Cancer patients

Prosta.te Ca.ncer, Estrogen has an inhibitory effect on the prostate in addition to its suppression of gonadotropin secretion by the pituitary. The three- and five-year survival rates in prostate cancer patients with metastatic disease improved when treated with DES (7) alone or along with castration. However, DES does not improve the survival rates in patients whose carcinoma is confined to the prostate. Small doses of DES (1 mg/d) appear to retard prostate cancer growth and could reduce the cardiovascular complications associated with larger doses (5 mg/d) (135) (see... 

The immunorestorative potential of inosiplex has been evaluated in several clinical conditions, including post-surgical trauma, cancer patients with concurrent viral infections, and cancer patients receiving radiotherapy or chemotherapy. For example, most (84%) of the surgery patients remained immunologicaHy depressed, but 56% of the inosiplex-treated surgery patients had complete restoration of normal skin test reactivity (probability level < 0.0005). The use of inosiplex as an adjuvant to chemotherapy or radiotherapy appears to be valuable in the prophylaxis against opportunistic infections. 

Pentoxifylline is stmcturaHy related to other methylxanthine derivatives such as caffeine [58-02-2] (1,3,7-trimethylxanthine), theobromine [83-67-0] (3,7-dimethylxanthine), and theophylline [58-55-9] (3,7-dihydro-1,3-dimethyl-1 H-piirine-2,6-dione or 1,3-dimethylxanthine), which also show radioprotective activity in some instances, suggesting that methylxanthines as a dmg class may radioprotect through a common mechanism (see Alkaloids). In a retrospective analysis of cervical and endometrial cancer patients receiving primary or adjuvant XRT, no association between caffeine consumption and incidence of acute radiation effects has been found. However, there was a decreased incidence of severe late radiation injury in cervical cancer patients who consumed higher levels of caffeine at the time of thek XRT (121). The observed lack of correlation between caffeine consumption and acute radiation effects is consistent with laboratory investigations using pentoxifylline. 

A clinical trial to evaluate misoprostol as a protector of normal tissue during a course of XRT in cancer patients suggests a reduction in acute normal tissue injury (215). A randomized, prospective, double-blind study indicates that topical misoprostol, administered as an oral rinse 15-20 min before irradiation using conventional 2-Gy (200 rad) fractions, five days a week over 6—7 weeks, significantly protects the oral mucosa from radiomucositis, a frequently observed normal tissue complication during XRT for head and neck cancer (215). 

A liquid chromatography-mass spectrometry (LC-MS) method that can quantitatively analyze urinar y normal and modified nucleosides in less than 30 min with a good resolution and sufficient sensitivity has been developed. Nineteen kinds of normal and modified nucleosides were determined in urine samples from 10 healthy persons and 18 breast cancer patients. Compounds were separ ated on a reverse phase Kromasil C18 column (2.1 mm I.D.) by isocratic elution mode using 20 mg/1 ammonium acetate - acetonitrile (97 3 % v/v) at 200 p.l/min. A higher sensitivity was obtained in positive atmospheric pressure chemical ionization mode APCI(-i-). 

Sections 9.1.6 (c) and 9.2.1 (h) drew attention to the hazards of using old equipment. Similar remarks apply to old software except that, unfortunately, it never wears out. I do not know of any incidents in the process industries due to this cause, but it was responsible for the loss of the European space rocket Ariane 5. A function that no longer served any purpose was left in for commonality reasons, and the decision to do so was not analyzed or fully understood [14]. In another incident, cancer patients received excessive doses of radiation because operators were able to enter data faster than the computer could process them. This had always been the case, but originally a hardwired interlock had prevented... 

In premenopausal women the ovary is the richest source of aromatase and hence estrogen. Aromatase is confined to the granulosa cells and is produced under the influence of gonadotropins (FSH and LH). Despite being a rich source of aromatase, three separate studies have shown that aromatase inhibitors are unable to sufficiently suppress ovarian estrogen production to postmenopausal levels. One explanation for this phenomenon may be a compensatory rise in gonadotrophins which maintains adequate estrogen production, despite the presence of the inhibitor. As such aromatase inhibitors cannot be used in premenopausal breast cancer patients. After menopause, ovarian... 

