Cancer clinical applications

FIGURE 132-1. Diagram of the chromosomal translocation that results in the Philadelphia chromosome. This abnormality is encountered in 90% to 95% of patients who have chronic myelogenous leukemia. (From Fishleder AK. Oncogenes and cancer clinical applications. Cleve Clin J Med 1990 57 721-726.)... 

There were some early clinical studies of carzinophilin, both alone [131,132] and in combination with mitomycin C, in humans [133]. Despite showing promising reduction in the number of cancer cells, there were significant toxic side effects and clinical application has not been pursued any further. 

MecalfD (1990) The colony stimulating factors. Discovery, development, and clinical applications. Cancer 65 185-195... 

The use of triphenylethylene SERMs as Pgp inhibitors for clinical application has been hampered by unacceptable toxicity at doses required to achieve adequate cellular concentration, which is likely due to the involvement of proteins with the ability to bind these compounds. For instance, toremifene is able to reverse MDR and to sensitize human renal cancer cells to vinblastine in vitro. However, in vivo toremifene is tightly bound to serum proteins, in particular a 1-acid glycoprotein (AAG), which may limit its tissue availability (Braybrooke et al. 2000). In agreement with this, Chatterjee and Harris (1990) have shown that tamoxifen and 4-OH-tamoxifen were similarly potent in reversing MDR in Chinese hamster ovary (CHO) cells with acquired resistance to adriamycin. However, the addition of AAG (0.5 to 2 mg/ml, the range found in vivo) to cell cultures decreased the effect of tamoxifen on reversing MDR, and at the highest AAG concentration there was a complete reversal of the effects of... 

Since the discovery of the anticancer potential of Taxol , a complex compound isolated from the bark extract of the Pacific yew tree, more than 20 years ago, there has been an increasing demand for the clinical application of this compound. First, the promising results of the 1991 clinical trials in breast cancer patients were announced, and soon after Bristol-Myers-Squibb trade-marked the name Taxol and used it as an anticancer drug. At that point, the only source of the drug was the bark of the endangered yew tree. Fortunately, it was soon discovered that a precursor of Taxol could be obtained from an extract of the tree needles instead of the bark. 

Chapter 7 outlines the basic mechanism and treatment of emesis, and in particular, that induced by chemotherapy of cancer. Finally, the chemistry, pharmacology and clinical applications of antagonists of the platelet-activating factor (PAF), an important mediator of many physiological and pathological conditions, are reviewed in Chapter 8. 

What has been achieved until now In the year 2001, several liposome and antibody based strategies have been or will soon be approved for clinical application, some for the treatment of cancer, some for the treatment of bacterial infections, some for chronic inflammatory diseases. Furthermore many monoclonal antibodies without a drug or pharmacologically active molecule attached are in the clinic. Their intrinsic targeting and effector function is obviously sufficient for the pharmacological effect. 

Sin L, Carducci M, Pearce L, et al. (2005) AACR-EORTC-NCI Int Conf on Molecular Targets and Cancer Therapeutics Discovery, Biology, and Clinical Applications, Philadelphia, November 14-18, 217 (Abstract C77)... 

The initial experience with the taxanes and especially with paclitaxel in the realm of combined modality therapy has had a substantial impact on the treatment of cancers both in the United States and worldwide. Paclitaxel delivered in concert with radiation provides a classical model of the development of clinically applicable treatment strategies from laboratory-based studies. The initial in vitro works of Tishler (39) and Choy (40) have translated in a very tangible way into approaches that are clinically applicable and in the next generation of randomized clinical trials their efficacy will be compared to more traditional chemotherapies in the combined modality setting. While the experience to date with both paclitaxel and docetaxel has been largely positive, the mortality rates in many of the solid tumor types remind us that much more needs to be done. 

As haemopoietic growth factors serve to stimulate the production of mature blood cells, their clinical application in diseases characterized by sub-optimal production of specific blood cell types was obvious. Several CSF preparations have gained regulatory approval, or are currently being assessed in clinical trials (Table 6.4). G-CSF and GM-CSF have proved useful in the treatment of neutropenia. All three CSF types are (or are likely to be) useful in the treatment of infectious diseases, some forms of cancer and the management of bone marrow transplants (Table 6.4), as they stimulate the differentiation/activation of white blood cell types most affected by such conditions. 

Sarhill, N., Walsh, D., Nelson, K.A. Hydromorphone pharmacology and clinical applications in cancer patients, Support. Care Cancer 2001, 9, 84-96. 

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