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Institution

Mayo Clinic

HealthcareRochester, Minnesota, United States
About: Mayo Clinic is a healthcare organization based out in Rochester, Minnesota, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 63387 authors who have published 169578 publications receiving 8114006 citations.


Papers
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Journal ArticleDOI
TL;DR: Lenalidomide plus low-dose dexamethasone is associated with better short-term overall survival and with lower toxicity than lenalidomid plus high-dose DexamethAsone in patients with newly diagnosed myeloma in this open-label non-inferiority trial.
Abstract: Summary Background High-dose dexamethasone is a mainstay of therapy for multiple myeloma. We studied whether low-dose dexamethasone in combination with lenalidomide is non-inferior to and has lower toxicity than high-dose dexamethasone plus lenalidomide. Methods Patients with untreated symptomatic myeloma were randomly assigned in this open-label non-inferiority trial to lenalidomide 25 mg on days 1–21 plus dexamethasone 40 mg on days 1–4, 9–12, and 17–20 of a 28-day cycle (high dose), or lenalidomide given on the same schedule with dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle (low dose). After four cycles, patients could discontinue therapy to pursue stem-cell transplantation or continue treatment until disease progression. The primary endpoint was response rate after four cycles assessed with European Group for Blood and Bone Marrow Transplant criteria. The non-inferiority margin was an absolute difference of 15% in response rate. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00098475. Findings 445 patients were randomly assigned: 223 to high-dose and 222 to low-dose regimens. 169 (79%) of 214 patients receiving high-dose therapy and 142 (68%) of 205 patients on low-dose therapy had complete or partial response within four cycles (odds ratio 1·75, 80% CI 1·30–2·32; p=0·008). However, at the second interim analysis at 1 year, overall survival was 96% (95% CI 94–99) in the low-dose dexamethasone group compared with 87% (82–92) in the high-dose group (p=0·0002). As a result, the trial was stopped and patients on high-dose therapy were crossed over to low-dose therapy. 117 patients (52%) on the high-dose regimen had grade three or worse toxic effects in the first 4 months, compared with 76 (35%) of the 220 on the low-dose regimen for whom toxicity data were available (p=0·0001), 12 of 222 on high dose and one of 220 on low-dose dexamethasone died in the first 4 months (p=0·003). The three most common grade three or higher toxicities were deep-vein thrombosis, 57 (26%) of 223 versus 27 (12%) of 220 (p=0·0003); infections including pneumonia, 35 (16%) of 223 versus 20 (9%) of 220 (p=0·04), and fatigue 33 (15%) of 223 versus 20 (9%) of 220 (p=0·08), respectively. Interpretation Lenalidomide plus low-dose dexamethasone is associated with better short-term overall survival and with lower toxicity than lenalidomide plus high-dose dexamethasone in patients with newly diagnosed myeloma. Funding National Cancer Institute, Rockville, MD, USA.

869 citations

Journal ArticleDOI
Joseph Berkson1
TL;DR: It is shown here how the Logistic Function can be applied to Bio-Assay to provide real-time information on the response of a drug to an experimental substance.
Abstract: (1944). Application of the Logistic Function to Bio-Assay. Journal of the American Statistical Association: Vol. 39, No. 227, pp. 357-365.

