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Abstract Background Cancer heterogeneity is a main obstacle for the development of effective therapies, as its replication in in vitro preclinical models is challenging. Around 96% of developed drugs are estimated to fail from discovery to the clinical trial phase probably because of the unsuitability and unreliability of current preclinical models (Front Pharmacol 9:6, 2018; Nat Rev Cancer 8: 147–56, 2008) in replicating the overall biology of tumors, for instance the tumor microenvironment. Breast cancer is the most frequent cancer among women causing the greatest number of cancer-related deaths. Breast cancer can typically be modeled in vitro through the use of tumoroids; however, current approaches using mouse tumoroids fail to reproduce crucial aspect of human breast cancer, while access to human cells is limited and the focus of ethical concerns. New models of breast cancer, such as companion dogs, have emerged given the resemblance of developed spontaneous mammary tumors to human breast cancer in many clinical and molecular aspects; however, they have so far failed to replicate the tumor microenvironment. The present work aimed at developing a robust canine mammary tumor model in the form of tumoroids which recapitulate the tumor diversity and heterogeneity. Results We conducted a complete characterization of canine mammary tumoroids through histologic, molecular, and proteomic analysis, demonstrating their strong similarity to the primary tumor. We demonstrated that these tumoroids can be used as a drug screening model. In fact, we showed that paclitaxel, a human chemotherapeutic, could kill canine tumoroids with the same efficacy as human tumoroids with 0.1 to 1 μM of drug needed to kill 50% of the cells. Due to easy tissue availability, canine tumoroids can be produced at larger scale and cryopreserved to constitute a biobank. We have demonstrated that cryopreserved tumoroids keep the same histologic and molecular features (ER, PR, and HER2 expression) as fresh tumoroids. Furthermore, two cryopreservation techniques were compared from a proteomic point of view which showed that tumoroids made from frozen material allowed to maintain the same molecular diversity as from freshly dissociated tumor. Conclusions These findings revealed that canine mammary tumoroids can be easily generated and may provide an adequate and more reliable preclinical model to investigate tumorigenesis mechanisms and develop new treatments for both veterinary and human medicine.

A rare but severe complication of curative-intent radiation therapy is the induction of second primary cancers. These cancers preferentially develop not inside the planning target volume (PTV) but around, over several centimeters, after a latency period of 1–40 years. We show here that normal human or mouse dermal fibroblasts submitted to the out-of-field dose scattering at the margin of a PTV receiving a mimicked patient’s treatment do not die but enter in a long-lived senescent state resulting from the accumulation of unrepaired DNA single-strand breaks, in the almost absence of double-strand breaks. Importantly, a few of these senescent cells systematically and spontaneously escape from the cell cycle arrest after a while to generate daughter cells harboring mutations and invasive capacities. These findings highlight single-strand break-induced senescence as the mechanism of second primary cancer initiation, with clinically relevant spatiotemporal specificities. Senescence being pharmacologically targetable, they open the avenue for second primary cancer prevention.

Summary: During normal mammary gland development, s-SHIP promoter expression marks a distinct type of mammary stem cells, at two different stages, puberty and early mid-pregnancy. To determine whether s-SHIP is a marker of mammary cancer stem cells (CSCs), we generated bitransgenic mice by crossing the C3(1)-SV40 T-antigen transgenic mouse model of breast cancer, and a transgenic mouse (11.5kb-GFP) expressing green fluorescent protein from the s-SHIP promoter. Here we show that in mammary tumors originating in these bitransgenic mice, s-SHIP promoter expression enriches a rare cell population with CSC activity as demonstrated by sphere-forming assays in vitro and limiting dilution transplantation in vivo. These s-SHIP-positive CSCs are characterized by lower expression of Delta-like non-canonical Notch ligand 1 (DLK1), a negative regulator of the Notch pathway. Inactivation of Dlk1 in s-SHIP-negative tumor cells increases their tumorigenic potential, suggesting a role for DLK1 in mammary cancer stemness. : Bourette and colleagues assess renewal and differentiation potential of s-SHIP-expressing cells in mouse mammary tumors, by in vitro sphere-forming assay and in vivo transplantation. Their data indicate that s-SHIP expression marks a distinct population of mammary cancer stem cells and unveils a potential role of Dlk1, a negative regulator of the Notch pathway, in the regulation of mammary tumor cell stemness. Keywords: breast cancer, CSC, s-SHIP, transgenic mouse, mammary tumor, DLK1, notch, SHIP1

