Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemot...Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.展开更多
Candida albicans(C.albicans)represents one of the most prevalent opportunistic fungal pathogens in cancer patients.Although the association between C.albicans and cancer has been recognized for decades,the causal rela...Candida albicans(C.albicans)represents one of the most prevalent opportunistic fungal pathogens in cancer patients.Although the association between C.albicans and cancer has been recognized for decades,the causal relationship,whether C.albicans infection is a consequence of cancer or a direct contributor to cancer development-remains a subject of intensive investigation.Recently,the complex interplay between microbes and cancer has garnered significant attention within the scientific community,with growing interest in elucidating the underlying molecular mechanisms.This review systematically examines the biological characteristics of C.albicans,its multifaceted interactions with the host,and its relationship with the intestinal microbiota.Additionally,it provides a comprehensive analysis of the association between C.albicans and the development of various malignancies,with particular emphasis on digestive tract cancers.The review also identifies critical knowledge gaps and apparent contradictions in existing research,highlighting potential avenues for breakthroughs that will advance the efficient and accurate screening,diagnosis,and treatment of cancer.展开更多
Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biologic...Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biological functions in human prostate cancer(PCa).Methods:In this study,we systematically evaluated the expression and prognostic significance of UHMK1 in public databases,followed by validation through immunohis-tochemistry(IHC)in PCa specimens.Both gain-of-function and loss-of-function experiments were conducted to elucidate the role of UHMK1 in vitro and in vivo.Additionally,a series of molecular and biochemical assays were performed to investigate the regulatory mechanisms underlying UHMK1 activity.Results:Our findings revealed that UHMK1 expression was significantly upregulated in PCa tissues and correlated with poor patient prognosis,as demonstrated by analysis of public datasets and confirmed by immunohistochemical staining.Functional studies showed that UHMK1 depletion suppressed tumor cell proliferation and metastasis,while its overexpression promoted these processes.Mechanistically,we identified that UHMK1 phosphorylates nuclear receptor coactivator 3(NCOA3),which subsequently activates activating transcription factor 4(ATF4)to upregulate methylenetetrahydrofolate dehy-drogenase 2(MTHFD2)transcription.Interestingly,MTHFD2 was found to reciprocally enhance UHMK1 expression,establishing a positive feedback loop.Conclusions:In conclusion,our data suggest that the UHMK1-MTHFD2 axis forms a positive feedback loop that drives PCa progression.Targeting this loop represents a promising therapeutic strategy for restraining prostate cancer development and progression.展开更多
Colorectal cancer(CRC)continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current therapies.Dysregulation of the Wnt/β-catenin pathway plays a fundam...Colorectal cancer(CRC)continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current therapies.Dysregulation of the Wnt/β-catenin pathway plays a fundamental role in the genesis and progression of several types of cancer,including CRC.In many subtypes of CRC,hyperactivation of theβ-catenin pathway is associated with mutations of the adenomatous polyposis coli gene.However,it can also be associated with other causes.In recent years,studies of the tumor microenvironment(TME)have demonstrated its importance in the development and progression of CRC.In this tumor nest,several cell types,structures,and biomolecules interact with neoplastic cells to pave the way for the spread of the disease.Cross-communications between tumor cells and the TME are then established primarily through paracrine factors,which trigger the activation of numerous signaling pathways.Crucial advances in the field of oncology have been made in the last decade.This 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 TME.Through this analysis,our main objective was to increase the understanding of this complex disease considering a more global context.Since 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.展开更多
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 instabil...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.展开更多
The study aimed to test if Briganti’s 2012 nomogram could be associated with the risk of prostate cancer (PCa) progression in European Association of Urology (EAU) intermediate-risk patients treated with robotic surg...The study aimed to test if Briganti’s 2012 nomogram could be associated with the risk of prostate cancer (PCa) progression in European Association of Urology (EAU) intermediate-risk patients treated with robotic surgery. From January 2013 to December 2021, 527 consecutive patients belonging to the EAU intermediate-risk class were selected. Briganti’s 2012 nomogram, which predicts the risk of pelvic lymph node invasion (PLNI), was assessed as a continuous and dichotomous variable that categorized up to the median of 3.0%. Disease progression defined as biochemical recurrence and/or metastatic progression was evaluated by Cox proportional hazards (univariate and multivariate analysis). After a median follow-up of 95.0 months (95% confidence interval [CI]: 78.5–111.4), PCa progression occurred in 108 (20.5%) patients who were more likely to present with an unfavorable nomogram risk score, independently by the occurrence of unfavorable pathology including tumor upgrading and upstaging as well as PLNI. Accordingly, as Briganti’s 2012 risk score increased, patients were more likely to experience disease progression (hazard ratio [HR] = 1.060;95% CI: 1.021–1.100;P = 0.002);moreover, it also remained significant when dichotomized above a risk score of 3.0% (HR = 2.052;95% CI: 1.298–3.243;P < 0.0001) after adjustment for clinical factors. In the studied risk population, PCa progression was independently predicted by Briganti’s 2012 nomogram. Specifically, we found that patients were more likely to experience disease progression as their risk score increased. Because of the significant association between risk score and tumor behavior, the nomogram can further stratify intermediate-risk PCa patients, who represent a heterogeneous risk category for which different treatment paradigms exist.展开更多
BACKGROUND Cancer stem cells(CSCs)are a subpopulation of cancer cells with the potential of self-renewal and differentiation.CSCs play critical roles in tumorigenesis,recurrence,metastasis,radiation tolerance and chem...BACKGROUND Cancer stem cells(CSCs)are a subpopulation of cancer cells with the potential of self-renewal and differentiation.CSCs play critical roles in tumorigenesis,recurrence,metastasis,radiation tolerance and chemoresistance.AIM 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 immunohistochemistry.Each 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 score.Low 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≥4.Specimens were categorized as either high or low expression,and the correlation between the expression of DCLK1 or Lgr5 and clinicopathological factors was investigated.RESULTS DCLK1 and Lgr5 expression levels were significantly positively correlated.CRC patients with high DCLK1,Lgr5 and DCLK1/Lgr5 expressions had poorer progression-free survival and overall survival.Moreover,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.展开更多
Extracting exosomes from bodily fluids offers a promising approach to overcoming inherent limitations,enabling the identification of potential biomarkers,especially those present in low abundance.^(1)PC-3 cells,known ...Extracting exosomes from bodily fluids offers a promising approach to overcoming inherent limitations,enabling the identification of potential biomarkers,especially those present in low abundance.^(1)PC-3 cells,known for their high metastatic potential compared with LNCaP cells,are widely used as a model for prostate cancer progression.^(2,3)How-ever,the mechanisms underlying their metastatic charac-teristics remain unclear.Therefore,there is a critical need to investigate diagnostic methods for prostate cancer,as current techniques have various limitations that can lead to overtreatment due to their lack of precision.展开更多
Digestive tract cancers(DTCs)are cancers that occur in the gastrointestinal tract and related organs,including esoph-ageal,gastric,and colorectal cancer.Since these types of cancer share similar endoderm developmental...Digestive tract cancers(DTCs)are cancers that occur in the gastrointestinal tract and related organs,including esoph-ageal,gastric,and colorectal cancer.Since these types of cancer share similar endoderm developmental origins,the genomic and other molecular features can possess many similarities.Therefore,it is urgent to explore the com-monalities of molecular characteristics and signaling path-ways in the tumor microenvironment among these diseases.展开更多
As a pivotal micro RNA(mi RNA),miR-4284 exhibits noteworthy aberrant expression levels across various cancers and diseases,exerting a crucial role in modulating cancer progression and prognosis.This article endeavors ...As a pivotal micro RNA(mi RNA),miR-4284 exhibits noteworthy aberrant expression levels across various cancers and diseases,exerting a crucial role in modulating cancer progression and prognosis.This article endeavors to comprehensively elucidate the regulatory mechanisms of miR-4284 in cancer,delving deeply into its impact on tumor cell proliferation,invasion,and metastasis by intervening in key signaling pathways such as p65,mitogen-activated protein kinase(MAPK),and transforming growth factor-β(TGF-β).Moreover,this article examines the potential associations of miR-4284 with diverse current therapeutic strategies,such as cancer prediction models,synergistic effects of chemotherapeutic agents,mechanisms of ultrasound-targeted microbubble destruction technology,and enhancement of radiotherapy.However,despite the significant strides made in miR-4284 research,certain limitations persist.Looking ahead,we anticipate that larger-scale and more in-depth studies will further unveil the functional mechanisms of miR-4284 and elucidate its role in therapeutic drug efficacy,thus furnishing robust theoretical underpinnings for the clinical application of miR-4284.展开更多
