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| 1 | Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97显示文摘ALM To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97. andbiological characteristics of the target clones selected by in vivo screening were studied.``RESULTS Two clones with high MHCC97-H and IowMHCC9--L1 metastatic potential were isolated from theparent cell line. Compared with MHCC97-L. MHCC97-H hadsmaller cell size average cell diameter 43 um vs 50 μmand faster in vitro and in vivo growth rate tumor celldoubling time was 34.2 h vs 60.0 h. The main ranges ofchromosomes were 5.5 58 in MHCC97-H and 57 62 inMHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was 137.5 - 11 .0) cellsfield for MHC_C99--H vs 17.7 - 6.3) field for MHCC97-L.The proportions of cells in GO Gl phase. S phase, and G_ M phase for MHCC97-H MHCC97-L were 0.56 6.65.0.28 0.25 and 0.l6 0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5 wk after orthotopic implantation of tumor tissue were ( 24666 μg. L for MHCC97-H and (91- 66) μg' L 1 for MHCC97L. The pulmonary metastatic rate was 100% (10-10) vs40% 4- 10).``CONCLUSION Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis. | Yan Li Zhao-You Tang Sheng-Long Ye Yin-Kun Liu Jie Chen Qiong Xue Jun Chen Dong-Mei Gao Wei-Hua Bao Liver Cancer Institute and Zhongshan Hospital of Fudan University (Former Liver Cancer Institute of Shanghai Medical University),Shanghai 200032,China | 2001 | World Journal of Gastroenterology2001，7，5： | 111 |
| 2 | Specific molecular markers in hepatocellular carcinoma显示文摘BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor, and early diagnosis and monitoring metastasis of HCC is of the utmost importance. Circulating diagnostic and prognostic biomarkers could be used in proper postoperative treatment of patients at an early stage of HCC development. This review summarizes recent studies of the specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. DATA SOURCES: An English-language literature search was conducted using MEDLINE (June 1998 to September 2006) on researches of some valuable specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. RESULTS: Hepatoma tissues can synthesize various tumor-related proteins, polypeptides, and isoenzymes, such as alpha-fetoprotein (AFP), hepatoma-specific gamma-glutamyl transpeptidase (HS-GGT), etc, and then secrete into blood. The valuable early diagnostic and prognostic biomarkers could predict the development and metastases of HCC. Recent researches have confirmed that circulating hepatoma-specific AFP subfraction, transforming growth factor (TGF)-β1, HS-GGT, and free insulin-like growth factor (IGF)-Ⅱ may be more specific markers than total AFP level for early diagnosis for HCC. The circulating genetic markers such as AFP-mRNA, TGF-β1-mRNA, IGF-Ⅱ-mRNA, etc from peripheral blood mononuclear cells of HCC patients have been most extensively used in monitoring distal metastasis or postoperative recurrence of HCC. CONCLUSIONS: Hepatoma tissues synthesize and secrete valuable molecular markers into blood. The analyses of circulating hepatoma-specific biomarkers are usefulto early diagnosis of HCC or monitoring metastasis or postoperative recurrence of HCC. | Yao, Deng-Fu Dong, Zhi-Zhen Yao, Min | 2007 | Hepatobiliary & Pancreatic Diseases International2007，6，3： | 55 |
| 3 | Recurrence or metastasis of HCC:predictors,early detection and experimental antiangiogenic therapy显示文摘AIM To investigate the predictors forrecurrence or metastasis of HCC,and toevaluate the effect of antiangiogenic therapy onthe growth of transplantable human HCC in nudemice.METHODS RT-PCR was used to measure theexpression of matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)in 56 pairs of nontumorous liver andtumor samples.Sixty blood samples from humanHCC were examined by nested RT-PCR to find outAFP mRNA.Recombinant human endostatin andpolyclonal antibody against VEGF wereadministered to treat human HCC transplanted innude mice.RESULTS Thirty of 56 HCC samples showedstronger expression of MMP-9 in tumoroustissues than in nontumorous tissues.Fifteen ofthe 26 patients with relative expression level ofMMP-9 more than 0.34 developed tumorrecurrence or metastasis,whereas only 7 of 30patients with relative expression level less than0.34 developed tumor recurrence(P<0.05).There was no significant difference in therelative expression level of VEGF betweenpatients with postoperative recurrence ormetastasis and those without recurrence.AFPmRNA was detectable in 53.3% of patients withHCC.The sensitivity and specificity of AFPmRNA as a marker to detect hematogenousdissemination of HCC cells was 81.8% and84.4%,respectively.Recombinant human endostatin and polyclonal antibody against VEGFinhibited the growth of transplantable HCC innude mice by 52.2% and 45.7%,respectively.CONCLUSION MMP-9 expression in HCCcorrelates with the postoperative recurrence ormetastasis of HCC.Patients with high level ofMMP-9 expression in HCC are susceptible tometastasis.AFP mRNA could serve as anindicator of hematogenous spreading of HCCcells in circulation and a predictor of recurrenceor metastasis of HCC.Antiangiogenesis may bean adjuvant therapy for HCC. | Jiang YF Yang ZH Hu JQ | 2000 | World Journal of Gastroenterology2000，6，1： | 57 |
| 4 | Alterations in metastatic properties of hepatocellular carcinoma cell following H-ras oncogene transfection显示文摘AIM To demonstrate the relationship betweenH-ras oncogene and hepatocellular carcinoma(HCC) metastasis.METHODS Activated H-ras oncogene wastransfected into SMMC 7721, a cell line derivedfrom human HCC, by calcium phosphatetransfection method. Some metastasis-relatedparameters were detected in vitro, includingadhesion assay, migration assay, expression ofcollagenase ⅣV (c ⅣV ase) and epidermal growthfactor receptor (EGFR).RESULTS The abilities of H-ras-transfected cellclones in adhesion to laminin (LN) or fibronectin(FN), migration, c Ⅳ ase secretion increasedmarkedly, and the expression of EGFR elevatedmoderately. More importantly, these alterationswere consistent positively with the expressionof p21, the protein product of H-ras oncogene.CONCLUSION H-ras oncogene could inducethe metastatic phenotype of HCC cell in vitro toraise its metastatic potential. | Qing Wang~1 Zhi Ying Lin~2 Xiao Li Feng~3 ~1Department of Microbiology,Medical Center of Fudan University.the former Shanghai Medical University,Shanghai 200032,China ~2Liver Cancer Institute,Zhongshan Hospital,Shanghai 200032,China ~3Shanghai Institute of Biochemistry,Academy Sinica,Shanghai 200031,ChinaQing Wang earned master degree from Shanghai Medical University in 1996,now a senior lecturer of microbiology,specialized in the role of oncogcncs on tumor metastasis,having 8 papers published. | 2001 | World Journal of Gastroenterology2001，7，3： | 48 |
| 5 | Molecular mechanism about lymphogenous metastasis of hepatocarcinoma cells in mice显示文摘AIM To investigate the correlation between lymphogenous metastasis and matrix metalloproteinases (MMPs) activity and the expression of Fas Iigand of tumor cells in lymph nodes.METHODES Fifty-six inbred 615-mice were equally divided into 2 groups and inoculated with Hca-F and Hca-P cells. Their lymph node metastatic rates were examined.Growth fraction of lymphocytes in host lymph nodes was detected by flow cytometry. The Hca-F and Hca-P cells were cultured with extract of lymph node, liver or spleen.The quantity of MMPs in these supernatants was examined by zymographic analysis. The expression of Fas ligand,PCNA, Bcl-2 protein of Hca-F and Hca-P cells in the mice were examined by immunohistochemistry. The apoptosis signals of macrophages in lymph nodes were observed with in situ DNA fragmentation.RESULTS On the 28th day post-inoculation, the lymph node metastatic rate of Hca-F was 80% (16/20), whereas that of Hca-P was 25% (5/20). The growth fraction of lymphocytes was as follows: in the Hca-F cells, the proliferating peak of lymphocytes appeared on the 14th day post-inoculation and then decreased rapidly, while in HcaP cells, the peak appeared on the 7th day post-inoculation and then kept at a high