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1.
Future Oncol ; 20(2): 83-94, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37701998

ABSTRACT

Aim: To assess maintenance preference and trade-offs for patients with advanced epithelial ovarian cancer. Methods: Patients completed a time trade-off exercise ranking five maintenance approaches. Patients' preferred approach was compared with alternatives to determine the progression-free time they would trade off to remain on their preferred approach. Results: Of 152 patients (median age 53 years, 68% White), 56% chose one of four maintenance medications, mostly to feel proactive and 44% chose active surveillance. Compared with their preferred approach, patients were willing to trade a mean progression-free time before switching of 2.3 months for once-daily oral medications, 3.2 months for twice-daily oral medications, 5.5 months for intravenous infusions every 3 weeks (iv. q3), 6.1 months for active surveillance and 7.5 months for iv. q3 and twice-daily oral. Conclusion: Findings highlight the importance of patients' awareness of all maintenance approaches and involving them in the decision-making process.


What is the article about? The VOCAL study looked at maintenance approach preferences of patients with advanced epithelial ovarian cancer. Maintenance approach refers to the methods used after a patient has completed their initial chemotherapy to prevent disease progression for as long as possible. US patients completed an online survey, ranking five different maintenance approaches: No medication (active surveillance); Once-daily oral medication (e.g. pills); Twice-daily oral medication; Medication by intravenous infusion every 3 weeks; Medication by intravenous infusion every 3 weeks and oral twice-daily. Patients were asked to assume the same time to disease progression for all five approaches and the same side effects for the four approaches involving medications (2­5). Each patient then indicated how much time to disease progression they were willing to trade off to remain on their preferred approach before switching to an alternative. What were the results? Overall, 152 patients completed the survey (median age: 53 years, 68% White). Most patients preferred a medication approach (56%, n = 85) to active surveillance (44%, n = 67). Of the 85 patients who preferred medication, 66% (n = 56) reported this was to feel proactive in preventing their cancer returning. Once-daily oral medication was the most acceptable alternative to the patients' preferred maintenance approach, given they were willing to trade the least 'disease-free' time (2.3 months) before accepting a switch. What do the results mean? Individual patient preferences vary, and healthcare professionals should work with patients to determine which approach is most appropriate for them.


Subject(s)
Ovarian Neoplasms , Humans , Female , Middle Aged , Ovarian Neoplasms/drug therapy , Carcinoma, Ovarian Epithelial
2.
Dis Model Mech ; 12(4)2019 04 09.
Article in English | MEDLINE | ID: mdl-30926586

ABSTRACT

Extensive loss of dopaminergic neurons and aggregation of the protein α-synuclein into ubiquitin-positive Lewy bodies represents a major neuropathological hallmark of Parkinson's disease (PD). At present, the generation of large nuclear-associated Lewy bodies from endogenous wild-type α-synuclein, translationally regulated under its own promoter in human cell culture models, requires costly and time-consuming protocols. Here, we demonstrate that fully differentiated human SH-SY5Y neuroblastoma cells grown in three-dimensional cell culture develop Lewy-body-like pathology upon exposure to exogenous α-synuclein species. In contrast to most cell- and rodent-based PD models, which exhibit multiple diffuse α-synuclein aggregates throughout the cytoplasm, a single large nuclear inclusion that is immunopositive for α-synuclein and ubiquitin is rapidly obtained in our model. This was achieved without the need for overexpression of α-synuclein or genetic modification of the cell line. However, phosphorylation of α-synuclein within these inclusions was not observed. The system described here provides an ideal tool to screen compounds to therapeutically intervene in Lewy body formation, and to investigate the mechanisms involved in disease progression in synucleinopathies.


Subject(s)
Dopaminergic Neurons/pathology , Models, Biological , Parkinson Disease/pathology , Biomarkers/metabolism , Brain-Derived Neurotrophic Factor/pharmacology , Cell Differentiation/drug effects , Cells, Cultured , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Humans , Lewy Bodies/drug effects , Lewy Bodies/metabolism , Phenotype , Protein Aggregates/drug effects , Tretinoin/pharmacology , alpha-Synuclein/metabolism
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