BACKGROUND Hepatocellular carcinoma(HCC) is one of the most common malignant tumors worldwide, and novel methods for early/rapid diagnosis of HCC are needed.Terahertz(THz) spectroscopy is considered to have the potent...BACKGROUND Hepatocellular carcinoma(HCC) is one of the most common malignant tumors worldwide, and novel methods for early/rapid diagnosis of HCC are needed.Terahertz(THz) spectroscopy is considered to have the potential to distinguish between normal liver tissue and HCC tissue; however, there are few reports on it.We conduct this observational study to explore the feasibility of THz imaging for the diagnosis of HCC.AIM To evaluate the feasibility of THz for discriminating between HCC and normal liver tissues using fresh tissue specimens obtained from HCC patients who had undergone surgery.METHODS Normal liver tissue and HCC tissue were cryosectioned into 50 μm-thick slicesand placed on cover glass. Two adjacent tissue sections were separated subjected to histopathological examination by hematoxylin and eosin staining or THz transmission examination, and THz images were compared with pathologically mapped images. We determined the typical tumor and normal liver tissue regions by pathological examination; the corresponding areas of adjacent sections were examined by THz transmission.RESULTS The transmission rate of HCC tissue was 0.15-0.25, and the transmission rate of typical HCC tissue was about 0.2. THz transmittance in normal liver tissue is slightly higher than 0.4, but there were many influencing factors, including the degree of liver cirrhosis, fat components, ice crystals in frozen sections, and apoptosis.CONCLUSION In conclusion, this study shows that THz imaging can detect HCC tissue. Further research will yield more detailed data of the THz transmission rates of HCC tissue with different degrees of differentiation.展开更多
BACKGROUND Human epidermal growth factor receptor 2(HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal...BACKGROUND Human epidermal growth factor receptor 2(HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal adenocarcinomas(CRCs) remains uncertain, its relevance as a therapeutic target has been established. We undertook the present study to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables.AIM To correlate HER2 protein expression and HER2 gene amplification with clinicopathological features and survival in surgically resected CRC.METHODS About 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining(IHC) to assess HER2 protein expression, and 141 selected tumors were further evaluated by fluorescence in situ hybridization(FISH) to assess HER2 gene amplification. Follow-up information was availablefor 1058 patients, and using this information we investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs, and evaluated the relationship between overexpression and clinicopathological parameters and prognosis.RESULTS HER2 IHC scores of 3+, 2+, 1+, and 0 were seen in 31(2.6%), 105(8.8%), 475(39.7%), and 584(48.9%) tumors, respectively. HER2 gene amplification was seen in 24/29 tumors with an IHC score of 3+(82.8%; unreadable in 2/31), 12/102 tumors with an IHC score of 2+(11.8%; unreadable in 2/104), and 0 tumors with IHC score of 1+(0/10). HER2 gene amplification was seen in 36/1191 tumors(3.0%; unreadable in 4/1195). Among the tumors with HER2 IHC scores of 3+and 2+, the mean percentage of tumor cells with positive IHC staining was 90%(median 100%, range 40%-100%) and 67%(median 75%, range 5%-95%),respectively(P < 0.05). Among tumors with IHC scores of 2+, those with HER2 gene amplification had a higher number of tumors cells with positive IHC staining(n = 12, mean 93%, median 95%, range 90%-95%) than those without(n =90, mean 70%, median 50%, range 5%-95%)(P < 0.05). HER2 gene status was significantly associated with distant tumor metastasis and stage(P = 0.028 and0.025). HER2 protein overexpression as measured by IHC or HER2 gene amplification as measured by FISH was not associated with overall survival(OS)or disease-specific survival for the overall group of 1058 patients. However,further stratification revealed that among patients with tubular adenocarcinomas who were 65 years old or younger(n = 601), those exhibiting HER2 gene amplification had a shorter OS than those without(mean: 47.9 mo vs 65.1 mo, P =0.04). Among those patients with moderately to poorly differentiated tubular adenocarcinomas, those with positive HER2 tumor IHC scores(2+, 3+) had a shorter mean OS than those with negative HER2 IHC scores(0, 1+)(47.2 mo vs64.8 mo, P = 0.033). Moreover, among patients with T2 to T4 stage tumors, those with positive HER2 IHC scores also had a shorter mean OS than those with negative HER2 IHC scores(47.1 mo vs 64.8 mo, P = 0.031).CONCLUSION HER2 protein levels are correlated with clinical outcomes, and positive HER2 expression as measured by IHC confers a worse prognosis in those patients 65 years old or younger with tubular adenocarcinomas.展开更多
