Publications by authors named "David Sherris"

63 Publications

Complications Secondary to Nonsurgical Rhinoplasty: A Systematic Review and Meta-analysis.

Otolaryngol Head Neck Surg 2021 Feb 16:194599820987827. Epub 2021 Feb 16.

Department of Otolaryngology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA.

Objective: The popularity of nonsurgical rhinoplasty with injectable fillers continues to rise, and it is important to understand the scope of potential adverse outcomes. The purpose of our study is to determine the prevalence and types of adverse outcomes secondary to nonsurgical rhinoplasty.

Data Sources: PubMed, Cochrane, Embase.

Review Methods: The data sources were explored using the following combination of terms: (("inject*" OR "nonsurgical" OR "augmentation" OR "filler") AND "rhinoplast*") AND ("complication" OR "adverse" OR "embol*"). Studies on human nonsurgical rhinoplasty using injectable fillers were included. A quantitative meta-analysis was performed on articles with low risk of bias.

Results: The search yielded 37 publications for review, with 23 included cohort studies and 14 case reports with 8604 patients undergoing nonsurgical rhinoplasty with reported complications. The overall rate of adverse outcome across all cohort studies was 2.52%. The most commonly reported complications were bruising (1.58%) and hematoma (0.13%). While uncommon, there are several reports of major complications including 30 episodes of vessel occlusion (0.35%), 7 reports of skin necrosis (0.08%), 8 reports of vision loss (0.09%), and 6 reports of infection (0.07%).

Conclusion: Overall, nonsurgical rhinoplasty with injectable fillers is safe with low rates of complications. However, serious complications, such as vision loss, skin necrosis, and vessel occlusion, can occur. Further studies are needed to optimize delivery of injectable fillers in the nose to decrease the rate of adverse outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0194599820987827DOI Listing
February 2021

Influence of Social Media on Facial Plastic and Reconstructive Surgeons.

Facial Plast Surg Aesthet Med 2021 Feb 5. Epub 2021 Feb 5.

Department of Otolaryngology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/fpsam.2020.0452DOI Listing
February 2021

Characterization of Medical Malpractice Litigation after Rhinoplasty in the United States.

Aesthet Surg J 2020 Dec 17. Epub 2020 Dec 17.

Department of Otolaryngology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, United States.

Background: Rhinoplasty is one of the most common operations performed with favorable results and high patient satisfaction. However, when complications occur or when the desired outcome is not achieved, patients may seek litigation on the premise that there was a violation in the standard of care. Knowledge of malpractice claims can inform rhinoplasty surgeons on how to minimize risk of future litigation as well as improve patient satisfaction.

Objectives: 1) To identify motives for seeking medical malpractice litigation after rhinoplasty; 2) To examine outcomes of malpractice litigation after rhinoplasty in the United States.

Methods: The Westlaw legal database was reviewed for all available court decisions related to malpractice after rhinoplasty. Data collected and analyzed included plaintiff gender, location, specialty of defendant(s), plaintiff allegation, and adjudicated case outcomes.

Results: Twenty-three cases were identified between 1960 and 2018, located in 12 states in the United States. Plaintiffs were 70% female. Otolaryngologists were cited in 11 cases while 12 cases involved a plastic surgeon. All cases alleged negligence. Cases involved "technical" errors (69.6%), "unsatisfactory" outcomes (39.1%), inadequate follow-up or aftercare (30.4%), issues with the informed consent process (21.7%), unexpectedly extensive surgery (8.7%), improper medication administration (4.3%), and failure to recognize symptoms (4.3%). Twenty of the 23 adjudicated cases (86.9%) were ruled in favor of the surgeon. Contributing factors in cases alleging malpractice included poor aesthetic outcome/disfigurement (60.7%), new (post-surgical) onset/persistent nasal symptoms (30.4%), postoperative pain (21.7%), orbital/ocular injury (17.4%), burns (4%), nerve damage (4%), and issues with sleep (4%).

Conclusions: Malpractice litigation after rhinoplasty favored the surgeon in the majority of the adjudicated cases reviewed. The most common reason for litigating was dissatisfaction with aesthetic outcomes. Rhinoplasty surgeons may mitigate possible litigation by developing a positive doctor-patient relationship, clearly understanding the patient's surgical expectations, obtaining detailed informed consent while maintaining frequent and caring communication with the patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/asj/sjaa380DOI Listing
December 2020

Open Structure Approach to the European or Caucasian Nose.

Authors:
David A Sherris

Otolaryngol Clin North Am 2020 Apr 13;53(2):237-254. Epub 2020 Feb 13.

Department of Otolaryngology, Jacobs School of Medicine and Biomedical Sciences, 1237 Delaware Avenue, Buffalo, NY 14209, USA. Electronic address:

This article discusses common abnormalities found in the European or Caucasian nose. The treatments of the disorders via open structure rhinoplasty techniques are presented in a case-based manner. Multiple references are provided for further study of these techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.otc.2019.12.003DOI Listing
April 2020

The Brain Penetrating and Dual TORC1/TORC2 Inhibitor, RES529, Elicits Anti-Glioma Activity and Enhances the Therapeutic Effects of Anti-Angiogenetic Compounds in Preclinical Murine Models.

Cancers (Basel) 2019 Oct 21;11(10). Epub 2019 Oct 21.

Department of Biotechnological and Applied Clinical Sciences, Division of Radiation Oncology, University of L'Aquila, 67100 L'Aquila, Italy.

Glioblastoma multiforme (GBM) is a devastating disease showing a very poor prognosis. New therapeutic approaches are needed to improve survival and quality of life. GBM is a highly vascularized tumor and as such, chemotherapy and anti-angiogenic drugs have been combined for treatment. However, as treatment-induced resistance often develops, our goal was to identify and treat pathways involved in resistance to treatment to optimize the treatment strategies. Anti-angiogenetic compounds tested in preclinical and clinical settings demonstrated recurrence associated to secondary activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway. Here, we determined the sensitizing effects of the small molecule and oral available dual TORC1/TORC2 dissociative inhibitor, RES529, alone or in combination with the anti-VEGF blocking antibody, bevacizumab, or the tyrosine kinase inhibitor, sunitinib, in human GBM models. We observed that RES529 effectively inhibited dose-dependently the growth of GBM cells in vitro counteracting the insurgence of recurrence after bevacizumab or sunitinib administration in vivo. Combination strategies were associated with reduced tumor progression as indicated by the analysis of Time to Tumor Progression (TTP) and disease-free survival (DSF) as well as increased overall survival (OS) of tumor bearing mice. RES529 was able to reduce the in vitro migration of tumor cells and tubule formation from both brain-derived endothelial cells (angiogenesis) and tumor cells (vasculogenic mimicry). In summary, RES529, the first dual TORC1/TORC2 dissociative inhibitor, lacking affinity for ABCB1/ABCG2 and having good brain penetration, was active in GBM preclinical/murine models giving credence to its use in clinical trial for patients with GBM treated in association with anti-angiogenetic compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11101604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826425PMC
October 2019

Neurotoxins.

Facial Plast Surg 2019 Jun 12;35(3):230-238. Epub 2019 Jun 12.

Department of Otolaryngology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York.

Botulinum toxin is integral to the practice of facial plastic surgery. Since it was approved by the U.S. Food and Drug Administration for the temporary improvement of glabellar rhytids in 2002, botulinum toxin has achieved a growing number of off-label clinical applications. These include the management of facial rhytids, brow ptosis, excessive gingival display, masseteric hypertrophy, platysmal banding, facial nerve paralysis, hypertrophic scars, and keloids. Many forms of botulinum toxin have been developed, and their safety and efficacy have been thoroughly established. This article will review the aesthetic and functional uses of botulinum toxin as it relates to the field of facial plastic and reconstructive surgery. In addition, the authors will discuss the suggested quantity of units per injection site based on onabotulinumtoxinA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0039-1688844DOI Listing
June 2019

Therapeutic Antibodies for Nasal Polyposis Treatment: Where Are We Headed?

Clin Rev Allergy Immunol 2020 Oct;59(2):141-149

Department of Otolaryngology, Jacobs School of Medicine and Biomedical Sciences, Gromo Institute and Sinus Center, University at Buffalo, The State University of New York, 1237 Delaware Avenue, Buffalo, NY, 14209, USA.

This review article aims to outline what is known in the pathophysiology of chronic rhinosinusitis with nasal polyposis (CRSwNP) and describe the mechanism of the biologic agents being investigated for this disease. Chronic rhinosinusitis with nasal polyposis is an inflammatory disease of the nasal and paranasal mucosa, which causes symptoms of nasal obstruction, hyposmia, and rhinorrhea. Conventional therapy for CRSwNP includes intranasal corticosteroids (INCS) and polypectomy, but INCS offer only modest benefits, and recurrence after surgery is common. Therefore, effective pharmacologic therapies for CRSwNP are being actively sought. Monoclonal antibodies have been successful in other chronic diseases involving eosinophilic inflammation, such as chronic urticaria and asthma. Thus, researchers have begun expanding their scope and investigating the efficacy of these drugs in the treatment of nasal polyposis. The monoclonal antibodies under investigation (omalizumab (anti IgE), dupilumab (anti IL-4/IL-13), and reslizumab and mepolizumab (both anti IL-5), benralizumab (anti IL-5Rα), and etokimab (anti IL-33)) target key players in the pathophysiology of nasal polyposis (NP). Dupilumab has just completed phase III trials for CRSwNP with positive results, while omalizumab, mepolizumab, and benralizumab are currently in phase III trials for this indication. At this time, while there are no FDA-approved biologics for use in NP, research has highlighted the contributions of IL-4, IL-5, IL-13, and IgE as disease mediators in the pathogenesis of NP. The current FDA-approved treatment of intranasal steroids does not provide significant relief for many patients; therefore, these phase III trials of monoclonal antibodies bring hope for an exciting new treatment option.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12016-019-08734-zDOI Listing
October 2020

Sinusitis: A New Sinonasal Pathogen.

Ear Nose Throat J 2020 Jul 9;99(6):NP62-NP63. Epub 2019 May 9.

Department of Otolaryngology, University at Buffalo, Buffalo, NY, USA.

Background: The pathogens most commonly associated with acute bacterial rhinosinusitis include , and . The pathogens most commonly associated with chronic rhinosinusitis include and various anaerobic organisms, including , , and . This case report illustrates a case of chronic rhinosinusitis associated with the organism, a well-known animal pathogen that has never been documented in the sinonasal cavity before.

Methods: The medical records of an adult patient who presented to the otolaryngology office were reviewed. The literature available was reviewed.

Results: A 62-year-old man presented with chronic rhinosinusitis refractory to medical management. He was taken to the operating room for functional endoscopic sinus surgery and cultures were obtained, which returned positive for . He had no known animal contacts at home or work. He improved with surgery and appropriate antibiotic therapy.

Conclusions: has never before been reported as a human pathogen in the sinonasal cavities. Otolaryngologists must routinely obtain cultures of mucus or tissue during sinus surgery in order to ensure appropriate antibiotic treatment after surgery and resolution of patient symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0145561319848990DOI Listing
July 2020

Association of Corrugator Supercilii and Procerus Myectomy With Endoscopic Browlift Outcomes.