Abstract Background Metastatic melanoma is one of the most aggressive forms of cancer in humans. Among its types, mucosal melanomas represent one of the most highly metastatic and aggressive forms, with a very poor prognosis. Because they are rare in Caucasian individuals, unlike cutaneous melanomas, there has been fewer epidemiological, clinical and genetic evaluation of mucosal melanomas. Moreover, the lack of predictive models fully reproducing the pathogenesis and molecular alterations of mucosal melanoma makes its treatment challenging. Interestingly, dogs are frequently affected by melanomas of the oral cavity that are characterized, as their human counterparts, by focal infiltration, recurrence, and metastasis to regional lymph nodes, lungs and other organs. In dogs, some particular breeds are at high risk, suggesting a specific genetic background and strong genetic drivers. Altogether, the striking homologies in clinical presentation, histopathological features, and overall biology between human and canine mucosal melanomas make dogs invaluable natural models with which to investigate tumor development, including tumor ætiology, and develop tailored treatments. Methods We developed and characterized two canine oral melanoma cell lines from tumors isolated from dog patients with distinct clinical profiles; with and without lung metastases. The cells were characterized using immunohistochemistry, pharmacology and genetic studies. Results We have developed and immunohistochemically, genetically, and pharmacologically characterized. Two cell lines (Ocr_OCMM1X & Ocr_OCMM2X) were produced through mouse xenografts originating from two clinically contrasting melanomas of the oral cavity. Their exhaustive characterization showed two distinct biological and genetic profiles that are potentially linked to the stage of malignancy at the time of diagnosis and sample collection of each melanoma case. These cell lines thus constitute relevant tools with which to perform genetic and drug screening analyses for a better understanding of mucosal melanomas in dogs and humans. Conclusions The aim of this study was to establish and characterize xenograft-derived canine melanoma cell lines with different morphologies, genetic features and pharmacological sensitivities that constitute good predictive models for comparative oncology. These cell lines are relevant tools to advance the use of canine mucosal melanomas as natural models for the benefit of both veterinary and human medicine.

Comparative oncology has shown that naturally occurring canine cancers are of valuable and translatable interest for the understanding of human cancer biology and the characterization of new therapies. This work was part of a comparative oncology project assessing a new, clinical-stage topoisomerase II inhibitor and comparing it with etoposide in dogs with spontaneous lymphoma with the objective to translate findings from dogs to humans. Etoposide is a topoisomerase II inhibitor widely used in various humans' solid and hematopoietic cancer, but little data is available concerning its potential antitumor efficacy in dogs. Etoposide phosphate is a water-soluble prodrug of etoposide which is expected to be better tolerated in dogs. The objectives of this study were to assess the safety, the tolerability and the efficacy of intravenous etoposide phosphate in dogs with multicentric lymphoma. Seven dose levels were evaluated in a traditional 3+3 phase I design. Twenty-seven owned-dogs with high-grade multicentric lymphoma were enrolled and treated with three cycles of etoposide phosphate IV injections every 2 weeks. Adverse effects were graded according to the Veterinary Cooperative Oncology Group criteria. A complete end-staging was realized 45 days after inclusion. The maximal tolerated dose was 300 mg/m2. At this dose level, the overall response rate was 83.3% (n = 6, 3 PR and 2 CR). Only a moderate reversible gastrointestinal toxicity, no severe myelotoxicity and no hypersensitivity reaction were reported at this dose level. Beyond the characterization of etoposide clinical efficacy in dogs, this study underlined the clinical and therapeutic homologies between dog and human lymphomas.