BACKGROUND Hepatocellular carcinoma is one of the most common malignant tumors worldwide. Currently, the most accurate diagnosis imaging modality for hepatocellular carcinoma is enhanced magnetic resonance imaging. Ho...BACKGROUND Hepatocellular carcinoma is one of the most common malignant tumors worldwide. Currently, the most accurate diagnosis imaging modality for hepatocellular carcinoma is enhanced magnetic resonance imaging. However, it is still difficult to distinguish cirrhosis lesions, and novel diagnosis modalities are still needed.AIM To investigate the feasibility of hyperspectral analysis for discrimination of rabbit liver VX2 tumor.METHODS In this study, a rabbit liver VX2 tumor model was established. After laparotomy,under direct view, VX2 tumor tissue and normal liver tissue were subjected to hyperspectral analysis.RESULTS The spectral signature of the liver tumor was clearly distinguishable from that of the normal tissue, simply from the original spectral curves. Specifically, two absorption peaks at 600-900 nm wavelength in normal tissue disappeared but a new reflection peak appeared in the tumor. The average optical reflection at the whole waveband of 400-1800 nm in liver tumor was higher than that of the normal tissue.CONCLUSION Hyperspectral analysis can differentiate rabbit VX2 tumors. Further research will continue to perform hyperspectral imaging to obtain more information for differentiation of liver cancer from normal tissue.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer and a leading cause of tumor-related death.Patients with large HCC(≥8 cm)are at an advanced stage and have poor prognosis,and hepatic resection may not be su...BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer and a leading cause of tumor-related death.Patients with large HCC(≥8 cm)are at an advanced stage and have poor prognosis,and hepatic resection may not be suitable,and the incidence of postoperative recurrence is high.AIM To evaluate recurrence and mid-term survival of patients with large HCC treated by transcatheter arterial chemoembolization(TACE)and radiofrequency ablation(RFA).METHODS This was a retrospective study.From 2010 to 2013,46 consecutive patients with large HCC were treated with simultaneous TACE and RFA.Thirty-five of 46 patients had a single tumor.Progression-free survival(PFS)and overall survival(OS)were analyzed at 2 years and 3 years,respectively.RESULTS Forty-six patients treated by simultaneous TACE and RFA had no significant complications and treatment was successful.After 3 years,median PFS and OS were 10.21±1.58 mo and 26.44±2.26 mo,retrospectively.The survival rate was 67.5%after 2 years and 55.67%after 3 years.CONCLUSION These preliminary data show that simultaneous TACE and RFA are safe and effective for large HCC.展开更多
Background: Currently, treatment of symptomatic polycystic liver disease (PLD) is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as lapa...Background: Currently, treatment of symptomatic polycystic liver disease (PLD) is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as laparoscopic fenestration and percutaneous cyst aspiration with sclerotherapy demonstrated disappointing results due to multiple lesions. Because the cysts in PLD are mostly supplied from hepatic arteries but not from portal veins, transcatheter arterial embolization (TAE) of the hepatic artery branches that supply the major hepatic cysts can lead to shrinkage of the cyst and liver size, relieve symptoms, and improve nutritional status. This study aimed to evaluate the effectiveness of TAE with a mixture of N-butyl-2-cyanoacrylate (NBCA) and iodized oil for patients with severe symptomatic PLD during a more than 2-year follow-up, Methods: Institutional review board had approved this study. Written informed consent was obtained from all patients. From February 2007 to December 2014, twenty-three patients (20 women and 3 men; mean age, 49.0 ± 14.5 years) infeasible for surgical treatments underwent TAE. Changes in the abdominal circumferences, volumes of intrahepatic cysts, hepatic parenchyma volume, and whole liver, clinical symptoms, laboratory data, and complications were evaluated after TAE. Results: Technical success was achieved in all cases. No procedure-related major complications occurred. The median follow-up period after TAE was 48.5 months (interquartile range, 30.0-72.0 months). PLD-related severe symptoms were improved remarkably in 86% of the treated patients; TAE failed to benefit in