Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells.

Chondroitin sulfates (CSs) and dermatan sulfates (DSs) are enriched in the microenvironment of neural stem cells (NSCs) during development and in the adult neurogenic niche, and have been implicated in mechanisms governing neural precursor migration, proliferation and differentiation. In contrast to previous studies, in which a chondroitinaseABC-dependent unselective deglycosylation of both CSs and DSs was performed, we used chondroitin 4-O-sulfotransferase-1 (Chst11/C4st1)- and dermatan 4-O-sulfotransferase-1 (Chst14/D4st1)-deficient NSCs specific for CSs and DSs, respectively, to investigate the involvement of specific sulfation profiles of CS and DS chains, and thus the potentially distinct roles of CSs and DSs in NSC biology. In comparison to wild-type controls, deficiency for Chst14 resulted in decreased neurogenesis and diminished proliferation of NSCs accompanied by increased expression of GLAST and decreased expression of Mash-1, and an upregulation of the expression of the receptors for fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF). By contrast, deficiency in Chst11 did not influence NSC proliferation, migration or differentiation. These observations indicate for the first time that CSs and DSs play distinct roles in the self-renewal and differentiation of NSCs.

[Transbronchial needle aspiration as a diagnostic method in lung cancer and non-malignant mediastinal adenopathy]. / Przezoskrzelowa biopsja iglowa wezlów chlonnych sródpiersia i wnek w rozpoznawaniu, ocenie stopnia zaawansowania i wznowy raka pluca oraz w rozpoznawaniu chorób nienowotworowych.

INTRODUCTION: The aim of the study was to assess the diagnostic yield of transbronchial needle aspiration (TBNA) in mediastinal or hilar adenopathy in: lung cancer, staging of NSCLC, sarcoidosis and other non-malignant diseases. MATERIAL AND METHODS: Transbronchial needle aspiration was performed in 347 consecutive patients - 402 biopsies in groups of lymph nodes: subcarinal (7) - 179, all paratracheal (2R, 2L, 4R, 4L) - 168 and hilar (10R, 10L) - 55, with no real-time imaging guidance, preceded by computed tomography (CT), using 22-gauge needles. All negative results in NSCLC patients were verified by transcervical extended bilateral mediastinal lymphadenectomy (TEMLA) and the remaining patients underwent mediastinoscopy or thoracotomy. RESULTS: TBNA technique was diagnostic in 67.1% of lung cancer patients and in 59.0% of patients with sarcoidosis. In the group of all lung cancer patients specificity was 100%, sensitivity 88.5%, accuracy 91.8% and negative predictive value 77.9% and in diagnosing of lymph nodes involvement in NSCLC was respectively 100%, 86.6%, 90.7% and 76.6%. The high diagnostic yield was comparable for all mediastinal groups. In 80% of NSCLC patients with false negative results of TBNA there was observed partial involvement of metastatic lymph nodes, confirmed by TEMLA. CONCLUSIONS: The diagnostic value of TBNA is very high in diagnostics of lung cancer, NSCLC staging and sarcoidosis but much lower in lymphomas, tuberculosis and other non-malignant diseases.

Comparison of endobronchial ultrasound and/or endoesophageal ultrasound with transcervical extended mediastinal lymphadenectomy for staging and restaging of non-small-cell lung cancer.

BACKGROUND: To compare the diagnostic yield of endobronchial ultrasound (EBUS) and/or endoesophageal ultrasound (EUS) with transcervical extended mediastinal lymphadenectomy (TEMLA) for primary staging and repeated staging (restaging) of non-small-cell lung cancer (NSCLC). METHODS: In this retrospective study, all consecutive patients undergoing primary staging and restaging after neoadjuvant chemo- or chemo-radiotherapy for NSCLC with EBUS, EUS, or EBUS combined with EUS (CUS) with fine needle aspiration biopsy and cytological examination and subsequent TEMLA from January 1, 2007 to December 31 2010, were included. RESULTS: Primary staging was performed in 623 patients: EBUS in 351, EUS in 72, and CUS in 200 patients. TEMLA was performed for primary staging in 276 patients. There was no mortality and morbidity after EBUS or EUS. One patient died after TEMLA and morbidity rate after TEMLA was 7.2%. There was a significant difference between EBUS or EUS and TEMLA for sensitivity (87.8% and 96.2%; p < 0.01) and negative predictive value (82.5% and 99.6%; p < 0.01) in favor of TEMLA. In the restaging group, endoscopic staging was performed in 88 patients and TEMLA in 78 patients. There was a significant difference between EBUS or EUS and TEMLA for sensitivity (64.3% and 100%; p < 0.01) and negative predictive value (82.1% and 100%; p < 0.01) in favor of TEMLA. CONCLUSIONS: The results of this largest reported series comparing the endoscopic and surgical primary staging and restaging of NSCLC showed a significantly higher diagnostic yield of TEMLA when compared with that of EBUS or EUS.

Dermatan 4-O-sulfotransferase1 ablation accelerates peripheral nerve regeneration.

Chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans are major components of the extracellular matrix implicated in neural development, plasticity and regeneration. While it is accepted that CS are major inhibitors of neural regeneration, the contributions of DS to regeneration have not been assessed. To enable a novel approach in studies on DS versus CS roles during development and regeneration, we generated a mouse deficient in the dermatan 4-O-sulfotransferase1 (Chst14(-/-)), a key enzyme in the synthesis of iduronic acid-containing modules found in DS but not CS. In wild-type mice, Chst14 is expressed at high levels in the skin and in the nervous system, and is enriched in astrocytes and Schwann cells. Ablation of Chst14, and the assumed failure to produce DS, resulted in smaller body mass, reduced fertility, kinked tail and increased skin fragility compared with wild-type (Chst14(+/+)) littermates, but brain weight and gross anatomy were unaffected. Neurons and Schwann cells from Chst14(-/-) mice formed longer processes in vitro, and Chst14(-/-) Schwann cells proliferated more than Chst14(+/+) Schwann cells. After femoral nerve transection/suture, functional recovery and axonal regrowth in Chst14(-/-) mice were initially accelerated but the final outcome 3months after injury was not better than that in Chst14(+/+) littermates. These results suggest that while Chst14 and its enzymatic products might be of limited importance for neural development, they may contribute to the regeneration-restricting environment in the adult mammalian nervous system.