Biology subjects

Rouzier, R.

Publications and source records attributed to Rouzier, R..

3 recordsLinked to original sources

bioRxiv2025

Long-term patient-derived ovarian cancer organoids closely recapitulate tumor of origin and clinical response

There is an urgent need of precision medicine for ovarian cancer patients to identify patients who respond to chemotherapy and PARP inhibitors, a therapy targeting homologous recombination deficiency (HRD). Here we established a panel of 37 long-term patient-derived tumor organoids (PDTO) models of various histological subtypes from 224 patients and demonstrated that they mimic the histological and molecular characteristics of original tumors. Screening of chemotherapeutic drugs showed that PDTO exhibit heterogeneous responses, and that response of PDTO from high-grade serous ovarian carcinoma to carboplatin recapitulated patient response to first-line treatment. Additionally, the detection of HRD phenotype of PDTO using functional assay was associated with the results of the HRD test Genomic Instability Scar (GIScar). Although larger-scale investigations are needed to confirm the predictive potential of PDTO, these results provide further evidence of the potential interest of ovarian PDTO for functional precision medicine even if many challenges remain to be addressed.

cancer biology↗

bioRxiv2019

Centrosome amplification favours survival and impairs ovarian cancer progression

Centrosome amplification, the presence of more than two centrosomes in a cell is a common feature of most human cancer cell lines. However, little is known about centrosome numbers of human cancers and whether amplification or other numerical aberrations are frequently present. To address this question, we have analyzed a large cohort of human epithelial ovarian cancers (EOCs) from 100 patients. Using state-of-the-art microscopy, we have determined the Centrosome-Nucleus Index (CNI) of each tumor. We found that EOCs show infrequent centrosome amplifications. Strikingly, the large majority of these tumors presented low CNIs. We show that low CNI tumors are enriched in the mesenchymal subgroup and correlate with poor patient survival. Our findings highlight a novel paradigm linking low centrosome number with highly aggressive behavior in ovarian cancers and show that the CNI signature may be used to stratify ovarian cancers.

cancer biology↗

bioRxiv2019

Absenteeism and indirect costs during the year following the diagnosis of an operable breast cancer

IntroductionThe consequences of disease on work for individual patients as well as the consequences of absenteeism from work are subjects of interest for decision-makers.\n\nMethodsWe analyzed duration of absenteeism and related indirect costs for patients with a paid job during the year following diagnosis of early-stage breast cancer in the prospective OPTISOINS01 cohort. A human capital and friction costs approaches were considered for evaluation of lost working days. For this analysis, the friction period was estimated from recent French data. Statistical analysis included simple and multiple linear regression to identify determinants of absenteeism and indirect costs.\n\nResults93% of patients had at least one period of sick leave, with an average of 2 periods of sick leave and a mean total duration of 186 days. 24% of patients returned to work part-time after an average sick leave of 114 days (i.e. 41 LWD). Estimated indirect costs were {euro}22,722.00 and {euro}7,724.00 per patient, for the human capital and friction cost approaches, respectively. In the multiple linear regression model, factors associated with absenteeism were: invasive tumor (p=.043), mastectomy (p=.038), redo surgery (p=.002), chemotherapy (p=.027), being a manager (p=.025) or a craftsman (p=.005).\n\nConclusionBreast cancer is associated with long periods of absenteeism during the year following diagnosis, but almost all patients were able to return to work. Major differences in the results were observed between the friction cost and human capital approaches, highlighting the importance of considering both approaches in such studies.

epidemiology↗