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2.
Neurosci Lett ; 826: 137714, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38479554

RESUMO

Social isolation, a known stressor, can have detrimental effects on both physical and mental health. Recent scientific attention has been drawn to the gut-brain axis, a bidirectional communication system between the central nervous system and gut microbiota, suggesting that gut microbes may influence brain function. This study aimed to explore the impact of social isolation on the intestinal barrier and gut microbiota. 40 male BALB/c mice were either individually housed or kept in groups for 8 and 15 weeks. Socially isolated mice exhibited increased anxiety-like behavior, with significant differences between the 8-week and 15-week isolation groups (P < 0.05). After 8 weeks of isolation, there was a reduction in tight junction protein expression in the intestinal mechanical barrier. Furthermore, after 15 weeks of isolation, both tight junction protein and mucin expression, key components of the intestinal chemical barrier, decreased. This was accompanied by a substantial increase in inflammatory cytokines (IL-6 mRNA, IL-10, and TNF-α) in colon tissue in the 15-week isolated group (P < 0.05). Additionally, Illumina MiSequencing revealed significant alterations in the gut microbiota of socially isolated mice, including reduced Firmicutes and Bacteroides compared to the control group. Lactobacillus levels also decreased in the socially isolated mice.


Assuntos
Microbioma Gastrointestinal , Camundongos , Masculino , Animais , Microbioma Gastrointestinal/fisiologia , Citocinas/metabolismo , Isolamento Social , Fator de Necrose Tumoral alfa , Proteínas de Junções Íntimas , Camundongos Endogâmicos C57BL
3.
Mol Carcinog ; 62(3): 293-302, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36342357

RESUMO

Dihydroartemisinin (DHA) has recently attracted increasing attention for its low toxicity and high antitumor activity. DHA has been reported to have synergistic anticancer effects with a variety of drugs in the clinic; however, the molecular mechanism by which DHA inhibits tumorigenesis and improves oxaliplatin cytotoxicity in colon cancer cells is still not well understood. In this study, we found that DHA can inhibit cell proliferation and colony formation in a dose-dependent manner. Prohibitin 2 (PHB2) is a potential target by which DHA exerts its antitumor and cytotoxic effects. The function and molecular mechanism of PHB2 in colon cancer tumorigenesis were fully studied to determine the regulatory mechanism between DHA and PHB2. We found that PHB2, a mitochondrial inner membrane scaffold protein, has a higher expression level in colon cancer tissues than in adjacent nontumor tissues and is mainly localized in mitochondria. Overexpression of PHB2 can promote cell proliferation and colony formation in vitro and accelerate tumor growth in vivo. We also found that the expression level of PHB2 was inversely related to the cytotoxicity of DHA and oxaliplatin in colon cancer cells. The molecular mechanism of PHB2 in tumorigenesis and cancer therapy was further studied. The results showed that 20 µM DHA can downregulate PHB2 expression in a ubiquitylation-dependent manner and subsequently block PHB2-induced RCHY1 upregulation and p53 and p21 downregulation. In this process, RCHY1 is necessary for PHB2 to play a tumor-promoting role. Thus, PHB2 and RCHY1 are effective targets for colon cancer therapy, and DHA has synergistic anticancer effects with oxaliplatin via promoting PHB2 degradation in colon cancer cells.


Assuntos
Antineoplásicos , Neoplasias do Colo , Humanos , Oxaliplatina/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transdução de Sinais , Neoplasias do Colo/tratamento farmacológico , Carcinogênese , Linhagem Celular Tumoral , Ubiquitina-Proteína Ligases
4.
Int. microbiol ; 25(4): 723-732, Nov. 2022. graf
Artigo em Inglês | IBECS | ID: ibc-216240