four patients (four patients did not benefit from TAE). The mean maximum abdominal circumference decreased significantly from 1 06.0± 8.0 cm to 87.0 ± 15.0 cm (P = 0.021). The mean intrahepatic cystic volume reduction rates compared with pre-TAE were 36% at 12 months, 37% at 24 months, and 38% at 36 months after TAE (P 〈 0.05). The mean liver volume reduction rates were 32% at 12 months, 31% at 24 months, and 33% at 36 months (P 〈 0.05). Conclusions: TAE with the mixture of NBCA and iodized oil appears to be a safe and effective treatment method for patients with symptomatic PLD, especially for those who are not good candidates for surgical treatments, to improve both hepatic volume and hepatic cysts volume.展开更多
Background:Insulin gene enhancer protein 1,(ISL1),a LIM-homeodomain transcription factor,is involved in multiple tumors and is associated with insulin secretion and metabolic phenotypes.However,the role of ISL1 in sti...Background:Insulin gene enhancer protein 1,(ISL1),a LIM-homeodomain transcription factor,is involved in multiple tumors and is associated with insulin secretion and metabolic phenotypes.However,the role of ISL1 in stimulating glycolysis to promote tumorigenesis in gastric cancer(GC)is unclear.In this study,we aimed to characterize the expression pattern of ISL1 in GC patients and explore its molecular biological mechanism in glycolysis and tumorigenesis.Methods:We analyzed the expression and clinical significance of ISL1 in GC using immunohistochemistry and real-time polymerase chain reaction(PCR).Flow cytometry and IncuCyte assays were used to measure cell proliferation after ISL1 knockdown.RNA-sequencing was performed to identify differentially expressed genes,followed by Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and Gene Set Enrichment Analysis(GSEA)to reveal key signaling pathways likely regulated by ISL1 in GC.Alteration of the glycolytic ability of GC cells with ISL1 knockdown was validated by measuring the extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)and by detecting glucose consumption and lactate production.The expression of glucose transporter 4(GLUT4)and ISL1 was assessed by Western blotting,immunohistochemistry,and immunofluorescent microscopy.The luciferase reporter activity and chromatin immunoprecipitation assays were performed to determine the transcriptional regulation of ISL1 on GLUT4.Results:High levels of ISL1 and GLUT4 expression was associated with short survival of GC patients.ISL1 knockdown inhibited cell proliferation both in vitro and in vivo.KEGG analysis and GSEA for RNA-sequencing data indicated impairment of the glycolysis pathway in GC cells with ISL1 knockdown,which was validated by reduced glucose uptake and lactate production,decreased ECAR,and increased OCR.Mechanistic investigation indicated that ISL1 transcriptionally regulated GLUT4 through binding to its promoter.Conclusion:ISL1 facilitates glycolysis and tumorigenesis in GC via the transcriptional regulation of GLUT4.展开更多
基金Supported by the National Natural Science Foundation of China,No.11622542 and No.51677145
文摘BACKGROUND Hepatocellular carcinoma(HCC) is one of the most common malignant tumors worldwide, and novel methods for early/rapid diagnosis of HCC are needed.Terahertz(THz) spectroscopy is considered to have the potential to distinguish between normal liver tissue and HCC tissue; however, there are few reports on it.We conduct this observational study to explore the feasibility of THz imaging for the diagnosis of HCC.AIM To evaluate the feasibility of THz for discriminating between HCC and normal liver tissues using fresh tissue specimens obtained from HCC patients who had undergone surgery.METHODS Normal liver tissue and HCC tissue were cryosectioned into 50 μm-thick slicesand placed on cover glass. Two adjacent tissue sections were separated subjected to histopathological examination by hematoxylin and eosin staining or THz transmission examination, and THz images were compared with pathologically mapped images. We determined the typical tumor and normal liver tissue regions by pathological examination; the corresponding areas of adjacent sections were examined by THz transmission.RESULTS The transmission rate of HCC tissue was 0.15-0.25, and the transmission rate of typical HCC tissue was about 0.2. THz transmittance in normal liver tissue is slightly higher than 0.4, but there were many influencing factors, including the degree of liver cirrhosis, fat components, ice crystals in frozen sections, and apoptosis.CONCLUSION In conclusion, this study shows that THz imaging can detect HCC tissue. Further research will yield more detailed data of the THz transmission rates of HCC tissue with different degrees of differentiation.
