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ACSL3 regulates breast cancer progression via lipid metabolism reprogramming and the YES1/YAP axis
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作者 Shirong Tan Xiangyu Sun +5 位作者 Haoran Dong Mozhi Wang Litong Yao Mengshen Wang Ling Xu Yingying Xu 《Cancer Biology & Medicine》 SCIE CAS CSCD 2024年第7期606-635,共30页
Objective:Mitochondrial fatty acid oxidation is a metabolic pathway whose dysregulation is recognized as a critical factor in various cancers,because it sustains cancer cell survival,proliferation,and metastasis.The a... Objective:Mitochondrial fatty acid oxidation is a metabolic pathway whose dysregulation is recognized as a critical factor in various cancers,because it sustains cancer cell survival,proliferation,and metastasis.The acyl-Co A synthetase long-chain(ACSL)family is known to activate long-chain fatty acids,yet the specific role of ACSL3 in breast cancer has not been determined.Methods:We assessed the prognostic value of ACSL3 in breast cancer by using data from tumor samples.Gain-of-function and lossof-function assays were also conducted to determine the roles and downstream regulatory mechanisms of ACSL3 in vitro and in vivo.Results:ACSL3 expression was notably downregulated in breast cancer tissues compared with normal tissues,and this phenotype correlated with improved survival outcomes.Functional experiments revealed that ACSL3 knockdown in breast cancer cells promoted cell proliferation,migration,and epithelial±mesenchymal transition.Mechanistically,ACSL3 was found to inhibitβ-oxidation and the formation of associated byproducts,thereby suppressing malignant behavior in breast cancer.Importantly,ACSL3 was found to interact with YES proto-oncogene 1,a member of the Src family of tyrosine kinases,and to suppress its activation through phosphorylation at Tyr419.The decrease in activated YES1 consequently inhibited YAP1 nuclear colocalization and transcriptional complex formation,and the expression of its downstream genes in breast cancer cell nuclei.Conclusions:ACSL3 suppresses breast cancer progression by impeding lipid metabolism reprogramming,and inhibiting malignant behaviors through phospho-YES1 mediated inhibition of YAP1 and its downstream pathways.These findings suggest that ACSL3 may serve as a potential biomarker and target for comprehensive therapeutic strategies for breast cancer. 展开更多
关键词 breast cancer lipid metabolism ACSL3 YAP METASTASIS
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RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer 被引量:2
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作者 Yi-Qun Li Fang-Zhou Sun +6 位作者 Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma 《Military Medical Research》 SCIE CAS CSCD 2024年第1期34-49,共16页
Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,Br... Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM. 展开更多
关键词 RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) breast cancer
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Targeting metabolism in breast cancer: How far we can go? 被引量:2
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作者 Jing-Pei Long Xiao-Na Li Feng Zhang 《World Journal of Clinical Oncology》 CAS 2016年第1期122-130,共9页
Adjuvant therapies for breast cancer have achieved great success in recent years and early breast cancer is now a curable or chronic disease. Targeted therapies, including endocrine therapy and human epidermal growth ... Adjuvant therapies for breast cancer have achieved great success in recent years and early breast cancer is now a curable or chronic disease. Targeted therapies, including endocrine therapy and human epidermal growth factor receptor-2 targeted therapy, marked a new era of breast cancer treatment. However, except for chemotherapy, an efficient drug treatment to improve the overall survival of breast cancer patients is still lacking for triple negative breast cancer. Furthermore, a certain proportion of breast cancer patients present with resistance to drug therapy, making it much more difficult to control the deterioration of the disease. Recently, altered energy metabolism has become one of the hallmarks of cancer, including breast cancer, and it may be linked to drug resistance. Targeting cellular metabolism is becoming a promising strategy to overcome drug resistance in cancer therapy. This review discusses metabolic reprogramming in breast cancer and the possible complex mechanism of modulation. We also summarize the recent advances in metabolic therapy targeted glycolysis, glutaminolysis and fatty acids synthesis in breast cancer. 展开更多