Bcl-2 is an anti-apoptotic oncoprotein and its protein levels are inversely correlated with prognosis in many cancers. However, the role of Bcl-2 in the progression of prostate cancer is not clear. Here we report that...Bcl-2 is an anti-apoptotic oncoprotein and its protein levels are inversely correlated with prognosis in many cancers. However, the role of Bcl-2 in the progression of prostate cancer is not clear. Here we report that Bcl-2 is required for the progression of LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent growth stage. The mRNA and protein levels of Bcl-2 are significantly increased in androgen-independent prostate cancer cells, shRNA-medi- ated gene silencing of Bcl-2 in androgen-independent prostate cancer cells promotes UV-induced apoptosis and suppresses the growth of prostate tumors in vivo. Growing androgen-dependent cells under androgen-deprivation conditions results in formation of androgen-independent colonies; and the transition from androgen-dependent to androgen-independent growth is blocked by ectopic expression of the Bcl-2 antagonist Bax or Bcl-2 shRNA. Thus, our results demonstrate that Bcl-2 is not only critical for the survival of androgen-independent prostate cancer cells, but is also required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage.展开更多
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 th...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 treatment.We further discuss the strategies to target and modify thetumor ECM to improve cancer therapy.展开更多
Neutrophils are recognized active participants in inflammatory responses and are intricately linked to cancer progression.In response to inflammatory stimuli,neutrophils become activated,releasing neutrophils extracel...Neutrophils are recognized active participants in inflammatory responses and are intricately linked to cancer progression.In response to inflammatory stimuli,neutrophils become activated,releasing neutrophils extracellular traps(NETs)for the capture and eradication of pathogens,a phenomenon termed NETosis.With a deeper understanding of NETs,there is growing evidence supporting their role in cancer progression and their involvement in conferring resistance to various cancer therapies,especially concerning tumor reactions to chemotherapy,radiation therapy(RT),and immunotherapy.This review summarizes the roles of NETs in the tumor microenvironment(TME)and their mechanisms of neutrophil involvement in the host defense.Additionally,it elucidates the mechanisms through which NETs promote tumor progression and their role in cancer treatment resistance,highlighting their potential as promising therapeutic targets in cancer treatment and their clinical applicability.展开更多
PIWI-interacting RNAs(pi RNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells.Recent studies have found that pi RNAs,as ti...PIWI-interacting RNAs(pi RNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells.Recent studies have found that pi RNAs,as tissue-specific molecules,both play oncogenic and tumor suppressive roles in cancer progression,including cancer cell proliferation,metastasis,chemoresistance and stemness.Additionally,the atypical manifestation of pi RNAs and PIWI proteins in various malignancies presents a promising strategy for the identification of novel biomarkers and therapeutic targets in the diagnosis and management of tumors.Nonetheless,the precise functions of pi RNAs in cancer progression and their underlying mechanisms have yet to be fully comprehended.This review aims to examine current research on the biogenesis and functions of pi RNA and its burgeoning importance in cancer progression,thereby offering novel perspectives on the potential utilization of pi RNAs and piwi proteins in the management and treatment of advanced cancer.展开更多
Increased matrix stiffness is a common phenomenon in solid tumor tissue and is regulated by both tumor and mesenchymal cells.The increase in collagen and lysyl oxidase family proteins in the extracellular matrix leads...Increased matrix stiffness is a common phenomenon in solid tumor tissue and is regulated by both tumor and mesenchymal cells.The increase in collagen and lysyl oxidase family proteins in the extracellular matrix leads to deposition,contraction,and crosslinking of the stroma,promoting increased matrix stiffness in tumors.Matrix stiffness is critical to the progression of various solid tumors.As a mechanical factor in the tumor microenvi-ronment,matrix stiffness is involved in tumor progression,promoting biological processes such as tumor cell proliferation,invasion,metastasis,angiogenesis,drug resistance,and immune escape.Reducing tissue stiffness can slow down tumor progression.Therefore targeting matrix stiffness is a potential option for tumor therapy.This article reviews the detailed mechanisms of matrix stiffness in different malignant tumor phenotypes and potential tumor therapies targeting matrix stiffness.Understanding the role and mechanisms of matrix stiffness in tumors could provide theoretical insights into the treatment of tumors and assist in the clinical development of new drug therapies.展开更多
Subject Code:H16With the support by the National Natural Science Foundation of China,a study by the research groups led by Prof.Dong Chenfang(董辰方)from Zhejiang University School of Medicine demonstrates that AKR1B1...Subject Code:H16With the support by the National Natural Science Foundation of China,a study by the research groups led by Prof.Dong Chenfang(董辰方)from Zhejiang University School of Medicine demonstrates that AKR1B1promotes basal-like breast cancer progression by apositive feedback loop that activates the展开更多
