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Clinical significance of exosomes as potential biomarkers in cancer

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World Journal of Clinical Cases 2019年第2期7卷 171-190页

作者： Chi-Hin Wong yang-chao chen School of Biomedical Sciences Faculty of Medicine The Chinese University of Hong Kong Shenzhen Research Institute The Chinese University of Hong Kong

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 *** To summarize the performance of exosomal biomarkers in cancer diagnosis and *** 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 *** 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 *** Exosomes can function as potential biomarkers in cancer diagnosis and prognosis.

关键词： Exosome Biomarker Cancer Diagnosis Prognosis

Novel therapeutic targets for pancreatic cancer

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World Journal of Gastroenterology 2014年第31期20卷 10825-10844页

作者： Shing-Chun Tang yang-chao chen School of Biomedical Sciences Faculty of Medicine the Chinese University of Hong Kong Shenzhen Research Institute The Chinese University of Hong Kong

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 p16INK4A 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.

关键词： Pancreatic cancer CTHRC1 RAC1 RalGEF-RAl Notch Signaling Nodal/Activin Signaling NDRG1 Hypoxic condition DR5 PAR2 HER3 IAP Non-coding RNA HDAC BMI1 EZH2 Pancreatic cancer stem cell Tumour microenvironment

Role of bile acids in carcinogenesis of pancreatic cancer: An old topic with new perspective

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World Journal of Gastroenterology 2016年第33期22卷 7463-7477页

作者： Hui-Yi Feng yang-chao chen School of Biomedical Sciences Faculty of Medicinethe Chinese University of Hong Kong

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.

关键词： Bile acids Pancreatic adenocarcinoma Pancreatitis Metabolic syndrome

Therapeutic potential of targeting acinar cell reprogramming in pancreatic cancer

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World Journal of Gastroenterology 2016年第31期22卷 7046-7057页

作者： Chi-Hin Wong You-Jia Li yang-chao chen School of Biomedical Sciences Faculty of Medicine The Chinese University of Hong Kong Shenzhen Research Institute The Chinese University of Hong Kong

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.

关键词： Acinar cells Acinar-to-ductal metaplasia Pancreatic ductal adenocarcinoma Signal transduction Reprogramming

Modified stapled hemorrhoidopexy for lower postoperative stenosis: A five-year experience

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World Journal of Gastrointestinal Surgery 2024年第9期16卷 2787-2795页

作者： Yu-Hong Liu Tzu-Chiao Lin chao-yang chen Ta-Wei Pu Division of Colon and Rectal Surgery Department of SurgeryTri-Service General HospitalNational Defense Medical CenterTaipei 105TaiwanChina Division of Colon and Rectal Surgery Department of SurgeryTri-Service General Hospital Songshan BranchNational Defense Medical CenterTaipei 105TaiwanChina

BACKGROUND Stapled hemorrhoidopexy(SH)is currently a widely accepted method for treating the prolapse of internal *** anal stenosis is a critical complication of SH.A remedy for this involves the removal of the circumferential staples of the anastomosis,followed by the creation of a hand-sewn *** studies have reported modified SH procedures to improve *** hypothesized that our modified SH technique may help reduce complications of anal stenosis after *** To compare outcomes of staple removal at the 3-and 9-o’clock positions during modified SH in patients with mixed *** This was a single-center,retrospective,observational *** with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1,2015,and January 1,2020,were *** operation time,blood loss,length of hospital stay,and incidence of minor or major complic-ations were *** Patients with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1,2015 and January 1,2020,were *** time,blood loss,length of hospital stay,and incidence of minor or major complications were *** investigated 187 patients(mean age,50.9 years)who had undergone our modified SH and 313 patients(mean age,53.0 years)who had undergone standard *** the modified SH group,54%of patients had previously undergone surgical intervention for hemorrhoids,compared with the 40.3%of patients in the standard SH *** modified SH group included five(2.7%)patients with anal stenosis,while 21(6.7%)patients in the standard SH group had complications of anal *** was a significant relationship between the rate of postoperative anal stenosis and the modified SH:0.251(0.085-0.741)and 0.211(0.069-0.641)in multiple regression *** modified SH technique is a safe surgical method for advanced grade hemorrhoids and might result in

关键词： Anal canal Hemorrhoids Prolapse Stapled hemorrhoidopexy Postoperative anal stenosis Modified stapled hemorrhoidopexy

Application of output feedback sliding mode control to active flutter suppression of two-dimensional airfoil

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Science China(Technological Sciences) 2010年第5期53卷 1338-1348页