869 citations

Journal Article
TL;DR: The excitement and attention focused on cellular oncogenes in recent years is now turning toward growth factors, not only as they concern the control of normal cell growth but also the involvement of growth factor-initiated pathways in the etiology of cancer.
Abstract: Growth factors, defined as polypeptides that stimulate cell proliferation, are major growth-regulatory molecules for cells in culture and probably also for cells in vivo. Nontransformed cells show an absolute requirement for growth factors for proliferation in culture and generally more than one growth factor is required. Under usual culture conditions, growth factors are more rapidly depleted than other media components and thus become rate limiting for proliferation. The loss of or decreased requirement for specific growth factors is a common occurrence in neoplastically transformed cells and may lead to a growth advantage, a cardinal feature of cancer cells. Recent work with transforming growth factors, the platelet-derived growth factor, and oncogenes has produced some insight into the mechanisms through which alterations in growth factor-receptor-response pathways could lead to a growth advantage. Evidence has been derived for autocrine secretion in which the cell produces its own growth factor. Many transformed mesenchymal cells produce PDGF (the product of the c-sis proto-oncogene) and certain transformed cells both produce and respond in a growth-stimulatory manner to TGF beta. With TGF beta, which is a growth inhibitor for certain epithelial and other cell types, the loss of the normal inhibitory response in transformed cells could have the same result as the activation of a growth-stimulatory response. Two proto-oncogenes, erbB and fms, encode growth factor receptors. In the erbB case, the viral erbB aberrant receptor produced is truncated and appears to be constitutively activated without the need for a growth factor. Recent studies suggest that the p21 product of the ras oncogene may be an obligatory intermediate in transducing the growth factor signal. Activation of ras may, therefore, activate the growth factor pathway without the need for either a growth factor or its receptor. The transcription of myc and fos is induced by growth factor stimulation of quiescent cells. The protein products of both are nuclear associated and conceivably could be involved in regulating other genes important in the control of cell proliferation. Activation or inappropriate expression of either myc or fos could produce the same end result as stimulation of a growth factor pathway leading to a growth advantage. Study of the molecular mechanism(s) of growth factor action has just begun. The excitement and attention focused on cellular oncogenes in recent years is now turning toward growth factors, not only as they concern the control of normal cell growth but also the involvement of growth factor-initiated pathways in the etiology of cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

868 citations

Journal ArticleDOI
TL;DR: Among 161 necropsy cases of aortic dissection, 87 (54%) were type I, 34 (21%) type II, and 40 (25%) type III, and an intimal tear was identified in each, and the major risk factors were systemic hypertension, the Marfan syndrome, and, for type I and II dissections, congenitally bicuspid or unicommissural aorti valves.
Abstract: Among 161 necropsy cases of aortic dissection, 87 (54%) were type I, 34 (21%) type II, and 40 (25%) type III, and an intimal tear was identified in each. Systemic hypertension had been present in 63 of 121 cases (52%) with type I or II dissection and in 30 of 40 (75%) with type III dissection. Aortic dissection involved 7 of 16 cases (44%) with the Marfan syndrome. In the 154 cases without the Marfan syndrome, grade 3 or 4 medial degeneration (cystic medial necrosis) was observed in the ascending aorta in only 27 (18%). The risk of aortic dissection in persons with congenitally bicuspid and unicommissural aortic valves, respectively, was 9 and 18 times that in subjects with tricuspid aortic valves. The mean age of those with aortic dissection and tricuspid, bicuspid and unicommissural aortic valves was 63, 55 and 40 years, respectively, and aortic dissection was more common in men than in women. Grade 3 or 4 atherosclerosis involved the intimal tear in only 11 of 121 type I or II dissections (9%) but 32 of 40 type III dissections (80%). Accordingly, the major risk factors for aortic dissection were systemic hypertension, the Marfan syndrome, and, for type I and II dissections, congenitally bicuspid or unicommissural aortic valves. Aortic medial degeneration was a less important risk factor. Rupture of ulcerocalcific aortic atheromas may have initiated the intimal tear in some type III dissections.

867 citations

Journal ArticleDOI
TL;DR: The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor complicating neural stem cell therapy.
Abstract: Background Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. Methods and Findings A boy with ataxia telangiectasia (AT) was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA) typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. Conclusions This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

867 citations


Authors

Showing all 64325 results

NameH-indexPapersCitations
Eugene Braunwald2301711264576
Peter Libby211932182724
Cyrus Cooper2041869206782
Rob Knight2011061253207
Robert M. Califf1961561167961
Eric J. Topol1931373151025
Dennis W. Dickson1911243148488
Gordon B. Mills1871273186451
Julie E. Buring186950132967
Patrick W. Serruys1862427173210
Cornelia M. van Duijn1831030146009
Paul G. Richardson1831533155912
John C. Morris1831441168413
Valentin Fuster1791462185164
Ronald C. Petersen1781091153067
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023268
20221,216
202112,779
202011,352
201910,004
20188,870