BACKGROUND Breast cancer is a leading cause of cancer-related mortality among women worldwide,with invasive ductal carcinoma(IDC)being the most prevalent subtype.Lymph node metastasis is the primary prognostic indicat...BACKGROUND Breast cancer is a leading cause of cancer-related mortality among women worldwide,with invasive ductal carcinoma(IDC)being the most prevalent subtype.Lymph node metastasis is the primary prognostic indicator,typically evaluated via biopsy of the ipsilateral sentinel or axillary lymph nodes.Contralateral axillary metastasis(CAM)without ipsilateral involvement is exceedingly rare,particularly in early-stage breast cancer.This report presents a case of CAM in a patient with triple-negative breast cancer(TNBC),underscoring diagnostic and therapeutic complexities.CASE SUMMARY A 73-year-old female presented with left-sided early-stage IDC in February 2023.Despite a modified radical mastectomy and pathologically negative ipsilateral lymph nodes,a postoperative positron emission tomography(PET)scan detected fluorodeoxyglucose-avid nodes in the contralateral axilla.Biopsy confirmed metastatic ductal carcinoma with triple-negative status,resulting in an upstaged diagnosis of metastatic breast cancer,stage IV,M1.The patient underwent six cycles of adjuvant chemotherapy,with follow-up PET imaging showing regression of the contralateral lesion.This case highlights the importance of advanced imaging in TNBC for precise staging and treatment optimization.CONCLUSION This case highlights the aggressive nature of TNBC and the need for advanced imaging to ensure accurate staging and effective management.展开更多
The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important,but the diagnostic criteria,terminology,and grading system are not the...The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important,but the diagnostic criteria,terminology,and grading system are not the same in the East and West.A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists,but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of invasion.Although the Vienna classification was introduced to reduce diagnostic discrepancies,it has been difficult to adopt due to different concepts for gastric epithelial neoplastic lesions.Korean pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western medicine.Japan is geographically close to Korea,and academic exchanges are active.Additionally,Korean doctors are familiar with Western style medical terminology.As a result,the terminology,definitions,and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in Korea.To solve this problem,the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis:(1) a diagnosis of carcinoma is based on invasion;(2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching,budding,or marked glandular crowding;(3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts,the lesion is considered high grade dysplasia;(4) if severe cytologic atypia is present,careful inspection for invasive foci is necessary,because the risk for invasion is very high;and(5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern,papillae,ridges,vesicular nuclei,high nuclear/cytoplasmic ratio,loss of nuclear polarity,thick and irregular nuclear membrane,and nucleoli.展开更多
AIM： To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity o...AIM： To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity of esophageal squamous cell carcinoma （ESCC） among the Kashmiri population of Northern India. METHODS： All cases （n = 51） and controls （n = 150） were permanent residents of the Kashmir valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for individual cancer cases （n = 45） and inpatient controls （n = 150） with non-cancer disease included information on family history of cancer, thirty prevailing common dietary risk factors along with patient＇s age group. Correlation of genetic lesion in p53 exons to animistic data from these parameters was generated by Chi-square test to all 45 histologically confirmed ESCC cases along with healthy controls.RESULTS： Thirty-five of 45 （77.8%） histologically characterized tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample obtained from adjacent region from the same patient showed gerrnline mutation. The SSCP analysis demonstrated that most common p53 gene alterations were found in exon 6 （77.7%）, that did not correlate with the age of the individual and clinicopathological parameters but showed significant concordance （P 〈 0.05） with familial history of cancer （CD = 58）, suggesting germline predisposition at an unknown locus, and dietary habit of consuming locally grown Brassica vegetable ＂Hakh＂ （CD = 19.5）, red chillies （CD = 20.2）, hot salty soda tea （CD = 2.37） and local baked bread （CD = 1.1）. CONCLUSION： Our study suggests that somatic chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer patients of an ethnically homogenous population of Kashmir valley are closely related to continued exposure to various common dietary risk factors, especially hot salty tea, meat, baked bread and ＂Hakh＂, that are rich in nitrosoamines and familial cancer history.展开更多
Objective: To explore the relationship of XRCC1 Arg 399 Gln polymorphism and AFB1-related hepatocellular carcinoma (HCC) risk in Guangxi population. Methods: The DNA samples from peripheral blood white blood cells wer...Objective: To explore the relationship of XRCC1 Arg 399 Gln polymorphism and AFB1-related hepatocellular carcinoma (HCC) risk in Guangxi population. Methods: The DNA samples from peripheral blood white blood cells were obtained from subjects including 140 HCC and 536 controls. The XRCC1 gene 399 codon polymorphism was detected by PCR-RFLP technique. Results: The frequency of XRCC1 399 Arg/Gln & Gln/Gln genotype in HCC patients (48.57%) was significantly higher that in normal controls (32.46%), and XRCC1 399 Arg/Gln & Gln/Gln genotype was associated with increased risk of HCC (adjusted odds ratios (OR)=2.18, 95% confidence interval (CI) 1.27～3.74). In addition, in the cohort of low/median level of AFB1 exposure, the codon 399 Gln allele was associated with a conspicuous significantly increasing risk for HCC (adjusted OR=2.06, 95% CI=1.01～4.20). Conclusion: The results indicate that the XRCC1 399 Gln allele is a potentially important determinant of susceptibility to AFB1-related HCC.展开更多
Objective: To evaluate the value of fasting plasma glucose (FPG) in screening a high-risk population for gestational diabetes mellitus (GDM). Study design: D uring an 8-month period, 1,685 pregnant women underwent the...Objective: To evaluate the value of fasting plasma glucose (FPG) in screening a high-risk population for gestational diabetes mellitus (GDM). Study design: D uring an 8-month period, 1,685 pregnant women underwent the one-step 75 g ora l glucose tolerance test (OGTT) as a part of a universal screening program. The receiver operating characteristic (ROC) curve was used to analyze the performanc e of the FPG. Results: 333 (19.8%) women had GDM (WHO criteria). The area under the ROC curve of FPG to detect GDM was 0.639 (95%CI 0.603-0.674), which refle cted the degree of the FPG histogram overlap in women with and without GDM. A FP G threshold of 4.7 mmol/L reached the minimally acceptable sensitivity of 78.1% with a corresponding unacceptable specificity of 32.2%. 508 (31%) women were b elow this threshold, at a negative predictive value of 85.6%. The FPG at higher thresholds with acceptable specificity had poor sensitivity and positive predi ctive value to be useful. Conclusion: Though the high false positive rate at any FPG threshold with adequate sensitivity makes the FPG an inappropriate test for GDM screening, the FPG has the potential to avoid nearly one-third of the cumb ersome OGTTs at the expense of missing one-fifth of pregnant women with milder GDM.展开更多
Background and aims:Hepatocellular carcinoma(HCC)is a tumor of high heterogeneity and complexity,which poses significant challenges to effective treatment and patient prognosis because of its immune evasion characteri...Background and aims:Hepatocellular carcinoma(HCC)is a tumor of high heterogeneity and complexity,which poses significant challenges to effective treatment and patient prognosis because of its immune evasion characteristics.To address these issues,single-cell technology and machine learning methods have emerged as a promising approach to identify genes associated with immune escape in HCC.This study aimed to develop a prognostic risk score model for HCC by identifying intrinsic immune-evasion genes(IIEGs)through single-cell technology and machine learning,providing insights into immune infiltration,enhancing predictive accuracy,and facilitating the development of more effective treatment strategies.Materials and methods:The study utilized data from The Cancer Genome Atlas database to analyze gene expression profiles and clinical data related to intrinsic immune evasion in patients with HCC.Various tools,including the Human Protein Atlas,cBioPortal,single-cell analysis,machine learning,and Kaplan-Meier plot,were used to analyze IIEGs.Functional enrichment analysis was conducted to explore potential mechanisms.In addition,the abundance of infiltrating cells in the tumor microenvironment was investigated using single-sample gene set enrichment analysis,CIBERSORT,xCELL,and tumor immunophenotype