Showing papers by "Susumu Kobayashi published in 2001"

Clinical significance of serum vascular endothelial growth factor in esophageal squamous cell carcinoma.

Abstract: BACKGROUND Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis in malignant tumors. An increased in the serum VEGF concentration (S-VEGF) has been found in patients with various solid tumors and appears to be correlated with tumor burden. The objective of the current study was to determine the correlation between pretreatment S-VEGF and clinicopathologic features in patients with esophageal squamous cell carcinoma. METHODS Pretreatment S-VEGF was measured by enzyme-linked immunoadsorbent assay in 24 healthy controls and 96 patients with esophageal squamous cell carcinoma (82 patients with primary tumors and 14 with recurrent tumors). Chemoradiotherapy was performed in 35 patients followed by response evaluation. RESULTS S-VEGF was found to be significantly elevated in patients with primary esophageal carcinoma (P = 0.0011). Significant differences were observed when S-VEGF was categorized by tumor size (P = 0.0002), tumor depth (P = 0.0082), lymph node metastasis (P = 0.0002), distant metastasis (P = 0.028), and International Union Against Cancer TNM stage (P 451 pg/mL) S-VEGF level was associated with poor survival (P < 0.001). Multivariate analysis found S-VEGF to be a significant and independent prognostic factor (P < 0.001). CONCLUSIONS In the current study, a high S-VEGF was found to be associated with tumor progression, poor treatment response, and poor survival in patients with squamous cell carcinoma of the esophagus. Cancer 2001;92:663–9. © 2001 American Cancer Society.

Preclinical Study of Adenoviral p53 Gene Therapy for Esophageal Cancer

Abstract: An alteration of the p53 gene function is a major factor in the development of esophageal cancer. Recently, p53 gene therapy has been applied for clinical studies in lung cancer and head and neck cancer. However, no preclinical studies have yet demonstrated an anticancer effect of adenoviral-mediated wild-type p53 gene therapy on esophageal cancer. We herein evaluated the effect of p53 adenoviral gene therapy on human esophageal squamous cell carcinoma to test the ability of clinical application. A normal esophageal epithelial cell line (EN53F) and two human esophageal cancer cell lines (ECGI-10 and T.Tn) with a p53 alteration were used. The transduction efficiency, p53 protein expression, p21 protein expression, the induction of apoptosis, and growth suppression were assessed by using the recombinant adenoviral vector Ad5CMV-p53. The transduction efficiency was 60%-80% at 100 plaque-forming units (PFU)/cell and 80%-100% at 300PFU/cell. A significant growth suppression following an Ad5CMV-p53 infection was observed in both cancer cell lines. A Western blot analysis confirmed the presence of both exogenous p53 protein expression and p21 protein induction. Apoptotic cell death was observed with TUNEL staining. T.Tn xenografts in nude mice transduced with Ad5CMV-p53 demonstrated significant growth suppression. These data suggest that Ad5CMV-p53 may thus be a potentially effective therapeutic agent for locally advanced esophageal cancer.

Immortalization of human esophageal keratinocytes by E6 and E7 of human papillomavirus type 16.

Abstract: Transduction of human papillomavirus type 16 (HPV16) E6/E7 into primary culture of human esophageal keratinocytes using a recombinant adenovirus prolonged the life-span, while untreated cells senesced within 14-16 population doublings (PDLs). Up-regulation of telomerase activity and acquisition of serum-resistant growth were observed in the esophageal keratinocytes with extended life-span between 50 and 100 PDLs, and drastically increased after 100 PDLs. A keratinocyte sample with a polymorphism of Pro/Pro at codon 72 of p53 showed resistance to HPV16 E6/E7-induced life-span-extension and immortalization, in contrast to others with p53 polymorphisms of Arg/Arg or Arg/Pro, which did not. The high efficiency of E6/E7-induction by adenovirus vector also revealed the M1 and M2 stages of keratinocyte immortalization first described in this report.