关键词 breast cancer TARGETED therapy metabolism Drug resistance CHEMOTHERAPY
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Advance in metabolism and target therapy in breast cancer stem cells 被引量:3
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作者 Xu Gao Qiong-Zhu Dong 《World Journal of Stem Cells》 SCIE 2020年第11期1295-1306,共12页
Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell properties.Recent studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumo... Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell properties.Recent studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumor relapse is thought to be caused by the presence of these cells.CSC-targeted therapies have also been proposed to overcome therapeutic resistance in breast cancer after the traditional therapies.Additionally,the metabolic properties of cancer cells differ markedly from those of normal cells.The efficacy of metabolic targeted therapy has been shown to enhance anti-cancer treatment or overcome therapeutic resistance of breast cancer cells.Metabolic targeting of breast CSCs(BCSCs)may be a very effective strategy for anti-cancer treatment of breast cancer cells.Thus,in this review,we focus on discussing the studies involving metabolism and targeted therapy in BCSCs. 展开更多
关键词 breast cancer Cancer stem cells metabolism Oxidative phosphorylation Tumor relapse Target therapy
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Leptin influences estrogen metabolism and increases DNA adduct formation in breast cancer cells
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作者 Samia Shouman Mohamed Wagih Marwa Kamel 《Cancer Biology & Medicine》 SCIE CAS CSCD 2016年第4期505-513,共9页
Objective: The elevated incidence of obesity has been paralleled with higher risks of breast cancer. High adiposity increases leptin secretion from adipose tissue, which in turn increases cancer cell proliferation. Th... Objective: The elevated incidence of obesity has been paralleled with higher risks of breast cancer. High adiposity increases leptin secretion from adipose tissue, which in turn increases cancer cell proliferation. The interplay between leptin and estrogen is one of the mechanisms through which leptin influences breast carcinogenesis. An unbalanced estrogen metabolism increases the formations of catechol estrogen quinones, DNA adducts, and cancer mutations. This study aims to investigate the effect of leptin on some estrogen metabolic enzymes and DNA adduction in breast cancer cells.Methods: High performance liquid chromatography(HPLC) was performed to analyze the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine. Reporter gene assay, real time reverse transcription polymerase chain reaction(real time RT-PCR), and Western blot were used to assess the expression of estrogen metabolizing genes and enzymes: Cytochrome P-4501B1(CYP1B1), Nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase1(NQO1), and Catechol-O-methyl transferase(COMT).Results: Leptin significantly increased the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine.Furthermore, leptin significantly upregulated CYP1B1 promoter activity and protein expression. The luciferase promoter activities of NQO1 and m RNA levels were significantly reduced. Moreover, leptin greatly reduced the reporter activities of the COMT-P1 and COMT-P2 promoters and diminished the protein expression of COMT.Conclusions: Leptin increases DNA adduct levels in breast cancer cells partly by affecting key genes and enzymes involved in estrogen metabolism. Thus, increased focus should be directed toward leptin and its effects on the estrogen metabolic pathway as an effective approach against breast cancer. 展开更多
关键词 breast cancer LEPTIN estrogen metabolism DNA adducts
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Manifestation of Key Molecular Genetic Markers in Pharmacocorrection of Endogenous Iron Metabolism in MCF-7 and MCF-7/DDP Human Breast Cancer Cells
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作者 Vasyl’ Chekhun Natalia Lukianova +3 位作者 Dmytro Demash Tetiana Borikun Svyatoslav Chekhun Yulia Shvets 《CellBio》 2013年第4期217-227,共11页
