G Giaccone

Summary

Affiliation: University Hospital Vrije Universiteit
Country: The Netherlands

Publications

  1. ncbi request reprint Clinical trials report on ongoing trials in lung cancer
    G Giaccone
    Division of Medical Oncology, University Hospital Vrije Universiteit, 1117 De Boelelaan, HV 1081 Amsterdam, The Netherlands
    Expert Opin Investig Drugs 6:1939-50. 1997
  2. ncbi request reprint A phase I-II study of gemcitabine and paclitaxel in advanced non-small-cell lung cancer patients
    G Giaccone
    University Hospital Vrije Universiteit Amsterdam, The Netherlands
    Ann Oncol 11:109-12. 2000
  3. ncbi request reprint Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients with advanced non-small-cell lung cancer. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group
    G Giaccone
    Division of Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    J Clin Oncol 16:2133-41. 1998
  4. ncbi request reprint Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer
    A C Dingemans
    Department of Medical Oncology, University Hospital, Vrije Universiteit, Amsterdam, The Netherlands
    Lung Cancer 32:117-28. 2001
  5. ncbi request reprint Pharmacology of the paclitaxel-cisplatin, gemcitabine-cisplatin, and paclitaxel-gemcitabine combinations in patients with advanced non-small cell lung cancer
    J R Kroep
    Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands
    Cancer Chemother Pharmacol 58:509-16. 2006
  6. pmc Determinants of CPT-11 and SN-38 activities in human lung cancer cells
    J van Ark Otte
    University Hospital Vrije Universiteit, Department of Medical Oncology, Amsterdam, The Netherlands
    Br J Cancer 77:2171-6. 1998
  7. ncbi request reprint 5-Fluorouracil induced Fas upregulation associated with apoptosis in liver metastases of colorectal cancer patients
    H H Backus
    Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Ann Oncol 12:209-16. 2001
  8. ncbi request reprint Phase I clinical and pharmacokinetic study of oral S-1 in patients with advanced solid tumors
    C J van Groeningen
    University Hospital Vrije Universiteit, Netherlands Cancer Institute, and NDDO Oncology, Amsterdam, The Netherlands
    J Clin Oncol 18:2772-9. 2000
  9. ncbi request reprint Phase II trial of cisplatin and gemcitabine in patients with advanced gastric cancer
    S M De Lange
    Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands
    Ann Oncol 15:484-8. 2004
  10. ncbi request reprint Combination of gemcitabine and cisplatin for advanced non-small cell lung cancer: a phase II study with emphasis on scheduling
    C Huisman
    Department of Pulmonary Diseases, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Lung Cancer 33:267-75. 2001

Collaborators

Detail Information

Publications50

  1. ncbi request reprint Clinical trials report on ongoing trials in lung cancer
    G Giaccone
    Division of Medical Oncology, University Hospital Vrije Universiteit, 1117 De Boelelaan, HV 1081 Amsterdam, The Netherlands
    Expert Opin Investig Drugs 6:1939-50. 1997
    ..A large number of small Phase I and II trials are being performed, in particular including new cytotoxic agents. This review focuses on randomised Phase III trials, and those mainly conducted by large co-operative groups...
  2. ncbi request reprint A phase I-II study of gemcitabine and paclitaxel in advanced non-small-cell lung cancer patients
    G Giaccone
    University Hospital Vrije Universiteit Amsterdam, The Netherlands
    Ann Oncol 11:109-12. 2000
    ..This regimen proved to be safe and easy to administer on an out-patient setting, and constitutes now one of the arms of the current EORTC randomized study for advanced NSCLC...
  3. ncbi request reprint Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients with advanced non-small-cell lung cancer. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group
    G Giaccone
    Division of Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    J Clin Oncol 16:2133-41. 1998
    ..To compare two cisplatin based chemotherapy schedules in patients with advanced non-small-cell lung cancer (NSCLC)...
  4. ncbi request reprint Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer
    A C Dingemans
    Department of Medical Oncology, University Hospital, Vrije Universiteit, Amsterdam, The Netherlands
    Lung Cancer 32:117-28. 2001
    ..In one tumor sample, a newly described mutation in the B/DNBS region of the topo IIalpha gene was detected, which does not appear to be related to drug resistance...
