of human diseases, including CPS1D, cardiovascular disease, cancers, and others. In particular, CPS1 expression varies among cancers, being overexpressed in some cancers and downregulated in others, suggesting that CPS1 may be a promising cancer therapeutic target. In addition, some small-molecule inhibitors of CPS1 have been reported, which have not been confirmed experimentally in malignancies, meaning their future role is far from certain. In this review, we describe the structure and function of CPS1, highlight its important roles in various human diseases, and further discuss the potential diagnostic and therapeutic implications of small molecule compounds targeting CPS1.
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Doença da Deficiência da Carbamoil-Fosfato Sintase I , Animais , Humanos , Doença da Deficiência da Carbamoil-Fosfato Sintase I/patologia , Doença da Deficiência da Carbamoil-Fosfato Sintase I/terapia , Carbamoil-Fosfato/metabolismo , Amônia/metabolismo , Carbamoil-Fosfato Sintase (Amônia)/química , Carbamoil-Fosfato Sintase (Amônia)/metabolismo , Ureia , Mamíferos/metabolismoRESUMO
A meta-analysis investigation was executed to measure the wound healing rates (WHRs) and wound problems (WPs) of conventional circumcision (CC) compared with ring circumcision (RC). A comprehensive literature investigation till March 2023 was applied and 2347 interrelated investigations were reviewed. The 16 chosen investigations enclosed 25 838 individuals, with circumcision, were in the chosen investigations' starting point, 3252 of them were RC, and 2586 were CC. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the WHRs and WPs of CC compared with RC by the dichotomous or continuous approaches and a fixed or random model. RC had a significantly lower wound infection rate (WIR) (OR, 0.58; 95% CI, 0.37-0.91, P = .002) and wound bleeding rate (WBR) (OR, 0.22; 95% CI, 0.12-0.42, P < .001) compared with those with CC. However, RC and CC had no significant difference in WHR (OR, 2.18; 95% CI, -0.73 to 5.09, P = .14), wound edema rate (WER) (OR, 1.11; 95% CI, 0.92-1.33, P = .28), and wound dehiscence rate (WDR) (OR, 0.98; 95% CI, 0.60-1.58, P = .93). RC had significantly lower WIR, and WBR, however, no significant difference in WHR, WER, and WDR compared with those with CC. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta-analysis.
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Circuncisão Masculina , Fimose , Masculino , Humanos , Fimose/cirurgia , Circuncisão Masculina/efeitos adversos , Complicações Pós-Operatórias , Cicatrização , Duração da Cirurgia , EdemaRESUMO
The response to neoadjuvant chemotherapy (NAC) is highly correlated with survival in breast cancer (BC) patients. The early prediction of the response to NAC could facilitate treatment adjustments on a patient-by-patient basis, which would improve patient outcomes and survival. Conventional techniques used for detecting circulating microRNAs (miRNAs), which act as biomarkers for the early prediction of NAC efficacy in BC patients, are associated with limitations such as low sensitivity and specificity. We designed a highly sensitive graphene oxide (GO)-based qRT-PCR method for detecting miRNAs associated with the chemotherapeutic response in BC patients. The results showed that miRNA levels at both the baseline and end of the first NAC cycle could help distinguish NAC responders from NAC nonresponders; BC patients with lower plasma miRNA levels were more likely to achieve pathological complete remission. Thus, GO-based qRT-PCR could facilitate early prediction of NAC efficacy in BC patients.