algorithms.The expression of glycosylphosphatidylinositol anchor attachment 1(GPAA1)was examined in the clinical sample of HCC by quantitative real-time polymerase chain reaction,Western blotting,and immunohistochemical staining.Results:Univariate Cox analysis identified 63 IIEGs associated with the prognosis of HCC.Using random forest,least absolute shrinkage and selection operator regression analysis,and support vector machine,a risk score model consisting of six IIEGs(carbamoyl-phosphate synthetase 2,aspartate transcarbamylase,and dihydroorotase(CAD),phosphatidylinositol glycan anchor biosynthesis class U(PIGU),endoplasmic reticulum membrane protein complex subunit 3(EMC3),centrosomal protein 55(CEP55),autophagyrelated 10(ATG10),and GPAA1)developed,which was validated using 10 pairs of HCC and adjacent non-cancerous samples.Based on the calculated median risk score,HCC samples were categorized into high-and low-risk groups.The Kaplan-Meier curve analysis showed that the high-risk group had a worse prognosis compared with the low-risk group.Time-dependent receiver operating characteristic analysis demonstrated the accurate predictive capability of the risk score model for HCC prognosis.Furthermore,immune infiltration analysis showed a positive correlation between the risk score model and 40 immune checkpoint genes as well as Th2 cells.Conclusions:A prognostic risk score model was formulated by six IIEG signatures and showed promise in predicting the prognosis of patients diagnosed with HCC.The utilization of the IIEG risk score as a novel prognostic index,together with its significance as a valuable biomarker for immunotherapy in HCC,provides benefit for patients with HCC in determining therapeutic strategies for clinical application.展开更多
The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound...The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound has been shown to directly inhibit its activity. Here, we evaluate piceatannol, a naturally occurring polyphenolic compound, as a potential targeting agonist of Beclin-1, to assess its efficacy as an antitumor agent against gastric cancer. More specifically, we determine the effects of piceatannol treatment on cell viability using a monitoring system and colony forming assay. Piceatannol was found to efficiently inhibit the proliferation of several human gastric cancer cell lines. Autophagic flux is increased by piceatannol treatment, and correlates with inhibition of cell proliferation and colony formation. Additionally, microscale thermophoresis and surface plasmon resonance results show a direct interaction between piceatannol and Beclin-1, which reduces the phosphorylation activity of Beclin-1 at the Ser-295 site. Notably, piceatannol impairs the binding of Beclin-1 to Bcl-2 and enhances the recruitment of binding of UV radiation resistance-associated gene protein, which further triggers Beclin-1-dependent autophagy signaling. An increase in autophagic activity via treatment with the mTOR inhibitor, everolimus, effectively sensitizes piceatannol-induced antitumor effects. Xenograft models confirmed that piceatannol inhibits tumor development and elicits a potent synergistic effect with everolimus in vivo. Taken together, the findings of this study strongly support the application of combinatorial piceatannol and everolimus therapy in future clinical trials for gastric cancer patients.展开更多
Background and aim:The transcriptional co-activator Yes-associated protein-1(YAP1)has been impli-cated as an oncogene and is overexpressed in different kinds of human cancers,especially hepatocellular carcinoma(HCC).H...Background and aim:The transcriptional co-activator Yes-associated protein-1(YAP1)has been impli-cated as an oncogene and is overexpressed in different kinds of human cancers,especially hepatocellular carcinoma(HCC).However,the role of YAP1 has not been reported in residual/recurrent HCC after transarterial chemoembolization(TACE).Our aim is to determine whether YAP1 is overexpressed in the residual/recurrent HCC after TACE.Methods:A total of 105 tumor tissues from 71 patients including 30 cases of primary HCC without prior treatment,35 cases of residual/recurrent HCC post TACE,and 6 cases of hepatoblastoma were included in the immunohistochemical study.YAP1 immunoreactivity was blindly scored as 0,1+,2+or 3+in density and percentages of positive cells.Results:About 33.3%(10/30)of primary HCC without prior treatment showed 2+of YAP1 immunore-activity.While 82.8%(29/35)of residual/recurrent HCCs after TACE treatment displayed 2-3+of YAP1 immunoreactivity,which was significantly higher compared to primary HCC without prior treatment(P=0.0002).YAP1 immunoreactivity was moderately to strongly positive(2-3+)in 100%of the hep-atoblastoma,particularly in the embryonal components(3+in 100%cases).Conclusions:YAP1 is significantly upregulated in the residual/recurrent HCCs post TACE treatment,suggesting that YAP1 may serve as a sensitive diagnostic marker and a treatment target for residual/recurrent HCC post TACE.展开更多
Acquired resistance is a major problem limiting the clinical efficacy of treatments for metastatic colorectal cancer(mCRC).Histological transformation is an important mechanism underlying the acquired resistance of no...Acquired resistance is a major problem limiting the clinical efficacy of treatments for metastatic colorectal cancer(mCRC).Histological transformation is an important mechanism underlying the acquired resistance of non-small cell lung cancer and prostate cancer to targeted therapy.However,no report has examined the role of histological transformation in mCRC.Here,we report the first case of histologically transformed large cell neuroendocrine carcinoma from primary colon adenocarcinoma during antiangiogenesis and anti-PD-1 combination therapy.The histologic conversion was confirmed by the observation that the transformed large cell neuroendocrine carcinoma lesion retained the original mutational signature found in the primary tumor.Sequential tumor biopsy and dynamic changes in tumor markers demonstrated the transformed process.The histological transformation not only resulted in discordant responses to the same treatment but also significantly shortened overall survival.This case calls for more attention to histological transformation in mCRC.Tumor rebiopsy upon disease progression and monitoring dynamic changes in tumor markers would help to identify such cases.展开更多
文摘BACKGROUND Breast cancer is a leading cause of cancer-related mortality among women worldwide,with invasive ductal carcinoma(IDC)being the most prevalent subtype.Lymph node metastasis is the primary prognostic indicator,typically evaluated via biopsy of the ipsilateral sentinel or axillary lymph nodes.Contralateral axillary metastasis(CAM)without ipsilateral involvement is exceedingly rare,particularly in early-stage breast cancer.This report presents a case of CAM in a patient with triple-negative breast cancer(TNBC),underscoring diagnostic and therapeutic complexities.CASE SUMMARY A 73-year-old female presented with left-sided early-stage IDC in February 2023.Despite a modified radical mastectomy and pathologically negative ipsilateral lymph nodes,a postoperative positron emission tomography(PET)scan detected fluorodeoxyglucose-avid nodes in the contralateral axilla.Biopsy confirmed metastatic ductal carcinoma with triple-negative status,resulting in an upstaged diagnosis of metastatic breast cancer,stage IV,M1.The patient underwent six cycles of adjuvant chemotherapy,with follow-up PET imaging showing regression of the contralateral lesion.This case highlights the importance of advanced imaging in TNBC for precise staging and treatment optimization.CONCLUSION This case highlights the aggressive nature of TNBC and the need for advanced imaging to ensure accurate staging and effective management.
文摘The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important,but the diagnostic criteria,terminology,and grading system are not the same in the East and West.A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists,but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of invasion.Although the Vienna classification was introduced to reduce diagnostic discrepancies,it has been difficult to adopt due to different concepts for gastric epithelial neoplastic lesions.Korean pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western medicine.Japan is geographically close to Korea,and academic exchanges are active.Additionally,Korean doctors are familiar with Western style medical terminology.As a result,the terminology,definitions,and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in Korea.To solve this problem,the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis:(1) a diagnosis of carcinoma is based on invasion;(2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching,budding,or marked glandular crowding;(3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts,the lesion is considered high grade dysplasia;(4) if severe cytologic atypia is present,careful inspection for invasive foci is necessary,because the risk for invasion is very high;and(5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern,papillae,ridges,vesicular nuclei,high nuclear/cytoplasmic ratio,loss of nuclear polarity,thick and irregular nuclear membrane,and nucleoli.
