RU2017126701A - Способ детекции нуклеосом, содержащих нуклеотиды - Google Patents
Способ детекции нуклеосом, содержащих нуклеотиды Download PDFInfo
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- RU2017126701A RU2017126701A RU2017126701A RU2017126701A RU2017126701A RU 2017126701 A RU2017126701 A RU 2017126701A RU 2017126701 A RU2017126701 A RU 2017126701A RU 2017126701 A RU2017126701 A RU 2017126701A RU 2017126701 A RU2017126701 A RU 2017126701A
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- dna
- nucleosome
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- 108010047956 Nucleosomes Proteins 0.000 title claims 23
- 210000001623 nucleosome Anatomy 0.000 title claims 23
- 238000000034 method Methods 0.000 title claims 15
- 239000002773 nucleotide Substances 0.000 title 1
- 239000013060 biological fluid Substances 0.000 claims 14
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims 12
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims 12
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims 12
- 239000011230 binding agent Substances 0.000 claims 8
- RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 claims 6
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims 6
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims 6
- 229930010555 Inosine Natural products 0.000 claims 6
- 206010028980 Neoplasm Diseases 0.000 claims 6
- 239000000090 biomarker Substances 0.000 claims 6
- 201000011510 cancer Diseases 0.000 claims 6
- 229960003786 inosine Drugs 0.000 claims 6
- 229940035893 uracil Drugs 0.000 claims 6
- 229940075420 xanthine Drugs 0.000 claims 6
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims 3
- CLGFIVUFZRGQRP-UHFFFAOYSA-N 7,8-dihydro-8-oxoguanine Chemical compound O=C1NC(N)=NC2=C1NC(=O)N2 CLGFIVUFZRGQRP-UHFFFAOYSA-N 0.000 claims 3
- 210000004369 blood Anatomy 0.000 claims 3
- 239000008280 blood Substances 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 238000005259 measurement Methods 0.000 claims 3
- 210000001124 body fluid Anatomy 0.000 claims 2
- 239000010839 body fluid Substances 0.000 claims 2
- 210000001072 colon Anatomy 0.000 claims 2
- 210000004072 lung Anatomy 0.000 claims 2
- 210000000214 mouth Anatomy 0.000 claims 2
- 210000000496 pancreas Anatomy 0.000 claims 2
- 210000002381 plasma Anatomy 0.000 claims 2
- 210000002966 serum Anatomy 0.000 claims 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 210000003679 cervix uteri Anatomy 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 238000003745 diagnosis Methods 0.000 claims 1
- 210000003238 esophagus Anatomy 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 238000012544 monitoring process Methods 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 claims 1
- 210000000664 rectum Anatomy 0.000 claims 1
- 210000003491 skin Anatomy 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
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Claims (43)
1. Применение основания ДНК, связанного с внеклеточной нуклеосомой, в качестве биомаркера в образце биологической жидкости в диагностике рака, причем основание ДНК выбрано из: урацила, инозина, ксантина, гипоксантина или модифицированного основания.
2. Применение по п.1, где внеклеточная нуклеосома представляет собой мононуклеосому или олигонуклеосому.
3. Применение по п.1, где основание ДНК, связанное с внеклеточной нуклеосомой, измеряют в образце крови.
4. Применение по п.1, где рак представляет собой рак мочевого пузыря, молочной железы, ободочной кишки, шейки матки, пищевода, почки, толстой кишки, легкого, полости рта, яичника, поджелудочной железы, предстательной железы, прямой кишки, кожи или желудка.
5. Применение по п.4, где рак представляет собой рак ободочной кишки, легкого, полости рта или поджелудочной железы.
6. Применение по п.1, где модифицированное основание выбрано из: 5-метилцитозина, 5-гидроксиметилцитозина или 7,8-дигидро-8-оксогуанина.
