Ⅳ型胶原酶与肝细胞癌侵袭转移性的关系

目的揭示Ⅳ型胶原酶与肝细胞癌（ＨＣＣ）侵袭转移性的关系。方法通过明胶酶谱法对ＨＣＣ癌、癌旁肝组织及血浆中Ⅳ型胶原酶含量进行测定,并与反映ＨＣＣ侵袭转移性的病理指标进行统计学分析。结果ＨＣＣ及其癌旁肝组织均有Ⅳ型胶原酶表达;ＨＣＣ组织中Ⅳ型胶原酶含量升高及基质金属蛋白酶２（ＭＭＰ２）活性形式的出现与ＨＣＣ侵袭转移性有关;血浆中Ⅳ型胶原酶含量的升高与ＨＣＣ侵袭转移有关。结论Ⅳ型胶原酶与ＨＣＣ侵袭转移性有关。     

原发性肝细胞癌患者转化生长因子β1的基因表达及临床意义

目的研究转化生长因子β１（ＴＧＦβ１）ｍＲＮＡ在原发性肝细胞癌患者中的表达及其临床意义。方法用ＲＴ－ＰＣＲ加ＤｏｔＢｌｏｔ法检测原发性肝细胞癌患者肝组织和外周血单个核细胞（ＰＢＭＣ）中ＴＧＦ－β１ｍＲＮＡ水平，并以正常肝组织和正常人的ＰＢＭＣ为对照。结果ＴＧＦ－β１ｍＲＮＡ水平在原发性肝细胞癌患者组肝组织（２．２２±０．８４，ｎ＝１６）和ＰＢＭＣ中（１．８３±１．２，ｎ＝２５）比较，差异无显著性（Ｐ＞０．０５），但两者均高于正常肝组织（０．９４±０．７６，ｎ＝５）和正常人的ＰＢＭＣ（０．６２±０．４０，ｎ＝１６）水平。结论ＴＧＦ－β１ｍＲＮＡ水平与原发性肝细胞癌有关，ＰＢＭＣ中ＴＧＦ－β１ｍＲＮＡ检测可望作为一项代替肝组织活检的指标，其表达水平与肝癌有关。     

MAGE-1基因在肝细胞性肝癌中的表达

目的探讨ＭＡＧＥ－１基因编码的肿瘤相关抗原作为肝细胞性肝癌（ＨＣＣ）主动免疫治疗攻击靶点的可能性。方法用ＲＴ－ＰＣＲ的方法检测了３９例ＨＣＣ及癌旁组织、３种人肝癌细胞株和５例非ＨＣＣ病例肝组织中ＭＡＧＥ－１基因的表达。结果ＨＣＣ癌组织中ＭＡＧＥ－１基因表达率明显高于癌分组织中的表达率,５８．９％（２／３９）对１０．３％（４／３９）,Ｐ＜００１。３种细胞株均为阳性表达。结论ＭＡＧＥ－１基因可作为主动免疫治疗的攻击靶点,以进一步研究设计新的ＨＣＣ免疫治疗策略。     

肝癌患者血浆和肿瘤组织中PAI-1变化

目的研究纤溶酶原激活物抑制剂（ＰＡＩ－１）与肝癌临床生物学特性的关系。方法用ＰＡＩ－１试剂盒检测３０例肝细胞癌（ＨＣＣ）患者血浆和肿瘤组织中ＰＡＩ－１变化，取正常人血浆和肝组织作对照。结果ＨＣＣ患者血浆和肿瘤组织中ＰＡＩ－１与对照组比明显升高，分别为１２．８±２．７５Ａｕ／ｍｌ比６．８５±２．２１Ａｕ／ｍｌ，０．８１±０．１２Ａｕ／ｍｇ比０．３８±０．１４Ａｕ／ｍｇ（Ｐ均＜０．０５）。侵袭性与非侵袭性ＨＣＣ病例比较，血浆ＰＡＩ－１为１４．９６±１．１１Ａｕ／ｍｌ比１１．４２±１．５９Ａｕ／ｍｌ（Ｐ＜０．０５）。血浆ＰＡＩ－１明显升高的ＨＣＣ患者预后较差。结论ＨＣＣ患者血浆和肿瘤组织中ＰＡＩ－１明显升高，ＰＡＩ－１与ＨＣＣ侵袭性和预后密切相关。     

