Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the efficacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE), osteoporotic complications, and palliation of bone pain, among others. Zoledronic acid is the only bisphosphonate effective in decreasing SREs associated with bone metastases from advanced renal cell carcinoma and prostate cancer. Regarding prostate cancer, zoledronic acid effectively prevents both bone loss in patients with locally advanced disease receiving androgen deprivation therapy and SREs in men with hormone-refractory or hormone-sensitive metastatic disease. Zoledronic acid has an acceptable safety profile and tolerability, and has been effective at significantly decreasing the incidence, delaying the onset, and reducing the overall risk of experiencing an SRE compared to placebo. It is the only bisphosphonate currently approved for the prevention and treatment of skeletal complications in patients with bone metastases due to all solid tumors.
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PMID:Zoledronic acid in the management of metastatic bone disease. 1872 15

Bisphosphonates (BPs), as inhibitors of osteoclasts, are widely used in the management of metastatic bone disease and in the prevention of osteomalacia and osteoporosis. Recent cases of bone necrosis of the jaws have been associated with the use of bisphosphonate therapy. A case is presented of a patient with osteonecrosis of the maxilla with a history of long-term bisphosphonate therapy for metastatic breast cancer. The authors treated the patient and suggest appropriate patient management guidelines with reference to current knowledge. Although a definitive treatment for bisphosphonate-associated osteonecrosis has not yet been established, clinicians must be aware of the pharmacologic properties of several bisphosphonates currently available and their indications, susceptible risk factors in the development of osteonecrosis of the jaws, the clinical signs and symptoms, and recommendations for patient management, including prevention and early recognition. BPs, potent inhibitors of osteoclast-mediated bone resorption, were first introduced more than 20 years ago. Since then, they have been used widely in the management of bone diseases, including hypercalcemia related to malignancy, myeloma-related bone disease, Paget's disease and osteoporosis. They have also been shown to inhibit tumor cell proliferation and inhibit angiogenesis. These additional features have made BPs useful in the treatment of metastatic disease, including breast and prostate cancer, resulting in a rise in the medical use of these drugs. However, recent reports suggest that BPs, particularly the nitrogen-containing BPs pamidronate (Aredia) and zoledronic acid (Zometa), both manufactured by Novartis of East Hanover, NJ, are capable of causing bisphosphonate-associated osteonecrosis of the jaw (BON). With 2.5 million patients treated with pamidronate and/or zoledronate worldwide, BON occurs in about one per 10,000 treated patients (Novartis, unpublished data, 2004). Currently, the total number of reported cases associated with alendronate (Fosamax, Merck and Co. Inc., White-house Station, NJ) the most commonly prescribed oral bisphosphonate, is approximately 170 worldwide (C. Arsver, oral communication, March 2006). This corresponds to a spontaneous BON incidence of approximately 0.7 cases per 100,000-years exposure. However, there is insufficient data to determine why the osteonecrosis reported seems to particularly affect the jaw, with a slightly higher rate in the mandible than the maxilla. This report concerns the management of a patient with BON. Information provided includes: the pharmacologic properties of the several bisphosphonates currently available; the pathobiological mechanism; the clinical presentation of the oral lesions; and recommendations for the oral management of patients who have received BP therapy, with consideration of a preventative approach based on current knowledge.
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PMID:Bisphosphonate-associated osteonecrosis: a clinician's reference to patient management. 1876 52

Docetaxel, a semi-synthetic taxane analogue, is used effectively in the treatment of metastatic prostate cancer. Zoledronic acid, the most potent member of bisphosphonates, has shown pleiotropic anti-tumoral effects on prostate cancer cells. We have explored the possible additive/synergistic effects and the apoptotic pathways induced by combination treatment of docetaxel and zoledronic acid in hormone and drug refractory, PC-3 and DU-145 prostate cancer cells. Combination of docetaxel and zoledronic acid synergistically inhibits cell growth in PC-3 and DU-145 cells. Moreover, this effect was due to downregulation of antiapoptotic protein Bcl-2 in PC-3 and DU-145 cells. In conclusion, docetaxel/zoledronic acid combination is potentially a novel and effective approach for the treatment of prostate cancer.
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PMID:Docetaxel/zoledronic acid combination triggers apoptosis synergistically through downregulating antiapoptotic Bcl-2 protein level in hormone-refractory prostate cancer cells. 1910 99

