Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed multi-drug resistant variants of three human lung cancer cell lines by growth in increasing concentrations of adriamycin (ADM). Each of the lines shows reduced ADM content after acute drug exposure when compared with the corresponding parent line. The resistance to ADM may in each case be partially overcome by the concurrent use of 6.6 microM verapamil (VRP) (a calcium transport blocker). In small cell line NCI-H69 the growth inhibitory effect of VRP alone is greater in the resistant variant than in the parent line. Little or no change in the ADM sensitivity of parent cells is brought about by concentrations of VRP up to 15-20 microM. In the resistant line, a dose-related effect of VRP is seen with little effect below 1.0 microM and a gradual loss of resistance at higher doses. ADM-resistant cells of line NCI-H69 show only a small degree of resistance to two anthracyclines (aclacinomycin A and Ro 31-1215). This can be further reduced when these drugs are combined with verapamil.
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PMID:Drug resistance in human lung cancer cell lines: cross-resistance studies and effects of the calcium transport blocker, verapamil. 301 60

The metabolism of arachidonic acid (AA) was studied in two pulmonary bronchioloalveolar-carcinoma cell lines (NCI-H322 and NCI-H358) and two small cell lung carcinoma cell lines (NCI-H69 and NCI-H128). Exogenous AA was metabolized only in the NCI-H322 and NCI-H358 cells. There was no detectable metabolism of AA in NCI-H69 or NCI-H128 cells, either in the presence or the absence of the calcium ionophore A23187. The major metabolite of AA isolated from both NCI-H322 and NCI-H358 cells was prostaglandin E2 (PGE2). Prostaglandin endoperoxide synthase activities, expressed as immunoreactive PGE2 (pmol/min/mg protein), were 10.3 +/- 0.28 (SD) and 4.8 +/- 0.48 in NCI-H358 and NCI-H322 cells, respectively. The rate of production of PGE2 by both NCI-H358 and NCI-H322 cells was linear up to 10 min. Production of PGE2 in both cell lines was dependent upon substrate concentration and was maximal above 17 microM AA. Moreover, PGE2 did not undergo further metabolism by either the NCI-H358 or the NCI-H322 cells. Aspirin (0.1 mM), a cyclooxygenase inhibitor, decreased PGE2 production by 77 and 60% in NCI-H358 and NCI-H322 cells, respectively. In the presence of exogenous AA the calcium ionophore, A23187 (20 microM), stimulated PGE2 production in NCI-H322 cells by almost 2-fold, although it did not affect PGE2 production in the NCI-H358 cells. In contrast, A23187 stimulated the endogenous production of PGE2 in both NCI-H322 and NCI-H358 cells by 4- and 9-fold respectively. In addition, both the NCI-H358 and NCI-H322 cell lines were susceptible to the cytotoxic effects of the anticancer agent mitoxantrone in both a time and concentration dependent manner. In contrast, the two cell lines lacking detectable prostaglandin synthesis activity, NCI-H69 and NCI-H128 were unaffected by treatment with mitoxantrone. These results illustrate that there are major differences in the abilities of human lung cancer cell lines to biosynthesize and release PGE2. It is conceivable that such differences might have exploitable diagnostic and/or therapeutic implications.
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PMID:Metabolism of arachidonic acid in human lung cancer cell lines. 303 46

Recent studies of vegetarian diets and their effects on morbidity and mortality are reviewed. Vegetarian diets are heterogeneous as are their effects on nutritional status, health, and longevity. Mortality rates are similar or lower for vegetarians than for nonvegetarians. Risks of dietary deficiency disease are increased on vegan but not on all vegetarian diets. Evidence for decreased risks for certain chronic degenerative diseases varies. Both vegetarian dietary and lifestyle practices are involved. Data are strong that vegetarians are at lesser risk for obesity, atonic constipation, lung cancer, and alcoholism. Evidence is good that risks for hypertension, coronary artery disease, type II diabetes, and gallstones are lower. Data are only fair to poor that risks of breast cancer, diverticular disease of the colon, colonic cancer, calcium kidney stones, osteoporosis, dental erosion, and dental caries are lower among vegetarians. Reduced risks for chronic degenerative diseases can also be achieved by manipulations of omnivorous diets and lifestyles.
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PMID:Health aspects of vegetarian diets. 304 2