Prophylactic excision of the gallbladder and bile duct for patients with pancreaticobiliary maljunction.

Abstract: Hypothesis Pancreaticobiliary maljunction (PBM) is a high-risk factor for biliary tract carcinogenesis because of a continuous reflux of pancreatic juice into the biliary tract. It remains to be disclosed whether we should perform prophylactic excision of gallbladders and bile ducts. Design A person-year method. Setting A university hospital. Patients We studied 68 patients with PBM treated between August 1, 1974, and December 31, 1999. Main Outcome Measures Relative risks (observed number–expected number ratios) of gallbladder and bile duct carcinomas according to type of bile duct dilation (ie, cystic dilation, diffuse dilation, and nondilation). Results Observed number–expected number ratios of gallbladder carcinomas were high: 291.3 in 43 patients with cystic dilation, 167.2 in 16 patients with diffuse dilation, and 419.6 in 7 patients with nondilation. Observed number–expected number ratios of bile duct carcinomas were 194.2 in 43 patients with cystic dilation before surgery and 142.8 in 39 patients with cystic dilation after long postsurgical follow-up. All these values were statistically significant ( P Conclusions The gallbladder carries a high risk for carcinogenesis in all types of dilation in patients with PBM. The bile duct carcinomas of PBM were exclusively identified by the type of cystic dilation. Prophylactic cholecystectomy should be recommended for all dilation types, and prophylactic excision of bile ducts including cholecystectomy should be performed in patients with PBM and cystic dilation. Complete excision of extrahepatic dilated bile ducts and careful follow-up for carcinogenesis in residual dilated bile ducts should be recommended for patients with PBM and cystic dilation.

P21WAF1/CIP1 messenger RNA expression in hepatitis B, C virus-infected human hepatocellular carcinoma tissues.

Abstract: BACKGROUND The primary objective of this study was to clarify the significance of p21WAF1/CIP1(p21) gene expression in the tumorgenicity of hepatitis B virus (HBV) and hepatitis C virus (HCV) infected human hepatocelluar carcinoma (HCC). METHODS The authors performed Northern blot hybridization to compare the p21 messenger (m) RNA expression levels among 16 HCC cases. They detected tissue HBVx mRNA (Northern blot) and plus- and minus-strand HCV RNA (reverse transcription–polymerase chain reaction) in liver tissues. They also measured alanine transaminase (ALT) levels and indocyanine green retention rate at 15 minutes (ICG-R15). RESULTS The p21 transcripts of tumor (T) tissues could be identified with lower intensity than nontumor (N) tissues in all 4 HBVx mRNA(+) cases, 8 of 10 HCV RNA(+) cases, and 1 of 3 B(−), C(−) cases (1 case was positive for both viruses). p21 mRNA expression levels of N tissues were significantly higher in HCV RNA(+) cases than in HBVx mRNA(+) cases. p21 mRNA expression levels of N tissues were significantly correlated with serum ALT levels. CONCLUSIONS In HCV hepatitis, p21 mRNA expression is up-regulated to control cell cycle under regeneration stress. Once the liver develops HCC, the p21 mRNA expression decreases to prominently low levels. The up-regulated p21 expression may play a role as a guard to prevent hepatocytes from tumorgenicity in HCV hepatitis. Cancer 2001;91:2096–103. © 2001 American Cancer Society.

A proposal of no-touch isolation technique in pancreatoduodenectomy for periampullary carcinomas.

Abstract: Background/Aims: The procedure of pancreatoduodenectomy for periampullary cancera accompanies a risk to shed cancer cells into a portal vein while handling the pancreas head lesion. This manipulation may subsequently cause a liver metastasis. We devised the no-touch isolation technique for pancreatoduodenectomy without removing a portal vein, for the purpase of preventing the manipulated shedding of cancer cells into a portal vein and liver metastasia. Methodology: The fundamental procedure of this technique is that isolation of portal vein precedes the handling of tumor mass. Isolation of a portal vein is carried out with the ligature of its surrounding veins after dividing of ducdenum and pancreas. We applied the no-touch isolation technique for 10 cases, which consisted of 6 cases of distal bile duet carcinoma and 4 cases of smpullary carcinoma, between May 1993 and July 2000. Results: There was neither operative mortality nor liver metastasis cases in these cases. Conclusions: The no-touch isolation technique without removing a portal vein might be recommended as a safe and reasonable procedure for periampullary cancer patients who have the potential for subsequent liver metastasis.

Total Synthesis of Madindoline A

Abstract: The total synthesis of madindolin A was achieved. Stereoselective construction of the quaternary carbon in the cyclopentenedione moiety was accomplished by alkylation of dienolate bearing a chiral auxiliary. The coupling of sterically hindered aldehyde 17 and acid-sensitive amine 30 was achieved by developing a new reductive amination method using Sn (OTf)2 and NaBH(OAc)3. After the reductive coupling, the cyclopentenedione skeleton of madindoline was constructed by intramolecular condensation of triketone 5.

Deacetylravidomycin M, a new inhibitor of IL-4 signal transduction, produced by Streptomyces sp. WK-6326. I. Taxonomy, fermentation, isolation and biological activities.

Abstract: Streptomyces sp. WK-6326, a soil isolate, was found to produce an inhibitor of interleukin (IL)-4 signal transduction. Two structurally related compounds, a novel one designated deacetylravidomycin M and the known deacetylravidomycin, were isolated from the culture broth by solvent extraction, silica gel column chromatography and HPLC. Deacetylravidomycin M inhibited IL-4-induced CD23 expression in U937 cells without any cytotoxic effect, whereas deacetylravidomycin showed no inhibitory activity.

Arterio-portal shunt in liver rescued by hepatectomy after arterial embolization.

Abstract: Arterio-portal shunts are generally treated with transcatheter arterial embolization, as a therapeutic measure for bleeding of esophageal varices. However, transcatheter arterial embolization is frequently associated with reestablishment of arterio-portal shunts. We now report our experience with partial hepatectomy to remove the arterio-portal shunt associated with esophageal varices, which recurred after transcatheter arterial embolization. The patient was a 60-year-old female, who had massive hematemesis caused by rupture of esophageal varices. Doppler sonography and arteriography demonstrated an arterio-portal shunt in the right anterior superior segment of the liver. Temporary hemostasis was achieved with transcatheter arterial embolization, however, hemorrhage recurred one month later. The second transcatheter arterial embolization failed to manage the shunt and varices. The patient developed hepatic coma. After recovery from coma, she was referred to our hospital. We carried out partial hepatectomy, which provided remarkable hemodynamic improvement; the portal vein flow changed from hepatofugal to hepatopetal. Esophageal varices and hepatic coma have totally disappeared. This patient has had no complaint and has remained free of esophageal varices, for 3 years postoperatively. She is having a normal life. The partial hepatectomy to remove the arterio-portal shunt induced complete resolution of the arterio-portal shunt, as well as dramatic improvement in portal flow and hepatic coma. Our experience in the present case suggests that partial hepatectomy should be considered as a radical therapy for arterio-portal shunt, without insistence on transcatheter arterial embolization.

Copper metabolism after living donor liver transplantation for hepatic failure of Wilson's disease from a gene mutated donor