基金Special Scientific Research Key Project for Capital Health Development,China,No.2018-2Z-1026
文摘BACKGROUND Human epidermal growth factor receptor 2(HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal adenocarcinomas(CRCs) remains uncertain, its relevance as a therapeutic target has been established. We undertook the present study to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables.AIM To correlate HER2 protein expression and HER2 gene amplification with clinicopathological features and survival in surgically resected CRC.METHODS About 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining(IHC) to assess HER2 protein expression, and 141 selected tumors were further evaluated by fluorescence in situ hybridization(FISH) to assess HER2 gene amplification. Follow-up information was availablefor 1058 patients, and using this information we investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs, and evaluated the relationship between overexpression and clinicopathological parameters and prognosis.RESULTS HER2 IHC scores of 3+, 2+, 1+, and 0 were seen in 31(2.6%), 105(8.8%), 475(39.7%), and 584(48.9%) tumors, respectively. HER2 gene amplification was seen in 24/29 tumors with an IHC score of 3+(82.8%; unreadable in 2/31), 12/102 tumors with an IHC score of 2+(11.8%; unreadable in 2/104), and 0 tumors with IHC score of 1+(0/10). HER2 gene amplification was seen in 36/1191 tumors(3.0%; unreadable in 4/1195). Among the tumors with HER2 IHC scores of 3+and 2+, the mean percentage of tumor cells with positive IHC staining was 90%(median 100%, range 40%-100%) and 67%(median 75%, range 5%-95%),respectively(P < 0.05). Among tumors with IHC scores of 2+, those with HER2 gene amplification had a higher number of tumors cells with positive IHC staining(n = 12, mean 93%, median 95%, range 90%-95%) than those without(n =90, mean 70%, median 50%, range 5%-95%)(P < 0.05). HER2 gene status was significantly associated with distant tumor metastasis and stage(P = 0.028 and0.025). HER2 protein overexpression as measured by IHC or HER2 gene amplification as measured by FISH was not associated with overall survival(OS)or disease-specific survival for the overall group of 1058 patients. However,further stratification revealed that among patients with tubular adenocarcinomas who were 65 years old or younger(n = 601), those exhibiting HER2 gene amplification had a shorter OS than those without(mean: 47.9 mo vs 65.1 mo, P =0.04). Among those patients with moderately to poorly differentiated tubular adenocarcinomas, those with positive HER2 tumor IHC scores(2+, 3+) had a shorter mean OS than those with negative HER2 IHC scores(0, 1+)(47.2 mo vs64.8 mo, P = 0.033). Moreover, among patients with T2 to T4 stage tumors, those with positive HER2 IHC scores also had a shorter mean OS than those with negative HER2 IHC scores(47.1 mo vs 64.8 mo, P = 0.031).CONCLUSION HER2 protein levels are correlated with clinical outcomes, and positive HER2 expression as measured by IHC confers a worse prognosis in those patients 65 years old or younger with tubular adenocarcinomas.
文摘BACKGROUND Hepatocellular carcinoma is one of the most common malignant tumors worldwide. Currently, the most accurate diagnosis imaging modality for hepatocellular carcinoma is enhanced magnetic resonance imaging. However, it is still difficult to distinguish cirrhosis lesions, and novel diagnosis modalities are still needed.AIM To investigate the feasibility of hyperspectral analysis for discrimination of rabbit liver VX2 tumor.METHODS In this study, a rabbit liver VX2 tumor model was established. After laparotomy,under direct view, VX2 tumor tissue and normal liver tissue were subjected to hyperspectral analysis.RESULTS The spectral signature of the liver tumor was clearly distinguishable from that of the normal tissue, simply from the original spectral curves. Specifically, two absorption peaks at 600-900 nm wavelength in normal tissue disappeared but a new reflection peak appeared in the tumor. The average optical reflection at the whole waveband of 400-1800 nm in liver tumor was higher than that of the normal tissue.CONCLUSION Hyperspectral analysis can differentiate rabbit VX2 tumors. Further research will continue to perform hyperspectral imaging to obtain more information for differentiation of liver cancer from normal tissue.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer and a leading cause of tumor-related death.Patients with large HCC(≥8 cm)are at an advanced stage and have poor prognosis,and hepatic resection may not be suitable,and the incidence of postoperative recurrence is high.AIM To evaluate recurrence and mid-term survival of patients with large HCC treated by transcatheter arterial chemoembolization(TACE)and radiofrequency ablation(RFA).METHODS This was a retrospective study.From 2010 to 2013,46 consecutive patients with large HCC were treated with simultaneous TACE and RFA.Thirty-five of 46 patients had a single tumor.Progression-free survival(PFS)and overall survival(OS)were analyzed at 2 years and 3 years,respectively.RESULTS Forty-six patients treated by simultaneous TACE and RFA had no significant complications and treatment was successful.After 3 years,median PFS and OS were 10.21±1.58 mo and 26.44±2.26 mo,retrospectively.The survival rate was 67.5%after 2 years and 55.67%after 3 years.CONCLUSION These preliminary data show that simultaneous TACE and RFA are safe and effective for large HCC.
