Cale Fahrenholtz

Wake Forest School of Medicine · Department of Cancer Biology

To evaluate the use of glucosamine functionalized multiwalled carbon nanotubes (glyco-MWCNTs) for breast cancer targeting. Two types of glucosamine functionalized MWCNTs were developed (covalently linked glucosamine and non-covalently phospholipid-glucosamine coated) and evaluated for their potential to bind and target breast cancer cells in vitro...

Inhibition of the mitogenic insulin-like growth factor receptor 1 (IGF-1R) signaling axis is a compelling treatment strategy for prostate cancer. Combining the IGF-1R inhibitor ganitumab (formerly AMG 479) with standard of care androgen- deprivation therapy greatly delays prostate cancer recurrence in xenograft models; however, a significant propor...

Significance Therapeutic options for recurrent castration-resistant prostate cancer (CRPC) are limited and more effective treatment regimens are needed. Antagonists of growth hormone-releasing hormone (GHRH) inhibit growth of experimental models of human cancer cells, including prostate cancer, by suppressing the actions of tumoral growth factors,...

Prostate cancer is the most commonly diagnosed malignancy in men. While tumors initially respond to androgen-deprivation therapy, the standard care for advanced or metastatic disease, tumors eventually recur as castration-resistant prostate cancer. Upregulation of the insulin-like growth factor receptor type 1 (IGF-1R) signaling axis drives growth...

Increased androgen receptor (AR) transcriptional activity mediated by coactivator proteins may drive castration-resistant prostate cancer (CRPC) growth. Vav3, a Rho GTPase guanine nucleotide exchange factor (GEF), is overexpressed in human prostate cancers, particularly in models of CRPC progression. Vav3 coactivates AR in a Vav3 pleckstrin homolog...

Neurofibromatosis Type 1 (NF1) is a common neurogenic condition characterized by heterozygous loss of function mutations in the neurofibromin gene. NF1 patients are susceptible to the development of neurofibromas, including plexiform neurofibromas (pNFs), which occurs in about half of all cases. Plexiform neurofibroma are benign peripheral nerve sh...

Neurofibromatosis type 1 (NF1) is among the most common neurogenic disorders, characterized by loss of function mutations in the neurofibromin gene (NF1). NF1 patients are extremely susceptible to developing neurofibromas, which can transform into deadly malignant peripheral nerve sheath tumors (MPNSTs). At the center of these tumors are NF1-null S...

Molecular profiling of tumors shows that triple-negative breast cancer (TNBC) can be stratified into mesenchymal (claudin-low breast cancer; CLBC) and epithelial subtypes (basal-like breast cancer; BLBC). Subtypes differ in underlying genetics and in response to therapeutics. Several reports indicate that therapeutic strategies that induce lipid pe...

Background Ionizing radiation (IR) is commonly used in triple-negative breast cancer (TNBC) treatment regimens. However, off-target toxicity affecting normal tissue and grueling treatment regimens remain major limitations. Hyperthermia is one of the greatest IR sensitizers, but only if heat is administered simultaneously or immediately prior to ion...

Abstract Silver nanoparticles (AgNPs) show promise for treatment of aggressive cancers including triple‐negative breast cancer (TNBC) in preclinical cancer models. For clinical development of AgNP‐based therapeutics, it will be necessary to clearly define the specific physicochemical features of the nanoparticles that will be used, and to tie these...

Castration-resistant prostate cancer (CRPC) recurs after androgen deprivation therapy (ADT) and is incurable. Reactivation of androgen receptor (AR) signaling in the low androgen environment of ADT drives CRPC. This AR activity occurs through a variety of mechanisms, including up-regulation of AR coactivators such as VAV3 and expression of constitu...

The epithelial-to-mesenchymal transition (EMT) is an evolutionarily conserved process that is required for normal development. However, EMT is often dysregulated and hijacked by cancers during tumor progression. Cancer cells that have undergone EMT and acquired a mesenchymal phenotype harbor several distinct traits, including increased tumor initia...

We investigated the effects of silver nanoparticle (AgNP) exposure in three ovarian cancer cell lines (A2780, SKOV3, and OVCAR3). We found that AgNPs were highly cytotoxic toward A2780 and SKOV3 cells but OVCAR3 cells were less sensitive to AgNPs. In agreement with the cytotoxicity data, AgNPs caused DNA damage in A2780 and SKOV3 cells, but not in...

There is a growing interest in the use of multiwalled carbon nanotubes (MWCNTs) to treat diseases of the brain. Little is known about the effects of MWCNTs on human brain microvascular endothelial cells (HBMECs), which make up the blood vessels in the brain. In our studies, we evaluate the cytotoxicity of MWCNTs and acid oxidized MWNCTs, with or wi...

