33 research outputs found
sj-docx-1-tam-10.1177_17588359231173181 – Supplemental material for Oxaliplatin prior to PARP inhibitor in BRCA-mutated ovarian cancer
Supplemental material, sj-docx-1-tam-10.1177_17588359231173181 for Oxaliplatin prior to PARP inhibitor in BRCA-mutated ovarian cancer by Maria Ornella Nicoletto, Alessandra Baldoni, Francesco Cavallin, Andrea Grego, Cristina Falci, Margherita Nardin, Enzo Mammano, Eleonora Lai and Valter Torri in Therapeutic Advances in Medical Oncology</p
Autophagy inhibition reduces chemoresistance and tumorigenic potential of human ovarian cancer stem cells
Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors with a high mortality rate owing to tumor relapse after anticancer therapies. It is widely accepted that a rare tumor cell population, known as cancer stem cells (CSC), is responsible for tumor progression and relapse; intriguingly, these cells are able to survive nutrient starvation (such as in vitro culture in the absence of glucose) and chemotherapy treatment. Recent data also indicated that chemotherapy resistance is associated with autophagy activation. We thus decided to investigate both in vitro and in vivo the autophagic activity and the effects of the perturbation of this pathway in CSC isolated from EOC ascitic effusions. Ovarian CSC, identified according to their CD44/CD117 co-expression, presented a higher basal autophagy compared with the non-stem counterpart. Inhibition of this pathway, by in vitro chloroquine treatment or CRISPR/Cas9 ATG5 knockout, impaired canonical CSC properties, such as viability, the ability to form spheroidal structures in vitro, and in vivo tumorigenic potential. In addition, autophagy inhibition showed a synergistic effect with carboplatin administration on both in vitro CSC properties and in vivo tumorigenic activity. On the whole, these results indicate that the autophagy process has a key role in CSC maintenance; inhibition of this pathway in combination with other chemotherapeutic approaches could represent a novel effective strategy to overcome drug resistance and tumor recurrence
Intrapleural paclitaxel for malignant pleural effusion from ovarian and breast cancer: A phase II study with pharmacokinetic analysis
Leggere, Interpretare e Ri-configurare il convento di Santa Maria della Sanità a Napoli | Reading, Interpreting and Re-configuring the Convent of Santa Maria della Sanità in Naples
The history of architectural thought is profoundly intertwined with the literary tradition of description, an approach rooted in the rhetoric of ekphrasis, which uses text to evoke a visual and sensory experience almost equivalent to that provided by the image itself. Through expressive use and pathos in textual composition, the written word becomes a means to ‘imagine’ and understand the described object, enhancing the reader’s perceptual experience and facilitating critical analysis. In the outlined context and within the framework of research conducted on the monastic complex of Santa Maria della Sanità in Naples, the proposed contribution advances the analysis of an unpublished narrativedescriptive source titled Vita del P. Maestro F. Domenico di S. Tommaso (1689), written by Dominican friar Ottaviano Bulgarini of the Order of Preachers of Sanità, to honor the memory of Fra’ Domenico Ottomano, born Osman, the son of Sultan Ibrahim and the young Giacoma of the noble Beccarini family from Manfredonia.
Specifically, it is in the sixth of the ten books that comprise the volume where the author recounts how Fra’ Domenico arrived in Naples to attend the
novitiate school in the convent of Sanità, concluding with a detailed description of the convent itself, in response to the Fathers’ desire to show the
young novice “all the parts of that sumptuous and renowned monastery.” Through this detailed textual description, the reader is led on a captivating mental journey, rediscovering the spaces of the ancient convent. The combination of such richly detailed descriptions contributes to this study by offering a reassessment and integration of previously examined documentary and iconographic sources, as well as a reinterpretation of the convent’s architectural configuration
Trabectedin plus pegylated liposomal doxorubicin: retrospective analysis in heavily pretreated platinum-sensitive ovarian cancer
Purpose: This retrospective analysis evaluated treatment with trabectedin plus pegylated liposomal doxorubicin (PLD) in 34 heavily pretreated patients (median number of previous lines, 3; range, 2-10) with platinum-sensitive relapsed ovarian cancer (ROC) at a single center in Italy.
Methods: Trabectedin/PLD treatment consisted of trabectedin administered every 3 weeks as a 3-hour intravenous (i.v.) infusion at a dose of 1.1 mg/m(2), immediately after PLD 30 mg/m(2) i.v. infusion. Study objectives were the evaluation of the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).
Results: Three complete responses and 8 partial responses were observed, with an ORR of 32.4% (95% CI, 17.4-50.5%). Median PFS was 6.1 months (95% CI, 4.4-8.9 months). Median OS was 16.3 months (95% CI, 6.8-23.5). Most responses (9 of 11) were found in patients with partially platinum-sensitive disease (ORR 40.9% in this subset; median PFS 6.8 months and median OS 20.8 months). Grade 3 treatment-related adverse events consisted of nausea/vomiting (n = 5; 14.7%), mucositis (n = 2; 5.9%), alanine aminotransferase increase, anemia and neutropenia (n = 1 each; 2.9%).
Conclusions: The overall findings appear consistent with those previously observed in a randomized controlled clinical trial, and support the use of trabectedin/PLD in heavily pretreated patients with platinum-sensitive ROC, especially those with partially platinum-sensitive disease
Mitogenomes from Two Uncommon Haplogroups Mark Late Glacial/Postglacial Expansions from the Near East and Neolithic Dispersals within Europe
The current human mitochondrial (mtDNA) phylogeny does not equally represent all human populations but is biased in favour of representatives originally from north and central Europe. This especially affects the phylogeny of some uncommon West Eurasian haplogroups, including I and W, whose southern European and Near Eastern components are very poorly represented, suggesting that extensive hidden phylogenetic substructure remains to be uncovered. This study expanded and re-analysed the available datasets of I and W complete mtDNA genomes, reaching a comprehensive 419 mitogenomes, and searched for precise correlations between the ages and geographical distributions of their numerous newly identified subclades with events of human dispersal which contributed to the genetic formation of modern Europeans. Our results showed that haplogroups I (within N1a1b) and W originated in the Near East during the Last Glacial Maximum or pre-warming period (the period of gradual warming between the end of the LGM, ~19 ky ago, and the beginning of the first main warming phase, ~15 ky ago) and, like the much more common haplogroups J and T, may have been involved in Late Glacial expansions starting from the Near East. Thus our data contribute to a better definition of the Late and postglacial re-peopling of Europe, providing further evidence for the scenario that major population expansions started after the Last Glacial Maximum but before Neolithic times, but also evidencing traces of diffusion events in several I and W subclades dating to the European Neolithic and restricted to Europe
Establishment and characterization of xenografts and cancer cell cultures derived from BRCA1 -/- epithelial ovarian cancers
The BRCA1 gene is responsible for a high number of hereditary breast and ovarian cancers that cluster in families with a strong genetic predisposition. Despite intense investigation, the accumulating findings on BRCA1 biological functions have not yet been translated into specific therapeutic approaches, also due to the lack of suitable experimental models. The purpose of this study was to establish and characterize cell cultures and xenografts from patients with BRCA1 -/- ovarian cancers. We derived two ovarian cancer cell lines, termed PD-OVCA1 and PD-OVCA2, both from patients previously treated with chemotherapy, that propagate in SCID mice as well as in vitro for a limited number of passages. Both cell lines expressed cytokeratins and the CA125 tumour marker. A detailed molecular characterization highlighted both constitutive and somatic genetic events that abrogate BRCA1 gene function. Both cell lines were shown to lose the wild type BRCA1 allele; intriguingly, these deletions wer..