Effects of the nanocomposite and its components (magnetic fluid, cisplatin) on the level of endogenous iron exchange and the key links of genetic and epigenetic regulation of apoptotic program of sensitive and resista... Effects of the nanocomposite and its components (magnetic fluid, cisplatin) on the level of endogenous iron exchange and the key links of genetic and epigenetic regulation of apoptotic program of sensitive and resistant MCF-7 cells were examined. We showed genetic and epigenetic mechanisms of action of nanocomposite of magnetic fluid and cisplatin. Nanocomposite caused elevation of number of cells in apoptosis in sensitive and especially resistant MCF-7 cells compared to cisplatin alone. It was proved that impact of nanocomposite on MCF-7/S and MCF-7/DDP cells caused more significant changes in expression of apoptosis regulators p53, Bcl-2 and Bax. We also suggested that changes in endogenous iron homeostasis and activation of free radical processes caused significant impact on apoptosis. Those changes included changes in methylation and expression of transferrin, its receptors, ferritin heavy and light chains (predominantly in resistant cell line), which caused activation of free radical synthesis and development of oxidative stress. We also showed that nanocomposite impact resulted into significant changes in expression of miRNA-34a and miRNA-200b, which regulated apoptosis, cell adhesion, invasion and activity of ferritin heavy chains gene. Thus, use of nanocomposite containing cisplatin and ferromagnetic as exogenous source of Fe ions caused changes of endogenous iron levels in sensitive and resistant cells allowing to increase specific activity of cytostatics and overcome factors, which promoted MDR development. Pharmacocorrection of endogenous iron metabolism allowed increasing antitumor activity of cisplatin and overcoming drug resistance. 展开更多
关键词 NANOCOMPOSITE Iron metabolism Apoptosis ROS Drug Resistance breast Cancer Cells
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Glucose Metabolism in Breast Cancer and its Implication in Cancer Therapy
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作者 Ning Li Wen Tan +4 位作者 Jing Li Ping Li Simon Lee Yitao Wang Yuewen Gong 《International Journal of Clinical Medicine》 2011年第2期110-128,共19页
It is well known that malignant cells have accelerated glucose uptake and metabolism in order to maintain their fast proliferation rates. With the increased influx of glucose into cancer cells, glycolysis is facilitat... It is well known that malignant cells have accelerated glucose uptake and metabolism in order to maintain their fast proliferation rates. With the increased influx of glucose into cancer cells, glycolysis is facilitated through a coordinated regulation of metabolic enzymes and pyruvate consumption. Shiftting from mitochondrial oxidative phosphorylation to glycolysis and other pathways such as pentose phosphate pathway (PPP) and de novo fatty acid synthesis in the breast tumor provides not only energy but also the materials needed for cell proliferation. Glucose augmentation in tumor cells can be due to the elevated level of glucose transporter (GLUT) proteins, such as the over-expression of GLUT1 and expression of GLUT5 in breast cancers. Moreover, other factors such as hypoxia-inducible factor-1 (HIF-1), estrogen and growth factors are important modulators of glucose metabolism in the progression of breast carcinomas. Therapies targeting at the glycolytic pathway, fatty acid synthesis and GLUTs expression are currently being investigated. Restoring tumor cells to its normal glucose metabolic state would endow tumor specific and accessible treatment that targets glucose metabolism. 展开更多
关键词 breast Cancer GLUCOSE Transport GLYCOLYSIS FATTY Acid Synthesis MITOCHONDRIAL metabolism
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Synchronous multiple primary malignant neoplasms in breast,kidney,and bilateral thyroid:A case report
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作者 Miao-Miao Jia Bin Yang +3 位作者 Chao Ding Ya-Rong Yao Jun Guo Hai-Bo Yang 《World Journal of Clinical Cases》 SCIE 2023年第7期1513-1520,共8页
BACKGROUND Multiple primary malignant neoplasms(MPMNs)are rare,while synchronous MPMNs(SMPMNs)are even less common.Owing to the progression of medical technology and the extension of life expectancy,its incidence is g... BACKGROUND Multiple primary malignant neoplasms(MPMNs)are rare,while synchronous MPMNs(SMPMNs)are even less common.Owing to the progression of medical technology and the extension of life expectancy,its incidence is gradually increasing.CASE SUMMARY Although reports of breast and thyroid dual cancers are common,cases of an additional diagnosis of kidney primary cancer within the same individual are rare.CONCLUSION We present a case of simultaneous MPMN of three endocrine organs,reviewing the relevant literature to enhance our understanding of SMPMNs while emphasizing the increasingly important need for accurate diagnosis and multidisciplinary management whenever this challenging situation arises. 展开更多
关键词 SYNCHRONOUS Multiple primary malignant neoplasms breast cancer Kidney cancer Bilateral thyroid cancer Tumor neoplasm Case report
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Violence against Women with Breast Neoplasms
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作者 Bianca Maria Oliveira Luvisaro Clicia Valim Cortes Gradim 《Journal of Pharmacy and Pharmacology》 2016年第11期639-648,共10页
The aim of this study is to assess the occurrence and type of violence suffered by women with breast cancer in the High Complexity Care Unit of a municipality in the South of Minas and patients in a support group of t... The aim of this study is to assess the occurrence and type of violence suffered by women with breast cancer in the High Complexity Care Unit of a municipality in the South of Minas and patients in a support group of the University of the South of Minas Gerais. For that aim, a descriptive-exploratory methodology was applied through the quantitative method. Data were collected through a semi-structured form applied in individual interviews over a period of three months. We interviewed 57 patients and among those, 20 women (35.08%) reported having experienced some form of violence at some stage of their life, and the most frequently mentioned was the psychological violence followed by physical aggression. Although it was possible to identify that violence against affected these women, complaints against the aggressor were not affected. 展开更多
关键词 VIOLENCE woma breast neoplasms NURSING
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The accuracy of magnetic resonance imaging and ultrasound in evaluating the size of early-stage breast neoplasms
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作者 Zheng Wang Hongzhi Chen +3 位作者 Xiaobin Ma Zhijun Dai Shuai Lin Huafeng Kang 《Oncology and Translational Medicine》 2016年第4期169-173,共5页
Objective Breast cancer is the most frequently diagnosed cancer in women. Accurate evaluation of the size and extent of the tumor is crucial in selecting a suitable surgical method for patients with breast cancer. Bot... Objective Breast cancer is the most frequently diagnosed cancer in women. Accurate evaluation of the size and extent of the tumor is crucial in selecting a suitable surgical method for patients with breast cancer. Both overestimation and underestimation have important adverse effects on patient care. This study aimed to evaluate the accuracy of breast magnetic resonance imaging(MRI) and ultrasound(US) examination for measuring the size and extent of early-stage breast neoplasms.Methods The longest diameter of breast tumors in patients with T_(1–2)N_(0–1)M_0 invasive breast cancer preparing for breast-conserving surgery(BCS) was measured preoperatively by using both MRI and US and their accuracy was compared with that of postoperative pathologic examination. If the diameter difference was within 2 mm, it was considered to be consistent with pathologic examination.Results A total of 36 patients were imaged using both MRI and US. The mean longest diameter of the tumors on MRI, US, and postoperative pathologic examination was 20.86 mm ± 4.09 mm(range: 11–27 mm), 16.14 mm ± 4.91 mm(range: 6–26 mm), and 18.36 mm ± 3.88 mm(range: 9–24 mm). US examination underestimated the size of the tumor compared to that determined using pathologic examination(t = 3.49, P < 0.01), while MRI overestimated it(t =-6.35, P < 0.01). The linear correlation coefficients between the image measurements and pathologic tumor size were r = 0.826(P < 0.01) for MRI and r = 0.645(P < 0.01) for US. The rate of consistency of MRI and US compared to that with pathologic examination was 88.89% and 80.65%, respectively, and there was no statistically significant difference between them(χ~2 = 0.80, P > 0.05).Conclusion MRI and US are both effective methods to assess the size of breast tumors, and they maintain good consistency with pathologic examination. MRI has a better correlation with pathology. However, we should be careful about the risk of inaccurate size estimation. 展开更多
关键词 breast neoplasm magnetic resonance imaging(MRI) ultrasound pathology
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Metabolic reprogramming in triple-negative breast cancer 被引量:13
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作者 Zhanyu Wang Qianjin Jiang Chenfang Dong 《Cancer Biology & Medicine》 SCIE CAS CSCD 2020年第1期44-59,共16页
Since triple-negative breast cancer(TNBC)was first defined over a decade ago,increasing studies have focused on its genetic and molecular characteristics.Patients diagnosed with TNBC,compared to those diagnosed with o... Since triple-negative breast cancer(TNBC)was first defined over a decade ago,increasing studies have focused on its genetic and molecular characteristics.Patients diagnosed with TNBC,compared to those diagnosed with other breast cancer subtypes,have relatively poor outcomes due to high tumor aggressiveness and lack of targeted treatment.Metabolic reprogramming,an emerging hallmark of cancer,is hijacked by TNBC to fulfill bioenergetic and biosynthetic demands;maintain the redox balance;and further promote oncogenic signaling,cell proliferation,and metastasis.Understanding the mechanisms of metabolic remodeling may guide the design of metabolic strategies for the effective intervention of TNBC.Here,we review the metabolic reprogramming of glycolysis,oxidative phosphorylation,amino acid metabolism,lipid metabolism,and other branched pathways in TNBC and explore opportunities for new biomarkers,imaging modalities,and metabolically targeted therapies. 展开更多
关键词 metabolic reprogramming triple-negative breast cancer aerobic glycolysis Warburg effect cancer stem cell targeted therapy
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Presence of circulating tumor cells is associated with metabolic-related variables in postoperative patients with early-stage breast cancer 被引量:1
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作者 Yumei Shi Guochun Zhang +5 位作者 Yulei Wang Chongyang Ren Lingzhu Wen Wenzhen Zhu Xiaoqing Chen Ning Liao 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2018年第3期340-350,共11页
Objective:Although circulating tumor cells(CTCs)have been well-established as promising prognostic biomarkers in both early breast cancer and metastatic settings,little is known regarding the prognostic relevance o... Objective:Although circulating tumor cells(CTCs)have been well-established as promising prognostic biomarkers in both early breast cancer and metastatic settings,little is known regarding the prognostic relevance of CTCs in the long-term postoperative monitoring of patients with non-metastatic breast cancer(non-MBC).In this study,we investigated the associations of CTCs with clinicopathological features and metabolic-related variables,such as obesity and hyperglycemia.Methods:In this retrospective study,we recruited 264 patients with postoperative stage Ⅰ–Ⅲ breast cancer at Guangdong General Hospital from January 2009 to December 2015.The prevalence and number of CTCs were assessed using the Cell Search System at a median time of 19.0 months[interquartile range(IQR),7.8–33.0]after surgery.The CTC assay results were correlated with the clinicopathological features and metabolic-related variables.A multivariate logistic regression analysis was performed to further determine the independent predictors of CTCs.Results:CTCs were detected in 10.6%of all patients.The positive rate of CTCs in patients with infiltrating ductal carcinoma was lower than that in patients with other pathological types(9.0%vs.28.6%,P=0.020).More importantly,the presence of CTCs was correlated with blood glucose level(P=0.015)and high-density lipoprotein level(P=0.030).The multivariate logistic regression analysis showed that the pathological type[odds ratio(OR):1.757,95%CI:1.021–3.023;P=0.042]and blood glucose level(OR:1.218,95%CI:1.014–1.465;P=0.035)were independent predictors of the presence of CTCs.Conclusions:This study revealed potential associations between CTCs and metabolic-related factors in Chinese patients with non-MBC and supports the hypothesis that metabolic dysfunction in breast cancer patients might influence the biological activity of metastatic breast cancer,leading to a higher prevalence of CTCs. 展开更多
关键词 breast cancer circulating tumor ceils HYPERGLYCEMIA metabolic-related variables
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Diffusion tensor imaging and proton magnetic resonance spectroscopy in brain tumor Correlation between structure and metabolism
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作者 Zhigang Min Chen Niu +2 位作者 Netra Rana Huanmei Ji Ming Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第10期930-937,共8页
Proton magnetic resonance spectroscopy and diffusion tensor imaging are non-invasive techniques used to detect metabolites and water diffusion in vivo. Previous studies have confirmed a positive correlation of individ... Proton magnetic resonance spectroscopy and diffusion tensor imaging are non-invasive techniques used to detect metabolites and water diffusion in vivo. Previous studies have confirmed a positive correlation of individual fractional anisotropy values with N-acetylaspartate/creatine and N-acetylaspartate/choline ratios in tumors, edema, and normal white matter. This study divided the brain parenchyma into tumor, pedtumoral edema, and normal-appearing white matter according to MRI data, and analyzed the correlation of metabolites with water molecular diffusion. Results demonstrated that in normal-appearing white matter, N-acetylaspartate/creatine ratios were positively correlated with fractional anisotropy values, negatively correlated with radial diffusivities, and positively correlated with maximum eigenvalues. Maximum eigenvalues and radial diffusivities in peritumoral edema showed a negative correlation with choline, N-acetylaspartate, and creatine. Radial diffusivities in tumor demonstrated a negative correlation with choline. These data suggest that the relationship between metabolism and structure is markedly changed from normal white matter to peritumoral edema and tumor. Neural metabolism in the peritumoral edema area decreased with expanding extracellular space. The normal relationship of neural function and microstructure disappeared in the tumor region. 展开更多
关键词 neural regeneration NEUROIMAGING brain neoplasms magnetic resonance spectroscopy diffusiontensor imaging metabolism diffusion anisotropy EDEMA nerve fiber extracellular space correlation analysis grants-supported paper NEUROREGENERATION
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The Anti-Tumor Effect of a High Caloric Diet in the PyMT Mouse Breast Cancer Model Is Initiated by an Increase in Metabolic Rate
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作者 Linda C. Enns Warren C. Ladiges 《Journal of Cancer Therapy》 2012年第5期718-730,共13页
Obesity is associated with an increased risk of mortality from certain types of cancer, including cancer of the breast. Because obesity is associated with multiple risk factors, however, the exact reasons remain uncle... Obesity is associated with an increased risk of mortality from certain types of cancer, including cancer of the breast. Because obesity is associated with multiple risk factors, however, the exact reasons remain unclear. The objective of this study was to determine which of the risk factors associated with obesity are related to enhanced tumor development. The MMTV-PyMT mouse model develops mammary tumors which share numerous characteristics with those of humans. We challenged these mice with a high fat/high carbohydrate, high caloric (HC) diet, and looked for relationships between enhanced primary tumor development and adiposity, various aspects of glucose homeostasis, and metabolic factors. The HC diet enhanced tumor progression in PyMT mice. While mice on the HC diet also developed increased adiposity, hyperglycemia and hyperinsulinemia, none of these risk factors was found to be associated with the observed increases in tumor growth. Rather, we found that while overall, tumor growth was enhanced in HC diet-fed mice compared to those maintained