Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present studies examined renal calcium (Ca) clearance in an animal model of malignancy-associated humoral hypercalcemia (MAHH) (a human squamous cell lung carcinoma carried in athymic mice). Three groups of animals--controls, normocalcemic tumor-bearing animals and hypercalcemic tumor-bearing animals--were studied in the basal state and during Ca infusion. Baseline Ca clearance was slightly but significantly elevated in the tumor-bearing hypercalcemic animals compared with the other two groups of animals. This clearance value was, however, inappropriately low for the serum Ca value. In the control and in the normocalcemic tumor-bearing animals, Ca clearance increased markedly during Ca infusion. This increase in renal Ca clearance was markedly blunted in the hypercalcemic animals compared with both the controls and the normocalcemic tumor-bearing animals. We conclude that increased renal Ca resorption contributes significantly to the pathogenesis of hypercalcemia of malignancy.
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PMID:Increased renal calcium reabsorption in an animal model of hypercalcemia of human malignancy. 319 67

A decrease in renal tubular reabsorption of inorganic phosphate (Pi) can be observed in hypercalcemia of malignancy. In the present study we investigated the effect of serum-free conditioned medium (CM) from cells, derived from a lung carcinoma (BEN) of a hypercalcemic patient, and of PTH on cyclic AMP (cAMP) production and sodium-dependent Pi transport (NaPiT) in epithelia of two renal cell lines. In opossum kidney cells (OK), PTH is known to enhance cAMP production and inhibit NaPiT; in contrast, in LLC-PK1 cells, PTH has no effect on NaPiT since this kidney cell line is devoid of PTH receptors. In OK cells, BEN CM induced a three- to fourfold increase of cAMP production, which was blunted by the PTH inhibitors bPTH(3-34) and bPTH(7-34). NaPiT, as assessed by measuring the initial rate of Pi uptake, was inhibited in a dose-dependent manner by BEN CM, with an effect maximal between 1h30 and 6 hr of incubation (40 +/- 4% and 47 +/- 4%, respectively), corresponding to the effect produced by 1-3 nM bPTH(1-34). The Na-dependent transport of a glucose analog was affected neither by BEN CM nor by PTH. In LLC-PK1 cells, neither BEN CM nor PTH altered cAMP production nor NaPiT after 1h30 of incubation. At 6 hr, BEN CM caused a slight decrease in NaPiT. In conclusion, these results constitute the first evidence of a direct and selective inhibition by tumor-derived factor(s) of NaPiT in cultured renal epithelia. Most of the renal NaPiT inhibitory activity produced by the lung tumor required the presence of a PTH receptor-adenylate cyclase system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Factor derived from human lung carcinoma associated with hypercalcemia mimics the effects of parathyroid hormone on phosphate transport in cultured renal epithelia. 321 17

Overproduction of parathyroid hormone-related protein (PTHrP) is a major cause of hypercalcemia of malignancy in patients with solid tumors. We measured plasma levels of the protein by a radioimmunoassay (RIA) against PTHrP(53-84) and by an immunoradiometric assay (IRMA) against PTHrP (1-86). Of 16 affected patients 7 had elevated PTHrP levels in both assays and 4 had elevated levels in the RIA only. Median levels were about tenfold higher in these patients when measured by RIA (median of 34 versus 2.2 pmol/l). Measurements from both assays were, however, highly correlated with each other in this patient group (P < 0.01). PTHrP was not elevated in 10 normocalcemic patients with lung carcinoma. During long-term follow-up of a patient with a mesothelioma of the pleura, PTHrP levels measured with both assays decreased during chemotherapy in parallel with a normalization of serum calcium. In another hypercalcemic patient suffering from renal carcinoma, PTHrP measured by IRMA decreased by 40% within 12 h after nephrectomy, whereas PTHrP measured by RIA did not show a significant decline. Direct comparison of the assay results thus pointed to the existence of heterogeneity of circulating forms of PTHrP in plasma. In conclusion, both immunoassays detected elevated levels of PTHrP in a fraction of patients with hypercalcemia of malignancy and thus may be a tumor marker during treatment of malignancies.
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PMID:Levels of parathyroid hormone-related protein in hypercalcemia of malignancy: comparison of midregional radioimmunoassay and two-site immunoradiometric assay. 845 57

Humoral hypercalcaemia of malignancy (HHM) commonly results from the excessive production of a parathyroid hormone-related protein (PTHrP) by tumours. We have previously shown malignancy is associated with increased DNA methylation in the 5' region of the PTHrP gene. In a series of patients with lung carcinoma and relatively high serum calcium levels, 3 patients showed substantially increased PTHrP gene methylation while 5 patients showed no change in methylation status in this region. Patients showed marked tumour-specific expression of PTHrP through the P1 and P3 promoters with more general tumour and non-tumour expression through the P2 promoter. The lack of potential key regulatory CpG sites in the P1 promoter and the complete demethylation in the P2 and P3 promoters suggests methylation does not influence tumour-specific expression of PTHrP. Although demethylation may be a prerequisite for P2 and P3 expression, the overexpression of the PTHrP gene in cancer cells must be mediated through mechanisms other than DNA methylation.
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PMID:Increased upstream methylation has no influence on the overexpression of the parathyroid hormone-related protein gene in squamous cell carcinoma of the lung. 1104 52

Bisphosphonates are considered a cornerstone for the treatment of hypercalcemia of malignancy, whereas calcitonin has not been found to be as potent. We report a case of severe hypercalcemia of malignancy that developed while the patient was taking alendronate that responded to the use of calcitonin. A 73-year-old woman developed hypercalcemia of malignancy while taking weekly alendronate. The patients' serum calcium remained above 15 mg/dL despite hydration and loop diuretics for 48 hours in addition to the bisphosphonates, and resistance was suspected. Intravenous calcitonin produced a dramatic decrease within 12 hours and normal serum calcium within 24 hours of treatment. Calcitonin might be useful for hypercalcemia of malignancy resistant to bisphosphonates.
Clin Lung Cancer 2007 Jul
PMID:Malignancy-related hypercalcemia developing on a bisphosphonate but responding to calcitonin. 1768 Oct 97

The purpose of this study was to identify the risk factors for skeletal-related events (SREs) in patients with advanced non-small cell lung cancer (NSCLC). SREs were defined as pathologic fractures, spinal cord compression, requirement for radiation therapy, other radiological intervention, or surgery to the bone, and hypercalcemia of malignancy. Time-to-the first SRE and SRE-free survival, and their associations with the patient characteristics were evaluated retrospectively in 642 patients with metastatic NSCLC who received systemic chemotherapy. A total of 118 (18.4%) patients developed SREs during or after the initial chemotherapy. Of these, 107 required radiotherapy to the bone, 5 developed hypercalcemia of malignancy, 3 developed compression fracture of the vertebrae, 2 required surgical treatment of the bone, and 1 underwent radiofrequency ablation therapy to the bone. The first SRE occurred within 12 months in 80 (67.8%) of the 107 patients. The results of multivariate analysis revealed that male sex, performance status (PS) of 2-3 and multiple bone metastases were risk factors for the first SRE, with hazard ratios (HRs) (95% confidence interval [CI]) to the reference of 1.44 (0.98-2.11), 2.21 (0.97-5.03) and 4.43 (2.91-6.76), respectively. SRE-free survival showed a similar trend. The HRs (CI) of male sex, PS of 2 and multiple bone metastases were 1.64 (1.30-2.06), 3.72 (2.31-5.98) and 1.80 (1.40-2.31), respectively. In conclusion, the presence of multiple bone metastases was significantly associated with the development of SRE in patients with advanced NSCLC treated by systemic chemotherapy. Male sex and poor performance status may be additional risk factors for the development of SREs in these patients.
Lung Cancer 2009 Aug
PMID:Risk factors for skeletal-related events in patients with non-small cell lung cancer treated by chemotherapy. 1908 Nov 61

Lung cancer is one of the most common cancers diagnosed worldwide. As the disease progresses, patients with lung cancer can develop metastasis to the bone. However, because early-stage bone disease may be asymptomatic, bone metastases often go undiagnosed, resulting in delayed initiation of treatment to prevent skeletal complications. In the absence of bone-targeted therapies, patients with metastatic bone disease are at increased risk for potentially debilitating skeletal-related events (SREs) including pathologic fracture, spinal cord compression, hypercalcemia of malignancy, and the requirement for surgery or radiation therapy to bone. The majority of patients with bone metastases from lung cancer will develop SREs, and this number is expected to increase with the improvement of primary therapies that are prolonging the lives of patients. Zoledronic acid is the only bisphosphonate that has been extensively studied in patients with bone metastases from lung cancer, and it has demonstrated efficacy in delaying the onset and reducing the risk of SREs in this setting. Preventing SREs with zoledronic acid may preserve the quality of life and functional independence of these patients. Recent exploratory analyses of a phase III study in patients with bone metastases from lung cancer or other solid tumors revealed that zoledronic acid also normalizes biochemical markers of bone metabolism and may also improve survival in specific patient subsets. Additional ongoing clinical trials are assessing further benefits and antitumor activity of zoledronic acid in the adjuvant setting in the prevention of bone metastases in patients with lung cancer.
Clin Lung Cancer 2009 Jul
PMID:Skeletal disease contributes substantially to morbidity and mortality in patients with lung cancer. 1963 38