7. Способ детекции присутствия в образце биологической жидкости основания ДНК, связанного с внеклеточной нуклеосомой, в качестве биомаркера, включающий следующие стадии:
(i) контакт образца биологической жидкости с первым связующим веществом, которое связывается с нуклеосомами;
(ii) контакт нуклеосом или образца биологической жидкости со вторым связующим веществом, которое связывается с основанием ДНК;
(iii) детекцию или количественное определение связывания указанного второго связующего вещества с основанием ДНК в образце биологической жидкости; и
(iv) использование присутствия или степени такого связывания в качестве меры присутствия в образце биологической жидкости основания ДНК, связанного с нуклеосомами,
причем основание ДНК выбрано из: урацила, инозина, ксантина, гипоксантина или модифицированного основания.
8. Способ по п.7, где модифицированное основание выбрано из: 5-метилцитозина, 5-гидроксиметилцитозина или 7,8-дигидро-8-оксогуанина.
9. Способ по п.7, где связующее вещество представляет собой антитело.
10. Способ по п.7, где образец биологической жидкости представляет собой кровь, сыворотку или плазму.
11. Способ детекции присутствия в образце биологической жидкости основания ДНК, связанного с внеклеточной нуклеосомой, в качестве биомаркера, включающий следующие стадии:
(i) контакт образца биологической жидкости с первым связующим веществом, которое связывается с основанием ДНК;
(ii) контакт нуклеосом или образца биологической жидкости со вторым связующим веществом, которое связывается с нуклеосомами;
(iii) детекцию или количественное определение связывания указанного второго связующего вещества с нуклеосомами в образце биологической жидкости; и
(iv) использование присутствия или степени такого связывания в качестве меры присутствия в образце биологической жидкости основания ДНК, связанного с нуклеосомами,
причем основание ДНК выбрано из: урацила, инозина, ксантина, гипоксантина или модифицированного основания.
12. Способ по п.11, где модифицированное основание выбрано из: 5-метилцитозина, 5-гидроксиметилцитозина или 7,8-дигидро-8-оксогуанина.
13. Способ по п.11, где связующее вещество представляет собой антитело.
14. Способ по п.11, где образец представляет собой кровь, сыворотку или плазму.
15. Способ детекции состояния заболевания животного субъекта или человека, включающий следующие стадии:
(i) детекцию или измерение основания ДНК, связанного с внеклеточной нуклеосомой, в качестве биомаркера в биологической жидкости субъекта; и
(ii) использование уровня связанного с нуклеосомами основания ДНК, измеренного для определения состояния заболевания субъекта,
причем основание ДНК выбрано из: урацила, инозина, ксантина, гипоксантина или модифицированного основания, и
причем заболевание представляет собой рак.
16. Способ по п.15, где основание ДНК, связанное с внеклеточной нуклеосомой, определяют или измеряют как один из параметров измерений.
17. Способ оценки животного субъекта или человека в отношении пригодности для терапевтического лечения, включающий следующие стадии:
(i) детекцию или измерение основания ДНК, связанного с внеклеточной нуклеосомой, в качестве биомаркера в биологической жидкости субъекта; и
(ii) использование уровня связанного с нуклеосомами основания ДНК, определяемого в качестве параметра при выборе подходящего лечения для субъекта,
причем основание ДНК выбрано из: урацила, инозина, ксантина, гипоксантина или модифицированного основания, и
причем лечение проводят для лечения рака.
18. Способ по п.17, в котором основание ДНК, связанное с внеклеточной нуклеосомой, определяют или измеряют как один из параметров измерений.
19. Способ наблюдения лечения животного субъекта или человека, включающий следующие стадии:
(i) детекцию или измерение основания ДНК, связанного с внеклеточной нуклеосомой, в качестве биомаркера в биологической жидкости субъекта;
(ii) повторную детекцию или измерение основания ДНК, связанного с внеклеточной нуклеосомой, в биологической жидкости субъекта в один или несколько моментов времени; и
(iii) использование любых изменений уровня связанного с нуклеосомами основания ДНК, определяемого в качестве параметра любых изменений состояния субъекта,
причем основание ДНК выбрано из: урацила, инозина, ксантина, гипоксантина или модифицированного основания, и
причем лечение проводят для лечения рака.
20. Способ по п.19, где основание ДНК, связанное с внеклеточной нуклеосомой, определяют или измеряют как один из параметров измерений.
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