RESUMO

Background/aims: The aim was to characterize a bacterium causing intestinal mucosal barrier damage and to identify the possible invasion mechanism. Materials and methods: The intestinal permeability and tight junction protein levels were detected in guinea pigs infected with Escherichia coli D-09 via immunofluorescence analysis and western blotting. In order to explain this invasion mechanism at the gene level, whole genome sequencing analysis was performed on this bacterium. Results: The results showed an increased intestinal permeability and upregulated expression of the leaky protein claudin-2 in both the colon and liver of the infected animals. In addition, the draft genome of E. coli D-09 comprised 42 scaffolds (size, > 645 bp) with a total size of 4,679,567 bp. A total of 4379 protein coding genes were identified, which contained 45 antibiotic resistance and 86 virulence-related genes and covered 88.0% of the whole genome. Conclusions: This study verified that the human-derived enteroinvasive E. coli strain could destroy intestinal barrier function in guinea pigs. Additionally, our data first characterized the genome features of E. coli O124:K72 D-09, which may provide new insights into the possible invasion mechanism.(AU)


Assuntos
Humanos , Animais , Escherichia coli , Cobaias , Colecistite Aguda , Sequenciamento Completo do Genoma , Mucosa Intestinal , Gastroenterologia , Microbiologia
5.
Genet Res (Camb) ; 2022: 9282484, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36101744

RESUMO

Sirtuin 2 (SIRT2), as a member of the sirtuin family, has representative features of evolutionarily highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase activity. In addition, SIRT2, as the only sirtuin protein colocalized with tubulin in the cytoplasm, has its own functions and characteristics. In recent years, studies have increasingly shown that SIRT2 can participate in the regulation of gene expression and regulate signal transduction in the metabolic pathway mainly through its post-translational modification of target genes; thus, SIRT2 has become a key centre in the metabolic pathway and participates in the pathological process of metabolic disorder-related diseases. In this paper, it is discussed that SIRT2 can regulate all aspects of gene expression, including epigenetic modification, replication, transcription and translation, and post-translational modification, which enables SIRT2 to participate in energy metabolism in life activities, and it is clarified that SIRT2 is involved in metabolic process-specific signal transduction mechanisms. Therefore, SIRT2 can be involved in metabolic disorder-related inflammation and oxidative stress, thereby triggering the occurrence of metabolic disorder-related diseases, such as neurodegenerative diseases, tumours, diabetes, and cardiovascular diseases. Currently, although the role of SIRT2 in some diseases is still controversial, given the multiple roles of SIRT2 in regulating physiological and pathological signal transduction, SIRT2 has become a key target for disease treatment. It is believed that with increasing research, the clinical application of SIRT2 will be promoted.


Assuntos
Doenças Neurodegenerativas , Sirtuína 2 , Humanos , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Estresse Oxidativo , Processamento de Proteína Pós-Traducional/genética , Transdução de Sinais/genética , Sirtuína 2/genética , Sirtuína 2/metabolismo
6.
Gland Surg ; 11(8): 1383-1394, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36082086

RESUMO

Background: A novel endoscopic-assisted technique (NET) was created by our team for nipple-sparing mastectomy (NSM) and latissimus dorsi muscle flap (LDMF) reconstruction that enables the procedure to be conducted through a single axillary incision. The authors hypothesized that the NET has the advantages of the traditional ET (TET) and a reduced operation time. The purpose of this study is to compare the advantages and disadvantages of NET, TET and open surgery. Methods: A retrospective cohort study was performed on patients who underwent LDMF reconstruction after NSM using open surgery, the TET, or the NET between January 2013 and June 2021. The following outcomes were compared: the operation time, size of the LDMF, the complication rate, hospital length of stay, hospital costs, aesthetic results (the BREAST-Q questionnaire), and quality of life (QoL). The BREAST-Q questionnaire and QoL were underwent preoperatively and 1, 3, and 12 months postoperatively. Results: A total of 17 ETs (comprising 10 NETs and 7 TETs) and 28 open surgery procedures were identified and analyzed, the baseline characteristics were comparable in terms of age, body mass index (BMI), tumor location, cup size, and disease stage of the three groups. The mean operation time of the NET group (395.8±176.0 min) in the exploration stage was shorter than that of the TET group (531.6±69.6 min) and equivalent to that of the open surgery group (400.9±67.3 min). The overall postoperative complication rates of the ET and open surgery groups were 35.3% and 60.7%, respectively (P=0.09). The aesthetic results in relation to patients' satisfaction with their breasts (P=0.001) and backs (P=0.001) were better in the ET group than the open surgery group beginning at 1 month postoperatively. The ET group had better psychosocial well-being beginning at 1 month postoperatively (P=0.002) and sexual well-being beginning at 3 months postoperatively (P<0.001) than the open surgery group. Conclusions: LDMF reconstruction after NSM using the ET is associated with lower complication rates, good aesthetic results, and a better QoL than open surgery procedures. The NET is a promising approach, a more convenient procedure, and has a shorter surgery time than TET, however, this conclusion needs to be further validated by randomized clinical trial (RCT) research with a larger sample size.

7.
Front Oncol ; 12: 957511, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35978806

RESUMO

Introduction: Adenylyl cyclase isoform 6 (ADCY6) is a member of membrane-bound adenylate cyclase family that converts adenosine triphosphate (ATP) into cAMP and pyrophosphate. An increasing number of researchers have studied the role of ADCY6 in cancer. However, its specific role in breast cancer remains unknown. Methods: Bioinformatics and clinical data were used to analyse the expression of ADCY6 in breast cancer. ADCY6 DNA methylation was analysed using DNA methylation-specific PCR and Bisulfite Sanger sequencing. Using lentiviral stable miRNA transfection together with cell biology functional assays and gene expression/target analysis, we investigated the interaction between miR-27a-3p, TET1 and ADCY6 in breast cancer. Results: We found that ADCY6 is expressed at low levels in breast cancer and leads to increases in the proliferation, invasion and migration of breast cancer cells. The low expression of ADCY6 is due to the lower demethylation of ten-eleven translocation methylcytosine dioxygenase 1 (TET1), and the methylation of ADCY6 can be altered by TET1. More importantly, bioinformatics analysis showed that TET1 is regulated by miR-27a-3p and regulates the methylation of ADCY6 to affect the EMT process of breast cancer cells, thereby affecting the malignant biological behaviour of breast cancer. Conclusions: Our study demonstrates that the methylation modification of ADCY6 is regulated by TET1 and leads to ADCY6 activation. miR-27a-3p negatively regulates the expression of TET1 and affects the EMT process of breast cancer through ADCY6, thereby promoting the malignant biological behaviour of breast cancer. Our results may provide new research ideas and directions for DNA methylation and EMT changes in breast cancer.

8.
Front Oncol ; 12: 972383, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033472

RESUMO

Background and aims: CCL5 is considered to contribute to the biological function of a variety of cancer types, but its specific mechanism is still unclear. This study aimed to reveal the mechanism of CCL5 in the invasion, metastasis, and prognosis of breast cancer. Methods: The expression of CCL5 in tumor tissue and serum was measured with a Luminex protein detection kit, and the correlation between CCL5 and clinical parameters was evaluated. Kaplan-Meier analysis was used to analyze the effect of CCL5 on the prognosis of breast cancer patients. Protein interaction network analysis and gene coexpression were used to determine the receptor that has the strongest interaction with CCL5. Enrichment analysis was used to study the possible pathway by which CCL5 affects breast cancer progression. We used immunofluorescence staining and flow cytometry to estimate the fraction of immunity-related components in the tumor microenvironment. Results: The expression level of CCL5 in breast cancer patients was positively correlated with the degree of axillary lymph node metastasis; CCL5 in tumor tissue was correlated with estrogen receptor status (P = 0.034), progesterone receptor (P = 0.009), nuclear grade (P = 0.013), clinical stage (P < 0.001) and molecular subtype (P = 0.024) in breast cancer patients. Breast cancer patients with high CCL5 expression had worse disease-free survival (P = 0.031) and breast cancer-specific survival (P = 0.043); however, CCL5 had no effect on overall survival (P = 0.077). CCL5 affected tumor progression through CCR5, and the T-cell-related immune pathway may be the main pathway; the CD4+/CD8+, CCR5+/CD4+ and Treg/CCR5+ cell ratios were significantly increased in the lymph node metastasis group. Conclusion: CCL5 affects the Treg/CD4+CCR5+ cell ratio in breast cancer patients through CCR5, thus affecting breast cancer metastasis and prognosis.

