Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient is reported who developed the first symptoms of spinal motor neuron affection 20 years prior to his death at the age of 79. In the course of the disease dementia and spasticity of the legs occurred. The patient died of metastasizing carcinoma of the colon. The autopsy revealed amyloid angiopathy of the brain and cervical spinal cord, corresponding to the clinical symptomatology. So far, 11 cases of amyloid angiopathy have been reported in which dementia was preceded by dysarthric speech, ataxia and/or spasticity of the legs. We assume that these cases represent a distinct nosological entity, different from a variant course of Alzheimer's disease. The atypical symptomatology may cause problems in the diagnosis of amyloid angiopathy of the CNS.
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PMID:Congophilic angiopathy with cerebrospinal symptoms. 365 49

Women who self-select to take postmenopausal hormones have lower risks of coronary heart disease, their leading cause of mortality. Women and their primary health care providers must weigh this and other clear (osteoporosis), and possible (stroke, colon cancer, and Alzheimer's disease) benefits against clear (endometrial cancer) and possible (breast cancer) risks. Because all existing data derive only from observational studies, reliable information on the balance of risks and benefits must await the results of the Women's Health Initiative, a large-scale, randomized clinical trial.
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PMID:Postmenopausal hormones and coronary heart disease. 887 56

The increasing proportion of elderly people in the population is presenting politics, society and also medicine with significant new challenges. Gerontology and geriatrics play a role in every area of preventive and curative medicine. Since the life expectancy of women is about 8 years longer than that of men and the greater portion of an aging society will be female, gynaecology takes on special significance. The necessity of developing old-age gynaecology becomes more and more urgent, particularly in view of the fact that postmenopausal women still have more than one third of their lives before them, a period which they would like to and should spend in good mental, psychological and physical condition. Postmenopausal hormone replacement therapy has been remarkably successful in treating climateric complaints and in positively affecting the entire organism. The ability of women to virtually avert later consequences of the hormone deficiency, including osteoporosis-induced fractures, heart attacks and strokes, by means of long-term hormone replacement is one of the great achievements of our time. Furthermore, the importance of hormone replacement therapy in the possible reduction of certain types of genital cancer, as endometrial and ovarial carcinoma, cannot be overstated. Gynaecology has taken a great step toward enabling older women to spend this third stage of their lives free of unnecessary disease or suffering. There is a consensus in literature and among medical experts today that the advantages of estrogen replacement during and following menopause have been proven and are to be highly regarded. The advantages and risks of hormone therapy will be explored from the special standpoint of morbidity and mortality ratings, particularly for the disease patterns of osteoporosis, Alzheimer's disease, heart attack, stroke, as well as breast, endometrial, ovarial and colon cancer. For insurance medicine, these aspects are of paramount significance. Quantification with regard to morbidity and mortality statistics is a challenge that will have to be faced in the years to come.
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PMID:[Menopause and postmenopause. Prognostic criteria in insurance medicine]. 896 48

Postmenopausal estrogen deficiency may result in a wide variety of physiologic disorders, including vasomotor symptoms, urogenital atrophy, an increase in the risk of coronary heart disease, osteoporotic fractures, and Alzheimer's disease. The growing body of evidence, including much that is newly published, demonstrating that hormone replacement therapy (HRT) can largely prevent or mitigate these sequelae, will be reviewed in this paper. The efficacy of HRT in alleviating vasomotor and urogenital discomfort, the most common symptoms of postmenopausal estrogen deficiency, is well established. Evidence from over 30 epidemiologic studies indicates that estrogen reduces the risk of coronary heart disease (CHD) by 50%. The risk of major CHD has been found to be markedly reduced in women who receive combined estrogen/progestogen therapy compared to nonusers (or estrogen-alone users). Estrogen is recommended as the modality of choice to prevent bone loss: data supporting a positive effect of estrogen on the risk of wrist and vertebral fracture are quite favorable. Similarly, outcomes of recent investigations have demonstrated a positive impact of HRT on both psychological function and the risk of osteoarthritis. In addition, HRT substantially reduces the risk of colon cancer. Moreover, the potential for HRT to delay the progression or reduce the risk for developing Alzheimer's disease is a new area of research that shows promise. Improvements in quality-of-life assessments have also been reported in conjunction with the relief of menopausal symptoms by HRT. Clinicians should be aware of the large amount of new evidence that strengthens the case for wider use of HRT. Based on these new data, physicians may conclude that HRT would benefit the majority of their postmenopausal patients and thus encourage HRT use in the absence of known risk factors.
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PMID:Benefits of hormone replacement therapy--overview and update. 939 82

