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Π Π°Π±ΠΎΡ‚Π°Π΅ΠΌ вмСстС Π΄ΠΎ ΠΏΠΎΠ±Π΅Π΄Ρ‹

Π˜Π½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΈΡ€ΡƒΡŽΡ‰Π°Ρ ΠΈ антипролифСративная активности ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ΠΎΠ² Π΄Ρ†Π ΠΠš Π² ΠΊΡƒΠ»ΡŒΡ‚ΡƒΡ€Π°Ρ… ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠ³ΠΎ происхоТдСния

Π”ΠΈΡΡΠ΅Ρ€Ρ‚Π°Ρ†ΠΈΡΠŸΠΎΠΌΠΎΡ‰ΡŒ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈΠ£Π·Π½Π°Ρ‚ΡŒ ΡΡ‚ΠΎΠΈΠΌΠΎΡΡ‚ΡŒΠΌΠΎΠ΅ΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹

Π’ Π½Π°ΡΡ‚оящСС врСмя ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· ΠΏΠ΅Ρ€Π²ΠΎΠΎΡ‡Π΅Ρ€Π΅Π΄Π½Ρ‹Ρ… Π·Π°Π΄Π°Ρ‡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΠΈ являСтся ΠΏΠΎΠ²Ρ‹ΡˆΠ΅Π½ΠΈΠ΅ эффСктивности лСчСния ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅ΠΉ, ΠΊΠ°ΠΊ ΠΏΡƒΡ‚Π΅ΠΌ Ρ€Π°Π·Ρ€Π°Π±ΠΎΡ‚ΠΊΠΈ Π½ΠΎΠ²Ρ‹Ρ… ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠ² лСчСния, Ρ‚Π°ΠΊ ΠΈ ΠΏΡƒΡ‚Π΅ΠΌ ΡΠΎΠ²Π΅Ρ€ΡˆΠ΅Π½ΡΡ‚Π²ΠΎΠ²Π°Π½ΠΈΡ Ρ‚Ρ€Π°Π΄ΠΈΡ†ΠΈΠΎΠ½Π½Ρ‹Ρ… тСрапСвтичСских ΠΏΠΎΠ΄Ρ…ΠΎΠ΄ΠΎΠ². Π₯ирургичСскоС Π²ΠΌΠ΅ΡˆΠ°Ρ‚Π΅Π»ΡŒΡΡ‚Π²ΠΎ, Ρ€Π°Π΄ΠΈΠ°Ρ†ΠΈΠΎΠ½Π½ΠΎΠ΅ ΠΎΠ±Π»ΡƒΡ‡Π΅Π½ΠΈΠ΅ ΠΈ Ρ…имиотСрапия ΠΎΡΡ‚Π°ΡŽΡ‚ΡΡ классичСскими ΠΈ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ распространСнными ΠΌΠ΅Ρ‚ΠΎΠ΄Π°ΠΌΠΈ лСчСния онкологичСских Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. К ΡΠΎΠΆΠ°Π»Π΅Π½ΠΈΡŽ… Π§ΠΈΡ‚Π°Ρ‚ΡŒ Π΅Ρ‰Ρ‘ >

Π‘ΠΎΠ΄Π΅Ρ€ΠΆΠ°Π½ΠΈΠ΅

  • Бписок сокращСний

Π“Π»Π°Π²Π° 1. ΠšΠΎΡ€Ρ€Π΅ΠΊΡ†ΠΈΡ Π½Π°Ρ€ΡƒΡˆΠ΅Π½ΠΈΠΉ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π° с ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ siPHK (ΠΎΠ±Π·ΠΎΡ€ Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Ρ‹).

1.1. Π’Π²Π΅Π΄Π΅Π½ΠΈΠ΅: РСгуляция ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π° ΠΈ Π΅Π΅ Π½Π°Ρ€ΡƒΡˆΠ΅Π½ΠΈΡ ΠΊΠ°ΠΊ мишСни для дСйствия ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… РНК.

1.2. РСгуляция ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π°.

1.2.1. Π¦ΠΈΠΊΠ»ΠΈΠ½Ρ‹ ΠΈ Ρ†ΠΈΠΊΠ»ΠΈΠ½-зависимыС ΠΊΠΈΠ½Π°Π·Ρ‹.

1.2.2. РСгуляция активности Ρ†ΠΈΠΊΠ»ΠΈΠ½ΠΎΠ² ΠΈ Ρ†ΠΈΠΊΠ»ΠΈΠ½-зависимых ΠΊΠΈΠ½Π°Π·.

1.2.3. «Π’ΠΎΡ‡ΠΊΠΈ ΠΏΡ€ΠΎΠ²Π΅Ρ€ΠΊΠΈ» ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π°.

1.3. ΠΠ°Ρ€ΡƒΡˆΠ΅Π½ΠΈΡ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π° ΠΈ ΠΈΡ… ΠΏΡ€ΠΈΡ‡ΠΈΠ½Ρ‹.

1.3.1. Her2 (c-erb-B2/Neu).

1.3.2. Π¦ΠΈΠΊΠ»ΠΈΠ½ Π’1.

1.3.3. ΠŸΡ€ΠΎΡ‚Π΅ΠΈΠ½ΠΊΠΈΠ½Π°Π·Π° Π‘ (РКБ).

1.4. ΠšΠ»Π΅Ρ‚ΠΎΡ‡Π½Π°Ρ Π΄ΠΈΡ„Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΡ€ΠΎΠ²ΠΊΠ°.

1.4.1. ΠŸΡ€ΠΎΡ†Π΅ΡΡΡ‹ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠΉ Π΄ΠΈΡ„Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΡ€ΠΎΠ²ΠΊΠΈ.

1.4.2. Π˜Π½Π΄ΡƒΠΊΡ‚ΠΎΡ€Ρ‹ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠΉ Π΄ΠΈΡ„Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΡ€ΠΎΠ²ΠΊΠΈ.

1.5. Π˜Π½Π³ΠΈΠ±ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ экспрСссии Π³Π΅Π½ΠΎΠ² с ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ siPHK.

1.5.1. РНК — интСрфСрСнция.

1.5.2. Активация систСмы Π²Ρ€ΠΎΠΆΠ΄Π΅Π½Π½ΠΎΠ³ΠΎ ΠΈΠΌΠΌΡƒΠ½ΠΈΡ‚Π΅Ρ‚Π° ΠΏΠΎΠ΄ дСйствиСм Π΄Ρ†Π ΠΠš.

1.5.3. ΠšΠ»ΠΈΠ½ΠΈΡ‡Π΅ΡΠΊΠΈΠ΅ испытания ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ΠΎΠ² Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ siPHK.

1.5.4. Π˜Π½Π΄ΡƒΠΊΡ†ΠΈΡ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠΉ Π΄ΠΈΡ„Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΡ€ΠΎΠ²ΠΊΠΈ с ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ siPHK.

Π˜Π½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΈΡ€ΡƒΡŽΡ‰Π°Ρ ΠΈ антипролифСративная активности ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ΠΎΠ² Π΄Ρ†Π ΠΠš Π² ΠΊΡƒΠ»ΡŒΡ‚ΡƒΡ€Π°Ρ… ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠ³ΠΎ происхоТдСния (Ρ€Π΅Ρ„Π΅Ρ€Π°Ρ‚, курсовая, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½Π°Ρ)

Π’ Π½Π°ΡΡ‚оящСС врСмя ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· ΠΏΠ΅Ρ€Π²ΠΎΠΎΡ‡Π΅Ρ€Π΅Π΄Π½Ρ‹Ρ… Π·Π°Π΄Π°Ρ‡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΠΈ являСтся ΠΏΠΎΠ²Ρ‹ΡˆΠ΅Π½ΠΈΠ΅ эффСктивности лСчСния ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅ΠΉ, ΠΊΠ°ΠΊ ΠΏΡƒΡ‚Π΅ΠΌ Ρ€Π°Π·Ρ€Π°Π±ΠΎΡ‚ΠΊΠΈ Π½ΠΎΠ²Ρ‹Ρ… ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠ² лСчСния, Ρ‚Π°ΠΊ ΠΈ ΠΏΡƒΡ‚Π΅ΠΌ ΡΠΎΠ²Π΅Ρ€ΡˆΠ΅Π½ΡΡ‚Π²ΠΎΠ²Π°Π½ΠΈΡ Ρ‚Ρ€Π°Π΄ΠΈΡ†ΠΈΠΎΠ½Π½Ρ‹Ρ… тСрапСвтичСских ΠΏΠΎΠ΄Ρ…ΠΎΠ΄ΠΎΠ². Π₯ирургичСскоС Π²ΠΌΠ΅ΡˆΠ°Ρ‚Π΅Π»ΡŒΡΡ‚Π²ΠΎ, Ρ€Π°Π΄ΠΈΠ°Ρ†ΠΈΠΎΠ½Π½ΠΎΠ΅ ΠΎΠ±Π»ΡƒΡ‡Π΅Π½ΠΈΠ΅ ΠΈ Ρ…имиотСрапия ΠΎΡΡ‚Π°ΡŽΡ‚ΡΡ классичСскими ΠΈ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ распространСнными ΠΌΠ΅Ρ‚ΠΎΠ΄Π°ΠΌΠΈ лСчСния онкологичСских Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. К ΡΠΎΠΆΠ°Π»Π΅Π½ΠΈΡŽ, Π΄Π°ΠΆΠ΅ комплСкс соврСмСнных ΠΏΡ€ΠΎΡ‚ΠΈΠ²ΠΎΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… мСроприятий, часто Π½Π΅ ΠΏΡ€ΠΈΠ²ΠΎΠ΄ΠΈΡ‚ ΠΊ ΠΏΠΎΠ»Π½ΠΎΠΉ элиминации ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ. ΠŸΠΎΡΡ‚ΠΎΠΌΡƒ, нСсмотря Π½Π° Π·Π°ΠΌΠ΅Ρ‚Π½Ρ‹Π΅ достиТСния Π² ΠΎΠ±Π»Π°ΡΡ‚ΠΈ Ρ‚Π΅Ρ€Π°ΠΏΠΈΠΈ онкологичСских Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, ΡƒΠ²Π΅Π»ΠΈΡ‡Π΅Π½ΠΈΠ΅ эффСктивности лСчСния злокачСствСнных ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅ΠΉ ΠΈ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ токсичности Ρ…ΠΈΠΌΠΈΠΎΡ‚Π΅Ρ€Π°ΠΏΠΈΠΈ ΠΏΡƒΡ‚Π΅ΠΌ создания лСкарствСнных срСдств Π³Π΅Π½-Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½ΠΎΠ³ΠΎ дСйствия ΡΠ²Π»ΡΡŽΡ‚ΡΡ ΠΈΡΠΊΠ»ΡŽΡ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎ Π°ΠΊΡ‚ΡƒΠ°Π»ΡŒΠ½Ρ‹ΠΌΠΈ.

Π’Π°ΠΆΠ½ΡƒΡŽ Ρ€ΠΎΠ»ΡŒ Π² ΠΏΡ€ΠΎΡ†Π΅ΡΡΠ΅ злокачСствСнной трансформации ΠΊΠ»Π΅Ρ‚ΠΎΠΊ ΠΈΠ³Ρ€Π°ΡŽΡ‚ Π³Π΅Π½Ρ‹, гипСрэкспрСссия ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… ΠΏΡ€ΠΈΠ²ΠΎΠ΄ΠΈΡ‚ ΠΊ Π½Π΅ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΠΈΡ€ΡƒΠ΅ΠΌΠΎΠΉ ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΠΈ (Π±Π΅Π»ΠΊΠΈ-рСгуляторы ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π°) [ 1 ], Π±Π»ΠΎΠΊΠΈΡ€ΠΎΠ²Π°Π½ΠΈΡŽ Π°ΠΏΠΎΠΏΡ‚ΠΎΠ·Π° [ 2 ], Π½Π°Ρ€ΡƒΡˆΠ΅Π½ΠΈΡŽ процСссов Π΄ΠΈΡ„Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΡ€ΠΎΠ²ΠΊΠΈ [3], ΠΏΠΎΠ²Ρ‹ΡˆΠ΅Π½ΠΈΡŽ уровня гСнСтичСской Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΠΈ [4], Π° Ρ‚Π°ΠΊΠΆΠ΅ ΠΊ ΡƒΡΠΈΠ»Π΅Π½ΠΈΡŽ ΠΈΠ½Π²Π°Π·ΠΈΠ²Π½Ρ‹Ρ… свойств ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²ΠΎΠΉ ΠΊΠ»Π΅Ρ‚ΠΊΠΈ [5−9]. НаиболСС часто, Π² ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Π½Π°Π±Π»ΡŽΠ΄Π°Π΅Ρ‚ΡΡ экспрСссия ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Ρ„ΠΎΡ€ΠΌ ΠΈΠ»ΠΈ гипСрэкспрСссия Π½ΠΎΡ€ΠΌΠ°Π»ΡŒΠ½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹Ρ… Π³Π΅Π½ΠΎΠ², ΠΊΠΎΠ΄ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… Ρ€Π΅Ρ†Π΅ΠΏΡ‚ΠΎΡ€Ρ‹, транскрипционныС Ρ„Π°ΠΊΡ‚ΠΎΡ€Ρ‹, Ρ‚ΠΈΡ€ΠΎΠ·ΠΈΠ½-ΠΊΠΈΠ½Π°Π·Ρ‹ ΠΈ Π΄Ρ€ΡƒΠ³ΠΈΠ΅ рСгуляторныС Π±Π΅Π»ΠΊΠΈ.

ΠŸΡƒΡ‚ΠΈ ΠΏΠ΅Ρ€Π΅Π΄Π°Ρ‡ΠΈ сигналов Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ΅ Π²ΠΊΠ»ΡŽΡ‡Π°ΡŽΡ‚ мноТСство Π΄ΡƒΠ±Π»ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… Π΄Ρ€ΡƒΠ³ Π΄Ρ€ΡƒΠ³Π° элСмСнтов, поэтому ΠΏΡ€ΠΈ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΠΈ экспрСссии ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ„Π°ΠΊΡ‚ΠΎΡ€Π°, ΡƒΡ‡Π°ΡΡ‚Π²ΡƒΡŽΡ‰Π΅Π³ΠΎ Π² ΠΏΠ΅Ρ€Π΅Π΄Π°Ρ‡Π΅ сигнала, Π²ΠΎΠ·ΠΌΠΎΠΆΠ½Π° компСнсация Π΅Π³ΠΎ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΈ ΠΏΡƒΡ‚Π΅ΠΌ Π°ΠΊΡ‚ΠΈΠ²Π°Ρ†ΠΈΠΈ Π°Π»ΡŒΡ‚Π΅Ρ€Π½Π°Ρ‚ΠΈΠ²Π½ΠΎΠ³ΠΎ сигнального ΠΏΡƒΡ‚ΠΈ [9]. Π’ ΡΠ²ΡΠ·ΠΈ с ΡΡ‚ΠΈΠΌ, поиск ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹Ρ… мишСнСй для Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½ΠΎΠ³ΠΎ дСйствия тСрапСвтичСских Π°Π³Π΅Π½Ρ‚ΠΎΠ² Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠΉ ΠΏΡ€ΠΈΡ€ΠΎΠ΄Ρ‹ являСтся Π°ΠΊΡ‚ΡƒΠ°Π»ΡŒΠ½ΠΎΠΉ Π·Π°Π΄Π°Ρ‡Π΅ΠΉ.

РНК-интСрфСрСнция прСдставляСт собой процСсс Π΄Π΅Π³Ρ€Π°Π΄Π°Ρ†ΠΈΠΈ мРНК-мишСни, ΠΊΠΎΡ‚ΠΎΡ€Ρ‹ΠΉ индуцируСтся ΠΏΠΎΠ΄ дСйствиСм Π΄Π²ΡƒΡ†Π΅ΠΏΠΎΡ‡Π΅Ρ‡Π½Ρ‹Ρ… ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… РНК Π΄Π»ΠΈΠ½ΠΎΠΉ Π½Π΅ ΠΌΠ΅Π½Π΅Π΅ 21−23 звСньСв, Π³ΠΎΠΌΠΎΠ»ΠΎΠ³ΠΈΡ‡Π½Ρ‹Ρ… участку Π΄Π°Π½Π½ΠΎΠΉ мРНК[10]. Π­Ρ‚ΠΎΡ‚ процСсс являСтся эффСктивным способом рСгуляции экспрСссии Π³Π΅Π½ΠΎΠ² Π² ΡΡƒΠΊΠ°Ρ€ΠΈΠΎΡ‚ичСских ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ…, появившимся Π² ΠΏΡ€ΠΎΡ†Π΅ΡΡΠ΅ ΡΠ²ΠΎΠ»ΡŽΡ†ΠΈΠΈ.

