Mohini Lutchman Keith R Solomon and Michael R Freeman

Cholesterol, a sterolic lipid, accumulates in solid tumors. Biochemical mechanisms essential to cholesterol metabolism are altered with age and with the transition to the malignant state. In cell membranes, cholesterol is a mediator of the liquid-ordered state, a biophysical condition that provokes sequestration within discrete membrane microdomains of certain signaling proteins and other lipids. Cholesterol-enriched membrane domains, commonly referred to as lipid rafts, serve as platforms for...

In Vivo Prostate Tumor Targeting And Imaging

Akerman et al. first reported the use of QD-peptide conjugates to target tumor vasculatures, but the QD probes were not detected in living animals (52). Nonetheless, their in vitro histological results revealed that QDs homed to tumor vessels guided by the peptides and were able to escape clearance by the reticuloendothelial system. Most recently, Gao et al. reported a new class of multifunctional QD probes for simultaneous targeting and imaging of tumors in live animals (25). This class of QD...

Info

In vivo MRI detection of switchable ferritin expression in C6 rat glioma tumors. MRI of ferritin expressing tumors at different times after inoculation of C6-TET-EGFP-HA-ferritin tumor cells in the hind limb of nude mice. Tetracycline (TET) and sucrose were supplied in drinking water, starting 2 days before inoculation. (A) Rj and R2 maps of tumor regions overlaid on the MRI scans are shown for two representative mice from each group. (B) Rj and R2 values at the tumor site in the...

Donald S Coffey PhD

Johns Hopkins University School of Medicine, Baltimore, MD 2007 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. All authored papers, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily...

Introduction

Prostate cancer (CaP) is the second-leading cause of cancer deaths among men in the Western world. In 2004, approx 230,000 men were diagnosed and 30,000 men died from advanced disease. Understanding the biology of CaP is essential to the development of novel therapeutic strategies. To do this effectively, researchers need access to cell lines, animal models, and biospecimens. Ideally, these should reflect characteristics of the disease from early diagnosis through the period of...

Xiaohu Gao Yun Xing Leland W K Chung and Shuming

Quantum dots (QDs), tiny light-emitting particles on the nanometer scale, are emerging as a new class of fluorescent probes for cancer cell imaging and molecular profiling. In comparison with organic dyes and fluorescent proteins, QDs have unique optical and electronic properties, such as size-tunable light emission, improved signal brightness, resistance against photobleaching, and simultaneous excitation of multiple fluorescence colors. These properties are most promising for improving the...

Ar Structure And Function In The Prostate

The androgen hormone dihydrotestosterone (DHT) is the principal regulator of prostate development and growth during embryonal development and puberty (5). In the adult prostate, it is required for maintenance of tissue homeostasis and secretory function. The circulating steroid hormone, testosterone, diffuses into the cells and is there converted by the 5-a reductase enzymes to the more potent androgen, DHT (6). DHT and other androgen hormones present in the prostate cells bind to a...

Summary

Focal atrophy is an extremely common histological alteration in the human prostate. Although most investigators during the last several decades have assumed that it is not relevant to prostate cancer, some pathologists suggested that prostate cancers might arise from atrophy as early as the 1930s (1). Chronic inflammation is a major contributing cause of cancer in many organ systems. Only in the last few years have investigators begun to examine whether chronic inflammation, which is virtually...

Immunotherapy

Prostate cancer, like most cancers, has developed mechanisms to evade the host immune system. Such mechanisms include the downregulation of class I MHC molecules on the tumor cell surface (198) as well as the downregulation of the co-stimulatory B7 molecules (199). These means of evasion result in decreased presentation of tumor antigens to CTLs. The goal of immunotherapy is to enhance the host immune response to prostate cancer cells. Current approaches involve ex vivo gene therapy of...

Summary And Conclusion

Where is the study of prostate cancer susceptibility taking us Hopefully, by extensive study of prostate cancer pedigrees, we can more effectively optimize the predictive information of family history. It will most likely be important to provide more clinical detail of the prostate cancers that compose the family history, rather than making all cases with a positive biopsy of equal significance. In addition, defining genes that affect prostate cancer risk in families as well as sporadic disease...

Pleiotropic Effects Of Cholesterol Synthesis Inhibition

HMG-CoA reductase inhibitors have been demonstrated to exert potent anticancer effects in cell culture and animal models. In vitro studies on cell lines have shown that statins can inhibit tumor cell growth (56) by inducing cell cycle arrest or apoptosis (57-59). These activities have been observed in breast and leukemia culture models and during treatment of xenotransplanted EJ3-derived colorectal tumors in mice (60,61). Several studies of lovastatin's effects on human lymphoma, glioma,...

