Browsing by Subject "Drug Therapy"

Now showing 1 - 4 of 4
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    Bone-Induced Expression of Integrin β3 Enables Targeted Nanotherapy of Breast Cancer Metastases
    (American Association for Cancer Research, 2017-11-15) Ross, Michael H.; Esser, Alison K.; Fox, Gregory C.; Schmieder, Anne H.; Yang, Xiaoxia; Hu, Grace; Pan, Dipanjan; Su, Xinming; Xu, Yalin; Novack, Deborah V.; Walsh, Thomas; Colditz, Graham A.; Lukaszewicz, Gabriel H.; Cordell, Elizabeth; Novack, Joshua; Fitzpatrick, James. A.J.; Waning, David L.; Mohammad, Khalid S.; Guise, Theresa A.; Lanza, Gregory M.; Weilbaecher, Katherine N.; Medicine, School of Medicine
    Bone metastases occur in approximately 70% of metastatic breast cancer patients, often leading to skeletal injuries. Current treatments are mainly palliative and underscore the unmet clinical need for improved therapies. In this study, we provide preclinical evidence for an antimetastatic therapy based on targeting integrin β3 (β3), which is selectively induced on breast cancer cells in bone by the local bone microenvironment. In a preclinical model of breast cancer, β3 was strongly expressed on bone metastatic cancer cells, but not primary mammary tumors or visceral metastases. In tumor tissue from breast cancer patients, β3 was significantly elevated on bone metastases relative to primary tumors from the same patient (n = 42). Mechanistic investigations revealed that TGFβ signaling through SMAD2/SMAD3 was necessary for breast cancer induction of β3 within the bone. Using a micelle-based nanoparticle therapy that recognizes integrin αvβ3 (αvβ3-MPs of ∼12.5 nm), we demonstrated specific localization to breast cancer bone metastases in mice. Using this system for targeted delivery of the chemotherapeutic docetaxel, we showed that bone tumor burden could be reduced significantly with less bone destruction and less hepatotoxicity compared with equimolar doses of free docetaxel. Furthermore, mice treated with αvβ3-MP-docetaxel exhibited a significant decrease in bone-residing tumor cell proliferation compared with free docetaxel. Taken together, our results offer preclinical proof of concept for a method to enhance delivery of chemotherapeutics to breast cancer cells within the bone by exploiting their selective expression of integrin αvβ3 at that metastatic site.
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    Chemotherapy-Related Tumour Lysis Syndrome
    (Association of Kenya Physicians, 2007) Busakhala, N. W.; Association of Kenya Physicians Scientific Conference (11th : Mar. 2007 : Eldoret, Kenya)
    Two types of tumour lysis syndrome (TLS) ; 1. Laboratory TLS: 25% increase in potassium, phosphate and uric acid, or decline in calcium from baseline. Occur within 4 days of initiating chemotherapy. Patients on standard of care. Minimum of two out of four criteria. 2. Clinical tumour lysis syndrome: Laboratory TLS plus renal failure, cardiac arrhythmias or sudden death. A new definition has been suggested by Cairo and Bishop to include values above upper limit of normal. Study used Hande and Garrow definition.
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    Patient Race/Ethnicity and Patient-Physician Race/Ethnicity Concordance in the Management of Cardiovascular Disease Risk Factors for Patients With Diabetes
    (American Diabetes Association, 2010-03) Traylor, Ana H.; Subramanian, Usha; Uratsu, Connie S.; Mangione, Carol M.; Selby, Joe V.; Schmittdiel, Julie A.; Medicine, School of Medicine
    OBJECTIVE Patient-physician race/ethnicity concordance can improve care for minority patients. However, its effect on cardiovascular disease (CVD) care and prevention is unknown. We examined associations of patient race/ethnicity and patient-physician race/ethnicity concordance on CVD risk factor levels and appropriate modification of treatment in response to high risk factor values (treatment intensification) in a large cohort of diabetic patients. RESEARCH DESIGN AND METHODS The study population included 108,555 adult diabetic patients in Kaiser Permanente Northern California in 2005. Probit models assessed the effect of patient race/ethnicity on risk factor control and treatment intensification after adjusting for patient and physician-level characteristics. RESULTS African American patients were less likely than whites to have A1C <8.0% (64 vs. 69%, P < 0.0001), LDL cholesterol <100 mg/dl (40 vs. 47%, P < 0.0001), and systolic blood pressure (SBP) <140 mmHg (70 vs. 78%, P < 0.0001). Hispanic patients were less likely than whites to have A1C <8% (62 vs. 69%, P < 0.0001). African American patients were less likely than whites to have A1C treatment intensification (73 vs. 77%, P < 0.0001; odds ratio [OR] 0.8 [95% CI 0.7–0.9]) but more likely to receive treatment intensification for SBP (78 vs. 71%, P < 0.0001; 1.5 [1.3–1.7]). Hispanic patients were more likely to have LDL cholesterol treatment intensification (47 vs. 45%, P < 0.05; 1.1 [1.0–1.2]). Patient-physician race/ethnicity concordance was not significantly associated with risk factor control or treatment intensification. CONCLUSIONS Patient race/ethnicity is associated with risk factor control and treatment intensification, but patient-physician race/ethnicity concordance was not. Further research should investigate other potential drivers of disparities in CVD care.
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    What Will It Take to Reap the Clinical Benefits of Pharmacogenomics?
    (Food & Drug Law Journal, 2006) Evans, Barbara J.
    Genetically targeted drug and biologic therapies promise a new era of personalized medicine, but there has been frustration with how slowly these therapies are moving from concept to actual clinical application. Various legal and regulatory barriers threaten to delay translation of basic discoveries into approved products and to slow the clinical uptake of new therapeutic products as they become available. There is a pressing need to reach consensus on what these barriers are, so that they can be addressed in a timely and effective manner. This paper explores what some of the key barriers may be. It examines: (1) legal, regulatory, and commercial barriers to “successive improvement” of existing drugs through improved targeting strategies; (2) barriers to cooperative, multi-party development of targeted therapies; (3) methodological problems in assessing the incremental health and economic benefits of an improved targeting strategy; (4) limitations of traditional product labeling as a medium for communicating timely, clear information about drug targeting to clinicians and the need to create new mechanisms within the medical profession to manage and communicate this information; and (5) difficulty defining the appropriate line between regulation of medical products and regulation of medical practice, in the case of targeted therapies.