Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha-fetoprotein (AFP) is a tumor-associated fetal marker, associated both with tumor growth and with birth defects. AFP, whose precise function is unknown, has been classified as belonging to a protein superfamily together with albumin and vitamin D-binding (Gc) protein. AFP has been shown to bind various ligands in vitro including fatty acids, estrogens, thyroid hormones and retinoic acids. The steroid/thyroid nuclear receptor superfamily of proteins has recently become a major focus of biomedical investigation regarding regulation of gene expression. These receptors are thought to bind to DNA-hormone response elements (HRE) that affect growth, development, differentiation, reproduction and homeostasis. The HREs are known to share DNA sequences with the various members of the nuclear receptor superfamily. In the present report, the possibility of a leucine-zipper dimerization (heptad) motif in the carboxy-terminal third domain of both rodent and human AFP is postulated. The presence of nine such hydrophobic repeats in the third domain of the AFP molecule mimics the heptad dimerization repeats found in the retinoic acid, thyroid, c-erbA and other members of the nuclear receptor superfamily. Computer analysis revealed that the most conservative matching occurred between AFP and the retinoic acid class of receptors. However, other superfamily members displayed 40-60% homology with 5 of 9 AFP heptads. These findings could provide a possible mechanism for explaining the growth-regulatory properties (both inhibition and enhancement) that have been ascribed to AFP in the last decade.
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PMID:An apparent dimerization motif in the third domain of alpha-fetoprotein: molecular mimicry of the steroid/thyroid nuclear receptor superfamily. 768 18

Comparative pathology may serve as a practical tool for therapy by comparison of normal and abnormal structures of the digestive tract in animals and men. A better understanding of colon cancer as the most common solid neoplasm after lung cancer in the industrialized world is sought. In the so-called developed nations and in animals colon cancer is less frequent. The pathogenesis of colon cancer involves environmental and genetic factors. Several types of colorectal cancer can be discerned and the species distribution ranges from invertebrates to man. Colorectal neoplastic progression is species-specific. An intraspecies-specific comparison of large bowel cancer is also valuable. Alteration of signal transduction pathways and somatic mutations of oncogenes are described, as well as the occurrence, research and current treatment. Metastasis of neoplasms of the colon and of the rectum can be studied by intraspecies-specific comparison. Sections of this review deal with vitamin D and cancer and close with present therapies for colorectal cancer.
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PMID:Interspecies comparative pathology of colorectal neoplasms: relevance for treatment. 772 40

Considerable evidence that alterations in protein kinase C (PKC) are intimately involved in important physiologic and pathologic processes in many cells, including colonic epithelial cells, has accumulated. In this regard, phorbol esters, a class of potent PKC activators, have been found to induce a number of cellular events in normal or transformed colonocytes. In addition, our laboratory has demonstrated that the major active metabolite of vitamin D3, 1,25(OH)2D3, also rapidly (seconds-minutes) activated PKC and increased intracellular calcium in isolated rat colonocytes. These acute responses, however, were lost in vitamin D deficiency and partially restored with the in vivo repletion of 1,25(OH)2D3. The Ca(2+)-independent or novel isoforms of PKC expressed in the rat colon and the isoform-specific responses of PKC to acute treatment with phorbol esters or 1,25(OH)2D3 have not been previously characterized. Moreover, the effects of vitamin D status on PKC isoform expression, distribution, and response to agonists are also unknown. In the present experiments, in addition to PKC-alpha, rat colonocytes were found to express the novel isoforms delta, epsilon, and zeta by Western blotting using isoform-specific PKC antibodies. The tumor-promoting phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate, caused time- and concentration-dependent translocations of all these isoforms except PKC-zeta. In vitamin D deficiency, there were no alterations in colonic PKC isoform expression but significant changes in the subcellular distribution of PKC-alpha, -delta, and -zeta. Acute treatment of colonocytes from D-sufficient, but not D-deficient, rats with 1,25(OH)2D3 caused a rapid transient redistribution of only PKC-alpha from the soluble to the particulate fraction. The alterations in PKC isoform distribution and PKC-alpha responsiveness to 1,25(OH)2D3 in vitamin D deficiency were partially, but significantly, restored with 5-7 d in vivo repletion of this secosteroid. Both 12-O-tetradecanoyl phorbol 13-acetate and 1,25(OH)2D3 activated endogenous PKC, as assessed by inhibition of myristoylated alanine-rich C kinase substrate back-phosphorylation by exogenous PKC. These studies indicate that PKC-alpha, -delta, and/or -epsilon likely mediate important phorbol ester-stimulated events described in the rat colon. In contrast, PKC-alpha is implicated in the rapid (s-min) PKC-dependent events initiated by 1,25(OH)2D3 in rat colonocytes.
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PMID:1,25-Dihydroxyvitamin D3 and 12-O-tetradecanoyl phorbol 13-acetate cause differential activation of Ca(2+)-dependent and Ca(2+)-independent isoforms of protein kinase C in rat colonocytes. 773 87

