Раковая наука и терапия

???????? B — ??? ?????????? ? ?????? ?????????????? ??????????? ????????, ??????? ????????? ? ????? ?????? ????????? ?????????, ????? ??? ?????????????? ??????, ????????? ? ???????? ????????. ????? ???? ??????????, ??? ???????? B ?????? ????????? ????? ?? ?????????? ??????? ???????????????? ??????? ?????? ?? ?????????? ? ????? ???. ? ?????????? ??????? ???????????? ???? ????????????? ???? ?? ????????? ????????????? ??????????? ????????? B, ??????? ????? ???????? ???????????? ??? ???????, ???? ? ???????? ?????? ??? ?????????? ????????. ?????????? ??????????? ????????? B ??? ??? ????????????, ? ?? ???? ?? ??? ? ????????? ????? ?? ?????? ?????? ??????????? ?????????. ????????? ?????????, ????? ??? VBY-825 ? ??????????? ?????????? ???????????, ???????? ???? ??????????????? ??? ?????? ??????????, ? ?? ????? ??? ??????, ????? ??? ???????, ???????? ? IGFBP-4, ????? ?????????????? ? ???????? ??????? ??? ?????????? ??????? ??????????? ????????? B ??? ???????????? ?????????????. ?????????, ??? ????????? ???????? ??????????? ????????? ??? ??????? ?????? ?????????, ?? ????????? ? ?????????? B, ????? ??? ?????????? ? ????????????, ????? ?????? ???????, ???????, ??? ???? ????????, ?????????? ???????? B ? ?? ?????? ????? ???? ???????????? ? ???????? ?????? ??? ?????????? ?????? ?????????? ????????? B, ?? ? ????? ????? ?? ????? ?????? ??-?? ?????????? ???????? ??????? ????????????. ?????????? ????????????, ????????? ?? ????? ?????????? ??????????? ????????? B, ?????? ???? ????????????? ?? ??????????????? ??????? ?????????? ????????? B ? ?????????????, ?????????? ?/??? ?????????????? ?????? ??????, ??????????? ? ???????????????? ???????. ???? ????????, ??? ???? ??????????????? ?????? ???????? ????????????????? ? ?????????????? ? ?????? ?????????? ??????.

???????????????? ???????? (MtBIO) ???????? ????????? ???????? ??? ?????????? ? ????????? ??????, ? ???? ??????????, ??? ?? ????????? ? ???????????????????. ??????????????????? ???????? ??????? ???????????? ? ??????? ????????? ? ????? ????????. ????????? ???????????? ????????, ??? ????????? MtBIO ????? ???????? ? ?????? ??????? ??????. ??????? ??????????? ?? MtBIO ??? ???? ???????? ????? ???? ?????????????? ??????????????? ????????, ????????, ????? ??????????? ???????????????????. ????????????? ???? MtBIO ????? ??????????? ? ?????? ?? ??? ???????? ? ???? ??????.

????????? ?????????? ?????????????? ?????????? ????????? (NGS) ??? ????? ??????? ???????? ? ?????????????, ??????? ????? ??? ??????????? ???? ????? ??????????????? ?????????????? ????? ??????????. ?????????????, ?????????????? ??????????? NGS ????? ????????? ??? ?????????????? ? ????????? ????? ?? ??????????. ?????? ??? ??? ???? ???????? ???????????? ???????? ????????????? NGS ? ??????????? ???????????. ????? ?????????? ?????????? ??????? ?????????? ???????????? ????, ????? ????????????? ???????? ????????????, ? ??????????? ?????????????? ????????? ? ??????? ???????? ?????????: ?????????????? ?? ???????.

