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Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier 2017 University of Arkansas, Fayetteville

Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier

Biological Sciences Undergraduate Honors Theses

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death among women in the United States (1). While treatments involving radiation and chemotherapy currently exist, disease must be detected early in order for the treatments to be somewhat effective, and there is no effective treatment after metastasis occurs (2). Additionally, current therapies do not mitigate tumor immunosuppression. Decreasing the tumor-associated immunosuppressive conditions while activating antitumor immunity could prevent recurrence and metastasis, possibly leading to an effective treatment for cancer (3). Tumor cell vaccines could possibly address this issue and have become a ...


Parp Inhibitor Upregulates Pd-L1 Expression And Enhances Cancer-Associated Immunosuppression, Shiping Jiao 2017 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Parp Inhibitor Upregulates Pd-L1 Expression And Enhances Cancer-Associated Immunosuppression, Shiping Jiao

UT GSBS Dissertations and Theses (Open Access)

With recent approvals for therapeutic antibodies that block CTLA4, PD-1 and PD-L1, immune checkpoints have emerged as new targets in cancer therapy. In addition, there is accumulating evidence highlighting the role of cancer-associated immunity in patient response to cytotoxic anticancer agents. Inhibitors of poly (ADP-ribose) polymerase (PARP) have shown substantial cytotoxic effects against tumors with defects in DNA damage responses. However, whether a crosstalk between PARP inhibition and immune checkpoints exists remains unclear. Here, it has been shown that PARP inhibitors (PARPis) upregulate PD-L1 expression in multiple cancer cell lines, human xenograft tumors, and syngeneic mouse tumors. Mechanistically, PARPi inactivates ...


Choriocarcinoma With Brain, Lung And Vaginal Metastases Successfully Treated Without Brain Radiation Or Intrathecal Chemotherapy: A Case Report, Anja Frost, Jonathan Sherman, M. Katayoon Rezaei, Alivia Aron, Micael Lopez-Acevedo 2017 George Washington University

Choriocarcinoma With Brain, Lung And Vaginal Metastases Successfully Treated Without Brain Radiation Or Intrathecal Chemotherapy: A Case Report, Anja Frost, Jonathan Sherman, M. Katayoon Rezaei, Alivia Aron, Micael Lopez-Acevedo

Neurological Surgery Faculty Publications

Highlights:

  • • There is no consensus on optimal treatment for GTN and brain metastases.
  • • Brain metastasis treated with craniotomy and intravenous, EMA-CO chemotherapy
  • • Intravenous high-dose methotrexate may be adequate to treat brain metastases.


Systematic Analysis Of Whole Exome Sequencing Determines Ret G691s Polymorphism As Germline Variant In Melanoma, Brent J. Smith Jr, Jennifer D. Hintzsche, Carol M. Amato, Aik-Choon Tan, Keith R. Wells, Allison J. Applegate, Rita T. Gonzalez, Jodie R. Barr, William A. Robinson 2017 Marshall University Joan C. Edwards School of Medicine

Systematic Analysis Of Whole Exome Sequencing Determines Ret G691s Polymorphism As Germline Variant In Melanoma, Brent J. Smith Jr, Jennifer D. Hintzsche, Carol M. Amato, Aik-Choon Tan, Keith R. Wells, Allison J. Applegate, Rita T. Gonzalez, Jodie R. Barr, William A. Robinson

Marshall Journal of Medicine

Abstract

The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by glial cell derived neutrotrophic factor (GDNF). Previous studies have found that a single nucleotide polymorphism (SNP), RETp (G691S), in the juxtamembrane domain enhances the signaling pathway and promotes tumor growth by GDNF in pancreatic and thyroid cancer in addition to melanoma. It is uncertain however whether this SNP is a germline variant or somatic mutation. A prior study reported that the RETp variant was a germline SNP in desmoplastic and non-desmoplastic melanomas. In the present study, we examined both melanoma tissue samples and matching peripheral blood DNA ...


Investigating E2f Independent Cell Cycle Control And Tumor Suppression By Prb, Michael J. Thwaites 2017 The University of Western Ontario

Investigating E2f Independent Cell Cycle Control And Tumor Suppression By Prb, Michael J. Thwaites

Electronic Thesis and Dissertation Repository

Cellular division is primarily controlled at the G1 to S-phase transition of the cell cycle by the retinoblastoma tumor-suppressor protein (pRB). The ability of pRB to restrict S-phase entry is primarily attributed to the repression of E2F transcription factors required to upregulate cell cycle target genes necessary for cellular division. Interestingly, while pRB is disrupted in the vast majority of human cancers, mutations typically target upstream regulators of pRB leading to inactivation through hyperphosphorylation. The rarity of direct pRB mutations suggests that the regulation of the cell cycle by pRB may involve additional mechanisms outside of E2F repression, as this ...


Metastasis-Associated Protein 1 Is An Upstream Regulator Of Dnmt3a And Stimulator Of Insulin-Growth Factor Binding Protein-3 In Breast Cancer., S Deivendran, Hezlin Marzook, T R Santhoshkumar, Rakesh Kumar, M Radhakrishna Pillai 2017 George Washington University

Metastasis-Associated Protein 1 Is An Upstream Regulator Of Dnmt3a And Stimulator Of Insulin-Growth Factor Binding Protein-3 In Breast Cancer., S Deivendran, Hezlin Marzook, T R Santhoshkumar, Rakesh Kumar, M Radhakrishna Pillai

Biochemistry and Molecular Medicine Faculty Publications

Despite a recognized role of DNA methyltransferase 3a (DNMT3a) in human cancer, the nature of its upstream regulator(s) and relationship with the master chromatin remodeling factor MTA1, continues to be poorly understood. Here, we found an inverse relationship between the levels of MTA1 and DNMT3a in human cancer and that high levels of MTA1 in combination of low DNMT3a status correlates well with poor survival of breast cancer patients. We discovered that MTA1 represses DNMT3a expression via HDAC1/YY1 transcription factor complex. Because IGFBP3 is an established target of DNMT3a, we investigated the effect of MTA1 upon IGFBP3 expression ...


Breast Lesions Detected Via Breast Specific Gamma Imaging: Descriptor Characteristics And Positive Predictive Value, Jason Ching, Rachel Brem 2017 George Washington University

Breast Lesions Detected Via Breast Specific Gamma Imaging: Descriptor Characteristics And Positive Predictive Value, Jason Ching, Rachel Brem

GW Research Days 2016 - Present

Background:

Breast Specific Gamma Imaging (BSGI) is increasingly being used as a diagnostic tool for the detection of breast cancer, using technetium 99m sestamibi to identify physiological differences between cancerous and normal breast tissue. Our study retrospectively evaluates pathologic correlates to positive BSGI findings in the detection of breast cancer.

Methods:

A retrospective review was performed of patients with positive BSGI examinations (200 total) during a 1-year period. Using biopsy/surgical pathology or 2 years mammography/ultrasound/MRI follow-up as correlation, we determined the positive predictive values of BSGI findings when categorized by: (i) character of suspicious region [mass, non-mass ...


Mutations In Braf Are Associated With Higher Levels Of Immune Infiltrates In Microsatellite-Stable Colon Cancer, Jake Rubin, Eduard Porta Parto 2017 George Washington University

Mutations In Braf Are Associated With Higher Levels Of Immune Infiltrates In Microsatellite-Stable Colon Cancer, Jake Rubin, Eduard Porta Parto

GW Research Days 2016 - Present

While BRAF is among the most well-established oncogenes in human cancers, more recently it has garnered attention for its role in suppressing antitumor immunity, especially in melanoma. Because tumor-infiltrating lymphocyte (TIL) density is strongly prognostic in colorectal cancer (CRC)7, we decided to investigate the connection between TIL density and the BRAF-activating V600E mutation in CRC.

We used ESTIMATE to quantify immune infiltrate in samples from the TCGA colon adenocarcinoma (COAD) dataset (n = 216). This is an algorithm that uses the gene-expression signature of 141 immune-related genes to infer the presence of immune cells in the tumor infiltrate. COAD samples ...


