Objective:To investigate the effects of arecoline on HPV-positive cervical cells and unveil its underlying mechanism in cervical carcinogenesis.Methods:The cytotoxicity of arecoline was determined and the effect of su...Objective:To investigate the effects of arecoline on HPV-positive cervical cells and unveil its underlying mechanism in cervical carcinogenesis.Methods:The cytotoxicity of arecoline was determined and the effect of subtoxic concentrations of arecoline on the expression of viral oncoproteins and transcriptional factors was examined in CaSki and SiHa cells.HPV16 promoter activity was evaluated in a plasmid containing HPV16 long control region(pGL3-HPV16LCR)-transfected cells.Cell proliferation,cell migration,and number of colonies were assessed by MTT,wound healing assay,and colony-forming assay,respectively.Results:Arecoline at 0.01μg/mL significantly upregulated HPV16 E6 and E7 oncoproteins in both CaSki and SiHa cells.It also upregulated the expression level of c-Fos and c-Jun mRNAs,and c-Myc protein in CaSki and SiHa cells.In addition,arecoline at subtoxic concentrations(0.0025 and 0.01μg/mL)significantly induced HPV16 promoter activity in pGL3-16LCR-transfected cells.It also promoted SiHa and CaSki cell proliferation,migration,and colony formation.Conclusions:Arecoline at subtoxic concentrations promotes the proliferation,migration,and colony formation of CaSki and SiHa cells via upregulation of c-Fos,c-Jun,c-Myc,and HPV16 E6 and E7 expressions.展开更多
Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instea...Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instead integrate their genetic material into the host genome thus,affecting cell cycle and tumor suppression.This deregulation also leads to impaired immune function and promotes tumor progression by disrupting the removal of infected cells.Generally,innate immunity consists of two important members,including mitochondria and cell deaths,which impact each other as well.Due to the close correlation between viruses,cell death pathways(apoptosis,necroptosis,and pyroptosis),and mitochondria(mitochondrial antiviral-signaling protein and reactive oxygen species generation),targeting these immune system representatives may offer therapeutic strategies to control the progression of oncogenic viral infections.Some previous studies have covered the association of oncogenic viruses with mitochondria and cell death pathways,respectively,but mitochondria and cell death interact with each other,separately,and this interaction may play a role in the progression of cancer induced by oncogenic viruses.Hence,the purpose of this review is to discuss the relationship between cell death,mitochondria,and viral oncogenesis,focusing on the most surveyed oncogenic viruses’mechanisms of action.展开更多
This editorial comments on the review by Da Silva et al,published in the World Journal of Clinical Oncology which focuses on the molecular perspectives of lung cancer.With the rapid development of molecular technology...This editorial comments on the review by Da Silva et al,published in the World Journal of Clinical Oncology which focuses on the molecular perspectives of lung cancer.With the rapid development of molecular technology,new diagnostic methods are constantly emerging,including liquid biopsy,the identification of gene mutations,and the monitoring biomarkers,thus providing precise in-formation with which to identify the occurrence and development of lung cancer.Biomarkers,such as circulating tumor cells,circulating tumor DNA,and cir-culating RNA can provide helpful information for clinical application.Common types of genetic mutations and immune checkpoints include epidermal growth factor receptor,anaplastic lymphoma kinase,c-ROS proto-oncogene 1,progra-mmed death-1 and cytotoxic T-lymphocyte-associated protein.According to specific biomarkers,targeted therapy and immunotherapy can improve survival outcomes based on the types of gene mutation and immune checkpoints.The application of molecular approaches can facilitate our ability to control the progression of disease and select appropriate therapeutic strategies for patients with lung cancer.展开更多
Melanoma is an aggressive type of skin cancer notorious for its resistance to chemotherapy,radiotherapy and immunotherapy,which greatly impacts its lethality.The hedgehog(HH)signaling cascade,originally known for its ...Melanoma is an aggressive type of skin cancer notorious for its resistance to chemotherapy,radiotherapy and immunotherapy,which greatly impacts its lethality.The hedgehog(HH)signaling cascade,originally known for its roles in embryonic development,regulates growth,proliferation and cancer stem cell(CSC)self-renewal.The glioma-associated oncogene homolog(GLI)transcription factors play crucial roles in melanoma.However,oncogenic B-Raf proto-oncogene,serine/threonine kinase(BRAF)steals the spotlight by driving the aberrant activation of HH-GLI1/2 