Acute changes in free and extracellular vesicle-associated circulating miRNAs and myokine profile in professional sky-runners during the Gran Sasso d'Italia vertical run.

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: A case report]. / Carcinome neuroendocrine à petites cellules des voies urinaires excrétrices supérieures: à propos d'un cas.

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.

A double-blind, randomised comparison of the anti-emetic efficacy of two intravenous doses of dolasetron mesilate and granisetron in patients receiving high dose cisplatin chemotherapy.

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 (> or = 80 mg/m2) 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 (> or = 80 mg/m2) 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.

Combined external irradiation and interstitial implantation for T1 and T2 epidermoid carcinomas of base of tongue: the Creteil experience (1971-1981).

Forty-eight patients with T1 or T2 epidermoid carcinomas of the base of tongue were treated at the Henri Mondor Hospital between 1971 and 1981. Forty-one patients received moderate dose 60Co external beam irradiation (mean: 48.6 Gy) to the primary tumor and regional nodes, followed by an interstitial iridium 192 implant to the primary tumor (mean: 32 Gy). This completed the treatment for the 30 node negative patients, but those with clinically positive nodes were managed by either an additional electron beam boost to the involved nodes or a neck dissection. Seven tumors were treated exclusively by implantation to the base of tongue (mean: 63 Gy). Five-year crude disease-free survival is 50% with 35% of patients dying of recurrent disease. Definitive local control for T1 lesions is 85% (11/13) and for T2 is 71% (25/35). A dose response effect was observed with local control of 79% (26/33) obtained with a combined dose greater than or equal to 75 Gy, but only 50% (4/8) for less than or equal to 70 Gy. For N0 patients definitive regional control is 97% and for N1-3 is 89%. Minor or moderate soft tissue ulceration was observed in 12 patients, including 3 cases that progressed to osteonecrosis. None required surgical intervention. No correlation exists between necrosis and tumor size or total dose.

Definitive radiation treatment for early stage carcinoma of the soft palate and uvula: the indications for iridium 192 implantation.

From 1971 to 1984 59 T1 and T2 carcinomas of the soft palate and uvula were treated definitively by irradiation at the Henri Mondor hospital. Included are ten patients previously irradiated to the oropharyngeal area for either a carcinoma of the soft palate or another malignancy. Sixteen patients were treated by external irradiation alone, 14 by Iridium 192 implantation, and 29 by a combination of the two. Two techniques of implantation were used: the guide gutter technique (33 patients) and the plastic tube technique (10 patients). Clinically negative neck nodes (51/59) either received prophylactic telecobalt therapy (39/51) or were surveilled (12/51). Clinically involved nodes (8/59) were managed either by external irradiation alone (4/8) or combined with neck dissection (4/8). Local failure was 25% (4/16) after exclusive telecobalt therapy, 18% (5/19) after combined telecobalt therapy and implantation, and 0% (0/14) after Iridium 192 implantation alone. No local failures were seen with the plastic tube technique (0/10) as compared to 15% (5/33) for guide gutters. Only two nodal failures were observed (2/59: 3%). Crude 5-year disease-free survival was 33%. Severe complications were limited to one osteonecrosis, one soft tissue necrosis, and one partial palatal incompetence. Salivary impairment was reduced when implantation was used for part or all of the treatment. We recommend 45 Gy external radiation followed by 30 Gy from Iridium 192 implantation using the plastic tube method unless there has been prior oropharyngeal irradiation, in which case we give 60 Gy from implantation alone. For clinically negative neck nodes, we recommend 45 Gy prophylactic external neck irradiation. For clinically positive lymph nodes, this should be followed by either a 25 to 30 Gy boost to the involved nodes or a neck dissection.

Salvage irradiation of oropharyngeal cancers using iridium 192 wire implants: 5-year results of 70 cases.

Between May 1971 and November 1980, 70 patients with recurrent or new oropharyngeal cancers arising in previously irradiated tissues were treated using iridium 192 afterloading techniques. The actuarial local control was 72% at 2 years and 69% at 5 years. Although local control of the tumor was achieved in the majority of these patients, only 10 patients remained alive at 5 years (14%). Patients with lesions of the faucial arch and posterior pharyngeal wall had the best results; local control was achieved in 100% of these patients. Patients with lesions of the base of tongue and of the glosso-tonsillar sulcus had poorer results; local control was achieved in 61%. Because these results compare favorably with the results of previously published series, we recommend re-irradiation with brachytherapy for recurrent or new malignancies arising in a previously irradiated oropharynx. When the lesion is located in the faucial arch, brachytherapy is the treatment of choice. When the lesion is located in the base of tongue, brachytherapy is a reasonable option.

[Update on exclusive radiotherapy of T1 and T2 of the faucial arch]. / Mise au point sur la radiothérapie exclusive des T1 et T2 de l'arche vélo-amygdalienne.

From April 1971 to October 1984, 71 patients with T1 or T2 tumors of the faucial arch were treated according to the following protocol: Telecobalt therapy to the primary site and to the neck nodes to a dose of 45 Gy. Brachytherapy to the primary site to a dose of 25 to 30 Gy using iridium 192. For node positive patients, boost dose to involved neck nodes with electrons, or radical neck dissection. Seven patients with T1N0 tumors were treated exclusively by 60 Gy iridium implantation. The crude disease free survival is 66% for the group of patients with tumors of the tonsillar region and 41% for those with tumors of the soft palate or uvula. Local control of tonsillar tumors was 98% while that of tumors of the soft palate was 85%. Regional control was 98% for the N0 group and 87% for the N1-3 group. Five cases of soft tissue ulceration were observed, all of which healed spontaneously within a few months. Less salivary impairment was seen than after treatment by external irradiation alone. While these promising results have encouraged the use of this protocol, the introduction of the plastic tube technique has expanded the indications to include almost all T1 and T2 tumors of the faucial arch without obvious extension to the base of tongue or retromolar trigone.