JP5690588B2 - 肝細胞癌のサブタイプを決定し、肝癌幹細胞を検出するための方法 - Google Patents
肝細胞癌のサブタイプを決定し、肝癌幹細胞を検出するための方法 Download PDFInfo
- Publication number
- JP5690588B2 JP5690588B2 JP2010511218A JP2010511218A JP5690588B2 JP 5690588 B2 JP5690588 B2 JP 5690588B2 JP 2010511218 A JP2010511218 A JP 2010511218A JP 2010511218 A JP2010511218 A JP 2010511218A JP 5690588 B2 JP5690588 B2 JP 5690588B2
- Authority
- JP
- Japan
- Prior art keywords
- hcc
- mir
- sample
- expression
- biomarker
- 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.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56966—Animal cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57438—Specifically defined cancers of liver, pancreas or kidney
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/112—Disease subtyping, staging or classification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
Description
マイクロRNA(またはmiRNA)は多くの生物に存在し、主に3’非翻訳領域におけるmRNAの部分的相補部位と塩基対を形成することによってmRNAの翻訳および分解に重要な調節的役割を果たす小さい非コードRNA遺伝子産物(例えば〜22ヌクレオチド)である(非特許文献1、非特許文献2、非特許文献3)。miRNAは、細胞ヌクレアーゼであるDroshaによってプロセッシングされる長い前駆体RNAとして発現され、その後、エクスポーチン−5依存的な機構によって細胞質に輸送される(非特許文献4、非特許文献5)。その後、miRNAはDICER酵素によって切断され、RNA誘導サイレンシング様複合体と関連するおよそ17〜24ヌクレオチドのmiRNAを生ずる(非特許文献6、非特許文献7)。
臨床標本
肝組織は、2002年〜2003年の間に肝臓ガン研究所および中山病院(復旦大学、上海、中国)で根治的切除を受けた被験者からインフォームドコンセントを行なった上で得られた。研究は、肝臓ガン研究所および国立衛生研究所の施設内倫理委員会により承認された。試料登録基準には、HBV感染またはHBV関連肝硬変の既往歴、2人の独立した病理学者によって診断されたHCC、臨床像および病理学的特徴に関する詳細情報だけでなく、肝内再発、肝内静脈転移、リンパ節転移、肝外転移、無疾患、全生存、および死因を含めた少なくとも3年間の詳細な経過観察データを含む基準が含まれた。最新のTNM分類は、切除を受けたHCC被験者に関してCLIPおよびOKUDAを含めたその他の病期診断システムよりも優れており、それ故に、miRNA予測能の解析用に初期の被験者(TMN病期IおよびII)を階層化するために選ばれた(非特許文献20、非特許文献21)。前向き研究により、2002年に更新された新しいTNM分類システムよりもBCLCシステムが優れていることが明らかとなり、それ故に、BCLCによって類別された初期の被験者(病期0およびA)に基づくCox比例ハザードモデリングも行なった。244人の中国人HCC被験者由来の原発性HCCおよび対応する非癌肝組織で遺伝子発現プロファイルを実施した。それらの中で、93%が肝硬変を基礎疾患に有し、68%の血清α−フェトプロテイン(AFP)レベルが>20ng/mLであった。合計134例の明確に定義された症例を練習群として用いた。それらの中で、30例が、門脈の主要分岐(n=25)、下大静脈(n=2)、または総胆管(n=4;1例は下大静脈中に腫瘍血栓も有する)に見られる腫瘍塞栓を伴う原発性HCC病変を有しており、104例が、経過観察(3年)で見出される転移/再発が全くない単発性HCCを有していた。検証解析では、切除の時点で幾つかのHCC病期診断法により予後を正確に決定することができなかった110例の独立した症例の試験群を用いた。試験症例には、43例の多結節性HCCおよび67例の単発性HCCが含まれていた。43例の多結節性HCC症例のうち、18例は肝内再発を発症し、1例は肝内再発に加えて肝外転移を発症した。67例の単発性HCC症例のうち、4例の被験者が凝集結節の出現を伴う単発性腫瘍を有し、10例の被験者が肝内転移および/または肝外転移を発症した一方で、49例の被験者は経過観察(3年)で確認される肝内再発を発症した。さらに、無疾患被験者から得た8つの正常肝組織(非特許文献22に記載されている)を正常対照として含めた。
RNAの単離およびmiRNAアレイの方法論を、非特許文献23および非特許文献24に記載されたように実施した。244例のHCC症例の解析において、腫瘍組織または非腫瘍組織から対になるようにRNAを単離し、群分けによる偏りを避けるために、miRNA解析用にランダムな順序で試料を選択した。合計488個のマイクロアレイを行なった。マイクロアレイプラットフォーム(V2.0)は、250個の非重複ヒトmiRNAおよび200個のマウスmiRNAから構成された。miRNAマイクロアレイプラットフォームの頑健性を検討するために、miRNAを解析し、発現が244個の組織とそれらの対になる周辺非癌肝組織とを区別することができるかどうかを明らかにした。単変量の対応のあるt−検定を伴う教師あり分類比較法および1000回のクラス標識の置換を伴う多変量検定を、≦1に設定した誤り発見率と99%の信頼度で用いて、HCC腫瘍組織(T)とそれらの対になる非腫瘍組織(NT)とを有意に見分けることができる209個の非重複miRNAを同定した。これらの有意なmiRNAは、T試料およびNT試料を明瞭に分け、階層的クラスタリング解析で例証された。10%の相互検証および100回のランダム置換を伴う多変量のクラス予測アルゴリズム解析によって、これらのmiRNAが、最近隣予測因子により97%を越える精度で統計的に有意なT試料およびNT試料を予測(p<0.01)することができるということが示された。これらの最初の解析によって、miRNAアレイが頑健であり、腫瘍と非癌肝組織の有意差を同定することができるということが示された。
Alexander Sturn(IBMT−TUG、グラーツ、オーストリア)によって開発されたGENESISソフトウェアV1.5によって、教師なし階層的クラスタリング解析を行なった。BRB ArrayToolsソフトウェアV3.3を、以前に記載されたように(非特許文献23、非特許文献22)教師あり解析のために用いた。Excelに基づくWinSTATソフトウェアを用いて、予測結果に基づいて被験者の生存率を比較するために、Kaplan−Meier生存解析を用いた。Cox−Mantelのログランク検定により統計的p値を作成した。STATA 9.2(テキサス州カレッジ・ステーション)を用いて、16個の臨床的変数の、被験者の生存率または再発率に対する効果を解析するために、Cox比較ハザード回帰を用いた。統計的有意性は、p<0.05と定義した。ターゲットスキャン解析は、Ben Lewis(非特許文献25)によって開発されたウェブサイトツールに基づいた。年齢、性別、HBV活性状況、切除前のAFP、肝硬変、アラニントランスフェラーゼ(ALT)、チャイルド・ピュー(Child−Pugh)スコア、腫瘍の大きさ、腫瘍の被包化、結節の種類、微小血管浸潤の状況、エドモンドソン(Edmondson)グレード、ならびにBCLC病期診断(非特許文献26)、CLIP分類(非特許文献27)、Okuda病期診断(非特許文献28)およびTNF分類(非特許文献29)を含めた幾つかのHCC予後診断システムを含む、被験者の全生存率および無再発生存率に対する臨床的変数の効果を解析するために、Cox比較ハザード回帰を用いた。
TRIzol(インビトロジェン、カリフォルニア州カールスバッド)を用いて全RNAを抽出し、TACSTD1、BAMBI、DKK1、CCND1、CTNNB1、およびMYCの発現を、アプライドバイオシステムズ7700 Sequence Detection System(カリフォルニア州フォスターシティ)を用いて3通りで測定した。使用したプローブは以下であった:TACSTD1、Hs00158980_m1;CTNNB1、HS00170025_m1;BAMBI、HS00180818、DKK1、Hs00183740_m1、CCND1、Hs00277039_m1、CTNNB1、MYC、Hs00153408_m1;18S、Hs999999901_s1(アプライドバイオシステムズ)。全ての手順を製造元のアドバイスに従って行なった。
製造元の取扱説明書に従ってEnvision+キット(ダコUSA、カリフォルニア州カーピンテリア)を用いて免疫組織化学的解析を行なった。1次抗体を以下の通り用いた:抗β−カテニンモノクローナル抗体クローン14(BD Transduction Laboratories、カリフォルニア州サンホセ)および抗EpCAMモノクローナル抗体クローンVU−1D9(Oncogene Research Products、カリフォルニア州サンディエゴ)。
細胞をチャンバースライド上で培養し、示した化学物質で48時間処理した。その後、細胞を4%パラホルムアルデヒドで10分間、メタノールで20分間固定し、リン酸緩衝化生理食塩水中でインキュベートした。試料を10%正常ロバ血清で室温にて1時間ブロッキングし、1次抗体で37℃にて1時間染色し、次いでアレクサ568 テキサスレッド結合抗マウス抗体(Molecular Probes、オレゴン州ユージーン)で染色した。
組換えTcf−4を大腸菌でGST融合タンパク質として発現させ、抽出した。製造元の取扱説明書に従ってLightShift Chemiluminescent EMSAキット(Pierce、イリノイ州ロックフォード)を用いてEMSAを行なった。EpCAMプロモーターの推定Tcf結合部位ならびに上流および下流の10個の隣接するヌクレオチドを含む2本鎖DNAオリゴヌクレオチドを構築し、プローブとして用いた。突然変異体TBE1およびTBE2プローブも用いた。
公知のHCC細胞株、Hep3BタイプB、MHCC97タイプC、Smmc7721タイプD、HUH1、およびHUH7を日常的に培養した。機能アッセイのために、細胞にpMSCV−mir−181b−1をトランスフェクトした。HUH7細胞を、mir−181の阻害剤である2’−O−メチルmir−181アンチセンスでも処理した。
本実施例は、miRNA発現が、HCC組織と非癌組織とを区別することができ、HCCの4つのサブタイプを識別することができることを示す。
本実施例は、mir−181がHSC−HCCと関連し、肝癌幹細胞の機能に寄与することを示す。
本実施例は、mir−181発現が、wnt−β−カテニンシグナル伝達の活性化に関与することを示す。
Claims (16)
