- Browse by Author
Browsing by Author "Spencer, Cleandrea"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Increased Incidence of Lymphosarcoma in Long-Term Murine Survivors of Lethal Radiation: A Classification of Subtypes(Office of the Vice Chancellor for Research, 2013-04-05) Spencer, Cleandrea; Chua, Hui Lin; Plett, Arthur; Sampson, Carol; Joshi, Mandar; Roberts, Christopher S.; Lipking, Kelsey; Orschell, Christie M.; Sandusky, George E.Residual bone marrow damage (RBMD) persists for years following exposure to radiation and is thought to be due to decreased self-renewal of hematopoietic stem cells (HSC). We previously examined RBMD in murine survivors of lethal radiation modeling a terrorist event [800cGy total-body irradiation (TBI)]. We reported severely deficient HSC potential up to 20mo post-TBI compared to non-TBI age-matched controls, evidenced by minimal engraftment skewed to myeloid cells. CBC and BM cellularity were decreased in TBI mice, most dramatically in old age (>16mo). The percentage of some hematopoietic progenitors was consistently increased in TBI mice (~1.4x higher than non-TBI) possibly due to an increased cell cycling rate compared to non-TBI cells. Of interest, we now report the occurrence of a thymic mass developing in 13-24% of TBI mice 2-19 months post-TBI, compared to <1% of non-TBI. We characterized the Lymphosarcoma into the following groups based on the St. Jude pathology subclassification: Diffuse Lymphosarcoma involving multiple organs, Thymic lymphoma (usually associated with thymic and around the heart), Lymphosarcoma (potentially starting in the spleen and peri-pancreatic lymph nodes (Ab=abdomen)), and follicular lymphoma seen as a diffuse proliferation of lymphocytes in the white pulp area in the spleen. Thymic lymphomas were the most common, followed by Lymphosarcoma (Ab), follicular lymphoma (restricted to white pulp area in the spleen) and diffuse Lymphosarcoma. Immunostain markers revealed the thymic lymphomas were from T-cell lineage and the abdominal Lymphosarcoma were mainly from B-cell lineage. A few mice had disease involving the bone marrow. Taken together, these data suggest that the increased cycling among primitive hematopoietic cells in survivors of lethal radiation may contribute to stem cell exhaustion and subsequent RBMD, as well as predispose survivors to hematopoietic neoplasias.Item QUALITY CONTROL FROM A SUBSET OF HUMAN SURGICAL TISSUE SPECIMENS FROM THE IU SIMON CANCER CENTER TISSUE PROCUREMENT AND DISTRIBUTION CORE COLLECTED IN 2009-2010: AN H&E AND RIN VALUE ASSESSMENT(Office of the Vice Chancellor for Research, 2011-04-08) Spencer, Cleandrea; Sandusky, George; Rodgers, Matt; Carr, Katherine A.; Mitchell, ColleenQuality control (QC) of human tissue specimens for research is critical for the development of new bio-markers and their ability to determine clinical trial outcomes. In this study, we evaluated sixty-nine samples for both RNA and histology quality control measures from the IU Simon Cancer Center Tissue Bank. The IU Simon Cancer Center Tissue Bank is a centralized tissue procurement resource established to collect high quality tissue for basic clinical and translational research, collecting approximately 550 clinical cases per year using an informed consent and HIPAA signed document. All tissues are collected and processed in liquid nitrogen within 30 minutes of removal. The tissue samples are sliced and diced into 100 to 150 mg sample size. Each sample is placed into individual 2ml cryovials. Two representative samples are placed in 10% neutral buffered formalin. Two investigators QC the slides by microscopy to evaluate the following: percent of tumor, percent of necrosis, percent of fibrosis/inflammation, and percent of normal adjacent tissue. RNA was extracted using the Purescript RNA isolation kit (Gentra). Fifty-four of sixty-nine cases passed both histology and RNA (RIN value) QC. Of the fifteen cases that did not pass our QC criteria, thirteen cases did not pass the histology QC due to lack of tumor content (below 50%) in the sample, while the remaining two cases failed the RNA QC. Seventy-eight percent of samples passed our QC measures. The results were consistent with the existing literature on tissue quality control in human surgical tissue specimens.Item QUANTITATIVE IMMUNOHISTOCHEMISTRY USING THE APERIO WHOLE SLIDE IMAGING SYSTEM EVALUATING ANGIOGENESIS AND HYPOXIA MARKERS IN PANCREATIC CARCINOMA MOUSE MODEL TREATED WITH VEHICLE CONTROL, E3330, AND A STAT 3 INHIBITOR(Office of the Vice Chancellor for Research, 2012-04-13) Spencer, Cleandrea; Sandusky, George; Fishel, Melissa; Kelley, Mark R.Investigation of the signaling pathways and molecular mechanisms that are major contributors to pancreatic tumor progression and its resistance to traditional therapies is lacking. Human apurinic endonuclease/redox factor 1 (APE/Ref-1) mediates repair of radiation-induced DNA lesions and regulates transcription via redox-based activation. Transcriptional factors HIF-1α, NFκB, and AP-1 are regulated by Ref-1 and are implicated in pancreatic tu-mor growth and the response to hypoxia. CD31 and CA IX (carbonic anhy-drase) were biomarkers used in an in vivo study to evaluate the effective-ness of E3330, an APE 1 inhibitor, in a pancreatic mouse model. Immunostained slides were scanned using the Aperio automated whole slide scanning system (Scanscope CS) and were viewed using ImageScopeTM. Single fields of view from each WSDI measuring ∼10,000,000 μm2 and rep-resenting the whole area of the tumor were selected for analysis using the Aperio positive pixel algorithm. The preclinical xenograft model evaluated human pancreatic carcinoma cell lines grown in NOD/SCID mice treated with the E3330 compound, a STAT 3 inhibitor, and an untreated vehicle control group. Immunohisto-chemistry (IHC) was used to predict effectiveness of treatment for pancreat-ic carcinoma based on CD31 and CA IX biomarker expression. IHC slides were quantified using both a traditional pathology hand count and the Aperio Imaging Analysis System. The positive pixel algorithm data closely mirrored the hand count for two biomarkers (CD31 and CA IX). In the E3330 treated group, the data showed CD31 (angiogenesis) was significantly knocked down with increased CA IX expression compared to the vehicle control. Hypoxia of the tumor cells was up in both treated groups. In summary, the Aperio im-aging analysis system matched the hand count pathology data. The drug ef-fects with E3330 exhibited both anti-angiogenesis and tumor hypoxia activi-ty in the tumors. This project was supported by the Center for Research and Learning’s Diversity Scholars Re-search Program.