????? ?? ???????????? ????????????? ???????? NGS, ??????? ????????? ??????????? ? 341 ????????? ? ??????????????? ?? ??????? ? ??????? ??? ???????????? ? ????? ??????????? ??????????????? ??????????? ? ???????????? ?????? ??????????????? ?????? ??? ??????????? ????????? ?????????????? ?????????? ?????????. ????????? ?????????? ? ????? NGS ? ?????? ??????? ????? ????? ?? ????? http://www.sheffieldchildrens.nhs.uk/our-services/sheffield-diagnostic-genetics-service/. ??? ???????? ? ????? ??????? ????????????? «?????? ????????», ????????????? GATK ? ????????? ?????, ? ????? ?????????????? ????????, ?????????? ????????? ????? ??????????? ????????? ? ??????????? ??????? ?????????, ????????? ?? ???????. ??? ????????? ????????? ?????????????????? ?????????? ? ??????? ???????? ?????????????. ????? ????, ????????????? ??????????? ??????? ???????? ??????????, ??? 30X — ??? ?????, ? ??????? ?????????????????? ?????????? ??????????? ? >99,9% ??????????????.

???? ?????????? ????????? ?? ?????? ?????? ????? ???????? ?????????? ? ???????, ? ?? ???????, ??? ???? ?????????? ??????? ??????? ? NGS ? ???????? ?????????? ???????? ??? ? ??????????? ??????????????? ????????????.

Introduction: Lifeguard (LFG) is an anti-apoptotic protein that inhibits programmed cell death mediated by Fas in tumour cells. The exact mechanism of action and the molecular function from LFG in the carcinogenesis of human breast cells is not clear. But the expression of LFG mRNA correlates with LEF-1 transcription factor activity.

Methods: In the present study, chemotherapeutic-induced apoptotic effects were studied using MCF-7 cells as an in vitro test model. Molecular (Western blot and RT-PCR) techniques were used to investigate LFG expression. To investigate the breast cancer cell proliferation in presence of siRNA-LFG we performed fluorescent cell viability assays.

Results: The results indicated that, a decrease of LFG expression using siRNA correlates with an increased sensitivity to Trastzumab and Erlotinib. Moreover, cell cycle analysis of LEF-1 siRNA-transfected human breast cancer cells revealed a significant arrest in G2 phase.

Conclusion: Taken together, our results indicate a pivotal role of LFG in the regulation of apoptosis in MCF-7 breast cancer cells.

Background and objective: The androgen receptor (AR) is a member of the steroid receptor subfamily with well-known biological and therapeutic importance in prostate cancer. There is evidence that the androgen signalling pathway may play a critical role also in normal and malignant breast tissue. They are highly expressed in triple negative breast cancer (TNBC) but it is not clear if AR expression is correlated with survival in advanced TNBC. Therefore, in the present study we investigated the prognostic value of AR expression in metastatic TNBC.

Patients and methods: Stage IV TNBC was included in the analysis. Patients with poor performance status (ECOG>2) were excluded. Tumors with >10% nuclear-stained cells were considered to be positive for AR. Univariate and multivariate analyses were performed.

Results: From a database of 208 TNBC patients, 24 cases of advanced TNBC were identified; out of 24 patients, 33% were AR positive. The median age at diagnosis was 61 years (range 30-78 years). All patients included in the study received first-line chemotherapy for their disease. Median progression free-survival (mPFS) and overall survival (OS) were 3.5 months (range 0.3-27.3 months) and 25.9 months (range 2.52-122.2 months), respectively. Univariate analysis showed that AR negative advanced TNBC had a significantly worse PFS (3.2 vs 7.9 months; p=0.02; HR=2.57, 95% CI 1.15-10.53) and OS (20.5 vs 47.4 months; p=0.01; HR=2.88, 95% CI 1.32- 9.43). Multivariate analysis confirms that AR expression was an independent prognostic factor of PFS (p=0.04; HR=2.19, 95% CI 1.52-5.91), as well as for OS (p=0.05; HR=2.21, 95% CI 0.98-2.55).

Conclusions: Our preliminary results suggested that the assessment of AR expression may be a useful tool to identify patients with a good or a poor prognosis. Furthermore, since that about one third of metastatic TNBC expressed ARs, they may represent a target for novel potential treatment options in advanced TNBC.

????: ????? ??????? ???????????? ???? ????????? ??????????? ?????, ?????????? ? ?????????????? ????????? ???????? ????? ??????? ?? 3 ?? ?? 10 ?? ? ?????? ? ???? ?? ????????? ??????? ???? Pencil Beam (PB) ? ??????? ??????? ? ?????????????? ?????????????? (IMRT) ??? ????????? ???????? ??????? ???? ?????? ? ???, ???? (????????? ????? ?????) ? ?????. ????????: ? ??????? ????????? ? ???????? ?????? ???????????? ??????? ????????????????, ????????? ? ???????? ????? ???????, ???? ?????????. ???? ?? ??? ????, ? ?????????????? ????????? ???????????? ??????? (TPS) ?????????? ?????????? ? ?????????????? ?? ????????????? ??????? ??????? (IMRT), ???????????????? ???? ??-?? ??????? ????? ??? ??? ???????? ?????????. ????????? ? ??????: ?????????? ?????????, ?? ??????? ?????? ???????? ? ????????? ?????? ? ???, ???? ? ????? ??????????????, ??????????????? ??? ????????????. ????? IMRT ???? ??????? ??? ??????????? ??? 6600 ???, 5000 ??? ? 5400 ??? ??? ???????? ?????? ? ???, ???? ? ????????? ????? ?????????????? ? ?????????????? Oncentra v 4.3 TPS. ??? ??????? ???????? ??? ???????? ?????? ???? ? ??????? ?????????? Pencil Beam (PB) ? ?????????????? ???????? ????? ???? 3,0 ??, 5,0 ?? ? 10,0 ??. ??????????: ????? ???? ??????? ? ???????????? ? ?????????????? ICRU, ? ??????????? ???? ???? ????????? ? ???????????? ? ?????????????? Quantec. ???????? ? ????? ??? ????????? ???????? ????? ? ??????? ???????? ? ??????? ????? ???? ???????????????? ? ??????? ? ???????. ??????????: ? ?????, ??????? ?????????? ??????? ????? ?? ????????? ????, ??-????????, ?????????????. ?????? ????????????? 3 ?? ??? ??????????? ?????????? ???????? ????, ???????? ? ???????? ? ??????? ??????????.

?????????????? ?????? ??????????? ? ??????????????? ???????? ???? ??????????? ? ??????? ??????????? ??????? ????????? ??????????????? ???????????????. ??? ???? ??????? (??) ?????????????? ?????????? ???????? ????????? ???????????? (???).
????: ????? ?????? ???????????? ???????? ?????? ????????? ???????, ???????????? ??? ?? ?????????????? ??????. ??????: 52 ?????? ?? ???? ???????? ????????????????? ?? CD34, CD105 ? D2-40. ?????????????? ?????? ???????????????? ????? ??????????? ??? ??????? ??????? ????? ???????? ???????????? (??) ? ???? «??????? ??????» ? ?????????????? ???? ????????? ???????????????? ?????????? (100x, 200x ? 400x). ????? ??? ?????????????? ????? ??????? ?????????? ??????? ?? ??????? ????????????????? ???? (?????????? ? ??2) ? ???????????? ????? ????? ?????????? ????????.
??????????: MVD, ?????????? ??? CD34, ???????? 203 ??/??2 (100x), 311 ??/??2 (200x) ? 490 ??/??2 (400x). MVD ??? CD105 ???????? 127 ??/??2 (100x), 213 ??/??2 (200x) ? 347 ??/??2 (400x). MVD, ?????????? ??? D2-40, ???????? 35 ??/??2 (100x), 69 ??/??2 (200x) ? 170 ??/??2 (400x). ?? ??????????, ??? MVD, ?????????? ??? 100-??????? ??????????, ??? ????, ??? ??? 200-???????, ??? ???? ????, ??? ??? 400-???????. ??? ???????? ???? ????????????? ????????? ? ????????? ??????????????? ??? ???? ???? ????????. MVD, ?????????? ??? CD34, ??? ????, ??? ??? CD105. MVD ??? ????????????? ???????, ?????????? ? ??????? D2-40, ??? ????, ??? MVD ??? CD34 ? CD105.
??????????: ???? ?????????? ??????????, ??? ?????????? ??????????????????? ??????? ?????? ??????????? ? ??????????????? ??? GC ????? ????????? ? ????????? ? ???????? MDV, ??? ???????? ????????????????? ??????????? ? ????????? ????? ?????????? ?????????????? ? ???????????. ?????????? ????????????????? ?????? ??????????? MVD ??? ????????? ??????????? ? ????????????? ??? ??????????????? ???????? ??? GC ? ?????? ????? ????????.