JPH0921806A - Tissue examination method - Google Patents
Tissue examination methodInfo
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- JPH0921806A JPH0921806A JP7192642A JP19264295A JPH0921806A JP H0921806 A JPH0921806 A JP H0921806A JP 7192642 A JP7192642 A JP 7192642A JP 19264295 A JP19264295 A JP 19264295A JP H0921806 A JPH0921806 A JP H0921806A
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- Prior art keywords
- tissue
- vpf
- breast cancer
- diagnosis
- tumor
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、組織抽出液中におけ
る、血管新生を誘導する因子として知られている血管内
皮細胞増殖因子あるいは血管透過性因子(vascular endo
thelial growthfactor or vascular permeability fact
or, 以下ＶＰＦと略す)と呼ばれている因子の存在量を
測定することにより、当該組織の腫瘍状態を予測する方
法に関するものであり、医薬業界、特に検査薬業界さら
には生化学検査業界において利用されるものである。FIELD OF THE INVENTION The present invention relates to a vascular endothelial growth factor or vascular endothelium factor, which is known as a factor for inducing angiogenesis in a tissue extract.
thelial growthfactor or vascular permeability fact
or, hereinafter, abbreviated as VPF), the present invention relates to a method for predicting the tumor state of a relevant tissue by measuring the abundance of a factor, which is used in the pharmaceutical industry, particularly in the test drug industry and further in the biochemical test industry. It is used.
【０００２】[0002]
【従来の技術】最近、生体内に存在する生理活性物質す
なわち非常に微量で薬理作用を現わす物質などの微量物
質を診断マーカーや治療効果の判定あるいは術後のモニ
タリングなどの指標として用いることが広く行われてい
る。一方、血管新生すなわち毛細血管内皮細胞の増殖、
移動および組織への浸潤という現象は胎児の生長、創傷
治癒、癌細胞の増殖などの生理的または病理的現象にお
いて重要な役割を果たしていることが知られ[(Folkman,
J.,Cancer Res.46:467(1986)]、血管新生を誘導する因
子として、直接的に血管内皮細胞に作用する塩基性線維
芽細胞増殖因子(basic fibroblast growth factor,bFG
F)、酸性線維芽細胞増殖因子(acidic fibroblast growt
h factor,aFGF)、血小板由来内皮細胞増殖因子(platele
t-derived endothelial cell growth factor,PD-ECGF)
などが、また間接的に血管内皮細胞に作用する物質とし
てtransforming growth factor-α(TGF-α)、transform
ing growth factor-β(TGF-β)、angiogenin、tumor ne
crosis factor-α(TNF-α)などが見つけられている[Fol
kman,J. & Shing,Y.,J.Biol.Chem.,267:10931(1992)]。2. Description of the Related Art In recent years, it has been known to use a trace amount of a physiologically active substance present in a living body, that is, a substance exhibiting a pharmacological action in a very small amount, as a diagnostic marker, an indicator for judging a therapeutic effect or monitoring after surgery. Widely used. On the other hand, angiogenesis, the proliferation of capillary endothelial cells,
The phenomena of migration and tissue invasion are known to play important roles in physiological or pathological phenomena such as fetal growth, wound healing, and cancer cell proliferation [(Folkman,
J., Cancer Res. 46: 467 (1986)], basic fibroblast growth factor (bFG) acting directly on vascular endothelial cells as a factor inducing angiogenesis.
F), acidic fibroblast growt
h factor, aFGF), platelet-derived endothelial cell growth factor (platele
t-derived endothelial cell growth factor, PD-ECGF)
But also as a substance that acts indirectly on vascular endothelial cells, transforming growth factor-α (TGF-α), transform
ing growth factor-β (TGF-β), angiogenin, tumor ne
crosis factor-α (TNF-α) has been found [Fol
kman, J. & Shing, Y., J. Biol. Chem., 267: 10931 (1992)].
