On the structure of contraction operators with applications to invariant subspaces

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26407/1/0000494.pd

Neo/adjuvant chemotherapy does not improve outcome in resected primary synovial sarcoma: a study of the French Sarcoma Group

Background: There are only scarce data about the benefit of adjunctive chemotherapy in patients with localized synovial sarcoma (SS). Patients and methods: Data from 237 SS patients recorded in the database of the French Sarcoma Group were retrospectively analyzed. The respective impact of radiotherapy, neo-adjuvant chemotherapy and adjuvant chemotherapy on overall survival (OS), local recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS) were assessed after adjustment to prognostic factors. Results: The median follow-up was 58 months (range 1-321). Adjuvant, neo-adjuvant chemotherapy and postoperative radiotherapy were administered in 112, 45 and 181 cases, respectively. In all, 59% of patients treated with chemotherapy received an ifosfamide-containing regimen. The 5-year OS, LRFS and DRFS rates were 64.0%, 70% and 57%, respectively. On multivariate analysis, age >35 years old, grade 3 and not-R0 margins were highly significant independent predictors of worse OS. After adjustment to prognostic factors, radiotherapy significantly improved LRFS but not DRFS or OS. Neither neo-adjuvant nor adjuvant chemotherapy had significant impact on OS, LRFS or DRFS. Conclusion: As for other high-grade soft-tissue sarcomas, well-planned wide surgical excision with adjuvant radiotherapy remains the cornerstone of treatment for SS. Neo-adjuvant or adjuvant chemotherapy should not be delivered outside a clinical trial settin

Dilation theory and systems of simultaneous equations in the predual of an operator algebra. II

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46272/1/209_2005_Article_BF01163170.pd

Coupling evolutionary dynamics of fungal effectors and functional genomics : towards understanding mechanisms of Venturia inaequalis virulence and identifying durable resistance genes in apple

During infection, pathogens secrete small secreted proteins (SSPs), called effectors, that promote disease. Plant receptors encoded by resistance R genes might recognize such effectors (also called avirulence factors AVRs), resulting in plant immunity. Pathogens evade recognition thanks to the emergence of virulent alleles present in populations. It has been demonstrated that avirulent effectors are crucial for the pathogen infection cycle and that their loss-of-function may induce a substantial fitness cost. This kind of effector is expected to be under purifying selective pressure. Here, we aim at identifying the effector repertoire of Venturia inaequalis, the agent of apple scab, assessing its evolutionary dynamics and studying the role of candidate effectors in virulence. We sequenced de novo 90 strains, collected on apple and on their wild relatives and differing in their host range or virulence to study allelic polymorphism at 880 putative effector loci. The top-20 hits for highly conserved sequences were selected as candidates for further functional analyses. In planta gene expression showed a significant induction of these conserved SSP at the early stage of plant infection. Their functions were investigated using targeted deletion mutants. Remarkably, loss of two conserved SSPs resulted in reduced aggressiveness without any alteration in growth in vitro. GFP-tagged protein and heterologous expression were used to assess their sub-cellular localization in infected apple leaves. Involvement of theses SSP in the modulation of host defence was also investigated using an apple full-transcript microarray. Highly conserved effectors will be used to screen for novel R genes in Malus genotypes characterized for their high resistance to scab. This combined knowledge should enable us to understand strategies used by the pathogen to overcome defences in apple and consequently to build more durable resistance towards apple scab

Tumor Heterogeneity of Fibroblast Growth Factor Receptor 3 (FGFR3) Mutations in Invasive Bladder Cancer: Implications for Peri-Operative anti-FGFR3 Treatment

Background: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. Patients: and methods We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201).Results: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type.Conclusions: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting