Classical chemotherapy

Higher concentrations of active drug at the tumor, compared to the concentrations accessible by classical chemotherapy. 

V. Malhotra, and M.C. Perry, Classical chemotherapy Mechanisms, toxicities and the therapeutic window. Cancer Biol Iher, 2 (4 Suppl 1), S2-4, 2003. 

Lectins also play a significant role in the development of cancer, being implicated in processes including cell replication, migration and formation of metastases. Thus inhibiting these cell surface interactions offers an alternative approach to classical chemotherapy in the treatment of cancer. 

In malaria chemotherapy, resistant parasites have significantly reduced the efficiency of classic antifolate drugs. In the search for novel inhibitors of... 

The answer is c. (Katzung, pp 608-609, 932-9.13.) Methotrexate is classified as an anti metabolite with therapeutic uses in cancer chemotherapy and as an immunosuppressive agent indicated in the treatment of severe active classical rheumatoid arthritis. Leucovorin is related to methotrexate in that it is an antagonist of its actions. It can supply a source of reduced folate for the methylation reactions that are prevented by methotrexate. 

Electrochemistry plays an increasingly important role in biology and medicine and the electrochemical treatment of tumors (ECT) is receiving considerable attention as a viable alternative to the more classical tumor treating approaches of surgery and chemotherapy. Dr. A. Vijh, a specialist in this area, describes both the phenomenology and the proposed physicochemical mechanisms of ECT in a comprehensive chapter. 

Spatial cooperation is a term coined to describe a situation when disease in one particular anatomic site is missed by one modality but is treated adequately by another. The essence of this is that radiation is a local therapy that will not impact on metastatic disease beyond the planned field borders. Systemic cytotoxic chemotherapy is traditionally used to address the potential distant spread of cancer. In the original description of this mechanism there is no assumption of an interaction between the drugs and radiation with the idea being that the best radiation and best chemotherapy be administered independently of toxicities. The classic example used in several textbooks to illustrate this is the treatment of childhood leukemia with systemic chemotherapy, while their central nervous system, a potential sanctuary site where disease is not treated adequately by chemotherapy, is treated by radiation (28). The reality of the interaction between radiation and chemotherapy is that the dose and timing of radiation are adjusted accordingly to minimize their impact on the neural tissues. 

Cyclicity of administration is vital in the use of 5-FU as a radiosensitizer. The concept of cyclical treatment has been well established in cancer chemotherapy and alien to classical radiation therapy (where it is termed split-course therapy). 5-FU radio-sensitizes tumor tissue as well as normal cells. However, this normal tissue radio-sensitizationis limited to the irradiated field. Suitable fractionation (i.e., cyclical therapy) can permit rapid normal tissue recovery (23). The results of infused 5-FU and radiation in head and neck cancer supports the principle that cyclical treatment with 5-FU does not suffer from the limitations apparent in split-course radiation treatments. 

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. 

Therapy in those with ectopic erythropoietin production depends upon correcting the hormone level by removing whatever tissue is responsible for its production and examples include nephrectomy for renal carcinoma or the classical, albeit rare, cerebellar haemangioblastoma. Where metastases have occurred appropriate cytotoxic chemotherapy is needed and response in haematocrit becomes a rough indicator of the success with which the tumour is responding to therapy. In some individuals venesections are necessary to control the raised haemoglobin. 

In the field of radiation therapy, it is recognized that there are other promising approaches to improve the efficiency of the treatment such as better individual adaptation of fractionation or association with drugs to modulate the radiation sensitivity. Combination of radiotherapy with the two other classical methods of cancer treatment, surgery, and chemotherapy may also be optimized. 

The development of antibacterial chemotherapy during the past 75 years has spearheaded the successful use of today s drugs to combat bacterial infections. Studies in (3-lactam chemistry were stimulated when (3-lactam ring, the four membered heterocycle, was recognized as a key structural feature as well as a key therapeutic feature of the bicyclic (3-lactam antibiotics such as penicillins, cephalosporins, and other classical antibiotics. The last two decades have registered the discovery of several nonclassical bicyclic (3-lactam antibiotics, e.g., thienamycin and carba-penems of natural origin like olivanic acids, carpetimycin, pluracidomycin, and aspareomycins. 

