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1.
Ann Surg Oncol ; 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655352

RESUMO

BACKGROUND: The influence of social determinants of health (SDH) on participation in clinical trials for pancreatic cancer is not well understood. In this study, we describe trends and identify disparities in pancreatic cancer clinical trial enrollment. PATIENTS AND METHODS: This is a retrospective study of stage I-IV pancreatic cancer patients in the 2004-2016 National Cancer Database. Cohort was stratified into those enrolled in clinical trials during first course of treatment versus not enrolled. Bivariate analysis and logistic regression were used to understand the relationship between SDH and clinical trial participation. RESULTS: A total of 1127 patients (0.4%) enrolled in clinical trials versus 301,340 (99.6%) did not enroll. Enrollment increased over the study period (p < 0.001), but not for Black patients or patients on Medicaid. The majority enrolled had metastatic disease (65.8%). On multivariate analysis, in addition to year of diagnosis (p < 0.001), stage (p < 0.001), and Charlson score (p < 0.001), increasing age [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.96-0.97], non-white race (OR 0.54, CI 0.44-0.66), living in the South (OR 0.42, CI 0.35-0.51), and Medicaid, lack of insurance, or unknown insurance (0.41, CI 0.31-0.53) were predictors of lack of participation. Conversely, treatment at an academic center (OR 6.36, CI 5.4-7.4) and higher neighborhood education predicted enrollment (OR 2.0, CI 1.55-2.67 for < 7% with no high school degree versus > 21%). DISCUSSION: Age, race, insurance, and geography are barriers to clinical trial enrollment for pancreatic cancer patients. While overall enrollment increased, Black patients and patients on Medicaid remain underrepresented. After adjusting for cancer-specific factors, SDH are still associated with clinical trial enrollment, suggesting need for targeted interventions.

2.
Cancer Med ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34581026

RESUMO

Long noncoding RNAs (lncRNAs) play a crucial role in cancer aerobic glycolysis. However, glycolysis-related lncRNAs are still underexplored in breast cancer. In this study, we identified the five most glycolysis-related lncRNAs in breast cancer to construct a prognostic signature, which could distinguish between patients with unfavorable and favorable prognoses. To investigate the role of signature lncRNAs in breast cancer, we profiled their expression levels in breast cancer progression cell line model. Real-time PCR revealed that the five lncRNAs could contribute to breast cancer initiation or progression. Furthermore, we observed that the levels of four lncRNAs expression had a significant trend of gradient upregulation with the addition of glycolysis inhibitor in breast cancer cells. Afterward, random forest and logistic regression were conducted to assess the model's performance in stratifying glycolysis status. Finally, a nomogram including the lncRNA signature and clinical features was developed, and its efficacy in predicting the survival time and clinical utility was evaluated using a calibration curve, concordance index, and decision curve analysis. In this study, gene set enrichment analysis showed that the mTOR pathway, a central pathway in tumor initiation and progression, was significantly enriched in the high-risk group. In addition, gene set variation analysis was performed to validate our findings in two independent datasets. Subsequent weighted gene co-expression network analysis, followed by enrichment analysis, indicated that downstream cell growth-related signaling was strikingly activated in the high-risk group, and may directly promote tumor progression and escalate mortality risk in patients with high-risk scores. Overall, our findings may provide novel insight into lncRNA-related metabolic regulation, and help to develop promising prognostic indicators and therapeutic targets for breast cancer patients.

3.
Protein Cell ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554412

RESUMO

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes ß-coronavirus lineage B (ß-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-ß-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against ß-CoV-B and newly emerging SARS-CoV-2 variants of concern.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34567216

