Triple‐negative breast cancer (TNBC) exhibits a higher level of glycolytic capacity and are commonly associated with an inflammatory microenvironment, but the regulatory mechanism and metabolic ...crosstalk between the tumor and tumor microenvironment (TME) are largely unresolved. Here, we show that glucose transporter 3 (GLUT3) is particularly elevated in TNBC and associated with metastatic progression and poor prognosis in breast cancer patients. Expression of GLUT3 is crucial for promoting the epithelial‐to‐mesenchymal transition and enhancing invasiveness and distant metastasis of TNBC cells. Notably, GLUT3 is correlated with inflammatory gene expressions and is associated with M1 tumor‐associated macrophages (TAMs), at least in part by C‐X‐C Motif Chemokine Ligand 8 (CXCL8). We found that expression of GLUT3 regulates CXCL8 production in TNBC cells. Secretion of CXCL8 participates in GLUT3‐overexpressing TNBC cells‐elicited activation of inflammatory TAMs, which further enhances GLUT3 expression and mobility of TNBC cells. Our findings demonstrate that aerobic glycolysis in TNBC not only promotes aggressiveness of tumor cells but also initiates a positive regulatory loop for enhancing tumor progression by modulating the inflammatory TME.
Glucose transporter 3 upregulation in triple‐negative breast cancer induces an inflammatory microenvironment by lactate/C‐X‐C Motif Chemokine Ligand 8‐mediated activation of M1 tumor‐associated macrophages, which promotes breast cancer progression and metastasis.
To compare the prognostic performance between different comorbidity assessments of survival in patients with operated lung cancer.
A total of 4508 lung cancer patients treated by surgery between 2003 ...and 2012 were identified through Taiwan's National Health Insurance Research Database. Information on pre-existing comorbidities prior to the cancer diagnosis was obtained and adapted to the Charlson comorbidity index, age-adjusted Charlson comorbidity index (ACCI) and Elixhauser comorbidity index scores. The influence on survival was analysed using a Cox proportional hazard model. The discriminatory ability of the comorbidity indices were evaluated using Akaike information criterion and Harrell's C-statistic.
The mean age of the study cohort was 64.95 ± 11.15 years, and 56.28% of the patients were male. The median follow-up time was 2.59 years, and the 3-year overall survival was 73.94%. Among these patients, 2134 (47.3%) patients received adjuvant therapy. The Charlson comorbidity index and ACCI scores correlated well with survival and higher scores were associated with an increased 3-year mortality risk (hazard ratio = 1.21, 95% confidence interval = 1.03-1.42 and hazard ratio = 1.43, 95% confidence interval = 1.08-1.90, respectively) in multivariate analysis. The ACCI scores provided better discriminatory ability with a smaller Akaike information criterion and greater Harrell's C-statistic for 3-year overall survival compared to the Charlson comorbidity index or Elixhauser comorbidity index scores.
The operated lung cancer patients with severe comorbidities were associated with worse survival. The ACCI appears to be a more appropriate prognostic indicator and should be considered for use in clinical practice.
Objectives
To assess the impact of age on the survival of patients with head and neck squamous cell carcinoma (HNSCC) using different statistical methods.
Design
A retrospective population‐based ...study.
Setting
Surveillance, Epidemiology, and End Results database.
Subjects and methods
A total of 28 639 patients with newly diagnosed HNSCC were enrolled between 1 January 2007 and 31 December 2013. The effect of age on 5‐year disease‐specific survival was calculated using a Kaplan‐Meier method and compared using log‐rank tests. A Cox proportional hazards model was used for a multivariate analysis. A classification and regression tree (CART) analysis that partitioned patients with significantly different Kaplan‐Meier curves was introduced to identify the important cancer‐related parameters influencing survival.
Results
Uni‐ and multivariate analyses indicated that patients who were older than 60 years had poorer 5‐year disease‐specific survival regardless of tumour subsite and tumor‐node‐metastasis (TNM) stage. However, the CART analysis determined that age played only a minor role in survival after comparing with other prognosticators. The relative importance of age using the Gini index was as follows: 3.21% for oral cancer, 8.32% for oropharyngeal cancer, 2.56% for hypopharyngeal cancer and 16.51% for laryngeal cancer.
Conclusions
Different to traditional statistical methods, the CART analysis which was used to identify homogeneous populations revealed that the impact of age varied for different patient groups according to the presence or absence of other prognosticators. This important information could help to guide our clinical decisions and future researches.