【０００３】これらのなかでもＶＰＦは、マウス、ラッ
ト、モルモット、ウシおよびヒトの正常または腫瘍細胞
株で分泌されており、また組織別では脳、下垂体、腎
臓、卵巣に存在することが明らかにされており[(Ferrar
a,N., et.al. Endocrine Reviews 13:18(1992)]、ヒト
ＶＰＦは乳癌の血管新生と転移[Weider,N, et.al. N.En
gl.J.Med. 324:1(1991)]や腎細胞癌の血管新生[医学の
あゆみ,168:231(1994)]、あるいは網膜疾患における血
管新生[Adamis,A.P. et.al., Biochem.Biophys.Res.Com
m.,193:631(1993)]に関与していることが報告されてい
る。これらのことより、腫瘍細胞株で分泌されたＶＰＦ
量を測定することは、癌の診断や転移の予測あるいは治
療効果の判定などに有用であるとされ種々の検討がなさ
れている。さらに、血管新生のマーカーとして腫瘍組織
内の微小血管密度が予後因子として注目されており、乳
癌においても微小血管密度が高い患者は予後が悪いこと
が報告されている。また、乳癌の場合、ＶＰＦの発現と
微小血管密度に高い相関性があることが示されている(T
oi et al., Jpn J. Cancer Res, vol. 85, p.1045-104
9, 1994)。[0003] Among them, VPF is secreted in normal or tumor cell lines of mouse, rat, guinea pig, bovine and human, and is clearly found to exist in brain, pituitary gland, kidney and ovary by tissue. [(Ferrar
a, N., et.al. Endocrine Reviews 13:18 (1992)], human VPF is angiogenesis and metastasis of breast cancer [Weider, N, et.al. N.En.
gl.J.Med. 324: 1 (1991)] and angiogenesis of renal cell carcinoma [Ayumi of Medicine, 168: 231 (1994)], or angiogenesis in retinal diseases [Adamis, AP et.al., Biochem. Biophys.Res.Com
m., 193: 631 (1993)]. Based on these facts, VPF secreted by tumor cell lines
Measuring the amount is considered to be useful for diagnosing cancer, predicting metastasis, or judging the therapeutic effect, and various studies have been made. Furthermore, microvascular density in tumor tissue has been attracting attention as a prognostic factor as a marker of angiogenesis, and it has been reported that patients with high microvascular density also have poor prognosis in breast cancer. In the case of breast cancer, it has been shown that there is a high correlation between the expression of VPF and the density of microvessels (T
oi et al., Jpn J. Cancer Res, vol. 85, p. 1045-104
9, 1994).
【０００４】しかしながら、ＶＰＦの発現や微小血管密
度の測定は、各々ＶＰＦ及びfactorＶIIIに対する特異
抗体を用いた免疫組織染色法により測定しているため、
定量性が悪く、再現性のよい測定をすることが非常に困
難なものである。However, VPF expression and microvessel density are measured by immunohistochemical staining using specific antibodies against VPF and factor VIII, respectively.
It is very difficult to measure with good reproducibility because of poor quantitativeness.
【０００５】[0005]
【発明が解決しようとする課題】本発明者らは乳癌の診
断、特に予後の診断に有効に利用される方法として、腫
瘍組織内ＶＰＦの発現や微小血管密度を測定する代わり
に、より簡便で定量性のある方法を見いだすために検討
を行ったのである。DISCLOSURE OF THE INVENTION As a method effectively used for the diagnosis of breast cancer, in particular, the diagnosis of prognosis, the present inventors have adopted a simpler method instead of measuring the expression of VPF in tumor tissue and the microvessel density. The study was conducted in order to find a quantitative method.
【０００６】[0006]
【課題を解決するための手段】本発明者等は、腫瘍組織
内ＶＰＦ濃度を測定することにより、当該組織の腫瘍状
態を予測することができ、更には乳癌の診断、特に予後
の診断にそれがが応用し得ることを見出して本発明を完
成したのである。すなわち、本発明は、ヒト組織抽出液
中のＶＰＦ(血管透過性因子)の存在量を測定して当該組
織の腫瘍状態を予測することを特徴とする組織検査方法
に関するものである。[Means for Solving the Problems] The present inventors can predict the tumor state of a tumor tissue by measuring the VPF concentration in the tumor tissue, and further use it for the diagnosis of breast cancer, especially for the diagnosis of prognosis. The present inventors have completed the present invention by finding that they can be applied. That is, the present invention relates to a tissue inspection method characterized by measuring the amount of VPF (vascular permeability factor) present in a human tissue extract to predict the tumor state of the tissue.