Alternative Approaches To Find Prostate Cancer Susceptibility Genes

Another important approach to find prostate cancer susceptibility genes has been to perform association studies in populations of men with and without prostate cancer, typically without regard to family history. These case control studies have been greatly aided by the increased understanding of the variability of the human genome sequence among different individuals and the concept that common diseases may be caused by common genetic variants in the population (65). Thus, by simply examining...

Osteoclastic Bone Metastases

RANKL is a key osteoclastogenic factor. Several lines of evidence support the role of RANKL in CaP-mediated osteolysis. Although a bone metastatic CaP cell line has been shown to express OPG (112), that same line overexpresses RANKL (113). Additionally, in normal prostate, OPG protein was detected in luminal epithelial and stromal cells (5-65 and 15-70 , respectively) and RANKL immunoreactivity was observed in 15 to 50 of basal epithelial cells, 40 to 90 of luminal epithelial Osteogenic Factors...

Contribution Of Nonsteroidal Activation Of The Ar To Prostate Cancer Progression

Most steroid receptors can be activated in a ligand-independent manner or in a synergistic manner by a ligand and a cytokine or other compound that increases intracellular kinase levels. For example, human estrogen receptor-a exhibits ligand-independent activation, whereas progesterone and glucocorticoid receptor activity is regulated in a cooperative manner. This type of activation of the AR is of importance for advanced stage prostate cancer. Because of androgen-ablation therapy, the levels...

Important Expression Changes In Cap Progression

Expression profiling may also be very important in identifying the driving genetic changes in individual prostate tumors. For example, despite its importance in terms of therapeutics and biologi- Fig. 4. Transcript and protein expression of myosin light chain kinase (MYLK). (A) Oncomine (www. oncomine.org) was used to visualize the normalized expression of MYLK across eight data sets (Lapointe et al. 40 1 Dhanasekaran et al. 26 2 Welsh et al. 28 3 Luo et al. 29 4 LaTulippe et al. 41 5 Luo et...

Telomerase Regulation

Telomerase regulation is complex and occurs at multiple levels, including gene transcription, mRNA splicing, posttranslational modifications, proper assembly of enzyme subunits, and recruitment and access to the telomere itself (172-178). Known transcriptional regulators of hTERT include the positive regulator, c-Myc, and the negatively acting regulators, menin, Rak, SIP1, and the c-Myc antagonist, Mad1 (179). c-Myc mRNA is reportedly increased in prostate cancer, is correlated with a worse...

How Cancer Cells Respond To A Changing Tumor Microenvironment

Cancer cells are capable of mimicking the characteristics of cells in the tumor microenvironment. Dramatic examples include osteomimicry, the ability of cancer cells to express genes normally highly restricted to bone cells before, during, or after metastasis through the synthesis, secretion, and accumulation of bone-like proteins, such as osteocalcin (OC), osteopontin, bone sialoprotein (BSP), and osteonectin, even forming mineralizing bone under certain culture conditions (29,52,53). Cancer...

Keratin Expression

Prostate epithelial cell types are defined by location, morphology, and the expression of specific gene products (reviewed in refs. 65-68). Focal atrophy lesions are very heterogeneous in morphology and in terms of which molecular markers they express. In terms of keratins, normal luminal cells contain strong staining for keratins 8 and 18 and absent staining for keratins 5 and 14. Basal cells, by contrast, stain strongly for keratins 5 and most, albeit not all, also stain strongly for keratin...

Molecular Imaging For Cancer Gene Therapy

With a better understanding of the molecular mechanisms underlying cancer development and the rapid advances in imaging capabilities, it is now possible to detect tumors, monitor their growth, measure their invasive ability, and visualize the effect of anticancer therapy in living subjects. Previously, the two ways to detect tumors and monitor their growth were biopsy or surgery, both invasive procedures. In the last decade, several noninvasive imaging technologies have been developed, which...

Identifying Gene Expression Correlates Of Gleason Score

Several studies, including those that also profiled metastatic samples or attempted to predict recurrence, have attempted to identify expression patterns that correlate with Gleason grade or score. Theoretically, these studies should be able to shed biological insight into molecular changes that characterize the observed histological patterns. Welsh et al. profiled 9 normal prostate samples, 23 localized tumors, and 1 metastatic CaP sample on Affymetrix U95a GeneChips containing probes for...