JAMA Facial Plast Surg 2019 Sep;21(5):375-380

Jacobs School of Medicine and Biomedical Sciences, Department of Otolaryngology, University at Buffalo, Buffalo, New York.

Importance: Glabellar wrinkling is a critical component of upper facial aging.

Objective: To compare the long-term outcomes on the wrinkle lines of the glabella and forehead following browlifts with vs without corrugator and procerus muscle resection.

Design, Setting, And Participants: A prospective cohort comparative trial was conducted of 23 patients who underwent browlift procedures by a single surgeon at a single institution (16 with glabellar muscle resection and 7 without muscle resection) between May 1, 2016, and July 1, 2017. All analysis took place between May 1, 2016, and May 14, 2018. The mean follow-up period was 16 months (range, 12-21 months). Sixteen of the 23 patients underwent a browlift with muscle resection procedure alone or in combination with other facial rejuvenation procedures to the brow, midface, jowl, and neck. Four of the 23 patients underwent browlifts only, and 19 had browlifts with other procedures. Seven of the 23 patients had browlift procedures without muscle resection and were designated as controls.

Interventions: Endoscopic browlift surgery was performed either with procerus and corrugator muscle resection or without muscle resection.

Main Outcomes And Measures: Neutral gaze and dynamic photographs of the upper face obtained preoperatively and after the 1-year postoperative mark were reviewed and scored in a blinded fashion by 2 physicians not affiliated with the study team using a modified Fitzpatrick Wrinkle Assessment score (FWA; from 0 [no wrinkling] to 5 [deep wrinkling with redundant skin]).

Results: The 23 study patients had a mean age of 60 years (range, 48-74 years); 21 were women, and 2 were men. There was a significant difference between the myectomy and control groups in the 12-month postoperative improvement in dynamic glabellar FWA scores (2.56 vs 1.07, P = .01). There was a difference between the myectomy and control groups in the improvements in resting glabellar FWA scores at 12-month follow-up, but it did not reach statistical significance (1.28 vs 1.00, P = .38). The 12-month postoperative improvements in dynamic (1.19 vs 1.29, P = .86) and resting forehead (1.0 vs 1.1, P = .70) FWA scores were not significantly different.

Conclusions And Relevance: In this study, the use of procerus and corrugator myectomy techniques appeared to achieve a superior long-term reduction in glabellar wrinkles vs forehead rejuvenation techniques without muscle resection.

Level Of Evidence: 3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamafacial.2018.2084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499133PMC
September 2019

Characterization of Small Molecules Inhibiting the Pro-Angiogenic Activity of the Zinc Finger Transcription Factor Vezf1.

Molecules 2018 07 3;23(7). Epub 2018 Jul 3.

Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.

Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of anti-angiogenic therapies that treat various diseases, including cancer. The role of transcription factor Vezf1 in vascular development and regulation of angiogenesis has been defined by several earlier studies. Through construction of a computational model for Vezf1, work here has identified a novel small molecule drug capable of inhibiting Vezf1 from binding to its cognate DNA binding site. Using structure-based design and virtual screening of the NCI Diversity Compound Library, 12 shortlisted compounds were tested for their ability to interfere with the binding of Vezf1 to DNA using electrophoretic gel mobility shift assays. We identified one compound, T4, which has an IC50 of 20 μM. Using murine endothelial cells, MSS31, we tested the effect of T4 on endothelial cell viability and angiogenesis by using tube formation assay. Our data show that addition of T4 in cell culture medium does not affect cell viability at concentrations lower or equal to its IC 50 but strongly inhibits the network formation by MSS31 in the tube formation assays. Given its potential efficacy, this inhibitor has significant therapeutic potential in several human diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules23071615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100598PMC
July 2018

Flap Basics I: Rotation and Transposition Flaps.

Facial Plast Surg Clin North Am 2017 Aug 30;25(3):313-321. Epub 2017 May 30.

Department of Otolaryngology, University at Buffalo, 1237 Delaware Avenue, Buffalo, NY 14209, USA. Electronic address:

In many cases of complex facial defects, because of advanced cutaneous malignancies, primary wound closure is impossible. In these instances, ideal results can be obtained through recruitment of adjacent tissue with the use of local flaps. Advances in local flap techniques have raised the bar in facial reconstruction; however, acceptable results to the surgeon and patient require high levels of planning and surgical technique. Defects resulting from Mohs surgery and other traumatic injuries can typically be repaired with local flaps. A well-planned and executed local flap can lead to excellent cosmetic results with minimal distortion of the surrounding facial landmarks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fsc.2017.03.004DOI Listing
August 2017

Correlation of Symptoms, Clinical Signs, and Biomarkers of Inflammation in Postsurgical Chronic Rhinosinusitis.

Ann Otol Rhinol Laryngol 2017 Jun 4;126(6):455-462. Epub 2017 Apr 4.

1 Department of Otorhinolaryngology, University at Buffalo School of Medicine and Biomedical Sciences, The State University of New York, Gromo Institute and Sinus Center, Buffalo, New York, USA.

Objective: The study aimed to evaluate symptoms described by patients with chronic rhinosinusitis with polypoid changes/nasal polyps and their correlation with computed tomography (CT), nasal endoscopy, and intranasal biomarkers.

Study Design: Prospective multicenter study symptom data from postsurgical adult chronic rhinosinusitis study participants with recurrent disease refractory to medical therapy were analyzed in comparison with objective data.

Methods: Using logistic regression analysis, participant-rated 16-question surveys from 258 participants were assessed for correlation with nasal endoscopy scores, CT percentage of sinus occlusion, and intranasal biomarkers of fungal antigens (Alternaria and Aspergillus), eosinophilic inflammation (eosinophil-derived neurotoxin [EDN] and major basic protein [MBP]), and inflammatory cytokines (interleukins 5 and 13).

