Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 5th International Conference and Exhibition on Pathology Chicago IL, USA.

Day 2 :

  • Track 2: Hematopathology
    Track 5: Gastrointestinal and Liver Pathology
    Track 6: Oral and Maxillofacial Pathology

Session Introduction

Adrian M Padurean

NeoGenomics, USA

Title: Recommendations for collecting and processing good quality bone marrow specimens

Time : 10:55-11:20

Speaker
Biography:

Adrian M Padurean is currently the Medical Director of the NeoGenomics Florida Laboratory. He has received his Medical degree from Institutul de Medicina in Timisora, Romania. He has conducted medical research in the field of Cardiovascular Biology at Massachusetts General Hospital/Harvard Medical School and Mount Sinai Medical Center, New York. Subsequently, he has also completed his Pathology Residency at Regions Hospital in St. Paul, Minnesota and Hematopathology Fellowship training at the University of Minnesota. He has earned MBA in Healthcare Administration from the Quinlan School of Business at Loyola University Chicago.

Abstract:

Morphology was the sole criterion for diagnosing hematolymphoid malignancies for about 60 years until the REAL classification added in 1994 immunophenotyping to morphology. In 2001 the WHO revolutionized the world of hematopathology by introducing cytogenetics establishing the current tripod of morphology, immunophenotpying and cytogenetics necessary to diagnose and manage patients suffering from hematolymphoid ailments. Despite the remarkable technological progress that provided us with all these ancillary studies, morphological evaluation remains the initial and most important criterion in diagnosing hematolymphoid malignancies. Furthermore, the premise for a good morphological evaluation rests on obtaining and processing high quality specimens. A good quality specimen is also necessary for obtaining accurate flow immunophenotyping, cytogenetic or molecular results. In 2008 the new WHO blue book introduced for the first time recommendations with regard to the minimum length of a bone marrow core biopsy (at least 1.5 cm in length). However, the authors shied away from stipulating guidelines for the other specimens that are usually collected at the time of a bone marrow biopsy (aspirates, touch imprints, specimens for ancillary studies). This presentation will try to put together different aspects of collecting and processing bone marrow biopsies and aspirations in hope that this information will help in obtaining high quality specimens.

Wenqing Cao

New York University School of Medicine, USA

Title: MACC1 and its Clinical Significance as a Biomarker and Therapeutic Target in Colon Cancer

Time : 11:20-11:45

Speaker
Biography:

Wenqing Cao received her MD from Tongji Medical University. She subsequently completed a residency in Anatomic and Clinical Pathology at Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, and a Gastrointestinal Pathology fellowship at the Mount Sinai Medical Center. She is currently Associate Professor at the New York UniversitySchool of Medicine/NYU Langone Medical Center. Since 1998, Dr. Cao has done extensive basic and clinical translational research in GI malignancies. Dr. Cao has published more than 28 papers in reputed journals and has been serving as editorial board members.

Abstract:

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Among the leading causes of cancer-related death, CRC is the third in men and second in women in developed countries, and third in both men and women in developing countries. The five year survival is over 90% in patients with early stages of cancer, 65% in patients with regional lymph node metastasis, but only 10% for patients with distant metastasis. Approximate one third of CRC patients had distant metastasis at the time when cancer was diagnosed.To improve the CRC patient outcome, in past decades, extensive research have suggested promising/potential biomarkers for early diagnosing CRC and predicting its metastasis/prognosis. The metastasis-associated in colon cancer-1 (MACC1) gene was identified by a genome-wide search for genes differentially expressed by analyzing normal tissues, primary tumors, and metastatic lesions in CRC. Further studies suggest that MACC1 functions as a transcriptional activator for proto-oncogene MET expression. MACC1 overexpression is associated with crucial steps of transition from adenoma to carcinoma and progression from low stage to high stage CRC.Overexpression of MACC1 in CRC is associated with distant metastasis and poor prognosis. In animal studies, downregulating MACC1 expression inhibit CRC growth and metastasis formation. Here, we discuss MACC1,a recently revealed potential biomarker for CRC diagnosis, prognoses, and a potential therapeutic target for anti-tumor and anti-metastasis intervention strategies.

Speaker
Biography:

Jiaqi Shi has received her MD and PhD from the Hunan Medical University and Postdoctoral training from University of Arizona. She has completed her Pathology Residency and GasteroIntestinal Pathology Fellowship Training at University of Michigan (UM) in 2015. Currently, she is an Assistant Professor in the Department of Pathology at UM. Among her many awards, she has won the prestigious 2011 Benjamin Castleman Award from the United States and Canadian Academy of Pathology (USCAP). She has published more than 30 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

The differential diagnosis between an intraductal papillary mucinous neoplasm (IPMN) and intraductal tubulopapillary neoplasm (ITPN) can be difficult sometimes. IPMN is a mucinous cystic ductal neoplasm of the pancreas, whereas ITPN is mostly a solid intraductal neoplasm of the pancreas with no or minimum mucin. Therefore, gross examination and imaging is helpful to distinguish between these two entities. However, there is histologic overlap that could lead to erroneous diagnosis. Some of the histologic features in IPMN can resemble ITPN. Immunohistochemical stains of MUC5AC and MUC6 can also be helpful. Most of the IPMNs are positive for MUC5AC and negative for MUC6, with the exception of oncocytic type IPMN, while the opposite is true for ITPN. There are 4 subtypes of IPMN based on the epithelial cell lineage: Gastric, intestinal, pancreatobiliary and oncocytic types. Differentiating IPMN subtypes has clinical significance as they are associated with diverse prognosis. In the end, the most important question to address when evaluating IPMN or ITPN resection specimens is whether there is an invasive carcinoma component, because the prognosis is largely dependent on the answer of this question. A thorough examination of the lesion is desired to rule out an invasion.

Speaker
Biography:

Alan Y Martinez has completed his Dental degree in Honduras and his Oral and Maxillofacial Surgery Residency in Peru. He is currently In charge of the division of oral and maxillofacial surgery at the MetroHealth System a level 1 trauma center in Cleveland, OH. He has published 6 articles in English and Spanish in different oral and maxillofacial surgery topics and he is a Reviewer of several journals.

Abstract:

Necrotizing fasciitis (NF) is a rare soft tissue infection of the subcutaneous tissue and superficial fascia that results in rapidly progressive necrosis with secondary involvement of the skin and muscle and a high mortality. Cervicofacial NF (CNF) is an extremely rare entity, accounting for only 2.6-5 % of all NF. There are several different historical descriptions and references to NF dating back to Hippocrates in 500 B.C., who described diffuse non-healing wounds. Pouteau and Gillespie in 1783 and 1785 described malignant and gangrenous ulcers, respectively. In 1871 Joseph Jones, a confederate army surgeon during the U.S. civil war, was the first to accurately describe NF calling it a “hospital gangrene” (Jones, 1871). Meleney in 1924 described 20 cases of hemolytic streptococcal gangrene (Meleney, 1924). Wilson in 1952 coined the term necrotizing fasciitis (Wilson, 1952). Yet, there is very little information on presentation, management and outcome of patients with NF specifically involving the head and neck. NF is classified as one of three types based on microbiologic findings: Type-1 is a polymicrobic infection with a combination of anaerobic and aerobic bacteria, Type-2 is a monomicrobial infection mainly due to group A beta hemolytic streptococci (GAS) and less commonly other streptococci and staphylococci and type 3 is a mono microbial infection due to marine vibrios. The clinical manifestations of NF include: Swelling, redness, pain, fever, blebs, bullae and crepitus. CNF is most commonly a sequalae of odontogenic infection. Less commonly CNF may occur as a consequence of soft tissue trauma. It may rarely occur in the absence of a known inciting factor or a known portal of entry of bacteria as was true in one of our patients (case #1). The spontaneous occurrence of necrotizing fasciitis has been reported to account for up 20% of patients. Cervicofacial necrotizing fasciitis is a rare disease associated with a high morbidity and mortality. Early diagnosis and rapid aggressive radical surgical treatment are the main factors associated with reduced morbidity and mortality.

