OtoRhinoLaryngology News: 01/11/18

Πέμπτη 11 Ιανουαρίου 2018

Surgery in elderly patients with intracranial meningioma: neuropsychological functioning during a long term follow-up

Abstract

Surgical treatment of elderly patients with meningioma is has proved to be safe, especially when patients are selected using dedicated surgical scores. These scores take into account tumor size, edema, location and patient's co-morbidities. Neuropsychological functioning (NPF) of this kind of patients has been poorly studied in literature and it is not taken into account by these scores. Aim of our study was to describe the long-term outcome in terms of NPF of elderly patients undergoing surgery. Patients older than 70 years of age affected by intracranial meningioma and selected with the Clinical-Radiological Grading Score were included in our study. Neuropsychological testing was performed using a dedicated battery of tests before surgery, 3 and 12 months after surgery. Clinical, neurological and radiological outcomes were studied as well. Forty-one patients with a median age of 74 years were included in this study. Preoperatively only 1/41 patients showed a normal NPF with all tests scoring normally. Four out of 39 patients showed a complete neuropsychological recovery after 3 months; while 10/37 patients had a complete recovery after 12 months. NPF showed a trend of progressive improvement after surgery. Our study is the first experience reported in literature describing a long term follow-up in elderly patients after surgery for intracranial meningioma. In our series, surgery determined an improvement of NPF over time; especially with a low complication rate related to the selection of patients obtained through the CRGS. Further studies need to be performed in order to understand how brain edema, tumor size, volume and tumor location affect NPF in both short and long term.

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Reversible symptoms present in a patient with Balo's concentric sclerosis

Edyta Dziadkowiak, Mieszko Zagrajek, Anna Zimny, Bogusław Paradowski

Neurology India 2018 66(1):268-268

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Neurosurgery as it was

RN Roy

Neurology India 2018 66(1):2-3

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Sertraline-induced reversible myopathy with rhabdomyolysis and trismus

Boby V Maramattom, Joe Thomas, Nanda Kachhare

Neurology India 2018 66(1):235-237

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Changing trends in surgery for suprasellar lesions

Bhawani Shanker Sharma, Dattaraj Paramanand Sawarkar

Neurology India 2018 66(1):4-8

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Russel Brain: Some reflections on genius and other essays

Sunil Pandya

Neurology India 2018 66(1):290-293

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Evolution of concepts in the management of vestibular schwannomas: Lessons learnt from Prof B Ramamurthi's article published in 1970

Sunil Kumar Gupta, Manjul Tripathi

Neurology India 2018 66(1):9-19

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Dirofilariasis mimicking an osteoma

M Sreekumar, Jayashree Goethe, Roshith H Chekkattu

Neurology India 2018 66(1):255-256

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Authors' Reply: Magnesium supplementation in intracerebral hematoma: The hope and the hype!

Mukesh K Bhaskar, Bal Krishna Ojha, Rajesh Verma

Neurology India 2018 66(1):282-283

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Cerebrospinal fluid shunts – How they work: The basics

Sandip Chatterjee, L Harischandra

Neurology India 2018 66(1):24-35

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Association of hemolysis, elevated liver enzymes, low platelets syndrome with posterior reversible encephalopathy and intracranial hypotension

Zahide Yılmaz, Nuray Voyvoda, Pinar Bekdik Şirinocak, Hasan Terzi

Neurology India 2018 66(1):226-227

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Current status of dystonias including Meige's syndrome

Madhuri Behari

Neurology India 2018 66(1):36-37

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Lumber nerve root cavernous angioma

Shu-xin Sun, Ji Zhang, Ji-cheng Sun, Zhi-jie Chen, Xiang-heng Zhang, Zheng-he Chen, Jing-xiu Huang, Yu Jiang, Yong-gao Mou, Zhong-ping Chen, Ke Sai

Neurology India 2018 66(1):244-245

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Botulinum toxin in patients with Meige's syndrome

Nirosen Vijiaratnam, Tissa Wijeratne

Neurology India 2018 66(1):38-39

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Nasu–Hakola Disease

Bedia Samanci, Çağri Ulukan, Tuncay Gündüz, Murat Kürtüncü, Mefkure Eraksoy

Neurology India 2018 66(1):263-263

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Management of intracranial arterial dissection

Girish Rajpal, Vikas Naik

Neurology India 2018 66(1):40-42

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The Indo-US Collaborative Stroke Registry and infrastructure development project

Dheeraj Khurana, Jeyaraj Pandian, PN Sylaja, Subhash Kaul, MV Padma Srivastava, Suruchi Thakur, Deepti Arora, Tijy Thankachan, Aneesh B Singhal

Neurology India 2018 66(1):276-278

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Endovascular management of vertebral artery dissecting aneurysms

Vipul Gupta, Rajsrinivas Parthasarathy

Neurology India 2018 66(1):43-45

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Subgaleoatrial or subgaleopleural shunt?

Suryanarayanan Bhaskar, Mayank Garg

Neurology India 2018 66(1):285-286

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Predictors of severe postoperative hyperglycemia after cardiac surgery in infants: a single-center, retrospective, observational study

Abstract

Purpose

Hyperglycemia is a common issue in infants after cardiac surgery for congenital heart disease. Poor glycemic control is suspected to be associated with adverse postoperative outcomes. This study was performed to investigate clinical factors contributing to hyperglycemia in the perioperative period in infats.

Methods

A total of 69 infants (aged 1–12 months) who were admitted to Yokohama City University Hospital Intensive Care Unit (ICU) after surgical repair of congenital heart diseases with cardiopulmonary bypass (CPB) were retrospectively analysed. Hyperglycemia was defined as blood glucose ≥ 250 mg/dL on ICU admission. Clinical background, operative factors, and postoperative factors were compared between the hyperglycemic and non-hyperglycemic groups. Additionally, multivariate analysis was performed to identify factors contributing to hyperglycemia.

Results

Nineteen (27.5%) and 50 (72.5%) infants were classified into the hyperglycemic and non-hyperglycemic groups, respectively. Hyperglycemic infants were significantly younger, shorter, and weighed less, with a higher rate of chromosomal abnormalities. Intraoperatively, they also experienced longer CPB and surgery times and had higher peak lactate levels and higher inotropic requirements. Hyperglycemia was related to longer mechanical ventilation and longer ICU stays. Multivariate analysis detected intraoperative hyperglycemia, longer CPB time, younger age and chromosomal abnormality as significant factors.

Conclusion

Adding to hyperglycemia during the operation, longer CPB time younger age and chromosomal abnormality were identified as predictors of high blood glucose levels at ICU admission.

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Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model

Abstract

Vaccination with DNA that encodes cancer antigens is a simple and convenient way to raise immunity against cancer and has already shown promise in the clinical setting. Conventional plasmid DNA is commonly used which together with the encoded antigen also includes bacterial immunostimulatory CpG motifs to target the DNA sensor Toll-like receptor 9. Recently DNA vaccines using doggybone DNA (dbDNA™), have been developed without the use of bacteria. The cell-free process relies on the use of Phi29 DNA polymerase to amplify the template followed by protelomerase TelN to complete individual closed linear DNA. The resulting DNA contains the required antigenic sequence, a promoter and a poly A tail but lacks bacterial sequences such as an antibiotic resistance gene, prompting the question of immunogenicity. Here we compared the ability of doggybone DNA vaccine with plasmid DNA vaccine to induce adaptive immunity using clinically relevant oncotargets E6 and E7 from HPV. We demonstrate that despite the inability to trigger TLR9, doggybone DNA was able to induce similar levels of cellular and humoral immunity as plasmid DNA, with suppression of established TC-1 tumours.

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Satisfaction in rhinoplasty: the possible impact of anxiety and functional outcome

Abstract

Background

Rhinoplasty is a complex but commonly applied surgical procedure. Patient satisfaction is the least discussed but one of the most important determinants of surgical success.

Objectives

Evaluation of the patient satisfaction together with surgeon satisfaction were the main goals of this study. The roles of anxiety, gender, age and follow-up period were also studied.

Patients and methods

53 eligible patients operated by the first two authors within the previous 2 years were enrolled in the study. The medical records were reviewed for demographic data as well as the details of the surgical procedure. Functional and esthetic satisfactions of the patients were evaluated by VAS and ROE respectively. Surgeon satisfaction was evaluated by VAS in crosswise manner. Anxiety was measured by STAI_s and STAI_t scales.

Results

The analysis concerning esthetic results as well as functional results did not reveal any significant difference between the two surgeons (p = 0.132, p = 0.43 respectively). ROE scores were significantly different among patients with "good" and "very good" functional results. The difference between surgeon satisfaction and patient satisfaction was found to be insignificant (p = 0.273). Correlation analysis yielded a positive correlation between STAI_I and STAI_II (Pearson r = 0.335, p = 0.014) but not between STAI scores and ROE scores. Moreover, there was no relation between anxiety scores and the functional results. Likely, gender as well as age, follow-up, and surgical technique were not found to have any effect on patient satisfaction either.

Conclusion

Patient satisfaction is preferential in rhinoplasty. In our patient series, patient satisfaction was shown to be correlated with functional outcome but not with surgeon satisfaction. Anxiety was not found to have a significant impact on results of rhinoplasty. Our results should be interpreted cautiously keeping in mind that our patients' primary drive for rhinoplasty was functional.

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Inpatient treatment of patients with idiopathic sudden sensorineural hearing loss: a population-based healthcare research study

Abstract

Purpose

The aim was to determine inpatient treatment rates of idiopathic sudden sensorineural hearing loss (ISSNHL) with focus on diagnostics, treatment, and outcome.

Methods

A retrospective population-based study in the federal state Thuringia in 2011 and 2012 was performed on all 490 inpatients (51% females, median age: 60 years) treated for ISSNHL (Median duration: 7 days). The association between analyzed parameters and the probability of recovery was tested using univariable and multivariable statistics.

Results

The inpatient treatment rate for ISSNHL was 11.23 per 100,000. 172 patients (35%) had an outpatient treatment prior to inpatient treatment. For pure-tone audiometry of the three most affected frequencies (3PTAmax), the initial median hearing loss was 66.67 dB, the median absolute hearing gain ΔPTA_abs was 10.0 dB, and the median relative hearing gain in relation with the contralateral side ΔPTA_{rel contral} was 30.86%. 51% of the patients reached a ΔPTA_abs of ≥ 10 dB. About 2 of 5 patients recovered to a ΔPTA_{rel contral} ≥ 50% or reached ≤ 10 dB of contralateral ear. The multivariate analysis revealed that an ISSNHL on the left side [Hazard ratio (HR) = 1.6.88; confidence interval (CI) = 1.161–2.454], no down-sloping audiogram type (HR = 2.016; CI = 1.391–2.921), and no prior outpatient prednisolone treatment (HR = 2.374; CI = 1.505–3.745) were independent factors associated with better recovery (ΔPTA_abs ≥ 10 dB).

Conclusion

Inpatient treatment of ISSNHL is variable in daily practice. The population-based recovery rate was worse than reported in clinical trials. More standardization and clearer criteria for outpatient, inpatient, and salvage therapy are needed.

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Respiratory dysfunction progresses with age in Kcna1-null mice, a model of sudden unexpected death in epilepsy

Summary

Objective

Increased breathing rate, apnea, and respiratory failure are associated with sudden unexpected death in epilepsy (SUDEP). We recently demonstrated the progressive nature of epilepsy and mortality in Kcna1^−/− mice, a model of temporal lobe epilepsy and SUDEP. Here we tested the hypothesis that respiratory dysfunction progresses with age in Kcna1^−/− mice, thereby increasing risk of respiratory failure and sudden death (SD).

Methods

Respiratory parameters were determined in conscious mice at baseline and following increasing doses of methacholine (MCh) using noninvasive airway mechanics (NAM) systems. Kcna1^+/+, Kcna1^+/−, and Kcna1^−/− littermates were assessed during 3 age ranges when up to ~30%, ~55%, and ~90% of Kcna1^−/− mice have succumbed to SUDEP: postnatal day (P) 32-36, P40-46, and P48-56, respectively. Saturated arterial O₂ (SaO₂) was determined with pulse oximetry. Lung and brain tissues were isolated and Kcna1 gene and protein expression were evaluated by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blot techniques. Airway smooth muscle responsiveness was assessed in isolated trachea exposed to MCh.

Results

Kcna1^−/− mice experienced an increase in basal respiratory drive, chronic oxygen desaturation, frequent apnea-hypopnea (A-H), an atypical breathing sequence of A-H-tachypnea-A-H, increased tidal volume, and hyperventilation induced by MCh. The MCh-provoked hyperventilation was dramatically attenuated with age. Of interest, only Kcna1^−/− mice developed seizures following exposure to MCh. Seizures were provoked by lower concentrations of MCh as Kcna1^−/− mice approached SD. MCh-induced seizures experienced by a subset of younger Kcna1^−/− mice triggered death. Respiratory parameters of these younger Kcna1^−/−mice resembled older near-SD Kcna1^−/− mice. Kcna1 gene and protein were not expressed in Kcna1^+/+ and Kcna1^+/− lungs, and MCh-mediated airway smooth muscle contractions exhibited similar half-maximal effective concentration( EC₅₀) in isolated Kcna1^+/+ and Kcna1^−/− trachea.

Significance

The Kcna1^−/− model of SUDEP exhibits progressive respiratory dysfunction, which suggests a potential increased susceptibility for respiratory failure during severe seizures that may result in sudden death.

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Satisfaction in rhinoplasty: the possible impact of anxiety and functional outcome

Abstract

Background

Rhinoplasty is a complex but commonly applied surgical procedure. Patient satisfaction is the least discussed but one of the most important determinants of surgical success.

Objectives

Evaluation of the patient satisfaction together with surgeon satisfaction were the main goals of this study. The roles of anxiety, gender, age and follow-up period were also studied.

Patients and methods

Results

Conclusion

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Inpatient treatment of patients with idiopathic sudden sensorineural hearing loss: a population-based healthcare research study

Abstract

Purpose

The aim was to determine inpatient treatment rates of idiopathic sudden sensorineural hearing loss (ISSNHL) with focus on diagnostics, treatment, and outcome.

Methods

Results

Conclusion

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Sex Differences in Thermal, Stress, and Inflammatory Responses to Minocycline Administration in Rats with Traumatic Brain Injury

Journal of Neurotrauma , Vol. 0, No. 0.

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Treatment of Traumatic Brain Injury with Vepoloxamer (Purified Poloxamer 188)

Journal of Neurotrauma , Vol. 0, No. 0.

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Impact of Complete Spinal Cord Injury on Healing of Skin Ulcers in Mouse Models

Journal of Neurotrauma , Vol. 0, No. 0.

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Response to Phillips et al.: “An Autonomic Neuroprosthesis: Non-Invasive Electrical Spinal Cord Stimulation Restores Autonomic Cardiovascular Function in Individuals with Spinal Cord Injury”

Journal of Neurotrauma , Vol. 0, No. 0.

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Spinal Cord Injury Disrupts Resting-State Networks in the Human Brain

Journal of Neurotrauma , Vol. 0, No. 0.

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Exacerbation of Acute Traumatic Brain Injury by Circulating Extracellular Vesicles

Journal of Neurotrauma , Vol. 0, No. 0.

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Longitudinal Improvement in Balance Error Scoring System Scores among NCAA Division-I Football Athletes

Journal of Neurotrauma , Vol. 0, No. 0.

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Erythropoietin Attenuates the Brain Edema Response after Experimental Traumatic Brain Injury

Journal of Neurotrauma , Vol. 0, No. 0.

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CSF neurogranin or tau distinguish typical and atypical Alzheimer disease

Abstract

Objective

To assess whether high levels of cerebrospinal fluid neurogranin are found in atypical as well as typical Alzheimer's disease.

Methods

Immunoassays were used to measure cerebrospinal fluid neurogranin in 114 participants including healthy controls (n = 27), biomarker-proven amnestic Alzheimer's disease (n = 68), and the atypical visual variant of Alzheimer's (n = 19) according to international criteria. CSF total-tau, Aβ42, and neurofilament light concentrations were investigated using commercially available assays. All affected individuals had T1-weighted volumetric MR images available for analysis of whole and regional brain volumes. Associations between neurogranin, brain volumes, total-tau, Aβ42, and neurofilament light were assessed.

Results

Median cerebrospinal fluid neurogranin concentrations were higher in typical and atypical Alzheimer's compared to controls (P < 0.001 and P = 0.005). Both neurogranin and total-tau concentrations, but not neurofilament light and Aβ42, were higher in typical Alzheimer's compared to atypical patients (P = 0.004 and P = 0.03). There were significant differences in the left hippocampus and right and left superior parietal lobules in atypical patients, which were larger (P = 0.03) and smaller (P = 0.001 and P < 0.001), respectively, compared to typical patients. We found no evidence of associations between neurogranin and brain volumes but a strong association with total-tau (P < 0.001) and a weaker association with neurofilament light (P = 0.005).

Interpretation

These results show significant differences in neurogranin and total-tau between typical and atypical patients, which may relate to factors other than disease topography. The differential relationships between neurogranin, total-tau and neurofilament light in the Alzheimer's variants, provide evidence for mechanistically distinct and coupled markers of neurodegeneration.

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Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model

Abstract

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Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model

Abstract

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Protective Effects of Estradiol and Dihydrotestosterone following Spinal Cord Injury

Journal of Neurotrauma , Vol. 0, No. 0.

