Autophagy, as a special programmed cell death, is a critical degradative process that eliminates intracellular abnormal proteins or damage organelles to balance cell energy and favor cell metabolism ...with autophagy-related (ATG) proteins. Autophagy activation is being increasingly recognized as an essential hallmark in tumorigenesis through influencing the metabolism of stromal cells in the tumor microenvironment (TME) which comprises of tumor cells, cancer-associated fibroblasts (CAFs), cancer-associated endothelial cells (CAEs), immune cells and adipocytes. Tumor cells can reuse autophagy-involved recycling to maintain mitochondrial function and energy supply to meet the metabolic demand of their growth and proliferation. However, the mechanism through which autophagy can promote a crosstalk between tumor and stroma cells is not clear. Reprogramed metabolism is one of the main characteristics of TME leading to higher adaptability of tumor cells with diverse mechanisms. The activation of autophagy has expanded our understanding on the interaction between tumor metabolism and TME. The aim of this review is to report recent advances on the metabolic cross-talk between stromal cells and solid tumor cells induced by autophagy in TME and revealed potential therapeutic targets.
Breast cancer is one of the most common female malignant cancers. Biorhythm disorder largely increases the risk of breast cancer. We aimed to investigate the biological functions and molecular ...mechanisms of circadian gene TIMELESS circadian regulator (TIM) in estrogen receptor (ER)-positive breast cancer and provide a new therapeutic target for breast cancer patients. Here, we explored that the expression of TIM was elevated in breast cancer, and high expression of TIM in cancer tissues was associated with poor prognosis, especially in the ER-positive breast cancer patients. In addition, we found that TIM promoted cell proliferation and enhanced mitochondrial respiration. TIM interacted with specificity protein 1 (Sp1) which contributes to upregulate the expression of alkaline ceramidase 2 (ACER2). Moreover, ACER2 is responsible for TIM-mediated promotive effects of cell growth and mitochondrial respiration. Collectively, our research unveiled a novel function of TIM in sphingolipid metabolism through interaction with Sp1. It provides a new theoretical explanation for the pathogenesis of breast cancer, and targeting TIM may serve as a potential therapeutic target for ER-positive breast cancer.
We aimed to explore whether the expression of serum miR-222-3p might contribute to early prediction of therapeutic response, clinical outcomes, and adverse events for HER2-positive breast cancer ...patients receiving neoadjuvant therapy (NAT).
A total of 65 HER2-positive breast cancer patients receiving NAT were analyzed. The concentration of serum miR-222-3p was detected by quantitative real-time PCR. Logistic regression analysis was used to identify the association of serum miR-222-3p with pathological complete response (pCR). The relationship of serum miR-222-3p with disease-free survival (DFS) and overall survival (OS) was examined via log-rank test and Cox proportional hazards analysis. The ordered logistic regression was applied to evaluate the association between serum miR-222-3p and adverse events.
The miR-222-3p low group was more likely to achieve pCR odds ratio (OR) = 0.258,
= 0.043. The interaction between miR-222-3p and presenting Ki67 level was also detected for pCR (OR = 49.230,
= 0.025). The miR-222-3p low group was correlated with superior DFS (
= 0.029) and OS (
= 0.0037). The expression of serum miR-222-3p was the independent protective factor for trastuzumab-induced cardiotoxicity (
< 0.05) and anemia (
= 0.013).
Serum miR-222-3p is the potential factor to predict pCR, survival benefit and trastuzumab-induced cardiotoxicity for HER2-positive breast cancer patients receiving NAT.
This paper aims to investigate the seismic performance of a novel type of steel–concrete hybrid supporting structure consisting of reinforced concrete (RC) tubular columns, steel solid web girder ...platform, and A-shaped steel frames. It is typically used to house air-cooled condensers (ACC) in thermal power plants (TPPs). First, the finite-element (FE) model was implemented in ABAQUS and the simulation approaches were validated by pseudo-dynamic test results of a scaled steel-concrete hybrid supporting structure. Then, the elasto-plastic time-history analysis of the steel solid web girder-RC tubular column hybrid structure was conducted. The El Centro (NS) record was scaled to peak ground acceleration (PGA) of 0.07, 0.20, 0.40 and 0.62 g to reflect the frequent, basic, rare, and very rare earthquakes. The dynamic characteristics, base shear force, lateral deformation performance, stiffness deterioration, and damage evolution characteristics were analyzed. The numerical results showed that the first vibration mode of this hybrid structure is torsion, due to its small torsional stiffness and the nonuniform distribution characteristics of stiffness and mass in the vertical direction; the lateral deformation shape is shear mode; and the damage mainly occurred on the RC tubular columns, while the steel components did not yield under severe earthquakes. In general, the overall seismic performance of the steel solid web girder-RC tubular column hybrid structural system could meet the seismic design requirements with respect to the high-intensity earthquakes.
