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Nuclear morphometry, nucleomics and prostate cancer progression

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Asian Journal of Andrology 2012年第3期14卷 375-384,I0005页

作者： Robert W Veltri Christhunesa S Christudass Sumit Isharwal Fisher Biomarker ＆ Biorepository Laboratory The Brady Urological Research Institute Baltimore MD 21287 USA The Brady Urological Research Institute Johns Hopkins Hospital Baltimore MD 21287 USA Urologic Surgery University of Minnesota Medical School Minneapolis MN 55455 USA

Prostate cancer （PCa） results from a multistep process. This process includes initiation, which occurs through various aging events and multiple insults （such as chronic infection, inflammation and genetic instability through reactive oxygen species causing DNA double-strand breaks）, followed by a multistep process of progression. These steps include several genetic and epigenetic alterations, as well as alterations to the chromatin structure, which occur in response to the carcinogenic stress-related events that sustain proliferative signaling. Events such as evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis are readily observed. In addition, in conjunction with these critical drivers of carcinogenesis, other factors related to the etiopathogenesis of PCa, involving energy metabolism and evasion of the immune surveillance system, appear to be involved. In addition, when cancer spread and metastasis occur, the ＇tumor microenvironment＇ in the bone of PCa patients may provide a way to sustain dormancy or senescence and eventually establish a ＇seed and soil＇ site where PCa proliferation and growth may occur over time. When PCa is initiated and progression ensues, significant alterations in nuclear size, shape and heterochromatin （DNA transcription） organization are found, and key nuclear transcriptional and structural proteins, as well as multiple nuclear bodies can lead to precancerous and malignant changes. These series of cellular and tissue-related malignancy-associated events can be quantified to assess disease progression and management.

关键词： active surveillance cancer metastasis cancer progression digital image analysis molecular biomarkers morphologicalbiomarkers nuclear morphometry nuclear proteins and nuclear structure prostate cancer

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway:Providing understanding of the complex mechanisms of chemoresistance

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World Journal of Gastroenterology 2022年第26期28卷 3027-3046页

作者： María Belén Novoa Díaz María Julia Martín Claudia Gentili Departamento de Biología Bioquímica y FarmaciaUniversidad Nacional del Sur(UNS)-INBIOSUR(CONICET-UNS)Bahía Blanca 8000Argentina Departamento de Química Universidad Nacional del Sur(UNS)-INQUISUR(CONICET-UNS)Bahía Blanca 8000Argentina

Colorectal cancer(CRC)continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current *** of the Wnt/β-catenin pathway plays a fundamental role in the genesis and progression of several types of cancer,including *** many subtypes of CRC,hyperactivation of theβ-catenin pathway is associated with mutations of the adenomatous polyposis coli ***,it can also be associated with other *** recent years,studies of the tumor microenvironment(TME)have demonstrated its importance in the development and progression of *** this tumor nest,several cell types,structures,and biomolecules interact with neoplastic cells to pave the way for the spread of the ***-communications between tumor cells and the TME are then established primarily through paracrine factors,which trigger the activation of numerous signaling *** advances in the field of oncology have been made in the last *** Minireview aims to actualize what is known about the central role of the Wnt/β-catenin pathway in CRC chemoresistance and aggressiveness,focusing on crosscommunication between CRC cells and the *** this analysis,our main objective was to increase the understanding of this complex disease considering a more global *** many treatments for advanced CRC fail due to mechanisms involving chemoresistance,the data here exposed and analyzed are of great interest for the development of novel and effective therapies.

关键词： Colorectal cancer β-catenin pathway Tumor stroma Tumor microenvironment factors cancer progression Drug resistance

Role of doublecortin-like kinase 1 and leucine-rich repeat-containing G-protein-coupled receptor 5 in patients with stage Ⅱ/Ⅲ colorectal cancer:cancer progression and prognosis

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World Journal of Gastroenterology 2020年第43期26卷 6853-6866页

作者： Xue-Ling Kang Li-Rui He Yao-Li Chen Shu-Bin Wang Department of Oncology Peking University Shenzhen HospitalShenzhen-Peking University-Hong Kong University of Science and Technology Medical CenterShenzhen 518036Guangdong ProvinceChina Department of Gastrointestinal Surgery Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina Department of Pathology Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina Department of Oncology Peking University Shenzhen HospitalShenzhen Key Laboratory of Gastrointestinal Cancer Translational ResearchChina Cancer Institute of Shenzhen-Peking University-Hong Kong University of Science and Technology Medical CenterShenzhen 518036Guangdong ProvinceChina

BACKGROUND cancer stem cells(CSCs)are a subpopulation of cancer cells with the potential of self-renewal and *** play critical roles in tumorigenesis,recurrence,metastasis,radiation tolerance and *** To assess the expression patterns and clinical potential of doublecortin-like kinase 1(DCLK1)and leucine-rich repeat-containing G-protein-coupled receptor 5(Lgr5),as prognostic CSC markers of colorectal cancer(CRC).METHODS The expression of DCLK1 and Lgr5 in CRC tissue sections from 92 patients was determined by *** case was evaluated using a combined scoring method based on signal intensity staining(scored 0-3)and the proportion of positively stained cancer cells(scored 0-3).The final staining score was calculated as the intensity score multiplied by the proportion *** expression of DCLK1 and Lgr5 was defined as a score of 0-3;high expression of DCLK1 and Lgr5 was defined as a score of≥*** were categorized as either high or low expression,and the correlation between the expression of DCLK1 or Lgr5 and clinicopathological factors was *** DCLK1 and Lgr5 expression levels were significantly positively *** patients with high DCLK1,Lgr5 and DCLK1/Lgr5 expressions had poorer progression-free survival and overall ***,high expression of DCLK1 was an independent prognostic factor for recurrence and overall survival in patients with CRC by multivariate analysis(P=0.026 and P=0.049,respectively).CONCLUSION DCLK1 may be a potential CSC marker for the recurrence and survival of CRC patients.

关键词： Colorectal cancer cancer stem cells Doublecortin-like kinase 1 Leucine-rich repeat-containing G-protein-coupled receptor 5 cancer prognosis cancer progression

Extracellular matrix in cancer progression and therapy

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Medical Review 2022年第2期2卷 125-139页

作者： Xiuxiu He Byoungkoo Lee Yi Jiang Department of Medical Physics Memorial Sloan-Kettering Cancer CenterNew YorkNYUSA The Jackson Laboratory for Genomic Medicine FarmingtonCTUSA Department of Mathematics and Statistics Georgia State University25 Park PlaceAtlantaGA 30303USA

The tumor ecosystem with heterogeneous cellularcompositions and the tumor microenvironment has increasingly become the focus of cancer research in recent years. Theextracellular matrix (ECM), the major component of the tumor microenvironment, and its interactions with the tumorcells and stromal cells have also enjoyed tremendouslyincreased attention. Like the other components of the tumormicroenvironment, the ECM in solid tumors differs significantly from that in normal organs and tissues. We reviewrecent studies of the complex roles the tumor ECM plays incancer progression, from tumor initiation, growth to angiogenesis and invasion. We highlight that the biomolecular,biophysical, and mechanochemical interactions between theECM and cells not only regulate the steps of cancer progression, but also affect the efficacy of systemic cancer *** further discuss the strategies to target and modify thetumor ECM to improve cancer therapy.

关键词： cancer invasion cancer metabolism cancer progression cancer therapy cell-ECM interaction extracellular matrix metastasis

Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression

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Monoacylglycerol lipase regulates cannabinoid receptor 2-dep...

Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene

中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Wei Xiang Hongming Miao Department of Biochemistry and Molecular Biology Third Military Medical University

Metabolic reprogramming greatly contributes to the regulation of macrophage ***,the mechanism of lipid accumulation and the corresponding function in tumor-associated macrophages(TAMs) remain *** primary investigation in colon cancer and confirmation in other cancer models,here we determine that deficiency of monoacylglycerol lipase(MGLL) results in lipid overload in ***,macrophage MGLL inhibits CB2 cannabinoid receptordependent tumor progression in inoculated and genetic cancer ***,MGLL deficiency promotes CB2/TLR4-dependent macrophage activation,which further suppresses the function of tumor-associated CD8+ T *** with CB2 antagonists delays tumor progression in inoculated and genetic cancer ***,we verify that expression of macrophage MGLL is decreased in cancer tissues and positively correlated with the survival of cancer *** together,our findings identify MGLL as a switch for CB2/TLR4-dependent macrophage activation and provide potential targets for cancer therapy.

关键词： MGLL CB2 macrophage activation CD8+ T cell TAM cancer progression

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Oncology Research 2024年第7期32卷 1185-1195页

作者： XIAOBI HUANG CHUNYUAN CHEN YONGYANG CHEN HONGLIAN ZHOU YONGHUA CHEN ZHONG HUANG YULIU XIE BAIYANG LIU YUDONG GUO ZHIXIONG YANG GUANGHUA CHEN WENMEI SU Department of Pulmonary Oncology Affiliated Hospital of Guangdong Medical UniversityZhanjiang524001China Department of Thoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiang524001China Department of Orthopedics Affiliated Hospital of Guangdong Medical UniversityZhanjiang524001China Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases Affiliated Hospital of Guangdong Medical UniversityZhanjiang524001China

Background:Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as *** dysregulation has been closely associated with ***00265 is upregulated in lung adenocarcinoma and is a prognostic biomarker of this ***,the mechanism underlying its function in cancer progression remains poorly ***:Here,the regulatory role of LINC00265 in lung adenocarcinoma was examined using lung cancer cell lines,clinical samples,and ***:We found that high levels of LINC00265 expression were associated with shorter overall survival rate of patients,whereas knockdown of LINC00265 inhibited proliferation of cancer cell lines and tumor growth in *** blot andﬂow cytometry analyses indicated that silencing of LINC00265 induced autophagy and ***,we showed that LINC00265 interacted with and stabilized the transcriptional co-repressor Switch-independent 3a(SIN3A),which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent *** of SIN3A also reduced proliferation of lung cancer cells,which was correlated with the induction of *** observations raise the possibility that LINC00265 functions to promote the oncogenic activity of SIN3A in lung ***:Ourﬁndings thus identify SIN3A as a LINC00265-associated protein and should help to understand the mechanism underlying LINC00265-mediated oncogenesis.

关键词： LINC00265 Autophagy Lung adenocarcinoma(LUAD) cancer progression Switch-independent 3a(SIN3A)

Multifaceted roles and functions of SOX30 in human cancer

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cancer Innovation 2024年第2期3卷 11-27页

作者： Na Sun Cheng Wang Pingping Gao Rui Wang Yi Zhang Xiaowei Qi Department of Breast and Thyroid Surgery The Southwest Hospital of Army Medical UniversityChongqingChina

SRY-box transcription factor 30(SOX30)participates in tumor cell apoptosis in lung *** occurrence of somatic SOX30 mutations,the expression signature of SOX30 in normal and cancer tissues,the correlation of SOX30 with immune cells and immune-related genes,and the clinical significance of SOX30 in various cancers have stimulated interest in SOX30 as a potential cancer ***30 influences drug sensitivity and tumor immunity in specific cancer *** this review,we have comprehensively summarized the latest research on the role of SOX30 in cancer by combining bioinformatics evidence and a literature *** summarize recent research on SOX30 in cancer regarding somatic mutations,trials,transcriptome analysis,clinical information,and SOX30-mediated regulation of malignant ***,we report on the diagnostic value of SOX30 mRNA expression levels across different cancer *** review on the role of SOX30 in cancer progression may provide insights into possible research directions for SOX30 in cancer and a theoretical basis for guiding future studies.

关键词： cancer progression prognosis SOX30

Pan-cancer analysis of ORAI family proteins and their genomic alterations

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Medical Data Mining 2024年第4期7卷 41-49页

作者： Zhan-Bo Wu Wen-Shuai Zhang Dan-Yang Ren Xin Li Department of cancer Immunotherapy Tianjin Cancer Hospital Airport HospitalTianjin 300308China Tianjin Medical University cancer Institute and Hospital National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Pathology Tianjin Cancer Hospital Airport HospitalTianjin 300308China

Background:The ORAI family of proteins,comprising ORAI1,ORAI2,and ORAI3,plays a crucial role in the regulation of intracellular calcium signaling,which is essential for various cellular functions including proliferation,differentiation,and *** of calcium signaling has been implicated in cancer pathogenesis,influencing tumor progression,metastasis,and resistance to *** study aims to provide a comprehensive analysis of the ORAI family members across a broad spectrum of ***:Publicly available datasets from The cancer Genome Atlas and the Gene Expression Omnibus were *** sequencing data,mutation profiles,copy number variation data,and methylation data across different cancer types were *** expression analysis,survival analysis,copy number variation analysis,mutation analysis,methylation analysis,immune cell infiltration analysis using the Cibersort algorithm,and gene set enrichment analysis were conducted using R ***:ORAI1 and ORAI3 were significantly upregulated in glioblastoma multiforme,whereas ORAI2 was notably downregulated in kidney chromophobe and pancreatic ***2 exhibited higher mutation rates and copy number gains in multiple cancers compared to ORAI1 and *** hypermethylation of ORAI2 in head and neck squamous cell carcinoma,esophageal carcinoma,and glioblastoma multiforme negatively correlated with its gene ***1 and ORAI3 expression positively correlated with regulatory T cells infiltration,whereas ORAI2 showed a negative correlation with CD8^(+)T cell *** set enrichment analysis revealed that ORAI1 and ORAI2 are associated with immune-related pathways,while ORAI3 is linked to MYC targets and oxidative ***:Our pan-cancer analysis reveals significant differential expression,genomic alterations,and epigenetic regulation of ORAI family members across various ***1 and ORAI3 appear to promote an immunosuppr

关键词： ORAI family calcium signaling cancer progression immune cell infiltration gene expression

Function of cancer cell-derived extracellular matrix in tumor progression

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Journal of cancer Metastasis and Treatment 2016年第1期2卷 357-364页

作者： Gao-Feng Xiong Ren Xu Markey cancer Center LexingtonKY 40536USA Department of Pharmacology and Nutritional Sciences University of KentuckyLexingtonKY 40536USA

Extracellular matrix(ECM)is an essential component of the tumor *** development and progression are associated with increased ECM deposition and *** chemical and physical signals elicited from ECM are necessary for cancer cell proliferation and *** is well recognized that stromal cells are a major source of ECM ***,recent studies showed that cancer cells are also an active and important component in ECM *** cells deposit a significant amount of collagen,fibronectin,and tenascin C(TNC).Recent studies demonstrate that these cancer cell-derived ECM proteins enhance cancer cell survival and promote cancer cell colonization at distant ***-related enzymes and chaperone proteins,such as prolyl-4-hydroxylase,lysyl-hydroxylase,lysyl oxidase,and heat shock protein 47,are also highly expressed in cancer *** of these enzymes significantly reduces cancer growth,invasion,and *** factors suggest that the cancer cell-derived ECM is crucial for cancer progression and ***,targeting these ECM proteins and ECM-related enzymes is a potential strategy for cancer treatment.

关键词： Tumor microenvironment extracellular matrix cancer progression metastasis