Results: Study participant assessments revealed increased CT occlusion in participants presenting with greater inability to smell ( P < .019). Mucosal inflammation identified on nasal endoscopy was positively correlated with congestion ( P < .028), runny nose ( P < .002), and ear pain ( P < .007). Elevated EDN was positively correlated in patients with bothersome congestion ( P < .031) and runny nose ( P < .011). Sneezing was positively correlated with multiple markers: Alternaria ( P < .024), interleukin-13 ( P < .027), MBP ( P < .034), and interleukin-5 ( P < .019).

Conclusion: Nasal endoscopy, not CT imaging, has the strongest correlation with the 2 cardinal symptoms of congestion and runny nose in CRS patients; these correlate with biomarkers of eosinophilic inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0003489417701939DOI Listing
June 2017

Cutaneous Landmarks of the Supratrochlear Nerve in Forehead Rejuvenation Surgery.

JAMA Facial Plast Surg 2017 Jul;19(4):337-338

Department of Otolaryngology, University at Buffalo, Buffalo, New York.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamafacial.2016.2258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815104PMC
July 2017

The Novel mTOR Complex 1/2 Inhibitor P529 Inhibits Human Lung Myofibroblast Differentiation.

J Cell Biochem 2017 08 18;118(8):2241-2249. Epub 2017 Apr 18.

Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin-Madison School of Medicine and Public Health, 600 Highland Ave, Madison, Wisconsin, 53792.

Idiopathic pulmonary fibrosis is a progressive and deadly disorder with very few therapeutic options. Palomid 529 (8-(1-hydroxyethyl)-2-methoxy-3-(4-methoxybenzyloxy)-benzo[c]chromen-6-one; P529) is a novel dual inhibitor of mechanistic target of rapamycin complex 1/2 (mTORC1/2). In these studies, we investigated the effect of P529 on TGF-β-dependent signaling and myofibroblast differentiation. TGF-β-induced phosphorylation of the mTORC1 targets, p70 S6 kinase 1 (S6K1), and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), were both dose dependently inhibited by P529 in human lung fibroblasts with maximal inhibition occurring between 10 and 20 μM. mTORC2-mediated phosphorylation of Akt at the S473 site was partially inhibited with a similar dose dependency, as was TGF-β-induced myofibroblast differentiation. Protein levels of TGF-β-induced fibronectin and collagen were similarly decreased by P529. At this dose, there was also inhibition of mRNA transcript levels for Col1 and α-SMA, suggesting inhibition of transcriptional activation. However, there was no effect of P529 on canonical TGF-β-induced Smad signaling, as assessed by receptor-associated Smad2/3 phosphorylation, Smad2/3/4 translocation, or Smad-driven gene expression, as assessed by Smad-binding element driven luciferase. Conversely, activation of mTORC1/2 signaling was dependent on TGF-β type I receptor (ALK5) signaling and on Smad2/3 expression. P529 treatment disrupted TGF-β-induced actin stress fiber formation during myofibroblast differentiation, the deposition of new extracellular fibronectin matrix, and linear wound closure by fibroblasts. Likewise, mTOR knockdown inhibited TGF-β-induced myofibroblast differentiation. In conclusion, P529 inhibits TGF-β-induced myofibroblast differentiation, actin stress fiber formation, and matrix protein expression and deposition. Inhibition of mTORC1/2 by P529 may be a promising approach to inhibit in vivo fibrosis. J. Cell. Biochem. 118: 2241-2249, 2017. © 2017 Wiley Periodicals, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.25878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568785PMC
August 2017

Prosthetics for nasal perforations: a systematic review and meta-analysis.

Otolaryngol Head Neck Surg 2015 May 8;152(5):803-10. Epub 2015 Apr 8.

Department of Otolaryngology, University at Buffalo, The State University of New York, Buffalo, New York, USA.

Objective: Prosthetics serve as an option for nasoseptal perforation treatment in patients who have active systemic disease, are poor surgical candidates, or wish to avoid surgery. Through systematic review of the literature on prosthetics for nasoseptal perforation treatment, the objective of the present study is to critically appraise previous studies, evaluate the success rate for nasoseptal prosthetics, provide evidence-based guidelines for nasoseptal prosthetic use, and identify areas for further investigation.

Data Sources: Cochrane Controlled Trials Register, EMBASE, PubMed, and Web of Science.

Review Methods: Data sources were queried for relevant articles published from 1965 to 2013. Articles were selected for inclusion if they presented primary data for human nasoseptal perforation treatment utilizing prosthetic materials. Each included article's level of evidence and risk of bias were identified and grades of recommendation were assigned. A quantitative meta-analysis was performed on articles with low risk of bias.

Results: The search yielded 4756 abstracts for review, with 23 included case series and 5 case reports; 706 total cases of prosthetic nasoseptal perforation treatment were identified. All articles provided level 4 evidence, with an overall conclusion grade of C for improvement in nasoseptal perforation symptoms, prosthetic in situ rate, and complication rate. Meta-analysis of 6 low-risk-of-bias studies with 297 patients demonstrated an overall success rate of 65%.

Conclusions: The literature provides level 4 evidence for the efficacy and safety of prosthetics for nasoseptal perforation treatment with favorable success rates and few reports of complications--only 1 fungal infection and 9 unspecified infections-in 706 cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0194599815577084DOI Listing
May 2015

An immunologic test for chronic rhinosinusitis based on free intranasal eosinophilic major basic protein.

Int Forum Allergy Rhinol 2015 Jan 29;5(1):28-35. Epub 2014 Sep 29.

Department of Otorhinolaryngology, University at Buffalo, The State University of New York, Buffalo, NY.

