14 research outputs found
A Non-randomized, Observational Trial of Short-term Pre-operative Endocrine Therapy in ER Positive Breast Cancer to Investigate Changes in Genomic Expression Using the Oncotype DX® Recurrence Score®
Mechanism of Cancer Cell Death Induced by Depletion of an Essential Replication Regulator
Background: Depletion of replication factors often causes cell death in cancer cells. Depletion of Cdc7, a kinase essential for initiation of DNA replication, induces cancer cell death regardless of its p53 status, but the precise pathways of cell death induction have not been characterized. Methodology/Principal Findings: We have used the recently-developed cell cycle indicator, Fucci, to precisely characterize the cell death process induced by Cdc7 depletion. We have also generated and utilized similar fluorescent cell cycle indicators using fusion with other cell cycle regulators to analyze modes of cell death in live cells in both p53-positive and-negative backgrounds. We show that distinct cell-cycle responses are induced in p53-positive and-negative cells by Cdc7 depletion. p53-negative cells predominantly arrest temporally in G2-phase, accumulating CyclinB1 and other mitotic regulators. Prolonged arrest at G2-phase and abrupt entry into aberrant M-phase in the presence of accumulated CyclinB1 are followed by cell death at the post-mitotic state. Abrogation of cytoplasmic CyclinB1 accumulation partially decreases cell death. The ATR-MK2 pathway is responsible for sequestration of CyclinB1 with 14-3-3s protein. In contrast, p53-positive cancer cells do not accumulate CyclinB1, but appear to die mostly through entry into aberrant S-phase after Cdc7 depletion. The combination of Cdc7 inhibition with known anti-cancer agents significantly stimulates cell death effects in cancer cells in a genotype-dependent manner, providing a strategic basis for future combination therapies
Quantitative gene expression by RT-PCR in the tubular, cribriform, mucinous, and papillary histologic subtypes of invasive breast cancer.
Quantitative gene expression by RT-PCR in classic and variant lobular carcinoma in ER+ breast cancer.
A Nonrandomized Observational Trial of Short- Term Preoperative Endocrine Therapy in ER- Positive Breast Cancer to Investigate Change in Genomic Expression Using the 21-Gene Breast Cancer Assay
Time trends in characteristics at diagnosis and subsequent survival for Caucasian, Japanese and Hawaiian women with breast cancer in Hawaii
Validation Study of a Quantitative Multigene Reverse Transcriptase–Polymerase Chain Reaction Assay for Assessment of Recurrence Risk in Patients With Stage II Colon Cancer
Prognostic Utility of the 21-Gene Assay in Hormone Receptor–Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features
Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial
aerial view, Chaifetz Arena as situated on campus, November 14, 201