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Zeng XT, Liang X, Hong ZL, Chen S, Yang JC, Lin YC, Wu SS. Initial investigation on ultrasound-guided percutaneous biopsy of lesions in the first hepatic hilum with fusion of ultrasound and multimodal imaging cognitive guidance. Front Oncol 2024; 14:1297153. [PMID: 38720805 PMCID: PMC11077297 DOI: 10.3389/fonc.2024.1297153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 03/21/2024] [Indexed: 05/12/2024] Open
Abstract
Purpose This study aims to evaluate the efficacy and safety of ultrasound-guided percutaneous biopsy of the first hepatic hilum lesion, and examine its clinical value of diagnosis and treatment. Methods We conducted a retrospective study on patients diagnosed with the first hepatic hilum lesions at Fujian Provincial Hospital between February 2015 and October 2022. We selected patients who had lesions in the first hepatic hilum(including a 2cm surrounding area of the left/right hepatic ducts and upper-middle segment of the common bile duct) and the liver periphery(in the peripheral area of the liver, outside of the above-mentioned first hepatic porta region). These patients underwent percutaneous ultrasound-guided core needle biopsy (PUS-CNB) with cognitive fusion guidance using CT, MRI, or PET-CT. We compared the safety and efficacy of PUS-CNB in the first hepatic hilum and the liver periphery to explore the value of PUS-CNB in optimizing the clinical treatment of the first hepatic hilum lesions. Results The studied includes 38 cases of the first hepatic hilum cases (18 females; 20 males), 23 presented with mass-forming tumors while the remaining 15 exhibited diffuse infiltrative tumors, with an average diameter of 4.65± 2.51 cm. The percutaneous biopsy procedure, conducted under ultrasound guidance, had an average operation time of 14.55 ± 2.73 minutes, and resulted in a postoperative bleeding volume of approximately 10.79 ± 2.79 ml. The diagnostic success rate was noted to be as high as 92.11% among the participants who underwent percutaneous biopsy of the first hepatic hilum. Procedural complications, such as bleeding, bile leakage, intestinal perforation, infection or needle tract seeding, did not occur during or after the biopsy procedure. Affected by biopsy results, 5 altered their clinical treatment plans accordingly, 24patients received non-surgical treatment, 9 underwent surgical treatment, 5 underwent radiofrequency ablation for the lesions. The study comprised a total of 112 cases for percutaneous biopsy of the liver periphery. The safety and effectiveness of the two biopsy techniques were comparable, with diagnostic success rates of 92.11% VS. 94.34%, respectively (p = 0.61). Conclusion Cognitive fusion of ultrasound and multi-modal imaging for the first hepatic hilum lesion puncture biopsy is a safe and effective diagnostic procedure, with better diagnostic rate, may improve clinical value of diagnosis and treatment of various diseases.
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Affiliation(s)
- Xian-Tao Zeng
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Xia Liang
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Zhi-Liang Hong
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Sheng Chen
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Jian-Chuan Yang
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
| | - Yu-cheng Lin
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of Ultrasonography, Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, China
| | - Song-Song Wu
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
- Fujian Provincial Key Laboratory of Critical Care Medicine, Fuzhou, China
- Department of Ultrasound, Fujian Provincial Hospital, Fuzhou, China
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Li X, Yan L, Xue H. Serum epithelial membrane protein 1 serves as a feasible biomarker in extrahepatic cholangiocarcinoma. Int J Biol Markers 2021; 36:33-39. [PMID: 34569869 DOI: 10.1177/17246008211035142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Extrahepatic cholangiocarcinoma is a malignancy that originates from bile duct epithelium with an unfavorable prognosis. Epithelial membrane protein 1 was first discovered in 1995, functioning as an oncogene or anti-tumor gene in various cancers. However, the clinical role of epithelial membrane protein 1 extrahepatic cholangiocarcinoma remained unclear. METHODS Differentially expressed genes were identified using Gene Ontology and the Kyoto Encyclopedia and Genomes pathway analysis. Out of 183 extrahepatic cholangiocarcinoma patients and 61 healthy controls, the expression level of epithelial membrane protein 1 was detected and compared using reverse transcription-quantitative polymerase chain reaction analysis and western blot assay. Meanwhile, the diagnosis and prognosis of EMP1 in ECCA were measured by receiver operating characteristic and Kaplan-Meier analysis. Finally, the relationship between epithelial membrane protein 1 expression and clinicopathological indexes were compared to further verify the clinical role of epithelial membrane protein 1 in extrahepatic cholangiocarcinoma. RESULTS After analyzing data from GSE76297, GSE89749, and GSE26566GO, we found 1554 down-regulated and 1065 up-regulated genes. Through Gene Ontology and Kyoto Encyclopedia and Genomes analysis, extracellular matrix organization, extracellular structure organization, cholesterol metabolism, interleukin-17 signaling pathway, and vitamin digestion and absorption were significantly enriched and involved in targeted differentially expresses genes. Epithelial membrane protein 1 messenger ribonucleic acid was notably decreased in serum samples from extrahepatic cholangiocarcinoma patients, compared with that in healthy controls. Receiver operating characteristic analysis revealed that the area under the curve of epithelial membrane protein 1 messenger ribonucleic acid for the diagnosis of extrahepatic cholangiocarcinoma was 0.9281 (95% CI = 0.8967-0.9595). Moreover, the correlation analysis presented that epithelial membrane protein 1 expression was negatively correlated with lymph node metastasis, tumour node metastasis stage, cancer antigen 19-9 level, and carcinoembryonic antigen level. CONCLUSION Aberrant expression of epithelial membrane protein 1 contributed to distinguishing extrahepatic cholangiocarcinoma patients and healthy controls, and a low expression level of epithelial membrane protein 1 indicated an unfavorable prognosis. Hence, epithelial membrane protein 1 was a feasible and credible biomarker for extrahepatic cholangiocarcinoma diagnosis and prognosis, with high accuracy, sensitivity, and specificity.
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Affiliation(s)
- Xiang Li
- Department of Hepatobiliary Surgery, Chongqing University Three Gorges Hospital, China
| | - Lang Yan
- Department of Hepatobiliary Surgery, Chongqing University Three Gorges Hospital, China
| | - Hao Xue
- Department of Hepatobiliary Surgery, Chongqing University Three Gorges Hospital, China
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Gu X, Wang C, Deng H, Qing C, Liu R, Liu S, Xue X. Exosomal piRNA profiling revealed unique circulating piRNA signatures of cholangiocarcinoma and gallbladder carcinoma. Acta Biochim Biophys Sin (Shanghai) 2020; 52:475-484. [PMID: 32369104 DOI: 10.1093/abbs/gmaa028] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 01/21/2020] [Accepted: 03/13/2020] [Indexed: 01/02/2023] Open
Abstract
Cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC) are biliary tract cancers with poor five-year survival and high recurrence rates. Both CCA and GBC patients suffer from lack of circulating diagnostic biomarkers at the early stage. Extracellular vesicles, especially exosomes, have been emerged as promising diagnostic sources for cancers due to easy and quick accessibility. Hence, identification of exosomal biomarkers provides a novel strategy for CCA and GBC diagnosis. Here, five CCA patients and four GBC patients were enrolled for exosomal small RNA sequencing. Our data showed that exosomal piwi-interacting RNA (piRNA) populations were altered in the plasma of CCA and GBC patients. In comparison to healthy individuals, 694 and 323 piRNAs were upregulated in CCA and GBC, respectively, while 36 and 191 piRNAs were downregulated. Interestingly, sequencing results predicted that piR-2660989, piR-10506469, piR-20548188, piR-10822895, piR-hsa-23209, and piR-18044111 were upregulated in both CCA and GBC plasma. Importantly, we further included blood samples from 50 health individuals, 40 CCA patients, and 25 GBC patients and found that piR-10506469 were significantly increased in the exosomes of plasma from both CCA and GBC patients. Moreover, we analyzed the expression levels of differentially expressed exosomal piRNAs in the plasma of CCA and GBC patient before and after surgeries and found that piR-10506469 and piR-20548188 were significantly decreased in patients underwent surgeries. Taken together, our data revealed that exosomal piRNAs those are differentially expressed in CCA and GBC plasma may serve as potential biomarkers for the diagnosis of CCA and GBC.
