Dosiomics-based prediction of radiation-induced hypothyroidism in nasopharyngeal carcinoma patients

PurposeTo predict the incidence of radiation-induced hypothyroidism (RHT) in nasopharyngeal carcinoma (NPC) patients, dosiomics features based prediction models were established.Materials and methodsA total of 145 NPC patients treated with radiotherapy from January 2012 to January 2015 were included. Dosiomics features of the dose distribution within thyroid gland were extracted. The minimal-redundancy-maximal-relevance (mRMR) criterion was used to rank the extracted features and selected the most relevant features. Machine learning (ML) algorithms including logistic regression (LR), support vector machine (SVM), random forest (RF), and k-nearest neighbor (KNN) were utilized to establish prediction models, respectively. Nested sampling and hyper-tuning methods were adopted to train and validate the prediction models. The dosiomics-based (DO) prediction models were evaluated through comparing with the dose-volume factor-based (DV) models in terms of the area under the receiver operating characteristic (ROC) curve (AUC). The demographics factors (age and gender) were included in both DO model and DV model.ResultsAge, V45 and 37 dosiomics features exhibited significant correlations with RHT in univariate analysis. For prediction performance, DO prediction models exhibited better results with the best AUC value 0.7 while DV prediction models 0.61. In DO prediction models, the AUC values displayed a trend from ascending to descending with the increasing of selected features. The highest AUC value was achieved when the number of selected features was 3. In DV prediction model, similar trend was not observed.ConclusionThis study established a prediction model based on the dosiomics features with better performance than conventional dose-volume factors, leading to early predict the possible RHT among NPC patients who had received radiotherapy and take precaution measures for NPC patients.     

Immunoglobulin allotypes in patients with nasopharyngeal carcinoma

Gm phenotypes and the Km(1) allotype were studied in Tunisian patients with nasopharyngeal carcinoma (NPC). A highly significant association was found between the Km(1) allotype and the NPC disease. Two rare Gm haplotypes, Gm(1, 17; 11, 15, 21) and Gm(1, 3, 5, 11), were found to be significantly increased among the NPC patients.     

Increased expression of annexin A7 in temporal lobe tissue of patients with refractory epilepsy

Annexin A7 is a member of the family of annexins, which are thought to function in the regulation of calcium homeostasis and the fusion of vesicles. Refractory epilepsy may be related to the imbalance of calcium homeostasis. Our aims are to investigate the expression of Annexin A7 in epileptic brains in comparison with human controls and to explore Annexin A7's possible role in refractory epilepsy. We examined the expression of Annexin A7 via immunohistochemistry, double-label immunofluorescence and western blot. The expression of Annexin A7 was shown to be significantly increased in patients with refractory epilepsy. Double-label immunofluorescence and confocal microscopy disclosed Annexin A7 immunoreactivity in the neurons, which were recognized by the antibody of neuron specific enolase (NSE). The result showed that Annexin A7 may be involved in the pathophysiology of refractory epilepsy and may play a role in developing and maintaining the epilepsy.     

鼻咽癌患者鼻咽灌洗液菌群检测及结果分析

目的 采用聚合酶链式反应－变性梯度凝胶电泳（PCR-DGGE）技术,通过观察鼻咽癌患者与健康对照者鼻咽灌洗液菌群的变化,初步探讨菌群异常在鼻咽癌发生中的作用。方法 以7例明确诊断且尚未治疗的鼻咽鳞癌患者和5例健康对照者为研究对象,提取鼻咽灌洗液DNA,观察两组研究对象菌群分布差异,进行相似性、多样性分析。结果 鼻咽癌患者与健康对照者之间鼻咽灌洗液的菌群分布存在差异,与健康对照者比较,咽颊炎链球菌和不动杆菌数量增加,但嗜热链球菌数量减少。结论 鼻咽癌患者鼻咽灌洗液菌群分布与健康对照者比较出现明显差异,可为鼻咽癌预防及治疗提供实验依据。     

Aberrant cytosolic acyl-CoA thioester hydrolase in hippocampus of patients with mesial temporal lobe epilepsy

Summary. A series of enzyme alterations has been shown to be associated with several forms of epilepsy, in mesial temporal lobe epilepsy (MTLE), however, information is limited. It was therefore the aim of the study to determine brain enzyme protein expression using a proteomic screening approach. Hippocampi of controls and patients with drug-resistant MTLE were used for evaluation of protein expression. We applied two-dimensional electrophoresis (2-DE) with mass spectrometrical identification and immunoblotting. 2-DE revealed a remarkably decreased spot identified as cytosolic acyl-CoA thioester hydrolase (BACH; EC 3.1.2.2) in patients with MTLE. Western blotting showed absence of bands at 37kDa in MTLEs using an antibody against mouse BACH and at 140kDa in MTLEs using anti-rat BACH. This study demonstrates that BACHs were deranged in hippocampus of MTLE patients. This finding may well contribute to the understanding of the still elusive pathomechanisms involved in MTLE.J. W. Yang and T. Czech have equally contributed to the paper.     

Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy

Summary. Mesial temporal lobe epilepsy (MTLE), the most common form of epilepsy, is characterised by cytoarchitectural abnormalities including neuronal cell loss and reactive gliosis in hippocampus. Determination of aberrant cytoskeleton protein expression by proteomics techniques may help to understand pathomechanism that is still elusive. We searched for differential expression of hippocampal proteins by an analytical method based on two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry unambiguously identifying 77 proteins analysed in eight control and eight MTLE hippocampi. Proteins were quantified and we observed 18 proteins that were altered in MTLE. Cytoskeleton proteins tubulin α-1 chain, β-tubulin, profilin II, neuronal tropomodulin were significantly reduced and one actin spot was missing, whereas ezrin and vinculin were significantly increased in MTLE. Proteins of several classes as e.g. antioxidant proteins (peroxiredoxins 3 and 6), chaperons (T-complex protein 1-α, stress-induced-phosphoprotein 1), signaling protein MAP kinase kinase 1, synaptosomal proteins (synaptotagmin I, α-synuclein), NAD-dependent deacetylase sirtuin-2 and 26S protease regulatory subunit 7 protein, neuronal-specific septin 3 were altered in MTLE. Taken together, the findings may represent or lead to cytoskeletal impairment; aberrant antioxidant proteins, chaperons, MAP kinase kinase 1 and NAD-dependent deacetylase sirtuin-2 may have been involved in pathogenetic mechanisms and altered synaptosomal protein expression possibly reflects synaptic impairment in MTLE. J. W. Yang and T. Czech have equally contributed to the paper.     

Proton magnetic resonance spectroscopy in patients with solitary and sporadic temporal lobe epileptic seizures

Proton magnetic resonance spectroscopy (¹H MRS) is an optional diagnostic method for potential epilepsy surgery candidates. The aim of this study was to determine the credibility of ¹H MRS examination in a group of patients suffering from solitary and sporadic epileptic seizures generated in temporal lobe. We recorded a 100% sensitivity of ¹H MRS in a group of ten patients in terms of detection of a pathological process in the temporal lobe. ¹H MRS also enabled determination of lateralization of the pathological process in three patients with bilateral epileptiform abnormalities on electroencephalography. Based on these results we suggest new perspectives on ¹H MRS as a part of standard diagnostic algorithm for solitary and sporadic temporal lobe epileptic seizures, particularly in cases with normal electroencephalography and magnetic resonance imaging findings.     

Scanning electronic microscopy study of nasopharyngeal carcinoma

The nasopharyngeal carcinoma is a greatly interesting model of study. Its morphology has been studied in 8 patients affected by squamous cells carcinoma (4 cases) and by undifferentiated carcinoma (4 cases). By means of a fibre-optic pharyngoscope equipped with mechanical biopsy forceps, biopsies have been taken and subsequently studied by scanning electron microscopy (SEM). Squamous cells carcinoma is characterized by large, flattened elements, generally equipped with a network of microridges. Irregular microvilli or smooth apices have been observed too. Desquamating elements often accumulated in waves or vortices, as far as little cornified structures have been described. Undifferentiated carcinoma shows a great morpho-structural disorder. In a rugged surface, it is possible to observe element highly varying for size and shape. The apical plasmalemma is characterized by pleomorphic microvilli, while it must be emphasized the presence of little pseudopod-like extrusions of some cellular apices. Ciliated elements have been observed too, whose apical specializations are distorted or irregularly disposed. Necrotic zones are particularly frequent, in which bacteria or mycetes proliferate. The role of SEM in the study of this tumour is emphasized, because of the close relation between epithelial patterns and natural history of nasopharyngeal carcinoma.     

