Comparison of androgen-independent growth and androgen-dependent growth in BPH and cancer tissue from the same radical prostatectomies in sponge-gel matrix histoculture

Geller, Jack; Partido, Christine; Sionit, Lida; Youngkin, Tyler; Nachtsheim, Dan; Espanol, Mike; Tan, Yuying; Hoffman, Robert M.

doi:10.1002/(sici)1097-0045(19970601)31:4<250::aid-pros6>3.0.co;2-o

Cited by 15 publications

(3 citation statements)

References 7 publications

(13 reference statements)

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“…Histoculture of both benign and malignant human prostate tissue was shown to be valuable in studying tissue growth and identifying inhibitors of growth in vitro (Geller et al, 1992(Geller et al, , 1994(Geller et al, , 1997. Because prostate tissue consists of both epithelial and stromal tissue, theoretically there may be no need for additional AntiCancer, Inc., San Diego, CA.…”

Section: Resultsmentioning

confidence: 99%

Effect of Genistein and Genistein Analogs on Growth of Human Prostate Tissue In Vitro

Geller¹,

Olbina²,

Miljković³

et al. 1999

Journal of Medicinal Food

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that prostate disease is significantly less prevalent in Asia, where the intake of soy products is very high, than in the United States, where intake is low (Gu et al., 1994). We therefore undertook a study of the effects of genistein, a major component of soy, on growth of human-patient benign prostatic hyperplasia (BPH) and prostate cancer tissue in three-dimensional sponge-gel supported histoculture (SSH) (Hoffman, 1998). More recently, we improved the sensitivity of the histoculture method by the use of total immersion in the histoculture medium; we have called this technique total immersion histoculture (TIH) (Olbina et al, 1998).Surgical specimens of human BPH and cancer were histocultured with the SSH and TIH techniques in parallel for 5 days to study the effect of genistein on growth, as measured by inhibition of 3-H-thymidine incorporation per microgram of protein on day 5. RESULTS AND DISCUSSIONWe compared inhibition of growth after treatment of BPH and cancer tissue with genistein in SSH or TIH. Inhibition of growth was expressed as percentage of control growth of the tissue treated with dihydrotestosterone (DHT) alone. Incorporation of 3H-thymidine dramatically increased in control histocultures, by twofold to fivefold, in TIH compared with the same tissue in SSH (Fig. 1).We observed significantly increased growth inhibition of BPH and cancer tissue treated with 18.4 /xmol/L of genistein with TIH, compared with SSH. The average inhibition in TIH was 73% (range 67-79%), compared with a mean decrease of 31% (range 6-68%) in SSH (Fig. 2). This inhibition was statistically significant (P < .05).To examine the sensitivity of TIH, we treated BPH and cancer tissue in TIH with decreasing concentrations of genistein. We observed 40% growth inhibition of tissue treated with 4.6 /¿mol/L and 26% inhibition with 2.3 /¿mol/L, with a mean coefficient of variation (CV) of 13%. Both of these values represent significant differences (P < .05). In contrast, inhibition was not significant with concentrations lower than 9.2 ¿imol/L genistein in SSH (CV range, 8-29%) (Fig. 3).Inhibitory effects on 3H-thymidine incorporation of 20 ¿tmol/L of hydroxyflutamide, a known antiandrogen, were compared using the same tissue in SSH and TIH. In all experiments, the incorporation of 3H-thymidine was three to four times higher for TIH in control histocultures. The inhibition caused by 2 x 10-5 mol/L hydroxyflutamide was 40-60% in TIH. In SSH, inhibition by 2 X 10-5 mol/L hydroxyflutamide was 17-18%, and in some experiments it was not detectable to all.

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Section: Resultsmentioning

confidence: 99%

Effect of Genistein and Genistein Analogs on Growth of Human Prostate Tissue In Vitro

Geller¹,

Olbina²,

Miljković³

et al. 1999

Journal of Medicinal Food

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“…This strategy allowed a 2-fold improvement over historical control of 30%. PDMEs were also used successfully in prostate (Centenera et al, 2018; Risbridger et al, 2018) and breast cancer (Carranza-Torres et al, 2015), with 100% survival after 96 h. In some studies, the PDMEs were not simply immersed in media but sometimes placed on substrates such as titanium or stainless grids, or gelatin sponges (Geller et al, 1997; Centenera et al, 2012, 2013, 2018; Schiewer et al, 2012; Risbridger et al, 2018). This prevented cell outgrowth from tumor tissues, which may often occur, as seen in prostate cancer PDMEs for example, maintaining viability for up to one week of culture (Centenera et al, 2013).…”

Section: Engineering Patient-specific Tumor Microenvironment Modelsmentioning

confidence: 99%

Addressing Patient Specificity in the Engineering of Tumor Models

Bray

Hutmacher

2019

Front. Bioeng. Biotechnol.