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Sex Differences in Thermal, Stress, and Inflammatory Responses to Minocycline Administration in Rats with Traumatic Brain Injury

Journal of Neurotrauma , Vol. 0, No. 0.

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Treatment of Traumatic Brain Injury with Vepoloxamer (Purified Poloxamer 188)

Journal of Neurotrauma , Vol. 0, No. 0.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D1ksw5

Impact of Complete Spinal Cord Injury on Healing of Skin Ulcers in Mouse Models

Journal of Neurotrauma , Vol. 0, No. 0.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2mmwGoz

Response to Phillips et al.: “An Autonomic Neuroprosthesis: Non-Invasive Electrical Spinal Cord Stimulation Restores Autonomic Cardiovascular Function in Individuals with Spinal Cord Injury”

Journal of Neurotrauma , Vol. 0, No. 0.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D1knsh

Spinal Cord Injury Disrupts Resting-State Networks in the Human Brain

Journal of Neurotrauma , Vol. 0, No. 0.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D6vkZK

Exacerbation of Acute Traumatic Brain Injury by Circulating Extracellular Vesicles

Journal of Neurotrauma , Vol. 0, No. 0.

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Longitudinal Improvement in Balance Error Scoring System Scores among NCAA Division-I Football Athletes

Journal of Neurotrauma , Vol. 0, No. 0.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D2xklw

Erythropoietin Attenuates the Brain Edema Response after Experimental Traumatic Brain Injury

Journal of Neurotrauma , Vol. 0, No. 0.

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Corrigendum

Future Oncology, Ahead of Print.

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Evaluation of the eighth American Joint Committee on Cancer staging system for malignant melanoma of the skin

Future Oncology, Ahead of Print.

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Bioinformatic analysis of PFN2 dysregulation and its prognostic value in head and neck squamous carcinoma

Future Oncology, Ahead of Print.

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Identification of CDK2 as a novel target in treatment of prostate cancer

Future Oncology, Ahead of Print.

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Generalized nonmotor (absence) seizures—What do absence, generalized, and nonmotor mean?

Summary

Objective

Clinical absences are now classified as "generalized nonmotor (absence) seizures" by the International League Against Epilepsy (ILAE). The aim of this paper is to critically review the concept of absences and to put the accompanying focal and motor symptoms into the context of the emerging pathophysiological knowledge.

Methods

For this narrative review we performed an extensive literature search on the term "absence," and analyzed the plethora of symptoms observed in clinical absences.

Results

Arising from the localization and the involved cortical networks, motor symptoms may include bilateral mild eyelid fluttering and mild myoclonic jerks of extremities. These motor symptoms may also occur unilaterally, analogous to a focal motor seizure with Jacksonian march. Furthermore, electroencephalography (EEG) abnormalities may exhibit initial frontal focal spikes and consistent asymmetries. Electroclinical characteristics support the cortical focus theory of absence seizures. Simultaneous EEG/functional magnetic resonance imaging (fMRI) measurements document cortical deactivation and thalamic activation. Cortical deactivation is related to slow waves and disturbances of consciousness of varying degrees. Motor symptoms correspond to the spike component of the 3/s spike-and-wave-discharges. Thalamic activation can be interpreted as a response to overcome cortical deactivation. Furthermore, arousal reaction during drowsiness or sleep triggers spikes in an abnormally excitable cortex. An initial disturbance in arousal mechanisms ("dyshormia") might be responsible for the start of this abnormal sequence.

Significance

The classification as "generalized nonfocal and nonmotor (absence) seizure" does not covey the complex semiology of a patient's clinical events.

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O-GlcNAcylation in Oral Squamous Cell Carcinoma

Abstract

Background

Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc). However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC). Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.

Methods

Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFR^tyr1173 and anti-phosphorylated-Akt^ser473 antibodies following standard immunohistochemistry. The immunohistochemical (IHC) score was determined using the Fromowitz standard. Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.

Results

The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFR^tyr1173 and phosphorylated-Akt^ser473 were significantly higher in OSCC than normal tissues (p < 0.001 and p < 0.01, respectively). Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ. In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFR^tyr1173 and phosphorylated-Akt^ser473 (p < 0.01 and p < 0.001, respectively). The IHC scores of O-GlcNAc or OGT were not determined to correlate with histological grading.

Conclusion

Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.

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Vaccines for the Paramyxoviruses and Pneumoviruses: Successes, Candidates, and Hurdles

Viral Immunology , Vol. 0, No. 0.

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Efficient Removal of Methyl Blue Using Nanoporous Carbon from the Waste Biomass

Abstract

The nanoporous carbon using waste straw as carbon source was well prepared for effective dye removal from aqueous solution. The structure and surface properties of nanoporous carbon were characterized by X-ray diffraction, Raman spectroscopy, N₂ adsorption–desorption, and X-ray photoelectron spectroscopy. The results revealed that the nanoporous carbon exhibited large specific surface area and porous structure with abundant functional groups on the surface. In the adsorption experiments, the nanoporous carbon showed high dye adsorption capacity and rapid removal rate under higher pH value, initial dye concentration, and dosage of adsorbents. Moreover, the adsorption isotherm data fitted well to the Langmuir model, suggesting the monolayer adsorption. The maximum adsorption capacity could reach 555.56 mg/g, much higher than the recent reports. Besides, the adsorption kinetics fitted well to the pseudo-second-order model and the correlation coefficients were greater than 0.999. Thermodynamic study results indicated that dye adsorption onto the hierarchical nanoporous carbon was spontaneous and thermodynamically favorable. Therefore, with larger specific surface area and porous structure, the nanoporous carbon showed great potential as efficient adsorbents for dye in the aqueous environment.

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No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy

No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy

No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy, Published online: 11 January 2018; doi:10.1038/bjc.2017.410

No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy

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RNF126 as a biomarker of a poor prognosis in invasive breast cancer and CHK1 inhibitor efficacy in breast cancer cells

Purpose: 1) To investigate expression of the E3 ligase, RNF126, in human invasive breast cancer (BC) and its links with BC outcomes. 2) To test the hypothesis that RNF126 determines the efficacy of inhibitors targeting the cell cycle checkpoint kinase, CHK1. Experimental Design: A retrospective analysis by immunohistochemistry (IHC) compared RNF126 staining in 110 invasive BC and 78 paired adjacent normal tissues with clinicopathologic data. Whether RNF126 controls CHK1 expression was determined by chromatin immunoprecipitation and a CHK1 promoter driven luciferase reporter. Staining for these two proteins by IHC using tissue microarrays was also conducted. Cell killing/replication stress induced by CHK1 inhibition was evaluated in cells, with or without RNF126 knockdown, by MTT/colony formation, replication stress biomarker immunostaining and DNA fiber assays. Results: RNF126 protein expression was elevated in BC tissue samples. RNF126 was associated with a poor clinical outcome after multivariate analysis and was an independent predictor. RNF126 promotes CHK1 transcript expression. Critically, a strong correlation between RNF126 and CHK1 proteins was identified in BC tissue and cell lines. The inhibition of CHK1 induced a greater cell killing and a higher level of replication stress in BC cells expressing RNF126 compared to RNF126 depleted cells. Conclusions: RNF126 protein is highly expressed in invasive BC tissue. The high expression of RNF126 is an independent predictor of a poor prognosis in invasive BC and is considered a potential biomarker of a cancer's responsiveness to CHK1 inhibitors. CHK1 inhibition targets BC cells expressing higher levels of RNF126 by enhancing replication stress.

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Evaluation of overall response rate and progression-free survival as potential surrogate endpoints for overall survival in immunotherapy trials

Purpose: With the approval of immunotherapies for a variety of indications, methods to assess treatment benefit addressing the response patterns observed are important. We evaluated RECIST criteria based objective response rate (ORR) and progression-free survival (PFS) as potential surrogate endpoints of overall survival (OS), and explored a modified definition of PFS by altering the threshold percentage determining disease progression to assess the association with survival benefit in immunotherapy trials. Experimental Design: Thirteen randomized, multicenter, active control trials containing immunotherapeutic agents submitted to FDA were analyzed. Associations between treatment effects of ORR, PFS, modified PFS and OS were evaluated at individual and trial-levels. Patient-level responder analysis was performed for PFS and OS. Results: The coefficient of determination (R2) measured the strength of associations, where values near 1 imply surrogacy and values close to zero suggest no association. At the trial-level, associations between hazard ratios (HR) of PFS and OS was R2 = 0.1303, and between the odds ratio of ORR and HR of OS was R2 = 0.1277. At the individual level, the Spearman rank correlation coefficient between PFS and OS was 0.61. Trial-level associations between modified PFS and OS ranged between 0.07 - 0.1, and individual level correlations were approximately 0.6. HRs of PFS and OS for responders versus non-responders were 0.129 (95% CI: 0.11, 0.15) and 0.118 (95% CI: 0.11, 0.13), respectively. Conclusions: While responders exhibited longer survival and PFS than non-responders, the trial-level and individual level associations were weak between PFS/ORR and OS. Modifications to PFS did not improve associations.