9.
Adv Ther ; 39(10): 4707-4722, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35953665

RESUMO

INTRODUCTION: We aimed to evaluate whether radiotherapy (RT) after breast-conserving surgery (BCS) can be omitted in elderly patients with early-stage, hormone receptor-negative breast cancer. METHODS: Patients aged 65 years and older with T1-2N0-1, hormone receptor-negative breast cancer in 2010-2015 were extracted from the Surveillance, Epidemiology, and End Results program. Propensity score matching was used to balance the baseline of different groups. Survival analysis was performed using Kaplan-Meier plot and log-rank test. Independent risk factors were identified by multivariate Cox analysis. A nomogram predicting breast cancer-specific survival (BCSS) and a risk stratification model were constructed and validated. RESULTS: A total of 4465 patients were included and 27.7% (1237/4465) patients did not receive postoperative RT. RT was significantly associated with improved overall survival (OS) (HR = 0.552 P < 0.001) and BCSS (HR = 0.559, P < 0.001) in the matched cohort. The same results were found after adjusting independent risk factors by multivariate analysis. On the basis of the nomogram predicting BCSS of patients without RT by incorporating independent risk factors (age, race, HER2 status, T stage, and N stage), we built a risk stratification model which indicated that RT improved OS (HR = 0.511, P < 0.001) and BCSS (HR = 0.517, P < 0.001) in the high-risk group (total score > 150), but not in the low-risk group (total score ≤ 120). The C-index and all calibration curves demonstrated sufficient accuracies and good predictive capabilities. CONCLUSIONS: RT is indeed beneficial for the whole cohort in this study. However, it may be omitted in the low-risk subgroup without significantly sacrificing survival. For patients in the high-risk group, RT following BCS remained beneficial. This study highlights the need for prospective randomized trials to study RT de-escalation strategies.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Idoso , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Hormônios , Humanos , Mastectomia Segmentar/métodos , Estadiamento de Neoplasias , Nomogramas , Estudos Prospectivos , Programa de SEER
10.
Int Microbiol ; 25(4): 723-732, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35725861

RESUMO

BACKGROUND/AIMS: The aim was to characterize a bacterium causing intestinal mucosal barrier damage and to identify the possible invasion mechanism. MATERIALS AND METHODS: The intestinal permeability and tight junction protein levels were detected in guinea pigs infected with Escherichia coli D-09 via immunofluorescence analysis and western blotting. In order to explain this invasion mechanism at the gene level, whole genome sequencing analysis was performed on this bacterium. RESULTS: The results showed an increased intestinal permeability and upregulated expression of the leaky protein claudin-2 in both the colon and liver of the infected animals. In addition, the draft genome of E. coli D-09 comprised 42 scaffolds (size, > 645 bp) with a total size of 4,679,567 bp. A total of 4379 protein coding genes were identified, which contained 45 antibiotic resistance and 86 virulence-related genes and covered 88.0% of the whole genome. CONCLUSIONS: This study verified that the human-derived enteroinvasive E. coli strain could destroy intestinal barrier function in guinea pigs. Additionally, our data first characterized the genome features of E. coli O124:K72 D-09, which may provide new insights into the possible invasion mechanism.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Animais , Claudina-2/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Cobaias , Humanos , Intestinos/microbiologia , Proteínas de Junções Íntimas/metabolismo
11.
Mol Med Rep ; 24(4)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34414461

