Cancer chemotherapy, research

Patrizia Diana was born in Palermo in 1967. She graduated in pharmacy with honors at the University of Palermo in March 1990. From April 1990 to August 1992, she was a research fellow at the Medicinal Chemistry Department of the University of Palermo. She has been working as researcher in medicinal chemistry (September 1992-March 2000) and associate professor of medicinal chemistry (April 2000-to date) at the University of Palermo. From May 1994 to May 1995, she worked with Professor Malcolm F. G. Stevens ar the CRC Experimental Cancer Chemotherapy Research Group for a fellowship. Since 2005, she has been vice-director of the Dipartimento Farmacochimico Toss, e Biol. She is a member of the Societa Chimica Italiana and International Society of Heterocyclic Chemistry. 

So, the 20th century actually led to an almost total disappearance of C. sativa for medicinal purposes. The only source for THC, which became the focus of scientific research, was fhe rafher fedious exfracfion and purification from confiscated hashish or marihuana. In 1972 the first commercially viable total synthesis of A9-THC was established and it became the first cannabinoid available as a modern medicine in the form of soft gel capsules (the active ingredient being called dronabinol from tetrahydrocannabinol) under the trade name Marinol for the prevention of nausea and vomiting during cancer chemotherapy. 

The indication prevention of nausea and vomiting during cancer chemotherapy came from experiences of marihuana-smoking patients, not from pharmacological research [129]. 

The authors wish to express their sincere appreciation to Dr. Tazuko Tashiro of Cancer Chemotherapy Center of the Japanese Foundation for Cancer Research for the screening test of the survival effect against p388 lymphocytic leukemia in mice ip/ip. 

Hariparsad, N., Sane, R.S., Strom, S.C. and Desai, PB. (2006) In vitro methods inhuman drug biotransformation research implications for cancer chemotherapy. Toxicology In Vitro An International Journal Published in Association with BIBRA, 20 (2), 135-153. 

Conners, T. A. Roberts, J. J. In Platinum Coordination Complexes in Cancer Chemotherapy Recent Results in Cancer Research , Springer-Verlag, New York, 1974, 48. 

The serendipitous discovery of the antitumor activity of cisplatin opened a huge field of research, leading to significant advances and successes in cancer chemotherapy [181]. Cisplatin and its analogues are reactive complexes that exhibit pharmacokinetic, pharmacodynamic, and toxicological behaviors so closely interdependent as to be all but impossible to untangle. Our focus here is and remains metabolism, but some considerations regarding activity and toxicity are also addressed. 

After over half a century of chemotherapy research, cancer remains one of the most difficult life-threatening diseases to treat, a consequence of factors that include limitations of animal models, tiunour diversity, drug resistance and the side effects of therapy. Although there have been successes, most notably in treatment of testicular cancer [1], chemotherapy can currently still offer only a modest increase in survival time in the majority of advanced disease cases [2], The incidence of cancer is increasing due to ageing populations in most countries, and it has been estimated that in 20 years time there will be 20 million new cancer patients worldwide each year [3]. An optimistic view, however, is that in the coming decades advances in prevention, detection and treatment will see cancer becoming considered not as a fatal but as a chronic disease [3]. 

The same multigenic approach can apply to cancer pharmacogenomic research, which may be especially relevant to cancer therapies that do not have an obvious candidate polymorphism in metabolism genes and do not have a major protein target, such as cisplatin-based chemotherapy and radiation therapy as well as combinatorial therapy with multiple agents. We will use cisplatin-based chemotherapy as a prototype to illustrate the application of using a pathway-based approach in pharmacogenomic studies. 

The 5-HT3 receptors are found in both the peripheral nervous system and central nervous system (CNS), where they mediate last synaptic transmission at synapses (3). In the CNS, they are located predominantly at intemeurones, where they modulate the release of a range of neurotransmitters (4-9). There is some evidence that 5-HT3 receptors play roles in brain reward mechanisms and in neurological phenomena such as anxiety, psychosis, nociception, and cognitive function (10,11), and in the first few years following the discovery of these receptors, there was also much interest in the therapeutic potential of 5-HT3 receptor antagonists for antipsychotic, antinociceptive, and other psychiatric disorders (12-15). This potential has not yet been realized, but there is still active research in this area (16), and their current major therapeutic target is against emesis in cancer chemotherapy and irritable bowel syndrome (17,18). 

Mailing to Sobels (October 1970), EMS. Ethyl methanesulfonate and methyl methane-sulfonate were standard alkylating agents used in routine chemical mutagenesis research. Cyclophosphamide, a known teratogen, was a compound used in cancer chemotherapy. 

Iliadis, A. and Barbolosi, D., Optimizing drug regimens in cancer chemotherapy by an efficacy-toxicity mathematical model, Computers and Biomedical Research, Vol. 33, No. 3, 2000, pp. 211-226. 

Elucidation of the role of the 205 proteasome in protein degradation and as a target for cancer chemotherapy could not have been achieved without small molecule inhibitors, some of which have served strictly as research tools, while others have progressed through preclinical development and clinical trials.18,28,29 These molecules represent a variety of structural classes, including peptide boronic acids such as bortezomib and CEP-187 70,30 epoxyketones (e.g. carfilzomib)31 and the y-lactam-(3-lactone family of inhibitors (Figure 12.1). 

XuRNER G.C., Du, F., Varshavsky, A., Peptides accelerate their uptake by activating a ubiqrutin-dependent proteolytic pathway. Nature 2000, 405, 579-583. Almond, J.B., Cohen, G.M., Xhe proteasome a novel target for cancer chemotherapy. Leukemia 2002, 16, 433—443. Kisselev, a. F., Goldberg, A.L., Proteasome inhibitors from research tools to dmg candidates. Chem. Biol. 2001, 8, 739-758. 

After retiring in 1975, he continued active research but moved to a new application of catalytic chemistry. He synthesized new platinum-containing molecules that are derivatives of the same family known as dv-platinum, which was discovered to have antitumor activity. Turkevich s candy-coated cfv-platinum derivatives were also useful clinical agents in cancer chemotherapy. Even at the end of his life, Turkevich was still doing experiments with colleagues in medicine and chemistry. 

---