Heterogeneity of epithelial and stromal cells of head and neck squamous cell carcinomas in ex vivo chemoresponse

Horn, Iris-Susanne; Wichmann, Gunnar; Mozet, Christian; Dietz, Andreas; Dollner, Ralph; Tschöp, Katrin; Boehm, Andreas

doi:10.1007/s00280-009-1124-4

Cited by 13 publications

(11 citation statements)

References 24 publications

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“…Fresh tumor biopsies were digested and after 3 days of exposure to various drugs adherent colonies were fixed and counted to determine the IC-50 [ 50 , 51 ]. The overall chemoresponse was dominated by stromal cell multidrug resistance [ 52 , 53 , 54 ]. Stromal cells were resistant to drug combinations in 98% of the experiments, whereas epithelial colonies were sensitive to cisplatin/5-FU in 16%, to carboplatin/5-FU in 8.3%, to cisplatin/docetaxel in 33% and to carboplatin/docetaxel in 8.3%.…”

Section: Resultsmentioning

confidence: 99%

“…Several groups investigated the impact of stromal cell contamination on culture and treatment sensitivity and concluded that most colonies consisted of fibroblasts. The SF2 is then mainly determined by fibroblast SF2 instead of overall or tumor SF2, and therefore this may contribute as well in not mimicking the correct response in vivo [ 45 , 48 , 49 , 50 , 51 , 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

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Feasibility of Primary Tumor Culture Models and Preclinical Prediction Assays for Head and Neck Cancer: A Narrative Review

Dohmen¹,

Swartz²,

Brekel³

et al. 2015

Cancers

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Primary human tumor culture models allow for individualized drug sensitivity testing and are therefore a promising technique to achieve personalized treatment for cancer patients. This would especially be of interest for patients with advanced stage head and neck cancer. They are extensively treated with surgery, usually in combination with high-dose cisplatin chemoradiation. However, adding cisplatin to radiotherapy is associated with an increase in severe acute toxicity, while conferring only a minor overall survival benefit. Hence, there is a strong need for a preclinical model to identify patients that will respond to the intended treatment regimen and to test novel drugs. One of such models is the technique of culturing primary human tumor tissue. This review discusses the feasibility and success rate of existing primary head and neck tumor culturing techniques and their corresponding chemo- and radiosensitivity assays. A comprehensive literature search was performed and success factors for culturing in vitro are debated, together with the actual value of these models as preclinical prediction assay for individual patients. With this review, we aim to fill a gap in the understanding of primary culture models from head and neck tumors, with potential importance for other tumor types as well.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Feasibility of Primary Tumor Culture Models and Preclinical Prediction Assays for Head and Neck Cancer: A Narrative Review

Dohmen¹,

Swartz²,

Brekel³

et al. 2015

Cancers

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“…36 For predicting the drug response prior to cancer therapy, an ex vivo histo-culture approach has been proposed. 37,38 In this approach, the tissue biopsies isolated from patients are minced and incubated with target drugs for an extended period of time ranging from a couple of days to over a week. Following the extended incubation of clinical samples with chemotherapy drugs, the response is assessed using the MTT assay.…”

Section: Discussionmentioning

confidence: 99%

Optical molecular imaging approach for rapid assessment of response of individual cancer cells to chemotherapy

et al. 2012

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Predicting the response of individual patients to cytotoxic chemotherapy drugs is critical for developing individualized therapies. With this motivation, an optical molecular imaging approach was developed to detect cisplatin induced changes in the uptake and intracellular retention of choline. Intracellular uptake of choline was characterized using a click chemistry reaction between propargyl choline and Alexa-488 azide. Cisplatin induced changes in the uptake of propargyl choline in cells and tumor spheroids were compared with similar measurements using a fluorescent analogue of deoxyglucose and conventional cell viability assays. Uptake and intracellular retention of propargyl choline decreased with an increase in concentration of cisplatin. Intracellular uptake of propargyl choline was significantly reduced within 3 h of incubation with a sub-lethal dose of cisplatin. Results demonstrate that the imaging approach based on propargyl choline was more sensitive in detecting the early response of cancer cells to cisplatin as compared to the imaging based on fluorescent analogue of deoxyglucose and cell viability assays. Imaging measurements in tumor spheroids show a significant decrease in the uptake of propargyl choline following treatment with cisplatin. Overall, the results demonstrate a novel optical molecular imaging approach for rapid measurement of the response of individual cancer cells to cisplatin treatment.

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“…Der Assay wird über das Mitführen einer Zelllinie in parallelem Ansatz unter Verwendung der identischen Verdünnun-gen, die beim Tumor getestet werden, qualitätskontrolliert und ermöglicht durch die separate Erfassung von Kolonien maligner Epithelzellen und Stromazellen [18,19] eine verbesserte Bestimmung der Chemoresponse [20]. Dazu trägt insbesondere bei, dass Biopsate ab etwa 60-100 mg gestatten, zwei oder mehr Pharmaka auch in Kombination zu testen.…”

Section: Flavino-assayunclassified

Pharmacological characterization of head and neck cancer in ex-vivo tests

Wichmann

Dietz

2011

HNO

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Precise knowledge about the chance of success of a given pharmacologic therapy of head and neck squamous cell carcinoma (HNSCC) before starting therapy would be very desirable to guide the selection of the most suitable or the most efficient combination out of the ever-growing spectrum of available pharmaceuticals. This selection has hitherto been made at best on the basis of the availability of guideline-conformant and approved combinations according to results of published clinical studies and approved general effectiveness in HNSCC. However, the inhomogeneous biology of HNSCC depending on localization, varying metastatic behavior, TNM and UICC stage in the context of the patient's general condition and risk status according to lifestyle and occupational exposure make it impossible to accurately predict the success of pharmacological therapy regimens for the individual HNSCC based on today's clinical and pathohistological diagnostics. A solution may lie in the testing of biopsy specimens ex vivo before starting therapy. The present review describes recent advances in ex-vivo tests and discusses the requirements for their inclusion in the decision-making process.

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Heterogeneity of epithelial and stromal cells of head and neck squamous cell carcinomas in ex vivo chemoresponse

Abstract: (191 words)Background: Valid prediction of effectiveness of chemotherapeutic agents in

Cited by 13 publications

References 24 publications

Feasibility of Primary Tumor Culture Models and Preclinical Prediction Assays for Head and Neck Cancer: A Narrative Review

Feasibility of Primary Tumor Culture Models and Preclinical Prediction Assays for Head and Neck Cancer: A Narrative Review

Optical molecular imaging approach for rapid assessment of response of individual cancer cells to chemotherapy

Pharmacological characterization of head and neck cancer in ex-vivo tests

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