The modification of gene expression profile, a first step in adaptation to exercise, leads to changes in the level of molecules associated with skeletal muscle activity and energy metabolism—such as ...myokines—as well as those involved in their transcriptional regulation, like microRNA. This study aimed to investigate the influence of strenuous exercise on circulating microRNAs and their possible association with myokine response. Pre-competition and post-competition plasma samples were collected from 14 male athletes participating in a vertical run (+1,000 m gain, 3,600 m length). Circulating total (t-miRNA) and extracellular vesicle-associated (EV-miRNA) miRNAs were extracted from the pooled plasma. Nanoparticle tracking analysis was performed to investigate pre- and post-competition EV concentration and size distribution. A panel of 179 miRNAs was assayed by qPCR and analyzed by Exiqon GenEx v6 normalized on the global mean. t-miRNA and EV-miRNAs whose level was ≥5-fold up- or down-regulated were validated for each single subject. Target prediction on MirWalk v3.0, Gene-Ontology, and pathway enrichment analysis on Panther v17.0 were performed to define the potential biological role of the identified miRNAs. A panel of 14 myokines was assayed in each sample by a multiplex immunoassay. In whole plasma, five miRNAs were upregulated and two were downregulated; in the EV fraction, five miRNAs were upregulated and three were downregulated. Nanoparticle tracking analysis revealed a similar EV size distribution in pre- and post-competition samples and a decreased concentration in post-competition samples related to pre-competition samples. Gene-Ontology and pathway enrichment analysis revealed that the identified t-miRNAs and EV-miRNAs were potentially involved in metabolism regulation in response to exercise. Correlation between fold-change of the post-competition relative to pre-competition plasma level of both t-miRNAs and EV-miRNAs and myokines further confirmed these results. This study provides an example of a systemic response to acute endurance exercise, in which circulating miRNAs play a pivotal role.
Small cell neuroendocrine carcinoma of the upper urinary tract is extremely rare. To our knowledge, only 25 cases have been reported in the literature. The current study reports the case of an ...80-year-old patient who suffered from macroscopic haematuria. A first screening by thoracic-abdominal-pelvic CT scan showed a mass located in the patient's left ureter and a left nephro-ureterectomy was consequently performed. The pathological examination of the resected specimen allowed the diagnosis of a small cell neuroendocrine carcinoma of the left ureter. After four months of follow-up, a PET-CT detected an isolated local recurrence on the left common iliac lymphadenopathy. After seven cycles of chemotherapy (carboplatin-etoposide), we observed a partial response followed by a new progression. It was then decided to perform an image-guided radiotherapy at a dose of 46.8 Gy, at 1.8 Gy per fraction, during 37 days to the left common iliac lymphadenopathy. After 16 months of follow-up, a complete metabolic remission was achieved. Indeed, this observation, followed by a short literature review, demonstrates the interest of radiotherapy for the treatment of a rare cancer: the small cell neuroendocrine carcinoma of the upper urinary tract.
Les carcinomes neuroendocrines à petites cellules des voies urinaires excrétrices supérieures sont des tumeurs très rares dont il n’existe à notre connaissance que 25 cas dans la littérature. Nous ...rapportons ici le cas d’un patient de 80ans qui souffrait d’hématurie macroscopique. Une tomodensitométrie thoraco-abdominopelvienne a mis en évidence une tumeur de l’uretère pelvien gauche et le patient a eu une néphro-urétérectomie élargie gauche. Le diagnostic histologique était alors celui d’un carcinome neuroendocrine à petites cellules de l’uretère pelvien gauche. Après 4 mois de surveillance, une tomographie par émission de positons (TEP) a détecté une récidive locale isolée sous forme d’une adénopathie iliaque primitive gauche. Cette récidive a répondu partiellement à sept cures de carboplatine et d’étoposide, puis a échappé à la chimiothérapie. Il a alors été décidé de réaliser une irradiation guidée par l’image conformationnelle de l’adénopathie iliaque primitive gauche de 46,8Gy en 26 fractions et 37jours. Après un suivi de 16 mois, le patient était toujours en situation de rémission métabolique complète. Cette observation, suivie d’une brève revue de la littérature, permet donc de montrer l’intérêt de la radiothérapie dans la prise en charge d’une tumeur très rare, le carcinome neuroendocrine à petites cellules des voies urinaires excrétrices supérieures.
Small cell neuroendocrine carcinoma of the upper urinary tract is extremely rare. To our knowledge, only 25 cases have been reported in the literature. The current study reports the case of an 80-year-old patient who suffered from macroscopic haematuria. A first screening by thoracic-abdominal-pelvic CT scan showed a mass located in the patient's left ureter and a left nephro-ureterectomy was consequently performed. The pathological examination of the resected specimen allowed the diagnosis of a small cell neuroendocrine carcinoma of the left ureter. After four months of follow-up, a PET-CT detected an isolated local recurrence on the left common iliac lymphadenopathy. After seven cycles of chemotherapy (carboplatin-etoposide), we observed a partial response followed by a new progression. It was then decided to perform an image-guided radiotherapy at a dose of 46.8Gy, at 1.8Gy per fraction, during 37days to the left common iliac lymphadenopathy. After 16 months of follow-up, a complete metabolic remission was achieved. Indeed, this observation, followed by a short literature review, demonstrates the interest of radiotherapy for the treatment of a rare cancer: the small cell neuroendocrine carcinoma of the upper urinary tract.
This multicentre, double-blind, double-dummy, randomised trial was designed to compare the efficacy and safety of single intravenous doses of dolasetron mesilate and granisetron in the prevention of ...acute emesis and nausea due to high-dose (⩾ 80 mg/m
2) cisplatin. Single intravenous doses of 1.8 or 2.4 mg/kg of dolasetron mesilate or 3 mg of granisetron hydrochloride were administered in a volume of 50 ml over a 5-min period, beginning 30 min prior to cisplatin (⩾ 80 mg/m
2) administration. The number and timing of emetic episodes, time to administration of escape anti-emetic medication, severity of nausea by visual analogue scale (VAS), and safety were monitored for 24 h after the start of cisplatin-containing chemotherapy. Investigators' evaluations of overall efficacy and patients' satisfaction with therapy were recorded at the end of the 24-h study period. Of the 474 patients evaluable for efficacy, complete responses were achieved by 54, 47 and 48% of patients given dolasetron mesilate 1.8 mg/kg, dolasetron mesilate 2.4 mg/kg and granisetron, respectively. Statistically, treatment groups had comparable complete and complete plus major responses, times to first emesis, and use of escape medication; patient maximum nausea severity and treatment satisfaction ratings; and physician nausea severity and overall efficacy assessments. For the majority of efficacy endpoints, 1.8 mg/kg dolasetron mesilate produced numerically superior responses compared with the 2.4 mg/kg dose. Gender and prior chemotherapy were significant predictors of complete response; males and chemotherapy-naive patients had higher responses. The overall incidences of adverse events were comparable among the treatment groups; headache and diarrhoea were most common. In conclusion, 1.8 and 2.4 mg/kg of dolasetron mesilate and granisetron (3 mg) were equally effective in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, because no additional benefit was observed with 2.4 mg/kg of dolasetron mesilate and numerically greater responses were observed with the 1.8 mg/kg dose, the lower dose of 1.8 mg/kg is optimal for further clinical development.
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