Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncologic emergencies can occur in cancer patients who have a good prognosis. In all of them, the challenge to the clinician is to diagnose and treat before irreversible complications occur. In febrile patients with neutropenia, cultures of body fluids should be obtained and therapy should be started immediately with broad-spectrum antibiotics. If spinal cord compression is suspected, either magnetic resonance spectroscopy or complete myelography can be done to confirm the diagnosis. Prompt workup in cancer patients with headaches or seizures may avoid neurologic consequences. For brain metastases, immediate treatment with dexamethasone (Decadron, Dexone, Hexadrol) is indicated. For hypercalcemia, a number of drugs that inhibit bone resorption, resulting in lower serum calcium levels, are now available. Malignant cardiac tamponade is relatively rare but potentially lethal; emergency pericardiocentesis often results in marked improvement.
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PMID:Oncologic emergencies. Treating acute problems resulting from cancer and chemotherapy. 827 94

We report a case of primary lung cancer in a 16-year-old boy. A histologic diagnosis of squamous cell carcinoma was made by bronchoscopic biopsy before surgery. The serum alphafetoprotein (AFP) level was markedly elevated at 193 ng/dl. Preoperative and postoperative evaluation revealed no evidence of scrotal mass. We performed right pneumonectomy with combined resection of the invaded portion of the left atrium under extracorporeal circulation. Despite the rapid improvement in the patient's general condition after surgery, the AFP level continued to increase without a transient decrease and reached 3160 ng/ml on the 23rd postoperative day. When the patient was readmitted because of dyspnea and headache on the 36th postoperative day, hypercalcemia of 13.9 mg/dl was noted, and this was resistant to subsequent treatment. The patient died on the 46th postoperative day.
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PMID:AFP-producing squamous cell carcinoma of the lung in an adolescent. 860 92

9-cis-Retinoic acid (9-cis-RA) and all-trans-RA (ATRA) are naturally occurring hormones. The nuclear receptors that mediate the effects of retinoids are the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). ATRA binds RAR with high affinity but does not bind to RXR, whereas 9-cis-RA, an isomer of ATRA, is a ligand that binds and transactivates both RARs and RXRs. The goals of this study were to determine the safety, tolerability, pharmacokinetics, and metabolic profile of 9-cis-RA in advanced cancer patients. Forty-one patients received oral 9-cis-RA (ALRT1057; Panretin capsules) at doses ranging from 5-140 mg/m2/day. Twenty-six patients were treated once daily with up to 140 mg/m2; a subsequent cohort of 15 patients were treated twice daily (b.i.d.) at 100-140 mg/m2/day (50, 60, and 70 mg/m2 b.i.d.) to evaluate a b.i.d. dosing regimen. Headache was the most frequent adverse event and was dose limiting in 3 of 41 patients. Skin toxicity was the next most common toxicity and was seen in 11 of 41 patients; it was typically mild and limited to skin dryness and erythema. Other toxicities included conjunctivitis, flushing, diarrhea, transaminitis, hypercalcemia, and asymptomatic hypertryglyceridemia. Toxicities were typically dose related, occurred primarily above 83 mg/m2/day, and were not ameliorated by b.i.d. dosing. No tumor responses were observed. The mean day 1 area under the plasma concentration-time curve and peak plasma concentration values were dose-proportional over all dose levels, whereas day 15 area under the plasma concentration-time curve and peak plasma concentration values were nonlinear above 83 mg/m2/day, suggesting that 9-cis-RA induced its own metabolism at doses equal to and above 140 mg/m2/day. 9-cis-RA is a retinoid receptor pan agonist with a more favorable pharmacokinetic and toxicity profile than that observed with previously studied retinoids and merits further investigation.
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PMID:Phase I study of 9-cis-retinoic acid (ALRT1057 capsules) in adults with advanced cancer. 962 60

Retinoids are commonly used for the treatment of nonmalignant skin disorders and occasionally for the treatment of various neoplasms including epidemic Kaposi sarcoma (KS). Dry skin and mucus membranes, muscle and joint aches, alopecia, headaches, and liver and lipid abnormalities are the most frequent medication-related side effects. Very rarely, this class of drugs is associated with the development of hypercalcemia. The authors report the case of a man with acquired immunodeficiency syndrome (AIDS)-associated KS who, while participating in a phase II clinical trial of LGD 1057 (9-cis-retinoic acid) for treatment of epidemic KS, developed hypercalcemia, mental status changes, and renal insufficiency. The etiologic factors of retinoid-induced hypercalcemia are imperfectly understood, but with drug withdrawal his serum calcium, mental acuity, and renal function quickly normalized. Hypercalcemia occurs infrequently in the setting of AIDS and when present, is usually mediated by opportunistic infections. Clinicians should be alert to this potentially life-threatening iatrogenic complication that responds favorably to drug withdrawal.
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PMID:Retinoid-induced hypercalcemia in a patient with kaposi sarcoma associated with acquired immunodeficiency syndrome. 978 12

Retinoids have been shown to be potent inhibitors of epithelial carcinogenesis. Recent evidence has demonstrated that retinoid actions are mediated through nuclear receptors, which are proteins encoded by the retinoic acid receptor and retinoid X receptor gene families. These receptors are activated by binding to specific retinoids; of the known naturally occurring retinoids, 9-cis retinoic acid is unique in its ability to bind to both receptor families. Because of its unique receptor-binding characteristics, 9-cis retinoic acid may have biological activity not possible with other retinoids. For this reason, we conducted a Phase I trial of 9-cis retinoic acid in adult patients with solid tumors. Twenty-two patients were treated twice daily with p.o. 9-cis retinoic acid at doses ranging from 20 mg/m2/day to 150 mg/m2/day. The patients had non-small cell lung cancer (n = 8), breast cancer (n = 5), colorectal cancer (n = 3), head and neck cancer (n = 2), nonmelanoma skin cancer (n = 2), or ovarian cancer (n = 2). The dose-limiting (WHO grade III) toxic effects, which occurred at the 150-mg/m2/day dose level, were headaches and diarrhea. Less severe (grades I and II) toxic effects included cheilitis, dry skin, conjunctivitis, fatigue, hypertriglyceridemia, alkaline phosphatase elevation, myalgia/arthralgia, and hypercalcemia. Of the 15 patients evaluable for tumor response, no objective responses were observed. Pharmacokinetic analysis revealed a reduction in peak 9-cis retinoic acid plasma levels with chronic administration. Based on this study, the recommended Phase II dose of 9-cis retinoic acid in adult patients with solid tumors is 100 mg/m2/day administered in a divided dose twice daily.
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PMID:Phase I trial of 9-cis retinoic acid in adults with solid tumors. 981 71

The retinoid response is mediated by families of nuclear receptors, the retinoic acid receptors (RARs), and the retinoid X receptors. All-trans retinoic acid (RA) binds only RARs and induces its own metabolism. In contrast, 9-cis RA is a newly identified agonist for both RARs and retinoid X receptors. We undertook a dose-ranging study to examine the safety, clinical tolerance, and pharmacokinetics of 9-cis RA in patients with advanced cancer. Thirty-four patients received once daily p.o. doses of 9-cis RA (administered as LGD1057) ranging from 5 to 230 mg/m2 for 4 weeks. Pharmacokinetic studies were performed on 28 patients at seven dose levels. 9-cis RA was generally well tolerated. Headache was the most common dose-limiting adverse effect. Other prominent reactions included facial flushing, myalgia, dyspnea, hypertriglyceridemia, and hypercalcemia. Relative to other retinoids, mucocutaneous reactions were mild. No major antitumor responses were observed. Pharmacokinetic analysis revealed that the day 1 area under the plasma concentration x time curves (AUCs) were proportional to the dose. Up through doses of 140 mg/m2, the day 1 AUCs were similar to those on days 15 and 29. At higher doses, however, AUCs tended to decline with repeat dosing. 9-cis RA is a novel compound that exploits a newly identified pathway of retinoid receptor biology that may be relevant to tumor cell proliferation and differentiation. We recommend a dose of 140 mg/m2 for single-agent trials utilizing a once-daily schedule of administration.
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PMID:Initial clinical trial of the retinoid receptor pan agonist 9-cis retinoic acid. 981 92

Calcium (Ca) and magnesium (Mg) are involved in many processes related to depression. Evaluations of serum and plasma Ca and Mg levels in depressive disorders do not show consistent results. The few studies that examined their cerebrospinal fluid (CSF) levels tended to find no differences between depressed patients and controls. Because both hypercalcemia and hypomagnesemia are associated with depression, and as Mg may function as a Ca antagonist, it is suggested that the relationship between these cations could be different in depressed patients and controls. We examined CSF and serum Ca and Mg in acutely depressed patients diagnosed as having major depressive disorder or being in a depressive episode of bipolar disorder. Controls were subjects undergoing lumbar puncture as part of an evaluation for headache or suspected meningitis and found to demonstrate no physical or mental disorder. Serum and CSF Ca/Mg ratios were found to be elevated in the depressed patients compared with the controls. A retrospective analysis of previous trials assessing serum/plasma or CSF Ca and Mg does not seem to refute the findings of this study. We further discuss our findings in their relation to the acuteness of the depressive disorders.
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PMID:High serum and cerebrospinal fluid Ca/Mg ratio in recently hospitalized acutely depressed patients. 1007 61

LGD1069 [Targretin; 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphtalenyl) propenyl] benzoic acid] is a novel synthetic retinoid X receptor-selective retinoid that has been recently identified. The goals of this study were to determine the safety, toxicity, pharmacokinetics (PKs), and metabolic profile of LGD1069 in advanced cancer patients. Sixty patients received oral LGD1069 at doses ranging from 5-1000 mg/m2/day with PK sampling performed on days 1 and 15. No dose-limiting toxicities (DLTs) were observed up to the 500 mg/m2/day dose level. DLT observed at and above 650 mg/m2/day included skin desquamation, hyperbilirubinemia, transaminase elevation, leukopenia, and diarrhea. Asymptomatic, dose-related alterations in lipid and thyroid metabolism were also observed. DLTs frequently observed with retinoic acid receptor-selective retinoids and pan agonists, including headache, mucocutaneous toxicity, and hypercalcemia, were not dose-limiting with LGD1069. Day 1 LGD1069 Cmax and area under the curve values increased dose-proportionately up to 800 mg/m2/day. Repeat-dose (day 15) area under the curve values varied between 25 and 105% of day 1 values. Although no objective tumor responses were observed, tumor progression may have been substantially arrested or delayed in non-small cell lung cancer (5 of 16) and in head and neck cancer (1 of 5), as well as other tumor types. At the higher dose levels, the molar concentration of LGD1069 was up to 10-fold higher than observed with other retinoids, yet toxicity was minimal. LGD1069 is an retinoid X receptor-selective retinoid agonist with a more favorable PK and toxicity profile than previously studied retinoids and merits further investigation as a chemopreventive and anticancer agent. On the basis of this Phase I trial, the recommended Phase II dose is 500 mg/m2/day.
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PMID:A Phase I study of LGD1069 in adults with advanced cancer. 1043 65

We conducted a phase II study to determine the efficacy and toxicity of 9-cis-retinoic acid (9-cis RA), a pan-retinoid receptor agonist, in the treatment of patients with relapsed and refractory NHL. Patients were eligible if they had histologically documented relapsed or refractory T cell or indolent B cell NHL. The first three patients enrolled received 70 mg/m2 of 9-cis RA orally twice a day, but the remaining patients received a single oral daily dose of 100 mg/m2. After 6 weeks of therapy, tumor response was assessed objectively. Response rate and toxicity were determined in all 29 eligible patients based on an intent-to-treat analysis. Four patients (14%) responded (3 PRs and 1 CR; 95% CI 4%-33%). One patient had a minor response, and eight had stable disease. Responses were observed in two (11%) of 19 patients with B-cell lymphoma and in two (20%) of 10 patients with T-cell lymphoma. The median time-to-treatment failure for the 29 eligible patients was 8 weeks. The most frequent toxic effects were dry skin, headache, hypertriglyceridemia, and hypercalcemia. Five patients discontinued therapy due to toxic side effects, but no toxic deaths occurred during the study. We conclude that 9-cis RA has a modest activity in relapsed and refractory NHL. In this study, responses were observed in patients with B-cell lymphomas and those with T-cell lymphomas.
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PMID:Experience with 9-cis retinoic acid in patients with relapsed and refractory non-Hodgkin's lymphoma. 1142 31

A 54 year old man presented with frontal headaches for one year. A CT scan of the head revealed a pituitary mass. He denied a change in vision or galactorrhea, but did have decreased frequency of erections and a recent episode of renal stones. On physical exam, the cranial nerves were normal. Visual field exam revealed mild bilateral temporal defects. The genitalia were normal and the testes were soft. Laboratory evaluation revealed: Na, 134 mM/l; K, 6.7 mM/l; Cl, 104 mM/l; HCO3, 22 mM/l; BUN, 47 mg/dl; Cr, 8.3 mg/dl; Ca, 12.5 mg/dl; Phos, 5.5 mg/dl; prolactin, 32.0 ng/ml; T4, 4.46 microg/dl; TSH, 2.07 microU/ml; LH, 18.1 mIU/ml; FSH 3.2 mIU/ml; alpha subunit 1.6 ng/ml; testosterone 255 ng/dl; cortisol, 20.3 microg/dl; cortisol after 250 microg cortrosyn, 38.5 microg/dl (time 60 minutes); growth hormone, 1.4 ng/ml; IGF-1, 47 ng/ml; PTH, <1 pg/ml; 25-hydroxyvitamin D, 14 ng/ml; 1,25-dihydroxyvitamin D, 69 pg/ml. These results were felt to be consistent with a non-PTH-mediated hypercalcemia, such as humoral hypercalcemia of malignancy, or a vitamin D-mediated hypercalcemia, such as lymphoma, sarcoidosis or tuberculosis. Head MRI demonstrated a 3.5 x 3.5 x 2.5 cm heterogeneous mass enlarging the sella, deforming the clivus and compressing the cavernous sinus, basilar artery and left side of the optic chiasm. There was a small focus of high signal in the superior part of the mass on the T1-weighted image from either a proteinaceous cyst with early calcium deposition or sub-acute blood. These radiographic findings were felt to be consistent with a pituitary adenoma. The patient was treated with intravenous hydration and thyroxine 50 microg daily and underwent a transsphenoidal resection of the pituitary lesion. Pathologic examination revealed a pituitary adenoma with multiple granulomas and crystalline material; this was consistent with sarcoid within the adenoma. Post-operatively, the serum LH fell to 5.5 mIU/ml. A subsequent transbronchial biopsy revealed multiple non-caseating granulomas. A serum ACE level was elevated at 132.6 U/l. He received oral prednisone 60 mg daily with resolution of the hypercalcemia. Neurosarcoidosis occurs in 5 to 15% of patients with sarcoidosis and can involve the hypothalamus and pituitary gland. This is the first reported case of sarcoidosis occurring within a pituitary adenoma.
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PMID:Sarcoidosis within a pituitary adenoma. 1213 93


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