Gastric cancer(GC)is one of the most aggressive malignancies worldwide and is characterized by its poor prognosis and resistance to conventional therapies.Autophagy and long non-coding RNAs(lncRNAs)play critical yet c...Gastric cancer(GC)is one of the most aggressive malignancies worldwide and is characterized by its poor prognosis and resistance to conventional therapies.Autophagy and long non-coding RNAs(lncRNAs)play critical yet complex roles in GC,functioning as both tumor suppressors and promoters depending on the disease stage and context.Autophagy influences cellular homeostasis and metabolism,whereas lncRNAs regulate gene expression through epigenetic modifications,RNA sponging,and protein interactions.Notably,the interplay between lncRNAs and autophagy modulates tumor progression,metastasis,chemoresistance,and the tumor microenvironment.This study explored the intricate relationship between lncRNAs and autophagy in GC,highlighting their roles in pathogenesis and treatment resistance.By addressing current knowledge gaps and proposing innovative therapeutic strategies,we have emphasized the potential of targeting this dynamic interplay for improved diagnostic and therapeutic outcomes.展开更多
Recent advances in next-generation sequencing and bioinformatics have driven growing interest in the distinct roles of intratumoral microbiota,particularly intracellular bacteria,during tumor evolution.These bacteria ...Recent advances in next-generation sequencing and bioinformatics have driven growing interest in the distinct roles of intratumoral microbiota,particularly intracellular bacteria,during tumor evolution.These bacteria increase the likelihood of metastasis,play important roles in cancer progression,and impact therapy efficiency.The present review explores the sources,mechanisms of invasion into cancer cells,and potential survival strategies of intracellular bacteria in neoplasms,highlighting their critical role in cancer development.We also examine the heterogeneity and intricate interplay of intratumoral microbial communities with immune and cancer cells,emphasizing their potential roles in modulating host genetics,epigenetics,and immunity.Finally,we discuss novel approaches to targeting intracellular bacteria,particularly engineered drug delivery systems,and synthetic biology,which aim to enhance bacterial clearance,reprogram the tumor immune microenvironment,and enhance the efficacy of chemotherapy and immunotherapy.As a result,this review provides new insights to guide future investigations and support the development of microbiota-based interventions in oncology.展开更多
BACKGROUND Gastric cancer(GC)poses a substantial risk to human health due to its high prevalence and mortality rates.Nevertheless,current therapeutic strategies remain insufficient.Single-cell RNA sequencing(scRNA-seq...BACKGROUND Gastric cancer(GC)poses a substantial risk to human health due to its high prevalence and mortality rates.Nevertheless,current therapeutic strategies remain insufficient.Single-cell RNA sequencing(scRNA-seq)offers the potential to provide comprehensive insights into GC pathogenesis.AIM To explore the distribution and dynamic changes of cell populations in the GC tumor microenvironment using scRNA-seq techniques.METHODS Cancerous tissues and paracancerous tissues were obtained from patients diagnosed with GC at various stages(I,II,III,and IV).Single-cell suspensions were prepared and analyzed using scRNA-seq to examine transcriptome profiles and cell-cell interactions.Additionally,quantitative real-time polymerase chain reaction(qRT-PCR)and flow cytometry were applied for measuring the expression of cluster of differentiation(CD)2,CD3D,CD3E,cytokeratin 19,cytokeratin 8,and epithelial cell adhesion molecules.RESULTS Transcriptome data from 73645 single cells across eight tissues of four patients were categorized into 25 distinct cell clusters,representing 10 different cell types.Variations were observed in these cell type distribution.The adjacent epithelial cells in stages II and III exhibited a degenerative trend.Additionally,the quantity of CD4 T cells and CD8 T cells were evidently elevated in cancerous tissues.Interaction analysis displayed a remarkable increase in interaction between B cells and other mast cells in stages II,III,and IV of GC.These findings were further validated through qRT-PCR and flow cytometry,demonstrating elevated T cells and declined epithelial cells within the cancerous tissues.CONCLUSION This study provides a comprehensive analysis of cell dynamics across GC stages,highlighting key interactions within the tumor microenvironment.These findings offer valuable insights for developing novel therapeutic strategies.展开更多
BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA prog...BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA progression through the ERK1/2 signaling cascade.AIM To determine the mechanism of the IL-22/IL-22R1 pathway in CCA and provide new directions for its clinical treatment.METHODS IL-22R1 expression was assessed in human and rat CCA tissues utilizing immunohistochemical techniques,Western blot analysis,and quantitative reverse transcription PCR.The impact of IL-22 on CCA cells was assessed in vitro via tests for proliferation,migration,invasion,and apoptosis assays.The rat models of thioacetamide-induced CCA and subcutaneous xenografts in nude mice were used to assess the in vivo effects.ERK1/2 inhibitors were applied to elucidate the mechanistic role of the pathway.RESULTS IL-22R1 was overexpressed in CCA cell lines and tissues.IL-22 treatment increased the phosphorylation of ERK1/2,promoting tumor cell proliferation,migration,invasion,and resistance to apoptosis.ERK1/2 inhibition considerably reversed these effects both in vitro and in vivo.CONCLUSION The IL-22/IL-22R1 axis promotes CCA progression by activating ERK1/2 signaling.Targeting this pathway with ERK1/2 inhibitors offers potential therapeutic strategies for CCA.展开更多
文摘Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.