Linc00665 is a novel long non-coding RNA that can promote the progression of breast cancer, but its value in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer has not been ...reported. We aim to analyze the correlation between Linc00665 expression and pathological complete response (pCR) in breast cancer patients.
The present study examined the predictive role of Linc00665 expression in pCR after NAC using both univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to evaluate the performance of Linc00665 in predicting pCR. The Kyoto Encyclopedia of Gene and Genome (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) were also conducted to determine the biological processes where Linc00665 may participate in.
The present study study totally enrolled 102 breast cancer patients. The univariate analysis showed that Linc00665 level, human epidermal growth factor receptor 2 (HER2) status and hormone receptor (HR) status were correlated with pCR. The multivariate analysis showed that Linc00665 expression was an independent predictor of pCR (OR = 0.351, 95% CI: 0.125-0.936, P = 0.040), especially in patients with HR-positive/HER2-negative subtype (OR = 0.272, 95% CI: 0.104-0.664, P = 0.005). The KEGG analysis indicated that Linc00665 may be involved in drug metabolism. The GSEA analysis revealed that Linc00665 is correlated to DNA damage repair.
Linc00665 may be a potential novel predictive biomarker for breast cancer in NAC, especially for HR-positive/HER2-negative patients.
Background:
EPIC1 is an oncogenic long non-coding ribonucleic acid (RNA) that promotes cell growth and cell-cycle progression and inhibits apoptosis in several cancer cell lines. However, clinical ...studies on EPIC1 in breast cancer, specifically in the neoadjuvant setting, are relatively few.
Methods:
Patients treated with weekly paclitaxel–cisplatin-based neoadjuvant chemotherapy after core-needle biopsy were included in the study. Real-time quantitative polymerase chain reaction assays were performed to detect EPIC1 expression.
Results:
Among all patients included in this study (n = 111), higher EPIC1 expression was associated with estrogen receptor negativity, human epidermal growth factor receptor 2 positivity, higher Ki67 index, and higher histologic grade. Multivariate analysis suggested that EPIC1 expression was an independent predictive factor for pathological complete response, with a significant interaction between EPIC1 expression and age. The Kaplan–Meier Plotter dataset suggested that the EPIC1 high-expression group showed a worse 10-year distant metastasis-free survival and post-progression survival when compared with the EPIC1 low-expression group. The Cancer Genome Atlas dataset suggested that the overall survival in the EPIC1 high-expression group was inferior to that in the EPIC1 low-expression group, specifically in hormone receptor (HorR)-positive patients and patients aged <50 years. Pathway analysis revealed the top pathways that indicated the potential mechanisms of EPIC1 in chemoresistance, including the daunorubicin and doxorubicin metabolic processes.
Conclusions:
Our study suggests that EPIC1 may be a promising biomarker for both neoadjuvant chemosensitivity and long-term clinical outcomes in breast cancer, specifically in the HorR-positive premenopausal subgroup. It may also help identify candidate responders and determine treatment strategies.
Background
Distant metastasis is a sign of poor prognosis for cancer patients. Extrahepatic liver cancer metastases commonly spread to the lung. Remodelling of the metastatic microenvironment is ...essential for tumour metastasis. Neutrophil‐associated metastatic microenvironment contributes to the early metastatic colonisation of cancer cells in the lung.
Method
The lung metastasis models were constructed via treated cancer cells by tail vein injection into mice. And samples of lung were harvested at the indicated time to analyze tumor growth and immune cells in the microenvironment. Tumors and lung metastasis specimens were obtained via surgical operations for research purposes. Neutrophils were obtained from peripheral blood of patients with liver cancer or healthy donors (HD).
Results
Hepatocellular carcinoma cells reduce the secretion of histidine‐rich glycoprotein (HRG), regulate the recruitment and activation of neutrophils in the metastatic microenvironment and promote the production of neutrophil extracellular traps (NETs), thereby promoting liver cancer lung metastasis. HRG binds to FCγR1 on the neutrophil membrane while inhibiting PI3K and NF‐κB activation, thereby reducing IL‐8 secretion to reduce neutrophil recruitment. Meanwhile, HRG inhibited IL8‐MAPK and NF‐κB pathway activation and ROS production, resulting in reduced NETs formation.
