Medicine and Health Sciences Commons^™

Il-24 Promotes Apoptosis Through Camp-Dependent Pka Pathways In Human Breast Cancer Cells, Leah Persaud, Jason Mighty, Xuelin Zhong, Ashleigh Francis, Marifer Mendez, Hilal Muharam, Stephen M. Redenti, Dibash Das, Bertal Huseyin Aktas, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is a tumor-suppressing protein, which inhibits angiogenesis and induces cancer cell-specific apoptosis. We have shown that IL-24 regulates apoptosis through phosphorylated eukaryotic initiation factor 2 alpha (eIF2α) during endoplasmic reticulum (ER) stress in cancer. Although multiple stresses converge on eIF2α phosphorylation, the cellular outcome is not always the same. In particular, ER stress-induced apoptosis is primarily regulated through the extent of eIF2α phosphorylation and activating transcription factor 4 (ATF4) action. Our studies show for the first time that cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) activation is required for IL-24-induced cell death in a variety of …

Dual Inhibition Of Bcl-2/Bcl-Xl And Xpo1 Is Synthetically Lethal In Glioblastoma Model Systems, Enyuan Shang, Yiru Zhang, Chang Shu, Chiaki Tsuge Ishida, Elena Bianchetti, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

XPO1 has recently emerged as a viable treatment target for solid malignancies, including glioblastoma (GBM), the most common primary malignant brain tumor in adults. However, given that tumors become commonly resistant to single treatments, the identification of combination therapies is critical. Therefore, we tested the hypothesis that inhibition of anti-apoptotic Bcl-2 family members and XPO1 are synthetically lethal. To this purpose, two clinically validated drug compounds, the BH3-mimetic, ABT263, and the XPO1 inhibitor, Selinexor, were used in preclinical GBM model systems. Our results show that inhibition of XPO1 reduces cellular viability in glioblastoma cell cultures. Moreover, addition of ABT263 significantly …

Oxytocin And Cancer: An Emerging Link, Ben Lerman, Trisheena Harricharran, Olorunseun O. Ogunwobi

Publications and Research

The neuropeptide hormone oxytocin, which is released from the posterior pituitary gland, is involved in a number of physiological processes. Understanding of its effects is gradually increasing due to new research in this area. While mostly recognized as a reproductive system hormone, oxytocin also regulates other organ systems such as the brain and cardiovascular system. Recently, research has focused on unraveling its involvement in cancer, and emerging evidence suggests a potential role for oxytocin as a cancer biomarker. This review summarizes observations linking oxytocin and cancer, with a special emphasis on prostate cancer, where it may promote cell proliferation. Research …

Leveraging Pet To Image Folate Receptor Α Therapy Of An Antibody-Drug Conjugate, Christian Brand, Ahmad Sadique, Jacob L. Houghton, Kishore Gangagari, Jose F. Ponte, Jason S. Lewis, Naga Vara Kishore Pillarsetty, Joseph A. Konner, Thomas Reiner

Publications and Research

Background: The folate receptor α (FRα)-targeting antibody-drug conjugate (ADC), IMGN853, shows great antitumor activity against FRα-expressing tumors in vivo, but patient selection and consequently therapy outcome are based on immunohistochemistry. The aim of this study is to develop an antibody-derived immuno-PET imaging agent strategy for targeting FRα in ovarian cancer as a predictor of treatment success. Methods: We developed [89Zr]Zr-DFO-M9346A, a humanized antibody-based radiotracer targeting tumorassociated FRα in the preclinical setting. [89Zr]Zr-DFO-M9346A’s binding ability was tested in an in vitro uptake assay using cell lines with varying FRα expression levels. The diagnostic potential of [89Zr]Zr-M9346A was evaluated in KB and …

Consensus On Molecular Subtypes Of High-Grade Serous Ovarian Carcinoma, Gregory M. Chen, Lavanya Kannan, Ludwig Geistlinger, Victor Kofia, Zhaleh Safikhani, Deena Ma Gendoo, Giovanni Parmigiani, Michael Birrar, Benjamin Haibe-Kains, Levi Waldron

Publications and Research

Purpose: The majority of ovarian carcinomas are of high-grade serous histology, which is associated with poor prognosis. Surgery and chemotherapy are the mainstay of treatment, and molecular characterization is necessary to lead the way to targeted therapeutic options. To this end, various computational methods for gene expression-based subtyping of high-grade serous ovarian carcinoma (HGSOC) have been proposed, but their overlap and robustness remain unknown.

Experimental Design: We assess three major subtype classifiers by meta-analysis of publicly available expression data, and assess statistical criteria of subtype robustness and classifier concordance. We develop a consensus classifier that represents the subtype classifications of …

Identifying An Early Treatment Window For Predicting Breast Cancer Response To Neoadjuvant Chemotherapy Using Immunohistopathology And Hemoglobin Parameters, Quing Zhu, Susan Tannenbaum, Scott H. Kurtzman, Patricia Defusco, Andrew Ricci Jr., Hamed Vavadi, Feifei Zhou, Chen Xu, Alex Merkulov, Poornima Hegde, Mark Kane, Liqun Wang, Kert Sabbath

Publications and Research

Background

Breast cancer pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) varies with tumor subtype. The purpose of this study was to identify an early treatment window for predicting pCR based on tumor subtype, pretreatment total hemoglobin (tHb) level, and early changes in tHb following NAC.

Methods

Twenty-two patients (mean age 56 years, range 34–74 years) were assessed using a near-infrared imager coupled with an Ultrasound system prior to treatment, 7 days after the first treatment, at the end of each of the first three cycles, and before their definitive surgery. Pathologic responses were dichotomized by the Miller-Payne system. Tumor …

Antioxidants And Cancer: Theories, Techniques, And Trials In Preventing Cancer, Gloria M. Calaf, Francisco Aguayo, Consolato M. Sergi, Angeles Juarranz, Debasish Roy

Publications and Research

No abstract provided.

Translation Control By P53, Justina Kasteri, Dibash K. Das, Xuelin Zhong, Leah Persaud, Ashleigh Francis, Hilal Muharam, Moira Sauane

Publications and Research

The translation of mRNAs plays a critical role in the regulation of gene expression and therefore, in the regulation of cell proliferation, differentiation and apoptosis. Unrestricted initiation of translation causes malignant transformation and plays a key role in the maintenance and progression of cancers. Translation initiation is regulated by the ternary complex and the eukaryotic initiation factor 4F (eIF4F) complex. The p53 tumor suppressor protein is the most well studied mammalian transcription factor that mediates a variety of anti-proliferative processes. Post-transcriptional mechanisms of gene expression in general and those of translation in particular play a major role in shaping the …

Resveratrol And Pterostilbene Exhibit Anticancer Properties Involving The Downregulation Of Hpv Oncoprotein E6 In Cervical Cancer Cells, Kaushiki Chatterjee, Dina Alsharif, Christina Mazza, Palwasha Syar, Mohamed Al Sharif, Jimmie E. Fata

Publications and Research

Cervical cancer is one of the most common cancers in women living in developing countries. Due to a lack of affordable effective therapy, research into alternative anticancer compounds with low toxicity such as dietary polyphenols has continued. Our aim is to determine whether two structurally similar plant polyphenols, resveratrol and pterostilbene, exhibit anticancer and anti-HPV (Human papillomavirus) activity against cervical cancer cells. To determine anticancer activity, extensive in vitro analyses were performed. Anti-HPV activity, through measuring E6 protein levels, subsequent downstream p53 effects, and caspase-3 activation, were studied to understand a possible mechanism of action. Both polyphenols are effective agents …

Liposomal Tricurin, A Synergistic Combination Of Curcumin, Epicatechin Gallate And Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, And Eliminates Glioblastoma (Gbm) And Gbm Stem Cells, Sumit Mukherjee, Juliet N. E. Baidoo, Samay Sampat, Andrew Manusco, Lovena David, Leah S. Cohen, Shuiqin Zhou, Probal Banerjee

Publications and Research

Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12–15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (M): 32:8:100 (termed 32 M+ TriCurin). We have now prepared liposomal TriCurin (TrLp) and demonstrated …

Peptide Density Targets And Impedes Triple Negative Breast Cancer Metastasis, Daxing Liu, Peng Guo, Craig Mccarthy, Biran Wang, Yu Tao, Debra Auguste

Publications and Research

The C-X-C chemokine receptor type 4 (CXCR4, CD184) pathway is a key regulator of cancer metastasis. Existing therapeutics that block CXCR4 signaling are dependent on single molecule-receptor interactions or silencing CXCR4 expression. CXCR4 localizes in lipid rafts and forms dimers therefore CXCR4 targeting and signaling may depend on ligand density. Herein, we report liposomes presenting a CXCR4 binding peptide (DV1) as a threedimensional molecular array, ranging from 9k to 74k molecules μm−2, target triple negative breast cancer (TNBC). TNBC cells exhibit a maxima in binding and uptake of DV1functionalized liposomes (L-DV1) in vitro at a specific density, which yields a …

Readability Of Prostate Cancer Information Online: A Cross-Sectional Study, Corey H. Basch, Danna Ethan, Sarah A. Maclean, Joseph Fera, Phillip Garcia, Charles E. Basch

Publications and Research

Reading and understanding health information, both components of health literacy, can influence patient decisions related to disease management. Older adults, the population of males at greatest risk for prostate cancer, may have compromised capacity to understand and use health information. The purpose of this study was to determine the readability of prostate cancer materials on the Internet using five recommended readability tests. Using a cleared Internet browser, a search was conducted for “prostate cancer.” The URLs of the first 100 websites in English were recorded to create the sample. The readability scores for each website were determined using an online, …