#1
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Ïðîìèñàí
Óâàæàåìûé Àëåêñàíäð Àíäðååâè÷!
Õîòåëîñü áû óçíàòü Âàøå ìíåíèå ïî ïîâîäó Áàäà "Ïðîìèñàí" (èçìåíèëîñü ëè îíî ÷åðåç 3 ãîäà- ÷èòàëà Âàø îòçûâ î íåì â 2008ã.). Íà ïðîøåäøåì íåäàâíî ôîðóìå àêóøåð-ãèíåêîëîãîâ "Ìàòü è äèòÿ" ïîñåòèëà âûñòóïëåíèå ïðîôåññîðîâ Êèñåëåâà (áèîëîã), Ñèäîðîâîé (àêóøåð-ãèíåêîëîã), Óíàíÿí, Àïîëèõèíîé (àêóøåð-ãèíåêîëîã) è Àêóëåíêî (ãåíåòèê). Âñå îíè ïîçèöèîíèðîâàëè ïðîìèñàí, êàê ïðåïàðàò, ðåêîìåíäóåìûé äëÿ ïàòîãåíåòè÷åñêîé ïðîôèëàêòèêè ðàêà ìîëî÷íîé æåëåçû è ðàêà øåéêè ìàòêè, ïîñëåîïåðàöèîííûì áîëüíûì äëÿ ïðîôèëàêòèêè ðåöèäèâîâ ðàêà. Åñëè îáúÿñíèòü â äâóõ ñëîâàõ îíè ïðåäïîëàãàþò, ÷òî â îñíîâå ðàçâèòèÿ íåîïëàñòè÷åñêîãî ïðîöåññà ëåæèò àíîìàëüíîå ìåòèëèðîâàíèå ãåíîâ-ñóïðåññîðîâ îïóõîëåâîãî ðîñòà (è èõ èíàêòèâàöèÿ). Ïðîöåññ ìåòèëèðîâàíèÿ îáðàòèì è ïîäâåðãàåòñÿ ôàðìàêîëîãè÷åñêîìó âîçäåéñòâèþ. Ïðîìèñàí- ïðåïàðàò ìóëüòèòàðãåòíîãî äåéñòâèÿ, ñïîñîáñòâóåò äåìåòèëèðîâàíèþ è, òàêèì îáðàçîì, àêòèâàöèè ýòèõ ãåíîâ. ß äî ñèõ ïîð ñêåïòè÷åñêè îòíîñèëàñü ê äàííîãî ðîäà ïðåïàðàòàì, à òåïåðü ïðî÷èòàëà ïàðó çàðóáåæíûõ ñòàòåé ïðî èñïîëüçîâàíèå èíäîë-3-êàðáèíîëà è ýïèãàëëîêàòåõèí-3-ãàëëàòà è äóìàþ, à ìîæåò, äåéñòâèòåëüíî, ñòîèò èñïîëüçîâàòü ïðîìèñàí äëÿ ïðîôèëàêòèêè íàñëåäñòâåííîãî ðàêà è åãî ðåöèäèâîâ? Ñ óâàæåíèåì, Ø.À. |
#2
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Ìî¸ ìíåíèå (è íå òîëüêî ìî¸) - íå èçìåíèëîñü.
Ïî èíäîë-3-êàðáèíîëó ÷èòàéòå, îïÿòü æå, íàó÷íûå ñòàòüè â ñåðüåçíûõ ðåöåíçèðóåìûõ æóðíàëàõ. |
#3
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À Âû ïîïðîáóéòå, íå áóäòå õàíæîé. Íàâåðíÿêà â òåðàïèè ïðèìåíÿåòå òî, ÷òî íå îïèñàíî â ðåöåíçèðóåìûõ æóðíàëàõ. Ê òîìó æå ïðî èíäîë-3-êàðáèíîë è ýïèãàëëîêàòíõèí îïèñàíû.