RESUMO

Amyloid-ß peptide (Aß) accumulation is a detrimental factor in cerebral ischemia/reperfusion (I/R) injuries accounting for dementia induced by ischemic stroke. In addition to blood brain barrier (BBB), the glymphatic system mediated by aquaporin-4 (AQP-4) on astrocytic endfeet functions as an important pathway for the clearance of Aß in the brain. Cerebral I/R induced astrocytic pyroptosis potentially causes the AQP-4 polarization loss and dysfunctional BBB-glymphatic system exacerbating the accumulation of Aß. Furthermore, Aß toxicity has been identified as a trigger of pyroptosis and BBB damage, suggesting an amplified effect of Aß accumulation after cerebral I/R. Therefore, based on our previous work, this study was designed to explore the intervention effects of Tongxinluo (TXL) on astrocytic pyroptosis and Aß accumulation after cerebral I/R in rats. The results showed that TXL intervention obviously alleviated the degree of pyroptosis by downregulating expression levels of cleaved caspase-11/1, N-terminal gasdermin D, nucleotide-binding oligomerization domain-like receptors pyrin domain containing 3 (NLRP3), interleukin-6 (IL-6), and cleaved IL-1ß and abated astrocytic pyroptosis after cerebral I/R. Moreover, TXL intervention facilitated to restore AQP-4 polarization and accordingly relieve Aß accumulation around astrocytes in ischemic cortex and hippocampus as well as the formation of toxic Aß (Aß 1-42 oligomer). Our study indicated that TXL intervention could exert protective effects on ischemic brain tissues against pyroptotic cell death, inhibit astrocytic pyroptosis, and reduce toxic Aß accumulation around astrocytes in cerebral I/R injuries. Furthermore, our study provides biological evidence for the potential possibility of preventing and treating poststroke dementia with TXL in clinical practice.

5.
Front Oncol ; 11: 660242, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513664

RESUMO

Background: Recent years, the global prevalence of breast cancer (BC) was still high and the underlying molecular mechanisms remained largely unknown. The investigation of prognosis-related biomarkers had become an urgent demand. Results: In this study, gene expression profiles and clinical information of breast cancer patients were downloaded from the TCGA database. The differentially expressed genes (DEGs) were estimated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A risk score formula involving five novel prognostic associated biomarkers (EDN2, CLEC3B, SV2C, WT1, and MUC2) were then constructed by LASSO. The prognostic value of the risk model was further confirmed in the TCGA entire cohort and an independent external validation cohort. To explore the biological functions of the selected genes, in vitro assays were performed, indicating that these novel biomarkers could markedly influence breast cancer progression. Conclusions: We established a predictive five-gene signature, which could be helpful for a personalized management in breast cancer patients.

6.
Cancer Biother Radiopharm ; 36(8): 624-631, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34375126

RESUMO

First introduced in 1976, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has become an indispensable tool for diagnosis and prognostic evaluation of tumors, heart disease, as well as other conditions, including inflammation and infection. Because 18F-FDG can accurately reflect the glucose metabolism level of organs and tissues, it is known as a "century molecule" and is currently the main agent for PET imaging. The degree of 18F-FDG uptake by cells is related to both the rate of glucose metabolism and glucose transporter expression. These, in turn, are strongly influenced by hypoxia, in which cells meet their energy needs through glycolysis, and 18F-FDG uptake increased due to hypoxia. 18F-FDG uptake is a complex process, and hypoxia may be one of the fundamental driving forces. The correct interpretation of 18F-FDG uptake in PET imaging can help clinics make treatment decisions more accurately and effectively. In this article, we review the application of 18F-FDG PET in tumors, myocardium, and inflammation. We discuss the relationship between 18F-FDG uptake and hypoxia, the possible mechanism of 18F-FDG uptake caused by hypoxia, and the associated clinical implications.

7.
Breast ; 59: 314-320, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34388697

RESUMO

PURPOSE: Low socioeconomic status (SES) is associated with advanced stage, lower-quality care, and higher mortality among breast cancer patients. The purpose of this study is to examine the association between neighborhood SES (nSES), surgical management, and disease-specific mortality in de novo metastatic breast cancer (MBC) patients in the Surveillance, Epidemiology, and End Results (SEER) Program. METHODS: MBC patients ages 18 to 85+ years diagnosed from 2010 through 2016 were identified in SEER. The cohort was divided into low, middle, and high nSES based on the NCI census tract-level index. Univariable and multivariable analyses were used to examine the relationship between nSES, surgery, and disease specific mortality in MBC patients. RESULTS: There were 24,532 de novo MBC patients who met study criteria, with 28.7 % undergoing surgery. Over the study period, surgery utilization decreased across all nSES groups. However, lower nSES was associated with a higher odds of undergoing surgery (low OR 1.25 [1.15-1.36] p < 0.001; middle OR 1.09 [1.01-1.18] p = 0.022; ref high). Living in an area with lower SES was associated with a worse disease specific mortality (low HR 1.24 [1.25, 1.44; ], middle 1.20 [1.1-1.29]: ref high). Specifically, there was a 9.26 month mean survival differences between the lowest (41.02 ± 0.47 months) and highest (50.28 ± 0.47 months) nSES groups. CONCLUSION: These results suggest area of residence may contribute to differences in surgical management and clinical outcomes among de novo MBC patients. Future studies should examine the contributions of patient characteristics and preferences within the context of surgeon recommendations.


