Cancer immunology (systemic effects of breast cancer) — MMTV-PyMT mouse mammary cancer model for studying systemic monocyte changes

LY5, a new small molecule designed to block STAT3, would slow the growth and spread of osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma.

LY5 killed sarcoma cells in culture and was well absorbed by mouth, but it did not slow tumour growth or prevent lung metastasis in mice. Knocking down STAT3 itself did not reproduce LY5's effects on the cells.

Why it matched: mechanism: Cell cycle & proliferation · failed the same way: Held in the model species, not beyond it

ZBTB38, a transcription factor highly expressed in germinal centre B cells and plasma cells, would be needed for normal antibody responses, as related family members are.

Mice lacking ZBTB38 in blood cells had normal germinal centre B cell numbers, normal antibody responses after immunisation, and normal memory B cell recall. Very few genes changed in B cells without ZBTB38.

Why it matched: mechanism: Gene expression & RNA · failed the same way: Held in the model species, not beyond it

A 25-minute acid treatment (pH 5.7) would turn mouse blood cells into pluripotent stem cells, as Obokata et al. (2014) reported.

Acid-treated spleen cells from newborn Oct4-GFP mice did not express the stem cell marker Oct4-GFP after 3 to 6 days, and qPCR found no rise in Oct4, Sox2 or Nanog. Lung fibroblasts gave the same result.

Why it matched: failed the same way: Held in the model species, not beyond it