ASO Author Reflections: Is There Still a Role for Intraperitoneal Oxaliplatin for Colorectal Peritoneal Metastases?

International audienc

Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: A multicenter study.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method used in patients with peritoneal cancer (PC) of primary or secondary origin. Intraperitoneal use of oxaliplatin raises concerns about toxicity, especially abdominal pain. The objective of this study was to assess the tolerance of PIPAC with oxaliplatin (PIPAC-Ox) in a large cohort of patients and to identify the risk factors for high grade toxicity, discontinuation of treatment and impaired survival. This retrospective cohort study included all consecutive patients treated with PIPAC-Ox (92 mg/m <sup>2</sup> ) in five centers specialized in the treatment of PC. The procedure was repeated every 6 weeks. Outcomes of interest were Common Terminology Criteria for Adverse Events (CTCAE), symptoms and survival (Kaplan-Meier). Univariate risk factors were included in a multinominal regression model to control for bias. Overall, 251 PIPAC-Ox treatments were performed in 101 patients (45 female) having unresectable PC of various origins: 66 colorectal, 15 gastric, 5 ovarian, 3 mesothelioma, 2 pseudomyxoma, 10 other malignancies (biliary, pancreatic, endocrine) respectively. The median PCI was 19 (IQR: 10-28). Postoperative abdominal pain was present in 23 patients. Out of the 9 patients with grade 3 abdominal pain, only 3 needed a change of PIPAC drug. CTCAE 4.0 toxicity grade 4 or higher was encountered in 16(15.9%) patients. The patients had a mean of 2.5 procedures/patient (SD = 1.5). 50 subjects presented with symptom improvement. Oxaliplatin-based PIPAC appears to be a safe treatment that offers good symptom control and promising survival for patients with advanced peritoneal disease

X-ray and Infrared Microanalyses of <i>Mona Lisa</i>'s Ground Layer and Significance Regarding Leonardo da Vinci's Palette

An exceptional microsample from the ground layer of Leonardo da Vinci's Mona Lisa was analyzed by high-angular resolution synchrotron X-ray diffraction and micro Fourier transform infrared spectroscopy, revealing a singular mixture of strongly saponified oil with high lead content and a cerussite (PbCO3)-depleted lead white pigment. The most remarkable signature in the sample is the presence of plumbonacrite (Pb5(CO3)3O(OH)2), a rare compound that is stable only in an alkaline environment. Leonardo probably endeavored to prepare a thick paint suitable for covering the wooden panel of the Mona Lisa by treating the oil with a high load of lead II oxide, PbO. The review of Leonardo's manuscripts (original and latter translation) to track the mention of PbO gives ambiguous information. Conversely, the analysis of fragments from the Last Supper confirms that not only PbO was part of Leonardo's palette, through the detection of both litharge (α-PbO) and massicot (β-PbO) but also plumbonacrite and shannonite (Pb2OCO3), the latter phase being detected for the first time in a historical painting.</p

High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland

Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (θsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/θ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role

M19 Modulates Skeletal Muscle Differentiation and Insulin Secretion in Pancreatic β-Cells through Modulation of Respiratory Chain Activity

Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion