Visualization of advanced human prostate cancer lesions in living mice by a targeted gene transfer vector and optical imaging

Adams, Jason Y.; Johnson, Mai; Sato, Makoto; Berger, Frank; Gambhir, Sanjiv S.; Carey, Michael; Iruela‐Arispe, M. Luisa; Wu, Lily

doi:10.1038/nm743

Cited by 162 publications

(107 citation statements)

References 16 publications

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“…UM-UC-3 cells were treated with 100 mM YM529 for 2, 6, or 24 h and cell lysates were collected, separated into cytosolic and membrane fractions, and subjected to Western blotting analysis using an anti-Ras antibody. viscera by measuring these photon signals (Adams et al, 2002;Hollingshead et al, 2004;Uhrbom et al, 2004;Nogawa et al, 2005a, c). Therefore, we have introduced this quantitative method into this study.…”

Section: Growth Inhibition and Induction Of Apoptosis By Ym529 In Vitromentioning

confidence: 99%

A third-generation bisphosphonate, minodronic acid (YM529), successfully prevented the growth of bladder cancer in vitro and in vivo

et al. 2006

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Minodronic acid (YM529) is a third-generation bisphosphonate (BP) that has been shown to directly and indirectly prevent proliferation, induce apoptosis, and inhibit metastasis of various types of cancer cells. In this study, we have investigated the therapeutic efficacy of YM529 against bladder cancer, both in vitro and in vivo. YM529 inhibited geranylgeranylation as well as farnesylation and reduced the growth of all seven bladder cancer cell lines in a dose-and time-dependent manner in vitro. YM529 demonstrated a good synergistic or additive antiproliferative effect when administered in combination with cisplatin or paclitaxel. Immunohistochemical study revealed YM529 inhibited the prenylation of Rap1A in vivo. YM529 administered systemically did not markedly inhibit the growth of visceral metastases but it showed a significant anticancer effect on bone metastases monitored by an in vivo imaging system. Moreover, intravesical YM529 demonstrated significant growth inhibition in a bladder cancer orthotopic model. No adverse effects were associated with the systemic as well as the intravesical treatment regimens. In conclusion, our study suggests that YM529 may be a potent anticancer agent for bladder cancer. The efficacy and safety of this BP as an agent for combination chemotherapies against bladder cancer should be verified by early-phase clinical trials.

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Section: Growth Inhibition and Induction Of Apoptosis By Ym529 In Vitromentioning

confidence: 99%

A third-generation bisphosphonate, minodronic acid (YM529), successfully prevented the growth of bladder cancer in vitro and in vivo

et al. 2006

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“…Due to its highly specific nature, the PSA promoter has been frequently used in prostate cancer-targeted gene therapy approaches [3,15,16]. A modified PSA promoter-driven luciferase reporter adenoviral vector construct showed preferential expression in prostate gland and tumors, by three orders of magnitude, compared with liver tissue [17,18]. Human α-lactalbumin (hALA) is an enzyme involved in lactose production, and it is expressed in the lactating mammary gland and in a high proportion of breast cancer cases [19].…”

