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)

Clinical trials are the most widely accepted tools in the search for more effective supportive care drugs/interventions. The aim of our study was to determine Central Eastern European countries' (CEEC) involvement and future interest in conducting supportive care clinical trials. Our study was a part of an ESMO/MASCC program launched to support the development of supportive care in CEEC. The study was designed as a mailed questionnaire survey within the ESMO CEE Task Force. It involves national representatives from 18 countries. The purpose of the questionnaire was to assess the involvement and interest in conducting clinical trials in 13 representative supportive care fields: antiemetic therapy, cancer pain control, infections/febrile neutropenia, mucositis, fatigue, hypercalcemia, dyspnea, anorexia/cachexia, psychosocial support, toxicity reducing agents, hematopoietic growth factors, communication/education and quality of life. A total of 15 completed questionnaires were returned (83.3%). CEEC were mainly involved in clinical trials of hematopoietic growth factors (7/15), quality of life (6/15), antiemetic therapy (5/15), and cancer pain control (4/15). Increased interest was observed in the trials of fatigue, dyspnea, psychosocial support, infections / febrile neutropenia, communication / education and toxicity reducing agents. Clusters of CEEC that are similar in terms of their previous involvement and future interest in supportive care trials were identified. Our survey may prove to be a significant first step for CEEC active involvement in multinational clinical trials, which are crucial for improving supportive care standards.
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PMID:Are Central Eastern European countries involved in clinical trials of supportive care? 1202 29

Cancer has many effects on the veterinary patient. One group of syndromes that must be paid particular attention to is the paraneoplastic diseases. These are a group of changes that occur in the body at sites distant from the actual tumor. Paraneoplastic syndromes can affect many different body systems. Paraneoplastic diseases are important to recognize for many reasons. Often the paraneoplastic change is the earliest indication of cancer and, thus, neoplasia must be included on any differential list when typical paraneoplastic changes are found in the routine medical work-up. Paraneoplastic syndromes can also be used as markers of remission. Many of the paraneoplastic changes will disappear when remission is achieved, and will reappear once the period of remission had come to an end. Identification of paraneoplastic changes is also important in that often they must be treated before treatment of the primary disease can occur. Treating the remote effects of cancer will increase quality of life. Although many different paraneoplastic syndromes exist, hypercalcemia, hypoglycemia, cachexia and anemia are the most clinically significant in the veterinary patient. Chronic treatment most commonly involves removal or treatment of the primary or inciting neoplastic process. The acute treatment of these syndromes can occur quickly. Rapid identification and treatment will allow the patient to have a better prognosis and will help to improve quality of life.
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PMID:Common paraneoplastic syndromes. 1283 Oct 75

Parathyroid hormone-related protein (PTHrP) plays a central role in humoral hypercalcemia of malignancy (HHM), which is one of the most frequent paraneoplastic syndromes. PTHrP produced by the tumor acts through a common PTH/PTHrP receptor to promote bone resorption, inhibit calcium excretion from the kidney, and induce hypercalcemia. Patients with HHM often develop cachexia associated with typical symptoms such as anorexia, malaise, nausea, constipation, polyuria, polydipsia, and confusion. The etiology of the cachexia is not fully understood but is thought to be caused by hypercalcemia and various cytokines such as interleukin-6, tumor necrosis factor-alpha, leukemia inhibitory factor, and others. In this study, we investigated the role of PTHrP in hypercalcemia and cachexia in HHM by using humanized anti-PTHrP antibody. A mouse monoclonal antibody that binds to PTHrP amino acid sequence 1-34 and inhibits PTHrP function has been humanized to create a specific and potent agent for the treatment of patients with HHM. The mouse monoclonal antibody has been shown to have antihypercalcemic activity against nude mice bearing human tumors. Because a mouse antibody is highly immunogenic in human patients, the complementarity-determining regions from the mouse antibody were grafted into a human antibody. The resulting humanized antibody specifically recognizes PTHrP(1-34) and neutralizes PTHrP functions in vitro and in vivo. The humanized anti-PTHrP antibody was administered intravenously to HHM model animals bearing tumors such as LC-6 human lung carcinoma. These animals showed symptoms similar to those of patients with HHM (eg, hypercalcemia and cachexia). The humanized anti-PTHrP antibody-treated animals responded with normalization of blood ionized calcium level through an improvement of bone metabolism and calcium excretion. Moreover, the treated animals also showed an improvement in body weight, ultromotivity, metabolic alkalosis, food consumption, water intake, serum phosphorus, and renal function. Consequently, the humanized antibody-treated animals experienced complete resolution of hypercalcemia and cachexia. These results suggest that the humanized antibody would be an effective and beneficial agent for patients with HHM, and that PTHrP is a major pathogenetic factor of hypercalcemia and cachexia in patients with HHM.
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PMID:Treatment of malignancy-associated hypercalcemia and cachexia with humanized anti-parathyroid hormone-related protein antibody. 1461 38

Paraneoplastic syndromes are common complications of lung cancer. Although most frequently associated with advanced disease, paraneoplastic syndromes may also occur at early stages. Occasionally, the paraneoplastic syndrome may be the presenting symptom of lung cancer. For most paraneoplastic syndromes, the best treatment is to treat the underlying malignancy. However, in many cases, treatment of moderate efficacy or urgent therapy is required. Specific recommendations for the management of the most common paraneoplastic syndromes, including cachexia, hypercalcemia, and hyponatremia, are provided.
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PMID:Management of paraneoplastic syndromes in lung cancer. 1469 57

There have been a number of reports suggesting inhibition of prostaglandin production may impact tumor-mediated wasting and levels of associated humoral factors such as hypercalcemia. These reductions were achieved using traditional nonsteroidal anti-inflammatory drugs (NSAIDs), which are often contraindicated in cancer patients. This is especially true during chemotherapeutic regimens due to concerns of bleeding from gastrointestinal and hematopoietic toxicities associated with inhibition of the housekeeping cyclooxygenase enzyme COX-1. Here, we report that celecoxib, one of the new class of selective COX-2 inhibitors, has the potential to reverse tumor-mediated wasting and associated humoral factors such as interleukin (IL)-6 and hypercalcemia in preclinical models of cachexia. Tumor bearing mice in late stage cachexia regained weight within days of the start of celecoxib treatment. Two models were tested. The first was the Colon 26 (Col26) syngeneic murine model that induces high levels of circulating IL-6 and hypercalcemia. The second was the human head and neck 1483 HNSCC xenograft model, which is less inflammatory and produces less prostaglandin than Col26. Despite the observation that no significant impact on tumor growth was observed between vehicle and celecoxib-treated animals over the course of the studies, celecoxib rapidly reversed weight loss in both cachectic models. With the added safety of celecoxib over traditional NSAIDs, these results suggest a possible therapeutic use for celecoxib for treating tumor-mediated wasting.
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PMID:Inhibition of cyclooxygenase-2 by celecoxib reverses tumor-induced wasting. 1471 36

Mice bearing LP07 lung adenocarcinoma show some characteristics that are similar to those present in patients with NSCLC. LP07 tumor-bearing mice develop the paraneoplastic syndromes of cachexia, leukocytosis and hypercalcemia. These symptoms may be partly due to a systemic inflammatory response. Our aim was to determine if treatment with NSAIDs would lower tumor and metastasis growth and their accompanying syndromes. The nonselective COX inhibitor indomethacin and the selective COX-2 inhibitor celecoxib reduced tumor growth and metastasis outcome in s.c. LP07 tumor-bearing mice. Both drugs also inhibited the development of leukocytosis and the weight loss associated with LP07 progression. Serum levels of the inflammatory cytokines IL-1beta and IL-6, mediators of cachexia, were modulated by NSAIDs. Inhibition of in vitro migration and invasion and reduction in angiogenesis were attained when cells were treated with either indomethacin or celecoxib. MMP-9 activity was also reduced in conditioned media from LP07 cells treated with celecoxib. These data suggest that several processes implicated in tumor progression can be modulated with NSAID treatment. Improvement in performance status through modulation of cachexia may offer a possibility for combining anti-inflammatory treatments with more aggressive therapies.
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PMID:Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs. 1517 Jun 63