基金Supported by funding (100%) from the Department of Science and Technology, New Delhi through the Fast Track Young Scientist Project Award to Dr. Imtiyaz Murtaza, No. SR/FTP/LS-A-91/2001
文摘AIM： To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity of esophageal squamous cell carcinoma （ESCC） among the Kashmiri population of Northern India. METHODS： All cases （n = 51） and controls （n = 150） were permanent residents of the Kashmir valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for individual cancer cases （n = 45） and inpatient controls （n = 150） with non-cancer disease included information on family history of cancer, thirty prevailing common dietary risk factors along with patient＇s age group. Correlation of genetic lesion in p53 exons to animistic data from these parameters was generated by Chi-square test to all 45 histologically confirmed ESCC cases along with healthy controls.RESULTS： Thirty-five of 45 （77.8%） histologically characterized tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample obtained from adjacent region from the same patient showed gerrnline mutation. The SSCP analysis demonstrated that most common p53 gene alterations were found in exon 6 （77.7%）, that did not correlate with the age of the individual and clinicopathological parameters but showed significant concordance （P 〈 0.05） with familial history of cancer （CD = 58）, suggesting germline predisposition at an unknown locus, and dietary habit of consuming locally grown Brassica vegetable ＂Hakh＂ （CD = 19.5）, red chillies （CD = 20.2）, hot salty soda tea （CD = 2.37） and local baked bread （CD = 1.1）. CONCLUSION： Our study suggests that somatic chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer patients of an ethnically homogenous population of Kashmir valley are closely related to continued exposure to various common dietary risk factors, especially hot salty tea, meat, baked bread and ＂Hakh＂, that are rich in nitrosoamines and familial cancer history.
基金This work was supported by the NationalNatural Science Foundation of China(No.39860032)
文摘Objective: To explore the relationship of XRCC1 Arg 399 Gln polymorphism and AFB1-related hepatocellular carcinoma (HCC) risk in Guangxi population. Methods: The DNA samples from peripheral blood white blood cells were obtained from subjects including 140 HCC and 536 controls. The XRCC1 gene 399 codon polymorphism was detected by PCR-RFLP technique. Results: The frequency of XRCC1 399 Arg/Gln & Gln/Gln genotype in HCC patients (48.57%) was significantly higher that in normal controls (32.46%), and XRCC1 399 Arg/Gln & Gln/Gln genotype was associated with increased risk of HCC (adjusted odds ratios (OR)=2.18, 95% confidence interval (CI) 1.27～3.74). In addition, in the cohort of low/median level of AFB1 exposure, the codon 399 Gln allele was associated with a conspicuous significantly increasing risk for HCC (adjusted OR=2.06, 95% CI=1.01～4.20). Conclusion: The results indicate that the XRCC1 399 Gln allele is a potentially important determinant of susceptibility to AFB1-related HCC.
文摘Objective: To evaluate the value of fasting plasma glucose (FPG) in screening a high-risk population for gestational diabetes mellitus (GDM). Study design: D uring an 8-month period, 1,685 pregnant women underwent the one-step 75 g ora l glucose tolerance test (OGTT) as a part of a universal screening program. The receiver operating characteristic (ROC) curve was used to analyze the performanc e of the FPG. Results: 333 (19.8%) women had GDM (WHO criteria). The area under the ROC curve of FPG to detect GDM was 0.639 (95%CI 0.603-0.674), which refle cted the degree of the FPG histogram overlap in women with and without GDM. A FP G threshold of 4.7 mmol/L reached the minimally acceptable sensitivity of 78.1% with a corresponding unacceptable specificity of 32.2%. 508 (31%) women were b elow this threshold, at a negative predictive value of 85.6%. The FPG at higher thresholds with acceptable specificity had poor sensitivity and positive predi ctive value to be useful. Conclusion: Though the high false positive rate at any FPG threshold with adequate sensitivity makes the FPG an inappropriate test for GDM screening, the FPG has the potential to avoid nearly one-third of the cumb ersome OGTTs at the expense of missing one-fifth of pregnant women with milder GDM.