Dihydrofolate reductase (DHFR), a classic target in antimicrobial and anticancer chemotherapy, has been shown to be a useful therapeutic target in plasmodium, toxoplasma, and eimeria species. Pyrimethamine is the prototypical DHFR inhibitor, exerting inhibitory effects in all three groups. However, pyrimethamine resistance in P falciparum has become widespread in recent years. This is largely attributable to specific point mutations in P falciparum DHFR that have rendered the enzyme less susceptible to the inhibitor. 

The common side effects of long-term corticosteroid therapy are summarized in Figure 27.13. [Note Increased appetite is not necessarily an adverse effect, since it is one of the reasons for the use of prednisone in cancer chemotherapy.] The classic Cushing-like syndrome—redistribution of body fat, puffy face, increased body hair growth, acne, insomnia and increased appetite—are observed when excess corticosteroids are present. Increased frequency of... 

Cancer is one of the major causes of death in the western world. It refers to approximately 150 diseases that exhibit some common characteristics an uncontrolled growth of cells and the ability to invade and damage normal tissues either locally, or at distant sites in the body. Nowadays, three classical approaches exist to treat cancer surgical excision, irradiation, and chemotherapy. The role of each depends on the type of cancer and its development stage. 

Ang, W.H., Dyson, P.J. Classical and non-classical ruthenium based anticancer dmgs towards targeted chemotherapy. Eur. J. Inorg. Chem. 4003 018 (2006)... 

Poly (ADP-ribose) polymerase-1 (PARP-1) facilitates the repair of DNA strand breaks (Calabrese et al, 2004). Inhibiting PARP-1 increases the cytotoxicity of DNA-damaging chemotherapy and radiation therapy in vitro. But classical PARP-1 inhibitors have limited clinical utility. AG14361 is, to our knowledge, the first high-potency... 

With the rapid advances in macromolecule crystallography, the PDB (http //www.rcsb.org/pdb/) currently contains about 12,600 macromolecular NMR or crystal structures. While this may not represent all macromolecular structures, it does represent the large majority. Most of the major scientific journals require simultaneous deposition of macromolecular crystal data into the PDB as the journal article is published. Besides structural proteins, and the classic crystal structures such as hemoglobin and lysozyme, the data base includes many enzymes or representative enzymes from classes that could be good targets for chemotherapy. 

However, in view of its apparent success, this work is bound to advance further our understanding of the modes of action and structure-activity relationships of non-classical antimetabolites, and to produce new leads for the rational design of future drugs for chemotherapy. It should be remembered that it was the rational approach , based on the concepts of antimetabolites and of dihydrofolate reductase inhibitors as chemotherapeutic agents, that has... 

In the area of classical antimetabolites, a host of highly active new nucleosides have been found that show promise in the chemotherapy of cancer and viral diseases. Classical antimetabolites appear to have a virtual monopoly in the field of antiviral agents. After the discovery of the first effective drugs against,the Herpes virus 28b, c 25), a new breakthrough may have been... 

Another classical example of a tissue-specific toxicity is the effect of o,//-DDD on the 11 /3-hydroxylase, a key steroidogenic enzyme present only in the adrenal tissue. In this particular case, the enzymes effecting steroid production are the specific targets for adrenal toxicants. Steroid hydroxylases contain hemoproteins, constituents that make them vulnerable to toxicants and oxidative stress54. The adrenotoxic effects of DDT and its derivatives, and the sensitivity of the 11 /3-hydroxylase to DDT have been detected in numerous species, including humans. A derivative of DDT, under the name mitotane, was in fact used clinically in chemotherapy treatments for tumors in the adrenal cortex93 as it specifically destroys adrenal cells. The use of mitotane is similar... 

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