Medical Specialties Commons^™

A Rare Case Of Three Years Disease Free Survival In A Locally Advanced Parathyroid Carcinoma Successfully Excised By Complete Surgical Resection, Abdul Ahad Sohail, Bushra Ayub, Syed Akbar Abbas, Shafqat Ali Sheikh, Talha Ahmed Qureshi, Muhammad Usman Tariq, Asad Diwan

Department of Surgery Docs

Parathyroid carcinoma (PC) is one of the rarest malignancies making approximately 0.005% of all cancers. It may arise sporadically or less commonly, in conjunction with genetic endocrine syndromes. Due to the rarity of the disease, no general consensus or definitive guidelines exist for its pre-operative diagnosis, management, or follow up. Surgical tumor removal is the gold standard treatment to prevent its recurrence. Parathyroid carcinoma has a high recurrence rate ranging from 40 to 60% in recent literature. We report a case of a seventy-year-old elderly female with locally advanced parathyroid carcinoma successfully surgically excised completely with a 3 year disease …

Igf1r Immunohistochemistry In Ewing's Sarcoma As Predictor Of Response To Targeted Therapy., Elizabeth Gonzalez, Marilyn Bui, Atif Ahmed

Manuscripts, Articles, Book Chapters and Other Papers

Objectives: Ewing's sarcoma is an aggressive malignancy of bone and soft tissue in children and young adults. Despite advances in modern therapy, metastasis can occur and results in high mortality. The objective of this study was to identify whether the signaling transduction proteins, insulin growth factor receptor (IGF1R) and S6 kinase (S6K), can predict poor prognosis in Ewing's sarcoma.

Methods: After the Institutional Research Board approval, immunohistochemical experiments on tissue microarray slides containing 32 archived Ewing's sarcoma tumor samples were performed with antibodies against IGF1Rb and p-S6K. Immunohistochemical staining results were correlated with patients' clinical data including clinical stage and …

Igf1r Immunohistochemistry In Ewing's Sarcoma As Predictor Of Response To Targeted Therapy., Elizabeth Gonzalez, Marilyn Bui, Atif Ahmed

Manuscripts, Articles, Book Chapters and Other Papers

Objectives: Ewing's sarcoma is an aggressive malignancy of bone and soft tissue in children and young adults. Despite advances in modern therapy, metastasis can occur and results in high mortality. The objective of this study was to identify whether the signaling transduction proteins, insulin growth factor receptor (IGF1R) and S6 kinase (S6K), can predict poor prognosis in Ewing's sarcoma.

Methods: After the Institutional Research Board approval, immunohistochemical experiments on tissue microarray slides containing 32 archived Ewing's sarcoma tumor samples were performed with antibodies against IGF1Rb and p-S6K. Immunohistochemical staining results were correlated with patients' clinical data including clinical stage and …

Host Immune Response To Enterovirus And Parechovirus Systemic Infections In Children., Anjana Sasidharan, Wail M. Hassan, Christopher J. Harrison, Ferdaus Hassan, Rangaraj Selvarangan

Manuscripts, Articles, Book Chapters and Other Papers

Background: Enterovirus (EV) and parechovirus type A3 (PeV-A3) cause infections ranging from asymptomatic to life-threatening. Host immune responses in children, particularly innate responses to PeV-A3, remain largely unknown. The aim of this study was to determine aspects of the cytokine/chemokine responses to EV and PeV-A3 in cerebrospinal fluid (CSF) and plasma obtained from children with systemic/central nervous system infection.