RESUMO

Myocardial injury is the primary manifestation of multiple organ dysfunction during sepsis, however, the mechanisms underlying sepsis­induced myocardial injury remain unclear. Similarly, no effective therapeutics have yet been developed for myocardial injury. In the present study, the role of the NOD­like receptor 3 (NLRP3) inflammasome on cardiac function were characterized and the effects of different ulinastatin (UTI) doses in protecting a septic rat model from myocardial injury were elucidated. To evaluate UTI efficacy on cardiac function, its effects on anti­inflammatory mediators were analyzed and its cardioprotective effects were investigated. It was demonstrated that circulatory levels of tumor necrosis factor­α and interleukin­1ß were elevated during sepsis. It was also observed that NLRP3 and caspase­1 expression enhanced post­cecal ligation and puncture (CLP), and that high UTI levels protected against myocardial injury induced by sepsis. To the best of our knowledge, this is the first study to demonstrate that the mechanisms underpinning UTI­mediated myocardial protection were due to the downregulation of the NLRP3/caspase­1/IL­1ß signaling pathway. Based on these findings, it is proposed that UTI exerts beneficial effects during sepsis­induced myocardial injury.


Assuntos
Anti-Inflamatórios/farmacologia , Glicoproteínas/farmacologia , Traumatismos Cardíacos/tratamento farmacológico , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sepse/metabolismo , Animais , Caspase 1/metabolismo , Ceco/metabolismo , Modelos Animais de Doenças , Ligadura , Masculino , Miocárdio/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Punções , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa
12.
Front Oncol ; 11: 634569, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094915

RESUMO

INTRODUCTION: Breast atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are precursor stages of invasive ductal carcinoma (IDC). This study aimed to investigate the pathogenesis of breast cancer by dynamically analyzing expression changes of hub genes from normal mammary epithelium (NME) to simple ductal hyperplasia (SH), ADH, DCIS, and finally to IDC. METHODS: Laser-capture microdissection (LCM) data for NME, SH, ADH, DCIS, and IDC cells were obtained. Weighted gene co-expression network analysis (WGCNA) was performed to dynamically analyze the gene modules and hub genes associated with the pathogenesis of breast cancer. Tissue microarray, immunohistochemical, and western blot analyses were performed to determine the protein expression trends of hub genes. RESULTS: Two modules showed a trend of increasing expression during the development of breast disease from NME to DCIS, whereas a third module displayed a completely different trend. Interestingly, the three modules displayed inverse trends from DCIS to IDC compared with from NME to DCIS; that is, previously upregulated modules were subsequently downregulated and vice versa. We further analyzed the module that was most closely associated with DCIS (p=7e-07). Kyoto Gene and Genomic Gene Encyclopedia enrichment analysis revealed that the genes in this module were closely related to the cell cycle (p= 4.3e-12). WGCNA revealed eight hub genes in the module, namely, CDK1, NUSAP1, CEP55, TOP2A, MELK, PBK, RRM2, and MAD2L1. Subsequent analysis of these hub genes revealed that their expression levels were lower in IDC tissues than in DCIS tissues, consistent with the expression trend of the module. The protein expression levels of five of the hub genes gradually increased from NME to DCIS and then decreased in IDC. Survival analysis predicted poor survival among breast cancer patients if these hub genes were not downregulated from DCIS to IDC. CONCLUSIONS: Five hub genes, RRM2, TOP2A, PBK, MELK, and NUSAP1, which are associated with breast cancer pathogenesis, are gradually upregulated from NME to DCIS and then downregulated in IDC. If these hub genes are not downregulated from DCIS to IDC, patient survival is compromised. However, the underlying mechanisms warrant further elucidation in future studies.

