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With fast recovery time and effective in situ tumor tissue killing ability, thermal ablation has become a popular treatment for tumors compared with chemotherapy and radiation. The thermal dose measurement of current technology is usually accompanied by monitoring a large area impedance across two ablation catheters and the localized impedance measurement is difficult to achieve. In this work, thermal‐resistive sensor and impedance sensor are fabricated on the curved surface of a capillary tube with 1 mm outer diameter. The device is applied for real‐time in situ tissue impedance monitoring during thermal ablation. The calibrated thermal‐resistive sensors have an average temperature coefficient of resistance (TCR) of 0.00161 ± 5.9% °C‐1 with an accuracy of ±0.7 °C. By adding electro‐polymerized PEDOT:PSS (poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate)) on the 300 µm diameter gold electrodes, the interface impedance reduces two orders from 408 to 3.7 kΩ at 100 Hz. The Randles equivalent circuit model fittings show a two‐order improvement in the electrode capacitance from 7.29 to 753 nF. In the ex vivo porcine liver laser ablation test, the temperature of the porcine liver tissue can reach 70°C and the impedance would drop by 50% in less than 5 minutes. The integration of laser ablation fiber with the impedance and temperature sensors can further expand the laser ablation technique to smaller scale and for precise therapeutics.

Background Gliosarcoma (GSM) is a distinct and aggressive variant of glioblastoma multiforme (GBM) with worse prognosis and few treatment options. It is often managed with the same treatment modalities with temozolomide (TMZ) as in GBM. However, the therapeutic benefits on GSM from such treatment regimen is largely unknown. Patient-derived xenograft (PDX) models have been used widely to model tumor progression, and subsequently to validate biomarkers and inform potential therapeutic regimens. Here, we report for the first time the successful development of a PDX model of secondary GSM. Methods Tissue obtained from a tumor resection revealed a secondary GSM arising from GBM. The clinical, radiological, and histopathological records of the patient were retrospectively reviewed. Samples obtained from surgery were cultured ex vivo and/or implanted subcutaneously in immunocompromised mice. Histopathological features between the primary GBM, secondary GSM, and GSM PDX are compared. Results In explant culture, the cells displayed a spindle-shaped morphology under phase contrast microscopy, consistent with the sarcomatous component. GSM samples were subcutaneously engrafted into immunocompromised mice after single-cell suspension. Xenografts of serial passages showed enhanced growth rate with increased in vivo passage. We did not observe any histopathological differences between the secondary GSM and its serial in vivo passages of PDX tumors. Conclusions Our PDX model for GSM retained the histopathological characteristics of the engrafted tumor from the patient. It may provide valuable information to facilitate molecular and histopathological modelling of GSM and be of significant implication in future research to establish precise cancer medicine for this highly malignant tumor.

Trauma and Injury Severity Score (TRISS) has been the benchmark of mortality riskin trauma centers for over 30 years. TRISS utilizes the Injury Severity Score (ISS) as an index ofanatomical injury. This study investigated the efficacy of a new type of index of anatomical injury called the ICD-derived Injury Severity Score (ICISS) compared to the ISS using a logisticregression analysis and a global chi-square test of the areas under the Receiver OperatorCharacteristic (ROC) curves. We found that the empirically derived ICISS performed as well as the consensus derived ISS with no statistical differences between their respective area under the ROC curves.

This was followed by an interactive discussion of investigation and management plan. Appropriate radiological imaging such as an MRI brain scan was shown to the group using the “share‐screen” function. Other clinical information such as laboratory results can likewise be displayed. The session was completed after thorough discussion on the appropriate treatment plan with respect to the patient’s scenario.

The bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) is a mitochondrial one-carbon folate metabolic enzyme whose role in cancer was not known until recently. MTHFD2 is highly expressed in embryos and a wide range of tumors but has low or absent expression in most adult differentiated tissues. Elevated MTHFD2 expression is associated with poor prognosis in both hematological and solid malignancy. Its depletion leads to suppression of multiple malignant phenotypes including proliferation, invasion, migration, and induction of cancer cell death. The non-metabolic functions of this enzyme, especially in cancers, have thus generated considerable research interests. This review summarizes current knowledge on both the metabolic functions and non-enzymatic roles of MTHFD2. Its expression, potential functions, and regulatory mechanism in cancers are highlighted. The development of MTHFD2 inhibitors and their implications in pre-clinical models are also discussed.