on a regular diet, it was attenuated in individuals by an HC diet-induced increase in metabolic rate and decrease in respiratory exchange ratio. Tumor size in HC diet-fed mice was directly related to p38 phosphorylation and Bcl-2 inhibition, and the degree of vascularization of these tumors was closely and indirectly related to the rate of mouse oxygen consumption. The data suggest that an increase in metabolic rate and oxygen consumption, induced by the introduction of a high caloric diet, has a protective effect against tumor growth by increasing the activity levels of the tumor suppressor p38 and decreasing the activity of the antiapoptoic protein Bcl-2, as well as by reducing hypoxia-induced tumor vascularization. 展开更多
关键词 OBESITY breast Cancer metabolism Oxygen ROS P38 HYPOXIA
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Delineation of fatty acid metabolism in gastric cancer:Therapeutic implications
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作者 Yu Fu Bin Wang +3 位作者 Peng Fu Lei Zhang Yi Bao Zhen-Zhen Gao 《World Journal of Clinical Cases》 SCIE 2023年第20期4800-4813,共14页
BACKGROUND The prognosis of gastric cancer is extremely poor.Metabolic reprogramming involving lipids has been associated with cancer occurrence and progression.AIM To illustrate fatty acid metabolic mechanisms in gas... BACKGROUND The prognosis of gastric cancer is extremely poor.Metabolic reprogramming involving lipids has been associated with cancer occurrence and progression.AIM To illustrate fatty acid metabolic mechanisms in gastric cancer,detect core genes,develop a prognostic model,and provide treatment options.METHODS Raw data from The Cancer Genome Atlas and Gene Expression Omnibus databases were collected and analyzed.Differentially expressed fatty acid metabolism genes were identified and incorporated into a risk model based on least absolute shrinkage and selection operator regression analysis.Then,patients from The Cancer Genome Atlas were assigned to high-and low-risk cohorts according to the mean value of the risk score as the threshold,which was verified in the Gene Expression Omnibus database.Relationships between chemotherapeutic sensitivity and tumor microenvironment features were assessed.RESULTS An integrated evaluation was performed in this study.Fatty acid metabolismrelated genes were used to construct the risk model.Patients classified into the high-risk cohort were considered to be resistant to chemotherapy based on results of the“pRRophetic”R package.Patients in the high-risk cohort were associated with type Ⅰ/Ⅱ interferon activation,increased inflammation level,immune cell infiltration,and tumor immune dysfunction based on the exclusion algorithm,indicating the potential benefit of immunotherapy in these patients.CONCLUSION We constructed a fatty acid-related risk score model to assess the comprehensive fatty acid features in gastric cancer and validated its vital role in prognosis,chemotherapy sensitivity,and immunotherapy. 展开更多
关键词 Stomach neoplasms Fatty acids metabolism Risk assessment IMMUNOTHERAPY
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Guidelines for diagnosis and treatment of advanced breast cancer in China(2022 edition)
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作者 Binghe Xu Fei Ma 《Journal of the National Cancer Center》 2024年第2期107-127,共21页
Breast cancer is the most common cancer among women worldwide.It has been estimated that about 416000 new cases and over 117000 deaths of breast cancer occurred in China in 2020.Among the new cases of breast cancer di... Breast cancer is the most common cancer among women worldwide.It has been estimated that about 416000 new cases and over 117000 deaths of breast cancer occurred in China in 2020.Among the new cases of breast cancer diagnosed each year,3-10%have distant metastasis at the time of initial diagnosis.In addition,approxi-mately 30%of patients with early-stage breast cancer may eventually experience recurrence or metastases.The 5-year survival rate of patients with advanced breast cancer is only 20%with a median overall survival of 2-3 years.Although advanced breast cancer remains incurable at present,new therapeutic options and multidisci-plinary treatment could be utilized to alleviate symptoms,improve quality of life,and prolong patients’survival.The choice of treatment regimens for patients with advanced breast cancer is very important,and the optimal treatment strategy beyond the first-and second-line therapy is often lacking.Herein,the China Advanced Breast Cancer Guideline Panel discussed and summarized recent clinical evidence,updated the guidelines for the diag-nosis and treatment of advanced breast cancer based on the 2020 edition,and formulated the“Guidelines for diagnosis and treatment of advanced breast cancer in China(2022 edition)”for clinicians’reference. 展开更多