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A prospective cohort-study of 122 adult patients presenting to an otolaryngologist's office with globus pharyngeus

Abstract

Objectives

To investigate the epidemiology of globus pharyngeus in adult patients presenting to the otolaryngologist's office. Also the predictors of persisting symptoms, prevalence of anxiety and the effect of clinical assessment were analyzed.

Design

This was a prospective cohort study. Follow-up was done using a postal questionnaire.

Setting

One otolaryngologists' office comprising three medical doctors.

Participants

122 consecutive globus patients presenting to one otolaryngology office in a one-year period.

Main outcome measures

Globus incidence, gender- and age-distribution, predictors of persisting symptoms and the patient's health related concerns.

Results

3.8% of first-time visits were regarding globus. The mean age was 48 years [range 20-88 y] and a female predominance was found (ratio 1.49). 84% experienced anxiety, mainly due to fear of cancer. The most common pathological findings were reflux (15.6%) and post-infectious inflammation (10.6%). 21.4% of questionnaire-responders reported full remission of their symptoms. Three predictors regarding symptom persistence were identified: Male gender (OR 1.52), smoking (OR 3.4) and difficulties in breathing (OR 8.7). Patients with concomitant foreign body sensation were less likely to have persisting symptoms (OR 0.42). No cases of malignant disease were encountered. 94.7% was reassured by the office visit.

Conclusion

The incidence of globus is 3.8% in the otolaryngologist's office. Female gender and concomitant foreign body sensation were predictive for presenting to the clinic even if symptom remission had occurred. Male gender, smoking and self-perceived breathing difficulties were predictive for persisting symptoms. Globus is an anxiety causing symptom, but reassurance is provided by clinical examination by the otolaryngologist.

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Five-year outcome of endoscopic laser cricopharyngeal myotomy: our experience in 10 patients

Abstract

Cricopharyngeal spasm is a failure of the cricopharyngeus muscle to relax and can be a cause of dysphagia.

Endoscopic laser cricopharyngeal myotomy with mucosal repair is associated with reduced operative times, inpatient stay and lower morbidity with favourable subjective short-term outcomes, although long-term outcomes are less well known.

In our cohort of patients, the majority had a subjectively improved swallow in the long-term although some did have regression of symptoms but remained better than pre-operatively.

Subjectively our cohort of patients appeared to favour less well in the long-term with regards to reflux symptoms, the majority fairing worse than pre-operatively at least 5 years previously.

This paper would suggest that as clinicians we can advise patients that in the long-term, laser cricopharyngeal myotomy will improve and maintain swallowing symptoms but that their reflux symptoms may be exacerbated over time.

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Nasoseptal Flap for Skull Base Reconstruction in Children

J Neurol Surg B
DOI: 10.1055/s-0037-1617435

Objective The endoscopic endonasal approach is being increasingly used for the resection and reconstruction of anterior skull base (ASB) lesions. Vascularized nasoseptal flaps (NSF) have become the workhorse for the reconstruction of ASB defects, resulting in a significant decrease in the incidence of cerebrospinal fluid (CSF) leaks. The objective of this study was to investigate the efficacy and safety of NSF in children. Methods This is a retrospective analysis of the medical records of all patients under the age of 18 years who underwent endoscopic repair of ASB lesions with the use of NSF at our tertiary medical center between 1/2011 and 8/2016. Results Twelve children underwent ASB defect repair for both benign and malignant neoplasms using the endoscopic endonasal NSF technique. Four children had previously undergone ASB surgery. The male-to-female ratio was 1:1, the average age was 12.3 years, the average hospitalization time was 8.3 days, and the maximum follow-up period was 24 months, during which craniofacial growth appeared to be unimpaired. A lumbar drain was used postoperatively in six cases. Crust formation and synechia were observed in two cases. There was one case of a major long-term complication (a CSF leak followed by meningitis). Conclusions Endoscopic endonasal NSF was both an effective and a safe technique for ASB defect reconstruction in 12 children for both benign and malignant neoplasms. It had a high success rate and a low complication rate. No apparent negative influence on craniofacial growth was observed in our series.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents | Abstract | Full text

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One-piece Orbitozygomatic Craniotomy for Resection of Rathke's Cleft Cyst: Operative Video

J Neurol Surg B
DOI: 10.1055/s-0037-1620277

Objective The video stars orbitozygomatic resection of Rathke's cleft cyst with suprasellar extension in a 37-year-old male patient presenting with severe headaches and bitemporal hemianopia. Clinical and radiological characteristics along with surgical technique (positioning, bony opening, surgical dissection and debulking, closure), histopathology, and postoperative course are described. Methods Preoperative MRI demonstrated a noncontrast-enhancing cystic lesion in the sella with suprasellar extension causing compression of both optic nerves. A one-piece orbitozygomatic craniotomy was performed. The tumor was encountered in the interoptic space. First, the cyst was decompressed and fluid appearing like motor oil was aspirated. Both optic nerves were decompressed and dissected free from the cyst wall. Intraoperatively, the most challenging aspect was separating the tumor from surrounding vascular structures, including bilateral A1 arteries and the left carotid bifurcation. A combination of sharp and blunt dissection was utilized to free the tumor from adhesions to critical neurovascular structures. Once freed, the suprasellar aspect of the tumor was mobilized into the operative cavity and debulked. Finally, the sellar component of the tumor was removed all the way down to the sellar floor. Postoperative MRI demonstrated decompressed bilateral optic nerves with an intact pituitary stalk with preservation of normal pituitary gland. Histopathology identified pathognomonic features consistent with diagnosis of Rathke's cleft cyst, including flattened ciliated epithelium and presence of Rathke's cleft remnants. Results Postoperatively, bilateral improvement in vision was noted with transient diabetes insipidus. Patient was discharged home on postoperative day 4. Conclusion A one-piece orbitozygomatic craniotomy is an effective and safe strategy for resection of Rathke's cleft cysts with suprasellar extension.The link to the video can be found at: https://youtu.be/-Yqtcd2gLSs.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents | Abstract | open access Full text

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Contralateral Minimum Anterior and Posterior Combined Petrosal Approach for Retrochiasmatic Craniopharyngiomas: An Alternative Technique

J Neurol Surg B
DOI: 10.1055/s-0037-1620248

Retrochiasmatic craniopharyngiomas (RC) are a challenge for the neurosurgeon to treat surgically, restrained by their location in the interpeduncular fossa, surrounded by vital neurovascular structures, narrow corridor and poor visibility. Many approaches are possible and elucidated in the literature, which the surgeon chooses, based on multiple factors, such as the size of tumor, calcification, laterality, preoperative neurological deficits and the endocrine function status, recurrence, postradiotherapy status, or significant superior and/or posterior extension.1 2 We describe a contralateral minimum anterior and posterior (CL-MAPC) petrosal approach for a case of recurrent RC, in a 37-year-old female patient operated before using a pterional approach, now presented with left homonymous hemianopia and panhypopituitarism (Fig. 1). We preferred a contralateral approach to protect the ipsilateral optic tract (OT) from retraction injury, which formed an obstacle to the tumor from ipsilateral side. Apart from various benefits described by the author previously for RC, using MAPC petrosal approach, the CL-MAPC offers a safe corridor, protecting the ipsilateral OT, visualization of tumor origin usually posterior to chiasm, wider corridor if PCoM could be sacrificed, as it was done in this case, and pituitary stalk identification, with a probability of its functional preservation, unlike a necessity of pituitary transposition in EEA, though the endocrine outcome is poor after a radical resection irrespective of the approach chosen.1 3 4 There was complete excision of the tumor with preservation of visual function postoperatively. We recommend the use of CL-MAPC as an alternative to EEA in some specific indications when the tumor is large, calcified, obscuring OT on the ipsilateral side and with significant lateral extension, which may be limiting factors in EEA (Fig. 2).The link to the video can be found at: https://youtu.be/gWCJmh4_evs.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents | Abstract | open access Full text

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Clinical Considerations of the Role of Palbociclib in the Management of Advanced Breast Cancer Patients With and Without Visceral Metastases

Abstract

Background

This report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor−positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) with or without visceral metastases.

Patients and methods

Pre- and postmenopausal women with disease progression following prior ET (PALOMA-3; N=521) and postmenopausal women untreated for ABC (PALOMA-2; N=666) were randomized 2:1 to ET (fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression-free survival (PFS), safety, and patient-reported quality of life (QoL) were evaluated by prior treatment and visceral involvement.

Results

Visceral metastases incidence was higher in patients with prior resistance to ET (58.3%, PALOMA-3) than in patients naive to endocrine therapy in the ABC setting (48.6%, PALOMA-2). In patients with prior resistance to ET and visceral metastases, median PFS (mPFS) was 9.2 months with palbociclib plus fulvestrant versus 3.4 months with placebo plus fulvestrant [hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35 − 0.61], and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In patients with nonvisceral metastases, mPFS was 16.6 versus 7.3 months, HR, 0.53; 95% CI, 0.36 − 0.77. In patients naive to endocrine therapy in the advanced disease setting, mPFS was 19.3 months with palbociclib plus letrozole versus 12.9 months with placebo plus letrozole (HR, 0.63; 95% CI, 0.47 − 0.85); ORR was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not reached with palbociclib plus letrozole versus 16.8 months with placebo plus letrozole (HR, 0.50; 95% CI, 0.36 − 0.70). In patients with prior resistance to ET with visceral metastases, palbociclib plus fulvestrant significantly delayed deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported QoL was maintained with palbociclib plus letrozole in patients naive to endocrine-based therapy for ABC.

Conclusions

Palbociclib plus ET prolonged mPFS in patients with visceral metastases, increased ORRs, and in patients previously treated for ABC, delayed QoL deterioration, presenting a standard treatment option among patients with visceral metastases amenable to endocrine-based therapy.

Clinical trial registration

NCT01942135, NCT01740427

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Watson for Oncology and breast cancer treatment recommendations: agreement with an expert multidisciplinary tumor board

Abstract

Background

Breast cancer oncologists are challenged to personalize care with rapidly changing scientific evidence, drug approvals, and treatment guidelines. Artificial intelligence (AI) clinical decision-support systems (CDSSs) have the potential to help address this challenge. We report here the results of examining the level of agreement (concordance) between treatment recommendations made by the AI CDSS Watson for Oncology (WFO) and a multidisciplinary tumor board for breast cancer.

Patients and methods

Treatment recommendations were provided for 638 breast cancers between 2014 and 2016 at the Manipal Comprehensive Cancer Center, Bengaluru, India. WFO provided treatment recommendations for the identical cases in 2016. A blinded second review was carried out by the center's tumor board in 2016 for all cases in which there was not agreement, to account for treatments and guidelines not available before 2016. Treatment recommendations were considered concordant if the tumor board recommendations were designated 'recommended' or 'for consideration' by WFO.

Results

Treatment concordance between WFO and the multidisciplinary tumor board occurred in 93% of breast cancer cases. Subgroup analysis found that patients with stage I or IV disease were less likely to be concordant than patients with stage II or III disease. Increasing age was found to have a major impact on concordance. Concordance declined significantly (P ≤ 0.02; P < 0.001) in all age groups compared with patients <45 years of age, except for the age group 55–64 years. Receptor status was not found to affect concordance.

Conclusion

Treatment recommendations made by WFO and the tumor board were highly concordant for breast cancer cases examined. Breast cancer stage and patient age had significant influence on concordance, while receptor status alone did not. This study demonstrates that the AI clinical decision-support system WFO may be a helpful tool for breast cancer treatment decision making, especially at centers where expert breast cancer resources are limited.

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Validation of the Modified Surgeon Periorbital Rating of Edema and Ecchymosis (SPREE) Questionnaire: A Prospective Analysis of Facial Plastic and Reconstructive Surgery Procedures

Facial plast Surg
DOI: 10.1055/s-0037-1615282

Although periorbital edema and ecchymosis are commonly encountered after facial plastic and reconstructive surgery procedures, there is currently no validated grading scale to qualify these findings. In this study, the modified "Surgeon Periorbital Rating of Edema and Ecchymosis (SPREE)" questionnaire is used as a grading scale for patients undergoing facial plastic surgery procedures. This article aims to validate a uniform grading scale for periorbital edema and ecchymosis using the modified SPREE questionnaire in the postoperative period. This is a prospective study including 82 patients at two different routine postoperative visits (second and seventh postoperative days), wherein the staff and resident physicians, physician assistants (PAs), patients, and any accompanying adults were asked to use the modified SPREE questionnaire to score edema and ecchymosis of each eye of the patient who had undergone a plastic surgery procedure. Interrater and intrarater agreements were then examined. Cohen's kappa coefficient was calculated to measure intrarater and interrater agreement between health care professionals (staff physicians and resident physicians); staff physicians and PAs; and staff physicians, patients, and accompanying adults. Good to excellent agreement was identified between staff physicians and resident physicians as well as between staff physicians and PAs. There was, however, poor agreement between staff physicians, patients, and accompanying adults. In addition, excellent agreement was found for intraobserver reliability during same-day visits. The modified SPREE questionnaire is a validated grading system for use by health care professionals to reliably rate periorbital edema and ecchymosis in the postoperative period. Validation of the modified SPREE questionnaire may improve ubiquity in medical literature reporting and related outcomes reporting in future.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents | Abstract | Full text

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A quantitative CT imaging signature predicts survival and complements established prognosticators in stage I non-small cell lung cancer

Publication date: Available online 10 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Juheon Lee, Bailiang Li, Yi Cui, Xiaoli Sun, Jia Wu, Hui Zhu, Jinming Yu, Michael F. Gensheimer, Billy W. Loo, Maximilian Diehn, Ruijiang Li
BackgroundPrognostic biomarkers are needed to guide the management of early stage non-small cell lung cancer (NSCLC). This work aims to develop an image-based prognostic signature and assess its complementary value to existing biomarkers.MethodsWe retrospectively analyzed outcomes of stage I NSCLC in seven cohorts. Based on an analysis of 39 CT features characterizing tumor and its relation to neighboring pleura, we developed a prognostic signature in an institutional cohort (n=117) and tested it in an external cohort (n=88). A third cohort of 89 patients with CT and gene expression data was employed to create a surrogate genomic signature of the imaging signature. We conducted further validation using data from five gene expression cohorts (n=639), and built a composite signature by integrating with the cell-cycle progression (CCP) score and clinical variables.ResultsAn imaging signature consisting of pleural contact index and normalized inverse difference was significantly associated with overall survival in both imaging cohorts (p=0.0005 and 0.0009). Functional enrichment analysis revealed that genes highly correlated with the imaging signature were related to immune response, such as lymphocyte activation and chemotaxis (false discovery rate<0.05). A genomic surrogate of the imaging signature remained a significant predictor of survival adjusting for known prognostic factors (hazard ratio: 1.81, 95% CI: 1.34-2.44, p<0.0001), and stratified patients within subgroups as defined by stage, histology, or CCP score. A composite signature outperformed the genomic surrogate, CCP score, and clinical model alone (p<0.01) regarding concordance index (0.70 vs 0.62-0.63).ConclusionThe proposed CT imaging signature reflects fundamental biologic differences in tumors and predicts overall survival in patients with stage I NSCLC. When combined with established prognosticators, the imaging signature improves survival prediction.

Teaser

We identified a CT imaging signature that predicts overall survival in stage I NSCLC. The imaging signature is associated with immune response and may serve as a noninvasive prognostic biomarker in stage I NSCLC.

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Smartphone-Based Point-of-Care Urinalysis Under Variable Illumination

Urine tests are performed by using an off-the-shelf reference sheet to compare the color of test strips. However, the tabular representation is difficult to use and more prone to visual errors, especially when the reference color-swatches to be compared are spatially apart. Thus, making it is difficult to distinguish between the subtle differences of shades on the reagent pads. This manuscript represents a new arrangement of reference arrays for urine test strips (urinalysis). Reference color swatches are grouped in a doughnut chart, surrounding each reagent pad on the strip. The urine test can be evaluated using naked eye by referring to the strip with no additional sheet necessary. Along with this new strip, an algorithm for smartphone based application is also proposed as an alternative to deliver diagnostic results. The proposed colorimetric detection method evaluates the captured image of the strip, under various color spaces and evaluates ten different tests for urine. Thus, the proposed system can deliver results on the spot using both naked eye and smartphone. The proposed scheme delivered accurate results under various environmental illumination conditions without any calibration requirements, exhibiting performances suitable for real-life applications and an ease for a common user.

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Late normal tissue response in the rat spinal cord after carbon ion irradiation

The present work summarizes the research activities on radiation-induced late effects in the rat spinal cord carried out within the "clinical research group ion beam therapy" funded by the German Research Foun...

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Dynamic changes in 18F-borono-L-phenylalanine uptake in unresectable, advanced, or recurrent squamous cell carcinoma of the head and neck and malignant melanoma during boron neutron capture therapy patient selection

We evaluated dynamic changes in 18F–borono-L-phenylalanine (18F–BPA) uptake in unresectable, advanced, or recurrent squamous cell carcinoma of the head and neck (SCC) and malignant melanoma (MM) during boron neut...