Background: A histologic hallmark of chronic rhinosinusitis (CRS) is an eosinophilic inflammation, present with and without nasal polyposis and independent of atopy. Eosinophils migrate through nasal tissue including the epithelium into the nasal airway mucus, where they form clusters and degranulate, releasing granule proteins including the toxic major basic protein (MBP). Specific biomarkers for CRS, which could be used as a diagnostic test for CRS with a high sensitivity and specificity, are presently lacking. Recently, an enzyme-linked immunosorbent assay (ELISA)-based test for MBP in nasal airway mucus received regulatory approval.

Methods: A new assay was specifically developed to detect released MBP in airway mucus. MBP levels in nasal mucus of 85 randomly selected CRS patients diagnosed by endoscopy, computed tomography (CT) scans and symptoms were compared to 13 healthy controls and 5 disease controls (allergic rhinitis).

Results: Overall, 92% (78/85) of CRS patients' mucus were positive for MBP (mean 7722 ng/mL) vs none of 13 healthy controls and none of 5 allergic rhinitis patients (<7.8 ng/mL; p < 0.000000000002). In this study, the MBP ELISA had a 92% sensitivity and 100% specificity for CRS.

Conclusion: Free MBP in nasal mucus can be used as a biomarker to diagnose CRS. The MBP ELISA represents the first immunologically-based test to potentially distinguish CRS from the eosinophilic inflammation in allergic rhinitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.21421DOI Listing
January 2015

Advances in prostate cancer research and treatment.

Biomed Res Int 2014 18;2014:708383. Epub 2014 Aug 18.

Department of Experimental Medicine, Sapienza University, 00161 Rome, Italy ; Laboratory of Radiobiology and Division of Radiotherapy, Department of Applied, Clinical and Biotechnological Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2014/708383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151599PMC
April 2015

Torc1/Torc2 inhibitor, Palomid 529, enhances radiation response modulating CRM1-mediated survivin function and delaying DNA repair in prostate cancer models.

Prostate 2014 Jun 8;74(8):852-68. Epub 2014 Apr 8.

Division of Radiation Oncology, Department of Clinical and Applied Sciences and Biotechnologies, University of L'Aquila, L'Aquila, Italy; Department of Clinical and Applied Sciences and Biotechnologies, Laboratory of Radiobiology, University of L'Aquila, L'Aquila, Italy; Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy; Department of Clinical and Applied Sciences and Biotechnologies, School of Sexology, University of L'Aquila, L'Aquila, Italy.

Background: P529, a Torc1/Torc2 inhibitor, has demonstrated its potential as a radiosensitizer. However the molecular mechanisms underlying this phenomenon still need to be elucidated. Aim of this study is to dissect molecular mechanisms regulating the radiosensitizing properties of P529 in a wide panel of prostate cancer models.

Methods: Six tumor cell lines and xenograft models were used for in vitro and in vivo studies. Clonogenic survival, apoptotic, autophagic, and senescence assays were used to examine the effects of ionizing radiation (IR) alone and in combination with P529. CRM1, survivin, GSK-3β, and DNA-DSBs expression and modulation, upon P529 and RT, were monitored by western blot. In vivo treatment response upon P529, irradiation or combination of P529 with IR was monitored by tumor volume, time to progression (TTP), and immunohistochemical analysis.

Results: P529 treatment induced significantly more apoptosis and DNA double-strand break (DSB) when combined with radiotherapy resulting in cellular radiosensitization and growth delay of irradiated tumor xenografts. Upon P529 treatment Rad51, DNA-PKcs, and Ku70 protein expression was downregulated, indicating delayed DNA double-strand damage repair. The radiosensitizing properties of P529 were partially linked to GSK-3β, cyclin-D1, and c-myc modulation with associated inhibition of CRM1-mediated nuclear export of survivin. Importantly, autophagy and tumor senescence were involved in the enhanced P529 radioresponse.

Conclusions: Impaired DNA double-strand damage repair, inhibition of CRM1-mediated nuclear export of survivin, modulation of cyclin-D1 and c-myc with associated pro-apoptotic and autophagic and senescent events explain the radiosensitizing properties of P529 in preclinical models of prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pros.22804DOI Listing
June 2014

Computed tomography scans as an objective measure of disease severity in chronic rhinosinusitis.

Otolaryngol Head Neck Surg 2014 Feb 3;150(2):305-11. Epub 2013 Dec 3.

State University of New York at Buffalo, Department of Otolaryngology, Buffalo, New York, USA.

Objectives: A truly objective method of measuring disease severity in chronic rhinosinusitis (CRS) has only recently existed. We evaluated computed tomography (CT) scans of CRS patients using this novel objective 3D computerized system and compared results with a novel 2D computerized analysis of a single coronal slice through the osteomeatal complex (OMC) and subjective methods including Lund-Mackay and Zinreich's modified Lund-Mackay.

Study Design: Prospective multicenter study.

Setting: Two academic tertiary referral centers.

Subjects And Methods: Forty-six adults with a diagnosis of CRS underwent CT examination and received an intramuscular triamcinolone injection, dosage weight dependent, followed by CT scan 4 to 5 weeks later. Recruitment lasted 21 months. Scans were evaluated with all 4 scoring methods over 5 months.

Results: The Lin's concordance class correlation (CCC) of the OMC method revealed the best correlation to the 3D volumetric computerized values (0.915), followed by the Zinreich (0.904) and Lund-Mackay methods (0.824). Posttreatment results demonstrated that both the OMC (0.824) and Zinreich's (0.778) methods had strong agreement with the 3D volumetric methods and were very sensitive to change, whereas the Lund-Mackay (0.545) had only moderate agreement.

