Nickkholgh B.,Wake Forest Institute for Regenerative Medicine WFIRM |
Fang X.,Wake Forest Institute for Regenerative Medicine WFIRM |
Winters S.M.,Wake forest University |
Raina A.,Wake forest University |
And 5 more authors.
Prostate | Year: 2016
Background African-American men with prostate cancer (PCa) present with higher-grade and -stage tumors compared to Caucasians. While the disparity may result from multiple factors, a biological basis is often strongly suspected. Currently, few well-characterized experimental model systems are available to study the biological basis of racial disparity in PCa. We report a validated in vitro cell line model system that could be used for the purpose. Methods We assembled a PCa cell line model that included currently available African-American PCa cell lines and LNCaP (androgen-dependent) and C4-2 (castration-resistant) Caucasian PCa cells. The utility of the cell lines in studying the biological basis of variance in a malignant phenotype was explored using a multiplex biomarker panel consisting of proteins that have been proven to play a role in the progression of PCa. The panel expression was evaluated by Western blot and RT-PCR in cell lines and validated in human PCa tissues by RT-PCR. As proof-of-principle to demonstrate the utility of our model in functional studies, we performed MTS viability assays and molecular studies. Results The dysregulation of the multiplex biomarker panel in primary African-American cell line (E006AA) was similar to metastatic Caucasian cell lines, which would suggest that the cell line model could be used to study an inherent aggressive phenotype in African-American men with PCa. We had previously demonstrated that Protein kinase D1 (PKD1) is a novel kinase that is down regulated in advanced prostate cancer. We established the functional relevance by over expressing PKD1, which resulted in decreased proliferation and epithelial mesenchymal transition (EMT) in PCa cells. Moreover, we established the feasibility of studying the expression of the multiplex biomarker panel in archived human PCa tissue from African-Americans and Caucasians as a prelude to future translational studies. Conclusion We have characterized a novel in vitro cell line model that could be used to study the biological basis of disparity in PCa between African-Americans and Caucasians. Prostate 76:245-258, 2016. © 2015 Wiley Periodicals, Inc.
Sadri-Ardekani H.,Wake Forest Institute for Regenerative Medicine WFIRM |
Atala A.,Wake Forest Institute for Regenerative Medicine WFIRM
Advanced Drug Delivery Reviews | Year: 2015
Regenerative medicine has opened new avenues for treating patients with severe reproductive system disorders, such as congenital abnormalities, cancer, trauma, infection, inflammation and iatrogenic injuries. Over the past two decades, scientists have advanced the field of reproductive tissue engineering to restore normal sexual function and preserve fertility in both female and male patients. In this review, we summarize recent advances in the use of cell, tissue, and organ-based regenerative medicine strategies for clinical application in reproductive system disorders. © 2014 Elsevier B.V.
Ross C.L.,Wake Forest Institute for Regenerative Medicine WFIRM |
Teli T.,WFIRM |
Alternative Therapies in Health and Medicine | Year: 2016
Context • During cell-communication processes, endogenous and exogenous signaling affects normal and pathological developmental conditions. Exogenous influences, such as extra-low-frequency (ELF) electromagnetic fields (EMFs) have been shown to affect pain and inflammation by modulating G-protein coupling receptors (GPCRs), downregulating cyclooxygenase-2 (Cox-2) activity, and downregulating inflammatory modulators, such as tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) as well as the transcription factor nuclear factor kappa B (NF-κB). EMF devices could help clinicians who seek an alternative or complementary treatment for relief of patients chronic pain and disability. Objective • The research team intended to review the literature on the effects of EMFs on inflammatory pain mechanisms. Design • We used a literature search of articles published in PubMed using the following key words: low-frequency electromagnetic field therapy, inflammatory pain markers, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), opioid receptors, G-protein coupling receptors, and enzymes. Setting • The study took place at the Wake Forest School of Medicine in Winston-Salem, NC, USA. Results • The mechanistic pathway most often considered for the biological effects of EMF is the plasma membrane, across which the EMF signal induces a voltage change. Oscillating EMF exerts forces on free ions that are present on both sides of the plasma membrane and that move across the cell surface through transmembrane proteins. The ions create a forced intracellular vibration that is responsible for phenomena such as the influx of extracellular calcium (Ca2+) and the binding affinity of calmodulin (CaM), which is the primary transduction pathway to the secondary messengers, cAMP and cGMP, which have been found to influence inflammatory pain. Conclusions • An emerging body of evidence indicates the existence of a frequency-dependent interaction between the mechanical interventions of EMF and cell signaling along the peripheral inflammatory pain pathway. © 2016, InnoVision Communications. All rights reserved.
PubMed | Wake Forest Institute for Regenerative Medicine WFIRM
Type: | Journal: Advanced drug delivery reviews | Year: 2015
Regenerative medicine has opened new avenues for treating patients with severe reproductive system disorders, such as congenital abnormalities, cancer, trauma, infection, inflammation and iatrogenic injuries. Over the past two decades, scientists have advanced the field of reproductive tissue engineering to restore normal sexual function and preserve fertility in both female and male patients. In this review, we summarize recent advances in the use of cell, tissue, and organ-based regenerative medicine strategies for clinical application in reproductive system disorders.