Speaker
Biography:

Izak Dimenstein is graduated from Mechnikov Medical Academy in Leningrad, former USSR, in 1964 and completed his PhD program at the same institution in 1969. He has worked as a clinical and anatomical pathologist in Leningrad, USSR. Since 1995, he worked as a pathologists’ assistant and grossing technologist at Mount Sinai Chicago Hospital and Loyola University Chicago Medical Center developed a website entitled “Grossing Technology in Surgical Pathology” (www. grossing-technology.com) in 2002. He has retired from Loyola University Chicago Medical Center in 2008. Currently, his main area of interest is the summarization materials on grossing technology and bone grossing techniques.

Abstract:

Grossing maxillofacial pathology specimens is often challenging. It requires following certain principle and employment a variety of techniques to avoid wrong practices and increase the turnaround time. Although in the most cases the main diagnosis is known, the pathologist is required to evaluate the extend of the tumor and interrelationships between involved tissues. Based on extensive personal experience, the optimal sampling is in the fresh state because fixation makes tissue brittle and discolored that is an impediment to present bone and surrounding tissue relationship. Due to fragility or variety of most specimens’ configuration, the use of mechanical power saws is limited. The main technical requirement to get a representative section is the specimen immobilization, which involves employment of different kind of tools and contrivances. In our experience, hard-pressed packing cartons are optimal for secure immobilization. The author is advocating the “third hand immobilization” principle for precise or serial sections. Decalcification monitoring and embedding follow-up are additional requirements for high quality microscope slide for the pathologist’s reliable diagnosis.

Speaker
Biography:

Suliman Ouda is a professor in the Department of Basic Oral and Clinical Sciences, Faculty of Dentistry in King Abdulaziz University.

Abstract:

Purpose: The present study was conducted on undergraduate dental students to asses and compares the levels of salivary stress biomarkers including cortisol, immulnoglobulin A and α-amylase enzyme during periods of academic assessments and non assessments and to relate these biomarkers to students' academic performance. Methods: Saliva samples were collected from undergraduate dental students; one before taking a final assessment exam and another during non assessment period. Salivary stress biomarkers concentrations were obtained using Enzyme Linked Immunosorbent Assay (ELISA). Results: The level of salivary stress biomarkers including s-cortisol, α-amylase and immulnoglobulin A significantly increased during periods of assessment exams as compared to non assessment (p=0,000, 0.001 and 0.003 consecutively). The study found a significant correlation between salivary α-amylase and academic performance especially among male students (p=0.008) and those in their final academic year (p=0.040). Conclusion: We conclude that the stress of academic assessment can markedly increase the level of salivary stress biomarkers. Students who show less academic performance generally depict higher levels of salivary α-amylase, especially male students and those in their final academic year.

Speaker
Biography:

Hexige Saiyin has completed his MD from Shanghai Medical University and worked as a Lecture in Fudan University. He has completed his PhD study in the School of Life Science, Fudan University. He has also worked as a Visiting Assistant Professor in MD Anderson Cancer Center in Houston. He has discovered the "hairy" micro vessels which contain many basal cellular projections in PDAC, named the projection as "basal microvilli". He is an Assistant Professor in the School of life Sciences, Fudan University. He has published more than 50 papers in reputed journals.