The Role Of Estradiol Metabolism In Urogenital Schistosomiasis-Induced Bladder Cancer, Nuno Vale, Maria Gouveia, Gabriel Rinaldi, Julio Santos, Lucio Lara Santos, Paul J. Brindley, Jose Correia da Costa 2017 George Washington University

The Role Of Estradiol Metabolism In Urogenital Schistosomiasis-Induced Bladder Cancer, Nuno Vale, Maria Gouveia, Gabriel Rinaldi, Julio Santos, Lucio Lara Santos, Paul J. Brindley, Jose Correia Da Costa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Urogenital schistosomiasis is a neglected tropical disease that can lead to bladder cancer. How urogenital schistosomiasis induces carcinogenesis remains unclear, although there is evidence that the human blood fluke Schistosoma haematobium, the infectious agent of urogenital schistosomiasis, releases estradiol-like metabolites. These kind of compounds have been implicated in other cancers. Aiming for enhanced understanding of the pathogenesis of the urogenital schistosomiasisinduced bladder cancer, here we review, interpret, and discuss findings of estradiol-like metabolites detected in both the parasite and in the human urine during urogenital schistosomiasis. Moreover, we predict pathways and enzymes that are involved in the production of these ...


Principles Of Radiation Oncology, Richard S. Pieters, Linda Ding, Harry Bushe, Jesse N. Aronowitz 2017 University of Massachusetts Medical School

Principles Of Radiation Oncology, Richard S. Pieters, Linda Ding, Harry Bushe, Jesse N. Aronowitz

Cancer Concepts: A Guidebook for the Non-Oncologist

This chapter in Cancer Concepts: a Guidebook for the Non-Oncologist describes the principles of Radiation Oncology. Radiation Oncology utilizes ionizing radiation to treat cancer (and occasionally a few benign conditions). Radiotherapy or radiation therapy (RT) was initially developed in conjunction with diagnostic radiology, but has evolved into a separate specialty. Currently, more than fifty percent of cancer patients undergo RT at some point during the course of their cancer. Most receive treatment with curative intent (radical therapy); however, patients with incurable disease receive shorter, gentler courses of therapy to relieve cancer-induced symptoms.


Ipsilateral Lower Limb Weakness After Sarcoma Treatment: A Case Report, Jennifer Baima, Amanda Doodlesack, Jennifer LaFemina 2017 University of Massachusetts Medical School

Ipsilateral Lower Limb Weakness After Sarcoma Treatment: A Case Report, Jennifer Baima, Amanda Doodlesack, Jennifer Lafemina

Orthopedics and Physical Rehabilitation Publications and Presentations

Case Diagnosis: Our patient experienced worsening left foot neuropathy following chemotherapy and radiation treatment for sarcoma.

Case Description: A 24-year-old man underwent local resection of a 12cm x 8cm x 14.5cm rhabdomyosarcoma in the left vastus lateralis. Then, he was treated with vincristine for 40 weeks and radiation to the left lateral thigh with a maximum dose of 50.4 Gy. The sciatic nerve was outside the target area and received a lower dose. While undergoing chemotherapy, the patient experienced bilateral dysesthesias in his fingertips and feet. He had no history of neuropathy prior to treatment. After chemotherapy was ...


Metastatic Melanoma To The Bladder: Case Report And Review Of The Literature., Rohit V. Patil, Solomon L Woldu, Elena Lucas, Andrew M Quinn, Franto Francis, Vitaly Margulis 2017 George Washington University

Metastatic Melanoma To The Bladder: Case Report And Review Of The Literature., Rohit V. Patil, Solomon L Woldu, Elena Lucas, Andrew M Quinn, Franto Francis, Vitaly Margulis

Urology Faculty Publications

A 49-year-old Caucasian woman presented to the dermatology clinic for follow-up of malignant melanoma with a complaint of painless gross hematuria. Two years prior she was diagnosed with malignant melanoma from a skin lesion on her left flank treated with wide excision, negative axillary sentinel lymph node biopsy, and adjuvant radiotherapy. Subsequently, she had no evidence of disease until urologic evaluation of her hematuria revealed two lesions in her bladder and cytopathology demonstrated findings consistent with malignant melanoma. We review literature on melanoma metastatic to the bladder and discuss the potential role of metastasectomy and other treatment strategies in such ...