Successful recollection of remote autobiographical memories by amnesic patients with medial temporal lobe lesions

Current views about the organization of human memory make strikingly different predictions about the integrity of remote autobiographical memory following damage to the medial temporal lobe. We have carried out a detailed analysis of narrative content in memory-impaired patients for whom neuropsychological and neuroanatomical information is available. All eight patients were able to recall detailed memories from their early lives. The recollections of the patients and the recollections of 25 matched controls contained the same number of details (+/-5%) and were also similar by several other measures. The results support the view that autobiographical memories eventually become independent of the medial temporal lobe as time passes after learning. A number of other considerations suggest that the neocortex ultimately supports the capacity for recollecting remote autobiographical memory.     

Mitochondrial DNA profiling via genomic analysis in mesial temporal lobe epilepsy patients with hippocampal sclerosis

Introduction

Mitochondria have an essential role in neuronal excitability and neuronal survival. In addition to energy production, mitochondria also play a crucial role in the maintenance of intracellular calcium homeostasis, generation of reactive oxygen species and mechanisms of cell death. There is a relative paucity of data about the role of mitochondria in epilepsy. Mitochondrial genome analysis is rarely carried out in the investigation of some diseases. In mesial temporal lobe epilepsies (MTLE) cases, genome analysis has never been used previously. The aim of this study is to show mitochondrial dysfunctions using genome analysis in patients with MTLE-hippocampal sclerosis (HS).

Methods

44 patients with MTLE-HS and 86 matched healthy unrelated controls were included in this study. The patients were divided into four groups according to their clinical presentation as the following: Group 1 consists of patients with intractable epilepsy who refused operation; Group 2 of operated seizure free patients; Group 3 of operated patients with seizures; and Group 4 unoperated seizure free patients with or without antiepileptic drugs. Blood samples were used to isolate DNA. Parallel tagged sequencing was employed to allow pyrosequencing of 130 samples. Complete mtDNA is amplified in two overlapping fragments (11 and 9 kb). The PCR amplicons were pooled in equimolar ratios. Titanium kits were used to produce shotgun libraries according to the manufacturer's protocol.

Results

The average coverage in total was 130 ± 30 and an average of 2365127 bases and 337 bp fragment length was received from all samples. The mean mtDNA heteroplasmy in patients was 26.35 ± 12.3 and in controls 25.03 ± 9.34. Three mutations had prominently high significance in patient samples. The most significantly associated variation was located in the MT-ATP-8 gene (8502 A > T, Asn46Ile) whereas the other two were in the MT-ND4 (11994 C > T, Thr412Ile) and MT-ND5 (13231 A > C, Lys299Gln) genes.

Conclusions

We have observed that three mutations were significantly related to the presence of epilepsy. These mutations were found at the 8502, 11994, and 13231 bp of mtDNA, which resulted in amino acid changes at the MT-ATP-8, MT-ND4 and MT-ND5 genes. Finding mutations can lead us to knowing more about the pathophysiology of the MTLE disease.     

Distinctive microRNA expression in early stage nasopharyngeal carcinoma patients

The goal of this study was to investigate microRNAs (miRs) expression at different stages of nasopharyngeal carcinoma (NPC). MiR expression profiling at various stages of NPC was performed by miR array and further verified using quantitative real‐time RT‐PCR. Pathway enrichment analysis was carried out to identify the functional pathways regulated by the miRs. The expression of a selected group of identified miRs was verified in stage I NPC by in situ hybridization (ISH). A total of 449 miRs were identified with significantly different expressions between NPC tissues and normal pharyngeal tissues. Eighty‐four miRs were dysregulated only in stage I NPC, among which 45 miRs were up‐regulated and the other 39 were down‐regulated. Pathway enrichment assay revleaed that three significantly down‐regulated and three significantly up‐regulated miRs involved in 12 pathways associating with tumour formation and progression. Quantitative RT‐PCR confirmed the miR array result. In addition, the low expression levels of hsa‐miR‐4324, hsa‐miR‐203a and hsa‐miR‐199b‐5p were further validated in stage I NPC by ISH. This present study identifed the miR signature in stage I NPC, providing the basis for early detection and treatment of NPC.     