mdr-1、CD44v、和nm23-H1基因产物与肝癌侵袭及转移的关系

为探讨ｍｄｒ－１,ＣＤ４４ｖ和ｎｍ２３－Ｈ１基因产物蛋白与肝癌侵袭,转移预后的关系。用免疫组织化学技术检测４６例肝癌患者ＣＤ４４ｖ和ｎｍ２３－Ｈ１和ｍｄｒ－１基因蛋白的表达。结果 显示肝癌组织ｍｄｒ－１,ＣＤ４４ｖ和ｎｍ２３－Ｈ１（６０．０８％）,明显高于正常组织和癌旁组织（Ｐ〈０．０５）;肝癌转移组的ｍｄｒ－１,ＣＤ４４ｖ阳性表达率高于ｎｍ２３－Ｈ１阳性表达率,差异显著（Ｐ〈０．０５）;肝癌非转     

小鼠高低转移性肝癌3号染色体微卫星不稳定性的研究

为探讨微卫星不稳定性（ｍｉｃｒｏ－ｓａｔｅｌｌｉｔｅ ｉｎｓｔａｂｉｌｉｔｙ，ＭＳＩ）与肝癌发生及转移的关系，我们应用微卫星多态性标记对小鼠高、低转移性肝癌细胞系ＭＳＩ进行了研究。 １．材料与方法：（１）标本收集：小鼠高、低转移性肝癌细胞系Ｈｃａ／１６Ａ３－Ｆ（Ｆ）和Ｈｃａ／Ａ２－Ｐ（Ｐ）由大连医科大学病理学教研室凌茂英教授惠赠，ＳＰＦ级Ｃ３Ｈ小鼠购自上海西普尔－必凯实验动物有限公司。（２）基因组ＤＮＡ的提取：采用常规蛋白酶Ｋ消化，苯酚－氯仿－异戊醇抽提基因组ＤＮＡ，另取正常Ｃ３Ｈ小鼠肝组织作对照…     

上皮钙粘蛋白（E—cadherin）在高侵袭性肝细胞癌中的表达

目的旨在探讨上皮型钙粘蛋白（Ｅ－ｃａｄｈｅｒｉｎ）与肝癌侵袭的关系。方法选择２５例原发性肝细胞癌及相应癌旁组织、２例门静脉癌栓标本和裸鼠高、低转移人肝癌模型（ＬＣＩＤ２０和ＬＣＩＤ２５），Ｅ－ｃａｄｈｅｒｉｎｍＲＮＡ的表达采用半定量逆转录ＰＣＲ（ＲＴ－ＰＣＲ）检测。结果Ｅ－ｃａｄｈｅｒｉｎ在２５例肝细胞癌和相应的癌旁组织中基因表达值为８２．９％±５４．９％和４９．５％±２６．９％，两者差异有显著性（Ｐ＜０．０５）。２例门静脉癌栓标本均不表达Ｅ－ｃａｄｈｅｒｉｎ，裸鼠高转移人肝癌模型（ＬＣＩＤ２０）也不表达Ｅ－ｃａｄｈｅｒｉｎ，而低转移模型（ＬＣＩＤ２５）的表达值为６７．４的±１６．０％。高侵袭性肝癌和低侵袭性肝癌Ｅ－ｃａｄｈｅｒｉｎ表达指数分别为４８．９％±３８．０％和７９．１％±１９．１％，两者差异无显著性（Ｐ＞０．０５）。Ｅ－ｃａｄｈｅｒｉｎ表达指数与肿瘤包膜和大小无关。结论肝细胞癌组织Ｅ－ｃａｄｈｅｒｉｎ表达低于其相应的癌旁组织，高侵袭性肝癌较低侵袭性肝癌表达更低，Ｅ－ｃａｄｈｅｒｉｎ的丧失或低表达是肝癌获得高侵袭转移能力的因素之一。     