Π’Π²Π΅Π΄Π΅Π½ΠΈΠ΅

Π² ΠΊΠ»Π΅Ρ‚ΠΊΡƒ Π·1РНК ΠΎΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½Π½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ позволяСт эффСктивно ΡΠ½ΠΈΠ·ΠΈΡ‚ΡŒ ΡƒΡ€ΠΎΠ²Π΅Π½ΡŒ экспрСссии Π³Π΅Π½ΠΎΠ², ассоциированных с Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ΠΌ, Π΄ΠΎ ΡƒΡ€ΠΎΠ²Π½Ρ, ΡΠΎΠΎΡ‚Π²Π΅Ρ‚ΡΡ‚Π²ΡƒΡŽΡ‰Π΅Π³ΠΎ ΡƒΡ€ΠΎΠ²Π½ΡŽ этой мРНК Π² Π½ΠΎΡ€ΠΌΠ°Π»ΡŒΠ½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ…. На ΡΠ΅Π³ΠΎΠ΄Π½ΡΡˆΠ½ΠΈΠΉ дСнь ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΈΡ€ΡƒΡŽΡ‰ΠΈΠ΅ РНК Ρ€Π°ΡΡΠΌΠ°Ρ‚Ρ€ΠΈΠ²Π°ΡŽΡ‚ΡΡ Π½Π΅ Ρ‚ΠΎΠ»ΡŒΠΊΠΎ ΠΊΠ°ΠΊ пСрспСктивныС лСкарствСнныС ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚Ρ‹, Π½ΠΎ ΠΈ ΠΊΠ°ΠΊ эффСктивный инструмСнт для поиска молСкулярных мишСнСй для дСйствия лСкарствСнных ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ΠΎΠ². ИсслСдования ΠΏΠΎΠΊΠ°Π·Ρ‹Π²Π°ΡŽΡ‚, Ρ‡Ρ‚ΠΎ Π² ΠΊΠ°ΠΆΠ΄ΠΎΠΌ ΠΊΠΎΠ½ΠΊΡ€Π΅Ρ‚Π½ΠΎΠΌ случаС онкологичСского заболСвания экспрСссия большого числа Π³Π΅Π½ΠΎΠ², Π°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΠΎΠ²Π°Π½Π° ΠΈΠ»ΠΈ рСпрСссирована ΠΏΠΎ ΡΡ€Π°Π²Π½Π΅Π½ΠΈΡŽ с Π½ΠΎΡ€ΠΌΠ°Π»ΡŒΠ½Ρ‹ΠΌΠΈ Ρ€ΠΎΠ΄ΠΈΡ‚Π΅Π»ΡŒΡΠΊΠΈΠΌΠΈ ΠΊΠ»Π΅Ρ‚ΠΊΠ°ΠΌΠΈ, ΠΈ, исходя ΠΈΠ· ΡΡ‚ΠΎΠ³ΠΎ, установлСниС Ρ…Ρ€ΠΎΠ½ΠΎΠ»ΠΎΠ³ΠΈΠΈ событий злокачСствСнной трансформации являСтся ΠΏΡ€ΠΎΠ±Π»Π΅ΠΌΠ°Ρ‚ΠΈΡ‡Π½Ρ‹ΠΌ [9]. Π’Π΅ΠΌ Π½Π΅ ΠΌΠ΅Π½Π΅Π΅, ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΠ΅ экспрСссии Π³Π΅Π½ΠΎΠ², ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Π΅ ΠΊΠΎΠ΄ΠΈΡ€ΡƒΡŽΡ‚ Π±Π΅Π»ΠΊΠΈ, Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½ΠΎ располоТСнныС Π½Π° ΠΏΠ΅Ρ€Π΅ΡΠ΅Ρ‡Π΅Π½ΠΈΠΈ рСгуляторных каскадов ΠΈΠ»ΠΈ Π² Π½Π°Ρ‡Π°Π»Π΅ этих каскадов, ΠΌΠΎΠΆΠ΅Ρ‚ привСсти ΠΊ Π²ΠΎΡΡΡ‚Π°Π½ΠΎΠ²Π»Π΅Π½ΠΈΡŽ контроля Π½Π°Π΄ Π΄Π΅Π»Π΅Π½ΠΈΠ΅ΠΌ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ [11]. ВзаимодСйствия Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… Π³Π΅Π½ΠΎΠ², ΡƒΡ‡Π°ΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΡ… Π² ΠΏΡ€ΠΎΡ†Π΅ΡΡΠ°Ρ… ΠΊΠ°Π½Ρ†Π΅Ρ€ΠΎΠ³Π΅Π½Π΅Π·Π° интСнсивно ΠΈΡΡΠ»Π΅Π΄ΡƒΡŽΡ‚ΡΡ, Π½ΠΎ Ρ€ΠΎΠ»ΡŒ ΠΊΠ°ΠΆΠ΄ΠΎΠ³ΠΎ Π³Π΅Π½Π° Π² ΡΠ»ΠΎΠΆΠ½ΠΎΠΉ систСмС с Π±ΠΎΠ»Π΅Π΅ Ρ‡Π΅ΠΌ ΠΎΠ΄Π½ΠΈΠΌ гСнСтичСским Π½Π°Ρ€ΡƒΡˆΠ΅Π½ΠΈΠ΅ΠΌ Ρ‚Ρ€Π΅Π±ΡƒΠ΅Ρ‚ ΡƒΠ³Π»ΡƒΠ±Π»Π΅Π½Π½ΠΎΠ³ΠΎ изучСния [12]. ΠΠ°Ρ€ΡƒΡˆΠ΅Π½ΠΈΠ΅ рСгуляции Π³Π΅Π½ΠΎΠ², ΠΊΠΎΠ΄ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚Ρ‹ ΠΏΠ΅Ρ€Π΅Π΄Π°Ρ‡ΠΈ сигналов ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π° рассматриваСтся ΠΊΠ°ΠΊ ΠΊΠ»ΡŽΡ‡Π΅Π²ΠΎΠΉ Ρ„Π°ΠΊΡ‚ΠΎΡ€ Π² Ρ€Π°Π·Π²ΠΈΡ‚ΠΈΠΈ Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… Ρ‚ΠΈΠΏΠΎΠ² ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅ΠΉ Ρƒ Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ°[9, И, 12], Ρ‚Π΅ΠΌ Π½Π΅ ΠΌΠ΅Π½Π΅Π΅, тСрапСвтичСская Π·Π½Π°Ρ‡ΠΈΠΌΠΎΡΡ‚ΡŒ ингибирования Ρ‚Π°ΠΊΠΈΡ… Π³Π΅Π½ΠΎΠ² Π² ΠΎΠΏΡƒΡ…олях Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠ³ΠΎ происхоТдСния ΠΌΠΎΠΆΠ΅Ρ‚ сущСствСнно ΠΎΡ‚Π»ΠΈΡ‡Π°Ρ‚ΡŒΡΡ, поэтому для Π²Ρ‹Π±ΠΎΡ€Π° Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ эффСктивных мишСнСй трСбуСтся сравнСниС Π°Π½Ρ‚ΠΈΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½ΠΎΠ³ΠΎ дСйствия ΠΈΠ³ΠΈΠ±ΠΈΡ‚ΠΎΡ€ΠΎΠ² ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π»ΡŒΠ½Ρ‹Ρ… мишСнСй Π½Π° ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠ³ΠΎ происхоТдСния.

ЦСль ΠΈ Π·Π°Π΄Π°Ρ‡ΠΈ исслСдования

ЦСлью настоящСй Ρ€Π°Π±ΠΎΡ‚Ρ‹ являлось созданиС спСцифичСских ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€ΠΎΠ² экспрСссии Π³Π΅Π½ΠΎΠ², ΡƒΡ‡Π°ΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΡ… Π² Ρ€Π΅Π³ΡƒΠ»ΡΡ†ΠΈΠΈ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π°: НСг2 (с-Π΅Π³Π¬-Π’2, ΠΏΠ΅ΠΉ), ББНВ1 (Ρ†ΠΈΠΊΠ»ΠΈΠ½ Π’1) ΠΈ Π ΠšΠ‘ (ΠΏΡ€ΠΎΡ‚Π΅ΠΈΠ½ΠΊΠΈΠ½Π°Π·Π° Π‘), Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ Π΄Ρ†Π ΠΠš ΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ влияния этих ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€ΠΎΠ² Π½Π° ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΡŽ ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠ³ΠΎ происхоТдСния. Π’ Ρ…ΠΎΠ΄Π΅ исслСдования Ρ€Π΅ΡˆΠ°Π»ΠΈΡΡŒ ΡΠ»Π΅Π΄ΡƒΡŽΡ‰ΠΈΠ΅ Π·Π°Π΄Π°Ρ‡ΠΈ:

1. Π˜ΡΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚ΡŒ ΡΡ„Ρ„Π΅ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒ ΠΈ Π΄Π»ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ ΠΈΠ½Π³ΠΈΠ±ΠΈΡ€ΡƒΡŽΡ‰Π΅Π³ΠΎ дСйствия ΠΌΠ°Π»Ρ‹Ρ… ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… РНК Ρ„Π ΠΠš), Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½Ρ‹Ρ… Π½Π° ΠΌΠ ΠΠš Π³Π΅Π½ΠΎΠ² НСг2, Π‘Π‘Π¨1 ΠΈ Π ΠšΠ‘ Π² ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠ³ΠΎ происхоТдСния.

2. Π˜ΡΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚ΡŒ влияниС Π΄Π»ΠΈΠ½Π½Ρ‹Ρ… Π΄Ρ†Π ΠΠš, Π³ΠΎΠΌΠΎΠ»ΠΎΠ³ΠΈΡ‡Π½Ρ‹Ρ… мРНК Π³Π΅Π½ΠΎΠ² с-ΠœΡƒΡ ΠΈ ΠžΠ Π  Π½Π° ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΡŽ ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ°.

3. Π˜ΡΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚ΡŒ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ скорости ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΠΈ ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠ³ΠΎ происхоТдСния, ΠΏΠΎΠ΄Π²Π΅Ρ€Π³Π½ΡƒΡ‚Ρ‹Ρ… Π΄Π΅ΠΉΡΡ‚Π²ΠΈΡŽ Π·1РНК, Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½Ρ‹Ρ… Π½Π° ΠΌΠ ΠΠš Π³Π΅Π½ΠΎΠ² НСг2, Π‘Π‘Π«Π’1 ΠΈ Π ΠšΠ‘, послС восстановлСния экспрСссии Π³Π΅Π½ΠΎΠ²-мишСнСй.

4. Π˜ΡΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚ΡŒ влияниС ΠΏΠΎΠ»ΡƒΡ‡Π΅Π½Π½Ρ‹Ρ… Π·1РНК Π½Π° ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π³Π΅Π½Π½ΠΎΠΉ экспрСссии Π² ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ° ΠΈ ΠΈΡ… ΠΆΠΈΠ·Π½Π΅ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡ‚ΡŒ.

Π²Ρ‹Π²ΠΎΠ΄Ρ‹.

1. Π Π°Π·Ρ€Π°Π±ΠΎΡ‚Π°Π½Ρ‹ siPHK (siHer, siCyc, siPKC), Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½Ρ‹Π΅ ΠΊ ΠΌΠ ΠΠš Π³Π΅Π½ΠΎΠ² Her2, CCNB1 ΠΈ Π ΠšΠ‘. Показано, Ρ‡Ρ‚ΠΎ Π΄Π°Π½Π½Ρ‹Π΅ siPHK спСцифично ΠΈΠ½Π³ΠΈΠ±ΠΈΡ€ΡƒΡŽΡ‚ ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΡŽ Π³Π΅Π½ΠΎΠ²-мишСнСй Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… ΠšΠ’-3−1, SK-N-MC, MCF-7 ΠΈ HL-60: наибольшСС сниТСниС уровня мРНК-мишСнСй (Π΄ΠΎ 10 — 20% ΠΎΡ‚ ΠΊΠΎΠ½Ρ‚роля) достигаСтся Ρ‡Π΅Ρ€Π΅Π· 3 суток послС трансфСкции, Π° ΠΈΡΡ…ΠΎΠ΄Π½Ρ‹ΠΉ ΡƒΡ€ΠΎΠ²Π΅Π½ΡŒ экспрСссии восстанавливаСтся Ρ‡Π΅Ρ€Π΅Π· 7 суток.

2. Показано, Ρ‡Ρ‚ΠΎ ΠΈΠ½Π³ΠΈΠ±ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ экспрСссии Π³Π΅Π½ΠΎΠ² Her2, CCNB1 ΠΈ Π ΠšΠ‘ с Ρ€Π°Π·Π½ΠΎΠΉ ΡΡ„Ρ„Π΅ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒΡŽ замСдляСт Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ ΠšΠ’-3−1, SK-N-MC, MCF-7, ΠΎΠ΄Π½Π°ΠΊΠΎ Π½Π΅ Π²Π»ΠΈΡΠ΅Ρ‚ Π½Π° ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΡŽ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ HL-60. ΠžΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½ΠΎ, Ρ‡Ρ‚ΠΎ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ Π²Ρ‹Ρ€Π°ΠΆΠ΅Π½Π½Ρ‹ΠΉ Π°Π½Ρ‚ΠΈΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½Ρ‹ΠΉ эффСкт Π½Π°Π±Π»ΡŽΠ΄Π°Π΅Ρ‚ΡΡ Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ°Ρ… нСйробластомы SK-N-MC ΠΏΠΎΠ΄ дСйствиСм siCyc, Π° Ρ€ΠΎΡΡ‚ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ MCF-7 Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ эффСктивно тормозится ΠΏΠΎΠ΄ дСйствиСм siPKC. Π‘Ρ€Π°Π²Π½Π΅Π½ΠΈΠ΅ Π°Π½Ρ‚ΠΈΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½ΠΎΠ³ΠΎ дСйствия siPHK, Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½Ρ‹Ρ… ΠΊ ΠΌΠ ΠΠš Π³Π΅Π½ΠΎΠ² Her2, CCNB1 ΠΈ Π ΠšΠ‘, Π½Π° ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Π΅ ΠΊΠ»Π΅Ρ‚ΠΊΠΈ Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠ³ΠΎ происхоТдСния Π²Ρ‹ΠΏΠΎΠ»Π½Π΅Π½ΠΎ Π²ΠΏΠ΅Ρ€Π²Ρ‹Π΅.

3. ΠŸΠΎΠ»ΡƒΡ‡Π΅Π½Ρ‹ Π΄Ρ†Π ΠΠš, Π³ΠΎΠΌΠΎΠ»ΠΎΠ³ΠΈΡ‡Π½Ρ‹Π΅ мРНК Π³Π΅Π½ΠΎΠ² с-ΠœΡƒΡ (dsMyc) ΠΈ GFP (dsEGFP) Π΄Π»ΠΈΠ½ΠΎΠΉ 473 ΠΈ 448 ΠΏ.Π½., соотвСтствСнно. Показано, Ρ‡Ρ‚ΠΎ ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ dsMyc, Π΄Π΅ΠΉΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΠΉ ΠΊΠ°ΠΊ ΠΏΠΎ ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΡƒ РНК-ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΠΈ, Ρ‚Π°ΠΊ ΠΈ Ρ‡Π΅Ρ€Π΅Π· ΠΈΠ½Π΄ΡƒΠΊΡ†ΠΈΡŽ ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΎΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΠΎΡ‚Π²Π΅Ρ‚Π°, сниТаСт ΡƒΡ€ΠΎΠ²Π΅Π½ΡŒ экспрСссии ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΎΠ½-Ρ‡ΡƒΠ²ΡΡ‚Π²ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠ³ΠΎ Π³Π΅Π½Π° с-ΠœΡƒΡ Π±ΠΎΠ»Π΅Π΅ эффСктивно, Ρ‡Π΅ΠΌ ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ dsEGFP, Π΄Π΅ΠΉΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΠΉ Ρ‚ΠΎΠ»ΡŒΠΊΠΎ ΠΏΠΎ ΠΏΡƒΡ‚ΠΈ ΠΈΠ½Π΄ΡƒΠΊΡ†ΠΈΠΈ ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΎΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΠΎΡ‚Π²Π΅Ρ‚Π°. ΠŸΡ€ΠΈ этом ΠΎΠ±Π° ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚Π° Π΄Ρ†Π ΠΠš со ΡΡ€Π°Π²Π½ΠΈΠΌΠΎΠΉ ΡΡ„Ρ„Π΅ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒΡŽ Π·Π°ΠΌΠ΅Π΄Π»ΡΡŽΡ‚ Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ ΠšΠ’-3−1 ΠΈ SK-N-MC.

4. Π’ΠΏΠ΅Ρ€Π²Ρ‹Π΅ ΠΈΠ·ΡƒΡ‡Π΅Π½ΠΎ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ скорости ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΠΈ исслСдованных ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹Ρ… Π»ΠΈΠ½ΠΈΠΉ послС восстановлСния экспрСссии Π³Π΅Π½ΠΎΠ² Her2, CCNB1 ΠΈ Π ΠšΠ‘. Показано, Ρ‡Ρ‚ΠΎ ΡΠΊΠΎΡ€ΠΎΡΡ‚ΡŒ дСлСния ΠΊΠ»Π΅Ρ‚ΠΎΠΊ ΠšΠ’-3−1 восстанавливаСтся послС достиТСния исходного уровня экспрСссии Π³Π΅Π½ΠΎΠ²-мишСнСй, Π² Ρ‚ΠΎ Π²Ρ€Π΅ΠΌΡ ΠΊΠ°ΠΊ ΡΠΊΠΎΡ€ΠΎΡΡ‚ΡŒ дСлСния SK-N-MC остаСтся Π² 3 — 10 Ρ€Π°Π· сниТСнной Π΄ΠΎ 12 суток послС воздСйствия siHer, siCyc ΠΈ siPKC, Π° Ρ‚Π°ΠΊΠΆΠ΅ Π΄Π»ΠΈΠ½Π½Ρ‹Ρ… Π΄Ρ†Π ΠΠš.

5. Показано, Ρ‡Ρ‚ΠΎ Π²Π²Π΅Π΄Π΅Π½ΠΈΠ΅ Π² ΠΊΠ»Π΅Ρ‚ΠΊΠΈ siPHK, Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½Ρ‹Ρ… ΠΊ ΠΌΠ ΠΠš Π³Π΅Π½ΠΎΠ² Her2, CCNB1 ΠΈ Π ΠšΠ‘ Π½Π΅ Π²Ρ‹Π·Ρ‹Π²Π°Π΅Ρ‚ Π³ΠΈΠ±Π΅Π»ΠΈ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ, Π° ΠΏΠΎΠ΄Π°Π²Π»ΡΠ΅Ρ‚ ΠΈΡ… Π΄Π΅Π»Π΅Π½ΠΈΠ΅, Ρ‡Ρ‚ΠΎ подтвСрТдаСтся Π΄Π°Π½Π½Ρ‹ΠΌΠΈ морфологичСского Π°Π½Π°Π»ΠΈΠ·Π°. Напротив, доля ΠΌΠ΅Ρ€Ρ‚Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Π² ΠΏΠΎΠΏΡƒΠ»ΡΡ†ΠΈΠΈ, трансфСцированной Π΄Π»ΠΈΠ½Π½ΠΎΠΉ Π΄Ρ†Π ΠΠš Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎ увСличиваСтся, Ρ‡Ρ‚ΠΎ связано с ΠΈΠ½Π΄ΡƒΠΊΡ†ΠΈΠ΅ΠΉ ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΎΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΠΎΡ‚Π²Π΅Ρ‚Π° ΠΈ Π²Ρ‹Π·Π²Π°Π½Π½ΠΎΠΉ ΠΈΠΌ Π³ΠΈΠ±Π΅Π»ΡŒΡŽ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ.

6. Π‘ ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ ΠΏΠΎΠ»Π½ΠΎΠ³Π΅Π½ΠΎΠΌΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° транскриптома ΠΊΠ»Π΅Ρ‚ΠΎΠΊ SK-N-MC, трансфСцированных siCyc ΠΈ siPKC, ΠΎΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½ΠΎ, Ρ‡Ρ‚ΠΎ послС восстановлСния экспрСссии Π³Π΅Π½ΠΎΠ²-мишСнСй, экспрСссия ΠΎΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½Π½Ρ‹Ρ… Π³Π΅Π½ΠΎΠ² (EN02, AK3L1, ALDOC, TXNIP, Π’ NIP, DDIT4 ΠΈ Π΄Ρ€.) остаСтся ΠΈΠ·ΠΌΠ΅Π½Π΅Π½Π½ΠΎΠΉ, Ρ‡Ρ‚ΠΎ ΠΌΠΎΠΆΠ΅Ρ‚ ΠΎΠ±ΡƒΡΠ»Π°Π²Π»ΠΈΠ²Π°Ρ‚ΡŒ Π΄Π»ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠ΅ Π°Π½Ρ‚ΠΈΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ‚ΠΈΠ²Π½ΠΎΠ΅ дСйствиС исслСдуСмых siPHK Π² ΡΡ‚ΠΎΠΉ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠΉ Π»ΠΈΠ½ΠΈΠΈ.

3.10.

Π—Π°ΠΊΠ»ΡŽΡ‡Π΅Π½ΠΈΠ΅

.

ΠΠ°Ρ€ΡƒΡˆΠ΅Π½ΠΈΡ рСгуляции ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π°, ΡΠ²Π»ΡΡŽΡ‰ΠΈΠ΅ΡΡ ΠΏΡ€ΠΈΡ‡ΠΈΠ½ΠΎΠΉ развития ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ, ΠΌΠΎΠ³ΡƒΡ‚ Π±Ρ‹Ρ‚ΡŒ Π²Ρ‹Π·Π²Π°Π½Ρ‹ гипСрэкспрСссиСй ΠΈΠ»ΠΈ экспрСссиСй Ρ…ΠΈΠΌΠ΅Ρ€Π½Ρ‹Ρ… ΠΈΠ»ΠΈ ΠΌΡƒΡ‚Π°Π½Ρ‚Π½Ρ‹Ρ… Π²Π°Ρ€ΠΈΠ°Π½Ρ‚ΠΎΠ² рСгуляторных Ρ„Π°ΠΊΡ‚ΠΎΡ€ΠΎΠ², ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Π΅ относятся ΠΊ Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹ΠΌ классам Π±Π΅Π»ΠΊΠΎΠ². ΠŸΠΎΡΡ‚ΠΎΠΌΡƒ ΡƒΠ½ΠΈΠ²Π΅Ρ€ΡΠ°Π»ΡŒΠ½Ρ‹ΠΌ ΠΏΠΎΠ΄Ρ…ΠΎΠ΄ΠΎΠΌ для подавлСния ΠΈΡ… ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΠΈ являСтся использованиС ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… РНК, Π²Ρ‹Π·Ρ‹Π²Π°ΡŽΡ‰ΠΈΡ… Π΄Π΅Π³Ρ€Π°Π΄Π°Ρ†ΠΈΡŽ мРНК-мишСни ΠΏΠΎ ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΡƒ РНК-ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΠΈ. Π’Π°ΠΊΠΈΠ΅ ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΈΡ€ΡƒΡŽΡ‰ΠΈΠ΅ РНК ΠΌΠΎΠ³ΡƒΡ‚ Π½Π΅ Ρ‚ΠΎΠ»ΡŒΠΊΠΎ Ρ€Π°ΡΡΠΌΠ°Ρ‚Ρ€ΠΈΠ²Π°Ρ‚ΡŒΡΡ, ΠΊΠ°ΠΊ ΠΏΡ€ΠΎΡ‚ΠΎΠΏΠΈΡ‚Ρ‹ лСкарствСнных ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ΠΎΠ² Π½ΠΎΠ²ΠΎΠ³ΠΎ поколСния, Π½ΠΎ ΠΈ ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΠΎΠ²Π°Ρ‚ΡŒΡΡ для поиска Π½ΠΎΠ²Ρ‹Ρ… молСкулярных мишСнСй для ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ΠΎΠ² Π΄Ρ€ΡƒΠ³ΠΎΠ³ΠΎ Ρ‚ΠΈΠΏΠ° дСйствия. Ряд ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ΠΎΠ² Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ Π·1РНК ΡƒΠΆΠ΅ ΠΏΡ€ΠΎΡ…ΠΎΠ΄ΠΈΡ‚ клиничСскиС испытания, ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Π΅ позволят Π²Ρ‹ΡΠ²ΠΈΡ‚ΡŒ ΠΊΠ°ΠΊ тСрапСвтичСский ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π», Ρ‚Π°ΠΊ ΠΈ ΠΈΡ… Π²ΠΎΠ·ΠΌΠΎΠΆΠ½Ρ‹Π΅ ΠΏΠΎΠ±ΠΎΡ‡Π½Ρ‹Π΅ эффСкты. ΠŸΠΎΡΠΊΠΎΠ»ΡŒΠΊΡƒ Ρ†Π΅ΠΏΡŒ ΠΏΠ΅Ρ€Π΅Π΄Π°Ρ‡ΠΈ рСгуляторных сигналов Π² ΠΊΠ»Π΅Ρ‚ΠΊΠ΅ носит каскадный Ρ…Π°Ρ€Π°ΠΊΡ‚Π΅Ρ€ ΠΈ ΡΠΎΡΡ‚ΠΎΠΈΡ‚ ΠΈΠ· ΠΌΠ½ΠΎΠΆΠ΅ΡΡ‚Π²Π° Π΄ΡƒΠ±Π»ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… Π΄Ρ€ΡƒΠ³ Π΄Ρ€ΡƒΠ³Π° ΠΏΡƒΡ‚Π΅ΠΉ, Ρ‚ΠΎ Π²Π°ΠΆΠ½ΠΎΠΉ Π·Π°Π΄Π°Ρ‡Π΅ΠΉ являСтся поиск Ρ‚Π°ΠΊΠΈΡ… молСкулярных мишСнСй, ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΠ΅ экспрСссии ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… ΠΏΡ€ΠΈΠ²ΠΎΠ΄ΠΈΠ»ΠΎ Π±Ρ‹ ΠΊ Π½Π΅ΠΎΠ±Ρ€Π°Ρ‚ΠΈΠΌΡ‹ΠΌ ΠΈ Π½Π΅ΠΊΠΎΠΌΠΏΠ΅Π½ΡΠΈΡ€ΡƒΠ΅ΠΌΡ‹ΠΌ послСдствиям для ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²ΠΎΠΉ ΠΊΠ»Π΅Ρ‚ΠΊΠΈ, ΠΊ ΠΎΡΡ‚Π°Π½ΠΎΠ²ΠΊΠ΅ Π΅Π΅ Π΄Π΅Π»Π΅Π½ΠΈΡ.

Π’ Π½Π°ΡΡ‚оящСй Ρ€Π°Π±ΠΎΡ‚Π΅ Π½Π°ΠΌΠΈ Π±Ρ‹Π»Π° ΠΏΡ€Π΅Π΄Π»ΠΎΠΆΠ΅Π½ΠΈΠ° ΠΈ ΠΎΠΏΡ€ΠΎΠ±ΠΈΡ€ΠΎΠ²Π°Π½Π° схСма исслСдования влияния ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… РНК Π½Π° ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΡŽ ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Π½Π° ΠΏΡ€ΠΈΠΌΠ΅Ρ€Π΅ вгРНК, Π³ΠΎΠΌΠΎΠ»ΠΎΠ³ΠΈΡ‡Π½Ρ‹Ρ… мРНК Π³Π΅Π½ΠΎΠ² НСг2, Π‘Π‘Π«Π’1 ΠΈ Π ΠšΠ‘, Π° Ρ‚Π°ΠΊΠΆΠ΅ Π΄Π»ΠΈΠ½Π½Ρ‹Ρ… Π΄Ρ†Π ΠΠš Π³ΠΎΠΌΠΎΠ»ΠΎΠ³ΠΈΡ‡Π½Ρ‹Ρ… мРНК Π³Π΅Π½ΠΎΠ² с-ΠœΡƒΡ ΠΈ ΠžΠ Π . ΠžΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½ΠΎ, Ρ‡Ρ‚ΠΎ Π΄Π°Π½Π½Ρ‹Π΅ ΠΈΠ½Ρ‚Π΅Ρ€Ρ„Π΅Ρ€ΠΈΡ€ΡƒΡŽΡ‰ΠΈΠ΅ РНК с Ρ€Π°Π·Π½ΠΎΠΉ ΡΡ„Ρ„Π΅ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒΡŽ Π·Π°ΠΌΠ΅Π΄Π»ΡΡŽΡ‚ Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠ³ΠΎ происхоТдСния, Ρ‡Ρ‚ΠΎ ΡƒΠΊΠ°Π·Ρ‹Π²Π°Π΅Ρ‚ Π½Π° Π½Π΅ΠΎΠ±Ρ…ΠΎΠ΄ΠΈΠΌΠΎΡΡ‚ΡŒ ΠΈΠ΄Π΅Π½Ρ‚ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠΈ ΠΈΠ½Π΄ΠΈΠ²ΠΈΠ΄ΡƒΠ°Π»ΡŒΠ½Ρ‹Ρ… молСкулярных мишСнСй для Ρ‚Π΅Ρ€Π°ΠΏΠΈΠΈ ΠΊΠ°ΠΆΠ΄ΠΎΠ³ΠΎ Ρ‚ΠΈΠΏΠ° ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ заболСвания. Π’Ρ€Π°Π΄ΠΈΡ†ΠΈΠΎΠ½Π½ΠΎΠΉ мишСнью для Π³Π΅Π½-Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½Ρ‹Ρ… ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ΠΎΠ², ΠΏΡ€Π΅Π΄Π½Π°Π·Π½Π°Ρ‡Π΅Π½Π½Ρ‹Ρ… для лСчСния ΠΎΠΏΡƒΡ…ΠΎΠ»ΠΈ ΠΌΠΎΠ»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹ являСтся Π³Π΅Π½ НСг2, ΠΎΠ΄Π½Π°ΠΊΠΎ Π½Π°ΠΌΠΈ ΠΎΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½ΠΎ, Ρ‡Ρ‚ΠΎ Π·Π½Π°Ρ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎ Π±ΠΎΠ»Π΅Π΅ эффСктивной мишСнью для блокирования ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΠΈ ΠΊΠ»Π΅Ρ‚ΠΎΠΊ ΠΎΠΏΡƒΡ…ΠΎΠ»ΠΈ ΠΌΠΎΠ»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹ МБР-7 являСтся Π³Π΅Π½ РКБ. НаиболСС эффСктивными мишСнями для подавлСния роста нСйробластомы Π‘Πš-М-МБ ΡΠ²Π»ΡΡŽΡ‚ΡΡ Π³Π΅Π½Ρ‹ Π‘Π‘ΠœΠ’1 ΠΈ Π ΠšΠ‘, ΠΈΠ½Π³ΠΈΠ±ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ экспрСссии этих Π³Π΅Π½ΠΎΠ² Π²Ρ‹Π·Ρ‹Π²Π°Π΅Ρ‚ Π΄Π»ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠ΅ сниТСниС скорости ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΠΈ, ΠΊΠΎΡ‚ΠΎΡ€ΠΎΠ΅ сохраняСтся Π΄Π°ΠΆΠ΅ послС восстановлСния исходного уровня экспрСссии Π³Π΅Π½ΠΎΠ²-мишСнСй. Π”Π°Π½Π½Ρ‹Π΅ Π³Π΅Π½Ρ‹ ΠΌΠΎΠ³ΡƒΡ‚ Ρ€Π°ΡΡΠΌΠ°Ρ‚Ρ€ΠΈΠ²Π°Ρ‚ΡŒΡΡ ΠΊΠ°ΠΊ пСрспСктивныС мишСни для Ρ‚Π΅Ρ€Π°ΠΏΠΈΠΈ нСйробластом ΠΈ Ρ€Π°ΠΊΠ° ΠΌΠ°Π»ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹.

ΠŸΠΎΠ»ΡƒΡ‡Π΅Π½Π½Ρ‹Π΅ Π½Π°ΠΌΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€Ρ‹ экспрСссии Π³Π΅Π½ΠΎΠ² НСг2, Π‘Π‘Π«Π’1 ΠΈ Π ΠšΠ‘ ΠΌΠΎΠ³ΡƒΡ‚ Ρ€Π°ΡΡΠΌΠ°Ρ‚Ρ€ΠΈΠ²Π°Ρ‚ΡŒΡΡ ΠΊΠ°ΠΊ ΠΏΡ€ΠΎΡ‚ΠΎΡ‚ΠΈΠΏΡ‹ лСкарствСнных срСдств, для сдСрТивания роста ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ, ΠΏΠ΅Ρ€Π΅ΠΆΠΈΠ²ΡˆΠΈΡ… Ρ…ΠΈΠΌΠΈΠΎΡ‚Π΅Ρ€Π°ΠΏΠΈΡŽ, ΠΈ, Ρ‚Π°ΠΊΠΈΠΌ ΠΎΠ±Ρ€Π°Π·ΠΎΠΌ, ΠΌΠΎΠ³ΡƒΡ‚ ΡΡ‚Π°Ρ‚ΡŒ ΠΎΠ΄Π½ΠΈΠΌ ΠΈΠ· ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚ΠΎΠ² комплСксной Ρ‚Π΅Ρ€Π°ΠΏΠΈΠΈ ΠΏΡ€ΠΈ ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… заболСваниях ΠΈ Π½Π΅ΠΉΡ€ΠΎΠ±Π»Π°ΡΡ‚ΠΎΠΌΠ°Ρ…, Π² Ρ‡Π°ΡΡ‚ности. Π˜Π΄Π΅Π½Ρ‚ΠΈΡ„ΠΈΡ†ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Π΅ молСкулярныС мишСни ΠΌΠΎΠ³ΡƒΡ‚ Π±Ρ‹Ρ‚ΡŒ ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΠΎΠ²Π°Π½Ρ‹ Ρ‚Π°ΠΊΠΆΠ΅ для поиска низкомолСкулярных ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€ΠΎΠ² Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΉ этих Π±Π΅Π»ΠΊΠΎΠ², для получСния лСкарствСнных срСдств Π½ΠΎΠ²ΠΎΠ³ΠΎ поколСния. ΠžΠΏΡ€ΠΎΠ±ΠΈΡ€ΠΎΠ²Π°Π½Π½Π°Ρ Π½Π°ΠΌΠΈ тСхнологичСская ΠΏΠ»Π°Ρ‚Ρ„ΠΎΡ€ΠΌΠ° ΠΌΠΎΠΆΠ΅Ρ‚ ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΠΎΠ²Π°Ρ‚ΡŒΡΡ ΠΏΡ€ΠΈ скринингС молСкулярных мишСнСй для ΠΏΡ€ΠΎΡ‚ΠΈΠ²ΠΎΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ΠΎΠ² ΠΈ ΠΌΠΎΠΆΠ΅Ρ‚ Π±Ρ‹Ρ‚ΡŒ использована для Ρ€Π°ΡΡˆΠΈΡ€Π΅Π½Π½Ρ‹Ρ… исслСдований Ρ€Π°Π·Π»ΠΈΡ‡Π½ΠΎΠΉ Ρ†Π΅Π»Π΅Π²ΠΎΠΉ направлСнности.

ΠŸΠΎΠΊΠ°Π·Π°Ρ‚ΡŒ вСсь тСкст

Бписок Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Ρ‹

  1. Bishop JM. Retroviruses and Cancer Genes. // Advances in Cancer Research. 1982. V. 37. P. 1−32.
  2. Dive C. Avoidance of apoptosis as a mechanism of drug resistance. // Journal of Internal Medicine. 1997. V. 242. P. 139−45.
  3. Campbell SL, Khosravi-Far R, Rossman KL, Clark GJ, Der CJ. Increasing complexity of Ras signaling. // Oncogene. 1998. V. 17. P. 1395−413.
  4. Albertson DG, Collins C, McCormick F, Gray JW. Chromosome aberrations in solid tumors. //Nature Genetics. 2003. V. 34. P. 369−76.
  5. Bernhard EJ, Muschel RJ, Hughes EN. Mr 92,000 Gelatinase Release Correlates with the Metastatic Phenotype in Transformed Rat Embryo Cells. // Cancer Research. 1990. V. 50. P. 3872−7.
  6. Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular-Permeability Factor Vascular Endothelial Growth-Factor, Microvascular Hyperpermeability, and Angiogenesis. // American Journal of Pathology. 1995. V. 146. P. 1029−39.
  7. Malumbres M, Barbacid M. To cycle or not to cycle: A critical decision in cancer. // Nature Reviews Cancer. 2001. V. 1. P. 222−31.
  8. Malumbres M, Hunt SL, Sotillo R, Martin J, Odajima J, Martin A et al. Driving the cell cycle to cancer. // New Trends in Cancer for the 21 St Century. 2003. V. 532. P. 111.
  9. Sulic S, Panic L, Dikic I, Volarevic S. Deregulation of cell growth and malignant transformation. // Croatian Medical Journal. 2005. V. 46. P. 622−38.
  10. Mello CC, Conte D. Revealing the world of RNA interference. // Nature. 2004. V. 431. P. 338−42.
  11. Sandhu C, Slingerland J. Deregulation of the cell cycle in cancer. // Cancer Detection and Prevention. 2000. V. 24. P. 107−18.
  12. Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. // Cell Proliferation. 2003. V. 36. P. 131−49.
  13. Park MT, Lee SJ. Cell cycle and cancer. // Journal of Biochemistry and Molecular Biology. 2003. V. 36. P. 60−5.
  14. Malumbres M, Carnero A. Cell cycle deregulation: a common motif in cancer. // Prog Cell Cycle Res. 2003. V. 5. P. 5−18.
  15. Cook CC, Higuchi M. The awakening of an advanced malignant cancer: An insult to the mitochondrial genome. // Biochim Biophys Acta. 2011.
  16. Norbury C, Nurse P. Animal-Cell Cycles and Their Control. // Annual Review of Biochemistry. 1992. V. 61. P. 441−70.
  17. Murray AW, Kirschner MW. Dominoes and Clocks the Union of 2 Views of the Cell-Cycle. // Science. 1989. V. 246. P. 614−21.
  18. Edgar BA, Schubiger G. Parameters Controlling Transcriptional Activation During Early Drosophila Development. // Cell. 1986. V. 44. P. 871−7.
  19. Kimelman D, Kirschner M, Scherson T. The Events of the Midblastula Transition in Xenopus Are Regulated by Changes in the Cell-Cycle. // Cell. 1987. V. 48. P. 399 407.
  20. Newport J, Kirschner M. A Major Developmental Transition in Early Xenopus-Embryos .2. Control of the Onset of Transcription. // Cell. 1982. V. 30. P. 687−96.
  21. Hartwell LH, Weinert TA. Checkpoints Controls That Ensure the Order of Cell-Cycle Events. // Science. 1989. V. 246. P. 629−34.
  22. Fisher RP, Morgan DO. A Novel Cyclin Associates with Mol5/Cdk7 to Form the Cdk-Activating Kinase. // Cell. 1994. V. 78. P. 713−24.
  23. Morgan DO. Principles of Cdk Regulation. //Nature. 1995. V. 374. P. 131−4.
  24. Pines J. Cyclins and Cyclin-Dependent Kinases Theme and Variations. // Advances in Cancer Research, Vol 66. 1995. V. 66. P. 181−212.
  25. Rickert P, Seghezzi W, Shanahan F, Cho H, Lees E. Cyclin C/CDK8 is a novel CTD kinase associated with RNA polymerase II. // Oncogene. 1996. V. 12. P. 2631−40.
  26. Peng JM, Marshall NF, Price DH. Identification of a cyclin subunit required for the function of Drosophila P-TEFb. // Journal of Biological Chemistry. 1998. V. 273. P. 13 855−60.
  27. Okamoto K, Beach D. Cyclin-G Is A Transcriptional Target of the P53 Tumor-Suppressor Protein. // Embo Journal. 1994. V. 13. P. 4816−22.
  28. Evans T, Rosenthal ET, Youngblom J, Distel D, Hunt T. Cyclin A Protein Specified by Maternal Messenger-Rna in Sea-Urchin Eggs That Is Destroyed at Each Cleavage Division. // Cell. 1983. V. 33. P. 389−96.
  29. Pines J. Cyclins Wheels Within Wheels. // Cell Growth & Differentiation. 1991. V. 2. P. 305−10.
  30. Sherr CJ. G1 Phase Progression Cycling on Cue. // Cell. 1994. V. 79. P. 551−5.
  31. Assoian RK, Zhu XY. Cell anchorage and the cytoskeleton as partners in growth factor dependent cell cycle progression. // Current Opinion in Cell Biology. 1997. V. 9. P. 93−8.
  32. Ohtsubo M, Theodoras AM, Schumacher J, Roberts JM, Pagano M. Human Cyclin-E, A Nuclear-Protein Essential for the G (l)-To-S Phase-Transition. // Molecular and Cellular Biology. 1995. V. 15. P. 2612−24.
  33. Girard F, Strausfeld U, Fernandez A, Lamb NJC. Cyclin-A Is Required for the Onset of Dna-Replication in Mammalian Fibroblasts. // Cell. 1991. V. 67. P. 1169−79.
  34. Walker DH, Mailer JL. Role for Cyclin-A in the Dependence of Mitosis on Completion of Dna-Replication. //Nature. 1991. V. 354. P. 314−7.
  35. King RW, Jackson PK, Kirschner MW. Mitosis in Transition. // Cell. 1994. V. 79. P. 563−71.
  36. Arellano M, Moreno S. Regulation of CDK/cyclin complexes during the cell cycle. // International Journal of Biochemistry & Cell Biology. 1997. V. 29. P. 559−73.
  37. Glotzer M, Murray AW, Kirschner MW. Cyclin Is Degraded by the Ubiquitin Pathway. //Nature. 1991. V. 349. P. 132−8.
  38. Rechsteiner M, Rogers SW. PEST sequences and regulation by proteolysis. // Trends in Biochemical Sciences. 1996. V. 21. P. 267−71.
  39. Carnero A, Hannon GJ. The INK4 family of CDK inhibitors. // Cyclin Dependent Kinase (Cdk) Inhibitors. 1998. V. 227. P. 43−55.
  40. Harper JW, Elledge SJ, Keyomarsi K, Dynlacht B, Tsai LH, Zhang PM et al. Inhibition of Cyclin-Dependent Kinases by P21. // Molecular Biology of the Cell. 1995. V. 6. P. 387−400.
  41. Hengst L, Reed SI. Inhibitors the Cip/Kip family. // Cyclin Dependent Kinase (Cdk) Inhibitors. 1998. V. 227. P. 25−41.
  42. Reynisdottir I, Polyak K, Iavarone A, Massague J. Kip/Cip and Ink4 Cdk Inhibitors Cooperate to Induce Cell-Cycle Arrest in Response to Tgf-Beta. // Genes & Development. 1995. V. 9. P. 1831−45.
  43. Waga S, Li R, Stillman B. p53-induced p21 controls DNA replication. // Leukemia. 1997. V. 11 Suppl 3. P. 321−3.
  44. Hinds PW, Mittnacht S, Dulic V, Arnold A, Reed SI, Weinberg RA. Regulation of Retinoblastoma Protein Functions by Ectopic Expression of Human Cyclins. // Cell. 1992. V. 70. P. 993−1006.
  45. Montagnoli A, Fiore F, Eytan E, Carrano AC, Draetta GF, Hershko A, Pagano M. Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation. // Genes & Development. 1999. V. 13. P. 1181−9.
  46. Voitenleitner C, Fanning E, Nasheuer HP. Phosphorylation of DNA polymerase alpha-primase by cyclin A-dependent kinases regulates initiation of DNA replication in vitro. // Oncogene. 1997. V. 14. P. 1611−5.
  47. Zhao JY, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. // Genes & Development. 2000. V. 14. P. 2283−97.
  48. Lew DJ, Kornbluth S. Regulatory roles of cyclin dependent kinase phosphorylation in cell cycle control. // Current Opinion in Cell Biology. 1996. V. 8. P. 795−804.
  49. Jeffrey PD, Ruso AA, Polyak K, Gibbs E, Hurwitz J, Massague J, Pavletich NP. Mechanism of Cdk Activation Revealed by the Structure of A Cyclina-Cdlc2 Complex. //Nature. 1995. V. 376. P. 313−20.
  50. Paulovich AG, Hartwell LH. A Checkpoint Regulates the Rate of Progression Through S-Phase in Saccharomyces-Cerevisiae in Response to Dna-Damage. // Cell. 1995. V. 82. P. 841−7.
  51. Bradbury EM, Inglis RJ, Matthews HR. Control of cell division by very lysine rich histone (Fl) phosphorylation. //Nature. 1974. V. 247. P. 257−61.
  52. Sherr CJ, Roberts JM. Inhibitors of Mammalian G (l) Cyclin-Dependent Kinases. // Genes & Development. 1995. V. 9. P. 1149−63.
  53. Polyak K, Lee MH, Erdjumentbromage H, Koff A, Roberts JM, Tempst P, Massague J. Cloning of P27(Kipl), A Cyclin-Dependent Kinase Inhibitor and A Potential Mediator of Extracellular Antimitogenic Signals. // Cell. 1994. V. 78. P. 59−66.
  54. Lee MH, Reynisdottir I, Massague J. Cloning Or P57(Kip2), A Cyclin-Dependent Kinase Inhibitor with Unique Domain-Structure and Tissue Distribution. // Genes & Development. 1995. V. 9. P. 639−49.
  55. Pan ZQ, Reardon JT, Li L, Floresrozas H, Legerski R, Sancar A, Hurwitz J. Inhibition of Nucleotide Excision-Repair by the Cyclin-Dependent Kinase Inhibitor P21. // Journal of Biological Chemistry. 1995. V. 270. P. 22 008−16.
  56. Waga S, Li R, Stillman B. p53-induced p21 controls DNA replication. // Leukemia. 1997. V. 11 Suppl3.P. 321−3.
  57. Eldeiry WS, Tokino T, Velculescu YE, Levy DB, Parsons R, Trent JM et al. Wafl, A Potential Mediator of P53 Tumor Suppression. // Cell. 1993. V. 75. P. 817−25.
  58. Hannon GJ, Beach D. P15(Ink4B) Is A Potential Effector of Tgf-Beta-Induced Cell-Cycle Arrest. //Nature. 1994. V. 371. P. 257−61.
  59. Peng CY, Graves PR, Thoma RS, Wu ZQ, Shaw AS, PiwnicaWorms H. Mitotic and G (2) checkpoint control: Regulation of 14−3-3 protein binding by phosphorylation of Cdc25C on serine-216. // Science. 1997. V. 277. P. 1501−5.
  60. Yang J, Winkler K, Yoshida M, Kornbluth S. Maintenance of G (2) arrest in the Xenopus oocyte: a role for 14−3-3-mediated inhibition of Cdc25 nuclear import. // Embo Journal. 1999. V. 18. P. 2174−83.
  61. Heald R, Mcloughlin M, Mckeon F. Human Wee-1 Maintains Mitotic Timing by Protecting the Nucleus from Cytoplasmically Activated Cdc2 Kinase. // Cell. 1993. V. 74. P. 463−74.
  62. Liu F, Stanton JJ, Wu ZQ, PiwnicaWorms H. The human Mytl kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex. // Molecular and Cellular Biology. 1997. V. 17. P. 571−83.
  63. Buchkovich K, Duffy LA, Harlow E. The Retinoblastoma Protein Is Phosphorylated During Specific Phases of the Cell-Cycle. // Cell. 1989. V. 58. P. 1097−105.
  64. Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ. Direct Binding of Cyclin-D to the Retinoblastoma Gene-Product (Prb) and Prb Phosphorylation by the Cyclin D-Dependent Kinase Cdk4. // Genes & Development. 1993. V. 7. P. 331−42.
  65. Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T. Retinoblastoma protein recruits histone deacetylase to repress transcription. // Nature.1998. V. 391. P. 597−601.
  66. Bradbury E.M., Inglis R.J., Matthews H.R. Control of cell division by very lysine rich histone (Fl) phosphorylation//Nature. 1974. V. 247. P. 257−261.
  67. Blangy A, Lane HA, d’Herin P, Harper M, Kress M, Nigg EA. Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. // Cell. 1995. V. 83. P. 1159−69.
  68. Courvalin JC, Segil N, Blobel G, Worman HJ. The Lamin-B Receptor of the Inner Nuclear-Membrane Undergoes Mitosis-Specific Phosphorylation and Is A Substrate for P34Cdc2-Type Protein-Kinase. // Journal of Biological Chemistry. 1992. V. 267. P. 19 035−8.
  69. Heald R, Mckeon F. Mutations of Phosphorylation Sites in Lamin-A That Prevent Nuclear Lamina Disassembly in Mitosis. // Cell. 1990. V. 61. P. 579−89.
  70. Hoffmann I, Clarke PR, Marcote MJ, Karsenti E, Draetta G. Phosphorylation and Activation of Human Cdc25-C by Cdc2 Cyclin-B and Its Involvement in the Self-Amplification of Mpf at Mitosis. // Embo Journal. 1993. V. 12. P. 53−63.
  71. Poehlmann A, Roessner A. Importance of DNA damage checkpoints in the pathogenesis of human cancers. // Pathology Research and Practice. 2010. V. 206. P. 591−601.
  72. Pardee A.B. A restriction point for control of normal animal cell proliferation // Proc. Natl Acad. Sci. USA. 1974. V. 71. P. 1286−1290.
  73. Fang GW, Yu HT, Kirschner MW. The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. // Genes & Development. 1998. V. 12. P. 1871−83.
  74. Amon A. The spindle checkpoint. // Current Opinion in Genetics & Development.1999. V. 9. P. 69−75.
  75. Perry JJP, Cotner-Gohara E, Ellenberger T, Tainer JA. Structural dynamics in DNA damage signaling and repair. // Current Opinion in Structural Biology. 2010. V. 20. P. 283−94.
  76. Huen MSY, Chen J J. Assembly of checkpoint and repair machineries at DNA damage sites. // Trends in Biochemical Sciences. 2010. V. 35. P. 101−8.
  77. Levine AJ. p53, the cellular gatekeeper for growth and division. // Cell. 1997. V. 88. P. 323−31.
  78. Agarwal ML, Taylor WR, Chernov MV, Chernova OB, Stark GR. The p53 network. // Journal of Biological Chemistry. 1998. V. 273. P. 1−4.
  79. Ko LJ, Prives C. p53: Puzzle and paradigm. // Genes & Development. 1996. V. 10. P. 1054−72.
  80. Oren M. Regulation of the p53 tumor suppressor protein. // Journal of Biological Chemistry. 1999. V. 274. P. 36 031−4.
  81. Zhang YP, Xiong Y, Yarbrough WG. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. // Cell. 1998. V. 92. P. 725−34.
  82. Owenschaub LB, Zhang W, Cusack JC, Angelo LS, Santee SM, Fujiwara T et al. Wild-Type Human P53 and A Temperature-Sensitive Mutant Induce Fas/Apo-1 Expression. // Molecular and Cellular Biology. 1995. V. 15. P. 3032−40.
  83. Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B. A model for p53-induced apoptosis. //Nature. 1997. V. 389. P. 300−5.
  84. Gottlieb E, Oren M. p53 facilitates pRb cleavage in IL-3-deprived cells: novel pro-apoptotic activity of p53. //Embo Journal. 1998. V. 17. P. 3587−96.
  85. Siliciano JD, Canman CE, Taya Y, Sakaguchi K, Appella E, Kastan MB. DNA damage induces phosphorylation of the amino terminus of p53. // Genes & Development. 1997. V. 11. P. 3471−81.
  86. Hermeking H, Lengauer C, Polyak K, He TC, Zhang L, Thiagalingam S et al. 14−3-3 sigma is a p53-regulated inhibitor of G2/M progression. // Molecular Cell. 1997. V. 1. P. 3−11.
  87. Pardee AB. A Growth-Control Event Defective in Tumors A Citation-Classic Commentary on A Restriction Point for Control of Normal Animal-Cell Proliferation by Pardee, A.B. // Current Contents/Life Sciences. 1992. P. 11.
  88. Sanchez Y, Wong C, Thoma RS, Richman R, Wu RQ, PiwnicaWorms H, Elledge SJ. Conservation of the Chkl checkpoint pathway in mammals: Linkage of DNA damage to Cdk regulation through Cdc25. // Science. 1997. V. 277. P. 1497−501.
  89. Taylor WR, Stark GR. Regulation of the G2/M transition by p53. // Oncogene. 2001. V. 20. P. 1803−15.
  90. Zeng Y, Forbes KC, Wu ZQ, Moreno S, Piwnica-Worms H, Enoch T. Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cdsl or Chkl. // Nature. 1998. V. 395. P. 507−10.
  91. Ho A, Dowdy SF. Regulation of G (l) cell-cycle progression by oncogenes and tumor suppressor genes. // Curr Opin Genet Dev. 2002. V. 12. P. 47−52.
  92. MacLeod K. Tumor suppressor genes. // Curr Opin Genet Dev. 2000. V. 10. P. 81−93.
  93. Motoyama N, Naka K. DNA damage tumor suppressor genes and genomic instability. // Curr Opin Genet Dev. 2004. V. 14. P. 11−6.
  94. Jansen-Durr P. How viral oncogenes make the cell cycle. // Trends Genet. 1996. V. 12. P. 270−5.
  95. Jansen-Durr P. Viral oncogenesis and cell cycle control. // Virus Res. 1996. V. 42. P. 187−91.
  96. Ho A, Dowdy SF. Regulation of G (l) cell-cycle progression by oncogenes and tumor suppressor genes. // Curr Opin Genet Dev. 2002. V. 12. P. 47−52.
  97. Zachos G, Spandidos DA. Expression of ras proto-oncogenes: regulation and implications in the development of human tumors. // Crit Rev Oncol Hematol. 1997. V. 26. P. 65−75.
  98. Auerkari EI. Methylation of tumor suppressor genes pl6(INK4a), p27(Kipl) and E-cadherin in carcinogenesis. // Oral Oncol. 2006. V. 42. P. 5−13.
  99. Hwang-Verslues WW, Chang KJ, Lee EY, Lee WH. Breast cancer stem cells and tumor suppressor genes. // J Formos Med Assoc. 2008. V. 107. P. 751−66.
  100. Vurusaner B, Poli G, Basaga H. Tumor suppressor genes and ROS: complex networks of interactions. 11 Free Radic Biol Med. 2012. V. 52. P. 7−18.
  101. Buzard GS. Studies of oncogene activation and tumor suppressor gene inactivation in normal and neoplastic rodent tissue. // Mutat Res. 1996. V. 365. P. 43−58.
  102. Rubin P, Williams JP, Devesa SS, Travis LB, Constine LS. Cancer genesis across the age spectrum: associations with tissue development, maintenance, and senescence. // Semin Radiat Oncol. 2010. V. 20. P. 3−11.
  103. Irigaray P, Newby JA, Lacomme S, Belpomme D. Overweight/obesity and cancer genesis: more than a biological link. // Biomed Pharmacother. 2007. V. 61. P. 665−78.
  104. . П. МишСни дСйствия ΠΎΠ½ΠΊΠΎΠ³Π΅Π½ΠΎΠ² ΠΈ ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… супрСссоров: ΠΊΠ»ΡŽΡ‡ ΠΊ ΠΏΠΎΠ½ΠΈΠΌΠ°Π½ΠΈΡŽ Π±Π°Π·ΠΎΠ²Ρ‹Ρ… ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΠΊΠ°Π½Ρ†Π΅Ρ€ΠΎΠ³Π΅Π½Π΅Π·Π° // Биохиия. 2000. — Π’. 65, № 1. -Π‘. 5−33.
  105. Sherr CJ. Cancer cell cycles. // Science. 1996. V. 274. P. 1672−7.
  106. McDonald ER, El-Deiry WS. Cell cycle control as a basis for cancer drug development (review). // International Journal of Oncology. 2000. V. 16. P. 871−86.
  107. Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, Klehmannhieb E et al. A P16(Ink4A)-Insensitive Cdk4 Mutant Targeted by Cytolytic T-Lymphocytes in A Human-Melanoma. // Science. 1995. V. 269. P. 1281−4.
  108. Easton J, Wei T, Lahti JM, Kidd VJ. Disruption of the cyclin D cyclin-dependent kinase INK4 retinoblastoma protein regulatory pathway in human neuroblastoma. // Cancer Research. 1998. V. 58. P. 2624−32.
  109. Yamamoto H, Monden T, Miyoshi H, Izawa H, Ikeda K, Tsujie M et al. Cdk2/cdc2 expression in colon carcinogenesis and effects of cdk2/cdc2 inhibitor in colon cancer cells. // International Journal of Oncology. 1998. V. 13. P. 233−9.
  110. Kim JH, Kang MJ, Park CU, Kwak HJ, Hwang Y, Koh GY. Amplified CDK2 and cdc2 activities in primary colorectal carcinoma. // Cancer. 1999. V. 85. P. 546−53.
  111. McKenzie SJ. Diagnostic utility of oncogenes and their products in human cancer. // Biochim Biophys Acta. 1991. V. 1072. P. 193−214.
  112. Konopka JB, Witte ON. Detection of c-abl tyrosine kinase activity in vitro permits direct comparison of normal and altered abl gene products. // Mol Cell Biol. 1985. V. 5. P. 3116−23.
  113. Konopka JB, Witte ON. Activation of the abl oncogene in murine and human leukemias. // Biochim Biophys Acta. 1985. V. 823. P. 1−17.
  114. Davis RL, Konopka JB, Witte ON. Activation of the c-abl oncogene by viral transduction or chromosomal translocation generates altered c-abl proteins with similar in vitro kinase properties. // Mol Cell Biol. 1985. V. 5. P. 204−13.
  115. Lukas J, Lukas C, Bartek J. Mammalian cell cycle checkpoints: signalling pathways and their organization in space and time. // DNA Repair (Amst). 2004. V. 3. P. 9 971 007.116. van den Heuvel S. Cell-cycle regulation. // WormBook. 2005. P. 1−16.
  116. Berchuck A, Kamel A, Whitaker R, Kerns B, Olt G, Kinney R et al. Overexpression of Her-2/Neu Is Associated with Poor Survival in Advanced Epithelial Ovarian-Cancer. // Cancer Research. 1990. V. 50. P. 4087−91.
  117. Berchuck A, Rodriguez G, Kinney RB, Soper JT, Dodge RK, Clarkepearson DL, Bast RC. Overexpression of Her-2 Neu in Endometrial Cancer Is Associated with Advanced Stage Disease. // American Journal of Obstetrics and Gynecology. 1991. V. 164. P. 15−21.
  118. Hynes NE, Stern DF. The Biology of Erbb-2 Neu Her-2 and Its Role in Cancer. // Biochimica et Biophysica Acta-Reviews on Cancer. 1994. V. 1198. P. 165−84.
  119. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, Mcguire WL. Human-Breast Cancer Correlation of Relapse and Survival with Amplification of the Her-2 Neu Oncogene. // Science. 1987. V. 235. P. 177−82.
  120. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE et al. Studies of the Her-2/Neu Proto-Oncogene in Human-Breast and Ovarian-Cancer. // Science. 1989. V. 244. P. 707−12.
  121. Tandon AK, Clark GM, Chamness GC, Ullrich A, Mcguire WL. Her-2 Neu Oncogene Protein and Prognosis in Breast-Cancer. // Journal of Clinical Oncology. 1989. V. 7. P. 1120−8.
  122. Yarden Y. Biology of HER2 and its importance in breast cancer. // Oncology. 2001. V. 61.P. 1−13.
  123. Klein G. Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men. // Cell. 1983. V. 32. P. 311−5.
  124. Gerbitz A, Mautner J, Geltinger C, Hortnagel K, Christoph B, Asenbauer H et al. Deregulation of the proto-oncogene c-myc through t (8−22) translocation in Burkitt’s lymphoma. // Oncogene. 1999. V. 18. P. 1745−53.
  125. Depinho RA, Sehr eiber-Agus N, Alt FW. mye family oncogenes in the development of normal and neoplastic cells. // Adv Cancer Res. 1991. V. 57. P. 1−46.
  126. Schwab M. MYCN in neuronal tumours. // Cancer Lett. 2004. V. 204. P. 179−87.
  127. Thomas WD, Raif A, Hansford L, Marshall G. N-myc transcription molecule and oncoprotein. // Int J Biochem Cell Biol. 2004. V. 36. P. 771−5.
  128. Wu R, Lin L, Beer DG, Ellenson LH, Lamb BJ, Rouillard JM et al. Amplification and overexpression of the L-MYC proto-oncogene in ovarian carcinomas. // Am J Pathol. 2003. V. 162. P. 1603−10.
  129. Nau MM, Brooks BJ, Battey J, Sausville E, Gazdar AF, Kirsch IR et al. L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. // Nature. 1985. Y. 318. P. 69−73.
  130. Nesbit CE, Tersak JM, Prochownik EV. MYC oncogenes and human neoplastic disease. // Oncogene. 1999. V. 18. P. 3004−16.
  131. Tabin CJ, Bradley SM, Bargmann CI, Weinberg RA, Papageorge AG, Scolnick EM et al. Mechanism of activation of a human oncogene. //Nature. 1982. V. 300. P. 143−9.
  132. Reddy EP, Reynolds RK, Santos E, Barbacid M. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. // Nature. 1982. V. 300. P. 149−52.
  133. Yuasa Y, Srivastava SK, Dunn CY, Rhim JS, Reddy EP, Aaronson SA. Acquisition of transforming properties by alternative point mutations within c-bas/has human proto-oncogene. //Nature. 1983. V. 303. P. 775−9.
  134. Bos JL, Toksoz D, Marshall CJ, Verlaan-de VM, Veeneman GH, van der Eb AJ et al. Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia. //Nature. 1985. V. 315. P. 726−30.
  135. Bos JL, Verlaan-de VM, van der Eb AJ, Janssen JW, Deiwel R, Lowenberg B, Colly LP. Mutations in N-ras predominate in acute myeloid leukemia. // Blood. 1987. V. 69. P. 1237−41.
  136. Needleman SW, Kraus MH, Srivastava SK, Levine PH, Aaronson SA. High frequency of N-ras activation in acute myelogenous leukemia. // Blood. 1986. V. 67. P. 753−7.
  137. Machado-Silva A, Perrier S, Bourdon JC. p53 family members in cancer diagnosis and treatment. // Semin Cancer Biol. 2010. V. 20. P. 57−62.
  138. Chen F, Wang W, El-Deiry WS. Current strategies to target p53 in cancer. // Biochem Pharmacol. 2010. V. 80. P. 724−30.
  139. Benjamin CL, Melnikova VO, Ananthaswamy HN. P53 protein and pathogenesis of melanoma and nonmelanoma skin cancer. // Adv Exp Med Biol. 2008. V. 624. P. 26 582.
  140. Benjamin CL, Ananthaswamy HN. p53 and the pathogenesis of skin cancer. // Toxicol Appl Pharmacol. 2007. V. 224. P. 241−8.
  141. Korenaga D, Takesue F, Yasuda M, Honda M, Nozoe T, Inutsuka S. The relationship between cyclin B1 overexpression and lymph node metastasis in human colorectal cancer. // Surgery. 2002. V. 131. P. S114-S120.
  142. Soria JC, Jang SJ, Khuri FR, Hassan K, Lin D, Hong WK, Mao L. Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its clinical implication. // Cancer Research. 2000. V. 60. P. 4000−4.
  143. Chae SW, Sohn JH, Kim DH, Choi YJ, Park YL, Kim K et al. Overexpressions of Cyclin Bl, cdc2, pi6 and p53 in human breast cancer: the clinicopathologic correlations and prognostic implications. // Yonsei Med J. 2011. V. 52. P. 445−53.
  144. Aaltonen K, Amini RM, Heikkila P, Aittomaki K, Tamminen A, Nevanlinna H, Blomqvist C. High cyclin Bl expression is associated with poor survival in breast cancer. // Br J Cancer. 2009. V. 100. P. 1055−60.
  145. Alvaro V, Touraine P, Vozari RR, Baigrenier F, Birman P, Joubert D. Protein-Kinase-C Activity and Expression in Normal and Adenomatous Human Pituitaries. // International Journal of Cancer. 1992. V. 50. P. 724−30.
  146. Kopp R, Noelke B, Sauter G, Schildberg FW, Paumgartner G, Pfeiffer A. Altered Protein-Kinase-C Activity in Biopsies of Human Colonic Adenomas and Carcinomas. // Cancer Research. 1991. V. 51. P. 205−10.
  147. Obrian CA, Vogel VG, Singletary SE, Ward NE. Elevated Protein Kinase-C Expression in Human-Breast Tumor-Biopsies Relative to Normal Breast-Tissue. // Cancer Research. 1989. V. 49. P. 3215−7.
  148. Weichert W, Gekeler V, Denkert C, Dietel M, Hauptmann S. Protein kinase C isoform expression in ovarian carcinoma correlates with indicators of poor prognosis. // International Journal of Oncology. 2003. Y. 23. P. 633−9.
  149. Llambi F, Green DR. Apoptosis and oncogenesis: give and take in the BCL-2 family. // Curr Opin Genet Dev. 2011. V. 21. P. 12−20.
  150. Lindsay J, Esposti MD, Gilmore AP. Bcl-2 proteins and mitochondria-specificity in membrane targeting for death. // Biochim Biophys Acta. 2011. V. 1813. P. 532−9.
  151. Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, Green DR. The BCL-2 family reunion. // Mol Cell. 2010. V. 37. P. 299−310.
  152. Buggins AG, Pepper CJ. The role of Bcl-2 family proteins in chronic lymphocytic leukaemia. // Leuk Res. 2010. V. 34. P. 837−42.
  153. Aaltonen K, Amini RM, Heikkila P, Aittomaki K, Tamminen A, Nevanlinna H, Blomqvist C. High cyclin B1 expression is associated with poor survival in breast cancer. // British Journal of Cancer. 2009. V. 100. P. 1055−60.
  154. Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW et al. Human Epidermal Growth-Factor Receptor Cdna Sequence and Aberrant Expression of the Amplified Gene in A431 Epidermoid Carcinoma-Cells. // Nature. 1984. V. 309. P. 418−25.
  155. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. // Nature Reviews Molecular Cell Biology. 2001. V. 2. P. 127−37.
  156. Seshadri R, Matthews C, Dobrovic A, Horsfall DJ. The Significance of Oncogene Amplification in Primary Breast-Cancer. // International Journal of Cancer. 1989. V. 43. P. 270−2.
  157. Benz CC, Scott GK, Sarap JC, Johnson RM, Tripathy D, Coronado E et al. Estrogen-Dependent, Tamoxifen-Resistant Tumorigenic Growth of Mcf-7 Cells Transfected with Her2/Neu. // Breast Cancer Research and Treatment. 1992. V. 24. P. 85−95.
  158. Kern JA, Robinson RA, Gazdar A, Torney L, Weiner DB. Mechanisms of P185(Her2) Expression in Human Non-Small-Cell Lung-Cancer Cell-Lines. // American Journal of Respiratory Cell and Molecular Biology. 1992. Y. 6. P. 359−63.
  159. Williams TM, Weiner DB, Greene MI, Maguire HC. Expression of C-Erbb-2 in Human Pancreatic Adenocarcinomas. // Pathobiology. 1991. V. 59. P. 46−52.
  160. Hagting A, Karlsson C, Clute P, Jackman M, Pines J. MPF localization is controlled by nuclear export. // Embo Journal. 1998. V. 17. P. 4127−38.
  161. Li J, Meyer AN, Donoghue DJ. Nuclear localization of cyclin B1 mediates its biological activity and is regulated by phosphorylation. // Proceedings of the National Academy of Sciences of the United States of America. 1997. V. 94. P. 502−7.
  162. Toyoshima F, Moriguchi T, Wada A, Fukuda M, Nishida E. Nuclear export of cyclin B1 and its possible role in the DNA damage-induced G (2) checkpoint. // Embo Journal. 1998. V. 17. P. 2728−35.
  163. Yang J, Bardes ESG, Moore JD, Brennan J, Powers MA, Kornbluth S. Control of Cyclin B1 localization through regulated binding of the nuclear export factor CRM1. // Genes & Development. 1998. V. 12. P. 2131−43.
  164. Yang J, Song HB, Walsh S, Bardes ESG, Kornbluth S. Combinatorial control of cyclin B1 nuclear trafficking through phosphorylation at multiple sites. // Journal of Biological Chemistry. 2001. V. 276. P. 3604−9.
  165. Lehner CF, Ofarrell PH. The Roles of Drosophila Cyclin-A and Cyclin-B in Mitotic Control. // Cell. 1990. V. 61. P. 535−47.
  166. Viallard JF, Lacombe F, Dupouy M, Ferry H, Belloc F, Reiffers J. Flow cytometry study of human cyclin B1 and cyclin E expression in leukemic cell lines: Cell cycle kinetics and cell localization. // Experimental Cell Research. 1999. V. 247. P. 208−19.
  167. Shen ML, Feng YD, Gao C, Tao DD, Hu JB, Reed E et al. Detection of cyclin B1 expression in G (l)-phase cancer cell lines and cancer tissues by postsorting western blot analysis. // Cancer Research. 2004. V. 64. P. 1607−10.
  168. Hassan KA, El-Naggar AK, Soria JC, Liu D, Hong WK, Mao L. Clinical significance of cyclin B1 protein expression in squamous cell carcinoma of the tongue. // Clinical Cancer Research. 2001. V. 7. P. 2458−62.
  169. Hassan KA, Ang KK, El-Naggar AK, Story MD, Lee JI, Liu D et al. Cyclin B1 overexpression and resistance to radiotherapy in head and neck squamous cell carcinoma. // Cancer Research. 2002. V. 62. P. 6414−7.
  170. Takeno S, Noguchi T, Kikuchi R, Uchida Y, Yokoyama S, Muller W. Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma. // Cancer. 2002. V. 94. P. 2874−81.
  171. Yoshida T, Tanaka S, Mogi A, Shitara Y, Kuwano H. The clinical significance of Cyclin B1 and Weel expression in non-small-cell lung cancer. // Annals of Oncology. 2004. V. 15. P. 252−6.
  172. Jin P, Hardy S, Morgan DO. Nuclear localization of cyclin B1 controls mitotic entry after DNA damage. // Journal of Cell Biology. 1998. V. 141. P. 875−85.
  173. Park M, Chae HD, Yun J, Jung M, Kim YS, Kim SH et al. Constitutive activation of cyclin Bl-associated cdc2 kinase overrides p53-mediated G (2)-M arrest. // Cancer Research. 2000. V. 60. P. 542−5.
  174. Yin XY, Grove L, Datta NS, Katula K, Long MW, Prochownik EV. Inverse regulation of cyclin B1 by c-Myc and p53 and induction of tetraploidy by cyclin B1 overexpression. // Cancer Research. 2001. V. 61. P. 6487−93.
  175. Santana C, Ortega E, Garcia-Carranca A. Oncogenic H-ras induces cyclin B1 expression in a p53-independent manner. // Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis. 2002. V. 508. P. 49−58.
  176. Sarafan-Vasseur N, Lamy A, Bourguignon J, Le Pessot F, Hieter P, Sesboue R et al. Overexpression of B-type cyclins alters chromosomal segregation. // Oncogene. 2002. V. 21. P. 2051−7.
  177. Gollin SM. Mechanisms leading to chromosomal instability. // Seminars in Cancer Biology. 2005. V. 15. P. 33−42.
  178. Thompson SL, Bakhoum SF, Compton DA. Mechanisms of Chromosomal Instability. // Current Biology. 2010. V. 20. P. R285-R295.
  179. Michor F, Iwasa Y, Vogelstein B, Lengauer C, Nowak MA. Can chromosomal instability initiate tumorigenesis? // Seminars in Cancer Biology. 2005. V. 15. P. 43−9.
  180. Dong YY, Sui L, Watanabe Y, Sugimoto K, Tokuda M. Clinical relevance of cyclin B1 overexpression in laryngeal squamous cell carcinoma. // Cancer Letters. 2002. V. 177. P. 13−9.
  181. Li JQ, Kubo A, Wu F, Usuki H, Fujita J, Bandoh S et al. Cyclin Bl, unlike cyclin Gl, increases significantly during colorectal carcinogenesis and during later metastasis to lymph nodes. // International Journal of Oncology. 2003. V. 22. P. 1101−10.
  182. Nishizuka Y. Protein Kinases .5. Protein-Kinase-C and Lipid Signaling for Sustained Cellular-Responses. // Faseb Journal. 1995. V. 9. P. 484−96.
  183. Newton AC, Johnson JJ. Protein kinase C: a paradigm for regulation of protein function by two membrane-targeting modules. // Biochimica et Biophysica Acta-Reviews on Biomembranes. 1998. V. 1376. P. 155−72.
  184. Newton AC. Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. // Biochemical Journal. 2003. V. 370. P. 361−71.
  185. Jaken S. Protein kinase C isozymes and substrates. // Current Opinion in Cell Biology. 1996. V. 8. P. 168−73.
  186. Nishikawa K, Toker A, Johannes FJ, Zhou SY, Cantley LC. Determination of the specific substrate sequence motifs of protein kinase C isozymes. // Journal of Biological Chemistry. 1997. V. 272. P. 952−60.
  187. Zugaza JL, SinnettSmith J, VanLint J, Rozengurt E. Protein kinase D (PKD) activation in intact cells through a protein kinase C-dependent signal transduction pathway. // Embo Journal. 1996. V. 15. P. 6220−30.
  188. Paolucci L, Rozengurt E. Protein kinase D in small cell lung cancer cells: Rapid activation through protein kinase C. // Cancer Research. 1999. V. 59. P. 572−7.
  189. Nishizuka Y. Intracellular Signaling by Hydrolysis of Phospholipids and Activation of Protein-Kinase-C. // Science. 1992. V. 258. P. 607−14.
  190. Wetsel WC, Khan WA, Merchenthaler I, Rivera H, Halpem AE, Phung HM et al. Tissue and Cellular-Distribution of the Extended Family of Protein-Kinase-C Isoenzymes. // Journal of Cell Biology. 1992. V. 117. P. 121−33.
  191. Way KJ, Chou E, King GL. Identification of PKC-isoform-specific biological actions using pharmacological approaches. // Trends in Pharmacological Sciences. 2000. V. 21. P. 181−7.
  192. Parekh DB, Ziegler W, Parker PJ. Multiple pathways control protein kinase C phosphorylation. // Embo Journal. 2000. V. 19. P. 496−503.
  193. Shirakawa F, Mizel SB. Invitro Activation and Nuclear Translocation of Nf-Kappa-B Catalyzed by Cyclic Amp-Dependent Protein-Kinase and Protein Kinase-C. // Molecular and Cellular Biology. 1989. V. 9. P. 2424−30.
