Recurrence or metastasis of HCC:predictors,early detection and experimental antiangiogenic therapy

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.

Complex pattern of colon cancer recurrence including a kidney metastasis: A case report

We report a case of a 77-year-old female with a local recurrence of cancer after right hemicolectomy which infiltrated the pancreatic head affording pancreatoduodenectomy, who developed 3 years later recurrent tumor masses localized in the mesentery of the jejunum and in the lower pole of the left kidney. Partial nephrectomy and a segment resection of the small bowel were performed. Histological examination of both specimens revealed a necrotic metastasis of the primary carcinoma of the colon. Although intraluminal implantation of colon cancer cells in the renal pelvic mucosa from ureteric metastasis has been described, metastasis of a colorectal cancer in the kidney parenchyma is extremely rare and can be treated in an organ preserving manner. A complex pattern of colon cancer recurrence with unusual and rare sites of metastasis is reported.

Relationship between expression of CD44v6 and nm23-H1 and tumor invasion and metastasis in hepatocellular carcinoma

AIM To detect the expression of CD44v6 mRNA and nm23-H1 mRNA in hepatocellular carcinoma (HCC) by in situ hybridization, and to evaluate the relationship between their expression and also relationship between their expressions and tumor invasion and metastasis.METHODS CD44v6 cDNA probe was synthesized with PCR technique and the nm23-H1 cRNA probe by in vitro transcription. The expression of CD44v6 mRNA and nm23-H1 mRNA was detected by in situ hybridization.RESULTS In group with high invasion and metastasis potential, the positive rates of CD44v6 mRNA and nm23-H1 mRNA were 80% (8/10) and 40% (4/10), in group with poor invasion and metastasis potential, they were 21.7% (5/23) and 91.3% (21/23). There was a positive correlation between the expression of CD44v6 mRNA and tumor invasion and metastasis potential in HCC (P＜0.01), and a reverse correlation between the expression of nm23-H1 mRNA and tumor invasion and metastasis potential (P＜0.01) and a reverse correlation in the expression between CD44v6 mRNA and nm23-H1 mRNA in HCC (P＜0.01).CONCLUSION Detection of CD44v6 mRNA and nm23-H1 mRNA may be useful for tumor invasion and metastasis in HCC.INTRODUCTIONCD44 is a cell surface transmembrane glycoprotein. As a kind of adhesive molecule, it participates in cell-cell and cell-matrix adhesion and interactions. Many studies revealed a correlation between high-level expression of CD44, especially CD44v and tumor invasion, metastasis and prognosis. The exon 6v containing isoforms may be an independent diagnostic parameter[1,2]. Some other studies, however, had different results[3,4]. Some researches showed a reverse correlation between the expression of nm23-H1 mRNA and tumor metastasis[5,6]. In order to evaluate the relationship between the expression of CD44v6 mRNA and nm23-H1 mRNA and tumor invasive and metastatic potential in HCC and to evaluate the relationship in the expression between CD44v6 mRNA and nm23-H1 mRNA, we detected their expression in HCC by in situ hybridization.

Prediction of recurrence and prognosis in patients with hepatocellular carcinoma after resection by use of CLIP score

