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Disabled homolog 2 is required for migration and invasion of prostate cancer cells

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 312-321 doi: 10.1007/s11684-015-0401-3

摘要：

Disabled homolog 2 (DAB2) is frequently deleted or epigenetically silenced in many human cancer cells. Therefore, DAB2 has always been regarded as a tumor suppressor gene. However, the role of DAB2 in tumor progression and metastasis remains unclear. In this study, DAB2 expression was upregulated along with human prostate cancer (PCa) progression. DAB2overexpression or knockdown effects in LNCaP and PC3 cell lines were verified to address the biological functions of DAB2 in PCa progression and metastasis. LNCaP and PC3 cell lines were generated from human PCa cells with low and high metastatic potentials, respectively. The results showed that DAB2 shRNA knockdown can inhibit the migratory and invasive abilities of PC3 cells, as well as the tumorigenicity, whereas DAB2 overexpression enhanced LNCaP cell migration and invasion. Further investigation showed that DAB2 regulated the cell migration associated genes in PC3 cells, and the differential DAB2 expression between LNCaP and PC3 cells was partly regulated by histone 4 acetylation. Therefore, DAB2 may play an important role in PCa progression and metastasis.

关键词： DAB2     prostate cancer     migration     invasion     acetylation    

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Human microbiome and prostate cancer development: current insights into the prevention and treatment

Solmaz Ohadian Moghadam, Seyed Ali Momeni

《医学前沿（英文）》 2021年 第15卷 第1期   页码 11-32 doi: 10.1007/s11684-019-0731-7

摘要： The huge communities of microorganisms that symbiotically colonize humans are recognized as significant players in health and disease. The human microbiome may influence prostate cancer development. To date, several studies have focused on the effect of prostate infections as well as the composition of the human microbiome in relation to prostate cancer risk. Current studies suggest that the microbiota of men with prostate cancer significantly differs from that of healthy men, demonstrating that certain bacteria could be associated with cancer development as well as altered responses to treatment. In healthy individuals, the microbiome plays a crucial role in the maintenance of homeostasis of body metabolism. Dysbiosis may contribute to the emergence of health problems, including malignancy through affecting systemic immune responses and creating systemic inflammation, and changing serum hormone levels. In this review, we discuss recent data about how the microbes colonizing different parts of the human body including urinary tract, gastrointestinal tract, oral cavity, and skin might affect the risk of developing prostate cancer. Furthermore, we discuss strategies to target the microbiome for risk assessment, prevention, and treatment of prostate cancer.

关键词： microbiome     prostate cancer     prevention     treatment     molecular pathological epidemiology (MPE)     biomarker    

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Detection and monitoring prostate specific antigen using nanotechnology approaches to biosensing

Grant Perry, Fernando Cortezon-Tamarit, Sofia I. Pascu

《化学科学与工程前沿（英文）》 2020年 第14卷 第1期   页码 4-18 doi: 10.1007/s11705-019-1846-8

摘要： Prostate cancer has a high incidence in men and remains the second cause of mortality due to cancer. As the development of the disease is greatly correlated to age, the identification of novel detection methods reliable, efficient, and cost effective is a matter of significant importance in the ageing population of western societies. The detection of the prostate specific antigen (PSA) in blood samples has been the preferred method for the detection and monitoring of prostate cancer over the past decades. Despite the indications against its use in massive population screening, PSA still remains the best studied biomarker for prostate cancer and the detection of its different forms and incorporation in multiplexed designs with other biomarkers still remains a highly valuable indicator in the theranostics of prostate cancer. The latest developments in the use of nanomaterials towards the construction of PSA biosensors are reviewed hereby. The incorporation of gold nanoparticles, silica nanoparticles and graphene nanostructures to biosensing devices has represented a big leap forward in terms of sensitivity, stability and miniaturization. Both electrochemical and optical detection methods will be reviewed herein for the detection of PSA.

关键词： biosensing     immunosensor     PSA     prostate cancer     fluorescence    

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Effects of miR-200c on the migration and invasion abilities of human prostate cancer Du145 cells and

null

《医学前沿（英文）》 2014年 第8卷 第4期   页码 456-463 doi: 10.1007/s11684-014-0353-z

摘要：

microRNAs (miRNAs) have played a key role in human tumorigenesis, tumor progression, and metastasis. On the one hand, miRNAs are aberrantly expressed in many types of human cancer; on the other hand, miRNAs can function as tumor suppressors or oncogenes that target many cancer-related genes. This study aimed to investigate the effects of miRNA-200c (miR-200c) on the biological behavior and mechanism of proliferation, migration, and invasion in the prostate cancer cell line Du145. In this study, Du145 cells were transfected with miR-200c mimics or negative control miR-NC by using an X-tremeGENE siRNA transfection reagent. The relative expression of miR-200c was measured by RT-PCR. The proliferation, migration, and invasion abilities of Du145 cells were detected by CCK8 assays, migration assays and invasion assays, respectively. The expressions of ZEB1, E-cadherin, and vimentin were observed by western blot. Results showed that DU145 cells exhibited a high expression of miR-200c compared with immortalized normal prostate epithelial cell RWPE-1. Du145 cells were then transfected with miR-200c mimics and displayed lower abilities of proliferation, migration, and invasion than those transfected with the negative control. The protein levels of ZEB1 and vimentin were expressed at a low extent in Du145 cells, which were transfected with miR-200c mimics; by contrast, E-cadherin was highly expressed. Hence, miR-200c could significantly inhibit the proliferation of the prostate cancer cell line Du145; likewise, miR-200c could inhibit migration and invasion by epithelial-mesenchymal transition.

关键词： miR-200c     proliferation     migration     invasion     prostate cancer     Du145 cell     ZEB1    

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Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes

《医学前沿（英文）》 2023年 第17卷 第2期   页码 231-239 doi: 10.1007/s11684-022-0939-9

摘要： To evaluate the safety and efficacy of neoadjuvant radiohormonal therapy for oligometastatic prostate cancer (OMPC), we conducted a 3 + 3 dose escalation, prospective, phase I/II, single-arm clinical trial (CHiCTR1900025743), in which long-term neoadjuvant androgen deprivation was adopted 1 month before radiotherapy, comprising intensity modulated radiotherapy to the pelvis, and stereotactic body radiation therapy to all extra-pelvic bone metastases for 4‒7 weeks, at 39.6, 45, 50.4, and 54 Gy. Robotic-assisted radical prostatectomy was performed after 5‒14 weeks. The primary outcome was treatment-related toxicities and adverse events; secondary outcomes were radiological treatment response, positive surgical margin (pSM), postoperative prostate-specific antigen (PSA), pathological down-grading and tumor regression grade, and survival parameters. Twelve patients were recruited from March 2019 to February 2020, aging 66.2 years in average (range, 52‒80). Median baseline PSA was 62.0 ng/mL. All underwent RARP successfully without open conversions. Ten patients recorded pathological tumor down-staging (83.3%), and 5 (41.7%) with cN1 recorded negative regional lymph nodes on final pathology. 66.7% (8/12) recorded tumor regression grading (TRG) –I and 25% (3/12) recorded TRG-II. Median follow-up was 16.5 months. Mean radiological progression-free survival (RPFS) was 21.3 months, with 2-year RPFS of 83.3%. In all, neoadjuvant radiohormonal therapy is well tolerated for oligometastatic prostate cancer.

关键词： neoadjuvant     radiotherapy     oligometastatic     prostate cancer     radical prostatectomy    

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Ultrasound-guided prostate percutaneous intervention robot system and calibration by informative particle

《机械工程前沿（英文）》 2022年 第17卷 第1期   页码 3-3 doi: 10.1007/s11465-021-0659-x

摘要： Applying a robot system in ultrasound-guided percutaneous intervention is an effective approach for prostate cancer diagnosis and treatment. The limited space for robot manipulation restricts structure volume and motion. In this paper, an 8-degree-of-freedom robot system is proposed for ultrasound probe manipulation, needle positioning, and needle insertion. A novel parallel structure is employed in the robot system for space saving, structural rigidity, and collision avoidance. The particle swarm optimization method based on informative value is proposed for kinematic parameter identification to calibrate the parallel structure accurately. The method identifies parameters in the modified kinematic model stepwise according to parameter discernibility. Verification experiments prove that the robot system can realize motions needed in targeting. By applying the calibration method, a reasonable, reliable forward kinematic model is built, and the average errors can be limited to 0.963 and 1.846 mm for insertion point and target point, respectively.

关键词： ultrasound image guidance     prostate percutaneous intervention     parallel robot     kinematics identification     particle swarm optimization     informative value    

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人体前列腺特异性抗原携带含酮基-脱氧壬酮糖酸的N-聚糖 Article

Wei Wang, Tao Zhang, Jan Nouta, Peter A. van Veelen, Noortje de Haan, Theo M. de Reijke, Manfred Wuhrer, Guinevere S.M. Lageveen-Kammeijer

《工程（英文）》 2023年 第26卷 第7期   页码 119-131 doi: 10.1016/j.eng.2023.02.009

摘要：

Ketodeoxynononic acid (Kdn) is a rather uncommon class of sialic acid in mammals. However, associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression. Hitherto, there has been a lack of conclusive evidence that Kdn occurs on (specific) human glycoproteins (conjugated Kdn). Here, we report for the first time that Kdn is expressed on prostate-specific antigen (PSA) N-linked glycans derived from human seminal plasma and urine. Interestingly, Kdn was found only in an α2,3-linkage configuration on an antennary galactose, indicating a highly specific biosynthesis. This unusual glycosylation feature was also identified in a urinary PSA cohort in relation to prostate cancer (PCa), although no differences were found between PCa and non-PCa patients. Further research is needed to investigate the occurrence, biosynthesis, biological role, and biomarker potential of both free and conjugated Kdn in humans.

关键词： 酮基-脱氧壬酮糖酸     Kdn     糖基化     前列腺癌     前列腺特异性抗原    

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NES1/KLK10 and hNIS gene therapy enhanced iodine-131 internal radiation in PC3 proliferation inhibition

Jiajia Hu, Wenbin Shen, Qian Qu, Xiaochun Fei, Ying Miao, Xinyun Huang, Jiajun Liu, Yingli Wu, Biao Li

《医学前沿（英文）》 2019年 第13卷 第6期   页码 646-657 doi: 10.1007/s11684-018-0643-y

摘要： gene is thought to be a tumor-suppressor gene. Our previous study found that overexpression of gene in PC3 cell line could slow down the tumor proliferation rate, associated with a mild decrease in expression. The decrease could increase the sensitivity of radiotherapy to tumors. Thus, we supposed to have an “enhanced firepower” effect by combining overexpressed gene therapy and I radiation therapy uptake by overexpressed hNIS protein. We found a weak endogenous expression of hNIS protein in PC3 cells and demonstrated that the low expression of hNIS protein in PC3 cells might be the reason for the low iodine uptake. By overexpressing in PC3, the radioactive iodine uptake ability was significantly increased. Results of and tumor proliferation experiments and F-fluorothymidine ( F-FLT) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging showed that the combined gene therapy and I radiation therapy mediated by overexpressed hNIS protein had the best tumor proliferative inhibition effect. Immunohistochemistry showed an obvious decrease of expression and the lowest expression. These data suggest that via inhibition of expression, overexpressed might enhance the effect of radiation therapy of I uptake in overexpressed PC3 cells.

