The introduction of novel antimyeloma therapies, including thalidomide, lenalidomide and bortezomib, has expanded treatment options for patients with multiple myeloma. These compounds alter the natural history of multiple myeloma and help improve outcomes, but have different and specific toxicity profiles. The major adverse events associated with these treatments are somnolence (thalidomide), venous thromboembolism (thalidomide and lenalidomide), myelosuppression (lenalidomide and bortezomib), gastrointestinal disturbance, and peripheral neuropathy (thalidomide and bortezomib). These adverse events are predictable, consistent, and manageable with patient monitoring, supportive care, and dose reduction and interruption where appropriate. Herein we evaluate the incidence of treatment-related adverse events associated with each of these compounds. We further review the management of these adverse events with a view to delivering optimal therapeutic outcomes in patients with newly diagnosed and relapsed and/or refractory multiple myeloma.
"Despite bortezomib having been considered as a promising drug for multiple myeloma (MM), resistance still arises in MM patients, caused by refractoriness, and acquisition of resistance after treatment (7, 12, 13). Development of chemoresistance is a major problem in curing the disease. "
[Show abstract][Hide abstract] ABSTRACT: Bortezomib has been known as the most promising anti-cancer drug for multiple myeloma (MM). However, recent studies reported that not all MM patients respond to bortezomib. To overcome such a stumbling-block, studies are needed to clarify the mechanisms of bortezomib resistance. In this study, we established a bortezomib-resistant cell line (U266/velR) and explored its biological characteristics. The U266/velR showed reduced sensitivity to bortezomib, and also showed cross-resistance to the chemically unrelated drug thalidomide. U266/velR cells had a higher proportion of CD138 negative subpopulation, known as stem-like feature, compared to parental U266 cells. U266/velR showed relatively less inhibitory effect of prosurvival NF-κB signaling by bortezomib. Further analysis of RNA microarray identified genes related to ubiquitination that were differentially regulated in U266/velR. Moreover, expression level of CD52 in U266 cells was associated with bortezomib response. Our findings provide basis for developing therapeutic strategies in bortezomib-resistant relapsed and refractory MM patients.
[Show abstract][Hide abstract] ABSTRACT: Individuals with cancer are at increased risk of developing thrombosis. The prevalence of thrombosis depends on tumor-related factors such as histological type, stage, the use of central venous catheters, or treatment with surgery, chemotherapy or radiotherapy, as well as general prothrombotic factors including advanced age, immobility, obesity, hereditary thrombophilias and comorbidities. Prophylactic or therapeutic treatment of thrombosis should be individualized and will depend on both the risk of thrombosis and bleeding. In this review we intend to update concepts that have changed substantially such as green food-free diet, or the indication of absolute bed rest in patients with recent thrombosis. We propose evidence-based therapeutic strategies regarding the most prevalent clinical problems encountered in patients with cancer and thrombosis.
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 03/2013; 65(2):174-82. · 0.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We consider the application of multiuser detection to the downlink of interference-limited multiple-input multiple-output (MIMO) cellular systems. MIMO systems have been shown to yield a tremendous capacity for a single link with white Gaussian noise. In a cellular environment, there will often be co-channel interference from other cells, which becomes the dominating channel impairment. Here space-time layered architectures and turbo processing techniques are combined with multiuser detection techniques for combating intercell interference. Among various multiuser detection methods examined, linear MMSE and successive interference cancellation have been shown to be feasible and effective. Based on these two multiuser detection schemes, one of which may outperform the other for different settings, an adaptive detection scheme is developed.
Vehicular Technology Conference, 2002. VTC Spring 2002. IEEE 55th; 02/2002
Pilar de la Puente, Feda Azab, Barbara Muz, Micah Luderer, Jack Arbiser, Abdel Kareem Azab
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