Surgical castration is still considered the 'gold standard' for androgen deprivation therapy which have become the mainstay for the management of advanced prostate cancer. The main drawback of this safe operation is that it may have a negative psychological effect, thus, in recent years, a decline in the utilization of bilateral orchiectomy which is the most cost-effective form of androgen deprivation therapy can be witnessed. Testicular prostheses have been shown to reduce the psychological impact resulting from loss or absence of a testicle in those patients. Besides, patients with advanced prostate cancer are at risk of skeletal complications and bisphosphonates are used in treatment. Zoledronic acid is the only bisphosphonate agent demonstrated to effectively reduce skeletal related events in patients with advanced prostate cancer metastatic to bone. Therefore, zoledronic acid releasing testicular prostheses can be used in the treatment of prostate cancer patients with bone metastases after bilateral orchiectomy. This technology has the potential to become the preferred clinical management tool for prostate cancer patients with bone metasthases after bilateral orchiectomy.
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PMID:Slow zoledronic acid releasing testis prostheses in the treatment of prostate cancer patients with bone metastases. 1940 41

We elaborate a magnetic nanovector to vectorize Zoledronate, an anti-cancer interest molecule of the hydroxmethylenebisphosphonate's family. In fact, Zoledronate is a powerful adjuvant in the treatment of bone diseases such as osteoporosis and Paget's disease. But, recent studies have shown that in addition to anti-osteoclastic properties, it presents antitumour properties notably in the case of breast and prostate cancer. However, these properties cannot be exploited due to their very high affinity to divalent cations and their preferentially accumulation in bone. To overcome this problem, one strategy is the vectorization trough maghemite nanocrystal functionalization. The specific surface coating permits to consider gamma Fe(2)O(3)@Zoledronate as a drug delivery vehicle for therapeutic activity. The anchoring to the nanoparticle's surface allowed to increase their hydrophobicity and also to change the therapeutic target, increasing the Zoledronate intestinal absorption instead of their accumulation in bone. We show that Zoledronate link the nanoparticle surface through phosphonate groups. The biological in vitro tests performed on breast cancer cell line, MDA-MB 231, showed that gamma Fe(2)O(3)@Zoledronate have antiproliferative activity. In addition, the gamma Fe(2)O(3) core could be used as MRI contrast agent for a good therapeutic evaluation.
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PMID:Superparamagnetic nanovector with anti-cancer properties: gamma Fe2O3@Zoledronate. 1945 25

Abstract Bone-seeking radiopharmaceuticals and bisphosphonates may be indicated in patients with cancer with painful osseous metastases to palliate pain symptoms or to prevent skeletal-related events. Both pharmaceuticals may have an additive or even synergistic palliative effect. The combined use of bone-seeking radiopharmaceuticals and bisphosphonates is, however, controversial because of assumed competition between both phosphonate-compounds at the bone level. We report a case of hormone-refractory prostate cancer (HRPC) with multiple painful osseous metastases. The patient was treated with samarium-153-ethylenediaminetetramethylphosphonic acid ((153)Sm-EDTMP; Quadramet, CIS bio International, Saclay, France) in combination with zoledronic acid (Zometa, Novartis, Stein, Switzerland). He was treated for 6 months with 4 weekly intervals of zoledronic acid in combination with 3 monthly intervals of (153)Sm-EDTMP. No negative interaction was found, toxicity was low, and efficacy high. He experienced a total relief of pain, a significant decrease of prostate-specific antigen (PSA) and, surprisingly, a significant decrease of tumor burden.
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PMID:Treatment of painful bone metastases in hormone-refractory prostate cancer with zoledronic acid and samarium-153-ethylenediaminetetramethylphosphonic acid combined. 1959 54

The anti-estrogen treatment for hormone-sensitive breast cancer and the androgen deprivation therapy for prostate cancer can lead to the development of osteoporosis and bone fractures. Metastases associated with prostate and breast cancer can also occur in bone. Bisphosphonates are used in these types of bone dysfunction. Zoledronic acid is the most potent bisphosphonate. In osteoporosis, zoledronic acid inhibits bone reabsorption and increases bone mineral density for at least a year after intravenous administration. The efficacy and safety of zoledronic acid in osteoporosis secondary to hormone-sensitive cancers (prostate and breast), and in the bone metastases associated with these cancers are reviewed.
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PMID:Clinical efficacy and safety of zoledronic acid in prostate and breast cancer. 1976 24

