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)

The endocrine system to maintain calcium homeostasis involves the active vitamin D, as well as parathyloid hormone (PTH). Based on this 'classical' calcium-regulatory function, 1,25-(OH)2D3 and 1 alpha OHD3 was developed as the drug for vitamin D resistant rickets, renal dystrophy, and osteoporosis. Psoriasis is a chronic skin disease which is characterized by hyperproliferation and abnormal differentiation of epidermis. As an anti-psoriatic drug, 1,24R-(OH)2D3 has been on clinical use. The efficacy for psoriasis is explainable by the differentiation-inducing activity of this compound. 1,25-(OH)2D3 was also reported to suppress proliferation and induce differentiation of tumor cells including breast cancer, colon cancer and so forth, suggesting the possible therapy of malignant tumors. In immune system, active vitamin D3 exerts various effects; 1,25-(OH)2D3 suppresses proliferation and cytokine production in T cells and antibody production in B cells. Animal models of autoimmune diseases and skin-graft suggest active vitamin D becomes a novel immuno suppressant. Since 1,25-(OH)2D3 induces the synthesis of nerve growth factor (NGF), it will be a new therapy for the treatment of neuronal degenerative diseases.
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PMID:[Novel pharmacological activity of a vitamin (novel pharmacological action of vitamin D)]. 950 3

Some recent studies of the effects of chemopreventive agents have begun to use new rodent models to improve the analysis of stages of colonic preneoplasia, and how chemopreventive agents modify progressive abnormal cell development. In one of the models of inherited predisposition to colon cancer, mice carrying a truncated Apc allele with a nonsense mutation in exon 15 have been generated by gene targeting and embryonic stem cell technology (Apc1638 mice). These mice develop multiple gastrointestinal lesions, including adenomas and carcinomas, focal areas of high-grade dysplasia (FAD), and polypoid hyperplasias with FADS. The incidence of inherited colonic neoplasms has now been modulated by a chemopreventive regimen. Colonic lesions significantly increased in Apc1638 mice on a Western-style diet, which has higher fat content and lower calcium and vitamin D compared to the same mice on AIN-76A diet. In another rodent model, Min mice were treated with sulindac, which markedly reduced the incidence of intestinal tumors. A third new rodent model containing a targeted mutation in the gene Mcc (mutated in colorectal cancer) recently became available for chemoprevention studies. These mice develop multiple types of neoplasms including adenocarcinomas, focal areas of gastrointestinal dysplasia, papillomas of the forestomach, and tumors in other organs including lung, liver, and lymphoid tissue. Feeding a Western-style diet to the Mcc mutant mice also resulted in significantly increased gastrointestinal lesions. These nutrient modifications also have been given to normal mice, demonstrating without any chemical carcinogen that a Western-style diet induced colonic tumorigenesis. Western-style diets also have now induced modulation of cell proliferation in other organs including mammary gland, pancreas, and prostate. These findings help develop new preclinical rodent models to aid the analysis of genetic and environmental factors leading to neoplasia, as well as new methods for evaluating the chemopreventive efficacy of specific nutrients and pharmacological agents.
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PMID:New rodent models for studies of chemopreventive agents. 958 60

The physiologically active metabolite of the vitamin D seco-steroid hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is a major regulator of mineral homeostasis. Recent evidence also suggests its role in regulating proliferation and differentiation of cells, including cancer cells. Therapeutic application of 1,25(OH)2D3 to hyperproliferative disease, such as cancer, is thwarted by its hypercalcemic activity. To overcome this problem, analogs of 1,25(OH)2D3 have been produced which retain growth regulating properties and exhibit decreased hypercalcemic activity. In the present study, the efficacy of the vitamin D2 analog, 1,24(S)-dihydroxyvitamin D2 (1,24(S)-(OH)2D2) in the inhibition of cancer cell proliferation and in inducing differentiation of cancer cells was compared to that of 1,25(OH)2D3. By the [3H]-thymidine incorporation procedure, 1,24(S)-(OH)2D2 is as equipotent as 1,25(OH)2D3 in inhibiting the proliferation of five different cell lines, ROS 17/2.8, the rat osteosarcoma cell line, MCF-7, the human breast cancer cell line, HD-11, the chick bone marrow v myc transformed cell line, HT-29, the human colon cancer cell line and HL-60, the human leukemia cell line. The inhibitory action was dose and time-dependent. The NBT reduction method indicated that 1,24(S)-(OH)2D2 induces the differentiation of the human leukemia cell (HL-60) to the same extent as 1,25(OH)2D3. Notwithstanding the vast similarity between 1,24(S)-(OH)2D2 and 1,25(OH)2D3 with regard to the above activities, they differ in their effects on calcium regulation. In conclusion, the present results encourage the use of 1,24(S)-(OH)2D2 for the treatment of cancer disease in vivo.
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PMID:The novel analog 1,24(S)-dihydroxyvitamin D2 is as equipotent as 1,25-dihydroxyvitamin D3 in growth regulation of cancer cell lines. 967 3

