EDUCATIONAL SECTION
Cell production rates in human tissues and tumours and their significance. Part II: clinical data

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Abstract

This paper reviews the available data for cell production rates of human tissues and tumours, measuredin vivo using halogenated pyrimidine labelling and laser cytometry. The technique has now been widely evaluated, and we draw general inferences from the proliferative data over a broad range of tumour and tissue types. Estimates of the S-phase duration, the time taken for DNA synthesis in cycling cells, are consistent over a narrow range with a median value of around 10 hours, notwithstanding the constraints of the experimental and statistical technique, in normal tissues and tumours. This suggests that Ts values may be a species-specific constant. The more easily measured labelled S-phase fraction, or labelling index, shows much greater intra and intertumour variation within any one tumour class. It may thus be a surrogate for time dependent measurements to a first order approximation. The cell production rate, described by the potential doubling time (Tpot), is remarkably rapid in most tumours, a median value of the order of 5 days, and much faster than clinical volume doubling times for most lesions. The rapid cell production rates in normal tissues and tumours highlight the importance of cell loss in the growth and modelling of biological structures. Cell production rate measurements do not adequately describe the biological aggressiveness of tumours. They may be used to refine adjuvant strategies for radiotherapy and chemotherapy in experimental research. Dynamic halogenated pyrimidine labelling has provided unique and valuable insights into the living biology of human tissues and tumours.

References (94)

  • R Nemoto et al.

    Immunochemical demonstration of S phase cells by anti-bromodeoxyuridine monoclonal antibody in human prostate adenocarcinoma

    J Urol

    (1989)
  • M Tachibana et al.

    Role of proliferative activity estimated by BrdUrd labeling index in determining predictive factors of recurrence in superficial intermediately malignant bladder tumors

    J Urol

    (1996)
  • KMG Haustermans et al.

    Cell kinetic measurements in prostate cancer

    Int J Radiat Biol Phys

    (1997)
  • GD Wilson et al.

    Studies with bromodeoxyuridine in head and neck cancer and accelerated radiotherapy

    Radiother Oncol

    (1995)
  • MI Saunders et al.

    Experience with CHART

    Int J Radiat Oncol Biol Phys

    (1991)
  • J Bourhis et al.

    In vivo measurement of the potential doubling time by flow cytometry in oropharyngeal cancer treated by conventional radiotherapy

    Int J Radiat Oncol Biol Phys

    (1993)
  • R Corvo et al.

    Potential doubling time in head and neck tumors treated by primary radiotherapy: preliminary evidence for a prognostic significance in local control

    Int J Radiat Oncol Biol Phys

    (1993)
  • AC Begg et al.

    The predictive value of cell kinetic measurements in a European trial of accelerated fractionation in advanced head and neck tumors: an interim report

    Int J Radiat Oncol Biol Phys

    (1990)
  • AC Begg et al.

    Predictive value of potential doubling time for radiotherapy of hand and neck tumour patients: results from the EORTC cooperative trial 22851

    Seminars in Radiat Oncol

    (1992)
  • J Bourhis et al.

    Potential doubling time and clinical outcome in head and neck squamous cell carcinomas treated with 70 GY in 7 weeks

    Int J Radiat Oncol Biol Phys

    (1996)
  • P Antognoni et al.

    Accelerated radiation therapy for locally advanced squamous cell carcinomas of the oral cavity and oropharynx selected according to tumor cell kinetics—a phase II multicenter study

    Int J Radiat Oncol Biol Phys

    (1996)
  • B Zackrisson et al.

    Predictive value of potential doubling time in head and neck cancer patients treated by conventional radiotherapy

    Int J Radiat Oncol Biol Phys

    (1997)
  • JC Horiot et al.

    Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial

    Radiother Oncol

    (1997)
  • A Begg et al.

    The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicentre analysis

    Radiother Oncol

    (1999)
  • DA Rew et al.