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Affiliation(s)
- Xinjin Gu
- Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese People’s Liberation Army General Hospital, Medical School of Chinese People’s Liberation Army, Beijing 100853, China
| | - Chen Wang
- Shanghai Institute of Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China
| | - Hui Deng
- Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Chong Qing
- Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Rong Liu
- Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese People’s Liberation Army General Hospital, Medical School of Chinese People’s Liberation Army, Beijing 100853, China
| | - Sanhong Liu
- Shanghai Institute of Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China
| | - Xinying Xue
- Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
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Sribuhom T, Thummanant Y, Phusrisom S, Kukongviriyapan V, Tontapha S, Amornkitbamrung V, Yenjai C. Styrenes from the Seeds of Atalantia monophylla. JOURNAL OF NATURAL PRODUCTS 2019; 82:2246-2251. [PMID: 31390210 DOI: 10.1021/acs.jnatprod.9b00361] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Four new dimeric styrenes, 1-4, were isolated from an EtOAc crude extract of the seeds of Atalantia monophylla. The biosynthetic pathway of 1 is proposed to involve a [2 + 2] cycloaddition, while 2-4 may be generated via a polar mechanism with a carbocation as the key intermediate. The structures of 1-4 were defined from spectroscopic analysis; experimental and calculated ECD spectra were used to characterize their absolute configurations. When tested against two different cancer cell lines, 1-4 were not determined to be cytotoxic (IC50 > 10 μM).
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Affiliation(s)
- Thurdpong Sribuhom
- Natural Products Research Unit, Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science , Khon Kaen University , Khon Kaen 40002 , Thailand
| | - Yutthapong Thummanant
- Natural Products Research Unit, Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science , Khon Kaen University , Khon Kaen 40002 , Thailand
| | - Suphanthip Phusrisom
- Department of Pharmacology, Faculty of Medicine , Khon Kaen University , Khon Kaen 40002 , Thailand
| | - Veerapol Kukongviriyapan
- Department of Pharmacology, Faculty of Medicine , Khon Kaen University , Khon Kaen 40002 , Thailand
| | - Sarawut Tontapha
- Integrated Nanotechnology Research Centre, Department of Physics, Faculty of Science , Khon Kaen University , Khon Kaen 40002 , Thailand
| | - Vittaya Amornkitbamrung
- Integrated Nanotechnology Research Centre, Department of Physics, Faculty of Science , Khon Kaen University , Khon Kaen 40002 , Thailand
| | - Chavi Yenjai
- Natural Products Research Unit, Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science , Khon Kaen University , Khon Kaen 40002 , Thailand
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Zhou H, Xu J, Wang S, Peng J. Role of cantharidin in the activation of IKKα/IκBα/NF‑κB pathway by inhibiting PP2A activity in cholangiocarcinoma cell lines. Mol Med Rep 2018; 17:7672-7682. [PMID: 29620225 PMCID: PMC5983964 DOI: 10.3892/mmr.2018.8860] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 02/08/2018] [Indexed: 12/15/2022] Open
Abstract
Cantharidin (CAN), a potent inhibitor of serine/threonine‑protein phosphatase 2A (PP2A), is widely used in clinical practice, particularly in the treatment of advanced cancer due to its specific action on these types of cancer. In the present study, the inhibitory effect of CAN was examined in two cholangiocarcinoma cell lines (QBC939 and Hucc‑t1). Following treatment with CAN, cell viability was effectively reduced in QBC939 and Hucc‑t1 cells and normal human intrahepatic biliary epithelial cells. However, a slight increase in reactive oxygen species levels in QBC939 cells treated with CAN was observed post‑treatment. CAN significantly inhibited cell migration and invasion in a dose‑dependent manner. Western blot analysis demonstrated that the nuclear factor‑κB (NF‑κB) pathway was stimulated by CAN, which was confirmed by the upregulated phosphorylation levels of inhibitor of NF‑κB kinase subunit α (IKKα) and NF‑κB inhibitor α (IκBα) in cells, and an increased NF‑κB p65 subunit level in the nucleus. The expression levels of 72 kDa type IV collagenase (MMP2) and matrix metalloproteinase 9 (MMP9) were downregulated by CAN. Notably, there was a negative association between MMP2 and MMP9 expression levels, and NF‑κB p65, although NF‑κB p65 regulates the expression of MMP2 and MMP9 and has a positive association with these proteins in various types of cancer. Notably, it was observed that CAN exerted specific inhibition on PP2A activity and thereby resulted in the activation of the IKKα/IκBα/NF‑κB pathway. Therefore, CAN‑induced cell inhibition maybe partially dependent on the activation of the IKKα/IκBα/NF‑κB pathway. In conclusion, it was demonstrated that CAN selectively and effectively inhibited cholangiocarcinoma cell migration and invasion. The present study may provide a novel insight into the use of CAN as a therapeutic candidate in the treatment of cholangiocarcinoma.
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Affiliation(s)
- Huijiang Zhou
- Department of General Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, P.R. China
| | - Jiangfeng Xu
- Department of General Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, P.R. China
| | - Shuai Wang
- Department of General Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, P.R. China
| | - Jinfeng Peng
- Department of General Surgery, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, P.R. China
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Duan RD. Alkaline sphingomyelinase (NPP7) in hepatobiliary diseases: A field that needs to be closely studied. World J Hepatol 2018; 10:246-253. [PMID: 29527260 PMCID: PMC5838443 DOI: 10.4254/wjh.v10.i2.246] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Revised: 01/13/2018] [Accepted: 01/24/2018] [Indexed: 02/06/2023] Open
Abstract
Alkaline sphingomyelinase cleaves phosphocholine from sphingomyelin, platelet-activating factor, lysophosphatidylcholine, and less effectively phosphatidylcholine. The enzyme shares no structure similarities with acid or neutral sphingomyelinase but belongs to ecto-nucleotide pyrophosphatase/phosphodiesterase (NPP) family and therefore is also called NPP7 nowadays. The enzyme is expressed in the intestinal mucosa in many species and additionally in human liver. The enzyme in the intestinal tract has been extensively studied but not that in human liver. Studies on intestinal alkaline sphingomyelinase show that it inhibits colonic tumorigenesis and inflammation, hydrolyses dietary sphingomyelin, and stimulates cholesterol absorption. The review aims to summarize the current knowledge on liver alkaline sphingomyelinase in human and strengthen the necessity for close study on this unique human enzyme in hepatobiliary diseases.
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Affiliation(s)
- Rui-Dong Duan
- Gastroenterology and Nutrition Lab, Department of Clinical Sciences, Lund University, Lund S-22184, Sweden
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Berretta M, Cavaliere C, Alessandrini L, Stanzione B, Facchini G, Balestreri L, Perin T, Canzonieri V. Serum and tissue markers in hepatocellular carcinoma and cholangiocarcinoma: clinical and prognostic implications. Oncotarget 2017; 8:14192-14220. [PMID: 28077782 PMCID: PMC5355172 DOI: 10.18632/oncotarget.13929] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Accepted: 10/28/2016] [Indexed: 12/12/2022] Open
Abstract
HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options for advanced HCC remain limited and unsuccessful, resulting in a poor prognosis. Despite the major advances achieved in the diagnostic management of HCC, only one third of the newly diagnosed patients are presently eligible for curative treatments. Advances in technology and an increased understanding of HCC biology have led to the discovery of novel biomarkers. Improving our knowledge about serum and tissutal markers could ultimately lead to an early diagnosis and better and early treatment strategies for this deadly disease. Serum biomarkers are striking potential tools for surveillance and early diagnosis of HCC thanks to the non-invasive, objective, and reproducible assessments they potentially enable. To date, many biomarkers have been proposed in the diagnosis of HCC. Cholangiocarcinoma (CCA) is an aggressive malignancy, characterized by early lymph node involvement and distant metastasis, with 5-year survival rates of 5%-10%. The identification of new biomarkers with diagnostic, prognostic or predictive value is especially important as resection (by surgery or combined with a liver transplant) has shown promising results and novel therapies are emerging. However, the relatively low incidence of CCA, high frequency of co-existing cholestasis or cholangitis (primary sclerosing cholangitis –PSC- above all), and difficulties with obtaining adequate samples, despite advances in sampling techniques and in endoscopic visualization of the bile ducts, have complicated the search for accurate biomarkers. In this review, we attempt to analyze the existing literature on this argument.
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Affiliation(s)
| | - Carla Cavaliere
- Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto Taranto, Italy
| | - Lara Alessandrini
- Division of Pathology, National Cancer Institute, Aviano (PN), Italy
| | - Brigida Stanzione
- Department of Medical Oncology, National Cancer Institute, Aviano (PN), Italy
| | - Gaetano Facchini
- Department of Medical Oncology, National Cancer Institute, "G. Pascale" Foundation, Naples, Italy
| | - Luca Balestreri
- Department of Radiology, National Cancer Institute, Aviano (PN), Italy
| | - Tiziana Perin
- Division of Pathology, National Cancer Institute, Aviano (PN), Italy
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Sriwanitchrak P, Paemanee A, Roytrakul S, Viyanant V, Na-Bangchang K. Glycoproteomics analysis of plasma proteins associated with Opisthorchis viverrini infection-induced cholangiocarcinoma in hamster model. ASIAN PAC J TROP MED 2016; 9:1165-1171. [DOI: 10.1016/j.apjtm.2016.09.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Revised: 08/20/2016] [Accepted: 09/01/2016] [Indexed: 10/20/2022] Open
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Warner WA, Ramcharan W, Harnanan D, Umakanthan S, Maharaj R. A case of distal extrahepatic cholangiocarcinoma with two positive resection margins. Oncol Lett 2016; 12:4075-4079. [PMID: 27895774 DOI: 10.3892/ol.2016.5174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 08/25/2016] [Indexed: 11/05/2022] Open
Abstract
Cholangiocarcinoma is an uncommon primary malignancy of the biliary tract that is challenging to diagnose and treat effectively due to its relatively silent and late clinical presentation. The present study reports a case of a 60-year-old male with distal extrahepatic cholangiocarcinoma with a 3-week history of painless obstructive jaundice symptoms and subjective weight loss. Imaging revealed an obstructing lesion in the common bile duct, just distal to the entrance of the cystic duct. Pathology revealed moderately differentiated cholangiocarcinoma with two positive proximal resection margins. The two positive resection margins presented a challenge during surgery and points to an urgent need for further studies to better illuminate diagnostic and therapeutic options for patients with similar clinicopathological presentation.
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Affiliation(s)
- Wayne A Warner
- Division of Oncology, Siteman Cancer Center, Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Wesley Ramcharan
- Department of Clinical Surgical Sciences, University of The West Indies, Eric Williams Medical Sciences Complex, Champ Fleurs, Trinidad and Tobago
| | - Dave Harnanan
- Department of Clinical Surgical Sciences, University of The West Indies, Eric Williams Medical Sciences Complex, Champ Fleurs, Trinidad and Tobago
| | - Srikanth Umakanthan
- Department of Clinical Surgical Sciences, University of The West Indies, Eric Williams Medical Sciences Complex, Champ Fleurs, Trinidad and Tobago
| | - Ravi Maharaj
- Department of Clinical Surgical Sciences, University of The West Indies, Eric Williams Medical Sciences Complex, Champ Fleurs, Trinidad and Tobago
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Nakanuma Y, Miyata T, Uchida T. Latest advances in the pathological understanding of cholangiocarcinomas. Expert Rev Gastroenterol Hepatol 2016; 10:113-27. [PMID: 26492529 DOI: 10.1586/17474124.2016.1104246] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Cholangiocarcinomas (CCAs) are anatomically classified into intrahepatic, perihilar, and distal types. The gross pathological classification of intrahepatic CCAs divides them into mass-forming, periductal-infiltrating, and intraductal-growth types; and perihilar/distal CCAs into flat- and nodular-infiltrating and papillary types. Unique preinvasive lesions appear to precede individual gross types of CCA. Biliary intraepithelial neoplasia, a flat lesion, precedes periductal-, flat-, and nodular-infiltrating CCAs, whereas intraductal papillary neoplasm of the bile duct (IPNB) precedes the intraductal-growth and papillary type of CCAs. IPNBs are heterogeneous in their histological and pathological profiles along the biliary tree. Hepatobiliary cystadenomas/adenocarcinomas are reclassified as cystic IPNBs and hepatic mucinous cystic neoplasms. Peribiliary glands may participate in the development of CCAs. These latest findings present a new challenge for understanding the pathology of CCAs.
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Affiliation(s)
- Yasuni Nakanuma
- a Department of Diagnostic Pathology , Shizuoka Cancer Center , Shizuoka , Japan
| | - Takashi Miyata
- a Department of Diagnostic Pathology , Shizuoka Cancer Center , Shizuoka , Japan.,b Department of Hepatobiliary Pancreatic Surgery , Shizuoka Cancer Center , Shizuoka , Japan
| | - Tsuneyuki Uchida
- a Department of Diagnostic Pathology , Shizuoka Cancer Center , Shizuoka , Japan.,b Department of Hepatobiliary Pancreatic Surgery , Shizuoka Cancer Center , Shizuoka , Japan
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Jones K, Biederman L, Draganova-Tacheva R, Solomides C, Bibbo M. Diagnostic Yield of Endoscopic Ultrasound-Guided Fine-Needle Aspiration Cytology of Porta Hepatis Lesions: A Retrospective Study. Acta Cytol 2016; 60:154-60. [PMID: 27070208 DOI: 10.1159/000445764] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 03/22/2016] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has recently been used for the evaluation of various lesions arising in the porta hepatis. The purpose of this study is to evaluate the diagnostic yield of this increasingly utilized approach to porta hepatis lesions. STUDY DESIGN A retrospective study of 72 consecutive samples of porta hepatis lesions obtained via EUS-FNA between 2004 and 2015 was conducted. Clinical histories and endoscopic findings were available prior to the diagnostic interpretation. The diagnosis of each lesion was based on its cytologic features on smears, its histologic features on cell block, a comparison with any relevant prior specimens, immunohistochemistry and flow cytometric studies when applicable. RESULTS A total of 72 lesions (59 lymph nodes, 2 cysts and 11 masses) were biopsied in 70 patients. Adequate specimens were obtained in 65/72 cases (90%). Most of the lymph nodes were benign (n = 40, 67%) and most of the masses were malignant or suspicious (n = 8, 73%). A variety of diagnoses, primary and metastatic, were made, including hepatocellular carcinoma, cholangiocarcinoma and lymphoma. In addition, we have noted a significant increase in the number of EUS-FNAs in recent years. CONCLUSION EUS-FNA is an effective and increasingly utilized diagnostic approach for the evaluation of multiple types of lesions in the porta hepatis.