The active metabolite of vitamin D, 1,25 (OH)2D3, exerts its cell cycle regulating effects via binding to VDR (Vitamin D Receptor). This complex forms a heterodimer with RXR (Retinoic X Receptor). The VDR-RXR heterodimer binds to promoter regions of cell cycle regulating genes through a vitamin D response element (VDRE). The tumour suppressor gene cyclin kinase inhibitor (Cki) p21, one of the well known cell cycle regulating genes, is one of the genes regulated in this manner. Its tumour suppressive action is through inhibition of cell division. These molecular biological mechanisms and large epidemiological investigations give strong support for the benefits of vitamin D in preventing colon cancer and prostate cancer.
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PMID:[Molecular effects of vitamin D on cell cycle and oncogenesis]. 969 32

The best preventive care consists of a combination of office-based services: patient education, life style counseling, clinical vigilance through routine check ups, and the administration of timely screening. In a healthcare environment of tightened resources, tighter schedules, and increased patient demand for your time, it is nevertheless possible to offer substantive preventive care for older patients in an efficient and cost effective manner. Interventions for cardiovascular disease include weight loss, a low-fat diet, vitamin E, and folic acid. Screening is recommended for breast, cervical, and colon cancer, but prostate cancer screening is controversial. The value of mammograms in women over age 50 is well-established. Preventive measures for osteoporosis include calcium and vitamin D, estrogen replacement, and weight-bearing exercise.
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PMID:Simple, sensible preventive measures for managed care settings. 979 Nov 97

We present herein a case of sigmoid colon cancer associated with primary hyperparathyroidism (PHP). PHP is known to be associated with malignancy, and decreased intracolonic calcium (Ca) resulting from increased vitamin D (VD) levels may play a role in colorectal carcinogenesis. PHP was diagnosed in this patient by preoperative screening blood chemistry examination. The blood level of intact parathyroid hormone (PTH) was elevated and a parathyroid gland scintigram demonstrated abnormal uptake near the right lower lobe of the thyroid. There was no evidence of bone metastasis, and a sigmoid colectomy was performed with curative intent. The patient had an uneventful postoperative course without a critical elevation of the serum Ca level. This case report suggests that a relationship exists between PHP and colon cancer, and the possible mechanisms of this association are presented in our discussion.
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PMID:Sigmoid colon cancer associated with primary hyperparathyroidism: report of a case. 1048 59

Because the efficacy of 1alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2D3] in treatment of colon cancer might critically depend on its ability to specifically counteract epidermal growth factor (EGF)-stimulated tumor cell growth, we utilized human colon adenocarcinoma-derived cells in primary culture as well as the Caco-2 cell line to elucidate possible sites of interaction of 1alpha,25-(OH)2D3 with signaling from EGF receptor activation. In both types of colon cancer cells investigated, 10(-8) M 1alpha,25-(OH)2D3 reduced basal cell proliferation by about 50%, and prevented any rise in proliferation when colon cancer cells were treated with 25 ng/ml EGF: this can be explained by a marked inhibitory effect of 1alpha,25-(OH)2D3 on EGFR mRNA and protein expression. The steroid hormone also seemingly promotes EGF-induced internalization of apical and basolateral membrane EGFR. In addition, 1alpha,25-(OH)2D3 significantly reduced basal and EGF-stimulated expression of cyclin D1 at the mRNA and protein level in primary cultures as well as in the Caco-2 cell line. The ability of 1alpha,25-(OH)2D3 to interfere with a key event in cell cycle control and thereby to block mitogenic signaling from EGF could be seen as advantageous for the potential use of vitamin D compounds in colon cancer therapy.
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PMID:Mechanism of antimitogenic action of vitamin D in human colon carcinoma cells: relevance for suppression of epidermal growth factor-stimulated cell growth. 1048 63