Anastrazole is a nonsteroidal, type H, aromatase inhibitor that is 200 times more potent than aminoglutethimide. It is eliminated primarily via hqDatic metabolism, has a terminal half life of 50 h with steady state concentrations achieved approximately 10 days with once daily dosing regimens. It is administered orally at a dose of 1 mg/day that achieves near maximal aromatase inhibition and hence estrogen suppression in breast cancer patients. No effect on adrenal steroidogenesis has been observed at up to ten times the daily recommended dose. When used in the metastatic setting, anastrozole has been shown... 

Cachexia refers to a physical wasting due to loss of muscle and fat. Cachexia is often found in end-stage cancer patients but is also caused by autoimmune disorders or by infectious diseases such as AIDS and tuberculosis. 

EM-800 is a pure estrogen receptor antagonist that has recently been used clinically for breast cancer patients who have failed tamoxifen therapy. 

Erythropoietin is a growth factor produced by interstitial cells of the kidney in response to hypoxia. Erythropoietin stimulates haematopoiesis in the bone marrow. Recombinant human erythropoietin is used to treat anemias, e.g. anemia caused by chronic renal failure and anemia in AIDS and cancer patients. 

MMPs for therapeutic interventions is complicated by the fact that MMPs are indispensable for normal development and physiology and by their multifunctionality, possible functional redundancy or contradiction, and context-dependent expression and activity. This complexity was revealed by previous efforts to inhibit MMP activity in the treatment of cancer patients that yielded unsatisfactory results. Doxycycline, at subantimicrobial doses, inhibits MMP activity, and has been used in various experimental systems for this purpose. It is used clinically for the treatment of... 

The measurement of ER has become a standard assay in the clinical management of breast cancer. The presence of ERa identifies those breast cancer patients with a lower risk of relapse and better clinical outcome. Receptor status also provides a guideline for those tumors that may be responsive to hormonal intervention. But only about half of ER-positive patients respond to hormonal therapies. Of those who respond initially, most will eventually develop an estrogen unresponsive disease following a period of treatment even though ERa is often still present. Mutant receptors and constitutively active r eceptors as well as hormone-independent activation of the ERa are discussed. The involvement of ER 3 isoforms is under investigation. 

In breast cancer patients, total PR status is measured for hormonal treatment. The presence of PR is associated with increased survival rates and hormonal responsiveness of mammary tumors. PR agonists are widely used in contraception, HRT, breast cancer, and endometrial hyperplasia. Antiprogestins such as RU486 are used for blocking ovulation and preventing implantation, and in addition they are in clinical testing for the induction of labor and to control various neoplastic transformations. 

Positron emission tomography (PET) makes use of a short-lived positron emitter such as fluorine-18 to image human tissue with a degree of detail not possible with x-rays. It has been used extensively to study brain function (see illustration) and in medical diagnosis. For example, when the hormone estrogen is labelled with fluorine-18 and injected into a cancer patient, the fluorine-bearing compound is preferentially absorbed by the tumor. The positrons given off by the fluorine atoms are quickly annihilated when they meet... 

From the limited data on the kinetics and distribution of liposomes in man (Zonneveld and Crommelin, 1988) it can be concluded that the overall behavior of liposomes in man is similar to that observed in animals. Studies in cancer patients showed predominant lirer and spleen uptake of technetium-labeled liposomes (Richardson et al.,... 

Pilot study of amphotericin B entrapped in sonicated liposomes in cancer patients with fungal infections, Eur. J. Cancer cun. Oncol., 24, 527-538. 

H. Umezawa hoped to obtain immunostimulants from microbes, because, in cancer patients, the immune response is lowered. In 1972, H. Umezawa, T. Takeuchi, and M. Ishizuka (now Vice-Director of the Institute for Chemotherapy, a branch of IMC) found that the administration in mice of a small dose of diketocoriolin B, an oxidation derivative of the antitumor antibiotic coriolin B (1971), increases the number of mouse-spleen cells... 

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