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Biomedical subjects

J Shibata

Publications and source records attributed to J Shibata.

At least 37 records · Page 2Linked to original sources

[Continuous arterial infusion of low-dose cisplatin, 5-fluorouracil as adjuvant therapy in cytoreductive surgery for advanced hepatocellular carcinoma].

We investigated the effectiveness of continuous arterial infusion of low-dose CDDP, 5-FU for residual cancer after cytoreductive surgery for advanced hepatocellular carcinoma. Thirty-one patients with unresectable advanced hepatocellular carcinoma were classified into two groups by adjuvant therapy after reduction surgery: 1) Low-dose FP Group: 17 patients; continuous arterial infusion of low-dose CDDP, 5-FU via implanted port system; 2) Conventional group: 8 patients; Lipiodolization (6 cases) and transcatheter arterial embolization (2 cases). The five-year survival rate in the low-dose FP group was 34.8%, the efficacy was 64.7%, CR: 6 (35.3%); PR: 5; NC: 4; PD: 2. Thus, continuous arterial infusion of low-dose CDDP, 5-FU was effective as adjuvant therapy in cytoreductive surgery for advanced hepatocellular carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Antitumor activity of a novel podophyllotoxin derivative (TOP-53) against lung cancer and lung metastatic cancer.

We synthesized a potent new antitumor podophyllotoxin derivative (4beta-aminoalkyl-4'-O-demethyl-4-desoxypodophyllotoxin; TOP-53) in our search for a drug that has strong activity against lung cancer and lung metastatic cancer. TOP-53 exhibited twice the inhibitory activity of etoposide (VP-16) against topoisomerase II and induced DNA strand breaks but showed no inhibitory activity against tubulin polymerization. The in vitro cytotoxic activity of TOP-53 assessed as IC50 was 0.016-0.37 microg/ml and 0.26-8.9 microg/ml against marine tumor and human non-small cell lung cancer (NSCLC) cell lines, respectively. TOP-53 exerted significant efficacy equivalent to that of VP-16 on s.c.-implanted murine solid tumors (Colon 26, B16-BL6, and Lewis lung carcinoma) at doses 3-5 times lower than that of VP-16. In human tumor xenografts using NSCLC, TOP-53 was active for four of five tumors, whereas VP-16 was active for two of five tumors. Potent inhibitory activity of TOP-53 was also found against a lung tumor (Lewis lung carcinoma) and four lung metastatic tumors (NL-22 and NL-17 colon cancer, UV2237M fibrosarcoma, and K1735M2 melanoma). TOP-53 appeared to be more active against four of them than VP-16. Thus, TOP-53 is not only active against s.c.-implanted lung cancers but also strongly active against lung localized tumor and metastatic tumors in the lungs. The high selectivity of TOP-53 was attributed to its high distribution into the lung and its persistence. TOP-53 is expected to be highly effective against lung cancer including NSCLC and various lung metastatic tumors in the clinical field.

Animals↗

A case of obstructive icterus caused by incarceration of a pancreatic stone in the common channel of the pancreatobiliary ducts.

A 51-year-old man had repeated admissions and discharges from the hospital for alcohol dependence and alcoholic hepatitis. Thereafter, with a diagnosis of chronic pancreatitis, he was examined on an outpatient basis. He presented with right hypochondriac pain as the chief complaint, and was admitted to the hospital because of a suspected acute exacerbation of chronic pancreatitis. Pyrexia and jaundice were present from about the 5th hospital day, and he was admitted to Kurume University Hospital with a diagnosis of obstructive icterus. Percutaneous transhepatic biliary tract drainage (PTBD) was immediately performed. A roentgenogram revealed moderate dilatation of the extrahepatic bile ducts and stricture of the intrapancreatic common bile duct. No calculi were observed in the gallbladder or bile ducts by ultrasonography of the abdominal region. The main pancreatic duct was dilated to 10 mm, and a strong echo, probably a calculus, was observed in the main pancreatic duct. Pancreatoduodenectomy was performed with a diagnosis of stricture of the common bile duct due to chronic pancreatitis with a pancreatic stone. Examination of the excised specimens revealed a rigid pancreatic head; and when the common bile duct was incised, no stricture was observed. A milk-white calculus about 10 mm in diameter was observed in the common channel of the lower portion of the common bile duct. The orifice of the pancreatic duct was also observed at the same site. The common channel was about 20 mm long, and malfusion of the pancreatobiliary ducts was observed. The obstructive icterus was due to an impaction of the pancreatic stone at the confluence of the pancreatobiliary ducts. The calculus was composed of calcium carbonate, and the histopathological findings in the pancreas showed chronic pancreatitis.

Gallstones↗

[Usefulness of continuous arterial infusion chemotherapy for post operative multiple recurrence and residual hepatocellular carcinoma].

Twenty five patients with postoperative multiple recurrence and residual hepatocellular carcinoma received continuous arterial infusion of CDDP and 5-FU via implanted reservoir. For the next five days, 10 mg/body of CDDP and 250 mg/body of 5-FU using arterial infusion were administered. It was discontinued for two days as one course, and 4 courses were basally administered. The efficacy rate was 60%, and there were 7 (28%) CR (complete response) cases. The survival rate was 76.0% for 1 year and 36.5% for 3 years, which is a favorable result considering their advanced stage. Thus, this treatment seemed to be effective for multiple hepatocellular carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Comparative pharmacodynamic analysis of TAT-59 and tamoxifen in rats bearing DMBA-induced mammary carcinoma.

TAT-59 suppressed the growth of DMBA-induced mammary tumors in rats earlier and more strongly than tamoxifen (TAM). After oral administration of the drugs, DP-TAT-59, one of the main metabolites of TAT-59, was found in 10- to 15-fold higher concentrations in both the tumor and blood compared to 4-OH-TAM, an active metabolite of TAM. In a 3-day antiuterotrophic test, every detected metabolite of TAT-59 showed stronger antiestrogenic activity than did TAM. In a competition assay, the affinity of the metabolites for estrogen receptors ranged from that of estradiol to that of TAM. These results suggest that the superior antiestrogenic activity of TAT-59 compared to TAM was either due to its higher penetration into tumor tissue or to the stronger antiestrogenic activity of its metabolites.

9,10-Dimethyl-1,2-benzanthracene↗

Clinical study of IgA antibody against hepatitis C virus core antigen in patients with type C chronic liver disease.

Immunoglobulin A class antibody to hepatitis C virus core antigen (IgA anti-HCc) was measured in the serum of 128 patients with type C chronic liver disease. Fifty-eight patients (45.3%) were seropositive. IgA anti-HCc was detected in only one of 20 patients with chronic persistent hepatitis; however, 52.3% (46/88) of patients with chronic active hepatitis and 55% (11/20) of patients with liver cirrhosis were seropositive. Histological examination revealed that 22 (71.0%) of 31 patients with severe disease activity were seropositive compared to 35 (44.9%) of 78 patients with moderate (P < 0.05) and one (5.3%) of 19 patients with mild (P < 0.01) histological changes. IgA anti-HCc was measured sequentially in 65 patients who underwent interferon therapy. There was a significant difference between responders and other patients in the mean ratio of IgA anti-HCc titers one month after therapy. Three months after therapy, IgA anti-HCc was detectable in only two of 15 responders who were IgA anti-HCc seropositive at the start of therapy. In contrast, IgA anti-HCc reappeared three months after therapy despite a temporary decrease to undetectable levels in all nonresponders. We conclude that IgA anti-HCc is a useful marker to identify the presence of active type C liver disease and that the disappearance of IgA anti-HCc three months after interferon therapy predicts a good response in treated patients.

Adolescent↗

Follow-up of 2,733 Japanese patients with myocardial infarction.

Two thousand, seven hundred and thirty-three patients with acute myocardial infarction (AMI) who were admitted to our 11 institutions between 1983 and 1988, examined by coronary arteriography and discharged alive, were followed for an average of 2.9 years. During the follow-up period, 212 patients (7.6%) died. The factors that governed the prognosis of myocardial infarction after discharge were advanced age, female gender, obesity, previous infarction, angina pectoris more than 1 month before the onset of AMI, post-infarction angina, multiple-vessel diseases, advanced stage by Killip's and/or Forrester's classification on admission, elevated pulmonary capillary arterial pressure, decreased cardiac index, decreased left ventricular ejection fraction, increased left ventricular end-diastolic volume and left ventricular aneurysm before hospital discharge. Patients with ventricular tachycardia or ventricular fibrillation during hospitalization showed a poor prognosis. In contrast, patients who received intracoronary thrombolysis, or emergent and/or elective percutaneous transluminal coronary angioplasty showed a favorable prognosis.