Obesity is a well‐known risk factor for breast cancer formation and is associated with elevated mortality and a poor prognosis. An obesity‐mediated inflammatory microenvironment is conducive to the ...malignant progression of tumors. However, the detailed molecular mechanism is still needed to be clarified. Herein, we identified that breast cancer cells from mice with diet‐induced obesity exhibited increased growth, invasiveness, and stemness capacities. A transcriptome analysis revealed that expressions of interleukin 33 (IL33) signaling pathway‐related genes were elevated in obesity‐associated breast cancer cells. Importantly, IL33 expression was significantly associated with the yes‐associated protein (YAP) signature, and IL33 was transcriptionally regulated by YAP. Suppression of IL33 reduced tumor migration and invasion, while the addition of IL33 activated nuclear factor (NF)‐κB signaling and revived tumor mobility in YAP‐silenced cells. Furthermore, suppression of YAP attenuated IL33 expression which was accompanied by relief of obesity‐mediated immunosuppression. Clinical analyses showed that IL33 expression was markedly associated with macrophage and regulatory T cell infiltration. These findings reveal a crucial role of the YAP/IL33 axis in promoting aggressiveness and immunosuppression of obesity‐associated breast cancer progression.
Aim
To examine the mediating effect of sleep quality on the relationship between lower urinary tract symptoms and health‐related quality of life in women with type‐II diabetes.
Design
A ...cross‐sectional study.
Methods
A study questionnaire comprising three valid instruments was used to obtain data about lower urinary tract symptoms, sleep quality and physical and mental component summary health‐related quality of life between July 2017 and December 2018 (n = 343). Pearson's correlation coefficients were estimated initially to examine the relationships between the three variables. Multiple regression models were tested using a regression‐based approach Hayes PROCESS macro for SPSS to examine the significance of proposed mediation effects.
Results
Most participants experienced at least one urinary symptom (n = 268, 78.1%). The total number of types of lower urinary tract symptoms experienced by participants was significantly inversely correlated with physical and mental component summary health‐related quality of life, and sleep quality. Participants' sleep quality was significantly correlated with physical and mental component summary health‐related quality of life. The relationships of lower urinary tract symptoms with physical and mental component summary health‐related quality of life were, respectively, fully and partially mediated by sleep quality.
Conclusion
Sleep quality played a mediating role on the relationship between lower urinary tract symptoms and health‐related quality of life. Our findings could lead to improvements of diabetes care in nursing and healthcare practices.
Impact
Understanding the role of sleep quality in the adverse effects of lower urinary tract symptoms on health‐related quality of life contributes to the development and delivery of appropriate strategies to promote optimal health‐related quality of life. We recommended including assessments of lower urinary tract symptoms, sleep and health‐related quality of life in routine diabetes management. Nurses and healthcare professionals should concurrently reduce lower urinary tract symptoms and improve sleep to achieve this population's optimal health‐related quality of life.
Patients or public contribution
We recruited a sample of older women with type‐II diabetes at the endocrinology and metabolism outpatient departments of two hospitals. Study participants provided responses on the study questionnaires. The two hospitals provided needed supports (e.g., height/weight scales, suitable places for interview) during the data collection process.
Background
This study investigated the effects of adjuvant radiotherapy on outcomes in early‐stage major salivary gland cancers.
Methods
A total of 655 patients were identified, including 355 (54.2%) ...received adjuvant radiotherapy and 300 (45.8%) had surgery alone. The effect of adjuvant radiotherapy on 5‐year locoregional recurrence and disease‐specific survival (DSS) was calculated using the Kaplan–Meier method, Wilcoxon rank sum test, and Cox proportional hazards model.
Results
There were no significant differences in locoregional recurrence and DSS between patients receiving adjuvant radiotherapy and those not in both univariate and multivariable analysis. Although patients with positive margin status had a higher locoregional recurrence and those with moderate/poor differentiation had a worse DSS, stratified analysis still indicated there were no protective effects from the use of adjuvant radiotherapy.
Conclusions
The use of adjuvant radiation therapy was not associated with improved locoregional recurrence and DSS, even for those with high‐risk histopathological factors.
Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) patients. This study aims to determine whether combining radiotherapy with sorafenib administration increases its ...efficacy. The study cohort included 4763 patients with diagnosed advanced HCC who received sorafenib between January 2012 and December 2015, as reported in medical records in the Taiwan Cancer Registry database. The effect of sorafenib with or without radiotherapy on survival was calculated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Patients receiving sorafenib plus radiotherapy had greater 1-year survival than did those receiving sorafenib alone (P < 0.001). Uni- and multivariate analyses also showed that radiotherapy increased survival after adjusting for confounders (adjusted HR 0.57; 95% CI 0.51-0.63). Further stratified analysis according to the timing of radiotherapy relative to sorafenib treatment revealed that patients who underwent radiotherapy after sorafenib had greater 1-year survival than did those undergoing radiotherapy within sorafenib use or sorafenib alone (adjusted HR 0.39; 95% CI 0.27-0.54). Combined treatment with sorafenib and radiotherapy results in greater HCC patient survival and should be considered an option for treating this challenging disease.
Background
The purpose of this study was to determine failure patterns and clinicopathologic prognostic factors in patients with locally advanced buccal cancer after postoperative intensity‐modulated ...radiotherapy (IMRT).
Methods
Eighty‐two patients with locally advanced (American Joint Committee on Cancer AJCC stage III/IV) buccal cancer who underwent surgery followed by postoperative IMRT between January 2007 and October 2012 were retrospectively analyzed.
Results
Eighteen patients had local recurrences as the first recurrent site and 11 had supramandibular notch recurrences; the majority of recurrences were classified as marginal failures. The median time from the first local or regional recurrence to death was 5.9 months. In multivariate analyses of survivals, the initial masticator space involvement was the most important prognostic factor. Masticator space involvement, N classification, and maxillectomy were the significant prognostic predictors for supramandibular notch recurrences.
Conclusion
Postoperative IMRT for buccal cancer should not include the surgical beds alone, rather, it should be based on the potential patterns of spread.
To evaluate the potential benefit of HyperArc (HA) fractionated stereotactic radiotherapy (FSRT) for the benign brain lesion. Sixteen patients with a single deep-seated, centrally located benign ...brain lesion treated by CyberKnife (CK, G4 cone-based model) were enrolled. Treatment plans for HA with two different optimization algorithms (SRS NTO and ALDO) and coplanar RapidArc (RA) were generated for each patient to meet the corresponding treatment plan criteria. These four FSRT treatment plans were divided into two groups-the homogeneous delivery group (HA-SRS NTO and coplanar RA) and the inhomogeneous delivery group (HA-ALDO and cone-based CK)-to compare for dosimetric outcomes. For homogeneous delivery, the brain V5, V12, and V24 and the mean brainstem dose were significantly lower with the HA-SRS NTO plans than with the coplanar RA plans. The conformity index, high and intermediate dose spillage, and gradient radius were significantly better with the HA-SRS NTO plans than with the coplanar RA plans. For inhomogeneous delivery, the HA-ALDO exhibited superior PTV coverage levels to the cone-based CK plans. Almost all the doses delivered to organs at risk and dose distribution metrics were significantly better with the HA-ALDO plans than with the cone-based CK plans. Good dosimetric distribution makes HA an attractive FSRT technique for the treatment of benign brain lesions.
Cell adhesion affects carcinogenesis, tumor progression, and metastasis. We datamined a published transcriptome (GSE12452) of nasopharyngeal carcinoma (NPC) and identified SSX2IP as a significantly ...upregulated gene in NPC carcinogenesis among genes associated with cell adhesion (GO:0007155). Consequently, we assessed SSX2IP protein expression and its prognostic significance in 124 patients with NPC using immunohistochemistry and the H‐score method. The status of SSX2IP immunoexpression correlated with clinical and pathological characteristics, as well as oncological outcomes. High levels of SSX2IP expression were significantly associated with more advanced primary tumor and TNM stages. Kaplan–Meier and log‐rank analyses revealed that high levels of SSX2IP expression, and advanced tumor stage and lymph node metastasis were significantly associated with lower rates of local recurrence‐free survival (LRFS), distant metastasis‐free survival (DMeFS), and disease‐specific (DSS) survival. Multivariate analysis showed that high levels of SSX2IP expression significantly predicted DSS (hazard ratio HR, 4.290; 95% confidence interval CI, 2.271–8.102; p < 0.001), DMeFS (HR, 4.159’ 95% CI, 2.072–8.345; p < 0.001), and LRFS (HR, 3.007’ 95% CI,: 1.418–6.378; p = 0.004). We associated high levels of SSX2IP immunoexpression with aggressive pathological features and worse oncological outcomes, suggesting its potential therapeutic value for patients with NPC.
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