Assuntos
Neoplasias da Mama , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Estudos de Coortes , Feminino , Humanos , Renda , Pessoa de Meia-Idade , Características de Residência , Classe Social , Adulto Jovem
8.
Neural Plast ; 2021: 4504363, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434229

RESUMO

Neuroinflammation-related amyloid-beta peptide (Aß) accumulation after cerebral ischemia/reperfusion (I/R) accounts for cerebral I/R injuries and poststroke dementia. Recently, pyroptosis, a proinflammatory cell death, has been identified as a crucial pathological link of cerebral I/R injuries. However, whether pyroptosis acts as a trigger of Aß accumulation after cerebral I/R has not yet been demonstrated. Blood-brain barrier (BBB) and glymphatic system mediated by aquaporin-4 (AQP-4) on astrocytic endfeet are important pathways for the clearance of Aß in the brain, and pyroptosis especially occurring in astrocytes after cerebral I/R potentially damages BBB integrity and glymphatic function and thus influences Aß clearance and brain homeostasis. In present study, the method of middle cerebral artery occlusion/reperfusion (MCAO/R) was used for building models of focal cerebral I/R injuries in rats. Then, we used lipopolysaccharide and glycine as the agonist and inhibitor of pyroptosis, respectively, Western blotting for detections of pyroptosis, AQP-4, and Aß 1-42 oligomers, laser confocal microscopy for observations of pyroptosis and Aß locations, and immunohistochemical stainings of SMI 71 (a specific marker for BBB integrity)/AQP-4 and Nissl staining for evaluating, respectively, BBB-glymphatic system and neuronal damage. The results showed that pyroptosis obviously promoted the loss of BBB integrity and AQP-4 polarization, brain edema, Aß accumulation, and the formation of Aß 1-42 oligomers and thus increased neuronal damage after cerebral I/R. However, glycine could inhibit cerebral I/R-induced pyroptosis by alleviating cytomembrane damage and downregulating expression levels of cleaved caspase-11/1, N-terminal gasdermin D, NLRP3 (nucleotide-binding domain, leucine-rich repeat containing protein 3), interleukin-6 (IL-6) and IL-1ß and markedly abate above pathological changes. Our study revealed that pyroptosis is a considerable factor causing toxic Aß accumulation, dysfunctional BBB-glymphatic system, and neurological deficits after cerebral I/R, suggesting that targeting pyroptosis is a potential strategy for the prevention of ischemic stroke sequelae including dementia.

9.
J Int Med Res ; 49(7): 3000605211032859, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34334002

RESUMO

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a benign, self-limiting inflammatory disorder of unknown etiology and pathogenesis. This report presents a rare case involving a man with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) hypermetabolism caused by KFD mimicking malignant lymphoma. The PET/CT maximum intensity projection showed multiple hypermetabolic lymphadenopathies and homogeneous FDG uptake in the bone marrow and spleen. Malignant lymphoma was initially suspected. The patient then underwent excision biopsy of one enlarged right cervical lymph node that was selected because it showed the highest FDG uptake in PET/CT, and examination of this biopsy specimen confirmed the diagnosis of KFD. PET/CT is useful for assessing the general condition of patients and can help to select lymph nodes for excision biopsy based on the highest FDG uptake. However, KFD can predispose to localized FDG uptake and limit the specificity of PET/CT by mimicking malignancy. Thus, positive results of PET/CT should be interpreted with caution.


Assuntos
Linfadenite Histiocítica Necrosante , Linfoma , Fluordesoxiglucose F18 , Linfadenite Histiocítica Necrosante/diagnóstico por imagem , Humanos , Linfonodos/diagnóstico por imagem , Linfoma/diagnóstico por imagem , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons
10.
Artigo em Inglês | MEDLINE | ID: mdl-34383180

