Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advanced solid tumors are often aggressive and recurrent, and overall survival remains relatively poor despite contemporary therapeutic interventions. Bone metastases are common in these patients, and skeletal-related events, including bone pain, pathologic fractures, and potentially life-threatening hypercalcemia of malignancy, undermine the quality of patient survival. Bisphosphonates are widely used in the treatment of bone metastases associated with breast cancer and multiple myeloma, but have not been extensively investigated in the treatment of patients with solid tumors other than breast or prostate cancer. However, a new-generation nitrogen-containing bisphosphonate, zoledronic acid, has shown significant clinical benefits in indications in which other bisphosphonates have failed. In a phase III clinical trial in patients with bone metastases from solid tumors other than breast or prostate cancer, treatment with zoledronic acid (4 mg via 15-minute infusion) was well tolerated and significantly decreased the incidence of skeletal-related events and increased the time to first skeletal-related event compared with placebo-treated patients. This was the first demonstration of palliative efficacy for bisphosphonate therapy in patients with bone metastases from a wide variety of solid tumors.
 ...
PMID:Efficacy and safety of zoledronic acid in the treatment of bone metastases associated with lung cancer and other solid tumors. 1258 92

Gallium nitrate has been shown to be an effective treatment for patients with cancer-related hypercalcemia. Clinical studies have also suggested the drug may have considerably broader use in other diseases associated with accelerated bone loss including multiple myeloma, bone metastases, Paget's disease, and osteoporosis. The actions of gallium nitrate on bone are quite distinct from those of bisphosphonates. Preclinical studies show that gallium preferentially accumulates in trace amounts in metabolically active regions of bone. When present, gallium favorably alters the mineral properties to enhance hydroxyapatite crystallization and reduce mineral solubility. The drug also acts on the cellular components of bone to reduce bone resorption by decreasing acid secretion by osteoclasts. This effect appears to be mediated by inhibition of the ATPase-dependent proton pump of the osteoclast's ruffled membrane. Gallium does not inhibit the development or recruitment of osteoclasts to bone tissue, unlike many bisphosphonates that may induce osteoclast apoptosis. Together, these pharmacologic actions may yield a skeletal system with increased calcium and phosphate content and improved biomechanical strength. Gallium nitrate has potent antiresorptive effects on bone that can be achieved at considerably lower doses than are currently used for cancer-related hypercalcemia. Parenteral and oral formulations of gallium appear to have high activity in bone resorptive disorders, and thus development should be vigorously pursued in these diseases.
 ...
PMID:The effects of gallium nitrate on bone resorption. 1277 54

The aim of this review is to detail the pathophysiologic mechanisms occurring during bone metastases. osteolytic and osteosclerotic metastases are observed after migration of malignant cells coming from a primitive tumour which can localize and grow inside the hematopoietic bone marrow. Bone lesions observed during hematologic malignancies (lymphomas and myeloma) are not detailed here. The various cytokine networks that are occurring in bone metastases are detailed: in both cases there is a "vicious circle" between the the tumoral cells and bone cells responsible for the physiological remodeling of bone. The knowledge of these interferences permits to understand the use of anti-osteoclastic treatments (bisphosphonates) in osteolytic as well as osteosclerotic metastases.
 ...
PMID:[Pathophysiology of bone metastases]. 1281 4

Bisphosphonates (BPs) suppress cancer cell colonization in bone associated with cancers such as breast cancer and multiple myeloma. The mechanism of the suppressive action of BPs is thought to be due to an inhibition of osteoclastic bone resorption which releases bone-stored growth factors that feed cancer cells colonizing bone. Recently, data are accumulating that BP suppresses growth and induces apoptosis in cancer cells in culture, suggesting that BP directly influences survival of cancer cells in an osteoclast-independent manner. These results raise the possibility that BP inhibits cancer growth in organs other than bone. However, evidence is limited that BP reduces tumor growth in non-bone sites in cancer patients. In this review, we discuss the effectiveness of BP on breast cancer colonization in non-bone sites and our results in animal models with metastases. With currently available clinical and in vivo experimental data, BPs are definitely beneficial for the treatment of cancer patients who manifest clinically detectable bone metastases. However, it is not recommended that BP be given as a preventative to patients with visceral metastases and of no evidence of bone metastases. Whether individual BP with different chemical structure has unique biological or biochemical action is an intriguing question but open at the moment.
 ...
PMID:Bisphosphonate actions on cancer. 1287 4

