Biomedical subjects

Masato Sakon

Publications and source records attributed to Masato Sakon.

At least 91 records · Page 5Linked to original sources

PubMed2003

[A case of liver metastasis of pancreatic duct carcinoma successfully treated with gemcitabine].

We report a patient in whom systemic chemotherapy using gemcitabine was effective against liver metastases of pancreatic cancer. A 72-year-old woman underwent pancreatoduodenectomy with lymphadenectomy and partial resection of the portal vein following a diagnosis of pancreatic cancer, and her postoperative course was uneventful. The diagnosis was stage III anaplastic ductal carcinoma (t2n1P0H0M0). One year and 3 months after the operation, however, her serum level of carbohydrate antigen 19-9 (CA19-9) was found to be elevated, and CT examination revealed a mass in the liver that was diagnosed as liver that was metastases. Systemic chemotherapy was performed with a regimen of gemcitabine 600 mg/m2/week for 3 weeks, followed by a week rest, for the first three courses. On and after fourth course, gemcitabine 1,000 mg/m2/week was administered. The serum CA19-9 level was down from 882 U/ml to normal after 5 courses of chemotherapy and CT examination revealed that liver metastases had completely vanished. Although no evidence of deterioration was observed, the patient died of infectious pneumonia 10 months after recurrence. The prognosis of liver metastases of pancreatic cancer is quite unfavorable. However, if remission is achieved with gemcitabine, the patient has the possibility to obtain a better outcome.

Aged↗

PubMed2003

Overexpression of CDC25A phosphatase is associated with hypergrowth activity and poor prognosis of human hepatocellular carcinomas.

PURPOSE AND EXPERIMENTAL DESIGN: CDC25 genes are cell cycle-activating phosphatases that positively regulate the activity of cyclin-dependent kinase. CDC25A and CDC25B, being oncogenes, are overexpressed in a variety of human malignancies. To investigate the potential roles of CDC25s in hepatocellular carcinoma (HCC), expression of CDC25A and CDC25B was examined in human HCC samples. RESULTS: Reverse transcription-PCR showed that overexpression of CDC25A and CDC25B mRNAs was found in 9 of 13 (69%) and 4 of 13 (31%) HCCs, respectively. Immunohistochemistry of 59 HCCs showed marked increase in CDC25A expression, but not CDC25B, in HCC compared with noncancer tissues, and high expression of CDC25A in 33 of 59 (56%) HCCs. Overexpression of CDC25A in HCC was confirmed by Western blot analysis. High expression of CDC25A was associated with dedifferentiated phenotype and portal vein invasion (P = 0.001 and 0.031, respectively), and expression of CDC25A correlated well with proliferating cell nuclear antigen labeling index (P = 0.005). Univariate analysis indicated that high expression of CDC25A and proliferating cell nuclear antigen were both significant predictive factors for shorter disease-free survival (P = 0.004 and 0.039, respectively). Multivariate analysis indicated that CDC25A was an independent prognostic marker for disease-free survival (risk ratio for cancer relapse, 2.98; P = 0.029), even when analyzed with several clinicopathologic factors. On the other hand, expression of CDC25B did not correlate with any clinicopathological features. CONCLUSION: Our findings suggest that CDC25A, but not CDC25B, could be used as an independent prognostic marker for HCC. Our data would also contribute to forward understanding of tumor biology of HCC that is associated with cell cycle regulation.

Adult↗

PubMed2003

Growth inhibition of pancreatic cancer cells through activation of peroxisome proliferator-activated receptor gamma/retinoid X receptor alpha pathway.

Peroxisome proliferator-activated receptor gamma (PPARgamma), a ligand activated transcription factor, forms a heterodimer with retinoid X receptor alpha (RXRalpha), and its transcriptional activity is thought to be maximal in the presence of both PPARgamma and RXRalpha ligands. Though previous studies suggested that thiazolidinediones (TZDs), known as PPARgamma ligands, inhibit the growth of certain types of cancer cells, little is known about the growth inhibitory effects mediated though activation of PPARgamma/RXRalpha. We examined the effects of troglitazone (one type of TZDs) and 9-cis retinoic acid, a RXRalpha ligand, on activation of PPARgamma/RXRalpha and growth inhibition of human pancreatic cancer cell lines (AsPC1, BxPC3, PSN1, PCI6, Panc1, KMP-4, and KMP-7). Combined treatment of troglitazone and 9-cis retinoic acid showed enhanced transcriptional activity and enhanced antiproliferative effects. In PSN1 cells, G1 cell cycle arrest and apoptosis were induced by troglitazone and these effects were enhanced with additional 9-cis RA. Our findings suggest that activation of PPARgamma/RXRalpha pathway might play an important role in growth inhibition of pancreatic cancer cells via G1 cell cycle arrest and apoptosis. This nuclear receptor might be a suitable molecular target for treatment of pancreatic cancers.

