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Chromosomal aberrations related to metastasis of human solid tumors

World Journal of Gastroenterology 2002年第5期8卷 769-776页

作者： lun-xiu qin liver cancer institute and zhongshan hospital,fudan university,shanghai,china liver cancer institute zhongshan hospital Fudan University Shanghai China. lxqin@***

The central role of sequential accumulation of genetic alterations during the development of cancer has been firmly established since the pioneering cytogenetic studies successfully defined recurrent chromosome changes in spedfic types of tumor. In the course of carcinogenesis, cells experience several genetic alterations that are associated with the transition from a preneoplastic lesion to an invasive tumor and finally to the metastatic state. Tumor progression is characterized by stepwise accumulation of genetic *** does the dominant metastatic clone. Modern molecular genetic analyses have clarified that genomic changes accumulate during the development and progression of cancers. In comparison with the corresponding primary tumor,additional events of chromosomal aberrations (including gains or allelic losses) are frequently found in metastases, and the incidence of combined chromosomal alterations in the primary tumor, plus the occurrence of additional aberrations inthe distant metastases, correlated significantly with decreased postmetastatic survival. The deletions at 3p, 4p, 6q, 8p, 10q,11p, 11q, 12p, 13q, 16q, 17p, 18q, 21q, and 22q, as well as the over-representations at 1q, 8q, 9q, 14q and 15q, have been found to associate preferentially with the metastatic phenotype of human cancers. Among of them, the deletions on chromosomes 8p, 17p, 11p and 13p seem to be more significant, and more detail fine regions of them, including 8p11, 8p21-12, 8p22, 8p23, 17p13.3, 11p15.5, and 13q12-13 have been suggested harboring metastasis-suppressor *** the past decade, several human chromosomes have been functionally tested through the use of microcell-mediated chromosome transfer (MMCT), and metastasis-suppressor activities have been reported on chromosomes 1, 6, 7, 8, 10,11, 12, 16, and 17. However, it is not actually known at what stage of the metastatic cascade these alterations have *** is still controversial with the association between

关键词：染色体变异实质肿瘤肿瘤转移综述

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Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 117-122页

作者： Xin Yang Lu Lu Wen-Wei Zhu Yi-Feng Tao Cong-Huan Shen Jin-Hong Chen Zheng-Xin Wang lun-xiu qin Hepatobiliary Surgery and liver Transplantation Centers Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan UniversityShanghai 200040China

Hepatectomy is still the major curative treatment for patients with liver ***,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic *** vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver *** to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver *** efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar ***,the application of ELRA for liver malignances has gained more ***,standardization of clinical practice norms and international consensus are still *** prognostic impact in these oncologic patients also needs further *** this review,we summarized the principles and recent progresses on ELRA.

关键词： Ex vivo liver resection liver auto-transplantation Oncology liver malignancies

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The prognostic molecular markers in hepatocellular carcinoma

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World Journal of Gastroenterology 2002年第3期8卷 385-392页

作者： lun-xiu qin Zhao-You Tang,liver cancer institute and zhongshan hospital,fudan university,shanghai,china liver cancer institute and zhongshan hospital Fudan university 136 Yi Xue Yuan Road Shanghai 200032 China.

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) leve

关键词： Apoptosis Carcinogens Carcinoma, Hepatocellular Cell Adhesion Cell Division Cell Nucleus Extracellular Matrix Genes, p53 Humans liver Neoplasms Neovascularization, Pathologic Ploidies Prognosis Proteome Telomerase Tumor Markers, Biological

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The prognostic significance of clinical and pathological features in hepatocellular carcinoma

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World Journal of Gastroenterology 2002年第2期8卷 193-199页

作者： lun-xiu qin Zhao-You Tang,liver cancer institute and zhongshan hospital,fudan university,shanghai,china liver cancer institute Zhongshan Hospital 136 Yi Xue Yuan Road Shanghai 200032 China.

The prognosis of patients with HCC still remains dismal. The life expectancy of HCC patients is hard to predict because of the high possibility of postoperative recurrence. Many factors, such as patient's general conditions, macroscopic tumor morphology, as well as tumor histopathology features, have been proven of prognostic significance. Female HCC patient often has a better prognosis than male patient, which might be due to the receptor of sex hormones. Younger patients often have tumors with higher invasiveness and metastatic potentials, and their survival and prognosis are worse than the older ones. Co-existing hepatitis status and hepatic functional reserve have been confirmed as risk factors for recurrence. Serum alpha-fetoprotein (AFP) is useful not only for diagnosis, but also as a prognostic indicator for HCC patients. AFP mRNA has been proposed as a predictive marker of HCC cells disseminated into the circulation and for metastatic recurrence. Many pathologic features, such as tumor size, number, capsule state, cell differentiation, venous invasion, intrahepatic spreading, and advanced pTNM stage, are the best-established risk factors for recurrence and important aspects affecting the prognosis of patients with HCC. Marked inflammatory cell infiltration in the tumor could predict a better prognosis. Clinical stage is still the most important factor influencing on the prognosis. Extratumor spreading and lymph nodal metastasis are independent predictors for poor outcome. Some new predictive systems have recently been proposed. Different strategies of treatment might have significant different effects on the patients' prognosis. To date, surgical resection is still the only potentially curative treatment for HCC, including localized postoperative recurrences. Extent of resection, blood transfusion, occlusion of porta hepatis, and blood loss affect the survival and prognosis of HCC patients. Regional therapies provide alternative ways to improve the prognosis

关键词： Age Factors Carcinoma, Hepatocellular Hepatitis Humans liver Cirrhosis liver Neoplasms Neoplasm Staging Prognosis Recurrence Sex Factors alpha-Fetoproteins

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Hepatocellular carcinoma with obstructive jaundice: diagnosis, treatment and prognosis

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World Journal of Gastroenterology 2003年第3期9卷 385-391页

作者： lun-Xin qin Zhao-You Tang liver cancer institute and zhongshan hospital, fudan university, shanghai, china liver cancer institute Fudan University 136 Yi Xue Yuan Road Shanghai 200032 China. zytang@***

Obstructive jaundice as the main clinical feature is uncommon in patients with hepatocellular carcinoma (HCC). Only 1-12 %of HCC patients manifest obstructive jaundice as the initial complaint. Such cases are clinically classified as 'icteric type hepatoma', or 'cholestatic type of HCC'. Identification of this group of patients is important, because surgical treatment may be beneficial. HCC may involve the biliary tract in several different ways: tumor thrombosis, hemobilia,tumor compression, and diffuse tumor infiltration. Bile duct thrombosis (BDT) is one of the main causes for obstructive jaundice, and the previously reported incidence is 1.2-9 %.BDT might be benign, malignant, or a combination of *** thrombi could be blood clots, pus, or *** thrombi could be primary intrabiliary malignant tumors, HCC with invasion to bile ducts, or metastatic cancer with bile duct invasion. The common clinical features of this type of HCC include: high level of serum AFP; history of cholangitis with dilation of intrahepatic bile duct; aggravating jaundice and rapidly developing into liver dysfunction. It is usually difficult to make diagnosis before operation, because of the low incidence rate, ignorant of this disease, and the difficulty for the imaging diagnosis to find the BDT preoperatively. Despite recent remarkable improvements in the imaging tools for diagnosis of HCC, such cases are still incorrectly diagnosed as cholangiocarcinoma or choledocholithiases. Ultrasonography (US) and CT are helpful in showing hepatic tumors and dilated intrahepatic and/or extrahepatic ducts containing dense material corresponding to tumor debris. Direct cholangiography including percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP)remains the standard procedure to delineate the presence and level of biliary obstruction. Magnetic resonance cholangiopancreatography (MRCP) is superior to ERCP in interpreting the cause and

关键词：肝细胞癌梗阻性黄疸合并症肝动脉灌注栓塞化疗诊断临床特点

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Risk factors for postoperative complications after liver resection

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Hepatobiliary & Pancreatic Diseases International 2005年第3期4卷 370-374页

作者： Hui-Chuan Sun, lun-xiu qin, Lu Wang, qin-Hai Ye, Zhi-Quan Wu, Jia Fan and Zhao-You Tang liver cancer institute and zhongshan hospital, fudan university, shanghai 200032, china liver cancer institute and zhongshan hospital Fudan University Shanghai 200032 China. sunhc@***

liver resection is still a complicated operation with a high risk of postoperative morbidity. This study was undertaken to analyze the risk factors for postoperative complications after liver resection. METHODS:From 2001 to 2004, a total of 146 patients underwent liver resection for malignant or benign lesions. Postoperative complications after the resection were classified as surgical and medical, their incidences were analyzed *** risk factors for both surgical and medical complications were analyzed. To increase the safety of liver resection, surgical techniques were modified after April 2003, including control of inflow or outflow and intra- operative test with methylene blue. RESULTS:Before April 2003, a series of 58 patients received liver resection. Modified surgical techniques were used in liver resections for 88 patients after April 2003.A total of 36 patients (24.7%) had postoperative complications. Surgical and medical complications occurred in 24 and 13 patients respectively (One patient had both surgical and medical complications). Perioperative blood transfusion was related to a higher risk of surgical complications (Phospitalization were decreased after the use of modified surgical techniques (Pliver resection may help to decrease postoperative medical complications also.