Íó è êíèæêè è ñòàòüè òîãî æå Êèñåëåâà, Ñèäîðîâîé ïî÷èòàéòå. Õîòÿ, â Îäåññå âñåãäà ñâîÿ íàóêà. Îáîñîáëåííàÿ. |
#4
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Öèòàòà:
Ðåêîìåíäóåòñÿ: (à íå "Ïîêàçàíèÿ"; Âàì, êàê âðà÷ó, èçâåñòíà ðàçíèöà äóìàþ?)  êà÷åñòâå äîïîëíèòåëüíîãî èñòî÷íèêà ôëàâîíîèäîâ (ýïèãàëëîêàòåõèí-3-ãàëëàòà) è ìèíåðàëüíûõ âåùåñòâ. È ãäå òàì îíêîïàòîëîãèÿ? Íó à çåëåíûé ÷àé ÿ è òàê ïüþ. À Âû ïîêà ïðî÷òèòå ýòîò òåêñò: Special Lecture Enzyme Induction and Dietary Chemicals as Approaches to Cancer Chemoprevention: The Seventh DeWitt S. Goodman Lecture ...... Potential Problems Associated with the Use of Enzyme Induction as an Approach to Cancer Chemoprevention Although the induction of CYP enzymes that metabolize carcinogens usually inhibits carcinogenesis in experimental animals (presumably because detoxification pathways are enhanced to a greater extent than activation pathways), sometimes carcinogenesis is enhanced as occurs for the effect of phenobarbital administration on safrole carcinogenesis (63) . Some enzyme inducers that inhibit carcinogenesis when given together with a carcinogen are tumor promoters when given after the carcinogen (e.g., phenobarbital, indole 3-carbinol, and DDT; Refs. 47 , 119, 120, 121, 122, 123, 124, 125, 126 ). ... Additional studies by Michnovicz, Bradlow, and their colleagues (171 , 172) showed a stimulatory effect of indole-3-carbinol administration on the 2-hydroxylation of estradiol in humans, and they suggested that indole-3-carbinol may be an effective chemopreventive agent for breast cancer in women (173 , 174) . However, the use of indole-3-carbinol as a chemopreventive agent against estrogen-dependent human cancers through induction of estrogen 2-hydroxylation should receive more careful evaluation because indole-3-carbinol is a promoter of liver tumors in initiated animals (120, 121, 122, 123, 124, 125, 126) . In addition, (a) some studies suggest that total catechol estrogen production is positively associated with an increased risk of breast cancer in women (175, 176, 177) ; (b) indole-3-carbinol [a prodrug for the formation of the potent Ah-receptor agonist, indolo(3,2-b)carbazole; Ref. 178 ], as well as other Ah-receptor agonists such as TCDD, have been reported to increase the rates of formation of both 2- and 4-hydroxyestradiol in liver and in estrogen target cells (166 , 179, 180, 181) ; and (c) 4-hydroxyestradiol has carcinogenic activity when administered to Syrian hamsters or newborn mice, whereas 2-hydroxyestradiol has very low or no carcinogenic activity (182, 183, 184, 185) . Although treatment of animals or humans with indole-3-carbinol to stimulate the 2-hydroxylation of estradiol may be an effective way of inhibiting estrogen-induced carcinogenesis, and studies in this area should be encouraged, the significance of the tumor promoting activity of indole-3-carbinol and its stimulatory effect on the formation of the potentially toxic 4-hydroxyestradiol should receive more attention before its widespread use in humans.... Another potential problem associated with the use of enzyme induction as an approach to cancer chemoprevention is that enzyme inducers can stimulate the metabolism and alter the action of therapeutic drugs thereby leading to drug interactions in patients, and the metabolism and action of important normal body constituents (such as vitamin D, arachidonic acid, thyroid hormone, and steroid hormones) may also be modified. Although the scientific community is searching for monospecific inducers of Phase II enzymes, several inducers of Phase II enzymes (e.g., butylated hydroxyanisole, sulforaphane, oltipraz, and some related compounds) can also induce or inhibit Phase I enzymes (111, 112, 113, 114 , 127) . The current state of our knowledge indicates that the selective induction of carcinogen-detoxifying enzymes (Phase I and/or Phase II enzymes) may be a useful approach for inhibiting carcinogenesis in individuals or populations at high unavoidable risk because of exposure to high levels of specific carcinogens, but this approach may not be useful in the general population. The possibility that enzyme inducers that increase cellular antioxidant defense systems may have a broad protective effect in the general population is a promising approach that requires additional research. Careful benefit/risk assessments need to be made before and during clinical trials with chemopreventive inducers of Phase I and/or Phase II enzymes. |
#5
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Âû ñäåëàëè âûâîä îòíîñèòåëüíî ïðîìèñàíà òîëüêî ïî îäíîé ôðàçå â îäíîé ñòàòüå äåñÿòèëåòíåé äàâíîñòè? Ìîãó Âàì íàêèäàòü íåñêîëüêî áîëåå ñâåæèõ ññûëîê, íàïðèìåð âîò ýòóÆ The indole-3-carbinol (I3C) metabolite 3,3′-diindolylmethane (DIM) is a proposed cancer prevention agent for various tumor types, including breast cancer. Here, we show that DIM up-regulates expression of the tumor suppressor protein BRCA1 in carcinoma and normal cell types. Up-regulation of BRCA1 was dose and time dependent, and it was observed at physiologically relevant micromolar and submicromolar DIM concentrations when cells were exposed for 72 hours. Treatment with the parent compound (I3C) or DIM (1 μmol/L) protected against cell killing due to H2O2 and other oxidants, and the protection was abrogated by knockdown of BRCA1. DIM stimulated signaling by the antioxidant transcription factor NFE2L2 (NRF2) through the antioxidant response element in a BRCA1-dependent manner. We further showed that DIM rapidly stimulated phosphorylation of BRCA1 on Ser 1387 and Ser 1524 and that these phosphorylations are required for protection against oxidative stress. DIM-induced phosphorylation of BRCA1 on Ser 1387 was dependent on ataxia-telangiectasia mutated. Finally, in our assay systems, H2O2-induced cell death was not due to apoptosis. However, a significant component of cell death was attributable to autophagy, and both DIM and BRCA1 inhibited H2O2-induced autophagy. Our findings suggest that low concentrations of DIM protect cells against oxidative stress via the tumor suppressor BRCA1 by several distinct mechanisms. [Cancer Res 2009;69(15):6083–91]
Âîîáùå ìîæíî è â PubMed è â CancerRes ìíîãîå óâèäåòü áîëåå íîâîãî. Èñòî÷íèê ôëàâîíîèäîâ â èíñòðóêöèè íàïèñàíî, ïîòîìó êàê ýòî äåéñòâèòåëüíî ÁÀÄ, íî åñëè îí ýôôåêòèâåí, ÷òî äîêàçàíî, ïî÷åìó åãî íå íàçíà÷àòü? Ïðè ìóòàöèè BRCA ó Âàñ êàêàÿ òàêòèêà âåäåíèÿ ïàöèåíòêè? Ïðîôèëàêòè÷åñêàÿ ìàñòýêòîìèÿ? Íå âñåãäà îïðàâäàíî è ãóìàííî. Âåäü æåíùèíà â ýòîì ñëó÷àå - çäîðîâàÿ. À Ïðîìèñàí çàñòàâëÿåò íåìóòèðîâàííóþ àëëåëü ðàáîòàòü çà "ñëîìàííóþ" è âûðàáîòêà áåëêà BRCA â ýòîì ñëó÷àå íîðìàëèçóåòñÿ. |
#6
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Òàêæå ïî ïîâîäó ýòîé ñòàòüè õî÷ó ñêàçàòü ñëåäóþùåå:
1) Åñëè ñèëüíî îçàäà÷èòüñÿ, àáñîëþòíî íà êàæäîå “äà” (äàæå íà òî, ÷òî 2õ2=4) â Èíòåðíåòå ìîæíî íàéòè ñâîå “íåò”, òàê êàêîå-òî êîëè÷åñòâî ëåò íàçàä, âûøëà “î÷åíü óáåäèòåëüíàÿ”ñòàòüÿ î êàíöåðîãåííîñòè DIM (!) 2) Âñå 7 ñòàòåé, íà êîòîðûå ññûëàåòñÿ àâòîð, ïðîèçâåäåíû îäíîé ëàáîðàòîðèåé, êîòîðàÿ ëîêàëèçîâàíà íà Ãàâàéÿõ (êðîìå ïàðû – îò äðóãîé ëàáîðàòîðèè), ÷òî òîæå, â ïðèíöèïå, Øòàòû, è òàì î÷åíü çàìå÷àòåëüíî îòäûõàòü, îäíàêî… 3)  ýòèõ ñòàòüÿõ èñïîëüçóåòñÿ ñïåöèôè÷åñêàÿ ýêñïåðèìåíòàëüíàÿ ìîäåëü in vivo, â êîòîðîé I3C äàåòñÿ æèâîòíûì äî ââåäåíèÿ êàíöåðîãåíà, âìåñòå ñ êàíöåðîãåíîì è ïîñëå íåãî. Ïðè ýòîì ñàìè àâòîðû ïèøóò, ÷òî â ïåðâîì è âòîðîì ñëó÷àå îíè âèäÿò îíêîïðîôèëàêòè÷åñêîå äåéñòâèå I3C, à â ïîñëåäíåì íåò. Ïðè÷åì îíêîïðîìîòîðíîå äåéñòâèå I3C âîçðàñòàåò ñïóñòÿ íåäåëè è ìåñÿöû ïîñëå ïðèåìà êàíöåðîãåíà. Çäåñü ìîæíî ñïåêóëèðîâàòü ñêîëüêî óãîäíî – ïî÷åìó îíè âèäÿò ñåé ýôôåêò. Ìîæåò ñàì êàíöåðîãåí âëèÿåò íà ìåòàáîëèçì I3C è ñìåùàåò åãî ìåòàáîëèçì íå ñòîðîíó DIM (÷òî åñòü íîðìà), à â ñòîðîíó îáðàçîâàíèÿ íåêîãî äðóãîãî ìåòàáîëèòà, ìîæåò åùå ÷òî. Ïðè ýòîì îíè íè ñëîâà íå ãîâîðÿò î DIM – ñèëüíåéøàì àíòèýñòðîãåíå è îíêîïðîòåêòîðå. ß ïîäîçðåâàþ, ÷òî ýòè ó÷åíûå èìåþò ñïåöèôè÷åñêèé ãðàíò (íà ÷òî åñòü óêàçàíèÿ – ññûëêà íà íåêèé ñåëüñêî-õîçÿéñòâåííûé èñòî÷íèê ôèíàíñèðîâàíèÿ), ãäå èçó÷àþò ñóäüáó õèìèêàòîâ, êîòîðûå ïîïàäàþò â îðãàíèçì. Îá ýòîì åñòü ñëîâà â èõ ñòàòüÿõ (èçó÷àåìûå èìè êàíöåðîãåíû îáð-ñÿ ïðè íåäîáðîñîâåñòíîì õðàíåíèè ïèùåâûõ ïðîäóêòîâ). Ïðè âñåì ïðè ýòîì îíè æå ñàìè ïðèâîäÿò êó÷ó ñòàòåé îá îíêîïðîôèëàêòè÷åñêîì äåéñòâèè èíäîëîâ è êðåñòîöâåòíûõ, â òîì ÷èñëå è â îòíîøåíèè ðàêà ïå÷åíè. ß óæå íå ãîâîðþ î òûñÿ÷àõ äðóãèõ ñòàòåé îò òûñÿ÷ äðóãèõ (ðàçíûõ) àâòîðîâ. |
#7
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Öèòàòà:
Öèòàòà:
Èëè Âàì, êàê âðà÷ó, íàäî îáúÿñíÿòü ðàçíèöó ìåæäó äàííûìè ïîëó÷åííûìè in vitro è âûâîäàìè õîðîøî ñïëàíèðîâàííîãî, ðàíäîìèçèðîâàííîãî èññëåäîâàíèÿ? |
#8
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Öèòàòà:
Öèòàòà:
Ãäå îïóáëèêîâàíû äàííûå ðåçóëüòàòû? Î÷åíü èíòåðåñíî ïîñìîòðåòü êàê ýòî âñå îïðåäåëÿëîñü... |
#9
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Âñå íàëåòåëè íà êîñâåííûå âîïðîñû, à íå íà âîïðîñ, ÷òî âû äåëàåòå ñ ïàöèåíòàìè (çäîðîâûìè ëþäüìè), ó êîòîðûõ ìóòèðîâàí brca.
Âû-òî íà ÷òî? Èññëåäóéòå! Åùå ðàç ïîâòîðþñü, èëè âàì ëåã÷å ñèñüêó îòòÿïàòü? Ìîäåðàòîðû çäåñü (åïòè) åùå òå. Àäüþ! Ôòîðóðàöèë ôîðåâåð! Ïðîøëûé âåê. Äàæå îáèäíî, íàäåÿëñÿ îäåññêàÿ íàóêà âñå-òàêè îïðàâäàåò ñåáÿ, íåñìîòðÿ. Íà ïðîâîêàöèþ. Ìîäåðàòîð- õåëîó! Îïÿòü øòðàôíûå î÷êè íà÷èñëèòå?) |
#10
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