Conclusion: Computerized CT analysis provides the most comprehensive, objective, and reproducible method of measuring disease severity and is very sensitive to change induced by treatment intervention. A 2D coronal image through the OMC provides a valid, user-friendly method of assessing CRS and is representative of CRS severity in all sinuses. Zinreich's subjective method correlated well overall, but the Lund-Mackay method lagged behind in disease representation and sensitivity to change.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0194599813513881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3986264PMC
February 2014

RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription.

Nat Commun 2013 ;4:2824

1] Center for Vascular Biology Research, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA [2] ImClone Systems (a wholly owned subsidiary of Eli Lilly and Company), New York, New York 10016, USA.

Mechanisms governing the distinct temporal dynamics that characterize post-natal angiogenesis and lymphangiogenesis elicited by cutaneous wounds and inflammation remain unclear. RhoB, a stress-induced small GTPase, modulates cellular responses to growth factors, genotoxic stress and neoplastic transformation. Here we show, using RhoB null mice, that loss of RhoB decreases pathological angiogenesis in the ischaemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge. We link these unique and opposing roles of RhoB in blood versus lymphatic vasculatures to the RhoB-mediated differential regulation of sprouting and proliferation in primary human blood versus lymphatic endothelial cells. We demonstrate that nuclear RhoB-GTP controls expression of distinct gene sets in each endothelial lineage by regulating VEZF1-mediated transcription. Finally, we identify a small-molecule inhibitor of VEZF1-DNA interaction that recapitulates RhoB loss in ischaemic retinopathy. Our findings establish the first intra-endothelial molecular pathway governing the phased response of angiogenesis and lymphangiogenesis following injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms3824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868161PMC
July 2014

Dual mTORC1 and mTORC2 inhibitor Palomid 529 penetrates the blood-brain barrier without restriction by ABCB1 and ABCG2.

Int J Cancer 2013 Sep 1;133(5):1222-33. Epub 2013 Apr 1.

Department of Clinical Chemistry Preclinical Pharmacology, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Hospital), Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Palomid 529, a novel dual mTORC1/2 inhibitor has displayed interesting activities in experimental models and is a candidate for clinical evaluation. We have assessed the interaction of Palomid 529 with ATP-binding cassette (ABC) drug efflux transporters ABCB1 (P-gp/P-glycoprotein) and ABCG2 (BCRP/Breast Cancer Resistant Protein) by in vitro transwell assays, and their effects on the brain penetration using drug disposition analysis of i.v. and oral Palomid 529 in wild-type (WT) and Abcb1 and/or Abcg2 knockout (KO) mice. Palomid 529 lacked affinity for these transporters in vitro, in contrast to GDC-0941, a small molecule PI3K inhibitor, which we used as control substance for in vitro transport. The plasma AUCi.v. of micronized and DMSO formulated Palomid 529 was similar in WT and KO mice. Importantly, the brain and brain tumor concentration of Palomid 529 at a high dose (54 mg/kg) was also similar in both strains, whereas a less than 1.4-fold difference (p < 0.05) was found at the low (5.4 mg/kg) dose. Because of poor solubility, the oral bioavailability of micronized Palomid 529 was only 5%. Olive oil or spray-dried formulation greatly improved the bioavailability up to 50%. Finally, Palomid 529 effectively inhibits the orthotopic U87 glioblastoma growth. In summary, Palomid 529 is the first mTOR targeting drug lacking affinity for ABCB1/ABCG2 and having good brain penetration. This warrants further evaluation of Palomid 529 for treatment of high-grade gliomas and other intracranial malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.28126DOI Listing
September 2013

Botulinum toxin to minimize facial scarring.

Facial Plast Surg 2012 Oct 1;28(5):525-35. Epub 2012 Oct 1.

Department of Surgery, Division of Plastic and Reconstructive Surgery, The Mount Sinai Hospital, New York, New York 14209, USA.

Chemoimmobilization with botulinum toxin A is an ideal biochemical agent that allows near-total elimination of muscle pull on the healing facial wound. The goal of chemoimmobilization of facial cutaneous wounds is to eliminate dynamic tension on the healing tissues to improve wound healing and minimize scarring for optimal aesthetic results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0032-1325641DOI Listing
October 2012

Keloid disease can be inhibited by antagonizing excessive mTOR signaling with a novel dual TORC1/2 inhibitor.

Am J Pathol 2012 Nov 11;181(5):1642-58. Epub 2012 Sep 11.

Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, United Kingdom.

Keloid disease (KD) is a fibroproliferative lesion of unknown etiopathogenesis that possibly targets the PI3K/Akt/mTOR pathway. We investigated whether PI3K/Akt/mTOR inhibitor, Palomid 529 (P529), which targets both mammalian target of rapamycin complex 1 (mTORC-1) and mTORC-2 signaling, could exert anti-KD effects in a novel KD organ culture assay and in keloid fibroblasts (KF). Treatment of KF with P529 significantly (P < 0.05) inhibited cell spreading, attachment, proliferation, migration, and invasive properties at a low concentration (5 ng/mL) and induced substantial KF apoptosis when compared with normal dermal fibroblasts. P529 also inhibited hypoxia-inducible factor-1α expression and completely suppressed Akt, GSK3β, mTOR, eukaryotic initiation factor 4E-binding protein 1, and S6 phosphorylation. P529 significantly (P < 0.05) inhibited proliferating cell nuclear antigen and cyclin D and caused considerable apoptosis. Compared with rapamycin and wortmannin, P529 also significantly (P < 0.05) reduced keloid-associated phenotypic markers in KF. P529 caused tissue shrinkage, growth arrest, and apoptosis in keloid organ cultures and substantially inhibited angiogenesis. pS6, pAkt-Ser473, and mTOR phosphorylation were also suppressed in situ. P529 reduced cellularity and expression of collagen, fibronectin, and α-smooth muscle actin (substantially more than rapamycin). These pre-clinical in vitro and ex vivo observations are evidence that the mTOR pathway is a promising target for future KD therapy and that the dual PI3K/Akt/mTOR inhibitor P529 deserves systematic exploration as a candidate agent for the future treatment of KD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajpath.2012.08.006DOI Listing
November 2012

Improving the detection of fungi in eosinophilic mucin: seeing what we could not see before.

Otolaryngol Head Neck Surg 2012 Nov 11;147(5):943-9. Epub 2012 Jun 11.

University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA.

Objective: To investigate the improvement in histologic detection of fungi with Gomori methenamine silver (GMS) stain by trypsin predigestion in the mucus of patients with chronic rhinosinusitis (CRS).

Study Design: Prospective, single group, descriptive analysis.

Setting: Multi-institutional.

Subjects And Methods: Thirty-four sinus specimens from 12 surgical patients with CRS were stained with hematoxylin and eosin, GMS stain, GMS with trypsin digestion, immunofluorescence stains for chitinase, and anti-Alternaria. All patients received skin testing, total IgE serology, and radioallergosorbent tests (RAST) for 23 fungal-specific IgE antibodies.

Results: The conventional GMS stain detected fungi in only 9 of 34 (27%) specimens. Predigesting the specimen with trypsin dramatically improved the visualization of fungi (31/34, 91%). The chitinase immunofluorescence visualized fungi in 32 of 34 (94%), and anti-Alternaria visualized 33 of 34 specimens (97%). Only 8 of 12 (75%) patients had detectable allergies.

Conclusions: This report describes a simple modification of the conventional GMS stain that can significantly improve the visualization of fungi on histology and explains the lack of detection in previous studies. These novel, more sensitive histologic methods reveal the presence of fungi within the eosinophilic mucin in allergic and also nonallergic CRS patients, further questioning a crucial role of an IgE-mediated pathophysiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0194599812451010DOI Listing
November 2012

Potential Therapeutic Roles for Inhibition of the PI3K/Akt/mTOR Pathway in the Pathophysiology of Diabetic Retinopathy.

J Ophthalmol 2011 30;2011:589813. Epub 2011 Oct 30.

Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA, USA.

Novel therapeutics such as inhibitors of PI3K/Akt/mTOR pathway presents a unique opportunity for the management of diabetic retinopathy (DR). Second generation mTOR inhibitors have the prospect to be efficacious in managing various stages of disease progression in DR. During early stages, the mTOR inhibitors suppress HIF-1α, VEGF, leakage, and breakdown of the blood-retinal barrier. These mTOR inhibitors impart a pronounced inhibitory effect on inflammation, an early component with diverse ramifications influencing the progression of DR. These inhibitors suppress IKK and NF-κB along with downstream inflammatory cytokines, chemokines, and adhesion molecules. In proliferative DR, mTOR inhibitors suppress several growth factors that play pivotal roles in the induction of pathological angiogenesis. Lead mTOR inhibitors in clinical trials for ocular indications present an attractive treatment option for chronic use in DR with favorable safety profile and sustained ocular pharmacokinetics following single dose. Thereby, reducing dosing frequency and risk associated with chronic drug administration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2011/589813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205601PMC
August 2012

High-performance liquid chromatography analysis of a novel small-molecule, anti-cancer drug, Palomid 529, in human and mouse plasma and in mouse tissue homogenates.

J Chromatogr B Analyt Technol Biomed Life Sci 2011 Dec 29;879(32):3823-31. Epub 2011 Oct 29.

Department of Clinical Chemistry/Preclinical Pharmacology, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Hospital), Amsterdam, The Netherlands.

Palomid 529 (8-(1-Hydroxy-ethyl)-2-methoxy-3-(4-methoxy-benzyloxy)-benzo[c]chromen-6-one), is a novel non-steroidal small-molecule drug, which inhibits both mTORC1 and mTORC2 assembly, and elicits both anti-angiogenic and direct anti-tumor effects in vivo. We have developed and validated a sensitive and selective method for the quantification of Palomid 529 in human and mouse plasma and in a range of mouse tissue samples. Sample pretreatment involved liquid-liquid extraction with tert-butyl methyl ether yielding a recovery of >75%. Palomid 529 and the internal standard Palomid 545 were separated using a GraceSmart RP18 column (2.1 mm × 150 mm) packed with 5 μm C-18 material and a mobile phase comprised of 50% (v/v) acetonitrile and 50% (v/v) water delivered at a flow rate of 0.2 ml/min, and were detected by UV absorbance at a wavelength of 315 nm. Within the linear range of the calibration curve (10-10,000 ng/ml), acceptable accuracy and precision was achieved for all tested matrices. The validation results show that the method was selective and reproducible. Palomid 529 was stable in plasma upon 3 repeated freeze-thaw cycles and during storage for up to 24h at ambient temperature. However, pre-treated samples waiting for HPLC analyses need to be kept under dimmed light conditions at ambient temperature since a significant degradation of both Palomid 529 and Palomid 545 was observed when exposed to light. A pilot pharmacokinetic study in mice demonstrated the applicability of this method for pharmacokinetic purposes. Even at a low dose of 5.4 mg/kg this assay was still sensitive enough to determine the drug concentration in plasma samples obtained up to 24h after administration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2011.10.028DOI Listing
December 2011

Human acellular dermal matrix grafts for rhinoplasty.

Aesthet Surg J 2011 Sep;31(7 Suppl):95S-100S

Department of Otolaryngology, University at Buffalo, Buffalo, New York 14209, USA.