AIM: The survival time of patients with hepatocellular carcinoma (HCC) after resection is hard to predict. Both residual liver function and tumor extension factors should be considered. A new scoring system has recently been proposed by the Cancer of the Liver Italian Program (CLIP). CLIP score was confirmed to be one of the best ways to stage patients with HCC. To our knowledge, however, the literature concerning the correlation between CLIP score and prognosis for patients with HCC after resection was not published. The aim of this study is to evaluate the recurrence and prognostic value of CLIP score for the patients with HCC after resection. METHODS: A retrospective survey was carried out in 174 patients undergoing resection of HCC from January 1986 to June 1998. Six patients who died in the hospital after operation and 11 patients with the recurrence of the disease were excluded at 1 month after hepatectomy. By the end of June 2001, 4 patients were lost and 153 patients with curative resection have been followed up for at least three years. Among 153 patients, 115 developed intrahepatic recurrence and 10 developed extrahepatic recurrence, whereas the other 28 remained free of recurrence. Recurrences were classified into early (【 or =3 year) and late (】3 year) recurrence. The CLIP score included the parameters involved in the Child-Pugh stage (0-2), plus macroscopic tumor morphology (0-2), AFP levels (0-1), and the presence or absence of portal thrombosis (0-1). By contrast, portal vein thrombosis was defined as the presence of tumor emboli within vascular channel analyzed by microscopic examination in this study. Risk factors for recurrence and prognostic factors for survival in each group were analyzed by the chi-square test, the Kaplan-Meier estimation and the COX proportional hazards model respectively. RESULTS: The 1-, 3-, 5-, 7-,and 10-year disease-free survival rates after curative resection of HCC were 57.2%, 28.3%, 23.5%, 18.8%, and 17.8%, respectively. Median survival time was 28, 10, 4, and 5 mo for CLIP score 0, 1, 2, 3, and 4 to 5, respectively. Early and late recurrence developed in 109 patients and 16 patients respectively. By the chi-square test, tumor size, microsatellite, venous invasion, tumor type (uninodular, multinodular, massive), tumor extension (【 or = or 】50% of liver parenchyma replaced by tumor), TNM stage, CLIP score, and resection margin were the risk factors for early recurrence, whereas CLIP score and Child-Pugh stage were significant risk factors for late recurrence. In univariate survival analysis, Child-Pugh stages, resection margin, tumor size, microsatellite, venous invasion, tumor type, tumor extension, TNM stages, and CLIP score were associated with prognosis. The multivariate analysis by COX proportional hazards model showed that the independent predictive factors of survival were resection margins and TNM stages. CONCLUSION: CLIP score has displayed a unique superiority in predicting the tumor early and late recurrence and prognosis in the patients with HCC after resection.

Expression of nm23 gene in hepatocellular carcinoma tissue and its relation with metastasis

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Effects of thalidomide on angiogenesis and tumor growth and metastasis of human hepatocellular carcinoma in nude mice

AIM: To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS: Twenty-four nude mice were randomly divided into therapy group and control group, 12 mice in each group. Thalidomide dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group, and an equivalent volume of 0.5% CMC in control group. Mice were sacrificed on the 30th d, tumor size and weight and metastases in liver and lungs were measured. CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density (MVD) was counted. Serum concentrations of TNF-α and ALT and AFP were also tested.RESULTS: MVD and VEGF mRNA in therapy group were less than those in control group (31.08±16.23 vessels/HP vs 80.00±26.27 vessels/HP, 0.0538±0.0165 vs 0.7373±0.1297,respectively, P＜0.05). No statistical difference was observed in tumor size and weight and metastases in liver and lungs.TNF-α was significantly lower in therapy group than in control group (28.64±4.64 ng/L vs42.69±6.99 ng/L, P＜0.05). No statistical difference in ALT and AFP was observed between groups.CONCLUSION: Thalidomide can significantly inhibitangiogenesis and metastasis of hepatocellular carcinoma.Italso has inhibitory effects on circulating TNF-α.

Prognostic value of postoperative complication for early recurrence after curative resection of hepatocellular carcinoma

Background: Postoperative complications may adversely affect oncological outcomes. The aim of this study was to evaluate the impact of postoperative complications on early-phase recurrence after curative resection for hepatocellular carcinoma(HCC).Methods: We included 145 HCC patients who underwent initial and curative resection between January2004 and December 2013. Postoperative complications of grade III or higher based on Clavien–Dindo classification were defined as clinically relevant postoperative complications. Recurrence within two years after hepatectomy was defined as early-phase recurrence.Results: Thirty-eight patients(26%) developed postoperative complications. The only predictive factor for postoperative complication was longer operative duration(P = 0.037). The disease-specific survival rate of patients with complication was lower than that of patients without complications(P = 0.015). Earlyphase recurrence was observed in 20/38(53%) patients who suffered postoperative complications and36/107(34%) patients with no complications, which was statistically significant(P = 0.039). Multivariate analysis identified four factors contributing to early-phase recurrence: high serum AFP level(P = 0.042),multiple tumors(P < 0.001), poor differentiation(P = 0.036) and presence of postoperative complication(P = 0.039).Conclusions: Postoperative complication is an independent prognostic factor for early-phase recurrence after curative resection of HCC. Close observation of patients with postoperative complications may be a necessary treatment strategy for HCC.

Clinicopathologic risk factors and prognostic evaluation in hepatocellular carcinoma recurrence after surgery

AIM To analyze the clinicopathologic risk factors in hepatocellular carcinoma recurrence after surgery. METHODS Significance test (χ 2 and Student t test) of the single and multiple factors, and Wilcoxon Cox tropic examination were used, a retrospective clinicopathologic analysis was made in 156 cases of hepatocellular carcinoma after hepatectomy. RESULTS Of the 156 cases, 68 4%, 57 3%, 46 7%, 31 5% and 28 6% had 1, 2, 3, 4 and 5 postoperative tumor free years respectively with a total recurrence rate of 53 2% (83/156). In the 83 recurrent cases, 65 were of intrahepatic sabclinical type, with a re resection rate of 78 3% (65/83). The relevant factors involved in recurrence were: males, tumor number and size, capsule infiltration, portal veins involvement, etc. Those factors obviously influenced the prognosis of the patients with postoperative hepatocellular carcinoma ( P <0 05). 63 1% tumor nodes (41/65) of recurrent liver cancinomas were located at the ipsilateral segment of the primary ones. CONCLUSION Males, tumor number and size, capsule infiltration and portal veins involvement are the factors for postoperative hepatocellular carcinoma recurrence after surgery. The recurrence is mainly unicentral. Right front lobe is the liver segment with a high recurrence rate.

Do the expressions of gap junction gene connexin messenger RNA in noncancerous liver remnants of patients with hepatocellular carcinoma correlate with postoperative recurrences?

AIM: To investigate whether the changes of gap junction gene connexin messenger RNA in the noncancerous liver tissue of patients with hepatocellular carcinoma (HCC) could play a significant role in its postresection recurrence.METHODS: Seventy-nine consecutive patients having undergone curative resection for HCC entered this study.Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, connexin (Cx) 26, connexin (Cx)32 and connexin (Cx) 43 mRNAs were determined prospectively in noncancerous liver tissues from these 79 patients and in the liver tissues from 15 controls. The correlations between connexin mRNA expression and the clinicopathological variables and outcomes (tumor recurrence and recurrence related mortality) were studied.RESULTS: Compared with liver tissues of control patients,the expression of Cx 32 mRNA in noncancerous liver tissues was significantly lower (mean: 0.715 vscontrol 1.225,P＜0.01), whereas the decreased Cx 26 mRNA (mean:0.700 vs of control 1.205,P＞0.05) and increased Cx 43 mRNA (mean: 0.241 vscontrol 0.100, P＞0.05) had no statistical significance. We defined the value of Cx 32 mRNA or Cx 26mRNA below 0.800 as a lower value. By multivariate analysis for noncancerous livers, a lower value of Cx 32 mRNA correlated significantly with a risk of HCC recurrence and recurrence-related mortality. The lower value of Cx 26 mRNA did not correlate with recurrence and mortality. The increased value of Cx43 mRNA also did not correlate with postoperative recurrence and recurrence-related mortality. By multivariate analysis, other significant predictors of HCC recurrence included vascular permeation, cellular dedifferentiation, and less encaps-ulation. The other significant parameter of recurrence related mortality was vascular permeation.CONCLUSION: The decreased expression of Cx 32 mRNA in noncancerous liver tissues plays a significant role in the prediction of postoperative recurrence of HCC.

Recurrence of hepatocellular carcinoma with rapid growth after spontaneous regression

We report an 80-year-old man who presented with sponta- neous regression of hepatocellular carcinoma(HCC).He complained of sudden right flank pain and low-grade fever. The level of protein induced by vitamin K antagonist(PIVKA)- II was 1 137 mAU/mL.A computed tomography scan in November 2000 demonstrated a low-density mass located in liver S4 with marginal enhancement and a cystic mass of 68 mm×55 mm in liver S6,with slightly high density content and without marginal enhancement.Angiography revealed that the tumor in S4 with a size of 25 mm×20 mm was a typical hypervascular HCC,and transarterial chemoembolization was performed.However,the tumor in S6 was hypovascular and atypical of HCC,and thus no therapy was given.In December 2000,the cystic mass regressed spontaneously to 57 min×44 mm,and aspiration cytology revealed bloody fluid,and the mass was diagnosed cytologically as class I. The tumor in S4 was treated successfully with a 5 mm margin of safety around it.The PIVKA-II level normalized in February 2001.In July 2001,the tumor regressed further but presented with an enhanced area at the posterior margin.In November 2001,the enhanced area extended,and a biopsy revealed well-differentiated HCC,although the previous tumor in S4 disappeared.Angiography demonstrated two tumor stains,one was in S6,which was previously hypovascular, and the other was in S8.Subsequently,the PIVKA-II level started to rise with the doubling time of 2-3 wk,and the tumor grew rapidly despite repeated transarterial embolization with gel foam.In February 2003,the patient died of bleeding into the peritoneal cavity from the tumor that occupied almost the entire right lobe.Considering the acute onset of the symptoms,we speculate that local ischemia possibly due to rapid tumor growth,resulted in intratumoral bleeding and/or hemorrhagic necrosis,and finally spontaneous regression of the initial tumor in S6.

