Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6Chi monocytes and differentiation to pro-angiogenic myeloid cells

Cancer and cardiovascular disease (CVD) share common risk factors such as dyslipidemia, obesity and inflammation. However, the role of pro-atherogenic environment and its associated low-grade inflammation in tumor progression remains underexplored. Here we show that feeding C57BL/6J mice with a non-obesogenic high fat high cholesterol diet (HFHCD) for two weeks to induce mild dyslipidemia, increases the pool of circulating Ly6Chi monocytes available for initial melanoma development, in an IL-1β-dependent manner. Descendants of circulating myeloid cells, which accumulate in the tumor microenvironment of mice under HFHCD, heighten pro-angiogenic and immunosuppressive activities locally. Limiting myeloid cell accumulation or targeting VEGF-A production by myeloid cells decrease HFHCD-induced tumor growth acceleration. Reverting the HFHCD to a chow diet at the time of tumor implantation protects against tumor growth. Together, these data shed light on cross-disease communication between cardiovascular pathologies and cancer

SARCOME PRIMITIF DU MYOCARDE (PARTICULARITES DIAGNOSTIQUES, ICONOGRAPHIQUES, EVOLUTIVES ET THERAPEUTIQUES : A PROPOS D'UNE OBSERVATION ET D'UNE REVUE DE LA LITTERATURE)

BESANCON-BU Médecine pharmacie (250562102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Chemotherapy treatment induces an increase of autophagy in the luminal breast cancer cell MCF7, but not in the triple-negative MDA-MB231

International audienceAutophagy is one of the chemotherapy resistance mechanisms in breast cancer. The aim of this study was to determine the level of recruitment of the autophagy pathway in the triple-negative breast cancer (TNBC) cell line MDA-MB231 compared with that in the control luminal breast cancer cell line MCF7 before and after treatment with chemotherapy drugs. Furthermore, we investigated the relationship between autophagy and EGFR, MUC1 and IL17-receptors as activators of autophagy. Immunohistochemistry was performed in cell culture blocks using LC3b, MUC1-C, EGFR, IL17A, IL17-RA and IL17-RB antibodies. We found that the basal autophagy level in MDA-MB231 was high, whereas it was low in MCF7. However, in contrast to MDA-MB231, the autophagy level was increased in MCF7 upon treatment with chemotherapy agents. Interestingly, we observed that the expression levels of MUC1-C, EGFR, IL17-RA, and IL17-RB were not modified by the same treatments. Furthermore, the chemotherapy treatments did not increase autophagy in TNBC cells without affecting the expression levels of MUC1-C, EGFR, IL17-RA or IL17-RB

The Interleukin-17 Family of Cytokines in Breast Cancer

International audienceBreast cancer (BC) is the most common cancer in women worldwide and remains a major cause of mortality with an expected 137,000 death this year in Europe. Standard management of metastatic BC comprises hormonotherapy, chemotherapy, and targeted therapies. Cyclin dependent kinase (CDK) and mammalian target of rapamycin (mTOR) inhibitors have recently proved their efficiency in hormonal receptor expressing BC. Checkpoint proteins inhibition is being evaluated in phase 3 studies. Since inflammation is constantly present in cancers, research teams have focused their attention on the interleukin-17 (IL-17) family of proinflammatory cytokines. Preclinical experiments have reported both pro and antitumor effects depending on the conditions. In the present article, we review the accumulating evidences about the roles of IL-17 in BC and discuss whether this family of cytokines could be a new target in anticancer treatments

Evaluation de la Chimiothérapie Hyperthermique Intra Péritonéale (CHIP) dans le cancer de l'ovaire

Le risque de développement locorégional des cancers de l'ovaire sous la forme de carcinose péritonéale a conduit au développement de chirurgies de cytoréduction optimale, complétées par une chimiothérapie intrapéritonéale avec hyperthermie (CHIP). L'objectif principal de cette étude est d'évaluer la faisabilité et l'acceptabilité de cette technique. Matériel et méthode : Cette étude rétrospective monocentrique a évalué 43 procédures de CHIP entre 1995 et 2009. Toutes les patientes ont eu une cytoréduction chirurgicale complète, associée à une CHIP avec du Cisplatine. Les complications ont été répertoriées. La survie globale a été mesurée, et des facteurs pronostics ont été recherchés. Résultats : Les complications post opératoires se sont composées d'un décès par choc septique (2.32%) et de six complications majeures (13.95%). Les médianes de survie globale et sans progression sont respectivement de 53.6 et 39 mois. Les patientes ayant bénéficié d'une cytoréduction initiale complète de la carcinose péritonéale ont des survies globales de 131 mois, contre 84 mois en l'absence de résection complète (p<0.0001). Conclusion : La cytoréduction chirurgicale combinée à la CHIP est une procédure réalisable en pratique avec des taux de morbi-mortalité acceptable. Le facteur résection initiale complète de la carcinose augmenterait de manière significative la survieST ETIENNE-BU Médecine (422182102) / SudocSudocFranceF

Léiomyosarcomes utérins (particularités diagnostiques et prise en charge thérapeutique à propos de 20 cas)

ST ETIENNE-BU Médecine (422182102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Facteurs pronostiques de survie des cancers bronchiques non a petites cellules de stades IIIb pleural et IV traitées par chimiothérapie

