Medical Anatomy Commons^™

Her-2 Heterogeneity In Breast Cancer: A Case Study, Kinnari Patel, Theodore Parsons

Department of Pathology Honors Program Student Research Symposium

CASE

The patient is a 75 year-old female with a history of stage 1 invasive ductal carcinoma of the left breast measuring 1.2 cm. Core biopsy of the mass demonstrated Nottingham grade 3 invasive ductal carcinoma; ER negative, PR negative, HER-2 negative (1+). The patient underwent mastectomy in April 2013. Mastectomy confirmed Nottingham grade 3 invasive ductal carcinoma pT1c/pN0/pMX with peritumoral lymphovascular invasion and invasive tumor less than 1 mm from the superoanterior margin. Due to comorbidities the patient was not considered a candidate for adjuvant chemotherapy.

In January 2014 the patient presented with a mastectomy site recurrence. Needle core …

Personalized Immune Therapy For Cancer A Potential Game-Changing Treatment, Emily Evron, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

T-CELL RECEPTOR, NORMALLY

T-cell receptors reside on the surface of T-cells, and recognize a specific antigen presented by an MHC molecule

Next, the T-cells become either CD4 or CD8 cells

Co-stimulation is a key step in activating the T-cell; B7 proteins on the surface of antigen-presenting cells interact with CD28/CTLA-4 receptors on the T-cell.

Haploidentical Hematopoietic Stem Cell Transplantation: Rationale, Development, And Jefferson’S Method, Susan Mcilvaine, Dolores Grosso, Rn, Crnp, Dnp, Beth Colombe

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

There are many indications for hematopoietic stem cell transplantation. In addition to hematologic malignancies, transplants are performed in certain non-hematologic malignancies, for marrow disorders such as Sickle Cell Anemia, and for various inherited disorders such as SCID. Traditionally, transplants have been performed between donors and recipients that are a complete HLA match (typically matched siblings). That is, patients have identical HLA alleles on both copies of chromosome 6. HLA alleles code for major histocompatibility complex molecules, which are the proteins that cause transplant rejection when a mismatch between donor and recipient is present. Thus, matched transplants have been historically …

Small Cell Carcinoma Of The Bladder: A Rare Entity, Andrew H. Matthews, Ruth Birbe, Md

Department of Pathology Honors Program Student Research Symposium

BACKGROUND

Primary small cell carcinoma of the urinary bladder is a rare tumor, accounting for less than 1% of the annual 70,000 cases of urinary bladder cancer.¹ Accordingly, little data is available beyond case series to guide diagnosis or treatment. Overall prognosis remains poor with five year survival often markedly below 50%. Current staging and treatment remains largely based on extrapolation from small cell carcinoma of the lung. We review two recent cases of bladder small cell carcinoma with a focus on comparing and contrasting with lung small carcinoma.

Giant Cell Tumor Of Soft Tissue: A Case Study, Rachel Schneider, Brian J. O'Hara

Department of Pathology Honors Program Student Research Symposium

BACKGROUND

Giant cell tumors of soft tissue are relatively uncommon tumors. They are considered to be the soft tissue counterpart to giant cell tumors of bone. Both tumors consist of multi-nucleated giant cells evenly distributed throughout a background of epithelioid mononuclear cells, and are usually benign, but can be locally invasive. Giant cell tumors of soft tissue typically occur in patients over age 40, and show no gender or racial predilection. They present as firm, well demarcated masses, which are not connected to the underlying muscle, tendon, or bone. Giant cell tumors of soft tissue are generally small, and tend …

Small Cell Carcinoma Of The Breast, Victor Carlson, Paolo Cotzia, Md, Juan P. Palazzo, Md

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

Small cell carcinoma of the breast (SCCB) is a rare, highly aggressive neoplasm first reported in 1983. With striking histologic similarity to small cell carcinoma of the lung, it is comprised of small cells with relatively large, hyperchromatic nuclei and scanty cytoplasm. While capable of hormone secretion, this is a rare occurrence in this variant of small cell carcinoma. Patients typically present with a suspicious breast mass confirmed on imaging, with variable lymph node invasion.

Fibrosing Cholestatic Hepatitis C Post-Liver Transplantation: A Case Study, Layla Hatem, Wei Jiang, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Introduction:

Liver Transplantation:

• Hepatitis C infection is the most common indication for liver transplantation in the US
• HCV infection of the liver allograft occurs within hours from circulating virions.

