北山 丈二

66歳女.顔面・体幹・四肢に掻痒を伴う紅斑が出現し受診した.初診時現症としてGottron徴候,爪上皮の延長,爪郭部点状出血などを認め,臨床検査でCKとLDHの上昇を認めた.皮膚生検で基底層の液状変性と真皮上層のムチン沈着を,筋生検で筋線維の大小不同や硝子様変性を認めたため皮膚筋炎と診断した.全身精査で発見されたBorrmann 3型胃癌の全摘出術後,皮膚・筋症状は速やかに消失し,CKとLDHも正常化した

59歳女.3年ほど前から左乳房腫瘤が徐々に増大してきたため来院し,乳房X線像,超音波検査および吸引細胞診で乳癌と診断された.便潜血反応が陽性で,注腸検査・大腸内視鏡検査にてS状結腸に3/4周性で5cm長のpolypoid lesionを認め,C型肝炎による著明な腹水を伴う肝硬変も認められた.2ヵ月後に左乳癌に対して単純乳房切除術を施行し,病理検査所見ではT4bN1M0,stage IIIb,papillotubular carcinomaと診断された.術後7ヵ月,肝機能コントロール後に再入院し,S状結腸病変の精査では病変は全周性・15cm大に増大しており,傍大動脈に著明なリンパ節腫大を認めたため開腹手術を施行した.開腹時の腫瘍の進展度から根治性は望めず,消化管穿孔や出血の危険性があること,全身状態が不良であることなどを考慮し,Hartmann術を施行した.摘出標本の病理検査所見から乳癌のS状結腸転移と考えられた.本症例は開腹術後8ヵ月に癌性胸腹膜炎で死亡した

通常の病理組織学的診断において診断されなかったリンパ節転移が,免疫組織学的染色や分子生物学的手法により検出されるようになり,微小転移として臨床的に注目を浴びるようになってきた.大腸癌のリンパ節転移についてみると,免疫染色,MASA法,RT-PCR法による微小転移の検出報告がなされているが,免疫染色は予後との相関が論議中であり,他の二つは意義を問うには十分な情報が得られていないのが現状である.微小転移の臨床的意義については今後さらなる検討が必要である

Resistance to 5-fluorouracil (5-FU) has been frequently found in the treatment of digestive tract cancer patients. Our previous study suggested that high expression of endogenous Bcl-X-L, might be associated with resistance to 5-FU in colorectal cancer. The aim of this study is to analyze the role of Bcl-X-L in 5-FU resistance and to explore a new therapeutic strategy using Bcl-X-L antisense, First, western blot analysis shows that Bcl-X-L rather than Bcl-2 is overexpressed in primary adenocarcinoma of colon. Second, when Colo320 cells, with undetectable endogenous Bcl-X-L expression, were transfected with Bcl-X-L gene, they acquired high resistance to 5-FU, Finally, antisense oligodeoxynucleotides (ODNs) that targeted the start codon of Bcl-X-L mRNA (AS1) prove to be the most effective in DLD1 cells with high endogenous Bcl-X-L expression, Bcl-X-L protein expression was decreased in a dose-dependent manner when the cells mere treated with AS1 ODNs, while non sense and sense controls and 5-FU had no effect on Bcl-X-L protein. 5-FU treatment induced a level of apoptosis 10-fold higher in DLD1 cells than in untreated control cells, while the same dose of 5-FU induced a 55-fold higher level of apoptosis in DLD1 cells treated with Bcl-X-L antisense oligodeoxynucleotides (P=0.0003). Moreover, AS1 ODNs coupled with 5-FU decreased viable colon cancer cells 40% more than did 5-FU alone (P<0.05). These results suggest that Bcl-X-L is an important factor for 5-FU resistance and the suppression of Bcl-X-L expression by the specific antisense ODNs can increase the sensitivity of colon canter cells to 5-FU.

It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized, COX-1 and COX-2, Multiple studies have shown that COX-2 is expressed at high levels in colorectal tumours and play a role in colorectal tumorigenesis. Recently it has been reported that selective inhibition of COX-2 inhibits colon cancer cell growth. In this study we investigated the effect of a selective COX-2 inhibitor (JTE-522) on haematogenous metastasis of colon cancer. For this purpose, we selected a murine colon cancer cell line, colon-26, that constitutively expresses the COX-2 protein. The subclone P expressed a high level of COX-2 and the subclone 5 expressed a low level. The colon-26 subclones were injected into the tail vein of BALB/c mice. JTE-522 was given intraperitoneally every day from the day prior to cancer cell injection, and the mice were sacrificed 16 days after cell injection. Lung metastases were compared between groups with and without JTE-522. In the mice injected with subclone P, the number of lung metastatic nodules was significantly reduced in the treated group. However, in the mice injected with subclone 5, there was little difference between the control and the treated groups. These results indicate that there may be a direct link between inhibition of haematogenous metastasis of colon cancer and selective inhibition of COX-2, and that selective COX-2 inhibitors may be a novel class of therapeutic agents not only for colorectal tumorigenesis but also for haematogenous metastasis of colon cancer. (C) 1999 Cancer Research Campaign.