signaling.Oncogenic BRAF-driven HH-GLI1/2 signaling imparts invasive phenotype to melanoma cells and sustains CSC self-renewal.Interestingly,the transcriptional activities of GLI1 and GLI2 are suppressed by acetylation,a process that is counteracted by the deacetylating actions of histone deacetylase(HDAC)1/2.Therefore,inhibiting HDAC1/2 might keep GLI proteins in inactive acetylated form,thus representing an attractive druggable target.Notably,both HDAC1 and HDAC2 are induced by HH signaling,creating a positive feedback loop where HH signaling upregulates the expression of both HDAC1 and HDAC2.Selective inhibition of BRAF/HH/HDAC/GLI signaling axis is likely to unravel new therapeutic opportunities in melanoma.However,the precise contribution of oncogenic BRAF-driven HH signaling to therapy resistance and CSC renewal remains unclear and requires thorough investigation.In this article,we endeavored to explore the crosstalk between oncogenic BRAF and HH signaling,and the pivotal role this interaction plays in the self-renewal of melanoma stem cells.A better understanding of the molecular mechanisms governing these interactions is essential for improving melanoma treatment strategies and identifying new therapeutic targets.展开更多
The dysregulation of cyclin-dependent kinase 12(CDK12),which may result from genomic alterations or modulation by upstream effectors,is implicated in cancer oncogenesis and progression.CDK12 overexpression or activati...The dysregulation of cyclin-dependent kinase 12(CDK12),which may result from genomic alterations or modulation by upstream effectors,is implicated in cancer oncogenesis and progression.CDK12 overexpression or activation is sufficient to induce tumor initiation,recurrence,and therapeutic resistance.However,CDK12 may also exert tumor-suppressive functions in a context-dependent manner.Therefore,caution is warranted when targeting CDK12 in future clinical trials.A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance precision oncology.This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer.Subsequently,we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts.Finally,we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology,offering insights into future directions for innovative cancer treatment strategies.展开更多
Lipid metabolism plays a pivotal role in gastric cancer(GC)progression,characterized by complex metabolic reprogramming that supports tumor growth and survival.This narrative review comprehensively examines the dysreg...Lipid metabolism plays a pivotal role in gastric cancer(GC)progression,characterized by complex metabolic reprogramming that supports tumor growth and survival.This narrative review comprehensively examines the dysregulation of lipid metabolism-associated genes,including fatty acid synthase(FASN),ATPcitrate lyase,acetyl-CoA carboxylases,FA binding proteins,sterol regulatory element-binding proteins,and other key enzymes.These genes facilitate critical oncogenic processes by enhancing FA synthesis,modifying cellular signaling,and supporting cancer cell proliferation,migration,and therapy resistance.Metabolic adaptations observed in GC include increased de novo lipogenesis,altered enzymatic activities,and modified protein lipidation,which contribute to tumor aggressiveness.The review highlights the potential of targeting these metabolic pathways as a therapeutic strategy,demonstrating how inhibiting specific enzymes like FASN,ATP-citrate lyase,and stearoyl-CoA desaturase 1 can induce apoptosis,disrupt cancer stem cell properties,and potentially overcome treatment resistance.By elucidating the intricate interactions between lipid metabolism genes and cancer progression,this review provides insights into novel diagnostic and therapeutic approaches for managing GC.展开更多
Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed ...Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.展开更多
In the article“Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene”(Oncology Research.2024,Vol.32,No.7,pp.1185–1195.doi:10....In the article“Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene”(Oncology Research.2024,Vol.32,No.7,pp.1185–1195.doi:10.32604/or.2023.030771,https://www.techscience.com/or/v32n7/57163),an inadvertent error occurred during the compilation of Fig.3H.This needed corrections to ensure the accuracy and integrity of the data presented.展开更多
