| 1. |
- Kyle, RA, et al.
(författare)
-
Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group
- 2003
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 121:5, s. 749-757
-
Tidskriftsartikel (refereegranskat)abstract
- The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is greater than or equal to 30 g/l and/or bone marrow clonal cells greater than or equal to 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.
|
|
| 2. |
|
|
| 3. |
- Palumbo, A., et al.
(författare)
-
Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma
- 2008
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 22:2, s. 414-423
-
Tidskriftsartikel (refereegranskat)abstract
- The incidence of venous thromboembolism (VTE) is more than 1%omicron annually in the general population and increases further in cancer patients. The risk of VTE is higher in multiple myeloma (MM) patients who receive thalidomide or lenalidomide, especially in combination with dexamethasone or chemotherapy. Various VTE prophylaxis strategies, such as low-molecular-Weight heparin (LMWH), warfarin or aspirin, have been investigated in small, uncontrolled clinical studies. This manuscript summarizes the available evidence and recommends a prophylaxis strategy according to a risk-assessment model. Individual risk factors for thrombosis associated with thalidomide/lenalidomide-based therapy include age, history of VTE, central venous catheter, comorbidities (infections, diabetes, cardiac disease), immobilization, surgery and inherited thrombophilia. Myeloma-related risk factors include diagnosis and hyperviscosity. VTE is very high in patients who receive high-dose dexamethasone, doxorubicin or multiagent chemotherapy in combination with thalidomide or lenalidomide, but not with bortezomib. The panel recommends aspirin for patients with <= 1 risk factor for VTE. LMWH (equivalent to enoxaparin 40 mg per day) is recommended for those with two or more individual/myeloma-related risk factors. LMWH is also recommended for all patients receiving concurrent high-dose dexamethasone or doxorubicin. Full-dose warfarin targeting a therapeutic INR of 2-3 is an alternative to LMWH, although there are limited data in the literature with this strategy. In the absence of clear data from randomized studies as a foundation for recommendations, many of the following proposed strategies are the results of common sense or derive from the extrapolation of data from many studies not specifically designed to answer these questions. Further investigation is needed to define the best VTE prophylaxis.
|
|
| 4. |
|
|
| 5. |
- Cromer, M. Kyle, et al.
(författare)
-
Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas
- 2015
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:13, s. 4062-4067
-
Tidskriftsartikel (refereegranskat)abstract
- Insulinomas are pancreatic islet tumors that inappropriately secrete insulin, producing hypoglycemia. Exome and targeted sequencing revealed that 14 of 43 insulinomas harbored the identical somatic mutation in the DNA-binding zinc finger of the transcription factor Yin Yang 1 (YY1). Chromatin immunoprecipitation sequencing (ChIP-Seq) showed that this T372R substitution changes the DNA motif bound by YY1. Global analysis of gene expression demonstrated distinct clustering of tumors with and without YY1(T372R) mutations. Genes showing large increases in expression in YY1(T372R) tumors included ADCY1 (an adenylyl cyclase) and CACNA2D2 (a Ca2+ channel); both are expressed at very low levels in normal beta-cells and show mutation-specific YY1 binding sites. Both gene products are involved in key pathways regulating insulin secretion. Expression of these genes in rat INS-1 cells demonstrated markedly increased insulin secretion. These findings indicate that YY1(T372R) mutations are neomorphic, resulting in constitutive activation of cAMP and Ca2+ signaling pathways involved in insulin secretion.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Androsiuk, P., et al.
(författare)
-
Genetic status of Norway spruce (Picea abies) breeding populations for northern Sweden
- 2013
-
Ingår i: Silvae Genetica. - : J.D. Sauerlaender's Verlag. - 0037-5349. ; 62:3, s. 127-136
-
Tidskriftsartikel (refereegranskat)abstract
- Efficient use of any breeding resources requires a good understanding of the genetic value of the founder breeding materials for predicting the gain and diversity in future generations. This study evaluates the distribution of genetic variation and level of relatedness among and within nine breeding populations of Norway spruce for Northern Sweden using nuclear microsatellite markers. A sample set of 456 individuals selected from 140 stands were genotyped with, 15 SSR loci. Over all loci each individual was identified with unique multilocus genotype. High genetic diversity (average H-e=0.820) and low population differentiation (F-ST = 0.0087) characterized this material. Although low in F-ST, the two northernmost populations were clustered as a distinct group diverged from the central populations. The population differentiation pattern corresponds well with the post glacial migration history of Norway spruce and the current gene flow and human activity in the region. The average inbreeding coefficient was 0.084 after removal loci with high frequency of null alleles. The estimated relatedness of the trees gathered in the breeding populations was very low (average kinship coefficient 0.0077) and not structured. The high genetic variation and low and not structured relatedness between individuals found in the breeding populations confirm that the Norway spruce breeding stock for northern Sweden represent valuable genetic resources for both long-term breeding and conservation programs.
|
|
| 10. |
|
|