Cold Atmospheric Plasma, A Novel Promising Anti-Cancer Treatment Modality., Dayun Yan, Jonathan H Sherman, Michael Keidar 2017 George Washington University

Cold Atmospheric Plasma, A Novel Promising Anti-Cancer Treatment Modality., Dayun Yan, Jonathan H Sherman, Michael Keidar

Neurological Surgery Faculty Publications

Over the past decade, cold atmospheric plasma (CAP), a near room temperature ionized gas has shown its promising application in cancer therapy. Two CAP devices, namely dielectric barrier discharge and plasma jet, show significantly anti-cancer capacity over dozens of cancer cell lines in vitro and several subcutaneous xenograft tumors in vivo. In contrast to conventional anti-cancer approaches and drugs, CAP is a selective anti-cancer treatment modality. Thus far establishing the chemical and molecular mechanism of the anti-cancer capacity of CAP is far from complete. In this review, we provide a comprehensive introduction of the basics of CAP, state of the ...


Group Medical Visits To Provide Gynecologic Care For Women Affected By Breast Cancer, Sally R. Greenwald, Sarah Watson, Mindy Goldman, Tami S. Rowen 2017 University of California, San Francisco

Group Medical Visits To Provide Gynecologic Care For Women Affected By Breast Cancer, Sally R. Greenwald, Sarah Watson, Mindy Goldman, Tami S. Rowen

Journal of Patient-Centered Research and Reviews

Purpose

Women with breast cancer have complex and unique gynecologic needs that are challenging to effectively and comprehensively meet in a traditional gynecology visit format. Group medical visits are an effective and well-received model of care in other disease settings and can provide comprehensive health education as an adjunct to one-on-one evaluation and treatment. There are limited data regarding the use of this type of health care delivery in providing gynecology-focused care to women affected by breast cancer.

Methods

A group medical visit model was created for gynecology providers to see new breast cancer patient consults. From May 2012 to ...


Hic1 (Hypermethylated In Cancer 1) Sumoylation Is Dispensable For Dna Repair But Is Essential For The Apoptotic Dna Damage Response (Ddr) To Irreparable Dna Double-Strand Breaks (Dsbs)., Sonia Paget, Marion Dubuissez, Vanessa Dehennaut, Joe Nassour, Brennan T Harmon, Nathalie Spruyt, Ingrid Loison, Corinne Abbadie, Brian R Rood, Dominique Leprince 2017 George Washington University

Hic1 (Hypermethylated In Cancer 1) Sumoylation Is Dispensable For Dna Repair But Is Essential For The Apoptotic Dna Damage Response (Ddr) To Irreparable Dna Double-Strand Breaks (Dsbs)., Sonia Paget, Marion Dubuissez, Vanessa Dehennaut, Joe Nassour, Brennan T Harmon, Nathalie Spruyt, Ingrid Loison, Corinne Abbadie, Brian R Rood, Dominique Leprince

Surgery Faculty Publications

The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) encodes a transcriptional repressor mediating the p53-dependent apoptotic response to irreparable DNA double-strand breaks (DSBs) through direct transcriptional repression of SIRT1. HIC1 is also essential for DSB repair as silencing of endogenous HIC1 in BJ-hTERT fibroblasts significantly delays DNA repair in functional Comet assays. HIC1 SUMOylation favours its interaction with MTA1, a component of NuRD complexes. In contrast with irreparable DSBs induced by 16-hours of etoposide treatment, we show that repairable DSBs induced by 1 h etoposide treatment do not increase HIC1 SUMOylation or its interaction with MTA1. Furthermore, HIC1 SUMOylation ...


Vamorolone, A Dissociative Steroidal Compound, Reduces Pro-Inflammatory Cytokine Expression In Glioma Cells And Increases Activity And Survival In A Murine Model Of Cortical Tumor., Elizabeth Wells, Madhuri Kambhampati, Jesse M Damsker, Heather Gordish-Dressman, Sridevi Yadavilli, Oren J Becher, Jamila Gittens, Mojca Stampar, Roger J. Packer, Javad Nazarian 2016 George Washington University

Vamorolone, A Dissociative Steroidal Compound, Reduces Pro-Inflammatory Cytokine Expression In Glioma Cells And Increases Activity And Survival In A Murine Model Of Cortical Tumor., Elizabeth Wells, Madhuri Kambhampati, Jesse M Damsker, Heather Gordish-Dressman, Sridevi Yadavilli, Oren J Becher, Jamila Gittens, Mojca Stampar, Roger J. Packer, Javad Nazarian

Integrative Systems Biology Faculty Publications

Corticosteroids, such as dexamethasone, are routinely used as palliative care in neuro-oncology for their anti-inflammatory benefits, however many patients experience dose limiting side effects caused by glucocorticoid response element (GRE)-mediated transcription. The purpose of this study was to use a murine model to investigate a new steroid alternative, vamorolone, which promises to reduce side effects through dissociating GRE-mediated transcription and NF-κB -mediated anti-inflammatory actions. To compare vamorolone to dexamethasone in reducing pro-inflammatory signals in vitro, murine glioma cells were treated with dexamethasone, vamorolone or vehicle control. Changes in mRNA expression were assessed using the nanostring inflammatory platform. Furthermore, drug ...


Is Current Evidence That Avoidance Of Inhalation Agents And Opioids May Decrease Metastasis Strong Enough For Crnas To Show A Willingness To Change Practice?, Michael Wesley Tillman 2016 University of Southern Mississippi

Is Current Evidence That Avoidance Of Inhalation Agents And Opioids May Decrease Metastasis Strong Enough For Crnas To Show A Willingness To Change Practice?, Michael Wesley Tillman

Doctoral Nursing Capstone Projects

Metastasis following the surgical resection of primary site breast cancer is a medical issue, which plagues mastectomy patients. The intention of this project was to synthesize current literature in order to make a presentation and disseminate it to Certified Registered Nurse Anesthetists (CRNAs) in southern Mississippi and assess the providers' willingness to change practice. CRNAs took part in a Qualtrics survey after viewing a PowerPoint presentation of evidence regarding anesthesia and metastasis. The presentation illustrated the anesthetic techniques and pharmacological agents utilized, which either mitigate or potentiate a patient's risk for metastasis. The survey assessed for a willingness to ...


Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang 2016 The University of Texas Md Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang

UT GSBS Dissertations and Theses (Open Access)

Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interplay between metastatic tumor cells and extrinsic signals at individual metastatic organ sites critically impacts the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumor cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that primary tumor cells with normal expression of PTEN, an important ...


Establishing A Clinically Relevant Mouse Model Of Human Aml To Test Novel Transmethylation Inhibitors., Aditya Barve 2016 University of Louisville

Establishing A Clinically Relevant Mouse Model Of Human Aml To Test Novel Transmethylation Inhibitors., Aditya Barve

Electronic Theses and Dissertations

Acute myeloid leukemia (AML) is a highly heterogeneous clonal disorder characterized by an accumulation of malignant immature myeloid progenitors in the bone marrow (BM) that hinder normal hematopoiesis. Patient AML exhibits a dramatic heterogeneity in terms of cytogenetics, disease morphology, and associated prognoses and/or chemotherapeutic sensitivity. Thus it becomes clearly evident that the investigation of novel therapeutics for AML will require model systems that are capable of recapitulating this stark heterogeneity in a patient specific manner. Furthermore, it is now understood that the surrounding bone marrow (BM) microenvironment and supporting cells play a critical role in leukemic progression as ...


Braf And Epithelial-Mesenchymal Transition In Papillary Thyroid Carcinoma - Challenging The Roles Of Snail And E-Cadherin, Brendon Mitchell, Dominick Leone, Shi Yang, Ashraf Khan, Meera Mahalingam, Jagdish Dhingra 2016 University of Florida

Braf And Epithelial-Mesenchymal Transition In Papillary Thyroid Carcinoma - Challenging The Roles Of Snail And E-Cadherin, Brendon Mitchell, Dominick Leone, Shi Yang, Ashraf Khan, Meera Mahalingam, Jagdish Dhingra

Open Access Articles

OBJECTIVE: In papillary thyroid carcinoma (PTC), while the role of BRAF is well established, the contribution of BRAF to epithelial-mesenchymal transition is not.

STUDY DESIGN/SETTING: To elucidate the relationship between BRAF, surrogates of epithelial-mesenchymal transition (Snail, E-cadherin) and established histopathologic prognosticators in papillary thyroid carcinoma.

SUBJECTS/METHODS: In this IRB approved cross-sectional study, 50 cases of archived annotated PTC samples were retrieved and immunohistochemically stained for Snail and E-cadherin protein. A semi-quantitative scoring system (incorporating proportion and intensity) was utilized.

RESULTS: Snail and E-cadherin expression were noted in 44% and 84% of BRAF mutant and, in 29% and 95 ...


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