Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice

Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT, a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase TIBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9 ± 2.0, 77.4 ± 12.7 and 93.6 ± 4.6% (P<0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 µg ≈ 0.99, 4.96 nmol) on TIBAT in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) elevated TIBAT similarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7 ± 2.23% and 6.6 ± 1.4% in sham and denervated mice (P<0.05), respectively, and this effect was similar between groups (P=NS). OT produced corresponding reductions in whole body fat mass (P<0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice

Intensity-modulated radiotherapy of nasopharyngeal carcinoma: a comparative treatment planning study of photons and protons

<p>Abstract</p> <p>Background</p> <p>The aim of this treatment planning study was to investigate the potential advantages of intensity-modulated (IM) proton therapy (IMPT) compared with IM photon therapy (IMRT) in nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Eight NPC patients were chosen. The dose prescriptions in cobalt Gray equivalent (Gy_E) for gross tumor volumes of the primary tumor (GTV-T), planning target volumes of GTV-T and metastatic (PTV-TN) and elective (PTV-N) lymph node stations were 72.6 Gy_E, 66 Gy_E, and 52.8 Gy_E, respectively. For each patient, nine coplanar fields IMRT with step-and-shoot technique and 3D spot-scanned three coplanar fields IMPT plans were prepared. Both modalities were planned in 33 fractions to be delivered with a simultaneous integrated boost technique. All plans were prepared and optimized by using the research version of the inverse treatment planning system KonRad (DKFZ, Heidelberg).</p> <p>Results</p> <p>Both treatment techniques were equal in terms of averaged mean dose to target volumes. IMPT plans significantly improved the tumor coverage and conformation (<it>P </it>< 0.05) and they reduced the averaged mean dose to several organs at risk (OARs) by a factor of 2–3. The low-to-medium dose volumes (0.33–13.2 Gy_E) were more than doubled by IMRT plans.</p> <p>Conclusion</p> <p>In radiotherapy of NPC patients, three-field IMPT has greater potential than nine-field IMRT with respect to tumor coverage and reduction of the integral dose to OARs and non-specific normal tissues. The practicality of IMPT in NPC deserves further exploration when this technique becomes available on wider clinical scale.</p

Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma

This study estimated the risk of second primary malignancies after Hodgkin's lymphoma (HL) in relation to family history of cancer, age at diagnosis and latency, among 6946 patients treated for HL in Sweden in 1965–1995 identified through the Swedish Cancer Register (SCR). First-degree relatives (FDRs) to the HL patients and their malignancies were then ascertained together with their malignancies through the Multi-Generation Registry and SCR. The HL patient cohort was stratified on the number of FDRs with cancer, and standardised incidence ratios (SIRs) of developing SM were analysed. In the HL cohort, 781 SM were observed 1 year or longer after HL diagnosis. The risk for developing SM increased with the number of FDRs with cancer, SIRs being 2.26, 3.01, and 3.45 with 0, 1, or ⩾2 FDRs with cancer, respectively. Hodgkin's lymphoma long-term survivors treated at a young age with a family history of cancer carry an increased risk for developing SM and may represent a subgroup where standardised screening for the most common cancer sites could be offered in a stringent surveillance programme

High incidence of late effects found in Hodgkin's lymphoma survivors, following recall for breast cancer screening

Assessment of late effects in a cohort of female Hodgkin's lymphoma patients treated with mantle radiotherapy, identified from the DoH breast cancer screening recall showed high mortality and frequent undiagnosed abnormalities in tissues affected by radiotherapy. With increasing age, this patient group may suffer premature cardiac and respiratory morbidity

State-of-the-art management of nasopharyngeal carcinoma: current and future directions

Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer. Approximately 70% of patients with newly diagnosed NPC present with locally advanced disease. Phase III clinical trials support the addition of chemotherapy to radiotherapy for the initial treatment of these patients. Once metastatic disease develops, practices become varied. Further experience needs to be gained with both targeted therapies and immunotherapy to gauge whether they will improve treatment outcomes in NPC

Intensity modulated radiotherapy (IMRT) in the treatment of children and Adolescents - a single institution's experience and a review of the literature

<p>Abstract</p> <p>Background</p> <p>While IMRT is widely used in treating complex oncological cases in adults, it is not commonly used in pediatric radiation oncology for a variety of reasons. This report evaluates our 9 year experience using stereotactic-guided, inverse planned intensity-modulated radiotherapy (IMRT) in children and adolescents in the context of the current literature.</p> <p>Methods</p> <p>Between 1999 and 2008 thirty-one children and adolescents with a mean age of 14.2 years (1.5 - 20.5) were treated with IMRT in our department. This heterogeneous group of patients consisted of 20 different tumor entities, with Ewing's sarcoma being the largest (5 patients), followed by juvenile nasopharyngeal fibroma, esthesioneuroblastoma and rhabdomyosarcoma (3 patients each). In addition a review of the available literature reporting on technology, quality, toxicity, outcome and concerns of IMRT was performed.</p> <p>Results</p> <p>With IMRT individualized dose distributions and excellent sparing of organs at risk were obtained in the most challenging cases. This was achieved at the cost of an increased volume of normal tissue receiving low radiation doses. Local control was achieved in 21 patients. 5 patients died due to progressive distant metastases. No severe acute or chronic toxicity was observed.</p> <p>Conclusion</p> <p>IMRT in the treatment of children and adolescents is feasible and was applied safely within the last 9 years at our institution. Several reports in literature show the excellent possibilities of IMRT in selective sparing of organs at risk and achieving local control. In selected cases the quality of IMRT plans increases the therapeutic ratio and outweighs the risk of potentially increased rates of secondary malignancies by the augmented low dose exposure.</p