level. With the extract of lymph node, the quantity of the MMP-9 activity increased (P<0.01) and active MMP-9 and MMP-2 were produced by both Hca-F and Hca-P tumor cells, which did not produce MMPs without the extract of lymph node or with the extracts of the liver and spleen. The expression of Fas Ligand of Hca-F cells was stronger than that of Hca-P cells (P<0.01). The expressions of PCNA and Bcl-2 protein of Hca-F cells in the tumors of inoculated area were the same as that of Hca-P cells. In situ DNA fragmentation showed that the positive signals of macrophages were around HcaF cells.CONCLUSION Secretion of MMPs which was associated with metastatic ability of Hca-F and Hca-P tumor cells depends on the environment of lymph nodes. The increased expression of Fas ligand protein of Hca-F tumor cells with high lymphogenous metastatic potential in lymph nodes may help tumor cells escape from being killed by host lymphocytes. | Li Hou Ying Li Yong-Hua Jia Bo Wang Yi Xin Mao-Ying Ling Shen Lü Department of Pathology,Dalian Medical University,Dalian 116027,Liaoning Province,ChinaDepartment of Biochemistry,Dalian Medical University,Dalian 116027,Liaoning Province,China | 2001 | World Journal of Gastroenterology2001，7，4： | 47 |
| 6 | Relationship between phenotypes of cell-function differentiation and pathobiological behavior of gastric carcinomas显示文摘AIM To reveal the correlation between thefunctional differentiation phenotypes of gastriccarcinoma cells and the invasion and metastasisby a new way of cell-function classification.METHODS Surgically resected specimens of361 gastric carcinomas (GC) were investigatedwith enzyme-, mucin-, and tumor-related markerimmunohistochemist ry. According to thedirection of cell-function differentiation,stomach carcinomas were divided into fivefunctionally differentiated types.iation type (AFDT): there were 82 (22.7%)patients including 76 (92.7%) aged 45 years.Sixty-nine (84.1%) cases belonged to theintestinal type. Thirty-eight (46.3%) expressedCD44v6 and 9 (13.6%) of 66 male patientsdeveloped liver metastasis. The 5-year survivalrate of patients in this group (58.5%) was higherMucin secreting function differentiation type(MSFDT): 54 (15%) cases. Fifty-three (98.1%)tumors had penetrated the serosa, 12 (22.2%)expressed ER and 22 (40.7%) expressedCD44v6. The postoperative 5-year survival ratefunction differentiation type (AMPFDT): therewere 180 (49.9%) cases, including 31 (17.2%)aged yanger than 45 years. The tumor was morecommon in women (62, 34.4%,) and expressedmore frequently estrogen receptors (ER) ( 129,81.7%) than other types (P<0.01). Ovarymetastasis was found in 12 (19.4%) out of 62female subjects. The patients with this type GChad the lowest 5-year survival rate (24.7%)differentiation type (SFDT): 13 (3.6%) cases.Nine (69.2%) tumors of this type derived fromAPUD system, the other 4 (30.7%) were ofdifferent histological differentiation. Sixty percent of the patients survived at least five years.(8.9%) cases. Nineteen (59.4%) cases hadlymph node metastases but no one with liver orovary metastasis. The 5-year survival rate was28.1%.CONCLUSION This new cell-functionclassification of GC is helpful in indicating thecharacteristics of invasion and metastasis of GCwith different cell-function differentiationphenotypes. Further study is needed to disclosethe correlation between the cell-functionaldifferentiation phenotypes and the relevantgenotypes and the biological behavior of gastriccarcinoma. | Yan Xin Xiao Ling Li Yan Ping Wang Su Min Zhang Hua Chuan Zheng Dong Ying Wu Yin Chang Zhang The Fourth Laboratory of Cancer Institute, China Medical University, Shenyang 110001, Liaoning Province, China | 2001 | World Journal of Gastroenterology2001，7，1： | 38 |
