A Synergistic Strategy Combining Chemotherapy and Photodynamic Therapy to Eradicate Prostate Cancer.

Prostate cancer is the most prevalent cancer among men in the United States and is a leading cause of cancer-related death. Prostate specific membrane antigen (PSMA) has been established as a biomarker for prostate cancer diagnosis and treatment. This study aimed to develop a novel theranostic agent, PSMA-1-MMAE-Pc413, which integrates a PSMA-targeting ligand, the photosensitizer Pc413, and the microtubular inhibitor monomethyl auristatin E (MMAE) for synergistic therapeutic efficacy.

Evaluation of a photodynamic therapy agent using a canine prostate cancer model.

Background: Male dogs can develop spontaneous prostate cancer, which is similar physiologically to human disease. Recently, Tweedle and coworkers have developed an orthotopic canine prostate model allowing implanted tumors and therapeutic agents to be tested in a more translational large animal model. We used the canine model to evaluate prostate-specific membrane antigen (PSMA)-targeted gold nanoparticles as a theranostic approach for fluorescence (FL) imaging and photodynamic therapy (PDT) of early stage prostate cancer.

Can targeted nanoparticles distinguish cancer metastasis from inflammation?

Targeting ligands have been widely used to increase the intratumoral accumulation of nanoparticles and their uptake by cancer cells. However, these ligands aim at targets that are often also upregulated in inflamed tissues. Here, we assessed the ability of targeted nanoparticles to distinguish metastatic cancer from sites of inflammation.

Targeted Chemoradiotherapy of Prostate Cancer Using Gold Nanoclusters with Protease Activatable Monomethyl Auristatin E.

Combined radiotherapy (RT) and chemotherapy are prescribed to patients with advanced prostate cancer (PCa) to increase their survival; however, radiation-related side effects and systematic toxicity caused by chemotherapeutic drugs are unavoidable. To improve the precision and efficacy of concurrent RT and chemotherapy, we have developed a PCa-targeted gold nanocluster radiosensitizer conjugated with a highly potent cytotoxin, monomethyl auristatin E, PSMA-AuNC-MMAE, for RT and chemotherapy of PCa. This approach resulted in enhanced uptake of NCs by PSMA-positive cancer cells, targeted chemotherapy, and increased efficacy of RT both and .

Development of a novel castration-resistant orthotopic prostate cancer model in New Zealand White rabbit.

Background: Prostate cancer (PCa) models in mice and rats are limited by their size and lack of a clearly delineated or easily accessible prostate gland. The canine PCa model is currently the only large animal model which can be used to test new preclinical interventions but is costly and availability is sparse. As an alternative, we developed an orthotopic human prostate tumor model in an immunosuppressed New Zealand White rabbit.

Molecular imaging of orthotopic prostate cancer with nanobubble ultrasound contrast agents targeted to PSMA.

Ultrasound imaging is routinely used to guide prostate biopsies, yet delineation of tumors within the prostate gland is extremely challenging, even with microbubble (MB) contrast. A more effective ultrasound protocol is needed that can effectively localize malignancies for targeted biopsy or aid in patient selection and treatment planning for organ-sparing focal therapy. This study focused on evaluating the application of a novel nanobubble ultrasound contrast agent targeted to the prostate specific membrane antigen (PSMA-targeted NBs) in ultrasound imaging of prostate cancer (PCa) in vivo using a clinically relevant orthotopic tumor model in nude mice.

Nanoparticles Yield Increased Drug Uptake and Therapeutic Efficacy upon Sequential Near-Infrared Irradiation.

Nanoparticles offer great opportunities for precision medicine. However, the use of nanoparticles as smart photosensitizers that target tumor biomarkers and are responsive to the tumor microenvironment has yet to be explored. Herein, prostate cancer (PCa)-selective theranostic gold nanoparticles (AuNPs) for precise cancer imaging and therapy are developed.

Targeted Radiosensitizers for MR-Guided Radiation Therapy of Prostate Cancer.

Adjuvant radiotherapy is frequently prescribed to treat cancer. To minimize radiation-related damage to healthy tissue, it requires high precision in tumor localization and radiation dose delivery. This can be achieved by MR guidance and targeted amplification of radiation dose selectively to tumors by using radiosensitizers.

Prostate-specific membrane antigen targeted gold nanoparticles for prostate cancer radiotherapy: does size matter for targeted particles?

Since the introduction of PSA testing, significantly more men have been diagnosed and treated for prostate cancer. Localized prostate cancer typically is treated with prostatectomy, however there is still a high risk of recurrence after surgery, and adjuvant radiation has been shown to mitigate disease progression. X-ray therapy is frequently used as an adjuvant to treat prostate cancer, but is an imperfect tool.

Targeted Gold Nanocluster-Enhanced Radiotherapy of Prostate Cancer.

For over a hundred years, X-rays have been a main component of the radiotherapeutic approaches to treat cancer. Yet, to date, no radiosensitizer has been developed to selectively target prostate cancer. Gold has excellent X-ray absorptivity and is used as a radiotherapy enhancing material.

Sink or float? Characterization of shell-stabilized bulk nanobubbles using a resonant mass measurement technique.

Nano-sized shell-stabilized gas bubbles have applications in various fields ranging from environmental science to biomedical engineering. A resonant mass measurement (RMM) technique is demonstrated here as a new and only method capable of simultaneously measuring the size and concentration of buoyant and non-buoyant particles in a nanobubble sample used as a next-generation ultrasound contrast agent.

Prostate-Specific Membrane Antigen Targeted Gold Nanoparticles for Theranostics of Prostate Cancer.

Prostate cancer is one of the most common cancers and among the leading causes of cancer deaths in the United States. Men diagnosed with the disease typically undergo radical prostatectomy, which often results in incontinence and impotence. Recurrence of the disease is often experienced by most patients with incomplete prostatectomy during surgery.

Treatment of Invasive Brain Tumors Using a Chain-like Nanoparticle.

Glioblastoma multiforme is generally recalcitrant to current surgical and local radiotherapeutic approaches. Moreover, systemic chemotherapeutic approaches are impeded by the blood-tumor barrier. To circumvent limitations in the latter area, we developed a multicomponent, chain-like nanoparticle that can penetrate brain tumors, composed of three iron oxide nanospheres and one drug-loaded liposome linked chemically into a linear chain-like assembly.

Microscopic detection of quenched activity-based optical imaging probes using an antibody detection system: localizing protease activity.

Purpose: The family of cathepsin proteases plays an important physiological role in both normal physiology and in the physiology of many human diseases. This activity, which is upregulated in many cancers, can be exploited for tumor imaging both in vivo and ex vivo. To characterize the behavior of a topically applied quenched fluorescent activity-based probe, GB119, ex vivo, we developed a basic immunohistochemistry technique to identify unquenched GB119 within tissue.

On-command drug release from nanochains inhibits growth of breast tumors.

Purpose: To evaluate the ability of radiofrequency (RF)-triggered drug release from a multicomponent chain-shaped nanoparticle to inhibit the growth of an aggressive breast tumor.

Methods: A two-step solid phase chemistry was employed to synthesize doxorubicin-loaded nanochains, which were composed of three iron oxide nanospheres and one doxorubicin-loaded liposome assembled in a 100-nm-long linear nanochain. The nanochains were tested in the 4T1-LUC-GFP orthotopic mouse model, which is a highly aggressive breast cancer model.

Expanding the utility of beta-galactosidase complementation: piece by piece.

The ability to image and quantify multiple biomarkers in disease necessitates the development of split reporter fragment platforms. We have divided the beta-galactosidase enzyme into unique, independent polypeptides that are able to reassemble and complement enzymatic activity in bacteria and in mammalian cells. We created two sets of complementing pairs that individually have no enzymatic activity.

Spatial and temporal aspects of cAMP signalling in cardiac myocytes.

1. beta(1)-Adrenoceptor and M(2) muscarinic receptor regulation of cAMP production plays a pivotal role in autonomic regulation of cardiac myocyte function. However, not all responses are easily explained by a uniform increase or decrease in cAMP activity throughout the entire cell.

Cytoplasmic cAMP concentrations in intact cardiac myocytes.

In cardiac myocytes there is evidence that activation of some receptors can regulate protein kinase A (PKA)-dependent responses by stimulating cAMP production that is limited to discrete intracellular domains. We previously developed a computational model of compartmentalized cAMP signaling to investigate the feasibility of this idea. The model was able to reproduce experimental results demonstrating that both beta(1)-adrenergic and M(2) muscarinic receptor-mediated cAMP changes occur in microdomains associated with PKA signaling.

Expression of Bmi-1 in epidermis enhances cell survival by altering cell cycle regulatory protein expression and inhibiting apoptosis.

The polycomb group (PcG) genes are epigenetic suppressors of gene expression that play an important role in development. In this study, we examine the role of Bmi-1 (B-cell-specific Moloney murine leukemia virus integration site 1) as a regulator of human epidermal keratinocyte survival. We identify Bmi-1 mRNA and protein expression in epidermis and in cultured human keratinocytes.

cAMP microdomains and L-type Ca2+ channel regulation in guinea-pig ventricular myocytes.

Many different receptors can stimulate cAMP synthesis in the heart, but not all elicit the same functional responses. For example, it has been recognized for some time that prostaglandins such as PGE1 increase cAMP production and activate PKA, but they do not elicit responses like those produced by beta-adrenergic receptor (betaAR) agonists such as isoproterenol (isoprenaline), even though both stimulate the same signalling pathway. In the present study, we confirm that isoproterenol, but not PGE1, is able to produce cAMP-dependent stimulation of the L-type Ca(2+) current in guinea pig ventricular myocytes.

The distal and proximal regulatory regions of the involucrin gene promoter have distinct functions and are required for in vivo involucrin expression.

Involucrin is a marker of human keratinocyte differentiation. Previous studies show that the human involucrin gene promoter has two distinct regulatory regions - the proximal regulatory region (PRR) and the distal regulatory region (DRR). To study the role of these regions in vivo, we have constructed human involucrin promoter transgenic mice and monitored the impact of specific promoter mutations on involucrin gene expression.

Involucrin expression in the corneal epithelium: an essential role for Sp1 transcription factors.

Purpose: Identifying the mechanism(s) that regulate gene expression during the transition of the limbal stem cell to a differentiated superficial cell is an important area of interest in the corneal epithelium.

Methods: However, the factors that regulate gene expression during this process are not well understood. In the present study, the human involucrin (hINV) gene was used as a model to study gene expression in the corneal epithelium.