JPH11171788A - Relapse suppressant for hepatocellular carcinoma c - Google Patents
Relapse suppressant for hepatocellular carcinoma cInfo
- Publication number
- JPH11171788A JPH11171788A JP9341386A JP34138697A JPH11171788A JP H11171788 A JPH11171788 A JP H11171788A JP 9341386 A JP9341386 A JP 9341386A JP 34138697 A JP34138697 A JP 34138697A JP H11171788 A JPH11171788 A JP H11171788A
- Authority
- JP
- Japan
- Prior art keywords
- hepatocellular carcinoma
- relapse
- suppressant
- therapy
- interferon
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、インターフェロン
-βを有効成分とするC型肝細胞癌の再発を抑制する薬剤
に関する。TECHNICAL FIELD The present invention relates to an interferon.
The present invention relates to a drug that suppresses recurrence of hepatocellular carcinoma containing type-β as an active ingredient.
【０００２】[0002]
【従来の技術】C型慢性肝炎は大半が除々に肝硬変を経
て肝細胞癌（肝癌）になるとされ、肝硬変から肝癌への
発生は年率約７％である。現在、肝細胞癌に対し、canc
er free状態に持ち込める治療法として、外科的手技と
しての肝切除、局所治療としての超音波誘導エタノール
局注療法（PEIT）と超音波誘導マイクロ波焼却療法（PM
CT）、ならびに血管カテーテル術を用いた腫瘍栄養血管
塞栓療法（TAE）とchemo-lipiodolizationあるいはRese
rviorを用いた反復制癌剤動注療法（TAI）等が行われて
いる（山崎 晋他：頻度 切除療法.肝胆膵31：223-23
0,1995）。2. Description of the Related Art It is said that most of chronic hepatitis C gradually undergoes cirrhosis and becomes hepatocellular carcinoma (liver cancer), and the incidence of liver cancer from cirrhosis is about 7% annually. Currently, for hepatocellular carcinoma,
Hepatic resection as a surgical procedure, ultrasound-guided ethanol local injection (PEIT) and ultrasound-induced microwave incineration (PM)
CT), as well as tumor nutritional vascular embolization (TAE) using vascular catheterization and chemo-lipiodolization or Rese
Repetitive anticancer drug arterial infusion therapy (TAI) using rvior (Shin Yamazaki et al .: Frequency resection therapy. Hepatobiliary pancreas 31: 223-23
0,1995).
【０００３】一方、インターフェロン（以下「IFN」と
いう）には血管新生抑制作用、血管誘導因子（bFGF）産
生抑制作用および腫瘍細胞の侵潤抑制作用などが認めら
れることが報告されている（Sidky YA他：Inhibition o
f Angiogenesis by Interferon：Effect on Tumor-and
Lymphocyte-induced Vascular Response. Cancer Res.4
7：5155-5161,1987.）、（Gohji K他：Human Recombina
nt Interferons-Betaand-Gamma Decrease Gelatinase P
roduction and Invasion by Human KG-2 Renalcarcinom
a Cells. Int.J.Cancer 58：380-384,1994. ）。On the other hand, it has been reported that interferon (hereinafter referred to as "IFN") has an inhibitory action on angiogenesis, an inhibitory action on angiogenesis factor (bFGF) production and an inhibitory action on tumor cell invasion (Sidky YA). Other: Inhibition o
f Angiogenesis by Interferon: Effect on Tumor-and
Lymphocyte-induced Vascular Response.Cancer Res. 4
7: 5155-5161, 1987.), (Gohji K et al .: Human Recombina)
nt Interferons-Betaand-Gamma Decrease Gelatinase P
roduction and Invasion by Human KG-2 Renalcarcinom
a Cells. Int. J. Cancer 58: 380-384, 1994.).
【０００４】[0004]
【発明が解決しようとする課題】しかしながら、根治療
法後も高い比率（年率約２２％）で肝癌の再発を来すこ
とが認められている。すなわち根治療法後も、再発と再
治療を繰り返しながら、大半が最後には癌がコントロー
ルできなくなるか肝不全となり死亡し、現在のところ、
肝癌の再発を抑制する治療法はない。However, it has been recognized that liver cancer recurs at a high rate (about 22% per year) even after root treatment. In other words, even after the radical treatment, while repeating recurrence and re-treatment, most died of cancer finally lost control or liver failure, at present,
There is no cure to prevent recurrence of liver cancer.