文摘Candida albicans(C.albicans)represents one of the most prevalent opportunistic fungal pathogens in cancer patients.Although the association between C.albicans and cancer has been recognized for decades,the causal relationship,whether C.albicans infection is a consequence of cancer or a direct contributor to cancer development-remains a subject of intensive investigation.Recently,the complex interplay between microbes and cancer has garnered significant attention within the scientific community,with growing interest in elucidating the underlying molecular mechanisms.This review systematically examines the biological characteristics of C.albicans,its multifaceted interactions with the host,and its relationship with the intestinal microbiota.Additionally,it provides a comprehensive analysis of the association between C.albicans and the development of various malignancies,with particular emphasis on digestive tract cancers.The review also identifies critical knowledge gaps and apparent contradictions in existing research,highlighting potential avenues for breakthroughs that will advance the efficient and accurate screening,diagnosis,and treatment of cancer.
基金supported by the National Natural Science Foundation of China(Grant Nos.81902617 and 82100816)Guangdong Natural Science Foundation(Grant No.2021A1515012322)Guangzhou Basic and Applied Basic Research Subject-Young Doctor’s“Sailing”Project(Grant No.2024A04J4702).
文摘Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biological functions in human prostate cancer(PCa).Methods:In this study,we systematically evaluated the expression and prognostic significance of UHMK1 in public databases,followed by validation through immunohis-tochemistry(IHC)in PCa specimens.Both gain-of-function and loss-of-function experiments were conducted to elucidate the role of UHMK1 in vitro and in vivo.Additionally,a series of molecular and biochemical assays were performed to investigate the regulatory mechanisms underlying UHMK1 activity.Results:Our findings revealed that UHMK1 expression was significantly upregulated in PCa tissues and correlated with poor patient prognosis,as demonstrated by analysis of public datasets and confirmed by immunohistochemical staining.Functional studies showed that UHMK1 depletion suppressed tumor cell proliferation and metastasis,while its overexpression promoted these processes.Mechanistically,we identified that UHMK1 phosphorylates nuclear receptor coactivator 3(NCOA3),which subsequently activates activating transcription factor 4(ATF4)to upregulate methylenetetrahydrofolate dehy-drogenase 2(MTHFD2)transcription.Interestingly,MTHFD2 was found to reciprocally enhance UHMK1 expression,establishing a positive feedback loop.Conclusions:In conclusion,our data suggest that the UHMK1-MTHFD2 axis forms a positive feedback loop that drives PCa progression.Targeting this loop represents a promising therapeutic strategy for restraining prostate cancer development and progression.
基金Supported by Agencia Nacional de Promoción Científica y Tecnológica,No. PICT-2013-1441Consejo Nacional de Investigaciones Científicas y Técnicas,No. PIP11220150100350+4 种基金Instituto Nacional del Cáncer Asistencia Financiera ⅡRESOL 493/14, No. 2002-4395-14-1Instituto Nacional del Cáncer Asistencia Financiera Ⅲ-2016-2017, RESOL-2016-1006-E-APN-MS,No. 2002-3862-16-1Universidad Nacional del Sur (PGI)Argentina,No. 24/B230 and No. 24/B303
文摘Colorectal cancer(CRC)continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current therapies.Dysregulation of the Wnt/β-catenin pathway plays a fundamental role in the genesis and progression of several types of cancer,including CRC.In many subtypes of CRC,hyperactivation of theβ-catenin pathway is associated with mutations of the adenomatous polyposis coli gene.However,it can also be associated with other causes.In recent years,studies of the tumor microenvironment(TME)have demonstrated its importance in the development and progression of CRC.In this tumor nest,several cell types,structures,and biomolecules interact with neoplastic cells to pave the way for the spread of the disease.Cross-communications between tumor cells and the TME are then established primarily through paracrine factors,which trigger the activation of numerous signaling pathways.Crucial advances in the field of oncology have been made in the last decade.This 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 TME.Through this analysis,our main objective was to increase the understanding of this complex disease considering a more global context.Since 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.
文摘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.