Osteoblastic Bone Metastases

Osteoblastic Lesion

There are many challenges to determining the mechanisms that contribute to the selective development of CaP in bone (80-82). These include mechanisms of homing and attachment to bone and invasion into bone. However, once in the bone, CaP tumors have pathobiology that seems to be somewhat unique to cancer skeletal metastases. Specifically, CaP skeletal metastases are most often radiographically characterized as osteoblastic (i.e., increased mineral density at the site of the lesion) as opposed...

Abnormal Dna Methylation Changes In Prostate Cancer

The first gene found to be silenced via somatic CpG island hypermethylation in prostate cancer was GSTP1, encoding the n-class glutathione-S-transferase (GST), an enzyme capable of detoxifying electrophilic and oxidant carcinogens (28) (Fig. 1). This genome change remains the most common somatic genome abnormality of any kind (> 90 of cases) reported thus far for prostate cancer, appearing earlier and more frequently than other gene defects that arise during prostate cancer development (29)....

Acute Inflammation

Acute inflammation can vary from essentially none to extensive regions of abscess formation with massive tissue destruction that is associated with acute bacterial prostatitis. More often, there are small foci of acute inflammation involving small groups of acini that may contain frank epithelial Fig. 5. Acute inflammation in the prostate. H& E. (A) Simple atrophy with polymorphonuclear neutrophils infiltration lumen (lu), stroma (st), and causing localized epithelial necrosis. Original...

Steroid Hormone Regulation Of Telomerase In The Prostate

In the prostate, telomerase activity is subject to regulation by steroid hormones, particularly andro-gens. Normal prostate tissues free of cancer, as well as cultured normal prostate epithelial cells, are typically negative for telomerase activity in the presence of androgen (Table 1). However, androgen withdrawal leads to the activation of telomerase. This was first observed in the involuted residual prostate and seminal vesicles of the Copenhagen rat, in which telomerase activity becomes...

LNCaP and PC346

For many years, LNCaP and PC-346 were the only xenografts available for progression studies (50-52). LNCaP produces PSA but has a mutated androgen receptor. This mutation results in a promiscuous androgen receptor that can bind to other steroids (53). PC-346 also produces PSA and has a wild-type androgen receptor. Although both lines are androgen sensitive, they are not androgen dependent androgen withdrawal generally resulted in no more than a 10 reduction in tumor volume, although, with...

Opg Report Where Tumor Detected

Histological appearance of LNCaP tumors growing in adult human bone fragments implanted into NOD SCID mice. Specimens obtained at 2 weeks (A and B), 4 weeks (C), 6 weeks (D and E), and 8 weeks (F) after LNCaP cell injection. (A) Metastatic foci were formed in bone marrow sinuses at 2 weeks after the inoculation of prostate cancer cells. Little initial response of bone marrow stromal cells was detected around the tumors (H& E, original magnification & times 100). (B)...

LAPC4 and LAPC9

LAPC-4, derived from a lymph node, and LAPC-9, derived from a bone metastasis, are two lines developed by the University of California, Los Angeles group under the direction of Charles Sawyers (45,47). Both xenografts produce PSA and show the desired pattern of significantly decreased PSA and tumor volume after castration, with restoration of PSA and tumor growth over time. Importantly, both of the xenografts express the wild-type androgen receptor. These characteristics make these xenografts...

Chromosomal Aberrations

Prostate cancer cells do not grow well in vitro, which is why traditional cytogenetics (G-banding) has been very uninformative in elucidating genetic alterations of prostate cancer. Typically, karyotyping has indicated normal 46XY chromosomes, obviously caused by overgrowth of normal fibroblasts (3). The development of modern molecular genetic methods, such as the analysis of loss of heterozygosity (LOH) and comparative genomic hybridization (CGH), has, however, enabled characterization of the...

Conclusions And The Injury And Regeneration Hypothesis Of Prostate Carcinogenesis

Focal prostate atrophy has several recognizable morphological patterns. It is rapidly becoming of great interest to many investigators. Although its etiology remains unknown, its relation to inflammation, PIN, BPH, and carcinoma is being explored by a number of new molecular approaches, as well as by traditional pathological association studies. Prostate inflammation also has several morphological patterns and is exceedingly common. Except in relatively rare cases in which infection can be...