BACKGROUND Krüppel-like factor-5(KLF5)is a zinc-finger transcription factor related to tumor progression.However,the relationship between KLF5 and lung cancer remains to be identified.AIM To investigate the clini...BACKGROUND Krüppel-like factor-5(KLF5)is a zinc-finger transcription factor related to tumor progression.However,the relationship between KLF5 and lung cancer remains to be identified.AIM To investigate the clinical value of KLF5 and interference with KLF5 mRNA transcription on the effects of biological behaviors in lung squamous-cell carcinoma(LUSC).METHODS Lung KLF5 mRNA data were extracted from bioinformatics databases.Blood and tissues from a cohort of patients with benign or malignant lung diseases were collected with ethical committee consent to validate KLF5 expression via multiplex immunofluorescence and immunohistochemistry,Western blot,Enzyme Linked Immunosorbent Assay or quantitative polymerase chain reaction.Furthermore,KLF5 mRNA was silenced in lung A549 cells to validate biological behaviors in vitro and nude mouse xenograft growth in vivo,respectively.RESULTS A cohort of bioinformatics databases revealed high KLF5 mRNA expression in LUSC(P<0.001)but lower KLF5 mRNA expression in lung adenocarcinoma.Upregulated KLF5 in the lung or sera of patients with lung cancer(P<0.001)were confirmed that related to poor differentiation,lymph node or distant metastasis.Furthermore,the incidence of KLF5 levels greater than 500 ng/mL in LUSC patients was 86.7%,which was significantly greater(P<0.001)than that in cases with benign lung diseases(13.3%)or healthy controls.Functionally,silencing KLF5 mRNA with a specific shRNA significantly suppressed A549 cell proliferation,decreased cell migration,increased the ratio of G2 phase cells in vitro,and inhibited the growth of nude mouse xenografts in vivo.CONCLUSION KLF5 is a novel diagnostic biomarker or potential therapeutic target for LUSC.展开更多
Objective To evaluate the expression pattern of non-SMC condensin II complex subunit D3(NCAPD3)in hepatocellular carcinoma(HCC)tissues,assess its association with clinical characteristics,and explore the effects of NC...Objective To evaluate the expression pattern of non-SMC condensin II complex subunit D3(NCAPD3)in hepatocellular carcinoma(HCC)tissues,assess its association with clinical characteristics,and explore the effects of NCAPD3 on HCC cells and the potential underlying mechanisms.Methods NCAPD3 expression in HCC tumors and adjacent noncancerous tissues was quantified via quantitative PCR.Patients were divided into high-and low-expression groups on the basis of NCAPD3 levels,and associations with clinical parameters were assessed.The effects of NCAPD3 knockdown and the phosphatidylinositol-3-kinase(PI3K)agonist Y-P 740 on cell functions were examined via cell proliferation,Transwell migration,and invasion assays.Differentially expressed genes following NCAPD3 knockdown in SMMC-7721 cells were identified via mRNA sequencing.Western blotting was performed to measure NCAPD3,AKT serine/threonine kinase 1(AKT1),and phosphorylated AKT1 levels.Results NCAPD3 mRNA expression was notably upregulated in HCC tissues as compared with that in adjacent noncancer tissues.A positive correlation was observed between NCAPD3 expression and both lymphatic and distant metastases in patients with HCC.NCAPD3 knockdown reduced the proliferation and metastasis of SMMC-7721 and Huh-7 cells.mRNA sequencing revealed 140 downregulated genes and 125 upregulated genes.Further validation experiments confirmed that NCAPD3 modulated the PI3K-AKT signalling pathway and that the PI3K agonist Y-P 740 counteracted the effects of NCAPD3 knockdown.Conclusions Elevated NCAPD3 expression was strongly correlated with HCC metastasis.NCAPD3 inhibition impedes HCC cell growth and metastatic potential by suppressing the PI3K–AKT signalling pathway.展开更多
BACKGROUND Over 150000 new diagnoses of colorectal cancer(CRC)are diagnosed yearly,and 1 in 5 patients have distant metastases on diagnosis.Previous estimates approximate that brain metastases(BM)occur in 0.6%to 3.2%o...BACKGROUND Over 150000 new diagnoses of colorectal cancer(CRC)are diagnosed yearly,and 1 in 5 patients have distant metastases on diagnosis.Previous estimates approximate that brain metastases(BM)occur in 0.6%to 3.2%of patients with CRC.AIM To describe the updated literature about the incidence and risk factors of BM in CRC as well as their treatment with surgery,chemotherapy,and radiation.METHODS We systematically searched the literature published between January 1,2010 and April 1,2025 in PubMed,Cochrane,Scopus,and EMBASE.All studies about BM from CRC were included.Studies only containing information about the treatment of primary CRC or primary brain tumors were not included.Articles were categorized and described as incidence,surgery,chemotherapy,or radiation to provide an overview of the state of research on BM from CRC.RESULTS Our primary search resulted in 1648 articles that were eventually screened to 147.These articles were analyzed to provide the state of current literature on incidence and risk factors of BM from CRC as well as how these metastases are treated with chemotherapy,radiation,and surgery.CONCLUSION Prognosis is influenced by tumor burden,performance status,and emerging molecular markers.Stereotactic radiotherapy and surgical resection provide favorable outcomes for select patients,whereas chemotherapy and immunotherapy remain areas of limited evidence.Continued research is needed to identify highrisk patients and optimize multidisciplinary treatment approaches.展开更多
Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal ma-lignancies with limited treatment efficacy.Advances in precision oncology,enabled by next-generation sequencing,have highlighted key molecular ta...Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal ma-lignancies with limited treatment efficacy.Advances in precision oncology,enabled by next-generation sequencing,have highlighted key molecular targets.Kirsten rat sarcoma viral oncogene homolog mutations,present in up to 90%of cases,drive aggressive biology,though most variants remain undruggable;allele-specific inhibitors and exosome-based RNA interference are under exploration.Breast cancer susceptibility gene 1/2 mutations occur in 4%-7%of patients,con-ferring sensitivity to platinum agents and poly(ADP-ribose)polymerase inhi-bitors.Other rare but actionable alterations-such as v-raf murine sarcoma viral oncogene homolog B1(V600),neurotrophic tyrosine receptor kinase,fibroblast growth factor receptor 2,and RET fusions-show benefit in tumor-agnostic trials,broadening options for selected subgroups.Immunotherapy is limited,as high tumor mutational burden and mismatch repair deficiency are uncommon in PDAC,though predictive when present.Co-mutations in tumor protein p53,cyclin-dependent kinase inhibitor 2A,and SMAD4 further stratify prognosis and influence therapy response.Cross-cancer analyses underscore the necessity of PDAC-specific strategies despite shared genomic drivers.Collectively,these insights support routine germline and somatic testing,enrollment in biomarker-matched trials,and rational combination strategies,establishing molecular profiling as central to advancing precision treatment in pancreatic cancer.展开更多
Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(HBV) and/or hepatitis C virus(HCV) is a major risk factor in the development of ...Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(HBV) and/or hepatitis C virus(HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.展开更多
Objective To construct hu-PBL/SCID chimeras and to investigate the development of lymphoma and oncogenicity of the Epstein-Barr virus (EBV). Methods Human peripheral blood lymphocytes (PBLs) were isolated from healthy...Objective To construct hu-PBL/SCID chimeras and to investigate the development of lymphoma and oncogenicity of the Epstein-Barr virus (EBV). Methods Human peripheral blood lymphocytes (PBLs) were isolated from healthy adult donors and transplanted intraperitoneally into severe combined immunodeficient(SCID) mice. Mice with hu-PBL engraftment from healthy EBV seronegative donors were injected intraperitoneally with EBV-containing supernatant from suspension culture of B95-8 cell line (active infection), whereas mice receiving lymphocytes from healthy EBV seropositive donors were not re-infected with B95-8 derived EBV (latent infection). Pathological examination and molecular analysis were performed on experime-ntal animals and induced neoplasms. Results In the early stage of this experiment, 12 mice died of acute graft-versus-host disease, mortality was 34.3% (12/35 mice) with an average life span of 17.5 days. In 19 survival hu-PBL/SCID chimeric recipients from 12 healthy donors, tumor incidence was 84.2% (16/19 mice). The average survival time of tumor-bearing mice was 65.5 days. EBV-related neoplasms in SCID mice were nodular tumors with aggressive and fatal features. Histological morphology of tumors exhibited diffuse large cell lymphomas. Immunohistochemistry revealed that LCA (CD45) and L26 (CD20) were positive, but both PS1 (CD3) and UCHL-1 (CD45RO) were negative, and EBV products ZEBRA, LMP1, and EBNA2 were expressed in a small number of tumor cells. EB virus particles were seen in the nuclei of some tumor cells by electron microscopy, and EBV DNA could be amplified in the tumor tissues by PCR. In situ hybridization indicated that the nuclei of tumor cells contained human-specific Alu sequence. Conclusions EBV-induced tumors were human B-cell malignant lymphomas. We obtained direct causative evidence dealing with EBV-associated tumor deriving from normal human cells.展开更多
AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto dete...AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.展开更多