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Neoplasias da Mama , MicroRNA Circulante , MicroRNAs , Humanos , Feminino , Terapia Neoadjuvante/métodos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , MicroRNAs/genéticaRESUMO
BACKGROUND: Human papillomavirus (HPV) infection and related diseases are difficult clinical challenges. The efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating condyloma acuminata is remarkable, with high virus clearance and low recurrence rates. Podophyllotoxin (POD) is the first-line drug with a significant therapeutic effect on condyloma acuminata. However, no studies have determined whether POD-combined ALA-PDT improves high-risk (HR)-HPV-infected cell killing. We aimed to investigate whether POD-combined ALA-PDT could promote HPV-infected cell death more effectively than the single treatment and explore the underlying mechanism. METHODS: In HeLa and SiHa cells, flow cytometry, EdU assay and LDH release test were used to detect apoptosis, cell proliferation change and necrosis, respectively. To investigate whether the combined therapy might activate apoptosis and induce endoplasmic reticulum (ER) stress, flow cytometry was used to determine intracellular levels of ROS and calcium, and Western blotting was used to determine the expression of related proteins. Mitochondrial membrane depolarization was detected by JC-1 assay. Immunofluorescence staining and Western blotting were used to detect the activation of autophagy. RESULTS: Podophyllotoxin -combined ALA-PDT inhibited the proliferation and promoted apoptosis and necrosis more effectively than the single treatment at the same intensity and concentration. The activation of the caspase-dependent apoptosis pathway, ER stress and autophagy was more substantial in POD-combined ALA-PDT than with single treatments. CONCLUSION: Podophyllotoxin -combined ALA-PDT effectively promoted cell death through several pathways in HeLa and SiHa cells. This combination might be a promising therapeutic strategy for the HR-HPV infection.
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Condiloma Acuminado , Infecções por Papillomavirus , Fotoquimioterapia , Ácido Aminolevulínico/uso terapêutico , Apoptose , Morte Celular , Condiloma Acuminado/tratamento farmacológico , Humanos , Necrose/tratamento farmacológico , Infecções por Papillomavirus/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Podofilotoxina/farmacologia , Podofilotoxina/uso terapêuticoRESUMO
In this study, we aim to investigate the clinical features and outcomes of multichanneled aortic dissection (MCAD) and double-channeled aortic dissection (DCAD) in acute type B aortic dissection (TBAD) patients who underwent thoracic endovascular aortic repair (TEVAR).In total, 479 consecutive acute TBAD patients treated with TEVAR from April 2002 to May 2020 were retrospectively enrolled in this study. The MCAD group was defined as those of multichanneled morphology by initial computed tomography angiography (CTA) (n = 61), whereas the DCAD group was defined as those with double-channeled morphology by initial CTA (n = 418). The clinical and morphological characteristics and short-term and long-term adverse events (30-day and > 30 days) were recorded and evaluated.No significant differences were noted between the 2 groups as regards demographics, comorbidity profiles, or initial feature of CTA. The incidence of true lumen compression was found to be significantly lower in the MCAD group compared with the DCAD group (8.2% versus 20.8%, P < 0.05). During the 65.37 ± 40.06 months of follow-up, there were no statistically significant differences in terms of 30-day mortality or the incidence of early adverse events between the 2 groups. The incidence rates of 5-year cumulative freedom from all-cause mortality and 5-year cumulative freedom from AD-related mortality were not significantly different between the MCAD and DCAD groups, whereas the 5-year cumulative freedom from adverse events were lower in the MCAD group compared to DCAD group (51.1% versus 72.5%, P < 0.05). In multivariate Cox regression models, only age > 60 years, pleural effusion, branch involvement, and length of the stent were independent predictors of mortality, whereas age > 60 years, pulse, pleural effusion, true lumen compression, widest diameter of the descending aorta, branch involvement, and length of stent were independent predictors of adverse aortic events.No significant difference was noted between the MCAD and DCAD groups in the 5-year mortality following, whereas patients with MCAD were found to have significantly lower AD-related events than patients with DCAD in long-term follow-up.
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Dissecção Aórtica , Procedimentos Endovasculares , Derrame Pleural , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Dissecção Aórtica/cirurgia , Angiografia por Tomografia ComputadorizadaRESUMO
With the continuous development of Unmanned Aerial Vehicle (UAV) technology, UAVs are widely used in military and civilian fields. Multi-UAV networks are often referred to as flying ad hoc networks (FANET). Dividing multiple UAVs into clusters for management can reduce energy consumption, maximize network lifetime, and enhance network scalability to a certain extent, so UAV clustering is an important direction for UAV network applications. However, UAVs have the characteristics of limited energy resources and high mobility, which bring challenges to UAV cluster communication networking. Therefore, this paper proposes a clustering scheme for UAV clusters based on the binary whale optimization (BWOA) algorithm. First, the optimal number of clusters in the network is calculated based on the network bandwidth and node coverage constraints. Then, the cluster heads are selected based on the optimal number of clusters using the BWOA algorithm, and the clusters are divided based on the distance. Finally, the cluster maintenance strategy is set to achieve efficient maintenance of clusters. The experimental simulation results show that the scheme has better performance in terms of energy consumption and network lifetime compared with the BPSO and K-means-based schemes.