关键词： hepatocellular carcinoma resection complications

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Downstaging followed by resection plays a role in improving prognosis of unresectable hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2004年第4期3卷 495-498页

作者： Zhao-You Tang,Xin-Da Zhou, Zeng-Chen Ma, Zhi-Quan Wu, Jia Fan, lun-xiu qin and Yao Yu shanghai, china liver cancer institute & zhongshan hospital, fudan university, shanghai 200032 , china liver cancer institute of fudan university 136 Yi Xue Yuan Road Zhongshan Hospital Shanghai 200032 China. zytang@***

BACKGROUND: Curable outcome of unresectable hepato- cellular carcinoma ( HCC) was seldom encountered in the past. This study was designed to assess the role of down- staging followed by resection ( downstaging-resection) in the improvement of prognosis of unresectable HCC. METHODS: During the period of 1958-2003 , a total of 1085 patients were verified surgically to be unresectable. Of these patients, 139 received downstaging-resection, with a rate of 84.2% for coexisting cirrhosis and a median tumor diame- ter of 11.1 cm. Resection of the right lobe, hepatic hilum and bilateral cancer accounted for 97. 8% of the patients. Downstaging including hepatic artery ligation ( HAL) + he- patic artery chemo-infusion ( HAI ) was performed in 65.5% of the patients, HAL + HAI + radiotherapy/radioim- munotherapy in 29. 5%, and HAL or HAI alone in 5.0%. Retrospective analysis was made of the survival of patients with unresectable HCC, downstaging-resection rate and treatment pattern. RESULTS: In the 139 patients with downstaging-resection, the median interval between the first and second operation was 7.2 months and the 5-year survival rate calculated from the first operation was 48. 7%. In the 1085 patients with un- resectable HCC, their 5-year survival was 0% in the period of 1958-1973, 11.5% in the period of 1974-1988 and 19.3% in the period of 1989-2003. These figures were correlated with the increasing downstaging-resection rate from 0%, 9.0% to 15.6%, and the increasing percentage of triple or double combination treatment from 32.2%, 60.4% to 69.7%. The 5-year survival in triple treatment group was 24. 9%, double treatment 15.2%, and single treatment only 10.9%, which was also correlated with the downstaging-re- section rate of 34.6%, 16.2% and 1.8% respectively. CONCLUSIONS: Downstaging-resection plays a role in improving prognosis of unresectable HCC. Triple and double treatments provide a higher downstaging-resection rate and may result in better prognosis.

关键词： hepatocellular carcinoma downstaging cytoreduction resection multimodality treatment

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Diagnosis and treatment of hepatic angiomyolipoma in 26 cases

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World Journal of Gastroenterology 2003年第8期9卷 1856-1858页

作者： Ning Ren lun-xiu qin Zhao-You Tang Zhi-Quan Wu Jia Fan, liver cancer institute and zhongshan hospital, fudan university, shanghai 200032, china liver cancer institute Fudan University Shanghai 200032 China. ningren@***

AIM: To summarize the experience of the diagnosis and treatment of hepatic angiomyolipoma (HAML).METHODS: The clinical, imaging and pathological features,and treatment strategies of 26 patients with HAML treated at the authors′institute between October 1998 and January 2003 were retrospectively analyzed. All the patients received liver resection and were followed up till the *** assays were performed with a panel of ***: There was an obvious female predominance (21:5), and most of the patients (18/26) had no *** high echo was found in ultrasonography and punctiform or filiform vascular distribution pattern was found in color Doppler-sonography in most of the lesions (21/26).All of the 5 lesions further enhanced with Levovist showed early and prolonged enhancement. At contrast-enhanced spiral CT, the soft-tissue components of 24 lesions were markedly enhanced in the arterial phase and 18 lesions remained enhanced in the portal venous phase. MRI was performed in 9 patients, and showed hypointensity or hyperintensity on T1-weighted images and heterogeneous hyperintensity on T2-weighted images. Histopathologically,all lesions were composed of adipose tissues, smooth muscle and blood vessels with different proportions. Most lesions showed positive immunohistochemical staining for HMB45(26/26), A103 (24/26) and SMA (24/26). All of the 26 patients showed a benign course with no sign of ***: Preoperative radiological diagnosis of HAML is possible. The demonstration of intratumoral fat and central vessels is helpful in the diagnosis. HMB45, A103 and SMA are promising markers for pathologic diagnosis of HAML,and surgical resection is effective for the treatment of HAML.

