Drug Targeting Organ-Specific Strategies

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References 197 [137] Abbas AK, Lichtman AH, Pober JS, Cellular and Molecular Immunology, pp. 424–438. W. B. Saunders Company, Philadelphia, 1997. [138] Elson CO, Sartor RB, Tennyson GS, Riddell RH, Gastroenterology 1995, 109, 1344–1367. [139] Smith JD, Breslow JL, J. Intern. Med. 1997, 242, 99–109. [140] Cybulsky MI, Gimbrone Jr MA, Science 1991, 251, 788–791. [141] Carew TE, Schwenke DC, Steinberg D, Proc. Natl Acad. Sci. USA 1987, 84, 7725–7729. [142] Mori N, Horie Y, Gerritsen ME, Anderson DC, Granger DN, Gut 1999, 44, 186–195. [143] Keelan ETM, Licence ST, Peters AM, Binns RM, Haskard DO, Am. J. Physiol. 1994, 266, H278–H290. [144] Silber A, Newman W, Reimann KA, Hendricks E, Walsh D, Ringler DJ, Lab. Invest. 1994, 70, 163–175. [145] Grabbe S, Schwarz T, Immunol. Today 1998, 19, 37–44. [146] Austrup F, Vestweber D, Borges E, Lohning M, Brauer R, Herz U, Renz H, Hallmann R, Scheffold A, Radbruch A, Hamann A, Nature 1997, 385, 81–83. [147] von Asmuth EJU, Smeets EF, Ginsel LA, Onderwater JJM, Leeuwenberg JFM, Buurman WA, Eur. J. Immunol. 1992, 22, 2519–2526. [148] Kuijpers TW, Raleigh M, Kavanagh T, Janssen H, Calafat J, Roos D, Harlan JM, J. Immunol. 1994, 152, 5060–5069. [149] Chuang PI, Young BA, Thiagarajan RR, Cornejo C, Winn RK, Harlan JM, J. Biol. Chem. 1997, 272, 24813–24818. [150] Yoshida M, Szente BE, Kiely JM, Rosenzweig A, Gimbrone Jr MA, J. Immunol. 1998, 161, 933–941. [151] Bergers G, Javaherian K, Lo KM, Folkman J, Hanahan D, Science 1999, 284, 808–812. [152] Bombeli T, Schwartz BR, Harlan JM, Blood 1999, 93, 3831–3838. [153] Gastroenterology, Electronic reference and review, Lippincott-Raven.
8 Strategies for Specific Drug Targeting to Tumour Cells Jos G. W. Kosterink, Wijnand Helfrich, Lou F. M. H. de Leij 8.1 Introduction Cancer is the second most common cause of death among adults in most Western countries. Great progress has been made in the treatment of selected malignancies and approximately 50% of all malignancies can be cured by current treatment strategies. The majority of these cures are achieved by surgery, that is if the disease has not spread throughout the whole body. Radiotherapy and chemotherapy used alone or in combination have greatly improved the management of patients with a variety of solid and haematologic malignancies. Chemotherapy has curative potentials in patients with various haematologic malignancies, testicular cancer and germ cell tumours. Despite improvements in the treatment of most metastatic solid tumours, these remain largely incurable. Reasons for this are insufficient tumour selectivity of anti-cancer agents and poor penetration within the tumour mass [1,2]. Another problem is that after surgical removal of the solid tumour, metastatic cells that are resistant to conventional chemotherapy often remain. The same holds for tumours with high metastatic capacity and high proliferation rates, even though these might be sensitive initially to chemoor radiotherapy. Relapse may occur with therapy-resistant recurrences. New therapeutic approaches are under investigation to address these obstacles. The purpose of this chapter is to describe briefly the pathology of cancer, the cell types involved in cancer disease, the currently available therapeutics and problems/hurdles to tumour-directed drug delivery/targeting.The following will be discussed in more detail: surface epitopes for targeting, molecular targets within the cells for therapeutic intervention, suitable targeting devices, drugs of choice for targeting and in-vitro and in-vivo techniques which are available to study the various approaches. Finally the current clinical experience with targeted anti-cancer drugs will be discussed. 8.2 Cancer Pathology 8.2.1 Cell Biology of Cancer Drug Targeting Organ-Specific Strategies. Edited by G. Molema, D. K. F. Meijer Copyright © 2001 Wiley-VCH Verlag GmbH ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic) In the cell cycle, dividing cells undergo one mitosis (M) after another, passing through G 1,S (DNA synthesis phase), and G 2 phases. Some cells leave the cycle temporarily, entering a G 0 state from which they can be rescued by appropriate mitogenic stimuli. Other cells leave the cycle permanently, entering terminal differentiation.