The Plasticity Of Cancer And Stromal Fibroblasts

The developmental fate of a normal cell is regulated temporally and spatially by precise inductive cues from the cell microenvironment (25). In response to the signaling molecules, the gene expression profiles and the behaviors of a differentiating cell are subjected to changes allowing the normal differentiation program of developing organs to result. The genomic stability of the normal cell is desired and expected, and essential for survival (26). However, in the case of cancer, many of the...

Aatcc

Telomeres shorten as a result of cell division and oxidative stress. In the absence of compensatory mechanisms, telomeres shorten with each cell division and or because of unrepaired oxidative DNA damage. Note that the G-rich single-strand overhang is, in reality, much longer (approx 35-600 nucleotides), and that telomere losses are larger in magnitude than depicted here in this conceptual diagram (approx 100 base pairs lost per cell division, hundreds of base pairs lost for oxidative...

Candidate Prostate Cancer Susceptibility Genes Identified Through Linkage Studies

As described under Subheading 2, overwhelming evidence now exists to support a strong genetic influence in the etiology of at least some fraction of prostate cancer cases. However, the definition and characterization of this genetic influence is far more nebulous. Several major approaches have Fig. 2. Regions of implicated to harbor prostate cancer susceptibility genes from linkage studies of prostate cancer families. (Adapted from Simard et al. 2003). Fig. 2. Regions of implicated to harbor...

Prostate Epithelial Stem Cells

The existence of prostate epithelial stem cells and their putative role in prostate cancer development was proposed by Isaacs and Coffey (26-28). The stem cell model described in this paper is very similar to the one described above. Prostate cancers arise from prostate secretory acini. These acini are characterized by two cell layers that can be discriminated morphologically as undifferentiated basal cells and luminal cells primarily composed of terminally differentiated exocrine...

Cellular Imaging And Tracking

The use of QDs for sensitive and multicolor cellular imaging has seen major recent advances, because of significant improvements in QD synthesis, surface chemistry, and conjugation (Fig. 4). Wu et al. linked polymer-protected QDs to streptavidin and showed detailed cell skeleton structures using confocal microscopy (5). The improved photostability of QDs allowed acquisition of many consecutive focal-plane images and their reconstruction into a high-resolution 3D projection. The high electron...

William G Nelson Srinivasan Yegnasubramanian Patrick J Bastian Masashi Nakayama and Angelo M De Marzo

Prostatic carcinogenesis proceeds via the acquisition of both genetic and epigenetic alterations. The epi-genetic changes, principally in DNA methylation patterns and in chromatin structure, are equivalent to genetic changes, and often lead to defects in the functions of critical genes, which contribute to malignant cell behaviors. Epigenetic alterations also tend to appear at the earliest stages of prostate cancer development. As such, analysis of epigenetic genome changes has not only led to...

Enhancing The Activity Of Tissuespecific Promoters

As stated in the preceding discussion, promoters that are active only in certain tissues or inducible promoters play an essential role in the development of site-selective vectors for cancer gene therapy. Some promoters can be used directly because they combine strong transcriptional activity with high specificity. A good example of this category is the melanocyte-specific tyrosinase promoter (113). Commonly, however, TSPs suffer from weak transcriptional activity, which greatly limits their...

Closing Remarks

Molecular imaging has already had a significant impact on many areas of biology. The next few years will see further advances in this field, including gene therapy monitoring, where it will provide a realistic hope for better assessment of efficacy and safety aspects of preclinical and clinical development of gene therapy. The recent advances made in gene transfer imaging using enhanced PSA promoters and TSTA-based vector systems will substantially contribute to the development of gene therapy...

And Metastatic Samples To Understand Cap Progression

Although these studies do not seem to have uncovered the defining expression signature associated with CaP recurrence, they provide evidence that genetic differences can distinguish between high- and low-risk tumors. Further, these genetic differences may be poorly accounted for by, or independent of, the clinical and pathological parameters currently used to predict recurrence. Perhaps more importantly, these current studies provide important insight into CaP progression, particularly in the...

Tpr

Endosulfine-a NICE-1 protein Supervillin G protein pathway suppressor 2 Histone deacetylase 7A Contactin 1 Sorting nexin 5 F-box protein 6 Leukemia inhibitory factor receptor Synaptopodin 2 F-box and WD-40 domain protein 2 Ubiquitin specific protease 53 5'-nucleotidase, cytosolic III Translocated promoter region Regulator of G protein signaling 5 N-acylsphingosine aminohydrolase-like Chromobox homolog 3 a Meta-analysis (23) of three independent data sets (26,36,51) identified 34 dysregulated...