- 被験者の肝腫瘍組織の肝細胞癌(HCC)サブタイプを試験する方法であって:
前記被験者からの肝腫瘍組織の試料を、mir−221(配列番号25)を含む1つ以上のバイオマーカーの発現について解析し;そして
前記1つ以上のバイオマーカーの発現が上方制御されているか下方制御されているかを決定する、
ことを含み、前記試料中のmir−221発現が上方制御されている場合は胆管上皮様肝細胞癌(BDE−HCC)を示し、前記試料中のmir−221発現が下方制御されている場合は成熟肝細胞様肝細胞癌(MH−HCC)を示す、前記方法。 - 前記試料を、マイクロアレイ技術、PCR増幅、RNAハイブリダイゼーション、in situハイブリダイゼーション、ゲル電気泳動、およびそれらの組み合わせから成る群より選択される1つ以上の方法によって解析する、請求項1記載の方法。
- 少なくともmir−221(配列番号25)よって特定されるバイオマーカーを解析する場合に、バイオマーカーの発現を胆管上皮様肝細胞癌(BDE−HCC)の存在と関連付ける、請求項1記載の方法。
- 少なくともmir−221(配列番号25)によって特定されるバイオマーカーを解析する場合に、バイオマーカーの発現を成熟肝細胞様肝細胞癌(MH−HCC)の存在と関連付ける、請求項1記載の方法。
- 生物学的試料中のBDE−HCC細胞またはMH−HCC細胞を検出する方法であって:
肝腫瘍組織、肝正常組織、またはそれらの組み合わせを含む試料をアッセイして、mir−221(配列番号25)を含む少なくとも1つのバイオマーカーの有無を検出し;そして
前記少なくとも1つのバイオマーカーの発現を前記試料中のBDE−HCC細胞またはMH−HCC細胞の有無と関連付ける、
ことを含み、前記試料中のmir−221が過剰発現している場合はBDE−HCC細胞の存在を示し、前記試料中のmir−221が発現不足である場合はMH−HCC細胞の存在を示す、前記方法。 - 前記HCC細胞の存在を前記試料中の肝細胞癌の存在と関連付けることをさらに含む、請求項5記載の方法。
- 前記試料中の前記少なくとも1つのバイオマーカーの有無を、マイクロアレイ技術、PCR増幅、RNAハイブリダイゼーション、in situハイブリダイゼーション、ゲル電気泳動、およびそれらの組み合わせから成る群より選択される1つ以上の技術によって解析する、請求項5記載の方法。
- 関連付けが、前記被験者の予後の決定に役立つ、請求項6記載の方法。
- 関連付けが、HCCを有する被験者の予後の判断基準となる、請求項6記載の方法。
- 関連付けが、HCCサブタイプについての前記被験者の処置に役立つ、請求項8または9記載の方法。
- 関連付けが、HCCサブタイプを有する被験者の処置の基準となる、請求項8または9記載の方法。
- 前記処置が、肝切除、移植、経皮的エタノール注射、高周波アブレーション、化学塞栓術、化学療法、遺伝子治療、β−カテニン阻害、およびそれらの組み合わせから成る群より選択される少なくとも1つの手順を含む、請求項10または11記載の方法。
- 前記処置が、β−カテニン阻害剤を被験者に投与することを含む、請求項10または11記載の方法。
- HCCを有する被験者の肝腫瘍組織の生物学的試料中のHSC−HCCサブタイプを検出する方法であって:
EpCAM+AFP+幹細胞が前記試料中に存在するかどうかを検出することを含み、
EpCAM+AFP+幹細胞の存在は、前記試料中のHSC−HCCサブタイプの存在を示す、前記方法。 - 少なくともmir−221バイオマーカーについて前記試料をアッセイすることをさらに含む、請求項14記載の方法。
- 前記幹細胞を、免疫蛍光、in situハイブリダイゼーション、免疫組織化学解析、凍結アクチベーター細胞選別、サイドポピュレーション解析、細胞表面マーカー検出法、およびそれらの組み合わせから成る群より選択される方法によって検出する、請求項15記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US94283307P | 2007-06-08 | 2007-06-08 | |
US60/942,833 | 2007-06-08 | ||
PCT/US2008/007196 WO2008153987A2 (en) | 2007-06-08 | 2008-06-09 | Methods for determining hepatocellular carcinoma subtype and detecting hepatic cancer stem cells |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2010528659A JP2010528659A (ja) | 2010-08-26 |
JP5690588B2 true JP5690588B2 (ja) | 2015-03-25 |
Family
ID=40130411
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010511218A Expired - Fee Related JP5690588B2 (ja) | 2007-06-08 | 2008-06-09 | 肝細胞癌のサブタイプを決定し、肝癌幹細胞を検出するための方法 |
Country Status (8)
Country | Link |
---|---|
US (2) | US8465917B2 (ja) |
EP (3) | EP2559772B1 (ja) |
JP (1) | JP5690588B2 (ja) |
CN (3) | CN103602724B (ja) |
AU (1) | AU2008262252B2 (ja) |
CA (1) | CA2690144A1 (ja) |
ES (3) | ES2537349T3 (ja) |
WO (1) | WO2008153987A2 (ja) |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1937845B1 (en) | 2005-08-01 | 2015-06-10 | The Ohio State University Research Foundation | Micro-rna-based methods and compositions for the diagnosis, prognosis and treatment of breast cancer |
EP1937280B1 (en) | 2005-09-12 | 2014-08-27 | The Ohio State University Research Foundation | Compositions for the therapy of bcl2-associated cancers |
EP2487253B1 (en) | 2006-01-05 | 2015-06-24 | The Ohio State University Research Foundation | MicroRNA-based methods and compositions for the diagnosis and treatment of solid cancers |
US7943318B2 (en) | 2006-01-05 | 2011-05-17 | The Ohio State University Research Foundation | Microrna-based methods and compositions for the diagnosis, prognosis and treatment of lung cancer |
EP2591794A1 (en) | 2006-01-05 | 2013-05-15 | The Ohio State University Research Foundation | MicroRNA expressions abnormalities in pancreatic endocrine and acinar tumors |
EP1996731A2 (en) | 2006-03-20 | 2008-12-03 | The Ohio State University Research Foundation | Microrna fingerprints during human megakaryocytopoiesis |
EP2455494B1 (en) | 2006-07-13 | 2013-12-18 | The Ohio State University Research Foundation | Micro-RNA-based methods and compositions for the diagnosis and treatment of colon related diseases |
AU2007346101B2 (en) | 2006-09-19 | 2013-08-15 | The Ohio State University Research Foundation | TCL1 expression in chronic lymphocytic leukemia (CLL) regulated by miR-29 and miR-181 |
EP2087135B8 (en) | 2006-11-01 | 2013-07-24 | The Ohio State University Research Foundation | Microrna expression signature for predicting survival and metastases in hepatocellular carcinoma |
CN103555825B (zh) | 2007-01-31 | 2015-09-30 | 俄亥俄州立大学研究基金会 | 用于急性髓细胞白血病(aml)的诊断、预后和治疗的基于微rna的方法和组合物 |
JP5690588B2 (ja) | 2007-06-08 | 2015-03-25 | アメリカ合衆国 | 肝細胞癌のサブタイプを決定し、肝癌幹細胞を検出するための方法 |
CN101918424A (zh) | 2007-06-15 | 2010-12-15 | 俄亥俄州立大学研究基金会 | 用于靶向由Drosha介导的微小RNA加工的致癌ALL-1融合蛋白 |
EP2808398A1 (en) | 2007-07-31 | 2014-12-03 | The Ohio State University Research Foundation | Methods for reverting methylation by targeting DNMT3A and DNMT3B |
ES2627059T3 (es) | 2007-08-03 | 2017-07-26 | The Ohio State University Research Foundation | Regiones ultraconservadas que codifican ARNnc |
CA2696887C (en) | 2007-08-22 | 2016-06-28 | The Ohio State University Research Foundation | Methods and compositions for inducing deregulation of epha7 and erk phosphorylation in human acute leukemias |
