Pancreatic cancer has become the fourth leading cause of cancer death in the last two decades. Only 3%-15% of patients diagnosed with pancreatic cancer had 5 year survival rate. Drug resistance, high metastasis, poor ...Pancreatic cancer has become the fourth leading cause of cancer death in the last two decades. Only 3%-15% of patients diagnosed with pancreatic cancer had 5 year survival rate. Drug resistance, high metastasis, poor prognosis and tumour relapse contributed to the malignancies and difficulties in treating pancreatic cancer. The current standard chemotherapy for pancreatic cancer is gemcitabine, however its efficacy is far from satisfactory, one of the reasons is due to the complex tumour microenvironment which decreases effective drug delivery to target cancer cell. Studies of the molecular pathology of pancreatic cancer have revealed that activation of KRAS, overexpression of cyclooxygenase-2, inactivation of p16<sup>INK4A</sup> and loss of p53 activities occurred in pancreatic cancer. Co-administration of gemcitabine and targeting the molecular pathological events happened in pancreatic cancer has brought an enhanced therapeutic effectiveness of gemcitabine. Therefore, studies looking for novel targets in hindering pancreatic tumour growth are emerging rapidly. In order to give a better understanding of the current findings and to seek the direction in future pancreatic cancer research; in this review we will focus on targets suppressing tumour metastatsis and progression, KRAS activated downstream effectors, the relationship of Notch signaling and Nodal/Activin signaling with pancreatic cancer cells, the current findings of non-coding RNAs in inhibiting pancreatic cancer cell proliferation, brief discussion in transcription remodeling by epigenetic modifiers (e.g., HDAC, BMI1, EZH2) and the plausible therapeutic applications of cancer stem cell and hyaluronan in tumour environment.展开更多
BACKGROUND Exosomes are microvesicles, measuring 30-100 nm in diameter. They are widely distributed in body fluids, including blood, bile, urine and saliva. Cancer-derived exosomes carry a wide variety of DNA, RNA, pr...BACKGROUND Exosomes are microvesicles, measuring 30-100 nm in diameter. They are widely distributed in body fluids, including blood, bile, urine and saliva. Cancer-derived exosomes carry a wide variety of DNA, RNA, proteins and lipids, and may serve as novel biomarkers in cancer.AIM To summarize the performance of exosomal biomarkers in cancer diagnosis and prognosis.METHODS Relevant publications in the literature were identified by search of the "PubMed"database up to September 11, 2018. The quality of the included studies was assessed by QUADAS-2 and REMARK. For assessment of diagnostic biomarkers,47 biomarkers and 2240 patients from 30 studies were included.RESULTS Our results suggested that these exosomal biomarkers had excellent diagnostic ability in various types of cancer, with good sensitivity and specificity. For assessment of prognostic markers, 50 biomarkers and 4797 patients from 42 studies were included. We observed that exosomal biomarkers had prognostic values in overall survival, disease-free survival and recurrence-free survival.CONCLUSION Exosomes can function as potential biomarkers in cancer diagnosis and prognosis.展开更多
The role of bile acids in colorectal cancer has been well documented,but their role in pancreatic cancer remains unclear. In this review,we examined the risk factors of pancreatic cancer. We found that bile acids are ...The role of bile acids in colorectal cancer has been well documented,but their role in pancreatic cancer remains unclear. In this review,we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors. Alcohol intake,smoking,and a high-fat diet all lead to high secretion of bile acids,and bile acid metabolic dysfunction is a causal factor of gallstones. An increase in secretion of bile acids,in addition to a long common channel,may result in bile acid reflux into the pancreatic duct and to the epithelial cells or acinar cells,from which pancreatic adenocarcinoma is derived. The final pathophysiological process is pancreatitis,which promotes dedifferentiation of acinar cells into progenitor duct-like cells. Interestingly,bile acids act as regulatory molecules in metabolism,affecting adipose tissue distribution,insulin sensitivity and triglyceride metabolism. As a result,bile acids are associated with three risk factors of pancreatic cancer: obesity,diabetes and hypertriglyceridemia. In the second part of this review,we summarize several studies showing that bile acids act as cancer promoters in gastrointestinal cancer. However,more question are raised than have been solved,and further oncological and physiological experiments are needed to confirm the role of bile acids in pancreatic cancer carcinogenesis.展开更多
Pancreatic ductal adenocarcinoma(PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of eff...Pancreatic ductal adenocarcinoma(PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of effective prognosis, diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be the origin of PDAC. During pancreatitis or combined with activating KRasG12 D mutation, acinar cells lose their cellular identity and undergo a transdifferentiation process called acinarto-ductal-metaplasia(ADM), forming duct cells which may then transform into pancreatic intraepithelial neoplasia(Pan IN) and eventually PDAC. During ADM, the activation of mitogen-activated protein kinases, Wnt, Notch and phosphatidylinositide 3-kinases/Akt signaling inhibits the transcription of acinar-specific genes, including Mist and amylase, but promotes the expression of ductal genes, such as cytokeratin-19. Inhibition of this transdifferentiation process hinders the development of Pan IN and PDAC. In addition, the transdifferentiated cells regain acinar identity, indicating ADM may be a reversible process. This provides a new therapeutic direction in treating PDAC through cancer reprogramming. Many studies have already demonstrated the success of switching Pan IN/PDAC back to normal cells through the use of PD325901, the expression of E47, and the knockdown of Dickkopf-3. In this review, we discuss the signaling pathways involved in ADM and the therapeutic potential of targeting reprogramming in order to treat PDAC.展开更多