Hepatocellular carcinoma(HCC) is a primary cancer of the liver that is predominant in developing countries and is responsible for nearly 600000 deaths each year worldwide. Similar to many other tumors, the development...Hepatocellular carcinoma(HCC) is a primary cancer of the liver that is predominant in developing countries and is responsible for nearly 600000 deaths each year worldwide. Similar to many other tumors, the development of HCC must be understood as a multistep process involving the accumulation of genetic and epigenetic alterations in regulatory genes, leading to the activation of oncogenes and the inactivation or loss of tumor suppressor genes. Extensive research over the past decade has identified a number of molecular biomarkers, including aberrant expression of HCCrelated genes and microRNAs. The challenge facing HCC research and clinical care at this time is to address the heterogeneity and complexity of these genetic and epigenetic alterations and to use this information to direct rational diagnosis and treatment strategies. The multikinase inhibitor sorafenib was the first molecularly targeted drug for HCC to show some extent of survival benefits in patients with advanced tumors. Although the results obtained using sorafenib support the importance of molecular therapies in the treatment of HCC, there is still room for improvement. In addition,no molecular markers for drug sensitivity, recurrence and prognosis are currently clinically available. In this review, we provide an overview of recently published articles addressing HCC-related genes and microRNAs to update what is currently known regarding genetic and epigenetic aspects of the pathogenesis of HCC and propose novel promising candidates for use as diagnostic and therapeutic targets in HCC.展开更多
文摘Objective:To investigate the effects of arecoline on HPV-positive cervical cells and unveil its underlying mechanism in cervical carcinogenesis.Methods:The cytotoxicity of arecoline was determined and the effect of subtoxic concentrations of arecoline on the expression of viral oncoproteins and transcriptional factors was examined in CaSki and SiHa cells.HPV16 promoter activity was evaluated in a plasmid containing HPV16 long control region(pGL3-HPV16LCR)-transfected cells.Cell proliferation,cell migration,and number of colonies were assessed by MTT,wound healing assay,and colony-forming assay,respectively.Results:Arecoline at 0.01μg/mL significantly upregulated HPV16 E6 and E7 oncoproteins in both CaSki and SiHa cells.It also upregulated the expression level of c-Fos and c-Jun mRNAs,and c-Myc protein in CaSki and SiHa cells.In addition,arecoline at subtoxic concentrations(0.0025 and 0.01μg/mL)significantly induced HPV16 promoter activity in pGL3-16LCR-transfected cells.It also promoted SiHa and CaSki cell proliferation,migration,and colony formation.Conclusions:Arecoline at subtoxic concentrations promotes the proliferation,migration,and colony formation of CaSki and SiHa cells via upregulation of c-Fos,c-Jun,c-Myc,and HPV16 E6 and E7 expressions.
文摘Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instead integrate their genetic material into the host genome thus,affecting cell cycle and tumor suppression.This deregulation also leads to impaired immune function and promotes tumor progression by disrupting the removal of infected cells.Generally,innate immunity consists of two important members,including mitochondria and cell deaths,which impact each other as well.Due to the close correlation between viruses,cell death pathways(apoptosis,necroptosis,and pyroptosis),and mitochondria(mitochondrial antiviral-signaling protein and reactive oxygen species generation),targeting these immune system representatives may offer therapeutic strategies to control the progression of oncogenic viral infections.Some previous studies have covered the association of oncogenic viruses with mitochondria and cell death pathways,respectively,but mitochondria and cell death interact with each other,separately,and this interaction may play a role in the progression of cancer induced by oncogenic viruses.Hence,the purpose of this review is to discuss the relationship between cell death,mitochondria,and viral oncogenesis,focusing on the most surveyed oncogenic viruses’mechanisms of action.
文摘This editorial comments on the review by Da Silva et al,published in the World Journal of Clinical Oncology which focuses on the molecular perspectives of lung cancer.With the rapid development of molecular technology,new diagnostic methods are constantly emerging,including liquid biopsy,the identification of gene mutations,and the monitoring biomarkers,thus providing precise in-formation with which to identify the occurrence and development of lung cancer.Biomarkers,such as circulating tumor cells,circulating tumor DNA,and cir-culating RNA can provide helpful information for clinical application.Common types of genetic mutations and immune checkpoints include epidermal growth factor receptor,anaplastic lymphoma kinase,c-ROS proto-oncogene 1,progra-mmed death-1 and cytotoxic T-lymphocyte-associated protein.According to specific biomarkers,targeted therapy and immunotherapy can improve survival outcomes based on the types of gene mutation and immune checkpoints.The application of molecular approaches can facilitate our ability to control the progression of disease and select appropriate therapeutic strategies for patients with lung cancer.
基金Supported by the Science and Engineering Research Board,No.PDF/2016/002730.