JP2011504093A (ja) | 2007-10-26 | 2011-02-03 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイション | 脆弱性ヒスチジン三連構造(fhit)相互作用を同定するための方法およびその使用 |
US9125923B2 (en) | 2008-06-11 | 2015-09-08 | The Ohio State University | Use of MiR-26 family as a predictive marker for hepatocellular carcinoma and responsiveness to therapy |
ITMI20091538A1 (it) * | 2009-09-07 | 2011-03-08 | Istituto Naz Di Genetica Mole Colare Ingm | Profili di espressione di micro-rna nel sangue periferico di pazienti affetti da epatocarcinoma o cirrosi epatica e loro usi |
US8916533B2 (en) | 2009-11-23 | 2014-12-23 | The Ohio State University | Materials and methods useful for affecting tumor cell growth, migration and invasion |
CN103648505B (zh) | 2010-11-12 | 2016-09-28 | 俄亥俄州立大学研究基金会 | 与微rna-21、错配修复和结肠直肠癌相关的材料和方法 |
BR112013011942A2 (pt) | 2010-11-15 | 2016-11-01 | Univ Michigan | formulação, forma de dosagem de droga para administração transmucosa oral, sistema transmucoso de fornecimento de droga, método de tratamento e profilaxia de uma doença ou distúrbio, método de tratamento, formulação, método para tratamento ou prevenção de carcinoma de célula escamosa de cabeça e pescoço (hnscc), método para quimioprevenção de um câncer oral ou condição pré-cancerosa, método para aumentar a concentração de uma composição de retinida, método de tratamento e profilaxia de uma doença ou condição, método de ratamento de um sujeito apresentando uma condição médica sintomática, método de tratamento de um câncer oral ou condição pré-cancerosa num paciente, método para fazer um sistema de fornecimento de droga bucal, método para aumentar a liberação e permeação de uma composição de retinida. |
AU2012225506B2 (en) | 2011-03-07 | 2016-11-17 | The Ohio State University | Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer |
CN102353791A (zh) * | 2011-06-30 | 2012-02-15 | 倪润洲 | 一种分离检测afp亚型的新方法 |
CA2852066A1 (en) | 2011-10-14 | 2013-04-18 | The Ohio State University | Methods and materials related to ovarian cancer |
WO2013067048A1 (en) * | 2011-10-31 | 2013-05-10 | The Ohio State University | Materials and methods related to mir-221 and hepatocellular carcinoma |
JP2015501843A (ja) | 2011-12-13 | 2015-01-19 | オハイオ・ステイト・イノベーション・ファウンデーション | miR−21およびmiR−29a、エキソソーム阻害、およびがん転移に関する方法および組成物 |
CN104685065B (zh) | 2012-01-20 | 2017-02-22 | 俄亥俄州立大学 | 浸润性和预后的乳腺癌生物标志物标签 |
US8846316B2 (en) | 2012-04-30 | 2014-09-30 | Industrial Technology Research Institute | Biomarker for human liver cancer |
CN104990905B (zh) * | 2015-06-30 | 2017-12-29 | 曲凯 | 一种基于固相酶联免疫荧光斑点的肝癌转移诊断试剂盒 |
KR101917771B1 (ko) | 2017-06-01 | 2018-11-12 | 한국화학연구원 | 비알콜성 지방간 질환 유래 간암 줄기세포 검출용 마이크로 rna 및 이의 용도 |
Family Cites Families (169)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3854480A (en) | 1969-04-01 | 1974-12-17 | Alza Corp | Drug-delivery system |
US3832253A (en) | 1973-03-21 | 1974-08-27 | Baxter Laboratories Inc | Method of making an inflatable balloon catheter |
US4196265A (en) | 1977-06-15 | 1980-04-01 | The Wistar Institute | Method of producing antibodies |
US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
US4172124A (en) | 1978-04-28 | 1979-10-23 | The Wistar Institute | Method of producing tumor antibodies |
US4608337A (en) | 1980-11-07 | 1986-08-26 | The Wistar Institute | Human hybridomas and the production of human monoclonal antibodies by human hybridomas |
US4667014A (en) | 1983-03-07 | 1987-05-19 | Syntex (U.S.A.) Inc. | Nonapeptide and decapeptide analogs of LHRH, useful as LHRH antagonists |
US4452775A (en) | 1982-12-03 | 1984-06-05 | Syntex (U.S.A.) Inc. | Cholesterol matrix delivery system for sustained release of macromolecules |
US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
CA1200416A (en) | 1983-05-13 | 1986-02-11 | Societe Des Produits Nestle S.A. | Food process |
US5019369A (en) | 1984-10-22 | 1991-05-28 | Vestar, Inc. | Method of targeting tumors in humans |
US4701409A (en) | 1984-11-15 | 1987-10-20 | The Wistar Institute | Detection of B-cell neoplasms |
US4693975A (en) | 1984-11-20 | 1987-09-15 | The Wistar Institute | Human hybridroma fusion partner for production of human monoclonal antibodies |
US5015568A (en) | 1986-07-09 | 1991-05-14 | The Wistar Institute | Diagnostic methods for detecting lymphomas in humans |
US5202429A (en) | 1986-07-09 | 1993-04-13 | The Wistar Institute | DNA molecules having human BCL-2 gene sequences |
US5075109A (en) | 1986-10-24 | 1991-12-24 | Southern Research Institute | Method of potentiating an immune response |
US4987071A (en) | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
EP0341904B1 (en) | 1988-05-09 | 1995-03-29 | Temple University of the Commonwealth System of Higher Education | Method for predicting the effectiveness of antineoplastic therapy in individual patients |
US5198338A (en) | 1989-05-31 | 1993-03-30 | Temple University | Molecular probing for human t-cell leukemia and lymphoma |
US5149628A (en) | 1989-11-15 | 1992-09-22 | Temple University | Methods for detecting bcl-3 gene in human leukemias |
JPH04167172A (ja) | 1990-10-31 | 1992-06-15 | Nec Corp | ベクトルプロセッサ |