【０００５】[0005]
【課題を解決するための手段】上記目的は以下の本発明
により達成される。すなはち本発明は、IFN-βを有効成
分とするC型肝細胞癌再発抑制治療剤である。The above object is achieved by the present invention described below. That is, the present invention is a therapeutic agent for suppressing recurrence of hepatocellular carcinoma type C containing IFN-β as an active ingredient.
【０００６】[0006]
【発明実施の形態】本発明に用いられるIFN-βは、天然
型のもの、化学合成により製造されるもの、遺伝子組み
換え技術により製造されるもののいずれであってもよ
い。特に、ヒト二倍体線維芽細胞によって産生される天
然型IFN-βを好ましく用いる。BEST MODE FOR CARRYING OUT THE INVENTION IFN-β used in the present invention may be any of natural type, one produced by chemical synthesis, and one produced by genetic recombination technology. In particular, natural IFN-β produced by human diploid fibroblasts is preferably used.
【０００７】天然型IFN-βは腫瘍化細胞株およびウイル
スを用いない生産方法が特徴である。通常、ガラスもし
くはプラスチックなどの表面、またはDEAE化デキストラ
ンやポリアクリルアミドあるいはポリスチレンの微小粒
子表面上に細胞を吸着させ培養させる。培養されたIFN-
β産生細胞はプライミング処理（IFN-β産生時に少量の
IFN-βで細胞を前処理するとしない場合に比較してIFN-
βの産生量が増加する。IFN 自体がIFN産生増強などの
産生調節機構に関与していることを示す。プライミング
によりIFN mRNA量が増加する、IFN mRNAの転写速度が早
くなる等の報告がある。）と超誘発法（細胞を誘発剤 P
oly I: PolyC等の合成二本鎖RNAで刺激した後、代謝阻
害物質であるアクチノマイシンD:AMDとシクロヘキシミ
ド:CHで処理することでIFN産生を増強する。まず、CHに
よりmRNAから蛋白質が翻訳されるのを阻害し、IFNのmRN
Aを細胞内に蓄積させ、CH除去して一斉にIFN蛋白質を合
成させる。この時にAMDを加えることで逆にリプレッサ
ーのmRNAの阻害を行いIFN合成阻害のフィードバックシ
ステムを制御する。リプレッサーの存在は仮定であるが
調節システムの存在は確認されている。）することで、
培養液中に効率よく産生される。得られた産生液中のIF
N-βは、一般的には低濃度であり、IFN-βの他に細胞由
来または添加物由来の多くの夾雑物を含む。IFN-βの濃
縮精製方法として、ブルー色素を結合させた不溶性担体
および金属キレート基結合担体を用いるクロマトグラフ
ィーによる方法が好ましい。すなわち、粗IFN-β含有液
をブルー色素を結合させた不溶性担体と接触させた後、
溶出液を用いて該IFN-βを溶液として回収し、ついでこ
のIFN-β溶液を亜鉛などの金属をキレート化させたキレ
ート基結合担体と接触させた後、溶出液を用いて回収
し、濃縮精製されたIFN-βを得るという方法である。[0007] Native IFN-β is characterized by a production method without using tumorigenic cell lines and viruses. Usually, cells are adsorbed and cultured on the surface of glass or plastic, or the surface of microparticles of DEAE-dextran, polyacrylamide or polystyrene. Cultured IFN-
β-producing cells are primed (a small amount of IFN-β
IFN-β compared to the case without pretreatment of cells with IFN-β
β production increases. This shows that IFN itself is involved in production regulation mechanisms such as enhancement of IFN production. There have been reports that priming increases the amount of IFN mRNA and increases the transcription rate of IFN mRNA. ) And the super-induction method (cell inducer P
After stimulation with synthetic double-stranded RNA such as oly I: PolyC, treatment with actinomycin D: AMD and cycloheximide: CH, which are metabolic inhibitors, enhances IFN production. First, it inhibits the translation of protein from mRNA by CH.
A accumulates in the cells, removes CH, and simultaneously synthesizes IFN proteins. At this time, the addition of AMD reversely inhibits the mRNA of the repressor and controls the feedback system of IFN synthesis inhibition. The presence of a repressor is hypothetical, but the presence of a regulatory system has been confirmed. )by doing,
Produced efficiently in culture. IF in the resulting production solution
N-β is generally low in concentration and contains many contaminants derived from cells or additives in addition to IFN-β. As a method for concentrating and purifying IFN-β, a method using chromatography using an insoluble carrier to which a blue dye is bound and a metal chelate group-bound carrier is preferable. That is, after contacting the crude IFN-β-containing solution with an insoluble carrier to which a blue dye has been bound,
The IFN-β is recovered as a solution using the eluate, and then the IFN-β solution is brought into contact with a chelating group-binding carrier obtained by chelating a metal such as zinc, and then recovered using the eluate and concentrated. This is a method of obtaining purified IFN-β.