Oncogenic osteomalacia is a syndrome characterized by phosphaturia, hypophosphatemia, reduced vitamin D levels, and osteomalacia. The cause is not known, but all patients have had a tumor; usually of mesenchymal origin. Removal of the tumor reverses the metabolic abnormalities. We report a patient with osteomalacia, severe hypophosphatemia, elevated alkaline phosphatase, low 1,25-dihydroxyvitamin D3, and phosphaturia. A tumor was identified in the infratemporal fossa. The tumor was removed, and all of the biochemical abnormalities resolved over the subsequent 8 months. The bone density returned to normal values. The tumor had the appearance of a paraganglioma and was used to establish a cell culture line called JH-55. Electron microscopy of the original tumor and the JH-55 cells demonstrated the presence of neurosecretory granules. A bioassay using opossum kidney cells was used to evaluate phosphate transport. Conditioned medium from the JH-55 cells inhibited phosphate reabsorption by the kidney tubular cells. Maximal inhibition required a 24-h incubation period and was not altered by the presence of an inhibitor of protein synthesis (10 micrograms/mL cycloheximide). Immunoassays revealed no detectable PTH-related peptide or intact PTH in the JH-55 medium. The cause of this paraneoplastic syndrome is not known, but all of the evidence is consistent with the action of a hormone that produces phosphaturia. This putative factor is distinct from other hormones that cause phosphaturia.
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PMID:Oncogenic osteomalacia: evidence for a humoral phosphaturic factor. 774 10

A 38-year-old woman was admitted to our hospital with symptoms and signs of hypocalcemia in 1977 and a diagnosis of primary hypoparathyroidism was made with a positive Ellsworth Howard test. She was then lost to follow up until 1992 when she returned this time with symptoms and signs of hypercalcemia. An inguinal lymph node was biopsied showing non-Hodgkin's lymphoma, diffuse pleomorphic type and monoclonal integration of proviral human T-cell lymphotropic virus-1 DNA was detected in lymph node cells indicating ATLL. Serum parathyroid hormone-related peptide (PTHrP) was slightly elevated and the tumor cells were positively stained with anti-PTHrP serum. Combination chemotherapy with vincristine, adriamycin, cyclophosphamide and prednisolone was given to the patient with disappearance of the lymphadenopathy and subsequent normalization of PTHrP levels. Interestingly, the signs and symptoms of hypocalcemia reappeared after the treatment requiring replacement therapy with calcium and vitamin D.
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PMID:A patient with primary hypoparathyroidism developing hypercalcemia associated with adult T-cell leukemia/lymphoma. 781 15

An expanded role for vitamin D (1 alpha,25-(OH)2D3) in mammalian systems has been suggested by recent evidence that its receptor (vitamin D receptor [VDR]) is present not only in classical target organs, but in a variety of normal tissues and organs, tumor tissues, and cancer cell lines. Vitamin D is involved not only in the regulation of calcium homeostasis and bone metabolism, but in the regulation of cell proliferation, differentiation, and immune responses. The role vitamin D may play in normal lung growth, development, and maintenance is unknown. Likewise, its part in lung tumorigenesis is unclear. The present study examined VDR binding activity and VDR expression in normal mouse lung and ethylnitrosourea-induced lung adenomas. Binding of 1 alpha,25-(OH)2D3 was specific and saturable over the concentration range of 0.01 to 0.50 nM, with an affinity (Kd) of 0.93 x 10(-10) M and a total binding capacity (Bmax) of 22 fmol/mg of protein. Scatchard analysis yielded a convex curve, which suggests positive receptor cooperativity. The calculated Hill coefficient equals 1.69, at a receptor concentration of 0.4 nM, consistent with dimerization of the receptor. Western blot analysis showed the presence of 60 kD VDR protein in tumor homogenates, while Northern blot analysis detected the 4.4 kb VDR mRNA in tumor tissue preparations. Immunohistochemistry and in situ hybridization revealed that both adenomatous Clara cells and normal bronchiolar epithelial Clara cells expressed VDR, with the receptor protein present in their nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vitamin D3 receptor expression in N-ethylnitrosourea-induced mouse pulmonary adenomas. 791 16

Twenty eight patients of sporadic primary hyperparathyroidism seen over a period of 10 years were studied. There were 18 females and 10 males with a mean age of 35.9 years. Bone involvement was the commonest clinical presentation (90%) followed by renal involvement (65%) and more than half the patients (54%) had involvement of both the skeletal and renal systems. The tumor was clinically palapable in six patients. Thalliumtechnetium subtraction scan had a sensitivity of 87% followed by computerised tomography (70%), and ultrasound (65%) in diagnosing parathyroid pathology. All the patients underwent surgical excision of the abnormal gland (S). Adenomas constituted the single largest group (90%). Histologically, only 32% of the patients had chief cell morphology. Clear cell (32%) mixed cell, and oxyphil cell (7.2%) types accounted for the remaining adenomas. Majority of the patients (82%) had symptomatic postoperative hypocalcemia requiring intravenous calcium with or without vitamin D supplementation. In contrast to western reports most of our patients were young, presented late with florid bone and renal disease and had large palpable tumors.
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PMID:Primary hyperparathyroidism--an Indian study. 792 52