Current trends in the treatment of human tumors are with drug combinations that result in improved responses as well as the ability to use less toxic concentrations of the drugs. Recent reports have shown that COX-2 inhibitors and taxanes are effective in the suppression of human tumor growth. The bisphosphonate, zoledronic acid, primarily used in the treatment of bone metastases, also inhibits proliferation and induces apoptosis in human breast and prostate carcinoma and multiple myeloma. HER-2/neu overexpression has been suggested as a mechanism for resistance to both hormonal therapy as well as chemotherapy. This study examines the effects of combining a cyclooxygenase-2 inhibitor with zoledronic acid and/or docetaxel in a HER-2/neu transfected and control human breast cancer cell line. All three compounds produced dose-dependent growth inhibition in both cell lines. The HER-2/neu transfected MCF/18 cells, however, were less sensitive to zoledronic acid than the control MCF/neo cells, 9% to 53% inhibition and 18% to 67%, respectively. Enhanced growth inhibition was observed in both cell lines with the combination of docetaxel and SC236 and the combination of docetaxel and zoledronic acid. The combination of SC236 with zoledronic acid also gave an enhanced inhibitory effect in the MCF/neo line. This combination, however, was additive in the HER-2/neu transfected MCF/18 cell line. The triple combination of SC236, zoledronic acid and/or docetaxel resulted in a small increase in growth inhibition compared to that seen with the double combinations.
 ...
PMID:Effect of the combination of docetaxel, zoledronic acid, and a COX-2 inhibitor on the growth of human breast cancer cell lines. 1290 64

Radiotherapy is an established treatment for metastatic bone pain. It may be delivered as a localised low dose treatment for localised bone pain or systemically for more widespread symptoms using hemibody external beam radiotherapy or intravenous bone-seeking radioisotopes. Bisphosphonates have been shown to reduce morbidity from bone metastases when given to patients with asymptomatic disease from myeloma and primary breast and prostate cancers. They also reduce metastatic bone pain in these sites. In the absence of randomised data comparing radiotherapy with bisphosphonates in the same clinical setting, comparison of the response rates from individual trials of the two modalities suggests that the overall pain response in all tumour types from radiotherapy is around 80% compared to a similar rate in myeloma with bisphosphonates but only 40% in solid tumours. Optimal use of the two modalities requires further investigation but since they have different dose limiting toxicities their incorporation in a combined modality approach to metastatic bone pain is rational using the concepts of additive effect and spatial co-operation in which bisphosphonates provide background control alongside acute pain relief using radiotherapy. They are also an important alternative for bone pain where radiation tolerance has been reached or radiotherapy is not readily available.
 ...
PMID:Bisphosphonates and radiation therapy for palliation of metastatic bone disease. 1292 72

The knowledge and training of nursing staff is essential for the safety and comfort of patients receiving i.v. therapies. The use of i.v. bisphosphonates as an adjunct to standard antineoplastic therapies in patients with advanced cancer is becoming widespread. Zoledronic acid and pamidronate (Zometa and Aredia, Novartis Pharmaceuticals Corporation, East Hanover, NJ) are nitrogen-containing bisphosphonates. Pamidronate has been the standard of care for patients with osteolytic bone lesions from breast cancer or multiple myeloma. However, zoledronic acid, which has demonstrated increased potency and a broad clinical utility, is emerging as the new standard of care. In addition to treating hypercalcemia of malignancy, zoledronic acid is approved for treating patients with bone metastases (osteolytic or osteoblastic) from a wide range of solid tumors, including breast, prostate, and lung cancers, or osteolytic bone lesions from multiple myeloma. Zoledronic acid (4 mg via a 15-minute infusion) has a safety profile comparable with pamidronate (90 mg via a two-hour infusion) and has demonstrated comparable or superior efficacy to that of pamidronate in every patient population tested. The shorter infusion time of zoledronic acid compared with that of pamidronate may provide added convenience, but safety guidelines should be followed for all i.v. bisphosphonate therapies. These guidelines and nursing care of patients receiving i.v. bisphosphonates are reviewed.
 ...
PMID:Advances in supportive care of patients with cancer and bone metastases: nursing implications of zoledronic acid. 1292 73

The rate of calcification of new bone (accretion rate) was measured by a radioisotope technique in 20 patients with carcinoma of the breast, 14 patients with multiple myelomatosis, five patients with Paget's disease of bone, and in six patients with solitary, non-osseous tumours. The rate of bone destruction was assessed in these patients by the measurement of the rate of urinary calcium excretion. In the patients with carcinoma of the breast and bone metastases there was a marked increase both in the accretion rate and in the urinary calcium excretion suggesting an osteoblastic response to bone destruction. An osteoblastic response was also present in the patients with multiple myelomatosis but was not correlated with the urinary calcium excretion. In patients with Paget's disease of bone, high values of accretion rate were found indicating very active new bone formation.
 ...
PMID:SOME ASPECTS OF CALCIUM METABOLISM IN MALIGNANT DISEASE OF BONE. 1424 7

Bisphosphonates are now well established as successful agents for the prevention and treatment of postmenopausal osteoporosis, corticosteroid-induced bone loss and Paget's disease. Bisphosphonates have also recently become important in the management of cancer-induced bone disease, and they now have a widely recognized role for patients with multiple myeloma and bone metastases secondary to breast cancer and prostate cancer. Recent studies suggest that, besides the strong antiosteoclastic activity, the efficacy of such compounds in the oncological setting could also be due also to direct antitumor effect, exerted at different levels. Here, after a brief analysis of the chemical structure, we will review the antineoplastic and biological properties of bisphosphonates. We will start from well estabilished mechanisms of action and go on to discuss the latest evidence and hypotheses. In particular, we will review the antiresorptive properties in malignant osteolysis and the recent evidence of a direct antitumor effect. Furthermore, this review will analyze the influence of bisphosphonates on cancer growth factor release, their effect on cancer cell adhesion, invasion and viability, the proapoptotic potential on cancer cells, the antiangiogenic effect, and, finally, the immunomodulating properties of bisphosphonates on the gammadelta T cell population.
 ...
PMID:The antineoplastic role of bisphosphonates: from basic research to clinical evidence. 1450 45

Bisphosphonates have an established role in treating tumor-induced hypercalcemia and decreasing the incidence of skeletal-related events. Recent data suggest that these agents may also prevent skeletal metastases. This review explains how cancer metastasizes to bone and how bisphosphonates may block this process, with a summary of clinical trials supporting the use of bisphosphonates to treat and prevent bone metastases. For skeletal metastases in patients with breast cancer, multiple myeloma, or other solid tumors, bisphosphonates are important adjuncts to systemic therapy. Despite promising results in metastatic prostate cancer, additional trials are needed before bisphosphonates become part of standard treatment in this setting. Ongoing trials are evaluating the preventive role of the third-generation bisphosphonates in breast cancer patients. Until the results of these trials are presented, bisphosphonates should only become a component of adjuvant treatment in the context of a clinical trial. Bone loss, a common consequence of cancer treatment, should be treated with the usual measures indicated for the management of osteoporosis, including bisphosphonates.
 ...
PMID:Bisphosphonates in the prevention and treatment of bone metastases. 1456 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>