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)

The skeleton is one of the most common sites of metastasis in patients with lung cancer. It has been reported that the incidence of bone metastases in lung cancer patients is approximately 30-40%, and the median survival time (MST) of patients with such metastases is 6-7 months. Metastatic bone disease leads to various complications or skeletal related events (SREs), including pain, pathologic fracture, vertebral deformity and collapse, spinal cord compression, and hypercalcemia of malignancy. These events often lead to rapid deterioration in quality of life (QOL). The fundamental treatment for bone metastasis from advanced lung cancer is disease control by systemic chemotherapy. So the prevention and treatment of bone metastases is mainly dependent on an effective treatment against lung cancer itself. As a direct treatment for bone metastases, radiation therapy, surgery and bisphosphonates are the main ways.
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PMID:[Bone metastases in lung cancer]. 1837 26

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

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

Bone is the most common organ for tumor metastasis, especially in patients with cancers of the breast or prostate. Bone metastases disrupt skeletal metabolism and result in considerable skeletal morbidity, including intractable, chronic bone pain, hypercalcemia of malignancy, pathologic fracture and spinal-cord compression. In addition to the chronic pain caused by bone metastases, skeletal-related events (SREs) such as pathologic fractures and spinal-cord compression can result in acute increases in pain. These effects can severely impair mobility and contribute to a general decrease in quality of life. Palliative options to treat bone metastases include radiotherapy, analgesics, surgery and bisphosphonates. These drugs bind to the surface of the bone and impair osteoclast-mediated bone resorption, and reduce the tumor-associated osteolysis that is initiated by the development of skeletal metastases. In addition to preventing SREs, bisphosphonates can palliate bone pain caused by a variety of solid tumors. This Review summarizes the clinical trial data of bisphosphonates for the prevention of SREs and the palliation of bone pain. Among these agents, nitrogen-containing bisphosphonates are recognized as the most effective, and zoledronic acid has demonstrated the broadest clinical utility.
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PMID:Effect of bisphosphonates on pain and quality of life in patients with bone metastases. 1919 May 92

Bone metastases are associated with considerable morbidity and can result in skeletal-related events (SREs), including pathologic fractures, the need for palliative radiotherapy, spinal cord compression, the need for surgery to bone to prevent or treat a pathologic fracture or spinal cord compression, and hypercalcemia of malignancy. Such SREs have been associated with decreases in survival and increases in healthcare costs. Skeletal morbidity and bone pain from metastases can also reduce patients' functional capacity and undermine their quality of life. Patients who develop bone metastases from advanced cancers commonly receive bisphosphonates to not only delay the onset of SREs and reduce their frequency but also provide clinically meaningful palliative effects for bone pain. Ongoing research may lead to improvements in skeletal health monitoring and management for patients with malignant bone disease.
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PMID:Bone metastases from advanced cancers: clinical implications and treatment options. 1994 68

Bisphosphonates are the standard of care for preventing skeletal morbidity and treating hypercalcemia of malignancy in patients with bone metastases. Zoledronic acid (intravenous; 4 mg monthly) is approved to prevent skeletal-related events (SREs) in patients with bone metastases from several tumor types, and can improve survival in some subsets of patients with skeletal metastases and high baseline bone turnover. In the adjuvant setting, bisphosphonates have shown clinical efficacy for preventing cancer treatment-induced bone loss and promise for reducing disease recurrence. For example, early studies of clodronate showed the potential for bisphosphonates to prevent bone metastases and prolong survival, but results with clodronate have been inconsistent. Recently, the more active bisphosphonate zoledronic acid (4 mg every 6 months) prevented bone loss and significantly reduced the risk of disease-free survival events by 36% (P = .01) compared with adjuvant endocrine therapy alone in a large phase III trial (N = 1,803) in premenopausal women with early breast cancer. Notably, these benefits were not limited to bone, because the addition of zoledronic acid reduced disease recurrence at all sites. Similarly, twice-yearly zoledronic acid has reduced disease recurrence in large phase III trials in more than 1,600 postmenopausal women with early breast cancer. Several ongoing trials (involving more than 20,000 patients altogether) are evaluating the efficacy of bisphosphonates for prevention of metastases in breast, prostate, and lung cancers; and multiple myeloma. Results from these studies are likely to expand the role of bisphosphonates, especially zoledronic acid, in the adjuvant therapy setting.
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PMID:Bisphosphonates in the prevention of disease recurrence: current results and ongoing trials. 2002 70

Among exocrine pancreatic tumors, adenosquamous carcinoma (ASC) is a rare, aggressive subtype with a worse prognosis and a higher potential for metastases compared to its more conventional glandular counterpart, adenocarcinoma. The disease distribution shows an approximately 1:1 male/female ratio and a median survival of circa five months. Although such features as central necrosis and hypervascularity are suggestive of pancreatic ASC, more research is necessary to identify other, more specific markers for this tumor subtype. Humoral hypercalcemia of malignancy has also been described with ASC of the pancreas, likely as a result of PTHrP production by the squamous component of the tumor. Similar to the therapeutics of pancreatic adenocarcinoma, adjuvant chemotherapy or chemoradiotherapy is currently indicated for resectable ASC of the pancreas, while gemcitabine or gemcitabine combinations are used for a more advanced disease. Both pathologic and molecular features of pancreatic ASC characterize it as a distinct subtype of pancreatic cancer. As a result, its molecular and genetic makeup could be exploited for both diagnostic and therapeutic quests in the future.
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PMID:Adenosquamous carcinoma of the pancreas: a distinct clinicopathologic entity. 2069 20

Sphenoidal sinus carcinoma is a rare cause of hypercalcemia of malignancy. We report on a 37-year-old male with sphenoidal sinus carcinoma with intracranial extension who developed hypercalcemia of malignancy with progressing disease and demonstrated diffuse metastatic visceral calcifications of lungs, myocardium, stomach, kidneys and thyroid on follow-up 99mTc-methylene diphosphonate bone scan. In the absence of extensive skeletal metastases, bone scan help confirm humoral nature of hypercalcaeimia.
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PMID:Extensive visceral calcification demonstrated on Tc-99m MDP bone scan in patient with sphenoidal sinus carcinoma and hypercalcaemia of malignancy: a bad prognostic sign. 2117 11

Bone metastases add to the burden of breast cancer, with patients experiencing severe bone pain, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy. Nitrogen-containing bisphosphonates have become the standard treatment for skeletal-related events and bone pain, as well as for bone loss associated with chemotherapy and aromatase inhibitors. Emerging preclinical and clinical evidence indicates that bisphosphonates negatively affect multiple processes that support tumor growth and proliferation and formation of metastases. Several small clinical trials suggest that bisphosphonates can modify angiogenic factors, immune surveillance, and disseminated tumor cells detected in bone marrow. Emerging data suggest that bisphosphonates used for osteoporosis prevention may inhibit breast cancer development. Three large prospective studies have shown improved outcomes with the addition of zoledronic acid to conventional neoadjuvant or adjuvant therapy. This article focuses on current clinical trials examining the use of bisphosphonates in patients with breast cancer.
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PMID:Bisphosphonates in breast cancer: antitumor effects. 2155 88

A 9 yr old neutered male mixed-breed dog was presented for an anal sac apocrine gland adenocarcinoma with regional nodal metastases. At presentation, ionized calcium was 1.91 mmol/L (NOVA Stat reference range, 1.1-1.3 mmol/L). Surgical excision of the primary tumor and metastatic lymph nodes was performed. Following surgery, symptomatic hypocalcemia was noted. Repeated ionized calcium measurements confirmed hypocalcemia, and hypercalcemia of malignancy panels suggested parathyroid gland suppression as the cause. The calcium normalized with parenteral calcium administration, but calcium later became elevated with tumor recurrence and an increase in the parathormone-related peptide. Disrupted calcium homeostasis is a potential complication following the treatment of long-standing humoral hypercalcemia of malignancy.
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PMID:Hypocalcemia following surgical treatment of metastatic anal sac adenocarcinoma in a dog. 2205 67


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