【０００７】以下に本発明について詳細に説明する。本
発明において、ＶＰＦの測定には、標識免疫測定法を用
いるのが好ましく、標識免疫測定法としては、ヒトＶＰ
Ｆに対するモノクローナル抗体やポリクローナル抗体を
用いたサンドイッチ法等の酵素免疫測定法を挙げること
ができる。ヒトＶＰＦに関しては、その遺伝子について
は cＤＮＡがすでに単離されて塩基配列が決定され、ア
ミノ酸配列も推定されている。この遺伝子からアミノ酸
残基数の異なる４種類の蛋白(アミノ酸残基数が１２１
個、１６５個、１８９個、２０６個の４種類)が作ら
れ、それらの中で１２１個のアミノ酸残基数のもの(Ｖ
ＰＦ121)と１６５個のアミノ酸残基数のもの(ＶＰＦ16
5)が成熟蛋白であると言われており[(Ferrara,N., et.a
l. Endocrine Reviews 13:18(1992)]、本発明等は、既
に、ヒトＶＰＦ121に対するモノクローナル抗体及びポ
リクローナル抗体を取得しており、そのモノクローナル
抗体およびヒトＶＰＦ121に対するポリクローナル抗体
を用いた酵素免疫測定法によりＶＰＦが測定できること
を明らかにしており(特許出願済「ペプチドおよびモノ
クローナル抗体」出願日平成６年６月１０日)、さらに
酵素免疫測定法におけるＶＰＦの検出法において、数pg
/mlのＶＰＦを検出できる方法を明らかにしており(特許
出願済「血管透過性因子の測定方法」出願日平成７年５
月１６日)、それらの抗体や測定法が本発明にも適用さ
れ且つ本発明にとり好ましい方法である。標識免疫測定
法によりＶＰＦを測定する際の標識としては赤血球、ラ
テックス、放射性同位元素、酵素、発光物質、蛍光物
質、金属分子、金属ゲル、バクテリオファージなどが挙
げられるか、発光物質を用いるのが好ましい。すなわ
ち、本発明者等が先に提案した酵素の基質として発光基
質を用いて発生する光を測定する化学発光を応用した測
定方法、化学発光検出系酵素免疫測定法が好ましい方法
である。Hereinafter, the present invention will be described in detail. In the present invention, it is preferable to use a labeled immunoassay for the measurement of VPF.
An enzyme immunoassay such as a sandwich method using a monoclonal antibody or a polyclonal antibody against F can be mentioned. Regarding human VPF, cDNA for the gene has already been isolated and its nucleotide sequence has been determined, and its amino acid sequence has also been deduced. From this gene, four kinds of proteins with different numbers of amino acid residues (with 121 amino acid residues
, 165, 189, and 206), and 121 amino acid residues (V
PF121) and 165 amino acid residues (VPF16
5) is said to be a mature protein [(Ferrara, N., et.a
l. Endocrine Reviews 13:18 (1992)], the present invention has already obtained a monoclonal antibody and a polyclonal antibody against human VPF121, and the enzyme immunoassay method using the monoclonal antibody and the polyclonal antibody against human VPF121. It has been clarified that VPF can be measured (patent pending “Peptide and monoclonal antibody” filing date June 10, 1994). Furthermore, in the method for detecting VPF in enzyme immunoassay, several pg
We have clarified a method that can detect VPF / ml VPF (patent pending “Measurement method of vascular permeability factor” filing date 5/1995)
(May 16), those antibodies and assay methods are applicable to the present invention and are preferable methods for the present invention. Labels for measuring VPF by labeling immunoassay include erythrocytes, latex, radioisotopes, enzymes, luminescent substances, fluorescent substances, metal molecules, metal gels, bacteriophages, etc., or use luminescent substances. preferable. That is, preferred methods are a measurement method using chemiluminescence, which measures light generated by using a luminescent substrate as a substrate of the enzyme, and a chemiluminescence detection system enzyme immunoassay proposed by the present inventors.
【０００８】[0008]
【作用】本発明によれば、ヒト組織抽出液中のＶＰＦ
を、微量のものでも高感度に測定することができ、その
測定値から当該組織の腫瘍状態を予測でき、それを利用
して乳癌を診断し、乳癌の予後が予測できるのである。According to the present invention, VPF in human tissue extract is
Can be measured with high sensitivity even with a small amount, and the tumor state of the tissue can be predicted from the measured value, and breast cancer can be diagnosed and the prognosis of breast cancer can be predicted by using the measured value.
【０００９】[0009]
（１）抗ＶＰＦポリクローナル抗体の作製 単離したヒトＶＰＦ cＤＮＡをグルタチオンＳ-トラン
スフェラーゼ(ＧＳＴ)との融合蛋白(ＧＳＴ−ＶＰＦ)と
して大腸菌で産生させ、得られた蛋白を抗原として常法
に従ってウサギ抗ＶＰＦポリクローナル抗体を作製し
た。抗体価の上昇したウサギの血清を分離し、陰イオン
交換カラムクロマトグラフィーによりウサギ抗ＶＰＦポ
リクローナル抗体のＩgＧ画分を得た。(1) Preparation of anti-VPF polyclonal antibody The isolated human VPF cDNA was produced in Escherichia coli as a fusion protein (GST-VPF) with glutathione S-transferase (GST). VPF polyclonal antibodies were produced. The serum of the rabbit with an increased antibody titer was separated, and an IgG fraction of a rabbit anti-VPF polyclonal antibody was obtained by anion exchange column chromatography.
【００１０】（２）抗ＶＰＦポリクローナル抗体の酵素
標識 ＩgＧ画分の一部をペプシンで消化してＦ(ab')2を調製
後、ヒンジ法によりアルカリフォスファターゼ(ウシ小
腸由来)と結合させ、アルカリフォスファターゼ標識し
たウサギ抗ＶＰＦポリクローナル抗体を得た。(2) Enzyme Labeling of Anti-VPF Polyclonal Antibody A part of the IgG fraction is digested with pepsin to prepare F (ab ') 2, which is then ligated with alkaline phosphatase (from bovine small intestine) by the hinge method. A phosphatase-labeled rabbit anti-VPF polyclonal antibody was obtained.
【００１１】（３）腫瘍組織内ＶＰＦ濃度の測定 乳癌患者から摘出した腫瘍組織中のＶＰＦ濃度を以下に
示すように、化学発光検出法を用いた酵素免疫測定法に
より測定した。腫瘍組織(０.２g)は0.２５％Ｔriton Ｘ
−１００を含む５０mM Ｔris−Ｃl, pＨ７.４(２ml)中
でホモジナイズして抽出し、試料とした。抗ＶＰＦポリ
クローナル抗体(５μg/ml)を１００μl/wellずつ９６穴
プレートにまき４℃で一晩放置した後、０.１％ウシ血
清アルブミン(ＢＳＡ)、ＰＢＳで４回洗浄した。１％Ｂ
ＳＡ、０.１M塩化ナトリウム、０.１％アジ化ナトリウ
ム、０.２Ｍ炭酸ナトリウム緩衝液 PＨ９.５でブロッキ
ング（室温で１時間）した後、１％ウシ血清アルブミ
ン、０.４％ゲラチン、１mM塩化マグネシウム、２０mM
エチレンジアミン四酢酸ナトリウム、０.１M塩化ナトリ
ウム、０.１％アジ化ナトリウムを含む５０mMリン酸ナ
トリウム緩衝液 pＨ７.０（検体希釈液）で１０倍に希
釈した腫瘍組織抽出液あるいは同検体希釈液に溶解した
標準ＶＰＦを入れ室温で１時間放置した。０.０５％ツ
イーン２０、０.１４M塩化ナトリウム、５mM塩化カリウ
ムを含むトリス緩衝液 pＨ７.４（ＴＢＳ−Ｔ）で４回
洗浄後、アルカリフォスファターゼ標識抗ＶＰＦポリク
ローナル抗体を１００μl/wellずつ入れ室温で１時間反
応させた。ＴＢＳ−Ｔで４回、さらに０.１４M塩化ナト
リウム、５ｍＭ塩化カリウムを含むトリス緩衝液 pＨ
７.４で２回洗浄した後、１ｍＭ塩化マグネシウム、０.
