ABSTRACT
SCI is followed by dramatic upregulation of chondroitin sulfate proteoglycans (CSPGs) which limit axonal regeneration, oligodendrocyte replacement and remyelination. The recent discovery of the specific CSPGs signaling receptor protein tyrosine phosphatase sigma (RPTPσ) provided an opportunity to refine the therapeutic approach to overcome CSPGs inhibitory actions. In previously published work, subcutaneous (s.c.) delivery of 44⯵g/day of a peptide mimetic of PTPσ called intracellular sigma peptide (ISP), which binds to PTPσ and blocks CSPG-mediated inhibition, facilitated recovery after contusive SCI. Since this result could be of great interest for clinical trials, we independently repeated this study, but modified the method of injury as well as peptide application and the dosage. Following SCI at the Th10-segment, 40 rats were distributed in 3 groups. Animals in group 1 (20 rats) were subjected to SCI, but received no treatment. Rats in group 2 were treated with intraperitoneal (i.p.) injections of 44⯵g/day ISP (SCIâ¯+â¯ISP44) and animals of group 3 with s.c. injections of 500⯵g/day ISP (SCIâ¯+â¯ISP500) for 7â¯weeks after lesioning. Recovery was analyzed at 1, 3, 6, 9 and 12â¯weeks after SCI by determining (i) BBB-score, (ii) foot-stepping angle, (iii) rump-height index, (iv) number of correct ladder steps, (v) bladder score and (vi) sensitivity (withdrawal latency after thermal stimulus). Finally, we determined the amount of serotonergic fibers in the preserved neural tissue bridges (PNTB) around the lesion site. Our results show that, systemic therapy with ISP improved locomotor, sensory and vegetative recovery which correlated with more spared serotonergic fibers in PNTB.
Subject(s)
Receptor-Like Protein Tyrosine Phosphatases, Class 2/metabolism , Recovery of Function/physiology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Analysis of Variance , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Hyperalgesia/drug therapy , Hyperalgesia/physiopathology , Locomotion/drug effects , Peptides/therapeutic use , Psychomotor Performance/drug effects , Rats , Rats, Wistar , Receptor-Like Protein Tyrosine Phosphatases, Class 2/chemistry , Recovery of Function/drug effects , Serotonin/metabolism , Spinal Cord Injuries/drug therapy , Time Factors , Urinary Bladder/drug effects , Urinary Bladder/physiopathologyABSTRACT
BACKGROUND: The 8th edition of the AJCC TNM staging system presents for the first time a specific classification for esophageal carcinomas treated with neoadjuvant therapy (yTNM8). In this single center study, we applied the novel staging system in a "real life" case series and compared the prognostic value of yTNM8 with the preceding 7th edition (TNM7). METHODS: Out of 272 consecutive esophageal carcinomas that were treated during a 15-year period in one surgical center, all 198 cases that had undergone neoadjuvant therapy were reviewed and classified according to TNM7 and yTNM8. RESULTS: 50 ypT0 cases that had no specific staging in TNM7 were included into stages I (ypT0N0M0; nâ¯=â¯42), IIIA (ypT0N1M0; nâ¯=â¯6), IVA (ypT0N3M0; nâ¯=â¯1) and IVB (ypT0N0M1; nâ¯=â¯1) in yTNM8. Both systems showed significant prognostic impact (pâ¯<â¯0.0001 each). yTNM8 was superior regarding prognostication with lower values for goodness-of-fit criteria (Akaike Information Criterion 1589.331 vs 1593.239; and Schwarz Bayesian Criterion 1605.487 vs.1619.088). However, in TNM7, stage IIB tumors had better prognosis than stage IIA tumors, and likewise, stage IIIA tumors better compared to stage II in yTNM8. CONCLUSIONS: yTNM8 allows accurate staging of esophageal carcinomas treated by neoadjuvant therapy, with slightly improved prognostication compared to TNM7. Additional data acquisition will be necessary for further improvement of staging for esophageal carcinomas after neoadjuvant treatment.