关键词：肝血管肌脂瘤肝肿瘤 CT诊断手术治疗

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Recent progresses in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma:a review of literatures

Recent progresses in predictive biomarkers for metastatic re...

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第三届中国肿瘤学术大会

作者： lun - xiu qin, Zhao - You Tang liver cancer institute and zhongshan hospital, fudan university, shanghai, china

＜正＞ Molecular markers （biomarkers ） for hepatocellular carcinoma （HCC） metastasis and recurrence could provide additional information to that by traditional histopathological features. A large number of biomarkers have been shown to have potential predictive significance. One important aspect of that is to detect the transcripts of tumor associated antigens （such as AFP, MAGEs and CK19） , which is proposed as predictive markers of HCC cells disseminated into the circulation and for metastatic recurrence. Another important aspect is to analyze the molecular markers for cellular malignancy phenotype, including DNA ploidy, cellular proliferation index, cell cycle regulators, oncogenes and tumor suppressors （ especially p53 gene） , as well as telomerase activity. Molecular factors involved in the process of HCC invasion and metastasis, including adhesion molecules （E -cadherin, catenins, ICAM -1, laminin -5, CD44 variants, osteopontin） , proteinases responsible for the degradation of extracellular matrix （MMPs, uPA sytem） , as well as angiogenesis regulators （such as VEGF, inratumor MVD） , have also been shown to be potential predictors for HCC metastatic recurrence and clinical outcomes. One important new trend is to genome - widely delineate biomarkers with expression genomics and proteomics with reference to predicting metastatic recurrence, molecular diagnosis and classification, which has been drawing more attention recently. Body fluid （ particularly blood and urinary） testing for biomarkers is easily accessible and more useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations is another important direction. More attention should be paid to these areas in future. As further understanding of tumor biology, more and more new biomarkers with high sensitivity and specificity for HCC metastatic recurrence could be found and routinely used in clinical assays. However, the combination of the pathological

关键词： hepatocellular carcinoma recurrence metastasis molecular marker biomarker.

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The microcell mediated transfer of human chromosome 8 into highly metastatic rat liver cancer cell line C5F

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World Journal of Gastroenterology 2003年第3期9卷 449-453页

作者： Hu Liu Sheng-Long Ye Jinng Yang Zhao-You Tang Yin-Kun Liu lun-xiu qin Shuang-Jian Qiu Rui-Xia Sun liver cancer institute, Zhong Shan hospital, fudan university, shanghai 200032, china liver cancer institute Zhong Shan Hospital Fudan University Shanghai 200032 China.

AIM: Our previous research on the surgical samples of primary liver cancer with CGH showed that the loss of human chromosome 8p had correlation with the metastatic phenotype of liver cancer. In order to seek the functional evidence that there could be a metastatsis suppressor gene (s) for liver cancer on human chromosome 8, we tried to transfer normal human chromosome 8 into rat liver cancer cell line C5F, which had high metastatic potential to ***: Human chromosome 8 randomly marked with neo gene was introduced into C5F cell line by MMCT and positive microcell hybrids were screened by double selections of G418 and HAT. Single cell isolation cloning was applied to clone microcell hybrids. Finally, STS-PCR and WCP-FISH were used to confirm the ***: Microcell hybrids resistant to HAT and G418 were obtained and 15 clones were obtained by single-cell isolation cloning. STS-PCR and WCP-FISH proved that human chromosome 8 had been successfully introduced into rat liver cancer cell line C5F. STS-PCR detected a random loss in the chromosome introduced and WCP-FISH found a consistent recombination of the introduced human chromosome with the rat ***: The successful introduction of human chromosome 8 into highly metastatic rat liver cancer cell line builds the basis for seeking functional evidence of a metastasis suppressor gene for liver cancer harboring on human chromosome 8 and its subsequent cloning.

关键词： C5F细胞系肝癌动物模型微细胞调节转换器人染色体8 肿瘤转移

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