Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In parathyroidectomy, it has been recognized that a shift to a minimally invasive procedure may be accompanied by a possibility of missing thyroid pathology. However, only a few findings concerning preoperative thyroid evaluation have been reported. We investigated the prevalence of concomitant thyroid pathology by preoperative neck ultrasonography (US) in patients with primary hyperparathyroidism. There were 85 patients (66 women, 19 men; mean age 57 years) in the study group. The mean preoperative calcium level was 11.2mg/dL, and the mean intact parathyroid hormone level was 206 pg/mL. All patients underwent neck US following fine-needle aspiration biopsy (FNAB). Of the 85 patients, 21 (24.7%) had thyroid nodules. Among 21 patients with thyroid nodules, 9 (10.6%) had malignant thyroid tumors, while 12 (14.1%) patients had benign thyroid nodules including multinodular goiter. Of the 9 patients with malignant thyroid nodules, 4 had papillary carcinomas with lymph node metastases. The prevalence of thyroid disease associated with hyperparathyroidism is high, and evaluation of the thyroid pathology by US enables the shift from bilateral neck exploration to the minimally invasive parathyroid surgery.
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PMID:Preoperative evaluation of thyroid pathology in patients with primary hyperparathyroidism. 1727 51

The skeleton is a major site of breast cancer metastases. High bone turnover increases risk of disease progression and death. However, there is no direct evidence that high bone turnover is causally associated with the establishment and progression of metastases. In this study, we investigate the effects of high bone turnover in a model of breast cancer growth in bone. Female nude mice commenced a diet containing normal (0.6%; 'Normal-Ca') or low (0.1%; 'Low-Ca') calcium content. Mice were concurrently treated with vehicle or osteoprotegerin (1 mg/kg/d s.c; n = 16 per group). Three days later (day 0), 50,000 Tx-SA cells (variant of MDA-MB-231 cells) were implanted by intratibial injection. On day 0, mice receiving Low-Ca had increased serum parathyroid hormone (PTH) and tartrate-resistant acid phosphatase 5b levels, indicating secondary hyperparathyroidism and high bone turnover, which was maintained until day 17. Osteoprotegerin increased serum PTH but profoundly reduced bone resorption. On day 17, in mice receiving Low-Ca alone, lytic lesion area, tumor area, and cancer cell proliferation increased by 43%, 24%, and 24%, respectively, compared with mice receiving Normal Ca (P < 0.01). Osteoprotegerin treatment completely inhibited lytic lesions, reduced tumor area, decreased cancer cell proliferation, and increased cancer cell apoptosis. Increased bone turnover, due to dietary calcium deficiency, promotes tumor growth in bone, independent of the action of PTH. Breast cancer patients frequently have low dietary calcium intake and high bone turnover. Treatment to correct calcium insufficiency and/or treatment with antiresorptive agents, such as osteoprotegerin, may be of benefit in the adjuvant as well as palliative setting.
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PMID:Accelerated bone resorption, due to dietary calcium deficiency, promotes breast cancer tumor growth in bone. 1790 65

The role of parathyroid hormone-related peptide (PTHrP) in the regulation of hypercalcemia in patients with malignancies is well studied, but whether its expression in tumor tissue correlates with tumor progression is not clear at present. The majority of tumors that metastasize to the bone produce PTHrP, and PTHrP expression correlates with skeletal localization of tumors. About 95% of colorectal adenocarcinomas overexpress PTHrP mRNA and protein, and the expression level is higher in poorly differentiated than in well-differentiated adenocarcinomas. However, there is some controversy at present about the prognostic significance of PTHrP expression on primary tumor cells, and studies suggest that there might be tissue-specific responses. We will briefly present here existing evidences that suggest that the expression of PTHrP in the primary tumor tissue could have both positive and/or negative impact on tumor progression and clinical outcome of the disease.
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PMID:PTHrP and tumorigenesis: is there a role in prognosis? 1805 53

Bony metastases from prostate cancer are a significant cause of morbidity and mortality. These metastases are predominantly blastic (bone-forming) and commonly cause increased serum levels of parathyroid hormone (PTH) as calcium ions are transferred from serum into blastic bone. The epidemiologic and clinical significance of secondary hyperparathyroidism in advanced prostate cancer have not been widely appreciated. Prostate cancer bony metastases show increased expression of the PTH receptor (PTH-IR) and PTH promotes the growth and invasiveness of prostate cancer cells in bone. Thus, blastic metastases appear to induce a "vicious cycle" in which PTH resorbs normal bone to support the growth of blastic bone. Recognition of the potential role of PTH in the progression of skeletal metastases suggests novel opportunities for prostate cancer secondary prevention. In particular, we propose that suppressing serum PTH in advanced prostate cancer may reduce morbidity by decreasing fractures and pain caused by bone resorption and may reduce mortality by retarding the progression of metastatic disease.
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PMID:Prostate cancer, serum parathyroid hormone, and the progression of skeletal metastases. 1834 65

Hypercalcemia is the most common paraneoplastic syndrome in adult malignancies (10%-30%) and rare in pediatric cancers (0.5%-1.3%). Hypercalcemia in malignancies is categorized into two groups: 1) Humoral hypercalcemia of malignancy (HHM)-caused by substances that are produced by the tumor cells and secreted into the blood circulation such as parathyroid hormone-related protein (PTH-rP), parathyroid hormone-intact (PTH-i), the enzyme 1-alpha-hydroxylase that catalyzes the synthesis of the active form of vitamin D (1,25-dihydroxyvitamin D3), and other substances; 2) Hypercalcemia due to bone destruction by metastases. Hypercalcemia occurs in less than 5% of female genital tract malignancies and virtually in all cases (95%) it is HHM. Female genital tract malignancy-associated HHM is caused most often (80%) by PTH-rP. Ovarian cancer is the most common female genital tract malignancy that is associated with HHM. Although HHM occurs in only 5% of ovarian cancers, it occurs in a relatively high percentage in the following rare ovarian tumors: a). Small cell carcinoma of the ovary - a rare tumor that accounts for only 1% of all ovarian cancers and is associated with HHM in 66% of the cases; b). Clear cell carcinoma of the ovary - an uncommon tumor that accounts for 5% of all ovarian cancers and is associated with HHM in 5%-10% of the cases. Since dysgerminoma is the most common malignant ovarian tumor in children, in girls it is the second most common ovarian neoplasm, after ovarian small cell carcinoma, to be associated with HHM.
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PMID:[Hypercalcemia in malignancies of the female genital tract]. 1848 65

Bisphosphonates inhibit bone resorption and are widely used to treat osteolytic metastases and osteoporosis. Renal osteodystrophy patients have continuous bone loss due to chronically elevated parathyroid hormone (PTH). In this open-label study, ibandronate was evaluated for the treatment of reduced bone density in renal osteodystrophy. Patients (n=16) with end-stage renal disease (ESRD) and regular hemodialysis schedules were recruited. All patients had low bone mineral density (BMD; lumbar spine T-score <-1.0) and elevated PTH levels (>2-fold higher than normal). Patients received ibandronate 2 mg every 4 weeks for 48 weeks. Serum levels of markers of bone turnover, calcium, phosphate and magnesium were determined (week 0 [prior to treatment] vs. at week 48). BMD (n=11) increased significantly from 88.94 +/- 31.68 mg/mL calcium hydroxylapatite (CaHA) to 93.51 +/- 35.36 mg/mL CaHA (p=0.032). T-scores increased significantly from -3.08 +/- 1.11 to -2.78 +/- 1.27 (p<0.01). The mean PTH level initially increased before dropping to 18.99 pmol/L at week 48 (7.99% decrease vs. week 0; not significant). Bone turnover markers decreased, whereas calcium and magnesium levels remained stable and within normal ranges. Phosphate levels were variable throughout the study. Two patients did not complete the study, and 3 patients died due to concomitant cardiovascular disease. Calcitriol dosage increased from 1.5 to 1.83 microg/week. In patients with renal osteodystrophy and ESRD, ibandronate significantly increased BMD and decreased bone turnover.
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PMID:Treatment of reduced bone density with ibandronate in dialysis patients. 1865 40

We report two cases of squamous cell carcinoma of upper urinary tract with hypercalcemia. Case 1; a 54 year old female with primary squamous cell carcinoma (SCC) of right ureter showed marked hypercalcemia and leukocytosis. High levels of serum parathyroid hormone-related peptide (PTHrP) and granulocyte colony stimulating factor (G-CSF) were detected. Although chemotherapy of cisplatin and 5-fluorouracil with radiotherapy was effective, thereafter recurrence was occurred in renal pelvis, and the patient died 17 months after the initiation of therapy. Case 2; a 54 year old male of primary SCC of right renal pelvis with local lymphadenopathy and anterior mediastinal metastases showed marked hypercalcemia. High levels of PTHrP were detected. Although the patient was administered UFT with palliative radiotherapy to the anterior mediastinum, he died 2 months after the initiation of therapy. To our knowledge, the case 1 is the third case that of the high levels of serum PTHrP and G-CSF simultaneously in squamous cell carcinoma of upper urinary tract.
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PMID:[Two cases of squamous cell carcinoma of upper urinary tract with hypercalcemia]. 1893 54

Hypercalcemia of malignancy carries an extremely grim prognosis. The most common mechanism underlying hypercalcemia of malignancy is production by the tumor cells of cytokines responsible for osteoclastic differentiation and, therefore, lysis of the bone adjacent to the tumor. A minority of cases are attributable to increased renal reabsorption of calcium caused by a humoral factor, termed parathyroid hormone-related peptide, which is produced by some primary tumors. These two mechanisms can be involved in conjunction, particularly in patients with breast cancer. The development of osteolytic metastases initiates a vicious cycle in which bone degradation products, especially growth factors, stimulate the growth of the tumor cells located at the bone-tumor interface. Parathyroid hormone-related peptide is produced by many malignant tumors, most notably those of the breast. In addition to its endocrine effect on the kidney, it may have a paracrine effect consisting of enhancement of osteoclastic differentiation with osteolysis of the bone adjacent to the tumor. Other factors produced by primary tumor cells, such as proteases, intercellular adhesion molecules, or bone matrix proteins, may influence the propensity for the tumor to produce bone metastases. Bisphosphonates are usually effective in inducing a remission of hypercalcemia of malignancy and in improving the clinical manifestations of osteolytic metastases. Elucidation of the factors that influence the propensity for malignancies to metastasize to bone would improve our ability to use bisphosphonates optimally as adjuncts to tumor therapy.
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PMID:Role of Parathyroid Hormone Related Peptide (PTHrP) in Hypercalcemia of Malignancy and the Development of Osteolytic Metastases. 1907 66

We report a 47-year-old women who presented to her general practitioner and our hospital with weight loss of unknown etiology. Eight years previously she had undergone a hemithyroidectomy for nodular goiter with one cold nodule. Laboratory results revealed hypercalcemia, evidence of primary hyperparathyroidism and computer tomography of the thorax showed bilateral pulmonary metastasis. After undergoing CT-guided biopsy of a metastasis, histology revealed an endocrine primary tumor with low parathyroid hormone expression. In view of the history, clinical and biochemical findings we diagnosed a recently metastasized functioning parathyroid carcinoma, which eight years previously has been labeled as a benign atypical thyroid adenoma. The patient underwent surgical resection of all detected metastases. Afterwards the serum calcium and parathyroid hormone levels normalized. Parathyroid carcinoma is an uncommon tumor. In the absence of pathognomonic diagnostic criteria a definitive pathological diagnosis of parathyroid carcinoma often is not possible. The treatment of parathyroid carcinoma is essentially surgical. Patients with parathyroid carcinoma mostly die from uncontrollable hypercalcemia rather than from other tumor-related complications.
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PMID:[Rare cause of hypercalcemia]. 1921 66

Breast cancer frequently metastasizes to bone. Metastases result in skeletal morbidity including pathologic fractures, the need for radiation or surgery to bone, spinal cord compression and hypercalcemia. The pathophysiology of bone destruction is related to activation of osteoclasts by tumor-derived and bone marrow microenvironmental factors. One prominent osteoclast-activating factor associated with breast cancer is parathyroid hormone-related peptide (PTHrP). Bisphosphonates have been shown to impair osteoclast activity by decreasing recruitment from the monocyte macrophage cell line, inhibiting osteoclast function at the bone site and causing osteoclasts to undergo apoptosis. Clinical studies with bisphosphonates show an improvement in the control of hypercalcemia and a reduction in skeletal related morbidity with administration of pamidronate and zoledronic acid. Bisphosphonates have become the standard of care for osteolytic metastases associated with breast cancer. Recent data with zoledronic acid found that skeletal related morbidity may be reduced regardless of the radiographic picture of skeletal metastases. Thus, zoledronic acid may be valuable in osteolytic and osteoblastic disease as well as in disease with an osteolytic or osteoblastic radiographic appearance. In breast cancer with osteolytic disease, zoledronic acid may be more effective than pamidronate in reducing skeletal morbidity and prolonging the time to first skeletal event.
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PMID:The role of bisphosphonates in breast cancer. 1976 82


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