The "mechanistic target of rapamycin" (mTOR) is a central controller of growth, proliferation and/or motility of various cell-types ranging from adipocytes to immune cells, thereby linking metabolism and immunity. mTOR signaling is overactivated in obesity, promoting inflammation and insulin resistance. Therefore, great interest exists in the development of mTOR inhibitors as therapeutic drugs for obesity or diabetes. However, despite a plethora of studies characterizing the metabolic consequences of mTOR inhibition in rodent models, its impact on immune changes associated with the obese condition has never been questioned so far. To address this, we used a mouse model of high-fat diet (HFD)-fed mice with and without pharmacologic mTOR inhibition by rapamycin. Rapamycin was weekly administrated to HFD-fed C57BL/6 mice for 22 weeks. Metabolic effects were determined by glucose and insulin tolerance tests and by indirect calorimetry measures of energy expenditure. Inflammatory response and immune cell populations were characterized in blood, adipose tissue and liver. In parallel, the activities of both mTOR complexes (e. g. mTORC1 and mTORC2) were determined in adipose tissue, muscle and liver. We show that rapamycin-treated mice are leaner, have enhanced energy expenditure and are protected against insulin resistance. These beneficial metabolic effects of rapamycin were associated to significant changes of the inflammatory profiles of both adipose tissue and liver. Importantly, immune cells with regulatory functions such as regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were increased in adipose tissue. These rapamycin-triggered metabolic and immune effects resulted from mTORC1 inhibition whilst mTORC2 activity was intact. Taken together, our results reinforce the notion that controlling immune regulatory cells in metabolic tissues is crucial to maintain a proper metabolic status and, more generally, comfort the need to search for novel pharmacological inhibitors of the mTOR signaling pathway to prevent and/or treat metabolic diseases.

ObjectiveA genomic region near the CDKN2A locus, encoding p16(INK4a), has been associated to type 2 diabetes and atherosclerotic vascular disease, conditions in which inflammation plays an important role. Recently, we found that deficiency of p16(INK4a) results in decreased inflammatory signaling in murine macrophages and that p16(INK4a) influences the phenotype of human adipose tissue macrophages. Therefore, we investigated the influence of immune cell p16(INK4a) on glucose tolerance and atherosclerosis in mice.Methods and resultsBone marrow p16(INK4a)-deficiency in C57Bl6 mice did not influence high fat diet-induced obesity nor plasma glucose and lipid levels. Glucose tolerance tests showed no alterations in high fat diet-induced glucose intolerance. While bone marrow p16(INK4a)-deficiency did not affect the gene expression profile of adipose tissue, hepatic expression of the alternative markers Chi3l3, Mgl2 and IL10 was increased and the induction of pro-inflammatory Nos2 was restrained on the high fat diet. Bone marrow p16(INK4a)-deficiency in low density lipoprotein receptor-deficient mice did not affect western diet-induced atherosclerotic plaque size or morphology. In line, plasma lipid levels remained unaffected and p16(INK4a)-deficient macrophages displayed equal cholesterol uptake and efflux compared to wild type macrophages.ConclusionBone marrow p16(INK4a)-deficiency does not affect plasma lipids, obesity, glucose tolerance or atherosclerosis in mice.

Background Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR). Objective We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)–induced obesity. Methods Obesity was induced by means of HFD feeding, and allergic airway inflammation was subsequently induced by means of intranasal administration of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue inflammation, humoral response, cytokines, and innate and adaptive lymphoid populations were analyzed in the presence or absence of ILCs. Results HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and T H 2 and T H 17 pulmonary profiles. Notably, nonsensitized obese mice already exhibited increased lung ILC counts and tissue eosinophil infiltration compared with values in lean mice in the absence of AHR. The numbers of total and cytokine-expressing lung ILC2s and ILC3s further increased in HDM-challenged obese mice compared with those in HDM-challenged lean mice, and this was accompanied by high IL-33 and IL-1β levels and decreased ILC markers in visceral adipose tissue. Furthermore, depletion of ILCs with an anti-CD90 antibody, followed by T-cell reconstitution, led to a profound decrease in allergic airway inflammatory features in obese mice, including T H 2 and T H 17 infiltration. Conclusion These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s. [ABSTRACT FROM AUTHOR]

Background Remodeling of quiescent vessels with increases in permeability, vasodilatation, and edema are hallmarks of inflammatory disorders. Factors involved in this type of remodeling represent potential therapeutic targets. Objectives We investigated whether the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) β/δ, a regulator of metabolism, fibrosis, and skin homeostasis, is involved in regulation of this type of remodeling. Methods Wild-type and various Pparb/d mutant mice were used to monitor dermal acute vascular hyperpermeability (AVH) and passive systemic anaphylaxis–induced hypothermia and edema. PPARβ/δ-dependent kinase activation and remodeling of endothelial cell-cell junctions were addressed by using human endothelial cells. Results AVH and dilatation of dermal microvessels stimulated by vascular endothelial growth factor A, histamine, and thrombin are severely compromised in PPARβ/δ-deficient mice. Selective deletion of the Pparb/d -encoding gene in endothelial cells in vivo similarly limits dermal AVH and vasodilatation, providing evidence that endothelial PPARβ/δ is the major player in regulating acute dermal microvessel remodeling. Furthermore, endothelial PPARβ/δ regulatory functions are not restricted to the skin vasculature because its deletion in the endothelium, but not in smooth muscle cells, also leads to reduced systemic anaphylaxis, the most severe form of allergic reaction, in which an acute vascular response plays a key role. PPARβ/δ-dependent AVH activation likely involves the activation of mitogen-activated protein kinase and Akt pathways and leads to downstream destabilization of endothelial cell-cell junctions. Conclusion These results unveil not only a novel function of PPARβ/δ as a direct regulator of acute vessel permeability and dilatation but also provide evidence that antagonizing PPARβ/δ represents an important strategy to consider for moderating diseases with altered endothelial integrity, such as acute inflammatory and allergic disorders. [ABSTRACT FROM AUTHOR]

