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

Humoral hypercalcemia of malignancy (HHM) is a common paraneoplastic syndrome mediated by tumor-derived parathyroid hormone-related peptide (PTHRP), which bears structural and functional similarities to PTH. Thus the clinical features of HHM are very similar to those of primary hyperparathyroidism (1 degree HPT), a prototype of humoral hypercalcemia caused by PTH. On the other hand, HHM syndrome differs from 1 degree HPT in several aspects, including serum 1,25(OH)2D levels, acid-base balance, and bone remodeling process, the reason of which remains largely unknown. We approached these questions using a unique animal model of HHM, nude rats implanted with PTHRP-overproducing human carcinomas. In this review we will summarize the results and discuss the implications in understanding the disease mechanism.
 ...
PMID:Humoral hypercalcemia of malignancy: some enigmas on the clinical features. 776 74

Primary thymic carcinoma is a rare neoplasm that in contradistinction to thymoma, is not supposed to be associated with a paraneoplastic syndrome. A 73-year-old man, with new onset of disorientation, was found to have an elevated serum calcium level as the cause. Computed tomography demonstrated a mediastinal mass, pericardial invasion, and metastases to the lung. Examination of a biopsy specimen revealed thymic squamous cell carcinoma. Thus, a paraneoplastic syndrome, in this case hypercalcemia, does not exclude primary carcinoma of the thymus.
 ...
PMID:Squamous cell carcinoma of the thymus with paraneoplastic hypercalcemia. 777 75

Humoral hypercalcemia of malignancy is a paraneoplastic syndrome believed to be due to production by the tumor of substances that stimulate osteoclastic bone resorption primarily. The human renal cell carcinoma cell line RC-8, grown in nude mice, was investigated for factors involved in renal cancer-induced hypercalcemia. At a tumor load of 200 to 400 mm.3 the mice developed hypercalcemia and hypophosphatemia associated with a rise in serum 1,25-dihydroxyvitamin D concentration and cachexia. The tumor released 1) significant amounts of human interleukin-6 (IL-6) and 2) parathyroid hormone-related peptide (PTHrP) into the circulation. Cancer cells further expressed mRNA for both human IL-6 and PTHrP. No secretion of human tumor necrosis factor-alpha or interleukin-1 beta could be demonstrated in the circulation of the host. Antibodies to IL-6 caused a significant (p = 0.043) inhibition of tumor growth and decreased serum calcium concentrations compared with control animals. Our data suggest that IL-6 is involved, either directly or indirectly, in the development of hypercalcemia in renal cell carcinoma.
 ...
PMID:Hypercalcemia and cosecretion of interleukin-6 and parathyroid hormone related peptide by a human renal cell carcinoma implanted into nude mice. 786 50

Various tumors secrete tumor-specific substances capable of producing signs and symptoms in host organs not caused by direct tumor invasion or organ destruction. These symptoms are collectively referred to as "remote effects" or "paraneoplastic syndromes" of malignancy. Paraneoplastic syndromes are uncommon in childhood cancer. In Wilms tumor several distinct paraneoplastic syndromes have been reported: hypertension, erythrocytosis, hypercalcemia, Cushing syndrome, and acquired Von Willebrand disease. In addition some tumor-specific substances are known to be elevated in patients with a malignancy without causing specific symptoms. These so called "tumor markers" can be used to detect early recurrence in previously treated patients, or in the evaluation of patients undergoing adjuvant therapy. Five of particular interest are erythropoietin, neuron-specific enolase (NSE), hyaluronic acid (HA), hyaluronic acid-stimulating activity (HSA), and hyaluronidase.
 ...
PMID:Serum biological markers and paraneoplastic syndromes in Wilms tumor. 838 82

