Human tumours

Dimeric complexes like [Cl(NH3)Pt H2N(CH2)4NH2 Pt(NH3)Cl]Cl2 are also being investigated as they bind to DNA in a different way to that involved in cisplatin binding and are active in cisplatin-resistant human tumour cells. They are more potent than cisplatin in lung cancer models in vivo and are likely to go on clinical trials in the near future [204],... 

Interferon does not only inhibit vims replicahon, it also has mulhple effects on cell metabolism and slows down the growth and mulhplicahon of treated cells. This is probably responsible for its widely reported anhtumour effect Encouraging results have been reported from clinical trials of interferon against several human tumours such as osteogenic sarcoma, myeloma, lymphoma and breast cancer. 

Pulciani S, Santos E, Lauver AV, et al. 1982a. Oncogenes in solid human tumours. Nature 300 539-542. 

Zimmerman, RJ., Chan, A. and Leadon, S.A. (1989). Oxidative damage in murine tumour cells treated in vitro by recombinant human tumour necrosis factor. Cancer Res. 49, 1644-1648. 

Keffer J, Probert L, Cazlaris H, et al. Transgenic mice expressing human tumour necrosis factor a predictive genetic model of arthritis. EMBO J I99l 10(13) 4025 t031. 

Rosenberg, S.A., Progress in human tumour immunology and immunotherapy, Nature, 411,380,2001. 

Nigro, j. M., et ah. Mutations in the p53 gene occur in diverse human tumour types. Nature, 1989,... 

Webb MS, Harasym TO, Masin D, Bally MB, Mayer LD. Sphingomyelin-cholesterol liposomes significantly enhance the pharmacokinetic and therapeutic properties of vincristine in murine and human tumour models. Br J Cancer 1995 72 896. 

Schwendener RA, et al. In vitro activity of liposomal N" -octadecyl-l-P-D-arabinofuranosylcytosine (NOAC), a new lipophilic derivative of 1-P-d-arabinofuranocylcytosine on biopsized clonogenic human tumour cells and haematopoietic precursor cells. Invest New Drugs 2001 19 203. 

Figure 21.7 Control of the activity of Ras by a balance of the activities of guanine nucleotide exchange factor and GTPase. GAP is the abbreviation for GTPase-activating factor and GEF for guanine nucleotide exchange factor. Both are enzymes. Both the activities are controlled by stimuli from various cell surface receptors. Ras oncogenes are present in about 30% of all human tumours.

Colon (cultured human tumour derived colonic epithelial cells) DOC, LC 3,4,35,85,121... 

Colon (cultured human tumour derived epithelial cells)... 

Bianco R, Garofalo S, Rosa R, Damiano V, Gelardi T, Daniele G Marciano R, Ciardiello F, Tortora G. (2008) Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs. Br J Cancer 98 923-930. 

Interestingly, after intravenous administration of a radiolabelled folate conjugate ( -In-dium-diethylenetriaminepenta acid (DTPA)-folate) in the rat, the conjugate was rapidly excreted in the urine. Moreover, after intravenous administration to athymic mice with a human tumour cell implant, the radiotracer was not only taken up by the subcutaneous tumour but was also taken up by the kidneys in significant quantities [63], indicating substantial renal selectivity of the folate conjugate. In addition to the kidney, the liver also has a high concentration of the folate-receptor [64]. 

As in cancer predisposing syndromes, these genetic alterations are sometimes carried in the germline. Among human tumours, heritable mutations are an exception. Most alterations are acquired in somatic life in the form of chromosomal translocations, deletions, inversions, amplifications or point mutations. Certain oncogenic viruses play important roles in a few human tumours. Examples are human papilloma-virus in cervical cancer and skin tumours, Ep-stein-Barr virus in nasopharyngeal carcinoma and Burkitt s lymphoma, and human T-cell leukaemia viruses (e.g. HTLV-I, HTLV-II) in T-cell leukaemia. 

Overall, the pattern of perfnsion in human tumours is non-uniform, and hnman tnmours contain well-perfused, rapidly growing regions, as well as poorly-perfnsed, often necrotic, regions. So the first obstacle to effective systemic treatments is the heterogenidty of the distribution of areas of growth within the tnmonr. 

Studies in pre-clinical models with human tumours are often carried out in (immuno)defi-cient mice. However, particularly in the case of monoclonal antibody-directed therapy, it is important to recognize that these models, while useful, frequently over-predict activity and under-predict toxicity because the target antigen is tumour-specific in the animal but only tumour-associated in man. 

The corneal pocket assay and the window preparations are designed to measure vessel formation after addition of stimulators. These assays can for instance be used for the study of angiogenic potential of human tumours. These models are also suitable for pre-clinical testing of angiogenesis inhibitors. 

Ball, G., Mian, S., Holding, R, Allibone, R.O., Lowe, J., Ali, S., Li, G., McCardle, S., Ellis, I.O., Creaser, C., and Rees, R.C., An integrated approach utilizing neural networks and SELDI mass spectrometry for classification of human tumours and rapid identification of potential biomarkers. Bioinformatics, 18, 395 04, 2002. 

Ikegami Y, Yano S, Nakao K, Fujita F, Fujita M, Sakamoto Y, Murata N, Isowa K (1995) Antitumour activity of the new selective protdn kinase C inhibitor 4 -N-benzoyl staurosporine on murine and human tumour models. Arzneim Forsch 45 1225-1230... 

Baguley BC, Marshall ES, Holdaway KM, et al. Inhibition of growth of primary human tumour cell cultures by a 4-anilinoquinazoline inhibitor of the epidermal growth factor receptor family of tyrosine kinases. EurJ Cancer 1998 34 1086-1090. 

Duffy CP, Elliott CJ, O Connor RA, et al. Enhancement of chemotherapeutic drug toxicity to human tumour cells in vitro by a subset of non-steroidal anti-inflammatory drugs (NSAIDs). EurJ Cancer 1998 34 1250-1259. 

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