Parathyroid carcinoma is an uncommon cause of primary hyperparathyroidism; however, when this condition is severe, cancer must be suspected. We report on a 28-year-old male with severe hypercalcemia, cachexia, acute pancreatitis, urolithiasis, anemia and a severe skeletal involvement with multiple fractures. The patient had a 4-cm parathyroid tumor, that was surgically excised, along with the ipsilateral thyroid lobe. During the postoperative period, he had a severe and prolonged hungry bone syndrome, with a slow recovery of fractures, with functional and anatomical sequelae in the extremities. PTH levels were adequate for the serum calcium during the 16 months of follow-up.
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PMID:[Primary hyperparathyroidism with severe skeletal involvement in one patient with parathyroid carcinoma]. 1576 53

Hematologic malignancies such as multiple myeloma, adult T cell leukemia and malignant lymphoma are often complicated with bone lesions and/or hypercalcemia. The abnormal bone metabolism in these diseases are modified by co-existing cachexia, malnutrition, sex hormone deficiency and abnormal parathyroid function or by chemotherapy in a complex manner. Metabolic bone markers are not only clinically useful for evaluation and diagnosis of such bone abnormalities but may also be used to monitor the disease activity itself, particularly in multiple myeloma which almost inevitably involves bone destructive lesions.
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PMID:[Clinical application of metabolic bone markers in hematologic malignancies]. 1577 92

Elevated levels of IL-6 and IL-11 are associated with multiple myeloma, rheumatoid arthritis, hypercalcemia, cancer cachexia, and Castleman's disease. Madindoline A (MadA), isolated from Streptomyces nitrosporeus K93-0711, specifically inhibits the growth of IL-6- and IL-11-dependent cell lines, most likely by interfering with the homodimerization of gp130. This raises the possibility that MadA can be used as a model compound for the development of novel chemotherapeutic agents. In this report, we demonstrate that the binding of MadA to gp130 is specific and noncovalent, and displays a relatively low affinity. Furthermore, we show that the tricyclic 3a-hydroxytetrahydrofuro[2,3-b]indole (HFI) moiety of MadA alone is not sufficient for binding. Matrix-bound MadA precipitates a protein composed of the extracellular domain of gp130 fused to the Fc region of the immunoglobulin heavy chain. Binding is inhibited in a dose-dependent manner by preincubation with free MadA. The K(D) for binding of MadA to gp130 is 288 microM, as determined by surface plasmon resonance (SPR)-based biosensor analysis. The HFI portion of MadA does not bind to gp130 in either affinity precipitation or SPR analyses. Finally, MadA, but not the HFI portion, inhibits IL-6-dependent Stat3 tyrosine phosphorylation in HepG2 cells.
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PMID:Binding of madindoline A to the extracellular domain of gp130. 1608 84

We have previously demonstrated that parathyroid hormone-related protein (PTHrP) is a cachexia inducer, but it is still not known what PTHrP effects on target tissues induce the cachexia. Therefore, we examined the effects of anti-PTHrP antibody and osteoprotegerin (OPG) on PTHrP-producing tumor-induced cachexia. Nude mice bearing PTHrP-producing human lung cancer cells (HARA-B) exhibited cachexia with hypercalcemia 3-4 weeks after inoculation, accompanied by losses in body, adipose tissue, and muscle weight. OPG ameliorated hypercalcemia, as did neutralization of PTHrP with antibody; and it increased both body and adipose tissue weights. These increases in body and adipose tissue weight, however, were significantly less than those in mice treated with anti-PTHrP antibody. Simultaneous administration of OPG and anti-PTHrP antibody caused significant increases in body, adipose tissue, and muscle weight, along with an immediate decrease in blood ionized calcium levels. The increase in body weight was similar to that observed in mice treated with anti-PTHrP antibody alone, and the decrease in the blood ionized calcium levels was significantly greater than that in mice treated with OPG or anti-PTHrP antibody alone. These results suggest that an effect of PTHrP on target tissues other than hypercalcemia is involved in the development of cachexia. Expression of cachexia-inducing proinflammatory cytokines (interleukin-6 and leukemia inhibitory factor) is stimulated by PTHrP. This might be a mechanism by which PTHrP produces tumor-induced cachexia. It is also suggested that OPG and anti-PTHrP antibody synergistically act to ameliorate hypercalcemia, although the mechanism responsible for this is unclear.
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PMID:Effects of anti-parathyroid hormone-related protein monoclonal antibody and osteoprotegerin on PTHrP-producing tumor-induced cachexia in nude mice. 1636 93


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