  5. ncbi request reprint Pharmacology of the paclitaxel-cisplatin, gemcitabine-cisplatin, and paclitaxel-gemcitabine combinations in patients with advanced non-small cell lung cancer
    J R Kroep
    Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands
    Cancer Chemother Pharmacol 58:509-16. 2006
    ..To compare the pharmacology of the paclitaxel-cisplatin, gemcitabine-cisplatin and paclitaxel-gemcitabine combinations in patients with advanced non-small cell lung cancer (NSCLC)...
  6. pmc Determinants of CPT-11 and SN-38 activities in human lung cancer cells
    J van Ark Otte
    University Hospital Vrije Universiteit, Department of Medical Oncology, Amsterdam, The Netherlands
    Br J Cancer 77:2171-6. 1998
    ..The assessment of CE activity in clinical material of lung cancer patients undergoing treatment with CPT-11 may be warranted. However, other mechanisms may influence sensitivity to CPT-11, possibly including drug transport...
  7. ncbi request reprint 5-Fluorouracil induced Fas upregulation associated with apoptosis in liver metastases of colorectal cancer patients
    H H Backus
    Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Ann Oncol 12:209-16. 2001
    ..Since Fas mediated cell killing is important for cytotoxic T cells this indicates that clinical studies combining immunotherapy for activation of T cells and chemotherapy using 5-FU might be very effective...
  8. ncbi request reprint Phase I clinical and pharmacokinetic study of oral S-1 in patients with advanced solid tumors
    C J van Groeningen
    University Hospital Vrije Universiteit, Netherlands Cancer Institute, and NDDO Oncology, Amsterdam, The Netherlands
    J Clin Oncol 18:2772-9. 2000
    ....
  9. ncbi request reprint Phase II trial of cisplatin and gemcitabine in patients with advanced gastric cancer
    S M De Lange
    Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands
    Ann Oncol 15:484-8. 2004
    ..This phase II study was performed to determine the efficacy and toxicity of cisplatin and gemcitabine in patients with advanced gastric cancer...
  10. ncbi request reprint Combination of gemcitabine and cisplatin for advanced non-small cell lung cancer: a phase II study with emphasis on scheduling
    C Huisman
    Department of Pulmonary Diseases, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Lung Cancer 33:267-75. 2001
    ..Frequent omission of gemcitabine day 15 is a limitation of this schedule. This should be an important factor in a practical approach to decide on the most optimal schedule of the cisplatin plus gemcitabine combination...
  11. pmc Accelerated cisplatin and high-dose epirubicin with G-CSF support in patients with relapsed non-small-cell lung cancer: feasibility and efficacy
    C Huisman
    Department of Pulmonary Diseases, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Br J Cancer 85:1456-61. 2001
    ..Since the activity of this regimen is encouraging, it is probably best studied in untreated patients...
  12. pmc Prognostic role of clinical, pathological and biological characteristics in patients with locally advanced breast cancer
    A H Honkoop
    Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Br J Cancer 77:621-6. 1998
    ....
  13. pmc Sequence dependent effect of paclitaxel on gemcitabine metabolism in relation to cell cycle and cytotoxicity in non-small-cell lung cancer cell lines
    J R Kroep
    Department of Medical Oncology, University Hospital Vrije Universiteit, P O Box 7057, Amsterdam, MB, 1007, The Netherlands
    Br J Cancer 83:1069-76. 2000
    ..However, since paclitaxel increased dFdCTP accumulation, gemcitabine incorporation into RNA and the apoptotic index, the administration of paclitaxel prior to gemcitabine might be favourable as compared to reversed sequences...
  14. doi request reprint Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer
    J Sigmond
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    Ann Oncol 20:182-7. 2009
    ..In tumor samples, both gemcitabine and dFdU concentrations are high enough to enable radiosensitization, which warrants clinical studies using gemcitabine in combination with radiation...
  15. ncbi request reprint Hepatic arterial chemotherapy for colorectal cancer metastatic to the liver
    J M van Riel
    Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Oncology 59:89-97. 2000
    ..In this review about hepatic arterial chemotherapy we will discuss the theoretical and practical aspects, the results and complications, the selection of patients for hepatic arterial chemotherapy, and its future developments...
  16. ncbi request reprint Gemcitabine and cisplatin as induction regimen for patients with biopsy-proven stage IIIA N2 non-small-cell lung cancer: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC 08955)
    N Van Zandwijk
    Netherlands Cancer Institute and Free University, Amsterdam, The Netherlands
    J Clin Oncol 18:2658-64. 2000
    ....
  17. pmc Characterization of human soft-tissue sarcoma xenografts for use in secondary drug screening
    E Boven
    Department of Medical Oncology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Br J Cancer 78:1586-93. 1998
    ..Relatively low levels of topoisomerase IIalpha mRNA may partly account for intrinsic resistance against, for example, doxorubicin. Additional factors must contribute to moderate responsiveness to alkylating agents...
  18. ncbi request reprint Phase II study of cisplatin preceding gemcitabine in patients with advanced oesophageal cancer
    J R Kroep
    Department of Medical Oncology, VU Medical Centre, Amsterdam, The Netherlands
    Ann Oncol 15:230-5. 2004
    ..For oesophageal cancer there is no effective standard therapy. We studied the feasibility and efficacy of the cisplatin-gemcitabine combination chemotherapy in patients with unresectable oesophageal cancer...
  19. pmc Combined assessment of EGFR pathway-related molecular markers and prognosis of NSCLC patients
    M I Galleges Ruiz
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    Br J Cancer 100:145-52. 2009
    ..00015 as the P-value for a test of the additional impact of markers on prognosis, after taking stage into consideration. Confirmation of the impact of these markers in independent studies will be necessary...
  20. ncbi request reprint A phase I study of sequential intravenous topotecan and etoposide in lung cancer patients
    C Huisman
    Department of Pulmonary, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Ann Oncol 12:1567-73. 2001
    ..No objective responses were seen. CONCLUSION: Although the combined use of topoisomerase I and II inhibitors is attractive on theoretical grounds, excessive myelosuppression prevents substantial dose escalation...
  21. ncbi request reprint Analysis of deoxycytidine accumulation in gemcitabine treated patients
    R Honeywell
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    Nucleosides Nucleotides Nucleic Acids 25:1225-32. 2006
    ..The developed assay demonstrated good sensitivity and selectivity for CdR...
  22. ncbi request reprint Phase II study of tailored chemotherapy for advanced colorectal cancer with either 5-fluouracil and leucovorin or oxaliplatin and irinotecan based on the expression of thymidylate synthase and dihydropyrimidine dehydrogenase
    C H Smorenburg
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    Ann Oncol 17:35-42. 2006
    ..We performed a prospective study in which the choice of first-line chemotherapy with either 5-FU or a non-5-FU containing regimen was based on TS and DPD expression...
  23. ncbi request reprint Hepatic arterial 5-fluorouracil in patients with liver metastases of colorectal cancer: single-centre experience in 145 patients
    J M van Riel
    Department of Medical Oncology, University Hospital Vrije Universiteit Amsterdam, The Netherlands
    Ann Oncol 11:1563-70. 2000
    ..We performed an analysis of hepatic arterial 5-fluorouracil (5-FU) chemotherapy in 145 consecutive patients treated at a single institution...
  24. pmc CPT-11 sensitivity in relation to the expression of P170-glycoprotein and multidrug resistance-associated protein
    W J Jansen
    Department of Medical Oncology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Br J Cancer 77:359-65. 1998
    ..In conclusion, P-gp-positive cells show a low cross-resistance against CPT-11/SN38, which is only apparent with high P-gp expression in vivo. MRP does not seem to play a role in the sensitivity to CPT-11...
  25. ncbi request reprint Glufosfamide administered by 1-hour infusion as a second-line treatment for advanced non-small cell lung cancer; a phase II trial of the EORTC-New Drug Development Group
    G Giaccone
    Department of Medical Oncology, Vrije Universiteit Medical Center, 1117 De Boelelaan, HV 1081 Amsterdam, The Netherlands
    Eur J Cancer 40:667-72. 2004
    ..Median survival of all patients treated was 5.8 months (95% CI 4.2-7.9). In conclusion, glufosfamide administered by a 1-h infusion every 3 weeks has modest activity in advanced NSCLC patients after one prior platinum-based chemotherapy...
  26. ncbi request reprint Severe acute lung injury induced by gemcitabine
    R K Linskens
    Department of Medical Oncology, Department of Internal Medicine, Academic Hospital Vrije Universiteit, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
    Neth J Med 56:232-5. 2000
    ..Publications concerning severe pulmonary toxicity due to gemcitabine are sparse. Pathophysiology and treatment are considered and a review of the literature is presented...