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is a uniformly lethal malignancy with near 6 months median survival. It is a stroma-rich, vascular-poor and hypo-perfused tumor, which was considered to prevents efficient drug or nutrient delivery in tumor microenvironment. Paradoxically, the tumor cells have robust glucose uptake and rare necrosis, suggesting that the microvasculature has might adopted an alternative way for nutrient uptake and cellular trafficking. Using adapted thick tumor section immunostaining and three-dimensional (3D) construction imaging in human fresh tissue samples, we identified an undiscovered feature of the mature microvasculature in advanced PDAC tumors; long, hair-like projections on the basal surface of micro vessels that we refer to as ’basal microvilli’. Basal microvilli were also observed in intrahepatic cholangiocarcinoma (ICC) and metastatic pancreatic neuroendocrine tumor (panNET), but not in hepatocellular carcinoma, glioblastoma and renal clear cell carcinoma. Basal microvilli in PDAC are richer and denser than ICC and panNET. Functionally, these basal microvilli have an actin-rich cytoskeleton and endocytic and exocytic properties and contain glucose transporter-1 (GLUT-1)-positive vesicles. Clinically, as demonstrated by PET-CT, the tumor microvasculature with the longest and most abundant basal microvilli correlated with high glucose uptake of the PDAC tumor itself. In addition, these basal microvilli were found in regions of the tumor with low GLUT-1 expression, suggesting that their presence could be dependent upon the glucose concentration in the tumor milieu. Similar microvasculature features which contain glucose were also observed in a K-Ras-driven model of murine PDAC. Altogether, these basal microvilli mark a novel pathological feature of PDAC microvasculature and ICC and panNET. Because basal microvilli are pathological features with endo and exocytic properties, they may provide a non-conventional method for cellular trafficking in PDAC tumors.

Anshoo Agarwal

RAK Medical and Health Sciences University, UAE

Title: Cytomorphological spectrum of cysticercosis: A study of 72 cases
Speaker
Biography:

Anshoo Agarwal is the Professor & Chairperson (Pathology), RAK medical College and Health sciences University. She published more than 100 publications in National and International journals. Her main research focus is on Immunopathology & medical education.

Abstract:

Introduction: Cysticercosis is a worldwide infection caused by larval stage of a cestode, Taenia solium. Worm infestation is acquired by ingestion of undercooked pork containing the cysticerci. Cysticercosis is a common disease in most developing countries. It has its greatest prevalence in Mexico, other areas of Latin America, India, China, Africa and Europe. Cysticerci may present as single or multiple painless swellings in any organ or tissue of the body. The most common sites in order of frequency are the subcutaneous tissue, brain, muscle, heart, liver, lungs and peritoneum. These are usually mistaken clinically for dermatofibroma, neurofibroma, sebaceous cyst, dermoid cyst and calcified lymph nodes. Biopsy is a gold standard for definitive diagnosis of any lesion but nowadays fine needle aspiration cytology (FNAC) in the diagnosis of various parasitic lesions is well documented. In the present study we report clinical profile and cytomorphologic spectrum of cysticercosis findings on fine needle aspirates from 72 cases diagnosed as cysticercosis. Material & Methods: Over the period of 6 years, 72 cases of cysticercosis were diagnosed in the Department of Pathology, BPKIHS, Nepal & Shrivalli Nursing Home, Thane West, Maharashtra, India. All the patients presented with swellings of different regions of the body. FNA was performed with 22 gauge needle and 10 ml disposable plastic syringe. Aspirated materials were smeared onto the glass slides. Two slides were fixed immediately in 95% ethyl alcohol and stained with Papanicolaou stain. Two air dried smears were stained with May-Grunwald-Giemsa stain. Cases which were biopsied were processed for histopathological examination, stained with hematoxylin and eosin. Results: 38 patients were males and 34 patients were females. The age ranged from 1.5 to 76 years with majority of the patients (76.38%) being younger than 40 years of age. Most frequently affected site was upper extremity (47.28%). In 7 cases (9.73%) lingual cysticercosis was diagnosed in our study. Involvement of breast was seen in 4 cases (5.56%) which is a rare presentation. Clinically (98.7%) cases presented with a solitary lesion in the present study. Fine needle aspirates in our study yielded clear fluid in (32.27%) cases, blood mixed aspirate in (23.01%) cases and pus like aspirate in (44.72%) cases. Fragments are bluish fibrillary glial like structure. Outer wall layer was seen thrown into rounded wavy folds with tiny ovoid nuclei in a fribrillary stroma comprising of thin reticulin fibrils beneath it. In rest two of the cases (2.77%) diagnosis was suggested on associated other cytomorphologic features and inflammatory reaction comprising of eosinophils, neutrophils, histiocytes, epithelioid cells, lymphocytes and giant cells in varying proportions which were confirmed later on biopsy. In our study 24 cases (33.33%) were misdiagnosed clinically as cases of dermatofibroma, neurofibroma and sebaceous cyst. Conclusion: FNA cytology is a simple and reliable procedure for the diagnosis of cysticercosis. In principle, a mass produced by cestode should not be diagnosed by FNAB since it might cause anaphylaxis and/or dissemination of parasites.

  • Track 7: Digital Pathology and e-Pathology
    Track 8: Anatomical Pathology
    Track 9: Surgical Pathology

Session Introduction

Leon P Bignold

University of Adelaide, Australia

Title: The kinds of genomic events for the histopathologic complexities of tumors

Time : 14:35-15:00

Speaker
Biography:

Dr Bignold graduated in Medicine from the University of Western Australia, and has post-graduate qualifications in internal medicine, experimental pathology, and diagnostic histopathology. From the 1980s, he has practiced and taught general and diagnostic histopathology at the University of Adelaide and the South Australian state government pathology service (SA Pathology, formerly Institute of Medical and Veterinary Science). Dr Bignold has written many articles on how genomic instability might explain the histopathological features of tumors, as well as related issues. In 2015, he published "Principles of Tumors: a Translational Approach to Foundations", Elsevier, Academic Press, Waltham, MA. With colleagues, he has also published a study of the origins of tumor pathology: "David Paul Hansemann: Contributions to Oncology" Birkhäuser, Basel, (2007) and a volume on the history of medicine: "Virchow's Eulogies" Birkhäuser, Basel, (2008). In 2006, he edited a volume “Cancer: cell structures, carcinogens and genomic instability”. (EXS vol 96, 2006). http://link.springer.com/book/10.1007/3-7643-7378-4/page/1;

Abstract:

1. Tumors are accepted to arise by way of somatic mutation / genomic event, but no particular mutation has been found in all tumors. Conventional (Mendelian) genetics may be able to account for combinations of traits by mutations of complex loci. The occurrence of tumors in different types could be explained by the existence of one or a small number of different tumorigenic-when-mutant complex loci for each tumor type (1). Variability in tumors may be explicable by variable functional morphisms / particular nucleotide alterations in genes in the complex loci. 2. The kinds of mutations (genomic events) which can affect complex loci are mainly (i) Oligonucleotide deletions or insertions causing frameshift mutations. (ii) Chromosomal-type errors, which are mainly deletions, amplifications, inversions and transpositions. These can be so large as to be visible in chromosomes by microscopy (hundreds of megabases), or so small that they can only be demonstrated by various probe-hybridization methods (tens of kilo bases). (iii) A lesion comprising dense clusters of nucleotide errors in lengths of DNA up to a replication 'bubble' (approximately 150kb) long (2). These focal replicative infidelity lesions are difficult to detect. 3. Variable functional morphisms could occur with any of these mechanisms of genomic events in complex loci. 4. These issues may be resolvable by new methods for high throughput nucleotide sequencing. (1) Bignold LP "Principles of Tumors", Elsevier Academic, 2015, chapters 1 and 8 and Appendix 2. (2) Bignold LP. Carcinogen-induced impairment of enzymes for replicative fidelity of DNA and the initiation of tumours. Carcinogenesis. 2004 25:299-307.

Speaker
Biography:

Mark Priebe has presented numerous poster and podium presentations on Quality Assurance in Anatomic Pathology and he is a part of the speaker group for the Society for Improvement in Diagnostic Medicine. He is a Medical Technologist certified by the American Society of Clinical Pathology in both Medical Technology and Blood Banking. He is the Co-Inventor of the QualityStar external quality assurance program for anatomic pathology.

Abstract:

Every year, 1.6 million Americans are diagnosed with cancer. Getting the diagnosis right the first time is critical to designing the appropriate treatment plan and therapy. Pathology and radiology play significant roles in the diagnostic process. When things go wrong, 46% of the errors in diagnosis come from Pathology and Radiology, while 97% of the cancer diagnosis is based on the pathology specimen. Over the past 20 years, multiple studies have shown that the rate of major discrepancies identified for cancer patients referred to another institution range from 4.2-13.1% yet published data indicates the current intralab Quality Assurance (QA) ability to detect these discrepancies is only 0.8-1.7%. This clearly identifies a gap in our current quality practice and an opportunity to improve quality assurance initiatives. This abstract reviews the formal Quality Assurance programs and how they can be utilized to provide continuous quality improvement resulting in positive patient and institution outcomes.

Lorenzo Azzi

University of Insubria, Italy

Title: Burning Mouth Syndrome. What is new?

Time : 15:25-15:50

Speaker
Biography:

Lorenzo Azzi is a PhD student of the “Biotechnology, Biosciences and Surgical Technology” course at University of Insubria. He is an oral surgeon and oral pathologist. He is assistant director of the Unit of Oral Pathology, Ospedale di Circolo Fondazione Macchi, Varese. He is active member of the Italian Society of Oral Pathology and Medicine (SIPMO) and of the European Association of Oral Medicine (EAOM)

Abstract:

Burning Mouth Syndrome (BMS) is regarded as a puzzling condition for clinicians coming from different specialties. Once considered as a psychiatric disorder, in recent years a new hypothesis for a possible role of the peripheral nerve fibers in the pathogenesis of the syndrome has been suggesteded. The purpose of this presentation is to shed light on the very often controversial data collected from the scientific literature and to illustrate the different important findings of the research carried out in our Institute, which could provide a great help to better understand this mysterious pathology. Salivary fluids analysis, topical application of different molecules, psychological anamnesis, epidemiological data, laboratory and histological findings are described. A following detailed diagnostic and therapeutic approach adopted in our trial is described, supported by the most recent findings in literature and in our research protocols.

Break: 15:50-16:05
Speaker
Biography:

Munaf Desai is MD in Pathology from BJMC in 1995, Ahmadabad, India. He is a Specialist of histopathology and currently is the Head of Histopathology Cytology Unit at Al Qassimi Hospital Sharjah, UAE.

Abstract:

Introduction: Granular cell tumor (GCT) is a rare soft tissue neoplasm of neural differentiation that can occur at any site of the body. The tumor is usually benign with rare incidence of malignancy. The diagnosis of GCT requires histopathologic examination of the excised lesion. We present three histopathology case reports of GCT tumors at three different sites in three different patients. Case Presentation: Case 1: An excision biopsy of a painless soft tissue mass at elbow of a 26 years old female patient received for histopathologic examination. Case 2: Completely removed tumor from the right fronto-parietal mass with dural attachment of a 73 years old female patient with clinical diagnosis of meningioma was received for histopathologic diagnosis. Case 3: A skin lesion on the chest wall of a 24 years old male patient was excised and sent for histopathologic examination. The clinical diagnosis was ‘Dermaoid Cyst’. Diagnosis of benign GCT was given in all of them after microscopic examination of routine Hematoxylin & Eosin stained sections, periodic Acid-Schiff (PAS) special stain and appropriate immunohistochemistry markers. Conclusion: GCT is a rare mostly benign tumor and rarely diagnosed prior to histopathologic examination of the excised specimen. Immunocytochemistry study and PAS special stain are needed to give confirm diagnosis of GCT.

Speaker
Biography:

Kazuaki Nakane has obtained his PhD at Kanazawa University. He is a guest Associate Professor and a specially appointed Researcher in Osaka University. By using an idea of homology, he has developed a new image analysis method and applied this method to detect cancer lesion. He has also been successful in image analysis of complex images which seem to have mathematical structures.

Abstract:

Introduction: Recently, a new method based on the homology theory for analyzing histological digital images has been developed. The method evaluates the Betti numbers in a unit area of an image of a colon to determine the region of interest (ROI). The Betti number can be used to assess the degree of connectivity in tissue. Here, we change the binarizing threshold and investigate the relation between the change ratio of the Betti numbers and the different types of cancerous tissue. Materials & Method: Colonic specimens were provided by the Osaka Medical Center for Cancer and Cardiovascular Diseases. Data were gathered for internal quality control on a routine basis and all patients gave informed consent for data collection. Results: The calculated results can be approximated by quadratic functions. The distribution of the coefficient on the squared term and the x-coordinates of the vertices are shown. We can see a characteristic distribution for each type of cancerous tissue. Discussion: As the binarizing threshold decreases, the images gradually fade to white and the structure of the tissue is lost. Under the proposed procedure, in areas where the connections in the tissue are tight and clear, the one-dimensional Betti number changes slowly; conversely, where the connections are vague, such as in a background area filled with impurities, it changes very quickly. The state of this change can be considered an expression of the strength of the connectivity and it differs by type of cancerous tissue.

Speaker
Biography:

Hisataka Kitano is an Assistant Professor in Nihon University of school of Medicine, Division of Oral surgery, Japan. He began a study of Del1 in 2005 in the present laboratory. He clarified deposition into extracellular matrix of Del1, apoptotic function, endocytosis function. He studied cancer gene therapy using Del1 in vivo. He treated the oral neoplasia as an oral and maxillofacial surgeon at a Nihon university school of medicine, Itabashi hospital.

Abstract:

Introduction: Del1, an ECM protein, is known to show pro-angiogenic or anti-angiogenic activities depending on the experimental conditions. It consists of two discoidin domains (C1, C2) and three epidermal growth factor (EGF) motifs (E1, E2, E3), of which E2 has been reported to contain an RGD sequence that binds to integrin receptors and supports endothelial cell survival. In the present study, we provide evidence that an E3C1 fragment suppresses Notch signaling and angiogenesis in explanted tumor model. Materials & Methods: Cells of the human oral squamous cell carcinoma cell line, SCCKN, were injected into nude mice to generate explanted tumors. cDNAs encoding, the E3 and C1 domains of Del1 (E3C1), were inserted into pcDNA3D (pE3C1) and injected into the tumors every 7 days with a transfection reagent, jet-PEI. Tumor angiogenesis was evaluated by immunohistochemistry with antibodies for PECAM, von Willebrand factor and PDGF-beta and intravenous injection of Lycopersicon esculentum lectin. The signal transduction of notch was analyzed by western blotting. Results: Treatment with pE3C1 suppressed the growth of explanted tumors and improved life prognosis of mice. In localization with immunostaining of PECAM or von Willebrand factor, and angioglaphy with Lycopersicon esculentum lectin, vasculature without lumen was increased by gene therapy of Del1 fragment. Among the treatment with pE3C1 and control, the PDGF beta staining cells, which is marker of tip cells in angiogenesis, were increased. Western blotting of human umbilical endothelial cells cultured with an E3C1 recombinant protein showed the decreased expression of active notch and hey1. Discussion: The phenotype of tumor vascular by treated with pE3C1 was analogous to the phenotype of inhibited of notch. In our study, it is suggested that the effective angiogenesis was inhibited by E3C1 inhibition of notch function. There is an anti-angiogenic domain, E3C1, adjacent to the RGD in E2 of Del1. The presence of domains with opposing activities next to one another in the same protein could account for the seemingly ambiguous characteristics of Del1 activity on angiogenesis. The EGF domain of Del1 has amino acid sequence, CXDXXXXYXCXC, which was shared by notch and delta. Signaling way of the motif should be investigated for notch function.

Speaker
Biography:

Hisataka Kitano is an Assistant Professor in Nihon University of school of Medicine, Division of Oral surgery, Japan. He began a study of Del1 in 2005 in the present laboratory. He clarified deposition into extracellular matrix of Del1, apoptotic function, endocytosis function. He studied cancer gene therapy using Del1 in vivo. He treated the oral neoplasia as an oral and maxillofacial surgeon at a Nihon university school of medicine, Itabashi hospital.