  194. Goode N, Hughes K, Woodgett JR, Parker PJ. Differential Regulation of Glycogen-Synthase Kinase-3-Beta by Protein-Kinase-C Isotypes. // Journal of Biological Chemistry. 1992. V. 267. P. 16 878−82.
  195. Reyland ME, Anderson SM, Matassa AA, Barzen KA, Quissell DO. Protein kinase C delta is essential for etoposide-induced apoptosis in salivary gland acinar cells. // Journal of Biological Chemistry. 1999. V. 274. P. 19 115−23.
  196. Majumder PK, Pandey P, Sun XG, Cheng KD, Datta R, Saxena S et al. Mitochondrial translocation of protein kinase C delta in phorbol ester-induced cytochrome C release and apoptosis. // Journal of Biological Chemistry. 2000. V. 275. P. 21 793−6.
  197. Pongracz J, Tuffley W, Johnson GD, Deacon EM, Burnett D, Stockley RA, Lord JM. Changes in Protein-Kinase-C Isoenzyme Expression Associated with Apoptosis in U937 Myelomonocytic Cells. //Experimental Cell Research. 1995. V. 218. P. 430−8.
  198. Berra E, Municio MM, Sanz L, Frutos S, DiazMeco MT, Moscat J. Positioning atypical protein kinase C isoforms in the UV-induced apoptotic signaling cascade. // Molecular and Cellular Biology. 1997. V. 17. P. 4346−54.
  199. Sharif TR, Sharif M. Overexpression of protein kinase C epsilon in astroglial brain tumor derived cell lines and primary tumor samples. // International Journal of Oncology. 1999. V. 15. P. 237−43.
  200. Tsai CL, Wang LH, Wen ZH. Alteration of norepinephrine and serotonin contents in the discrete brain of male and female tilapia, Oreochromis Mossambicus, during the lower temperature acclimation. // Biogenic Amines. 2000. V. 15. P. 655−67.
  201. Mandil R, Ashkenazi E, Blass M, Kronfeld I, Kazimirsky G, Rosenthal G et al. Protein kinase C alpha and protein kinase C delta play opposite roles in the proliferation and apoptosis of glioma cells. // Cancer Research. 2001. V. 61. P. 46 129.
  202. Lin SB, Wu LC, Huang SL, Hsu HL, Hsieh SH, Chi CW, Au LC. In vitro and in vivo suppression of growth of rat liver epithelial tumor cells by antisense oligonucleotide against protein kinase C-alpha. // Journal of Hepatology. 2000. V. 33. P. 601−8.
  203. Gourdeau H, Fournier REK. Genetic-Analysis of Mammalian-Cell Differentiation. // Annual Review of Cell Biology. 1990. V. 6. P. 69−94.
  204. Mohn F, Schubeier D. Genetics and epigenetics: stability and plasticity during cellular differentiation. // Trends in Genetics. 2009. V. 25. P. 129−36.
  205. Wang L, Walker BL, Iannaccone S, Bhatt D, Kennedy PJ, Tse WT. Bistable switches control memory and plasticity in cellular differentiation. // Proceedings of the National Academy of Sciences of the United States of America. 2009. V. 106. P. 6638−43.
  206. Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. // Nature. 2007. V. 447. P. 425−32.
  207. Pesce M, Scholer HR. Oct-4: Control of totipotency and germline determination. // Molecular Reproduction and Development. 2000. V. 55. P. 452−7.
  208. Pesce M, Anastassiadis K, Scholer HR. Oct-4: Lessons of totipotency from embryonic stem cells. // Cells Tissues Organs. 1999. V. 165. P. 144−52.
  209. Meier K, Lehr CM, Daum N. Differentiation potential of human pancreatic stem cells for epithelial- and endothelial-like cell types. // Annals of Anatomy-Anatomischer Anzeiger. 2009. V. 191. P. 70−82.
  210. Zola H, Swart B, Nicholson I, Aasted B, Bensussan A, Boumsell L et al. CD molecules 2005: human cell differentiation molecules. // Blood. 2005. V. 106. P. 3123−6.
  211. Zola H, Swart B, Banham A, Barry S, Beare A, Bensussan A et al. CD molecules 2006 Human cell differentiation molecules. // Journal of Immunological Methods. 2007. V. 319. P. 1−5.
  212. Stelling J, Sauer U, Szallasi Z, Doyle FJ, Doyle J. Robustness of cellular functions. // Cell. 2004. V. 118. P. 675−85.
  213. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. // Cell. 2006. V. 126. P. 663−76.
  214. Quesenberry PJ, Dooner G, Colvin G, Abedi M. Stem cell biology and the plasticity polemic. // Experimental Hematology. 2005. V. 33. P. 389−94.
  215. Durston AJ, Timmermans JPM, Hage WJ, Hendriks HF J, Devries NJ, Heideveld M, Nieuwkoop PD. Retinoic Acid Causes An Anteroposterior Transformation in the Developing Central Nervous-System. //Nature. 1989. V. 340. P. 140−4.
  216. Dosch R, Gawantka V, Delius H, Blumenstock C, Niehrs C. Bmp-4 acts as a morphogen in dorsoventral mesoderm patterning in Xenopus. // Development. 1997. V. 124. P. 2325−34.
  217. McDowell N, Zorn AM, Crease DJ, Gurdon JB. Activin has direct long-range signalling activity and can form a concentration gradient by diffusion. // Current Biology. 1997. V. 7. P. 671−81.
  218. Schuldiner M, Benvenisty N. Factors controlling human embryonic stem cell differentiation. //Methods Enzymol. 2003. V. 365. P. 446−61.
  219. Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA, Benvenisty N. Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. // ProcNatl Acad Sci USA. 2000. V. 97. P. 11 307−12.
  220. Zimmerman CM, Mathews LS. Activin receptors: cellular signalling by receptor serine kinases. //Biochem Soc Symp. 1996. V. 62. P. 25−38.
  221. Schuldiner M, Eiges R, Eden A, Yanuka O, Itskovitz-Eldor J, Goldstein RS, Benvenisty N. Induced neuronal differentiation of human embryonic stem cells. // Brain Res. 2001. V. 913. P. 201−5.
  222. Samarut E, Rochette-Egly C. Nuclear retinoic acid receptors: Conductors of the retinoic acid symphony during development. // Mol Cell Endocrinol. 2011.
  223. Soprano DR, Teets BW, Soprano KJ. Role of retinoic acid in the differentiation of embryonal carcinoma and embryonic stem cells. // Vitam Horm. 2007. V. 75. P. 6995.
  224. Duester G. Retinoic acid synthesis and signaling during early organogenesis. // Cell. 2008. V. 134. P. 921−31.
  225. Carpenter G, Zendegui JG. Epidermal growth factor, its receptor, and related proteins. // Exp Cell Res. 1986. V. 164. P. 1−10.
  226. Carpenter G. Epidermal growth factor: biology and mechanism of action. // Birth Defects Orig Artie Ser. 1980. V. 16. P. 61−72.
  227. Carpenter G. The biochemistry and physiology of the receptor-kinase for epidermal growth factor. // Mol Cell Endocrinol. 1983. V. 31. P. 1−19.
  228. Aloe L. Rita Levi-Montalcini: the discovery of nerve growth factor and modern neurobiology. // Trends Cell Biol. 2004. V. 14. P. 395−9.
  229. Aloe L. Rita Levi-Montalcini and the discovery of NGF, the first nerve cell growth factor. // Arch Ital Biol. 2011. V. 149. P. 175−81.
  230. Gospodarowicz D. Fibroblast growth factor and its involvement in developmental processes. // Curr Top Dev Biol. 1990. V. 24. P. 57−93.
  231. Gospodarowicz D, Neufeld G, Schweigerer L. Fibroblast growth factor: structural and biological properties. // J Cell Physiol Suppl. 1987. V. Suppl 5. P. 15−26.
  232. Marie PJ. Fibroblast growth factor signaling controlling osteoblast differentiation. // Gene. 2003. V. 316. P. 23−32.
  233. Jiang WG, Martin TA, Parr C, Davies G, Matsumoto K, Nakamura T. Hepatocyte growth factor, its receptor, and their potential value in cancer therapies. // Crit Rev Oncol Hematol. 2005. V. 53. P. 35−69.
  234. Funakoshi H, Nakamura T. Hepatocyte growth factor: from diagnosis to clinical applications. // Clin Chim Acta. 2003. V. 327. P. 1−23.
  235. Dobaczewski M, Chen W, Frangogiannis NG. Transforming growth factor (TGF)-beta signaling in cardiac remodeling. // J Mol Cell Cardiol. 2011. V. 51. P. 600−6.
  236. Azhar M, Schultz JJ, Grupp I, Dorn GW, Meneton P, Molin DG et al. Transforming growth factor beta in cardiovascular development and function. // Cytokine Growth Factor Rev. 2003. V. 14. P. 391−407.
  237. Rizzino A. Transforming growth factor-beta: multiple effects on cell differentiation and extracellular matrices. // Dev Biol. 1988. V. 130. P. 411−22.
  238. Barnard JA, Lyons RM, Moses HL. The cell biology of transforming growth factor beta. //Biochim Biophys Acta. 1990. Y. 1032. P. 79−87.
  239. Yingling JM, Wang XF, Bassing CH. Signaling by the transforming growth factor-beta receptors. // Biochim Biophys Acta. 1995. V. 1242. P. 115−36.
  240. Zimmerman CM, Padgett RW. Transforming growth factor beta signaling mediators and modulators. // Gene. 2000. V. 249. P. 17−30.
  241. Chin D, Boyle GM, Parsons PG, Coman WB. What is transforming growth factor-beta (TGF-beta)? // Br J Plast Surg. 2004. V. 57. P. 215−21.
  242. Chao MV. Neurotrophin receptors: a window into neuronal differentiation. // Neuron. 1992. V. 9. P. 583−93.
  243. Chao MV, Rajagopal R, Lee FS. Neurotrophin signalling in health and disease. // Clin Sci (Lond). 2006. V. 110. P. 167−73.
  244. Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. //Nat RevNeurosci. 2003. V. 4. P. 299−309.
  245. Friedman WJ, Greene LA. Neurotrophin signaling via Trks and p75. // Exp Cell Res. 1999. V. 253. P. 131−42.
  246. Gentry JJ, Barker PA, Carter BD. The p75 neurotrophin receptor: multiple interactors and numerous functions. // Prog Brain Res. 2004. V. 146. P. 25−39.
  247. Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system. // Curr OpinNeurobiol. 2000. V. 10. P. 381−91.
  248. Bondy CA, Cheng CM. Insulin-like growth factor-1 promotes neuronal glucose utilization during brain development and repair processes. // Int Rev Neurobiol. 2002. V. 51. P. 189−217.
  249. Ricort JM. Insulin-like growth factor binding protein (IGFBP) signalling. // Growth Horm IGF Res. 2004. V. 14. P. 277−86.
  250. Randhawa R, Cohen P. The role of the insulin-like growth factor system in prenatal growth. // Mol Genet Metab. 2005. V. 86. P. 84−90.
  251. Fernandez S, Fernandez AM, Lopez-Lopez C, Torres-Aleman I. Emerging roles of insulin-like growth factor-I in the adult brain. // Growth Horm IGF Res. 2007. V. 17. P. 89−95.
  252. Noguchi T, Miyachi H, Katayama R, Naito M, Hashimoto Y. Cell differentiation inducers derived from thalidomide. // Bioorganic & Medicinal Chemistry Letters. 2005. V. 15. P. 3212−5.
  253. Chiu FC, Feng L, Chan SO, Padin C, Federoff HJ. Expression of Neurofilament Proteins During Retinoic Acid-Induced Differentiation of P19 Embryonal Carcinoma-Cells. // Molecular Brain Research. 1995. V. 30. P. 77−86.
  254. Paterno GD, Gillespie LL, Julien JP, Skup D. Regulation of neurofilament L, M and H gene expression during retinoic acid-induced neural differentiation of PI9 embryonal carcinoma cells. // Molecular Brain Research. 1997. V. 49. P. 247−54.
  255. Schimmelpfeng J, Weibezahn KF, Dertinger H. Quantification of NGF-dependent neuronal differentiation of PC-12 cells by means of neurofilament-L mRNA expression and neuronal outgrowth. // Journal of Neuroscience Methods. 2004. V. 139. P. 299−306.
  256. Condello S, Caccamo D, Curro M, Ferlazzo N, Parisi G, Ientile R. Transglutaminase 2 and NF-kappa B interplay during NGF-induced differentiation of neuroblastoma cells. // Brain Research. 2008. V. 1207. P. 1−8.
  257. Burdge GC, Rodway H, Kohler JA, Lillycrop KA. Effect of fatty acid supplementation on growth and differentiation of human IMR-32 neuroblastoma cells in vitro. // Journal of Cellular Biochemistry. 2000. V. 80. P. 266−73.
  258. Chamras H, Ardashian A, Heber D, Glaspy JA. Fatty acid modulation of MCF-7 human breast cancer cell proliferation, apoptosis and differentiation. // Journal of Nutritional Biochemistry. 2002. V. 13. P. 711−6.
  259. Zagon IS, McLaughlin PJ. Opioids and differentiation in human cancer cells. // Neuropeptides. 2005. V. 39. P. 495−505.
  260. Martirosyan AR, Rahim-Bata R, Freeman AB, Clarke CD, Howard RL, Strobl JS. Differentiation-inducing quinolines as experimental breast cancer agents in the MCF-7 human breast cancer cell model. // Biochemical Pharmacology. 2004. V. 68. P. 172 938.
  261. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. //Nature. 2001. V. 414. P. 105−11.
  262. Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. //NatureReviews Cancer. 2003. V. 3. P. 895−902.
  263. Dontu G, Al-Hajj M, Abdallah WA, Clarke MF, Wicha MS. Stem cells in normal breast development and breast cancer. // Cell Proliferation. 2003. V. 36. P. 59−72.
  264. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB. Identification of a cancer stem cell in human brain tumors. // Cancer Research. 2003. V. 63. P. 5821−8.
  265. Jiang HP, Lin J, Su ZZ, Collart FR, Huberman E, Fisher PB. Induction of Differentiation in Human Promyelocytic Hl-60 Leukemia-Cells Activates P21, Wafl/Cipl, Expression in the Absence of P53. // Oncogene. 1994. V. 9. P. 3397−406.
  266. Ferrero D, Tarella C, Gallo E, Ruscetti FW, Breitman TR. Terminal Differentiation of the Human Promyelocytic Leukemia-Cell Line, Hl-60, in the Absence of Cell-Proliferation. // Cancer Research. 1982. V. 42. P. 4421−6.
  267. Fischkoff SA, Pollak A, Gleich GJ, Testa JR, Misawa S, Reber TJ. Eosinophilic Differentiation of the Human Promyelocytic Leukemia-Cell Line, Hl-60. // Journal of Experimental Medicine. 1984. V. 160. P. 179−96.
  268. Oshima RG, Abrams L, Kulesh D. Activation of An Intron Enhancer Within the Keratin 18-Gene by Expression of C-Fos and C-Jun in Undifferentiated F9-Embryonal Carcinoma-Cells. // Genes & Development. 1990. V. 4. P. 835−48.
  269. Parmar S, Tallman MS. Acute promyelocytic leukaemia: a review. // Expert Opinion on Pharmacotherapy. 2003. V. 4. P. 1379−92.284,285,286,287,288,289,290,291.292,293.294.295,296,297,
  270. Fuchs E, Green H. Regulation of Terminal Differentiation of Cultured Human Keratinocytes by Vitamin-A. // Cell. 1981. V. 25. P. 617−25.
  271. De Luca LM. Retinoids and Their Receptors in Differentiation, Embryogenesis, and Neoplasia. // Faseb Journal. 1991. V. 5. P. 2924−33.
  272. Hong WK, Lippman SM, Itri LM, Karp DD, Lee JS, Byers RM et al. Prevention of 2Nd Primary Tumors with Isotretinoin in Squamous-Cell Carcinoma of the Head and Neck. //NewEngland Journal ofMedicine. 1990. V. 323. P. 795−801.
  273. Chen TC, Holick MF. Vitamin D and prostate cancer prevention and treatment. // Trends in Endocrinology and Metabolism. 2003. V. 14. P. 423−30.
  274. Galsky M, Kelly WK. The development of differentiation agents for the treatment of prostate cancer. // Seminars in Oncology. 2003. V. 30. P. 689−97.
  275. Reynolds CP, Matthay KK, Villablanca JG, Maurer B J. Retinoid therapy of high-risk neuroblastoma. // Cancer Letters. 2003. V. 197. P. 185−92.
  276. Asiedu C, Biggs J, Lilly M, Kraft AS. Inhibition of Leukemic-Cell Growth by the Protein-Kinase-C Activator Bryostatin-1 Correlates with the Dephosphorylation of Cyclin-Dependent Kinase-2. // Cancer Research. 1995. V. 55. P. 3716−20.
  277. Kraft AS, William F, Pettit GR, Lilly MB. Varied Differentiation Responses of Human Leukemias to Bryostatin 1. // Cancer Research. 1989. V. 49. P. 1287−93.
  278. Vrana JA, Saunders AM, Chellappan SP, Grant S. Divergent effects of bryostatin 1 and phorbol myristate acetate on cell cycle arrest and maturation in human myelomonocytic leukemia cells (U937). // Differentiation. 1998. V. 63. P. 33−42.
  279. Hoffman DR, Huberman E. The Control of Phospholipid Methylation by Phorbol Diesters in Differentiating Human Myeloid Hl-60 Leukemia-Cells. // Carcinogenesis. 1982. V. 3. P. 875−80.
  280. Avvisati G, Tallman MS. All-trans retinoic acid in acute promyelocyte leukaemia. // Best Pract Res Clin Haematol. 2003. V. 16. P. 419−32.
  281. Lin TL, Vala MS, Barber JP, Karp JE, Smith BD, Matsui W, Jones RJ. Induction of acute lymphocytic leukemia differentiation by maintenance therapy. // Leukemia. 2007. V. 21. P. 1915−20.
  282. Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A et al. All-trans-retinoic acid in acute promyelocytic leukemia. // N Engl J Med. 1997. V. 337. P. 1021−8.
  283. Fisher PB, Prignoli DR, Hermo H, Jr., Weinstein IB, Pestka S. Effects of combined treatment with interferon and mezerein on melanogenesis and growth in human melanoma cells. // J Interferon Res. 1985. V. 5. P. 11−22.
  284. Fisher PB, Grant S. Effects of interferon on differentiation of normal and tumor cells. //Pharmacol Ther. 1985. V. 27. P. 143−66.
  285. Llinares ME, Bermudez M, Fuster JL, Diaz MS, Gonzalez CM. Toxicity to topical dimethyl sulfoxide in a pediatric patient with anthracycline extravasation. // Pediatric Hematology and Oncology. 2005. V. 22. P. 49−52.
  286. Yu HN, Lee YR, Noh EM, Lee KS, Song EK, Han MK et al. Tumor necrosis factor-alpha enhances DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK pathway. // International Journal of Hematology. 2008. V. 87. P. 18 994.