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Cancer treatment is challenged by the heterogeneous nature of cancer, where prognosis depends on tumor type and disease stage, as well as previous treatments. Optimal patient stratification is critical for the development and validation of effective treatments, yet pre-clinical model systems are lacking in the delivery of effective individualized platforms that reflect distinct patient-specific clinical situations. Advances in cancer cell biology, biofabrication, and microengineering technologies have led to the development of more complex in vitro three-dimensional (3D) models to act as drug testing platforms and to elucidate novel cancer mechanisms. Mostly, these strategies have enabled researchers to account for the tumor microenvironment context including tumor-stroma interactions, a key factor of heterogeneity that affects both progression and therapeutic resistance. This is aided by state-of-the-art biomaterials and tissue engineering technologies, coupled with reproducible and high-throughput platforms that enable modeling of relevant physical and chemical factors. Yet, the translation of these models and technologies has been impaired by neglecting to incorporate patient-derived cells or tissues, and largely focusing on immortalized cell lines instead, contributing to drug failure rates. While this is a necessary step to establish and validate new models, a paradigm shift is needed to enable the systematic inclusion of patient-derived materials in the design and use of such models. In this review, we first present an overview of the components responsible for heterogeneity in different tumor microenvironments. Next, we introduce the state-of-the-art of current in vitro 3D cancer models employing patient-derived materials in traditional scaffold-free approaches, followed by novel bioengineered scaffold-based approaches, and further supported by dynamic systems such as bioreactors, microfluidics, and tumor-on-a-chip devices. We critically discuss the challenges and clinical prospects of models that have succeeded in providing clinical relevance and impact, and present emerging concepts of novel cancer model systems that are addressing patient specificity, the next frontier to be tackled by the field.

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“…Another important technique is an in vitro culture system that closely mimics in vivo conditions. To this end, we took advantage of collagen spongegel matrix histoculture introduced by Leighton (3) in the 1950s and further developed by us (4)(5)(6)(7)(8)(9)(10)(11)(12). Finally, we sought a rapid, nondestructive means for examining the cultured lung tissue so that continuous measurements could be made.…”

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confidence: 99%

Governing step of metastasis visualized in vitro

Chishima

Yang

Miyagi

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Metastasis is the ultimate life-threatening stage of cancer. The lack of accurate model systems thwarted studies of the metastatic cell's basic biology. To follow continuously the succeeding stages of metastatic colony growth, we heritably labeled cells from the human lung adenocarcinoma cell line ANIP 973 with green f luorescent protein (GFP) by transfection with GFP cDNA. Labeled cells were then injected intravenously into nude mice, where, by 7 days, they formed brilliantly f luorescing metastatic colonies on mouse lung [Chishima, T., Miyagi, Y., Wang, X., Yang, M., Tan Paget, more than 100 years ago, formulated his seed and soil hypothesis (i.e., the cells from a given tumor would ''seed'' only favorable ''soil'' offered by certain organs; ref. 1). He hypothesized that cancer cells must find a suitable ''soil'' in a target organ (i.e., one that supports colonization) for metastasis to occur. We recently reported that the ability of human colon cancer cells to colonize liver tissue governs whether a particular colon cancer will metastasize to the liver (2). In the model used in that study, human colon tumors were transplanted into the nude mouse colon as intact tissue blocks by surgical orthotopic implantation (i.e., to the corresponding organ). At the site of implantation in the mouse colon, all tumors were equally invasive locally into tissues and blood vessels. However, the metastatic behavior of implanted tumors closely depended on the metastatic behavior of the original human patient tumor. Only those tumors that originally metastasized to the liver in the donor patient did so in the mouse model. Furthermore, the cells of these metastasizing tumors could also colonize the liver directly after intrahepatic implantation. In contrast, cells from nonmetastatic colon tumors failed to engraft when implanted into liver tissue. Thus, the ability to colonize a distant organ is a critical aspect of metastatic spread in tumor progression. However, the colonization of distant tissues by micrometastasis formation and subsequent growth is still poorly understood due to lack of suitable experimental models.In this report, we describe a new system for the study of the metastatic process in vitro. Until now, envisioning an in vitro experimental system for replicating metastatic colony establishment and progression was not possible. Three recent developments make the described system realizable. One is the technology that underlies surgical orthotopic implantation. Tumor cells will closely replicate their original behavior in a heterologous species if implanted onto the corresponding organ. The experiments described here used human lung cancer cells growing on mouse lung. Another important technique is an in vitro culture system that closely mimics in vivo conditions. To this end, we took advantage of collagen spongegel matrix histoculture introduced by Leighton (3) in the 1950s and further developed by us (4-12). Finally, we sought a rapid, nondestructive means for examining the cultured lung tissue so that conti...

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Comparison of androgen-independent growth and androgen-dependent growth in BPH and cancer tissue from the same radical prostatectomies in sponge-gel matrix histoculture

Cited by 15 publications

References 7 publications

Effect of Genistein and Genistein Analogs on Growth of Human Prostate Tissue In Vitro

Effect of Genistein and Genistein Analogs on Growth of Human Prostate Tissue In Vitro

Addressing Patient Specificity in the Engineering of Tumor Models

Governing step of metastasis visualized in vitro

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