Yanfeng Qi - Academia.edu (original) (raw)

Papers by Yanfeng Qi

Understanding Biology Using Peptides

Semiconductor quantum dots have been used for labeling many biomacromolecules and small molecules... more Semiconductor quantum dots have been used for labeling many biomacromolecules and small molecules, but it remains a challenge to couple it with short active peptides that play critical roles in many physiological processes. Several binding methods for QDs and short peptides have been reported, but all with some limitations in amino acid sequence. In this paper, we report a method for synthesis of quantum dots labeled short peptides that is appropriate to any short peptide. The quantum dots (CdTe)-labeled short peptides were verified and characterized by RP-HPLC. The QDs-labeled peptides were applied to monitor the specific binding between two immune peptides and T cell surface receptors. The quantum dots-labeled immune peptides provide a powerful method for studying immunological functions of these peptides, and an effective strategy for monitoring their complex modulating processes in vivo.

Cancer research, Jan 9, 2015

Constitutively-active androgen receptor splice variants (AR-V) lacking the ligand-binding domain ... more Constitutively-active androgen receptor splice variants (AR-V) lacking the ligand-binding domain have been implicated in the pathogenesis of castration-resistant prostate cancer and in mediating resistance to newer drugs that target the androgen axis. AR-V regulate expression of both canonical AR targets and a unique set of cancer-specific targets that are enriched for cell cycle functions. However, little is known about how AR-V control gene expression. Here we report that two major AR-V, termed AR-V7 and ARv567es, not only homodimerize and heterodimerize with each other but also heterodimerize with full-length androgen receptor (AR-FL) in an androgen-independent manner. We found that heterodimeration of AR-V and AR-FL was mediated by N- and C-terminal interactions and by the DNA-binding domains of each molecule, whereas AR-V homoimerization was mediated only by DNA-binding domain interactions. Notably, AR-V dimerization was required to transactivate target genes and to confer cast...

The Journal of Urology, 2015

purpose of this study was to determine the tissue specific expression, co-localization, and ratio... more purpose of this study was to determine the tissue specific expression, co-localization, and ratio of AR and ARv7 in normal and hormonenaïve PCa. METHODS: Antibodies to detect full length AR and ARv7 were used on hormone-naïve tumor-adjacent normal prostate, high-grade intraepithelial neoplasia (HGPIN), primary PCa samples, and metastases (Mets). Tissue specific protein expression and co-localization of AR and ARv7 were quantified using multispectral imaging technology. Ratios of AR and ARv7 were determined. RESULTS: AR and ARv7 were observed in nuclei of stromal and epithelial cells from all normal and pathologic specimens. In epithelial tissue, nuclear expression of ARv7 was significantly increased in HGPIN and Mets compared to normal prostate, but not PCa. Expression of AR was increased in PCa and Mets but not HGPIN. The proportion of double negative (AR-/ARv7-) cells was lower in HGPIN, PCa, and Mets compared to normal prostate. The proportion of single positive AR-/ARv7þ was higher in HGPIN and the number of single positive ARþ/ARv7-cells was higher in PCa. Double positive ARþ/ ARv7þ cells were more abundant in Mets. In stromal tissues, expression of ARv7 was increased in HGPIN and Mets, but not PCa. Expression of AR was similar in HGPIN and PCa compared to normal prostate, but AR was significantly higher in Mets. The number of double negative AR-/ARv7-cells was lower in HGPIN and Mets. Single positive AR-/ARv7þ cells were increased in HGPIN. No changes were found in single positive ARþ/ARv7-cells. The proportion of double positive ARþ/ARv7þ cells was higher in Mets than normal tissue. The epithelial ratio of ARv7:AR was significantly higher in PCa than normal prostate tissue (p¼0.0003) but not HGPIN (p¼0.99) or Mets (p¼0.57). In the stroma, the ratio of ARv7:AR was higher in HGPIN (p¼0.02) but not PCa (p>0.99) or Mets (p>0.99). CONCLUSIONS: ARv7 is expressed in both the epithelia and stroma during early stages of prostate cancer, and expression of ARv7 is increased in HGPIN in the absence of changes in AR expression. These data support a potential role of ARv7 signaling in early stages of prostate cancer development.

American journal of clinical and experimental urology, 2013

Significant advances in our understanding of continued androgen receptor (AR) signaling in castra... more Significant advances in our understanding of continued androgen receptor (AR) signaling in castration-resistant prostate cancer have led to the development and FDA approval of two next-generation androgen-directed therapies, abiraterone and enzalutamide. These new therapies heralded a new era of prostate cancer therapy. However, disease progression during androgen-directed therapies remains the most critical challenge in the clinical management of prostate cancer. Accumulating evidence points to an important contribution of constitutively-active AR splice variants to AR-driven tumor progression during androgen-directed therapies. In this review, we will focus on the structure, activity, detection, clinical relevance, and mechanisms of production of AR splice variants.

Advances in Experimental Medicine and Biology, 2009

Oncotarget, Jan 30, 2014

Upregulation of constitutively-active androgen receptor splice variants (AR-Vs) has been implicat... more Upregulation of constitutively-active androgen receptor splice variants (AR-Vs) has been implicated in AR-driven tumor progression in castration-resistant prostate cancer. To date, functional studies of AR-Vs have been focused mainly on their ability to regulate gene expression independent of the full-length AR (AR-FL). Here, we showed that AR-V7 and ARv567es, two major AR-Vs, both facilitated AR-FL nuclear localization in the absence of androgen and mitigated the ability of the antiandrogen enzalutamide to inhibit AR-FL nuclear trafficking. AR-V bound to the promoter of its specific target without AR-FL, but co-occupied the promoter of canonical AR target with AR-FL in a mutually-dependent manner. AR-V expression attenuated both androgen and enzalutamide modulation of AR-FL activity/cell growth, and mitigated the in vivo antitumor efficacy of enzalutamide. Furthermore, ARv567es levels were upregulated in xenograft tumors that had acquired enzalutamide resistance. Collectively, this...

PloS one, 2014

Castration-resistant progression of prostate cancer after androgen deprivation therapies remains ... more Castration-resistant progression of prostate cancer after androgen deprivation therapies remains the most critical challenge in the clinical management of prostate cancer. Resurgent androgen receptor (AR) activity is an established driver of castration-resistant progression, and upregulation of the full-length AR (AR-FL) and constitutively-active AR splice variants (AR-Vs) has been implicated to contribute to the resurgent AR activity. We reported previously that ginsenoside 20(S)-protopanaxadiol-aglycone (PPD) can reduce the abundance of both AR-FL and AR-Vs. In the present study, we further showed that the effect of PPD on AR expression and target genes was independent of androgen. PPD treatment resulted in a suppression of ligand-independent AR transactivation. Moreover, PPD delayed castration-resistant regrowth of LNCaP xenograft tumors after androgen deprivation and inhibited the growth of castration-resistant 22Rv1 xenograft tumors with endogenous expression of AR-FL and AR-Vs...

PLoS ONE, 2012

A major challenge in breast cancer therapy is the lack of an effective therapeutic option for a p... more A major challenge in breast cancer therapy is the lack of an effective therapeutic option for a particularly aggressive subtype of breast cancer, triple-negative breast cancer. Here we provide the first preclinical evidence that a second-generation selenium compound, methylseleninic acid, significantly enhances the anticancer efficacy of paclitaxel in triple-negative breast cancer. Through combination-index value calculation, we demonstrated that methylseleninic acid synergistically enhanced the growth inhibitory effect of paclitaxel in triple-negative breast cancer cells. The synergism was attributable to more pronounced induction of caspase-mediated apoptosis, arrest of cell cycle progression at the G2/M checkpoint, and inhibition of cell proliferation. Treatment of SCID mice bearing MDA-MB-231 triple-negative breast cancer xenografts for four weeks with methylseleninic acid (4.5 mg/kg/day, orally) and paclitaxel (10 mg/kg/week, through intraperitoneal injection) resulted in a more pronounced inhibition of tumor growth compared with either agent alone. The attenuated tumor growth correlated with a decrease in tumor cell proliferation and an induction of apoptosis. The in vivo study also indicated the safety of using methylseleninic acid in the combination regime. Our findings thus provide strong justification for the further development of methylseleninic acid and paclitaxel combination therapy for the treatment of triple-negative breast cancer.

International Journal of Cancer, 2012

As a public health problem, prostate cancer engenders huge economic and life‐quality burden. Deve... more As a public health problem, prostate cancer engenders huge economic and life‐quality burden. Developing effective chemopreventive regimens to alleviate the burden remains a major challenge. Androgen signaling is vital to the development and progression of prostate cancer. Targeting androgen signaling via blocking the production of the potent ligand dihydrotestosterone has been shown to decrease prostate cancer incidence. However, the potential of increasing the incidence of high‐grade prostate cancers has been a concern. Mechanisms of disease progression after the intervention may include increased expression of androgen receptor (AR) in prostate tissue and expression of the constitutively active AR splice variants (AR‐Vs) lacking the ligand‐binding domain. Thus, novel agents targeting the receptor, preferentially both the full‐length and AR‐Vs, are urgently needed. In the present study, we show that ginsenoside 20(S)‐protopanaxadiol‐aglycone (PPD) effectively downregulates the expr...

International Journal of Cancer, 2013

The next-generation antiandrogen MDV3100 prolongs overall survival of patients with metastatic ca... more The next-generation antiandrogen MDV3100 prolongs overall survival of patients with metastatic castration-resistant prostate cancer (CRPC). However, patient responses are variable, and survival benefit remains relatively small. Developing effective modality to improve MDV3100 efficacy is urgently needed. Recent evidence suggests that constitutively active androgen receptor splice variants (AR-Vs) drive resistance to MDV3100. In our study, we show that methylselenol prodrug downregulates the expression and activity of both the full-length AR (AR-FL) and AR-Vs. The downregulation is independent of androgen and could be attributable to repressed transcription of the AR gene. Cotreatment with methylselenol prodrug and MDV3100 suppresses AR signaling more dramatically than either agent alone, and synergistically inhibits the growth of CRPC cells in vitro. The combinatorial efficacy is observed in not only AR-V-expressing cells but also cells expressing predominantly AR-FL, likely owing to the ability of the two drugs to block the AR signaling cascade at distinct steps. Ectopic expression of AR-FL or AR-V7 attenuates the combinatorial efficacy, indicating that downregulating AR-FL and AR-V7 is importantly involved in mediating the combinatorial efficacy. Significantly, methylselenol prodrug also downregulates AR-FL and AR-Vs in vivo and substantially improves the antitumor efficacy of MDV3100. These findings support a potential combination therapy for improving MDV3100 efficacy, and provide a rationale for evaluating the clinical application of combining methylselenol prodrug with MDV3100 for the treatment of CRPC.