WO1993012136A1 (en) | 1991-12-11 | 1993-06-24 | Thomas Jefferson University | Detection and treatment of acute leukemias resulting from chromosome abnormalities in the all-1 region |
US5633135A (en) | 1991-12-11 | 1997-05-27 | Thomas Jefferson University | Chimeric nucleic acids and proteins resulting from ALL-1 region chromosome abnormalities |
US6040140A (en) | 1991-12-11 | 2000-03-21 | Thomas Jefferson University | Methods for screening and treating leukemias resulting from all-1 region chromosome abnormalities |
US5674682A (en) | 1992-10-29 | 1997-10-07 | Thomas Jefferson University | Nucleic acid primers for detecting micrometastasis of prostate cancer |
JPH08502889A (ja) | 1992-10-29 | 1996-04-02 | トーマス・ジェファーソン・ユニバーシティ | 前立腺癌の微小転移を検出する方法 |
US5985598A (en) | 1994-10-27 | 1999-11-16 | Thomas Jefferson University | TCL-1 gene and protein and related methods and compositions |
US7175995B1 (en) | 1994-10-27 | 2007-02-13 | Thomas Jefferson University | TCL-1 protein and related methods |
US5695944A (en) | 1995-05-05 | 1997-12-09 | Thomas Jefferson University | Modulation of bcl-2 phosphorylation |
US5567586A (en) | 1995-05-18 | 1996-10-22 | Thomas Jefferson University | Methods of indentifying solid tumors with chromosome abnormalities in the ALL-1 region |
US6242212B1 (en) | 1996-02-09 | 2001-06-05 | Thomas Jefferson University | Fragile histidine triad (FHIT) nucleic acids and methods of producing FHIT proteins |
US5928884A (en) | 1996-02-09 | 1999-07-27 | Croce; Carlo M. | FHIT proteins and nucleic acids and methods based thereon |
US5849902A (en) | 1996-09-26 | 1998-12-15 | Oligos Etc. Inc. | Three component chimeric antisense oligonucleotides |
AU6659298A (en) | 1997-02-18 | 1998-09-08 | Thomas Jefferson University | Compositions that bind to pancreatic cancer cells and methods of using the same |
EP0972083A1 (en) | 1997-04-04 | 2000-01-19 | THE TEXAS A&M UNIVERSITY SYSTEM | Noninvasive detection of colonic biomarkers using fecal messenger rna |
EP1098968A4 (en) | 1998-07-20 | 2002-01-02 | Univ Jefferson | NITRILASE APPROVALS |
WO2000005419A1 (en) | 1998-07-24 | 2000-02-03 | Yeda Research And Development Company Ltd. | Prevention of metastasis with 5-aza-2'-deoxycytidine |
US7141417B1 (en) | 1999-02-25 | 2006-11-28 | Thomas Jefferson University | Compositions, kits, and methods relating to the human FEZ1 gene, a novel tumor suppressor gene |
EP1165586A4 (en) | 1999-03-15 | 2003-05-28 | Univ Jefferson | TCL-1B GENES AND PROTEINS AND RELATED METHODS AND METHODS |
US7163801B2 (en) | 1999-09-01 | 2007-01-16 | The Burnham Institute | Methods for determining the prognosis for cancer patients using tucan |
US6891031B2 (en) | 2000-02-18 | 2005-05-10 | The Regents Of The University Of California | Coordinate cytokine regulatory sequences |
WO2001068666A1 (en) | 2000-03-14 | 2001-09-20 | Thomas Jefferson University | Tcl1 enhances akt kinase activity and mediates its nuclear translocation |
CA2406366A1 (en) | 2000-04-11 | 2001-10-18 | Thomas Jefferson University | Muir-torre-like syndrome infhit deficient mice |
WO2001087958A2 (en) | 2000-05-16 | 2001-11-22 | Thomas Jefferson University | CRYSTAL STRUCTURE OF WORM NitFhit REVEALS THAT A Nit TETRAMER BINDS TWO Fhit DIMERS |
US7060811B2 (en) | 2000-10-13 | 2006-06-13 | Board Of Regents, The University Of Texas System | WWOX: a tumor suppressor gene mutated in multiple cancers |
US20020173478A1 (en) | 2000-11-14 | 2002-11-21 | The Trustees Of The University Of Pennsylvania | Post-transcriptional gene silencing by RNAi in mammalian cells |
US20040033502A1 (en) | 2001-03-28 | 2004-02-19 | Amanda Williams | Gene expression profiles in esophageal tissue |
US20050176025A1 (en) | 2001-05-18 | 2005-08-11 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of B-cell CLL/Lymphoma-2 (BCL-2) gene expression using short interfering nucleic acid (siNA) |
IL161100A0 (en) | 2001-09-28 | 2004-08-31 | Max Planck Gesellschaft | Identification of novel genes coding for small temporal rnas |
US7371736B2 (en) | 2001-11-07 | 2008-05-13 | The Board Of Trustees Of The University Of Arkansas | Gene expression profiling based identification of DKK1 as a potential therapeutic targets for controlling bone loss |
GB0128898D0 (en) | 2001-12-03 | 2002-01-23 | Biotech Res Ventures Pte Ltd | Materials and methods relating to the stabilization and activation of a tumour suppressor protein |
MXPA04008722A (es) | 2002-03-08 | 2005-07-13 | Eisai Co Ltd | Compuestos macrociclicos utiles como farmaceuticos. |
AU2003226279A1 (en) * | 2002-04-08 | 2003-10-27 | Ciphergen Biosystems, Inc. | Serum biomarkers in hepatocellular carcinoma |
ATE446675T1 (de) | 2002-04-29 | 2009-11-15 | Univ Jefferson | Humane chronische lymphozytische leukämie im mausmodell durch gezielte expression von tcl1 |
US7217568B2 (en) | 2002-05-31 | 2007-05-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of identifying and isolating stem cells and cancer stem cells |
US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
US20050260639A1 (en) | 2002-09-30 | 2005-11-24 | Oncotherapy Science, Inc. | Method for diagnosing pancreatic cancer |