Many factors, such as interleukin 1, transforming growth factor alpha, tumour necrosis factor alpha and beta, and prostaglandins, have been implicated in the pathogenesis of the humoral hypercalcaemia of malignancy (Mundy and Martin, 1982; Martin and Mundy, 1987; Mundy et al, 1984). Much interest in the past has also centred upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and found to encode a pre-pro-peptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the aminoterminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support of this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have an intron-exon arrangement that is more complex than the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have allowed detailed structure-function studies that have identified aminoterminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in a subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcaemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP has added to our understanding of the mechanisms of hypercalcaemia and may contribute to the understanding of other metabolic bone diseases, such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in normal cell physiology.
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PMID:Parathyroid hormone-related protein: a novel gene product. 307 45

In summary, carcinoma is the most frequent cancer that metastasizes to the skin; lung cancer in men and breast cancer in women. Clinically distinctive patterns of cutaneous metastasis of epithelial origin include alopecia neoplastica, pulsatile nodules, Sister Mary Joseph's nodules, morpheaform, and cellulitis-like lesions. Biopsying these lesions reveals adenocarcinoma, squamous cell carcinoma, or anaplastic carcinoma. The type of histologic pattern seen can be a clue to the organ of origin giving rise to the cutaneous metastasis. Skin that is damaged allows for circulating malignant cells, often of epithelial or leukemic origin, to lodge and proliferate locally (inflammatory oncotaxis). The commonest form of leukemia to affect the skin of elderly males is chronic lymphocytic leukemia. However, when leukemia involves the mucous membranes, acute myeloid leukemia (acute monocytic and acute myelomonocytic leukemia) is the most likely diagnosis. When papules, nodules, or plaques develop on the head, neck, or torso in a middle-aged male accompanied by lymphadenopathy, there must be a high index of suspicion that these lesions are metastatic lymphomatous deposits. Definitive histologic diagnosis on a skin biopsy specimen is difficult. In this situation, it is best to rely on histologic patterns seen in lymphoid tissue along with cellular marker studies. An elderly patient having bone pain, anemia, elevated blood calcium level, and renal failure along with purplish or skin-colored nodules and plaques on the trunk has a good chance of having multiple myeloma. Biopsying these lesions is most certain to reveal atypical plasma cells, and blood immunoelectrophoresis will demonstrate characteristic monoclonal gammopathy. There are two malignancies seen in children under 3 years of age that often times affect the skin in a characteristic fashion. Letterer-Siwe disease, which is distinguished from other histocytic disorders by its cell of origin, the Langerhans cell, clinically shows maculopapular and erosive lesions distributed in a seborrheic pattern. Neuroblastoma derived from cells of the neural crest demonstrates clinically widespread bluish papulonodules. Kaposi's sarcoma, a multifocal vascular malignancy, has a wide spectrum of clinical expression. Those patients who are immunocompromised secondary to concomitant disease or immunosuppressive therapy are more susceptible to a disseminated fulminant course accompanied by opportunistic infection. In conclusion, although specific signs of internal malignancy are less common than nonspecific ones, they are just as important; if the clinician managing the cancer patient is familiar with these clues to internal disease, proper patient management will ensue.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Specific cutaneous manifestations of internal malignancy. 307 47

Eleven hypercalcemic patients affected by various kinds of cancer were treated with dichloromethylene diphosphonate (Cl2MDP), 400 mg diluted in 500 ml of saline solution, i.v., during 3 h. Drug administration normalized plasma calcium levels in all treated patients, within 72 h for patients with lung cancer; within a longer period for other kinds of cancer. Moreover, Cl2MDP also reduced calciuria in treated patients. The use of the drug was not followed by side effects and was also well tolerated in patients with kidney insufficiency.
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PMID:Hypercalcemia in malignancies: treatment with dichloromethylene diphosphonate (Cl2MDP). 315 51

From 1975 to 1986, 15 cases (2%) of metastatic calcification associated with an underlying malignancy were found in a review of 702 autopsied cases with histories of malignancy. These underlying malignancies included 7 cases of lung cancer, 6 cases of malignant lymphoma, one case of breast cancer, and one of urinary bladder cancer. Squamous cell carcinoma was of the histological type most often associated with metastatic calcification in lung cancer, and ATL in malignant lymphoma. Hypercalcemia was found in 10 (83%) out of cases, and almost all were accompanied by renal dysfunction. Calcium deposits were most frequently observed in the kidneys and the lungs. It has been suggested that metastatic calcification in the lungs and kidneys of a patient with a history of malignancy showing hypercalcemia is sometimes accompanied by respiratory and renal dysfunction, causing the patient's condition to deteriorate.
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PMID:[Metastatic calcification associated with malignancy]. 323 Jun 35