Conclusions
Our study reveals that liver cancer regulates neutrophil recruitment and NETs formation in the metastatic microenvironment by reducing HRG secretion, thereby promoting tumour lung metastasis. The results of this study will contribute to the development of possible strategies for treating metastases.
Decreased secretion of HRG by liver cancer.
HRG suppresses NETs production from neutrophils.
NETs promote liver cancer lung metastasis.
This paper presents the numerical investigation on the seismic performance of a steel–concrete hybrid structure consisting of reinforced concrete (RC) tubular columns and steel braced truss with ...A-shaped steel frames, which is a novel supporting structural system to house air-cooled condensers (ACC) in large-capacity thermal power plants (TPPs). First, the finite element (FE) modeling approach for this hybrid structure using the software ABAQUS was validated by a range of pseudo-dynamic tests (PDTs) performed on a 1/8-scaled sub-structure. The failure process, lateral displacement responses, changing rules of dynamic characteristic parameters and lateral stiffness with increase of peak ground acceleration (PGA) were presented here. Then, nonlinear time-history analysis of the prototype structure was carried out. The dynamic characteristics, base shear force, lateral deformation capacity, stiffness deterioration and damage characteristics were investigated. Despite the structural complexity and irregularity, both experimental and numerical results indicate that the overall seismic performance of this steel–concrete hybrid supporting structure meets the seismic design requirements with respect to the high-intensity earthquakes.
This paper aims to provide an experimental support on seismic performance evaluation of the steel braced truss-RC (reinforced concrete) column hybrid structure, which could be applied as the ...air-cooled supporting structural system in large-capacity thermal power plants located in strong earthquake prone regions. A series of pseudo-dynamic tests (PDTs) and quasi-static tests (QSTs) were performed on a 1/8-scaled sub-structure. The dynamic characteristics, lateral deformation patterns, deterioration behavior, hysteretic behavior and failure mechanisms were investigated. Test results showed that the first vibration mode is torsion, which is caused by the small torsional stiffness of this kind of hybrid structure. The lateral deformation shape is shear mode, and the drift ratio of the structure above the corbel is significantly less than that of the column below the corbel. Earthquake energy is mainly dissipated by the RC pipe columns where cracks mainly occurred at the bottom of column and lower part of corbel. The failure mechanisms were identified indicating that the steel braces improved the global stiffness and modified the load transfer mechanism. This study affirms that the steel braced truss-RC column hybrid structure has the sufficient ductility and good energy dissipation capacity to satisfy the design requirements in high seismic regions.
Hypoxia-induced chemotherapy resistance is the main hindrance for solid tumor treatment. Hypoxia inducible factor-1α (HIF1α), an adaptive gene of hypoxia condition, played an important role in ...affecting chemotherapy sensitivity for many cancer types and various therapeutic regimens. This study focused on the impact of HIF1α on predicting response and survival of taxane-based neoadjuvant therapy (NAT) for breast cancer (BC) patients and the concrete mechanism that HIF1α mediated paclitaxel chemo-insensitivity. We evaluated HIF1α expression immunohistochemically from biopsies of 108 BC patients receiving paclitaxel–cisplatin NAT. Univariate and multivariate logistic regression analysis revealed that high HIF1α expression led to lower rate of pathological complete response (pCR) and worse prognosis. Analysis of GEO datasets also indicated negative association between HIF1α expression and response of taxane-based NAT in BC patients. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of differential expression genes (DEGs) in different HIF1α expression groups from TCGA database showed that HIF1α participated in interleukin 17 (IL-17) signaling pathway. Correlation analysis suggested that HIF1α was positively related to the IL-17 pathway. CXC motif chemokine ligand 10 (CXCL10) was the only DEG in the IL-17 pathway inversely relating to NAT response. Experiments
in vitro
verified that HIF1α/IL-17 pathway influences paclitaxel sensitivity to BC cells. Correlation analysis between HIF1α/IL-17A/CXCL10 and infiltration of immune cells in BC uncovered that high expression of all the above three genes were positively correlated to neutrophil infiltration in BC. Collectively, our findings shed novel insight into the mechanism of chemotherapy resistance and implied that HIF1α inhibitor may be a promising drug combined with traditional chemotherapeutic drug to increase the chemotherapy efficacy.
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