AU2003284083A1 (en) | 2002-10-11 | 2004-05-04 | Thomas Jefferson University | Novel tumor suppressor gene and compositions and methods for making and using the same |
US20050266443A1 (en) | 2002-10-11 | 2005-12-01 | Thomas Jefferson University | Novel tumor suppressor gene and compositions and methods for making and using the same |
CN102304570B (zh) | 2002-11-13 | 2015-01-21 | 托马斯杰斐逊大学 | 用于癌症诊断和治疗的组合物和方法 |
US7250496B2 (en) | 2002-11-14 | 2007-07-31 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory genes and uses thereof |
WO2004071464A2 (en) | 2003-02-12 | 2004-08-26 | Johns Hopkins University School Of Medicine | Diagnostic application of differentially-expressed genes in lympho-hematopoietic stem cells |
WO2004079013A1 (en) | 2003-03-03 | 2004-09-16 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Ecto-5’-nucleotidase (cd73) used in the diagnosis and the treatment of pancreatic cancer |
US7183384B2 (en) | 2003-03-06 | 2007-02-27 | A & G Pharmaceutical, Inc. | Monoclonal antibody 7H11 reactive with human cancer |
AU2003286741A1 (en) | 2003-05-02 | 2004-11-26 | Thomas Jefferson University | Methods and compositions for diagnosis and therapy of parkin-associated disorders |
US20050069918A1 (en) | 2003-05-29 | 2005-03-31 | Francois Claret | JAB1 as a prognostic marker and a therapeutic target for human cancer |
BRPI0411526A (pt) | 2003-06-18 | 2006-08-01 | Genelux Corp | vìrus de vaccinia e outros microrganismos recombinates modificados e usos dos mesmos |
US7683036B2 (en) * | 2003-07-31 | 2010-03-23 | Regulus Therapeutics Inc. | Oligomeric compounds and compositions for use in modulation of small non-coding RNAs |
US8106180B2 (en) | 2003-08-07 | 2012-01-31 | Whitehead Institute For Biomedical Research | Methods and products for expression of micro RNAs |
US20050037362A1 (en) | 2003-08-11 | 2005-02-17 | Eppendorf Array Technologies, S.A. | Detection and quantification of siRNA on microarrays |
US8412541B2 (en) | 2003-08-14 | 2013-04-02 | Edda Technology, Inc. | Method and system for intelligent qualitative and quantitative analysis for medical diagnosis |
US20050084883A1 (en) | 2003-08-25 | 2005-04-21 | The Johns Hopkins University School Of Medicine | Method of diagnosis and treatment of pancreatic endocrine neoplasms based on differential gene expression analysis |
JP2007505634A (ja) | 2003-09-22 | 2007-03-15 | ロゼッタ インファーマティクス エルエルシー | Rna干渉を用いる合成致死スクリーニング |
WO2005028675A2 (en) | 2003-09-24 | 2005-03-31 | Oncotherapy Science, Inc. | Methods for detecting, diagnosing and treating hepatocellular carcinomas (hcc) |
US20050186589A1 (en) | 2003-11-07 | 2005-08-25 | University Of Massachusetts | Interspersed repetitive element RNAs as substrates, inhibitors and delivery vehicles for RNAi |
US20050164252A1 (en) | 2003-12-04 | 2005-07-28 | Yeung Wah Hin A. | Methods using non-genic sequences for the detection, modification and treatment of any disease or improvement of functions of a cell |
US8034548B2 (en) | 2003-12-19 | 2011-10-11 | The Regents Of The University Of California | Methods and materials for assessing prostate cancer therapies |
EP1713938A2 (en) | 2004-02-09 | 2006-10-25 | Thomas Jefferson University | DIAGNOSIS AND TREATMENT OF CANCERS WITH MicroRNA LOCATED IN OR NEAR CANCER-ASSOCIATED CHROMOSOMAL FEATURES |
US20050256072A1 (en) | 2004-02-09 | 2005-11-17 | University Of Massachusetts | Dual functional oligonucleotides for use in repressing mutant gene expression |
CA2558366A1 (en) | 2004-02-23 | 2005-09-01 | Erasmus Universiteit Rotterdam | Classification, diagnosis and prognosis of acute myeloid leukemia by gene expression profiling |
US7365058B2 (en) | 2004-04-13 | 2008-04-29 | The Rockefeller University | MicroRNA and methods for inhibiting same |
IL179285A (en) | 2004-05-14 | 2011-04-28 | Rosetta Genomics Ltd | Micrornas and uses thereof |
EP2290071B1 (en) | 2004-05-28 | 2014-12-31 | Asuragen, Inc. | Methods and compositions involving microRNA |
US7635563B2 (en) | 2004-06-30 | 2009-12-22 | Massachusetts Institute Of Technology | High throughput methods relating to microRNA expression analysis |
US20060037088A1 (en) | 2004-08-13 | 2006-02-16 | Shulin Li | Gene expression levels as predictors of chemoradiation response of cancer |
EP1797183B1 (en) | 2004-09-02 | 2012-08-01 | Yale University | Regulation of oncogenes by micrornas |
US20060057670A1 (en) * | 2004-09-10 | 2006-03-16 | The Chinese University Of Hong Kong | Genomic markers of hepatitis B virus associated with hepatocellular carcinomas |
US7592441B2 (en) | 2004-10-04 | 2009-09-22 | Rosetta Genomics Ltd | Liver cancer-related nucleic acids |
US7642348B2 (en) | 2004-10-04 | 2010-01-05 | Rosetta Genomics Ltd | Prostate cancer-related nucleic acids |
FR2877350B1 (fr) | 2004-11-03 | 2010-08-27 | Centre Nat Rech Scient | IDENTIFICATION ET UTILISATION DE miRNAs IMPLIQUES DANS LA DIFFERENCIATION DE CELLULES ISSUES D'UNE LEUCEMIE MYELOIDE |
CA2850323A1 (en) | 2004-11-12 | 2006-12-28 | Asuragen, Inc. | Methods and compositions involving mirna and mirna inhibitor molecules |
