Раковая наука и терапия

?????? ??????????????????? ????????? ???????????????? ???? ?????? ? ??? ???? ???????????????? ??? ??????????????? ??????? ???????????????? ????? ?????. ????????? ???????????? ???? ????????????? ?? ??????? ???????, ? ???? ????????? ?????????????, ??? ??????? ??????? ????? ????????? ? ????????????? ?????????? ????? ?????, ??????? ????? ??????? ???????????? ???? ?????????? ????? ????? ???????? ??????? ? ?????????? ?????????????? ????, ? ????? ??????? ???????????? ???, ? ?????????? ????? ????????? ??? ???????????????? ? ???????? ?????????, ????? ????, ???????????? ???? ?????????? ?? ????????? ?????????????? ??????????????? ???????? ???????????????? ????? ????? ??? ??????????????? ???? ??????? ???.

??????: ???? ??????????? ??????? ??????? 80 ?????????, ???????????????? ?? ?????? ???????????????? ???? ??????? ??? ? ?????? ? 1991 ?? 2000 ???; ? ??????? ???????? ???? ??????? ???????, ???, ?????????????? ???????, ?????? ???????, ??????? ??????????????, ???????? ???????; ??????????????????? ???????????? ? ??????? ???????. ??? ?????? ???? ??????? ????? ? ??? ?? ?????????, ??? ????????? ??????? ???? ?????????? ?? ????????? ? ????????????? ???? ??? ????????????? ???????? ??-???????.

??????????: ? ?????????????? ??????? ???????? ??????? ????????? ???? ??????? ???????, ?? ??????? ????????? ???????? ???????, ????? ???????, ??????? ??????????????, ?????? ??????? ? ??????????????????? ????????????. ????????????? ?????? ??????????, ??? ??????? ??????? ???????? ?????? ??????????????? ???????? ? ?????????? ????? ????? ??? ???????????????? ???? ??????? ??? P<0,001.

??????????: ??????? ??????? ???????? ???????? ???????? ??? ??????????????? ?????????? ? ?????????, ? ??????? ??????? 4 ?? ????? ????????????? ??? ???????????? ??????????? ???????? ????????? ???????? ??? ???????????? ? ??????? ??????? ???????????????? ???? ??????? ???.

??????????? ? ????: ?????????????? ??? ?????? (???) ???????? ????? ?? ????? ??????? ??? ??????? ???????? ??-?? ??????? ???????? ????????????, ??????? ???????????????? ??????????????? ? ???????? ???????? ?????????????? ? ????????????. ??????? ????????? ??????? ???????? ????????????? ???? ????????????? 1 (TOP1), ????? ??? ?????????? ? ????????? ? ????????? ? ???????????? ?? ?????? ???????. ??? TOP1 ??????? ??????? ??????, ?????????? TOP1 ?? ???, ????????? ????????? ?????????????? ??????? ???. ????????????? ????????, ???????????? ???????? ???????? ??? ????????????? ??????????? ????? TOP1, ??????????? ? ??????????????? ?????????, ??????????? ? ?????????????? ???????? TOP1-???. ??????? ??? ??????????????? 1 (TDP1) ?????? ???????? ???? ? ???? ????????, ?, ???????? ?? ?? ????????, ? ????????? ????? ??? ?????? ? ?????????? ??????? ????? TDP1 ? ???? ? ?????????????? ??????????? ??? ???. ????? ????, ??????????, ??????????? ?? ?????? ?????? TDP1 ? TOP1 ? ????????? ??????? ??? ?? ??????? ?? ?????? TOP1.

?????? ? ??????????: ?? ???????? ? ???????????? ????????? ??????? ?????? TDP1 ? TOP1 ? ?????? ????? ?????? SCLC. ??????? ????? TDP1 ?????? ??????????? ? ???? TDP1 ? ?????????????? ??????????? TDP1, ?????????? ? ??????? ???? ??????? ????????????? ??????????? ???????? ??????????, ??? ???????????? ????????????? ?????????? ???????????????? ? ?????? ??????? TDP1 ? ???????? SCLC. ?? ????? ?????????????, ??? ???? ??????? ????? TDP1 ??? ?? ???? ?? ??????????? ? ????????????????? ? ??????????, ??????????? TDP1/TOP1 ?????? ??????????? ? ????????????????? ? 8 ?? 10 ????????????? ????? ??????.

??????????: ??? ???????????? ????????????? ?????? ????????? ??????? TDP1 ? TOP1 ? SCLC ? ???????????? ????????????? ?????????? ??????????? TDP1/TOP1 ??? ?????? ?????? SCLC ?? ?????????. ???????? ? ????????? ???????? ? ????????????? ??????????????? ??????? TDP1 ? ??????????? ?????????? ????? ???? ???????????? ? ???????? ???????????????? ??????????? ? ???????. ??? ?????????? ????? ?????? ? ????????????? ?????????, ???????, ????????, ??????? ?????? ?? ???? TOP1 ? ??????????? TDP1, ??????? ? ????????? ????? ????????? ? ?????? ??????????.

Background: Published data suggest that diabetes influences survival of patients with lung cancer. The anti-cancer effect of metformin confounds this association. We sought to study the association of diabetes and metformin with survival in patients undergoing resection of stage I non-small cell lung cancer (NSCLC).

Methods: Pathologic stage I NSCLC patients undergoing anatomic resection from 2002 to 2011 were studied. A diagnosis of diabetes and diabetic medication use were identified through records. Univariate and multivariate analyses examined the association of diabetes and metformin usage with overall survival (OS).

