Treatment of locally advanced unresectable pancreatic cancer remains a major clinical challenge due to pronounced heterogeneity and resistance to standard regimens.Increasing evidence highlights the critical role of t...Treatment of locally advanced unresectable pancreatic cancer remains a major clinical challenge due to pronounced heterogeneity and resistance to standard regimens.Increasing evidence highlights the critical role of the tumor microenvironment(TME)in shaping therapeutic response and driving drug resistance.In this minireview,we summarize recent advances in TME phenotyping and its potential to guide precision therapy.A four-dimensional framework integrating stromal,immune,genomic,and metabolic features has been proposed to better characterize TME heterogeneity.Preclinical and clinical studies indicate that strategies targeting the stroma,modulating immunity,or exploiting genomic vulnerabilities such as homologous recombination deficiency may enhance the efficacy of chemotherapy,immunotherapy,and targeted agents.Dynamic biomarkers,including circulating tumor DNA and carbohydrate antigen 19-9,also show promise for real-time therapy adaptation,although their clinical application remains limited.By synthesizing current evidence,we emphasize the importance of individualized treatment strategies that account for TME complexity.While encouraging,the translation of multiomics phenotyping and biomarker monitoring into routine clinical practice requires standardization,prospective validation,and integration of novel technologies.Future research should focus on establishing reproducible TME-guided models to enable dynamic and personalized therapy for patients with unresectable pancreatic cancer.展开更多
Objective： Hepatocellular carcinoma （HCC） is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. Thi...Objective： Hepatocellular carcinoma （HCC） is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. This study employed a quantitative proteomic strategy to analyze the differential expression of serum glycoproteins between HCC and normal control serum samples. Methods： Lectin affinity chromatography （LAC） was used to enrich glycoproteins from the serum samples. Quantitative mass spectrometric analysis combined with stable isotope dimethyl labeling and 2D liquid chromatography （LC） separations were performed to examine the differential levels of the detected proteins between HCC and control serum samples. Western blot was used to analyze the differential expression levels of the three serum proteins. Results： A total of 2,280 protein groups were identified in the serum samples from HCC patients by using the 2D LC-MS/MS method. Up to 36 proteins were up-regulated in the HCC serum, whereas 19 proteins were down-regulated. Three differential glycoproteins, namely, fibrinogen gamma chain （FGG）, FOS-like antigen 2 （FOSL2）, and a-l, 6-mannosylglycoprotein 6-^-N-acetylglucosaminyltransferase B （MGATSB） were validated by Western blot. All these three proteins were up-regulated in the HCC serum samples. Conclusion： A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC.展开更多
The porous NiTi(pNiTi)samples were produced by sintering evaporation using Ti−50.8Ni(at.%)gasatomized powders.The samples were analyzed by metallographic microscope and X-ray dispersive spectroscopy(XRD).A comparison ...The porous NiTi(pNiTi)samples were produced by sintering evaporation using Ti−50.8Ni(at.%)gasatomized powders.The samples were analyzed by metallographic microscope and X-ray dispersive spectroscopy(XRD).A comparison of nickel(Ni)release and cytocompatibility between pNiTi and dense NiTi(dNiTi)was made.The results showed that the pNiTi has good mechanical properties.Ni releases from pNiTi in vitro and in vivo are more serious than those form dNiTi.The proliferation and differentiation of cells cultured with the pNiTi extracting liquid are significantly worse,and the rate of early apoptosis is higher.In conclusion,pNiTi is mechanically similar to bone,but pNiTi releases more Ni and interferes with cell proliferation and differentiation.A significantly cautious approach should be adopted when using it as a medical implant.展开更多
Objective: To discuss the mRNA and protein expression of autophagy marker molecule Beclin1 in osteosarcoma tissue and their correlation with pathological features. Methods: A total of 60 patients with osteosarcoma rec...Objective: To discuss the mRNA and protein expression of autophagy marker molecule Beclin1 in osteosarcoma tissue and their correlation with pathological features. Methods: A total of 60 patients with osteosarcoma receiving surgical treatment in the hospital between April 2012 and January 2016 were selected, and the osteosarcoma tissue and adjacent normal tissue samples were collected during operation. Fluorescence quantitative PCR method was used to detect the expression of Beclin1 mRNA as well as proliferation and invasion gene expression in the tissue specimens, and the Beclin1 protein expression was detected by western-blot method. According to the median of Beclin1 mRNA and protein expression in osteosarcoma tissues, they were further grouped into high Beclin1 mRNA expression group (n=30) and low Beclin1 mRNA expression group (n=30) as well as high Beclin1 protein expression group (n=30) and low Beclin1 protein expression group (n=30). The differences in proliferation and invasion gene expression in osteosarcoma tissue with different Beclin1 mRNA and Beclin1 protein expression were compared. Results: Beclin1 mRNA and Beclin1 protein expression in osteosarcoma tissue were lower than those in adjacent normal tissue;proliferation gene KISS-1 mRNA expression in low Beclin1 mRNA expression group of osteosarcoma tissue was lower than that in high Beclin1 mRNA expression group while Six1, FoxM1, RIPK4 and STIM1 mRNA expression were higher than those in high Beclin1 mRNA expression group;invasion gene DLX1 mRNA expression was lower than that in high Beclin1 mRNA expression group while EFEMP1, MTA1, Notch1, HES1 and LEF-1 mRNA expression were higher than those in high Beclin1 mRNA expression group;proliferation gene KISS-1 mRNA expression in low Beclin1 protein expression group of osteosarcoma tissue was lower than that in high Beclin1 protein expression group while Six1, FoxM1, RIPK4 and STIM1 mRNA expression were higher than those in high Beclin1 protein expression group;invasion gene DLX1 mRNA expression was lower than that in high Beclin1 protein expression group while EFEMP1, MTA1, Notch1, HES1 and LEF-1 mRNA expression were higher than those in high Beclin1 protein expression group. Conclusion: Both mRNA and protein expression of autophagy marker molecule Beclin1 decrease in osteosarcoma tissue and are directly correlated with the proliferation and invasion activity of tumor cells.展开更多
文摘Treatment of locally advanced unresectable pancreatic cancer remains a major clinical challenge due to pronounced heterogeneity and resistance to standard regimens.Increasing evidence highlights the critical role of the tumor microenvironment(TME)in shaping therapeutic response and driving drug resistance.In this minireview,we summarize recent advances in TME phenotyping and its potential to guide precision therapy.A four-dimensional framework integrating stromal,immune,genomic,and metabolic features has been proposed to better characterize TME heterogeneity.Preclinical and clinical studies indicate that strategies targeting the stroma,modulating immunity,or exploiting genomic vulnerabilities such as homologous recombination deficiency may enhance the efficacy of chemotherapy,immunotherapy,and targeted agents.Dynamic biomarkers,including circulating tumor DNA and carbohydrate antigen 19-9,also show promise for real-time therapy adaptation,although their clinical application remains limited.By synthesizing current evidence,we emphasize the importance of individualized treatment strategies that account for TME complexity.While encouraging,the translation of multiomics phenotyping and biomarker monitoring into routine clinical practice requires standardization,prospective validation,and integration of novel technologies.Future research should focus on establishing reproducible TME-guided models to enable dynamic and personalized therapy for patients with unresectable pancreatic cancer.