| 7 | Role of autophagy in tumorigenesis,metastasis,targeted therapy and drug resistance of hepatocellular carcinoma显示文摘Autophagy is a 'self-degradative' process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolded proteins, protein aggregates, and damaged organelles. Autophagy plays a dual role in cancer, including in tumor progression and tumor promotion, suggesting that autophagy acts as a double-edged sword in cancer cells. Liver cancer is one of the greatest leading causes of cancer death worldwide due to its high recurrence rate and poor prognosis. Especially in China, liver cancer has become one of the most common cancers due to the high infection rate of hepatitis virus. In primary liver cancer, hepatocellular carcinoma (HCC) is the most common type. Considering the perniciousness and complexity of HCC, it is essential to elucidate the function of autophagy in HCC. In this review, we summarize the physiological function of autophagy in cancer, analyze the role of autophagy in tumorigenesis and metastasis, discuss the therapeutic strategies targeting autophagy and the mechanisms of drug-resistance in HCC, and provide potential methods to circumvent resistance and combined anticancer strategies for HCC patients. | Fang Huang Bing-Rong Wang Yi-Gang Wang | 2018 | World Journal of Gastroenterology2018，24，41： | 37 |
| 8 | Revisions to the Tumor,Node,Metastasis staging of lung cancer(8th edition):Rationale,radiologic findings and clinical implications显示文摘The Tumor, Node, Metastasis(TNM) staging system,adopted by the Union for International Cancer Control(UICC) and the American Joint Committee on Cancer(AJCC), has been recently revised, with the new 8^(th) edition of the staging manual being published in January 2017. This edition has few but important evidencebased changes to the TNM staging system used for lung cancer. Radiologists should be aware of the updated classification system to accurately provide staging information to oncologists and oncosurgeons. In this article, we discuss the rationale, illustrate the changes with relevance to Radiology, and review the clinical implications of the 8^(th) edition of the UICC/AJCC TNM staging system with regards to lung cancer. | Fernando U Kay Asha Kandathil Kiran Batra Sachin S Saboo Suhny Abbara Prabhakar Rajiah | 2017 | World Journal of Radiology2017，9，6： | 39 |
| 9 | Role of surgery in colorectal cancer liver metastases显示文摘Colorectal carcinoma(CRC)is the third most common cancer,and approximately 35%-55%of patients with CRC will develop hepatic metastases during the course of their disease.Surgical resection represents the only chance of long-term survival.The goal of surgery should be to resect all metastases with negative histological margins while preserving sufficient functional hepatic parenchyma.Although resection remains the only chance of long-term survival,management strategies should be tailored for each case.For patients with extensive metastatic disease who would otherwise be unresectable,the combination of advances in medical therapy,such as systemic chemotherapy(CTX),and the improvement in surgical techniques for metastatic disease,have enhanced prognosis with prolongation of the median survival rate and cure.The use of portal vein embolization and preoperative CTX may also increase the number of patients suitable for surgical treatment.Despite current treatment options,many patients still experience a recurrence after hepatic resection.More active systemic CTX agents are beingused increasingly as adjuvant therapy either before or after surgery.Local tumor ablative therapies,such as microwave coagulation therapy and radiofrequency ablation therapy,should be considered as an adjunct to hepatic resection,in which resection cannot deal with all of the tumor lesions.Formulation of an individualized plan,which combines surgery with systemic CTX,is a necessary task of the multidisciplinary team.The aim of this paper is to discuss different approaches for patients that are treated due to CRC liver metastasis. | ?zgür Akgül Erdin? ?etinkaya ?iyar Ers?z Mesut Tez | 2014 | World Journal of Gastroenterology2014，20，20： | 40 |
| 10 | Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential显示文摘Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient like metastatic model of human HCC in nude mice (LCI-D20)and a Iow metastatic model of human HCC in nude mice LCI-D35 ) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding.Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including antiangiogenesis, antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence. | Zhao-You Tang Fan-Xian Sun Jian Tian Sheng-Long Ye Yin-Kun Liu Kang-Da Liu Qiong Xue Jie Chen Jing-Lin Xia Lun-Xiu Qin Hui-Chuan Sun Lu Wang Jian Zhou Yan Li Zeng-Chen Ma Xin-Da Zhou Zhi-Quan Wu Zhi-Ying Lin Bing-Hui Yang Liver Cancer Institute of Fudan University and Zhongshan Hospital,Shanghai 200032,China | 2001 | World Journal of Gastroenterology2001，7，5： | 34 |
| 11 | Current oncologic applications of radiofrequency ablation therapies显示文摘Radiofrequency ablation (RFA) uses high frequency alternating current to heat a volume of tissue around a needle electrode to induce focal coagulative necrosis with minimal injury to surrounding tissues. RFA can be performed via an open, laparoscopic, or image guided percutaneous approach and be performed under general or local anesthesia. Advances in delivery mechanisms, electrode designs, and higher power generators have increased the maximum volume that can be ablated, while maximizing oncological outcomes. In general, RFA is used to control local tumor growth, prevent recurrence, palliate symptoms, and improve survival in a subset of patients that are not candidates for surgical resection. It's equivalence to surgical resection has yet to be proven in large randomized control trials. Currently, the use of RFA has been well described as a primary or adjuvant treatment modality of limited but unresectable hepatocellular carcinoma, liver metastasis, especially colorectal cancer metastases, primary lung tumors, renal cell carcinoma, boney metastasis and osteoid osteomas. The role of RFA in the primary treatment of early stage breast cancer is still evolving. This review will discuss the general features of RFA and outline its role in commonly encountered solid tumors. | Dhruvil R Shah Sari Green Angelina Elliot John P McGahan Vijay P Khatri | 2013 | World Journal of Gastrointestinal Oncology2013，5，4： | 33 |
| 12 | Prediction of risk factors for lymph node metastasis in early gastric cancer显示文摘AIM:To explore risk factors for lymph node metastases in early gastric cancer(EGC) and to confirm the appropriate range of lymph node dissection.METHODS:A total of 202 patients with EGC who underwent curative gastrectomy with lymphadenectomy in the Department of Surgery,Xinhua Hospital and Ruijin Hospital of Shanghai Jiaotong University Medical School between November 2003 and July 2009,were retrospectively reviewed.Both the surgical procedure and the extent of lymph node dissection were based on the recommendations of the Japanese gastric cancer treatment guidelines.The macroscopic type was classified as elevated(type Ⅰ or Ⅱa),flat(Ⅱb),or depressed(Ⅱc or Ⅲ).Histopathologically,papillary and tubular adenocarcinomas were grouped together as differentiated adenocarcinomas,and poorly differentiated and signet-ring cell adenocarcinomas were regarded as undifferentiated adenocarcinomas.Univariate and multivariate analyses of lymph node metastases and patient and tumor characteristics were undertaken.RESULTS:The lymph node metastases rate in patients with EGC was 14.4%.Among these,the rate for mucosal cancer was 5.4%,and 8.9% for submucosal cancer.Univariate analysis showed an obvious correlation between lymph node metastases and tumor location,depth of invasion,morphological classification and venous invasion(χ 2 = 122.901,P = 0.001;χ 2 = 7.14,P = 0.008;χ 2 = 79.523,P = 0.001;χ 2 = 8.687,P = 0.003,respectively).In patients with submucosal cancers,the lymph node metastases rate in patients with venous invasion(60%,3/5) was higher than in those without invasion(20%,15/75)(χ 2 = 4.301,P = 0.038).Multivariate logistic regression analysis revealed that the depth of invasion was the only independent risk factor for lymph node metastases in EGC [P = 0.018,Exp(B) = 2.744].Among the patients with lymph node metastases,29 cases(14.4%) were at N1,seven cases were at N2(3.5%),and two cases were at N3(1.0%).Univariate analysis of variance revealed a close relationship between the depth of invasion and lymph node metastases at pN 1(P = 0.008).CONCLUSION:The depth of invasion was the only independent risk factor for lymph node metastases.Risk factors for metastases should be considered when choosing surgery for EGC. | Gang Ren Rong Cai Wen-Jie Zhang Jin-Ming Ou Ye-Ning Jin Wen-Hua Li | 2013 | World Journal of Gastroenterology2013，19，20： | 31 |
| 13 | Liver metastasis is the only independent prognostic factor in AFP-producing gastric cancer显示文摘AIM:To investigate differences between common gastric cancer andα-fetoprotein(AFP)-producing gastric cancer according to the presence or absence of liver metastasis.METHODS:Between 1997 and 2011,1299 patients underwent gastrectomy for gastric cancer(GC)at our institute and their hospital records were reviewed retrospectively.Patients were immunohistochemically divided into two groups:23 patients(1.8%)with AFPproducing GC and 1276 patients(98.2%)without it.RESULTS:AFP-producing GC patients had a significantly higher incidence of deeper tumors,venous invasion,lymphatic invasion,lymph node metastasis,and liver metastasis and a poorer prognosis(P<0.005)than those without AFP-producing GC.However,multi-variate analysis revealed that AFP-positivity was not an independent prognostic factor.The prognosis of AFPproducing GC was similar to that of AFP-non producing GC according to the presence or absence of liver metastasis.Concerning recurrence,47.8%of patients(11/23)with AFP-producing GC and 20.0%of patients(256/1276)without AFP-producing GC exhibited recurrence.Liver metastasis[90.9%(10/11)]was the most prevalent in AFP-producing GC patients.Multivariate analysis revealed that liver metastasis was the only independent prognostic factor in AFP-producing GC(HR=17.6,95%CI:2.1-147.1;P=0.0081).CONCLUSION:AFP-producing GC is similar to common GC without liver metastasis,which should be specifically targeted in an effort to improve the prognosis of AFP-producing GC patients. | Shoji Hirajima Shuhei Komatsu Daisuke Ichikawa Takeshi Kubota Kazuma Okamoto Atsushi Shiozaki Hitoshi Fujiwara Hirotaka Konishi Hisashi Ikoma Eigo Otsuji | 2013 | World Journal of Gastroenterology2013，19，36： | 33 |
| 14 | Surgical treatment of hepatocellular carcinoma and related basic research with special reference to recurrence and metastasis显示文摘To summarize the progress of surgical treatment of hepatocellular carcinoma (HCC) and related basic research at the Liver Cancer Institute of Shanghai Medical University in the recent years, with special reference to recurrence and metastasis Methods Published and unpublished update clinical and experimental data in the above mentioned areas are summarized Results Surgical resection has played an important role in improving prognosis of HCC, the 5 year survival were 63 4% for small HCC resection (n=806), 39 6% for large HCC resection (n=1061), 64 7% for cytoreduction (using hepatic artery cannulation and ligation) and sequential resection of initially unresectable HCC (n=93), 56 0% for cytoreduction using transcatheter arterial chemoembolization (TACE) and followed by resection (n=65), and 22 4% for hepatic resection with removal of tumor thrombi in portal vein (n=103) Unfortunately, the 5 year recurrent rate after curative resection of HCC was up to 61 5%, which was mainly a result of intrahepatic “metastasis” and multicentric origin of HCC Clinically, re resection of subclinical recurrence yielded 56% of 5 year survival (n=202); prevention of recurrence by transcatheter arterial chemoembolization (TACE)+Interferon, or LAK/IL 2 therapy have decreased 3 year recurrent rate from 33% to 11%-18% In experimental aspect, metastatic human HCC model in nude mice (LCI D20) and HCC cell line with metastatic potential (MHCC97) have been established; studies on HCC invasiveness in the molecular level revealed similar results that reported in other solid cancers, and small HCC showed slightly better biological characteristics as compared with large HCC; microvessel density (MVD) that reflecting angiogenesis adversely correlated with 5 year survival of small HCC; experimental interventions using antisense H ras, bispecific antibody, BB94, as well as anti angiogenic agents (TNP470, suramin, CAI, heparin, antisense VEGF, etc ) have been demonstrated to inhibit tumor growth and lung metastasis in nude mice model Conclusions Recurrence and metastasis are the major obstacle to further improve prognosis of HCC, studies should be conducted both in clinical and experimental aspects, “HCC invasiveness” will be the major target to be studied, particularly in the molecular level, and anti angiogenesis will be one of the important | 汤钊猷 周信达 林芷英 杨秉辉 马曾辰 叶胜龙 吴志全 樊嘉 刘银坤 刘康达 钦伦秀 田健 孙惠川 贺斌 夏景林 邱双健 周俭 | 1999 | Chinese Medical Journal1999，，10： | 31 |
| 15 | Clinical significance of lymph node metastasis in gastric cancer显示文摘Gastric cancer,one of the most common malignancies in the world,frequently reveals lymph node,peritoneum,and liver metastases.Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection,which results in poor prognosis.Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer.Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials,it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year followup study.Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide,but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis.It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer.Besides,the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer. | Jing-Yu Deng Han Liang | 2014 | World Journal of Gastroenterology2014，20，14： | 32 |
| 16 | Clinicopathological analysis of patients with gastric cancer in 1200 cases显示文摘INTRODUCTIONGastric cancer is one of the most common fatal malignancies in the world. The prognosis is generally poor in advanced gastric cancer .The low survival is related to delayed diagnosis, metastasis and recurrence after operation .The aim of this paper was to find correlation between clinical factors was to find correlation between clinical factors and biologic behavior of gastric cancer in a series of 1200 patients undergoing surgical resection. | Wei Xin Niu Xin Yu Qin Han Liu Cheng Pei Wang Surgical Department, Zhongshan Hospital, Fu Dan University Medical Center, Shanghai 200032, China | 2001 | World Journal of Gastroenterology2001，7，2： | 29 |
| 17 | MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside显示文摘MicroRNAs(miRNAs) are small, single-stranded, noncoding RNAs that can post-transcriptionally regulate the expression of various oncogenes and tumor suppressor genes. Dysregulated expression of many miRNAs have been shown to mediate the signaling pathways critical in the multistep carcinogenesis of colorectal cancer(CRC). MiR NAs are stable and protected from RNase-mediated degradation, thereby enabling its detection in biological fluids and archival tissues for biomarker studies. This review focuses on the role and application of miRNAs in the prognosis and therapy of CRC. While stage Ⅱ CRC is potentially curable by surgical resection, a significant percentage of stage Ⅱ CRC patients do develop recurrence. MiRNA biomarkers may be used to stratify such high-risk population for adjuvant chemotherapy to provide better prognoses. Growing evidence also suggests that miRNAs are involved in the metastatic process of CRC. Certain of these miRNAs may thus be used as prognostic biomarkers to identify patients more likely to have micro-metastasis, who could be monitored more closely after surgery and/or given more aggressive adjuvant chemotherapy. Intrinsic and acquired resistance to chemotherapy severely hinders successful chemotherapy in CRC treatment. Predictive miRNA biomarkers for response to chemotherapy may identify patients who will benefit the most from a particular regimen and also spare the patients from unnecessary side effects. Selection of patients to receive the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Lastly, forced expression of tumor suppressor miRNA or silencing of oncogenic miRNA in tumors by gene therapy can also be adopted to treat CRC alone or in combination with other chemotherapeutic drugs. | Kenneth KW To Christy WS Tong Mingxia Wu William CS Cho | 2018 | World Journal of Gastroenterology2018，24，27： | 29 |
| 18 | Colorectal cancer:Metastases to a single organ显示文摘Colorectal cancer(CRC) is a common malignancy worldwide. In CRC patients, metastases are the main cause of cancer-related mortality. In a group of metastatic CRC patients, the metastases are limited to a single site(solitary organ); the liver and lungs are the most commonly involved sites. When metastatic disease is limited to the liver and/or lungs, the resectability of the metastatic lesions will dictate the management approach and the outcome. Less commonly, the site of solitary organ CRC metastasis is the peritoneum. In these patients, cytoreduction followed by hyperthermic intraperitoneal chemotherapy may improve the outcome. Rarely, CRC involves other organs, such as the brain, bone, adrenals and spleen, as the only site of metastatic disease. There are limited data to guide clinical practice in these cases. Here, we have reviewed the disease characteristics, management approaches and prognosis based on the metastatic disease site in patients with CRC with metastases to a single organ. | Sina Vatandoust Timothy J Price Christos S Karapetis | 2015 | World Journal of Gastroenterology2015，21，41： | 30 |
| 19 | Association between vascular endothelial growth factor and metastasis after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma显示文摘BACKGROUND: Hypoxia up-regulates vascular endothelialgrowth factor (VEGF) and stimulates the growth of hepa-tocellular carcinoma (HCC) cells. This study was designedto investigate the association between changes in plasmaVEGF levels after transcatheter arterial chemoembolization(TACE) and HCC progression, especially in relation tometastasis.METHODS: Plasma VEGF levels were measured by quati-tative sandwich enzyme-linked immunosorbent assay(ELISA R&D system). Plasma VEGF levels were measuredbefore, 3 days and 4 weeks after TACE in 30 patients withHCC. The development of metastasis was evaluated at theend of the third month after TACE.RESULTS: The plasma VEGF levels of the 30 patients withHCC were 154.47±90.17 pg/ml. The total plasma VEGFlevels after TACE increased compared with their basal levels(P<0.05), and the plasma VEGF levels had a tendency toincrease in patients with heterogenous uptake of iodizdoiland portal vein thrombosis. Follow-up for six monthsshowed metastatic foci in 20 patients (74%) with increasedplasma VEGF, but none of the patients with decreased plas-ma VEGF developed metastasis.CONCLUSION: Increased plasma VEGF expression is asso-ciated with the development of metastasis in HCC after TA-CE. | Zheng-Ping Xiong, Shu-Ren Yang, Zhao-Yu Liang, En-Hua Xiao, Xiao-Ping Yu,Shen-Ke Zhou and Zi-Shu Zhang, Department of Radiology , Hunan Provincial TumorHospital. Changsha 410006, China Department of Radiology, Xiangya Second Hospital of Central South Uni-versity, Changsha 410011, China | 2004 | Hepatobiliary & Pancreatic Diseases International2004，3，3： | 27 |
| 20 | Systemic inflammation in colorectal cancer: Underlying factors,effects, and prognostic significance显示文摘Systemic inflammation is a marker of poor prognosis preoperatively present in around 20%-40%of colorectal cancer patients.The hallmarks of systemic inflammation include an increased production of proinflammatory cytokines and acute phase proteins that enter the circulation.While the low-level systemic inflammation is often clinically silent,its consequences are many and may ultimately lead to chronic cancer-associated wasting,cachexia.In this review,we discuss the pathogenesis of cancer-related systemic inflammation,explore the role of systemic inflammation in promoting cancer growth,escaping antitumor defense,and shifting metabolic pathways,and how these changes are related to less favorable outcome. | Anne E Tuomisto Markus J Makinen Juha P Vayrynen | 2019 | World Journal of Gastroenterology2019，25，31： | 27 |
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