Introduction: Le diabète de type 2 (T2D) est un trouble métabolique de l’homéostasie du glucose. Il est caractérisé par une hyperglycémie chronique qui résulte en partie d’une production excessive de glucose par le foie conséquence au développement d’une résistance à l’insuline. Le T2D est une pathologie multifactorielle à la fois génétique et environnementale. Récemment des études d’associations de gènes (GWAS) dans différentes cohortes ont mis en évidence une forte corrélation entre le locus CDKN2A et le risque de développement du T2D en se basant sur certains paramètres métaboliques tel que la glycémie à jeun. Le locus CDKN2A code pour des protéines régulatrices du cycle cellulaire dont la protéine p16INK4a. p16INK4a est largement décrite dans la littérature pour son rôle suppresseur de tumeurs et comme marqueur de sénescence, cependant son rôle dans le contrôle de l’homéostasie hépatique du glucose n’a jamais été rapporté Matériels et méthodes: Afin de déterminer le rôle de p16INK4a dans le métabolisme hépatique du glucose, nous avons utilisé in vivo des souris sauvages (p16+/+) et déficientes pour p16INK4a (p16-/-) et in vitro des hépatocytes primaires ainsi que la lignée AML12. Résultats: Nous avons montré qu’après un jeune, les souris p16-/- présentent une hypoglycémie moins prononcée qui se traduit par une expression hépatique plus élevée de gènes de la néoglucogenèse tels que PEPCK, G6Pase et PGC1a. De plus, les hépatocytes primaires de souris p16-/- présentent une meilleur réponse au glucagon que ceux des p16+/+. Enfin, nous avons montré que la diminution d’expression de p16INK4a par siRNA dans les AML12 suffit à induire l’expression des gènes de la néoglucogenèse et potentialise la réponse de ces cellules à différents stimuli gluconéogenique. L’effet observé dépend de l’activation de la voie PKA-CREB-PGC1A. Conclusion: L’ensemble de ces données montrent pour la première fois que p16INK4a pourrait jouer un rôle un cours du développement du T2D. [Copyright &y& Elsevier]

Objectif: L’obésité est caractérisée par l’expansion excessive du tissu adipeux blanc associée à une inflammation chronique à ű bas bruit Ƈ initiée par le recrutement de cellules immunes dans le tissu. L’adipogenèse et la fonction des cellules immunes sont régulés par la voie du ű mechanistic Target Of Rapamycin Ƈ (mTOR). La voie mTOR est sur-activée lors de l’obésité, participant au développement de la résistance à l’insuline et du diabète de type 2. Ainsi la rapamycine, inhibiteur sélectif de la voie mTOR, est proposée comme une nouvelle piste thérapeutique dans le traitement des maladies métaboliques. Notre objectif est de préciser les effets métaboliques de la rapamycine et de définir s’ils sont associés à des altérations immunes et/ou inflammatoires. Matériels et méthodes: Des souris mâles C57BL/6J mises sous régime hyperlipidique reçoivent des injections hebdomadaires de rapamycine ou d’excipient. Les paramètres métaboliques et immuns sont suivis par l’utilisation de techniques de biologie moléculaire (Q-PCR, transcriptomique), biochimie (ELISAs, western-blot), cytométrie en flux et histologie. Résultats: Bien que limitant la prise de poids corporel, la rapamycine aggrave l’intolérance au glucose. Le recrutement massif de macrophages dans le tissu adipeux ainsi que la production accrue de cytokines inflammatoires (IL-6, MCP-1) chez les souris traitées pourraient expliquer l’effet délétère de la drogue sur l’homéostasie glucidique. Par ailleurs, l’augmentation du nombre des cellules immuno-régulatrices Gr1+CD11b+ (Myeloïd-derived suppressor cells ou MDSC) dans le tissu adipeux, pourrait expliquer le maintien de la sensibilité à l’insuline des souris traitées ; les MDSCs ayant récemment été décrites comme modérant l’inflammation et, conséquemment, améliorant la sensibilité à l’insuline de souris obèses. Conclusion: Notre étude suggère que l’effet paradoxal de la rapamycine sur le métabolisme énergétique pourrait résulter d’un contrôle exercé par la voie mTOR sur les cellules myéloïdes régulant l’inflammation du tissu adipeux blanc (macrophages et MDSCs). [ABSTRACT FROM AUTHOR]