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The therapeutic effect of dihydroartemisinin (DHA) against cutaneous squamous cell carcinoma (cSCC) has been previously demonstrated; however, the underlying mechanism remains unclear. This study sought to verify the therapeutic effect of DHA against cSCC and explore its underlying mechanism in A431 cSCC cells. This study reported that DHA inhibited A431 cells proliferation in a time- and concentration-dependent manner and promoted A431 cells apoptosis. Moreover, DHA inhibited the invasion and migration of A431 cells. Mechanistically, DHA promoted autophagy and inhibited activation of the absent in melanoma 2 (AIM2) inflammasome pathway and NF-κB/HIF-1α/VEGF pathway. Treatment of A431 cells with the mTOR inhibitor, and autophagy promoter, rapamycin also inhibited these two pathways. In conclusion, DHA inhibited activation of the AIM2 inflammasome pathway and NF-κB/HIF-1α/VEGF pathway by promoting autophagy in A431 cells, thus accounting for its therapeutic effect. Induction of autophagy by DHA may be mediated by inhibiting the mTOR pathway and promoting reactive oxygen species production.
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Artemisininas/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Inflamassomos/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Artemisininas/uso terapêutico , Autofagia/efeitos dos fármacos , Autofagia/imunologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamassomos/imunologia , Inflamassomos/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: 5-aminoketovaleric acid, as a precursor of the strong photosensitizer protoporphyrin IX (PpIX), mainly enters the mitochondria after entering the cell, and the formed PpIX is also mainly localized in the mitochondria. So at present the research on the mechanism of 5-aminoketovalerate photodynamic therapy (ALA-PDT) mainly focuses on its impact on mitochondria. There are few reports on whether ALA-PAT can affect the endoplasmic reticulum and trigger endoplasmic reticulum stress (ERS). AIMS/OBJECTIVES: Here we investigated the effects of ALA-PDT on endoplasmic reticulum and its underlying mechanisms in high-risk human papillomavirus (HR-HPV) infection. MATERIALS AND METHODS: The human cervical cancer cell line HeLa (containing whole genome of HR-HPV18) was treated with ALAPDT, and cell viability, ROS production, the level of Ca2+ in the cytoplasm and apoptosis were evaluated by CCK8, immunofluorescence and flow cytometry, respectively. The protein expression of the markers of ERS and autophagy and CamKKß-AMPK pathway was examined by western blot. RESULTS: The results showed that ALA-PDT inhibited cell viability of HeLa cells in vitro; ALA-PDT induced autophagy in HeLa cells ; ALA-PDT induced autophagy via the Ca2+-CamKKß-AMPK pathway, which could be suppressed by the inhibition of ERS;ALA-PDT induced ERS-specific apoptosis via the activation of caspase 12. CONCLUSIONS: Our study demonstrated that ALA-PDT could exert a killing effect by inducing HeLa cell apoptosis, including endoplasmic reticulum-specific apoptosis. Meanwhile, ERS via the Ca2+ -CamKKß-AMPK pathway promoted the occurrence of autophagy in HeLa cells. Inhibition of autophagy could increase the apoptosis rate of HeLa cells after ALA-PDT, suggesting that autophagy may be one of the mechanisms of PDT resistance; The Ca2+-CamKKß-AMPK pathway and autophagy may be targets to improve the killing effect of ALA-PDT in treating HR-HPV infection.