Nude mice bearing the human oral cavity carcinoma cell line OCC-1, and the lung cancer cell line LC-1, developed a triple paraneoplastic syndrome consisting of hypercalcemia, cachexia and leukocytosis. All of these abnormalities disappeared rapidly after surgical resection of the tumors, suggesting their ectopic humoral nature. Search for the factors responsible for the respective abnormalities revealed that the production of parathyroid hormone-related protein and colony-stimulating factors (CSFs), mainly granulocyte-CSF, by the tumors could explain the hypercalcemia and leukocytosis, respectively. With regard to the severe cachexia, the production of two cachexia-associated cytokines, interleukin-6 and leukemia inhibitory factor, was able to explain the syndrome in OCC-1 bearing nude mice; however, the factor responsible in LC-1 bearing nude mice could not be identified. The triple paraneoplastic syndrome that developed in these two animal models could be explained partly by concomitant production of the peptide hormone and cytokines by cancer cells. These animal models may be very useful for the evaluation of diagnostic and therapeutic modalities for humoral abnormalities.
 ...
PMID:Triple paraneoplastic syndrome of hypercalcemia, leukocytosis and cachexia in two human tumor xenografts in nude mice. 860

PTH-related peptide (PTHrP) is the major factor responsible for humoral hypercalcemia of malignancy. This paraneoplastic syndrome has been described in association with a number of malignancies, but rarely with carcinoma of the colon. Moreover, little is known about the molecular mechanisms that underlie PTHrP overexpression in tumors. Here we report a patient who presented with hypercalcemia 6 months after resection of a neuroendocrine colonic carcinoma (tumor I). At the time of admission, intact PTH was decreased, circulating PTHrP levels were elevated, and there was tumor recurrence (tumor II). Immunohistochemical staining of paraffin-embedded sections from tumor I did not stain for PTHrP, whereas cells from tumor II stained intensely positive. Southern blot analysis and differential PCR of genomic DNAs from tumor specimens and the patient's leukocytes demonstrated amplification of the PTHrP gene in tumor II. Moreover, staining for p53 protein was evident in tumor II, but not in tumor I, consistent with the presence of a mutant form of p53 and associated loss of tumor suppressor function in the recurrent tumor. PTHrP gene amplification was also detected in one of five other tumors associated with humoral hypercalcemia of malignancy. These findings suggest that a potential mechanism contributing to PTHrP overexpression in malignancies is gene amplification, which could arise from increased genomic instability associated with the progressive stages of neoplasia.
 ...
PMID:Amplification of the parathyroid hormone-related peptide gene in a colonic carcinoma. 876 40

Paraneoplastic manifestations are present in up to 20% of patients with renal cell carcinoma (RCC). There is convincing evidence that RCC tumor cells elaborate proteins that serve as mediators of endocrine (eg, ectopic production of parathyroid hormone-related protein or erythropoietin) as well as nonendocrine paraneoplastic syndromes. A paraneoplastic syndrome may be the initial clinical presentation of RCC in a significant number of patients, and recognition of these syndromes may facilitate early diagnosis. Most paraneoplastic syndromes associated with RCC remit after resection of the primary RCC or treatment of metastatic sites. The natural history of metastatic RCC is extremely variable. A significant proportion of patients may survive several years with slowly progressing metastatic disease. In these patients, the accurate diagnosis and management of paraneoplastic syndromes may be important in palliative management. Except for hypercalcemia, conventional medical therapies are seldom helpful. Other paraneoplastic manifestations of RCC include cachexia, fever, hepatic dysfunction, anemia, and amyloidosis, although our understanding of the underlying pathophysiology remains incomplete.
 ...
PMID:Paraneoplastic manifestations of renal cell carcinoma. 894 20

