BACKGROUND In recent years,a decrease in incidence and mortality of colorectal cancer(CRC)has been observed in developed nations,presumably through public disease awareness and increased screening efforts.However,a ri...BACKGROUND In recent years,a decrease in incidence and mortality of colorectal cancer(CRC)has been observed in developed nations,presumably through public disease awareness and increased screening efforts.However,a rising incidence of CRC in young patients below the age of 50 years has been reported in several studies.AIM To study tumor biology in CRC patients below 50 years of age.METHODS All patients with CRC were prospectively enrolled in our single-center oncologic database from January 2013 to December 2018 and were grouped and analyzed according to age(≥50 and<50 years).Clinical as well as histopathological features were analyzed and compared.The study was approved by the local Ethics Committee.Fisher’s exact test or t-test was used to test for differences between the groups,as appropriate.All statistical analysis was performed with IBM SPSS software Version 25(SPSS Inc,Armonk,NY,United States)and with RStudio using R Version 3.4.1(RStudio,Boston,MA,United States).RESULTS Seventeen percent of the 411 patients were younger than 50 years.Young patients were more often diagnosed with locally advanced T4-tumors and lymph node metastases(36.6%and 62%vs 17.7%and 42%;P<0.01).In addition,a higher frequency of poorly differentiated(G3)tumors(40%vs 22.4%P<0.05)was observed.More than every second patient below 40 years of age(51.8%)had distant metastases at diagnosis with a significant higher rate ring of signet cell differentiation compared to patients≥50 years(14.8%,P<0.05).Mutational status(KRAS,NRAS,BRAF,MSI)as well as selected behavioral risk factors showed no significant differences.CONCLUSION Distinct histopathologic features of increased biologic aggressiveness are found in patients with CRC of young-onset.Those patients present more frequently with more advanced tumor stages compared to older patients.Features of aggressive tumor biology underscore the need for earlier uptake of routine screening measures.展开更多
Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is ...Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.展开更多
Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with c...Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of18F-fludeoxyglucose(18F-FDG) and 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of18F-FDG and18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of18F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of18F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and18F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.展开更多
Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. ...Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.展开更多
Liver transplantation (LT) has become standard of care in patients with non-resectable early stage hepatocellular carcinoma (HCC) in liver cirrhosis.Currently,patient selection for LT is strictly based on tumor size a...Liver transplantation (LT) has become standard of care in patients with non-resectable early stage hepatocellular carcinoma (HCC) in liver cirrhosis.Currently,patient selection for LT is strictly based on tumor size and number,provided by the Milan criteria.This may,however,exclude patients with advanced tumor load but favourable biology from a possibly curative treatment option.It became clear in recent years that biological tumor viability rather than tumor macromorphology determines posttransplant outcome.In particular,microvascular invasion and poor grading reflect tumor aggressiveness and promote the risk of tumor relapse.Pretransplant biopsy is not applicable due to tumor heterogeneity and risk of tumor cell seeding.18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET),an established nuclear imaging device in oncology,was demonstrated to non-invasively correlate with unfavorable histopathologic features.Currently,there is an increasing amount of evidence that 18F-FDG-PET is very useful for identifying eligible liver transplant patients with HCC beyond standard criteria but less aggressive tumor properties.In order to safely expand the HCC selection criteria and the pool of eligible liver recipients,tumor evaluation with 18F-FDG-PETshould be implemented in pretransplant decision process.展开更多
Oncogenic multidrug resistance(MDR)is a multifactorial phenotype intimately linked to deregulated expression of detoxification transporters.Drug efflux transporters,particularly the MDR P-glycoprotein ABCB1,represent ...Oncogenic multidrug resistance(MDR)is a multifactorial phenotype intimately linked to deregulated expression of detoxification transporters.Drug efflux transporters,particularly the MDR P-glycoprotein ABCB1,represent a central mechanism by which not only chemotherapeutic drugs are extruded or sequestered to prevent drug delivery to their intracellular targets,but also for inhibiting apoptotic cell death cues,such as removal of proapoptotic signals.Several cell populations exhibiting the MDR phenotype co-exist within a tumor,such as cells forming the bulk tumor cell mass,cancer stem cells,and cancer persister cells.The key to regulation of ABCB1 expression is the cellular transcriptional machinery.Developmental signaling pathways(e.g,Hedgehog,Notch,Wnt/β-catenin,TGFβ,PITX2)are pivotal in governing cell proliferation,survival,differentiation and guiding cell migration during embryogenesis,and their reactivation during carcinogenesis,which is of particular significance for tumor initiation,progression,and metastasis,also leads to the upregulation of ABCB1.These pathways also drive and maintain cancer cell stemness,for which ABCB1 is used as a marker.In this review,the contribution of canonical and non-canonical developmental signaling pathways in transcriptional regulation of ABCB1 to confer MDR in cancer is delineated.展开更多