  27. ncbi request reprint Medical treatment of non-small-cell lung cancer
    J Buter
    Department of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
    Ann Oncol 16:ii229-32. 2005
  28. ncbi request reprint Assessment of IAP (inhibitor of apoptosis) proteins as predictors of response to chemotherapy in advanced non-small-cell lung cancer patients
    C G Ferreira
    Department of Medical Oncology, Academic Hospital Vrije Universitiet, Amsterdam, The Netherlands
    Ann Oncol 12:799-805. 2001
    ..3) The relation between expression of IAPs and chemosensitivity in cancer patients may be more complex than anticipated by in vitro data...
  29. ncbi request reprint Nuclear localization of survivin is a positive prognostic factor for survival in advanced non-small-cell lung cancer
    B Vischioni
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    Ann Oncol 15:1654-60. 2004
    ..Survivin is usually localized in the cytoplasm of cancer cells, but nuclear localization has also been described, and we recently reported that survivin is a nuclear-cytoplasmic shuttling protein...
  30. pmc DT-diaphorase activity in normal and neoplastic human tissues; an indicator for sensitivity to bioreductive agents?
    E Smitskamp-Wilms
    Department of Oncology, Free University Hospital, Amsterdam, The Netherlands
    Br J Cancer 72:917-21. 1995
    ..The degree of variation found for DTD (range 4-250 nmol min-1 mg-1), was not observed for these enzymes (CP450R, 0.8-7.8 nmol cytochrome c min-1 mg-1; Cb5R, 3.5-27.6 nmol min-1 mg-1).(ABSTRACT TRUNCATED AT 250 WORDS)..
  31. ncbi request reprint Subcellular localization and nucleocytoplasmic transport of the chromosomal passenger proteins before nuclear envelope breakdown
    J A Rodriguez
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    Oncogene 25:4867-79. 2006
    ..Furthermore, the specific effect of INCENP and Survivin on the localization of Aurora B and Borealin, respectively, suggests that different complexes of CPPs may exist not only during mitosis, as recently reported, but also before NEB...
  32. ncbi request reprint Iron absorption during epoetin alfa therapy for chemotherapy-associated anaemia
    J H Savonije
    Department of Medical Oncology, VU Medical Center, Amsterdam, The Netherlands
    Cancer Invest 24:562-6. 2006
    ..Red cell iron incorporation was not disturbed in the majority (89%) of patients...
  33. ncbi request reprint Recombinant human endostatin administered as a 28-day continuous intravenous infusion, followed by daily subcutaneous injections: a phase I and pharmacokinetic study in patients with advanced cancer
    A H G Hansma
    Vrije Universiteit Medical Center, Department of Medical Oncology, Amsterdam, The Netherlands
    Ann Oncol 16:1695-701. 2005
    ..Preclinical data suggest that continuous low dose administration of endostatin is much more potent than intermittent dosing. The feasibility of this approach is tested in a phase I study...
  34. pmc Immunocytochemical detection of deoxycytidine kinase in haematological malignancies and solid tumours
    I Hubeek
    Department of Paediatric Haematology Oncology, VU University Medical Centre, De Boelelaan 1117, PO Box 7057, 1007 MB, Amsterdam, The Netherlands
    J Clin Pathol 58:695-9. 2005
    ..Deoxycytidine kinase (dCK) is responsible for the activation of several clinically important deoxynucleoside analogues used for the treatment of haematological and solid malignancies...
  35. ncbi request reprint Epidermal growth factor receptor (EGFR) gene copy number detection in non-small-cell lung cancer; a comparison of fluorescence in situ hybridization and chromogenic in situ hybridization
    M I Gallegos Ruiz
    Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands
    Histopathology 51:631-7. 2007
    ..These limitations of FISH can be overcome by using chromogenic in situ hybridization (CISH). To test the applicability of CISH for EGFR gene copy number testing in NSCLC, a comparison of CISH and FISH was performed...
  36. ncbi request reprint Expression of the human major vault protein LRP in human lung cancer samples and normal lung tissues
    A M Dingemans
    Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Ann Oncol 7:625-30. 1996
    ..The recently discovered LRP protein has been shown to be involved in drug resistance and possibly in detoxification processes...
  37. ncbi request reprint The determination of gemcitabine and 2'-deoxycytidine in human plasma and tissue by APCI tandem mass spectrometry
    R Honeywell
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    J Chromatogr B Analyt Technol Biomed Life Sci 847:142-52. 2007
    ..In conclusion the analytical assay was very sensitive, reliable and robust for the determination of plasma and tissue concentrations of dFdC and CdR...
