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The aim of the present study was to evaluate the efficacy and safety of a neoadjuvant gemcitabine and nedaplatin chemotherapy regimen, followed by concurrent chemoradiotherapy or radiotherapy alone, in locoregionally advanced nasopharyngeal carcinoma (NPC). Eighty-six patients with stage III, IVA or IVB NPC, who received neoadjuvant chemotherapy [gemcitabine, 1,000 mg/m² on day 1 (d1) and d5; nedaplatin, 25 mg/m² on d 1-3] every 3 weeks for at least two cycles, followed by intensity-modulated radiotherapy every 3 weeks, with or without concurrent nedaplatin (25 mg/m², d1-3) between September 2010 and December 2013, were retrospectively analyzed. By comparing pretreatment and post-treatment MRI images, it was shown that seven patients achieved a complete response (8.5%), while 66 achieved a partial response (80.5%), following completion of neoadjuvant chemotherapy (combined response rate, 89.0%). Grade 3-4 toxicities following neoadjuvant chemotherapy included neutropenia (29.1%), leukopenia (11.6%), liver dysfunction (9.3%), thrombocytopenia (9.3%) and nausea/vomiting (8.1%). The median follow-up was 18 months (range, 5-44 months). The 2-year relapse-free survival, distant metastasis-free survival, progression-free survival and overall survival rates were 96.6, 85.4, 83.3 and 96.1%, respectively. Compared with alternative neoadjuvant chemotherapy regimens in combination with radiotherapy or concurrent chemoradiotherapy, the present gemcitabine and nedaplatin did not provide additional survival benefit and led to a higher frequency of liver dysfunction. Therefore, neoadjuvant gemcitabine and nedaplatin should be used with caution in locoregionally advanced NPC. [ABSTRACT FROM AUTHOR]

A new diketopiperazine alkaloid named spirotryprostatin K (1), and five known alkaloids, spiro[5H,10H-dipyrrolo[1,2-a:1',2'-d]pyrazine-2(3H),2'-[2H]-indole]-3',5,10(1'H) trione (2), 6-methoxyspirotryprostatin B (3), pseurotin A (4), N-β-acetyltryptamine (5), and lumichrome (6) were isolated from the endophytic fungus Aspergillus fumigatus. The structure and the absolute configuration of spirotryprostatin K were established by extensive spectroscopic analyses, acid hydrolysis and ECD calculations. Pseurotin A exhibited indirect anti-inflammatory activity by suppressing the lipopolysaccharide-induced proinflammatory factors in BV2 microglial cells, with an IC50 of 5.20 μM. [ABSTRACT FROM AUTHOR]

Introduction. All adult medulloblastoma (AMB) patients should be treated with craniospinal irradiation (CSI) postoperatively. Because of the long irradiation range, multiple radiation fields must be designed for conventional radiotherapy technology. CSI can be completed in only one session with helical tomotherapy (HT). We evaluated the dose of HT, volumetric intensity modulated arc therapy (VMAT), and three-dimensional conformal radiotherapy (3D-CRT) of AMB and the results of 5 cases of AMB treated with HT. Methods. Complete craniospinal and posterior cranial fossa irradiation with HT, VMAT, and 3D-CRT and dose evaluation were performed. And results of 5 cases of AMB treated with HT were evaluated. Results. A large volume of tissue was exposed to low dose radiation in the organs at risk (OAR), while a small volume was exposed to high dose radiation with HT. The conformity and uniformity of the targets were good with HT and VMAT, and the volume of targets exposed to high dose with VMAT was larger than that of HT. The uniformity of 3D-CRT was also good, but the dose conformity was poor. The main toxicity was hematologic toxicity, without 4th-degree bone marrow suppression. There was 3rd-degree inhibition in the white blood cells, hemoglobin, and platelets. The three female patients suffered menstrual disorders during the course of radiation. Two female patients with heavy menstruation suffered 3rd-degree anemia inhibition, and 2 patients suffered amenorrhea after radiotherapy. Although menstrual cycle was normal, the third patient was not pregnant. Conclusion. CSI with HT is convenient for clinical practice, and the side effects are mild. With good conformity and uniformity, VMAT can also be used for selection in CSI. For poor conformity, 3D-CRT should not be the priority selection for CSI. In female patients, the ovaries should be protected. [ABSTRACT FROM AUTHOR]