文摘The study aimed to test if Briganti’s 2012 nomogram could be associated with the risk of prostate cancer (PCa) progression in European Association of Urology (EAU) intermediate-risk patients treated with robotic surgery. From January 2013 to December 2021, 527 consecutive patients belonging to the EAU intermediate-risk class were selected. Briganti’s 2012 nomogram, which predicts the risk of pelvic lymph node invasion (PLNI), was assessed as a continuous and dichotomous variable that categorized up to the median of 3.0%. Disease progression defined as biochemical recurrence and/or metastatic progression was evaluated by Cox proportional hazards (univariate and multivariate analysis). After a median follow-up of 95.0 months (95% confidence interval [CI]: 78.5–111.4), PCa progression occurred in 108 (20.5%) patients who were more likely to present with an unfavorable nomogram risk score, independently by the occurrence of unfavorable pathology including tumor upgrading and upstaging as well as PLNI. Accordingly, as Briganti’s 2012 risk score increased, patients were more likely to experience disease progression (hazard ratio [HR] = 1.060;95% CI: 1.021–1.100;P = 0.002);moreover, it also remained significant when dichotomized above a risk score of 3.0% (HR = 2.052;95% CI: 1.298–3.243;P < 0.0001) after adjustment for clinical factors. In the studied risk population, PCa progression was independently predicted by Briganti’s 2012 nomogram. Specifically, we found that patients were more likely to experience disease progression as their risk score increased. Because of the significant association between risk score and tumor behavior, the nomogram can further stratify intermediate-risk PCa patients, who represent a heterogeneous risk category for which different treatment paradigms exist.
基金Supported by Sanming Project of Shenzhen,No.SZSM201612041Shenzhen Science and Technology Innovation Commission Project,No.GJHZ20180420180754917 and No.ZDSYS20190902092855097Postdoctoral Science Foundation of China,No.2018M633095.
文摘BACKGROUND Cancer stem cells(CSCs)are a subpopulation of cancer cells with the potential of self-renewal and differentiation.CSCs play critical roles in tumorigenesis,recurrence,metastasis,radiation tolerance and chemoresistance.AIM 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 immunohistochemistry.Each 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 score.Low 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≥4.Specimens were categorized as either high or low expression,and the correlation between the expression of DCLK1 or Lgr5 and clinicopathological factors was investigated.RESULTS DCLK1 and Lgr5 expression levels were significantly positively correlated.CRC patients with high DCLK1,Lgr5 and DCLK1/Lgr5 expressions had poorer progression-free survival and overall survival.Moreover,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.
基金supported by grants from the National Research Foundation of Korea(NRF)(No.2022R1A2C109179013,RS-2024-00451519,RS-2024-00359310,2018R1A5A1024340)the National Research Council of Science&Technology(NST)Aging Convergence Research Center(Korea)(No.CRC22012-200)the Ministry of Health and Welfare of Korea(No.HV22C012800).
文摘Extracting exosomes from bodily fluids offers a promising approach to overcoming inherent limitations,enabling the identification of potential biomarkers,especially those present in low abundance.^(1)PC-3 cells,known for their high metastatic potential compared with LNCaP cells,are widely used as a model for prostate cancer progression.^(2,3)How-ever,the mechanisms underlying their metastatic charac-teristics remain unclear.Therefore,there is a critical need to investigate diagnostic methods for prostate cancer,as current techniques have various limitations that can lead to overtreatment due to their lack of precision.
基金supported by the National Science Funds of China(No.82300219)the Natural Science Foundation of Shandong Province,China(Youth ProgramNo.ZR2023QH249).
文摘Digestive tract cancers(DTCs)are cancers that occur in the gastrointestinal tract and related organs,including esoph-ageal,gastric,and colorectal cancer.Since these types of cancer share similar endoderm developmental origins,the genomic and other molecular features can possess many similarities.Therefore,it is urgent to explore the com-monalities of molecular characteristics and signaling path-ways in the tumor microenvironment among these diseases.
基金supported by the Qiantang Scholars Fund in Hangzhou City University(No.210000-581835)
文摘As a pivotal micro RNA(mi RNA),miR-4284 exhibits noteworthy aberrant expression levels across various cancers and diseases,exerting a crucial role in modulating cancer progression and prognosis.This article endeavors to comprehensively elucidate the regulatory mechanisms of miR-4284 in cancer,delving deeply into its impact on tumor cell proliferation,invasion,and metastasis by intervening in key signaling pathways such as p65,mitogen-activated protein kinase(MAPK),and transforming growth factor-β(TGF-β).Moreover,this article examines the potential associations of miR-4284 with diverse current therapeutic strategies,such as cancer prediction models,synergistic effects of chemotherapeutic agents,mechanisms of ultrasound-targeted microbubble destruction technology,and enhancement of radiotherapy.However,despite the significant strides made in miR-4284 research,certain limitations persist.Looking ahead,we anticipate that larger-scale and more in-depth studies will further unveil the functional mechanisms of miR-4284 and elucidate its role in therapeutic drug efficacy,thus furnishing robust theoretical underpinnings for the clinical application of miR-4284.