Background The detection of large vessel occlusion (LVO) plays a critical role in the diagnosis and treatment of acute ischemic stroke (AIS). Identifying LVO in the pre-hospital setting or early stage of hospitalization would increase the patients' chance of receiving appropriate reperfusion therapy and thereby improve neurological recovery. Methods To enable rapid identification of LVO, we established an automated evaluation system based on all recorded AIS patients in Hong Kong Hospital Authority's hospitals in 2016. The 300 study samples were randomly selected based on a disproportionate sampling plan within the integrated electronic health record system, and then separated into a group of 200 patients for model training, and another group of 100 patients for model performance evaluation. The evaluation system contained three hierarchical models based on patients' demographic data, clinical data and non-contrast CT (NCCT) scans. The first two levels of modeling utilized structured demographic and clinical data, while the third level involved additional NCCT imaging features obtained from deep learning model. All three levels' modeling adopted multiple machine learning techniques, including logistic regression, random forest, support vector machine (SVM), and eXtreme Gradient Boosting (XGboost). The optimal cut-off for the likelihood of LVO was determined by the maximal Youden index based on 10-fold cross-validation. Comparisons of performance on the testing group were made between these techniques. Results Among the 300 patients, there were 160 women and 140 men aged from 27 to 104 years (mean 76.0 with standard deviation 13.4). LVO was present in 130 (43.3%) patients. Together with clinical and imaging features, the XGBoost model at the third level of evaluation achieved the best model performance on testing group. The Youden index, accuracy, sensitivity, specificity, F1 score, and area under the curve (AUC) were 0.638, 0.800, 0.953, 0.684, 0.804, and 0.847, respectively. Conclusion To the best of our knowledge, this is the first study combining both structured clinical data with non-structured NCCT imaging data for the diagnosis of LVO in the acute setting, with superior performance compared to previously reported approaches. Our system is capable of automatically providing preliminary evaluations at different pre-hospital stages for potential AIS patients.

Background Massive occurrences of interstitial loss of heterozygosity (LOH) likely resulting from gene conversions were found by us in different cancers as a type of single-nucleotide variations (SNVs), comparable in abundance to the commonly investigated gain of heterozygosity (GOH) type of SNVs, raising the question of the relationships between these two opposing types of cancer mutations. Methods In the present study, SNVs in 12 tetra sample and 17 trio sample sets from four cancer types along with copy number variations (CNVs) were analyzed by AluScan sequencing, comparing tumor with white blood cells as well as tissues vicinal to the tumor. Four published “nontumor”-tumor metastasis trios and 246 pan-cancer pairs analyzed by whole-genome sequencing (WGS) and 67 trios by whole-exome sequencing (WES) were also examined. Results Widespread GOHs enriched with CG-to-TG changes and associated with nearby CNVs and LOHs enriched with TG-to-CG changes were observed. Occurrences of GOH were 1.9-fold higher than LOH in “nontumor” tissues more than 2 cm away from the tumors, and a majority of these GOHs and LOHs were reversed in “paratumor” tissues within 2 cm of the tumors, forming forward-reverse mutation cycles where the revertant LOHs displayed strong lineage effects that pointed to a sequential instead of parallel development from “nontumor” to “paratumor” and onto tumor cells, which was also supported by the relative frequencies of 26 distinct classes of CNVs between these three types of cell populations. Conclusions These findings suggest that developing cancer cells undergo sequential changes that enable the “nontumor” cells to acquire a wide range of forward mutations including ones that are essential for oncogenicity, followed by revertant mutations in the “paratumor” cells to avoid growth retardation by excessive mutation load. Such utilization of forward-reverse mutation cycles as an adaptive mechanism was also observed in cultured HeLa cells upon successive replatings. An understanding of forward-reverse mutation cycles in cancer development could provide a genomic basis for improved early diagnosis, staging, and treatment of cancers. Electronic supplementary material The online version of this article (10.1186/s40246-018-0170-6) contains supplementary material, which is available to authorized users.