ST ETIENNE-BU Médecine (422182102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

From Randomised Clinical Trials to Clinical Practice: A Pragmatic Cost-Effectiveness Analysis of Paclitaxel in First-Line Therapy for Advanced Ovarian Cancer

Introduction: Paclitaxel plus cisplatin is considered to be the standard first-line therapy for advanced ovarian cancer. Previous to this study, economic data on this combination resulted from randomised clinical trials (RCTs). Therefore, the objective of this study was to compare the clinical and economic outcomes associated with paclitaxel-cisplatin (PC) and cyclophosphamide-cisplatin (CC) regimens using a pragmatic perspective based on daily clinical practice in a French university hospital. Method: A retrospective cost-effectiveness analysis, from the hospital-payer perspective, was carried out as a before-after case study in fifty-nine consecutive women with verified International Federation of Gynaecology and Obstetrics (FIGO) stage II, III or IV ovarian cancer treated between 1995 and 2000. Median overall survival (OS) was used as the primary endpoint. The quality-adjusted time was assessed by the quality-adjusted time without symptoms or toxicity (Q-TWiST) method. Direct medical costs were collected for each patient. Monetary values for French prices in the year 2000 were used and converted to US dollars using an exchange rate of $US1 = 7 French francs. Several univariate sensitivity analyses were carried out varying unit costs, medical practices and administration of paclitaxel. Results: The incremental cost of the PC regimen was$US10 Conclusion: Our study suggests that PC may be a cost-effective regimen for advanced ovarian cancer in a French university hospital setting. We reported higher incremental costs and lower clinical benefits than RCT-based findings, suggesting that RCT-based findings were clearly balanced by our pragmatic approach based on clinical practices. Observational studies can provide complementary and balanced data for decision making.Alkylating-agents, Cisplatin, Cost-effectiveness, Cost-utility, Cyclophosphamide, Ovarian-cancer, Paclitaxel, Taxanes, Platinum-complexes

Autophagy is decreased in triple-negative breast carcinoma involving likely the MUC1-EGFR-NEU1 signalling pathway.

International audienceTriple-negative breast carcinoma (TN) is a heterogeneous cancer type expressing EGFR in 75% of cases. MUC1 is a large type I sialylated glycoprotein comprising two subunits (α and β chains, also called respectively MUC1-VNTR and MUC1-CT), which was found to regulate EGFR activity through endocytic internalisation. Endocytosis and autophagy use the lysosome pathway involving NEU1. Recently, a molecular EGFR-MUC1-NEU1 complex was suggested to play a role in EGFR pathway. In the aim to understand the relationship between EGFR-MUC1-NEU1 complex and autophagy in breast carcinoma, we compared triple negative (TN) showing a high-EGFR expression with luminal (LUM) presenting low-EGFR level. We studied the expression of MUC1-VNTR, MUC1-CT and NEU1 in comparison with those of two molecular actors of autophagy, PI3K (p110β) and Beclin1. A total of 87 breast cancers were split in two groups following the immunohistochemical classification of breast carcinoma: 48 TN and 39 LUM. Our results showed that TN presented a high expression of EGFR and a low expression of MUC1-VNTR, MUC1-CT, NEU1, Beclin-1 and PI3Kp110β. Moreover, in TN, a positive statistical correlation was observed between Beclin-1 or PI3Kp110β and MUC1-VNTR or NEU1, but not with EGFR. In conclusion, our data suggest that autophagy is reduced in TN leading likely to the deregulation of EGFR-MUC1-NEU1 complex and its associated cellular pathways

Autophagy is decreased in triple-negative breast carcinoma involving likely the MUC1-EGFR-NEU1 signalling pathway.

International audienceTriple-negative breast carcinoma (TN) is a heterogeneous cancer type expressing EGFR in 75% of cases. MUC1 is a large type I sialylated glycoprotein comprising two subunits (α and β chains, also called respectively MUC1-VNTR and MUC1-CT), which was found to regulate EGFR activity through endocytic internalisation. Endocytosis and autophagy use the lysosome pathway involving NEU1. Recently, a molecular EGFR-MUC1-NEU1 complex was suggested to play a role in EGFR pathway. In the aim to understand the relationship between EGFR-MUC1-NEU1 complex and autophagy in breast carcinoma, we compared triple negative (TN) showing a high-EGFR expression with luminal (LUM) presenting low-EGFR level. We studied the expression of MUC1-VNTR, MUC1-CT and NEU1 in comparison with those of two molecular actors of autophagy, PI3K (p110β) and Beclin1. A total of 87 breast cancers were split in two groups following the immunohistochemical classification of breast carcinoma: 48 TN and 39 LUM. Our results showed that TN presented a high expression of EGFR and a low expression of MUC1-VNTR, MUC1-CT, NEU1, Beclin-1 and PI3Kp110β. Moreover, in TN, a positive statistical correlation was observed between Beclin-1 or PI3Kp110β and MUC1-VNTR or NEU1, but not with EGFR. In conclusion, our data suggest that autophagy is reduced in TN leading likely to the deregulation of EGFR-MUC1-NEU1 complex and its associated cellular pathways