scholarly journals Targeting the cMET pathway augments radiation response without adverse effect on hearing in NF2 schwannoma models

2018 ◽  
Vol 115 (9) ◽  
pp. E2077-E2084 ◽  
Author(s):  
Yingchao Zhao ◽  
Pinan Liu ◽  
Na Zhang ◽  
Jie Chen ◽  
Lukas D. Landegger ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Hearing Loss ◽  
Neurofibromatosis Type ◽  
Cyst Formation ◽  
High Dose ◽  
Slice Culture ◽  
Neurofibromatosis Type Ii ◽  
Hepatocyte Growth ◽  
Dose Radiation

Neurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth causes progressive hearing loss, and the standard treatment, including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allow hearing testing. Here, we developed a cerebellopontine angle (CPA) schwannoma model that faithfully recapitulates the tumor-induced hearing loss. Using this model, we discovered that cMET blockade by crizotinib (CRZ) enhanced schwannoma radiosensitivity by enhancing DNA damage, and CRZ treatment combined with low-dose radiation was as effective as high-dose radiation. CRZ treatment had no adverse effect on hearing; however, it did not affect tumor-induced hearing loss, presumably because cMET blockade did not change tumor hepatocyte growth factor (HGF) levels. This cMET gene knockdown study independently confirmed the role of the cMET pathway in mediating the effect of CRZ. Furthermore, we evaluated the translational potential of cMET blockade in human schwannomas. We found that human NF2-associated and sporadic VSs showed significantly elevated HGF expression and cMET activation compared with normal nerves, which correlated with tumor growth and cyst formation. Using organoid brain slice culture, cMET blockade inhibited the growth of patient-derived schwannomas. Our findings provide the rationale and necessary data for the clinical translation of combined cMET blockade with radiation therapy in patients with NF2.

scholarly journals Multicenter, Prospective, Phase II and Biomarker Study of High-Dose Bevacizumab as Induction Therapy in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannoma

2019 ◽  
Vol 37 (35) ◽  
pp. 3446-3454 ◽  
Author(s):  
Scott R. Plotkin ◽  
Dan G. Duda ◽  
Alona Muzikansky ◽  
Jeffrey Allen ◽  
Jaishri Blakeley ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Growth Factor ◽  
Phase Ii ◽  
Standard Dose ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
High Dose ◽  
Radiographic Response ◽  
Bevacizumab Treatment

PURPOSE Bevacizumab treatment at 7.5 mg/kg every 3 weeks results in improved hearing in approximately 35%-40% of patients with neurofibromatosis type 2 (NF2) and progressive vestibular schwannomas (VSs). However, the optimal dose is unknown. In this multicenter phase II and biomarker study, we evaluated the efficacy and safety of high-dose bevacizumab in pediatric and adult patients with NF2 with progressive VS. PATIENTS AND METHODS Bevacizumab was given for 6 months at 10 mg/kg every 2 weeks, followed by 18 months at 5 mg/kg every 3 weeks. The primary end point was hearing response defined by word recognition score (WRS) at 6 months. Secondary end points included toxicity, radiographic response, quality of life (QOL), and plasma biomarkers. RESULTS Twenty-two participants with NF2 (median age, 23 years) with progressive hearing loss in the target ear (median baseline WRS, 53%) were enrolled. Nine (41%) of 22 participants achieved a hearing response at 6 months (1 of 7 children and 8 of 15 adults; P = .08). Radiographic response was seen in 7 (32%) of 22 patients with VS at 6 months (7 of 15 adults and 0 of 7 children; P = .05). Common mild to moderate adverse events included hypertension, fatigue, headache, and irregular menstruation. Improvement in NF2-related QOL and reduction in tinnitus-related distress were reported in 30% and 60% of participants, respectively. Paradoxically, high-dose bevacizumab treatment was not associated with a significant decrease in free vascular endothelial growth factor but was associated with increased carbonic anhydrase IX, hepatocyte growth factor, placental growth factor, stromal cell-derived factor 1α, and basic fibroblast growth factor concentrations in plasma. CONCLUSION High-dose bevacizumab seems to be no more effective than standard-dose bevacizumab for treatment of patients with NF2 with hearing loss. In contrast to adults, pediatric participants did not experience tumor shrinkage. However, adult and pediatric participants reported similar improvement in QOL during induction. Novel approaches using bevacizumab should be considered for children with NF2.

scholarly journals Role of Tumor Necrosis Factor-  and TRAIL in High-Dose Radiation Induced Bystander Signaling in Lung Adenocarcinoma

2007 ◽  
Vol 67 (24) ◽  
pp. 11811-11820 ◽  
Author(s):  
M. M. Shareef ◽  
N. Cui ◽  
R. Burikhanov ◽  
S. Gupta ◽  
S. Satishkumar ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Lung Adenocarcinoma ◽  
Tumor Necrosis ◽  
High Dose ◽  
Radiation Induced ◽  
Dose Radiation ◽  
Necrosis Factor

scholarly journals Simultaneous cochlear implantation as a therapeutic option in vestibular schwannoma surgery: case report

2018 ◽  
Vol 44 (3) ◽  
pp. E9 ◽  
Author(s):  
Pedro Helo dos Santos Neto ◽  
Johnni Oswaldo Zamponi ◽  
Rogério Hamerschmidt ◽  
Gislaine Richter Minhoto Wiemes ◽  
Marcio S. Rassi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cochlear Implantation ◽  
Therapeutic Option ◽  
Neurofibromatosis Type ◽  
Hearing Preservation ◽  
Common Symptom ◽  
Profound Hearing Loss ◽  
Microsurgical Resection ◽  
Speech Recognition In Noise

Hearing loss is the most common symptom of vestibular schwannomas (VSs). The management of these lesions includes observation, radiosurgery, and microsurgical resection. Hearing preservation and rehabilitation are the major challenges after the tumor treatment. A 43-year-old man with previous left-sided profound hearing loss and tinnitus presented with a 2-mm left-sided intracanalicular VS. The decision was made to perform a simultaneous cochlear implantation (CI) and microsurgical resection of the tumor. The patient did well postoperatively, with significant improvement of tinnitus, sound localization, and speech recognition in noise. Previous reports of simultaneous CI and VS resection in patients with neurofibromatosis type 2 and sporadic VS in the only hearing ear have been described. The role of CI in patients with VS and normal contralateral hearing has been recently described, showing positive outcomes due to the binaural benefits. Tinnitus also can be treated by the implantation of the cochlear device. The simultaneous microsurgical removal of VS and implantation of a cochlear device is a feasible approach in patients with unilateral hearing loss and severe tinnitus.

Role of Bcl-xL in hepatocyte growth factor-elicited epithelial protection in idiopathic pulmonary fibrosis

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
S Skwarna ◽  
I Henneke ◽  
W Seeger ◽  
T Geiser ◽  
A Günther ◽  
...  
Keyword(s):  
Growth Factor ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Hepatocyte Growth Factor ◽  
Hepatocyte Growth

Pre-emptive Analgesia for Postoperative Pain Relief in Children – Role of Paracetamol

2009 ◽  
pp. 9-16
Author(s):  
Rubina Yasmin ◽  
AKM Akhtaruzzaman ◽  
Paresh Chandra Sarker ◽  
Neaz Ahmed ◽  
Ranadhir Kumar Kundu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Postoperative Pain ◽  
Diclofenac Sodium ◽  
Total Duration ◽  
Pain Scale ◽  
Prospective Clinical Study ◽  
High Dose ◽  
Induction Of Anaesthesia

This prospective clinical study was carried out in the Dept. of Anaesthesia, Analgesia and Intensive Care Medicine, BSMMU, Dhaka, during the period of May 2003 to July 2003. The study was done to emphasize the importance of giving analgesics preemptively instead of waiting for the child to complain of pain and to produce smooth recovery after surgery by decreasing immediate postoperative pain in children by a simple, safe acceptable drug. The children scheduled for tonsillectomy under general anaesthesia were recruited in this study. The analgesic efficiency of rectal paracetamol in two doses, 25 mg/kg bodywt.(Gr-P25) and 50 mg/kg. bodywt. (Gr-P50) were compared with Diclofenac Sodium suppository 1mg/ kg body weight (Gr-D) given half an hour before induction of anaesthesia. Pain scoring was done by TPPPS (Toddler Pre-schooler postoperative pain scale). Heart rate and blood pressure were stable in Gr-P50 and Gr-D. Time of first demand of analgesic was delayed in Gr-P50 and Gr-D. Total paracetamol consumption in 24 hours was less in Gr-P50(181±14.25) and Gr-D (212±25) than Gr-P25(318± 26.39). Total duration of analgesia in Gr- P50 (657±9.94) mins. and in Gr- D(502±10.63) mins. and in Gr-P25(288±23.17) mins. Pre-emptive high dose rectal paracetamol appears to be more effective than diclofenac sodium suppository for postoperative analgesia in children undergoing tonsillectomy. Journal of BSA, Vol. 18, No. 1 & 2, 2005 p.9-16

Moderating Role of Stress, Anxiety, and Depression in the Relationship Between Tinnitus and Hearing Loss Among Patients

2020 ◽  
Vol 34 (4) ◽  
pp. 753-772
Author(s):  
Ammar Ahmed ◽  
Muhammad Aqeel ◽  
Tanvir Akhtar ◽  
Sammeen Salim ◽  
Bashir Ahmed
Keyword(s):  
Hearing Loss ◽  
Psychological Problems ◽  
Anxiety And Depression ◽  
Adaptation Level ◽  
Depression Anxiety Stress Scale ◽  
Neuropsychological Theory ◽  
Anxiety Depression ◽  
The Relationship ◽  
Moderating Role

Adaptation level theory of tinnitus and neuropsychological theory of tinnitus are extensively used frameworks for understanding emotional and psychological distress among tinnitus sufferers. Objective of the present study was to investigate potential associations between hearing loss, tinnitus, anxiety, depression, and stress. The Tinnitus Handicap Inventory (Newman, Jacobson, & Spitzer, 1996) and the Depression, Anxiety, Stress Scale (Lovibond & Lovibond, 1995)scales were administered to a sample of 110 tinnitus outpatients recruited from Audiology departments of Lahore and Rawalpindi hospitals. Results revealed tinnitus was positively linked with psychological problems. Additionally, it was established that tinnitus is a positive significant predictor for anxiety, stress and depression. The moderation models related to the interactions between psychological problems and hearing loss were negative significant predictors for tinnitus symptoms. Moreover, the comparative analysis between gender differences revealed a significant diversity in the levels of stress, anxiety, and depression. Results also elucidated that patients at initial stages of hearing loss were more prone towards reporting tinnitus symptoms along with emerging psychological problems.

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