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)

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

Pituitary metastasis and sarcoidosis are two causes of pituitary stalk thickening. Their association has been described ago three decades. In this setting, we report a case of panhypopituitarism revealing pituitary metastasis from a small-cell lung carcinoma associated with sarcoidosis. A 49 year-old smoking patient with type 2 diabetes was admitted for acute adrenal failure with polyuria polydipsia syndrome and a pituitary tumor syndrome. Hormone explorations confirmed anterior pituitary insufficiency. Water restriction revealed central diabetes insipidus. The hypothalamic-pituitary MRI revealed a 1-cm sellar mass with nodular thickening of the stalk. The chest radiograph showed a heterogeneous opacity in the left lung. The thoraco-abdominal scan demonstrated a mass in the left lung highly suggestive of malignancy and many enlarged mediastinal nodes, hepatic nodules, and hypertrophy of the left adrenal. Bronchoscopy was performed three times and showed infiltration of the left bronchial tree but histological examination of the bronchial biopsies was negative for all samples. Ultrasound-guided biopsy of the liver was achieved and histology demonstrated sarcoidosis. The diagnosis of sarcoidosis was incompatible with the deterioration of the patient's general status. Subsequent radiographic explorations showed an increase in the size of the tumor mass and histological evaluation of a scan-guided trans-thoracic biopsy demonstrated small-cell carcinoma. Small-cell lung carcinoma is the most common cancer with pituitary metastasis. The proposed link between sarcoidosis and malignancy has remained controversial but has not been proven false.
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PMID:[Panhypopituitarism revealing metastasis of small-cell lung carcinoma associated with sarcoidosis]. 1684 Sep 19

Tumor metastasis to the pituitary gland has been infrequently reported, and this is probably because only a small proportion of these patients are symptomatic. Most of the symptoms of this malady are related to diabetes insipidus. A 78-year-old man was diagnosed 2 years previously with stage IIIA adenocarcinoma of the lung and treated with sequential chemoradiation therapy and later with whole-brain radiation therapy because of newly developed brain metastasis; he was then admitted to our hospital with symptoms of polydipsia and polyuria. He was confirmed to have central diabetes insipidus that was caused by the pituitary metastasis from lung cancer. His symptoms resolved after treatment with desmopressin. Because of the rarity of this manifestation in lung cancer patients, we report on this case along with a brief review of the relevant literature.
Clin Lung Cancer 2007 Nov
PMID:Polyuria and polydipsia in a patient with non-small-cell lung cancer. 1818 62

Many studies, both national and international, have shown that tea has protective effects on many chronic diseases and their risk factors. In cancer prevention, our studies indicated that tea drinking could inhibit the carcinogenicity of various chemical carcinogens, including oral tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) in Golden hamsters, esophageal tumors in rats by blocking in vivo synthesis of N-Nitroso-methylbenzylamine (NMBzA), esophageal cancer induced by NMBzA in rats, precancerous liver lesions (r-GT and GST-P) induced by diethylnitrosamine (DENA) in rats, intestinal preneoplastic lesion (ACF) and intestinal tumors induced by 1,2-dimethyl-hydrazine (DMH) in rats, lung carcinoma induced by nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK) in A/J mice. Our studies have also shown that the protective effects of tea against cancer is a combined effects of various tea ingredients, among which the major ones are polyphenols and tea pigments. Based on animal studies, antioxidant properties, protection against DNA damage and modulation of immune functions were found to be the main mechanisms of anticancer effects of tea. In human trials, tea drinking showed protective effects against oxidative damage and DNA damage caused by cigarette smoking. Mixed tea drinking significantly blocked lesion progress in patients with oral mucosa leukoplakia, therefore, demonstrated its protective effects on oral cancer. Our studies have also shown effects of tea on prevention of cardiovascular diseases (CVD). For example, tea pigments was found to significantly inhibit LDL oxidation induced by Cu2+, Fe2+ in in vitro studies. In vivo studies showed that tea could prevent blood coagulation, facilitate fibrinogen dissolution, inhibit platelet aggregation, lower endothelin levels, enhance GSH-Px activities, protect against oxidated LDL-induced damage in endothelium cells, and prevent atherosclerosis of coronary arteries. The mechanisms of these protective effects of tea are possibly related to its antioxidant properties or its inhibition of lipid oxidation. Green tea and pigments was also found to inhibit cardiac hypertrophy induced by renal hypertension in rat models, whose mechanisms might, at least partly, involve its modulation on nitric oxide, angiotensin II and endothelin-1. Clinical intervention trials have indicated that tea and tea extracts decreased blood lipid, improved blood flow of coronary artery, and played an important role in atherosis inhibition and prevention. Our studies also showed that tea drinking has protective effects on diabetes. White tea drinking could significantly relieve symptoms including polyuria, polydipsia, polyphagia and weight loss in diabetic mice, decrease fasting plasma glucose level and improve glucose tolerance. In human trial, continuous white tea drinking could significantly improve symptoms of diabetic patients, such as relieve polydipsia, decrease plasma glucose levels, both fasting and 2 hours after meal, and increase insulin secretion. The effective rate for glucose lowering is 48% in clinical study.
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PMID:[Studies on tea and health]. 2227 81

Metastases in the sellar region are rare and are frequently found incidentally or in necropsies. Only 7% are reported to be symptomatic. Diabetes insipidus, anterior pituitary dysfunction, visual field defects, headache/pain and ophthalmoplegia are the most commonly reported symptoms. We present the cases of two male patients with a small-cell lung carcinoma whose first clinical symptoms were due to pituitary metastasis. One case presented with symptoms of cavernous sinus invasion and panhypopituitarism and the other case with diabetes insipidus. Both patients had a rapid progression of their disease despite chemotherapy and died after a few months. Pituitary metastases occur most commonly with breast cancer in women and lung cancer in men. The presence of polyuria and polydipsia in an oncologic patient should alert the physician for diabetes insipidus and, if confirmed, an imaging procedure of the pituitary gland is mandatory. Treatment for these tumors is often multimodal and includes surgery, radiation therapy, chemotherapy and hormone replacement. Although surgical series have not shown any significant survival benefits given by tumor resection, the patient's quality of life may be improved.
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PMID:[Two cases of pituitary metastases as initial presentation form of small cell lung cancer]. 2351 90