A5103005127- Pancreatic function and diabetes
- Cell death mechanisms and regulation
- Neuroendocrine Tumor Research Advances
- Diabetes and associated disorders
- Cancer-related Molecular Pathways
- NF-κB Signaling Pathways
- Vitamin C and Antioxidants Research
- Prostate Cancer Treatment and Research
- Ubiquitin and proteasome pathways
- interferon and immune responses
- Fibroblast Growth Factor Research
- Pancreatic and Hepatic Oncology Research
- RNA Research and Splicing
- Receptor Mechanisms and Signaling
- Mitochondrial Function and Pathology
- Histone Deacetylase Inhibitors Research
- Neuroblastoma Research and Treatments
- Protein Degradation and Inhibitors
- Cytokine Signaling Pathways and Interactions
- RNA Interference and Gene Delivery
- Lung Cancer Research Studies
- Genetics and Neurodevelopmental Disorders
- Radiomics and Machine Learning in Medical Imaging
- Nanoparticles: synthesis and applications
- Digital Imaging for Blood Diseases
Wake Forest University
2024
Atrium Health Wake Forest Baptist
2024
University of Iowa
2002-2023
National Institute of Diabetes and Digestive and Kidney Diseases
2010
University of Iowa Holden Comprehensive Cancer Center
2010
Pharmacologic concentrations of ascorbate may be effective in cancer therapeutics. We hypothesized that achievable with i.v. dosing would cytotoxic pancreatic for which the 5-year survival is <3%.Pancreatic cell lines were treated (0, 5, or 10 mmol/L) 1 hour, then viability and clonogenic determined. Pancreatic tumor cells delivered s.c. into flank region nude mice allowed to grow at time they randomized receive either (4 g/kg) osmotically equivalent saline (1 mol/L) i.p. 2 weeks.There was a...
AbstractWe investigated whether knocking down AR expression effects apoptosis after treatment with different apoptosis-inducing agents. We found that siRNA (si-AR) significantly decreased induced by topoisomerase inhibitors doxorubicin (DOX) and camptothecin (Campt). It is known DNA double-strand break inducing agents leads to activation (phosphorylation) of p53 in turn regulates the a variety apoptosis-related genes including microRNA(miR)-34a 34b/c. DOX 5 phosphorylation sites (Ser15, 20,...
Cancer is the second deadliest disease in United States, necessitating improvements tumor diagnosis and treatment. Current model systems of cancer are informative, but translating promising imaging approaches therapies to clinical practice has been challenging. In particular, lack a large-animal that accurately mimics human major barrier development effective diagnostic tools along with surgical therapeutic interventions. Here, we developed genetically modified porcine which animals express...
AbstractIt has recently been shown that the androgen receptor (AR) is main factor required for prostate cancer cells survival. We show knocking down AR expression by siRNA induces PI3K-independent activation of Akt, which was mediated calcium/calmodulin-dependent kinase II (CaMKII). further show, first time, express β, γ, and δ CaMKII genes, these genes under control activity: active in presence androgens inhibits gene whereas inhibition activity results elevated level enhanced CaMKII-β –γ...
Abstract Histone deacetylase inhibitors (HDACI) are potential therapeutic agents that inhibit tumor cell growth and survival. Although there several publications regarding the effects of HDACIs on prostate cancer growth, their mechanism(s) action remains undefined. We treated human lines with HDACI trichostatin A found induced death in androgen receptor (AR)–positive to higher extent compared AR-negative lines. then discovered other suppressed AR gene expression as well AR-positive breast...
Mechanisms of neuroendocrine tumor (NET) proliferation are poorly understood, and therapies that effectively control NET progression metastatic disease limited. We found amplification a putative oncogene, RABL6A, in primary human pancreatic NETs (PNET) correlated with high-level RABL6A protein expression. Consistent those results, stable silencing cultured BON-1 PNET cells revealed it is essential for their survival. Cells lacking predominantly arrested G1 phase moderate mitotic block....
Hyperactivated AKT/mTOR signaling is a hallmark of pancreatic neuroendocrine tumors (PNETs). Drugs targeting this pathway are used clinically, but tumor resistance invariably develops. A better understanding factors regulating and PNET pathogenesis needed to improve current therapies. We discovered that RABL6A, new oncogenic driver proliferation, required for AKT activity. Silencing RABL6A caused cell-cycle arrest coincided with selective loss AKT-S473 (not T308) phosphorylation...
Abstract It has been suggested that some nuclear transcription factors may participate in the regulation of mitochondrial functions through transcriptional control DNA. Very little is known about response within mitochondria to activation death receptors. Recent publications indicate factor-κB (NF-κB) localized mammalian cells. Because critical role execution many apoptotic pathways, we suggest NF-κB-dependent mechanisms operating at level contribute its regulating receptor signaling. We...