Background: The alkylating agent temozolomide (TMZ) is widely used in glioblastoma multiforme (GBM) therapy. Unfortunately, TMZ-resistance frequently occurs in recurrent GBM and is the major cause of treatment failure. The anti-malarial drug quinacrine (QC) harbors antitumor and chemosensitivity properties, but its interactions with TMZ in GBM remain unclear. This study aimed to investigate whether QC would sensitize TMZ in TMZ-sensitive and TMZ-resistant GBM cells as well as the underlying mechanisms. Materials and Methods: The cytotoxicity of QC and TMZ in TMZ-sensitive and TMZ-resistant GBM cells was evaluated using in vitro cell viability assay and colony formation assay. Cellular apoptosis and protein expression levels were determined using TUNEL assay and immunoblotting, respectively. Results: QC substantially enhanced TMZ cytotoxicity in both TMZ-sensitive and TMZ-resistant cells. Such cytotoxic effect was accompanied by changes in the expression levels of LC3II, p62 and cleaved caspase 3, and increased cellular apoptosis. The results suggested that QC could sensitize GBM cells to TMZ at least partially through apoptosis induction, in which autophagy inhibition might be involved. Conclusion: The antimalarial drug QC may hold promise as a potentiation of TMZ treatment in GBM, especially in cases of TMZ-resistance.

BACKGROUND High-grade glioma is currently incurable. It was reported that glioma may be auxotrophic to arginine due to the lack of urea cycle genes expressions, suggesting arginase may be a potential agent for high grade glioma. AIM: We investigated the efficacy of pegylated arginase I (pegArg-I) or in combination with other anti-cancer drugs for high-grade glioma in vitro and in vivo. METHODS 4 high-grade glioma cell lines (U87, U373, U138, D54) were treated with pegArg-I in vitro. The molecular mechanism of pegArg-I-induced cytotoxicity was tested in U87. The ultra-morphological changes of pegArg-I-treated U87 was investigated by both scanning and transmission electron microscopy. Orthotopic glioma xenograft model with luciferase-transfected U87 cell line was tested for anti-cancer efficacy of peg-Arg I in vivo. RESULTS We showed that pegArg-I induced significant cell death in all 4 cell lines in vitro. Temozolomide, difluoromethyornithine and chloroquine (CQ) were then tested together with pegArg-I in U87 in vitro. We found that only CQ showed additive effect with pegArg-I against glioma in vitro. Such additive cytotoxic effect may be associated with enhanced autophagy and necrosis as shown in transmission electron microscopy and autophagy markers’ expression by Western blotting. PegArg-I prolonged the survival of glioma mice, suggesting its possible anti-glioma efficacy. However, CQ+pegArg-I didn’t show further significant anti-cancer efficacy in vivo. CONCLUSION PegArg-I may be useful in slowing the progression of glioma, but additional drug candidate which works synergistically with pegArg-I remains to be explored.

The burnout syndrome is characterized by emotional exhaustion, depersonalization, and reduced personal achievement. Uncertainty exists about the prevalence of burnout among medical and surgical residents. Associations between burnout and gender, age, specialty, and geographical location of training are unclear. In this meta-analysis, we aimed to quantitatively summarize the global prevalence rates of burnout among residents, by specialty and its contributing factors. We searched PubMed, PsycINFO, Embase, and Web of Science to identify studies that examined the prevalence of burnout among residents from various specialties and countries. The primary outcome assessed was the aggregate prevalence of burnout among all residents. The random effects model was used to calculate the aggregate prevalence, and heterogeneity was assessed by I2 statistic and Cochran’s Q statistic. We also performed meta-regression and subgroup analysis. The aggregate prevalence of burnout was 51.0% (95% CI: 45.0−57.0%, I2 = 97%) in 22,778 residents. Meta-regression found that the mean age (β = 0.34, 95% CI: 0.28−0.40, p < 0.001) and the proportion of males (β = 0.4, 95% CI = 0.10−0.69, p = 0.009) were significant moderators. Subgroup analysis by specialty showed that radiology (77.16%, 95% CI: 5.99−99.45), neurology (71.93%, 95% CI: 65.78−77.39), and general surgery (58.39%, 95% CI: 45.72−70.04) were the top three specialties with the highest prevalence of burnout. In contrast, psychiatry (42.05%, 95% CI: 33.09−51.58), oncology (38.36%, 95% CI: 32.69−44.37), and family medicine (35.97%, 95% CI: 13.89−66.18) had the lowest prevalence of burnout. Subgroup analysis also found that the prevalence of burnout in several Asian countries was 57.18% (95% CI: 45.8−67.85); in several European countries it was 27.72% (95% CI: 17.4−41.11) and in North America it was 51.64% (46.96−56.28). Our findings suggest a high prevalence of burnout among medical and surgical residents. Older and male residents suffered more than their respective counterparts.