Results: 409 eligible patients were included in the analysis - excluding patients with neoadjuvant therapy, more than one lung cancer, or resection less than lobectomy. 71 (17.4%) patients were diabetics and 41 (10.0%) used metformin. With a median follow up of 44 months, univariate analysis demonstrates that diabetes had no effect on OS (P=0.75); however, metformin use was associated with improved OS (median survival not reached vs. 60 months; P=0.02). Metformin use remained an important predictor of good survival in multivariate analysis (HR=3.08; P<0.01) after adjusting for age, gender, pathologic stage, histology and smoking status.

Conclusion: Metformin use rather than diabetes is associated with improved long-term survival in Stage I NSCLC patients.

???????????: ???????????????? ????????? ???????????? ????? ????????? ?? ????? ?????????? ?????????? ??????????? ???????, ???????????? ??????? ? ?????? ? ?????. ???????? ???????? ?????? ????????? ??????????. ???????? ??????????? ? ?????? ???????? ? ?????????????? ?????????????. ???????? ?? ???????????? ??????????????? ?????????? ? ???????? ????????????????? ??????, ???????? ?????????? ???????? ??? ???????????? ???????? ?????????????? ??????? ??-?? ??? ??????? ???????????????? ???????. ??? ???????????? ???????????? ?????? ?????????? ???????????? ?????????? ? ??????????? ??? ?????? ??????????? ??? ????????????? ???????? ????????? ? ??????? ??????.

??????: ??? ???????????? in vitro ?????????????? ?????? ???? ?????? (LLC, Chago-k-1 ? MCA-205) ? ?????????????? ????????? ????? (MS1-VEGF, HMEC-1). ???????????? ? ?????????????? ?????? ??????????? ? ??????? ???????? ?????????? ? ?????????????? ??????? FITC ??????? ? β-????????; ??????? ??????? ??????????? ? ???? ?? ?????? ???????????? ? ??????? ?????????????? ??????????? ? BIOQUANT. In vivo ???????????? ???????????????? ? ??????????????? ????????????? ?????????????? ????????? ??????? (PCL) ??????????? ?? ????? C57BL/6 ? ????????????????????? ????????? ??????. ???????????????? ????????? ? PCL-????????? ???????????? ? ??????? ??????? ??????????. PCL, ??????? 111In, ? 3H-???????? ?????????????? ??? ?????????????? ???????????? ???????? ? ????????? ??????????????. ??????????????? ????????????? ???????????? ????? ??????????? ???????????? ????????.

??????????: ?????????? ????????????? ???? ???????? ?????????, ????? ???????? ??? ???????? ? DOTAP-PCL. ?? ???????? ? ~2-??????? (p=0,0214, 95% ?? ?????????? ?? 2,923 ?? 13,247) ?????????? ?????????? PCL-????????? ? ?????? ? ???????? ?? ????????? ? ?????????? ??????, ??? ??????? ? ????????????? ?????????? ??????? ????????? ? ??????, ?????????? ??????? PCL (p=0,0052, ???? ????????? (???? ???????-?????)).

??????: ??????????? ?? ?????? PCL, ??????????? ??????????, ????? ??????????? ??????????? ????????? ??????????? ???????????????? ???????, ????? ??? ????????. ????????? PCL ????? ?????????? ?????????? ?????????? ???????? ??? ????????? ? ???????? ????????. ??? ????????? ???????????????? ??????????, ???????????? ?????? ?????????? ????????? ????????? ???????.

??? ???????? ???????? ???????? ???????? ??????? ? ????????? ????????? ??? ????????. ????? ????? ??? ???????????? ???????, ????????? ????? ?????????????? ?????????????, ? ???????? ??? ????????? ? ?????? ???????? ????? ?? ?????? ????????, ??????????????? ??????????? ? ???????? ???????? ??????????? ??? ?????? ??? ?????????????? ??????. ???????? ???? ???????? ??????? ???????? ??????? ?????; ????? ? ???? ????????? ? ???????????? ??? ?????????? ??? ???????? ??? ?????? ????????? ????????. ? ???? ?????? ?? ??????? ????????????????? ????? ? ???????????? ???????, ??? ????????????? ?????, ??????? ????????? ????????? ? ?????????, ?? ???????? ?????, ?????????? ????????, ?????????????? ?????????, ???????????? ??????????? ? ????????? ? ???? ?????????, ??? ???????, ?? ?????? ???????.

??????? ?????????? ? ????????????? (???????????????) ???????? ?????/??????????? ??????, ??????? ?????? ???????? ???? ? ????? ? ???????????? ?????? ? ??????????????? ??? ??????????????? ??????????????? ?????? ??? ??????? ????. ????????????? ???????????? ????????, ??? ???????? 1 mTOR (mTORC1) ? mTORC2 ????? ???????????? ??? ????????????? ???? ????????, ???????? ??? ??????????????? ????????? ????????. ? ??????? ??????? ???? ???????? ?????????? mTORC1 ?????????????????? ?????????????? ????????????????? ?????????? ?????? ???? ???????? ??? ? ???????? ???????????, ??? ? ??? ????????????? ? ????????? ? ???????????????? ????????. ?? ????????? ???? ?????????????? ????????????? ??????????? ?????????? mTORC1 ? ????????? ????? ??????????? ? ???? I/II ????????? ? ???????? ????????? ? ????? ????????. ? ??????? ?????????? ?????????????? ? ??????????? mTORC1 ??????? ???? ??????????? ????? ?????????? ?????? mTOR (TORKinib), ??????? ?????????? ??? mTORC1, ??? ? mTORC2. ? ???? ?????? ?? ????????????? ??????? ??????????? ? ?????????????? ????????????? ??????????? ?????? ??????????? mTOR ? ????????? ? ????????????? ????? ????????.