AU2005316384B2 (en) | 2004-12-14 | 2012-02-09 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of MLL-AF4 and uses thereof |
US20060185027A1 (en) | 2004-12-23 | 2006-08-17 | David Bartel | Systems and methods for identifying miRNA targets and for altering miRNA and target expression |
WO2006069584A2 (en) | 2004-12-29 | 2006-07-06 | Exiqon A/S | NOVEL OLIGONUCLEOTIDE COMPOSITIONS AND PROBE SEQUENCES USEFUL FOR DETECTION AND ANALYSIS OF microRNAs AND THEIR TARGET mRNAs |
US8071306B2 (en) | 2005-01-25 | 2011-12-06 | Merck Sharp & Dohme Corp. | Methods for quantitating small RNA molecules |
DE602006016739D1 (de) | 2005-01-25 | 2010-10-21 | Rosetta Inpharmatics Llc | Verfahren zur quantifizierung kleiner rna-moleküle |
US20070065840A1 (en) | 2005-03-23 | 2007-03-22 | Irena Naguibneva | Novel oligonucleotide compositions and probe sequences useful for detection and analysis of microRNAS and their target mRNAS |
GB2425311A (en) * | 2005-04-15 | 2006-10-25 | Ist Superiore Sanita | Micro RNA against kit protein |
EP2631292A3 (en) * | 2005-04-29 | 2013-11-20 | The Rockefeller University | Human microRNAs and methods for inhibiting same |
US20090209621A1 (en) * | 2005-06-03 | 2009-08-20 | The Johns Hopkins University | Compositions and methods for decreasing microrna expression for the treatment of neoplasia |
US20070065844A1 (en) | 2005-06-08 | 2007-03-22 | Massachusetts Institute Of Technology | Solution-based methods for RNA expression profiling |
US20060292616A1 (en) | 2005-06-23 | 2006-12-28 | U.S. Genomics, Inc. | Single molecule miRNA-based disease diagnostic methods |
EP1937845B1 (en) | 2005-08-01 | 2015-06-10 | The Ohio State University Research Foundation | Micro-rna-based methods and compositions for the diagnosis, prognosis and treatment of breast cancer |
US20070213292A1 (en) | 2005-08-10 | 2007-09-13 | The Rockefeller University | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
US20070123482A1 (en) | 2005-08-10 | 2007-05-31 | Markus Stoffel | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
EP1937280B1 (en) | 2005-09-12 | 2014-08-27 | The Ohio State University Research Foundation | Compositions for the therapy of bcl2-associated cancers |
CN101312740A (zh) | 2005-10-05 | 2008-11-26 | 俄亥俄州立大学研究基金会 | Wwox基因、包含该基因的载体和在癌症治疗中的用途 |
US7390792B2 (en) | 2005-12-15 | 2008-06-24 | Board Of Regents, The University Of Texas System | MicroRNA1 therapies |
EP2487253B1 (en) | 2006-01-05 | 2015-06-24 | The Ohio State University Research Foundation | MicroRNA-based methods and compositions for the diagnosis and treatment of solid cancers |
US7943318B2 (en) | 2006-01-05 | 2011-05-17 | The Ohio State University Research Foundation | Microrna-based methods and compositions for the diagnosis, prognosis and treatment of lung cancer |
EP2591794A1 (en) | 2006-01-05 | 2013-05-15 | The Ohio State University Research Foundation | MicroRNA expressions abnormalities in pancreatic endocrine and acinar tumors |
US20090007281A1 (en) | 2006-01-13 | 2009-01-01 | Battelle Memorial Institute | Animal Model for Assessing Copd-Related Diseases |
EP1996731A2 (en) | 2006-03-20 | 2008-12-03 | The Ohio State University Research Foundation | Microrna fingerprints during human megakaryocytopoiesis |
WO2007112097A2 (en) | 2006-03-24 | 2007-10-04 | Children's Medical Center Corporation | Novel signature self renewal gene expression programs |
WO2007127190A2 (en) | 2006-04-24 | 2007-11-08 | The Ohio State University Research Foundation | Pre-b cell proliferation and lymphoblastic leukemia/high-grade lymphoma in mir155 transgenic mice |
EP2455494B1 (en) | 2006-07-13 | 2013-12-18 | The Ohio State University Research Foundation | Micro-RNA-based methods and compositions for the diagnosis and treatment of colon related diseases |
US20080193943A1 (en) | 2006-09-05 | 2008-08-14 | Abbott Laboratories | Companion diagnostic assays for cancer therapy |
WO2008036776A2 (en) | 2006-09-19 | 2008-03-27 | Asuragen, Inc. | Mir-15, mir-26, mir -31,mir -145, mir-147, mir-188, mir-215, mir-216 mir-331, mmu-mir-292-3p regulated genes and pathways as targets for therapeutic intervention |
AU2007346101B2 (en) | 2006-09-19 | 2013-08-15 | The Ohio State University Research Foundation | TCL1 expression in chronic lymphocytic leukemia (CLL) regulated by miR-29 and miR-181 |
JP2010504350A (ja) | 2006-09-19 | 2010-02-12 | アシュラジェン インコーポレイテッド | 治療的介入の標的としての、miR−200によって調節される遺伝子および経路 |
EP2487240B1 (en) | 2006-09-19 | 2016-11-16 | Interpace Diagnostics, LLC | Micrornas differentially expressed in pancreatic diseases and uses thereof |
KR101221066B1 (ko) * | 2006-10-30 | 2013-02-12 | 삼성전자주식회사 | 측면 방출 렌즈와 이를 구비한 백라이트 유닛 및액정표시장치 |
JP2010508353A (ja) | 2006-10-31 | 2010-03-18 | アキリオン ファーマシューティカルズ,インコーポレーテッド | エルブシタビン薬学的組成物 |
EP2087135B8 (en) | 2006-11-01 | 2013-07-24 | The Ohio State University Research Foundation | Microrna expression signature for predicting survival and metastases in hepatocellular carcinoma |
US8293684B2 (en) | 2006-11-29 | 2012-10-23 | Exiqon | Locked nucleic acid reagents for labelling nucleic acids |
WO2008070082A2 (en) | 2006-12-04 | 2008-06-12 | The Johns Hopkins University | Stem-progenitor cell specific micro-ribonucleic acids and uses thereof |
