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Introduction: Urothelial carcinomas are the fourth leading cause of cancer in humans. Their incidence is increasing by more than 50% in 25 years. The superficial forms (70% cases) require a close active surveillance to identify frequent recurrences and progression to invasive stage. Our main goal was to identify prognostic molecular markers for bladder cancer that could be used alone or in combination in routine clinical practice. In this aim, we evaluated the capability of the BCA-oligo test based on a CGH array to correctly classify tumoral grade/stage., Method: Urinary DNA was extracted from 81 patients with superficial bladder cancer and has been hybridized on the BCA-oligo array. The results from the molecular analysis were correlated with the tumoral grade and stage., Results: Several chromosomal alterations were significantly more frequent in tumors of higher grade and more advanced stage. A significant association was observed between a high grade and the presence of one of these alterations: loss on 6p, gain on 8q or 13q, loss or gain on 9q or 11q, with an odds ratio of 6.91 (95% CI=2.20-21.64; P=0.0009). Moreover, a significant association was found between a more advanced stage (pT1) and the presence of one of these alterations: loss on 6p, gain on 8q, loss or gain on 5p, with an odds ratio of 15.2 (95% CI=3.71-62.58; P=0.0002)., Conclusion: Our results showed that molecular analyses of superficial bladder cancers based on urinary DNA and the BCA-oligo test could be used as prognostic factor for the tumor evolution, allowing then a more adapted clinical management., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The lymphatic vascular system is widely developed among vertebrates. Lymphatic vessels provide the interstitial fluid (20% of the body weight) drainage through interstitial prelymphatic channels, capillaries, precollectors and collectors flowing into the venous blood. Endothelial cells of capillaries are overlapped and fixed to interstitial collagen and elastic fibres by anchoring filaments facilitating the fluid transfer. Precollectors and collectors have valves controlling the lymph flux direction. In addition to external mechanisms, the lymphangions of collectors have contracting muscle cells driving the flow. Lymphatic endothelial cells are routinely identified by the expression of podoplanin, LYVE-1 and VEGFR3. In the embryo, prelymphatic endothelial cells emerge from the cardinal veins and migrate into the mesenchyma forming embryonic lymphatic sacs. Prox1, Sox18 and COUP-TFII play a major role in the endothelial speciation, VEGFC as VEGFD combined to VEGFR3 in cell migration and proliferation and FoxC2 in valves development. In cancer or inflammation, various factors secreted by cancer cells and/or inflammatory cells induce a neolymphangiogenesis. Recently it has been shown that cells from the bone marrow could be potential precursors for lymphatic endothelial cells., (Copyright © 2013. Published by Elsevier Masson SAS.)

Epidermal growth factor receptor (EGFR) is a cell membrane tyrosine kinase receptor. Activating mutations at exon 19 and 21 of the EGFR gene are associated with the occurrence and development of lung adenocarcinoma. These gain of function mutations predict responsiveness to EGFR tyrosine kinase inhibitors (TKis), erlotinib or gefitinib and are also a favorable prognostic factor in lung cancer. Sequencing is the recommended technique to detect the mutations, but other more sensitive technics are under evaluation. Treatment as first line therapy by gefitinib is limited to lung cancer patients harboring an EGFR mutation. Erlotinib can be given regardless of the EGFR status as second or third line therapy, as well as maintenance therapy in patients with a stable disease after platinum based chemotherapy. In EGFR mutated tumors, most patients present a recurrence of the disease, despite an initial response on EGFR TKis. Two mechanisms of secondary resistance have been identified, the selection of the T790M mutation in EGFR exon 20 and the MET amplification. Other molecular anomalies as the ras mutations or the EMLA-ALK protein fusion are mutually exclusive with the EGFR mutations and are associated with primary resistance to EGFR TKis., (Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

In 7 patients who received renal transplant, systematic blood samples and cytoaspiration of the graft were performed every 3 days after grafting. In vitro TNF-alpha generation by circulating mononuclear cells and by cells infiltrating the graft were measured under basal conditions and after stimulation by recombinant IL-2 (50 U/ml). TNF-alpha concentration was determined by immunoradiometric assay (IRMA). Not enough cells could be collected by cytoaspiration to measure TNF-alpha concentration. In contrast, the generation of TNF-alpha by circulating mononuclear cells was detectable. It increased 24 to 48 hours before the rejection crisis and decreased after successful treatment and return of creatinin level to initial value. IL-2 increased TNF-alpha production and was more effective under normal conditions (10 to 15 fold increase) than during rejection episodes (1.3 to 2.4 fold). These results suggest that TNF-alpha is produced by mononuclear cells during rejection episodes and could be used as a marker of rejection. Further studies are required to determine its sensitivity and specificity.

The availability of accurate and inexpensive methods for measuring serum calcium levels has resulted in a rapid increase in the number of diagnoses of primary hyperparathyroidism, notably in its asymptomatic hypercalcemic forms. In addition, the development of a radioimmunoassay of the parathyroid hormone and, more recently, measurements of nephrogenous cyclic AMP during fasting and after calcium loading have led to the recognition of clinical variants of the disease, such as intermittent or borderline hypercalcemia and pure hypercalciuria with normal calcemia. The degree of hypercalcemia in stable primary hyperparathyroidism depends on renal tubular reabsorption of calcium rather than on bone resorption. The poor correlation observed between calcium tubular reabsorption rate and magnitude of parathyroid hormone hypersecretion suggests that as yet undetermined factors interfere with the effects of parathyroid hormone on renal tubules and probably account for the fluctuations in calcemia reported during serial determinations in patients. The sigmoid relationship between parathyroid hormone release and extracellular calcium concentrations has been analyzed from recent in vitro studies with dispersed parathyroid cells. In primary hyperplasia of the parathyroid glands hypersecretion of parathyroid hormone seems to depend principally upon the increase in tissue mass with normal sensitivity to calcium at cellular levels, whereas in adenoma the primary abnormality responsible for hypersecretion of parathyroid hormone would be an alteration in cell sensitivity to calcium, as indicated by an elevated "set point". Finally, while complicated primary hyperthyroidism requires surgery, our limited knowledge of the natural history of asymptomatic forms makes it impossible to decide which of these patients will ultimately need to be operated upon.