Benyi Li

• MD/PhD
• Managing Director at University of Kansas Medical Center

Background: Cystatins, encoded by the CST gene family, are a superfamily of cysteine protease inhibitors involved in a wide array of biological functions, including immune modulation and antimicrobial defense. Cystatin proteins are implicated in tumor progression through multiple mechanisms. However, their roles in bladder cancer remain poorly unde...

Introduction The human gamma-glutamyltransferase (GGT) is a membrane-bound extracellular glycoprotein with an enzymatic activity that cleaves gamma-glutamyl peptide bonds in glutathione and other peptides and transfers the gamma-glutamyl moiety to acceptors. It has been shown aberrant expression of GGT proteins in human cancers while their expressi...

Sideroflexin (SFXN) family genes encode for a group of mitochondrial proteins involved in cellular processes such as iron homeostasis, amino acid metabolism, and energy production. Recent studies showed that they were aberrantly expressed in certain human cancers. However, there is a paucity of information about their expression in prostate cancer....

Objectives Bladder cancer (BLCA) is a tumor that affects men more than women. The biological function and prognostic value of androgen-responsive genes (ARGs) in BLCA are currently unknown. To address this, we established an androgen signature to determine the prognosis of BLCA. Methods Sequencing data for BLCA from the TCGA and GEO datasets were...

Sideroflexin (SFXN) family genes encode for a group of mitochondrial proteins involved in cellular processes such as iron homeostasis, amino acid metabolism, and energy production. Recent studies showed that they were aberrantly expressed in certain human cancers. However, there is a paucity of information about their expression in prostate cancer....

Introduction Alternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect via the accumulation of radical oxygen species (ROS) in prostate cancer cells in vitro and in vivo. In this study, we tested its anti-cancer spectrum in multiple platforms. Methods We first tested its a...

Background: Alternol is a small molecular compound isolated from the fermentation of a mutant fungus obtained from Taxus brevifolia bark. Our previous studies showed that Alternol treatment induced reactive oxygen species (ROS)-dependent immunogenic cell death. This study conducted a comprehensive investigation to explore the mechanisms involved in...

Dysregulation of microRNAs (miRNAs) expression is closely related to cancers and managing miRNA expression holds great promise for cancer therapy. However, their wide clinical application has been hampered by their poor stability, short half-life and non-specific biodistribution in vivo. Herein, a novel biomimetic platform designated as RHAuNCs-miR...

Background Histone demethylase RIOX2 was cloned as a c-Myc downstream gene involved in cell proliferation and has been implicated as an oncogenic factor in multiple tumor types. Its expression profiles and correlation with disease progression in prostate cancers are unknown. Methods Transcriptomic profiles of Jumanji domain-containing protein gene...

Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs...

Background: Reliable biomarkers are rare for renal cell carcinoma (RCC) treatment selection. We aimed to discover novel biomarkers for precision medicine. The iron-regulating hormone hepcidin (HAMP) was reportedly increased in RCC patient sera and tissues. However, its potential implication as a prognostic biomarker remains exclusive. Methods: Mult...

Background Renal cell carcinoma (RCC) was sex-hormone responsive, and clinical trials using progesterone significantly reduced the incidence of distal metastasis after radical nephrectomy. Recently membrane-bound progesterone receptors (mPRs) were discovered to mediate the non-genomic effect of progesterone. Aberrant expressions of these mPRs were...

Background and objectives: Alzheimer’s disease is a progressive brain degeneration and is associated with a high prevalence of sleep disorders. Amyloid β peptide-42/40 (Aβ42/40) and Tau-pT181 are the core biomarkers in cerebrospinal fluid and blood. Accumulated data from studies in mouse models and humans demonstrated an aberrant elevation of these...

Progesterone-induced rapid non-genomic signaling events have been confirmed through several membrane progesterone receptors (mPR). Some mPRs were reported to correlate with cancer progression and patient prognosis. In this study, we conducted a comprehensive analysis of all progesterone receptor (PGR)-related genes in prostate cancer tissues and ex...