基金the Natural Science Foundation of Guangdong Province(No.2017A030310252,No.2022A1515012650)the Science and Technology Program of Guangzhou(No.2024A03J0919).
文摘Background and aims:Hepatocellular carcinoma(HCC)is a tumor of high heterogeneity and complexity,which poses significant challenges to effective treatment and patient prognosis because of its immune evasion characteristics.To address these issues,single-cell technology and machine learning methods have emerged as a promising approach to identify genes associated with immune escape in HCC.This study aimed to develop a prognostic risk score model for HCC by identifying intrinsic immune-evasion genes(IIEGs)through single-cell technology and machine learning,providing insights into immune infiltration,enhancing predictive accuracy,and facilitating the development of more effective treatment strategies.Materials and methods:The study utilized data from The Cancer Genome Atlas database to analyze gene expression profiles and clinical data related to intrinsic immune evasion in patients with HCC.Various tools,including the Human Protein Atlas,cBioPortal,single-cell analysis,machine learning,and Kaplan-Meier plot,were used to analyze IIEGs.Functional enrichment analysis was conducted to explore potential mechanisms.In addition,the abundance of infiltrating cells in the tumor microenvironment was investigated using single-sample gene set enrichment analysis,CIBERSORT,xCELL,and tumor immunophenotype algorithms.The expression of glycosylphosphatidylinositol anchor attachment 1(GPAA1)was examined in the clinical sample of HCC by quantitative real-time polymerase chain reaction,Western blotting,and immunohistochemical staining.Results:Univariate Cox analysis identified 63 IIEGs associated with the prognosis of HCC.Using random forest,least absolute shrinkage and selection operator regression analysis,and support vector machine,a risk score model consisting of six IIEGs(carbamoyl-phosphate synthetase 2,aspartate transcarbamylase,and dihydroorotase(CAD),phosphatidylinositol glycan anchor biosynthesis class U(PIGU),endoplasmic reticulum membrane protein complex subunit 3(EMC3),centrosomal protein 55(CEP55),autophagyrelated 10(ATG10),and GPAA1)developed,which was validated using 10 pairs of HCC and adjacent non-cancerous samples.Based on the calculated median risk score,HCC samples were categorized into high-and low-risk groups.The Kaplan-Meier curve analysis showed that the high-risk group had a worse prognosis compared with the low-risk group.Time-dependent receiver operating characteristic analysis demonstrated the accurate predictive capability of the risk score model for HCC prognosis.Furthermore,immune infiltration analysis showed a positive correlation between the risk score model and 40 immune checkpoint genes as well as Th2 cells.Conclusions:A prognostic risk score model was formulated by six IIEG signatures and showed promise in predicting the prognosis of patients diagnosed with HCC.The utilization of the IIEG risk score as a novel prognostic index,together with its significance as a valuable biomarker for immunotherapy in HCC,provides benefit for patients with HCC in determining therapeutic strategies for clinical application.
基金supported by the Natural Science Foundation of Beijing,China(7214215)the Beijing Municipal Administration of Hospitals Incubating Program(PZ2021025)+5 种基金the Science Foundation of Peking University Six Hospital(YJJ0008)the National Natural Science Foundation of China(82203579,81872502,81402308)the Science Foundation of Peking University Cancer Hospital(2020-23,2021-24,202126)the Clinical Medicine Plus X-Young Scholars Project(PKU2020LCXQ001)the“Double First Class”Disciplinary Development Foundation of Peking University(BMU2019LCKXJ011)The first author,Longtao Huangfu,would like to give special thanks to the Beijing Natural Science Foundation Committee for granting the first research grant。
文摘The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound has been shown to directly inhibit its activity. Here, we evaluate piceatannol, a naturally occurring polyphenolic compound, as a potential targeting agonist of Beclin-1, to assess its efficacy as an antitumor agent against gastric cancer. More specifically, we determine the effects of piceatannol treatment on cell viability using a monitoring system and colony forming assay. Piceatannol was found to efficiently inhibit the proliferation of several human gastric cancer cell lines. Autophagic flux is increased by piceatannol treatment, and correlates with inhibition of cell proliferation and colony formation. Additionally, microscale thermophoresis and surface plasmon resonance results show a direct interaction between piceatannol and Beclin-1, which reduces the phosphorylation activity of Beclin-1 at the Ser-295 site. Notably, piceatannol impairs the binding of Beclin-1 to Bcl-2 and enhances the recruitment of binding of UV radiation resistance-associated gene protein, which further triggers Beclin-1-dependent autophagy signaling. An increase in autophagic activity via treatment with the mTOR inhibitor, everolimus, effectively sensitizes piceatannol-induced antitumor effects. Xenograft models confirmed that piceatannol inhibits tumor development and elicits a potent synergistic effect with everolimus in vivo. Taken together, the findings of this study strongly support the application of combinatorial piceatannol and everolimus therapy in future clinical trials for gastric cancer patients.
基金This study was supported by the USA National Institutes of Health grant R01 CA187027(to N.Kang).
文摘Background and aim:The transcriptional co-activator Yes-associated protein-1(YAP1)has been impli-cated as an oncogene and is overexpressed in different kinds of human cancers,especially hepatocellular carcinoma(HCC).However,the role of YAP1 has not been reported in residual/recurrent HCC after transarterial chemoembolization(TACE).Our aim is to determine whether YAP1 is overexpressed in the residual/recurrent HCC after TACE.Methods:A total of 105 tumor tissues from 71 patients including 30 cases of primary HCC without prior treatment,35 cases of residual/recurrent HCC post TACE,and 6 cases of hepatoblastoma were included in the immunohistochemical study.YAP1 immunoreactivity was blindly scored as 0,1+,2+or 3+in density and percentages of positive cells.Results:About 33.3%(10/30)of primary HCC without prior treatment showed 2+of YAP1 immunore-activity.While 82.8%(29/35)of residual/recurrent HCCs after TACE treatment displayed 2-3+of YAP1 immunoreactivity,which was significantly higher compared to primary HCC without prior treatment(P=0.0002).YAP1 immunoreactivity was moderately to strongly positive(2-3+)in 100%of the hep-atoblastoma,particularly in the embryonal components(3+in 100%cases).Conclusions:YAP1 is significantly upregulated in the residual/recurrent HCCs post TACE treatment,suggesting that YAP1 may serve as a sensitive diagnostic marker and a treatment target for residual/recurrent HCC post TACE.
基金Beijing Excellent Talent Cultivation Subsidy Young Backbone Individual Project and Science Foundation of Peking University Cancer Hospital,Grant/Award Number:A002226the ethics committee of Peking University Cancer Hospital&Institute(2021KT30).
文摘Acquired resistance is a major problem limiting the clinical efficacy of treatments for metastatic colorectal cancer(mCRC).Histological transformation is an important mechanism underlying the acquired resistance of non-small cell lung cancer and prostate cancer to targeted therapy.However,no report has examined the role of histological transformation in mCRC.Here,we report the first case of histologically transformed large cell neuroendocrine carcinoma from primary colon adenocarcinoma during antiangiogenesis and anti-PD-1 combination therapy.The histologic conversion was confirmed by the observation that the transformed large cell neuroendocrine carcinoma lesion retained the original mutational signature found in the primary tumor.Sequential tumor biopsy and dynamic changes in tumor markers demonstrated the transformed process.The histological transformation not only resulted in discordant responses to the same treatment but also significantly shortened overall survival.This case calls for more attention to histological transformation in mCRC.Tumor rebiopsy upon disease progression and monitoring dynamic changes in tumor markers would help to identify such cases.
