Human Bladder Tumors in Organ Culture

Lawson, Anne; Riches, Andrew; Weaver, Jennifer

doi:10.1016/s0022-5347(17)45975-1

Cited by 7 publications

(4 citation statements)

References 5 publications

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“…The model validated in this study resembled that described by Lawson et al. [17] in which tumours were cultured at the interface between medium and gas and the three‐dimensional integrity of the tissue is maintained. Serum is a vital component in media sustaining human cultures, by providing cells with complexes of conventional hormones and growth factors which are required in undefined levels.…”

Section: Discussionsupporting

confidence: 63%

“…This study validated an ex vivo model which was then used to examine the apoptotic response in 41 bladder tumours after exposure to MMC. Previous studies have reported that it is possible to culture bladder tumours as explants, with success in 70–90% of moderately and poorly differentiated superficial tumours [14–18]. The advantage of explant models over single‐cell suspension culture systems is the preservation of tissue structural organization, cell‐to‐cell contacts and cell heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

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Induction of apoptosis by mitomycin‐C in an ex vivo model of bladder cancer

et al. 2000

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Objective To examine mitomycin-C (MMC)-induced apoptosis in an ex vivo model of super®cial TCC, and relate it to the in vivo response to chemotherapy. Materials and methods Dose-and time-response curves were constructed to determine the optimal conditions for the induction of apoptosis by MMC in an ex vivo model of super®cial bladder cancer. Subsequently, 41 individual tumours were exposed to MMC in the model and the effects assessed by measuring of apoptosis before and after chemotherapy. The relationships between tumour grade and stage and the intrinsic and induced apoptotic counts were determined. In tandem, in a clinical study, the relationship between in vivo response of a marker tumour to MMC and the ex vivo induction of apoptosis was determined. Results In the ex vivo model, apoptosis was induced at a MMC concentration of 0.5 mg/mL after an incubation time of 8 h. In 41 tumours the intrinsic apoptotic index (AI) was higher with increased grade and stage of tumour (P = 0.048). There was no correlation between the intrinsic AI and the AI after treatment with MMC (induced AI). In 21 tumours (51%) the induced AI did not increase above a predetermined response threshold and these tumours were considered resistant to MMC. Resistance to MMC was related to tumour grade (P = 0.037) with a trend for G3 pT1 tumours to be resistant to the therapy. There was a signi®cant association between ex vivo sensitivity and in vivo marker tumour response (P = 0.02). Conclusions Apoptosis is differentially induced in an ex vivo incubation model of super®cial TCC by MMC and evidence suggests that this response matches that seen in vivo. The measurement of apoptosis before therapy does not predict the apoptotic response of a tumour to chemotherapy. The ability to undergo apoptosis correlates with clinical outcome.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Induction of apoptosis by mitomycin‐C in an ex vivo model of bladder cancer

et al. 2000

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“…Several in vitro bladder cancer culture systems, in addition to our own, have been developed in recent years [Leighton et al, 1977;Abaza et al, 1978;Bulbul et al, 1986;[Reese et al, 1976;Leighton and Tchao, 1984;Leighton et al, 1985;Lawson et al, 1986;Leighton, 1991;Crook et al, 20001. These systems provide a unique approach for defining key genetic and epigenetic events associated with the development of bladder cancer in pure populations of tumor cells.…”

Section: 2 Pathologymentioning

confidence: 99%

“…The single-cell suspension culture requires a thorough digestion and excludes the use of tissue explants as cell source [Lindert and Terris, 2000;Reznikoff et al, 19831. Other culture systems, such as organ culture, gradient culture, and matrix culture, have been used with bladder cancers to test cytotoxic agents at clinically relevant concentrations [Leighton et al, 1977;Abaza et al, 1978;Bulbul et al, 1986;Reese et al, 1976;Lawson et al, 1986;Crook et al, 20001. …”

Section: Single-cell Suspension Culture and Other Culture Techniquesmentioning

confidence: 99%

The Establishment and Characterization of Bladder Cancer Cultures In Vitro

Fu¹,

Schwarze²,

Reznikoff³

et al. 2003

Culture of Human Tumor Cells

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An organoid culture assay (OCA) for determining the drug sensitivity of human tumors

Köpf-Maier

Kolon

1992

Intl Journal of Cancer

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A model for testing chemotherapeutic agents in vitro is described. It is based on an organoid culture method which allows human carcinomas to grow in vitro and to maintain many typical in vivo properties, including 3-dimensional architecture, growth of multiple cell types, expression of morphological differentiation and formation of histotypical structures. The preservation of drug sensitivity and resistance under the conditions of our organoid culture assay (OCA) was demonstrated by investigating 3 strains of a human hypopharynx carcinoma which differed by different sensitivity to cisplatin in in vivo conditions. These differences were retained in vitro and the modified neutral-red (NR) assay was especially suitable for revealing drug-induced cytotoxic damage in OCA. On the basis of our findings, the following approach is proposed for the in vitro testing of cytostatic drugs before they are administered to patients. (1) Removal of carcinomas from patients; (2) dense cell suspensions of these carcinomas to be dropped on membrane filters at the air-medium interface, resulting in growth of solid nodules of organized carcinoma tissues; (3) addition of cytostatic drugs to the growth medium for 2 or 3 days; (4) detachment and bisection of the culture nodules; (5) determination of viable cells by NR uptake and total cell mass by the sulforhodamin B (SRB) assay; (6) determination of quotient NR:SRB absorbance, related as percentage to control value: this indicates the fraction of viable cells and gives a measure of the cytotoxic injury caused by the applied cytotoxic drug. Thus, the OCA seems to be suitable for defining the patterns of drug sensitivity and resistance of individual human carcinomas in vitro within a few days.

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Human Bladder Tumors in Organ Culture

Abstract: We have established a reliable method for culturing transitional cell tumors of the human urinary bladder. Out of seventy-four set up in culture, forty-eight were successfully maintained and their behavior studied using metaphase arrest and 125IUdR uptake.

Cited by 7 publications

References 5 publications

Induction of apoptosis by mitomycin‐C in an ex vivo model of bladder cancer

Induction of apoptosis by mitomycin‐C in an ex vivo model of bladder cancer

The Establishment and Characterization of Bladder Cancer Cultures In Vitro

An organoid culture assay (OCA) for determining the drug sensitivity of human tumors

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