０２％アジ化ナトリウムを含む０.１Mジエタノールアミ
ン緩衝液 pＨ１０.０で５倍に希釈したルミフォス５３
０（和光純薬工業（株）製）を１００μl/wellずつ入
れ、３７℃で３０分間放置後、発光強度を測定した。(3) Measurement of VPF concentration in tumor tissue VPF concentration in tumor tissue excised from a breast cancer patient was measured by enzyme immunoassay using chemiluminescence detection method as shown below. Tumor tissue (0.2g) was 0.25% Triton X
A sample was prepared by homogenizing and extracting in 50 mM Tris-Cl, pH 7.4 (2 ml) containing -100. 100 μl / well of anti-VPF polyclonal antibody (5 μg / ml) was spread on a 96-well plate and left overnight at 4 ° C., and then washed 4 times with 0.1% bovine serum albumin (BSA) and PBS. 1% B
After blocking with SA, 0.1M sodium chloride, 0.1% sodium azide, 0.2M sodium carbonate buffer pH 9.5 (1 hour at room temperature), 1% bovine serum albumin, 0.4% gelatin and 1 mM. Magnesium chloride, 20 mM
Tumor tissue extract or the same sample diluent diluted 10-fold with 50 mM sodium phosphate buffer containing 7.0% sodium ethylenediamine tetraacetate, 0.1 M sodium chloride and 0.1% sodium azide, pH 7.0 (sample diluent). The dissolved standard VPF was added and left at room temperature for 1 hour. After washing 4 times with Tris buffer pH 7.4 (TBS-T) containing 0.05% Tween 20, 0.14 M sodium chloride, 5 mM potassium chloride, 100 μl / well of alkaline phosphatase-labeled anti-VPF polyclonal antibody was added at room temperature. The reaction was carried out for 1 hour. Tris buffer containing TBS-T four times and 0.14 M sodium chloride and 5 mM potassium chloride
After washing twice with 7.4, 1 mM magnesium chloride, 0.1.
Lumiphos 53 diluted 5 times with 0.1 M diethanolamine buffer pH 10.0 containing 02% sodium azide.
0 (manufactured by Wako Pure Chemical Industries, Ltd.) was put in 100 μl / well and left at 37 ° C. for 30 minutes, and then the emission intensity was measured.
【００１２】（４）腫瘍組織内ＶＰＦの発現の測定 腫瘍組織内ＶＰＦの発現は間接免疫組織染色法により乳
癌組織凍結切片をマウス抗ＶＰＦモノクローナル抗体で
免疫染色することにより行った。ＶＰＦ発現は染色の濃
淡に従い、＋または−で表示した。(4) Measurement of VPF Expression in Tumor Tissue Expression of VPF in tumor tissue was carried out by immunostaining a frozen section of breast cancer tissue with a mouse anti-VPF monoclonal antibody by the indirect immunohistological staining method. VPF expression was indicated by + or-according to the intensity of staining.
【００１３】（５）腫瘍組織内微小血管密度の測定 腫瘍組織内微小血管密度の測定は間接免疫組織染色法に
より乳癌組織凍結切片内のfactorＶIII抗原を測定する
ことにより行った。すなわち、乳癌組織凍結切片をヒト
factorＶIII抗原に対するモノクローナル抗体(Dako Jap
an, Tokyo)で免疫染色を行い、顕微鏡下で３カ所の１.
０mm2領域内に存在する染色された細胞の数をカウント
した。(5) Measurement of Microvessel Density in Tumor Tissue The microvessel density in tumor tissue was measured by measuring factor VIII antigen in frozen sections of breast cancer tissue by an indirect immunohistological staining method. That is, a frozen section of breast cancer tissue
Monoclonal antibody against factor VIII antigen (Dako Jap
immunostaining at (an, Tokyo) and under the microscope at 1.
The number of stained cells present within the 0 mm 2 area was counted.
【００１４】（６）腫瘍組織内ＶＰＦ発現および微小血
管密度と腫瘍組織抽出液中ＶＰＦ濃度との相関 乳癌腫瘍組織１３０例を用いて、腫瘍組織内ＶＰＦ発
現、微小血管密度および組織抽出液中ＶＰＦ濃度を測定
した結果、表１のようになった。微小血管密度は１００
カウント以下または１０１カウント以上で表示した。微
小血管密度が１００カウント以下の検体と１０１カウン
ト以上の検体との間で組織抽出液中ＶＰＦ濃度に有意な
差が見られた。また、同様に、ＶＰＦ発現の有無と組織
抽出液中ＶＰＦ濃度との間でも組織抽出液中ＶＰＦ濃度
に有意な差が見られた。したがって、微小血管密度ある
いはＶＰＦ発現を測定する代わりに、組織抽出液中ＶＰ
Ｆ濃度を測定する方法を用いることができることがわか
った。(6) Correlation between VPF expression in tumor tissue and microvessel density and VPF concentration in tumor tissue extract Using 130 cases of breast cancer tumor tissue, VPF expression in tumor tissue, microvessel density and VPF in tissue extract As a result of measuring the concentration, the results are shown in Table 1. Microvessel density is 100
It is displayed below the count or above 101 counts. A significant difference was observed in the VPF concentration in the tissue extract between the sample having a microvessel density of 100 counts or less and the sample having a microvessel density of 101 counts or more. Similarly, a significant difference was found in the VPF concentration in the tissue extract between the presence or absence of VPF expression and the VPF concentration in the tissue extract. Therefore, instead of measuring microvessel density or VPF expression, VP in tissue extract
It has been found that a method of measuring F concentration can be used.
【００１５】[0015]
【表１】 [Table 1]
【００１６】[0016]
【発明の効果】本発明によれば、腫瘍組織内ＶＰＦの発
現や微小血管密度を測定する代わりに、腫瘍組織抽出液
中のＶＰＦ濃度を測定することにより、両者よりも血管
発生の定量が簡便に且つ良好にでき、乳癌の診断および
乳癌の予後の診断に応用でき、本発明方法を利用した乳
癌の診断は、これまで乳癌の診断に用いられてきた微小
血管密度測定に代わる検査方法として臨床上非常に有用
なものである。INDUSTRIAL APPLICABILITY According to the present invention, instead of measuring the expression of VPF in tumor tissue and the microvessel density, the concentration of VPF in the tumor tissue extract is measured, whereby the quantification of blood vessel development is easier than both. And can be applied to the diagnosis of breast cancer and the prognosis of breast cancer, and the diagnosis of breast cancer using the method of the present invention is a clinical method as an alternative to the microvessel density measurement which has been used for the diagnosis of breast cancer. Above is very useful.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 大森 巌 茨城県つくば市大久保２番 東亞合成株式 会社つくば研究所内 (72)発明者 松尾 克彦 茨城県つくば市大久保２番 東亞合成株式 会社つくば研究所内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Iwao Omori Iku Omori, Tsukuba City, Ibaraki Prefecture 2nd Okubo Synthetic Co., Ltd. Tsukuba Research Institute (72) Inventor Katsuhiko Matsuo 2 Okubo, Tsukuba City Ibaraki Toagosei Co. Ltd. Tsukuba Synthetic Co., Ltd.
Claims (1)
量を測定して当該組織の腫瘍状態を予測することを特徴
とする組織検査方法。1. A tissue examination method, which comprises predicting a tumor state of a tissue by measuring the amount of a vascular permeability factor present in a human tissue extract.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7192642A JPH0921806A (en) | 1995-07-06 | 1995-07-06 | Tissue examination method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7192642A JPH0921806A (en) | 1995-07-06 | 1995-07-06 | Tissue examination method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0921806A true JPH0921806A (en) | 1997-01-21 |
Family
ID=16294652
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7192642A Pending JPH0921806A (en) | 1995-07-06 | 1995-07-06 | Tissue examination method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0921806A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023067865A1 (en) | 2021-10-21 | 2023-04-27 | 横浜ゴム株式会社 | Flush switch for aircraft lavatory unit |
-
1995
- 1995-07-06 JP JP7192642A patent/JPH0921806A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023067865A1 (en) | 2021-10-21 | 2023-04-27 | 横浜ゴム株式会社 | Flush switch for aircraft lavatory unit |
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