Metastatic renal cell carcinoma with occult primary: a multicenter prospective cohort.

Metastatic carcinoma of presumed renal origin (rCUP) has recently emerged as a new entity within the heterogeneous entity of Cancers of Unknown Primary (CUP) but their biological features and optimal therapeutic management remain unknown. We report the molecular characteristics and clinical outcome of a series of 25 rCUP prospectively identified within the French National Multidisciplinary Tumor Board for CUP. This cohort strongly suggests that rCUP share similarities with common RCC subtypes and benefit from renal-tailored systemic treatment.

[Collecting duct carcinoma and renal medullary carcinoma in the age of new therapies].

Collecting duct carcinoma (also known as Bellini tumour) and renal medullary carcinoma are two extremely rare and aggressive renal cancers. They are both less responsive to conventional treatments used in clear cell renal carcinoma. There are very few studies evaluating their optimal management and currently, at the metastatic stage, polychemotherapy based on platinum salts remains the most widely used.

Future treatment options in metastatic clear cell renal cell carcinoma.

The field of clear cell renal cell carcinoma (ccRCC) has undergone major changes in the last decade, both in terms of the understanding of the mechanisms of oncogenesis and the role of the tumor microenvironment in anti-tumor immunity, as well as in therapeutic developments. After the era of tyrosine kinase inhibitors (TKIs) targeting VEGFR and then the era of immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway, we are now entering the era of combination therapy for first-line metastatic cancer (m-ccRCC), such as combinations including a TKI and a PD-1 inhibitor or combinations of PD-1 and CTLA-4 blockers. In this extremely dynamic environment, new molecules with various mechanisms of action will appear in the very near future: immune response modulators (other ICIs, pro-inflammatory cytokines, gut microbiota modulators), new anti-angiogenic agents (new TKIs, anti-HIF-1α antibodies), agents affecting cell metabolism (glutaminase inhibitors, tryptophan regulators or adenosine A2A receptor antagonists) or epigenetic regulators (HDAC inhibitors).

Discovery and validation of a transcriptional signature identifying homologous recombination-deficient breast, endometrial and ovarian cancers.

Background: Molecular alterations leading to homologous recombination deficiency (HRD) are heterogeneous. We aimed to identify a transcriptional profile shared by endometrial (UCEC), breast (BRCA) and ovarian (OV) cancers with HRD.

Methods: Genes differentially expressed with HRD genomic score (continuous gHRD score) in UCEC/BRCA/OV were identified using edgeR, and used to train a RNAseq score (ridge-regression model) predictive of the gHRD score (PanCanAtlas, N = 1684 samples).

Potential competing risk of death in older high-risk endometrial carcinoma patients: Results from a multicentric retrospective cohort.

Introduction: Adjuvant therapeutic decisions in older endometrial carcinoma (EC) patients are challenged by a balance between more frequent aggressive EC and comorbidities. We assessed whether EC and comorbidities are competing or cumulative risks in older EC patients.

Methods: All consecutive patients treated for FIGO stage I-IV EC in two University Hospitals in Paris between 2010 and 2017 were retrospectively included.

Development and validation of a RNAseq signature for prognostic stratification in endometrial cancer.

Background: Despite recent advances in endometrial carcinoma (EC) molecular characterization, its prognostication remains challenging. We aimed to assess whether RNAseq could stratify EC patient prognosis beyond current classification systems.

Methods: A prognostic signature was identified using a LASSO-penalized Cox model trained on TCGA (N = 543 patients).

Development and validation of a host-dependent, PDL1-independent, biomarker to predict 6-month progression-free survival in metastatic non-small cell lung cancer (mNSCLC) patients treated with anti-PD1 immune checkpoint inhibitors (ICI) in the CERTIM Cohort: The ELY study.

Background: Immune checkpoint inhibitors (ICI) are dramatically active in a minority of non-small cell lung cancer (NSCLC) patients. We studied here the relationship between patients's metabolism and outcome under ICI.

Methods: Metastatic NSCLC patients underwent a nutritional assessment prior to initiating immunotherapy.

CAR T-cell Entry into Tumor Islets Is a Two-Step Process Dependent on IFNγ and ICAM-1.

Adoptive transfer of T cells expressing chimeric antigen receptors (CAR) has shown remarkable clinical efficacy against advanced B-cell malignancies but not yet against solid tumors. Here, we used fluorescent imaging microscopy and assays to compare the early functional responses (migration, Ca, and cytotoxicity) of CD20 and EGFR CAR T cells upon contact with malignant B cells and carcinoma cells. Our results indicated that CD20 CAR T cells rapidly form productive ICAM-1-dependent conjugates with their targets.

Association between Olaparib Exposure and Early Toxicity in BRCA-Mutated Ovarian Cancer Patients: Results from a Retrospective Multicenter Study.

Factors associated with olaparib toxicity remain unknown in ovarian cancer patients. The large inter-individual variability in olaparib pharmacokinetics could contribute to the onset of early significant adverse events (SAE). We aimed to retrospectively analyze the pharmacokinetic/pharmacodynamic relationship for toxicity in ovarian cancer patients from "real life" data.