Colon cancer is the commonest gastrointestinal cancer and the second leading cause of cancer deaths in the United States. Recent approaches to lowering the incidence of colon cancer have included attempts at dietary prevention and chemoprevention. International and national incidence rates for colon cancer suggest an inverse relationship with dietary calcium and/or vitamin D intake (or sun exposure). Several human intervention studies have suggested that supplemental calcium administration will change proliferative indices of risk for colon cancer from high to lower risk patterns. The principal current hypothesis for the action of calcium implies that calcium may precipitate or bring out of solution fatty acids and bile acids that are potentially toxic to the colorectal epithelium. Both calcium administration and dairy food administration are associated with lowering aqueous fecal concentrations of bile acids and fatty acids accompanied by a highly significant lowering of cytotoxicity in studies in vitro. There is biochemical and biological evidence in cell culture systems that exposure to calcium and/or vitamin D reduces the oncogenic properties of colon cancer cells. A recent blinded study of the administration of low-fat dairy foods demonstrated a significant improvement in several parameters of proliferation as well as in two differentiation markers from a high to a lower risk pattern. Furthermore, administration of calcium also has been shown to reduce the incidence of recurrent adenomatous polyps in individuals at increased risk for colon polyp formation because of the presence of prior colon adenomata. These combined data suggest that administration of supplemental calcium or low-fat dairy foods may have a significant effect upon colonic polyp and perhaps colon cancer incidence.
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PMID:Dairy foods and prevention of colon cancer: human studies. 1051 18

1alpha,25-dihydroxyvitamin D(3) and two synthetic analogs, 1alpha, 25-dihydroxy-16-ene-23-yne-vitamin D(3) (Ro 23-7553) and 1alpha, 25-dihydroxy-16-ene-24-oxo-vitamin D(3) (JK-1624-3), were tested for their ability to specifically inhibit growth and promote differentiation of human colon cancer cells in comparison with a series of 1beta-(hydroxymethyl) congeners of the natural hormone, such as 1beta-(hydroxymethyl)-3alpha,25(OH)(2)-16-ene,24-oxo-vitamin D(3) (JK-1624-2), 1beta-(hydroxymethyl)-3alpha, 25-dihydroxy-16-ene-26,27-dihomo vitamin D(3) (JK-1626-2), and 1beta-(hydroxymethyl)-3alpha,25-dihydroxy-22,24-diene-26,27- dihomo vitamin D(3) (MCW-EE). Western blot analysis revealed that reduction of cyclin D1 levels is a key mechanism by which the vitamin D compounds under investigation inhibit Caco-2 tumor cell growth. Both the 1alpha-hydroxy- as well as the 1beta-hydroxymethyl-type vitamin D compounds, which exhibit only low affinity for the vitamin D receptor, significantly reduced [(3)H]thymidine DNA labeling in confluent Caco-2 cell cultures. This suggests that high-affinity binding to the vitamin D receptor is not an absolute prerequisite for genomic action on tumor cell growth. Hybrid analogs JK-1624-2 and MCW-EE, although antimitotically active, were rather ineffective in promoting phenotypic differentiation of human colon cancer cells. However, because both compounds also do not promote osteoclast differentiation from hematopoetic bone marrow cells, they still could be used as antimitotic agents in cancer therapy, even at dose levels that, with other analogs, could cause hypercalcemia.
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PMID:Biological effects of 1alpha-hydroxy- and 1beta-(hydroxymethyl)-vitamin D compounds relevant for potential colorectal cancer therapy. 1052 58

Skeletal fragility at the end of the life span (osteoporosis) is a major source of morbidity and mortality. Adequate calcium intake from childhood to the end of the life span is critical for the formation and retention of a healthy skeleton. High intakes of calcium and vitamin D potentiate the bone loss prevention effects of hormone replacement therapy in postmenopausal women. Pregnancy and lactation are not risk factors for skeletal fragility, although lactation is associated with a transient loss of bone that cannot be prevented by calcium supplementation. Low calcium intake has been implicated in the development of hypertension, colon cancer, and premenstrual syndrome, and it is associated with low intakes of many other nutrients. Encouragement of increased consumption of calcium-rich foods has the potential to be a cost-effective strategy for reducing fracture incidence later in life and for increasing patients' dietary quality and overall health.
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PMID:The role of calcium in health and disease. 1060 43


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