文摘Bcl-2 is an anti-apoptotic oncoprotein and its protein levels are inversely correlated with prognosis in many cancers. However, the role of Bcl-2 in the progression of prostate cancer is not clear. Here we report that Bcl-2 is required for the progression of LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent growth stage. The mRNA and protein levels of Bcl-2 are significantly increased in androgen-independent prostate cancer cells, shRNA-medi- ated gene silencing of Bcl-2 in androgen-independent prostate cancer cells promotes UV-induced apoptosis and suppresses the growth of prostate tumors in vivo. Growing androgen-dependent cells under androgen-deprivation conditions results in formation of androgen-independent colonies; and the transition from androgen-dependent to androgen-independent growth is blocked by ectopic expression of the Bcl-2 antagonist Bax or Bcl-2 shRNA. Thus, our results demonstrate that Bcl-2 is not only critical for the survival of androgen-independent prostate cancer cells, but is also required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage.
基金This work was partially supported by the National Institute of Health grants from NCI(R01CA201340)NEI(1R01EY028450).
文摘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 treatment.We further discuss the strategies to target and modify thetumor ECM to improve cancer therapy.
基金supported by the National Natural Science Foundation of China(Nos.82072930,82222055,32270971,82001822)Guangzhou Science and Technology Bureau(No.202201020576)+1 种基金111 project(No.B20056)the Guangdong Province Outstanding Youth Award(No.2021B1515020066).
文摘Neutrophils are recognized active participants in inflammatory responses and are intricately linked to cancer progression.In response to inflammatory stimuli,neutrophils become activated,releasing neutrophils extracellular traps(NETs)for the capture and eradication of pathogens,a phenomenon termed NETosis.With a deeper understanding of NETs,there is growing evidence supporting their role in cancer progression and their involvement in conferring resistance to various cancer therapies,especially concerning tumor reactions to chemotherapy,radiation therapy(RT),and immunotherapy.This review summarizes the roles of NETs in the tumor microenvironment(TME)and their mechanisms of neutrophil involvement in the host defense.Additionally,it elucidates the mechanisms through which NETs promote tumor progression and their role in cancer treatment resistance,highlighting their potential as promising therapeutic targets in cancer treatment and their clinical applicability.
基金supported by the Basic and Applied Basic Research Foundation of Guangdong Province(2022A1515220184)the Natural Science Foundation of Guangdong Province(2021A1515010547)。
文摘PIWI-interacting RNAs(pi RNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells.Recent studies have found that pi RNAs,as tissue-specific molecules,both play oncogenic and tumor suppressive roles in cancer progression,including cancer cell proliferation,metastasis,chemoresistance and stemness.Additionally,the atypical manifestation of pi RNAs and PIWI proteins in various malignancies presents a promising strategy for the identification of novel biomarkers and therapeutic targets in the diagnosis and management of tumors.Nonetheless,the precise functions of pi RNAs in cancer progression and their underlying mechanisms have yet to be fully comprehended.This review aims to examine current research on the biogenesis and functions of pi RNA and its burgeoning importance in cancer progression,thereby offering novel perspectives on the potential utilization of pi RNAs and piwi proteins in the management and treatment of advanced cancer.
基金supported by grants from the National Natural Science Foundation of China(11832008)the Fundamental Research Funds for the Central Universities(2023CDJXY-051)the Open Foundation of Guangdong Provincial Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors(2021B0303010151).
文摘Increased matrix stiffness is a common phenomenon in solid tumor tissue and is regulated by both tumor and mesenchymal cells.The increase in collagen and lysyl oxidase family proteins in the extracellular matrix leads to deposition,contraction,and crosslinking of the stroma,promoting increased matrix stiffness in tumors.Matrix stiffness is critical to the progression of various solid tumors.As a mechanical factor in the tumor microenvi-ronment,matrix stiffness is involved in tumor progression,promoting biological processes such as tumor cell proliferation,invasion,metastasis,angiogenesis,drug resistance,and immune escape.Reducing tissue stiffness can slow down tumor progression.Therefore targeting matrix stiffness is a potential option for tumor therapy.This article reviews the detailed mechanisms of matrix stiffness in different malignant tumor phenotypes and potential tumor therapies targeting matrix stiffness.Understanding the role and mechanisms of matrix stiffness in tumors could provide theoretical insights into the treatment of tumors and assist in the clinical development of new drug therapies.
文摘Subject Code:H16With the support by the National Natural Science Foundation of China,a study by the research groups led by Prof.Dong Chenfang(董辰方)from Zhejiang University School of Medicine demonstrates that AKR1B1promotes basal-like breast cancer progression by apositive feedback loop that activates the
文摘Gastric cancer(GC)is one of the most aggressive malignancies worldwide and is characterized by its poor prognosis and resistance to conventional therapies.Autophagy and long non-coding RNAs(lncRNAs)play critical yet complex roles in GC,functioning as both tumor suppressors and promoters depending on the disease stage and context.Autophagy influences cellular homeostasis and metabolism,whereas lncRNAs regulate gene expression through epigenetic modifications,RNA sponging,and protein interactions.Notably,the interplay between lncRNAs and autophagy modulates tumor progression,metastasis,chemoresistance,and the tumor microenvironment.This study explored the intricate relationship between lncRNAs and autophagy in GC,highlighting their roles in pathogenesis and treatment resistance.By addressing current knowledge gaps and proposing innovative therapeutic strategies,we have emphasized the potential of targeting this dynamic interplay for improved diagnostic and therapeutic outcomes.