Abstract:

Introduction: Del1, an ECM protein, is known to show pro-angiogenic or anti-angiogenic activities depending on the experimental conditions. It consists of two discoidin domains (C1, C2) and three epidermal growth factor (EGF) motifs (E1, E2, E3), of which E2 has been reported to contain an RGD sequence that binds to integrin receptors and supports endothelial cell survival. In the present study, we provide evidence that an E3C1 fragment suppresses Notch signaling and angiogenesis in explanted tumor model. Materials & Methods: Cells of the human oral squamous cell carcinoma cell line, SCCKN, were injected into nude mice to generate explanted tumors. cDNAs encoding, the E3 and C1 domains of Del1 (E3C1), were inserted into pcDNA3D (pE3C1) and injected into the tumors every 7 days with a transfection reagent, jet-PEI. Tumor angiogenesis was evaluated by immunohistochemistry with antibodies for PECAM, von Willebrand factor and PDGF-beta and intravenous injection of Lycopersicon esculentum lectin. The signal transduction of notch was analyzed by western blotting. Results: Treatment with pE3C1 suppressed the growth of explanted tumors and improved life prognosis of mice. In localization with immunostaining of PECAM or von Willebrand factor, and angioglaphy with Lycopersicon esculentum lectin, vasculature without lumen was increased by gene therapy of Del1 fragment. Among the treatment with pE3C1 and control, the PDGF beta staining cells, which is marker of tip cells in angiogenesis, were increased. Western blotting of human umbilical endothelial cells cultured with an E3C1 recombinant protein showed the decreased expression of active notch and hey1. Discussion: The phenotype of tumor vascular by treated with pE3C1 was analogous to the phenotype of inhibited of notch. In our study, it is suggested that the effective angiogenesis was inhibited by E3C1 inhibition of notch function. There is an anti-angiogenic domain, E3C1, adjacent to the RGD in E2 of Del1. The presence of domains with opposing activities next to one another in the same protein could account for the seemingly ambiguous characteristics of Del1 activity on angiogenesis. The EGF domain of Del1 has amino acid sequence, CXDXXXXYXCXC, which was shared by notch and delta. Signaling way of the motif should be investigated for notch function.

Speaker
Biography:

Azin Mirzadeh got her Doctoral degree in Dentistry from University of Medical Science and Health Services School of Dentistry, Kerman-Iran. She has 5 publications in fields of Oral Pathology, Periodontology and Endodontics. She was a member of scientific committee in Dental Disease Research Center in Kerman-Iran. She got honor and award as a patent in field of Oral Surgery, with the title of, “The arch bar applicator for oral and maxillofacial surgery”. She is a professional membership in Iranian General Dentist association (IGDA). In 2014, she moved to the United States, and now she in the application process for dental schools.

Abstract:

Pregnancy tumor histologically coincides with oral pyogenic granuloma. It is a reactive hemorrhagic swelling that mostly occurs in gingiva of pregnant women and can cause some complications. The tumor usually grows rapidly and direct relationship has been observed between the growth rate of the tumor and decreased level of estrogen and progesterone, occurring during the course of pregnancy. Gingiva is the most common site involved; it usually occurs labially on maxillary anterior teeth but the tongue, lips, palate and oral mucosa might also be rarely involved. This study aimed to describe an extra gingival pregnancy tumor occurred on the tongue in a 28 years old female patient at 7th month of gestation. The lesion mass was 1.5 cm in greatest diameter on the right side of the dorsum of the tongue with mild spontaneous bleeding and it interfered with speech and mastication. The lesion was excised under local anesthesia during the pregnancy with no untoward reactions. The histopathological examination revealed granulation tissue with non neoplastic proliferation of endothelial cells, suggestive of pregnancy tumor. During pregnancy, careful oral hygiene, removal of dental plaque and use of soft toothbrushes are very important to avoid occurrence of pregnancy tumor.