Background Hepcidin is a polypeptide hormone mainly produced by hepatocytes to modulate systemic iron balance. A drastic downregulation of the hepcidin gene was found in liver cancers. However, there is a paucity of information about the clinical significance of hepcidin gene downregulation in liver cancers. Methods Hepcidin expression profiles we...

Background Liver cancer is a leading cause of cancer death worldwide, and novel prognostic factor is needed for early detection and therapeutic responsiveness monitoring. The orphan nuclear receptor NR0B2 was reported to suppress liver cancer development in a mouse model, and its expression levels were reduced in liver cancer tissues and cell lines...

Alternol is a naturally occurring compound that exerts antitumor activity in several cancers. However, whether Alternol induces antitumor immune response remains unknown. In this study, we investigated whether Alternol induced immunogenic cell death (ICD) in prostate cancer cells. Alternol triggered ICD in prostate cancer cells, as evidenced by the...

Background: Amyloid β peptide-42 (Aβ42) and phosphorylated Tau on Threonine 181 (Tau-pT181) are the core biomarkers in Alzheimer’s disease. Accumulated evidence showed an aberrant elevation of these biomarkers due to sleep disturbance. However, it is not clear if improving sleep quality reduces Aβ42 and Tau-pT181 in Alzheimer’s disease patients. Me...

Alternol and its oxidate isomer Alteronol are small compounds isolated from the fermentation of a mutant fungus obtained from Taxus brevifolia bark. Preclinical studies showed their potent anti-cancer activities, including attenuating cellular survival pathways, altering protein levels of cell cycle regulators, activating xanthine dehydrogenase to...

Background Mitoxantrone (MTX) is a synthetic compound used as a second line chemotherapeutic drug for prostate cancer. It has been reported to trigger immunogenic cell death (ICD) in animal model studies, but the underlying mechanism is not fully understood yet, especially not in prostate cancer cells.MethodsICD was determined by assessing the rele...

Alternol is a monomeric compound purified from the fermentation of a microbial strain obtained from the bark of the yew tree. Recent studies have confirmed that it has specific anti-prostate cancer efficacy in vitro and in vivo. In in vitro cell culture experiments Alternol inhibits prostate cancer cell proliferation by causing cell cycle arrest, r...

The natural compound Alternol was shown to induce profound oxidative stress and apoptotic cell death preferentially in cancer cells. In this study, a comprehensive investigation was conducted to understand the mechanism for Alternol-induced ROS accumulation responsible for apoptotic cell death. Our data revealed that Alternol treatment moderately i...

Cancer metabolism is emerging with great interest as a therapeutic target for cancer management. Prostate cancer is especially unique in this aspect since benign prostate tissue exhibits truncated Krebs cycle to secret citrate due to high level of prostatic zinc concentration but prostate cancer cells fully oxidize citrate for energy production thr...

Objectives: Distant metastasis is a critical factor for cancer-associated death. Our previous studies identified collapsin response mediator protein 4a (CRMP4a) as a metastasis suppressor in prostate cancers. Enhancing CRMP4 expression by promoter-targeted small activating RNAs reduced cell migration in vitro and abolished distal metastasis in mous...

Androgen receptor (AR) splice variants (ARVs) are implicated in development of castration-resistant prostate cancer (CRPC). Upregulation of ARVs often correlates with persistent AR activity after androgen deprivation therapy (ADT). However, the genomic and epigenomic characteristics of ARV-dependent cistrome and the disease relevance of ARV-mediate...

Purpose: Intratumoral androgen synthesis (IAS) is a key mechanism promoting androgen receptor (AR) reactivation and anti-androgen resistance in castration-resistant prostate cancer (CRPC). However, signaling pathways driving aberrant IAS remain poorly understood. Experimental Design: The effect of components of the AKT-RUNX2-osteocalcin (OCN)-GPRC...

The combination of photothermal therapy and chemotherapy (photothermal–chemotherapy) is a promising strategy for cancer therapy. Gold nanocages (AuNCs), with hollow and porous structures and unique optical properties, have become a rising star in the field of drug delivery. Here, we designed a novel targeted drug delivery system based on functional...

Metastasis is the sole cause of cancer death and there is no curable means in clinic. Cellular protein CRMP4 (DPYSL3 gene) was previously defined as a metastasis suppressor in human prostate cancers since its expression is dramatically reduced in lymphatic metastatic diseases and DPYSL3 overexpression in prostate cancer cells significantly suppress...

Background: Our previous studies demonstrated that the class IA PI3K/p110β is critical in castration-resistant progression of prostate cancer (CRPC) and that targeting prostate cancer with nanomicelle-loaded p110β-specific inhibitor TGX221 blocked xenograft tumor growth in nude mice, confirming the feasibility of p110β-targeted therapy for CRPCs....

Introduction and aims: Epigenetic alteration plays a major role in the development and progression of human cancers, including prostate cancer. Histones are the key factors in modulating gene accessibility to transcription factors and post-translational modification of the histone N-terminal tail including methylation is associated with either tra...

To explore a novel strategy in suppressing tumor metastasis, we took the advantage of a recent RNA activation (RNAa) theory and used small double-strand RNA molecules, termed as small activating RNAs (saRNA) that are complimentary to target gene promoter, to enhance transcription of metastasis suppressor gene. The target gene in this study is Dihyd...

Background: Glycogen synthase kinase 3β (GSK3B, GSK-3β) is a multi-functional protein kinase involved in various cellular processes and its activity elevates after serum deprivation. We have shown that inhibition of GSK-3β activity triggered a profound autophagic response and subsequent necrotic cell death after serum deprivation in prostate cance...

Background: Combination of androgen ablation along with early detection and surgery has made prostate cancer highly treatable at the initial stage. However, this cancer remains the second leading cause of cancer death among American men due to castration-resistant progression, suggesting that novel therapeutic agents are urgently needed for this l...

Lysosomal membrane permeabilization (LMP) has been shown to cause the release of cathepsins and other hydrolases from the lysosomal lumen to the cytosol and initiate a cell death pathway. Whether proteinuria triggers LMP in renal tubular epithelial cells (TECs) to accelerate the progression of renal tubulointerstitial injury remains unclear . In th...

Prostate cancers in the castration-resistant stage are life-threatening because they are not curable in clinic. The novel androgen receptor inhibitor Xandi (Enzalutamide) and the new CYP17 inhibitor Zytiga (Abiraterone) prolonged patient survival only a few months in advanced prostate cancers. Therefore, novel therapeutic agents for advanced prosta...

TGX-221 is a potent phosphoinositide 3-kinase (PI3K)beta inhibitor that has great therapeutic potential to treat prostate cancer. Chemical modification of TGX-221 at positions 2 and 9 was made. Five new TGX-221 analogs with different heterocyclic substituents of morpholine, 1-methylpiperazine, aniline, and thiazole-2-amine at positions 2 and 9 were...

Prostate cancers at the late stage of castration resistance are not responding well to most of current therapies available in clinic, reflecting a desperate need of novel treatment for this life-threatening disease. In this study, we evaluated the anti-cancer effect of a recently isolated natural compound Alternol in multiple prostate cancer cell l...

Autophagy is shown to be beneficial for renal tubular injury caused by nephrotoxic drugs. To investigate whether autophagy could protect renal tubular epithelial cells (TECs) from injury induced by urinary proteins, we studied the activity and action of autophagy in TECs after urinary protein overload in vivo and in vitro. We found that autophagic...

Androgens and their cognate, the androgen receptor (AR), play a critical role in the development and progression of prostate cancer. In prostate cancer cells, after androgen binding, the AR is activated and dimerized, followed by nuclear translocation to regulate gene expression as a transcriptional factor. During this process, G-protein/PI3K-relat...

Casein kinase 2 (CK2) is constitutively active with dual specificity and exists as a hetero-tetrameric complex of α, α', and β subunits. Its aberrant expression and elevated activity have been linked to many human cancers, including prostate cancer. As an effort to develop new chemotherapy for prostate cancers, in this study, we tested the effects...

