Prospective Study of the Effect of the 21-Gene Assay on Adjuvant Clinical Decision-Making in Japanese Women With Estrogen Receptor-Positive, Node-Negative, and Node-Positive Breast Cancer

AbstractBackgroundIn this study we investigated if the 21-gene assay result affects adjuvant decision-making in Japanese women with ER+ invasive EBC.Patients and MethodsA total of 124 consecutive eligible patients with ER+, HER2-negative EBC and 0 to 3 positive lymph nodes were enrolled. Treatment recommendations, physicians' confidence and patients' decisional conflict before and after knowledge of the Recurrence Score results of the 21-gene assay were recorded.ResultsOne-hundred four patients (84%) had N0 disease, including micrometastases, and 20 (16%) had N+ disease. Overall, recommendations changed in 33% (95% CI, 24%-43%) of N0 and 65% (95% CI, 41%-85%) of N+ patients. In 27 of 48 (56%) of N0 and 13 of 15 (87%) of N+ patients an initial recommendation for chemohormonal therapy was revised to only hormonal therapy after assay results, and in 7 of 56 (13%) of N0 and 0 of 5 N+ patients from only hormonal to combined chemohormonal therapy. Decisions appeared to follow the Recurrence Score results for low and high values. For patients with intermediate Recurrence Score values, overall recommendations for chemohormonal treatment tended to decrease after assay results. Physicians' confidence increased in 106 of 124 (85.5%; 95% CI, 78%-91%) cases. Patients' decisional conflict significantly improved as indicated by changes in the total score and the 5 defined subscores (P = .014 for Informed Subscore; P < .001 for all others).ConclusionResults from this prospective study in a Japanese population confirm an effect of the 21-gene assay results on adjuvant treatment decision-making, consistent with reported experiences from the United States and Europe

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

Iron(III) and Zinc(II) Calixarene Complexes: Synthesis, Structural Studies, and Use as Procatalysts for ε-Caprolactone Polymerization

Economic pressure, environmental issues and ever increasing demand are driving the shift from oil-based polymers to those available from renewable resources. Ring opening polymerisation of cyclic esters is currently a topical field with metal complex-induced coordination/insertion type polymerisation leading the way. Such a polymerisation method offers a wide range of advantages from control over the polymer structure to kinetic enhancement; however industrially available catalysts based on tin suffer from inherent toxicity and as a result a policy change from the Food and Drug Administration (FDA) is not unrealistic. This review underlines the efforts made in the past five years or so, and shows how low toxicity metals are attracting increasing attention in the field of e-caprolactone polymerisation

Hydrogen bonding receptors of tetraamide derivatives derived from thiacalix[4]arene in cone- and 1,3-alternate conformation

Novel ditopic receptors of tetraamide derivatives possessing four 2-pyridyl groups derived from thiacalix[4]arene in cone- and 1,3-alternate conformation were prepared. The structure of one of the tetraamide derivatives was confirmed by a single crystal X-ray analysis. The tetrathiacalix[4]arene tetraamides show strong intramolecular hydrogen bonding. The binding behaviour towards Ag+ and halides has been investigated by 1H NMR titration experiments