文摘BACKGROUND In recent years,a decrease in incidence and mortality of colorectal cancer(CRC)has been observed in developed nations,presumably through public disease awareness and increased screening efforts.However,a rising incidence of CRC in young patients below the age of 50 years has been reported in several studies.AIM To study tumor biology in CRC patients below 50 years of age.METHODS All patients with CRC were prospectively enrolled in our single-center oncologic database from January 2013 to December 2018 and were grouped and analyzed according to age(≥50 and<50 years).Clinical as well as histopathological features were analyzed and compared.The study was approved by the local Ethics Committee.Fisher’s exact test or t-test was used to test for differences between the groups,as appropriate.All statistical analysis was performed with IBM SPSS software Version 25(SPSS Inc,Armonk,NY,United States)and with RStudio using R Version 3.4.1(RStudio,Boston,MA,United States).RESULTS Seventeen percent of the 411 patients were younger than 50 years.Young patients were more often diagnosed with locally advanced T4-tumors and lymph node metastases(36.6%and 62%vs 17.7%and 42%;P<0.01).In addition,a higher frequency of poorly differentiated(G3)tumors(40%vs 22.4%P<0.05)was observed.More than every second patient below 40 years of age(51.8%)had distant metastases at diagnosis with a significant higher rate ring of signet cell differentiation compared to patients≥50 years(14.8%,P<0.05).Mutational status(KRAS,NRAS,BRAF,MSI)as well as selected behavioral risk factors showed no significant differences.CONCLUSION Distinct histopathologic features of increased biologic aggressiveness are found in patients with CRC of young-onset.Those patients present more frequently with more advanced tumor stages compared to older patients.Features of aggressive tumor biology underscore the need for earlier uptake of routine screening measures.
文摘Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.
基金supported by grants from the National Natural Science Foundation of China(81471736 and 81671760)the National Science and Technology Pillar Program during the Twelfth Five-Year Plan Period(2015BAI01B09)Project of Research Foundation of the Talent of Scientific and Technical Innovation of Harbin City(2016RAXYJ063)
文摘Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of18F-fludeoxyglucose(18F-FDG) and 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of18F-FDG and18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of18F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of18F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and18F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.
文摘Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.
文摘Liver transplantation (LT) has become standard of care in patients with non-resectable early stage hepatocellular carcinoma (HCC) in liver cirrhosis.Currently,patient selection for LT is strictly based on tumor size and number,provided by the Milan criteria.This may,however,exclude patients with advanced tumor load but favourable biology from a possibly curative treatment option.It became clear in recent years that biological tumor viability rather than tumor macromorphology determines posttransplant outcome.In particular,microvascular invasion and poor grading reflect tumor aggressiveness and promote the risk of tumor relapse.Pretransplant biopsy is not applicable due to tumor heterogeneity and risk of tumor cell seeding.18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET),an established nuclear imaging device in oncology,was demonstrated to non-invasively correlate with unfavorable histopathologic features.Currently,there is an increasing amount of evidence that 18F-FDG-PET is very useful for identifying eligible liver transplant patients with HCC beyond standard criteria but less aggressive tumor properties.In order to safely expand the HCC selection criteria and the pool of eligible liver recipients,tumor evaluation with 18F-FDG-PETshould be implemented in pretransplant decision process.
基金the Intramural Research Program at Witten/Herdecke University and Westmann-Westerdorp Foundation.The research of F.T.on ABCB1 was funded by DFG(German Research Foundation)Grants TH345 and the Centre for Biomedical Education and Research(ZBAF)at Witten/Herdecke University。
文摘Oncogenic multidrug resistance(MDR)is a multifactorial phenotype intimately linked to deregulated expression of detoxification transporters.Drug efflux transporters,particularly the MDR P-glycoprotein ABCB1,represent a central mechanism by which not only chemotherapeutic drugs are extruded or sequestered to prevent drug delivery to their intracellular targets,but also for inhibiting apoptotic cell death cues,such as removal of proapoptotic signals.Several cell populations exhibiting the MDR phenotype co-exist within a tumor,such as cells forming the bulk tumor cell mass,cancer stem cells,and cancer persister cells.The key to regulation of ABCB1 expression is the cellular transcriptional machinery.Developmental signaling pathways(e.g,Hedgehog,Notch,Wnt/β-catenin,TGFβ,PITX2)are pivotal in governing cell proliferation,survival,differentiation and guiding cell migration during embryogenesis,and their reactivation during carcinogenesis,which is of particular significance for tumor initiation,progression,and metastasis,also leads to the upregulation of ABCB1.These pathways also drive and maintain cancer cell stemness,for which ABCB1 is used as a marker.In this review,the contribution of canonical and non-canonical developmental signaling pathways in transcriptional regulation of ABCB1 to confer MDR in cancer is delineated.