转化生长因子-β1在肝细胞性肝癌中表达增强

目的转化生长因子－β１（ＴＧＦβ１）在细胞生长的负性调节上有重要作用,是肝细胞生长和增殖的强抑制物但肝癌（ＨＣＣ）患者肝组织中ＴＧＦβ１ｍＲＮＡ表达高．现检测ＨＣＣ患者外周血中ＴＧＦβ１ｍＲＮＡ表达,血清ＴＧＦβ１水平,以及肝组织中ＴＧＦβⅡ型受体（ＴＧＦβＲⅡ）的表达．方法ＨＣＣ患者外周血分离单个核细胞（ＰＢＭＣ）,提取总ＲＮＡ,用反转录聚合酶链反应（ＲＴＰＣＲ）技术扩增ＴＧＦβ１ｍＲＮＡ．血清ＴＧＦβ１水平测定用Ｐｒｏｍｅｇａ公司产的试剂盒．肝组织ＴＧＦβＲⅡ表达的分析用原位杂交法．结果ＨＣＣ患者２０例ＰＢＭＣＴＧＦβ１ｍＲＮＡ用ＲＴＰＣＲ检测阳性率达７０％,对照组阴性．ＨＣＣ患者４０例血清ＴＧＦβ１水平（２７５８ｍｇ／Ｌ±８１０ｍｇ／Ｌ）明显高于对照组（８２７ｍｇ／Ｌ±３７２ｍｇ／Ｌ）．原位杂交表明,ＴＧＦβＲⅡ在ＨＣＣ细胞的胞质中有弱表达．结论ＨＣＣ患者ＴＧＦβ１基因在转录水平和翻译水平上均显示表达增强．ＰＢＭＣ有可能代替肝组织用以检测ＴＧＦβ１ｍＲＮＡ的表达应用于基础与临床的研究．     

转化生长因子β1与病毒性肝炎肝纤维化的关系

目的：研究转化生长因子β＿１（ＴＧＦ－β＿１）与病毒性肝炎肝纤维化发生的关系。方法：对５４例病毒性肝炎肝组织进行ＴＧＦ－β＿１以及α－平滑肌肌动蛋白（α－ＳＭＡ）、Ⅳ型胶原（Ⅳ－Ｃ）免疫组织化学研究，并检测其中４９例血清Ⅲ型前胶原肽（ＰⅢＰ）、层粘蛋白（ＬＮ）、透明质酸（ＨＡ）、Ⅳ－Ｃ等。结果：随着肝纤维化程度的加重，ＴＧＦ－β＿１在肝组织中的表达逐渐明显。在慢性肝炎重度、肝硬变慢性重型肝炎中的表达强度明显高于慢性肝炎中度、轻度及急性肝炎。同时ＴＧＦ－β＿１在肝组织中的表达与血清ＰⅢＰ、ＬＮ、ＨＡ、Ⅳ－Ｃ以及α－ＳＭＡ和Ⅳ－Ｃ在肝组织中的表达呈明显的正相关。结论：ＴＧＦ－β＿１通过刺激贮脂细胞，大量合成细胞外间质，最终导致肝脏的纤维化。     

肝细胞癌发生中p16基因缺失与甲基化的研究

目的 探讨肝细胞癌（ｈｅｐａｔｏｃｅｌｌｕｌａｒ ｃａｒｃｉｎｏｍａ，ＨＣＣ）发生过程中抑癌基因Ｐ１６的存在及蛋白表达情况。方法 随机引物法标记制备Ｄｉｇ－ｐ１６ｃＤＮＡ探针，分子杂交及免疫组化方法检测肝细胞癌发生中Ｐ１６基因的存在及表达情况。结果 斑点杂交显示Ｐ１６探针敏感率为１．０ｐｇ。５６例ＨＣＣ癌组织及２８例癌旁组织ＤＮＡ与Ｐ１６探针点杂交的阳性率分别为５５．３６％（３１／５６）、８９．２     

Overexpression of MT3-MMP in hepatocellular carcinoma correlates with capsular invasion

BACKGROUND/AIMS: Extracellular matrix-degrading matrix metalloproteinases (MMPs) are invariably up-regulated in epithelial cancers and are key agonists of angiogenesis, invasion and metastasis. Recent studies have shown high levels of various MMPs, including MT1-MMP, MMP-1, MMP-2 and MMP-9, and their involvement in tumor progression in human hepatocellular carcinoma (HCC). However, the expression and role of MT3-MMP in HCC remains unclear. METHODOLOGY: We examined the immunohistochemical expression of MT3-MMP in surgically resected HCCs (n=58), hepatitis C virus (HCV) and hepatitis B virus (HBV)-related chronic hepatitis (n=34) and cirrhosis (n=24). RESULTS: MT3-MMP expression was observed in all non-cancerous liver tissues. In HCCs, 52% (30/58) of patients showed high MT3-MMP expression while the remaining 48% (28/58) of patients showed low expression. A clinicopathological survey demonstrated a significant correlation between high MT3-MMP expression and capsular invasion of carcinoma (p = 0.034) although there was no correlation between high MT3-MMP expression in HCC and overall survival or disease-free survival. CONCLUSIONS: MT3-MMP was expressed not only in chronic hepatitis and liver cirrhosis, but also in HCC, and high MT3-MMP expression correlated significantly with capsular invasion of carcinoma.     

Mechanism of metastasis by membrane type 1-matrix metalloproteinase in hepatocellular carcinoma

AIM: To investigate the precise role of membrane type 1-matrix metalloproteinase (MT1-MMP) in hepatocellular carcinoma (HCC) metastasis. METHODS: Human HCC cells Hep3B with overexpression of MT1-MMP were established by stable transfection, and compared with control cells carrying the empty vector. Cells were examined in vivo for their differences in the metastatic ability of athymic nude mice, and analyzed in vitro for their differences in invasion ability by invasion chamber coated with Matrigel, adhesion towards collagen I and migration through culture chamber. Cell proliferation and apoptosis in adherent and suspension status were evaluated by MTT and flow cytometry analysis. RESULTS: We found that overexpression of MT1-MMP could increase intrahepatic metastasis in nude mice with orthotopic implantation of HCC cells (incidence of 100% [MT1-MMP transfectants] vs 40% [vector control transfectants],P<0.05). MT1-MMP could also enhance cell invasion through Matrigel (107.7 vs 39.3 cells/field, P<0.001), adhesion towards matrix (0.30 vs 0.12 absorbance unit at 540 nm, P<0.001), cell migration (89.3 vs 39.0 cells/field, P<0.001), and cell proliferation (24.3 vs 40.5 h/doubling, P<0.001). We also observed that MT1-MMP supported cell survival (71.4% vs 23.9%, P<0.001) with reduced apoptosis (43.7% vs 51.0%,P<0.05) in an attachment-free environment. CONCLUSION: MT1-MMP overexpression could enhance metastasis. In addition to its active role in matrix degradation during tumor invasion, MT1-MMP enhances tumor cell survival upon challenge of detachment, which is important during metastasis when cells enter the circulation.     

Mechanism of metastasis by membrane type 1-matrix metalloproteinase in hepatocellular carcinoma

AIM: To investigate the precise role of membrane type1-matrix metalloproteinase (MT1-MMP) in hepatocellular carcinoma (HCC) metastasis.METHODS: Human HCC cells Hep3B with overexpression of MT1-MMP were established by stable transfection, and compared with control cells carrying the empty vector.Cells were examined in vivo for their differences in the metastatic ability of athymic nude mice, and analyzed in vitro for their differences in invasion ability by invasion chamber coated with Matrigel, adhesion towards collagen I and migration through culture chamber. Cell proliferation and apoptosis in adherent and suspension status were evaluated by MTT and flow cytometry analysis.RESULTS: We found that overexpression of MT1-MMP could increase intrahepatic metastasis in nude mice with orthotopic implantation of HCC cells (incidence of 100%[MT1-MMP transfectants] vs 40% [vector control transfectants], P＜0.05). MT1-MMP could also enhance cell invasion through Matrigel (107.7 vs 39.3 cells/field,P＜0.001), adhesion towards matrix (0.30 vs 0.12absorbance unit at 540 nm, P＜0.001), cell migration(89.3 vs 39.0 cells/field, P＜0.001), and cell proliferation(24.3 vs 40.5 h/doubling, P＜0.001). We also observed that MT1-MMP supported cell survival (71.4% vs 23.9%,P＜0.001) with reduced apoptosis (43.7% vs51.0%, P＜0.05)in an attachment-free environment.CONCLUSION: MT1-MMP overexpression could enhance metastasis. In addition to its active role in matrix degradation during tumor invasion, MT1-MMP enhances tumor cell survival upon challenge of detachment, which is important during metastasis when cells enter the circulation.     