References

C. (2000). Use of nude mouse xenograft models in prostate cancer research. Prostate 43, 263-271. 2. van Bokhoven, A., Varella-Garcia, M., Korch, C., et al. (2003). Molecular characterization of human prostate carcinoma cell lines. Prostate 57, 205-225. 3. Rosol, T. J., Tannehill-Gregg, S. H., LeRoy, B. E., Mandl, S., and Contag, C. H. (2003). Animal models of bone metastasis. Cancer 97, 748-757. 4. Navone, N. M., Logothetis, C. J., von Eschenbach, A. C., and...

Hh Signaling In Prostate Development

Shh is the most abundantly expressed Hh ligand in the developing mouse prostate (18). Ihh is also expressed but at comparatively low levels. Dhh expression has not been observed. Shh gene expression in the urogenital sinus (UGS) increases before the initiation of ductal budding at embryonic day 17.5 (E17.5). Expression is most abundant during the period of ductal budding in late gestation. Shh expression gradually diminishes through the first l0 days after birth, a period characterized by...

Imaging Modalities

Sensitive and quantitative analysis of protein function in living subjects has now been made possible by recent developments in molecular imaging techniques. Several imaging assays use optical reporters composed of either fluorescent proteins or bioluminescent proteins (bioluminescence imaging BLI ) to monitor gene expression. Other technologies, such as positron emission tomography (PET), and single-photon emission computed tomography (SPECT), rely on radiopharmaceuticals (tracers) and...

Chek2

The CHEK2 gene on 22q12.1, an upstream regulator of p53, functions in the ATM-dependent DNA damage signaling pathways, such as BRCA1 and BRCA2. It was first identified in Li-Fraumeni families, in which the observed mutations, most importantly 1100delC, were shown to result in truncated protein (83). Dong et al. (69) provided the first evidence of CHEK2 mutations in prostate cancer. They analyzed a total of 578 prostate cancer patients, of which a total of 28 (4.8 ) had germline CHEK2 mutations...

Contents

List of 1 Xenograft Models of Human Prostate Cancer Eva Corey and Robert L. 2 The Pathology of Human Prostatic Atrophy and Inflammation Angelo M. De 3 Tissue Microarrays in Prostate Cancer Research Milton W. Datta and Andr A. 5 Cancer-Host Interactions A Paradigm Shift Brings New Understanding and New Opportunities Leland W. K. Chung, Wen-Chin Huang, Shian-Ying Sung, Daqing Wu, Valerie Odero-Marah, and Haiyen E. Zhau 73 Androgen Receptor Function in Prostate Cancer Progression Helmut Klocker,...

Metastasis

Patients with advanced CaP experience metastases, for which there is currently no curative treatment. The process of tumor metastasis is highly specific and consists of multiple steps. To metasta- size successfully, the tumor cells must complete all steps of the process initial transformation and growth, local invasion, survival of immune defense, adhesion to the secondary site, establishment of micrometastases and growth at secondary sites. The mechanisms involved in dissemination of tumor...

Inhibition Of Cholesterol Synthesis And Cancer Therapy

HMG-CoA reductase catalyzes the rate-limiting step of cholesterol biosynthesis (Fig. 1). HMG-CoA reductase inhibitors are cholesterol-lowering drugs used in the treatment of lipid disorders, especially hypercholesterolemia. The statin family of HMG-CoA reductase inhibitors includes simvastatin, lovastatin, atorvastatin, fluvastatin, cerivastatin, and pravastatin. Recent clinical data from studies on cardiovascular disease and cancer chemoprevention suggest that prolonged statin therapy may...

Indirect Inhibition Of Telomerase

Dieses Resulting Process Mitos

Antisense approaches have been used aimed at degrading either the hTERT or hTR RNAs. Hammerhead ribozymes against both of these critical telomerase components have been produced (223,241-245). 2'-5' Oligoadenylate chimeric antisense oligonucleotides targeting hTR for destruction by RNAseL have shown effect against various cancer cell types, including prostate cancer, both in vitro and in vivo (246). Schindler et al., found phosphorothioate antisense oligonucleotides targeting hTERT effective in...

The Icpcg Study Of Prostate Cancer Susceptibility

To increase the power to discover prostate cancer susceptibility genes, the ICPCG, a multicenter collaborative research group (www.icpcg.org), increased sample size by combining genome-wide screen linkage data from 1233 prostate cancer families, and used dominant, recessive, and nonpara-metric models to analyze the data (63). Analysis of the complete family collection revealed suggestive evidence of linkage (logarithm of odds LOD > 1.86) at five regions 5q12, 8p21, 15q11, 17q21, and 22q12...