Direct formic acid fuel cells are a promising portable power-generating device, and the development of efficient anodic catalysts is essential for such a fuel cell. In this work Pt-Bi nanoparticles supported on micro-...Direct formic acid fuel cells are a promising portable power-generating device, and the development of efficient anodic catalysts is essential for such a fuel cell. In this work Pt-Bi nanoparticles supported on micro-fabri- cated gold wire array substrate were synthesized using an electrochemical deposition method for formic acid oxida- tion in fuel cells. The surface morphology and element components of the Pt-Bi/Au nanoparticles were character- ized, and the catalytic activities of the three Pt-Bi/Au nanoparticle electrodes with different Pt/Bi ratios for formic acid oxidation were evaluated. It was found that Pt4Bi96/Au had a much higher catalytic activity than Pt11Bis89/Au and Pt13Bis87/Au, and Pt4Bi96/Au exhibited a current density of 2.7mA.cm^-2, which was 27-times greater than that of Pt/Au. The electro-catalytic activity of the Pt-Bi/Au electrode for formic acid oxidation increased with the increasing Bi content, suggesting that it would be possible to achieve an efficient formic acid oxidation on the low Pt-loading. Therefore, the Pt-Bi/Au electrode offers a promising catalyst with a high activity for direct oxidation of formic acid in fuel cells.展开更多
Several methods have been developed to design and analyze moire magnifier, but these methods are all lack of quantitative consideration on the depth of moire imaging. In this paper, a new design method for moire magni...Several methods have been developed to design and analyze moire magnifier, but these methods are all lack of quantitative consideration on the depth of moire imaging. In this paper, a new design method for moire magnifier based on depth cues from disparity is proposed. By using of the proposed method, the period magnification, the rotation angle of moire pattern can also be calculated, and the moire depth can be analyzed, too. According to the design and analysis results using MATLAB, the period of arrays and the cross angle are the important influence factors as the moire pattern above or below the microlens array. Moreover, with our 3 D design method, we can design different moire magnifier with different size, direction angle and depth of moire pattern as required.展开更多
文摘Pancreatic cancer has become the fourth leading cause of cancer death in the last two decades. Only 3%-15% of patients diagnosed with pancreatic cancer had 5 year survival rate. Drug resistance, high metastasis, poor prognosis and tumour relapse contributed to the malignancies and difficulties in treating pancreatic cancer. The current standard chemotherapy for pancreatic cancer is gemcitabine, however its efficacy is far from satisfactory, one of the reasons is due to the complex tumour microenvironment which decreases effective drug delivery to target cancer cell. Studies of the molecular pathology of pancreatic cancer have revealed that activation of KRAS, overexpression of cyclooxygenase-2, inactivation of p16<sup>INK4A</sup> and loss of p53 activities occurred in pancreatic cancer. Co-administration of gemcitabine and targeting the molecular pathological events happened in pancreatic cancer has brought an enhanced therapeutic effectiveness of gemcitabine. Therefore, studies looking for novel targets in hindering pancreatic tumour growth are emerging rapidly. In order to give a better understanding of the current findings and to seek the direction in future pancreatic cancer research; in this review we will focus on targets suppressing tumour metastatsis and progression, KRAS activated downstream effectors, the relationship of Notch signaling and Nodal/Activin signaling with pancreatic cancer cells, the current findings of non-coding RNAs in inhibiting pancreatic cancer cell proliferation, brief discussion in transcription remodeling by epigenetic modifiers (e.g., HDAC, BMI1, EZH2) and the plausible therapeutic applications of cancer stem cell and hyaluronan in tumour environment.
基金supported by grants from the General Research Fund, Research Grants Council of Hong Kong (CUHK462713, 14102714, 14136416 and 14171217)National Natural Science Foundation of China (8142730 and 81672323)Direct Grant from CUHK to YC
文摘BACKGROUND Exosomes are microvesicles, measuring 30-100 nm in diameter. They are widely distributed in body fluids, including blood, bile, urine and saliva. Cancer-derived exosomes carry a wide variety of DNA, RNA, proteins and lipids, and may serve as novel biomarkers in cancer.AIM To summarize the performance of exosomal biomarkers in cancer diagnosis and prognosis.METHODS Relevant publications in the literature were identified by search of the "PubMed"database up to September 11, 2018. The quality of the included studies was assessed by QUADAS-2 and REMARK. For assessment of diagnostic biomarkers,47 biomarkers and 2240 patients from 30 studies were included.RESULTS Our results suggested that these exosomal biomarkers had excellent diagnostic ability in various types of cancer, with good sensitivity and specificity. For assessment of prognostic markers, 50 biomarkers and 4797 patients from 42 studies were included. We observed that exosomal biomarkers had prognostic values in overall survival, disease-free survival and recurrence-free survival.CONCLUSION Exosomes can function as potential biomarkers in cancer diagnosis and prognosis.
