Sentences with phrase «hypoxic csc»

Inhibition of ER - α blocked the hypoxic CSC response in all ER - α — positive cells, supporting the role of estrogen signaling in the hypoxic response.

As the mechanistic studies suggest that ER - α and Notch are central in mediating the unfavourable hypoxic CSC response in ER - α — positive breast cancer, they may offer an attractive combination treatment approach, which would consist of ER - α or Notch inhibitors combined with antiangiogenic drugs.

Interestingly, when signaling through Notch1 and Notch4 were specifically blocked only inhibition of Notch1 reduced the hypoxic CSC response (Fig. 3E).

These data support the hypothesis that ER - α plays an important role in the hypoxic CSC response in ER - α — positive cells and that signaling through this pathway is responsible, at least in part, for the increase in CSC.

We therefore asked whether activation of these pathways in ER - α — negative lines would modify their hypoxic CSC response.

In vivo model of hypoxic CSC effect.

Intraperitoneal injection of the HIF - 1α inhibitor, YC1, following tumor initiation reduces the hypoxic CSC effect in MCF7 xenografts and results in no correlation between xenograft size and MFC (Fig. 5C).

Future studies need to clarify whether smaller subgroups of breast cancer, defined according to expression array criteria, will behave in ways similar to ER - α — positive or negative breast cancer but it is clear that the 2 major disease subgroups, defined by ER - α status, show contrasting hypoxic CSC responses.

Our findings suggest that this is also true in breast cancer as EGFR inhibition blocked the hypoxic CSC effect in ER - α — positive tumors.

Not exact matches

The same ER - α — dependent contrasting hypoxic - CSC response was seen validating the initial observation.

No significant differences were seen between the normoxic and hypoxic anoikis - resistant populations collected from MCF7 cells and a single significant gene change (PIP) was seen in T47D (Table 1) suggesting that the CSC - enriched population remains virtually unchanged following hypoxic culture and the increase in MFC, HFC, and tumor initiating cells is, therefore, due to expansion of the population, perhaps by increased symmetric self - renewal of the CSC or de-differentiation of early progenitor cells, rather than simply the acquisition of anoikis resistance in non-CSC.

Recent reports show increased CSC activity following hypoxic exposure in breast cancer cell lines (18 — 20), but no reports have studied this rare population in primary human breast cancer samples.

Dormant tumor cells in a hypoxic bone marrow niche (19) will be enriched for CSC in ER - α — positive breast cancer but depleted in ER - α — negative cancers profoundly influencing the capacity for late disease recurrence.

There was a HIF - 1α — dependent CSC increase in ER - α — positive cancers following hypoxic exposure, which was blocked by inhibition of estrogen and Notch signaling.

Cancer stem cells (CSCs) in the hypoxic BM regions are blamed for the incurability of MM, because CSCs are often resistant to drugs currently used against BM cancers (including proteasome inhibitors and immunomodulatory agents).