Alitretinoin↗

PubMed2003

[General surgery].

Perioperative prophylaxis for pulmonary embolism (PE) is now an emerging issue in Japan because its frequency is increasing very rapidly. Although the optimal prophylaxis should be performed individually on the basis of clinical evidence, the available data on the incidence and prophylaxis of PE are limited in Japanese surgical patients. Both mechanical and pharmacological methods of prophylaxis have been developed. Intermittent pneumatic compression (IPC) appears to be effective. The importance of thromboprophylaxis with anticoagulants including heparin is also emphasized. A new guideline for PE prophylaxis is expected to be established based on Japanese clinical evidence.

Humans↗

PubMed2003

[A report of two cases--two patients of the extremely advanced hepatocellular carcinoma have responded completely for a long time after a combination therapy consisting of arterial chemotherapy and injection of interferon-alpha].

The prognosis of advanced hepatocellular carcinoma (HCC) is extremely poor. Patient 1 was a 43-year-old male with major portal tumor thrombi. He received combination therapy consisting of continuous arterial infusion (MTX 30 mg/m2, day 1, CDDP/5-FU 6 mg/m2: 250 mg/m2, day 1-14) and subcutaneous injection of IFN-alpha (500 x 10(4) U, 3 times a week, 4 weeks). Patient 2 was a 66-year-old male with major hepatic venous tumor thrombi. He received combination therapy consisting of continuous arterial infusion (5-FU 6 mg/m2: 250 mg/m2, day 1-14) and subcutaneous injection of IFN-alpha (500 x 10(4) U, 3 times a week, 4 weeks). Decrease in tumor was observed in both patients markers and marked regression of tumor was observed in both patients. They are still in complete response. This combination therapy is an effective strategy for advanced HCC.

Adult↗

PubMed2003

[A case of successful treatment of advanced hepatocellular carcinoma with tumor thrombi in the major portal branches and inferior vena cava with combined intraarterial 5-fluorouracil, adriamycin and cisplatin therapy].

The patient is a 75-year-old male. Abdominal ultrasound tomography in June 2002 revealed hepatocellular carcinoma with intrahepatic metastasis (IM3) and tumor thrombi (Vp4, Vv3) at S4 in the major portal and hepatic vein. From July 2002, he received hepatic arterial infusion therapy (FAP: 5-fluorouracil, CDDP and adriamycin) for these lesions. In December 2002, these lesions had disappeared completely after 6 sessions of arterial infusion therapy. The patient is still alive with no recurrence after 2 years since the beginning of this treatment. Recently, we treated 9 patients with combined arterial infusion chemotherapy (FAP), and the response rate (CR and PR) was 44% and no major side effect was observed. In conclusion, some patients may obtain longer survival through this treatment, even in cases of advanced HCC with tumor thrombus in the major trunks of portal vein and/or hepatic vein.

Aged↗

PubMed2003

[A case of long-term survival with TAE resistant multiple recurrence HCC successfully treated by hepatic resection].

A 55-year-old female was admitted to our hospital for a third recurrence of hepatoma. She was treated with transcatheter arterial embolization (TAE) in April and November 1996. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple tumors of S4/S8 and S7 in the liver. After the third TAE using SMANCS, Lipiodol and Spongel, abdominal CT revealed insufficient Lipiodol retention and the in efficacy of this treatment. A right lobectomy of the liver was performed for the TAE resistant multiple recurrence of HCC. After the surgery, the patient survived for over 5 years with no recurrence. It appears that this surgery may be a useful modality for TAE resistant multiple recurrence hepatoma in cases of good liver function and lesions limited to the hemi lobe.

Antineoplastic Agents↗

PubMed2003

[The chemotherapy for hepatocellular carcinoma].

For the difficulty of the giving sufficient dose because of the poor liver function and low sensitivity for the anti-cancer agents, the chemotherapy may not play a central role for the hepatocellular carcinoma (HCC) patients with liver cirrhosis. However, the chemotherapy must be the one of important possibility as a multimodal treatment for the advanced HCC, for which hepatic resection, TAE and other general therapy would not be effective. The intraarterial perfusion chemotherapy is common as a chemotherapy for HCC and it is not difficult to maintain; the effective rate is not sufficient. Recently, the combination therapy with subcutaneous IFN-alpha and intraarterial 5-FU showed a outstanding effective rate for intractable HCC with Vp3. For the further advance of the HCC treatment and prognosis, this therapy might be the promising treatment modality and expected of the development.

Administration, Oral↗

PubMed2002

Combined intraarterial 5-fluorouracil and subcutaneous interferon-alpha therapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal branches.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) invading into the major branches of the portal vein (Vp3) is extremely poor. METHODS: Eleven consecutive patients with HCC and Vp3 were treated with 2-6 cycles of a "basic" combination therapy consisting of continuous arterial infusion of 5-fluorouracil (450-500 mg/day, for the initial 2 weeks) and subcutaneous injection of interferon-alpha (5 million international units, 3 times/week, 4 weeks). In the first 3 patients, methotrexate (90 mg/day 1 of every week), cisplatin (10 mg/day), and leucovorin (30 mg/days 2 and 3 of every week) also were administered for the initial 2 weeks ("full" regimen). RESULTS: In 8 (73%) of 11 patients, an objective response (complete response [CR] or partial response [PR]) was observed with marked regression of tumor and decrease in tumor markers. The use of the full regimen was associated with objective response in all patients; instead, they developed thrombocytopenia or leukopenia. In the subsequent 8 patients with basic regimen, 5 patients showed CR (2 cases) or PR (3 cases; objective response rate, 63%), and leukopenia was observed only in 1 patient. CONCLUSIONS: Simple combination therapy with subcutaneous interferon-alpha and intraarterial 5-fluorouracil therefore is a promising treatment modality for intractable HCC with Vp3.

Adult↗

PubMed2002

Intrahepatic recurrences of hepatocellular carcinoma after hepatectomy: analysis based on tumor hemodynamics.

HYPOTHESIS: Surgical margin, i.e., the area of possible local intrahepatic metastasis, is controversial in hepatectomy for hepatocellular carcinoma. DESIGN: The blood drainage area of tumor was identified preoperatively by abdominal helical computed tomographic scan under hepatic arteriography and excised as surgical margin. The specimens were pathologically examined on the basis of the corresponding computed tomographic images. SETTING: University hospital. PATIENTS: From June 2, 1997, to April 24, 2000, 67 patients with hepatocellular carcinoma who underwent curative hepatic resection. MAIN OUTCOME MEASURE: Intrahepatic recurrence. RESULTS: Blood drainage area of tumor could be classified into the following types. The marginal type (drainage into the peritumorous area) was frequent (50 cases) and excised mostly by nonanatomic, limited resection. Portal vein type (drainage into the portal branches) was less common (12 cases) and resected mostly by anatomically systematic hepatectomy. The remaining 5 cases were of the hypovascular type and underwent limited resection. Multiple nodules were frequently found inside the drainage area (4 of 8 cases) and were moderate or poorly differentiated hepatocellular carcinoma, consistent with intrahepatic metastasis. Solitary nodules were mostly outside the drainage area (11 of 12 cases) and contained well-differentiated hepatocellular carcinoma (7 of 10 cases), suggesting multicentric carcinogenesis. Intrahepatic recurrences were commonly found in bilateral or contralateral lobes (17 of 19 cases) and divided into 2 groups with a few (< or =4) and multiple (> or =8) recurrent nodules. CONCLUSIONS: Surgical margin varied according to tumor hemodynamics. Tumor recurrences may result not only from multicentric carcinogenesis but also from intrahepatic metastasis via systemic circulation.

Adult↗

PubMed2002

Liver abscess formation after microwave coagulation therapy applied for hepatic metastases from surgically excised bile duct cancer: report of a case.

