Cell and Developmental Biology Commons^™

The Cancer Stem Cell Conundrum In Multiple Myeloma, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

No abstract provided.

Activation Of Amp-Activated Protein Kinase By 3,39-Diindolylmethane (Dim) Is Associated With Human Prostate Cancer Cell Death In Vitro And In Vivo, Di Chen, Sanjeev Banerjee, Qiuzhi C. Cui, Dejuan Kong, Fazlul H. Sarkar, Q. Ping Dou

Oncology Faculty Publications

There is a large body of scientific evidence suggesting that 3,39-Diindolylmethane (DIM), a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK) plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer cells. …

Real-Time Analysis Of Brain Tumor Cell Dynamics: Novel Thermoelectric Detection Of L-Glutamate And Cell Metabolism Using Microfluidics, Siva Mahesh Tangutooru

Doctoral Dissertations

This study describes the design, fabrication and applications of a novel thermoelectric microfluidic bio-sensor. The bio-sensor is used for real time detection of the L-glutamate (L-glu) dynamics and metabolism for brain tumor cells immobilized in a microfluidic device. The microfluidic device is fabricated using a polymer/glass laminating technique (Xurography). An antimony-bismuth thin-film thermopile (primary sensing element) is integrated to the microfluidic device. The brain tumor cells are immobilized over the thermopile covering measuring and reference junctions of the thermopile using a poly-l-lysine coating layer. L-glutamate oxidase (L-GLOD) is immobilized over the measuring junctions of the thermopile prior to the immobilization …

Melanoma Induction By Ultraviolet A But Not Ultraviolet B Radiation Requires Melanin Pigment, Frances P. Noonan, M. Raza Zaidi, Agnieszka Wolnicka-Glubisz, Miriam R. Anver, Jesse Bahn, Anastas Popratiloff, +9 Additional Authors

Anatomy and Regenerative Biology Faculty Publications

Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear. Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses. We show that melanoma induction by ultraviolet A (320–400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes. In contrast, ultraviolet B radiation (280–320 nm) initiates melanoma in a pigment-independent manner associated with direct ultraviolet B DNA damage. Thus, we identified two ultraviolet wavelength-dependent pathways for the induction of …

Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers

Markey Cancer Center Faculty Publications

Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of …

A Role For Reactive Oxygen Species In Photodynamic Therapy, Michael Price

Wayne State University Dissertations

Photodynamic therapy (PDT) is based on the ability of certain photosensitizing agents to selectively localize in neoplastic cells and their vasculature. Subsequent irradiation at a wavelength corresponding to a photosensitizer absorbance band excites the photosensitizer molecules, leading to energy transfer reactions and fluorescence. It was initially concluded that the phototoxic effect occurred when energy from the excited state of the photosensitizer was transferred to dissolved oxygen to form singlet oxygen. This product has a very brief half-life and will cause cellular damage only in the immediate vicinity of its formation. But an excited-state photosensitizer can also interact with oxygen to …

Chemotherapy: The Physiological Cost Of A Cure, Megan Ellis

A with Honors Projects

This project focuses on the common long term side effects of cancer treatments, apart from cure. In addition to physiological function changes, it focuses on the chemical composition of chemotherapy drugs.

A Mathematical Model For Cell Cycle-Specific Cancer Virotherapy, Joanna R. Wares, Joseph J. Crivelli, Juraj Földes, Peter S. Kim

Department of Math & Statistics Faculty Publications

Oncolytic viruses preferentially infect and replicate in cancerous cells, leading to elimination of tumour populations, while sparing most healthy cells. Here, we study the cell cycle-specific activity of viruses such as vesicular stomatitis virus (VSV). In spite of its capacity as a robust cytolytic agent,VSVcannot effectively attack certain tumour cell types during the quiescent, or resting, phase of the cell cycle. In an effort to understand the interplay between the time course of the cell cycle and the specificity of VSV, we develop a mathematical model for cycle-specific virus therapeutics. We incorporate the minimum biologically required time spent in the …

Targeting The Cancer Cell Cycle By Cold Atmospheric Plasma, Olga Volotskova, Teresa S. Hawley, Mary Ann Stepp, Michael Keidar

Anatomy and Regenerative Biology Faculty Publications

Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M increase in two different types of cancer cells with different degrees of tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. The expression of γH2A.X (pSer139), an oxidative stress reporter indicating …

Lenalidomide Targets The T-Cell Co-Stimulatory Pathway To Mediate Immune Modulation, Jessica Marie Mcdaniel

USF Tampa Graduate Theses and Dissertations

T-cells are lymphocytes that make up part of the adaptive arm of the immune system, and are essential for efficient protection from and eradication of viruses and pathogens. T-cells not only play an important role in protection from external agents, but also regulate and prevent activation towards self-peptides and detect and remove erratically growing cells. Alterations in T-cell activation and suppression contribute to auto-immunity, immunocompromised disorders, and cancer progression.

The immune system, and T-cells in particular, provides daily surveillance, recognition and destruction of aberrant cells. Although the immune system is proficient at suppressing malignant progression, tumor cells acquire various methods …

Novel Report Of Expression And Function Of Cd97 In Malignant Gliomas: Correlation With Wilms Tumor 1 Expression And Glioma Cell Invasiveness Laboratory Investigation, Archana Chidambaram, Helen L. Fillmore, Timothy E. Van Meter, Catherine I. Dumur, William C. Broaddus

Office of Research Faculty & Staff Publications

Object. The Wilms tumor 1 (WT1) protein—a developmentally regulated transcription factor—is aberrantly expressed in gliomas and promotes their malignant phenotype. However, little is known about the molecular allies that help it mediate its oncogenic functions in glioma cells.

Methods. The authors used short interfering RNA (siRNA) to suppress WT1 expression in glioblastoma (GBM) cells and evaluated the effect of this on GBM cell invasiveness. Gene expression analysis was then used to identify the candidate genes that were altered as a result of WT1 silencing. One candidate target, CD97, was then selected for further investigation into its role by suppressing …

Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin

Wayne State University Dissertations

Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, compromising p53 activity. Therefore, lymphoma is a suitable model for studying therapeutic value of disrupting HDM2-p53 association by small-molecule inhibitors (SMIs). HDM2 SMIs have been developed and are currently under various stages of preclinical and clinical investigation. This study examined various molecular mechanisms associated and biological effects of two different classes of HDM2 SMIs: the spiro-oxindoles (MI-219) and cis-imidazoline (Nutlin-3) in lymphoma cell lines and patient-derived B-lymphoma cells. Surprisingly, results revealed significant quantitative and qualitative differences between these two agents. At the molecular level, effect of Nutlin-3 was generally more …

Effective Non-Viral Delivery Of Sirna To Acute Myeloid Leukemia Cells With Lipid-Substituted Polyethylenimines, Breanne Landry

Pharmacy Faculty Articles and Research

Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ~0.5 and led to siRNA/polymer complexes of …