Complete response to radiation therapy of orbital metastasis from hepatocellular carcinoma

The incidence of hepatocellular carcinoma(HCC)is increasing in the United States,and 50%-75%o patients with HCC will develop metastatic disease Orbital metastases from HCC are extremely rare.We report the case of a 52-year-old male with known metastatic HCC,who presented with severe proptosis and diplopia.An orbital mass was identified on magnetic resonance imaging(MRI)and confirmed to have hypermetabolic activity on positron emission tomography/computed tomography.He received a palliative course of external beam radiation therapy to the right orbit.Intensity modulated radiation therapy (IMRT)was used to allow sparing of critical norma tissues in close proximity to the tumor.One month after completion of IMRT to 58 Gray in 30 fractions delivered over 6 wk,the patient had a complete clinical,radiologic(MRI)and symptomatic response The patient continues to have local control in the orbi 1.7 years after therapy completion.All critical norma structures were kept below the tolerance dose using IMRT,and no toxicities were observed.

Liver transplantation for hepatocellular carcinoma： is zero recurrence theoretically possible？

BACKGROUND： Hepatocellular carcinoma（HCC） recurrence remains a key issue after liver transplantation. This study aimed to determine a subgroup of HCC patients within the Milan criteria who could achieve a theoretical goal of zero recurrence rates after liver transplantation.METHODS： Between 1999 and 2009, 179 patients who received liver transplantation for HCC within the Milan criteria were retrospectively included. Analysis of the factors associated with HCC recurrence was performed to determine the subgroup of patients at the lowest risk of recurrence.RESULTS： Seventy-two percent of the patients received a bridging therapy, including 54 liver resections. Eleven（6.1%） patients recurred within a delay of 19±22 months and ultimately died. Factors associated with recurrence were serum alpha-fetoprotein level 〉400 ng/m L, satellite nodules, poor differentiation, microvascular invasion and cholangiocarcinoma component. Recurrence rates decreased from 6.1% to 3.1% in patients without any of these factors.CONCLUSIONS： Among HCC patients within the Milan criteria, selecting patients with factors based on histology would allow tending towards zero recurrence, and prior histological assessment by liver biopsy or resection may be essential to rule out poorly differentiated tumors, microvascular invasion,and cholangiocarcinoma component.

Relationship between ras p53 gene RNA and protein expression and HCC metastasis

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THE EFFECTS OF CHINESE DRUGS FOR SUPPORTING HEALTHY ENERGY AND REMOVING BLOOD STASIS ON POSTOPERATIVE METASTASIS OF GASTRIC CARCINOMA AND ORNITHINE DECARBOXYLASE

32 postoperative cases of gastric carcinoma were treated by traditional Chinese medicine (TCM) drugs for supporting healthy energy and removing blood stasis, and their therapeutic results were compared with those in the control group treated by western medicine. After 6 months of treatment, in the TCM group, the rate of metastatic recurrence was significantly reduced, and the level of ornithine decarboxylase was also markedly lowered. Therefore, it is considered that the action of anti-metastatic recurrence of TCM drugs in postoperative cases of gastric carcinoma is probably related to the lowered activity of ornithine decarboxylase.

Lessons learned from hepatocellular carcinoma may cause a paradigm shift in intraductal papillary mucinous neoplasms:a narrative review and discussion of conceptual similarities in tumor progression and recurrence

Although the natural history of recurrence/progression in patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas has not been studied thoroughly, the three principal mechanisms have been identified: (a) presence of residual disease at the transection margin, (b) presence of intraductal/intraparenchymal metastases and (c) development of new primary lesions. Mechanisms (a) and (b) result in metastatic lesions that are genetically related to the primary, while new primary lesions (mechanism c) are genetically distinct. Interestingly, recurrence/progression in IPMN displays conceptual parallels with the well-established paradigm of disease recurrence in patients with hepatocellular carcinoma (HCC). Specifically, patients with HCC may also develop recurrent tumors due to microscopic residual disease/intrahepatic metastasis which are genetically similar to the primary while the development of genetically unrelated, de novo HCC after curative-intent resection is also common. The latter has been attributed to the presence of a widespread genetic abnormality ( "field defect" ) in the liver (ie, cirrhosis). Given the conceptual similarities between IPMN and HCC, a pancreatic "field defect" may also be hypothesized to exist. This review does not suggest that HCC and IPMN have identical pathogeneses, but rather that they have conceptual similarities in tumor recurrence/progression;thus, lessons learned from HCC could be applied to IPMN research and subsequent management. Conceptual similarities in tumor progression and recurrence may also be observed between IPMN and other malignancies. However, HCC was selected because it is well studied and can serve as a paradigm.

The prognostic significance of clinical and pathological features in hepatocellular carcinoma

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 of HCC patients who have no opportunity to receive surgical treatment or postoperative recurrence. The combination of these treatment modalities is hopeful to further improve the prognosis. The efficacies of neoadjuvant (preoperative) or adjuvant (postoperative) chemotherapy or chemoembolization in preventing recurrence and on the HCC prognosis still remain great controversy, and deserve further evaluation. Biotherapy, including IFN-alpha therapy, will play more important role in preventing recurrence and metastasis of HCC after operation.

Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.

Rapid progression of hepatocellular carcinoma after Radiofrequency Ablation

AIM:To report the results of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) in cirrhotic patients and to describe the treatment related complications (mainly the rapid intrahepatic neoplastic progression). METHODS:Eighty-seven consecutive cirrhotic patients with 104 HCC (mean diameter 3.9 cm,1.3 SD) were submitted to RFA between January 1998 and June 2003.In all cases RFA was performed with percutaneous approach under ultrasound guidance using expandable electrode needles. Treatment efficacy (necrosis and recurrence) was estimated with dual phase computed tomography (CT) and alpha- fetoprotein (AFP)level. RESULTS:Complete necrosis rate after single or multiple treatment was 100%,87.7% and 57.1% in HCC smaller than 3 cm,between 3 and 5 cm and larger than 5 cm respectively (P=0.02).Seventeen lesions of 88(19.3%) developed local recurrence after complete necrosis during a mean follow up of 19.2 mo.There were no treatment-related deaths in 130 procedures and major complications occurred in 8 patients (6.1%).In 4 patients,although complete local necrosis was achieved,we observed rapid intrahepatic neoplastic progression after treatment.Risk factors for rapid neoplastic progression were high preoperative AFP values and location of the tumor near segmental portal branches. CONCLUSION:RFA is an effective treatment for hepatocellular carcinoma smaller than 5 cm with complete necrosis in more than 80% of lesions.Patients with elevated AFP levels and tumors located near the main portal branch are at risk for rapid neoplastic progression after RFA.Further studies are necessary to evaluate the incidence and pathogenesis of this underestimated complication.

Moving toward an understanding of the metastatic process in hepatocellular carcinoma

INTRODUCTIONClinical factors contributing to the therapeutic challenge of hepatocellular carcinoma (HCC) are manifold :tumors arise often in patients with compromised liver function ,therefore limiting therapeutic options ;symptoms develop only at later stages of tumor progression ,and tumors tend to invade normal stuctures or occur in multiple locations simultaneously.

Alterations in metastatic properties of hepatocellular carcinoma cell following H-ras oncogene transfection

AIM: To demonstrate the relationship between H-ras oncogene and hepatocellular carcinoma (HCC) metastasis. METHODS: Activated H-ras oncogene was transfected into SMMC 7721, a cell line derived from human HCC, by calcium phosphate transfection method. Some metastasis-related parameters were detected in vitro, including adhesion assay, migration assay, expression of collagenase IV(c IV ase) and epidermal growth factor receptor (EGFR). RESULTS: The abilities of H-ras-transfected cell clones in adhesion to laminin (LN) or fibronectin (FN), migration, c IV ase secretion increased markedly, and the expression of EGFR elevated moderately. More importantly, these alterations were consistent positively with the expression of p21, the protein product of H-ras oncogene. CONCLUSION: H-ras oncogene could induce the metastatic phenotype of HCC cell in vitro to raise its metastatic potential.