Adult↗

Factors governing re-infarction in patients with myocardial infarction in Japan.

The subjects consisted of 2,733 patients with acute myocardial infarction (AMI) who were admitted to our 11 institutions between 1983 and 1988, examined by coronary arteriography, and discharged alive. The patients were followed for an average of 2.9 years after discharge. During the follow-up period, re-infarction occurred in 172 patients (6.3%). The factors associated with re-infarction were total cholesterol of more than 250 mg/dl, HDL-cholesterol of less than 35 mg/dl and diabetes mellitus. The rate of re-infarction was also high in patients who had had a previous infarction before admission, angina pectoris before or after the onset of AMI or multiple-vessel disease. In contrast, intracoronary thrombolysis reduced the rate of re-infarction.

Angina Pectoris↗

Pancreatojejunal sutural insufficiency occurring after pancreatoduodenectomy and countermeasures.

Pancreatojejunal sutural insufficiency occurring after pancreatoduodenectomy and countermeasures are discussed. In the Department of Surgery at Kurume University School of Medicine, 318 patients underwent pancreatoduodenectomies. The present study includes 15 of these patients, all of whom had pancreatojejunal sutural insufficiency. The frequency of sutural insufficiency was 4.7%. Five patients had bile duct cancer, 5 had cancer of the papilla of Vater, 2 had a carcinoma of the pancreatic head, 1 each had gallbladder cancer, chronic pancreatitis, and papillitis. Six (40%) of the 15 patients died during hospitalization. The presence or absence of sutural insufficiency was confirmed mainly by radiography and determining the properties and amylase levels of the drainage fluid. There was no significant difference due to the method of anastomosis. End-to-side anastomosis had a rate of 5 (5.9%) of 85 patients, while end-to-end had 10 (4.3%) of 233 patients. The sutural insufficiency was manifested as a major leakage in 6 patients and a minor leakage in 9. The degree of lymph node dissection was D0 in 6.1%, D1 in 1.4%, D2 in 4.8% and D3 in 10.8%, with a high incidence of sutural insufficiency in D3 patients. The pancreatic duct diameter was smaller than 4 mm in 10, 5-7 mm in 4 and over 8 mm in 1 patient. The intraoperative pancreatic findings were a soft pancreas in 8, slightly hard in 3, and hard in 4 patients. Fibrosis of the pancreas was normal to slight in 11 and moderate in 4 patients. Drainage by relaparotomy was performed in 4 of the 6 patients with major leakages to control sutural insufficiency, and the other 2 underwent continuous aspiration with an intraperitoneal drain inserted during the operation. The 9 patients with minor leakage underwent conservative treatment including continuous aspiration via an intraperitoneal drain inserted during surgery, fasting, intravenous hyperalimentation, and antibiotic administration. All of the patients with major leakage died from an associated occurrence of hepatic insufficiency, renal insufficiency, intraperitoneal hemorrhage or diffuse peritonitis during hospitalization. However, 8 of the 9 patients with minor leakage had some healing, and the 1 remaining patient developed a pancreatic fistula. The frequency of pancreatojejunal sutural insufficiency was high in patients with minimal pancreatic fibrosis, with soft pancreatic tissue without dilatation of the pancreatic duct, and with relatively good pancreatic function.

Anastomosis, Surgical↗

[The study of continuous arterial infusion chemotherapy with CDDP and 5-FU in patients with hepatocellular carcinoma].

Between Feb. 1992 and April in 1995, 22 patients with hepatocellular carcinoma (10, recurrence; 12, unresectable) received continuous arterial infusion of CDDP and 5-FU via implanted reservoir. For the next five days, 10 mg/body of CDDP and 250 mg/body of 5-FU using arterial infusion were administered. It was discontinued for two days as one course, and 4 courses were basally administered. Patients were divided into 2 groups (6 hours group and 24 hours group) according to the duration of the administration of 5-FU. There were no differences in efficacy rate between the 2 groups (6 hours group, 64%; 24 hours group, 62.5%), but CR (complete response) cases appeared in only the 6 hours group. There were no severe side effects in the 2 groups, but systemic side effects appeared in 6 hours group more often than in 24 hours group. Only in the 24 hours group, 2 patients had the narrowing and obstruction of hepatic artery which was suggested to be caused by intimal injury due to continuous administration of 5-FU. Continuous arterial infusion chemotherapy with CDDP and 5-FU seemed to be effective. Further study on adequate time and volume of administration including pharmacokinetics is needed to enhance the clinical effectiveness of continuous arterial infusion of CDDP and 5-FU.

Aged↗

[Analysis of p53 expression and DNA ploidy pattern in esophageal cancer].

DNA ploidy pattern analyzed by cytofluorometry and p53 protein expression using immunohistochemical method were studied in 35 cases of esophageal cancer. p53 protein were positive in 19 cases (54%), and DNA aneuploidy pattern were detected in 26 cases (74%). There was no relationship between DNA ploidy pattern or p53 expression and clinico-pathological factors. DNA aneuploidy or p53 positive cases were significantly poor prognoses in five-year survival rate. DNA aneuploidy and p53 positive cases were worst in four groups. It is effective for evaluation of biological malignancy and detection of post operative schedules to study not only clinico-pathological factors but also DNA ploidy pattern and p53 expression in esophageal cancer.

DNA, Neoplasm↗

Overexpression and localization of cyclin D1 mRNA and antigen in esophageal cancer.

We examined the expression of cyclin D1 mRNA in two human carcinoma cell lines (A431 and TT) and 17 specimens of esophageal cancer with in situ hybridization. Cyclin D1 mRNA was overexpressed in the cytoplasm of cancer cells that showed cyclin D1 gene amplification by Southern blot hybridization. Cyclin D1 antigen was overexpressed in the nucleus of these cancer cells. The distribution of cyclin D1 mRNA-positive cells was similar to that of cyclin D1 antigen-positive cells in the cancer tissues. We then attempted to correlate overexpression of cyclin D1 antigen and prognosis, by using 55 formalin-fixed, paraffin-embedded specimens of esophageal cancer. The overall 5-year survival of patients with strongly staining tumors was significantly lower than that of patients with weakly or nonstaining tumors (7 versus 59%; P < 0.01). There was no significant correlation between cyclin D1 expression and other clinicopathological factors. These results suggest that cyclin D1 may play an important role in carcinogenesis and that cyclin D1 overexpression may be a useful prognostic factor in esophageal cancer.

Base Sequence↗

A study of reservoir implantation--especially with saphenous vein graft catheterization.

Intra-arterial infusion chemotherapy is commonly used to treat hepatocellular carcinomas (HCC) and metastatic liver cancer after hepatectomy or in unresectable patients, and it has been adopted at Kurume University Hospital as a treatment for HCC. As complications of reservoir implantation have been encountered, the implantation procedure needs improvement. Procedures were compared in a study with 109 patients who were available for follow-up observation among 116 patients who underwent reservoir implantation. Fifty-six of the patients received intraoperative implantation through the gastroduodenal artery (GDA catheterization), 31 received external catheterization (EXT catheterization) and 22 received catheterization using a saphenous vein graft (SVG catheterization). The complication rates were 75.0%, 9.7% and 13.9% and the one-year patencies were 44.1%, 70.6% and 79.4%, respectively. GDA catheterization was no better than the other two procedures and it had a higher incidence of complications and a lower patency. SVG catheterization achieved good patency, although it had a little higher incidence of complications than external catheterization. It was presumed to be a procedure that would ensure reservoir implantation even in patients with a winding or variation of hepatic artery.

Catheters, Indwelling↗

[The study of continuous arterial infusion chemotherapy with 5-FU and CDDP in patients with hepatocellular carcinoma].