Circulating interleukin-6 (IL-6) concentrations correlate with disease activity in severe inflammatory conditions, in sepsis and in some hematological malignancies. On the other hand, IL-6 is a potent stimulator of osteoclastogenesis and has been implicated as a contributory factor in the genesis of osteopenic conditions. We measured circulating IL-6 levels by a sensitive (detection limit of 10 U/ml) and specific bioassay in 103 patients with advanced cancer, including 41 with tumor-induced hypercalcemia before any specific hypocalcemic therapy. We related IL-6 concentrations to clinical features and to biochemical parameters of bone metabolism, including blood Ca, Ca2+, Pi, intact parathyroid hormone, parathyroid hormone-related protein, osteocalcin, 1,25-(OH)2-vitamin D and, as markers of bone resorption, the fasting urinary excretion of calcium (Ca/creatinine) and hydroxyproline. IL-6 levels were increased, i.e. detectable, in 23% of the patients, 8/41 (20%) hypercalcemic and 16/62 (26%) normocalcemic patients (NS); the distribution of the values was similar in the two groups. The presence of increased IL-6 concentrations was not related to any clinical characteristic, notably not to the survival nor to the existence of bone metastases, whether in hypercalcemic or normocalcemic patients; e.g., only 3/12 (25%) hypercalcemic subjects without bone metastases had elevated IL-6 levels. We found no significant correlations between IL-6 concentrations and any of the biochemical parameters studied. Hypercalcemic subjects with increased IL-6 had higher urinary Ca/creatinine levels than patients with normal IL-6 levels (P < 0.005) but this was not the case in normocalcemic subjects. Mean concentrations of inflammatory or other bone metabolism markers were not significantly different between patients with normal or with elevated IL-6 levels. In summary, circulating IL-6 levels were increased in 23% of 103 patients with advanced cancer, but the frequency of increased IL-6 concentrations was not related to the presence of hypercalcemia or to any marker of calcium metabolism or bone turnover. The pathogenic importance of circulating IL-6 in patients with solid tumors remains to be demonstrated and our data indicate that increased circulating levels of IL-6, possibly reflecting the activation of the immune system, only contribute in a minor way to the osteolytic process in patients with tumor-induced hypercalcemia.
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PMID:Circulating concentrations of interleukin-6 in cancer patients and their pathogenic role in tumor-induced hypercalcemia. 798 59

We evaluated the biological characteristics of lung cancer by measuring their contents of human 28 kDa vitamin D-dependent calcium binding protein (calbindin-D). Calbindin-D concentrations were determined in tumor tissue and normal lung tissue extracts from patients with lung cancer by enzyme immunoassay. The percentage of high calbindin-D containing tissues in small cell lung cancer (SCLC) was significantly higher than that in non-small cell lung cancer (NSCLC) and the calbindin-D concentration was low in normal lung extracts. In addition, most of the NSCLC which had a significantly high level of calbindin-D were at the advanced cancer stage with lymph node metastasis. Calbindin-D concentrations were also determined in lung cancer cell lines. The percentage of high calbindin-D containing cell lines was high in classic type SCLC, followed in order by variant type SCLC and NSCLC. In addition, in order to examine the usefulness of calbindin-D as a marker of neuroendocrine properties of lung cancer, we compared the sensitivity and specificity of calbindin-D for distinguishing classic from variant type SCLC with neuron-specific enolase (NSE) and aromatic L-amino acid decarboxylase (AADC) by relative operating characteristic curves. The diagnostic accuracy of AADC was the highest of the three and that of calbindin-D was as high as that of NSE. These findings suggest calbindin-D to be related to the neuroendocrine properties of lung cancer.
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PMID:Evaluation of biological characteristics of lung cancer by the human 28 kDa vitamin D-dependent calcium binding protein, calbindin-D28k. 800 21

We have used the vitamin D analogue, 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (Ro24-5531), for inhibition of mammary carcinogenesis induced by N-nitroso-N-methylurea (NMU) in Sprague-Dawley rats. Rats were first treated with a single dose of either 15 or 50 mg/kg body weight NMU and then fed Ro24-5531 (2.5 or 1.25 nmol/kg of diet) for 5-7 months. Ro24-5531 significantly extended tumor latency and lessened tumor incidence as well as tumor number in rats treated with the lower dose of NMU. In rats treated with the higher dose of NMU, Ro24-5531 was fed in combination with tamoxifen; in these experiments, Ro24-5531 significantly enhanced the ability of tamoxifen to reduce total tumor burden, as well as to increase the probability that an animal would be tumor free at the end of the experiment. In vitro, Ro24-5531 was 10-100 times more potent than 1,25-dihydroxyvitamin D3 for inhibition of proliferation of human breast cancer cell lines as well as primary cultures of cells from 2 patients with acute myelogenous leukemia. When fed chronically, Ro24-5531 did not elevate serum calcium in the present studies. We propose the new term, "deltanoids," for the set of molecules composed of vitamin D and its synthetic analogues, in a manner similar to the naming of "retinoids" for the corresponding set of molecules related to vitamin A.
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PMID:1 alpha,25-Dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531), a new deltanoid (vitamin D analogue) for prevention of breast cancer in the rat. 813 76


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