基金Supported by General Research Fund,Research Grants Council of Hong Kong,No.CUHK462211,No.CUHK462713 and No.14102714National Natural Science Foundation of China,No.81101888 and No.8142730Direct Grant from CUHK
文摘The role of bile acids in colorectal cancer has been well documented,but their role in pancreatic cancer remains unclear. In this review,we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors. Alcohol intake,smoking,and a high-fat diet all lead to high secretion of bile acids,and bile acid metabolic dysfunction is a causal factor of gallstones. An increase in secretion of bile acids,in addition to a long common channel,may result in bile acid reflux into the pancreatic duct and to the epithelial cells or acinar cells,from which pancreatic adenocarcinoma is derived. The final pathophysiological process is pancreatitis,which promotes dedifferentiation of acinar cells into progenitor duct-like cells. Interestingly,bile acids act as regulatory molecules in metabolism,affecting adipose tissue distribution,insulin sensitivity and triglyceride metabolism. As a result,bile acids are associated with three risk factors of pancreatic cancer: obesity,diabetes and hypertriglyceridemia. In the second part of this review,we summarize several studies showing that bile acids act as cancer promoters in gastrointestinal cancer. However,more question are raised than have been solved,and further oncological and physiological experiments are needed to confirm the role of bile acids in pancreatic cancer carcinogenesis.
基金Supported by the General Research Fund,Research Grants Council of Hong Kong,No.CUHK462211,No.CUHK462713 and No.14102714the National Natural Science Foundation of China,No.81101888 and No.8142730
文摘Pancreatic ductal adenocarcinoma(PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of effective prognosis, diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be the origin of PDAC. During pancreatitis or combined with activating KRasG12 D mutation, acinar cells lose their cellular identity and undergo a transdifferentiation process called acinarto-ductal-metaplasia(ADM), forming duct cells which may then transform into pancreatic intraepithelial neoplasia(Pan IN) and eventually PDAC. During ADM, the activation of mitogen-activated protein kinases, Wnt, Notch and phosphatidylinositide 3-kinases/Akt signaling inhibits the transcription of acinar-specific genes, including Mist and amylase, but promotes the expression of ductal genes, such as cytokeratin-19. Inhibition of this transdifferentiation process hinders the development of Pan IN and PDAC. In addition, the transdifferentiated cells regain acinar identity, indicating ADM may be a reversible process. This provides a new therapeutic direction in treating PDAC through cancer reprogramming. Many studies have already demonstrated the success of switching Pan IN/PDAC back to normal cells through the use of PD325901, the expression of E47, and the knockdown of Dickkopf-3. In this review, we discuss the signaling pathways involved in ADM and the therapeutic potential of targeting reprogramming in order to treat PDAC.
文摘Direct formic acid fuel cells are a promising portable power-generating device, and the development of efficient anodic catalysts is essential for such a fuel cell. In this work Pt-Bi nanoparticles supported on micro-fabri- cated gold wire array substrate were synthesized using an electrochemical deposition method for formic acid oxida- tion in fuel cells. The surface morphology and element components of the Pt-Bi/Au nanoparticles were character- ized, and the catalytic activities of the three Pt-Bi/Au nanoparticle electrodes with different Pt/Bi ratios for formic acid oxidation were evaluated. It was found that Pt4Bi96/Au had a much higher catalytic activity than Pt11Bis89/Au and Pt13Bis87/Au, and Pt4Bi96/Au exhibited a current density of 2.7mA.cm^-2, which was 27-times greater than that of Pt/Au. The electro-catalytic activity of the Pt-Bi/Au electrode for formic acid oxidation increased with the increasing Bi content, suggesting that it would be possible to achieve an efficient formic acid oxidation on the low Pt-loading. Therefore, the Pt-Bi/Au electrode offers a promising catalyst with a high activity for direct oxidation of formic acid in fuel cells.
基金supported by the National Key Basic Research Program of China(No.2016YFA0400902)
文摘Several methods have been developed to design and analyze moire magnifier, but these methods are all lack of quantitative consideration on the depth of moire imaging. In this paper, a new design method for moire magnifier based on depth cues from disparity is proposed. By using of the proposed method, the period magnification, the rotation angle of moire pattern can also be calculated, and the moire depth can be analyzed, too. According to the design and analysis results using MATLAB, the period of arrays and the cross angle are the important influence factors as the moire pattern above or below the microlens array. Moreover, with our 3 D design method, we can design different moire magnifier with different size, direction angle and depth of moire pattern as required.