    Cell proliferation rates in human tissues and tumours: Part I

    Eur J Surg Oncol

    (2000)
  • F Dolbeare

    Bromodeoxyuridine: a diagnostic tool in biology and medicine, Part I: Historical perspectives, histochemical methods and cell kinetics [Review]

    Histochem J

    (1995)
  • F Dolbeare

    Bromodeoxyuridine: a diagnostic tool in biology and medicine, Part II: Oncology, chemotherapy and carcinogenesis

    Histochem J

    (1995)
  • G Forster et al.

    Tumour growth rates in squamous carcinoma of the head and neck measured by in vivo bromodeoxyuridine

    Br J Cancer

    (1992)
  • AS Jones et al.

    A comparison of cellular proliferation markers in squamous cell carcinoma of the head and neck

    J Laryngol Otol

    (1994)
  • K Nylander et al.

    Cell kinetics of head and neck squamous cell carcinomas. Prognostic implications

    Acta Oncol

    (1994)
  • MH Bennett et al.

    Tumour proliferation assessed by combined histological and flow cytometric analysis: implications for therapy in squamous cell carcinoma in the head and neck

    Br J Cancer

    (1992)
  • S Marchal et al.

    Combined flow cytometry and immunohistochemistry analyses for the assessment of nasopharyngeal carcinoma cell kineticsin vivo by bromodeoxyuridine infusion

    Cytometry

    (1997)
  • M Benazzo et al.

    Proliferative characteristics of head and neck tumours. In vivo evaluation by BrdUrd incorporation and flow cytometry Orl

    J Oto-Rhino-Laryngol

    (1995)
  • VM Kotelnikov et al.

    In vivo labelling with halogenated pyrimidines of squamous cell carcinomas and adjacent non-involved mucosa of head and neck region

    Cell Proliferation

    (1995)
  • VM Kotelnikov et al.

    Cell kinetics of head and neck cancers

    Clin Cancer Res

    (1995)
  • VM Kotelnikov et al.

    Cyclin D1 expression in squamous cell carcinomas of the head and neck and in oral mucosa in relation to proliferation and apoptosis

    Clinical Cancer Res

    (1997)
  • LD Cooke et al.

    Prospective evaluation of cell kinetics in head and neck squamous carcinoma: the relationship to tumour factors and survival

    Br J Cancer

    (1994)
  • K Kakinuma et al.

    Proliferative potential of recurrent intracranial meningiomas as evaluated by labelling indices of BrdUrd and Ki-67, and tumour doubling time

    Acta Neurochirurgica

    (1998)
  • A Riccardi et al.

    Cell kinetics in human malignancies studied with in vivo administration of bromodeoxyuridine and flow cytometry

    Cancer Res

    (1988)
  • M Danova et al.

    Prognostic value of DNA ploidy and proliferative activity in human malignant gliomas

    Med Sci Res

    (1991)
  • M Shibuya et al.

    A new method for analyzing the cell kinetics of human brain tumors by double labeling with bromodeoxyuridine in situ and with iododeoxyuridine in vitro

    Cancer

    (1993)
  • H Scruikmans et al.

    S phase fraction, bromodeoxyuridine labelling index, duration of S phase, potential doubling time and DNA index in benign and malignant brain tumours

    Radiation Oncol Investigations

    (1997)
  • H Struikmans et al.

    Prognostic relevance of cell proliferation markers and DNA ploidy in gliomas

    Acta Neurochirurgica

    (1998)
  • GD Wilson

    Assessment of human tumour proliferation using bromodeoxyuridine—current status

    Acta Oncologica

    (1991)
  • DA Rew

    The in vivo proliferation kinetics of human solid tumors

    MChir Thesis, University of Cambridge, UK

    (1991)
  • K Haustermans et al.

    In vivo cell kinetic measurements in human oesophageal cancer: what can be learned from multiple biopsies?

    Eur J Cancer

    (1994)
  • K Haustermans

    In vivo growth kinetic measurements in human oesophageal cancer

    PhD Thesis, University of Leiden, Holland

    (1995)
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