In 1971, Vane showed that nonsteroid antiinflammatory drugs (NSAIDs) inhibited the biosynthesis of prostaglandins and proposed this as their mechanism of action. Much work around the world has followed. The aspirin-like drugs inhibit the binding of the prostaglandin substrate, arachidonic acid, to the active site of the enzyme. After characterization of the COX-1 enzyme in 1976, a second COX gene was discovered in 1991 encoding for the inducible COX-2. The constitutive isoform of COX, COX-1, has clear physiological functions. The inducible isoform, COX-2, is induced by pro-inflammatory stimuli in migratory cells and inflamed tissues. The range of activities of NSAIDs against COX-1 compared to COX-2 explains the variations in the side effects of NSAIDs at their antiinflammatory doses. Drugs which have the highest potency on COX-2 and less effect on COX-1 will have potent antiinflammatory activity with fewer side effects. All the results published so far support the hypothesis that the unwanted side effects of NSAIDs, such as damage to the gastric mucosa and kidneys, are due to their ability to inhibit COX-1, while their antiinflammatory (therapeutic effects) are due to inhibition of COX-2. Other roles for COX-2 inhibitors will surely be found in the next few years, for prostaglandin formation is under strong control in organs such as the kidney, lungs and uterus. COX-2 is also potently expressed in human colon cancer cells, and NSAIDs delay the progress of colon tumors possibly by causing apoptosis of the tumor cells. The risk of developing Alzheimer's disease, which may involve an inflammatory component, is lessened by chronic ingestion of NSAIDs. The new highly selective inhibitors of COX-2 will not only provide a means of delaying premature labor but will also lead to advances in cancer therapy and protection against Alzheimer's disease.
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PMID:Mechanism of action of antiinflammatory drugs. 956 41

Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are also important in ovulation and in the birth process. The discovery of COX-2 has made possible the design of drugs that reduce inflammation without removing the protective PGs in the stomach and kidney made by COX-1. These highly selective COX-2 inhibitors may not only be anti-inflammatory but may also be active in colon cancer and Alzheimer's disease.
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PMID:Cyclooxygenases 1 and 2. 959 50

Since fiscal year 1991, the U.S. Human Genome Project has spent $170.6 million in federal funds to help isolate genes associated with Huntington's disease, amyotrophic lateral sclerosis, neurofibromatosis types 1 and 2, myotonic dystrophy, and fragile X syndrome and to localize genes that predispose people to breast cancer, colon cancer, hypertension, diabetes, and Alzheimer's disease. Now comes the hard part. Biology's 21st century megaproject starts to look relatively manageable compared to another challenge facing the enterprise: sorting out ethical, legal, and social issues associated with using this information. "The Human Genome Project," wrote Senior Editor Barbara Jasny in the October 1 Science editorial, stretches "the limits of the technology and the limits of our ability to ethically and rationally apply genetic information to our lives."
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PMID:Ethical, legal, and social issues of the Human Genome Project: what to do with what we know. 971 68

Nonsteroidal anti-inflammatory drugs (NSAIDs) produce their therapeutic activities through inhibition of cyclooxygenase (COX), the enzyme that makes prostaglandins (PGs). They share, to a greater or lesser degree, the same side effects, including gastric and renal toxicity. Recent research has shown that there are at least two COX isoenzymes. COX-1 is constitutive and makes PGs that protect the stomach and kidney from damage. COX-2 is induced by inflammatory stimuli, such as cytokines, and produces PGs that contribute to the pain and swelling of inflammation. Thus, selective COX-2 inhibitors should be anti-inflammatory without side effects on the kidney and stomach. Of course, selective COX-2 inhibitors may have other side effects and perhaps other therapeutic potential. For instance, COX-2 (and not COX-1) is thought to be involved in ovulation and in labor. In addition, the well-known protective action of aspirin on colon cancer may be through an action on COX-2, which is expressed in this disease. Moreover, NSAIDs delay the progress of Alzheimer's disease. Thus, selective COX-2 inhibitors may demonstrate new important therapeutic benefits as anticancer agents, as well as in preventing premature labor and perhaps even retarding the progression of Alzheimer's disease.
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PMID:Anti-inflammatory drugs and their mechanism of action. 983 28

Animal and human data demonstrate that cyclooxygenase (COX)-2 upregulation in osteoarthritis and rheumatoid arthritis is associated with the pain and inflammation of the disease state. The COX-1 isoform, however, is a constitutive enzyme with homeostatic functions. Unlike conventional nonsteroidal anti-inflammatory drugs, which inhibit both forms of the COX enzyme, celecoxib inhibits COX-2 preferentially to COX-1 in vitro. Celecoxib reversed signs of arthritis and pain in an animal model as effectively as indomethacin. Data from murine studies as well as in vitro and epidemiologic data indicate that COX-2 plays a role in the development of colon cancer, and epidemiologic studies also suggest that COX inhibition can slow the progression of Alzheimer's disease.
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PMID:Role of cyclooxygenase-1 and -2 in health and disease. 1019 97

Emerging evidence suggests that cyclooxygenase-2 (COX-2) has diverse physiologic and pathophysiologic functions. It is expressed constitutively in the developing kidney and brain, playing a role in their proper maturation and function. Further, COX-2 expression may be up-regulated at certain sites: in the kidney during sodium restriction; in the microglia of cognitive centers within the hippocampus and cortex in Alzheimer's disease; and in intestinal adenomas and colon tumors. On the basis of COX-2 expression in Alzheimer's disease and colon cancer, COX-2-specific inhibitors may find clinical utility in the prevention or treatment of these conditions. Despite this apparently optimistic outlook for future uses of COX-2 inhibitors, most of the findings supporting this perspective are based on in vitro and in vivo models and must be rigorously corroborated in human studies, some of which are already planned.
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PMID:The clinical potential of cyclooxygenase-2-specific inhibitors. 1039 Jan 28


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