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Affiliation(s)
- Krister Jones
- Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University Hospital, Philadelphia, Pa., USA
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Kwak TW, Shin HJ, Jeong YI, Han ME, Oh SO, Kim HJ, Kim DH, Kang DH. Anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma. DRUG DESIGN DEVELOPMENT AND THERAPY 2015; 9:2201-14. [PMID: 25931814 PMCID: PMC4404940 DOI: 10.2147/dddt.s80205] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The aim of this study is to investigate the anticancer activity of streptochlorin, a novel antineoplastic agent, in cholangiocarcinoma. METHODS The anticancer activity of streptochlorin was evaluated in vitro in various cholangiocarcinoma cell lines for apoptosis, proliferation, invasiveness, and expression of various protein levels. A liver metastasis model was prepared by splenic injection of HuCC-T1 cholangiocarcinoma cells using a BALB/c nude mouse model to study the systemic antimetastatic efficacy of streptochlorin 5 mg/kg at 8 weeks. The antitumor efficacy of subcutaneously injected streptochlorin was also assessed using a solid tumor xenograft model of SNU478 cells for 22 days in the BALB/c nude mouse. RESULTS Streptochlorin inhibited growth and secretion of vascular endothelial growth factor by cholangiocarcinoma cells in a dose-dependent manner and induced apoptosis in vitro. In addition, streptochlorin effectively inhibited invasion and migration of cholangiocarcinoma cells. Secretion of vascular endothelial growth factor and activity of matrix metalloproteinase-9 in cholangiocarcinoma cells were also suppressed by treatment with streptochlorin. Streptochlorin effectively regulated metastasis of HuCC-T1 cells in a mouse model of liver metastasis. In a tumor xenograft study using SNU478 cells, streptochlorin significantly inhibited tumor growth without changes in body weight when compared with the control. CONCLUSION These results reveal that streptochlorin is a promising chemotherapeutic agent to the treatment of cholangiocarcinoma.
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Affiliation(s)
- Tae Won Kwak
- Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Hee Jae Shin
- Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Ansan, Republic of Korea
| | - Young-Il Jeong
- Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Myoung-Eun Han
- Department of Anatomy, School of Medicine, Pusan National University, Gyeongnam, Republic of Korea
| | - Sae-Ock Oh
- Department of Anatomy, School of Medicine, Pusan National University, Gyeongnam, Republic of Korea
| | - Hyun-Jung Kim
- Genewel Co Ltd. Gyeonggi-do, Pusan National University, Yangsan, Gyeongnam, Republic of Korea
| | - Do Hyung Kim
- School of Medicine, Pusan National University, Yangsan, Gyeongnam, Republic of Korea
| | - Dae Hwan Kang
- Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
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Pathologic classification of cholangiocarcinoma: New concepts. Best Pract Res Clin Gastroenterol 2015; 29:277-93. [PMID: 25966428 DOI: 10.1016/j.bpg.2015.02.006] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2014] [Revised: 01/12/2015] [Accepted: 02/07/2015] [Indexed: 02/06/2023]
Abstract
Herein, we propose a new pathologic classification of cholangiocarcinoma (CCA) based on recent progress in studies of preinvasive CCA lesions and the relationship of CCA to hepatic progenitor cells, as well as a new concept with respect to the pathologic similarities between biliary and pancreatic neoplasms. Depending on anatomical location, CCA is classifiable as intrahepatic (iCCA), perihilar (pCCA), and distal CCA (dCCA). iCCA is classifiable as the conventional type and the bile ductular type, whereas pCCA and dCCA mainly present as conventional adenocarcinoma. In addition, these three CCAs may present as the intraductal neoplasm type or rare variants. Bile ductular CCA resembles proliferating bile ductules and expressing hepatic progenitor cell phenotypes. Four types of preinvasive lesions are proposed: flat, papillary, tubular lesion, and cystic lesion. These lesions are eventually followed by invasive CCA. Interestingly, these preinvasive lesions have pancreatic counterparts. This CCA classification may introduce a new field of CCA research.
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Duan RD, Hindorf U, Cheng Y, Bergenzaun P, Hall M, Hertervig E, Nilsson Å. Changes of activity and isoforms of alkaline sphingomyelinase (nucleotide pyrophosphatase phosphodiesterase 7) in bile from patients undergoing endoscopic retrograde cholangiopancreatography. BMC Gastroenterol 2014; 14:138. [PMID: 25100243 PMCID: PMC4141583 DOI: 10.1186/1471-230x-14-138] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Accepted: 07/24/2014] [Indexed: 01/02/2023] Open
Abstract
Background Alkaline sphingomyelinase (NPP7) is an ecto-enzyme expressed in intestinal mucosa, which hydrolyses sphingomyelin (SM) to ceramide and inactivates platelet activating factor. It is also expressed in human liver and released in the bile. The enzyme may have anti-tumour and anti-inflammatory effects in colon and its levels are decreased in patients with colon cancer and ulcerative colitis. Active NPP7 is translated from a transcript of 1.4 kb, whereas an inactive form from a 1.2 kb mRNA was found in colon and liver cancer cell lines. While the roles of NPP7 in colon cancer have been intensively studied, less is known about the function and implications of NPP7 in the bile. The present study examines the changes of NPP7 in bile of patients with various hepatobiliary diseases. Methods Bile samples were obtained at endoscopic retrograde cholangiopancreatography (ERCP) in 59 patients with gallstone, other benign disease, tumour, and primary sclerosing cholangitis (PSC). The NPP7 activity was determined. The appearance of the 1.4 and 1.2 kb products in the bile was examined by Western blot. The results were correlated to the diseases and also plasma bilirubin and alkaline phosphatase. Results NPP7 activity in the tumour group was significantly lower than in the gallstone group (p < 0.05). The activity in the tumour plus PSC group was also lower than in gallstone plus other benign disease group (p < 0.05). Within the tumour group NPP7 activity was lowest in cholangiocarcinoma patients, being only 19% of that in gallstone patients. Bilirubin correlated inversely to NPP7 and was higher in the tumour than in the gallstone group. Western blot identified both the 1.4 kb and the 1.2 kb products in most bile samples. The density ratio for the 1.4/1.2 kb products correlated to NPP7 activity significantly. Two patients (one PSC and one cholangiocarcinoma) lacking NPP7 activity had only the 1.2 kb form in bile. Conclusion NPP7 activity and the ratio of 1.4/1.2 kb products in bile are significantly decreased in malignancy, particularly in cholangiocarcinoma. The implications of the finding in diagnosis of cholangiocarcinoma and 1.2 kb product in hepatobiliary diseases require further investigation.
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Affiliation(s)
- Rui-Dong Duan
- Gastroenterology & Nutrition Laboratory, BMC, B11, Department of Clinical Sciences in Lund, University of Lund, S-22184 Lund, Sweden.
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Skipworth JRA, Timms JF, Pereira SP. Novel diagnostic and prognostic biomarkers in biliary tract cancer. ACTA ACUST UNITED AC 2014; 7:487-99. [PMID: 23971898 DOI: 10.1517/17530059.2013.826646] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION The worldwide incidence of biliary tract carcinoma (BTC, tumours of the bile ducts and gall-bladder) continues to rise, with the only potentially curative treatment remaining surgical resection or transplantation, possible in only a minority of patients. Late presentation and a paucity of effective treatments mandate the development of techniques for early lesion detection. AREAS COVERED This article reviews currently available biomarkers for the diagnosis and prognosis of BTC, as well as recently published studies describing novel serum, bile and urinary biomarkers. EXPERT OPINION The incorporation of novel analysis techniques, such as digital image analysis and fluorescence in situ hybridization, into existing management algorithms enhances the accuracy of brush cytology taken at the time of therapeutic endoscopy. However, a key goal is the discovery of reliable non-invasive biomarkers with high sensitivity and specificity. Recent advances in gene sequencing and expression, clonal evolution and tumour heterogeneity in other cancers should advance understanding of BTC tumour biology and facilitate biomarker discovery.
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Affiliation(s)
- James R A Skipworth
- University College London, Division of Surgery and Interventional Science, 4th Floor, 74 Huntley Street, London, WC1E6AU, UK
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16
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Li C, Shen W, Shen S, Ai Z. Gene expression patterns combined with bioinformatics analysis identify genes associated with cholangiocarcinoma. Comput Biol Chem 2013; 47:192-7. [DOI: 10.1016/j.compbiolchem.2013.08.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2013] [Revised: 07/16/2013] [Accepted: 08/28/2013] [Indexed: 12/23/2022]
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Han JZ, Qin MF. Endoscopic metal biliary endoprosthesis combined with endoscopic nasobiliary drainage for palliative treatment of malignant biliary obstruction. Shijie Huaren Xiaohua Zazhi 2013; 21:547-552. [DOI: 10.11569/wcjd.v21.i6.547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the clinical effect of endoscopic metal biliary endoprosthesis (EMBE) combined with endoscopic nasobiliary drainage (ENBD) in the palliative treatment of malignant biliary obstruction.
METHODS: The clinical data for 68 patients with malignant biliary obstruction who underwent endoscopic retrograde cholangiopancreatography (ERCP) for EMBE and ENBD from April 2010 to October 2012 were reviewed and analyzed.
RESULTS: ERCP and biliary stent placement were successful in 64 of 68 cases, and the success rate was 94.12%. Jaundice obviously subsided in 95.31% of patients one week after stent placement. Postoperatively, liver function was improved significantly. There were 5 cases of complications, including hyperamylasemia in 3 cases, acute pancreatitis in 1 case and acute cholangitis in 1 case. Fifty-eight patients were followed postoperatively, and their average survival time was 10 mo ± 2.30 mo (3-26 mo). The half-year, 1-year and 2-year survival rates were 67.24% (39/58), 43.10% (25/58) and 5.17% (3/58), respectively. The average stent patency time was 4 mo ± 2.26 mo (0-9 mo).
CONCLUSION: EMBE combined with ENBD can effectively relieve biliary obstruction and improve liver function in patients with malignant biliary obstruction, and is a safe and effective palliative treatment with less invasiveness and fewer complications.
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Wang Q, Tang H, Yin S, Dong C. Downregulation of microRNA-138 enhances the proliferation, migration and invasion of cholangiocarcinoma cells through the upregulation of RhoC/p-ERK/MMP-2/MMP-9. Oncol Rep 2013; 29:2046-52. [PMID: 23446431 DOI: 10.3892/or.2013.2304] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Accepted: 01/25/2013] [Indexed: 11/06/2022] Open
Abstract
microRNAs (miRs) play an important role in tumor initiation and progression in many types of cancer, including cholangiocarcinoma (CC). miR-138 dysregulation is frequently observed in a variety of tumors. In the present study, miR-138 was found to be downregulated in CC tissues by quantitative real-time RT-PCR. Furthermore, its potential target molecule, Ras homolog gene family, member C (RhoC) protein, was found to be highly expressed in CC tissues examined by western blot analysis. Luciferase reporter assay further demonstrated that miR-138 directly targeted RhoC. We found that the introduction of miR-138 mimics to RBE and QBC939 CC cells could reduced RhoC mRNA and protein expression, and suppressed the proliferation, G1/S transition, migration and invasion of CC cells. However, transfection with a miR-138 inhibitor induced an inverse effect in CC cells. The expression of phosphorylated extracellular signal-regulated kinase (p-ERK), matrix metalloproteinase (MMP)-2 and MMP-9 decreased following transfection with miR-138, and increased following transfection with miR-138 inhibitor in CC cells. In conclusion, RhoC upregulation induced by miR-138 downregulation promotes the malignant progression of CC cells and the underlying mechanisms of this effect involve the increase in the expression of p-ERK/MMP-2/MMP-9. Consequently, miR-138/RhoC is a potential target for the clinical diagnosis and treatment of CC.
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Affiliation(s)
- Qi Wang
- Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
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20
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Halme L, Arola J, Numminen K, Krogerus L, Mäkisalo H, Färkkilä M. Biliary dysplasia in patients with primary sclerosing cholangitis: additional value of DNA ploidity. Liver Int 2012; 32:783-9. [PMID: 22098817 DOI: 10.1111/j.1478-3231.2011.02672.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2011] [Accepted: 09/27/2011] [Indexed: 01/26/2023]
Abstract
BACKGROUND Detection of biliary dysplasia in PSC is essential for proper timing of liver transplantation to prevent the development of cholangiocancer, which is considered a contraindication for liver transplantation in most centres. In patients with PSC, differential diagnosis of benign, premalignant and malignant biliary strictures is difficult. AIMS This prospective study aimed to evaluate the role of DNA analysis in combination with brush cytology, scored ERCP findings, and tumour markers to detect hepatobiliary dysplasia and malignancy. MATERIAL AND METHODS Brush samples for cytology and for evaluation of DNA content analysed with flow cytometry came from 102 consecutive PSC patients referred for ERCP. Symptoms, serum Ca19-9 and CEA were determined at the time of index biliary examination. ERCP findings were scored for intra- and extrahepatic changes. The end-points were liver transplantation or diagnosis of malignancy or dysplasia. RESULTS Most of the patients were asymptomatic at the time of ERCP: 73% had no symptoms, and 12% had only mild symptoms. An aneuploid DNA content was evident in 20 (20%) patients, and cells suspected for malignancy in 22 (21%). Seven patients had both aneuploidity and cytology (7%) suspicious for malignancy. An end-point, diagnosis of malignancy or liver transplantation was achieved in 42 patients. Combining DNA ploidity and cytology in patients at the end-point, sensitivity was 72%, specificity 82%, positive predictive value 86% and negative predictive value 67%. DISCUSSION AND CONCLUSION In this mostly asymptomatic PSC-patient population, 33% demonstrated abnormal brush cytology or aneuploidity. Determining DNA ploidy and brush cytology during ERCP offers a useful tool for identifying those PSC patients who are at high risk of developing cholangiocancer.
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Affiliation(s)
- Leena Halme
- Department of Gastroenterologic Surgery, Helsinki University Hospital, Helsinki, Finland.
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Xu J, Sasaki M, Harada K, Sato Y, Ikeda H, Kim JH, Yu E, Nakanuma Y. Intrahepatic cholangiocarcinoma arising in chronic advanced liver disease and the cholangiocarcinomatous component of hepatocellular cholangiocarcinoma share common phenotypes and cholangiocarcinogenesis. Histopathology 2011; 59:1090-9. [DOI: 10.1111/j.1365-2559.2011.04058.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Chung KD, Jeong YI, Chung CW, Kim DH, Kang DH. Anti-tumor activity of all-trans retinoic acid-incorporated glycol chitosan nanoparticles against HuCC-T1 human cholangiocarcinoma cells. Int J Pharm 2011; 422:454-61. [PMID: 22093956 DOI: 10.1016/j.ijpharm.2011.10.057] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2011] [Revised: 10/26/2011] [Accepted: 10/31/2011] [Indexed: 01/15/2023]
Abstract
The aim of this study is to investigate antitumor activity of all-trans retinoic acid (RA)-incorporated glycol chitosan (GC) nanoparticles. RA-incorporated GC nanoparticles were prepared by electrostatic interaction between RA and amine group of GC. RA-incorporated GC nanoparticles have spherical shape and their particle size was 317 ± 34.5 nm. They were simply reconstituted into aqueous solution without changes of intrinsic properties. RA-incorporated GC nanoparticles were evidently inhibited the proliferation of HuCC-T1 cholangiocarcinoma cells at higher than 20 μg/ml of RA concentration while empty GC vegicles did not affect to the viablity of tumor cells. Apoptosis and necrosis analysis of tumor cells with treatment of RA or RA-incorporated GC nanoparticles also supported these results. Invasion test using Matrigel also showed that invasion of tumor cells was significantly inhibited at higher than 20 μg/ml of RA concentration. Wound healing assay also showed that RA-incorporated GC nanoparticles were inhibited migration of tumor cells as similar to RA itself. Our results suggested that RA-incorporated GC nanoparticles is a promising vehicles for RA delivery to HuCC-T1 cholangiocarcinoma cells.