It has been suggested that the down-regulation of AR expression should be considered principal strategy for treatment hormone-refractory prostate cancer.We have previously shown inhibition induced PI3K-independent activation Akt was mediated by CaMKII. In this study, we found CaMKII inhibitor KN-93 a broader effect on apoptosis than just CaMKII: first, inhibits activity and induces cell death in PCa cells after androgen deprivation when many other drugs fail to kill cancer cells; second,...
The human prostatic carcinoma cell line DU145 has previously been found to be resistant treatment with TNF-family ligands. However, TRAIL, TNF-α, and anti-Fas antibodies (Ab) in combination the histone deacetylase inhibitor Trichostatin A (TSA) converted phenotype of from sensitive. TSA induced 15% death but simultaneous Ab resulted 55%, 70%, 40% death, respectively. Simultaneous did not increase level TSA-induced acetylation, release acetylated histones chromatin into cytosol. This was...
Caspase-2 can induce apoptosis in response to extrinsic and intrinsic signals. Unlike other caspases, this protein is not expressed solely nonnuclear compartments; a subpopulation constitutively localized the nucleus. As one of most evolutionarily conserved caspase-2 may have roles multiple cellular processes. However, its contribution nonapoptotic processes remains mystery. In study, we show that activity important for proliferation by cells androgen-dependent prostate cancer cell line...
Two main pathways of apoptosis in mammalian cells have been described: the death receptor pathway and mitochondrial pathway. different cell types identified for Fas-mediated apoptosis, each using almost exclusively one two signaling pathways. Human prostatic carcinoma line, PC3 is sensitive to but relation not clear.Cell viability was estimated by calcein assay. Apoptosis determined preparation DNA ladder. Expression Fas-associated domain-dominant negative (FADD-DN) Bcl-2, activation...
Bisindolylmaleimides (Bis) were originally described as protein kinase C inhibitors. Several studies have shown that Bis potentiate tumor necrosis factor (TNF) receptor family-mediated apoptosis in lymphoid and dendritic cells, but the inhibition of cannot account for these effects (Zhou, T., Song, L., Yang, P., Wang, Z., Lui, D., Jope, R. S. (1999) Nat. Med. 5, 42–48). We investigated effect four derivatives (I, II, VIII, IX) human prostatic carcinoma cell lines found IX was most potent...
We and others have previously described that the androgen-responsive human prostatic carcinoma cell line LNCaP is resistant to TRAIL TRAIL-mediated apoptosis in PI3K/Akt-dependent. In this study, we found remained treatment with after androgen deprivation even presence of PI3K/Akt pathway inhibitor wortmannin. This resistance was determined by failure form TRAIL-DISC decreased TRAIL-R1 TRAIL-R2 levels deprivation; capacity induce DISC formation completely restored DHT. wortmannin together...
AbstractThe histone deacetylase inhibitor Trichostatin A (TSA) has previously been found to induce caspase activity in the human prostate cancer cell line DU145 and LNCaP. TSA treatment resulted release of cytochrome c Smac/DIABLO from mitochondria DU145, activation caspase-9 both lines. We concluded that mediated its effect via mitochondrial pathway. The aim current study was determine how initiated cascade. results revealed caspase-2 plays an important role TSA-induced apoptosis....
AbstractTPCK is widely used as an inhibitor of chymotrypsin-like proteases but has recently been identified the PDK1/Akt pathway. In this study, we show that TPCK inhibits TRAIL-induced caspase activity potentiates wortmannin-dependent in prostatic carcinoma cell lines. The inhibitory was found to be death ligand-specific since TRAIL-mediated does not affect Fas-induced activity. Our data also impaired TRAIL-DISC formation presence responsible for inhibition. Further, induces p53 expression...
As G-banded chromosome analysis is a time-consuming and labor-intensive procedure, Cytogenetics laboratories are continuously seeking ways to enhance efficiency while maintaining high-quality diagnostics. Digital imaging has helped streamline this workflow by providing automated tools identify metaphases for analysis, separate chromosomes, classify them in karyogram. Although efficient reducing turnaround time, results of these digital technologies still require many manual interactions.
The BCR::ABL1 gene rearrangement creates a fusion on the Philadelphia chromosome, derivative chromosome 22 partner in classic t(9;22)(q34;q11.2) observed chronic myeloid leukemia (CML), B-lymphoblastic leukemia/lymphoma (BLL), and less commonly, other leukemias. Three proteins derived from different breakpoints BCR ABL1 genes are well-described: major breakpoint p210, minor p190, micro p230 proteins. occurs virtually all CML patients approximately 2.5% of children 25% adults with BLL. BLL...