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Expression of CD163 in hereditary gingival fibromatosis: a possible association with TGF-β1

Abstract

Background

Although several studies have discussed some of the molecular and cellular changes associated with hereditary gingival fibromatosis (HGF), its pathogenesis is still largely unclear. This study was directed to detect and outline the degree of relationship between the immunophenotyped macrophages (M2) expressing CD163 and TGF-β1 in patients with gingival overgrowth due to HGF.

Methods

Biopsies from 20 patients suffering from HGF and 20 normal control subjects were harvested, histologically and immunohistochemically stained then, analyzed and statistically compared and correlated for CD163 immunoexpression and TGF-β1.

Results

All HGF specimens expressed TGF-β1 by most of the connective tissue fibroblasts, with statistically high significant mean of area % (2.61±0.41) compared to normal controls (0.11±0.06) (p=0.001). All control specimens revealed negligible CD163 immunostaining of the few inflammatory cells found with a mean area of % (0.69±0.12), while the specimens of HGF cases showed statistically significant higher CD163 expression (3.39±0.75) at (p=0.007). A statistically significant higher mean % of M2-cells expressing CD163 in relation to the total number of the inflammatory cells was revealed in HGF (34.46±2.04) compared to the control group (16.36±2.39) (p-value ≤ 0.05). Moderate correlation between CD163 and TGF-β1 was detected in HGF (r =0.451), (p-value<0.05).

Conclusions

CD163 and TGF-β1 were clearly expressed in HGF cases compared to healthy control patients, with significant correlation. In HGF, the increase in CD 163-positive cells was specific and not dependent on the chronic gingival inflammation.

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WT1 peptide vaccine in Montanide in contrast to poly ICLC, is able to induce WT1-specific immune response with TCR clonal enrichment in myeloid leukemia

Abstract

Background

The optimal strategy for vaccination to induce CD8⁺ T cell responses against WT1 is not known.

Methods

A pilot randomized study in HLA-A02⁺ patients to receive vaccination with WT1 in Montanide or in poly ICLC, a TLR3 agonist, to explore the novel immune adjuvant was conducted. Seven patients were randomized. Four patients received WT1 in Montanide, and three with WT1 in poly ICLC. Five patients were in morphologic remission and two had residual morphologic disease at the study entry.

Results

All patients finished the induction phase without any major toxicity except mild transient local injection reaction. One patient on the Montanide arm developed aseptic ulceration at two vaccine sites which healed without antibiotics. Three of 4 patients on the Montanide arm had a decreased expression of WT1 after WT1 vaccination, and two of them demonstrated generation of WT1-specific cytotoxic CD8⁺ T cell responses with biased TCR beta chain enrichment. In contrast, no obvious WT1-specific immune responses were detected in two patients on the poly ICLC arm, nor was there clonal enrichment by TCR alpha/beta sequencing; however, these patients did also have decreased WT1 expression and remained in remission several years after the initiation of treatment.

Conclusions

WT1 peptide vaccine with Montanide as an adjuvant induces detectable WT1-specific CD8⁺ T cell responses with clonal TCR enrichment, which may be capable of controlling leukemia recurrence in the setting of minimal residual disease. Poly ICLC may induce anti-leukemic activity in the absence of detectable WT1 specific CD8⁺ T cell responses.

Trial registration NCT01842139, 7/3/2012 retrospectively registered; http://ift.tt/2D3ZsWg.

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Accuracy of FDG PET-CT response assessment following radiotherapy alone for head and neck squamous cell carcinoma: retrospective analysis of 45 patients

Abstract

FDG PET-CT is an established tool for response assessment following definitive concurrent chemoradiotherapy for head and neck squamous cell carcinoma with a high negative predictive value guiding treatment decisions.

Little data is available regarding the accuracy of FDG PET-CT for response assessment following definitive radiotherapy without chemotherapy.

We retrospectively analysed the accuracy of FDG PET-CT for response assessment following radiotherapy alone without planned neck dissection in 45 patients.

PET-CT had a high negative predictive value of 93% and positive predictive value of 88%.

Based upon the high negative predictive value, PET-CT can be used to avoid surgical intervention following radiotherapy alone

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Protocadherin8 Promotes Invasion and Metastasis via Laminin Subunit γ2 in Gastric Cancer

Abstract

Growing evidence suggests that protocadherins (PCDHs) play crucial roles in pathogenesis and progression of cancers including gastric cancer (GC). Protocadherin8 (PCDH8) was previously reported to be involved in metastasis of GC, but functional studies yielded inconsistent results and the molecular mechanism remained unknown. This study aimed to explore the clinical relevance, function and molecular mechanism of PCDH8 in GC. Data from the GEPIA and Kaplan-Meier plotter databases showed that high expression of PCDH8 was significantly correlated with poorer prognosis in GC. Ectopic expression of PCDH8 in GC cells promoted invasion and migration in vitro and metastasis in vivo, and knockdown of PCDH8 inhibited invasion and migration in vitro. RNA sequencing followed by Gene Set Enrichment Analysis found a remarkable enrichment in the extracellular matrix receptor interaction pathway, with the expression of laminin subunit γ2 (LAMC2) being significantly increased in the PCDH8-overexpressing group. High expression of LAMC2 was significantly correlated to poor prognosis in GC in GEPIA database. Up-regulation of LAMC2 following PCDH8 overexpression was further confirmed by immunohistochemistry in liver metastatic lesions of nude mice. To our knowledge, this is the first report of the metastasis-enhancing property and molecular mechanism through up-regulation of LAMC2 of PCDH8 in cancer. High expression of PCDH8 could be used as a biomarker for poor prognosis in clinical practice.

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Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation

Abstract

Although hereditary kidney cancer syndrome accounts for around five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, U.S.A. and the first kidney cancer associated gene, VHL was identified through kindred analysis of von Hippel-Lindau syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia-inducible factor (HIF), which provided basis for the development of tyrosine kinase inhibitors targeting the HIF-VEGF/PDGF pathway. Recent whole-exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms how an alteration of each kidney cancer associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer.

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Colonic perforation due to GI histoplasmosis in an immunocompetent host mimicking Crohn's disease

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The presence of small and diminutive proximal hyperplastic polyps is associated with higher rates of synchronous advanced neoplasia compared with patients without serrated lesions

The association of proximal small and diminutive hyperplastic polyps (HPs) with synchronous neoplasia (AN) is not well defined. However, sessile serrated polyps, even when small, are known to portend synchronous neoplastic risk. Currently, when proximal small hyperplastic polyps are detected, the USMTF does not recommend a change in surveillance interval. We aimed to compare the rates of synchronous AN in a screening colonoscopy cohort of patients with small and then diminutive proximal HPs in comparison, first to a cohort absent any serrated or proximal hyperplastic polyps, and then in comparison with a cohort with small proximal sessile serrated polyps (SSPs).

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No additional prognostic value for MRE11 in squamous cell carcinomas of the anus treated with chemo-radiotherapy

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EEG synchronization measures predict epilepsy-related BOLD-fMRI fluctuations better than commonly used univariate metrics

Because of their complementary properties, the simultaneous acquisition of the electroencephalogram (EEG) and blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been actively pursued. This is particularly important in the field of epilepsy, motivated by the need to map epileptic activity, as accurately as possible, in the brain of patients with drug-resistant focal epilepsy undergoing pre-surgical evaluation (Hoffmann et al., 2000; Ives et al., 1993; Lemieux et al., 2001; LeVan and Gotman, 2009; Salek-Haddadi et al., 2006).

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Epileptiform and periodic EEG activities induced by rapid sevoflurane anaesthesia induction

Sevoflurane is a fluorinated inhalated anaesthetic introduced into clinical practice in the 1990's. It is now widely used in both adults and children because of its rapid onset and short-lasting activity, pleasant odour and non-pungency (Eger 1994; Lerman et al., 1994). A rapid increase in the inspiratory concentration of sevoflurane, however, has been demonstrated to be associated with a transient hyperdynamic reaction in adult patients during controlled mild hypocapneic hyperventilation (Vakkuri et al., 1999).

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Clusterin Induces MUC5AC Expression via Activation of NF-κB in Human Airway Epithelial Cells.

Clusterin Induces MUC5AC Expression via Activation of NF-κB in Human Airway Epithelial Cells.

Clin Exp Otorhinolaryngol. 2018 Jan 11;:

Authors: Bae CH, Na HG, Choi YS, Song SY, Kim YD

Abstract
Objectives: Clusterin (CLU) is known as apolipoprotein J, and has three isoforms with different biological functions. CLU is associated with various diseases such as Alzheimer disease, atherosclerosis, and some malignancies. Recent studies report an association of CLU with inflammation and immune response in inflammatory airway diseases. However, the effect of CLU on mucin secretion of airway epithelial cells has not yet been understood. Therefore, the effect and brief signaling pathway of CLU on MUC5AC (as a major secreted mucin) expression were investigated in human airway epithelial cells.
Methods: In the tissues of nasal polyp and normal inferior turbinate, the presence of MUC5AC and CLU was investigated using immunohistochemical stain and Western blot analysis. In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effect and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway of CLU on MUC5AC expression were investigated using immunohistochemical stain, reverse transcription-polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and Western blot analysis.
Results: In the nasal polyps, MUC5AC and CLU were abundantly present in the epithelium on immunohistochemical stain, and nuclear CLU (nCLU) was strongly detected on Western blot analysis. In human NCI-H292 airway epithelial cells or the primary cultures of normal nasal epithelial cells, recombinant nCLU increased MUC5AC expression, and significantly activated phosphorylation of NF-κB. And BAY 11-7085 (a specific NF-κB inhibitor) and knockdown of NF-κB by NF-κB siRNA (small interfering RNA) significantly attenuated recombinant nCLU-induced MUC5AC expression.
Conclusion: These results suggest that nCLU induces MUC5AC expression via the activation of NF-κB signaling pathway in human airway epithelial cells.

PMID: 29316784 [PubMed - as supplied by publisher]

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Eric Topol's Top 10 Tech Advances Shaping Medicine

Dr Eric Topol identifies the latest tech advances in medicine that set the stage for the coming year.
Medscape

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Chinese Cervicocephalic artery dissection study (CCADS): rationale and protocol for a multicenter prospective cohort study

Cervicocephalic artery dissection (CAD) is an important etiology of stroke in the youth. Findings from recent studies suggest it a "group of disease entities" with different underlying etiologies, presentation...

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Reliability and Validity of the Turkish Version of the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V)

The main purpose of this study was to culturally adapt the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) to Turkish and to evaluate its internal consistency, validity, and reliability.

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Trends in Singing Voice Research: An Innovative Approach

The objectives of this study were to trace and describe research patterns in singing voice, to compare the amount of published research over time, to identify journals that published most papers on "singing voice," and to establish the most frequent research topics.

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Orthognathic surgery in Melnick–Needles syndrome: a review of the literature and report of two siblings

Melnick–Needles syndrome (MNS) is a rare congenital X-linked dominant skeletal dysplasia, characterized by exophthalmos, a prominent forehead, and mandibular hypoplasia and retrognathism. Dental features may include anodontia, hypodontia, or oligodontia. Increased collagen content, unpredictable collagen synthesis, and abnormal bony architecture have raised concerns regarding bone splitting intraoperatively and bone healing postoperatively. This report describes the cases of two sisters with MNS, who successfully underwent orthognathic surgery consisting of bilateral mandibular ramus osteotomies combined with advancement genioplasty and iliac crest bone grafting, to correct the classical MNS facial deformity of mandibular retrognathia.

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Impact of crack cocaine use on the occurrence of oral lesions and micronuclei

The aim of this study was to investigate the occurrence of oral lesions and micronuclei in crack cocaine users. A cross-sectional study was conducted involving 106 crack users and 106 non-users matched for age, sex, and tobacco use. Socio-demographic characteristics, the consumption of psychoactive substances, and the occurrence of fundamental lesions were investigated. Cellular changes in the oral mucosa (karyolysis, karyorrhexis, 'broken egg' events, and micronuclei) were determined by exfoliative cytology for 54 participants in each group.

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LncRNA GAS8-AS1 inhibits cell proliferation through ATG5-mediated autophagy in papillary thyroid cancer

Abstract

Purpose

The long non-coding RNA GAS8 antisense RNA 1 (lncRNA GAS8-AS1) is a tumor suppressor in papillary thyroid cancer (PTC), but the mechanisms underlying how GAS8-AS1 regulates PTC biology remain unclear. Here, we evaluated the molecular function of GAS8-AS1 in regulating autophagy in PTC cell lines.

Methods

GAS8-AS1 was overexpressed and knocked down in PTC cell lines by transfecting with expression plasmids or short interfering RNAs (siRNAs). Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8). qRT-PCR and western blot were used to determine changes in expression of autophagy-related genes. Autophagy was evaluated by immunofluorescence and transmission electron microscopy.

Results

Relative GAS8-AS1 expression was lower in the PTC cell lines, TPC1 and BCPAP, compared to a normal thyroid cell line. Overexpression of GAS8-AS1 inhibited proliferation, significantly increased the ratio of LC3-II/LC3-I, and reduced p62 expression, whereas GAS8-AS1 knockdown demonstrated opposite effects. In GAS8-AS1 overexpressing cell lines, LC3 immunofluorescence staining demonstrated increased punctate aggregates of LC3 staining, and transmission electron microscopy revealed increased numbers of autophagosomes. Autophagy-related gene 5 (ATG5) was markedly upregulated by GAS8-AS1 overexpression and downregulated by GAS8-AS1 knockdown. Finally, silencing of ATG5 attenuated autophagy activation and rescued the inhibition of cell proliferation caused by GAS8-AS1.

Conclusions

In PTC cell lines, GAS8-AS1 inhibited proliferation, activated autophagy, and increased ATG5 expression. Downregulation of ATG5 reversed GAS8-AS1-mediated activation of autophagy leading to cell death, revealing a novel mechanism of the GAS8-AS1-ATG5 axis in PTC cell lines. This provided a new experimental basis to explore the effects of lncRNA on autophagy in the treatment of thyroid cancer.

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Adverse Effect of Mobile Phone on Hearing in Healthy Individuals: A Clinical Study

Abstract

The mobile phone is a ubiquitous piece in this modern world. An estimated 85% of Americans, 80% of the British, and perhaps 75% of Indians use it, as of today. Mobile phones communicate by transmitting radio waves through a network of fixed antennas called base stations. Radio frequency waves are electromagnetic fields, and unlike ionizing radiation such as X-rays or gamma rays, can neither break chemical bonds nor cause ionization in the human body. 1000 participants from outpatient department of a tertiary care center over a period of one and a half years, were included in the study and were divided equally into case (> 1 year use) and control (< 1 year use) groups. Out of 500 cases, maximum 233(46.6%) subjects were using mobile since last 4–6 year and 134(26.8%) were using mobile since last 7–9 year and maximum 344(68.8%) subjects were using mobile 1–3 h/day and 145(29.0%) were using mobile 4–6 h/day.

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LncRNA GAS8-AS1 inhibits cell proliferation through ATG5-mediated autophagy in papillary thyroid cancer

Abstract

Purpose

Methods

Results

Conclusions

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A personal reminiscence of Michel Jouvet: the poet of paradoxical sleep

Others will surely write about the scientific accomplishments of Michel Jouvet, his appointments to many scientific academies, his time in the French underground movement during World War II, as well as the awards he received from around the world. However, I would like to present another side of one of the great figures of our time. He was born in Lons-le-Saunier, a town in the eastern part of France, and died in Villeurbanne, which borders Lyon. Michel Jouvet's teenage years were spent under Nazi occupation.

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Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer

Abstract

Background

The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients.

Methods

Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations.

Results

The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55–37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50–45.0, P = 0.176).

Conclusions

Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

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A SUV max -based propensity matched analysis of stereotactic body radiotherapy versus surgery in stage I non-small cell lung cancer: unveiling the role of 18F-FDG PET/CT in clinical decision-making

Abstract

Background

The value of maximum standard uptake value (SUV_max) was overlooked in current studies comparing stereotactic body radiotherapy (SBRT) versus surgery for stage I non-small cell lung cancer (NSCLC). Herein, we aimed to compare the 3-year outcomes based on patients for whom SUV_max were available, and to explore the role of SUV_max in clinical decision-making.

Methods

From January 2010 to June 2016, data of eligible patients were collected. Patient variables and clinical outcomes were compared in both unmatched and matched groups using propensity score matching (PSM). Multivariate analysis was performed for predictors of poor outcome. The relationship between treatment approach and survival outcome was also evaluated in subgroup patients stratified by SUV_max level.

Results

A total of 425 patients treated with either surgery (325) or SBRT (100) were included. Patients receiving SBRT were significantly older, had a higher level of SUV_max and were more likely to have tumor of centrally located. Multivariate analysis showed that SUV_max and tumor size were significant predictors for 3-year OS, LRC, and PFS, while better PFS was also related to peripheral tumor and surgery. The result of PSM analysis also showed that compared to SBRT, surgery could only achieve better PFS. Subgroup analysis indicated that surgery had added advantage of 3-year LRC and PFS for patients in high SUV_max group (SUV_max > 8), but not in low SUV_max group.

Conclusions

The study found a superior PFS after surgery while OS and LRC did not differ between SBRT and surgery. Surgery should be recommended for tumor of high SUV_max.

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Analysis of DNA modifications in aging research

Abstract

As geroscience research extends into the role of epigenetics in aging and age-related disease, researchers are being confronted with unfamiliar molecular techniques and data analysis methods that can be difficult to integrate into their work. In this review, we focus on the analysis of DNA modifications, namely cytosine methylation and hydroxymethylation, through next-generation sequencing methods. While older techniques for modification analysis performed relative quantitation across regions of the genome or examined average genome levels, these analyses lack the desired specificity, rigor, and genomic coverage to firmly establish the nature of genomic methylation patterns and their response to aging. With recent methodological advances, such as whole genome bisulfite sequencing (WGBS), bisulfite oligonucleotide capture sequencing (BOCS), and bisulfite amplicon sequencing (BSAS), cytosine modifications can now be readily analyzed with base-specific, absolute quantitation at both cytosine-guanine dinucleotide (CG) and non-CG sites throughout the genome or within specific regions of interest by next-generation sequencing. Additional advances, such as oxidative bisulfite conversion to differentiate methylation from hydroxymethylation and analysis of limited input/single-cells, have great promise for continuing to expand epigenomic capabilities. This review provides a background on DNA modifications, the current state-of-the-art for sequencing methods, bioinformatics tools for converting these large data sets into biological insights, and perspectives on future directions for the field.

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Comment on “The pros and cons of continuous glucose monitoring for patients with type 1 diabetes on multiple daily injections of insulin.”

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Establishment of a protocol to extend the lifespan of human hormone-secreting pituitary adenoma cells

Abstract

Purpose

The aim of this study was to generate immortalized human anterior pituitary adenoma cells. Reliable cell models for the study of human pituitary adenomas are as yet lacking and studies performed so far used repeated passaging of freshly excised adenomas, with the attendant limitations due to limited survival in culture, early senescence, and poor reproducibility.

Methods & Results

We devised a technique based upon repeated co-transfections of two retroviral vectors, one carrying the catalytic subunit of human telomerase, hTERT, the other SV40 large T antigen. This approach extended the lifespan of cells derived from a human growth hormone-secreting adenoma up to 18 months while retaining morphology of primary cells, growth hormone synthesis and growth hormone secretion.

Conclusions

Our attempt represents the first demonstration of successful lifespan extension of human growth hormone-secreting pituitary adenoma cells via co-transfection of hTERT and SV40T and paves the way to future attempts to obtain stable cell lines.

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Toward Optimizing Vestibular Evoked Myogenic Potentials: Normalization Reduces the Need for Strong Neck Muscle Contraction

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Background: The cervical vestibular evoked myogenic potential (cVEMP) represents an inhibitory reflex of the saccule measured in the ipsilateral sternocleidomastoid muscle (SCM) in response to acoustic or vibrational stimulation. Since the cVEMP is a modulation of SCM electromyographic (EMG) activity, cVEMP amplitude is proportional to muscle EMG amplitude. We sought to evaluate muscle contraction influences on cVEMP peak-to-peak amplitudes (VEMPpp), normalized cVEMP amplitudes (VEMPn), and inhibition depth (VEMPid). Methods: cVEMPs at 500 Hz were measured in 25 healthy subjects for 3 SCM EMG contraction ranges: 45-65, 65-105, and 105-500 μV root mean square (r.m.s.). For each range, we measured cVEMP sound level functions (93-123 dB peSPL) and sound off, meaning that muscle contraction was measured without acoustic stimulation. The effect of muscle contraction amplitude on VEMPpp, VEMPn, and VEMPid and the ability to distinguish cVEMP presence/absence were evaluated. Results: VEMPpp amplitudes were significantly greater at higher muscle contractions. In contrast, VEMPn and VEMPid showed no significant effect of muscle contraction. Cohen's d indicated that for all 3 cVEMP metrics contraction amplitude variations produced little change in the ability to distinguish cVEMP presence/absence. VEMPid more clearly indicated saccular output because when no acoustic stimulus was presented the saccular inhibition estimated by VEMPid was zero, unlike those by VEMPpp and VEMPn. Conclusion: Muscle contraction amplitude strongly affects VEMPpp amplitude, but contractions 45-300 μV r.m.s. produce stable VEMPn and VEMPid values. Clinically, there may be no need for subjects to exert high contraction effort. This is especially beneficial in patients for whom maintaining high SCM contraction amplitudes is challenging.
Audiol Neurotol 2017;22:282-291

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Calibration of peripheral perception of shape with and without saccadic eye movements

Abstract

The cortical representations of a visual object differ radically across saccades. Several studies claim that the visual system adapts the peripheral percept to better match the subsequent foveal view. Recently, Herwig, Weiß, and Schneider (2015, Annals of the New York Academy of Sciences, 1339(1), 97–105) found that the perception of shape demonstrates a saccade-dependent learning effect. Here, we ask whether this learning actually requires saccades. We replicated Herwig et al.'s (2015) study and introduced a fixation condition. In a learning phase, participants were exposed to objects whose shape systematically changed during a saccade, or during a displacement from peripheral to foveal vision (without a saccade). In a subsequent test, objects were perceived as less (more) curved if they previously changed from more circular (triangular) in the periphery to more triangular (circular) in the fovea. Importantly, this pattern was seen both with and without saccades. We then tested whether a variable delay between the presentations of the peripheral and foveal objects would affect their association—hypothetically weakening it at longer delays. Again, we found that shape judgments depended on the changes experienced during the learning phase and that they were similar in both the saccade and fixation conditions. Surprisingly, they were not affected by the delay between the peripheral and foveal presentations over the range we tested. These results suggest that a general associative process, independent of saccade execution, contributes to the perception of shape across viewpoints.

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Salience from multiple feature contrast: Evidence from saccade trajectories

Abstract

We used eye tracking to quantify the extent to which combinations of salient contrasts (orientation, luminance, and movement) influence a central salience map that guides eye movements. We found that luminance combined additively with orientation and movement, suggesting that the salience system processes luminance somewhat independently of the two other features. On the other hand, orientation and movement together influenced salience underadditively, suggesting that these two features are processed nonindependently. This pattern of results suggests that the visual system does not sum sources of salience linearly, but treats some sources of salience as redundant.

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Inside EMS Podcast: The development of airway, intubation skills

Download this podcast on iTunes, SoundCloud or via RSS feed In this Inside EMS Podcast episode, co-hosts Chris Cebollero and Kelly Grayson discuss the development of airway and intubation skills. With many systems removing intubation as a skill set for paramedics, how do we prepare for a better trained EMS provider" Learn more about the EMS1 Academy and schedule a free demo.

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Comment on “The pros and cons of continuous glucose monitoring for patients with type 1 diabetes on multiple daily injections of insulin.”

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Establishment of a protocol to extend the lifespan of human hormone-secreting pituitary adenoma cells

Abstract

Purpose

Methods & Results

Conclusions

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The Benefits of Singing and Strolling

We've heard of whistling while you work, but what about singing while you walk? Preliminary findings from a recent study (Harrison et al, 2017) suggest that those with mild to moderate Parkinson's disease may see improvement (i.e., less variability) in their gait if they sing a little tune while they stroll along. While previous research has demonstrated the benefit of "external rhythmic auditory stimuli" has on gait in those with Parkinson's, this is the first to use a self-mediated approach.

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Mangiferin prevents the growth of gastric carcinoma by blocking the PI3K-Akt signalling pathway

The aim of the present study was to investigate the effects of mangiferin on gastric carcinoma cells and to determine the possible mechanisms underlying such effects. The MTT assay was performed to evaluate the antiproliferative effect of mangiferin. Following treatment, apoptosis rates of SGC-7901 were established by flow cytometry and laser confocal microscopy, and western blot analysis was used to detect the expression of apoptosis-related proteins. The MTT assay showed that mangiferin inhibited the proliferation of SGC-7901 and BCG-823 cells in a dose-dependent and time-dependent manner. After SGC-7901 cells were exposed to mangiferin for 24, 48 and 72 h, the half-maximal inhibitory concentration values were 16.00, 8.63 and 4.79 µmol/l, respectively. SGC-7901 cell apoptosis induced by mangiferin was observed by Annexin V/PI doubling staining and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive staining. We found a significant decrease in Bcl-2, Bcl-xL and Mcl-1 expression and a significant increase in Bax, Bad and cleaved caspase-3 and caspase-9 expression in SGC-7901 cells by mangiferin treatment. Moreover, mangiferin significantly decreased the levels of p-PI3K, p-Akt and p-mTOR, but had no effects on those of PI3K, Akt and mTOR in epidermal growth factor-treated SGC-7901 cells. Interestingly, the proapoptotic effect of mangiferin on SGC-7901 cells was partially blocked by the Akt activator SC79, whereas LY294002 significantly increased mangiferin-induced apoptosis and growth inhibition. Taken together, our findings indicate that mangiferin effectively inhibits cell growth and induces apoptosis of gastric cancer cells through inhibiting the PI3K/Akt pathways with relative safety, and may be used as a novel chemotherapeutic agent against gastric cancer.

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Αρχειοθήκη ιστολογίου

Πέμπτη 11 Ιανουαρίου 2018

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