Introduction: L’obésité est associée à un état inflammatoire chronique de « bas grade » dans lequel le tissu adipeux blanc joue un rôle clé. En effet, les cellules immunes recrutées dans le tissu - principalement les macrophages - entretiennent le foyer inflammatoire, augmentant le risque de pathologies liées au surpoids, telle que l’insulinorésistance. La voie du mammalian target of rapamycin (mTOR) est sur-activée lors de l’obésité et est impliquée dans le développement de la résistance à l’insuline et du diabète de type 2. La rapamycine, drogue immunomodulatrice inhibant sélectivement la voie mTOR, représente donc une nouvelle piste thérapeutique dans le traitement des maladies métaboliques. Notre objectif est de définir si les effets métaboliques de la rapamycine sont associés à des altérations immunes et/ou inflammatoires. Matériels et méthodes: Des souris mâles C57BL6/J sous régime standard ou hyperlipidique ont reçus des injections hebdomadaires de rapamycine (2mg/kg, i.p.) ou d’excipient. L’évolution du poids corporel, de la prise alimentaire ainsi que la tolérance au glucose in vivo ont été déterminées. Les hormones et cytokines sériques ont été dosées par ELISA et Multiplex Arrays. La taille des adipocytes, le recrutement cellulaire et l’état inflammatoire du tissu adipeux ont été analysés par histologie, puces à ADN et PCR quantitative. Les cellules immunes du sang et de la rate ont été caractérisées par cytométrie en flux. Résultats: La rapamycine limite le gain de poids corporel tout en, paradoxalement, aggravant l’intolérance au glucose. Le recrutement cellulaire massif dans le tissu adipeux blanc (principalement les macrophages), ainsi que la production accrue de cytokines inflammatoires (notamment IL-6 et MCP-1) chez les souris traitées par la rapamycine pourraient expliquer l’effet de la drogue sur l’homéostasie glucidique. Conclusion: Cette étude montre que la rapamycine régule le métabolisme énergétique par un relai immun, impliquant notamment les macrophages du tissu adipeux blanc [Copyright &y& Elsevier]