The impact of body composition parameters on severe toxicity of nivolumab.

Background: The occurrence of severe, acute limiting toxicity in patients receiving anti-programmed cell death receptor-1 monoclonal antibodies, such as nivolumab, is largely unpredictable. Sarcopenia was found to be associated with anti-cytotoxic T-lymphocyte-associated protein 4 acute toxicity. We explore the clinical and pharmacological parameters influencing nivolumab toxicity, including body composition.

The tumor inflammation signature (TIS) is associated with anti-PD-1 treatment benefit in the CERTIM pan-cancer cohort.

Background: The 18-gene tumor inflammation signature (TIS) is a clinical research assay that enriches for clinical benefit to immune checkpoint blockade. We evaluated its ability to predict clinical benefit of immunotherapy in cancer patients treated with PD-1 checkpoint inhibitors in routine clinical care.

Methods: The CERTIM cohort is a prospective cohort which includes patients receiving immune checkpoint inhibitors in Cochin University hospital.

Multi-modal tomography to assess dechlorination treatments of iron-based archaeological artifacts.

Chloride ions are an important actor in the corrosion of iron-based archaeological artifact. To stop this degradation, excavated objects are subjected to dechlorination treatment. However, there is no guarantee that this will remove all chloride from the object, as some can be found deep inside the object.

Paleo-inspired Systems: Durability, Sustainability, and Remarkable Properties.

The process of mimicking properties of specific interest (such as mechanical, optical, and structural) observed in ancient and historical systems is designated here as paleo-inspiration. For instance, recovery in archaeology or paleontology identifies materials that are a posteriori extremely resilient to alteration. All the more encouraging is that many ancient materials were synthesized in soft chemical ways, often using low-energy resources and sometimes rudimentary manufacturing equipment.

[Constipation and cancer: Current strategies].

Digestive disorders, in particular constipation, are symptoms very often reported by cancer patients as having a major impact on their quality of life. An accurate diagnosis of bowel delayed transit and defecation disorders is required to best adapt therapeutic management. Constipation associated with cancer may be related to several causes, which can be placed in three nosological categories that sometimes overlap: chronic constipation prior to cancer and having its own evolution; constipation related to the cancer condition, in particular the occlusive syndrome, and constipation induced by cancer therapies.

X-ray Photochemistry of Prussian Blue Cellulosic Materials: Evidence for a Substrate-Mediated Redox Process.

Beside its promising applications in the design of multifunctional materials, batteries and biosensors, the pigment Prussian blue is still studied in heritage science because of its capricious fading behavior due to a complex light-induced redox mechanism. We studied model heritage materials composed of Prussian blue embedded into a cellulosic fiber substrate by means of X-ray absorption near-edge spectroscopy. Significant X-ray radiation damage was observed and characterized.

Application of the Wang-Landau algorithm to the dimerization of glycophorin A.

A two-step Monte Carlo procedure is developed to investigate the dimerization process of the homodimer glycophorin A. In the first step, the energy density of states of the system is estimated by the Wang-Landau algorithm. In the second step, a production run is performed during which various energetical and structural observables are sampled to provide insight into the thermodynamics of the system.

Factors affecting the health-related quality of life of patients with cervical dystonia and the impact of botulinum toxin type A injections.

The purpose of this study was to analyze the health-related quality of life (HRQL) of patients with cervical dystonia (CD) and the impact of botulinum toxin A (BTX-A) therapy in these patients. The authors recruited 101 patients with CD, all previously treated with BTX-A. Both before and 4 weeks after injection of BTX-A the patients were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), a Visual Analogue Scale for pain (VAS: 0-100%), the Short Form 36 health survey questionnaire (SF-36), and the Montgomery-Asberg Depression Rating Scale (MADRS).

Insertion of dipolar molecules in channels of a centrosymmetric organic zeolite: molecular modeling and experimental investigations on diffusion and polarity formation.

The mechanism of insertion of p-nitroaniline (PNA) and its diffusion behavior in channels of the hexagonal host structure of tris(o-phenylenedioxy)cyclotriphosphazene (TPP) was investigated by means of molecular modeling tools. Strong preferential sites in the bulk were found to be due to pi-pi and NH-pi interactions between PNA and channel walls of TPP. MD simulations showed that diffusion can be characterized by jumps from one site to the next, occurring mainly because of the dynamic flexibility of the host structure.

Prediction of solid solution formation in a family of diastereomeric salts. A molecular modeling study.

The possibility of solid solution behavior of diastereomeric salts, containing multiple resolving agents of the same family (Dutch Resolution), is predicted by molecular modeling. Super-cells containing different ratios of resolving agents in the diastereomeric salt are constructed and optimized, and their lattice energy is computed. The energy difference between these "simulated solid solutions" and the native structures is related in an understandable fashion to the probability of solid solution formation.

Simple model designed to generate new crystal structures derived from a mother phase; application to molecular compounds.

The basic principles of a model predicting new lattices from a known crystal structure are described. The first of the two-step procedure consists of extracting one- or two-dimensional periodic fragments (PF) from the mother structure. In the second step, symmetry operators are added to the PFs in order to generate one or several new three-dimensional lattices consistent with the 230 space groups.