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Article ; Online: A Novel Mouse Model of Diffuse Intrinsic Pontine Glioma Initiated in Pax3-Expressing Cells

Katherine L. Misuraca / Guo Hu / Kelly L. Barton / Alexander Chung / Oren J. Becher

Neoplasia : An International Journal for Oncology Research, Vol 18, Iss 1, Pp 60-

2016 Volume 70

Abstract: Diffuse intrinsic pontine glioma (DIPG) is a rare and incurable brain tumor that arises predominately in children and involves the pons, a structure that along with the midbrain and medulla makes up the brainstem. We have previously developed genetically ...

Abstract	Diffuse intrinsic pontine glioma (DIPG) is a rare and incurable brain tumor that arises predominately in children and involves the pons, a structure that along with the midbrain and medulla makes up the brainstem. We have previously developed genetically engineered mouse models of brainstem glioma using the RCAS/Tv-a system by targeting PDGF-B overexpression, p53 loss, and H3.3K27M mutation to Nestin-expressing brainstem progenitor cells of the neonatal mouse. Here we describe a novel mouse model targeting these same genetic alterations to Pax3-expressing cells, which in the neonatal mouse pons consist of a Pax3+/Nestin+/Sox2+ population lining the fourth ventricle and a Pax3+/NeuN+ parenchymal population. Injection of RCAS-PDGF-B into the brainstem of Pax3-Tv-a mice at postnatal day 3 results in 40% of mice developing asymptomatic low-grade glioma. A mixture of low- and high-grade glioma results from injection of Pax3-Tv-a;p53fl/fl mice with RCAS-PDGF-B and RCAS-Cre, with or without RCAS-H3.3K27M. These tumors are Ki67+, Nestin+, Olig2+, and largely GFAP− and can arise anywhere within the brainstem, including the classic DIPG location of the ventral pons. Expression of the H3.3K27M mutation reduces overall H3K27me3 as compared with tumors without the mutation, similar to what has been previously shown in human and mouse tumors. Thus, we have generated a novel genetically engineered mouse model of DIPG, which faithfully recapitulates the human disease and represents a novel platform with which to study the biology and treatment of this deadly disease.
Keywords	Medicine ; R ; Internal medicine ; RC31-1245 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	572
Publishing date	2016-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Obstructive jaundice due to intraductal tumour thrombus in recurrent hepatocellular carcinoma: what is the optimal therapeutic approach?

Xin, Koh Ye / Yee, Lee Ser / Yong, Timothy Tay Kwang / Fui, Alexander Chung Yaw

Hepato-gastroenterology

2014 Volume 61, Issue 135, Page(s) 1863–1866

Abstract: Icteric Hepatocellular Carcinoma (HCC) is known to cause intraluminal biliary obstruction by one of three mechanisms: hemobilia from the tumour, migration of tumor debris, or continuous growth along the biliary tree. It is however a very rare ... ...

Abstract	Icteric Hepatocellular Carcinoma (HCC) is known to cause intraluminal biliary obstruction by one of three mechanisms: hemobilia from the tumour, migration of tumor debris, or continuous growth along the biliary tree. It is however a very rare presentation of HCC and an important differential diagnosis in the approach to obstructive jaundice. We report a case of a recurrent intraductal hepatocellular carcinoma. The patient initially underwent surgical resection of segment five HCC nine months ago with clear margins. The patient now presents with obstructive jaundice and imaging showed a right intraductal tumour involving the confluence, left and common hepatic ducts. He underwent a right hepatectomy and bile duct tumour thrombectomy despite the apparent absence of a parenchymal tumour. Histological examination showed a 2 mm focus of parenchymal tumour with extension of the tumour into the bile duct. In this case report, we reviewed the literature and describe the different surgical approaches to intraductal hepatocellular carcinomas and discuss the pathological aspects of these bile duct tumour thrombus. We report the favourable outcome of surgical resection for intraductal hepatocellular carcinoma and emphasize that intraductal HCC is not a late stage of disease and adequate surgical resection can still provide a reasonable disease free survival.
MeSH term(s)	Bile Ducts, Intrahepatic/diagnostic imaging ; Bile Ducts, Intrahepatic/pathology ; Bile Ducts, Intrahepatic/surgery ; Biopsy ; Carcinoma, Hepatocellular/complications ; Carcinoma, Hepatocellular/diagnosis ; Carcinoma, Hepatocellular/surgery ; Cholestasis, Intrahepatic/diagnosis ; Cholestasis, Intrahepatic/etiology ; Cholestasis, Intrahepatic/surgery ; Hepatectomy ; Humans ; Jaundice, Obstructive/diagnosis ; Jaundice, Obstructive/etiology ; Jaundice, Obstructive/surgery ; Liver Neoplasms/complications ; Liver Neoplasms/diagnosis ; Liver Neoplasms/surgery ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Reoperation ; Tomography, X-Ray Computed ; Treatment Outcome
Language	English
Publishing date	2014-10
Publishing country	Greece
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	801013-4
ISSN	0172-6390
ISSN	0172-6390
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Article: Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma

Sharma, Ankur / Seow, Justine Jia Wen / Dutertre, Charles-Antoine / Pai, Rhea / Blériot, Camille / Mishra, Archita / Wong, Regina Men Men / Singh, Gurmit Singh Naranjan / Sudhagar, Samydurai / Khalilnezhad, Shabnam / Erdal, Sergio / Teo, Hui Min / Khalilnezhad, Ahad / Chakarov, Svetoslav / Lim, Tony Kiat Hon / Fui, Alexander Chung Yaw / Chieh, Alfred Kow Wei / Chung, Cheow Peng / Bonney, Glenn Kunnath /

Goh, Brian Kim-Poh / Chan, Jerry K.Y / Chow, Pierce K.H / Ginhoux, Florent / DasGupta, Ramanuj

Cell. 2020 Oct. 15, v. 183, no. 2

2020

Abstract: We employed scRNA sequencing to extensively characterize the cellular landscape of human liver from development to disease. Analysis of ∼212,000 cells representing human fetal, hepatocellular carcinoma (HCC), and mouse liver revealed remarkable fetal- ... ...

Abstract	We employed scRNA sequencing to extensively characterize the cellular landscape of human liver from development to disease. Analysis of ∼212,000 cells representing human fetal, hepatocellular carcinoma (HCC), and mouse liver revealed remarkable fetal-like reprogramming of the tumor microenvironment. Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including re-emergence of fetal-associated endothelial cells (PLVAP/VEGFR2) and fetal-like (FOLR2) tumor-associated macrophages. In a cross-species comparative analysis, we discovered remarkable similarity between mouse embryonic, fetal-liver, and tumor macrophages. Spatial transcriptomics further revealed a shared onco-fetal ecosystem between fetal liver and HCC. Furthermore, gene regulatory analysis, spatial transcriptomics, and in vitro functional assays implicated VEGF and NOTCH signaling in maintaining onco-fetal ecosystem. Taken together, we report a shared immunosuppressive onco-fetal ecosystem in fetal liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of the tumor ecosystem, provide novel targets for therapeutic interventions in HCC, and open avenues for identifying similar paradigms in other cancers and disease.
Keywords	ecosystems ; fetal development ; genes ; hepatoma ; humans ; immunosuppression ; landscapes ; liver ; macrophages ; mice ; therapeutics ; transcriptomics
Language	English
Dates of publication	2020-1015
Size	p. 377-394.e21.
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2020.08.040
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Article ; Online: Positron Emission Tomography with 2-Deoxy-2-[18F] Fluoro-DGlucose in the Detection of Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Brian KP Goh / Yaw-Fui Alexander Chung / David CE Ng / Khee-Chee Soo

JOP Journal of the Pancreas, Vol 8, Iss 3, Pp 350-

2007 Volume 354

Abstract: A 79-year-old Indian male was admitted with upper abdominal discomfort of 1-year duration which was associated with loss of weight and appetite. Clinical examination of the abdomen did not reveal any palpable masses. Laboratory investigations including a ...

Abstract	A 79-year-old Indian male was admitted with upper abdominal discomfort of 1-year duration which was associated with loss of weight and appetite. Clinical examination of the abdomen did not reveal any palpable masses. Laboratory investigations including a complete blood count, liver function tests and serum amylase were unremarkable. Standard serum tumor markers were within normal limits: carbohydrate antigen (CA) 19-9, 13.4 U/mL (reference range: 3-45 U/mL); carcinoembryonic antigen (CEA), 1.4 μg/L (reference range: 0.5-3.5 μg/L) and alphafetoprotein, 1.3 μg/L (reference range: 1-10 μg/L). A contrast-enhanced computed tomographic (CT) scan demonstrated a cystically dilated and tortuous pancreatic duct measuring 1.9 cm, suggestive of an intraductal papillary mucinous neoplasm (IPMN). The common bile duct was dilated up to the level of the ampulla and a 3.2x2.0 cm heterogeneous soft tissue mass was observed in the head of the pancreas which extended into the duodenum, suggestive of a malignant lesion (Images 1 and 2). Fusion positron emission tomography/computed tomography (PET/CT) was subsequently performed with 12.7 mCi of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) administered intravenously. A whole body PET/CT scan was performed 60 minutes later with CT data used for attenuation correction and anatomical correlation. This confirmed a metabolically active focus within the pancreatic head mass with a standard uptake value (SUVmax) of 3.5 compatible with carcinoma (Image 3).
Keywords	Diagnosis ; Pancreatic Neoplasms ; Positron-Emission Tomography ; Medicine ; R ; Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951 ; Diseases of the digestive system. Gastroenterology ; RC799-869
Subject code	610
Publishing date	2007-05-01T00:00:00Z
Publisher	E S Burioni Ricerche Bibliografiche
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Rectal arterio-portal fistula

Hao Yun Yap / Ser Yee Lee / Yaw Fui Alexander Chung / Kiang Hiong Tay / Albert Su-Chong Low / Choon Hua Thng / Krishnakumar Madhavan

World Journal of Gastroenterology, Vol 19, Iss 25, Pp 4087-

An unusual cause of persistent bleeding per rectum following a proximal spleno-renal shunt

2013 Volume 4090

Abstract: Gastrointestinal arterio-venous malformations are a known cause of gastrointestinal bleeding. We present a rare case of persistent rectal bleeding due to a rectal arterio-portal venous fistula in the setting of portal hypertension secondary to portal ... ...

Abstract	Gastrointestinal arterio-venous malformations are a known cause of gastrointestinal bleeding. We present a rare case of persistent rectal bleeding due to a rectal arterio-portal venous fistula in the setting of portal hypertension secondary to portal vein thrombosis. The portal hypertension was initially surgically treated with splenectomy and a proximal splenorenal shunt. However, rectal bleeding persisted even after surgery, presenting us with a diagnostic dilemma. The patient was re-evaluated with a computed tomography mesenteric angiogram which revealed a rectal arterio-portal fistula. Arterio-portal fistulas are a known but rare cause of portal hypertension, and possibly the underlying cause of continued rectal bleeding in this case. This was successfully treated using angiographic localization and super-selective embolization of the rectal arterio-portal venous fistula via the right internal iliac artery.The patient subsequently went on to have a full term pregnancy. Through this case report, we hope to highlight awareness of this unusual condition, discuss the diagnostic workup and our management approach.
Keywords	Portal hypertension ; Esophageal varices ; Splenorenal shunt ; Arteriovenous malformations ; Portal vein thrombosis ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Baishideng Publishing Group Co., Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Phuong H. D. Nguyen / Siming Ma / Cheryl Z. J. Phua / Neslihan A. Kaya / Hannah L. H. Lai / Chun Jye Lim / Jia Qi Lim / Martin Wasser / Liyun Lai / Wai Leong Tam / Tony K. H. Lim / Wei Keat Wan / Tracy Loh / Wei Qiang Leow / Yin Huei Pang / Chung Yip Chan / Ser Yee Lee / Peng Chung Cheow / Han Chong Toh /

Florent Ginhoux / Shridhar Iyer / Alfred W. C. Kow / Yock Young Dan / Alexander Chung / Glen K. Bonney / Brian K. P. Goh / Salvatore Albani / Pierce K. H. Chow / Weiwei Zhai / Valerie Chew

Nature Communications, Vol 12, Iss 1, Pp 1-

Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma

2021 Volume 1

Abstract: A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21556-y. ...

Abstract	A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21556-y.
Keywords	Science ; Q
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma

Florent Ginhoux / Shridhar Iyer / Alfred W. C. Kow / Yock Young Dan / Alexander Chung / Brian K. P. Goh / Salvatore Albani / Pierce K. H. Chow / Weiwei Zhai / Valerie Chew

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 13

Abstract: Intratumoural heterogeneity is a feature of liver cancer. Here, the authors demonstrate that heterogeneity exists at the immune cell level in liver cancer and show that tumours with high intratumoural immune heterogeneity demonstrated an immune ... ...

Abstract	Intratumoural heterogeneity is a feature of liver cancer. Here, the authors demonstrate that heterogeneity exists at the immune cell level in liver cancer and show that tumours with high intratumoural immune heterogeneity demonstrated an immune suppressive microenvironment, which was associated with tumour evolution and a poor prognosis.
Keywords	Science ; Q
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma.

Goh, Brian Kim-Poh / Chan, Jerry K Y / Chow, Pierce K H / Ginhoux, Florent / DasGupta, Ramanuj

Cell

2020 Volume 183, Issue 2, Page(s) 377–394.e21

Abstract	We employed scRNA sequencing to extensively characterize the cellular landscape of human liver from development to disease. Analysis of ∼212,000 cells representing human fetal, hepatocellular carcinoma (HCC), and mouse liver revealed remarkable fetal-like reprogramming of the tumor microenvironment. Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including re-emergence of fetal-associated endothelial cells (PLVAP/VEGFR2) and fetal-like (FOLR2) tumor-associated macrophages. In a cross-species comparative analysis, we discovered remarkable similarity between mouse embryonic, fetal-liver, and tumor macrophages. Spatial transcriptomics further revealed a shared onco-fetal ecosystem between fetal liver and HCC. Furthermore, gene regulatory analysis, spatial transcriptomics, and in vitro functional assays implicated VEGF and NOTCH signaling in maintaining onco-fetal ecosystem. Taken together, we report a shared immunosuppressive onco-fetal ecosystem in fetal liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of the tumor ecosystem, provide novel targets for therapeutic interventions in HCC, and open avenues for identifying similar paradigms in other cancers and disease.
MeSH term(s)	Adult ; Animals ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Cell Line ; Disease Models, Animal ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Female ; Folate Receptor 2/metabolism ; Gene Expression Profiling/methods ; Humans ; Liver/pathology ; Liver Neoplasms/genetics ; Macrophages/metabolism ; Male ; Membrane Proteins/metabolism ; Mice ; Receptors, Notch/genetics ; Receptors, Notch/metabolism ; Signal Transduction/genetics ; Transcriptome/genetics ; Tumor Microenvironment/genetics ; Vascular Endothelial Growth Factor Receptor-2/metabolism
Chemical Substances	FOLR2 protein, human ; Folate Receptor 2 ; Membrane Proteins ; PLVAP protein, human ; Receptors, Notch ; KDR protein, human (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
Language	English
Publishing date	2020-09-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2020.08.040
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Article ; Online: Ampullary carcinoma

Sheikh Anwar Abdullah, Tarun Gupta, Khairul Azhar Jaafar, Yaw Fui Alexander Chung, London Lucien Peng Jin Ooi, Steven Joseph Mesenas

World Journal of Gastroenterology, Vol 15, Iss 23, Pp 2908-

Effect of preoperative biliary drainage on surgical outcome

2009 Volume 2912

Abstract: AIM: To evaluate the influence of preoperative biliary drainage on morbidity and mortality after surgical resection for ampullary carcinoma.METHODS: We analyzed retrospectively data for 82 patients who underwent potentially curative surgery for ampullary ...

Abstract	AIM: To evaluate the influence of preoperative biliary drainage on morbidity and mortality after surgical resection for ampullary carcinoma.METHODS: We analyzed retrospectively data for 82 patients who underwent potentially curative surgery for ampullary carcinoma between September 1993 and July 2007 at the Singapore General Hospital, a tertiary referral hospital. Diagnosis of ampullary carcinoma was confirmed histologically. Thirty-five patients underwent preoperative biliary drainage (PBD group), and 47 were not drained (non-PBD group). The mode of biliary drainage was endoscopic retrograde cholangiopancreatography (n = 33) or percutaneous biliary drainage (n = 2). The following parameters were analyzed: wound infection, intra-abdominal abscess, intra-abdominal or gastrointestinal bleeding, septicemia, biliary or pancreatic leakage, pancreatitis, gastroparesis, and re-operation rate. Mortality was assessed at 30 d (hospital mortality) and also long-term. The statistical endpoint of this study was patient survival after surgery.RESULTS: The groups were well matched for demographic criteria, clinical presentation and operative characteristics, except for lower hemoglobin in the non-PBD group (10.9 ± 1.6 vs 11.8 ± 1.6 in the PBD group). Of the parameters assessing postoperative morbidity, incidence of wound infection was significantly less in the PBD than the non-PBD group [1 (2.9%) vs 12 (25.5%)]. However, the rest of the parameters did not differ significantly between the groups, i.e. sepsis [10 (28.6%) vs 14 (29.8%)], intra-abdominal bleeding [1 (2.9%) vs 5 (10.6%)], intra-abdominal abscess [1 (2.9%) vs 8 (17%)], gastrointestinal bleeding [3 (8.6%) vs 5 (10.6%)], pancreatic leakage [2 (5.7%) vs 3 (6.4%)], biliary leakage [2 (5.7%) vs 3 (6.4%)], pancreatitis [2 (5.7%) vs 2 (4.3%)], gastroparesis [6 (17.1%) vs 10 (21.3%)], need for blood transfusion [10 (28.6%) vs 17 (36.2%)] and re-operation rate [1 (2.9%) vs 5 (10.6%)]. There was no early mortality in either group. Median survival was 44 mo (95% CI: 34.2-53.8) in the PBD group and 41 mo (95% CI: 27.7-54.3; P = 0.86) in the non-PBD group.CONCLUSION: Biliary drainage before surgery for ampullary cancer significantly reduced postoperative wound infection. Overall mortality was not influenced by preoperative drainage.
Keywords	Ampullary carcinoma ; Preoperative biliary drainage ; Postoperative complications ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2009-06-01T00:00:00Z
Publisher	Baishideng Publishing Group Co. Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Renal artery stump to inferior vena cava fistula: unusual clinical presentation and transcatheter embolization with the Amplatzer vascular plug.

Taneja, Manish / Lath, Narayan / Soo, Tan Bien / Hiong, Tay Kiang / Htoo, Maung Myint / Richard, Lo / Fui, Alexander Chung Yaw

Cardiovascular and interventional radiology

2008 Volume 31 Suppl 2, Page(s) S92–5

Abstract: Fistulous communication between the renal artery stump and inferior vena cava following nephrectomy is rare. We describe the case of a 52-year-old man with a fistula detected on investigation for hemolytic anemia in the postoperative period. The patient ... ...

Abstract	Fistulous communication between the renal artery stump and inferior vena cava following nephrectomy is rare. We describe the case of a 52-year-old man with a fistula detected on investigation for hemolytic anemia in the postoperative period. The patient had had a nephrectomy performed 2 weeks prior to presentation for blunt abdominal trauma. The fistula was successfully occluded percutaneously using an Amplatzer vascular plug. The patient recovered completely and was discharged 2 weeks later.
MeSH term(s)	Angiography ; Arteriovenous Fistula/diagnostic imaging ; Arteriovenous Fistula/etiology ; Arteriovenous Fistula/therapy ; Contrast Media ; Embolization, Therapeutic/instrumentation ; Hematoma/diagnostic imaging ; Hematoma/surgery ; Humans ; Kidney/injuries ; Male ; Middle Aged ; Nephrectomy ; Renal Artery/injuries ; Tomography, X-Ray Computed ; Ultrasonography ; Vena Cava, Inferior ; Wounds, Nonpenetrating/diagnostic imaging ; Wounds, Nonpenetrating/surgery
Chemical Substances	Contrast Media
Language	English
Publishing date	2008-07
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	603082-8
ISSN	1432-086X ; 0342-7196 ; 0174-1551
ISSN (online)	1432-086X
ISSN	0342-7196 ; 0174-1551
DOI	10.1007/s00270-007-9232-1
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