Methods: A total of 74 salvaged CSF samples (27 with EV, 23 with PeV-A3, and 24 with neither EV nor PeV-A3) and 35 paired blood samples (10 with EV, 14 with PeV-A3, and 11 with neither) were studied. Concentrations of cytokines …

Active Deep Learning Method To Automate Unbiased Stereology Cell Counting, Saeed Alahmari

USF Tampa Graduate Theses and Dissertations

Cell quantification in histopathology images plays a significant role in understanding and diagnosing diseases such as cancer and Alzheimers. The gold-standard for quantifying cells in tissue sections is the unbiased stereology approach. Unfortunately, in unbiased stereology current practices rely on a well-trained human to manually count hundreds of cells in microscopy images. However, this human-based manual approach is time-consuming, labor-intensive, subject to human errors, recognition bias, fatigue, variable training, poor reproducibility, and inter-observer error. Thus, the lack of high-throughput technology for automating unbiased stereology analyses remains a major obstacle to further progress in a wide range of neuroscience and cancer …

Spermine Synthase And Myc Cooperate To Maintain Colorectal Cancer Cell Survival By Repressing Bim Expression, Yubin Guo, Qing Ye, Pan Deng, Yanan Cao, Daheng He, Zhaohe Zhou, Chi Wang, Yekaterina Y. Zaytseva, Charles E. Schwartz, Eun Young Lee, B. Mark Evers, Andrew J. Morris, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC), but the underlying mechanism is incompletely characterized. Here, we report that spermine synthase (SMS), a polyamine biosynthetic enzyme, is overexpressed in CRC. Targeted disruption of SMS in CRC cells results in spermidine accumulation, which inhibits FOXO3a acetylation and allows subsequent translocation to the nucleus to transcriptionally induce expression of the proapoptotic protein Bim. However, this induction is blunted by MYC-driven expression of miR-19a and miR-19b that repress Bim production. Pharmacological or genetic inhibition of MYC activity in SMS-depleted CRC cells dramatically induces Bim expression and apoptosis …

En Bloc Resection Of A Giant Retroperitoneal Liposarcoma: A Surgical Challenge, Talal Almas, Muneeb Ullah, Maryam Ehtesham, Absam Akbar, Muhammad Kashif Khan

Medical College Documents

Liposarcomas are exceedingly rare entities that evoke malignant transformation of connective tissue and fat cells.These tumours occur throughout the soft tissues of the body, afflicting a myriad of regions. In the adult population, liposarcomas represent the most prevalent subtype of sarcomas, and often arise de novo. Retroperitoneal liposarcomas (RLS) are a ubiquitous subset of sarcomas that, due to their deep location in the hollow abdomen, can grow to astronomical proportions before manifesting any noticeable symptoms; a prompt diagnosis of RLS is therefore often rendered dilatory. We hereby delineate the case of a 43-year-old woman who presented with vague left hemiabdominal …

Iq Driving Qi: The Asia Pacific Consortium On Osteoporosis (Apco): An Innovative And Collaborative Initiative To Improve Osteoporosis Care In The Asia Pacific, M Chandran, S K. Bhadada, P R. Ebeling, N L. Gilchrist, Aysha Habib Khan, P Halbout, S Lekamwasam, G Lyubomirsky, P J. Mitchell, T V. Nguyen, K L. Tiu, Asia Pacific Consortium On Osteoporosis

Department of Pathology and Laboratory Medicine

Asia Pacific Consortium on Osteoporosis (APCO) comprises of clinical experts from across the Asia Pacific region, uniting to develop solutions to problems facing osteoporosis management and care. The vision of APCO is to reduce the burden of osteoporosis and fragility fractures in the Asia Pacific region.
Introduction: The Asia Pacific (AP) region comprises 71 countries with vastly different healthcare systems. It is predicted that by 2050, more than half the world's hip fractures will occur in this region. The Asia Pacific Consortium on Osteoporosis (APCO) was set up in May 2019 with the vision of reducing the burden of osteoporosis …

The Clinical Features Of Co-Circulating Dengue Viruses And The Absence Of Dengue Hemorrhagic Fever In Pakistan, Erum Khan, Dhani Prakoso, Kehkashan Imtiaz, Faisal Malik, Joveria Farooqi, Maureen T. Long, Kelli L. Barr

Department of Pathology and Laboratory Medicine

Dengue virus (DENV) is the most common and widespread arboviral infection worldwide. Though all four DENV serotypes cocirculate in nature, the clinicopathological framework of these serotypes is undefined in Pakistan. A cross-sectional, observational study was performed to document the circulation of various arboviruses in the Sindh region of Pakistan. Here we describe a population of patients diagnosed with DENV spanning a 2-year period. This study used an orthogonal system of NS1 antigen ELISA followed by RT-PCR for DENV detection and subtyping. A total of 168 NS1 positive patients were evaluated of which 91 patients were serotyped via RT-PCR. There was …

Investigation Of Japanese Encephalitis Virus As A Cause Of Acute Encephalitis In Southern Pakistan, April 2015-January 2018, Tazeen Fatima, Abida Rais, Erum Khan, Susan L. Hills, Trudy V. Chambers, Aneeta Hotwani, Shahida Qureshi, Saad Shafqat, Saima Malik, Farah Qamar, Fatima Mir, Anthony A. Marfin, Anita K. M. Zaidi, Asif Raza Khowaja, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Background: Japanese encephalitis (JE) occurs in fewer than 1% of JE virus (JEV) infections, often with catastrophic sequelae including death and neuropsychiatric disability. JEV transmission in Pakistan was documented in 1980s and 1990s, but recent evidence is lacking. Our objective was to investigate JEV as a cause of acute encephalitis in Pakistan.
Methods: Persons aged ≥1 month with possible JE admitted to two acute care hospitals in Karachi, Pakistan from April 2015 to January 2018 were enrolled. Cerebrospinal fluid (CSF) or serum samples were tested for JEV immunoglobulin M (IgM) using the InBios JE DetectTM assay. Positive or equivocal samples …

Idiopathic Pulmonary Hemosiderosis - A Rare Cause Of Chronic Anemia, Ayesha Butt, Rashida Ahmed, Muhammad Dawood Amir Sheikh, Omar Khan, Nousheen Iqbal, Arshalooz Rahman, Javaid Khan

Medical College Documents

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease marked by alveolar bleeding and accumulation of hemosiderin in the lungs. Here we present three cases of IPH. The first case is of a 26-year-old male with anemia, hemoptysis and dyspnea. Bronchoscopy confirmed diffuse alveolar hemorrhage (DAH). A diagnosis of IPH was made after ruling out other causes of DAH and observing good response to steroids. The patient's condition improved with prednisolone and azathioprine. The second case is of 26-year-old female with severe anemia. Imaging suggested IPH and lung biopsy confirmed it. She died shortly afterwards. The third case is of a …

Establishing The College Of Pathologists Of East, Central And Southern Africa – The Regional East Central And Southern Africa College Of Pathology, Shahin Sayed, Rudo Mutasa, Ephata Kaaya, Victor Mudenda, Erasmus Rajiv, Edda Vuhahula, Jamilla Rajab, Robert Lukande, Edwin Walong, Angela Mutuku, Kenneth Fleming

Pathology, East Africa

Issues: The scarcity of pathologists in sub-Saharan Africa is a well established fact that is attributable to few training programmes in the region; this is further compounded by the lack of harmonised curricula, training and exams within and without member countries.

Description of the intervention: Through the Association of Pathologists of East, Central and Southern Africa, the College of Pathologists of East, Central and Southern Africa (COPECSA) was formed with the clear-cut goal of establishing a regional and internationally recognised college to support and inform good quality medical and laboratory practice by promoting leadership, mentorship and excellence in the safe …

Addressing The Shortage Of Pathologists In Africa: Creation Of A Mmed Programme In Pathology In Zambia, Victor Mudenda, Evans Malyangu, Shahin Sayed, Kenneth Fleming

Pathology, East Africa

Background: With approximately one pathologist for one million people compared to ratios of approximately 1 to 25 000 in the United States and United Kingdom, there is a severe shortage of pathologists in much of Africa. The situation is particularly severe in Zambia, where, in 2009, the ratio was 1 to 1.4 million.

Objective: To address this, a postgraduate Master of Medicine (MMed) training programme was launched in Lusaka in 2011.

Methods: The process and most significant challenges and lessons learned were documented, as they may be of value to other countries facing similar challenges.