Effects of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma: A real-world study

BackgroundTo evaluate the value of locoregional radiotherapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (dmNPC) and identify predictive factors for additional LRRT after palliative chemotherapy (PCT).MethodsOverall survival (OS) was the primary endpoint. Patients who underwent PCT and LRRT were categorized as the PCT+LRRT group; patients who only received palliative chemotherapy were categorized as the PCT group. Oligometastatic diseases (OMD) was defined as ≤5 metastatic lesions and ≤2 metastatic organs.ResultsA total of 168 patients were included for this study. The median OS of patients in the PCT+LRRT group was significantly higher than those in the PCT group (57 months vs. 22 months, P<0.001). Multivariate analyses (MVA) showed that LRRT (HR=0.533, 95% CI: 0.319–0.889, P = 0.016) and OMD (HR=0.548, 95% CI: 0.331–0.907, P = 0.019) were independent prognostic factors for dmNPC. Furthermore, Kaplan–Meier analyses showed that the 3-year OS of patients who received LRRT was significantly better than those who did not receive LRRT in the OMD subgroup (66.3% vs. 25.2%, P<0.001). While, the 3-year OS of patients who received LRRT and without LRRT was no different in the polymetastatic disease (PMD) subgroup (38.9% vs.11.5%, P = 0.115). MVA showed that LRRT was a favorable prognosticator in the OMD subgroup (HR=0.308, 95% CI: 0.159–0.598; P<0.001), and not a favorable prognosticator in the PMD subgroup (HR=0.510, 95% CI: 0.256–1.014, P = 0.055).ConclusionsLRRT has the potential to prolong OS in NPC patients with de novo OMD. These results suggest that OMD is a potential indicator for filtering beneficiaries from LRRT.     

Increased production of nitric oxide correlates with tumor growth in Algerian patients with nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is thought to arise because of chronic inflammation. The correlation between nitric oxide (NO) production, a biomarker of inflammation and NPC development remains unexplored. To investigate this question, we performed a profile analysis on plasma collected from untreated, treated, remissive, cured and relapsing patients. Nitrites were measured to assess NO activity. We observed that increased nitrites concentrations in untreated and relapsing patients associated with tumor development. Moreover, nitrites levels were similar in remissive, cured and healthy individuals. Altogether, our results suggest that NO might be an interesting blood biomarker to monitor tumor growth in NPC patients.     

A quantitative morphometric comparative analysis of the primate temporal lobe

Given their importance in language comprehension, the human temporal lobes and/or some of their component structures might be expected to be larger than allometric predictions for a nonhuman anthropoid brain of human size. Whole brain, T1-weighted MRI scans were collected from 44 living anthropoid primates spanning 11 species. Easyvision software (Philips Medical Systems, The Netherlands) was used to measure the volume of the entire brain, the temporal lobes, the superior temporal gyri, and the temporal lobe white matter. The surface areas of both the entire temporal lobe and the superior temporal gyrus were also measured, as was temporal cortical gyrification.Allometric regressions of temporal lobe structures on brain volume consistently showed apes and monkeys to scale along different trajectories, with the monkeys typically lying at a higher elevation than the apes. Within the temporal lobe, overall volume, surface area, and white matter volume were significantly larger in humans than predicted by the ape regression lines. The largest departure from allometry in humans was for the temporal lobe white matter volume which, in addition to being significantly larger than predicted for brain size, was also significantly larger than predicted for temporal lobe volume. Among the nonhuman primate sample, Cebus have small temporal lobes for their brain size, and Macaca and Papio have large superior temporal gyri for their brain size. The observed departures from allometry might reflect neurobiological adaptations supporting species-specific communication in both humans and old world monkeys.