Akio Ogawa

Lithocholic acid, a putative tumor promoter, inhibits mammalian DNA polymerase β

Lithocholic acid (LCA), one of the major components in secondary bile acids, promotes carcinogenesis in rat colon epithelial cells induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG), which methylates DNA. Base‐excision repair of DNA lesions caused by the DNA methylating agents requires DNA polymerase β (pol β). In the present study, we examined 17 kinds of bile acids with respect to inhibition of mammalian DNA polymerases in vitro. Among them, only LCA and its derivatives inhibited DNA polymerases, while other bile acids were not inhibitory. Among eukaryotic DNA polymerases α, β, δ, η, and γ, pol β was the most sensitive to inhibition by LCA. The inhibition mode of pol β was non‐competitive with respect to the DNA template‐primer and was competitive with the substrate, dTTP, with the Ki value of 10 μM. Chemical structures at the C‐7 and C‐12 positions in the sterol skeleton are important for the inhibitory activity of LCA. This inhibition could contribute to the tumor‐promoting activity of LCA.

Sulfated glycoglycerolipid from Archaebacterium inhibits eukaryotic DNA polymerase α, β and retroviral reverse transcriptase and affects methyl methanesulfonate cytotoxicity

A sulfated glycoglycerolipid, 1‐O‐(6′‐sulfo‐α‐d‐glucopyranosyl)‐2,3‐di‐O‐phytanyl‐sn‐glycerol (KN‐208), a derivative of the polar lipid isolated from an archaebacterium, strongly inhibited DNA polymerase (pol) α and pol β in vitro among 5 eukaryotic DNA polymerases (α, β, γ, δ, and ϵ). It also inhibited Escherichia coli DNA polymerase I Klenow fragment (E. coli pol I) and human immunodeficiency virus reverse transcriptase (HIV RT). The mode of inhibition of these polymerases was competitive with the DNA template primer and was non‐competitive with the substrate dTTP. KN‐208 inhibited pol β most strongly, with a Ki value of 0.05 μM, 10‐fold lower than that for pol α (0.5 μM) and 60‐ or 140‐fold lower than that for HIV RT (3 μM) or for E. coli pol I (7 μM), respectively. The loss of sulfate on the 6′‐position of glucopyranoside of this compound completely abrogated inhibition. However, the hydrophilic part of KN‐208, glucose 6‐sulfate alone, showed no inhibition. Other sulfated compounds containing different hydrophobic structures, such as dodecyl sulfate and cholesterol sulfate, exhibited a much weaker inhibition. Our results suggest that the whole molecular structure of KN‐208 is required for inhibition. KN‐208 was shown to be modestly cytotoxic for the human leukemic cell line K562. Interestingly, a subcytotoxic dose of KN‐208 increased the sensitivity of the human leukemic cells to an alkylating agent, methyl methanesulfonate, while it did not potentiate the effects of ultraviolet light or of cisplatin. Int. J. Cancer 76:512–518, 1998.© 1998 Wiley‐Liss, Inc.

Primary Malignant Lymphoma of the appendix. A Case Report.

症例は61歳の男性. 平成11年6月右下腹部痛を主訴に近医より当院紹介受診した. 右下腹部に有痛性の腫瘤を触知し急性虫垂炎の術前診断にて同日虫垂切除術を施行した. 病理組織学的には悪性リンパ腫 (diffuse large cell type) であった.腫大した体表リンパ節は触知せず術前の胸部単純X線写真, 他の消化管精査, 腹部CTにても異常所見認めず, 虫垂原発悪性リンパ腫と診断された. 術後化学療法追加した.虫垂原発悪性リンパ腫の本邦報告例は自験例を含め32例で, 文献的考察を含め報告する.

Carcinoma of the head of the pancreas with complete situs inversus and polycystic liver: Case report

A case of carcinoma of the pancreatic head associated with situs inversus (SI) and polycystic liver (PCL) is presented. The patient was a 71-year-old male with complaints of jaundice and general fatigue. Percutaneous transhepatic biliary drainage (PTBD) revealed complete obstruction of the lower end of the common bile duct (CBD). Endoscopic retrograde cholangiopancreatography (ERCP) revealed stenosis of the main pancreatic duct (MPD) in the head of the pancreas. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated multiple cysts in the liver as well as SI. Pylorus-preserving-pancreatoduodenectomy (PPPD) was performed by an operator who took his usual position on the patients right side. We had no particular difficulty during surgery, although we had to charge several procedures. We consider it reliable to take the usual positions during surgery, even in cases of SI.