Results: …

Labrad : Vol 46, Issue 2 - June 2020, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Pathophysiology of Lung Injury in Context with Novel Coronavirus 2019
• Imaging in COVID-19 Pandemic: Salient Features
• Qualitative Real-Time RT-PCR For Detection of SARS-Cov-2 RNA
• Coagulopathy and Anticoagulants in COVID-19
• AKUH Blood Bank During SARS-COV-2 Outbreak
• Significance of COVID-19 Whole Genome Sequencing
• Convalescent Plasma Therapy for COVID-19
• COVID-19: An Alarm Bell for Healthcare System in Pakistan!
• Emergency Online Undergraduate Medial Education During COVID 19
• Adopting Virtual Teaching During the Pandemic-An Overview of the Utility of ‘Microsoft Teams’ from an Educator’s Perspectiv
• The Best of the Recent Past
• Polaroid

Comparison Of Staphylococcus Aureus Nasal Carriage By Patients And Healthcare Workers In Selected Dialysis Centers In Nairobi And Neighbouring Counties, Enock Serem

Master of Medicine in Clinical Pathology

Background: Staphylococcus aureus (S. aureus) is a significant pathogen that causes both community and hospital acquired infections. The burden of S. aureus morbidity and mortality is disproportionately high in patients with end stage kidney disease undergoing dialysis. With the rising prevalence of non-communicable diseases leading to end stage renal disease and dialysis, the impact of S. aureus infections is projected to rise. Knowledge of nasal carriage of S. aureus and their antibiotic resistance profiles is essential in improving patient care through planning of infection prevention and control strategies as well as formulating appropriate empiric antibiotic guidelines. The aim of this …

Eggerthella Lenta Bacteraemia In Endometrial Adenocarcinoma - A Case Report From Pakistan, Tazeen Fatima, Rumina Hasan, Samia Tariq

Department of Pathology and Laboratory Medicine

We report a case of Eggerthella lenta bacteraemia. An elderly lady with metastasised endometrial adenocarcinoma presented with complaints of fever nausea vomiting and abdominal pain. CT scan of the abdomen showed enlarged liver with multiple metastatic lesions raising suspicion of small-bowel obstruction. Due to multiple comorbid conditions, surgery was contraindicated and she was treated empirically with meropenem and vancomycin. Blood culture received on admission grew Eggerthela lenta.

Prognosticating Covid-19: A Need For Africa-Specific Laboratory Predictors, Geoffrey Omuse, Janet Maranga, Abubakar Abdillah, Daniel Maina

Pathology, East Africa

No Abstract

Outcome Of Non-Malignant Papillary Lesions Of The Breast On Core Biopsy: An Experience From A Tertiary Care Center In Pakistan, Kulsoom Fatima, Shaista Afzal Saeed, Muhammad Usman Tariq

Department of Radiology

Background: Papillary lesions of the breast constitute a heterogeneous group ranging from non-malignant papillomas to papillary carcinoma. While surgical excision is recommended for atypical papilloma or papillary DCIS/ carcinoma on core biopsy, controversy persists in the management of benign papillomas which are diagnosed with core needle biopsy (CNB) since there are variable reported rates for tumor upgrade. The purpose of this study was to determine the outcome of papillary lesions of the breast diagnosed at image-guided CNB, after surgical excision or follow-up, and to identify potential predictors of high-risk lesions/malignancy on imaging.
Materials and methods: We retrospectively identified 52 non-malignant …

Breast Imaging Chameleon: Pseudoangiomatous Stromal Hyperplasia Presenting As Breast Malignancy, Rabail Raza, Kulsoom Fatima, Muhammad Usman Tariq

Department of Radiology

Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal proliferative lesion of the breast, often an incidental finding on breast biopsy specimens and rarely presents as a palpable lump. The case being reported is interesting as a lactating female presented with gross left breast enlargement due to a huge firm mass with skin thickening and palpable left axillary lymph nodes. A provisional diagnosis of left breast malignancy was made and the patient extensively worked up with ultrasound, CT scan, bone scan and core biopsy. The histopathology, however, revealed PASH of the breast. There was no invasive or in situ malignancy. The …