Long non-coding RNAs (LncRNAs) represent a novel class of RNAs with no functional protein-coding ability, yet it has become increasingly clear that interactions between lncRNAs with other molecules are responsible for important gene regulatory functions in various contexts. Given their relatively high expressions in the brain, lncRNAs are now thought to play important roles in normal brain development as well as diverse disease processes including gliomagenesis. Intriguingly, certain lncRNAs are closely associated with the initiation, differentiation, progression, recurrence and stem-like characteristics in glioma, and may therefore be exploited for the purposes of sub-classification, diagnosis and prognosis. LncRNAs may also serve as potential therapeutic targets as well as a novel biomarkers in the treatment of glioma. In this article, the functional aspects of lncRNAs, particularly within the central nervous system (CNS), will be briefly discussed, followed by highlights of the important roles of lncRNAs in mediating critical steps during glioma development. In addition, the key lncRNA players and their possible mechanistic pathways associated with gliomagenesis will be addressed.

Adducin (ADD) is a family of membrane skeleton proteins including ADD1, ADD2, and ADD3 that are encoded by distinct genes on different chromosomes. Adducin is primarily responsible for the assembly of spectrin-actin network that provides physical support to the plasma membrane and mediates signal transduction in various cellular physiological processes upon regulation by protein kinase C-dependent and calcium/calmodulin-dependent pathways. Abnormal phosphorylation, genetic variations, and alternative splicing of adducin may contribute to alterations in cellular functions involved in pathogenic processes. These alterations are associated with a wide range of diseases including cancer. This paper begins with a discussion on how adducin partakes in the structural formation of membrane skeleton, its regulation, and related functional characteristics, followed by a review on the pathogenesis of hypertension, biliary atresia, and cancer with respect to increased disease susceptibility mediated by adducin polymorphism and/or dysregulation. Given the functional diversity of adducin in different cellular compartments, we aim to provide a knowledge base whereby its pathophysiological roles can be better understood. More importantly, we aim to provide novel insights that may be of significance in turning the adducin model to clinical application.

Temozolomide (TMZ) is the first-line chemotherapeutic agent in the treatment of glioblastoma multiforme (GBM). Despite its cytotoxic effect, TMZ also induces cell cycle arrest that may lead to the development of chemoresistance and eventual tumor recurrence. Caffeine, a widely consumed neurostimulant, shows anticancer activities and is reported to work synergistically with cisplatin and camptothecin. The present study aimed to investigate the effects and the mechanisms of action of caffeine used in combination with TMZ in U87-MG GBM cells. As anticipated, TMZ caused DNA damage mediated by the ATM/p53/p21 signaling pathway and induced significant G2 delay. Concurrent treatment with caffeine repressed proliferation and lowered clonogenic capacity on MTT and colony formation assays, respectively. Mechanistic study showed that coadministration of caffeine and TMZ suppressed the phosphorylation of ATM and p53 and downregulated p21 expression, thus releasing DNA-damaged cells from G2 arrest into premature mitosis. Cell cycle analysis demonstrated that the proportion of cells arrested in G2 phase decreased when caffeine was administered together with TMZ; at the same time, the amount of cells with micronucleation and multipolar spindle poles increased, indicative of enhanced mitotic cell death. Pretreatment of cells with caffeine further enhanced mitotic catastrophe development in combined treatment and sensitized cells to apoptosis when followed by TMZ alone. In conclusion, our study demonstrated that caffeine enhanced the efficacy of TMZ through mitotic cell death by impeding ATM/p53/p21-mediated G2 arrest.

Glioblastoma multiforme (GBM) is the commonest primary brain tumour in adults characterized by relentless recurrence due to resistance towards the standard chemotherapeutic agent temozolomide (TMZ). Prolyl 4-hydroxylase, beta polypeptide (P4HB), an endoplasmic reticulum (ER) chaperone, is known to be upregulated in TMZ-resistant GBM cells. MicroRNAs (miRNAs) are non-protein-coding transcripts that may play important roles in GBM chemoresistance. We surmised that miRNA dysregulations may contribute to P4HB upregulation, hence chemoresistance. We found that miRNA-210 (miR-210) was P4HB-targeting and was highly downregulated in TMZ-resistant GBM cells. Forced overexpression of miR-210 led to P4HB downregulation and a reduction in TMZ-resistance. A reciprocal relationship between their expressions was also verified in clinical glioma specimens. Our study is the first to demonstrate a potential link between miR-210 and ER chaperone in determining chemosensitivity in GBM. The findings have important translational implications in suggesting new directions of future studies.

Earlier, prominent occurrences of interstitial loss-of-heterozygosities (LOHs) were found in different cancers as a type of single-nucleotide-variations (SNVs), at rates far exceeding those of the commonly investigated gain-of-heterozygosities (GOHs) type of SNVs. Herein, such co-occurrences of LOHs and GOHs were confirmed in 102 cases of four cancer types analyzed with three different next-generation sequencing platforms, comparing non-tumor, paratumor, and tumor tissues with white-blood-cell controls; and in 246 pan-cancer cases of whole-genome tumor-control pairs. Unexpectedly, large numbers of SNVs enriched with CG>TG GOHs and copy-number-variations (CNVs) proximal to these GOHs were detected in the non-tumor tissues, which were extensively reversed in paratumors showing prominent TG>CG LOHs with proximal CNVs, and less so in tumors to form forward-reverse mutation cycles. Lineage effects in the reversions, likely resulting from directional selection, supported a sequential rather than parallel mode of evolution as described in a 'Stage Specific Populations' model of cancer development.

© 2015 Elsevier Inc. All rights reserved. Background Implicit motor learning is characterized by low dependence on working memory and stable performance despite stress, fatigue, or multi-tasking. However, current paradigms for implicit motor learning are based on behavioral interventions that are often task-specific and limited when applied in practice. Objective To investigate whether cathodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) area during motor learning suppressed working memory activity and reduced explicit verbal-analytical involvement in movement control, thereby promoting implicit motor learning. Methods Twenty-seven healthy individuals practiced a golf putting task during a Training Phase while receiving either real cathodal tDCS stimulation over the left DLPFC area or sham stimulation. Their performance was assessed during a Test phase on another day. Verbal working memory capacity was assessed before and after the Training Phase, and before the Test Phase. Results Compared to sham stimulation, real stimulation suppressed verbal working memory activity after the Training Phase, but enhanced golf putting performance during the Training Phase and the Test Phase, especially when participants were required to multi-task. Conclusion Cathodal tDCS over the left DLPFC may foster implicit motor learning and performance in complex real-life motor tasks that occur during sports, surgery or motor rehabilitation.

Introduction The pipeline embolization device (PED) is a new endovascular stent designed for the treatment of challenging intracranial aneurysms (IAs). Its use has been extended to nonruptured and ruptured IAs of a variety of configurations and etiologies in both the anterior and posterior circulations. Methods We conducted a systematic review of ten eligible reports on its clinical efficacy and safety. Results There were 414 patients with 448 IAs. The majority of the IAs were large (40.2 %), saccular or blister-like (78.3 %), and were located mostly in the anterior circulation (83.5 %). The regimens of antiplatelet therapy varied greatly between and within studies. The mean number of the PED used was 2.0 per IA. Deployment was successful in around 95 % of procedures. Aneurysm obliteration was achieved in 82.9 % of IAs at 6-month. The overall incidences of periprocedural intracranial vascular complication rate and mortality rate were 6.3 and 1.5 %, respectively. Conclusion The PED is a safe and effective treatment for nonruptured IAs. Its use in the context of acute subarachnoid hemorrhage (SAH) should be cautioned. Its main limitations include the need for prolonged antiplatelet therapy, as well as the potential risks of IA rupture and non-IA-related intracerebral hemorrhages (ICH). Future studies should aim at identifying factors that predispose to incomplete obliteration, delayed rupture, and thromboembolic complications.

Surgical resections of large-to-giant pituitary adenomas (PA) are technically challenging procedures. Tumors with a fibrous consistency or ‘hour-glass’ configurations are particularly difficult to remove completely and safely through the transsphenoidal route alone. Although the transcranial approach can facilitate the removal of a large suprasellar mass, it may be associated with significant bleeding within the intradural space. A simultaneous microscopic transcranial and transsphenoidal approach has been described as an alternative surgical strategy. We have further modified this ‘above and below’ approach by adopting endoscopic techniques for the transsphenoidal part of the procedure. This modified approach has the advantages of requiring only one operating microscope, and permitting freer maneuvers and easier orientation for both surgical teams. We present two patients successfully treated with this approach. Complete tumor removal was achieved and both patients achieved satisfactory functional recovery.