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Preface Drug Targeting Organ-Specif
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Foreword Drug Targeting Organ-Speci
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X List of Contributors Henderik W.
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XII List of Contributors Grietje Mo
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Contents Drug Targeting Organ-Speci
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Contents XVII 3 Pulmonary Drug Deli
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Contents XIX 5.2.1.6 Identification
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Contents XXI 7.5 In Vitro Technique
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Contents XXIII 9.4 Tumour Vasculatu
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Contents XXV 12.8. Tissue Slices fr
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Dexa dexamethasone DIVEMA divinyl e
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LRP lung resistance related protein
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ROS reactive oxygen species RSV res
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Index a ADEPT 217, 224, 268, 291 ad
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e E. coli expression system 292 eff
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polymers, soluble 4, 218 - dendrime
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2 1 Drug Targeting: Basic Concepts
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24 2 Brain-Specific Drug Targeting
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54 3 Pulmonary Drug Delivery: Deliv
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4 Cell Specific Delivery of Anti-In
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The sinusoids are lined by the disc
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4.2.2.2 Phagocytosis and Transcytos
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ther inflammatory cells or accessor
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4.3 Hepatic Inflammation and Fibros
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process is not yet available. Sever
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this carrier to the KCs.When the ma
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e taken up rapidly by mannose recep
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y the transcriptional regulatory pr
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4.8 Testing Liver Targeting Prepara
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4.8 Testing Liver Targeting Prepara
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4.9 Targeting of Anti-inflammatory
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4.9 Targeting of Anti-inflammatory
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with monoclonal and bispecific anti
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References 117 [50] Coleman DL, Eur
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References 119 [133] Cronstein BN,
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5 Delivery of Drugs and Antisense O
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5.1 Introduction 123 convoluted tub
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treatment of the targeted cell and
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CL uptake (ml/min/g) centration pro
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5.2.1.4 Specific Binding of Alkylgl
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5.2 Renal Delivery Using Pro-Drugs
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5.2 Renal Delivery Using Pro-Drugs
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5.3 Renal Delivery Using Macromolec
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250 9 Tumour Vasculature Targeting
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256 10 Phage Display Technology for
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11 Development of Proteinaceous Dru
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carrier is an homogenous product. I
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11.3 The Homing Device 11.3 The Hom
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malian cell lines that have acquire
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jugates for the delivery of other a
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11.5 The Linkage Between Drug and C
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actions are directed towards these
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11.5 The Linkage Between Drug and C
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homing potential if the antigen rec
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ly used promoters include T7 RNA po
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the baculovirus expression vector,
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11.8 Recombinant DNA Constructs 297
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11.8 Recombinant DNA Constructs 299
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toxic activity. Anthrax and tetanus
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11.9 Recombinant Domains as Buildin
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References 305 [16] Milstein C, Wal
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References 307 [99] Verma R, Boleti
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12 Use of Human Tissue Slices in Dr
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are also extensively used in a vari
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Meanwhile many incubation systems h
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12.3 Incubation and Culture of Live
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to investigate the effect of differ
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The mechanisms of uptake and excret
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12.6 The Use of Liver Slices in Dru
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12.7 Efficacy Testing of the Drug T
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NO x µM 80 60 40 20 * * 12.7 Effic
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TNFα ng/ml 1.5 1 0.5 0 * Human (n=
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References 329 [33] Ikejima K, Enom
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References 331 [109] Dutt A, Priebe
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334 13 Pharmacokinetic/Pharmacodyna
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372 14 Drug Targeting Strategy: Scr
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