Aim: The oral anti-angiogenic therapy nintedanib prolongs progression-free survival (PFS) when combined with chemotherapy after primary surgery for advanced epithelial ovarian cancer. The randomized phase II CHIVA trial evaluated the impact of combining nintedanib with neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer., Methods: Patients with newly diagnosed unresectable FIGO stage IIIC-IV epithelial ovarian cancer received 3-4 cycles of carboplatin plus paclitaxel every 3 weeks as NACT before interval debulking surgery (IDS), followed by 2-3 post-operative cycles. Patients were randomized 2:1 to receive either nintedanib 200 mg twice daily or placebo on days 2-21 every 3 weeks during NACT (omitting peri-operative cycles), and then as maintenance therapy for up to 2 years. The primary endpoint was PFS., Results: Between January 2013 and May 2015, 188 patients were randomized (124 to nintedanib, 64 to placebo). PFS was significantly inferior with nintedanib (median 14.4 versus 16.8 months with placebo; hazard ratio 1.50, p = 0.02). Overall survival (OS) was also inferior (median 37.7 versus 44.1 months, respectively; hazard ratio 1.54, p = 0.054). Nintedanib was associated with increased toxicity (grade 3/4 adverse events: 92% versus 69%, predominantly hematologic and gastrointestinal), lower response rate by RECIST (35% versus 56% before IDS), and lower IDS feasibility (58% versus 77%) versus placebo., Conclusions: Adding nintedanib to chemotherapy and in maintenance as part of NACT for advanced epithelial ovarian cancer cannot be recommended as it increases toxicity and compromises chemotherapy efficacy (IDS, PFS, OS)., Clinicaltrials: govregistration: NCT01583322., Competing Interests: Declaration of Competing Interest Gwénaël Ferron: Advisory boards (Clovis, AstraZeneca, GSK, MSD, Roche, RanD Biotech, Olympus), lectures/symposia (AstraZeneca, Clovis, GSK, MSD, PharmaMar). Nicolas Delanoy: Advisory boards/honoraria (GSK, AstraZeneca, MSD, Clovis Oncology). Florence Joly: Advisory boards (Clovis, AstraZeneca, GSK, MSD, Seagen), lectures/symposia (AstraZeneca, Clovis, GSK, MSD); non-gynecology: Ipsen, Janssen, Sanofi, Bayer, Astellas, Pfizer, Amgen. Alain Lortholary: Advisory board fees (AstraZeneca, MSD Tesaro), speaker honoraria (Clovis Oncology, Roche), congress participation (Novartis, Pfizer, MSD, Lilly, Roche), member of CS3 sein UNICANCER. Benoît You: Consulting (MSD, AstraZeneca, GSK–Tesaro, Bayer, Roche/Genentech, ECS Progastrin, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, Seagen, Myriad). Nadine Dohollou: Consulting/expert (Daiichi, Lilly, Roche, Seagen), conferences/training (Daiichi, Lilly, Roche, Seagen), research grants/clinical trials (AstraZeneca, BMS, Boehringer Ingelheim, Genomic Health, Lilly, MSD, Novartis, Pfizer, Roche). Anne Floquet: Advisory boards (MSD, AstraZeneca, GSK, Clovis Oncology), congress participation (AstraZeneca, GSK, MSD, PharmaMar, Roche). Michel Fabbro: AstraZeneca, GSK, Clovis. Jérôme Alexandre: AstraZeneca, GSK, Clovis, MSD, Eisai, Novartis. Isabelle Ray-Coquard: Advisory/consultancy (Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Mersana, Deciphera, Novocure, Eisai, Sutro Pharma, Merck Sharp & Dohme, Pfizer/Merck Serono, PharmaMar, Roche), research grant/funding (Roche, BMS, MSD, GSK), travel/accommodation/expenses (AstraZeneca, Roche, GSK, Clovis)., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Management of elderly patients with cancer is challenging worldwide. Improvement of their care pathway should focus on unplanned hospitalizations. This study aimed to compare the geriatric and oncologic profiles of elderly patients with cancer, hospitalized for an acute pathology either in medical oncology or acute geriatric medicine units., Methods: Epidemiological, analytical, monocentric, transversal study performed in the geriatric and oncological short-stay units of the university hospital of Poitiers (France) from 07/01/2014 to 06/30/2015. Only patients with diagnosed cancer prior to hospitalization were included. The geriatric, oncological and hospitalization data were collected and analyzed., Results: In total, 230 patients were included (156 in geriatrics, 74 in oncology). Alteration of the general condition was the most frequent reason for admission. In multivariate age-adjusted analyses, factors associated with admission to a geriatric unit were co-morbidities (OR=0.18 [95% CI: 0.07-0.46], P<0.01) and dependence (OR=0.07 [95% CI: 0.01-0.36], P<0.01). Ongoing antineoplastic treatment (OR=2.60 [95%CI: 1.14-5.89], P=0.02) and metastatic cancer (OR=2.63 [95%CI: 1.18-5.86], P=0.02) influenced hospitalization in the oncology unit. During the hospital stay there was more frequent psychological support in oncology (OR=45.59 [95%CI: 9.79-212.23], P<0.01) and social support in Geriatrics (OR=0.13 [95% CI: 0.04-0.40], P<0.01)., Conclusion: This first comparative study showed a significant difference in profiles of elderly patients with cancer hospitalized for an acute problem, depending on the hospital unit. This finding paves the way of improvement of care pathway by formalizing links between these two departments to optimize care and referrals to the most appropriate care unit, according to patients condition, in case of unscheduled hospitalization., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

This study aimed to determine cancer prevalence occurring after the age of 75 in 45 French nursing homes (NH), as well as residents' characteristics and parameters associated with cancer-specific management. Descriptive retrospective study including 214 residents (mean age, 89.7 years) with cancer diagnosed after age 75. The studied parameters were sociodemographic, functional, nutritional and cognitive data; comorbidity assessment; date of tumoral diagnosis; cancer type; tumoral stage; treatment plan; multidisciplinary staff decision and oncologic follow-up. Our results showed that cancer prevalence in NH was 8.4 ± 1.1%, diagnosed before admission in 63% of cases. The most common tumoral sites were skin (26%), digestive tract and breast (18% for both); 12% had metastasis. Cognitive impairment was the most common comorbidity (42%), and 44% of the residents were highly dependent. Multivariate analysis showed that therapeutic decisions were associated with age. Older patients had less staging exploration (odd ratios [ORs], 0.90, 95% confidence interval [CI], 0.85-0.97) and underwent less cancer-specific treatment (ORs, 0.92; 95%CI, 0.86-0.99). Oncologic follow-up was more frequent in younger patients (ORs, 0.90; 95%CI, 0.81-0.99) and those with recent diagnosis (ORs, 0.37; 95%CI, 0.23-0.61). This study identified factors associated with substandard neoplastic management in elderly NH residents. It highlights needs for information, education and training in cancer detection to improve cancer consideration and care in NH., (© 2018 John Wiley & Sons Ltd.)

Objectives: The International Prostate Score Symptom (IPSS) and the question of quality of life (QOL-Q) associated were used in this study for monitoring patients treated for localized prostate cancer (P-Ca)., Patients and Methods: Three groups treated with radical prostatectomy (RP), external beam radiotherapy (RT) or brachytherapy (BRACHY) completed the self-administered questionnaire IPSS and Q-QOL before treatment (bef-TT), after 3 months and once a year for 5 years., Results: The study included 40 PR, 40 RT and 40 BRACHY. There was no difference between the three groups in bef-TT for the IPSS and Q-QOL or in the patients' characteristics, and P-Ca except for age and a higher PSA in the RT group (70.6 years old and 10.0 ng/mL vs. 66.5/66.2 and 7.1/6.2 for RP and CURIE respectively). The impact, no matter what treatment they received, was significant after the third month and then went back to the pre-AN1 at TT. The analysis by group treatment showed no significant difference between groups at 3months and during the first 4 years of follow-up. In the fifth year the RT group had a greater IPSS than BRACHY and PR groups (P<0.04)., Conclusion: This study showed no degradation of the IPSS or Q-QOL remote treatment of localized prostate cancer. Urinary incontinence has been partially exploring. His study would have allowed a better urinary quality of life analysis in these patients., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Purpose: Double-strand breaks, the most lethal DNA lesions induced by ionizing radiation, are mainly repaired by the nonhomologous end-joining system. The expression of the nonhomologous end-joining pathway has never been studied in prostate cancer, and its prognostic value for patients undergoing radiotherapy remains unknown., Methods: Pretreatment biopsies from 238 patients treated with exclusive external beam radiotherapy for localized prostate cancer with ≥ 2 years of follow-up were reviewed to reassess the Gleason score. Of these 238 cases, 179 were suitable for in situ analysis and were included in the tissue microarrays. Expression of the nonhomologous end-joining proteins Ku70, Ku80, DNA-dependent protein kinase, catalytic subunits (DNA-PKcs), and X-ray repair cross complementing 4-like factor was studied by immunohistochemistry, together with the proliferation marker Ki67., Results: The predictive value of the Gleason score for biochemical relapse (using the Phoenix criteria) was markedly improved after review (P<.0001) compared with the initial score (P=.003). The clinical stage, pretreatment prostate-specific antigen level, and perineural invasion status were also associated with progression-free survival (P=.005, P<.0001, and P=.03, respectively). High proliferation (>4%) tends to be associated with biochemical recurrence; however, the difference did not reach statistical significance (P=.06). Although the expression of Ku70, Ku80, and X-ray repair cross complementing 4-like factor was not predictive of relapse, positive DNA-PKcs nuclear staining was closely associated with biochemical recurrence (P=.0002). On multivariate analysis, only the Gleason score, prostate-specific antigen level, and DNA-PKcs status remained predictive of recurrence (P=.003, P=.002, and P=.01, respectively)., Conclusions: The results of the present study highly suggest that DNA-PKcs could be a predictive marker of recurrence after radiotherapy, independently of the classic prognostic markers, including the Gleason score modified after review., (Copyright © 2012 Elsevier Inc. All rights reserved.)