文摘Background: Currently, treatment of symptomatic polycystic liver disease (PLD) is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as laparoscopic fenestration and percutaneous cyst aspiration with sclerotherapy demonstrated disappointing results due to multiple lesions. Because the cysts in PLD are mostly supplied from hepatic arteries but not from portal veins, transcatheter arterial embolization (TAE) of the hepatic artery branches that supply the major hepatic cysts can lead to shrinkage of the cyst and liver size, relieve symptoms, and improve nutritional status. This study aimed to evaluate the effectiveness of TAE with a mixture of N-butyl-2-cyanoacrylate (NBCA) and iodized oil for patients with severe symptomatic PLD during a more than 2-year follow-up, Methods: Institutional review board had approved this study. Written informed consent was obtained from all patients. From February 2007 to December 2014, twenty-three patients (20 women and 3 men; mean age, 49.0 ± 14.5 years) infeasible for surgical treatments underwent TAE. Changes in the abdominal circumferences, volumes of intrahepatic cysts, hepatic parenchyma volume, and whole liver, clinical symptoms, laboratory data, and complications were evaluated after TAE. Results: Technical success was achieved in all cases. No procedure-related major complications occurred. The median follow-up period after TAE was 48.5 months (interquartile range, 30.0-72.0 months). PLD-related severe symptoms were improved remarkably in 86% of the treated patients; TAE failed to benefit in four patients (four patients did not benefit from TAE). The mean maximum abdominal circumference decreased significantly from 1 06.0± 8.0 cm to 87.0 ± 15.0 cm (P = 0.021). The mean intrahepatic cystic volume reduction rates compared with pre-TAE were 36% at 12 months, 37% at 24 months, and 38% at 36 months after TAE (P 〈 0.05). The mean liver volume reduction rates were 32% at 12 months, 31% at 24 months, and 33% at 36 months (P 〈 0.05). Conclusions: TAE with the mixture of NBCA and iodized oil appears to be a safe and effective treatment method for patients with symptomatic PLD, especially for those who are not good candidates for surgical treatments, to improve both hepatic volume and hepatic cysts volume.
基金Natural Science Foundation of Beijing,Grant/Award Number:7132051National Natural Science Foundation of China,Grant/Award Numbers:81301874,81972758,81872502,81802471+3 种基金Interdisciplinary Medicine Seed Fund of Peking University,Grant/Award Number:BMU2018MX018Beijing Municipal Administration of Hospitals’Youth Program,Grant/Award Number:QML20181102National High Technology Research and Development Program of China,Grant/Award Number:2014AA020603Science Foundation of Peking University Cancer Hospital,Grant/Award Numbers:2017-23,2020-6。
文摘Background:Insulin gene enhancer protein 1,(ISL1),a LIM-homeodomain transcription factor,is involved in multiple tumors and is associated with insulin secretion and metabolic phenotypes.However,the role of ISL1 in stimulating glycolysis to promote tumorigenesis in gastric cancer(GC)is unclear.In this study,we aimed to characterize the expression pattern of ISL1 in GC patients and explore its molecular biological mechanism in glycolysis and tumorigenesis.Methods:We analyzed the expression and clinical significance of ISL1 in GC using immunohistochemistry and real-time polymerase chain reaction(PCR).Flow cytometry and IncuCyte assays were used to measure cell proliferation after ISL1 knockdown.RNA-sequencing was performed to identify differentially expressed genes,followed by Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and Gene Set Enrichment Analysis(GSEA)to reveal key signaling pathways likely regulated by ISL1 in GC.Alteration of the glycolytic ability of GC cells with ISL1 knockdown was validated by measuring the extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)and by detecting glucose consumption and lactate production.The expression of glucose transporter 4(GLUT4)and ISL1 was assessed by Western blotting,immunohistochemistry,and immunofluorescent microscopy.The luciferase reporter activity and chromatin immunoprecipitation assays were performed to determine the transcriptional regulation of ISL1 on GLUT4.Results:High levels of ISL1 and GLUT4 expression was associated with short survival of GC patients.ISL1 knockdown inhibited cell proliferation both in vitro and in vivo.KEGG analysis and GSEA for RNA-sequencing data indicated impairment of the glycolysis pathway in GC cells with ISL1 knockdown,which was validated by reduced glucose uptake and lactate production,decreased ECAR,and increased OCR.Mechanistic investigation indicated that ISL1 transcriptionally regulated GLUT4 through binding to its promoter.Conclusion:ISL1 facilitates glycolysis and tumorigenesis in GC via the transcriptional regulation of GLUT4.