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)

A 45-year-old female manifested lower abdominal fullness and symptoms of hypercalcemia with nausea, vomiting, and thirst. Physical examination showed a right ovarian mass and laboratory data demonstrated hypercalcemia (14.6 mg/dl). The radiographic findings confirmed a right ovarian tumor without any evidence of bone metastasis. Tests revealed that her PTH, nephrogenic urinary cyclic AMP, and 1-25 (OH)2 Vitamin D were not high but that her prostaglandin E2 (PGE2) was elevated. After correction of her calcium elevation with infusion and prednisolone, right oophorectomy with tumor excision was performed. A histological examination of the tumor revealed a mucinous cysto-adenocarcinoma. The postoperative course has been uneventful, with normal calcium and PGE2 values. This case illustrates that hypercalcemia associated with an ovarian carcinoma (Malignancy-associated hypercalcemia) can be mediated by the patient's PGE2 in part.
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PMID:[A case of hypercalcemia with ovarian carcinoma]. 323 Jun 42

The case history is presented of a 45-year-old woman who was receiving chemotherapy for a pulmonary adenocarcinoma and who developed severe symptomatic hypercalcemia. Despite intensive treatment with fluids, loop diuretics, prednisone, calcitonin and repeated doses of mithramycin, she remained hypercalcemic. She was then treated with aminohydroxypropylidene diphosphonate (APD) with consequent rapid normalization of the serum calcium and disappearance of symptoms. We conclude that APD is a valuable supplement to the treatment of malignant hypercalcemia in that it may be effective when traditional therapies have failed.
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PMID:Treatment of refractory cancer-associated hypercalcemia with aminohydroxypropylidene diphosphonate. 323 57

Transplantation of CE mammary adenocarcinoma (CE maca) into normal mice produces both neutrophilia and hypercalcemia due to osteoclastic bone resorption. In order to explore the physiology of osteoclast formation in vivo, the time course of neutrophilia and osteoclast development was examined in mice that had been pretreated with busulfan prior to the CE maca implantation. Busulfan-treated tumor-bearing mice (BUTUM), busulfan-treated control mice (BUCON), tumor-bearing mice with no busulfan (TUM), and normal controls (CON) were sacrificed on days 4, 7, 11, 14, and 17 after tumor implantation. Leukocyte counts, serum calcium levels, marrow cellularity, and marrow colony-forming units (CFU) were determined. Osteoclasts were quantified histologically by the osteoclast: endosteum ratio (OER). BUCON bone marrow was hypoplastic with CFU remaining significantly lower than that of controls over the course of the experiment. In contrast, BUTUM marrow CFU increased dramatically with the growth of the tumor. The most predominant increase was observed in neutrophilic CFU. Development of hypercalcemia closely paralleled neutrophilia in both TUM and BUTUM mice, although these changes were significantly delayed in the BUTUM group. The neutrophil count and serum calcium levels remained within normal control levels for BUCON mice. The OER correlated with serum calcium, and it closely paralleled the neutrophil count in TUM and BUTUM mice. These results clearly indicated the stimulation of bone marrow neutrophilic granulocyte progenitors and osteoclasts by the CE maca, indicating that the bone marrow is the primary target of this tumor. There may be a closely related mechanism in osteoclast and granulocyte stimulation by one or more CE maca factors.
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PMID:Concurrent activation of granulocytes and osteoclasts in busulfan-suppressed bone marrow in response to transplantation of a mammary carcinoma in mice. 336 66