Gene Delivery Vectors

The antitumor effect of gene therapy in prostate cancer is achieved when a therapeutic gene, under the control of a promoter, is delivered directly to a target cell by a vector. The ideal vector would be specific for prostate cancer cells and would have a high rate of transgene delivery. Furthermore, a vector should be inexpensive to produce and administer, nontoxic to the patient, and nonmutagenic. Two categories of vectors are used for human gene therapy, viral and nonviral however, most...

Ar Coactivators And Prostate Cancer Development And Progression

Treatment of diverse cell lines with androgens results in variable induction of target genes. The most likely explanation for differential activation of the AR is cell-specific presence of proteins that enhance (coactivators) or diminish (co-repressors) AR activity. The fact that transcriptional activity of steroid receptors decreases after transfection of other steroid receptors led to the assumption that different steroid receptors compete for the same co-regulators. The first AR...

Meera Iyer and Sanjiv S Gambhir

Recent advances in molecular imaging techniques have opened the door to a new universe that allows for early detection and characterization of disease and evaluation of therapy. Noninvasive imaging of reporter gene expression using different imaging modalities has proved to be valuable for the in vivo assessment of molecular events in several areas including reporter gene expression, immune cell trafficking, protein-protein interactions, and cancer gene therapy. Multimodality imaging offers the...

Hh Signaling And Tumor Growth

Signaling Pathway

Whereas Shh signaling in prostate development is primarily a paracrine signaling from the epithelium to the stroma, both paracrine and autocrine signaling have been identified in prostate cancer and may each contribute to tumor growth (Fig. 4). Localization of Shh and Gli1 expression in normal prostate tissue and in specimens of localized prostate cancer by radioactive in situ hybridization showed Shh expression by the prostatic epithelium and Gli1 expression in the adjacent stroma (20). Ptc...

Wade Bushman

The Hedgehog (Hh) signaling pathway, first identified in Drosophila, is a conserved signaling pathway that plays critically important roles in the development of a variety of structures in the growing embryo. Recently, Hh signaling has been implicated as an important growth stimulus in cancers of several organs, including the prostate, where Hh signaling plays an important role in during embryonic development. In this chapter, we review the role of Hh signaling in prostate development and...

Novel Optical Properties

As briefly noted above in Section 2, Probe Development, QDs are made from inorganic semiconductors, and have novel optical properties that can be used to optimize signal-to-background ratios. First, QDs have very large molar extinction coefficients, on the order of 0.5 to 5 x 106 M cm (30), which makes them brighter probes under photon-limited in vivo conditions (in which light intensities Fig. 2. Methods for conjugating quantum dots (QDs) to biomolecules. (A) Traditional covalent cross-linking...

Therapeutic Targeting Of Epigenetic Gene Silencing For Prostate Cancer Prevention And Treatment

Dnmt Family Domain

Because the somatic changes in DNA methylation that drive epigenetic gene silencing in cancer cells, although functionally equivalent to gene deletion, do not involve irretrievable loss of DNA sequence information, such changes present an attractive rational therapeutic target for cancer treatment and prevention. As such, several approaches to reversal of CpG island hypermethylation-associated gene silencing have emerged. One strategy, now in late-stage clinical development, features the use of...

Contributors

Vasily Assikis, md Departments of Medical Oncology, Hematology Oncology, and Oncology, Piedmont Hospital, Atlanta, GA, and Emory University School of Medicine, Atlanta, GA Georg Bartsch, md Department of Urology, Innsbruck Medical University, Innsbruck, Austria Patrick J. Bastian, md Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Brady Urological Institute, Baltimore, MD Wade Bushman, md, phd Division of Urology, Department of Surgery, University of Wisconsin, Madison, WI Michael A....

Hyperpermeabilize

J., Gao, X. H., Bailey, R. E., Han, M. Y., and Nie, S. M. 2002 . Luminescent quantum dots for multiplexed biological detection and imaging. Curr. Opin. Biotechnol. 13, 40-46. 2. Han, M. Y., Gao, X. H., Su, J. Z., and Nie, S. M. 2001 . Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nat. Biotechnol. 19, 631-635. 3. Gao, X. H. and Nie, S. M. 2003 . Doping mesoporous materials with multicolor quantum dots. J. Phys. Chem. B 107,...