作者： yang chao,SONG chen,WU ZhiGang & XIE ChangChuan School of Aeronautic Science and Engineering,Beijing University of Aeronautics & Astronautics,Beijing 100191,China 1. School of Aeronautic Science and Engineering Beijing University of Aeronautics & Astronautics Beijing 100191 China

The effectiveness of the sliding mode control(SMC) method for active flutter suppression(AFS) and the issues concerning control system discretization and control input constraints were studied using a typical two-dimensional *** airfoil has a trailing-edge flap for flutter *** aeroelastic system involves a two-degrees-of-freedom motion(pitch and plunge),and the equations were constructed by utilizing quasi-steady aerodynamic *** control system,designed by the output feedback SMC method,was incorporated to suppress the pitch-plunge ***,the system discretization and the flap deflection constraints were ***,a classical Runge-Kutta(RK) algorithm was utilized for numerical *** results indicated that the close-loop system with the SMC system could be stable at a speed above the flutter ***,when the flap deflection limits are reached,the close-loop system with the simple discretized control system loses ***,control compensation developed by theoretical analysis was proposed to make the system stable *** parameter perturbations and the time delay effects were also discussed in this paper.

关键词： aeroelasticity flutter airfoil sliding mode control output feedback control

Risk factors predict microscopic extranodal tumor deposits in advanced stage Ⅲ colon cancer patients

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World Journal of Gastroenterology 2023年第11期29卷 1735-1744页

作者： Yi-Han Jhuang Yu-Ching Chou Yu-Chun Lin Je-Ming Hu Ta-Wei Pu chao-yang chen Division of Cardiovascular Surgery Tri-Service General HospitalNational Defense Medical CenterTaipei 114TaiwanChina School of Public Health National Defense Medical CenterTaipei 114TaiwanChina Department of Pathology Tri-Service General HospitalNational Defense Medical CenterTaipei 114TaiwanChina Division of Colorectal Surgery Tri-Service General HospitalNational Defense Medical CenterTaipei 114TaiwanChina Division of Colorectal Surgery Tri-Service General Hospital Song-shan BranchNational Defense Medical CenterTaipei 114TaiwanChina

BACKGROUND Colorectal cancer is a frequent cause of cancer-related mortality in patients with lymph node or distant *** tumor deposits(TDs)are considered prognostically distinct from lymph node *** To investigate risk factors for extranodal TDs in stage III colon *** This was a retrospective cohort *** selected 155 individuals diagnosed with stage III colon cancer from the database of the Cancer Registry of the Tri-Service General *** patients were allocated into the groups with/without *** Cox regression analysis and Kaplan-Meier method were *** primary outcomes investigate the association between the covariates and extranodal TDs,and prognostic significance of the covariates regarding the *** There were 136 individuals in the non-N1c group and 19 individuals in the N1c *** with lymphovascular invasion(LVI)had a higher risk of *** survival rates of patients with and without LVI were 6.64 years and 8.61 years,respectively(P=0.027).The N1c patients without LVI had higher overall survival than those who with LVI(7.73 years vs 4.42 years,P=0.010).CONCLUSION Patients having stage III colon cancer with LVI have a higher probability of having TDs than those with stage III colon cancer without *** III colon cancer patients with TDs and LVI could have poor prognosis and outcome.

关键词： Colon cancer Tumor deposits Lymphovascular invasion Risk factor

Cellular angiofibroma arising from the rectocutaneous fistula in an adult: A case report

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World Journal of Clinical Cases 2024年第10期12卷 1778-1784页

作者： Hao-En chen Yu-yang Lu Ruei-Yu Su Hong-Hau Wang chao-yang chen Je-Ming Hu Jung-cheng Kang Kuan-Hsun Lin Ta-Wei Pu Department of Surgery Taichung Armed Forces General HospitalTaichung 411Taiwan Department of Surgery Tri-Service General HospitalNational Defense Medical CenterTaipei 114Taiwan Department of Pediatrics Tri-Service General HospitalNational Defense Medical CenterTaipei 114Taiwan Department of Pathology Tri-Service General HospitalNational Defense Medical CenterTaipei 105Taiwan Department of Pathology and Laboratory Medicine Taoyuan Armed Forces General HospitalTaoyuan 32551Taiwan Department of Radiology Tri-Service General Hospital Songshan BranchNational Defense Medical CenterTaipei 105Taiwan Division of Colon and Rectal Surgery Department of SurgeryTri-Service General HospitalNational Defense Medical CenterTaipei 114Taiwan Division of Colon and Rectal Surgery Department of SurgeryTaiwan Adventist HospitalTaipei 105Taiwan Division of Thoracic Surgery Department of SurgeryTri-Service General HospitalNational Defense Medical CenterTaipei 114Taiwan Division of Colon and Rectal Surgery Department of SurgeryTri-Service General Hospital Songshan BranchNational Defense Medical CenterTaipei 105Taiwan

BACKGROUND Rectocutaneous fistulae are *** infection originates within the anal glands and subsequently extends into adjacent regions,ultimately resulting in fistula *** angiofibroma(CAF),also known as an angiomy ofibroblastoma-like tumor,is a rare benign soft tissue neoplasm predominantly observed in the scrotum,perineum,and inguinal area in males and in the vulva in *** describe the first documented case CAF that developed within a rectocutaneous fistula and manifested as a perineal *** SUMMARY In the outpatient setting,a 52-year-old male patient presented with a 2-year history of a growing perineal mass,accompanied by throbbing pain and minor scrotal *** examination revealed a soft,well-defined,non-tender mass at the left buttock that extended towards the perineum,without a visible *** initial assessment identified a soft tissue tumor,and the laboratory data were within normal *** and pelvic computed tomography(CT)revealed swelling of the abscess cavity that was linked to a rectal cutaneous fistula,with a track-like lesion measuring 6 cm×0.7 cm in the left perineal region and attached to the left *** examination found no significant inner orifices.A left medial gluteal incision revealed a thick-walled mass,which was excised along with the extending tract,and curettage was *** examination confirmed CAF *** patient achieved total resolution during follow-up assessments and did not require additional *** CT imaging supports perineal lesion diagnosis and *** angiofibromas,even with a cutaneous fistula,can be excised transperineally.

关键词： Angiofibroma Perineal mass Rectocutaneous fistula Anorectal fistula Anal fistula Case report

Cecocutaneous fistula diagnosed by computed tomography fistulography:A case report

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World Journal of Gastrointestinal Surgery 2022年第10期14卷 1161-1168页

作者： Tung-Yen Wu Kuang-Hua Lo chao-yang chen Je-Ming Hu Jung-cheng Kang Ta-Wei Pu Department of Surgery Tri-Service General Hospital Songsang BranchTaipei 105Taiwan Department of Surgery Taipei Veterans General HospitalTaipei 112Taiwan Division of Colon and Rectal Surgery Department of SurgeryTri-Service General HospitalTaipei 114Taiwan Division of Colon and Rectal Surgery Department of SurgeryTaiwan Adventist HospitalTaipei 105Taiwan Division of Colon and Rectal Surgery Department of SurgeryTri-Service General Hospital Songsang BranchNational Defense Medical CenterTaipei 105Taiwan

BACKGROUND Enterocutaneous fistula(ECF) is an abnormal communication between the skin and the gastrointestinal tract and is associated with considerable morbidity and mortality. To diagnose ECF, X-ray fistulography and abdominal computed tomography(CT) with intravenous or oral contrast are generally used. If the anatomic details obtained from CT are insufficient, CT fistulography may help diagnose and determine the extent of the abnormal channel. However, CT fistulography is seldom performed in patients with insufficient evidence of a *** SUMMARY A 35-year-old man with a prior appendectomy presented with purulence over the abdominal wall without gastrointestinal tract symptoms or a visible opening on the abdominal surface. His history and physical examination were negative for nausea, diarrhea, muscle guarding, and bloating. Local abdominal tenderness and redness over a purulent area were noted, which led to the initial diagnosis of cellulitis. He was admitted to our hospital with a diagnosis of cellulitis. We performed a minimal incision on the carbuncle to collect the pus. The bacterial culture of the exudate resulted positive for Enterococcus sp. ECF was thus suspected, and we arranged a CT scan for further investigation. CT images before intravenous contrast administration showed that the colon was in close contact with the abdominal wall. Therefore, we conducted CT fistulography by injecting contrast dye into the carbuncle during the CT scan. The images showed an accumulation of the contrast agent within the subcutaneous tissues, suggesting the formation of an abscess. The contrast dye tracked down through the muscles and peritoneum into the colon, delineating a channel connecting the subcutaneous abscess with the colon. This evidence confirmed cecocutaneous fistula and avoided misdiagnosing ECF without gastrointestinal tract symptoms as cellulitis. The patient underwent laparoscopic right hemicolectomy with re-anastomosis of the ileum and transverse c

关键词： Cecocutaneous fistula Enterocutaneous fistula Computed tomography fistulography Laparoscopy Hemicolectomy Case report