Parathyroid hormone (PTH)-like bioactivity, assayed as adenylate cyclase response in UMR 106-01 osteogenic sarcoma cells, was present in extracts of sheep fetal and maternal parathyroid glands and placenta. Preincubation of extracts with PTH(1-34) antiserum inhibited approximately 40% of the bioactivity in fetal parathyroid extracts, 50% in maternal parathyroid extracts, but only 10% of the bioactivity in the placental extract. Partial purification of placental extracts by chromatography yielded fractions containing PTH-like bioactivity which were similar in behaviour to that of PTH-related protein (PTHrP) from a human lung cancer cell line (BEN). An antiserum against synthetic PTHrP(1-16) partially inhibited the bioactivity of the placental extract and synthetic PTHrP(1-34), but had no effect on the bioactivity of bovine PTH(1-34) or bovine PTH(1-84). The placental PTH-like bioactivity was higher in mid- than in late gestation. Fetal parathyroid glands contained the highest PTH-like bioactivity. Thyroparathyroidectomy of one fetal twin lamb in each of 16 ewes between 110 and 125 days of gestation resulted in decreases of the plasma calcium concentration and reversal of the placental calcium gradient that existed between the ewe and the intact fetus. Perfusion of the placenta of each twin in anaesthetized ewes was carried out sequentially with autologous fetal blood in the absence of the exsanguinated fetus. The plasma calcium concentration in the blood perfusing the placenta of each twin increased, but reached a plateau at a lower concentration in the perfusing blood of thyroparathyroidectomized fetuses than in that of the intact fetuses. Addition of extracts of fetal parathyroid glands or of partially purified PTHrP resulted in further increases in plasma calcium in the autologous blood perfusing the placentae of thyroparathyroidectomized fetuses, but addition of bovine PTH(1-84) or rat PTH(1-34) had no effect. The presence of this PTH-like protein in the fetal parathyroid gland and placenta may contribute to the relative hypercalcaemia of the fetal lamb. This protein, which is similar to PTHrP associated with humoral hypercalcaemia of malignancy, stimulates the placental calcium pump responsible for maintaining a relative fetal hypercalcaemia during gestation.
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PMID:Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid glands and sheep placenta: comparisons with a similar protein implicated in humoral hypercalcaemia of malignancy. 337 58

The serum zinc, calcium and magnesium concentration as well as the possible relationship between these elements was determined by means of atomic absorption spectrophotometry in 150 patients with prostatic, lung, liver and breast neoplasms as well as with chronic leukemia, and in 80 normal subjects. These determinations showed that zinc concentration is increased in almost all the forms of cancer except prostatic and lung cancer in which the zinc values were below the lowest normal limits. From this study it also resulted that high zinc values favour the development of cancer. The antagonic relationship between zinc and calcium or magnesium in neoplasias proves the protective role played by the latter elements in the forms of cancer in such cases.
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PMID:Variations of zinc, calcium and magnesium in normal subjects and in patients with neoplasias. 342 2

The use of doxorubicin (Dx) in treating malignancies is limited by a potentially fatal cardiomyopathy. Prevention of this related cardiotoxicity has been attempted either by using doxorubicin analogues such as 4'-epidoxorubicin (4'-EpiDx) or by simultaneous administration of other pharmacological substances. Fifteen patients with breast and lung cancer divided into three groups, treated respectively with Dx alone, Dx and L-carnitine and 4'-EpiDx, were studied to assess the effects of these therapeutic regimens on left ventricular performance. For this purpose the maximum velocities of fibre shortening and lengthening (VcF), obtained by computerized M-Mode echocardiography were used as indices of systolic and diastolic function respectively. Data from patients and from 25 healthy subjects were evaluated by analysis of variance and Tukey test. No significant difference was found in baseline systolic and diastolic VcF values. Significantly lower systolic VcF (p less than 0.05) was shown by patients treated with Dx alone, while diastolic VcF was significantly lower in those treated with 4'-EpiDx after four cycles. Systolic VcF of patients treated with Dx and L-carnitine and with 4'-EpiDx did not significantly differ from controls even after six therapeutic cycles. These data demonstrate that systolic VcF is not affected by 4'-EpiDx or by Dx when administrated with L-carnitine. The reduction of diastolic VcF by 4'-EpiDx and not by Dx could be due to different effects of these drugs on the calcium transport since early isovolumic relaxation depends on an energy-dependent process of calcium removal.
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PMID:Echocardiographic assessment of anthracycline cardiotoxicity during different therapeutic regimens. 347 15


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