We report the case of a liver abscess associated with microwave coagulation therapy (MCT). A 67-year-old man underwent a pylorus-preserving pancreatoduodenectomy for bile duct cancer in August 1998. In June 1999, abdominal computed tomography (CT) showed three low-density areas in his liver. With a diagnosis of multiple metastatic liver tumors, we applied MCT to each liver tumor. The patient presented with fever after therapy. Abdominal CT showed a hepatic abscess, which was treated by percutaneous transhepatic abscess drainage under ultrasonography. A bacteriological examination of the pus material revealed the presence of Enterococcus faecalis and Candida albicans. Treatment resulted in a rapid resolution of symptoms. Our case indicated that care should be exercised in using MCT for the treatment of liver tumors in patients who have undergone reconstructive surgery of the biliary tract.

Aged↗

PubMed2002

A successful resection and long-term survival of a patient with intrahepatic recurrences of combined hepatocellular-cholangiocarcinoma: report of a case.

Because of the low incidence rate of combined hepatocellular-cholangiocarcinoma (combined HCC-CC), the clinicopathological features of a recurrent tumor of this disease remain to be elucidated. We describe a 47-year-old Japanese woman with a 5-cm diameter mass lesion in the liver. A hepatectomy and dissection of the local lymph nodes were performed and a histological examination of the resected specimen showed combined HCC-CC. After a follow-up of 15 months, intrahepatic recurrence was observed, and a hepatectomy was performed again followed by hepatic arterial infusion chemotherapy. A histological examination revealed that the recurrent tumors consisted of only cholangioacarcinoma. A disease-free survival was obtained for about 7 years after the recurrence. To improve the poor prognosis of combined HCC-CC, clinicopathological features of this disease and the therapy selection for recurrent tumors should be discussed.

Bile Duct Neoplasms↗

PubMed2002

Ischemia-reperfusion injury of the liver with special reference to calcium-dependent mechanisms.

Ischemia-reperfusion (I/R) injury is a complex process involving numerous intracellular signaling pathways, mediators, cells, and pathophysiological disturbances; its prevention during liver surgery is of utmost importance. In this review, we divide hepatic I/R injury into two phases, intracellular and extracellular, for a better understanding of the processes involved. Ca2+ and Ca2+-dependent reactions play an important role as a trigger in the former phase, while the subsequent generation of bioactive substances plays a predominant role in the latter phase. These findings indicate that a combination of different therapeutic approaches against Ca2+-dependent steps may help prevent I/R injury of the liver.

Apoptosis↗

PubMed2002

Expression of p57/Kip2 protein in extrahepatic bile duct carcinoma and intrahepatic cholangiocellular carcinoma.

BACKGROUND: Evaluation of the biological character of carcinomas requires understanding of cell cycle regulators. P57 (Kip2) belongs to the Cip/Kip family and is known to be one of the universal negative regulators of cell cycle. METHODS: In the present study, therefore, we investigated p57 expression in 37 extrahepatic bile duct carcinomas (BDC) and 28 intrahepatic cholangiocellular carcinomas (CCC). RESULTS: The average p57 labeling index (LI) in BDC and CCC were 60.8 +/- 7.9 and 58.6 +/- 18.6, respectively, which were significantly lower (p = 0.0008 and p = 0.0408, respectively) than those in normal duct epithelia (73.1 +/- 7.9, 70.4 +/- 8.2). p57 LI was significantly lower in BDC and CCC cases with biological aggressive phenotypes such as poor differentiation (p = 0.0260 and p = 0.0069), lymph node metastasis (p = 0.0274 and p = 0.0214), high Ki-67 LI (p = 0.0164 and p = 0.0343) and cyclin D1 overexpression (p = 0.0359 and p = 0.0255). CONCLUSION: These findings suggest that decreased p57 expression is related to the increased activity of cell proliferation and also the progression of these carcinomas.

Adult↗

PubMed2002

Overexpression of beta 1,4N-acetylgalactosaminyl- transferase mRNA as a molecular marker for various types of cancers.