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Ácido Aminolevulínico , Infecções por Papillomavirus , Fotoquimioterapia , Proteínas Quinases Ativadas por AMP/farmacologia , Ácido Aminolevulínico/farmacologia , Apoptose/efeitos dos fármacos , Cálcio , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático , Células HeLa , Humanos , Infecções por Papillomavirus/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Four lanthanide metal-organic frameworks (Ln-MOFs), namely {[Me2NH2][LnL]·2H2O}n (Ln = Eu 1, Tb 2, Dy 3, Gd 4), have been constructed from a new tetradentate ligand 1-(3,5-dicarboxylatobenzyl)-3,5-pyrazole dicarboxylic acid (H4L). These isostructural Ln-MOFs, crystallizing in the monoclinic P21/c space group, feature a 3D structure with 7.5 Å × 9.8 Å channels along the b axis and the point symbol of {410.614.84} {45.6}2. The framework shows high air and hydrolytic stability, which can keep stable after exposed to humid air for 30 days or immersed in water for seven days. Four MOFs with different lanthanide ions (Eu3+, Tb3+, Dy3+, and Gd3+) ions exhibit red, green, yellow, and blue emissions, respectively. The Tb-MOF emitting bright green luminescence can selectively and rapidly (<40 s) detect Fe3+ in aqueous media via a fluorescence quenching effect. The detection shows excellent anti-inference ability toward many other cations and can be easily recognized by naked eyes. In addition, it can also be utilized as a rapid fluorescent sensor to detect acetone solvent as well as acetone vapor. Similar results of sensing experiments were observed from Eu-MOF. The sensing mechanism are further discussed.
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As a new group of important effector molecules involved in multiple cancers, long noncoding RNAs (lncRNAs) have attracted much attention recently. Especially, evidences have indicated lncRNAs might be promising biomarkers and targets for cancer therapy. LINC00641 is a novel lncRNA, whose function remains totally unclear. The aim of our study was to determine the functions of LINC00641 in bladder cancer. We found that LINC00641 expression was significantly down-regulated in bladder cancer tissues. Down-regulation of LINC00641 in patients with bladder cancer predicts poor prognosis. Gain-of-function assays indicated that LINC00641 up-regulation markedly inhibited the proliferation, migration and invasion of bladder cancer cells. Xenograft assay also confirmed that LINC00641 overexpression suppressed bladder cancer growth in vivo. Mechanistically, LINC00641 was demonstrated to interact with miR-197-3p, whose target was KLF10. By up-regulating KLF10 level, LINC00641 suppressed the PTEN/PI3K/AKT pathway, leading to prevention of bladder cancer progression. Taken together, our study illustrated a novel signaling cascade of LINC00641/miR-197-3p/KLF10/PTEN/PI3K/AKT pathway regulating bladder cancer development.
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Fatores de Transcrição de Resposta de Crescimento Precoce/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais/genética , Neoplasias da Bexiga Urinária/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Progressão da Doença , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/diagnóstico , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Prognóstico , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genéticaRESUMO
INTRODUCTION: This study aimed to explore the expression profiles of fatty acid metabolism- related genes (FAMRGs) in patients with bladder cancer (BLCA). METHODS: The corresponding clinicopathological features of BLCA patients and RNA sequencing data were downloaded from TCGA and GSE13507. Univariate Cox regression was used to determine the prognostic value of FRGS in BLCA patients. LASSO regression analysis was then performed to select potential risk genes and eliminate genes that might overfit the model. Based on the independent prognostication-related FRGs, the nomogram survival model was established using the root mean square value of the R packet to predict the 1-year, 3-year, and 5-year survival rates of BLCA patients. By determining the area under the curve (AUC) value, the time-dependent receiver operating characteristic curve (ROC) was used to evaluate the prognostic efficiency of our model. RESULTS: A total of 243 DEFRGs were identified. Twenty FRGs were found to be related to the prognosis of BLCA in the TCGA database. Survival curves showed that high-risk patients had significantly shorter OS than low-risk cases (p < 0.001). The AUC of risk was 0.784, which was superior to age, sex, and stage, suggesting that the risk score was more favorable in predicting OS than traditional pathologic prognostic factors. The AUC was 0.757 at 1 year, 0.732 at 3 years, and 0.733 at 5 year-OS. CONCLUSION: In this study, we demonstrated that a FAMRG prognosis biomarker is associated with the tumor immune microenvironment in patients with BLCA.
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Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Neoplasias da Bexiga Urinária/genética , Nomogramas , Bases de Dados Factuais , Ácidos Graxos , Microambiente TumoralRESUMO
BACKGROUND: Oral squamous cell carcinoma (OSCC) is originating from oral mucosal epithelial cells. Autophagy plays a crucial role in cancer treatment by promoting cellular self-degradation and eliminating damaged components, thereby enhancing therapeutic efficacy. In this study, we aim to identify a novel autophagy-related biomarker to improve OSCC therapy. METHODS: We firstly utilized Cox and Lasso analyses to identify that ATF6 is associated with OSCC prognosis, and validated the results by Kaplan-Meier survival analysis. We further identified the downstream pathways and related genes by enrichment analysis and WGCNA analysis. Subsequently, we used short interfering RNA to investigate the effects of ATF6 knockdown on proliferation, migration, apoptosis, and autophagy in SCC-9 and SCC-15 cells through cell viability assay, transwell assay, EdU incorporation assay, flow cytometry analysis, western blot analysis and immunofluorescence analysis, etc. RESULTS: Bioinformatics analyses showed that ATF6 overexpression was associated with prognosis and detrimental to survival. In vitro studies verified that ATF6 knockdown reduced OSCC cell proliferation and migration. Mechanistically, ATF6 knockdown could promote cellular autophagy and apoptosis. CONCLUSION: We propose that ATF6 holds potential as a prognostic biomarker linked to autophagy in OSCC. This study provides valuable clues for further exploration of targeted therapy against OSCC.
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Fator 6 Ativador da Transcrição , Autofagia , Biomarcadores Tumorais , Carcinoma de Células Escamosas , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais , Humanos , Fator 6 Ativador da Transcrição/genética , Fator 6 Ativador da Transcrição/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Linhagem Celular Tumoral , Autofagia/genética , Proliferação de Células/genética , Movimento Celular/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Apoptose/genética , Estimativa de Kaplan-MeierRESUMO
BACKGROUND: Radiation esophagitis (RE) is one of the most common clinical symptoms of regi-onal lymph node radiotherapy for breast cancer. However, there are fewer studies focusing on RE caused by hypofractionated radiotherapy (HFRT). AIM: To analyze the clinical and dosimetric factors that contribute to the development of RE in patients with breast cancer treated with HFRT of regional lymph nodes. METHODS: Between January and December 2022, we retrospectively analysed 64 patients with breast cancer who met our inclusion criteria underwent regional nodal intensity-modulated radiotherapy at a radiotherapy dose of 43.5 Gy/15F. RESULTS: Of the 64 patients in this study, 24 (37.5%) did not develop RE, 29 (45.3%) developed grade 1 RE (G1RE), 11 (17.2%) developed grade 2 RE (G2RE), and none developed grade 3 RE or higher. Our univariable logistic regression analysis found G2RE to be significantly correlated with the maximum dose, mean dose, relative volume 20-40, and absolute volume (AV) 20-40. Our stepwise linear regression analyses found AV30 and AV35 to be significantly associated with G2RE (P < 0.001). The optimal threshold for AV30 was 2.39 mL [area under the curve (AUC): 0.996; sensitivity: 90.9%; specificity: 91.1%]. The optimal threshold for AV35 was 0.71 mL (AUC: 0.932; sensitivity: 90.9%; specificity: 83.9%). CONCLUSION: AV30 and AV35 were significantly associated with G2RE. The thresholds for AV30 and AV35 should be limited to 2.39 mL and 0.71 mL, respectively.
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Cellular mitophagy means that cells selectively wrap and degrade damaged mitochondria through an autophagy mechanism, thus maintaining mitochondria and intracellular homeostasis. In recent years, mitophagy has received increasing attention as a research hotspot related to the pathogenesis of clinical diseases, such as neurodegenerative diseases, cardiovascular diseases, cancer, metabolic diseases, and so on. It has been found that the regulation of mitophagy may become a new direction for the treatment of some diseases. In addition, numerous small molecule modulators of mitophagy have also been reported, which provides new opportunities to comprehend the procedure and potential of therapeutic development. Taken together, in this review, we summarize current understanding of the mechanism of mitophagy, discuss the roles of mitophagy and its relationship with diseases, introduce the existing small-molecule pharmacological modulators of mitophagy and further highlight the significance of their development.