Background: Prostate cancer is the major cause of cancer death in men and the androgen receptor (AR) has been shown to play a critical role in the progression of the disease. Our previous reports showed that knocking down the expression of the AR gene using a siRNA-based approach in prostate cancer cells led to apoptotic cell death and xenograft t...

TGX-221 is a potent, selective, and cell membrane permeable inhibitor of the PI3K p110β catalytic subunit. Recent studies showed that TGX-221 has antiproliferative activity against PTEN-deficient tumor cell lines including prostate cancers. The objective of this study was to develop an encapsulation system for parenterally delivering TGX-221 to the...

Glycogen synthase kinase 3β (GSK-3β) plays a critical role in the pathogenesis of Alzheimer's disease (AD), implicating amyloid-β (Aβ) production, neurofibrillary tangle formation, and neuronal apoptosis. The activation of 5′ AMP-activated protein kinase (AMPK) has been linked to aberrant processing of amyloid-β protein precursor (AβPP), and AMPK s...

Recent studies have revealed the scientific basis for the use of intravenous (i.v.) vitamin C or ascorbic acid (ascorbate) in treating cancers, and raised the possibility of using i.v. ascorbate as a prooxidant anticancer therapy. Through the production of H2O2, pharmacologic ascorbate can induce some cancer cell death in vitro and inhibit a number...

The androgen receptor (AR) is a ligand-dependent transcription factor that mediates androgenic hormone action in cells. We recently demonstrated the involvement of phosphoinositide 3-OH kinase (PI3K) p110beta in AR transactivation and gene expression. In this study, we determined the upstream signals that lead to PI3K/p110beta activation and AR tra...

TGX-221 is a highly potent phosphoinositide 3-kinase β (PI3Kβ) inhibitor that holds great promise as a novel chemotherapeutic agent to treat prostate cancer. However, poor solubility and lack of targetability limit its therapeutic applications. The objective of this present study is to develop a peptide-drug conjugate to specifically deliver TGX-22...

Background: Glycogen synthase kinase 3 (GSK-3) has been regarded as a potential therapeutic target for multiple human cancers. We previously reported that suppression of GSK-3 activity with lithium chloride (LiCl) or small chemical inhibitors impaired cellular DNA synthesis and reduced cell proliferation in prostate cancer cells. Therefore, in thi...

Metastasis is the chief cause of mortality from cancer, but the mechanisms leading to metastasis are poorly understood. We used a proteomics approach to screen for metastasis-associated proteins and found that collapsin response mediator protein-4 (CRMP4) expression was inversely associated with the lymph node metastasis of prostate cancer (PCa). S...

We sought to assess the associations of testosterones and sex hormone-binding globulin (SHBG) with metabolic syndrome and insulin resistance in men. We defined metabolic syndrome according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Among men aged >or=20 yea...

The androgen receptor (AR) is the most critical factor in prostate cancer progression. We previously demonstrated that silencing the AR using 2 unique small interfering RNAs (no. 8 and no. 31 AR siRNA) induces apoptotic cell death in AR-positive prostate cancer cells. To develop this AR siRNA technique into a therapy for prostate cancers, we genera...

Glycogen synthase kinase 3 beta (GSK-3beta) is constantly active in cells and its activity increases after serum deprivation, indicating that GSK-3beta might play a major role in cell survival under serum starvation. In this study, we attempted to determine how GSK-3beta promotes cell survival after serum depletion. Under full culture conditions (1...

Ascorbate (Vitamin C) has been shown to act as a pro‐oxidant agent under pharmacological concentrations, and thus can cause cancer cell death in vitro and inhibit tumor growth in animal models, through formation of H2O2. The cell death mechanisms induced by ascorbate need to be further elaborated. The goal of our study was to determine whether asco...

