For Cancer

Several of the naturally occurring indoles also have clinical importance. The dimeric vinca alkaloid vincristine and closely related compounds were among the first of the anti-mitotic class of chemotherapeutic agents for cancer[14]. The mitomycins[15] and derivatives of ellipticine[16] are other examples of compounds having anti-tumour activity. Reserpine, while not now a major drug, was one of the first compounds to show beneficial effects in treatment of mental disorders[17]... 

Adrenal Cortical Hormones" under "Hormones" in ECT 1st ed., VoL 7, pp. 495—513, by H. B. MacPhUlamy, Ciba Pharmaceutical Products and T. F. Gallagher, Sloan-Kettering Institute for Cancer Research "Steroids with Cortical Hormone Activity" in ECT 1st SuppL, pp. 849—888, by G. Aimer and A. Wettstein, Ciba Limited, Basle "Adrenal-Cortical Hormones" under "Hormones" in ECT 2nd ed., Vol. 11, pp. 77—93, by W. R. Ebedein, The Children s Hospital of Philadelphia in ECT 3rd ed., Vol 12, pp. 575—602, by V. Petrow, Consultant. 

This drug also is reported to activate macrophages, to iaduce polyclonal B-ceU activation as well as enhance specific antibody production m vivo, and to iaduce the synthesis of iaterferon and interleukin 1 (52). The iaduction of these important cytokiaes (and others) largely accounts for the profile of biological activity displayed by the pyrimidinones. Bropirimine is currentiy ia clinical evaluation for cancer, arthritis, and immunorestoration ia AIDS patients. 

U. HoUstein, Chem. Rev. 74, 625 (1974) "Sebnan A. Waksman Conference on Actinomycins Their Potential for Cancer Chemotherapy," Cancer Chemother. Rept. 58 (1974). 

When the data as a whole are reviewed for studies on humans exposed to ethylene oxide, no conclusion can be made that there is an increase in mortahty associated with those exposed to ethylene oxide. Two Swedish studies (247,248) indicated an increase in leukemia for workers exposed to multiple chemicals including ethylene oxide however, in a recent larger Swedish study (249) of workers exposed to only ethylene oxide, there was no association of any type of cancer increase for these workers. In a recent study sponsored by NIOSH, there was no significant increase in mortahty observed for cancer when all types are combined or for certain individual types of cancer, even for those people who worked the longest and were observed the longest. However, a statistically significant increase in mortahty from certain types of lymphoma was observed for male workers. This is contrary to the results observed for female workers. In addition, four other cohort studies of ethylene oxide-exposed workers have been pubhshed (250—253), but no unequivocal increase in the risk of cancer was observed. 

The differences for cancer were not statistically significant, but those for the other two categories of disease were (p < 0.05 i.e. only a 1 in 20 chance that the difference was accidental). For all causes, p < 0.001 i.e. only a 1 in 1000 chance that the difference was accidental. 

Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania... 

Sieiniatycki, j. (Fcl.) (1991). Risk Factors for Cancer in the Workplace, CRC Press, Boca Raroii, FI,. 

Ben May Laboratory for Cancer Research and Departments of Chemistry and Biochemistry University of Chicago Chicago, Illinois... 

FIGURE 19.24 A mechanism for the phosphoglycerate mutase reaction in rabbit muscle and in yeast. Zelda Rose of the Institute for Cancer Research in Philadelphia showed that the enzyme requires a small amount of 2,3-BPG to phosphorylate the histidine residue before the mechanism can proceed. Prior to her work, the role of the phosphohistidine in this mechanism was not understood. 

B. J. Allen, D. E. Moore and B. V. Harrington (eds.). Progress in Neutron Capture Therapy for Cancer (Proc. 4th Intemat. Conf.), Plenum, New York, 1992, 668 pp. 

In recent years there has been some interest in monastrol (62), a potentially important chemotherapeutic for cancer which acts as an inhibitor of mitotic kinesin Kappe and coworkers successfully synthesized racemic monastrol (62) using microwave-mediation in 60% yield from ethyl acetoacetate (6), 3-hydroxybenzaldehyde (63), and thiourea (3b) in the presence of PPE." ... 

Present address Sloan-Kettering Institute for Cancer Research, Rye, N. Y. 

Hall22 at the Sloan-Kettering Institute for Cancer Research has approached the problem of determining trace metals in biological tissues in a way that has the following noteworthy features (1) X-ray... 

Cancer treatment is a multimodality treatment, i.e., surgery is combined with radiotherapy and antineoplastic chemotherapy. The latter treatment mode is used mainly for cancers which have disseminated. Different forms of cancer differ in their sensitivity to chemotherapy with antineoplastic agents. The most responsive include lymphomas, leukemias, choriocarcinoma and testicular carcinoma, while solid tumors such as colorectal, pancreatic and squamous cell bronchial carcinomas generally show a poor response. The clinical use of antineoplastic agents is characterized by the following principles. 

Barker N, Clevers H (2006) Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov 12 997— 1014... 

Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National institutes of Health, Bethesda, MD, USA... 

The first clinical trials were performed in the 1970 s using a sodium salt derivative with an open E-ting (Fig. 1). However, the clinical efficacy was limited and severe bladder toxicity led to the termination of the clinical trials. The poor efficacy of the camptothecin sodium salt in those clinical trials was probably due to the fact that the open E-ring form of camptothecin (carboxylate derivative) is inactive as a Topi inhibitor. Following the identification of Topi as a target of camptothecin, water-soluble derivatives were produced by the pharmaceutical industry. Two of these water-soluble derivatives have been approved by the FDA for cancer treatment in the early 2000s topotecan and irinotecan. 

Catlett-Falcone R, Dalton WS, Jove R (1999) STAT proteins as novel targets for cancer therapy. Curr Opin Oncol 11 490-496... 

A number of inhibitors directed towards the active site of PKC have been developed [4]. Many of these have therapeutic potential and some are in clinical trials. The drug enzastaurin (LY317615) shows selectivity towards inhibiting PKC 3 and is currently in clinical trials for cancer. This drug has particular potential as a treatment for colon cancer because of the specific role ofPKC (311 in this disease (see above). A separate PKC (3 inhibitor, ruboxistaurin (LY333531) has been developed as a drug to treat the microvasculature complications of diabetes hyperactivation of both PKC (311 and PKC (31 contribute to diabetic retinopathy and microvasculature complications. 

Mikalsen T, Gerits N, Moens U (2006) Inhibitors of signal transduction protein kinases as targets for cancer therapy. Biotechnol Annu Rev 16 153-223... 

Molecular epidemiological studies to assess the risk associated with metabolic polymoiphisms for cancers of head-and-neck and the lung have shown that the overall... 

Retinoids, isothiocyanates and tea polyphenols have been identified as possible chemopreventive agents for cancers of the lung and oral cavity. While a number of trials have been conducted with retinoids or (3-carotene, the results were ambiguous and the causes are still being debated. 

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