Bone metastases are a substantial burden to men with advanced prostate cancer as they often cause pain and can cause fractures and spinal cord compression. Osteoblasts and osteoclasts are both pathologically activated in the setting of prostate cancer bone metastases. As osteoclast activation is associated with disease progression, skeletal complications and death, osteoclast-targeted therapies are a rational approach to disease management. Zoledronic acid is standard of care for castration-resistant prostate cancer with bone metastases as it reduces the risk for skeletal-related events. Additional trials are needed to better define the ideal dose, frequency and duration of zoledronic acid therapy. No bisphosphonate has yet been shown to prevent bone metastases or to benefit men with androgen-sensitive disease. Denosumab is an experimental osteoclast-targeted monoclonal antibody against receptor activator of nuclear factor-kappaB ligand. Two ongoing phase III trials are expected to define its efficacy in preventing bone metastases and disease-related skeletal events in men with prostate cancer. Androgen-deprivation therapy (ADT) for prostate cancer is associated with osteoporosis and fragility fractures. Several bisphosphonates have been shown to improve bone mineral density in men receiving ADT. Two recent phase III trials have shown that denosumab and toremifene reduce the incidence of fragility fractures in these men. The World Health Organization has developed a fracture risk assessment model (FRAX) for the general population to guide the selection of patients who may benefit from pharmacotherapy. In the absence of a prostate cancer-specific algorithm, we advocate the use of FRAX for men receiving ADT.
Prostate Cancer Prostatic Dis 2010 Mar
PMID:Bone health and prostate cancer. 1990 58

Bone metastases are severe complications of cancers associated with increased morbidity, pain, risk fracture, and reduced life span for patients. Bisphosphonates emerged as a relief treatment in bone metastases. A single dose of zoledronic acid (78 microg/kg) was injected into six Copenhagen rats 4 days before receiving an intraosseous inoculation of metastatic anaplastic tumor of lymph node and lung cell (MLL) prostate cancer cells. Rat femurs were analyzed for changes by microCT and histomorphometry; trabecular volume, trabecular characteristics, osteoid parameters, osteoblastic surfaces, and osteoclast number were measured. Values were compared to a group of SHAM animals, a group of SHAM animals having received zoledronic acid and animals inoculated with MLL cells. All rats were euthanized after 1 month. MLL cells induced osteolysis in the metaphysis with extension of the tumor to soft tissues through cortical perforations. Zoledronic acid induced a marked osteosclerosis in the primary spongiosa in both SHAM and rats inoculated with MLL. Osteosclerosis was obtained in the secondary spongiosa of MLL rats. The bisphosphonate preserved cortical integrity in all animals, and no extension to soft tissues was observed in most animals. The number of osteoclasts was elevated, indicating that there was no apoptosis of osteoclasts but they became inactive. Osteosclerosis was associated with increased osteoblastic surfaces. A single zoledronic acid injection turned osteolytic metastases into osteosclerotic and preserved cortical integrity.
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PMID:A single pretreatment by zoledronic acid converts metastases from osteolytic to osteoblastic in the rat. 1995 66

Zoledronic acid (ZDA) is commonly prescribed to treat and prevent skeletal complications in patients with multiple myeloma or bone metastases. Although hypocalcemia often develops by ZDA, there is little information about the risk factors for hypocalcemia mediated by ZDA. This study was conducted to assess the risk of ZDA-mediated hypocalcemia. We retrospectively reviewed the records of patients receiving ZDA in Mie University Hospital. The subjects were divided into two groups on the basis of whether hypocalcemia developed (19 patients) or not (30 patients). We compared patients' baseline characteristics between the two groups. The patients with hypocalcemia had lower albumin-adjusted serum calcium concentrations (median 9.2 mg/dl) before ZDA administration than the patients without hypocalcemia (median 9.8 mg/dl) (p< 0.01). Multivariate analysis revealed that an adjusted serum calcium concentration lower than 9.5 mg/dl before ZDA administration was an independent risk factor significantly contributing to the development of hypocalcemia (odds ratio 22.0, p< 0.01). Furthermore, the patients receiving corticosteroid had increased risk of ZDA mediated hypocalcemia (odds ratio 11.9, p<0.05). On the other hand, the patients with prostate cancer had a reduced risk for hypocalcemia after ZDA administration (odds ratio 0.06, p<0.05). In conclusion, a lower serum calcium concentration and co-administration of corticosteroid increased the risk of hypocalcemia after ZDA administration, while patients with prostate cancer might have a small risk of this incidence. These findings should provide useful information regarding the monitoring of serum calcium concentration in cancer patients receiving ZDA.
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PMID:Risk factors contributing to the development of hypocalcemia after zoledronic acid administration in patients with bone metastases of solid tumor. 2041 Jun 14


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