13.
Oncol Lett ; 21(5): 410, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33841571

RESUMO

Centromere proteins (CENPs) are involved in mitosis, and CENP gene expression levels are associated with chemotherapy responses in patients with breast cancer. The present study aimed to examine the roles and underlying mechanisms of the effects of CENP genes on chemotherapy responses and breast cancer prognosis. Using data obtained from the Gene Expression Omnibus (GEO) database, correlation and Cox multivariate regression analyses were used to determine the CENP genes associated with chemotherapy responses and survival in patients with breast cancer. Weighted gene co-expression network and correlation analyses were used to determine the gene modules co-expressed with the identified genes and the differential expression of gene modules associated with the pathological complete response (PCR) and residual disease (RD) subgroups. CENPA, CENPE, CENPF, CENPI, CENPJ and CENPN were associated with a high nuclear grade and low estrogen and progesterone receptor expression levels. In addition, CENPA, CENPB, CENPC and CENPO were independent factors affecting the distant relapse-free survival (DRFS) rates in patients with breast cancer. Patients with high expression levels of CENPA or CENPO exhibited poor prognoses, whereas those with high expression levels of CENPB or CENPC presented with favorable prognoses. For validation between databases, the Cancer Genome Atlas (TCGA) database analysis also revealed that CENPA, CENPB and CENPO exerted similar effects on overall survival. However, according to the multivariate analyses, only CENPA was an independent risk factor associated with DRFS in GEO database. In addition, in the RD subgroup, patients with higher CENPA expression levels had a worse prognosis compared with those with lower CENPA expression levels. Among patients with high expression levels of CENPA, the PI3K/Akt/mTOR pathway was more likely to be activated in the RD compared with the PCR subgroup. The same trend was observed in TCGA data. These results suggested that high CENPA expression levels plus upregulation of the PI3K/Akt/mTOR signaling pathway may affect DRFS in patients with breast cancer.

14.
Ann Transl Med ; 9(24): 1779, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35071473

RESUMO

BACKGROUND: Although the results of gene testing can guide early breast cancer patients with hormone receptor (HR)+, human epidermal growth factor receptor 2 (HER2)- to decide whether they need chemotherapy (CHT), there are still many patients worldwide whose problems cannot be resolved by genetic testing. METHODS: A total of 144,735 patients with HR+, HER2-, pT1-3N0-1 breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 were included. They were divided into CHT and no CHT groups, and after propensity score matching (PSM), overall survival (OS) and breast cancer-specific survival (BCSS) were tested using the Kaplan-Meier plot. The Cox proportional hazards regression model was used to identify independent prognostic factors. A nomogram was constructed to score each patient. Patients were divided into high- or low-risk groups according to their nomogram score using X-tile. RESULTS: Patients receiving CHT had better OS before and after matching (P<0.05), but BCSS was not significantly different between patients with and without CHT after matching. Independent prognostic factors were included to construct the nomogram, which could calculate the risk score for each patient, and then all patients were divided into two groups using X-tile: a risk score ≤238 was classified as the low-risk group and >238 was classified as the high-risk group. Patients in the high-risk group (score >238) could achieve better OS and from CHT; however, the low-risk group (score ≤238) could not. CONCLUSIONS: In this study, a well-validated nomogram and a risk stratification model was built. Patients in the high-risk group should receive CHT, while patients in low-risk group may be exempt from CHT.

15.
Ann Transl Med ; 9(22): 1689, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34988198

RESUMO

BACKGROUND: The biological function and molecular mechanism of nucleolar spindle-associated protein 1 (NUSAP1) in breast cancer remain controversial, this study aimed to reveal the mechanism of NUSAP1 in breast cancer cell metastasis and survival. METHODS: The expression of NUSAP1 expression was evaluated by immunohistochemistry and quantitative real-time polymerase chain reaction (RT-qPCR) in breast tissue samples. The correlation of NUSAP1 expression with the clinicopathological parameters of the patients and overall survival (OS) was evaluated. The protein expression was detected by Western blotting, the cell proliferation was evaluated by Edu staining and MTT assay, migration and invasion were tested by transwell and migration assay. Female BALB/c nude mice models for tumor growth and metastasis of breast cancer were evaluated in vivo. RESULTS: NUSAP1 is up-regulated in multiple cancers and is associated with a poor prognosis in breast cancer patients. Further analysis of the Gene Expression Omnibus (GEO) database and our included patients revealed that NUSAP1 expression gradually increased with pathological changes in breast tissue. Cell function assays confirmed that NUSAP1 was related to the proliferation, migration, and invasion of breast cancer cells. In vivo, NUSAP1 promoted lung metastasis in nude mice. We found that the NUSAP1 protein can promote tumor proliferation and metastasis by activating the AMPK/PPARγ signaling pathway. CONCLUSIONS: Our findings show that NUSAP1 promotes breast cancer proliferation and metastasis by activating the AMPK/PPARγ signaling pathway.

