Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer has a prodigious capacity to metastasize to bone. In women with advanced breast cancer and bone metastases, bisphosphonates reduce the incidence of hypercalcaemia and skeletal morbidity. Recent clinical findings suggest that some bisphosphonates reduce the tumour burden in bone with a consequent increase in survival, raising the possibility that bisphosphonates may have a direct effect on breast cancer cells. We have investigated the in vitro effects of bisphosphonates zoledronate, pamidronate, clodronate and EB 1053 on growth, viability and induction of apoptosis in three human breast cancer cell lines (MDA-MB-231, Hs 578T and MCF-7). Cell growth was monitored by crystal violet dye assay, and cell viability was quantitated by MTS dye reduction. Induction of apoptosis was determined by identification of morphological features of apoptosis using time-lapse videomicroscopy, identifying morphological changes in nucleis using Hoechst staining, quantitation of DNA fragmentation, level of expression of bcl-2 and bax proteins and identification of the proteolytic cleavage of Poly (ADP)-ribose polymerase (PARP). All four bisphosphonates significantly reduced cell viability in all three cell lines. Zoledronate was the most potent bisphosphonate with IC50 values of 15, 20 and 3 microM respectively in MDA-MB-231, MCF-7 and Hs 578T cells. Corresponding values for pamidronate were 40, 35 and 25 microM, whereas clodronate and EB 1053 were more than two orders of magnitude less potent. An increase in the proportion of cells having morphological features characteristic of apoptosis, characteristic apoptotic changes in the nucleus, time-dependent increase in the percentage of fragmented chromosomal DNA, down-regulation in bcl-2 protein and proteolytic cleavage of PARP, all indicate that bisphosphonates have direct anti-tumour effects on human breast cancer cells.
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PMID:Bisphosphonates induce apoptosis in human breast cancer cell lines. 1078 May 27

Platelets contribute to the development of metastasis, the most common cause of mortality in cancer patients, but the precise role that anti-platelet drugs play in cancer treatment is not defined. Metastatic tumor cells can produce platelet alphaIIb beta3 activators, such as ADP and thromboxane A(2) (TXA(2)). Inhibitors of platelet beta3 integrins decrease bone metastases in mice but are associated with significant bleeding. We examined the role of a novel soluble apyrase/ADPase, APT102, and an inhibitor of TXA(2) synthesis, acetylsalicylic acid (aspirin or ASA), in mouse models of experimental bone metastases. We found that treatment with ASA and APT102 in combination (ASA + APT102), but not either drug alone, significantly decreased breast cancer and melanoma bone metastases in mice with fewer bleeding complications than observed with alphaIIb beta3 inhibition. ASA + APT102 diminished tumor cell induced platelet aggregation but did not directly alter tumor cell viability. Notably, APT102 + ASA treatment did not affect initial tumor cell distribution and similar results were observed in beta3-/- mice. These results show that treatment with ASA + APT102 decreases bone metastases without significant bleeding complications. Anti-platelet drugs such as ASA + APT102 could be valuable experimental tools for studying the role of platelet activation in metastasis as well as a therapeutic option for the prevention of bone metastases.
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PMID:APT102, a novel adpase, cooperates with aspirin to disrupt bone metastasis in mice. 1826 Jan 28

Prostate cancer is the second most common and fifth most aggressive neoplasm among men worldwide. It is particularly incident in high human development index (HDI) nations, with an estimated one in seven men in the US receiving a prostate cancer diagnosis in their lifetime. A rapid rise and then fall in prostate cancer incidence in the US and Europe corresponded to the implementation of widespread prostate specific antigen (PSA) testing in 1986 and then subsequent fall from favor due to high rates of false positives, overdiagnosis, and overtreatment (as many as 20-50% of men diagnosed could have remained asymptomatic in their lifetimes). Though few risk factors have been characterized, the best known include race (men of African descent are at higher risk), genetics (e.g., BRCA1/2 mutations), and obesity. The Gleason scoring system is used for histopathological staging and is combined with clinical staging for prognosis and treatment. National guidelines have grown more conservative over the past decades in management, recommending watchful waiting and observation in older men with low to intermediate risk disease. Among higher risk patients, prostatectomy (robotic is preferred) and/or external beam radiotherapy is the most common interventions, followed by ADT maintenance. Following progression on androgen deprivation therapy (ADT) (known as castration-resistance), next generation endocrine therapies like enzalutamide, often in combination with cytotoxic agent docetaxel, are standard of care. Other promising treatments include Radium-223 for bone metastases, pembrolizumab for programmed death ligand-1 (PDL1) and microsatellite instability (MSI) high disease, and poly ADP ribose polymerase (PARP) inhibitors for those with mutations in homologous recombination (most commonly BRCA2).
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PMID:Epidemiology, Staging and Management of Prostate Cancer. 3269 38