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)

Squamous, large cell, and adenocarcinoma, collectively termed non-small cell lung cancer (NSCLC), are diagnosed in approximately 75% of patients with lung cancer in the United States. The treatment of these three tumor cell types is approached in virtually identical fashion because, in contrast to small cell carcinoma of the lung, NSCLC more frequently presents with localized disease at the time of diagnosis and is thus more often amenable to surgical resection but less frequently responds to chemotherapy and irradiation. Cigarette smoking is etiologically related to the development of NSCLC in the great majority of cases. Genetic mutations in dominant oncogenes such as K-ras, loss of genetic material on chromosomes 3p, 11p, and 17p, and deletions or mutations in tumor suppressor genes such as rb and p53 have been documented in NSCLC tumors and tumor cell lines. NSCLC is diagnosed because of symptoms related to the primary tumor or regional or distant metastases, as an incidental finding on chest radiograph, or rarely because of a paraneoplastic syndrome such as hypercalcemia or hypertrophic pulmonary osteoarthropathy. Screening smokers with periodic chest radiographs and sputum cytologic examination has not been shown to reduce mortality. The diagnosis of NSCLC is usually established by fiberoptic bronchoscopy or percutaneous fine-needle aspiration, by biopsy of a regional or distant metastatic site, or at the time of thoracotomy. Pathologically, NSCLC arises in a setting of bronchial mucosal metaplasia and dysplasia that progressively increase over time. Squamous carcinoma more often presents as a central endobronchial lesion, while large cell and adenocarcinoma have a tendency to arise in the lung periphery and invade the pleura. Once the diagnosis is made, the extent of tumor dissemination is determined. Since most NSCLC patients who survive 5 years or longer have undergone surgical resection of their cancers, the focus of the staging process is to determine whether the patient is a candidate for thoracotomy with curative intent. The dominant prognostic factors in NSCLC are extent of tumor dissemination, ambulatory or performance status, and degree of weight loss. Stages I and II NSCLC, which are confined within the pleural reflection, are managed by surgical resection whenever possible, with approximate 5-year survival of 45% and 25%, respectively. Patients with stage IIIa cancers, in which the primary tumor has extended through the pleura or metastasized to ipsilateral or subcarinal lymph nodes, can occasionally be surgically resected but are often managed with definitive thoracic irradiation and have 5-year survival of approximately 15%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Non-small cell lung cancer. Part II: Treatment. 171 39

A total of 14 men with inoperable or metastatic squamous cell carcinoma of the genital tract received methotrexate, bleomycin and cisplatin. In 12 patients the penis was the primary site. Metastases were usually advanced, and 4 patients had ulceration and infection in the inguinal region or perineum secondary to tumor. Two patients had tumor-related hypercalcemia. Of the patients 11 received the 3 drugs intravenously, whereas 3 received methotrexate intravenously, and bleomycin and cisplatin intra-arterially for large unilateral nodal metastasis. Of the 14 patients 10 responded, for a response rate of 72% (95% confidence interval 57 to 92%) and the median response duration was 6 months (range 4 to 24 months). Two patients (14%) who were treated intravenously achieved complete responses lasting 6 and 24+ months. Responses occurred in 3 patients with infection and in both patients with hypercalcemia. The combination of methotrexate, bleomycin and cisplatin has significant activity in patients with advanced squamous cell carcinoma of the male genital tract. This chemotherapy regimen should be evaluated in earlier disease in the adjuvant or neoadjuvant setting.
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PMID:Combination chemotherapy with methotrexate, bleomycin and cisplatin for advanced squamous cell carcinoma of the male genital tract. 171 41

Eighty-three autopsy cases of squamous cell carcinoma of the oral tongue were reviewed to identify retrospectively the causes of treatment failure. The cure rate for the primary cancers at autopsy was 48.2% (40 of 83). Regional lymph node metastases were found in 71.1% (59 of 83). Regional metastases and/or juxtaprimary recurrence frequently spread continuously and diffusely, forming bulky neck tumors in 38.6% (32 of 83). The incidence of distant lymph node metastasis (below the clavicle) and hematogenous metastasis was 35.4% (29 of 82) and 58.5% (48 of 82), respectively. The lung was the most common site of hematogenous metastases (52.4%, 43 of 82). Hematogenous metastasis occurred more frequently in the younger age group (less than 40 years of age; P = 0.03). Distant lymph node metastases were identified in the lung hilar, bifurcation, and paratracheal nodes in 89.7% (26 of 29) and had a statistically significant association with lung hematogenous metastasis. Univariate analysis revealed that gross appearance, tumor stage, clinical stage, presence of cervical lymph node metastasis, and interval from N0 to NX were significant predictors of survival time (duration from initial treatment to death). Rupture of the neck vessels was fatal in eight patients (9.6%), and hypercalcemia was seen in six (7.2%). Pulmonary infection was the direct cause of death in 33.7% of patients (28 of 83). Secondary malignant lesions occurred in 22.9% (19 of 83).
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PMID:Causes of oral tongue cancer treatment failures. Analysis of autopsy cases. 173 4

A 74-year-old male was urgently admitted to our hospital because of consciousness disturbance. Laboratory data showed remarkable hypercalcemia (7.8 mEq/L), hypophosphatemia, low % TRP, low intact PTH level, normal nephrogenic cyclic AMP and normal 1,25 (OH)2D level. Serum bone Gla protein, which was thought to express osteoblastic activity, was low. Serum tartarate resistant acid phosphatase and urinary excretion of hydroxyproline, which were thought to express osteoclastic activity, were high. CT scan showed an enlarged mass in the left renal pelvis, which was found to be a squamous cell carcinoma (SCC) by biopsy through percutaneous nephroscopy. Bone scintigram appeared normal. Therefore, we diagnosed it as renal pelvic SCC with humoral hypercalcemia of malignancy (HHM) and performed left nephrectomy. After nephrectomy, serum calcium returned to normal. But after a few weeks, lung metastasis appeared and serum calcium was reelevated. As to PTH related protein (PTHrP) which was thought to induce HHM, PTHrP content of the resected tumor measured by RIA assay was 13 pmol/g wet weight of tissue, which suggested that this tumor might have been producing PTHrP.
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PMID:[A case of renal pelvic squamous cell carcinoma accompanied with humoral hypercalcemia of malignancy]. 192 Oct 23

Most lung carcinomas with hypercalcemia are usually unresectable. However, this case was resectable and the serum calcium level was normalized after the operation. Messenger RNA of the precursor of PTH-related protein (PTHrP), a substance that may be one of the causes of hypercalcemia in malignant neoplasms, was identified in the tumor tissue of the patient. The patient was a 60-year-old man with squamous cell carcinoma originating from the posterior basal segment of the left lung and invading the main bronchus and left atrium. The serum calcium level was 14.3 mg/dl, preoperatively. Pneumonectomy with partial left atrium resection was carried out and the serum calcium level became normal postoperatively. Three months following the operation, this measurement was 9.4 mg/dl, but increased to 16.2 mg/dl at four months, at which time he experienced lumbago and chest pain. The patient died eight months following the operation from uncontrollable renal failure. In the tumor tissue, mRNA of PTHrP precursor was identified. To our knowledge, this is the first case of lung cancer that could be resected, and in which PTHrP was found present.
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PMID:Hypercalcemia induced by parathyroid hormone-related protein from lung cancer tissue. 193 11

In a consecutive series of 771 patients with pathologically verified squamous cell carcinoma of the head and neck, 28 patients (3.6%) had hypercalcemia (greater than 11.0 mg/dl) during the course of their disease. The buccal mucosa (16/205, 7.8%) and tongue (8/148, 5.4%) were the most frequent primary sites. Most of the patients were stage IV patients with recurrence and advanced disease. The prognosis was poor with a median survival of only 6 weeks. The possible etiology of their hypercalcemia included humoral factors, bone metastases and independent primary lung cancer. The treatment of hypercalcemia was evaluated in 22 patients. Success was noted in all patients initially receiving chemotherapy (10 cases) or radiotherapy (3 cases) with or without saline hydration plus furosemide diuretics. However, the response rate in patients (9 cases) initially receiving hydration plus furosemide diuretics alone was 22% (2/9), with 4 of 7 failure cases later responding to chemotherapy. It is suggested that hypercalcemia be treated with chemotherapy or radiotherapy quickly, along with hydration plus diuretics. Also, the serum calcium level must be checked in patients with advanced buccal or tongue cancer.
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PMID:Hypercalcemia in squamous cell carcinoma of the head and neck. 197 96

Recently, we have established a human squamous cell carcinoma of the maxilla (called MH-85) associated with hypercalcemia, leukocytosis, and cachexia in culture. MH-85 tumor cells caused the same paraneoplastic syndromes in tumor-bearing nude mice. We found that there was a sixfold increase in splenic size in MH-85 tumor-bearing mice. This increase paralleled tumor growth and was reversed by surgical removal of the tumor. Splenectomy in nude mice 1 wk before or 6 wk after tumor inoculation resulted in a decrease in tumor growth, and impairment of hypercalcemia, leukocytosis, and cachexia. In MH-85 tumor-bearing animals that had been pretreated by splenectomy, intravenous injection of fresh normal spleen cells caused an immediate reversal of leukocytosis, hypercalcemia, and cachexia. Since the presence of cachexia in both the patient and the mice carrying the tumor suggested tumor necrosis factor (TNF) may be overproduced, we injected polyclonal neutralizing antibodies raised against murine TNF into tumor-bearing mice. There was a rapid and reproducible decrease in blood ionized calcium, accompanied by suppression of osteoclast activity. No changes in blood ionized calcium were seen in mice injected with normal immune sera. In addition, there was an increase in body weight and decrease in white cell count. Plasma immunoreactive TNF was increased almost fourfold in tumor-bearing nude mice compared with control nude mice. Although TNF activity was undetectable in MH-85 culture supernatants, cells of the macrophage lineage, including spleen cells, released increased amounts of TNF when cultured with MH-85 tumor-conditioned media. These results suggest that splenic cytokines such as TNF may influence the development of the paraneoplastic syndromes of hypercalcemia, leukocytosis, and cachexia in these animals, as well as tumor growth. They also show that paraneoplastic syndromes may be due to factors produced by normal host cells stimulated by the presence of the tumor.
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PMID:Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice. 199 5

Hypercalcemia and leukocytosis may occur in conjunction as paraneoplastic syndromes associated with malignant disease. Here we describe a human squamous cell carcinoma of the maxilla that was associated with hypercalcemia and leukocytosis, and also cachexia. The primary tumor was surgically removed and established in permanent cell culture. When either primary tumors or cultured tumor cells were inoculated into nude mice, the nude mice developed the same paraneoplastic syndromes as those which occurred in the patient from whom the tumor was originally derived. The plasma calcium was increased two and one-half-fold and the WBC count 30-fold, and the body weight was decreased by 45% in tumor-bearing animals. Each of these paraneoplastic syndromes was alleviated by surgical excision of the tumor, indicating that the paraneoplastic syndromes were due to a factor or factors produced by the primary tumor. The development of each of these paraneoplastic syndromes in nude mice correlated positively with the other two syndromes. We examined the organs of tumor-bearing mice and found striking histopathologic abnormalities in the bones, spleen, and liver, but no infiltration with tumor cells. The bones showed marked evidence of osteoclastic bone resorption. This model of a human tumor associated with the hypercalcemia-leukocytosis paraneoplastic syndrome, together with cachexia, should make it possible to determine the mechanisms responsible for these paraneoplastic syndromes and their relationship to each other.
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PMID:Occurrence of hypercalcemia and leukocytosis with cachexia in a human squamous cell carcinoma of the maxilla in athymic nude mice: a novel experimental model of three concomitant paraneoplastic syndromes. 199 18

Increased levels of epidermal growth factor receptor (EGFR) have been shown on squamous cell carcinomas. Recently, we described a squamous cell carcinoma (MH-85) derived from the oral cavity which was associated with several paraneoplastic syndromes including hypercalcemia and cachexia. This tumor induced the same paraneoplastic syndromes in nude mice (BALB/c, nu/nu, male, 4-6 weeks old). Scatchard analysis revealed that there are two classes of EGFR in MH-85. The dissociation constant and number of binding sites for the high affinity receptors were 38 pM and 5 x 10(4)/cell, respectively, and 2.2 nM and 6 x 10(5) cell, respectively, for the low affinity receptors. Growth of MH-85 in culture was stimulated by epidermal growth factor (EGF) and inhibited by monoclonal antibody 108 to human EGFR, which recognizes the extracellular domain of the EGF receptor. Surgical removal of submandibular glands from male nude mice resulted in a dramatic decrease in plasma EGF levels and a significant reduction of tumor growth, hypercalcemia, and cachexia. When EGF (5 micrograms/mouse, every 2 days for 6 weeks, i.p.) was administered to these sialoadenectomized animals, tumor growth increased, with a parallel increase in hypercalcemia. When monoclonal antibody 108 (1 mg/mouse, i.p.) was given 1, 5, and 10 days after MH-85 tumor implantation, tumor formation was retarded, which resulted in delayed onset of hypercalcemia and cachexia. Moreover, when the antibody was injected 6 times in nude mice exhibiting large tumors and profound hypercalcemia and cachexia, there was a striking decrease in tumor growth, which was accompanied with a reversal of hypercalcemia and cachexia. These results indicate that growth of the human squamous cell carcinoma MH-85 is dependent on the EGFR pathway and that subsequent development of hypercalcemia and cachexia is dependent on tumor growth. They also suggest that agents which interfere with the EGFR pathway may have therapeutic potential as anticancer agents in some human tumors.
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PMID:Dependence of a human squamous carcinoma and associated paraneoplastic syndromes on the epidermal growth factor receptor pathway in nude mice. 201 5

In the course of a phase II study 15 patients (nine women and six men; mean age 58 [45-69] years) received 300 mg clodronate daily during a total of 16 episodes of tumour-induced hypercalcaemia. Four women had breast cancer, four patients had plasmocytoma and four had bronchial carcinoma. One woman each had leiomyosarcoma or squamous cell carcinoma of the uterus or pancreatic carcinoma, respectively. No other calcium-lowering treatment, such as forced diuresis, glucocorticoids, calcitonin or mithramycin, was employed. As early as two days after onset of treatment the serum calcium concentration fell significantly from 3.63 +/- 0.42 to 2.80 +/- 0.40 mmol/l. After a mean interval of 4.3 days the hypercalcaemia had been eliminated during 15 of the 16 episodes. The treatment was not adequate in one patient with paraneoplastic hypercalcaemia. The results indicate that this medication is to be recommended as a standard treatment of tumour-induced hypercalcaemia; side effects are minimal.
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PMID:[Monotherapy with clodronate for tumor-induced hypercalcemia]. 213 27


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