While clinical responses to palbociclib have been promising, metastatic breast cancer remains incurable due to the development of resistance. We generated estrogen receptor-positive (ER+) and ER-negative (ER−) cell line models and determined their permissiveness and cellular responses to an oncolytic adenovirus (OAd) known as Ad5/3-delta24. Analysis of ER+ and ER− palbociclib-resistant cells revealed two clearly distinguishable responses to the OAd. While ER+ palbociclib-resistant cells displayed a hypersensitive phenotype to the effects of the OAd, ER− palbociclib-resistant cells showed a resistant phenotype to the OAd. Hypersensitivity to the OAd in ER+ palbociclib-resistant cells correlated with a decrease in type I interferon (IFN) signaling, an increase in viral entry receptor expression, and an increase in cyclin E expression. OAd resistance in ER− palbociclib-resistant cells correlated with an increase in type I IFN signaling and a marked decrease in viral entry receptor. Using the OAd as monotherapy caused significant cytotoxicity to both ER+ and ER− palbociclib-sensitive cell lines. However, the addition of palbociclib increased the oncolytic activity of the OAd only in ER+ palbociclib-sensitive cells. Our studies provide a mechanistic base for a novel anti-cancer regimen composed of an OAd in combination with palbociclib for the treatment of ER+ breast cancer.
SUMMARY Seven cases of recurring digital fibroma were seen over a 35-year period. All demonstrated the classical clinical, macroscopic, and microscopic features of this distinct tumour, including the pathognomonic round, eosinophilic cytoplasmic inclusion bodies. Ultrastructurally, all seven cases were confirmed to be myofibroblastic in nature, and the morphology and intracellular topography of the inclusion bodies suggested their derivation from contractile protein. These findings establish recurring digital fibroma as a neoplastic lesion of the myofibroblast.
Four cases of a locally invasive sarcoma of the chest wall are described in children aged between 8 and 14 years. Although its morphology resembles a Ewing's sarcoma of bone there are light and electron microscopical features that are distinctive. The sarcoma is thought to represent an entity which has not previously been defined. Its clinical importance lies in the fact that the prognosis with appropriate treatment appears to be good. One child died after 2 1/2 years, but the others are alive 6, 8, and 16 years after presentation.
(47%) or workplace exposure (52%); the total percentage was 91%. 4. Most (78%) of lung cancers were diagnosed in an advanced non-operative stage. 5. The average lifetime from the moment of diagnosis till death was 6.45 months.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.