-Serum RNA levels are observed in the first several weeks.

-Acute hepatitis occurs in 2-6 months

-Chronic hepatitis occurs in 3-9 months

***Persistence of HCV infection is the rule after transplantation due to immune suppression

Chronic recurrent HCV infection post transplantation

• There are four distinct patterns of recurrent chronic HCV in the liver allograft.

-Usual chronic HCV (>70%)

-Fibrosing Cholestatic Hepatitis C (5-10%)

-Plasma cell-rich HCV

-HCV overlapping with rejection …

"What Happens In Romania..." Comes Back To The United States And Becomes A Quilt, Ashley Ehlers, Kaitlyn Torres

Senior Theses

Our senior thesis project is a quilt that chronicles our experiences on the Maymester trip to Romania through the Honors College, during which we were able to shadow surgeons in the Oncology Hospital and General Surgery III Hospital in Cluj-Napoca. In our quilt, we included some of the most common surgeries we saw while shadowing Romanian doctors: breast removal, gall bladder removal, appendix removal, removal of a section of the large intestine, and removal of the uterus. The final product of this quilt shows every level of the abdominal muscles and organs from the anterior skin to the kidneys.

To …

Bcl2 Expression And Bcl2/Myc Dual Expression Predicts Inferior Survival In Primary Central Nervous System Lymphoma, Guldeep Uppal, Md, Zi-Xuan (Zoe) Wang, Phd, Renu Bajaj, Phd, Mark T. Curtis, Md, Phd, Charalambos C. Solomides, Md, Jon Glass, Md, Peter M. Banks, Stephen C. Peiper, Md, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Background

Primary CNS lymphoma (PCNSL) is a rare type of diffuse large B-cell lymphoma (DLBCL) arising from and usually confined to CNS. Understating of the pathogenesis and prognostic markers is a challenge due to rarity of this neoplasm and paucity of the material available to study. Recent studies have shown that dual expression of MYC and BCL2 in DLBCL contributes to inferior overall survival. The prognostic value of MYC and BCL2 in PCNSL is not well studied.

Inputs Drive Cell Phenotype Variability., James Park, Anthony Brureau, Kate Kernan, Alexandria Starks, Sonali Gulati, Babatunde Ogunnaike, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

What is the significance of the extensive variability observed in individual members of a single-cell phenotype? This question is particularly relevant to the highly differentiated organization of the brain. In this study, for the first time, we analyze the in vivo variability within a neuronal phenotype in terms of input type. We developed a large-scale gene-expression data set from several hundred single brainstem neurons selected on the basis of their specific synaptic input types. The results show a surprising organizational structure in which neuronal variability aligned with input type along a continuum of sub-phenotypes and corresponding gene regulatory modules. Correlations …

Chronic Arsenic Exposure And Angiogenesis In Human Bronchial Epithelial Cells Via The Ros/Mir-199a-5p/Hif-1Α/Cox-2 Pathway., Jun He, Min Wang, Yue Jiang, Qiudan Chen, Shaohua Xu, Qing Xu, Bing-Hua Jiang, Ling-Zhi Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Environmental and occupational exposure to arsenic is a major public health concern. Although it has been identified as a human carcinogen, the molecular mechanism underlying the arsenic-induced carcinogenesis is not well understood.Objectives: We aimed to determine the role and mechanisms of miRNAs in arsenic-induced tumor angiogenesis and tumor growth.Methods: We utilized an in vitro model in which human lung epithelial BEAS-2B cells were transformed through long-term exposure to arsenic. A human xenograft tumor model was established to assess tumor angiogenesis and tumor growth in vivo. Tube formation assay and chorioallantoic membranes assay were used to assess tumor angiogenesis.Results: We …

A New Rhesus Macaque Assembly And Annotation For Next-Generation Sequencing Analyses, Aleksey V. Zimin, Adam S. Cornish, Mnirnal D. Maudhoo, Robert M. Gibbs, Xiongfei Zhang, Sanjit Pandey, Daniel T. Meehan, Kristin Wipfler, Steven E. Bosinger, Zachary P. Johnson, Gregory K. Tharp, Guillaume Marçais, Michael Roberts, Betsy Ferguson, Howard S. Fox, Todd Treangen, Steven L. Salzberg, James A. Yorke, Robert B. Norgren Jr.

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: The rhesus macaque (Macaca mulatta) is a key species for advancing biomedical research. Like all draft mammalian genomes, the draft rhesus assembly (rheMac2) has gaps, sequencing errors and misassemblies that have prevented automated annotation pipelines from functioning correctly. Another rhesus macaque assembly, CR_1.0, is also available but is substantially more fragmented than rheMac2 with smaller contigs and scaffolds. Annotations for these two assemblies are limited in completeness and accuracy. High quality assembly and annotation files are required for a wide range of studies including expression, genetic and evolutionary analyses.

RESULTS: We report a new de novo assembly of the …

Computational Analysis Of Transcriptional Circuitries In Human Embryonic Stem Cells Reveals Multiple And Independent Networks, Xiaosheng Wang, Chittibabu Guda

Journal Articles: Genetics, Cell Biology & Anatomy

It has been known that three core transcription factors (TFs), NANOG, OCT4, and SOX2, collaborate to form a transcriptional circuitry to regulate pluripotency and self-renewal of human embryonic stem (ES) cells. Similarly, MYC also plays an important role in regulating pluripotency and self-renewal of human ES cells. However, the precise mechanism by which the transcriptional regulatory networks control the activity of ES cells remains unclear. In this study, we reanalyzed an extended core network, which includes the set of genes that are cobound by the three core TFs and additional TFs that also bind to these cobound genes. Our results …

Tibial Tubercle Transfer To Correct Bilateral Patellar Tendinopathy In A Collegiate Football Player, Andrew D. Hamstra

Boise State University Theses and Dissertations

Objective: To present a case of a competitive football player with chronic patellar tendinopathy and the associated bilateral tibial tubercle transfer surgeries performed leading to the reduction of pain and return to participation.

Background: A 19 year-old male football athlete (height= 187.96 cm, mass= 112.037 kg) presented with chronic patellar tendinopathy that began in his high school career and continued to worsen with the increased physical demands associated with participation in collegiate sport.

Differential Diagnosis: Chondromalacia patella and Osgood Schlatters disease.

Treatment: After nonsurgical intervention resulted in no decrease of pain, bilateral tibial tubercle transfer surgery was conducted to correct …

The Genome Of Polymorphonuclear Neutrophils Maintains Normal Coding Sequences, Fengxia Xiao, Yeong C. Kim, Hongxiu Wen, Jiangtao Luo, Pei Xian Chen, Kenneth Cowan, San Ming Wang

Journal Articles: Genetics, Cell Biology & Anatomy

Genetic studies often use genomic DNA from whole blood cells, of which the majority are the polymorphonuclear myeloid cells. Those cells undergo dramatic change of nuclear morphology following cellular differentiation. It remains elusive if the nuclear morphological change accompanies sequence alternations from the intact genome. If such event exists, it will cause a serious problem in using such type of genomic DNA for genetic study as the sequences will not represent the intact genome in the host individuals. Using exome sequencing, we compared the coding regions between neutrophil, which is the major type of polymorphonuclear cells, and CD4+ T cell, …

Heterogeneity Of Functional Properties Of Clone 66 Murine Breast Cancer Cells Expressing Various Stem Cell Phenotypes, Partha Mukhopadhyay, Tracy Farrell, Gayatri Sharma, Timothy R. Mcguire, Barbara O'Kane, J. Graham Sharp

Journal Articles: Genetics, Cell Biology & Anatomy

INTRODUCTION:

Breast cancer grows, metastasizes and relapses from rare, therapy resistant cells with a stem cell phenotype (cancer stem cells/CSCs). However, there is a lack of studies comparing the functions of CSCs isolated using different phenotypes in order to determine if CSCs are homogeneous or heterogeneous.

METHODS:

Cells with various stem cell phenotypes were isolated by sorting from Clone 66 murine breast cancer cells that grow orthotopically in immune intact syngeneic mice. These populations were compared by in vitro functional assays for proliferation, growth, sphere and colony formation; and in vivo limiting dilution analysis of tumorigenesis.

RESULTS:

The proportion of …

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

A Preliminary Report Of Percutaneous Craniofacial Osteoplasty In A Rat Calvarium, William J. Parkes, Md, Jewel Greywoode, Md, Brian J. O'Hara, Md, Ryan N. Heffelfinger, Md, Howard Krein, Md, Phd

Department of Otolaryngology - Head and Neck Surgery Presentations and Grand Rounds

Objective: To evaluate the potential for injectable, permanent bone augmentation by assessing the biocompatibility and bioactivity of subperiosteal hydroxylapatite (Radiesse) deposition in a rat model.

Methods: Fourteen adult Sprague Dawley rats were injected in the parietal skull with hydroxylapatite (n=10) or a carrier gel control (n=4), using a subperiosteal injection technique on the right and a subcutaneous injection technique on the left. At 1, 3, and 6 months, 3 rats (1 negative control, 2 variables) were sacrificed. At 12 months, the remaining 5 rats were sacrificed. After each harvest, the calvaria were examined under both light and polarized microscopy.

Results: …

Micu1 Controls Both The Threshold And Cooperative Activation Of The Mitochondrial Ca(2+) Uniporter., György Csordás, Tünde Golenár, Erin L Seifert, Kimberli J Kamer, Yasemin Sancak, Fabiana Perocchi, Cynthia Moffat, David Weaver, Sergio De La Fuente Perez, Roman Bogorad, Victor Koteliansky, Jeffrey Adijanto, Vamsi K Mootha, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondrial Ca(2+) uptake via the uniporter is central to cell metabolism, signaling, and survival. Recent studies identified MCU as the uniporter's likely pore and MICU1, an EF-hand protein, as its critical regulator. How this complex decodes dynamic cytoplasmic [Ca(2+)] ([Ca(2+)]c) signals, to tune out small [Ca(2+)]c increases yet permit pulse transmission, remains unknown. We report that loss of MICU1 in mouse liver and cultured cells causes mitochondrial Ca(2+) accumulation during small [Ca(2+)]c elevations but an attenuated response to agonist-induced [Ca(2+)]c pulses. The latter reflects loss of positive cooperativity, likely via the EF-hands. MICU1 faces the intermembrane space and responds to …

Microglia And Complement In Alzheimer's Disease With Cerebral Amyloid Angiopathy, Matthew K. Zabel

Loma Linda University Electronic Theses, Dissertations & Projects

Alzheimer’s disease (AD) is the most common form of dementia and completely lacks any viable, long-term therapeutic intervention. This is partly due to an incomplete understanding of AD etiology and the possible confounding factors associated with its genotypic and phenotypic heterogeneity. Cerebral amyloid angiopathy (CAA) is a common, yet frequently overlooked, pathology associated with AD. A pathological hallmark of AD consists of extracellular amyloid-beta (Aβ) deposits, while CAA

manifests with deposition Aβ within the smooth muscle layer of cerebral arteries and arterioles. The role of Aβ in AD and CAA pathophysiology has long been controversial. Although it may have toxic …

Gender Differences In Frontal Plane Lower Extremity Kinetic Variability During Landing, Andrew Nordin

Interdisciplinary Research Scholarship Day

Investigations of human movement variability have been used as a
means of exploring neuromotor functioning, where performance variability is
thought to provide the system with flexibility and a mechanism for adaptation to
movement repetition [1,2,4,6]. Operationally, variability has been considered to
fall within optimal limits (Figure 1), while excessively high or low variability has
been implicated in injury susceptibility [1,2,4,6]. Landing has been explored
due to a high incidence of injury in athletic performance, as well as the ability
to easily control task demands through increases in landing height [3,4].
The purpose of this investigation was to evaluate changes in …

Discovery Of Molecular Associations Among Aging, Stem Cells, And Cancer Based On Gene Expression Profiling., Xiaosheng Wang

Journal Articles: Genetics, Cell Biology & Anatomy

The emergence of a huge volume of "omics" data enables a computational approach to the investigation of the biology of cancer. The cancer informatics approach is a useful supplement to the traditional experimental approach. I reviewed several reports that used a bioinformatics approach to analyze the associations among aging, stem cells, and cancer by microarray gene expression profiling. The high expression of aging- or human embryonic stem cell-related molecules in cancer suggests that certain important mechanisms are commonly underlying aging, stem cells, and cancer. These mechanisms are involved in cell cycle regulation, metabolic process, DNA damage response, apoptosis, p53 signaling …

Serotonergic Innervation And Serotonin Receptor Expression Of Npy-Producing Neurons In The Rat Lateral And Basolateral Amygdaloid Nuclei., M Bonn, A Schmitt, K-P Lesch, E J Van Bockstaele, E Asan

Department of Neuroscience Faculty Papers

Pharmacobehavioral studies in experimental animals, and imaging studies in humans, indicate that serotonergic transmission in the amygdala plays a key role in emotional processing, especially for anxiety-related stimuli. The lateral and basolateral amygdaloid nuclei receive a dense serotonergic innervation in all species studied to date. We investigated interrelations between serotonergic afferents and neuropeptide Y (NPY)-producing neurons, which are a subpopulation of inhibitory interneurons in the rat lateral and basolateral nuclei with particularly strong anxiolytic properties. Dual light microscopic immunolabeling showed numerous appositions of serotonergic afferents on NPY-immunoreactive somata. Using electron microscopy, direct membrane appositions and synaptic contacts between serotonin-containing axon …

Cytoplasmic Localization Of Alteration/Deficiency In Activation 3 (Ada3) Predicts Poor Clinical Outcome In Breast Cancer Patients., Sameer Mirza, Emad A. Rakha, Alaa Alshareeda, Shakur Mohibi, Xiangshan Zhao, Bryan J. Katafiasz, Jun Wang, Channabasavaiah B. Gurumurthy, Aditya Bele, Ian O. Ellis, Andrew R. Green, Hamid Band, Vimla Band

Journal Articles: Genetics, Cell Biology & Anatomy

Transcriptional activation by estrogen receptor (ER) is a key step to breast oncogenesis. Given previous findings that ADA3 is a critical component of HAT complexes that regulate ER function and evidence that overexpression of other ER coactivators such as SRC-3 is associated with clinical outcomes in breast cancer, the current study was designed to assess the potential significance of ADA3 expression/localization in human breast cancer patients. In this study, we analyzed ADA3 expression in breast cancer tissue specimens and assessed the correlation of ADA3 staining with cancer progression and patient outcome. Tissue microarrays prepared from large series of breast cancer …

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

Identification Of Potential Synthetic Lethal Genes To P53 Using A Computational Biology Approach, Xiaosheng Wang, Richard Simon

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND:

Identification of genes that are synthetic lethal to p53 is an important strategy for anticancer therapy as p53 mutations have been reported to occur in more than half of all human cancer cases. Although genome-wide RNAi screening is an effective approach to finding synthetic lethal genes, it is costly and labor-intensive.

METHODS:

To illustrate this approach, we identified potentially druggable genes synthetically lethal for p53 using three microarray datasets for gene expression profiles of the NCI-60 cancer cell lines, one next-generation sequencing (RNA-Seq) dataset from the Cancer Genome Atlas (TCGA) project, and one gene expression data from the Cancer …

Different Mechanisms Of Inflammation Induced In Virus And Autoimmune-Mediated Models Of Multiple Sclerosis In C57bl6 Mice., Abhinoy Kishore, Anurag Kanaujia, Soma Nag, A M Rostami, Lawrence C. Kenyon, Kenneth S Shindler, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system (CNS). Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59) induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE), a mainly CD4(+) T-cell-mediated disease, although CD8(+) T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as …

The Contributions Of Hif-Target Genes To Tumor Growth In Rcc., Ting Zhang, Xiaohua Niu, Lili Liao, Eun-Ah Cho, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Somatic mutations or loss of expression of tumor suppressor VHL happen in the vast majority of clear cell Renal Cell Carcinoma, and it's causal for kidney cancer development. Without VHL, constitutively active transcription factor HIF is strongly oncogenic and is essential for tumor growth. However, the contribution of individual HIF-responsive genes to tumor growth is not well understood. In this study we examined the contribution of important HIF-responsive genes such as VEGF, CCND1, ANGPTL4, EGLN3, ENO2, GLUT1 and IGFBP3 to tumor growth in a xenograft model using immune-compromised nude mice. We found that the suppression of VEGF or CCND1 impaired …

Purpose And Criteria For Blood Smear Scan, Blood Smear Examination, And Blood Smear Review., Gene Gulati, Jinming Song, Alina Dulau Florea, Jerald Gong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A microscopic examination of an appropriately prepared and well-stained blood smear by a knowledgeable laboratory professional is necessary and clinically useful in a number of circumstances and for a variety of reasons. In this article, an attempt is made to delineate the purpose and criteria for blood smear examination in a variety of circumstances that are encountered in everyday laboratory hematology practice. A blood smear scan serves to at least (a) verify the flagged automated hematology results and (b) determine if a manual differential leukocyte count needs to be performed. Blood smear examination/manual differential leukocyte count with complete blood count …