Demineralized extracts of bone matrix and conditioned media from cultured fetal rat calvaria have been reported to contain growth stimulatory activity for bone cells. To investigate the potential role of these local bone growth factors in the development of bone metastases, we chose the Walker 256 carcinosarcoma, a rat mammary tumor which causes osteolytic bone metastases and hypercalcemia. 45Ca-labeled, 19-day fetal Sprague-Dawley rat calvaria were cultured for 96 hours in BGJb medium. Walker cells from ascites tumors or cultures were grown in unconditioned media or in conditioned media harvested from the bone cultures, in the presence of 10% fetal calf serum. Media were changed every 2 days, cells were counted daily for 5 days, and 3H-thymidine uptake into acid insoluble residues was measured. The growth of tumor cells was 5-6-fold greater in conditioned media than in unconditioned media and the effect was dose dependent. Cells cultured in conditioned media demonstrated a approximately 3-fold enhancement of 3H-thymidine incorporation. Generation of growth stimulatory activity correlated with the extent of bone resorption, measured by release of 45Ca from the fetal parietal bones (r = 0.85; P less than 0.001). Conditioned media from bones cultured with 10(-7) M prostaglandin E2 (PGE2) contained greater amounts of growth stimulatory activity than untreated conditioned media, but PGE2 itself did not stimulate tumor cell growth. Addition of 3.5 mM PO4 to bone cultures blocked bone resorption and the generation of growth factors. Growth stimulatory activity was stable to heat (56 C for 30 minutes) and trypsin digestion, with an apparent molecular weight of less than 17,000 daltons by high-performance liquid chromatography. Conditioned medium also stimulated the growth of 13762 rat mammary adenocarcinoma cells, MB-MDA-231 human breast carcinoma cells, TE-85 osteosarcoma cells, a murine fibrosarcoma and rat embryonic fibroblasts, with the most potent effects noted for Walker tumor cells, the TE-85 osteosarcoma, and human breast carcinoma lines. These results suggest a mechanism by which bone resorption could promote the development of skeletal metastasis.
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PMID:Resorbing bone stimulates tumor cell growth. A role for the host microenvironment in bone metastasis. 345 36

Gallium nitrate is the anhydrate salt of the naturally occurring heavy metal. It has demonstrated antitumor activity in a variety of murine tumor models, including Walker carcinosarcoma 256, fibrosarcoma M-89, leukemia K-1964, adenocarcinoma 755, mammary carcinoma YMC, reticulum cell sarcoma A-RCS, lymphoma P1798, and osteosarcoma 124F. Preclinical studies performed in rats, rabbits, dogs, and monkeys showed the dose-limiting toxicity to be renal. The hepatic, pulmonary, gastrointestinal, hematologic, and integumentary systems were also involved. The major route of elimination is the kidneys, with 35%-71% of the infused dose excreted within 24 hours. Three phase I studies suggested the following phase II doses: 700-750 mg/m2 by short infusion, once every 2-3 weeks; 300 mg/m2/day by short infusion for 3 consecutive days, to be repeated every 2 weeks; and 300 mg/m2/day by continuous infusion for 7 consecutive days, to be repeated every 3-5 weeks. The major organ toxicity reported was renal; however, this can be adequately controlled either by hydration and osmotic diuresis or by use of continuous schedule. (Either maneuver appears to allow delivery of the recommended phase II dose with a less than 30% risk of change in serum creatinine.) In limited phase II evaluation, the drug has shown antitumor activity in patients with either refractory lymphomas or small cell lung carcinoma, with total objective response rates of 28% and 11%, respectively. In addition, it has been effective in the treatment of patients with cancer-related hypercalcemia by having an inhibitory effect on calcium reabsorption from bone. Single-agent phase II studies are planned in all major tumor types. Some are already ongoing in patients with genitourinary malignancies (renal, bladder, prostate, testicular), small cell lung carcinoma, and multiple myeloma. Metabolic studies are in progress at Memorial Sloan-Kettering Cancer Center to further elucidate the mechanism or mechanisms of the hypocalcemic effects.
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PMID:Gallium nitrate: the second metal with clinical activity. 353 51

A focus of increased uptake on a 201Tl minus 99mTc subtraction scintigram of the parathyroid glands was found in a patient with persistent hypercalcemia. This area was not caused by an abnormal parathyroid gland but by an enlarged lymph node containing metastatic tissue from an adenocarcinoma of the ovary.
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PMID:False-positive subtraction scintigram of the parathyroid glands due to metastatic tumor. 396 80

Hypercalcaemia due to malignant disease, in the absence of bone metastases, is generally regarded as a rare event. It occurred in 16% of a series of cases of bronchial carcinoma coming to necropsy. Hypercalcaemia is a relatively common complication of bronchial carcinoma. The hypercalcaemia is usually accompanied by hypophosphataemia and, in this respect, must be distinguished from the hypercalcaemia that may be found with breast carcinoma. It is frequently accompanied by hypokalaemic alkalosis; this must not be confused with the metabolic disorder that results from the production of ectopic ;ACTH'. The bones sometimes show changes of osteitis fibrosa akin to those seen in hyperparathyroidism. Cystic disease of bone recognizable radiologically is rare, probably because of the relatively short duration of the metabolic disturbance. The parathyroids are usually mildly atrophic. There is no evidence that the main pathogenetic mechanism is stimulation of the parathyroids by the tumour. Acceptable instances of parathyroid hyperplasia are very rare: the significance of these exceptional cases awaits further study.Squamous carcinoma of the bronchus is the type mainly incriminated. Oat-cell carcinoma and bronchial adenocarcinoma are involved less frequently than expected by chance. The significance of the tumour types implicated is discussed in relation to the possible pathogenesis.
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PMID:Bronchial carcinoma and hypercalcaemia. 536 47

Pulmonary cancers produce many hormonal polypeptides. There is a tumor-specific pattern to the appearance of abnormal adrenal function and inappropriate secretion of vasopressin, which are frequently found in small cell undifferentiated carcinoma but occur only very rarely, if at all, in squamous tumors. Humoral hypercalcemia, on the other hand, occurs almost entirely in squamous tumors and is rarely if ever seen in small cell or large cell tumors or in adenocarcinoma. In contrast, "big ACTH" and beta lipotropin are found in the plasma and tumor extracts of lung cancers of all types. Calcitonin and the beta chain of human chorionic gonadotropin are also found in the plasma of a considerable portion of patients with all histological types of lung cancers.
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PMID:The pattern of ectopic hormone production in lung cancer. 627 Sep 16

Histologic patterns of tumor-bone interaction were systematically evaluated in 80 cases of metastatic lung cancer involving bone. Patterns of tumor-bone interaction varied with the histologic type of lung cancer, reflecting the biochemical and biologic differences among the different types of lung cancer. Evidence presented here suggests that destruction of bone by metastatic lung cancer is mediated neither by direct contact of tumor cells with bone matrix nor by release of diffusible substances that lyse bone matrix. Among indirect mechanisms, the most prevalent and important was the activation of bone-lining cells by metastatic tumor. Epidermoid carcinomas in particular were associated with histologic patterns of classical bone remodelling, including osteoblastic, osteoclastic, and osteocytic activity. Adenocarcinomas showed a particularly high association with microfractures and manifested a stromal pattern consistent with release of prostaglandins. Ischemic necrosis of bone due to compression of vessels by expanding tumor mass is also a common and important mechanism. Correlation of histologic patterns with reported data on the frequency of metastases and syndromes of ectopic hormone production provides insight into the mechanism(s) of paraneoplastic hypercalcemia in patients with lung cancer.
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PMID:The cellular basis of metastatic bone disease in patients with lung cancer. 627 58

This paper presents 6 British patients with a diagnosis of oat cell carcinoma of the esophagus. Sixty-six patients have previously been reported in the literature, the majority (30) being British. Approximately two-thirds of these tumors have been reported as pure oat cell carcinoma of the esophagus. Four other histological patterns have been described: oat cell carcinoma with squamous carcinoma in situ; oat cell carcinoma with squamous carcinoma; oat cell carcinoma with adenocarcinoma; and oat cell carcinoma with carcinoid differentiation. A preponderance of males has also been noted, although this series shows a 2:1 female:male ratio. The tumor arises most commonly in the mid or lower esophagus. The cell of origin of these tumors in considered to be the Kulchitsky or APUD cell of neuroectodermal derivation. They may show neurosecretory granules on electron microscopy. Polypeptides have been identified within the tumor cells. One previous report describes a patient with primary oat cell carcinoma of the esophagus and hypercalcemia. A patient with the syndrome of inappropriate anti-diuretic hormone secretion is described in this paper. Survival is poor following radiotherapy, with a median survival of 3 months in this series. On reviewing the records of the Radiation Oncology Unit in Edinburgh, no patient with oat cell carcinoma of the esophagus was reported before 1972. This suggests that awareness of this tumor is increasing and, although rare, its incidence is greater than previously reported.
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PMID:Oat cell carcinoma of esophagus: a report of six British patients with a review of the literature. 632 9


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