Purpose: To study and report the clinical outcomes and patterns of failure in the patients with nasopharyngeal carcinoma (NPC) staged by magnetic resonance imaging (MRI) and treated with intensity-modulated radiotherapy (IMRT).Materials and Methods: From January 2007 to December 2011, 720 NPC patients without metastasis staged by MRI were treated with definitive IMRT at Zhejiang Cancer Hospital. The IMRT prescribed dose was 69 Gy to planning target volume (PTV) of gross disease in nasopharynx and 67.5 Gy to PTV of positive lymph nodes in 30 fractions, high risk, and low risk region PTV was 60 and 54 Gy in 30 fractions, respectively. The treatment outcomes and patterns of failure were observed.Results: Using the 7th edition of the American Joint Committee on Cancer staging system for NPC, the proportions of the 720 patients with Stages I, II, III, and IVa-b disease were 2.1% (15/720), 17.8% (128/720), 51.7% (372/720), and 28.5% (205/720), respectively. After the median follow-up period of 48 months (range: 3-89 months), a total of 146/720 (20.3%) patients had experienced failure: 37 (5.1%) at primary sites, 17 (2.4%) at regional sites, 79 (11.0%) at distant sites, and 13 (1.8%) at multiple sites. The 5-year overall survival, cancer-specific survival, disease-free survival, local relapse-free survival (LRFS), regional relapse-free survival, and distant metastasis (DM) free survival were 86.1%, 88.1%, 76.6%, 90.8%, 93.6%, and 87.2%, respectively. LRFS of T1 to T3 was all >90% and has no significant difference. In addition to N stage, T category, and neoadjuvant chemotherapy were independent predictors for DM in multivariate analysis.Conclusion: Our long-term outcome of large NPC series supports the effectiveness of IMRT for excellent local-regional control though up to 20% patients would develop DM, which becomes the main pattern of failure. T4 disease remained difficult to be cured not only for local recurrence but distant failure. A taxane-based combination chemotherapy might be useful to reduce DM in the induction setting and worth further studying. [ABSTRACT FROM AUTHOR]

Purpose: To study and report the clinical outcomes and patterns of failure in the patients with nasopharyngeal carcinoma (NPC) staged by magnetic resonance imaging (MRI) and treated with intensity-modulated radiotherapy (IMRT). Materials and Methods: From January 2007 to December 2011, 720 NPC patients without metastasis staged by MRI were treated with definitive IMRT at Zhejiang Cancer Hospital. The IMRT prescribed dose was 69 Gy to planning target volume (PTV) of gross disease in nasopharynx and 67.5 Gy to PTV of positive lymph nodes in 30 fractions, high risk, and low risk region PTV was 60 and 54 Gy in 30 fractions, respectively. The treatment outcomes and patterns of failure were observed. Results: Using the 7th edition of the American Joint Committee on Cancer staging system for NPC, the proportions of the 720 patients with Stages I, II, III, and IVa-b disease were 2.1% (15/720), 17.8% (128/720), 51.7% (372/720), and 28.5% (205/720), respectively. After the median follow-up period of 48 months (range: 3-89 months), a total of 146/720 (20.3%) patients had experienced failure: 37 (5.1%) at primary sites, 17 (2.4%) at regional sites, 79 (11.0%) at distant sites, and 13 (1.8%) at multiple sites. The 5-year overall survival, cancer-specific survival, disease-free survival, local relapse-free survival (LRFS), regional relapse-free survival, and distant metastasis (DM) free survival were 86.1%, 88.1%, 76.6%, 90.8%, 93.6%, and 87.2%, respectively. LRFS of T1 to T3 was all >90% and has no significant difference. In addition to N stage, T category, and neoadjuvant chemotherapy were independent predictors for DM in multivariate analysis. Conclusion: Our long-term outcome of large NPC series supports the effectiveness of IMRT for excellent local-regional control though up to 20% patients would develop DM, which becomes the main pattern of failure. T4 disease remained difficult to be cured not only for local recurrence but distant failure. A taxane-based combination chemotherapy might be useful to reduce DM in the induction setting and worth further studying. [ABSTRACT FROM AUTHOR]

ial septal defect (ASD) is a common cardiovascular malformation and an important contributor to substantial morbidity and mortality. Increasing evidence demonstrates that mutated NKX2-5, a gene encoding a homeobox transcription factor crucial to cardiogenesis, is a significant genetic determinant for congenital ASD. Nevertheless, the genetic basis for ASD in a majority of ASD patients remains largely unknown. In the current study, the entire coding region of NKX2-5 was sequenced initially for 58 unrelated probands with familial ASD. The relatives of the probands harboring identified mutations and 200 unrelated control individuals were subsequently genotyped. Three novel heterozygous NKX2-5 mutations (p.P43GfsX59, p.C46 W, and p.S179F) were identified respectively in three families with autosomal dominantly inherited ASD. These mutations, absent in 200 control individuals, cosegregated with ASD in the families that had complete penetrance. The findings expand the spectrum of mutations in NKX2-5 linked to ASD and contribute to genetic counseling, clinical interventions, and prenatal prevention of ASD for individuals with genetic susceptibility. [ABSTRACT FROM AUTHOR]