Large-pore mesoporous silica nanoparticles (MSN) were prepared and functionalized to serve as a highly robust and biocompatible delivery platform for platinum-acridine (PA) anticancer agents. The material showed a high loading capacity for the dicationic, hydrophilic hybrid agent [PtCl(en)(N-[acridin-9-ylaminoethyl]-N-methylpropionamidine)] dinitra...

s: AACR Special Conference: Engineering and Physical Sciences in Oncology; June 25-28, 2016; Boston, MA Glioblastoma multiforme (GBM) is the most common and most lethal primary brain tumor with a 5 year overall survival rate of approximately 5%. Currently, no therapy is curative and all have significant side effects. Focal thermal ablative therapi...

Triple negative breast cancers (TNBC) are characterized by loss of expression of hormone receptors and decreased expression of the human epidermal growth factor receptor 2 (HER2). TNBC patients do not benefit from current targeted breast cancer (BC) treatments. Molecular profiling of breast cancer has found that TNBC is largely comprised of basal-l...

A three-component drug-delivery system has been developed consisting of multi-walled carbon nanotubes (MWCNTs) coated with a non-classical platinum chemotherapeutic agent ([PtCl(NH3)2(L)]Cl (P3A1; L=N-(2-(acridin-9-ylamino)ethyl)-N-methylproprionimidamide) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (DSPE...

Glioblastoma multiforme (GBM) is the most common and most lethal primary brain tumor with a 5 year overall survival rate of approximately 5%. Currently, no therapy is curative and all have significant side effects. Focal thermal ablative therapies are being investigated as a new therapeutic approach. Such therapies can be enhanced using nanotechnol...

Triple-negative breast cancer (TNBC) lacks expression of the estrogen and progesterone receptors and does not overexpress the HER-2 receptor. Thus, current targeted therapies are rendered ineffective against this subtype of breast cancer, leaving a gap in treatment options for these patients. The use of nanotechnology has the potential to dramatica...

Triple-negative breast cancer (TNBC) accounts for 10-15% of breast cancers, has the highest levels of recurrence, and the lowest five-year survival of all breast cancer subtypes. TNBC does not express estrogen or progesterone receptors and does not overexpress HER2 receptors. Therefore, TNBC does not benefit from current FDA-approved targeted thera...

221 Background: Advanced hormone-sensitive prostate cancer (PCa) responds to androgen deprivation therapy (ADT). However, therapeutic options for castration-resistant disease are limited. As growth hormone-releasing hormone receptor (GHRH-R) and ligand GHRH are regulated in an autocrine fashion in PCa, GHRH-R inhibition represents a novel approach...

Advanced or metastatic prostate cancer is treated by androgen deprivation; however, patients inevitably relapse with castration-resistant prostate cancer (CRPC). CRPC remains dependent on androgen receptor (AR) signaling, which may include constitutive, ligand-independent action of naturally occurring AR splice variants. For example, the AR splice...

The treatment for advanced or metastatic prostate cancer is androgen deprivation therapy. Patients inevitably relapse and the cancer is now termed androgen-independent or castration resistant (CRPC). CRPC remains dependent on androgen receptor (AR) signaling. One of the proteins implicated in the reactivation of AR transcriptional activity in CRPC...

s: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA Prostate tumors are initially dependent on androgens for growth; thus the standard of care for advanced or metastatic prostate cancer is androgen deprivation therapy. While this treatment strategy diminishes tumor burden and gr...

Inhibition of Vav3 results in decreased growth selectively of AR-expressing prostate cancer cells A. PC3 cells transfected with AR, PSA-luc, beta galactosidase (B-gal) and either Vav3, Vav3.1 and Vav3, or empty vector (Ev) were treated with either vehicle or R1881 (1 nM) for 48 h. Cell lysates were then assayed for luciferase activity. Data from a...

Vav3 expressing VCaP cells exhibit decreased apoptosis in androgen-depleted media VCaP cells stably expressing Vav3 or GFP (control) were depleted of androgen and then replated in media containing either 10% FBS (+) or 10% CSS-FBS (−) and cultured for the indicated times. Lysates were probed with antibody against cleaved PARP or actin.

The oligodendrocyte progenitor cell (OPC) is one of the most studied progenitor cells of the body. It has been extensively researched in tissue culture and more recently in vivo using a wide range of markers that recognize transcription factors and cell surface markers and identify its earliest development from neural stem cells onward. Isolation o...