Ire1Α And Igf Signaling Predict Resistance To An Endoplasmic Reticulum Stress-Inducing Drug In Glioblastoma Cells., Jeffrey J Rodvold, Su Xian, Julia Nussbacher, Brian Tsui, T Cameron Waller, Stephen C Searles, Alyssa Lew, Pengfei Jiang, Ivan Babic, Natsuko Nomura, Jonathan H Lin, Santosh Kesari, Hannah Carter, Maurizio Zanetti

Articles, Abstracts, and Reports

To date current therapies of glioblastoma multiforme (GBM) are largely ineffective. The induction of apoptosis by an unresolvable unfolded protein response (UPR) represents a potential new therapeutic strategy. Here we tested 12ADT, a sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor, on a panel of unselected patient-derived neurosphere-forming cells and found that GBM cells can be distinguished into "responder" and "non-responder". By RNASeq analysis we found that the non-responder phenotype is significantly linked with the expression of UPR genes, and in particular ERN1 (IRE1) and ATF4. We also identified two additional genes selectively overexpressed among non-responders, IGFBP3 and IGFBP5. CRISPR-mediated deletion of …

Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen

Neurology Faculty Publications

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a …

Maternal Inflammatory Markers For Chorioamnionitis In Preterm Prelabour Rupture Of Membranes: A Systematic Review And Meta-Analysis Of Diagnostic Test Accuracy Studies, Angela Koech, Geoffrey Omuse, Abraham Mukaindo, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Background: There is no consensus on the role of inflammatory markers in identifying chorioamnionitis in preterm prelabour rupture of membranes (PPROM). We set out to evaluate the accuracy of maternal blood C-reactive protein (CRP), procalcitonin and interleukin 6 (IL6) in diagnosis of histological chorioamnionitis and/or funisitis (HCA/Funisitis) in PPROM.

Methods: We searched MEDLINE, EMBASE and The Cochrane Library from inception to January 2020 for studies where maternal blood CRP, procalcitonin or IL6 was assessed against a reference standard of HCA/Funisitis in PPROM. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess methodological quality. Hierarchical summary …

Screening For Triazole Resistance In Clinically Significant Aspergillus Species; Report From Pakistan, Safia Moin, Joveria Farooqi, Kausar Jabeen, Sidra Laiq, Afia Zafar

Department of Pathology and Laboratory Medicine

Background: Burden of aspergillosis is reported to be significant from developing countries including those in South Asia. The estimated burden in Pakistan is also high on the background of tuberculosis and chronic lung diseases. There is concern for management of aspergillosis with the emergence of azole resistant Aspergillus species in neighbouring countries in Central and South Asia. Hence the aim of this study was to screen significant Aspergillus species isolates at the Microbiology Section of Aga Khan Clinical Laboratories, Pakistan, for triazole resistance.
Methods: A descriptive cross-sectional study, conducted at the Aga Khan University Laboratories, Karachi, from September 2016-May 2019. …

Endorepellin Evokes An Angiostatic Stress Signaling Cascade In Endothelial Cells., Aastha Kapoor, Carolyn G Chen, Renato V Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endorepellin, the C-terminal fragment of the heparan sulfate proteoglycan perlecan, influences various signaling pathways in endothelial cells by binding to VEGFR2. In this study, we discovered that soluble endorepellin activates the canonical stress signaling pathway consisting of PERK, eIF2α, ATF4, and GADD45α. Specifically, endorepellin evoked transient activation of VEGFR2, which, in turn, phosphorylated PERK at Thr980 Subsequently, PERK phosphorylated eIF2α at Ser51, upregulating its downstream effector proteins ATF4 and GADD45α. RNAi-mediated knockdown of PERK or eIF2α abrogated the endorepellin-mediated up-regulation of GADD45α, the ultimate effector protein of this stress signaling cascade. To functionally validate these findings, we utilized an ex …

Anti-Signal Recognition Particle Antibody-Associated Severe Interstitial Lung Disease Requiring Lung Transplantation., Anam Qureshi, Daniel F. Brown Md, Lawrence Brent

Department of Pathology & Laboratory Medicine

Anti-signal recognition particle (SRP) antibodies are typically associated with immune-mediated necrotizing myopathy. Some patients with anti-SRP antibodies may have extramuscular manifestations including mild respiratory symptoms secondary to interstitial lung disease. We present a case of a 40-year-old female presenting with acute hypoxic respiratory failure secondary to anti-SRP antibody-associated interstitial lung disease with mildly elevated creatinine kinase but without evidence of necrotizing myopathy on muscle biopsy. After a complicated six-month hospitalization, the patient successfully received double lung transplantation and was eventually discharged on room air. Unexplained worsening interstitial infiltrates leading to persistent hypoxic respiratory failure in the setting of nonspecifically elevated …

Draft Genome Sequences Of Two Extensively Drug-Resistant Strains Of Acinetobacter Baumannii Isolated From Clinical Samples In Pakistan, Sara Lomonaco, Matthew A. Crawford, Christine Lascols, Debra J. Fisher, Kevin Anderson, David R. Hodge, Segaran P. Pillai, Stephen A. Morse, Erum Khan, Molly A. Hughes, Marc W. Allard, Shashi K. Sharma

Department of Pathology and Laboratory Medicine

Infections in immunocompromised patients that are caused by extensively drug-resistant (XDR) Acinetobacter baumannii strains have been increasingly reported worldwide. In particular, carbapenem-resistant A. baumannii strains are a prominent cause of health care-associated infections. Here, we report draft genome assemblies for two clinical XDR A. baumannii isolates obtained from hospitalized patients in Pakistan.

Expression Of Her-2/Neu In Oral Squamous Cell Carcinoma, Sana Mirza, Naila Hadi, Shahid Pervez, Sultan Zeb Khan, Sameer A. Mokeem, Tariq Abduljabbar, Nawwaf Al-Hamoudi, Fahim Vohra

Department of Pathology and Laboratory Medicine

Background: HER-2/neu is a member of the human epidermal growth factor (HER) family of transmembrane tyrosine kinases, which is significantly associated with the pathogenesis of various cancer types. The aim was to evaluate the expression of HER-2/neu in oral squamous cell carcinoma (OSCC) as a potential biomarker to target antigens for specific immunotherapy in OSCC.
Methods: One hundred and forty histologically diagnosed OSCC cases were identified. Four to five-micrometer thick formalin-fixed, paraffin-embedded tumor sections were stained with Haematoxylin and Eosin (H and E). Histological grade was assessed according to WHO/Broders classification, while tumors were staged according to the American Joint …

Efforts To Improve Diagnosis Of Bacteraemia By Reducing Blood Culture Contamination In An Emergency Department: Strategies And Outcome, Najma Shaheen, Mohammad Zeeshan, Naima Fasih, Joveria Farooqi, Kausar Jabeen, Seema Irfan

Department of Pathology and Laboratory Medicine

Objective: To assess the strategies and outcome for reducing blood culture contamination in order to improve the diagnosis of bacteraemia.
Methods: The interventional study was conducted at a tertiary care hospital in Karachi from January 1, 2013, to December 31, 2016. The blood culture contamination data related to the first year of the study was taken as the baseline pre-intervention data. Strategies were planned as intervention for improvement by consolidating training and education in the form of dedicated lectures, practising on mannequins and developing in-house video, replacing povidone with 2% chlorhexidine preparation spray plus 70% isopropyl alcohol swabs and inducting …

Oral Localization Of Scardovia Wiggsiae, Graydon Ramos Carr

UNLV Theses, Dissertations, Professional Papers, and Capstones

Early childhood caries is one of the most prevalent diseases in the United States among children. The formation of caries is a complex, multifactorial process that is still being studied. Researchers have thought for years that Streptococcus mutans was the primary causative agent of early childhood caries. The recent discovery of a novel cariogenic pathogen, Scardovia wiggsiae and its significant contribution to the etiology of early childhood caries has led oral health researchers to re-evaluate this microorganism and its link to this disease. While there have been several projects undertaken within the University of Nevada, Las Vegas School of Dental …

Catabolic Degradation Of Endothelial Vegfa Via Autophagy, Thomas Neill, Carolyn Chen, Simone Buraschi, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion …