[Show abstract][Hide abstract] ABSTRACT: We reported a 60-year-old male patient with hepatocellular carcinoma (HCC) of 5cm in diameter with advanced tumor thrombosis in the left main trunk of portal vein and bile duct. He was treated with multimodal treatments resulting in a long-term survival of more than 4 years. At first, he was treated with transcatheter arterial chemoembolization (TACE) in April 1999, but the therapeutic effect was insufficient. Therefore, we performed an extended left hepatic lobectomy in July. Since six HCCs appeared in a posterior segment in January 2000, we achieved microwave coagulation therapy under laparotomy. Because of diffuse relapse of HCCs in the same segment of the liver, we performed hepatic arterial chemotherapy (HAC) using low-dose CDDP and 5-FU. As a result, complete disappearance of the tumors was observed. A new lesion appeared in S7 in January 2001. We performed TACE, but relapsed in June, so we selected percutaneous radio-frequency ablation under CO2 angiography. Since a recurrent tumor was detected at the same therapeutic site with invasion to the diaphragm in September 2002, we performed a partial liver resection with synchronous excision of the diaphragm. We continued TACE and systemic chemotherapy for relapses in and out of the liver. Accordingly, he lived for over four years. We conclude that a long-term survival in this patient can be attributable to appropriate treatment selections and timing, such as hepatic resection, TACE, HAC and ablation therapies based on changes in diagnostic imaging and tumor markers. In addition, we have to pay attention to keep good hepatic reserve in order to continue treatment for recurrences of HCC.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2005; 32(11):1805-8.
[Show abstract][Hide abstract] ABSTRACT: Epidermal growth factor receptor (EGFR) mediated mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway was isolated as invasion-metastasis related factor in pancreatic cancer in our previous studies. Matrix metalloproteinase-7 (MMP-7) and tight junction (TJ) proteins are indicated to be involved in cancer invasion-metastasis. To clarify the underlying mechanism of involvement of MMP-7 in cancer invasion, western blotting, invasion assay and immunohistochemistry were performed in dissociated (PC-1.0 and AsPC-1) and non-dissociated (PC-1 and Capan-2) pancreatic cancer cells, as well as pancreatic cancer tissues. Intracellular MMP-7 protein presented as pre-proenzyme and its expression was decreased by AG1478 (EGFR inhibitor) or U0126 (MEK inhibitor) treatment in pancreatic cancer cells. Activated MMP-7 protein was only detected in the medium of PC-1.0 and AsPC-1 cells, but not detected in the medium of PC-1 and Capan-2 cells. Moreover, MMP-7 treatment significant induced the dissociation of cell colonies in PC-1 and Capan-2 cells. Synchronously, TJ structure was apparently disrupted and translocation of TJ proteins to cytoplasm or extracellular medium was induced in PC-1 and Capan-2 cells. Furthermore, MMP-7 treatment markedly increased the in vitro invasion of PC-1 and Capan-2 cells. In addition, MMP-7 expression at the invasive front was obviously stronger than that at the center of pancreatic cancer tissues. Activation of MMP-7 protein is closely involved in disruption of TJ structure and consequent induction of cell dissociation as well as invasion in pancreatic cancer. EGFR mediated MEK/ERK signaling pathway is implied to be involved in regulation of MMP-7 expression in pancreatic cancer cells.
International Journal of Oncology 06/2005; 26(5):1283-9. · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mitogen-activated protein kinase kinase 2 (MEK2) was isolated previously as a potential factor related to cancer cell dissociation in highly (PC-1.0) and weakly (PC-1) invasive pancreatic cancer cells. On the other hand, changes of structure and function of tight junction (TJ) are reported to be correlated with carcinogenesis and tumor development. In this study, immunocytochemistry and Western blot analysis were performed in pancreatic cancer cells using anti-claudin-1, MEK2 and phosphorylated MEK1/2 (p-MEK1/2) antibodies to reveal the correlation between TJ and cancer cell dissociation, as well as the involvement of MEK2 in regulation of TJ in cell dissociation of pancreatic cancer. After incubation with conditioned medium of PC-1.0 cells, plasma membrane distribution of claudin-1 was obviously disrupted, and expressions of MEK2 and p-MEK1/2, as well as dissociation of cell colonies, were significantly induced in PC-1 and CAPAN-2 cells. However, U0126 (a MEK1/2 inhibitor) treatment apparently induced the plasma membrane distribution of claudin-1 and aggregation of single cells in PC-1.0 and AsPC-1 cells, synchronously seriously suppressed MEK2 and p-MEK1/2 expression. Arrangement of expression and distribution of claudin-1 is closely related to cell dissociation status in pancreatic cancer cells through MEK2 activation.
International Journal of Oncology 01/2005; 25(6):1567-74. · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In our previous investigations, mitogen-activated protein kinase kinase 2 (MEK2)/extracellular signal-regulated kinase 2 (ERK2) signaling pathway was found to be correlated with the cell dissociation induced by dissociation factor (DF) in pancreatic cancer cells. In this study, the expressions of epidermal growth factor receptor (EGFR), phosphorylated EGFR (p-EGFR), and its downstream kinases MEK1/2 and ERK1/2, were analyzed to clarify the regulatory mechanism of cell dissociation in pancreatic cancer cells. Two hamster (PC-1.0 and PC-1) and two human (AsPC-1 and Capan-2) pancreatic cancer cell lines were used. Immunocytochemical study was performed using anti-EGFR, p-EGFR, phosphorylated MEK1/2 (p-MEK1/2), and phosphorylated ERK1/2 (p-ERK1/2) antibodies. DF-treatment markedly induced the expressions of EGFR, p-EGFR, p-MEK1/2, p-ERK1/2, as well as the dissociation of cell colonies in PC-1 and Capan-2 cells. In contrast, AG1478 (an EGFR inhibitor) treatment significantly induced the cell aggregation in PC-1.0 and AsPC-1 cells which usually grew as single cells, but strongly suppressed the expressions of EGFR, p-EGFR, p-MEK1/2, and p-ERK1/2. These observations demonstrate that activation of EGFR is closely involved in cell dissociation in pancreatic cancer through activating MEK/ERK signaling pathway.
International Journal of Oncology 12/2004; 25(5):1303-9. · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The patient was a 73-year-old male who was identified with an increase of serum PIVKA-II during a treatment for chronic hepatitis B. Hepatocellular carcinoma (HCC) of 60 mm in diameter with satellite nodules was diagnosed in segment 8 of the liver. In addition, portal vein tumor thrombosis (PVTT) of the right branch (Vp3) and metastases to bilateral lung and right adrenal gland were recognized. He received serial treatments with transcatheter arterial chemoembolization (TACE), radiation therapy and hepatic arterial chemotherapy with reservoir for primary liver tumor and PVTT. Soon after the treatments, PVTT was reduced in size and the serum level of PIVKA-II was decreased to 57 mAU/ml. After three months, the level of PIVKA-II had increased again and the size of the right adrenal metastasis grew to 50 mm in diameter. He received TACE to the right adrenal metastasis and percutaneous transhepatic portal chemoembolization to prevent further growth of PVTT. In spite of several treatments, the therapeutic effect was insufficient. Therefore, we performed right adrenalectomy and radio-frequency ablation of HCC in the liver S8. After the surgery, he received two times of TACE and the viable tumor had disappeared on CT and MRI. Prognosis of HCC with PVTT and distant metastasis is very poor. The two-year survival rate is less than 10%. However, it is possible to improve the prognosis of advanced HCC by multidisciplinary treatment with surgical intervention, local chemotherapy and radiation therapy.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2004; 31(11):1921-3.
[Show abstract][Hide abstract] ABSTRACT: The patient was a-54-year-old man. Sigmoidectomy was performed for sigmoid colon cancer in 1991. Partial liver resection in 1992 and microwave coagulation therapy (MCT) in 1994 were carried out for liver metastasis. Complete remission of the metastasis was achieved. In June 2002, multiple liver and lung metastases were identified. 5-FU, CDDP therapy was applied as systemic chemotherapy. The liver metastasis was improved and the level of CEA was reduced. However, a new lesion appeared in the right lobe of the liver, followed by an increase of the CEA level. Although CPT-11, 5-FU, CDDP therapy was applied, it was not effective. The reason was considered to be from the decrease of drug delivery resulting from an unbalanced blood supply in the right lobe of the liver. Right lobectomy and radio-frequency ablation was performed on June 17, 2003. The level of CEA was dramatically decreased. Additionally, CPT-11, 5-FU, CDDP therapy was applied. The patient has survived for 11 years after liver metastasis was first detected.
Gan to kagaku ryoho. Cancer & chemotherapy 09/2004; 31(8):1249-52.
[Show abstract][Hide abstract] ABSTRACT: We have performed ablation therapy for 4 patients who had hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). In order to avoid intrahepatic metastasis due to ablation, we treated portal venous embolization before ablation. After treatment, computed tomography revealed no viable area in the treated lesion and no dissemination in the portal vein. A complication was encountered in 1 patient, in the form of a collection of ascites due to portal hypertension. We conclude that ablation therapy is the choice for unresectable HCC with PVTT in multidisciplinary therapy.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2003; 30(11):1702-5.