【０００８】本発明のC型肝細胞癌再発抑制薬には、必
要により安定剤を添加することができる。安定剤として
は、ヒト血清アルブミン、特開昭５８−９２６１９号に
開示されたポリオール、特開昭５８−９２６２１号に開
示された有機酸緩衝剤などを例示することができる。さ
らに投与方法に応じて常用の担体などを適宜混合して製
剤化してもよい。剤形としては、注射剤、カプセル剤、
経鼻剤、座薬、経口薬、軟膏剤などの種々の形態のもの
が用いられる。A stabilizer can be added to the hepatocellular carcinoma type C recurrence inhibitor of the present invention, if necessary. Examples of the stabilizer include human serum albumin, a polyol disclosed in JP-A-58-92619, and an organic acid buffer disclosed in JP-A-58-92621. Further, a common carrier or the like may be appropriately mixed and formulated according to the administration method. Dosage forms include injections, capsules,
Various forms such as nasal preparations, suppositories, oral preparations and ointments are used.
【０００９】投与量は、投与対象、投与方法、症状など
に応じ適宜決定されるが、好ましくは３００〜６００万
単位／日の範囲で投与される。[0009] The dose is appropriately determined according to the administration subject, administration method, symptoms and the like, but is preferably administered in the range of 3 to 6 million units / day.
【００１０】投与対象は、C型肝細胞癌症例より、外科
切除、エタノール注入療法（PEIT）、経皮的マイクロ波
凝固治療法（PMCT）等の根治療法が施行され、非癌組織
が肝硬変あるいは慢性肝炎で、HCV抗体およびHCV-RNAが
陽性であることが認められるものである。[0010] The subject to be treated is surgical resection, ethanol injection therapy (PEIT), percutaneous microwave coagulation therapy (PMCT) or other root treatments from patients with hepatocellular carcinoma of the type C, and non-cancerous tissue is treated with cirrhosis or cirrhosis. HCV antibodies and HCV-RNA are confirmed to be positive in chronic hepatitis.
【００１１】[0011]
【実施例】以下、本発明を実施例に基づき具体的に説明
する。DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be specifically described below based on embodiments.
【００１２】実施例１ 58歳のC型肝細胞癌の男性で、経皮的マイクロ波凝固治
療（PMCT）後、IFN-β6MIUを連日4週間静脈内投与、そ
の後IFN-α9MIUを週3回20週間筋肉内投与を行った。肝
細胞癌の再発に対しては、alpha-fetoprotein（AFP）の
測定、超音波（US）、Computer tomography（CT）にて
経過観察した（表1）。なお、IFN治療開始時の genotyp
eはII型（1b）、HCV-RNA（b-DNAプローブ）は14Meq/ml
であった。その結果、IFN治療後、14ヵ月間の観察期間
で肝細胞癌は無再発であった。Example 1 A 58-year-old male with hepatocellular carcinoma type C, after percutaneous microwave coagulation therapy (PMCT), was intravenously administered with IFN-β6MIU for 4 weeks every day, and then with IFN-α9MIU three times a week. Intramuscular administration was performed for a week. The recurrence of hepatocellular carcinoma was monitored by alpha-fetoprotein (AFP) measurement, ultrasound (US), and computer tomography (CT) (Table 1). The genotyp at the start of IFN treatment
e is type II (1b), HCV-RNA (b-DNA probe) is 14Meq / ml
Met. As a result, hepatocellular carcinoma was recurrence-free after a 14-month observation period after IFN treatment.
【００１３】[0013]
【表１】 実施例２ 68歳のC型肝細胞癌の男性で、外科切除による根治療法
を行った。なお、genotypeはII型（1b）、HCV-RNA（b-D
NAプローブ）は4.4Meq/mlであった。その後、IFNの投与
は行わずに経過観察のみを続けたところ、観察開始6ヶ
月後にCTにて肝細胞癌の再発が認められた（表2）。[Table 1] Example 2 A 68-year-old male with C-type hepatocellular carcinoma underwent radical treatment by surgical resection. In addition, genotype is type II (1b), HCV-RNA (bD
NA probe) was 4.4 Meq / ml. After that, when only follow-up was continued without administration of IFN, CT showed hepatocellular carcinoma recurrence 6 months after the start of the observation (Table 2).
【００１４】[0014]
【表２】 [Table 2]
【００１５】[0015]
【発明の効果】以上の結果より、IFN-βの肝細胞癌再発
あるいは肝細胞癌発生に対する抑制効果が示唆され、抑
制治療薬として有用であることが示された。The above results suggest that IFN-β has a suppressive effect on hepatocellular carcinoma recurrence or hepatocellular carcinogenesis, indicating that it is useful as a suppressive therapeutic agent.
Claims (2)
肝細胞癌の根治療法後の再発抑制剤。1. An agent for inhibiting recurrence of a hepatocellular carcinoma type C after a root treatment method, comprising interferon-β as an active ingredient.
ノール注入療法（PEIT）、経皮的マイクロ波凝固治療法
（PMCT）、腫瘍栄養血管塞栓療法（TAE）、反復制癌剤
動注療法（TAI）である請求項１記載のC型肝細胞癌再発
抑制剤。2. The root cure for hepatocellular carcinoma type C is surgical resection, ethanol injection therapy (PEIT), percutaneous microwave coagulation therapy (PMCT), tumor nutritional vascular embolization therapy (TAE), and repetitive anticancer drug infusion therapy. The agent for suppressing recurrence of hepatocellular carcinoma type C according to claim 1, which is (TAI).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9341386A JPH11171788A (en) | 1997-12-11 | 1997-12-11 | Relapse suppressant for hepatocellular carcinoma c |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9341386A JPH11171788A (en) | 1997-12-11 | 1997-12-11 | Relapse suppressant for hepatocellular carcinoma c |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH11171788A true JPH11171788A (en) | 1999-06-29 |
Family
ID=18345668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9341386A Pending JPH11171788A (en) | 1997-12-11 | 1997-12-11 | Relapse suppressant for hepatocellular carcinoma c |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH11171788A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001080877A1 (en) * | 2000-04-20 | 2001-11-01 | Toray Industries, Inc. | Preventives for reinfection after liver transplantation |
| JP2004505009A (en) * | 2000-01-19 | 2004-02-19 | ユー， バオファ | Combinations for treating neoplasms |
| EP1545573A4 (en) * | 2002-09-05 | 2008-02-13 | Gen Hospital Corp | Asialo-interferons and the treatment of liver cancer |
| EP1549332A4 (en) * | 2002-09-05 | 2008-06-18 | Gen Hospital Corp | Modified asialo-interferons and uses thereof |
| US7927612B2 (en) | 2000-01-19 | 2011-04-19 | Baofa Yu | Combinations and methods for treating neoplasms |
| US8501243B2 (en) | 2006-09-07 | 2013-08-06 | Baofa Yu | Targeting cancer therapy combination |
| US11110303B2 (en) | 2014-11-26 | 2021-09-07 | Baofa Yu | Hapten-enhanced chemoimmunotherapy by ultra-minimum incision personalized intratumoral chemoimmunotherapy |
-
1997
- 1997-12-11 JP JP9341386A patent/JPH11171788A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004505009A (en) * | 2000-01-19 | 2004-02-19 | ユー， バオファ | Combinations for treating neoplasms |
| US7927612B2 (en) | 2000-01-19 | 2011-04-19 | Baofa Yu | Combinations and methods for treating neoplasms |
| WO2001080877A1 (en) * | 2000-04-20 | 2001-11-01 | Toray Industries, Inc. | Preventives for reinfection after liver transplantation |
| EP1545573A4 (en) * | 2002-09-05 | 2008-02-13 | Gen Hospital Corp | Asialo-interferons and the treatment of liver cancer |
| EP1549332A4 (en) * | 2002-09-05 | 2008-06-18 | Gen Hospital Corp | Modified asialo-interferons and uses thereof |
| US8501243B2 (en) | 2006-09-07 | 2013-08-06 | Baofa Yu | Targeting cancer therapy combination |
| US9000036B2 (en) | 2006-09-07 | 2015-04-07 | Baofa Yu | Compositions and methods for targeting of treating neoplasms |
| US11110303B2 (en) | 2014-11-26 | 2021-09-07 | Baofa Yu | Hapten-enhanced chemoimmunotherapy by ultra-minimum incision personalized intratumoral chemoimmunotherapy |
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