RESUMO

PURPOSE: Black breast cancer patients have worse clinical outcomes than their White counterparts. There are few studies comparing clinical outcomes between Black male breast cancer (MBC) and female breast cancer (FBC) patients. The objective of this study is to examine differences in presentation, treatment, and mortality between Black MBC and FBC. METHODS: The National Cancer Database was queried for all Black MBC and FBC patients, ages 18-90, with hormone receptor-positive breast cancer diagnosed between 2010 and 2016. Hormone receptor positivity was defined as estrogen receptor-positive, progesterone-positive and HER 2-negative cancer. Sociodemographic and clinical variables were compared between MBC and FBC patients on bivariable analysis. After propensity score matching, overall survival was evaluated using the log-rank test and Cox proportional hazards. RESULTS: Compared to FBC patients, MBC patients had higher rates of metastatic disease (stage 4, MBC 4.4% vs. FBC 2.6%, p < 0.001), larger tumors (tumor size < 2 cm, MBC 32.1 vs. FBC 49.1%, p < 0.001) and a higher percentage of poorly differentiated tumors (grade 3, MBC 28.5% vs. FBC 21.4%, p < 0.001). MBC patients had lower rates of hormone therapy (MBC 66.4% vs. FBC 80.7%, p < 0.001) and neoadjuvant chemotherapy (MBC 5.8% vs. FBC 7.5%, p = 0.05) than FBC. On propensity score matched analysis, Black MBC patients had a higher overall mortality (p25 of 60 months vs. 74 months) compared to FBC patients (p = 0.0260). CONCLUSION: Among hormone receptor-positive Black MBC and FBC patients, there are sex-based disparities in stage, hormone therapy use and overall survival.

11.
Mol Ther ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34450253

RESUMO

The protein-coding ability of circular RNAs (circRNAs) has recently been a hot topic, but the expression and roles of protein-coding circRNAs in triple-negative breast cancer (TNBC) remain uncertain. By intersecting circRNA sequencing data from clinical samples and cell lines, we identified a circRNA, termed circ-EIF6, which predicted a poorer prognosis and correlated with clinicopathological characteristics in a cohort of TNBC patients. Functionally, we showed that circ-EIF6 promoted the proliferation and metastasis of TNBC cells in vitro and in vivo. Mechanistically, we found that circ-EIF6 contains a 675-nucleotide (nt) open reading frame (ORF) and that the -150-bp sequence from ATG functioned as an internal ribosome entry site (IRES), which is required for translation initiation in 5' cap-independent coding RNAs. circ-EIF6 encodes a novel peptide, termed EIF6-224 amino acid (aa), which is responsible for the oncogenic effects of circ-EIF6. The endogenous expression of EIF6-224aa was further examined in TNBC cells and tissues by specific antibody. Moreover, EIF6-224aa directly interacted with MYH9, an oncogene in breast cancer, and decreased MYH9 degradation by inhibiting the ubiquitin-proteasome pathway and subsequently activating the Wnt/beta-catenin pathway. Our study provided novel insights into the roles of protein-coding circRNAs and supported circ-EIF6/EIF6-224aa as a novel promising prognostic and therapeutic target for tailored therapy in TNBC patients.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34254268

RESUMO

OBJECTIVE: Breast cancer is the leading cause of cancer death among Hispanic women. Unfortunately, few studies disaggregate Hispanic patients by race to understand its implications on treatment and clinical outcomes such as mortality. The aim of this study is to examine surgical management and overall mortality among different subgroups of women who self-identify as Hispanic. METHODS: Hispanic female patients, ages 18-90, stages I-III, diagnosed with breast cancer between 2010 and 2015 from the National Cancer Data Base were identified. The study cohort was divided into three ethnoracial categories: (1) Hispanic White (HW), 2) Hispanic Black (HB), and 3) Hispanic Other (HO). Descriptive statistics and multivariate models were constructed to determine the relationship between sociodemographic factors, clinical variables, surgical management, and mortality when disaggregated by race. RESULTS: There were 56,675 Hispanic women who met the study criteria. Most where HW (n=50,599, 89.3%) and the rest were HB (n=1,334, 2.4%) and HO (n=4,742, 8.3%). There was no difference between the three groups on receipt of breast conservation therapy (P=0.12). HB (48.5%) and HO (46.6%) women were more likely to undergo reconstruction than those who identified as HW (38.7%) (P<0.001). Additionally, HB (38.3%) women were more likely to undergo tissue-based reconstruction than HW (29.0%) and HO women (30%) (P=0.0008). There was no difference between the groups in the utilization of contralateral prophylactic mastectomy (CPM) (P=0.078). On multivariable analysis, there was no difference in mortality between HB and HW patients (HR 1.18, 95%CI 0.92-1.51; Ref HW). However, HO women had a 24% relative risk reduction in mortality (HR 0.76, 95% CI 0.63-0.92; HW ref). CONCLUSION: Findings from this study suggest there are ethnoracial disparities in reconstruction utilization and mortality among Hispanic women. Future studies should examine how culture, language, healthcare access, and patient preferences contribute to these disparities.

13.
BMJ Open ; 11(6): e044313, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103313

RESUMO

OBJECTIVES: This study aimed to explore the diagnostic significance of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT for predicting the presence of epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC). DESIGN: A systematic review and meta-analysis. DATA SOURCES: The PubMed, EMBASE and Cochrane library databases were searched from the earliest available date to December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: The review included primary studies that compared the mean maximum of standard uptake value (SUVmax) between wild-type and mutant EGFR, and evaluated the diagnostic value of 18F-FDG PET/CT using SUVmax for prediction of EGFR status in patients with NSCLC. DATA EXTRACTION AND SYNTHESIS: The main analysis was to assess the sensitivity and specificity, the positive diagnostic likelihood ratio (DLR+) and DLR-, as well as the diagnostic OR (DOR) of SUVmax in prediction of EGFR mutations. Each data point of the summary receiver operator characteristic (SROC) graph was derived from a separate study. A random effects model was used for statistical analysis of the data, and then diagnostic performance for prediction was further assessed. RESULTS: Across 15 studies (3574 patients), the pooled sensitivity for 18F-FDG PET/CT was 0.70 (95% CI 0.60 to 0.79) with a pooled specificity of 0.59 (95% CI 0.52 to 0.66). The overall DLR+ was 1.74 (95% CI 1.49 to 2.03) and DLR- was 0.50 (95% CI 0.38 to 0.65). The pooled DOR was 3.50 (95% CI 2.37 to 5.17). The area under the SROC curve was 0.68 (95% CI 0.64 to 0.72). The likelihood ratio scatter plot based on average sensitivity and specificity was in the lower right quadrant. CONCLUSION: Meta-analysis results showed 18F-FDG PET/CT had low pooled sensitivity and specificity. The low DOR and the likelihood ratio scatter plot indicated that 18F-FDG PET/CT should be used with caution when predicting EGFR mutations in patients with NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade
15.
Front Oncol ; 11: 657094, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33869063

RESUMO

Long non-coding RNAs(lncRNAs) play an important role in cancer initiation and progression. However, hub lncRNAs involved in breast cancer still remain underexplored. In this study, integrated bioinformatics analysis was used to define LINC01977 as a key oncogenic driver in breast cancer. Subsequently, in vitro assays showed that LINC01977 could significantly promote breast cancer progression and chemoresistance to doxorubicin. To further investigate its biological mechanism, we performed dual-luciferase reporter assay, real-time PCR, RNA immunoprecipitation (RIP), and rescue assay. Our results indicated that LINC01977 may function as ceRNA to prevent GOLM1 gene from miRNA-mediated repression by sponging miR-212-3p. Overall, LINC01977 can serve as a novel prognostic indicator, and help develop more effective therapeutic approaches for breast cancer patients.

16.
HPB (Oxford) ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33903049

RESUMO

BACKGROUND: There is an associated lag in achieving competency for robotic pancreaticoduodenectomy (PD), resulting in a learning curve. We hypothesize that the reported learning curve can be mitigated through a comprehensive graduated training protocol. METHODS: All patients (n = 237) who underwent an open (n = 197, 83.1%) or robotic (n = 40, 16.9%) PD between 2015-2019 were identified at The Ohio State University. The learning curve for operative time and surgical failure (defined as conversion to open, blood transfusion, or Clavien-Dindo complication grade ≥3) was analyzed using a risk adjusted cumulative summation technique. RESULTS: After 10 cases, operative time plateaued to a mean of 468.3 ± 96.3 minutes for robotic PD versus a mean of 332.5 ± 103.9 minutes for open PD (P < 0.001). There was no further apparent learning curve over time relative to rates of operative time or surgical failure. After propensity score-matching, patients undergoing robotic PD had a similar incidence of major complications, grade B/C postoperative pancreatic fistula, and delayed gastric emptying versus patients undergoing open PD (all P > 0.05). CONCLUSION: Completion of a comprehensive procedure-specific robotic training protocol for PD mitigated the learning curve for this operative approach by shifting the curve into the training/simulation phase rather than the live operating phase. These data hold important implications for the future training and accreditation of surgeons embarking on robotic PD.

17.
Oncogene ; 40(15): 2756-2771, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33714984

RESUMO

Emerging evidence has demonstrated that circular RNAs (circRNAs) play critical roles in the development and progression of human cancer. However, the biological functions and underlying mechanisms of circRNAs in triple-negative breast cancer (TNBC) remain to be investigated. In our present study, we found that the novel circRNA circHIF1A was significantly overexpressed in breast cancer tissues and that it was associated with metastasis, poor prognosis, and the TNBC subtype. Gain- and loss-of-function experiments were conducted to investigate the biological roles of circHIF1A in TNBC. Overexpression of circHIF1A significantly promoted TNBC growth and metastasis in vitro and in vivo, while knockdown of circHIF1A exerted the opposite effects. Mechanistically, circHIF1A modulated the expression and translocation of NFIB through posttranscriptional and posttranslational modifications, resulting in the activation of the AKT/STAT3 signaling pathway and inhibition of P21. The RNA binding protein FUS could regulate the biogenesis of circHIF1A by interacting with the flanking intron, and FUS was transcriptionally regulated by NFIB, thus forming the circHIF1A/NFIB/FUS positive feedback loop. Moreover, circHIF1A could be packaged into exosomes and was upregulated in the plasma of breast cancer patients. Our findings indicated that circHIF1A played a critical role in the growth and metastasis of TNBC via a positive feedback loop and that circHIF1A could be a promising biomarker for breast cancer diagnosis and a potential therapeutic target for TNBC treatment.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fatores de Transcrição NFI/metabolismo , RNA Circular/metabolismo , Proteína FUS de Ligação a RNA/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Progressão da Doença , Humanos , Camundongos , Fatores de Transcrição NFI/biossíntese , Fatores de Transcrição NFI/genética , RNA Circular/genética , Proteína FUS de Ligação a RNA/genética , Transfecção , Translocação Genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
19.
Dev World Bioeth ; 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33719125

RESUMO

Human dignity is a crucial concept in contemporary ethical, political and legal studies. However, people have different, even opposite understandings of human dignity, which has caused lots of confusion in related discourses. The Confucian notion of human dignity provides an important perspective for reflecting various theories of human dignity. In Confucian ethics, the basis of human dignity is the moral potential that every human being naturally has. Moral potential grants everyone universal dignity, while the development of moral potential grants people acquired dignity. Since all human beings have moral potential to the same extent, everyone owns universal dignity equally. Different people develop their moral potential to different extents. One's acquired dignity is positively associated with the development of her moral potential. Universal dignity is a moral status but acquired dignity is not. To pursue acquired dignity is the moral demand of universal dignity and protects people's universal dignity. Confucian discussions on human dignity provide not only a way to justify the equality of human moral status, but also a way to justify the moral obligation of protecting and developing human nature, thereby constituting a reliable theoretical basis for coping with ethical issues caused by biomedical technologies today.

20.
Ann Surg Oncol ; 28(11): 6489-6497, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33586065

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NAC), an increasingly used method for breast cancer patients, has the potential to downstage patient tumors and thereby have an impact on surgical options for treatment of the breast and axilla. Previous studies have identified racial disparities in tumor heterogeneity, nodal recurrence, and NAC completion. This report compares the effects of NAC response among non-Hispanic white women and black women in relation to surgical treatment of the breast and axilla. METHODS: A retrospective review of 85,303 women with stages 1 to 3 breast cancer in the National Cancer Database who received NAC between 1 January 2010 and 31 December 2016 was conducted. Differences in sociodemographic and clinical variables between black patients and white patients with breast cancer were tested. RESULTS: The study identified 68,880 non-Hispanic white and 16,423 non-Hispanic black women who received NAC. The average age at diagnosis was 54.8 years for the white women versus 52.5 years for the black women. A higher proportion of black women had stage 3 disease, more poorly differentiated tumors, and triple-negative subtype. The black women had lower rates of complete pathologic response, more breast-conservation surgery, and higher rates of axillary lymph node dissection, but fewer sentinel lymph node biopsies. Axillary management for the women who were downstaged showed more use of axillary lymph node dissection for black women compared with sentinel lymph node biopsy. CONCLUSIONS: The black patients were younger at diagnosis, had more advanced disease, and were more likely to have breast-conservation surgery. De-escalating axillary surgery is being adopted increasingly but used disproportionately for white women.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Axila/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Fatores Raciais , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela
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