US20090092974A1 (en) | 2006-12-08 | 2009-04-09 | Asuragen, Inc. | Micrornas differentially expressed in leukemia and uses thereof |
WO2008073919A2 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Mir-20 regulated genes and pathways as targets for therapeutic intervention |
CA2671299A1 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Functions and targets of let-7 micro rnas |
AU2007333107A1 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | miR-21 regulated genes and pathways as targets for therapeutic intervention |
US20090175827A1 (en) | 2006-12-29 | 2009-07-09 | Byrom Mike W | miR-16 REGULATED GENES AND PATHWAYS AS TARGETS FOR THERAPEUTIC INTERVENTION |
CN103555825B (zh) | 2007-01-31 | 2015-09-30 | 俄亥俄州立大学研究基金会 | 用于急性髓细胞白血病(aml)的诊断、预后和治疗的基于微rna的方法和组合物 |
TWI367949B (en) | 2007-04-10 | 2012-07-11 | Univ Nat Taiwan | Predicting post-treatment survival in cancer patients with microrn |
AU2008248319B2 (en) | 2007-04-30 | 2013-09-05 | The Ohio State University Research Foundation | Methods for differentiating pancreatic cancer from normal pancreatic function and/or chronic pancreatitis |
US20090005336A1 (en) | 2007-05-08 | 2009-01-01 | Zhiguo Wang | Use of the microRNA miR-1 for the treatment, prevention, and diagnosis of cardiac conditions |
US20090232893A1 (en) | 2007-05-22 | 2009-09-17 | Bader Andreas G | miR-143 REGULATED GENES AND PATHWAYS AS TARGETS FOR THERAPEUTIC INTERVENTION |
US20090131354A1 (en) | 2007-05-22 | 2009-05-21 | Bader Andreas G | miR-126 REGULATED GENES AND PATHWAYS AS TARGETS FOR THERAPEUTIC INTERVENTION |
WO2008154098A2 (en) | 2007-06-07 | 2008-12-18 | Wisconsin Alumni Research Foundation | Reagents and methods for mirna expression analysis and identification of cancer biomarkers |
JP5690588B2 (ja) | 2007-06-08 | 2015-03-25 | アメリカ合衆国 | 肝細胞癌のサブタイプを決定し、肝癌幹細胞を検出するための方法 |
AU2008261951A1 (en) | 2007-06-08 | 2008-12-18 | Asuragen, Inc. | miR-34 regulated genes and pathways as targets for therapeutic intervention |
CN101918424A (zh) | 2007-06-15 | 2010-12-15 | 俄亥俄州立大学研究基金会 | 用于靶向由Drosha介导的微小RNA加工的致癌ALL-1融合蛋白 |
EP2808398A1 (en) | 2007-07-31 | 2014-12-03 | The Ohio State University Research Foundation | Methods for reverting methylation by targeting DNMT3A and DNMT3B |
ES2627059T3 (es) | 2007-08-03 | 2017-07-26 | The Ohio State University Research Foundation | Regiones ultraconservadas que codifican ARNnc |
CA2696887C (en) | 2007-08-22 | 2016-06-28 | The Ohio State University Research Foundation | Methods and compositions for inducing deregulation of epha7 and erk phosphorylation in human acute leukemias |
US20090061424A1 (en) | 2007-08-30 | 2009-03-05 | Sigma-Aldrich Company | Universal ligation array for analyzing gene expression or genomic variations |
AU2008296022B2 (en) | 2007-09-06 | 2014-01-23 | The Ohio State University Research Foundation | MicroRNA signatures in human ovarian cancer |
JP5723156B2 (ja) | 2007-10-11 | 2015-05-27 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイションThe Ohio State University Research Foundation | 食道腺癌の診断及び治療のための方法及び組成物 |
JP2011504093A (ja) | 2007-10-26 | 2011-02-03 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイション | 脆弱性ヒスチジン三連構造(fhit)相互作用を同定するための方法およびその使用 |
US8575121B2 (en) | 2007-11-12 | 2013-11-05 | The United States of America as represented by the Secetary of the Department of Health and Human Services | Therapeutic applications of p53 isoforms in regenerative medicine, aging and cancer |
US20090123933A1 (en) | 2007-11-12 | 2009-05-14 | Wake Forest University Health Sciences | Microrna biomarkers in lupus |
US20100323357A1 (en) | 2007-11-30 | 2010-12-23 | The Ohio State University Research Foundation | MicroRNA Expression Profiling and Targeting in Peripheral Blood in Lung Cancer |
WO2009070805A2 (en) | 2007-12-01 | 2009-06-04 | Asuragen, Inc. | Mir-124 regulated genes and pathways as targets for therapeutic intervention |
WO2009086156A2 (en) | 2007-12-21 | 2009-07-09 | Asuragen, Inc. | Mir-10 regulated genes and pathways as targets for therapeutic intervention |
AU2009212543B2 (en) | 2008-02-01 | 2015-07-09 | The General Hospital Corporation | Use of microvesicles in diagnosis, prognosis and treatment of medical diseases and conditions |
WO2009100430A2 (en) | 2008-02-08 | 2009-08-13 | Asuragen, Inc | miRNAs DIFFERENTIALLY EXPRESSED IN LYMPH NODES FROM CANCER PATIENTS |
EP2260109A4 (en) | 2008-02-28 | 2011-06-08 | Univ Ohio State Res Found | METHODS AND COMPOSITIONS BASED ON MICRO-RNA FOR DIAGNOSING, PROGNOSING AND TREATING PROSTATE-RELATED DISORDERS |
JP2011517932A (ja) | 2008-02-28 | 2011-06-23 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイション | ヒト慢性リンパ球性白血病(ccl)と関連するマイクロrnaシグネチャーおよびその使用 |
JP2011516033A (ja) | 2008-02-28 | 2011-05-26 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイション | 急性骨髄性性白血病(aml)における細胞遺伝学および予後と関連するマイクロrnaシグネチャーおよびその使用 |
JP5662166B2 (ja) | 2008-02-28 | 2015-01-28 | ジ・オハイオ・ステイト・ユニバーシティ・リサーチ・ファウンデイションThe Ohio State University Research Foundation | 胃癌の診断、予後診断及び治療のためのマイクロrnaに基づいた方法及び組成物 |