文摘Melanoma is an aggressive type of skin cancer notorious for its resistance to chemotherapy,radiotherapy and immunotherapy,which greatly impacts its lethality.The hedgehog(HH)signaling cascade,originally known for its roles in embryonic development,regulates growth,proliferation and cancer stem cell(CSC)self-renewal.The glioma-associated oncogene homolog(GLI)transcription factors play crucial roles in melanoma.However,oncogenic B-Raf proto-oncogene,serine/threonine kinase(BRAF)steals the spotlight by driving the aberrant activation of HH-GLI1/2 signaling.Oncogenic BRAF-driven HH-GLI1/2 signaling imparts invasive phenotype to melanoma cells and sustains CSC self-renewal.Interestingly,the transcriptional activities of GLI1 and GLI2 are suppressed by acetylation,a process that is counteracted by the deacetylating actions of histone deacetylase(HDAC)1/2.Therefore,inhibiting HDAC1/2 might keep GLI proteins in inactive acetylated form,thus representing an attractive druggable target.Notably,both HDAC1 and HDAC2 are induced by HH signaling,creating a positive feedback loop where HH signaling upregulates the expression of both HDAC1 and HDAC2.Selective inhibition of BRAF/HH/HDAC/GLI signaling axis is likely to unravel new therapeutic opportunities in melanoma.However,the precise contribution of oncogenic BRAF-driven HH signaling to therapy resistance and CSC renewal remains unclear and requires thorough investigation.In this article,we endeavored to explore the crosstalk between oncogenic BRAF and HH signaling,and the pivotal role this interaction plays in the self-renewal of melanoma stem cells.A better understanding of the molecular mechanisms governing these interactions is essential for improving melanoma treatment strategies and identifying new therapeutic targets.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82260718,82460716 and 82111530101)Natural Science Foundation of Jiangxi Province,China(Grant Nos.:20224BAB216121,20232BAB216137 and 20242BAB25579)+1 种基金Jiangxi Provincial Thousand Talents Training Program for High Level Entrepreneurial and Innovative Talents,China(Program No.:jxsq2019201106)Ganzhou“Taking the Lead”Youth Project of Technology Innovation Empowerment(Project No.:JBGS20230001).
文摘The dysregulation of cyclin-dependent kinase 12(CDK12),which may result from genomic alterations or modulation by upstream effectors,is implicated in cancer oncogenesis and progression.CDK12 overexpression or activation is sufficient to induce tumor initiation,recurrence,and therapeutic resistance.However,CDK12 may also exert tumor-suppressive functions in a context-dependent manner.Therefore,caution is warranted when targeting CDK12 in future clinical trials.A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance precision oncology.This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer.Subsequently,we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts.Finally,we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology,offering insights into future directions for innovative cancer treatment strategies.
文摘Lipid metabolism plays a pivotal role in gastric cancer(GC)progression,characterized by complex metabolic reprogramming that supports tumor growth and survival.This narrative review comprehensively examines the dysregulation of lipid metabolism-associated genes,including fatty acid synthase(FASN),ATPcitrate lyase,acetyl-CoA carboxylases,FA binding proteins,sterol regulatory element-binding proteins,and other key enzymes.These genes facilitate critical oncogenic processes by enhancing FA synthesis,modifying cellular signaling,and supporting cancer cell proliferation,migration,and therapy resistance.Metabolic adaptations observed in GC include increased de novo lipogenesis,altered enzymatic activities,and modified protein lipidation,which contribute to tumor aggressiveness.The review highlights the potential of targeting these metabolic pathways as a therapeutic strategy,demonstrating how inhibiting specific enzymes like FASN,ATP-citrate lyase,and stearoyl-CoA desaturase 1 can induce apoptosis,disrupt cancer stem cell properties,and potentially overcome treatment resistance.By elucidating the intricate interactions between lipid metabolism genes and cancer progression,this review provides insights into novel diagnostic and therapeutic approaches for managing GC.
文摘Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.
文摘In the article“Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene”(Oncology Research.2024,Vol.32,No.7,pp.1185–1195.doi:10.32604/or.2023.030771,https://www.techscience.com/or/v32n7/57163),an inadvertent error occurred during the compilation of Fig.3H.This needed corrections to ensure the accuracy and integrity of the data presented.
基金Supported by Jiangsu Commission of Health of China,No.M2020096.
文摘BACKGROUND Krüppel-like factor-5(KLF5)is a zinc-finger transcription factor related to tumor progression.However,the relationship between KLF5 and lung cancer remains to be identified.AIM To investigate the clinical value of KLF5 and interference with KLF5 mRNA transcription on the effects of biological behaviors in lung squamous-cell carcinoma(LUSC).METHODS Lung KLF5 mRNA data were extracted from bioinformatics databases.Blood and tissues from a cohort of patients with benign or malignant lung diseases were collected with ethical committee consent to validate KLF5 expression via multiplex immunofluorescence and immunohistochemistry,Western blot,Enzyme Linked Immunosorbent Assay or quantitative polymerase chain reaction.Furthermore,KLF5 mRNA was silenced in lung A549 cells to validate biological behaviors in vitro and nude mouse xenograft growth in vivo,respectively.RESULTS A cohort of bioinformatics databases revealed high KLF5 mRNA expression in LUSC(P<0.001)but lower KLF5 mRNA expression in lung adenocarcinoma.Upregulated KLF5 in the lung or sera of patients with lung cancer(P<0.001)were confirmed that related to poor differentiation,lymph node or distant metastasis.Furthermore,the incidence of KLF5 levels greater than 500 ng/mL in LUSC patients was 86.7%,which was significantly greater(P<0.001)than that in cases with benign lung diseases(13.3%)or healthy controls.Functionally,silencing KLF5 mRNA with a specific shRNA significantly suppressed A549 cell proliferation,decreased cell migration,increased the ratio of G2 phase cells in vitro,and inhibited the growth of nude mouse xenografts in vivo.CONCLUSION KLF5 is a novel diagnostic biomarker or potential therapeutic target for LUSC.
基金supported by grants from Guangxi Nanning Qingxiu District Key Research and Development Program of Science and Technology Plan(no.2020050)Guangxi Medical and Health Appropriate Technology Development,Promotion and Application Project(no.S2021097)+1 种基金Guangxi Key Research and Development Program(no.AB22080064)Guangxi Natural Science Foundation(no.2017GXNSFAA198126).
文摘Objective To evaluate the expression pattern of non-SMC condensin II complex subunit D3(NCAPD3)in hepatocellular carcinoma(HCC)tissues,assess its association with clinical characteristics,and explore the effects of NCAPD3 on HCC cells and the potential underlying mechanisms.Methods NCAPD3 expression in HCC tumors and adjacent noncancerous tissues was quantified via quantitative PCR.Patients were divided into high-and low-expression groups on the basis of NCAPD3 levels,and associations with clinical parameters were assessed.The effects of NCAPD3 knockdown and the phosphatidylinositol-3-kinase(PI3K)agonist Y-P 740 on cell functions were examined via cell proliferation,Transwell migration,and invasion assays.Differentially expressed genes following NCAPD3 knockdown in SMMC-7721 cells were identified via mRNA sequencing.Western blotting was performed to measure NCAPD3,AKT serine/threonine kinase 1(AKT1),and phosphorylated AKT1 levels.Results NCAPD3 mRNA expression was notably upregulated in HCC tissues as compared with that in adjacent noncancer tissues.A positive correlation was observed between NCAPD3 expression and both lymphatic and distant metastases in patients with HCC.NCAPD3 knockdown reduced the proliferation and metastasis of SMMC-7721 and Huh-7 cells.mRNA sequencing revealed 140 downregulated genes and 125 upregulated genes.Further validation experiments confirmed that NCAPD3 modulated the PI3K-AKT signalling pathway and that the PI3K agonist Y-P 740 counteracted the effects of NCAPD3 knockdown.Conclusions Elevated NCAPD3 expression was strongly correlated with HCC metastasis.NCAPD3 inhibition impedes HCC cell growth and metastatic potential by suppressing the PI3K–AKT signalling pathway.
文摘BACKGROUND Over 150000 new diagnoses of colorectal cancer(CRC)are diagnosed yearly,and 1 in 5 patients have distant metastases on diagnosis.Previous estimates approximate that brain metastases(BM)occur in 0.6%to 3.2%of patients with CRC.AIM To describe the updated literature about the incidence and risk factors of BM in CRC as well as their treatment with surgery,chemotherapy,and radiation.METHODS We systematically searched the literature published between January 1,2010 and April 1,2025 in PubMed,Cochrane,Scopus,and EMBASE.All studies about BM from CRC were included.Studies only containing information about the treatment of primary CRC or primary brain tumors were not included.Articles were categorized and described as incidence,surgery,chemotherapy,or radiation to provide an overview of the state of research on BM from CRC.RESULTS Our primary search resulted in 1648 articles that were eventually screened to 147.These articles were analyzed to provide the state of current literature on incidence and risk factors of BM from CRC as well as how these metastases are treated with chemotherapy,radiation,and surgery.CONCLUSION Prognosis is influenced by tumor burden,performance status,and emerging molecular markers.Stereotactic radiotherapy and surgical resection provide favorable outcomes for select patients,whereas chemotherapy and immunotherapy remain areas of limited evidence.Continued research is needed to identify highrisk patients and optimize multidisciplinary treatment approaches.
