Preliminary results on a proposed histopathological assessment of predictive factors for basal cell carcinoma recurrence after primary free margin excision.

Background: Basal cell carcinoma (BCC) incidence is steadily increasing but therapeutic solutions remain limited and present a public health challenge. Aims: To identify predictive factors of BCC recurrence after primary free margin excision, with automated methods, by evaluating cell proliferation, the Hedgehog pathway activation and primary cilia. Materials and Methods: This case-control study included 32 patients (16 with recurrence occurring at least 6 months after complete resection, and 16 without recurrence) who underwent surgery for BCC. Formalin-fixed paraffin-embedded cutaneous resections were processed for immunohistochemistry or immunostaining with the following primary antibodies: mouse anti-MCM6, rabbit anti-ARL13B and rabbit anti-GLI1. Results: BCC recurrence after free margin excision was significantly linked to a higher proliferative index (p < 0.001) and a lower cilia count (p = 0.041) in the primary lesion. No significant differences were observed regarding cilia length (p = 0.39) or GLI1-positive nuclei. Discussion: The complex interplay between essential signaling pathways, cell proliferation and cilia requires further experimental investigations in the context of BCC recurrence. Conclusion: A higher proliferative index evaluated with MCM6 antibody could be a useful prognosis marker of BCC risk of recurrence. The lower cilia count in the primary lesion unveiled novel perspectives to understand BCC recurrence molecular mechanisms.

[Treatment of GERD in asthma]. / Traitement du reflux gastro-œsophagien dans l'asthme.

Gastro-oesophageal reflux disease (GORD) is one of the most frequent conditions associated with asthma. GORD has an impact on asthma control and quality of life of asthmatic patients. Its treatment relies on lifestyle modifications, anti-acidic treatment with proton pump inhibitors (PPI) and/or surgical management by fundoplication in some situations. The impact of lifestyle modifications has not been analysed on asthma outcomes alone. Several randomised controlled trials assessed the efficacy of PPI on asthma control, peak expiratory flow and/or quality of life. The impact of fundoplication in asthma has mainly been analysed in retrospective or prospective observational studies. This review highlights the limited impact of GORD treatment on asthma control. Current guidelines are to restrict GORD treatment in asthma to asthmatic patients with actual symptomatic GORD. Given the lack of controlled studies, the place of surgical management of GORD in asthma is currently not defined.

[Obesity and asthma: Mechanisms and therapeutic options]. / Asthme et obésité : mécanismes et pistes thérapeutiques.

Asthma and obesity are both common conditions, which lead to a substantial public health burden. The obese-asthma phenotype is characterized by poor asthma control, impaired lung function and decreased efficacy of inhaled treatment. However, this phenotype is highly heterogeneous and involves numerous mechanisms, including systemic inflammation and adipokines. A role for microbiota modifications and genetics has been suggested. Obese-asthma patient management currently consists in weight loss and usual anti-asthmatic treatment. New therapeutic options are being evaluated.

LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma.

Human clear cell renal cell carcinoma (CCC) remains resistant to therapies. The transcription factor LIM-class homeobox gene Lim1 is required for normal organogenesis, including nephrogenesis, by regulating cell movements, differentiation and growth. Its expression is controlled partly by the sonic hedgehog-Gli signaling pathway, which we have recently shown to be reactivated in human CCC. So far, no study has assessed whether Lim1 may be associated with tumorigenesis. Using a panel of human CCC cell lines expressing or not the von Hippel-Lindau tumor suppressor gene and 44 tumor/normal tissues pairs, we found that Lim1 is constitutively and exclusively reexpressed in tumors. Through Lim1 silencing or overexpressing, we show that Lim1 is a growth and survival factor in human CCC, at least through the activation of oncogenic pathways including the phosphoinositide kinase-3/Akt and nuclear factor-kappaB pathways. More importantly, in nude mice bearing human CCC tumors, Lim1 silencing abolished tumor growth through the same mechanism as in vitro. In Lim1-depleted cells and tumors, cell movements were substantially impaired because of the inhibition of expression of various proteins involved in metastatic spread, such as paxillin or tenascin-C. These findings establish that the developmental marker Lim1 acts as an oncogene in cancer cells and targeting Lim1 may constitute an innovative therapeutic intervention in human CCC.