  287. Lennard L, Lilleyman JS. Variable mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukemia. // J Clin Oncol. 1989. V. 7. P. 1816−23.
  288. Pearson AD, Amineddine HA, Yule M, Mills S, Long DR, Craft AW, Chessells JM. The influence of serum methotrexate concentrations and drug dosage on outcome in childhood acute lymphoblastic leukaemia. // Br J Cancer. 1991. V. 64. P. 169−73.
  289. Kitamura R, Ogata T, Tanaka Y, Motoyoshi K, Seno M, Takei I et al. Conophylline and betacellulin-delta4: an effective combination of differentiation factors for pancreatic beta cells. // Endocr J. 2007. V. 54. P. 255−64.
  290. Kojima I, Umezawa K. Conophylline: A novel differentiation inducer for pancreatic beta cells. // International Journal of Biochemistry & Cell Biology. 2006. V. 38. P. 923−30.
  291. Fire A, Xu SQ, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. // Nature. 1998. V. 391. P. 806−11.
  292. Downward J. Science, medicine, and the future RNA interference. // British Medical Journal. 2004. V. 328. P. 1245−8.
  293. Lingel A, Izaurralde E. RNAi: Finding the elusive endonuclease. // Rna-A Publication of the Rna Society. 2004. V. 10. P. 1675−9.
  294. Meister G, Tuschl T. Mechanisms of gene silencing by double-stranded RNA. // Nature. 2004. V. 431. P. 343−9.
  295. Schauer SE, Jacobsen SE, Meinke DW, Ray A. DICER-LIKE 1: blind men and elephants in Arabidopsis development. // Trends in Plant Science. 2002. V. 7. P. 48 791.
  296. Lee YS, Nakahara K, Pham JW, Kim K, He ZY, Sontheimer EJ, Carthew RW. Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. // Cell. 2004. V. 117. P. 69−81.
  297. Sashital DG, Doudna JA. Structural insights into RNA interference. // Current Opinion in Structural Biology. 2010. V. 20. P. 90−7.
  298. Shan G. RNA interference as a gene knockdown technique. // International Journal of Biochemistry & Cell Biology. 2010. V. 42. P. 1243−51.
  299. Sijen T., Fleenor J., Simmer F., Thijssen K. L., Parrish S., Timmons L., Fire A. On the role of RNA amplification in dsRNA-triggered gene silencing. // Cell. 2001. V. 107. P. 465−476.
  300. Castanotto D, Rossi JJ. The promises and pitfalls of RNA-interference-based therapeutics. //Nature. 2009. V. 457. P. 426−33.
  301. Fuchs U, mm-Welk C, Borkhardt A. Silencing of disease-related genes by small interfering RNAs. // Current Molecular Medicine. 2004. V. 4. P. 507−17.
  302. Tebes SJ, Krulc PA. The genesis of RNA interference, its potential clinical applications, and implications in gynecologic cancer. // Gynecol Oncol. 2005. V. 99. P. 736−41.
  303. Hohjoh H. Enhancement of RNAi activity by improved siRNA duplexes. // Febs Letters. 2004. V. 557. P. 193−8.
  304. Ui-Tei K, Naito Y, Takahashi F, Haraguchi T, Ohki-Hamazaki H, Juni A et al. Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. // Nucleic Acids Research. 2004. V. 32. P. 936−48.
  305. Sioud M. Therapeutic siRNAs. // Trends in Pharmacological Sciences. 2004. V. 25. P. 22−8.
  306. Goodbourn S, Didcock L, Randall RE. Interferons: cell signalling, immune modulation, antiviral responses and virus countermeasures. // Journal of General Virology. 2000. V. 81. P. 2341−64.
  307. Heim MH. Intracellular signalling and antiviral effects of interferons. // Digestive and Liver Disease. 2000. V. 32. P. 257−63.
  308. Samuel CE. Antiviral actions of interferons. // Clinical Microbiology Reviews. 2001. V. 14. P. 778−809.
  309. Sen GC. Viruses and interferons. // Annual Review of Microbiology. 2001. V. 55. P. 255−81.
  310. Stark GR, Kerr IM, Williams BRG, Silverman RH, Schreiber RD. How cells respond to interferons. // Annual Review of Biochemistry. 1998. V. 67. P. 227−64.
  311. Castelli JC, Hassel BA, Wood KA, Li XL, Amemiya K, Dalakas MC et al. A study of the interferon antiviral mechanism: Apoptosis activation by the 2−5A system. // Journal of Experimental Medicine. 1997. V. 186. P. 967−72.
  312. Clemens MJ. PKR A protein kinase regulated by double-stranded RNA. // International Journal of Biochemistry & Cell Biology. 1997. V. 29. P. 945−9.
  313. Matsumoto M, Funami K, Oshiumi H, Seya T. Toll-like receptor 3: A link between toll-like receptor, interferon and viruses. // Microbiology and Immunology. 2004. V. 48. P. 147−54.
  314. Underhill DM, Ozinsky A. Toll-like receptors: key mediators of microbe detection. // Current Opinion in Immunology. 2002. V. 14. P. 103−10.
  315. Sen GC, Sarkar SN. Transcriptional signaling by double-stranded RNA: role of TLR3. // Cytokine & Growth Factor Reviews. 2005. V. 16. P. 1−14.
  316. Meurs E, Chong K, Galabru J, Thomas NSB, Kerr IM, Williams BRG, Hovanessian AG. Molecular-Cloning and Characterization of the Human Double-Stranded-Rna Activated Protein-Kinase Induced by Interferon. // Cell. 1990. V. 62. P. 379−90.
  317. Xu Z, Williams BRG. The B56 alpha regulatory subunit of protein phosphatase 2A is a target for regulation by double-stranded RNA-dependent protein kinase PKR. // Molecular and Cellular Biology. 2000. V. 20. P. 5285−99.
  318. Patel RC, Vestal DJ, Xu Z, Bandyopadhyay S, Guo WD, Erme SM et al. DRBP76, a double-stranded RNA-binding nuclear protein, is phosphorylated by the interferon-induced protein kinase, PKR. // Journal of Biological Chemistry. 1999. V. 274. P. 20 432−7.
  319. Silverman RH, Williams BRG. Stress responses: Translational control perks up. // Nature. 1999. V. 397. P. 208-+.
  320. Samuel CE. The Eif-2-Alpha Protein-Kinases, Regulators of Translation in Eukaryotes from Yeasts to Humans. // Journal of Biological Chemistry. 1993. V. 268. P. 7603−6.
  321. Zandi E, Karin M. Bridging the gap: Composition, regulation, and physiological function of the I kappa B kinase complex. // Molecular and Cellular Biology. 1999. V. 19. P. 4547−51.
  322. Gil J, Esteban M. Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): Mechanism of action. //Apoptosis. 2000. V. 5. P. 107−14.
  323. Hartmann R, Justesen J, Sarkar SN, Sen GC, Yee VC. Crystal structure of the 2 'specific and double-stranded RNA-activated interferon-induced antiviral protein 2 '-5 '-oligoadenylate synthetase. // Molecular Cell. 2003. V. 12. P. 1173−85.
  324. Dong BH, Silverman RH. 2−5A-Dependent Rnase Molecules Dimerize During Activation by 2−5A. // Journal of Biological Chemistry. 1995. V. 270. P. 4133−7.
  325. XL, Blackford JA, Hassel BA. RNase L mediates the antiviral effect of interferon through a selective reduction in viral RNA during encephalomyocarditis virus infection. // Journal of Virology. 1998. V. 72. P. 2752−9.
  326. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappa B by Toll-like receptor 3. //Nature. 2001. V. 413. P. 732−8.
  327. Takeda K, Kaisho T, Akira S. Toll-like receptors. // Annual Review of Immunology. 2003. V. 21. P. 335−76.
  328. Takeda K, Akira S. Toll receptors and pathogen resistance. // Cellular Microbiology. 2003. V. 5. P. 143−53.
  329. Judge AD, Sood V, Shaw JR, Fang D, McClintock K, MacLachlan I. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. //NatureBiotechnology. 2005. V. 23. P. 457−62.
  330. Sioud M. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. //Journal of Molecular Biology. 2005. V. 348. P. 1079−90.
  331. Poeck H, Besch R, Maihoefer C, Renn M, Tormo D, Morskaya SS et al. 5 '-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma. // Nature Medicine. 2008. V. 14. P. 1256−63.
  332. Kortylewski M, Swiderski P, Herrmann A, Wang L, Kowolik C, Kujawski M et al. In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. //Nature Biotechnology. 2009. V. 27. P. 925-U88.
  333. Lares MR, Rossi JJ, Ouellet DL. RNAi and small interfering RNAs in human disease therapeutic applications. // Trends in Biotechnology. 2010. V. 28. P. 570−9.
  334. Kaufmann J, Ahrens K, Santel A. RNA interference for therapy in the vascular endothelium. // Microvascular Research. 2010. V. 80. P. 286−93.
  335. Shen J, Samul R, Silva RL, Akiyama H, Liu H, Saishin Y et al. Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1. // Gene Therapy. 2006. V. 13. P. 225−34.
  336. Dejneka NS, Wan SH, Bond OS, Kornbrust DJ, Reich SJ. Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes. // Molecular Vision.2008. V. 14. P. 997−1005.
  337. Kaiser PK, Symons RCA, Shah SM, Quinlan EJ, Tabandeh H, Do DV et al. RNAi-Based Treatment for Neovascular Age-Related Macular Degeneration by Sirna-027. // American Journal of Ophthalmology. 2010. V. 150. P. 33−9.
  338. Davis ME, Zuckerman JE, Choi CHJ, Seligson D, Tolcher A, Alabi CA et al. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. //Nature. 2010. V. 464. P. 1067-U140.
  339. Aleku M, Schulz P, Keil O, Santel A, Schaeper U, Dieckhoff B et al. Atu027, a Liposomal Small Interfering RNA Formulation Targeting Protein Kinase N3, Inhibits Cancer Progression. // Cancer Research. 2008. V. 68. P. 9788−98.
  340. Toudjarska I, Judge A, Brodsky J, McClintock K, de Jong SD, Ambegia E et al. Development of Aln-Vsp: An Rnai Therapeutic for Liver Malignancies. // Hepatology.2009. V. 50. P. 1149A.
  341. Keller M. Nanomedicinal delivery approaches for therapeutic siRNA. // International Journal of Pharmaceutics. 2009. V. 379. P. 210−1.
  342. Lam JK, Liang W, Chan HK. Pulmonary delivery of therapeutic siRNA. // Adv Drug Deliv Rev. 2011.
  343. Oh YK, Park TG. siRNA delivery systems for cancer treatment. // Advanced Drug Delivery Reviews. 2009. V. 61. P. 850−62.
  344. Leachman SA, Hickerson RP, Schwartz ME, Bullough EE, Hutcherson SL, Boucher KM et al. First-in-human Mutation-targeted siRNA Phase lb Trial of an Inherited Skin Disorder. // Molecular Therapy. 2010. V. 18. P. 442−6.
  345. Hickerson RP, Smith FJD, Reeves RE, Contag CH, Leake D, Leachman SA et al. Single-nucleotide-specific siRNA targeting in a dominant-negative skin model. // Journal of Investigative Dermatology. 2008. Y. 128. P. 594−605.
  346. Dannull J, Lesher DT, Holzknecht R, Qi W, Hanna G, Seigler H et al. Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity. // Blood. 2007. V. 110. P. 4341−50.
  347. Bollard CM, Gottschalk S, Leen AM, Weiss H, Straathof KC, Carrum G et al. Complete responses of relapsed lymphoma following genetic modification of tumorantigen presenting cells and T-lymphocyte transfer. // Blood. 2007. V. 110. P. 283 845.
  348. Kang JH, Rychahou PG, Ishola TA, Qiao JB, Evers BM, Chung DH. MYCN silencing induces differentiation and apoptosis in human neuroblastoma cells. // Biochemical and Biophysical Research Communications. 2006. V. 351. P. 192−7.
  349. Wurdak H, Zhu ST, Romero A, Lorger M, Watson J, Chiang CY et al. An RNAi Screen Identifies TRRAP as a Regulator of Brain Tumor-Initiating Cell Differentiation. // Cell Stem Cell. 2010. V. 6. P. 37−47.
  350. Li GH, Wei H, Lv SQ, Ji H, Wang DL. Knockdown of STAT3 expression by RNAi suppresses growth and induces apoptosis and differentiation in glioblastoma stem cells. // International Journal of Oncology. 2010. V. 37. P. 103−10.
  351. Hay DC, Sutherland L, Clark J, Burdon T. Oct-4 knockdown induces similar patterns of endoderm and trophoblast differentiation markers in human and mouse embryonic stem cells. // Stem Cells. 2004. Y. 22. P. 225−35.
  352. Schulte JH, Kirfel J, Lim S, Schramm A, Friedrichs N, Deubzer HE et al. Transcription factor AP2alpha (TFAP2a) regulates differentiation and proliferation of neuroblastoma cells. // Cancer Letters. 2008. V. 271. P. 56−63.
  353. Volkov AA, Kruglova NS, Meschaninova MI, Venyaminova AG, Zenkova MA, Vlassov VV, Chernolovskaya EL. Selective protection of nuclease-sensitive sites in siRNA prolongs silencing effect. // Oligonucleotides. 2009. V. 19. P. 191−202.
  354. Matveeva O, Nechipurenko Y, Rossi L, Moore B, Saetrom P, Ogurtsov AY et al. Comparison of approaches for rational siRNA design leading to a new efficient and transparent method. //Nucleic Acids Research. 2007. V. 35.
  355. Damha MJ, Ganeshan K, Hudson RHE, Zabarylo SV. Solid-Phase Synthesis of Branched Oligoribonucleotides Related to Messenger-Rna Splicing Intermediates. // Nucleic Acids Research. 1992. V. 20. P. 6565−73.
  356. Carmichael J, Degraff WG, Gazdar AF, Minna JD, Mitchell JB. Evaluation of A Tetrazolium-Based Semiautomated Colorimetric Assay Assessment of Chemosensitivity Testing. // Cancer Research. 1987. V. 47. P. 936−42.
  357. Chattopadhyay N, Kher R, Godbole M. Inexpensive Sds Phenol Method for Rna Extraction from Tissues. // Biotechniques. 1993. V. 15. P. 24-&.
  358. Tabara H, Grishok A, Mello CC. RNAi in C-elegans: Soaking in the genome sequence. // Science. 1998. V. 282. P. 430−1.
  359. Tuschl T. RNA interference and small interfering RNAs. // Chembiochem. 2001. V. 2. P. 239−45.
  360. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. // Nature. 2001. V. 411. P. 494−8.
  361. Dykxhoorn DM, Lieberman J. The silent revolution: RNA interference as basic biology, research tool, and therapeutic. // Annual Review of Medicine. 2005. V. 56. P. 401−23.
  362. Yuan JP, Yan RL, Kramer A, Eckerdt F, Roller M, Kaufmann M, Strebhardt K. Cyclin B1 depletion inhibits proliferation and induces apoptosis in human tumor cells. // Oncogene. 2004. V. 23. P. 5843−52.
  363. Kabilova TO, Chernolovskaya EL, Vladimirova AV, Vlassov VV. Inhibition of human carcinoma and neuroblastoma cell proliferation by anti-c-myc siRNA. // Oligonucleotides. 2006. V. 16. P. 15−25.
  364. Nishizuka Y. The Role of Protein Kinase-C in Cell-Surface Signal Transduction and Tumor Promotion. //Nature. 1984. V. 308. P. 693−8.
  365. Oates AC, Bruce AE, Ho RK. Too much interference: injection of double-stranded RNA has nonspecific effects in the zebrafish embryo. // Dev Biol. 2000. V. 224. P. 208.
  366. Kimchi A. Cytokine Triggered Molecular Pathways That Control Cell-Cycle Arrest. // Journal of Cellular Biochemistry. 1992. V. 50. P. 1−9.
  367. Roh H, Pippin J, Drebin JA. Down-regulation of HER2/neu expression induces apoptosis in human cancer cells that overexpress HER2/neu. // Cancer Research. 2000. V. 60. P. 560−5.
  368. Roh H, Pippin JA, Green DW, Boswell CB, Hirose CT, Mokadam N, Drebin JA. HER2/neu antisense targeting of human breast carcinoma. // Oncogene. 2000. V. 19. P. 6138−43.
  369. Ross JS, Fletcher JA. The HER-2/neu oncogene in breast cancer: Prognostic factor, predictive factor, and target for therapy. // Stem Cells. 1998. V. 16. P. 413−28.
  370. Ross JS, Fletcher JA. The HER-2/neu oncogene: prognostic factor, predictive factor and target for therapy. // Seminars in Cancer Biology. 1999. V. 9. P. 125−38.
  371. Faltus T, Yuan JP, Zimmer B, Kramer A, Loibl S, Kaufmann M, Strebhardt K. Silencing of the HER2/neu gene by siRNA inhibits proliferation and induces apoptosis in HER2/neu-overexpressing breast cancer cells. //Neoplasia. 2004. V. 6. P. 786−95.
  372. Wu TT, Hsieh YH, Hsieh YS, Liu JY. Reduction of PKC alpha decreases cell proliferation, migration, and invasion of human malignant hepatocellular carcinoma. // Journal of Cellular Biochemistry. 2008. V. 103. P. 9−20.
  373. Pines J, Hunter T. Cyclin-A and Cyclin-Bl in the Human Cell-Cycle. // Ciba Foundation Symposia. 1992. V. 170. P. 187−204.
  374. Yuan J, Kramer A, Matthess Y, Yan R, Spankuch B, Gatje R et al. Stable gene silencing of cyclin B1 in tumor cells increases susceptibility to taxol and leads to growth arrest in vivo. // Oncogene. 2006. V. 25. P. 1753−62.
  375. Matassa A, Kalkofen RL, Carpenter L, Biden TJ, Reyland ME. Inhibition of PKC alpha induces a PKC delta-dependent apoptotic program in salivary epithelial cells. // Cell Death and Differentiation. 2003. V. 10. P. 269−77.
  376. Blankinship MJ, Gregorevic P, Chamberlain JS. Gene therapy strategies for Duchenne muscular dystrophy utilizing recombinant adeno-associated virus vectors. // Molecular Therapy. 2006. V. 13. P. 241−9.
  377. Gao GP, Wilson JM, Wivel NA. Production of recombinant adeno-associated virus. // Advances in Virus Research, Vol 55. 2000. V. 55. P. 529−43.
  378. Snyder RO, Flotte TR. Production of clinical-grade recombinant adeno-associated virus vectors. // Current Opinion in Biotechnology. 2002. V. 13. P. 418−23.
  379. Choi MS, Yuk DY, Oh JH, Jung HY, Han SB, Moon DC, Hong JT. Berberine Inhibits Human Neuroblastoma Cell Growth through Induction of p53-dependent Apoptosis. // Anticancer Research. 2008. V. 28. P. 3777−84.
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