Commentary to:Heat shock protein 70 silencing enhances apoptosis inducing factor-mediated cell death in hepatocellular carcinoma HepG2 cellsQing Zhu, Yan-Ming Xu, Li-Feng Wang, Yong Zhang, Fang Wang, Jing Zhao, Lin-Tao Jia, Wanggang Zhang, An-Gang Yang

Autophagy is a vital basic phenomenon that widely exists in eukaryotic cells. As one type of programmed cell death, autophagy has gained much more attention in the past several years. Recent evidences suggest that the alterations in autophagy are associated with the genesis and development of cancers. It can affect cell apoptosis, angiogenesis and...

Lupeol, a dietary triterpene, was shown to decrease serum prostate-specific antigen levels and inhibit the tumorigenicity of prostate cancer (CaP) cells in vivo. Here, we show that Lupeol inhibits the proliferative potential of CaP cells and delineated its mechanism of action. Employing a focused microarray of human CaP-associated genes, we found t...

Phosphoinositide 3-OH kinases (PI3Ks) are a group of major intracellular signaling molecules. In our previous study, we found that inhibition of PI3K activity suppressed the androgen receptor (AR)-mediated gene expression in prostate cancer cells. The AR has been considered as a critical determinant for the development and progression of human pros...

Increased serum level of parathyroid hormone (PTH) was found in metastatic prostate cancers. Calcimimetic R-568 was reported to reduce PTH expression, to suppress cell proliferation and to induce apoptosis in parathyroid cells. In this study, we investigated the effect of R-568 on cellular survival of prostate cancer cells. Prostate cancer cell lin...

ATP-dependent chromatin remodeling by the mating type switching/sucrose non-fermenting (SWI/SNF) complex is a basic biological event in the body, which is required for all the key processes involved in DNA metabolism such as gene expression, DNA replication, repair, chromosomal recombination and mitosis. In the past few years, increasing evidence s...

Phosphoinositide 3-OH kinases (PI3Ks) are a group of major intracellular signaling molecules. In our previous study, we found that inhibition of PI3K activity suppressed the androgen receptor (AR)-mediated gene expression in prostate cancer cells. The AR has been considered as a critical determinant for the development and progression of human pros...

Phosphoinositide 3-OH kinases (PI3Ks) are a group of major intracellular signaling molecules. In our previous study, we found that inhibition of PI3K activity suppressed the androgen receptor (AR)-mediated gene expression in prostate cancer cells. The AR has been considered as a critical determinant for the development and progression of human pros...

Recently we reported that silencing the androgen receptor (AR) gene reduced Bcl-xL expression that was associated with a profound apoptotic cell death in prostate cancer cells. In this study we further investigated AR-regulated Bcl-xL expression. Prostate cancer cell line LNCaP and its sublines, LNCaP/PURO and LNCaP/Bclxl, were used for cell prolif...

To determine if AR gene silencing in prostate cancer cells via RNA interference mechanism leads to disruption of androgen-independent progression. We generated a recombinant AAV for long-term expression of a hairpin-structured AR siRNA in vivo. Then we determined the essential role of the androgen receptor in androgen-independent growth of prostate...

GPRC6A is a widely expressed orphan G-protein coupled receptor that senses extracellular amino acids, osteocalcin and divalent cations in vitro. The physiological functions of GPRC6A are unknown. In this study, we created and characterized the phenotype of GPRC6A(-/-) mice. We observed complex metabolic abnormalities in GPRC6A(-/-) mice involving m...

Prostate cancer is one of the common cancers in old men. Androgen ablation is a major option for the treatment of the metastatic diseases. However, most of the cancers progress to a more aggressive stage, so-called androgen-independent (or hormone refractory) relapse beyond any cure. The androgen receptor (AR) is an important factor in regulating t...

Androgen receptor (AR) is a critical factor in the development and progression of prostate cancer. We and others recently demonstrated that eliminating AR expression leads to apoptotic cell death in AR-positive prostate cancer cells. To understand the mechanisms of AR-dependent survival, we performed a genome-wide search for AR-regulated survival g...

Lithium is an existing drug for bipolar disorder and its uptake was recently linked to reduced tumor incidence compared to the general population. The major target of lithium action is glycogen synthase kinase 3 (GSK-3). Since GSK-3 expression and activation are associated with prostate cancer progression, the anti-cancer potential of lithium on pr...