16.
Front Oncol ; 10: 1718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042815

RESUMO

Objective: The application of sentinel lymph node biopsy (SLNB) in elderly patients with early breast cancer remains somewhat controversial. This study aimed to establish individualized nomograms to predict survival outcomes of elderly patients with and without SLNB and find out which patients could avoid SLNB. Methods: A total of 39,962 ≥70-year-old patients diagnosed with T1-T2 breast cancer in 2010-2015 were included from the Surveillance, Epidemiology, and End Results (SEER) program and were divided into the training set (n = 29,971) and the validation set (n = 9,991). Axillary surgery was not specified in the SEER database, and we defined removing one to five lymph nodes as SLNB. Survival analysis was performed using the Kaplan-Meier plot and log-rank test. Multivariate Cox analysis was utilized to identify risk factors for overall survival (OS) and breast-cancer-specific survival (BCSS). Nomograms and a risk stratification model were constructed. Results: In the training set, patients with SLNB had better OS (adjusted HR 0.57, P < 0.001) and BCSS (adjusted HR 0.55, P < 0.001) than patients without SLNB. Multivariate COX analysis identified age, marital status, grade, subtype, T stage, and radiation as independent risk factors for OS and BCSS in both SLNB and non-SLNB groups (all P < 0.05). They were subsequently incorporated to establish nomograms to predict 3- and 5-year OS and BCSS for patients with or without SLNB. The concordance index ranged from 0.687 to 0.820, and calibration curves in the internal set and external set all demonstrated sufficient accuracies and good predictive capabilities. Further, we generated a risk stratification model which indicated that SLNB improved OS and BCSS in high-risk group (OS: HR 0.49, P < 0.001; BCSS: HR 0.54, P < 0.001), but not in the low-risk group (all P > 0.05). Conclusion: Well-validated nomograms and a risk stratification model were constructed to evaluate survival benefit from SLNB in elderly patients with early-stage breast cancer. SLNB was important for patients in the high-risk group but could be omitted in the low-risk group without sacrificing survival. This study could assist clinicians and elderly patients to weigh the risk-benefit of SLNB and make individualized decisions. We look forward to more powerful evidence from prospective trials.

18.
Int J Rheum Dis ; 23(3): 381-391, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31863640

RESUMO

OBJECTIVES: To update Schall's classification for Sjögren's syndrome (SS) by the new quantitative stimulation test with dynamic salivary glands scintigraphy (qsDSGS) and to standardize quantitative salivary gland scintigraphy. METHODS: The histopathology, oral, ocular, serological examination and qsDSGS of 268 consecutive patients with suggestive SS were evaluated in this retrospective cohort study. The serological examination included 15 autoantibodies, antinuclear antibodies (ANA) and so on. The diagnostic thresholds of the functional parameters were set by the quantitative method, and the modified Schall's classification is well established and verified. RESULTS: Based on the quantitative analysis of qsDSGS, the peak uptake level (PUL) and stimulation excretion fraction (sEF) of each parotid gland were determined as the key imaging features, which had good diagnostic performance for SS. By the modified Schall's classification, all patients were classified into: Class 1 (normal; n = 44), Class 2 (mild to moderate involvement; n = 130), Class 3 (severe involvement; n = 56) and Class 4 (very severe involvement, non-function; n = 38). Using the threshold PUL ≤ 10 counts per sec/pixel as positivity, the modified Schall's classification could provide better diagnostic performance with 88.4% specificity, 71.3% sensitivity, 96.14% positive predictive value and 43.20% negative predictive value for SS (likelihood ratio 6.15). The trends of serologically positive frequencies against SSA/Ro, anti-SSB/La and ANA were significantly increased with the new classification. CONCLUSION: The modified Schall's classification by the new stimulation test with dynamic scintigraphy is eligible to standardize quantitative salivary gland scintigraphy for SS, and may be more convenient and suitable in daily practice for clinical research and management of SS.


Assuntos
Glândula Parótida/diagnóstico por imagem , Salivação , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Síndrome de Sjogren/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácido Ascórbico/administração & dosagem , Autoanticorpos/sangue , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Parótida/fisiopatologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Testes Sorológicos , Síndrome de Sjogren/sangue , Síndrome de Sjogren/classificação , Síndrome de Sjogren/fisiopatologia , Fatores de Tempo , Adulto Jovem
19.
Medicine (Baltimore) ; 98(40): e17481, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577783

RESUMO

Axillary lymph node metastasis (ALNM) is commonly the earliest detectable clinical manifestation of breast cancer when distant metastasis emerges. This study aimed to explore the influencing factors of ALNM and develop models that can predict its occurrence preoperatively.Cases of sonographically visible clinical stage T1-2N0M0 breast cancers treated with breast and axillary surgery at West China Hospital were retrospectively reviewed. Univariate and multivariate logistic regression analyses were performed to evaluate associations between ALNM and variables. Decision tree analyses were performed to construct predictive models using the C5.0 packages.Of the 1671 tumors, 541 (32.9%) showed axillary lymph node positivity on final surgical histopathologic analysis. In multivariate logistic regression analysis, tumor size (P < .001), infiltration of subcutaneous adipose tissue (P < .001), infiltration of the interstitial adipose tissue (P = .031), and tumor quadrant locations (P < .001) were significantly correlated with ALNM. Furthermore, the accuracy in the decision tree model was 69.52%, and the false-negative rate (FNR) was 74.18%. By using the error-cost matrix algorithm, the FNR significantly decreased to 14.75%, particularly for nodes 5, 8, and 13 (FNR: 11.4%, 9.09%, and 14.29% in the training set and 18.1%,14.71%, and 20% in the test set, respectively).In summary, our study demonstrated that tumor lesion boundary, tumor size, and tumor quadrant locations were the most important factors affecting ALNM in cT1-2N0M0 stage breast cancer. The decision tree built using these variables reached a slightly higher FNR than sentinel lymph node dissection in predicting ALNM in some selected patients.


Assuntos
Neoplasias da Mama/patologia , Metástase Linfática/patologia , Adulto , Axila , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , China , Árvores de Decisões , Feminino , Humanos , Modelos Logísticos , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco
20.
Pharmacol Res ; 148: 104461, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31542404

RESUMO

Intestinal epithelial barrier dysfunction is a key pathology of colitis. Autophagy of epithelial cells maintains homeostasis of the intestinal barrier by inhibiting apoptosis and stimulating degradation of the tight junction protein claudin-2. This study investigated the effects and mechanism of activity of sinensetin, a polymethylated flavonoid isolated from tangerine peel and citrus, on intestinal barrier dysfunction in colitis. Animal model of colitis were established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid and oral treatment with dextran sulfate sodium. Epithelial barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in Caco-2 cells, respectively. Epithelial cell autophagy assayed by autophagosome formation and expression of autophagy-related protein. Sinensetin reversed colitis-associated increase in intestinal permeability, significantly promoted epithelial cell autophagy, and further decreased epithelial cell apoptosis, and reduced mucosal claudin-2. Sinenstetin alleviated colitis symptoms rats and mice with colitis. Knockdown of 5' adenosine monophosphate-activated protein kinase (AMPK) reversed the promotion of epithelial autophagy by sinensetin. In conclusion, sinensetin significantly alleviated intestinal barrier dysfunction in colitis by promoting epithelial cell autophagy, and further inhibiting apoptosis and promoting claudin-2 degradation. The results highlighted novel potential benefits of sinensetin in colitis.


Assuntos
Autofagia/efeitos dos fármacos , Colite/tratamento farmacológico , Células Epiteliais/efeitos dos fármacos , Flavonoides/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células CACO-2 , Claudina-2/metabolismo , Colite/metabolismo , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo
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