文摘Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal ma-lignancies with limited treatment efficacy.Advances in precision oncology,enabled by next-generation sequencing,have highlighted key molecular targets.Kirsten rat sarcoma viral oncogene homolog mutations,present in up to 90%of cases,drive aggressive biology,though most variants remain undruggable;allele-specific inhibitors and exosome-based RNA interference are under exploration.Breast cancer susceptibility gene 1/2 mutations occur in 4%-7%of patients,con-ferring sensitivity to platinum agents and poly(ADP-ribose)polymerase inhi-bitors.Other rare but actionable alterations-such as v-raf murine sarcoma viral oncogene homolog B1(V600),neurotrophic tyrosine receptor kinase,fibroblast growth factor receptor 2,and RET fusions-show benefit in tumor-agnostic trials,broadening options for selected subgroups.Immunotherapy is limited,as high tumor mutational burden and mismatch repair deficiency are uncommon in PDAC,though predictive when present.Co-mutations in tumor protein p53,cyclin-dependent kinase inhibitor 2A,and SMAD4 further stratify prognosis and influence therapy response.Cross-cancer analyses underscore the necessity of PDAC-specific strategies despite shared genomic drivers.Collectively,these insights support routine germline and somatic testing,enrollment in biomarker-matched trials,and rational combination strategies,establishing molecular profiling as central to advancing precision treatment in pancreatic cancer.
文摘Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(HBV) and/or hepatitis C virus(HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.
基金Supportedby the National Natural Science Foundation of China(39730200) and by a specialgrantfrom Departmentof Education,Hunan Province(02B040 ).
文摘Objective To construct hu-PBL/SCID chimeras and to investigate the development of lymphoma and oncogenicity of the Epstein-Barr virus (EBV). Methods Human peripheral blood lymphocytes (PBLs) were isolated from healthy adult donors and transplanted intraperitoneally into severe combined immunodeficient(SCID) mice. Mice with hu-PBL engraftment from healthy EBV seronegative donors were injected intraperitoneally with EBV-containing supernatant from suspension culture of B95-8 cell line (active infection), whereas mice receiving lymphocytes from healthy EBV seropositive donors were not re-infected with B95-8 derived EBV (latent infection). Pathological examination and molecular analysis were performed on experime-ntal animals and induced neoplasms. Results In the early stage of this experiment, 12 mice died of acute graft-versus-host disease, mortality was 34.3% (12/35 mice) with an average life span of 17.5 days. In 19 survival hu-PBL/SCID chimeric recipients from 12 healthy donors, tumor incidence was 84.2% (16/19 mice). The average survival time of tumor-bearing mice was 65.5 days. EBV-related neoplasms in SCID mice were nodular tumors with aggressive and fatal features. Histological morphology of tumors exhibited diffuse large cell lymphomas. Immunohistochemistry revealed that LCA (CD45) and L26 (CD20) were positive, but both PS1 (CD3) and UCHL-1 (CD45RO) were negative, and EBV products ZEBRA, LMP1, and EBNA2 were expressed in a small number of tumor cells. EB virus particles were seen in the nuclei of some tumor cells by electron microscopy, and EBV DNA could be amplified in the tumor tissues by PCR. In situ hybridization indicated that the nuclei of tumor cells contained human-specific Alu sequence. Conclusions EBV-induced tumors were human B-cell malignant lymphomas. We obtained direct causative evidence dealing with EBV-associated tumor deriving from normal human cells.
文摘AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.
文摘Hepatocellular carcinoma(HCC) is a primary cancer of the liver that is predominant in developing countries and is responsible for nearly 600000 deaths each year worldwide. Similar to many other tumors, the development of HCC must be understood as a multistep process involving the accumulation of genetic and epigenetic alterations in regulatory genes, leading to the activation of oncogenes and the inactivation or loss of tumor suppressor genes. Extensive research over the past decade has identified a number of molecular biomarkers, including aberrant expression of HCCrelated genes and microRNAs. The challenge facing HCC research and clinical care at this time is to address the heterogeneity and complexity of these genetic and epigenetic alterations and to use this information to direct rational diagnosis and treatment strategies. The multikinase inhibitor sorafenib was the first molecularly targeted drug for HCC to show some extent of survival benefits in patients with advanced tumors. Although the results obtained using sorafenib support the importance of molecular therapies in the treatment of HCC, there is still room for improvement. In addition,no molecular markers for drug sensitivity, recurrence and prognosis are currently clinically available. In this review, we provide an overview of recently published articles addressing HCC-related genes and microRNAs to update what is currently known regarding genetic and epigenetic aspects of the pathogenesis of HCC and propose novel promising candidates for use as diagnostic and therapeutic targets in HCC.
