NF-kappa B genes have a major role in Inflammatory Breast Cancer

<p>Abstract</p> <p>Background</p> <p>IBC (Inflammatory Breast cancer) is a rare form of breast cancer with a particular phenotype. New molecular targets are needed to improve the treatment of this rapidly fatal disease. Given the role of NF-κB-related genes in cell proliferation, invasiveness, angiogenesis and inflammation, we postulated that they might be deregulated in IBC.</p> <p>Methods</p> <p>We measured the mRNA expression levels of 60 NF-κB-related genes by using real-time quantitative RT-PCR in a well-defined series of 35 IBCs, by comparison with 22 stage IIB and III non inflammatory breast cancers. Twenty-four distant metastases of breast cancer served as "poor prognosis" breast tumor controls.</p> <p>Results</p> <p>Thirty-five (58%) of the 60 NF-κB-related genes were significantly upregulated in IBC compared with non IBC. The upregulated genes were NF-κB genes (<it>NFKB1</it>, <it>RELA</it>, <it>IKBKG</it>, <it>NFKBIB</it>, <it>NFKB2</it>, <it>REL</it>, <it>CHUK</it>), apoptosis genes (<it>MCL1L</it>, <it>TNFAIP3/A20</it>, <it>GADD45B</it>, <it>FASLG</it>, <it>MCL1S</it>, <it>IER3L</it>, <it>TNFRSF10B/TRAILR2</it>), immune response genes (<it>CD40</it>, <it>CD48</it>, <it>TNFSF11/RANKL</it>, <it>TNFRSF11A/RANK</it>, <it>CCL2/MCP-1</it>, <it>CD40LG</it>, <it>IL15</it>, <it>GBP1</it>), proliferation genes (<it>CCND2</it>, <it>CCND3</it>, <it>CSF1R</it>, <it>CSF1</it>, <it>SOD2</it>), tumor-promoting genes (<it>CXCL12</it>, <it>SELE</it>, <it>TNC</it>, <it>VCAM1</it>, <it>ICAM1</it>, <it>PLAU/UPA</it>) or angiogenesis genes (<it>PTGS2/COX2</it>, <it>CXCL1/GRO1</it>). Only two of these 35 genes (<it>PTGS2/COX2 </it>and <it>CXCL1/GRO1</it>)were also upregulated in breast cancer metastases. We identified a five-gene molecular signature that matched patient outcomes, consisting of <it>IL8 </it>and <it>VEGF </it>plus three NF-κB-unrelated genes that we had previously identified as prognostic markers in the same series of IBC.</p> <p>Conclusion</p> <p>The NF-κB pathway appears to play a major role in IBC, possibly contributing to the unusual phenotype and aggressiveness of this form of breast cancer. Some upregulated NF-κB-related genes might serve as novel therapeutic targets in IBC.</p

Quelques problèmes combinatoires et leur implémentation

BOURGES-ENS Ingénieurs (180332301) / SudocPARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

CORRELATIONS HISTO-RADIOLOGIQUES DES MICROCALCIFICATIONS DANS LES LESIONS INFRACLINIQUES DU SEIN

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

The Development and Evaluation of a Large-Scale Self-Referral CBT-I Intervention for Men Who Have Insomnia: An Exploratory Study

Background: Whilst effective psychological treatments such as CBT-I have been developed for insomnia, few services provide CBT-I and awareness of CBT-I is low among referrers. In addition, men tend to seek help less frequently for their insomnia than women. This paper describes the development and evaluation of psycho-educational CBT-I workshops, each for up to 25 people, and designed to be acceptable to men. Method: The CBT-I programme was based on Morin and Espie (2003), and adapted into a self-referral one-day workshop format designed specifically to improve access. Workshops were held on Saturdays in leisure centres. A one group pretest-posttest design was used and assessments were collected before and 6 weeks after each workshop. Over a 6-month period, 74 men self-referred, and attended the Introductory Talks preceding the workshops. Of these, 49.3% had never sought help from their GP, 66.2% suffered from clinical insomnia (ISI) and 61.6% were experiencing elevated depression symptoms (BDI over 10). Results: At follow-up, the workshops were found to be effective in reducing insomnia and depression. Satisfaction ratings with the workshops were very high. Conclusions: Given these promising results, further work is now proposed for a larger controlled study with a longer-term follow-up

Méthotrexate intrathécal dans les méningites carcinomateuses du cancer du sein – Expérience avec le protocole utilisé à l’hôpital Saint-Louis

International audienceMethotrexate represents the standard intrathecal treatment of breast cancer meningeal carcinomatosis. However, its optimal schedule remains undefined. The aim of the present study was to evaluate results obtained with the methotrexate schedule used in Saint-Louis hospital (Paris). Patients followed in Saint-Louis hospital for breast cancer and who received intrathecal methotrexate were included in this retrospective monocentric study. Intrathecal treatment received contained methotrexate 12 mg/day (days: 1-5) and then 15 mg/week until progression or toxicity. Between 2003 and 2015, 41 patients were included. Primitive tumours were RH+/HER2-, HER2+ and triple-negative in respectively 66%, 14%, 5% and 15% of patients, 22% of them had meningeal carcinomatosis as metastatic disease initial manifestation. Objective response rate was 54%, median overall survival was 4.0 mois [CI 95%: 3-7.3] and 1-year survival rate was 15.2% (11.4%, 50% et 0% in RH+/HER2-, HER2+ and triple-negative subgroups; HR=0.45 [0.21-0.97] between HER2+ and RH+/HER2-). In univariate analysis, prognostic factors were brain involvement (p=0.049), initial cerebrospinal fluid protein level (p=0.0002) and concomitant systemic treatment received (p=0.049). This intrathecal methotrexate schedule demonstrates a similar median overall survival as the one obtained with a dose-dense schedule and an improved quality of life. Nevertheless, as the objective response and 1-year survival rates are slightly inferior, a dose-dense schedule remains still preferred in HER2+ patients or in those harboring a mainly meningeal progression