  38. ncbi request reprint The activity of raltitrexed (Tomudex) in malignant pleural mesothelioma: an EORTC phase II study (08992)
    P Baas
    The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
    Eur J Cancer 39:353-7. 2003
    ..We conclude that raltitrexed has activity as a single agent in the treatment of MPM, and that further studies with this drug in MPM are warranted...
  39. ncbi request reprint Twenty-five years of treating advanced NSCLC: what have we achieved?
    G Giaccone
    Division of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
    Ann Oncol 15:iv81-3. 2004
  40. ncbi request reprint Pleura mesothelioma: combined modality treatments
    T Cerny
    Vrije Universiteit Medical Center, Division of Medical Oncology, Amsterdam, The Netherlands
    Ann Oncol 13:217-25. 2002
  41. pmc Cortisol is transported by the multidrug resistance gene product P-glycoprotein
    C K van Kalken
    Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands
    Br J Cancer 67:284-9. 1993
    ..These results demonstrate that Pgp may function as a transporter for cortisol and suggest a physiological role of the protein in steroid handling by organs such as the adrenal...
  42. ncbi request reprint Pharmacokinetics of S-1, an oral formulation of ftorafur, oxonic acid and 5-chloro-2,4-dihydroxypyridine (molar ratio 1:0.4:1) in patients with solid tumors
    G J Peters
    Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands
    Cancer Chemother Pharmacol 52:1-12. 2003
    ....
  43. ncbi request reprint Gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer
    S M De Lange
    Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
    Eur J Cancer 38:1212-7. 2002
    ..Although the toxicity of this treatment was occasionally severe, the response and survival are encouraging and warrant further studies of this combination...
  44. ncbi request reprint A bone biopsy is mandatory in the optimal management of bone lesions in patients with a long-term history of malignancy of the breast
    M Hadithi
    Department of Internal Medicine, Academic Hospital Vrije Universiteit, P O Box 7057, 1007 MB, Amsterdam, The Netherlands
    Neth J Med 56:223-8. 2000
    ..One patient had Paget's disease, and the other had metastatic hepatocellular carcinoma...
  45. ncbi request reprint The epidermal growth factor receptor pathway and its inhibition as anticancer therapy
    M L Janmaat
    Department of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
    Drugs Today (Barc) 39:61-80. 2003
    ..These studies failed to demonstrate an increase in survival by adding ZD1839 together with chemotherapy in patients with advanced NSCLC...
  46. ncbi request reprint Downstream molecular determinants of response to 5-fluorouracil and antifolate thymidylate synthase inhibitors
    B van Triest
    Department of Oncology, University Hospital VU, Amsterdam, The Netherlands
    Ann Oncol 11:385-91. 2000
    ..This knowledge should be used to design clinical studies with the aim to deliver effective treatment to potentially sensitive patients both in the adjuvant setting and in advanced stage disease...
  47. ncbi request reprint Potent expansion of human natural killer T cells using alpha-galactosylceramide (KRN7000)-loaded monocyte-derived dendritic cells, cultured in the presence of IL-7 and IL-15
    N Nishi
    Department of Medical Oncology, University Hospital Vrije Universiteit, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
    J Immunol Methods 247:61-72. 2001
    ....
  48. ncbi request reprint Phase II trial of ZD0473 as second-line therapy in mesothelioma
    G Giaccone
    Free University Hospital, Amsterdam, The Netherlands
    Eur J Cancer 38:S19-24. 2002
    ..This trial also demonstrates that clinical trials in second-line mesothelioma patients are feasible...
  49. ncbi request reprint Phase II study of imatinib in patients with WHO B3 and C thymomas
    G Giaccone
    National Cancer Institute, Bethesda, MD VU Medical Center, Amsterdam, The Netherlands Leiden University Medical Center, Leiden, The Netherlands
    J Clin Oncol 26:14665. 2008
    ..C-Kit is highly expressed in thymic carcinomas (80%) but infrequent in thymomas. Scanty information is available on the role of C-Kit mutations in thymic carcinomas...
  50. ncbi request reprint Thymoma: update for the new millennium
    S B Johnson
    Division of Cardiothoracic Surgery, Department of Surgery, Academic Hospital, Vrije Universiteit, Amsterdam, The Netherlands
    Oncologist 6:239-46. 2001
    ..Novel antiproliferative systemic agents, with both cytotoxic and cytostatic mechanisms of action, are being tested in ongoing prospective clinical trials...