Section: Transcriptional Targetingmentioning

confidence: 99%

Transcriptionally targeted gene therapy to detect and treat cancer

Wu¹,

Johnson²,

Sato³

2003

Trends in Molecular Medicine

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The greatest challenge in cancer treatment is to achieve the highest levels of specificity and efficacy. Cancer gene therapy could be designed specifically to express therapeutic genes to induce cancer cell destruction. Cancer-specific promoters are useful tools to accomplish targeted expression; however, high levels of gene expression are needed to achieve therapeutic efficacy. Incorporating an imaging reporter gene in tandem with the therapeutic gene will allow tangible proof of principle that gene expression occurs at the correct location and at a sufficient level. Gene-based imaging can advance cancer detection and diagnosis. By combining the cancer-targeted imaging and therapeutic strategies, the exciting prospect of a 'one-two punch' to find hidden, disseminated cancer cells and destroy them simultaneously can potentially be realized.Multiple genetic alterations that confer growth advantages to tumor cells are accumulated during the transformation from normal to neoplastic growth [1]. The loss of growth suppressive genes or gain of oncogenes constitutes a common mechanism of oncogenesis. Based on this information, a rational therapeutic approach is to re-introduce the defective growth control genes into tumor cells. In addition, approaches of inducing apoptotic responses and enhancing anti-tumor immune responses have also been employed [2]. Due to the availability of multiple flexible therapeutic strategies, gene therapy is being actively investigated in clinical settings.Among the ~ 40 ongoing gene therapy clinical trials for cancer (searched via www.clinicaltrials.gov/), 18 of the trial protocols involve an immune activating scheme, ten studies employ a genetic correction strategy and five use a cytotoxic gene. With regard to genetic correction strategies, p53 is a major target. The recombinant adenovirus is the dominant viral gene delivery vector, and it is employed in 18 protocols. However, none of 40 protocols use a cancer-specific gene expression strategy. An oncolytic adenovirus CN706 containing prostate-specific antigen (PSA) promoter driven viral replication [3] is being evaluated in phase II clinical trial for prostate cancer [4].Because the goal of cancer gene therapy is to eradicate cancer cells, many therapeutic genes could be detrimental if unintentionally expressed in normal cells. Selectively targeting the cancer cells is useful to achieve safety and efficacy, especially when the gene therapy vector is directly delivered into patients. Based on features that distinguish cancerous from normal cells, three targeting strategies could be employed. Transcriptional targeting takes advantage of the fact that some cancer cells express a subset of exclusive genes, and uses these cancerspecific promoters to express the desired transgenes [5]. Transductional targeting refers to surface modification on the gene delivery vehicle to enhance interactions with the cancer cell membrane antigen, thereby improving gene transfer into the cancerous cell. A third promising approach is to exploit cancer-a...

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“…Bioluminescence imaging has been utilized to evaluate a number of nonviral and viral vector systems in small animal models. [14][15][16][17] These experiments have validated the use of noninvasive bioluminescence imaging of vector-based gene delivery as well as imaging of metastasis and cell trafficking. [3][4][5][6][7] Herpesvirus saimiri (HVS) is the prototype gamma-2 herpesvirus, or rhadinovirus.…”

Section: Introductionmentioning

confidence: 84%

Herpesvirus saimiri-based vector biodistribution using noninvasive optical imaging

et al. 2005

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Herpesvirus saimiri (HVS) is capable of infecting a range of human cell types with high efficiency and the viral genome persists as high copy number, circular, nonintegrated episomes which segregate to progeny upon cell division. This allows the HVS-based vector to stably transduce a dividing cell population and provide sustained transgene expression for an extended period of time both in vitro and in vivo. Here we assess the dissemination of HVS-based vectors in vivo following intravenous and intraperitoneal administration. Bioluminescence imaging of an HVS-based vector expressing luciferase demonstrates that the virus can infect and establish a persistent latent infection in a variety of mouse tissues. Moreover, the long-term in vivo maintenance of the HVS genome as a nonintegrated circular episome provided sustained expression of luciferase over a 10-week period. A particularly high level of transgene expression in the liver and the ability of HVS to infect and persist in hepatic stellate cells suggest that HVS-based vectors may have potential for the treatment of inherited and acquired liver diseases.

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Visualization of advanced human prostate cancer lesions in living mice by a targeted gene transfer vector and optical imaging

Cited by 162 publications

References 16 publications

A third-generation bisphosphonate, minodronic acid (YM529), successfully prevented the growth of bladder cancer in vitro and in vivo

A third-generation bisphosphonate, minodronic acid (YM529), successfully prevented the growth of bladder cancer in vitro and in vivo

Transcriptionally targeted gene therapy to detect and treat cancer

Herpesvirus saimiri-based vector biodistribution using noninvasive optical imaging

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