Slugs from Brazil

21 p. : ill. ; 24 cm.Includes bibliographical references (p. 17-21)

Genetic analysis of heterogeneous subsets of circulating tumour cells from high grade serous ovarian carcinoma patients

Circulating tumour cells (CTCs) are heterogenous and contain genetic information from the tumour of origin. They bear specific intra- and extra-cellular protein markers aiding in their detection. However, since these markers may be shared with other rare cells in the blood, only genetic testing can confirm their malignancy. Herein, we analyse different CTC subsets using single cell whole genome DNA sequencing to validate their malignant origin. We randomly selected putative CTCs identified by immunostaining that were isolated from 4 patients with high grade serous ovarian cancer (HGSOC) and one with benign cystadenoma. We specifically targeted CTCs positive for epithelial (CK/EpCAMpos), mesenchymal (vimentinpos), and pseudoendothelial (CK/EpCAMpos plus CD31pos) markers. We isolated these cells and performed whole genome amplification (WGA) and low-pass whole-genome sequencing (LP-WGS) for analysis of copy number alterations (CNA). Of the CK/EpCAMpos cells analysed from the HGSOC patients, 2 of 3 cells showed diverse chromosomal CNAs. However, the 4 pseudoendothelial cells (CK/EpCAMpos plus CD31pos) observed in the HGSOC cases did not carry any CNA. Lastly, two of the clusters of vimentin positive cells sequenced from those found in the benign cystadenoma case had CNA. Despite the low number of cells analysed, our results underscore the importance of genetic analysis of putative CTCs to confirm their neoplastic origin. In particular, it highlights the presence of a population of CK/EpCAMpos cells that are not tumour cells in patients with HGSOC, which otherwise would be counted as CTCs

A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours

This phase I study investigated the maximum tolerated dose and pharmacokinetics of a 3-weekly administration of BMS-188797, a paclitaxel derivate, at three dose levels (DLs) (80, 110 and 150 mg m−2 DL), combined with cisplatin (standard dose 75 mg m−2). In 16 patients with advanced malignancies treated, one patient experienced dose-limiting febrile neutropenia, sepsis and severe colitis at the 150 mg m−2 DL; at the 110 mg m−2 DL one episode of dose-limiting grade 3 diarrhoea/nausea occurred. Grade 3/4 haematological toxicities were leucopenia/neutropenia; grade 3 nonhaematological toxicities were neuropathy, nausea, diarrhoea and stomatits. Objective response was seen in four patients, with three complete remissions in ovarian and cervical cancer patients. Pharmacokinetics of BMS-188797 appeared linear through the 110 mg m−2, but not through the 150 mg m−2 DL. The mean±SD values for clearance, distribution volume at steady state and terminal half-life during cycle 1 were 317±60 ml min−1 m−2, 258±96 l m−2 and 30.8±7.7 h, respectively. The maximum tolerated and recommended phase II dose for BMS-188797 was 110 mg m−2 (1-h infusion, every 3 weeks) combined with cisplatin 75 mg m−2

Automatic Segmentation of Brain Structures for Radiation Therapy Planning

Delineation of structures to irradiate (the tumors) as well as structures to be spared (e.g., optic nerve, brainstem, or eyes) is required for advanced radiotherapy techniques. Due to a lack of time and the number of patients to be treated these cannot always be segmented accurately which may lead to suboptimal plans. A possible solution is to develop methods to identify these structures automatically. This study tests the hypothesis that a fully automatic, atlas-based segmentation method can be used to segment most brain structures needed for radiotherapy plans even tough tumors may deform normal anatomy substantially. This is accomplished by registering an atlas with a subject volume using a combination of rigid and non-rigid registration algorithms. Segmented structures in the atlas volume are then mapped to the corresponding structures in the subject volume using the computed transformations. The method we propose has been tested on two sets of data, i.e., adults and children/young adults. For the first set of data, contours obtained automatically have been compared to contours delineated manually by three physicians. For the other set qualitative results are presented

Changing youth? : continuities and ruptures in transitions into adulthood among Catalan young people

The globalisation process has an impact at the micro-level on life-course patterns: concretely, the trajectories of young people into adulthood are being sharply modified. At a European level, the extension, de-linearisation, reversibility and diversification of youth trajectories have been identified as major changes. However, the extent to which these changes affect young people within each country depends on their respective welfare regimes. This article analyses how the Mediterranean welfare regime shapes youth trajectories among Catalan young people and explores the hypothesis that these constraints will make those trajectories less sensitive to the general trends of change identified at a European level. The research is based on an analysis of the Catalan Youth Survey, an official statistic that contains retrospective data on Educational, Work, Housing and Family transitions. The results offer an integrated typology of youth transitions in Catalonia and show how the persistence of traditional patterns of transition are the logical result of the particular articulation of the welfare regime and cultural patterns among Catalan young people

Differential Forms on Log Canonical Spaces

The present paper is concerned with differential forms on log canonical varieties. It is shown that any p-form defined on the smooth locus of a variety with canonical or klt singularities extends regularly to any resolution of singularities. In fact, a much more general theorem for log canonical pairs is established. The proof relies on vanishing theorems for log canonical varieties and on methods of the minimal model program. In addition, a theory of differential forms on dlt pairs is developed. It is shown that many of the fundamental theorems and techniques known for sheaves of logarithmic differentials on smooth varieties also hold in the dlt setting. Immediate applications include the existence of a pull-back map for reflexive differentials, generalisations of Bogomolov-Sommese type vanishing results, and a positive answer to the Lipman-Zariski conjecture for klt spaces.Comment: 72 pages, 6 figures. A shortened version of this paper has appeared in Publications math\'ematiques de l'IH\'ES. The final publication is available at http://www.springerlink.co

Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes

Background: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer

Multi-marker immunofluorescent staining and pd-l1 detection on circulating tumour cells from ovarian cancer patients

Detection of ovarian cancer (OC) circulating tumour cells (CTCs) is primarily based on targeting epithelial markers, thus failing to detect mesenchymal tumour cells. More importantly, the immune checkpoint inhibitor marker PD-L1 has not been demonstrated on CTCs from OC patients. An antibody staining protocol was developed and tested using SKOV-3 and OVCA432 OC cell lines. We targeted epithelial (cytokeratin (CK) and EpCAM), mesenchymal (vimentin), and OC-specific (PAX8) markers for detection of CTCs, and CD45/16 and CD31 were used for the exclusion of white blood and vascular endothelial cells, respectively. PD-L1 was used for CTC characterisation. CTCs were enriched using the Parsortix™ system from 16 OC patients. Results revealed the presence of CTCs in 10 (63%) cases. CTCs were heterogeneous, with 113/157 (72%) cells positive for CK/EpCAM (epithelial marker), 58/157 (37%) positive for vimentin (mesenchymal marker), and 17/157 (11%) for both (hybrid). PAX8 was only found in 11/157 (7%) CTCs. In addition, 62/157 (39%) CTCs were positive for PD-L1. Positivity for PD-L1 was significantly associated with the hybrid phenotype when compared with the epithelial (p = 0.007) and mesenchymal (p = 0.0009) expressing CTCs. Characterisation of CTC phenotypes in relation to clinical outcomes is needed to provide insight into the role that epithelial to mesenchymal plasticity plays in OC and its relationship with PD-L1

Pegfilgrastim ± ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study

Background: TAC (docetaxel/doxorubicin/cyclophosphamide) is associated with high incidences of grade 4 neutropenia and febrile neutropenia (FN). This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC. Patients and methods: Patients with stage T2-T4 primary breast cancer were scheduled to receive 6-8 cycles of TAC. Primary prophylaxis was: ciprofloxacin 500 mg orally twice daily on days 5-14 (n = 253 patients; 1478 cycles), daily granulocyte colony-stimulating factor (G-CSF) (filgrastim 5 μg/kg/day or lenograstim 150 μg/m2/day) on days 5-10 (n = 377; 2400 cycles), pegfilgrastim 6 mg on day 2 (n = 305; 1930 cycles), or pegfilgrastim plus ciprofloxacin (n = 321; 1890 cycles). Results: Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN (5% and 7% versus 18% and 22% of patients; all P < 0.001), grade 4 neutropenia, and leukopenia. Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN (P < 0.01 versus pegfilgrastim alone) and fatal neutropenic events. Conclusion: Ciprofloxacin alone, or daily G-CSF from day 5-10 (as in common practice), provided suboptimal protection against FN and related toxic effects in patients receiving TAC. Pegfilgrastim was significantly more effective in this setting, especially if given with ciprofloxaci