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排序方式: 共有466条查询结果,搜索用时 15 毫秒
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Yanyan Gu Benjamin G. Barwick Mala Shanmugam Craig C. Hofmeister Jonathan Kaufman Ajay Nooka Vikas Gupta Madhav Dhodapkar Lawrence H. Boise Sagar Lonial 《Blood cancer journal》2020,10(12)
Protein homeostasis is critical for maintaining eukaryotic cell function as well as responses to intrinsic and extrinsic stress. The proteasome is a major portion of the proteolytic machinery in mammalian cells and plays an important role in protein homeostasis. Multiple myeloma (MM) is a plasma cell malignancy with high production of immunoglobulins and is especially sensitive to treatments that impact protein catabolism. Therapeutic agents such as proteasome inhibitors have demonstrated significant benefit for myeloma patients in all treatment phases. Here, we demonstrate that the 11S proteasome activator PA28α is upregulated in MM cells and is key for myeloma cell growth and proliferation. PA28α also regulates MM cell sensitivity to proteasome inhibitors. Downregulation of PA28α inhibits both proteasomal load and activity, resulting in a change in protein homeostasis less dependent on the proteasome and leads to cell resistance to proteasome inhibitors. Thus, our findings suggest an important role of PA28α in MM biology, and also provides a new approach for targeting the ubiquitin-proteasome system and ultimately sensitivity to proteasome inhibitors.Subject terms: Myeloma, Translational research 相似文献
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Vanessa P. Tolbert Christopher C. Dvorak Carla Golden Madhav Vissa Nura El-Haj Farzana Perwad Katherine K. Matthay Kieuhoa T. Vo 《Biology of blood and marrow transplantation》2019,25(10):2031-2039
High-risk neuroblastoma has a poor prognosis, and research studies have shown that increasing the intensity of therapy improves outcomes. Autologous hematopoietic cell transplant (aHCT) as consolidation therapy confers a significant survival advantage but is accompanied by significant morbidity. Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication caused by endothelial injury that often leads to hemolytic anemia, microthrombotic platelet consumption, and renal injury. Here we investigated the incidence, potential risk factors, and sequelae of TA-TMA in patients with high-risk neuroblastoma. We conducted a retrospective chart review of all patients (n = 141) with neuroblastoma in our institutions who underwent aHCT from 2000 to 2017. Ten patients (7%) developed TA-TMA. The patients in the TA-TMA group were similar to the rest of the subjects in demographics, disease burden, prior therapies, renal function, and timing of transplant. The type of conditioning regimen was the only statistically significant pretransplant variable (P < .001). Six of 15 patients (40%) intended to receive tandem transplants (cyclophosphamide/thiotepa and then carboplatin/etoposide/melphalan (CEM)), 4 of 68 patients (6%) who received conditioning with single CEM, and none of the 56 patients who received busulfan/melphalan were diagnosed with TA-TMA. Patients with TA-TMA were more likely to require intensive care unit transfer, have a longer length of stay in the hospital, and experience a delay or change in their subsequent therapy. In our cohort overall, patients with a delay in therapy after transplant appeared to have a worse overall survival, although the difference was not statistically significant. Because of this high incidence and significant morbidity, we have implemented standardized screening for TA-TMA during and after transplant. We anticipate that screening will lead to earlier intervention and decreased severity of disease. 相似文献
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Primary graft dysfunction after heart transplantation: Incidence,trends, and associated risk factors 下载免费PDF全文
Alina Nicoara David Ruffin Mary Cooter Chetan B. Patel Annemarie Thompson Jacob N. Schroder Mani A. Daneshmand Adrian F. Hernandez Joseph G. Rogers Mihai V. Podgoreanu Madhav Swaminathan Adam Kretzer Mark Stafford‐Smith Carmelo A. Milano Raquel R. Bartz 《American journal of transplantation》2018,18(6):1461-1470
Changes in heart transplantation (HT) donor and recipient demographics may influence the incidence of primary graft dysfunction (PGD). We conducted a retrospective study to evaluate PGD incidence, trends, and associated risk factors by analyzing consecutive adult patients who underwent HT between January 2009 and December 2014 at our institution. Patients were categorized as having PGD using the International Society for Heart & Lung Transplantation (ISHLT)–defined criteria. Variables, including clinical and demographic characteristics of donors and recipients, were selected to assess their independent association with PGD. A time‐trend analysis was performed over the study period. Three‐hundred seventeen patients met inclusion criteria. Left ventricular PGD, right ventricular PGD, or both, were observed in 99 patients (31%). Risk factors independently associated with PGD included ischemic time, recipient African American race, and recipient amiodarone treatment. Over the study period, there was no change in the PGD incidence; however, there was an increase in the recipient pretransplantation use of amiodarone. The rate of 30‐day mortality was significantly elevated in those with PGD versus those without PGD (6.06% vs 0.92%, P = .01). Despite recent advancements, incidence of PGD remains high. Understanding associated risk factors may allow for implementation of targeted therapeutic interventions. 相似文献
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Jayashree Kharge M.D. D.M. Ajit Pal Singh M.D. Thagachagere Ramegowda Raghu M.D. D.M. F.A.C.C. Madhav Hegde M.D. Ashalatha Bharata M.D. D.M. Cholenahally Nanjappa Manjunath M.D. D.M. 《Echocardiography (Mount Kisco, N.Y.)》2013,30(9):E265-E268
Idiopathic dilatation of the pulmonary artery (IDPA) is a rare anomaly presenting with enlargement of the pulmonary artery in the absence of an identifiable cause. The natural history of this silent but potentially life‐threatening disease can be unpredictable. We report a case of IDPA in an 80‐year‐old female with a massively dilated pulmonary artery. 相似文献