Robert Bok

Bio: Robert Bok is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Prostate cancer & Magnetic resonance imaging. The author has an hindex of 44, co-authored 113 publications receiving 6862 citations. Previous affiliations of Robert Bok include Rafael Advanced Defense Systems & University of California.

Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate

Abstract: This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-13C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo 13C MR data, it is possible to evaluate the distribution of agents such as [1-13C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-13C]lactate in tumor, with the ratio of [1-13C]lactate/[1-13C]pyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect 13C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized [1-13C]pyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized [1-13C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-13C]lactate/[1-13C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials.

Hyperpolarized 13C Lactate, Pyruvate, and Alanine: Noninvasive Biomarkers for Prostate Cancer Detection and Grading

Abstract: An extraordinary new technique using hyperpolarized (13)C-labeled pyruvate and taking advantage of increased glycolysis in cancer has the potential to improve the way magnetic resonance imaging is used for detection and characterization of prostate cancer The aim of this study was to quantify, for the first time, differences in hyperpolarized [1-(13)C] pyruvate and its metabolic products between the various histologic grades of prostate cancer using the transgenic adenocarcinoma of mouse prostate (TRAMP) model Fast spectroscopic imaging techniques were used to image lactate, alanine, and total hyperpolarized carbon (THC = lactate + pyruvate + alanine) from the entire abdomen of normal mice and TRAMP mice with low- and high-grade prostate tumors in 14 s Within 1 week, the mice were dissected and the tumors were histologically analyzed Hyperpolarized lactate SNR levels significantly increased (P < 005) with cancer development and progression (41 +/- 11, 74 +/- 17, and 154 +/- 24 in normal prostates, low-grade primary tumors, and high-grade primary tumors, respectively) and had a correlation coefficient of 095 with the histologic grade In addition, there was minimal overlap in the lactate levels between the three groups with only one of the seven normal prostates overlapping with the low-grade primary tumors The amount of THC, a possible measure of substrate uptake, and hyperpolarized alanine also increased with tumor grade but showed more overlap between the groups In summary, elevated hyperpolarized lactate and potentially THC and alanine are noninvasive biomarkers of prostate cancer presence and histologic grade that could be used in future three-dimensional (13)C spectroscopic imaging studies of prostate cancer patients

Angiogenesis inhibition by minocycline.

Abstract: We describe a new inhibitor of angiogenesis, minocycline, a semisynthetic tetracycline antimicrobial with anticollagenase properties. Minocycline was incorporated into controlled release polymers and tested in the rabbit cornea against neovascularization in the presence of the VX2 carcinoma. Inhibition by minocycline was shown to be comparable to that of the combination of heparin and cortisone, a potent inhibitor of angiogenesis. Minocycline decreased tumor-induced angiogenesis by a factor of 4.5, 4.4, and 2.9 at 7, 14, and 21 days, respectively. At the end of the experiment, whereas the corneas with empty polymers had large, invasive, exophytic tumors, none of the corneas with minocycline had such vascular masses. Recently, studies of agents that disrupt collagen synthesis and deposition have yielded several new angiogenesis inhibitors. We suggest that investigation of agents that disrupt collagenolysis may similarly identify other angiogenesis inhibitors and further clarify the mechanisms of angiogenesis.

Hyperpolarized C-13 spectroscopic imaging of the TRAMP mouse at 3T—Initial experience

Abstract: The transgenic adenocarcinoma of mouse prostate (TRAMP) mouse is a well-studied murine model of prostate cancer with histopathology and disease progression that mimic the human disease. To investigate differences in cellular bioenergetics between normal prostate epithelial cells and prostate tumor cells, in vivo MR spectroscopic (MRS) studies with non-proton nuclei, such as 13C, in the TRAMP model would be extremely useful. The recent development of a method for retaining dynamic nuclear polarization (DNP) in solution permits high signal-to-noise ratio (SNR) 13C MRI or MRSI data to be obtained following injection of a hyperpolarized 13C agent. In this transgenic mouse study, this method was applied using a double spin-echo (DSE) pulse sequence with a small-tip-angle excitation RF pulse, hyperbolic-secant refocusing pulses, and a flyback echo-planar readout trajectory for fast (10–14 s) MRSI of 13C pyruvate (pyr) and its metabolic products at 0.135 cm3 nominal spatial resolution. Elevated 13C lactate (lac) was observed in both primary and metastatic tumors, demonstrating the feasibility of studying cellular bioenergetics in vivo with DNP hyperpolarized 13C MRSI. Magn Reson Med, 2007. © 2007 Wiley-Liss, Inc.

Androgen Receptor in Prostate Cancer

Abstract: The normal development and maintenance of the prostate is dependent on androgen acting through the androgen receptor (AR). AR remains important in the development and progression of prostate cancer. AR expression is maintained throughout prostate cancer progression, and the majority of androgen-independent or hormone refractory prostate cancers express AR. Mutation of AR, especially mutations that result in a relaxation of AR ligand specificity, may contribute to the progression of prostate cancer and the failure of endocrine therapy by allowing AR transcriptional activation in response to antiandrogens or other endogenous hormones. Similarly, alterations in the relative expression of AR coregulators have been found to occur with prostate cancer progression and may contribute to differences in AR ligand specificity or transcriptional activity. Prostate cancer progression is also associated with increased growth factor production and an altered response to growth factors by prostate cancer cells. The kinase signal transduction cascades initiated by mitogenic growth factors modulate the transcriptional activity of AR and the interaction between AR and AR coactivators. The inhibition of AR activity through mechanisms in addition to androgen ablation, such as modulation of signal transduction pathways, may delay prostate cancer progression.

Cytokines in cancer pathogenesis and cancer therapy

Abstract: The mixture of cytokines that is produced in the tumour microenvironment has an important role in cancer pathogenesis. Cytokines that are released in response to infection, inflammation and immunity can function to inhibit tumour development and progression. Alternatively, cancer cells can respond to host-derived cytokines that promote growth, attenuate apoptosis and facilitate invasion and metastasis. A more detailed understanding of cytokine–tumour-cell interactions provides new opportunities for improving cancer immunotherapy.

Applications of Nanoparticles in Biology

Abstract: The wide variety of core materials available, coupled with tunable surface properties, make nanoparticles an excellent platform for a broad range of biological and biomedical applications. This Review provides an introduction to nanoparticle–biomolecular interactions as well as recent applications of nanoparticles in biological sensing, delivery, and imaging of live cells and tissues.