Rhinoplasty often relies on graft material for structural support in the form of cartilage, bone grafts, or fascia. In addition, pliable grafts are often helpful for contouring and can function as a barrier. Unfortunately, grafts carry the disadvantage of requiring an additional donor site, with associated complications. Human acellular dermal matrix (ADM) biological implants offer an exciting alternative for structural support and nonstructural implantation in rhinoplasty procedures. To examine the efficacy of ADM placement in rhinoplasty and septoplasty, the authors report the results from a series of 51 patients. In this series, there were no cases of infection, skin discoloration, seroma formation, septal perforation, significant resorption, extrusion, or other complications related to ADM placement. Therefore, the authors believe that ADM offers a safe and effective alternative to traditional grafting methods for functional and aesthetic rhinoplasty.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1090820X11418200DOI Listing
September 2011

The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate cancer cells.

Endocr Relat Cancer 2011 Aug 1;18(4):385-400. Epub 2011 Jul 1.

Laboratory of Radiobiology Division of Radiotherapy Oncology Endocrinology, Department of Experimental Medicine, University of L'Aquila, Italy.

One of the major obstacles in the treatment of hormone-refractory prostate cancer (HRPC) is the development of chemo-resistant tumors. The aim of this study is to evaluate the role of Palomid 529 (P529), a novel TORC1/TORC2 inhibitor, in association with docetaxel (DTX) and cisplatin (CP). This work utilizes a wide panel of prostatic cancer cell lines with or without basal activation of Akt as well as two in vivo models of aggressive HRPC. The blockade of Akt/mTOR activity was associated to reduced cell proliferation and induction of apoptosis. Comparison of IC50 values calculated for PTEN-positive and PTEN-negative cell lines as well as the PTEN transfection in PC3 cells or PTEN silencing in DU145 cells revealed that absence of PTEN was indicative for a better activity of the drug. In addition, P529 synergized with DTX and CP. The strongest synergism was achieved when prostate cancer (PCa) cells were sequentially exposed to CP or DTX followed by treatment with P529. Treatment with P529 before the exposure to chemotherapeutic drugs resulted in a moderate synergism, whereas intermediated values of combination index were found when drugs were administered simultaneously. In vivo treatment of a combination of P529 with DTX or CP increased the percentage of complete responses and reduced the number of mice with tumor progression. Our results provide a rationale for combinatorial treatment using conventional chemotherapy and a Akt/mTOR inhibitor as promising therapeutic approach for the treatment of HRPC, a disease largely resistant to conventional therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/ERC-11-0045DOI Listing
August 2011

Immunologic response to fungus is not universally associated with chronic rhinosinusitis.

Otolaryngol Head Neck Surg 2010 Nov;143(5):607-10

Department of Otorhinolaryngology, Gromo Institute & Sinus Center, University at Buffalo, The State University of New York, Buffalo, NY 14209, USA.

In the December 2009 issue of this journal, Orlandi et al presented a study in which peripheral blood mononuclear cells (PBMCs) from chronic rhinosinusitis (CRS) patients (5 from Texas, 5 from Utah) and seven nonhealthy controls were stimulated with fungal extracts. Despite the small numbers, they confirmed important aspects of previous studies: 1) CRS patients' PBMCs react to certain fungal stimuli by producing significantly (P < 0.05) higher amounts of interleukin (IL)-5 and IL-13 when compared to controls; 2) CRS patients have an enhanced humoral response (significantly elevated immunoglobulin [Ig] G levels to Alternaria); and 3) CRS patients react independently from an IgE-mediated allergy, as evidenced by that fact that nonallergic CRS patients also produced IL-5 in response to fungal stimuli. Unfortunately, the authors chose not to highlight their positive results. They emphasized what they failed to demonstrate, specifically an immune response to fungi above a certain threshold in some patients (Utah) with milder CRS. However, these results are potentially explained by the different methods used, and care should be applied when interpreting their results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.otohns.2010.07.001DOI Listing
November 2010

Muller cell reactivity and photoreceptor cell death are reduced after experimental retinal detachment using an inhibitor of the Akt/mTOR pathway.

Invest Ophthalmol Vis Sci 2009 Sep 15;50(9):4429-35. Epub 2009 Apr 15.

Neuroscience Research Institute, University of California, Santa Barbara, California 93106-5060, USA.

Purpose: To test the effect of Palomid 529, an inhibitor of the Akt/mTOR pathway, on Müller cell proliferation, subretinal glial scar formation, and photoreceptor survival after experimental retinal detachment (RD).

Methods: Palomid 529 (600 microg) in balanced salt solution or balanced salt solution alone was injected intravitreally immediately after RD into the right eyes of 12 rabbits. Ten micrograms of BrdU was injected intravitreally on day 3. Animals were killed on day 3 or 7, at which time retinal sections were labeled with anti-BrdU to detect dividing cells, with anti-vimentin to identify Müller cells, and with the isolectin B4 to identify microglia and macrophages. Outer nuclear layer (ONL) thickness was measured from fluorescence-labeled nuclear-stained sections. Labeling was imaged using confocal microscopy. Six additional animals received either drug or balanced salt solution injections into normal eyes, and paraffin sections were stained with hematoxylin and eosin.

Results: In the drug-treated eyes there was a significant decrease in the number of anti-BrdU-labeled Müller cells, the number and size of subretinal scars, and the number of isolectin B4-labeled cells. The ONL was also significantly thicker, and there was no evidence of toxic effects.

Conclusions: Palomid 529 is an effective suppressor of Müller cell proliferation, glial scar formation, and photoreceptor cell death in a rabbit model of RD. This suggests that inhibiting the Akt/mTOR signal transduction pathway may be an effective strategy to decrease proliferation and photoreceptor cell death induced by detachment and perhaps represents a novel therapy for related human diseases such as proliferative vitreoretinopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.09-3445DOI Listing
September 2009