Medicine and Health Sciences Commons^™

Perilymphatic Irx-2 Cytokine Therapy To Enhance Tumor Infiltrating Lymphocytes And Pd-L1 Expression Preceding Curative-Intent Therapy In Early Stage Breast Cancer, Joanna Pucilowska, Venkatesh Rajamanickam, Katherine Sanchez, Valerie Conrad, Alison Conlin, Shagheyegh Aliabadi-Wahle, Shu-Ching Chang, Gary Grunkemeier, Nikki Moxon, Staci Mellinger, Maritza Martel, James Egan, Monil Shah, David B Page

Books, Presentations, Posters, Etc.

Background: Cytokines are being explored as a therapeutic strategy to modulate the tumor microenvironment and facilitate immunotherapy benefit in breast cancer. Here, we investigate a locoregional therapeutic approach whereby cytokines (IRX-2) are administered into the subcutaneous peri-areolar tissue (in an anatomic distribution similar to sentinel lymph node mapping) to facilitate immune cell recruitment/activation within the draining lymph nodes and tumor in ESBC. IRX-2 is derived from ex vivo phytohemagglutinin-stimulated lymphocytes and contains multiple cytokines including IL-1β, IL-2, TNF-α, IFN-γ, IL-6, IL-8, and GM-CSF, with stable concentrations from lot to lot. Preclinically, IRX-2 activates T-cells and natural killer (NK) cells, facilitates …

Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi

Molecular and Cellular Biochemistry Faculty Publications

BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or …

The Impact Of Mental Health On Cancer Preventative Screenings, Chelsea Edirisuriya, Amy Leader, Phd

Phase 1

Among the mental health population of the United States, overall preventative health services, such as cancer screening rates, are remarkably low. Additionally, there is a significant 30% higher mortality rate due to cancer in psychiatric patients. This project established if there are disparities in cancer screening rates between the general population and the mental health population of Southeastern Pennsylvania. The project analyzed and compared the differences in cancer screenings for colorectal, breast, and cervical cancer among those currently diagnosed with a mental condition and the general population. Through p-value and Pearson chi-square statistical analysis of the Community Health Data Base …

Tumor Infiltrating Lymphocyte Recruitment After Peri-Lymphatic Irx-2 Cytokine Immunotherapy In Resectable Breast Cancer And Head And Neck Carcinoma, Joanna Pucilowska, Venkatesh Rajamanickam, Nikki Moxon, Monil Shah, Maritza Martel, Alison Conlin, James E. Egan, David B. Page

Society for Immunotherapy of Cancer 2018 Annual Meeting Posters

Background: The IRX-2 biologic is a subcutaneous injectable immunotherapy composed of IL-2 and other cytokines derived from stimulated lymphocytes. Preclinically, IRX-2 activates T cells, natural killer cells, macrophages, and dendritic cells, and facilitates maturation of antigen-presenting cells.Tumor-infiltrating lymphocytes (TILs) are associated with improved outcomes in many cancers including early stage breast cancer (ESBC) and head and neck squamous cell carcinoma (HNSCC). We report data on TIL recruitment associated with pre-operative IRX-2 in a phase Ib ESBC trial, as well as phase Ib and IIa HNSCC trials.

Methods: The pre-operative IRX-2 regimen was evaluated in both ESBC and HNSCC trials for …

Epidemiology Of Moderate Alcohol Consumption And Breast Cancer: Association Or Causation?, Samir Zakhari, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Epidemiological studies have been used to show associations between modifiable lifestyle habits and the incidence of breast cancer. Among such factors, a history of alcohol use has been reported in multiple studies and meta-analyses over the past decades. However, associative epidemiological studies that were interpreted as evidence that even moderate alcohol consumption increases breast cancer incidence have been controversial. In this review, we consider the literature on the relationship between moderate or heavy alcohol use, both in possible biological mechanisms and in variations in susceptibility due to genetic or epigenetic factors. We argue that there is a need to incorporate …

Study Of Alpha Mangostin As A Chemoprotective Agent For Breast Cancer Via Activation Of The P53 Pathway, Vanessa Van Oost

Pence-Boyce STEM Student Scholarship

Breast carcinoma is the most frequently diagnosed cancer among women and causes over 400,000 deaths yearly worldwide. Current treatments such as chemotherapy are not selective for cancerous tissues but are destructive to normal tissues as well. This causes a range of side effects including pain, nausea, hair loss, weakness, and more. Inactivation of p53 is an almost universal mutation within human cancer cells. The ability to activate the p53 pathway which protects cells from tumor formation is lost in 50% of cancers. Due to the prevalence of this mutation, p53 is a uniquely valuable target for applied research. Alpha mangostin …

Symptom Clusters And Quality Of Life Trajectories In Breast Cancer Patients Before And After Chemotherapy, Gaurav Kumar

Capstone Experience

Context. Breast cancer patients experience multiple concurrent symptoms before and after chemotherapy (CTX). Physical and psychological symptoms may persist after treatment and reduce the quality of life (QOL) of survivors.

Objectives. Identify differences in prevalence and severity of symptoms at three times within 1- year of starting CTX; and identify symptom cluster and QOL trajectories over these times in breast cancer patients.

Methods. Symptoms were identified in breast cancer patients (N=219) before the start of CTX (baseline), 30 days after the last CTX, and 1-year after the first CTX. Hospital Anxiety and Depression Scale and Symptom Experience Scale …

Oncoplastic Surgery: Is It Time To Change? From Innovation To Adoption Using Mentorship Program, Eman Khayat

Electronic Thesis and Dissertation Repository

Oncoplastic surgery is considered the standard of care for breast cancer therapy in numerous Western World countries, particularly in Europe. Despite the advancement of knowledge, Canada still lags in adoption of oncoplasty into the standard surgical practice. In our study, a mentorship program was used to introduce oncoplastic surgery to practicing breast surgeons at LHSC. The change in perception and adoption of oncoplastic surgery were evaluated using semi-structured interviews, before and after the intervention, by qualitative thematic analysis method. Mentorship program was validated as a superior method of learning new surgical techniques by practicing surgeons, demonstrating acceptance of different levels …

Loss Of Inter-Cellular Cooperation By Complete Epithelial-Mesenchymal Transition Supports Favorable Outcomes In Basal Breast Cancer Patients., Anne Grosse-Wilde, Rolf E Kuestner, Stephanie M Skelton, Ellie Macintosh, Aymeric Fouquier D'Hérouël, Gökhan Ertaylan, Antonio Del Sol, Alexander Skupin, Sui Huang

Articles, Abstracts, and Reports

According to the sequential metastasis model, aggressive mesenchymal (M) metastasis-initiating cells (MICs) are generated by an epithelial-mesenchymal transition (EMT) which eventually is reversed by a mesenchymal-epithelial transition (MET) and outgrowth of life-threatening epithelial (E) macrometastases. Paradoxically, in breast cancer M signatures are linked with more favorable outcomes than E signatures, and M cells are often dispensable for metastasis in mouse models. Here we present evidence at the cellular and patient level for the cooperation metastasis model, according to which E cells are MICs, while M cells merely support E cell persistence through cooperation. We tracked the fates of co-cultured E …

Experiences Of The Breast Cancer Patients Undergoing Radiotherapy At A Public Hospital Peshawar Pakistan, Gulzar Habibullah, Raisa Raisa, Shanaz Hussein Cassum, Rehana Elahi

School of Nursing & Midwifery

Objective: This study aimed to explore the experiences of female breast cancer patients undergoing radiotherapy (RT) in a public hospital in Peshawar, Pakistan.
Methods: This study employed a descriptive exploratory method. A purposive sample of 14 breast cancer women undergoing RT was selected for this study. Data were collected over the period of 5 months, using a semi-structured interview guide and conducting in-depth face-to-face interviews. These interviews were audio taped and transcribed by a bilingual transcriber. The translated version of the interview was coded, and the analysis was done manually.
Results: Four main categories emerged from data analysis, which were: …

Depression And Breast Cancer; Postoperative Short-Term Implications, Razvan V. Scaunasu, Ștefan Voiculescu, Bogdan Popescu, Roxana Popa, Denisa Bălălău, Laura Răducu, Cristina N. Cozma, Cristian R. Jecan

Journal of Mind and Medical Sciences

Introduction. Pre and postoperative psychological status is an important aspect in patients diagnosed with breast cancer, having a great impact on their quality of life. Considering the high incidence, mortality rate, and the added effect on self-image, breast cancer is considered a major stressor for women worldwide, almost 50% of these experiencing psychological distress. Methods. Our study retrospectively analysed the relationship between preoperative diagnosed depression and the number of medical care days, on patients diagnosed with breast cancer and admitted for surgical treatment in Colțea Clinical Hospital between 2017 and 2018. Results. We had 62 patients scheduled for breast cancer …

Cyclin D1-Mediated Microrna Expression Signature Predicts Breast Cancer Outcome, Guangxue Wang, Michael Gormley, Jing Qiao, Qian Zhao, Min Wang, Gabriele Disante, Shengqiong Deng, Lin Dong, Timothy G. Pestell, Xiaoming Ju, Mathew C. Casimiro, Sankar Addya, Adam Ertel, Ayden Tozeren, Qinchuan Li, Zuoren Yu, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Background: Genetic classification of breast cancer based on the coding mRNA suggests the evolution of distinct subtypes. Whether the non-coding genome is altered concordantly with the coding genome and the mechanism by which the cell cycle directly controls the non-coding genome is poorly understood.

Methods: Herein, the miRNA signature maintained by endogenous cyclin D1 in human breast cancer cells was defined. In order to determine the clinical significance of the cyclin D1-mediated miRNA signature, we defined a miRNA expression superset from 459 breast cancer samples. We compared the coding and non-coding genome of breast cancer subtypes.

Results: Hierarchical clustering of …

A Plasma Telomeric Cell-Free Dna Level In Unaffected Women With Brca1 Or/And Brca2 Mutations: A Pilot Study, Shatovisha Dey, Natascia Marino, Kanokwan Bishop, Paige N. Dahlgren, Aditi Shendre, Anna Maria Storniolo, Chunyan He, Hiromi Tanaka

Internal Medicine Faculty Publications

Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 mutation with age-matched controls …

Tumor Mutational Burden Is A Determinant Of Immune-Mediated Survival In Breast Cancer., Alexandra Thomas, Eric D Routh, Ashok Pullikuth, Guangxu Jin, Jing Su, Jeff W Chou, Katherine A Hoadley, Cristin Print, Nick Knowlton, Michael A Black, Sandra Demaria, Ena Wang, Davide Bedognetti, Wendell D Jones, Gaurav A Mehta, Michael L Gatza, Charles M Perou, David B Page, Pierre Triozzi, Lance D Miller

Articles, Abstracts, and Reports

Mounting evidence supports a role for the immune system in breast cancer outcomes. The ability to distinguish highly immunogenic tumors susceptible to anti-tumor immunity from weakly immunogenic or inherently immune-resistant tumors would guide development of therapeutic strategies in breast cancer. Genomic, transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) breast cancer cohorts were used to examine statistical associations between tumor mutational burden (TMB) and the survival of patients whose tumors were assigned to previously-described prognostic immune subclasses reflecting favorable, weak or poor immune-infiltrate dispositions (FID, WID or PID, respectively). …

Mir-29c Plays A Suppressive Role In Breast Cancer By Targeting The Timp3/Stat1/Foxo1 Pathway., Wan Li, Jie Yi, Xiangjin Zheng, Shiwei Liu, Weiqi Fu, Liwen Ren, Li Li, Dave S B Hoon, Jinhua Wang, Guanhua Du

Articles, Abstracts, and Reports

Background: miR-29c has been associated with the progression of many cancers. However, the function and mechanism of miR-29c have not been well investigated in breast cancers.

Methods: Real-time quantitative PCR was used to assess expression of miR-29c and DNMT3B mRNA. Western blot and immunochemistry were used to examine the expression of DNA methyltransferase 3B (DNMT3B) protein in breast cancer cells and tissues. The functional roles of miR-29c in breast cancer cells such as proliferation, migration, invasion, colony formation, and 3D growth were evaluated using MTT, transwell chambers, soft agar, and 3D Matrigel culture, respectively. In addition, the luciferase reporter assay …