PTHrP has had an unidentified role in medicine since 1930, when Albright described a patient with renal cortical cell carcinoma with hypercalcemia. Since then hypercalcemia has been recognized as the most common paraneoplastic syndrome. At that time the concept of "ectopic PTH syndrome" was introduced, and remained in literature until the true etiology was finally described. In the early 1970's Roof and Benson presented evidence that PTH in humoral hypercalcemia differed from "authentic" PTH. This marked the starting point for researchers to try identifying the molecule that mimicked PTH action and structure. This molecule, named parathyroid-related peptide, has been associated to hypercalcemia seen with solid tumors, such as squamous cell carcinoma of the lung and renal cortical cell carcinoma. PTHrP has been demonstrated to have similar actions to PTH but to differ in decreasing osteoblastic activity while increasing osteoclastic activity. The more fascinating finding was the presence of the PTHrP genes throughout the body, mostly the lactating breast as well as the heart, lungs and skin among others. Despite its identification, finding its physiological roles on normal tissue still remains to be clarified.
 ...
PMID:An update on the discovery, pathophysiological actions, clinical manifestations and possible physiology of parathyroid related peptide. 916 Mar 98

Renal Cell Carcinoma is the third most common malignoma in urology. Only little is known about the etiology and risk factors; the age peak lies at 60 and twice as many men than women are affected. The clinical picture presents with a wide spectrum. Over one third of all tumours are detected accidentally by ultrasound or computed tomography in asymptomatic patients. Most common symptoms are hematuria and flank pain, the classical trials including in addition a palpable mass is rare and by mo means an early symptom. Paraneoplastic syndromes include unspecific (increased blood sedimentation rate, weight loss, fever) and endocrine symptoms (hypertension, polyglobulia, hypercalcemia). Diagnosis is based on imaging procedures. By means of sonography renal cysts may be separated from solid, space-occupying tumors. For the latter CT plays a decisive role for staging, therapeutic planning and prognosis. Further radiologic investigations (angiography, MRI) are indicated only in special situations. Rarely a biopsy is necessary for the distinction between renal cell carcinoma and metastases of other primary tumors. The only curative treatment of localized carcinoma is radical nephrectomy. Partial resection is indicated in cases of a single kidney, bilateral tumors and possibly also for tumors smaller than 4 cm in diameter. Radiotherapy is only initiated for palliation of painful skeletal metastases. In case of distant metastases--mainly pulmonary--nephrectomy should only be performed if systemic treatment is planned or if local complaints (pain, hematuria leading to anemia) exist. Chemotherapeutic drugs have no influence on survival. The effect of gestagens on life quality is questionable. Adoptive immunotherapy with cytokines (Interferon-alpha, interleukin-2) appears most promising. These substances, however, not yet been introduced into routine therapy should only be used in prospective studies. Furthermore, renal cell carcinoma is a potential candidate for gene therapy. After tumor nephrectomy follow-up investigations should be performed twice a year, because of the possibility of curative surgical treatment of late solid metastases. Prognosis of tumors restricted to the organ is good. Five year survival after operation is about 90%. However, is distant metastases exist already at the time of diagnosis 5 year survival drops to less than 10%.
 ...
PMID:[Renal cell carcinoma--a current review]. 931 11

Treatment for the paraneoplastic syndrome associated with lung cancer was reviewed. The principle of the treatment of paraneoplastic syndrome is to control cancer as an underlying disease. Therefore, the standard therapy for Cushing's syndrome associated with lung cancer is surgical treatment if the tumor is operable. There is no standard therapy for Cushing's syndrome associated with advanced small-cell lung cancer. Metyrapone is used in combination with systemic chemotherapy. The effects of ketoconazole and octreotide are under investigation. To control hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion, fluid restriction is standard. When hyponatremia cannot be controlled with fluid restriction, demeclocycline can be used. For life-threatening hyponatremia, hypertonic saline with intravenous furosemide is administered under careful monitoring. Followed by hydration with saline, pamidronate is effective for the control of symptomatic hypercalcemia. Combined use of calcitonin facilitates rapid normalization of serum calcium for critically ill cases. Heparin is used for patients with recurrent episodes of thrombosis resulting from chronic disseminated intravascular coagulation, although the efficacy is controversial. Thrombocytes and coagulation factors are combined with heparin for patients with uncontrollable bleeding, although the efficacy is not established.
 ...
PMID:[Paraneoplastic syndrome]. 936 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>