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Affiliation(s)
- Kyu-Don Chung
- Department of Anesthesiology and Pain Medicine, College of Medicine, The Catholic University, Seoul 137-701, Republic of Korea
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Sandanayake NS, Sinclair J, Andreola F, Chapman MH, Xue A, Webster GJ, Clarkson A, Gill A, Norton ID, Smith RC, Timms JF, Pereira SP. A combination of serum leucine-rich α-2-glycoprotein 1, CA19-9 and interleukin-6 differentiate biliary tract cancer from benign biliary strictures. Br J Cancer 2011; 105:1370-1378. [PMID: 21970875 PMCID: PMC3241550 DOI: 10.1038/bjc.2011.376] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2011] [Revised: 08/17/2011] [Accepted: 08/23/2011] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Biliary tract cancer (BTC) and benign biliary strictures can be difficult to differentiate using standard tumour markers such as serum carbohydrate antigen 19-9 (CA19-9) as they lack diagnostic accuracy. METHODS Two-dimensional difference gel electrophoresis and tandem mass spectrometry were used to profile immunodepleted serum samples collected from cases of BTC, primary sclerosing cholangitis (PSC), immunoglobulin G4-associated cholangitis and healthy volunteers. The serum levels of one candidate protein, leucine-rich α-2-glycoprotein (LRG1), were verified in individual samples using enzyme-linked immunosorbent assay and compared with serum levels of CA19-9, bilirubin, interleukin-6 (IL-6) and other inflammatory markers. RESULTS We report increased LRG1, CA19-9 and IL-6 levels in serum from patients with BTC compared with benign disease and healthy controls. Immunohistochemical analysis also demonstrated increased staining of LRG1 in BTC compared with cholangiocytes in benign biliary disease. The combination of receiver operating characteristic (ROC) curves for LRG1, CA19-9 and IL-6 demonstrated an area under the ROC curve of 0.98. In addition, raised LRG1 and CA19-9 were found to be independent predictors of BTC in the presence of elevated bilirubin, C-reactive protein and alkaline phosphatase. CONCLUSION These results suggest LRG1, CA19-9 and IL-6 as useful markers for the diagnosis of BTC, particularly in high-risk patients with PSC.
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Affiliation(s)
- N S Sandanayake
- UCL Institute of Hepatology, University College London, 9th Floor Royal Free Hospital, Pond Street, London NW3 2PG, UK
- Cancer Proteomics Laboratory, EGA Institute for Women's Health, University College London, Gower Street, London, WC1E 6BT, UK
- Kolling Institute, University of Sydney, Royal North Shore Hospital, Reserve Road, St Leonards, New South Wales 2065, Australia
| | - J Sinclair
- Cancer Proteomics Laboratory, EGA Institute for Women's Health, University College London, Gower Street, London, WC1E 6BT, UK
| | - F Andreola
- UCL Institute of Hepatology, University College London, 9th Floor Royal Free Hospital, Pond Street, London NW3 2PG, UK
| | - M H Chapman
- UCL Institute of Hepatology, University College London, 9th Floor Royal Free Hospital, Pond Street, London NW3 2PG, UK
- Department of Gastroenterology, University College Hospitals NHS Foundation Trust, 235 Euston Road, London, NW1 2BU, UK
| | - A Xue
- Kolling Institute, University of Sydney, Royal North Shore Hospital, Reserve Road, St Leonards, New South Wales 2065, Australia
| | - G J Webster
- UCL Institute of Hepatology, University College London, 9th Floor Royal Free Hospital, Pond Street, London NW3 2PG, UK
- Department of Gastroenterology, University College Hospitals NHS Foundation Trust, 235 Euston Road, London, NW1 2BU, UK
| | - A Clarkson
- Department of Anatomical Pathology, Royal North Shore Hospital, Reserve Road, St Leonards, New South Wales 2065, Australia
| | - A Gill
- Department of Anatomical Pathology, Royal North Shore Hospital, Reserve Road, St Leonards, New South Wales 2065, Australia
| | - I D Norton
- Department of Gastroenterology, Royal North Shore Hospital, Reserve Road, St Leonards, New South Wales 2065, Australia
| | - R C Smith
- Kolling Institute, University of Sydney, Royal North Shore Hospital, Reserve Road, St Leonards, New South Wales 2065, Australia
| | - J F Timms
- Cancer Proteomics Laboratory, EGA Institute for Women's Health, University College London, Gower Street, London, WC1E 6BT, UK
| | - S P Pereira
- UCL Institute of Hepatology, University College London, 9th Floor Royal Free Hospital, Pond Street, London NW3 2PG, UK
- Department of Gastroenterology, University College Hospitals NHS Foundation Trust, 235 Euston Road, London, NW1 2BU, UK
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Anand MGAC, Purl CP, Dhar BAK. The value of molecular biomarkers in biliary tract cancer in the era of targeted therapy. J Clin Exp Hepatol 2011; 1:2-5. [PMID: 25755304 PMCID: PMC3940314 DOI: 10.1016/s0973-6883(11)60118-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2011] [Accepted: 06/19/2011] [Indexed: 12/12/2022] Open
Affiliation(s)
- Maj Gen Anil C Anand
- Senior Consultant (Medicine), Army Hospital (R&R), and Office of DGAFMS, Ministry of Defence, New Delhi
| | - Col Pankaj Purl
- Senior Advisor (Medicine & Gastroenterology), Head, Department of Gastroenterology, Command Hospital (SC), Pune
| | - Brig AK Dhar
- Consultant (Medicine & Oncology), Head, Department of Oncology, Army Hospital (R&R), Delhi Cantt., New Delhi
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Nakanuma Y, Sato Y, Harada K, Sasaki M, Xu J, Ikeda H. Pathological classification of intrahepatic cholangiocarcinoma based on a new concept. World J Hepatol 2010; 2:419-27. [PMID: 21191517 PMCID: PMC3010511 DOI: 10.4254/wjh.v2.i12.419] [Citation(s) in RCA: 233] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2010] [Revised: 10/28/2010] [Accepted: 11/04/2010] [Indexed: 02/06/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic differentiation. To date, ICC was largely classified into adenocarcinoma and rare variants. Herein, we propose to subclassify the former, based on recent progress in the study of ICC including the gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is, ICC is classifiable into the conventional (bile duct) type, the bile ductular type, the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma. Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites, IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB, particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma, mucinous/signet ring cell carcinoma, clear cell type, undifferentiated type, neuroendocrine carcinoma and so on. This classification of ICC may open up a new field of research of ICC and contribute to the clinical approach to ICC.
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Affiliation(s)
- Yasuni Nakanuma
- Yasuni Nakanuma, Yasunori Sato, Kenichi Harada, Mokoto Sasaski, Jing Xu, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
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Slug inhibition upregulates radiation-induced PUMA activity leading to apoptosis in cholangiocarcinomas. Med Oncol 2010; 28 Suppl 1:S301-9. [PMID: 21120639 DOI: 10.1007/s12032-010-9759-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2010] [Accepted: 11/16/2010] [Indexed: 01/06/2023]
Abstract
Resistance of cholangiocarcinoma to irradiation therapy is a major problem in cancer treatment. Slug, a snail family transcription factor, is a suppressor of PUMA (p53 upregulated modulator of apoptosis), which has been shown to be involved in the control of apoptosis. In this study, we investigated whether the modulation of Slug expression, using adeno-associated-virus-mediated transfer of siRNA targeting Slug gene (rAAV2-Slug siRNA), affects cholangiocarcinoma sensitivity to radiation. In the present study, we used rAAV2-Slug siRNA to downregulate the expression of Slug in QBC939 cholangiocarcinoma cell lines in vitro before γ-irradiation. In vivo studies were done with orthotopic cholangiocarcinoma, and radiosensitivity was evaluated both in vitro and in vivo. rAAV2-Slug siRNA transfection resulted in downregulation of the levels of Slug in QBC939 cells. In addition, rAAV2-Slug siRNA, in combination with radiation, increased levels of the PUMA, which contributes to the radiosensitivity of cholangiocarcinomas. Finally, treatment with rAAV2-Slug siRNA plus γ-irradiation completely regressed tumor growth in orthotopic cholangiocarcinomas model. In summary, integrating gene therapy with radiotherapy could have a synergistic effect, thereby improving the survival of patients with cholangiocarcinomas.
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The BH3-mimetic ABT-737 targets the apoptotic machinery in cholangiocarcinoma cell lines resulting in synergistic interactions with zoledronic acid. Cancer Chemother Pharmacol 2010; 67:557-67. [PMID: 20473610 DOI: 10.1007/s00280-010-1345-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2010] [Accepted: 04/23/2010] [Indexed: 02/07/2023]
Abstract
PURPOSE In TFK-1 and EGI-1 cholangiocarcinoma cell lines, zoledronic acid (ZOL) determines an S-phase block without apoptosis. Here, we investigated the occurrence of apoptosis stigmata when ZOL is associated to the BH3-mimetic ABT-737. METHODS In EGI-1 and TFK-1 cholangiocarcinoma cell lines untreated or treated with ABT-737 alone or in combination with ZOL, the pro-survival protein's pattern (BCL-2, BCL-XL, MCL-1, HSP72, HSP27) was investigated by biochemical criteria along with the occurrence of mitochondrial damage evaluated by cytofluorimetric analysis using a cationic dye. RESULTS ABT-737 induced growth inhibition and significantly affected the colony-forming ability of both EGI-1 and TFK-1 cells. However, activated PARP-1 or/and caspase-3 cleavage (apoptosis markers) were detected only at the highest ABT-737 concentrations used. Combined treatment showed synergistic effect by converting the predominant cytostatic effect of ZOL into a cytotoxic one as shown by striking increment of mitochondrial harmed cells along with PARP-1 activation and caspase-3 cleavage. CONCLUSION The lack of apoptosis following ZOL treatment in these cholangiocarcinoma cell lines appears to be multifactorial and could be ascribed to the large constitutive expression of pro-survival proteins. The efficacy of ZOL treatment requires a concomitant unleashing of apoptosis using a selective BH3-mimetic as ABT-737. The rational targeting of specific components of the apoptotic pathway may appear a useful approach to improve the treatment of refractory or relapsed cholangiocarcinoma. Combined treatment could be further explored in in vivo tumor model of cholangiocarcinoma.
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Wang W, Sun YP, Huang XZ, He M, Chen YY, Shi GY, Li H, Yi J, Wang J. Emodin enhances sensitivity of gallbladder cancer cells to platinum drugs via glutathion depletion and MRP1 downregulation. Biochem Pharmacol 2010; 79:1134-1140. [PMID: 20005210 DOI: 10.1016/j.bcp.2009.12.006] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2009] [Revised: 12/03/2009] [Accepted: 12/04/2009] [Indexed: 02/05/2023]
Abstract
Glutathione conjugation and transportation of glutathione conjugates of anticancer drugs out of cells are important for detoxification of many anticancer drugs. Inhibition of this detoxification system has recently been proposed as a strategy to treat drug-resistant solid tumors. Gallbladder carcinoma is resistant to many anticancer drugs, therefore, it is needed to develop a novel strategy for cancer therapy. In the present study, we tested the effect of emodin (1,3,8-trihydroxy-6-methylanthraquinone), a reactive oxygen species (ROS) generator reported by our group previously, in combination with cisplatin (CDDP), carboplatin (CBP) or oxaliplatin in treating the gallbladder carcinoma cell line SGC996. Our results showed that co-treatment with emodin could remarkably enhance chemosensitivity of SGC996 cells in comparison with cisplatin, carboplatin or oxaliplatin treatment alone. We found that the mechanisms may be attributed to reduction of glutathione level, and downregulation of multidrug resistance-related protein 1 (MRP1) expression in SGC996 cells. The experiments on tumor-bearing mice showed that emodin/cisplatin co-treatment inhibited the tumor growth in vivo via increasing tumor cell apoptosis and downregulating MRP1 expression. In conclusion, emodin can work as an adjunct to enhance the anticancer effect of platinum drugs in gallbladder cancer cells via ROS-related mechanisms.
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Affiliation(s)
- Wei Wang
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, China
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Hatzaras I, Schmidt C, Muscarella P, Melvin WS, Ellison EC, Bloomston M. Elevated CA 19-9 portends poor prognosis in patients undergoing resection of biliary malignancies. HPB (Oxford) 2010; 12:134-8. [PMID: 20495658 PMCID: PMC2826672 DOI: 10.1111/j.1477-2574.2009.00149.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2009] [Accepted: 11/08/2009] [Indexed: 12/12/2022]
Abstract
BACKGROUND Biliary tree malignancies including cholangiocarcinoma and gallbladder cancer are aggressive cancers with a high disease-specific mortality despite resection. The aim of the present study was to identify predictors of survival after resection. METHODS A retrospective review of all patients that underwent radical resection of biliary malignancies was performed. Demographics, elevated CA19-9 (>35 U/ml), treatment and outcome data were collected and compared according to tumour location. Kaplan-Meier survival curves were created and compared using log-rank analysis. Multivariate analysis was undertaken using Cox proportional hazards regression. RESULTS Ninety-one patients with biliary malignancies underwent surgical resection between 1992 and 2007. There were 46 (50.5%) extrahepatic cholangiocarcinomas (EHC), 23 (25.2%) intrahepatic cholangiocarcinomas (IHC) and 22 (24.2%) gallbladder carcinomas (GBC). The median (range) age was 64 (24-92) years. An elevated CA19-9 was recorded in 45 (55%) patients (52% of IHC, 63% of EHC, and 41% of GBC). The overall median (range) survival was 22.5 (0.3-153.3) months. All three groups were similar in terms of age, gender, pre-operative CA 19-9 level, completeness of resection and tumour histopathological characteristics. GBC were associated with the shortest median survival (14.3 months) followed by EHC (24.8 months) and IHC (30.4 months); however, this did not meet statistical significance (P= 0.971). Only elevated pre-operative CA 19-9 level (>35 U/ml) was predictive of poor median survival by univariate (P= 0.003) and multivariate analysis (15.1 months vs. 67.4, P= 0.047). CONCLUSIONS Elevated pre-operative CA 19-9 levels were found to be independent predictors of poor survival after attempted resection for biliary tree malignancies. It is recommended that CA19-9 be routinely measured prior resection.
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Affiliation(s)
- Ioannis Hatzaras
- Department of Surgery, The Ohio State University Columbus, OH 43210, USA
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Park J, Kim MH, Kim KP, Park DH, Moon SH, Song TJ, Eum J, Lee SS, Seo DW, Lee SK. Natural History and Prognostic Factors of Advanced Cholangiocarcinoma without Surgery, Chemotherapy, or Radiotherapy: A Large-Scale Observational Study. Gut Liver 2009; 3:298-305. [PMID: 20431764 PMCID: PMC2852727 DOI: 10.5009/gnl.2009.3.4.298] [Citation(s) in RCA: 131] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2009] [Accepted: 09/04/2009] [Indexed: 12/11/2022] Open
Abstract
Background/Aims We aimed to evaluate survival time and prognostic factors in patients with advanced unresectable cholangiocarcinoma who have not received surgery, chemotherapy, or radiotherapy. Methods A total of 1,377 patients, who were diagnosed with primary cholangiocarcinoma between 1996 and 2002, were reviewed retrospectively according to the following inclusion criteria: histologically proven primary adenocarcinoma arising from the bile-duct epithelium, advanced unresectable stages, no severe comorbidity that can affect survival time, and no history of surgery, chemotherapy, or radiotherapy. Results Of the 1,377 cases reviewed, 330 patients complied with the inclusion criteria and were thus eligible to participate in this study; 203 had intrahepatic cholangiocarcinoma and 127 had hilar cholangiocarcinoma. The overall survival time of the entire cohort (n=330) was median 3.9 months (range; 0.2 to 67.1). The survival time was significantly shorter in the intrahepatic cholangiocarcinoma group (3.0±5.3 months) than in the hilar cholangiocarcinoma group (5.9±10.1 months; Kaplan-Meier survival analysis). Multivariate analysis revealed that distant metastasis was a poor prognostic factor for intrahepatic cholangiocarcinoma (p< 0.001), baseline serum albumin >3.0 g/dL was a favorable prognostic factor (p=0.02), and baseline serum carcinoembryonic antigen level >30 ng/mL was a poor prognostic factor for hilar cholangiocarcinoma (p=0.01). Conclusions The median survival of advanced unresectable cholangiocarcinoma is dismal.
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Affiliation(s)
- Jongha Park
- Division of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Proteomic studies of cholangiocarcinoma and hepatocellular carcinoma cell secretomes. J Biomed Biotechnol 2009; 2010:437143. [PMID: 20069059 PMCID: PMC2801507 DOI: 10.1155/2010/437143] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2009] [Accepted: 09/28/2009] [Indexed: 01/02/2023] Open
Abstract
Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) occur with relatively high incidence in Thailand. The secretome, proteins secreted from cancer cells, are potentially useful as biomarkers of the diseases. Proteomic analysis was performed on the secreted proteins of cholangiocarcinoma (HuCCA-1) and hepatocellular carcinoma (HCC-S102, HepG2, SK-Hep-1, and Alexander) cell lines. The secretomes of the five cancer cell lines were analyzed by SDS-PAGE combined with LC/MS/MS. Sixty-eight proteins were found to be expressed only in HuCCA-1. Examples include neutrophil gelatinase-associated lipocalin (lipocalin 2), laminin 5 beta 3, cathepsin D precursor, desmoplakin, annexin IV variant, and annexin A5. Immunoblotting was used to confirm the presence of lipocalin 2 in conditioned media and cell lysate of 5 cell lines. The results showed that lipocalin 2 was a secreted protein which is expressed only in the conditioned media of the cholangiocarcinoma cell line. Study of lipocalin 2 expression in different types of cancer and normal tissues from cholangiocarcinoma patients showed that lipocalin 2 was expressed only in the cancer tissues. We suggest that lipocalin 2 may be a potential biomarker for cholangiocarcinoma.
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Cholangiocarcinoma: An emerging indication for photodynamic therapy. Photodiagnosis Photodyn Ther 2009; 6:84-92. [DOI: 10.1016/j.pdpdt.2009.05.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2009] [Revised: 05/07/2009] [Accepted: 05/08/2009] [Indexed: 12/22/2022]
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Weber A, Weyhern CV, Fend F, Schneider J, Neu B, Meining A, Weidenbach H, Schmid RM, Prinz C. Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma. World J Gastroenterol 2008; 14:1097-101. [PMID: 18286693 PMCID: PMC2689414 DOI: 10.3748/wjg.14.1097] [Citation(s) in RCA: 102] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.
METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.
RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).
CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.
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Bonney GK, Craven RA, Prasad R, Melcher AF, Selby PJ, Banks RE. Circulating markers of biliary malignancy: opportunities in proteomics? Lancet Oncol 2008; 9:149-58. [PMID: 18237849 DOI: 10.1016/s1470-2045(08)70027-5] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cholangiocarcinoma, a primary liver tumour that arises from biliary epithelial cells, is increasing in incidence and has poor prognosis. Diagnosis is difficult, particularly in patients with primary sclerosing cholangitis, who are at risk of developing the disease. Timely diagnosis is essential because surgical resection in early disease remains the only cure. The lack of a sensitive and specific early diagnostic marker and of alternative treatments are the main reasons why patients have limited survival. The use of proteomic-based approaches, which analyse the physiological or pathological complement of proteins (ie, the proteome) in cells, tissues, or biological fluids, has received substantial interest in biomarker discovery. Proteomics complements genomic studies and examines functional end-units quantitatively and qualitatively, including post-translational modifications which might vary with disease and might have key roles in protein function or localisation. Major advances in technology and bioinformatics have enhanced proteomic studies, resulting in increased understanding of the pathogenesis of many diseases and in biomarker discovery with effective use of tissues, cell lines, and biological fluids. We review the current status and promise of proteomic-based approaches in biomarker discovery for cholangiocarcinoma.
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Affiliation(s)
- Glenn K Bonney
- Cancer Research UK Clinical Centre, St James's University Hospital, Leeds, UK
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Rau S, Autschbach F, Riedel HD, Konig J, Kulaksiz H, Stiehl A, Riemann JF, Rost D. Expression of the multidrug resistance proteins MRP2 and MRP3 in human cholangiocellular carcinomas. Eur J Clin Invest 2008; 38:134-42. [PMID: 18226047 DOI: 10.1111/j.1365-2362.2007.01916.x] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Cholangiocellular carcinomas and gallbladder carcinomas are highly aggressive tumours with a poor prognosis and are generally regarded as chemoresistant tumours. Overexpression of ATP-binding cassette transporters of the multidrug resistance protein (MDR) and multidrug resistance-related protein (MRP) family in cancer cells is a major cause for the multidrug resistance phenotype in vitro and in vivo. To further define the role of MRP family members in biliary tract cancer, we studied the expression and localization of MRP2 and MRP3 in cholangiocellular carcinomas and gallbladder carcinomas. MATERIALS AND METHODS The expression and cellular localization of the multidrug resistance proteins MRP2 and MRP3 in human cholangiocellular carcinomas and gallbladder carcinomas were analysed by immunohistochemistry using isoform-specific antibodies. Expression of MRP isoforms was studied in vitro in Mz-ChA-1 cells derived from gallbladder adenocarcinoma by reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting and immunofluorescence microscopy. RESULTS Mz-ChA-1 cells constitutively expressed MDR P-glycoproteins, MRP1, MRP2 and MRP3 by RT-PCR, immunoblotting and immunofluorescence microscopy. MRP2 and MRP3 are expressed in the respective apical and basolateral membrane domains. MRP3 was the predominant MRP isoform in gallbladder carcinomas (93%) and cholangiocellular carcinomas (57%), whereas MRP2 expression was detected in only 29% of gallbladder carcinomas and was undetectable in cholangiocellular carcinomas. CONCLUSIONS Our findings suggest that the intrinsic multidrug resistance of cholangiocellular and gallbladder carcinomas seems to be independent of MRP2 expression while the expression of MRP3 may contribute to the MDR phenotype.
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Affiliation(s)
- S Rau
- University of Heidelberg, Heidelberg, Germany
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Charatcharoenwitthaya P, Lindor KD. Primary sclerosing cholangitis: patients with a rising alkaline phosphatase at annual follow-up. Clin Gastroenterol Hepatol 2007; 5:32-6. [PMID: 17234554 DOI: 10.1016/j.cgh.2006.10.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Liu XF, Zhang H, Zhu SG, Zhou XT, Su HL, Xu Z, Li SJ. Correlation of p53 gene mutation and expression of P53 protein in cholangiocarcinoma. World J Gastroenterol 2006; 12:4706-9. [PMID: 16937443 PMCID: PMC4087837 DOI: 10.3748/wjg.v12.i29.4706] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To characterize the tumor suppressor gene p53 mutations and study the correlation of p53 gene mutation and the expression of P53 protein in cholangiocarcinoma.
METHODS: A total of 36 unselected, frozen samples of cholangiocarcinoma were collected. p53 gene status(exon 5-8) and P53 protein were examined by automated sequencing and immunohistochemical staining, combined with the clinical parameters of patients.
RESULTS: p53 gene mutations were found in 22 of 36 (61.1%) patients. Nineteen of 36 (52.8%) patients were positive for P53 protein expression. There were significant differences in extent of differentiation and invasion between the positive and negative expression of P53 protein. However, there were no significant differences in pathologic parameters between the mutations and non-mutations.
CONCLUSION: The alterations of the p53 gene evaluated by DNA sequence analysis is relatively accurate. Expression of P53 protein could not act as an independent index to estimate the prognosis of cholangiocarcinoma.
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Affiliation(s)
- Xiao-Fang Liu
- Department of Hepatobiliary Surgery of Yantai Yuhuangding Hospital, Yantai 264000, Shangdong Province, China.
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