基金supported by the National Natural Science Foundation of China(82002612,82170029)the Fundamental Research Funds for the Central Universities,the College Students’Innovation and Entrepreneurship Training Program(202311512)+1 种基金the Macao Polytechnic University(RP/FCA-14/2023)the Science and Technology Development Fund of Macao(FDCT,0033/2023/RIB2).
文摘Recent advances in next-generation sequencing and bioinformatics have driven growing interest in the distinct roles of intratumoral microbiota,particularly intracellular bacteria,during tumor evolution.These bacteria increase the likelihood of metastasis,play important roles in cancer progression,and impact therapy efficiency.The present review explores the sources,mechanisms of invasion into cancer cells,and potential survival strategies of intracellular bacteria in neoplasms,highlighting their critical role in cancer development.We also examine the heterogeneity and intricate interplay of intratumoral microbial communities with immune and cancer cells,emphasizing their potential roles in modulating host genetics,epigenetics,and immunity.Finally,we discuss novel approaches to targeting intracellular bacteria,particularly engineered drug delivery systems,and synthetic biology,which aim to enhance bacterial clearance,reprogram the tumor immune microenvironment,and enhance the efficacy of chemotherapy and immunotherapy.As a result,this review provides new insights to guide future investigations and support the development of microbiota-based interventions in oncology.
基金Supported by Xinjiang Uygur Autonomous Region Natural Science Foundation,No.2020D01C199.
文摘BACKGROUND Gastric cancer(GC)poses a substantial risk to human health due to its high prevalence and mortality rates.Nevertheless,current therapeutic strategies remain insufficient.Single-cell RNA sequencing(scRNA-seq)offers the potential to provide comprehensive insights into GC pathogenesis.AIM To explore the distribution and dynamic changes of cell populations in the GC tumor microenvironment using scRNA-seq techniques.METHODS Cancerous tissues and paracancerous tissues were obtained from patients diagnosed with GC at various stages(I,II,III,and IV).Single-cell suspensions were prepared and analyzed using scRNA-seq to examine transcriptome profiles and cell-cell interactions.Additionally,quantitative real-time polymerase chain reaction(qRT-PCR)and flow cytometry were applied for measuring the expression of cluster of differentiation(CD)2,CD3D,CD3E,cytokeratin 19,cytokeratin 8,and epithelial cell adhesion molecules.RESULTS Transcriptome data from 73645 single cells across eight tissues of four patients were categorized into 25 distinct cell clusters,representing 10 different cell types.Variations were observed in these cell type distribution.The adjacent epithelial cells in stages II and III exhibited a degenerative trend.Additionally,the quantity of CD4 T cells and CD8 T cells were evidently elevated in cancerous tissues.Interaction analysis displayed a remarkable increase in interaction between B cells and other mast cells in stages II,III,and IV of GC.These findings were further validated through qRT-PCR and flow cytometry,demonstrating elevated T cells and declined epithelial cells within the cancerous tissues.CONCLUSION This study provides a comprehensive analysis of cell dynamics across GC stages,highlighting key interactions within the tumor microenvironment.These findings offer valuable insights for developing novel therapeutic strategies.
基金National Natural Science Foundation of China,No.82372194.
文摘BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA progression through the ERK1/2 signaling cascade.AIM To determine the mechanism of the IL-22/IL-22R1 pathway in CCA and provide new directions for its clinical treatment.METHODS IL-22R1 expression was assessed in human and rat CCA tissues utilizing immunohistochemical techniques,Western blot analysis,and quantitative reverse transcription PCR.The impact of IL-22 on CCA cells was assessed in vitro via tests for proliferation,migration,invasion,and apoptosis assays.The rat models of thioacetamide-induced CCA and subcutaneous xenografts in nude mice were used to assess the in vivo effects.ERK1/2 inhibitors were applied to elucidate the mechanistic role of the pathway.RESULTS IL-22R1 was overexpressed in CCA cell lines and tissues.IL-22 treatment increased the phosphorylation of ERK1/2,promoting tumor cell proliferation,migration,invasion,and resistance to apoptosis.ERK1/2 inhibition considerably reversed these effects both in vitro and in vivo.CONCLUSION The IL-22/IL-22R1 axis promotes CCA progression by activating ERK1/2 signaling.Targeting this pathway with ERK1/2 inhibitors offers potential therapeutic strategies for CCA.