基金supported by grants from the National Natural Science Foundation of China(Grant No.21205088)973 Project(Grant No.2011CB933100)+2 种基金National Science Fund for Distinguished Young Scholars(Grant No.81125019)Doctoral Research Fund from the Ministry of Education of China(Grant No.20121202120001)sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry
文摘Objective： Hepatocellular carcinoma （HCC） is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. This study employed a quantitative proteomic strategy to analyze the differential expression of serum glycoproteins between HCC and normal control serum samples. Methods： Lectin affinity chromatography （LAC） was used to enrich glycoproteins from the serum samples. Quantitative mass spectrometric analysis combined with stable isotope dimethyl labeling and 2D liquid chromatography （LC） separations were performed to examine the differential levels of the detected proteins between HCC and control serum samples. Western blot was used to analyze the differential expression levels of the three serum proteins. Results： A total of 2,280 protein groups were identified in the serum samples from HCC patients by using the 2D LC-MS/MS method. Up to 36 proteins were up-regulated in the HCC serum, whereas 19 proteins were down-regulated. Three differential glycoproteins, namely, fibrinogen gamma chain （FGG）, FOS-like antigen 2 （FOSL2）, and a-l, 6-mannosylglycoprotein 6-^-N-acetylglucosaminyltransferase B （MGATSB） were validated by Western blot. All these three proteins were up-regulated in the HCC serum samples. Conclusion： A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC.
文摘The porous NiTi(pNiTi)samples were produced by sintering evaporation using Ti−50.8Ni(at.%)gasatomized powders.The samples were analyzed by metallographic microscope and X-ray dispersive spectroscopy(XRD).A comparison of nickel(Ni)release and cytocompatibility between pNiTi and dense NiTi(dNiTi)was made.The results showed that the pNiTi has good mechanical properties.Ni releases from pNiTi in vitro and in vivo are more serious than those form dNiTi.The proliferation and differentiation of cells cultured with the pNiTi extracting liquid are significantly worse,and the rate of early apoptosis is higher.In conclusion,pNiTi is mechanically similar to bone,but pNiTi releases more Ni and interferes with cell proliferation and differentiation.A significantly cautious approach should be adopted when using it as a medical implant.
文摘Objective: To discuss the mRNA and protein expression of autophagy marker molecule Beclin1 in osteosarcoma tissue and their correlation with pathological features. Methods: A total of 60 patients with osteosarcoma receiving surgical treatment in the hospital between April 2012 and January 2016 were selected, and the osteosarcoma tissue and adjacent normal tissue samples were collected during operation. Fluorescence quantitative PCR method was used to detect the expression of Beclin1 mRNA as well as proliferation and invasion gene expression in the tissue specimens, and the Beclin1 protein expression was detected by western-blot method. According to the median of Beclin1 mRNA and protein expression in osteosarcoma tissues, they were further grouped into high Beclin1 mRNA expression group (n=30) and low Beclin1 mRNA expression group (n=30) as well as high Beclin1 protein expression group (n=30) and low Beclin1 protein expression group (n=30). The differences in proliferation and invasion gene expression in osteosarcoma tissue with different Beclin1 mRNA and Beclin1 protein expression were compared. Results: Beclin1 mRNA and Beclin1 protein expression in osteosarcoma tissue were lower than those in adjacent normal tissue;proliferation gene KISS-1 mRNA expression in low Beclin1 mRNA expression group of osteosarcoma tissue was lower than that in high Beclin1 mRNA expression group while Six1, FoxM1, RIPK4 and STIM1 mRNA expression were higher than those in high Beclin1 mRNA expression group;invasion gene DLX1 mRNA expression was lower than that in high Beclin1 mRNA expression group while EFEMP1, MTA1, Notch1, HES1 and LEF-1 mRNA expression were higher than those in high Beclin1 mRNA expression group;proliferation gene KISS-1 mRNA expression in low Beclin1 protein expression group of osteosarcoma tissue was lower than that in high Beclin1 protein expression group while Six1, FoxM1, RIPK4 and STIM1 mRNA expression were higher than those in high Beclin1 protein expression group;invasion gene DLX1 mRNA expression was lower than that in high Beclin1 protein expression group while EFEMP1, MTA1, Notch1, HES1 and LEF-1 mRNA expression were higher than those in high Beclin1 protein expression group. Conclusion: Both mRNA and protein expression of autophagy marker molecule Beclin1 decrease in osteosarcoma tissue and are directly correlated with the proliferation and invasion activity of tumor cells.