Between Feb. 1992 and March in 1994, 14 patients with hepatocellular carcinoma (7: recurrence, 7: unresectable) received continuous arterial infusion of 5-FU and CDDP via implanted reservoir. For the next five days, 10 mg/body of CDDP and 250 mg/body of 5-FU using arterial infusion were administered. It was discontinued for two days, as one course, and 4 courses were basally administered. The duration of the administration was 24 or 6 hours/day. Side effects consisted of nausea or loss of appetite for 7 (50%), suppression of bone marrow for 3 (21%), and they disappeared after the agents were discontinued. However, there were 3 patients with gastro-duodenal ulcer, so careful follow-up was necessary. The efficacy rate was 64% and two-year survival rate was 57% and thus this treatment seemed to be effective. Further study on the duration and dose of the administration is necessary to improve the therapeutic effect and QOL.

Aged↗

[Detection of thymidylate synthase mRNA in 5-fluorouracil resistant human colon adenocarcinoma cells].

To investigate the resistance against 5-fluorouracil (FU), thymidylate synthase (TS) mRNA level was measured by reverse transcription PCR (RT-PCR) technique and quantitated by a competitive-PCR method in human colon adenocarcinoma cell line, SNU-C1 and its FU resistant cell line, C1/FU. Using a set of primers covering 3'-untranslated region of mRNA, PCR products were amplified from cDNAs prepared from both SNU-C1 and C1/FU. However, only a cDNA extracted from C1/FU was amplified in a stationary growth phase. Then, the amount of mRNA was quantitated by competitive-PCR technique in both cell lines using another set of primer enable to amplify product in both stationary and logarithmic cell growth phase. The amount of mRNA in C1/FU was four times more than that of C1. The gene level in TS gene in genome DNA in these cell lines were not different incidentally. These data suggest that TS mRNA was more increased and can be more stable in C1/FU, accounting for FU resistance.

Adenocarcinoma↗

[A case of hepatocellular carcinoma whose lung metastases and tumor emboli in the inferior vena cava disappeared by oral administration of UFT].

A 65-year-old male with hepatocellular carcinoma was admitted to our hospital. Hepatic angiography showed a hypervascular tumor 8 cm in diameter in the right lobe of the liver with tumor emboli in the inferior vena cava and right atrium. Then, two chemoembolization treatments using gelform and cisplatin suspended in Lipiodol were performed. Although the size of the main tumor in the liver and tumor emboli was reduced, 6 months after the initial chemoembolization the serum levels of alfa-fetoprotein (AFP) and plasma des-gamma-carboxy prothrombin (DCP) rose to 14,000 ng/ml and 6.4 AU/ml, respectively, and multiple lung metastases were detected by CT scan. Then, 200 mg/day of UFT was administered orally. Four months after the administration, the levels of AFP and DCP markedly decreased to 95 ng/ml and 0.0 AU/ml, respectively, and the lung metastases and tumor emboli disappeared. Moreover, there were no side-effects including liver dysfunction.

Administration, Oral↗

Antitumor agents. 3. Synthesis and biological activity of 4 beta-alkyl derivatives containing hydroxy, amino, and amido groups of 4'-O-demethyl-4-desoxypodophyllotoxin as antitumor agents.

A series of 4 beta-alkyl (7-10), 4 beta-aminoalkyl (12a-y), and 4 beta-amidoalkyl derivatives (14a-g) of 4'-O-demethyl-4-desoxypodophyllotoxin have been synthesized, and their cytotoxicity, inhibition of DNA topoisomerase II (Topo II), and tubulin polymerization were evaluated. All derivatives of 12a-y and 14a-g did not inhibit tubulin polymerization. Many compounds exhibited cytotoxicity and inhibition of Topo II. In particular, 12o, 12s, 12t, and 12u strongly inhibited Topo II (IC50 (microM) 32.5, 60.9, 58.8, and 33.6, respectively) and were strong cytotoxicity against P388 cells (IC50 (M) 1.0, 4.1, 3.3, and 3.0 x 10(-9), respectively), compared with VP-16 (IC50 (microM) 59.2, IC50 (M) 1 x 10(-8), respectively). These compounds were nearly equal to or superior to VP-16 in antitumor activity in vivo (L1210, P388, and Lewis lung) and were more cytotoxic against various human cell lines in vitro than VP-16.

Animals↗