Favorable outcome of Ewing sarcoma family tumors to multiagent intensive preoperative chemotherapy: a single institution experience

BACKGROUND: Aim of our study was to evaluate the efficacy of multiagent intensive preoperative chemotherapy in patients with Ewing sarcoma family tumors (ESFT), in order to succeed a better percentage of necrosis before surgical resection. PROCEDURE: Eighteen patients with ESFT were treated with the same multiagent intensive preoperative protocol. 5/18 patients had bone Ewings sarcoma (EWS) and 13/18 had peripheral primitive neuroectodermal tumor (PNET). None had metastases at diagnosis. Chemotherapy consisted of 5 or 6 cycles with vincristine, cisplatin, cyclophosphamide, and Adriamycin, followed by 12 cycles of vincristine, cyclophosphamide, and actinomycin-D. Five patients with EWS underwent total resection after 5-6 cycles of preoperative chemotherapy and prosthetic replacement was performed in two of them. In 3/13 patients with PNET the tumor was resected at diagnosis and in 1/13 after 5 cycles of chemotherapy, while 9/13 patients received chemotherapy only and/or radiotherapy. RESULTS: In patients with EWS, the histologic specimens of the resected tumors showed that tissue necrosis was 100% in four patients and 95% in one patient. The good histologic response reflects the effectiveness of this regimen in all ESFT. No patient had topical recurrence or developed metastatic disease during follow-up period (2-13 years, mean time 7.4 years). All patients had the scheduled cycles without delays or dose reductions. There were no major side effects of chemotherapy. CONCLUSIONS: The intensive chemotherapy schedule, comprising of 5-6 cycles preoperatively, seems to maximize the percentage of tumor necrosis, thus improving outcome. Our study implies that this combined therapy may improve the prognosis of ESFT.     

Nerve echogenicity and intranerve CSA variability in high-resolution nerve ultrasound (HRUS) in chronic inflammatory demyelinating polyneuropathy (CIDP)

Journal of Neurology - HRUS is increasingly being used in the diagnosis and evaluation of autoimmune neuropathies such as CIDP. Recently, studies focused not only on changes of nerves size, but...     

Role of serotonin 5-HT2A and 5-HT2C receptors on brain stimulation reward and the reward-facilitating effect of cocaine

Rationale

The serotonin 5-HT_2A and 5-HT_2C receptors, which are found in abundance in the mesolimbocortical dopaminergic system, appear to modulate the behavioral effects of cocaine.

Objectives

The present series of studies set out to investigate the role of 5-HT_2A and 5-HT_2C receptors on brain reward and on the reward-facilitating effect of cocaine and localize the neural substrates within the mesolimbocortical dopaminergic system that are responsible for these effects.

Methods

Male Sprague-Dawley rats were implanted with stimulating electrodes and bilateral cannulae for the experiments involving microinjections and were trained to respond to electrical stimulation. In the first study, we examined the effects of systemic administration of selective 5-HT_2A and 5-HT_2C receptor agonists (TCB-2 and WAY-161503) and antagonists (R-96544 and SB-242084) on intracranial self-stimulation (ICSS). In the second study, we examined the effectiveness of TCB-2, WAY-161503, R-96544, and SB-242084 in blocking the reward-facilitating effect of cocaine. In the third study, we examined the effects of intra-medial prefrontal cortex (mPFC), intra-nucleus accumbens (NAC), and intra-ventral tegmental area (VTA) injection of WAY-161503 on the reward-facilitating effect of cocaine.

Results

Acute systemic administration of TCB-2 and WAY-161503 increased ICSS threshold. Systemic WAY-161503 attenuated the reward-facilitating effect of cocaine. This effect was reversed by pretreatment with SB-242084. Intracranial microinjections of WAY-161503 into the mPFC and the NAC shell/core, but not the VTA, attenuated the reward-facilitating effect of cocaine.

Conclusion

These data indicate that 5-HT_2C receptors within the mPFC and the NAC modulate the reinforcing effects of cocaine and provide evidence that 5-HT_2C receptor agonists could be a possible drug discovery target for the treatment of psychostimulant addiction.     

The role of the fat mass and obesity associated gene (<Emphasis Type="Italic">FTO</Emphasis>) in breast cancer risk

Background  

Obesity has been shown to increase breast cancer risk. FTO is a novel gene which has been identified through genome wide association studies (GWAS) to be related to obesity. Our objective was to evaluate tissue expression of FTO in breast and the role of FTO SNPs in predicting breast cancer risk.