OBJECTIVE: To determine GalNAcT mRNA expression in human carcinoma cell lines and primary tumor tissues. Assessment of the potential use of GalNAcT mRNA as a molecular marker for detection of metastatic cancer cells in the peripheral blood of patients with hepatocellular carcinoma. METHODS/RESULTS: We investigated GalNAcT mRNA expression in various human cancer cell lines and primary cancer tissues using RT-PCR assay for GalNAcT mRNA. The expression of GalNAcT mRNA was detected in 25 of 26 cancer cell lines tested and in the majority of primary tumors from different organs: 8 of 10 colon cancers, 9 of 9 breast cancers, 11 of 12 esophageal cancers, 14 of 14 gastric cancers, 4 of 18 pancreatic cancers, 6 of 12 biliary tract cancers, 17 of 18 hepatocellular carcinomas and 13 of 14 lung cancers. Semi-quantitative analysis with duplex RT-PCR showed that the amount of the GalNAcT mRNA was enhanced in cancer tissues as compared to the surrounding cancer-free tissues. Blood specimens of 5 of 14 patients with hepatocellular carcinoma were positive for GalNAcT mRNA, all of whom developed recurrent disease in less than 24 months. Peripheral blood samples of 30 normal subjects were negative for GalNAcT mRNA. CONCLUSION: Our results suggest that the RT-PCR assay for GalNAcT mRNA could be a potentially useful molecular marker for detecting cancer dissemination in blood circulation of patients with malignancy.

Adult↗

PubMed2002

Cancer cell contact causes oscillatory and polarized rise of cytoplasmic ionized calcium concentration in human umbilical vein endothelial cells.

The rise of cytoplasmic ionized Ca2+ concentration ([Ca2+]i) is an important factor in cellular signal transduction, which regulates a variety of cellular functions in vascular endothelial cells (vECs) such as morphological change, secretion of vaso-active molecules, or endothelial permeability. It is also known that the loss of vEC integrity plays pivotal roles in several physiological or pathological phenomena, such as inflammation or cancer metastasis. The aim of this study was to clarify the mode of cancer cell induced vEC retraction by cell to cell contact. Digital imaging analysis using Ca2+ indicator, fluo-3, clearly demonstrated an oscillatory intracellular and intercellular [Ca2+]i wave originated from the site of human breast cancer cell line MCF-7 cell contact in HUVECs, which was not inhibited by extracellular Ni2+ and was inhibited by pretreating the cells by paraformaldehyde. Although this phenomenon could be observed in malignant cells including murine malignant melanoma cell line, BL6, as well as benign cells including human fibroblast cell line, WI38, inert neutrophils did not cause vEC retraction nor [Ca2+]i oscillation. Thus, cancer cells could activate vECs by a cell to cell contact to cause retraction via common property of non-blood cells.

Animals↗

PubMed2002

[Development and research of the new therapy for hepatocellular carcinoma--combined interferon and 5-fluorouracil therapy].

The prognosis of hepatocellular carcinoma(HCC) invading the major branches of the portal vein(Vp3 or 4) is extremely poor. Recently, we reported the efficacy of the combination therapy with subcutaneous interferon(IFN)-alpha and intra-arterial 5-FU for intractable HCC with Vp3 or Vp4. Forty-eight consecutive patients with HCC and Vp3 or 4 were treated with the combination therapy consisting of continuous arterial infusion of 5-FU(450-500 mg/day, 5 days/week, for the initial 2 weeks) and subcutaneous injection of IFN(5 MIU, 3 times/week, 4 weeks). The treatment outcome of these cases was very good. In addition, it is considered direct antitumor effect, the angiogenesis depression effect, and the indirect antitumor effect through immunocompetent cell, may concerned, as the mechanism. In conclusion, combination therapy with subcutaneous IFN and intra-arterial 5-FU is therefore a promising treatment modality for intractable HCC with Vp3 or 4.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

[Hepatocellular carcinoma recurrence in PEI site--a case report].

The patient was 63-year-old male. Abdominal CT revealed a tumor at S2/S3, which led to a diagnosis of hepatocellular carcinoma, in April 1998. On April 15, 1998 transcathetereal arterial embolization was performed and on May 11, 1998 percutaneous ethanol injection therapy was given, but a viable lesion remained. On July 2, 1998, partial resection of S2/S3 was performed. There was an intrahepapic metastatic lesion at Glisson's site of the main tumor, which was suspected of implantation. In December 2000, the patient had a high AFP level, and a recurrent tumor was observed at S3 on abdominal CT. In June 2001, S3 subsegmentectomy was performed, because the recurrent tumor existed in the Glisson S3 area.

Carcinoma, Hepatocellular↗