Abstract: There is a genetic problem in living donor liver transplantation, involving Wilson's disease, because the majority of donors have a kinship relationship Recently, it was reported that the serum ceruloplasmin level is insufficient in some persons with one allele mutation The recipient was a 13-year-old male child, and the donor was a 22-year-old woman, who was his sister by a different father The gene analysis for Wilson's disease (ATP7B gene) was preoperatively carried out by the amplification refractory mutation system-PCR Homozygous and heterozygous deletion of 2871 cytosine (C) were detected in the recipient and donor, respectively, in the ATP7B gene Serum ceruloplasmin level was sufficient in the donor The right hepatic lobe graft was transplanted to the recipient Immediately after the liver transplantation, the copper metabolism improved to increase the serum ceruloplasmin levels up to the normal range, and decrease the urinary copper excretion However, the serum ceruloplasmin levels gradually decreased below the normal base line, although the urine copper levels continued to be low without any clinical symptoms We should perform gene analyses and confirm the serum ceruloplasmin levels in donors before living donor liver transplantation for Wilson's disease, to screen for their impairment of copper metabolism After living donor liver transplantation for Wilson's disease, we should carefully follow-up the transition of serum ceruloplasmin levels in the recipient

Deacetylravidomycin M, a new inhibitor of IL-4 signal transduction, produced by Streptomyces sp. WK-6326. II. Structure elucidation.

Abstract: The structure of deacetylravidomycin M, an inhibitor of interleukin-4 signal transduction, was elucidated to be 6H-benzo[d]naphtho[l, 2-b]pyran-6-one, 4-[3, 6-dideoxy-3-(dimethylamino)-α-altropyranosyl]-l-hydroxy-10, 12-dimethoxy-8-methyl- by spectroscopic studies including NMR measurements.

A study of metallic stents for the treatment of benign biliary stricture

Abstract: 良性胆管狭窄に対するメタリックステント(以下MS)留置の長期観察例を経験したので報告する.対象は7症例で,同時期に開腹下に胆管消化管バイパスをおいた7症例を対照群として成績を比較した.観察期間は8カ月から9年で原疾患は胆管空腸吻合後狭窄が3例,腫瘤形成性膵炎が2例,胆道結石術後が2例であった.留置前後のmortalityは0%, morbidityは14%であった.入院から治療完了までと入院期間は対照群に比べ有意に延長していた.再狭窄は1例に認め,開存率は1, 3, 5年それぞれ83.3%, 80.0%, 75%で,対照群は100%であった.外来では全例利胆薬と緩下剤にて胆汁の鬱滞を予防しており,胆汁の流出能の評価には胆道シンチグラフィーが有用であった.良性胆管狭窄に対するMS留置は論議の分かれるところであるが,われわれは2例の9年以上を含む経過良好な症例を経験し,注意深い術後の管理によって長期のpatencyを保ちうることが示唆された.

Clinicopathological Investigation of Tumor Angiogenesis and p53 Protein Expression in Tubular Adenocarcinoma of the Pancreas.

Abstract: 膵管状腺癌97例に対して, p53および腫瘍血管新生の評価としてCD34の免疫染色を行い, p53 labelling index とintratumoral microvessel density (IMD) を求め, 予後および臨床病理学的因子との関連, について検討した. 単変量解析では腫瘍部位, ts, v, ne, pw, stage, p53蛋白発現, IMDの8因子が有意で, 多変量解析ではpwとIMDの2因子が独立した予後因子であった (p<0.05). 肝再発および臨床病理学的因子との関連ではp53蛋白発現とIMDのいずれも術後肝転移率およびv因子と有意に相関した (p<0.05). またp53蛋白発現とIMDの間にも有意な相関を認めた (p=0.0004). 以上より膵管状腺癌ではp53の異常が腫瘍血管新生と静脈浸潤を促進し, 術後肝転移に影響している可能性が示唆された.

Asymmetric Total Synthesis of 9-Methoxystrobilurin K.

Abstract: Asymmetric total synthesis of a potent antifungal and cytostatic 9-methoxystrobilurin K was achieved by developing a convergent and versatile synthetic route.

Stereochemical Control of Tertiary Alcohol: Aldol Condensation of Lactate Derivatives.

Abstract: Stereoselective construction of aldol adducts having tertiary alcohol at the α position was achieved via a titanium(IV) enolate derived from a lactate derivative with an Evans chiral auxiliary. The stereochemistry at α-tertiary alcohol could be controlled by selecting the protective group of the starting lactate.