关键词： androgen-independent prostate cancer     normal epithelial cell-specific 1/kallikrein 10     sodium/iodide symporter     radiation therapy     proliferation    

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Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

《医学前沿（英文）》 2021年 第15卷 第6期   页码 942-942 doi: 10.1007/s11684-021-0876-z

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Progress and challenges in RET-targeted cancer therapy

《医学前沿（英文）》 2023年 第17卷 第2期   页码 207-219 doi: 10.1007/s11684-023-0985-y

摘要： The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

关键词： pralsetinib     selpercatinib     RET-alteration     lung cancer     thyroid cancer     tumor-agnostic therapy     drug resistance    

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Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

《医学前沿（英文）》 2018年 第12卷 第4期   页码 361-373 doi: 10.1007/s11684-018-0656-6

摘要：

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.

关键词： epithelial-to-mesenchymal transition     cancer     metastasis     cancer stem cell    

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Metformin for cancer prevention

Yonghua Yang

《医学前沿（英文）》 2011年 第5卷 第2期   页码 115-117 doi: 10.1007/s11684-011-0112-3

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Orlistat induces ferroptosis-like cell death of lung cancer cells

《医学前沿（英文）》 2021年 第15卷 第6期   页码 922-932 doi: 10.1007/s11684-020-0804-7

摘要： Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P<0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.

关键词： orlistat     ferroptosis     FAF2     lung cancer    

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Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

null

《医学前沿（英文）》 2012年 第6卷 第4期   页码 376-380 doi: 10.1007/s11684-012-0228-0

摘要：

The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance. Recent research shows that the forkhead transcription factor FOXM1 is a direct transcriptional target repressed by the forkhead protein FOXO3a, a vital downstream effector of the PI3K-AKT-FOXO signaling pathway. Intriguingly, FOXM1 and FOXO3a also compete for binding to the same gene targets, which have a role in chemotherapeutic drug action and sensitivity. An understanding of the role and regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of chemotherapeutic drug action and resistance in patients, and provide new insights into the design of novel therapeutic strategy and reliable biomarkers for prediction of drug sensitivity.

关键词： FOXO3a     FOXM1     transcription factor     cancer     drug resistance     tumorigenesis    

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Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic

《医学前沿（英文）》 doi: 10.1007/s11684-023-1050-6

摘要： Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

关键词： pancreatic cancer     cancer screening     single cell     molecular alterations     precancerous lesion     therapy resistance    

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标题 作者 时间 类型 操作

Disabled homolog 2 is required for migration and invasion of prostate cancer cells

null

期刊论文

Human microbiome and prostate cancer development: current insights into the prevention and treatment

Solmaz Ohadian Moghadam, Seyed Ali Momeni

期刊论文

Detection and monitoring prostate specific antigen using nanotechnology approaches to biosensing

Grant Perry, Fernando Cortezon-Tamarit, Sofia I. Pascu

期刊论文

Effects of miR-200c on the migration and invasion abilities of human prostate cancer Du145 cells and

null

期刊论文

Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes

期刊论文

Ultrasound-guided prostate percutaneous intervention robot system and calibration by informative particle

期刊论文

人体前列腺特异性抗原携带含酮基-脱氧壬酮糖酸的N-聚糖

Wei Wang, Tao Zhang, Jan Nouta, Peter A. van Veelen, Noortje de Haan, Theo M. de Reijke, Manfred Wuhrer, Guinevere S.M. Lageveen-Kammeijer

期刊论文

NES1/KLK10 and hNIS gene therapy enhanced iodine-131 internal radiation in PC3 proliferation inhibition

Jiajia Hu, Wenbin Shen, Qian Qu, Xiaochun Fei, Ying Miao, Xinyun Huang, Jiajun Liu, Yingli Wu, Biao Li

期刊论文

Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

期刊论文

Progress and challenges in RET-targeted cancer therapy

期刊论文

Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

期刊论文

Metformin for cancer prevention

Yonghua Yang

期刊论文

Orlistat induces ferroptosis-like cell death of lung cancer cells

期刊论文

Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

null

期刊论文

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic

期刊论文