关键词 breast neoplasms DIAGNOSIS TREATMENT GUIDELINE
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基于MRI的瘤周水肿特征对浸润性乳腺癌淋巴结转移负荷的预测价值
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作者 罗红兵 陈哲 +2 位作者 肖茜茜 任静 周鹏 《中国医学影像学杂志》 北大核心 2025年第1期55-62,共8页
目的分析基于MRI的瘤周水肿特征对乳腺癌淋巴结转移负荷的预测价值。资料与方法回顾性收集四川省肿瘤医院2017年9月—2019年2月有完整术前MRI资料和术后病理资料的213例浸润性乳腺癌。根据术后病理诊断的淋巴结转移数量,将病例分为高负... 目的分析基于MRI的瘤周水肿特征对乳腺癌淋巴结转移负荷的预测价值。资料与方法回顾性收集四川省肿瘤医院2017年9月—2019年2月有完整术前MRI资料和术后病理资料的213例浸润性乳腺癌。根据术后病理诊断的淋巴结转移数量,将病例分为高负荷淋巴结转移组47例(转移淋巴结总数>2枚)和低负荷淋巴结转移组166例(转移淋巴结总数≤2枚)。在T2WI序列上,分析每例的乳腺癌瘤周水肿(包括瘤周水肿类型和水肿程度)特征。在DCE-MRI序列上,根据乳腺影像报告和数据系统分类术语分析乳腺癌的MRI特征。通过单因素分析瘤周水肿等T2WI特征和乳腺癌MRI特征对淋巴结转移负荷的诊断价值,将有显著意义的特征进行多因素Logistic回归分析,并建立诊断模型。采用受试者工作特征曲线评价模型对乳腺癌淋巴结转移负荷的诊断效能,根据约登指数计算模型的诊断效能指标。结果本研究的高负荷转移淋巴结占22.1%(47/213)。单因素分析结果显示,瘤周水肿程度(OR=18.70,P<0.001)、瘤周水肿类型(OR=16.00,P<0.001)、肿瘤最长径(OR=1.40,P=0.025)和肿瘤最短径(OR=2.01,P=0.003)对高负荷淋巴结转移有预测价值;多因素Logistic回归分析结果显示,最终对浸润性乳腺癌高负荷淋巴结转移有价值的特征是瘤周水肿水肿特征,包括瘤周水肿程度(OR=8.02,P<0.001)和瘤周水肿类型(OR=5.53,P=0.001),最终诊断模型预测浸润性乳腺癌高负荷淋巴结转移的曲线下面积为0.842,敏感度为0.766,特异度为0.861,阳性预测值为0.610,阴性预测值为0.929。结论术前MRI的瘤周水肿特征对浸润性乳腺癌淋巴结转移负荷有很好的预测价值,尤其是对低负荷淋巴结转移状态预测价值更高。 展开更多
关键词 乳腺肿瘤 淋巴转移 磁共振成像 水肿 诊断 鉴别 预测
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三阴性乳腺癌中KIAA1522表达和作用研究
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作者 王磊 张洁 +1 位作者 刘春玲 李玉凤 《安徽医药》 CAS 2025年第1期44-48,共5页
目的分析三阴乳腺癌(TNBC)中KIAA1522激活对Wnt信号通路及促进肿瘤细胞转移的机制影响。方法该研究于2021年1月至2022年10月进行,收集唐山市人民医院手术治疗的三阴乳腺癌36例,TNBC癌组织依据有淋巴结转移(转移组)和无淋巴结转移(未转移... 目的分析三阴乳腺癌(TNBC)中KIAA1522激活对Wnt信号通路及促进肿瘤细胞转移的机制影响。方法该研究于2021年1月至2022年10月进行,收集唐山市人民医院手术治疗的三阴乳腺癌36例,TNBC癌组织依据有淋巴结转移(转移组)和无淋巴结转移(未转移组)分为两组,采用蛋白质印迹法和实时荧光定量逆转录PCR(RT-qPCR)法分别检测各组KIAA1522、含IQ模序的GTP酶活化蛋白1(IQGAP1)、β连环素(β-catenin)的蛋白及mRNA相对表达水平,免疫共沉淀法检测KIAA1522、IQGAP1分别与β-catenin的相互作用情况。结果转移组中KIAA1522、IQGAP1、β-catenin蛋白相对表达量(0.37±0.05、0.28±0.02、1.50±0.08)均高于未转移组(0.27±0.05、0.25±0.05、1.05±0.02)(P<0.05)。转移组中KIAA1522、IQGAP-1 mRNA相对表达量(0.95±0.03、1.08±0.10)高于未转移组(0.73±0.05、0.99±0.12)(P<0.05),两者呈正相关关系(r=0.55,P<0.05),β-catenin mRNA在二组中的相对表达量差异无统计学意义。免疫共沉淀显示在TNBC癌组织中KIAA1522蛋白与β-catenin蛋白无相互作用,而IQGAP1蛋白与β-catenin蛋白相互共沉淀。结论KIAA1522激活Wnt信号通路,促进TNBC肿瘤细胞的转移,机制可能与上调IQGAP1 mRNA,过表达的IQGAP1促进β-catenin蛋白累积并结合成蛋白复合物有关。 展开更多
关键词 三阴性乳腺癌 KIAA1522 WNT信号通路 含IQ摸序的GTP酶活化蛋白1 Β连环素 免疫共沉淀
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TERT启动子突变阳性的复发乳腺分泌性癌1例
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作者 邓旭 雷婷 《临床与实验病理学杂志》 北大核心 2025年第1期130-132,共3页
乳腺分泌性癌(secretory carcinoma of the breast, SCB)是一种罕见的乳腺恶性肿瘤,约占所有类型乳腺癌的0.02%,ETV6-NTRK3融合基因是其特征性基因改变。尽管多数情况下具有三阴表型,SCB通常预后良好,罕见复发、转移,但相关的分子基因... 乳腺分泌性癌(secretory carcinoma of the breast, SCB)是一种罕见的乳腺恶性肿瘤,约占所有类型乳腺癌的0.02%,ETV6-NTRK3融合基因是其特征性基因改变。尽管多数情况下具有三阴表型,SCB通常预后良好,罕见复发、转移,但相关的分子基因组学改变仍未明确。本文报道了1例TERT启动子突变的复发SCB患者的临床资料、组织学特征、免疫表型及分子基因组学改变,并复习相关文献,从而加深对SCB的认识。 展开更多
关键词 乳腺肿瘤 分泌性癌 ETV6-NTRK3 转移 病例报道
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基于临床及多模态超声特征风险评分模型鉴别乳腺BI-RADS 4A类良、恶性病变
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作者 刘启凡 崔帅 +5 位作者 郭文静 李伟 王海龙 李虎莎 姚俊东 张周龙 《中国介入影像与治疗学》 北大核心 2025年第1期22-26,共5页
目的 观察基于临床及多模态超声特征风险评分模型鉴别乳腺乳腺影像报告和数据系统(BI-RADS)4A类良、恶性病变的价值。方法 前瞻性纳入177例多模态乳腺超声提示BI-RADS 4A类病变患者,按7∶3比例分为训练集(n=123)与测试集(n=54)。以单因... 目的 观察基于临床及多模态超声特征风险评分模型鉴别乳腺乳腺影像报告和数据系统(BI-RADS)4A类良、恶性病变的价值。方法 前瞻性纳入177例多模态乳腺超声提示BI-RADS 4A类病变患者,按7∶3比例分为训练集(n=123)与测试集(n=54)。以单因素及多因素logistic回归分析临床及灰阶超声、CDFI、弹性成像超声参数,筛选乳腺BI-RADS 4A类良、恶性病变的独立鉴别因素并以之构建风险评分模型。以术后病理或随访结果为标准,利用受试者工作特征(ROC)曲线获取模型鉴别乳腺BI-RADS 4A类良、恶性病变的最佳截断值,评估模型鉴别效能。结果177例中,良性39例、恶性138例。患者年龄>58岁,病变直径>15.1 mm、形状不规则、血流1或2级和病变周围2 mm环状区域(shell)声触诊弹性成像值标准差(shell-STESD)>16.33 kPa均为乳腺BI-RADS 4A类恶性病变的独立危险因素。以6.5为最佳截断值,风险评分模型鉴别训练集高危与低危病例的敏感度为84.69%(83/98)、特异度为88.00%(22/25),在测试集中分别为77.50%(31/40)及71.43%(10/14)。结论 基于临床及多模态超声特征风险评分模型可有效鉴别乳腺BI-RADS 4A类良、恶性病变。 展开更多
关键词 乳腺肿瘤 病理学 超声检查 乳腺影像报告和数据系统 前瞻性研究
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