EP2268832A2 (en) | 2008-03-06 | 2011-01-05 | Asuragen, INC. | Microrna markers for recurrence of colorectal cancer |
WO2009154835A2 (en) | 2008-03-26 | 2009-12-23 | Asuragen, Inc. | Compositions and methods related to mir-16 and therapy of prostate cancer |
EP2285960B1 (en) | 2008-05-08 | 2015-07-08 | Asuragen, INC. | Compositions and methods related to mir-184 modulation of neovascularization or angiogenesis |
CN102112110A (zh) | 2008-06-06 | 2011-06-29 | 米尔纳医疗股份有限公司 | 用于RNAi试剂体内递送的新型组合物 |
US9125923B2 (en) | 2008-06-11 | 2015-09-08 | The Ohio State University | Use of MiR-26 family as a predictive marker for hepatocellular carcinoma and responsiveness to therapy |
EP2323677A4 (en) | 2008-08-12 | 2013-01-09 | Univ Ohio State Res Found | MICRO-RNA BASED COMPOSITIONS AND METHODS OF DIAGNOSIS, FORECAST AND TREATMENT OF MULTIPLE MYELOMA |
US20110311555A1 (en) | 2008-11-21 | 2011-12-22 | The Ohio State University | Tc11 as a Transcriptional Regulator |
US20110275534A1 (en) | 2008-12-05 | 2011-11-10 | The Ohio State University | MicroRNA-Based Methods and Compositions for the Diagnosis, Prognosis and Treatment of Ovarian Cancer Using a Real-Time PCR Platform |
EP2401405A4 (en) | 2009-02-26 | 2013-10-16 | Univ Ohio State Res Found | MICROARN IN NON-SMOKERS AND METHODS AND RELATED MATERIALS |
-
2008
- 2008-06-09 JP JP2010511218A patent/JP5690588B2/ja not_active Expired - Fee Related
- 2008-06-09 ES ES12179592.6T patent/ES2537349T3/es active Active
- 2008-06-09 US US12/663,586 patent/US8465917B2/en not_active Expired - Fee Related
- 2008-06-09 ES ES08768266.2T patent/ES2527648T3/es active Active
- 2008-06-09 CN CN201310394618.6A patent/CN103602724B/zh not_active Expired - Fee Related
- 2008-06-09 ES ES12179595.9T patent/ES2536907T3/es active Active
- 2008-06-09 CN CN201610142734.2A patent/CN105950706A/zh active Pending
- 2008-06-09 WO PCT/US2008/007196 patent/WO2008153987A2/en active Application Filing
- 2008-06-09 EP EP12179592.6A patent/EP2559772B1/en not_active Not-in-force
- 2008-06-09 CA CA2690144A patent/CA2690144A1/en not_active Abandoned
- 2008-06-09 CN CN200880025276.8A patent/CN101711287B/zh not_active Expired - Fee Related
- 2008-06-09 EP EP20120179595 patent/EP2559773B1/en not_active Not-in-force
- 2008-06-09 AU AU2008262252A patent/AU2008262252B2/en not_active Ceased
- 2008-06-09 EP EP08768266.2A patent/EP2152900B1/en not_active Not-in-force
-
2013
- 2013-06-12 US US13/916,154 patent/US20140018409A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
US20140018409A1 (en) | 2014-01-16 |
EP2152900B1 (en) | 2014-10-15 |
CN105950706A (zh) | 2016-09-21 |
AU2008262252B2 (en) | 2013-09-12 |
ES2537349T3 (es) | 2015-06-05 |
EP2559772A1 (en) | 2013-02-20 |
CN103602724B (zh) | 2016-03-16 |
CN101711287A (zh) | 2010-05-19 |
CN101711287B (zh) | 2016-04-27 |
WO2008153987A3 (en) | 2009-01-29 |
US20100197770A1 (en) | 2010-08-05 |
CA2690144A1 (en) | 2008-12-18 |
ES2536907T3 (es) | 2015-05-29 |
EP2152900A2 (en) | 2010-02-17 |
EP2559773A1 (en) | 2013-02-20 |
EP2559773B1 (en) | 2015-04-22 |
ES2527648T3 (es) | 2015-01-28 |
US8465917B2 (en) | 2013-06-18 |
WO2008153987A2 (en) | 2008-12-18 |
AU2008262252A1 (en) | 2008-12-18 |
EP2559772B1 (en) | 2015-04-15 |
EP2152900A4 (en) | 2010-08-04 |
CN103602724A (zh) | 2014-02-26 |
JP2010528659A (ja) | 2010-08-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5690588B2 (ja) | 肝細胞癌のサブタイプを決定し、肝癌幹細胞を検出するための方法 | |
US11220713B2 (en) | MicroRNAs as biomarkers for endometriosis | |
JP5723156B2 (ja) | 食道腺癌の診断及び治療のための方法及び組成物 | |
Takei et al. | The metastasis-associated microRNA miR-516a-3p is a novel therapeutic target for inhibiting peritoneal dissemination of human scirrhous gastric cancer | |
AU2017213457B2 (en) | Micro-RNA biomarkers and methods of using same | |
JP2012500389A (ja) | 多発性脊髄腫の診断、予後および治療のためのマイクロrnaに基づく組成物および方法 | |
KR20110015013A (ko) | 결장직장암의 평가 방법 및 여기에 사용하기 위한 조성물 | |
EP3775288A1 (en) | Mirnas for treatment and in vitro diagnosis of drug resistant tumors | |
EP2942399B1 (en) | Method for the diagnosis of breast cancer | |
AU2009337963A1 (en) | Prognosis of breast cancer patients by monitoring the expression of two genes | |
AU2013207631B2 (en) | Methods for determining hepatocellular carcinoma subtype and detecting hepatic cancer stem cells | |
TWI756634B (zh) | 用於大腸直腸癌預後之生物標記 | |
Zang et al. | Hsa_circ_0001479 accelerates tumorigenesis of gastric cancer and mediates immune escape | |
WO2015006543A1 (en) | Method for predicting and detecting tumor metastasis in kidney cancer |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110608 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120604 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130603 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130903 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140313 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140612 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150105 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150202 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5690588 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |