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Breast cancer-associated fibroblasts: their roles in tumor initiation, progression and clinical applications

null

《医学前沿（英文）》 2016年 第10卷 第1期   页码 33-40 doi: 10.1007/s11684-016-0431-5

摘要：

Breast cancer is the most common malignant tumor in women, and the incidence of this disease has increased in recent years because of changes in diet, living environment, gestational age, and other unknown factors. Previous studies focused on cancer cells, but an increasing number of recent studies have analyzed the contribution of cancer microenvironment to the initiation and progression of breast cancer. Cancer-associated fibroblasts (CAFs), the most abundant cells in tumor stroma, secrete various active biomolecules, including extracellular matrix components, growth factors, cytokines, proteases, and hormones. CAFs not only facilitate the initiation, growth, angiogenesis, invasion, and metastasis of cancer but also serve as biomarkers in the clinical diagnosis, therapy, and prognosis of breast cancer. In this article, we reviewed the literature and summarized the research findings on CAFs in breast cancer.

关键词： cancer-associated fibroblast     breast cancer     progression     prognosis    

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FGF23 associated bone diseases

null

《医学前沿（英文）》 2013年 第7卷 第1期   页码 65-80 doi: 10.1007/s11684-013-0254-6

摘要：

Recently, fibroblast growth factor 23 (FGF23) has sparked widespread interest because of its potential role in regulating phosphate and vitamin D metabolism. In this review, we summarized the FGF superfamily, the mechanism of FGF23 on phosphate and vitamin D metabolism, and the FGF23 related bone disease.

关键词： fibroblast growth factor 23     FGF receptor     phosphate metabolism     Klotho     bone disease    

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Platelet membrane-based and tumor-associated platelet- targeted drug delivery systems for cancer therapy

Yinlong Zhang, Guangna Liu, Jingyan Wei, Guangjun Nie

《医学前沿（英文）》 2018年 第12卷 第6期   页码 667-677 doi: 10.1007/s11684-017-0583-y

摘要： Platelets have long been known to play critical roles in hemostasis by clumping and clotting blood vessel injuries. Recent experimental evidence strongly indicates that platelets can also interact with tumor cells by direct binding or secreting cytokines. For example, platelets have been shown to protect circulating cancer cells in blood circulation and to promote tumor metastasis. In-depth understanding of the role of platelets in cancer progression and metastasis provides promising approaches for platelet biomimetic drug delivery systems and functional platelet-targeting strategies for effective cancer treatment. This review highlights recent progresses in platelet membrane-based drug delivery and unique strategies that target tumor-associated platelets for cancer therapy. The paper also discusses future development opportunities and challenges encountered for clinical translation.

关键词： platelet-mimicking delivery systems     tumor-associated platelets     cancer therapy     EPR effect    

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Regulation of exogenous bFGF gene mediated by recombinant adeno-associated virus

Ke SONG, Nianjing RAO, Meiling CHEN, Yingguang CAO

《医学前沿（英文）》 2009年 第3卷 第2期   页码 158-163 doi: 10.1007/s11684-009-0042-5

摘要： The regulatory effect of basic fibroblast growth factor (bFGF) mediated by recombinant adeno-associated virus (AAV) was investigated. Recombinant plasmid pAAV-S3-bFGF, and pSVneo were co-transfected into BHK-21 cells, then the recombinant AAV genome was replicated and packaged with the helper virus HSV1-rc/ΔUL2. The titer of the recombinant rAAV2-tet-off-bFGF was determined by dot-blot assay. MC3T3-E1 cells were infected with rAAV2-tet-off-bFGF. Regulatory effects of Doxycycline (Dox) on bFGF and osteogenic factors were assayed quantitatively by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The physical particle titer of rAAV2-tet-off-bFGF successfully constructed was 1.8×10 vector genomes/mL, and the virus could infect MC3T3-E1 cells effectively. In MC3T3-E1 cells treated with Dox, the expression levels of exogenous bFGF and osteogenic factors declined to varying degrees. It was concluded that rAAV2-tet-off-bFGF could infect MC3T3 cells efficiently, and this recombinant system could be regulated successfully by Dox .

关键词： tetracycline regulatory system     adeno-associated virus     basic fibroblast growth factor     gene regulation    

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Functional XPF polymorphisms associated with lung cancer susceptibility in a Chinese population

Dian-Ke YU PhD, Chen WU MD, Wen TAN MD, Dong-Xin LIN MD,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 82-89 doi: 10.1007/s11684-010-0014-9

摘要： Variation of individuals’ DNA repair capacity has been linked to cancer susceptibility. The xeroderma pigmentsum group F (XPF) plays a pivotal role in nucleotide-excision repair (NER) pathway. This study was to examine the functional significance of promoter polymorphisms and their association with lung cancer risk. The function of promoter polymorphisms was tested by a set of biochemical assays, and their effects on lung cancer risk were determined by a case-control analysis of 988 patients with lung cancer and 986 controls. The −673T allele showed a significantly higher transcriptional activity as compared with the −673C allele. The −673TT genotype was associated with a decreased risk of lung cancer compared with the CC genotype (adjusted OR=0.62, 95% CI=0.42–0.91; =0.015) and this effect was more significant among males (adjusted OR=0.55, 95% CI=0.35–0.86; =0.009), elder subjects (adjusted OR=0.51, 95% CI=0.30–0.86; =0.012), and light smokers (adjusted OR=0.35, 95% CI=0.14–0.88; =0.026). These findings suggest that functional polymorphisms influencing DNA repair capacity may confer susceptibility to lung cancer.

关键词： XPF     polymorphism     lung cancer    

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Advances on immune-related adverse events associated with immune checkpoint inhibitors

Yong Fan, Yan Geng, Lin Shen, Zhuoli Zhang

《医学前沿（英文）》 2021年 第15卷 第1期   页码 33-42 doi: 10.1007/s11684-019-0735-3

摘要： Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.

关键词： cancer     immunotherapy     immune checkpoint inhibitors     immune-related adverse events     review    

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Risk factors for ventilator-associated pneumonia among patients undergoing major oncological surgeryfor head and neck cancer

null

《医学前沿（英文）》 2017年 第11卷 第2期   页码 239-246 doi: 10.1007/s11684-017-0509-8

摘要：

Patients undergoing major oncological surgery for head and neck cancer (SHNC) have a particularly high risk of nosocomial infections. We aimed to identify risk factors for ventilator-associated pneumonia (VAP) in patients undergoing SHNC. The study included 465 patients who underwent SHNC between June 2011 and June 2014. The rate of VAP, risk factors for VAP, and biological aspects of VAP were retrospectively evaluated. The incidence of VAP was 19.6% (n=95) in patients who required more than 48 h of mechanical ventilation. Staphylococcus (37.7%), Enterobacteriaceae (32.1%), Pseudomonas(20.8%), and Haemophilus (16.9%) were the major bacterial species that caused VAP. The independent risk factors for VAP were advanced age, current smoking status, chronic obstructive pulmonary disease, and a higher simplified acute physiology score system II upon admission. Tracheostomy was an independent protective factor for VAP. The median length of stay in the ICU for patients who did or did not develop VAP was 8.0 and 6.5 days, respectively (P=0.006). Mortality among patients who did or did not develop VAP was 16.8% and 8.4%, respectively (P<0.001). The potential economic impact of VAP was high because of the significantly extended duration of ventilation. A predictive regression model was developed with a sensitivity of 95.3% and a specificity of 69.4%. VAP is common in patients who are undergoing SHNC and who require more than 48 h of mechanical ventilation. Therefore, innovative preventive measures should be developed and applied in this high-risk population.

关键词： ventilator-associated pneumonia (VAP)     pneumonia     risk factors     surgery for head and neck cancer (SHNC)    

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Potential of electron transfer and its application in dictating routes of biochemical processes associated

《医学前沿（英文）》 2021年 第15卷 第5期   页码 679-692 doi: 10.1007/s11684-021-0866-1

摘要： Metabolic reprogramming, such as abnormal utilization of glucose, addiction to glutamine, and increased de-novo lipid synthesis, extensively occurs in proliferating cancer cells, but the underneath rationale has remained to be elucidated. Based on the concept of the degree of reduction of a compound, we have recently proposed a calculation termed as potential of electron transfer (PET), which is used to characterize the degree of electron redistribution coupled with metabolic transformations. When this calculation is combined with the assumed model of electron balance in a cellular context, the enforced selective reprogramming could be predicted by examining the net changes of the PET values associated with the biochemical pathways in anaerobic metabolism. Some interesting properties of PET in cancer cells were also discussed, and the model was extended to uncover the chemical nature underlying aerobic glycolysis that essentially results from energy requirement and electron balance. Enabling electron transfer could drive metabolic reprogramming in cancer metabolism. Therefore, the concept and model established on electron transfer could guide the treatment strategies of tumors and future studies on cellular metabolism.

关键词： metabolic reprogramming     potential of electron transfer     cell proliferation     aerobic glycolysis     cancer metabolism    

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Altered intestinal microbiota associated with colorectal cancer

Hong Zhang, Ying Chang, Qingqing Zheng, Rong Zhang, Cheng Hu, Weiping Jia

《医学前沿（英文）》 2019年 第13卷 第4期   页码 461-470 doi: 10.1007/s11684-019-0695-7

摘要： The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal–luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in which is a butyrate-producing genera of bacteria, and a significant increase in in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identified. The observed abundance of bacterial species belonging to and may serve as a promising biomarker for the early detection of CRC.

关键词： colorectal cancer (CRC)     gut microbiota     intestinal     Eubacterium     Devosia    

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Bioinformatic exploration of MTA1-regulated gene networks in colon cancer

null

《医学前沿（英文）》 2016年 第10卷 第2期   页码 178-182 doi: 10.1007/s11684-016-0442-2

摘要：

Metastasis-associated gene 1 (MTA1) controls a series of biological processes in tumor progression. Tumor progression is a complex process regulated by a gene network. The global cancer gene regulatory network must be analyzed to determine the position of MTA1 in the molecular network and its cooperative genes by further exploring the biological functions of this gene. We used TCGA data sets and GeneCards database to screen MTA1-related genes. GO and KEGG pathway analyses were conducted with DAVID and gene network analysis via STRING and Cytoscape. Results showed that in the development of colon cancer, MTA1 is linked to certain signal pathways, such as Wnt/Notch/nucleotide excision repair pathways. The findings also suggested that MTA1 demonstrates the closest relationship in a coregulation process with the key molecules AKT1, EP300, CREBBP, SMARCA4, RHOA, and CAD. These results lead MTA1 exploration to an in-depth investigation in different directions, such as Wnt, Notch, and DNA repair.

关键词： metastasis-associated gene 1     colon cancer     bioinformatics    

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Evidence for lung repair and regeneration in humans: key stem cells and therapeutic functions of fibroblast

Xuran Chu, Chengshui Chen, Chaolei Chen, Jin-San Zhang, Saverio Bellusci, Xiaokun Li

《医学前沿（英文）》 2020年 第14卷 第3期   页码 262-272 doi: 10.1007/s11684-019-0717-5

摘要： Regeneration carries the idea of regrowing partially or completely a missing organ. Repair, on the other hand, allows restoring the function of an existing but failing organ. The recognition that human lungs can both repair and regenerate is quite novel, the concept has not been widely used to treat patients. We present evidence that the human adult lung does repair and regenerate and introduce different ways to harness this power. Various types of lung stem cells are capable of proliferating and differentiating upon injury driving the repair/regeneration process. Injury models, primarily in mice, combined with lineage tracing studies, have allowed the identification of these important cells. Some of these cells, such as basal cells, broncho-alveolar stem cells, and alveolar type 2 cells, rely on fibroblast growth factor (FGF) signaling for their survival, proliferation and/or differentiation. While pre-clinical studies have shown the therapeutic benefits of FGFs, a recent clinical trial for acute respiratory distress syndrome (ARDS) using intravenous injection of FGF7 did not report the expected beneficial effects. We discuss the potential reasons for these negative results and propose the rationale for new approaches for future clinical trials, such as delivery of FGFs to the damaged lungs through efficient inhalation systems, which may be more promising than systemic exposure to FGFs. While this change in the administration route presents a challenge, the therapeutic promises displayed by FGFs are worth the effort.

关键词： FGF     human lung     repair     regeneration     stem cells    

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延长腺相关病毒递送药物的半衰期提高治疗效果 Article

吴会芳, 胡丹, 李泉晓, 王春雨, 朱晓艺, 李威, 陈宾凡, 季萍, 黄可可, 黄爱玲, 黄竞荷, Dimiter S. Dimitrov, 吴艳玲, 应天雷

《工程（英文）》 2023年 第21卷 第2期   页码 203-213 doi: 10.1016/j.eng.2022.02.009

摘要： 在这项腺相关病毒（adeno-associated virus, AAV）基因治疗研究中，通过与免疫球蛋白G1（immunoglobulin G 1, IgG1）可溶性单体Fc 区（soluble monomeric研究表明，延长AAV递送的小分子双功能蛋白和成纤维细胞生长因子21（fibroblast growth factor 21, FGF21）的半衰期显著增加了它们在血液循环中的浓度。

关键词： 基因治疗     腺相关病毒     半衰期     成纤维细胞生长因子21     2型糖尿病    

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Crk-associated substrate, vascular smooth muscle and hypertension

TANG Dale

《医学前沿（英文）》 2008年 第2卷 第4期   页码 323-331 doi: 10.1007/s11684-008-0062-6

摘要： Hypertension is characterized by vascular smooth muscle constriction and vascular remodeling involving cell migration, hypertrophy and growth. Crk-associated substrate (CAS), the first discovered member of the adapter protein CAS family, has been shown to be a critical cellular component that regulates various smooth muscle functions. In this review, the molecular structure and protein interactions of the CAS family members are summarized. Evidence for the role of CAS in the regulation of vascular smooth muscle contractility is presented. Contraction stimulation induces CAS phosphorylation on Tyr-410 in arterial smooth muscle, creating the binding site for the Src homology (SH) 2/SH3 protein CrkII, which activates neuronal Wiskott-Aldrich syndrome protein (N-WASP)-mediated actin assembly and force development. The functions of CAS in cell migration, hypertrophy and growth are also summarized. Abelson tyrosine kinase (Abl), c-Src, focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (PYK2), protein tyrosine phosphatase-proline, glutamate, serine and threonine sequence protein (PTP-PEST) and SHP-2 have been documented to coordinate the phosphorylation and dephosphorylation of CAS. The downstream signaling partners of CAS in the context of cell motility, hypertrophy, survival and growth are also discussed. These new findings establish the important role of CAS in the modulation of vascular smooth muscle functions. Furthermore, the upstream regulators of CAS may be new biologic targets for the development of more effective and specific treatment of cardiovascular diseases such as hypertension.

关键词： Contraction stimulation     phosphatase-proline     molecular structure     discovered     hypertension    

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CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a sweet success?

《医学前沿（英文）》 2022年 第16卷 第3期   页码 322-338 doi: 10.1007/s11684-021-0901-2

摘要： Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.

关键词： cancer immunotherapy     chimeric antigen receptor     solid tumors     tumor-associated antigen     glycosylation     O-glycans     adoptive cell therapy    

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Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

《医学前沿（英文）》 2022年 第16卷 第3期   页码 459-466 doi: 10.1007/s11684-021-0841-x

摘要： Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.

关键词： Fanconi anemia     aplastic anemia     hematologic malignancy     germline predisposition    

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标题 作者 时间 类型 操作

Breast cancer-associated fibroblasts: their roles in tumor initiation, progression and clinical applications

null

期刊论文

FGF23 associated bone diseases

null

期刊论文

Platelet membrane-based and tumor-associated platelet- targeted drug delivery systems for cancer therapy

Yinlong Zhang, Guangna Liu, Jingyan Wei, Guangjun Nie

期刊论文

Regulation of exogenous bFGF gene mediated by recombinant adeno-associated virus

Ke SONG, Nianjing RAO, Meiling CHEN, Yingguang CAO

期刊论文

Functional XPF polymorphisms associated with lung cancer susceptibility in a Chinese population

Dian-Ke YU PhD, Chen WU MD, Wen TAN MD, Dong-Xin LIN MD,

期刊论文

Advances on immune-related adverse events associated with immune checkpoint inhibitors

Yong Fan, Yan Geng, Lin Shen, Zhuoli Zhang

期刊论文

Risk factors for ventilator-associated pneumonia among patients undergoing major oncological surgeryfor head and neck cancer

null

期刊论文

Potential of electron transfer and its application in dictating routes of biochemical processes associated

期刊论文

Altered intestinal microbiota associated with colorectal cancer

Hong Zhang, Ying Chang, Qingqing Zheng, Rong Zhang, Cheng Hu, Weiping Jia

期刊论文

Bioinformatic exploration of MTA1-regulated gene networks in colon cancer

null

期刊论文

Evidence for lung repair and regeneration in humans: key stem cells and therapeutic functions of fibroblast

Xuran Chu, Chengshui Chen, Chaolei Chen, Jin-San Zhang, Saverio Bellusci, Xiaokun Li

期刊论文

延长腺相关病毒递送药物的半衰期提高治疗效果

吴会芳, 胡丹, 李泉晓, 王春雨, 朱晓艺, 李威, 陈宾凡, 季萍, 黄可可, 黄爱玲, 黄竞荷, Dimiter S. Dimitrov, 吴艳玲, 应天雷

期刊论文

Crk-associated substrate, vascular smooth muscle and hypertension

TANG Dale

期刊论文

CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a sweet success?

期刊论文

Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

期刊论文