Matrix metalloproteinase (MMP) expression by differentiated thyroid carcinoma of children and adolescents

The factor(s) that control metastasis of thyroid carcinoma are unknown, but the matrix metalloproteinases (MMPs) are excellent candidates. MMP-1, membrane-type-1 MMP (MT1-MMP), and tissue inhibitor of MMP-1 (TIMP-1) have all been implicated, but the site of production and importance are disputed. In vitro, normal thyroid cells secrete TIMP-1, while thyroid cancer cells secrete TIMP-1 and MMP-1. However, previous pathological studies identified MMP-1 and TIMP-1 only in the stroma surrounding thyroid carcinoma. These data suggest that thyroid carcinoma or tumor-associated inflammatory cells might secrete a factor(s) which stimulates MMP-1 or TIMP-1 expression by surrounding tissues. We hypothesized that MMP-1, MT1-MMP, and TIMP-1 would be directly expressed by thyroid carcinoma and might promote invasion or metastasis. We used immunohistochemistry to determine the expression of MMP-1, MT1-MMP, and TIMP-1 in 32 papillary thyroid carcinoma (PTC), 10 follicular thyroid carcinoma (FTC) and 13 benign thyroid lesions from children and adolescents. The intensity of staining was graded from absent (grade 0) to intense (grade 3). Average MMP-1 expression (mean relative intensity units+/-SE) was significantly greater among PTC (1.97+/-0.15; p=0.004) and FTC (2.2+/-0.25; p=0.006) compared to benign lesions (1.30+/-0.15); but there was no relationship between MMP-1 expression and invasion, metastasis, or recurrence. Expression of MT1-MMP and TIMP-1 was similar for benign and malignant lesions; but recurrent PTC expressed lower levels of TIMP-1 when compared to non-recurrent PTC (p=0.049). Only the expression of TIMP-1 correlated with the presence of tumor-associated lymphocytes (r=0.35, p=0.032). We conclude that MMP-1, MT1-MMP and TIMP-1 are all expressed by thyroid carcinoma and could be important in promoting recurrence.     

Invasion and metastasis of hepatocellular carcinoma in relation to urokinase-type plasminogen activator, its receptor and inhibitor

This study was designed to investigate the relationship of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor type-1 (PAI-1) to invasion and metastasis of hepatocellular carcinoma (HCC). The expression of uPA, uPAR, and PAI-1 in HCC was determined by immunohistochemistry, Northern blot, and an LCI-D20 nude mouse metastatic model of HCC. The over-expression of uPA, uPAR, and PAI-1 was found in HCC, especially in the patients with portal cancer embolus, tumor invasion, and metastasis. Immunohistochemistry results showed that the rate of positive staining of uPA, uPAR, and PAI-1 were higher in HCC than those in the control groups consisting of cancer-adjacent tissue and normal liver tissue. In the case of HCC invasion, positive uPA and uPAR were seen in 16 and 19 out of 22 patients, respectively (P < 0.01 and P < 0.001, respectively, as compared with the patients without invasion). In those with portal cancer embolus and tumor metastasis, positive uPAR was eight out of eight and six out of six patients. In those with tumor recurrence, positive uPAR was 15 out of 17 patients (P < 0.01 vs no recurrence). In patients who died within 2 years after surgery, positive uPAR was 12 out of 12 patients (P < 0.01 vs survival), and positive PAI-1 was nine out of 12 patients (P < 0.05 vs survival). In those in which uPA, uPAR, and PAI-1 were all positive staining, stronger cancer invasiveness and higher mortality were found (P < 0.05 vs patients with all negative staining). In 30 patients tested with Northern blot analysis, the results were similar to those tested with immunohistochemistry. Higher expression of uPA mRNA and PAI-1 mRNA were detected in tumor tissues and embolus. In the patients with positive signals of uPA mRNA and PAI-1 mRNA, invasive cases were found in seven out of 19 and eight out of 18 patients, respectively, which were significantly higher than those showing negative signals (P < 0.05). In the LCI-D20 nude mouse metastatic model of HCC (MMHCC), PAI-1 activity in plasma and tumor tissue increased with tumor growth, invasion, and metastasis. At an advanced stage of MMHCC, PAI-1 activity rose to 15.4 ± 0.7 Au/ml in plasma and 0.8 ± 0.3 Au/mg in tumor extracts, which was significantly higher than 6.2 ± 1.8 Au/ml in plasma and 0.4 ± 0.1 Au/mg in extracts at an early stage (P < 0.05). PAI-1 activity related to the changes of serum AFP and tumor progress were r=0.9544 and r=0.9648, respectively (P < 0.05). The data suggest that the expression of uPA, uPAR, and PAI-1 is increased in HCC, and related to the invasiveness, metastasis, and prognosis of HCC. Received: 30 September 1999 / Accepted: 10 March 2000     

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

Metastatic human HCC model is needed for the studies onmechanism and intervention of metastatic recurrence,Byusing orthotopic implantation of histologically intacttissues of 30 surgical specimens,a patient-likemetastatic model of human HCC in nude mice (LCI-D20)and a low metastatic model of human HCC in nude mice(LCI-D35) have been established.All mice withtransplanted LCI-D20 tumors exhibited extremely highmetastatic ability including spontaneous metastasis toliver,lungs,lymph nodes and peritoneal seeding.Remarkable difference was also found in expression ofsome of the invasiveness related genes and growthfactors between the LCI-D20 and LCI-D35 tumors.PAI-1increased gradually following tumor progression in LCI-D20 model,and correlated with tumor size and AFP level.Phasic expression of tissue intercellular adhesionmolecule-1 in this model was also observed.Using cornealmicropocket model,it was demonstrated that the vascularresponse induced by LCI-D20 tumor was stronger than thatinduced by LCI-D35 tumor.Similar report on metastatichuman HCC model in nude mice and human HCC cell linewith metastatic potential was rarely found in theliterature.This LCI-D20 model has been widely used forthe studies on intervention of metastasis,including anti-angiogenesis,antisense approach,metalloproteinaseinhibitor,differentiation inducer,etc.It is concluded thatthe establishment of metastatic human HCC model in nudemice and human HCC cell line with metastatic potentialwill provide important models for the in vivo and in vitrostudy of HCC invasiveness,angiogenesis as well asintervention of HCC recurrence.     

Expression of intercellular adhesive molecule1 in liver cancer tissues and liver cancer metastasis

AIM: To study the relationship between intercellular adhesive molecule-1 (ICAM-1) and liver cancer metastasis and to search for factors to predict metastasis of liver cancer.METHODS: ICAM-1 expression in fresh tissues of normal liver and hepatocellular cancer (HCC) was examined by immunoperoxidase staining. The expression of ICAM-1 in human hepatoma, tumor surrounding tissues and normal livers were semiquantitatively analyzed by Dot immuno blot. Tissue ICAM-1 expression at mRNA level was detected by Northern blot.RESULTS: All 6 cases of normal liver samples were negative in anti-ICAM-1 immunohistochemical staining, 80.0% (36/45) of HCC presented various ICAM-1 expression. The number of positive cells was a little higher in large tumors, tumors with intact capsule and metastasis, but there was no significant difference. Two cases with cancer embolus also had high ICAM-1 expression. ICAM-1 concentration in HCC (13.43 ± 0.09) was higher than that in tumor surrounding tissues (5.89 ± 0.17, P < 0.01) and normal livers (4.27 ± 0.21, P < 0.01). It was also higher in metastasis group (20.24 ± 0.30) than in nonmetastasis group (10.23 ± 0.12, P < 0.05). Northern blot analysis revealed that ICAM-1 expression at mRNA level was also higher in HCC and cancer embolus than that in tumor surrounding tissues and normal livers.CONCLUSION: Tissue ICAM-1 could indicate the growth and metastasis of HCC, and may be an index that can predict liver cancer metastasis.     

Phase tissue intercellular adhesion molecule-1 expression in nude mice human liver cancer metastasis model

Ｐｈａｓｅｔｉｓｓｕｅｉｎｔｅｒｃｅｌｕｌａｒａｄｈｅｓｉｏｎｍｏｌｅｃｕｌｅ１ｅｘｐｒｅｓｓｉｏｎｉｎｎｕｄｅｍｉｃｅｈｕｍａｎｌｉｖｅｒｃａｎｃｅｒｍｅｔａｓｔａｓｉｓｍｏｄｅｌＳＵＮＪｉｎｇＪｉｎｇ,ＺＨＯＵＸｉｎＤａ,ＬＩＵＹｉｎＫ...     

Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma

BACKGROUND/AIM: Accumulation of copper (Cu) in hepatocellular carcinoma (HCC), especially in small tumors, is greater than that in the surrounding liver parenchyma. Metallothionein (MT) is considered to be present as Cu-MT, Zn,Cu-MT or Zn-MT. The aim of this study was to determine the presence and localization of Cu-MT and Zn-MT in HCC and surrounding liver parenchyma. METHODS: In 16 HCC patients, surgically resected specimens including HCC and surrounding liver parenchyma were evaluated. RESULTS: The level of Cu present in small HCC (<4 cm in diameter) was significantly greater than that in the surrounding liver parenchyma (p<0.05). However, the level of Cu in large HCC (>4 cm in diameter) was similar to that in the surrounding liver parenchyma. Analysis by Sephadex G-75 gel filtration revealed that the peak fraction due to Cu was identical to that due to MT in 14 (87.5%) of 16 HCC, the peak fraction due to Cu and Zn was identical to that due to MT in 2 (12.5%) HCC, and the peak fraction due to Zn was identical to that of MT in none of 16 HCC. CONCLUSIONS: Accumulation of Cu in small HCC, in which Cu was present as Cu-MT or Zn, Cu-MT, was greater than that in the surrounding liver parenchyma. Cu accumulation and the presence of MT in the liver may be related to carcinogenesis of HCC, because of the similarity of these findings in the experimental data of Long-Evans rats with a cinnamon-like coat color who develop HCC spontaneously.     

Phase tissue intercellular adhesion molecule-1 expression in nude mice human liver cancer metastasis model

AIM To study the phase cancer tissue intercellular adhesion molecule-1 (ICAM-1) expression of human cancer metastasis model in nude mice, and to analyze the relationship between ICAM-1 expression and the metastasis and recurrence of hepatocellular cancinoma (HCC).METHODS HCC tissues from liver cancer metastasis model in nude mice (LCI-D20) was orthotopically implanted, and ICAM-1 expression in HCC tissues at different growing time were detected by immunodot blot. Tumor size, intrahepatic and extrahepatic metastasis foci were observed by naked eyes and under light microscope.RESULTS ICAM-1 was positively correlated to the tumor growing time (r=0.88, P＜0.01) and tumor size r=0.5, P＜0.05). It was higher in metastatic HCC than in nonmetastatic HCC (8.24±0.95 vs 3.03±0.51, P＜0.01). ICAM-1 content in cancer tissues increased suddenly after metastasis occurred and then maintained in a high level. ICAM-1 was also higher in multimetastasis group than in monometastasis group (10.05±1.17 vs 5.48±0.49, P＜0.05).CONCLUSION Tissue ICAM-1 could predict not only the metastasis of human liver cancer metastasis model in nude mice early and sensitively, but also the metastasis degree. So tissue ICAM-1 may be a potential index indicating the status of metastasis of HCC patients.