ZFPM2, encoding a zinc finger protein and abundantly expressed in the brain, uterus and smooth muscles, plays important roles in cardiac and gonadal development. Abnormal expression of ZFPM2 in ovarian tumors and neuroblastoma has been reported but hitherto its genetic association with cancer and effects on gliomas have not been studied. In the present study, the hexamer insertion-deletion polymorphism rs71305152, located within a large haplotype block spanning intron 1 to intron 3 of ZFPM2, was genotyped in Chinese cohorts of glioma (n = 350), non-glioma cancer (n = 354) and healthy control (n = 463) by direct sequencing and length polymorphism in gel electrophoresis, and ZFPM2 expression in glioma tissues (n = 69) of different grades was quantified by real-time RT-PCR. Moreover, potential natural selection pressure acting on the gene was investigated. Disease-association analysis showed that the overall genotype of rs71305152 was significantly associated with gliomas (P = 0.016), and the heterozygous genotype compared to the combined homozygous genotypes was less frequent in gliomas than in controls (P = 0.005) or non-glioma cancers (P = 0.020). ZFPM2 mRNA expression was negatively correlated with the grades of gliomas (P = 0.002), with higher expression levels in the low-grade gliomas. In the astrocytoma subtype, higher ZFPM2 expression was also correlated with the rs71305152 heterozygous genotype (P = 0.028). In addition, summary statistics tests gave highly positive values, demonstrating that the gene is under the influence of balancing selection. These findings suggest that ZFPM2 is a glioma susceptibility gene, its genotype and expression showing associations with incidence and severity, respectively. Moreover, the balancing selection acting on ZFPM2 may be related to the important roles it has to play in multiple organ development or associated disease etiology.

In multiple myeloma, a long non-coding RNA, KIAA0495 (alias PDAM/TP73-AS1), had been found progressively downregulated from normal plasma cell to benign monoclonal gammopathy of undetermined significance to symptomatic myeloma. Herein, by methylation-specific PCR, the putative KIAA0495 promoter was found unmethylated in all healthy controls (N = 14) but methylated in 50 % of myeloma cell lines (N = 10). KIAA0495 methylation was shown inversely correlated with KIAA0495 expression. However, KIAA0495 methylation was detected in none of both primary myeloma samples at diagnosis (N = 61) and at relapse/progression (N = 16). Collectively, despite frequently methylated in cell lines, KIAA0495 methylation appeared unimportant in the pathogenesis or progression of myeloma. Electronic supplementary material The online version of this article (doi:10.1186/s12943-015-0444-8) contains supplementary material, which is available to authorized users.

BACKGROUND: Tumor invasion and vascularization are typical hallmarks in malignant glioma with the majority showing elevated expression and activation of the epidermal growth factor receptor (EGFR). Our group has previously shown that prolyl 4-hydroxylase, beta polypeptide (P4HB), an endoplasmic reticulum (ER) chaperone, was intimately related to chemoresistance in malignant glioma. The role of P4HB in determining other glioblastoma malignant phenotypes, however, remains unknown. METHODS: We studied both the in vitro and in vivo behaviors of globlastoma cells with established P4HB-overexpression. We also studied P4HB expression profiles in clinical specimens and publicly available microarray database. Hierarchical clustering graphically was performed to detect differential gene expression patterns between low and high P4HB tumors. The effect of P4HB in determining EGFR signaling and functioning were also studied. RESULTS: We found that inhibition of P4HB would dyregulate EGFR/MAPK-mediated angiogenic and invasive phenotypes of malignant glioma. Clinical analysis on human glioma specimens and Gene Expression Omnibus (GEO) expression profiles showed that excessive P4HB were correlated with high-grade malignancy, angiogenesis and invasion. Functionally, upregulation of P4HB conferred glioma cells with malignant characteristics including proliferation, invasion and angiogenesis in vitro, and tumor growth in orthotopic mouse model. Genetic and pharmacologic inhibitions of oncogenic P4HB were found to suppress EGFR/MAPK signaling. CONCLUSION: Our study is the first to describe a mechanistic link between P4HB-EGFR-mediated MAPK activation and glioma progression, invasion and angiogenesis. The findings uncovered a novel and promising anti-glioma mechanism related to P4HB-mediated retardation of EGFR/MAPK signal transduction. Targeting P4HB with small molecular agents may provide an alternative therapeutic approach by deactivating several critical downstream events that mediate the aggressive and resistant behaviors of glioblastoma.

Background To review currently available evidence on the use of adjuvant therapy to reduce the formation of postoperative intra-abdominal adhesions. Methods A search on Pubmed and the Cochrane library was undertaken using the keywords “abdominal”, “adhesion”, “postoperative”, “prevention” and “reduction”. Only randomised controlled trials, prospective non-randomised controlled studies and review articles published in the English language between 1990 and 2006 were included. Results Two prospective non-randomised controlled studies and 18 randomised controlled trials were included in this review. Adjuvant therapies reviewed included pharmacological agents (streptokinase, recombinant tissue plasminogen activator, vitamin E antioxidant molecules), and mechanical barriers (hyaluronic acid barriers, oxidised regenerated cellulose barriers, nanofibrous barriers and collagen foils). Hyaluronate/carboxymethylcellulose-based bioresorbable membrane (Seprafilm) appeared to be the most efficacious in reducing adhesion formation as well as decreasing the incidence of adhesion obstruction requiring reoperation in clinical studies. Drawbacks to the use of Seprafilm include high cost and complications such as haemorrhage and poor wound healing. Conclusions Only a limited number of adjuvant treatment methods are currently available for the reduction of postoperative adhesions. Seprafilm has been proven to be the efficacious method to reduce adhesions. Investigations into the novel therapies are showing promising results in experimental studies and clinical studies before their wider application.

Temozolomide (TMZ) is the standard chemotherapeutic agent for human malignant glioma, but intrinsic or acquired chemoresistance represents a major obstacle to successful treatment of this highly lethal group of tumours. Obtaining better understanding of the molecular mechanisms underlying TMZ resistance in malignant glioma is important for the development of better treatment strategies. We have successfully established a passage control line (D54-C10) and resistant variants (D54-P5 and D54-P10) from the parental TMZ-sensitive malignant glioma cell line D54-C0. The resistant sub-cell lines showed alterations in cell morphology, enhanced cell adhesion, increased migration capacities, and cell cycle arrests. Proteomic analysis identified a set of proteins that showed gradual changes in expression according to their 50% inhibitory concentration (IC(50)). Successful validation was provided by transcript profiling in another malignant glioma cell line U87-MG and its resistant counterparts. Moreover, three of the identified proteins (vimentin, cathepsin D and prolyl 4-hydroxylase, beta polypeptide) were confirmed to be upregulated in high-grade glioma. Our data suggest that acquired TMZ resistance in human malignant glioma is associated with promotion of malignant phenotypes, and our reported molecular candidates may serve not only as markers of chemoresistance but also as potential therapeutic targets in the treatment of TMZ-resistant human malignant glioma, providing a platform for future investigations., published_or_final_version, Springer Open Choice, 21 Feb 2012

Intracranial meningioma is a common condition in the elderly population. Surgical resection in this group of patients may be rendered more hazardous due to the patients' ageing physiology and to multiple comorbidities. This systematic review and meta-analysis aimed to summarise outcome data of elderly patients undergoing intracranial meningioma resection.Using Ovid Medline, longitudinal studies published from 2002 to October 2012 with patients aged ≥ 65 years that described outcomes after intracranial meningioma resection were reviewed. Outcome data included mortality, recurrence, complication rate and length of hospital stay (LoS). Grading score systems and covariates for predicting outcome were collected. Pooled estimates of mortality data were calculated in StatsDirect using a random effects method. I(2) statistic was used to assess heterogeneity.Thirteen eligible studies with a total of 7010 patients (mean age, 73.6 years) were included, in which 82% patients came from one study. The pooled estimates of 90-day and 1-year mortality from available data were 6.6% (95% confidence interval [CI], 4.6-9.1%; n = 735; I(2) = 32.1) and 9.6% (95% CI, 7.0-12.6%; n = 564; I(2) = 24.3), respectively. The overall complication rates ranged from 2.7% to 29.8%, and the overall incidence of complications was 20% per patient (range, 3-61%). Other outcome data were heterogeneous mainly due to incomparable study designs.Current evidence indicates satisfactory surgical outcomes in the elderly with intracranial meningiomas, though the risks of complications necessitate careful consideration when deciding to operate. Risk factor analysis emphasised the importance of considering pre-operative status and comorbidities during patient selection. Future research should address the causes and prevention of complications, and compare outcomes between younger and older patients using detailed stratifications of tumour characteristics.