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Ultima Vez Modificado: 1 de septiembre del 2002
UI - 12075197
AU - Ziegler CM; Flechtenmacher C; Muhling J
TI - Tender preauricular swelling.
SO - Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002 May;93(5):516-20
AD - University of Heidelberg, Heidelberg, Germany.
UI - 12126363
AU - Basu S; Gupta N; Malhotra H
TI - IgA myeloma presenting as diabetes mellitus with refractory anaemia.
SO - J Assoc Physicians India 2002 Jul;50():981-2
AD - Department of Haematology and Transfusion Medicine, Government Medical College and Hospital, Chandigarh.
UI - 11830399
AU - Delisle V; Tollis F; Truchan-Graczyk M; Rousselet-Chapeau MC; Ifrah N;
TI - Zandecki M; Genevieve F [Plasma cell leukemia: aggressive form of multiple myeloma]
SO - Ann Biol Clin (Paris) 2002 Jan-Feb;60(1):89-95
AD - Centre hospitalier universitaire, 49033 Angers cedex 01.
UI - 12043696
AU - Lee FC
TI - Second response to lower-dose thalidomide in a patient with multiple myeloma.
SO - Blood 2002 Jun 1;99(11):4248; discussion 4249
UI - 12043699
AU - Devine SM; Jahagirdar B; van Besien K
TI - Reduced duration of cytopenias following melphalan conditioning and autografting for multiple myeloma.
SO - Blood 2002 Jun 1;99(11):4251-2; discussion 4252
UI - 12170429
AU - Ponisch W; Niederwieser D
TI - Bendamustine in the treatment of multiple myeloma: results and future perspectives.
SO - Semin Oncol 2002 Aug;29(4 Suppl 13):23-6
AD - East German Study Group for Hematology and Oncology (OSHO), University of Leipzig, Philipp Rosenthalstrasse 23-25, D-4103 Liepzig, Germany.
Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells typically occurring in elderly patients. The clinical manifestations of this disease result primarily from the accumulation of monoclonal protein (paraprotein) in the serum and/or urine, anemia, lytic bone lesions, hypercalcemia, renal insufficiency, and immune deficiency. Multiple myeloma is incurable with standard chemotherapy. Melphalan and prednisone has been the mainstay of treatment for MM for about three decades. This regimen results in a clinical response in approximately 60% of patients and a median survival of approximately 36 months. A variety of combination therapies have also been used in MM, but have not been considered to offer a significant benefit compared with standard therapy. In early trials, bendamustine monotherapy was as effective as cyclophosphamide and various combination therapies in achieving remission in MM. This article describes a prospective, randomized, phase III study designed to compare the efficacy of bendamustine/prednisolone with a standard melphalan/prednisolone regimen. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 12150155
AU - Bezieau S; Avet-Loiseau H; Moisan JP; Bataille R
TI - Activating Ras mutations in patients with plasma-cell disorders: a reappraisal.
SO - Blood 2002 Aug 1;100(3):1101-2; discussion 1103
UI - 12130482
AU - Kroger N; Schwerdtfeger R; Kiehl M; Sayer HG; Renges H; Zabelina T;
TI - Fehse B; Togel F; Wittkowsky G; Kuse R; Zander AR Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma.
SO - Blood 2002 Aug 1;100(3):755-60
AD - Bone Marrow Transplantation, University Hospital Hamburg, Hamburg, Germany. email@example.com
We evaluated toxicity, engraftment, chimerism, graft-versus-host disease (GVHD), and response to a dose-reduced allograft after cytoreductive autografting in 17 patients with advanced stage II/III multiple myeloma (MM). After autografting with melphalan (200 mg/m2) the patients received after a median interval of 119 days (range 60-210) a dose-reduced regimen consisting of fludarabine (180 mg/m2), melphalan (100 mg/m2), and antithymocyte globulin (3 x 10 mg/kg) followed by allografting from related (n = 7), mismatched related (n = 2), or unrelated (n = 8) donors to induce a graft-versus-myeloma effect. After dose-reduced allografting all patients became neutropenic (< 0.2 x 10(9)/L) for at least 8 days. All patients engrafted with a median time for leukocyte (> 1 x 10(9)/L) and platelet (> 20 x 10(9)/L) counts of 16 (range, 11-24) and 23 days (range, 12-43), respectively. Complete donor chimerism was detected after a median of 30 days (range, 19-38). Acute GVHD stage II occurred in 4 patients (25%) and grade III GVHD in 2 patients (13%). Chronic GVHD developed in 40% of the patients, but only 1 patient experienced extensive chronic GVHD requiring further immunosuppressive therapy. Two patients died of alveolar hemorrhage and pneumonia, resulting in a day 100 mortality rate of 11%. The rate of complete remission with negative immunofixation increased from 18% after autografting to 73% after allografting. After a median follow-up of 17 months after autologous and 13 months after allogeneic transplantation 13 patients are alive and 12 of them free of relapse or progression. The tandem auto-allotransplant protocol is highly active and provides rapid engraftment with complete donor chimerism and tolerable toxicity.
UI - 12130509
AU - Chiriva-Internati M; Wang Z; Salati E; Bumm K; Barlogie B; Lim SH
TI - Sperm protein 17 (Sp17) is a suitable target for immunotherapy of multiple myeloma.
SO - Blood 2002 Aug 1;100(3):961-5
AD - Division of Hematology and Oncology, Texas Tech University Health Sciences Center, Amarillo 79106, USA.
Sperm protein 17 (Sp17) is a protein recently identified as a novel cancer-testis (CT) antigen in multiple myeloma (MM). Because this tumor antigen demonstrates a very restricted normal tissue expression, Sp17 may be an excellent target for tumor vaccine of MM. In this study, we determined the ability to generate Sp17-specific HLA class I-restricted cytotoxic T lymphocytes (CTLs) from the peripheral blood of 4 patients with MM, 3 consecutive Sp17(+) patients, and 1 Sp17(-) patient. Dendritic cells were generated from monocytes of 4 patients with MM and used to present a recombinant Sp17 protein to autologous T cells. Following 4 rounds of antigen stimulation, the CTLs were tested for their ability to kill autologous targets in an Sp17-dependent and HLA-class I- restricted manner in standard cytotoxicity assays. Despite previous chemotherapy and the immunosuppression so often associated with MM, CTL generation was successful in all 4 patients, irrespective of the Sp17 status of their tumors. Most importantly, the CTLs were able to lyse autologous tumor cells that expressed Sp17. Tumor cell lysis in all cases appeared to be mainly mediated by perforin and could be blocked by concanamycin A. We conclude that Sp17 is a suitable target for immunotherapy of MM. Our findings provide the basis for a clinical study aimed at inducing a cellular immune response directed at Sp17(+) MM.
UI - 9787135
AU - Chesi M; Nardini E; Lim RS; Smith KD; Kuehl WM; Bergsagel PL
TI - The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts.
SO - Blood 1998 Nov 1;92(9):3025-34
AD - Department of Medicine, the Division of Hematology and Oncology, Weill Medical College of Cornell University, New York, NY, USA.
Previously we reported that a karyotypically silent t(4;14)(p16. 3;q32.3) translocation is present in about 25% of multiple myeloma (MM) tumors, and causes overexpression of FGFR3, which is 50 to 100 kb telomeric to the 4p16 breakpoints. Frequent FGFR3 kinase activating mutations in MM with t(4;14) translocations substantiate an oncogenic role for FGFR3. We now report that the 4p16 breakpoints occur telomeric to and within the 5' introns of a novel gene, MMSET (Multiple Myeloma SET domain). In normal tissues, MMSET has a complex pattern of expression with a short form (647 amino acids [aa]) containing an HMG box and hath region, and an alternatively spliced long form (1365 aa) containing the HMG box and hath region plus 4 PHD fingers and a SET domain. Although t(4;14) translocation results in IgH/MMSET hybrid transcripts, overexpression of MMSET also occurs from endogenous promoters on 4p16. Given the homology to HRX/MLL1/ALL1 at 11q23 that is dysregulated by translocations in acute leukemia, we hypothesize that dysregulation of MMSET contributes to neoplastic transformation in MM with t(4;14) translocation. This is the first example of an IgH translocation that simultaneously dysregulates two genes with oncogenic potential: FGFR3 on der(14) and MMSET on der(4). Copyright 1998 by The American Society of Hematology
UI - 10089658
AU - Marcos Sanchez F; Solano Ramos F; Juarez Ucelay F; Arranz Nieto MJ;
TI - Duran Perez-Navarro A [An association of multiple myeloma and megaloblastic anemia]
SO - An Med Interna 1999 Jan;16(1):51-2
UI - 10686722
AU - Miramon Lopez J; Ruiz Cantero A; Morales Jimenez J; Lara Fernandez A;
TI - Hita Perez J [A new case of association of multiple myeloma and megaloblastic anemia]
SO - An Med Interna 1999 Dec;16(12):654-5; discussion 656
UI - 11490638
AU - Chindia ML; Riyat MS; Nyong'o A
TI - Multiple myeloma presenting as a painful mandibular swelling: a case report.
SO - Dent Update 2001 Jun;28(5):258-60
AD - Faculty of Dental Sciences, University of Nairobi, Kenya.
Multiple myeloma is a disease characterized by monoclonal proliferation of plasma cells, the most differentiated stage of B-cells. Primary manifestation of multiple myeloma in the jawbones is rare. In the case reported here, a 29-year-old woman who presented with a right mandibular swelling after extraction of a mobile painful tooth turned out to have multiple myeloma. Current diagnostic criteria and management strategies of the disease are discussed.
UI - 11435324
AU - Barlogie B; Desikan R; Eddlemon P; Spencer T; Zeldis J; Munshi N; Badros
TI - A; Zangari M; Anaissie E; Epstein J; Shaughnessy J; Ayers D; Spoon D; Tricot G Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients.
SO - Blood 2001 Jul 15;98(2):492-4
AD - Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
This report of a phase 2 trial of thalidomide (THAL) (200 mg/d; 200 mg increment every 2 weeks to 800 mg) for 169 patients with advanced myeloma (MM) (abnormal cytogenetics (CG), 67%; prior autotransplant, 76%) extends earlier results in 84 patients. A 25% myeloma protein reduction was obtained in 37% of patients (50% reduction in 30% of patients; near-complete or complete remission in 14%) and was more frequent with low plasma cell labeling index (PCLI) (below 0.5%) and normal CG. Two-year event-free and overall survival rates were 20% +/- 6% and 48% +/- 6%, respectively, and these were superior with normal CG, PCLI of less than 0.5%, and beta(2)-microglobulin of 3 mg/L. Response rates were higher and survival was longer especially in high-risk patients given more than 42 g THAL in 3 months (median cumulative dose) (landmark analysis); this supports a THAL dose-response effect in advanced MM.
UI - 11675360
AU - Hsu J; Shi Y; Krajewski S; Renner S; Fisher M; Reed JC; Franke TF;
TI - Lichtenstein A The AKT kinase is activated in multiple myeloma tumor cells.
SO - Blood 2001 Nov 1;98(9):2853-5
AD - Department of Medicine and Pathology, West Los Angeles Veterans Administration Medical Center and Jonsson Comprehensive Cancer Center, Los Angeles, CA 90073, USA.
Immunohistochemistry (IHC) was performed on archived bone marrow (BM) with a phosphospecific anti-AKT antibody. IHC on 26 BM biopsies from patients with multiple myeloma (MM) demonstrated phospho-AKT staining of malignant plasma cells in a cell membrane-specific pattern, whereas nonmalignant hematopoietic cells did not stain. Preabsorption of the antibody with phosphorylated AKT peptide, but not nonphosphorylated peptide, abrogated staining. Frequency of plasma cell staining in BMs of patients with stage I or smoldering MM was significantly less than that of stage III MM marrows. Plasma cells in 10 patients with monoclonal gammopathy of undetermined significance were not stained by the antibody. To investigate the significance of AKT activation, 2 cell lines initiated from cultures of primary MM cells were also studied. Both demonstrated constitutive AKT activation. Interruption of AKT activation and activity, achieved by either exposure to wortmannin or by ectopic expression of a dominant negative AKT mutant, resulted in inhibition of MM cell growth in vitro. These results indicate that activation of the AKT kinase is a characteristic of MM cells and suggest that AKT activity is important for MM cell expansion.
UI - 11806971
AU - Moreau P; Facon T; Attal M; Hulin C; Michallet M; Maloisel F; Sotto JJ;
TI - Guilhot F; Marit G; Doyen C; Jaubert J; Fuzibet JG; Francois S; Benboubker L; Monconduit M; Voillat L; Macro M; Berthou C; Dorvaux V; Pignon B; Rio B; Matthes T; Casassus P; Caillot D; Najman N; Grosbois B; Bataille R; Harousseau JL; Intergroupe Francophone du Myelome Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial.
SO - Blood 2002 Feb 1;99(3):731-5
AD - Service d'Hematologie, University Hospital Hotel-Dieu, Place Alexis Recordeau, 44093 Nantes cedex 01, France.
High-dose therapy has become a common treatment for myeloma. The objective of this study (Intergroupe Francophone du Myelome [IFM] 9502 trial) was to compare in a prospective and randomized trial the 2 most widely used conditioning regimens before autologous stem cell transplantation in newly diagnosed symptomatic patients younger than 65 years old: 8 Gy total body irradiation plus 140 mg/m(2) melphalan (arm A) versus 200 mg/m(2) melphalan (arm B). A total of 282 evaluable patients were compared--140 in arm A and 142 in arm B. Baseline characteristics and disease response to 4 cycles of the VAD regimen performed before randomization and autologous stem cell transplantation were identical in the 2 treatment arms. In arm B, hematologic recovery was significantly faster for both the duration of neutropenia and thrombocytopenia, transfusion requirements were also significantly lower, and the median duration of hospitalization was significantly shorter. In arm A, the incidence of severe mucositis was significantly increased. The median duration of event-free survival was similar in both arms (21 vs 20.5 months, P =.6), but the 45-month survival was 65.8% in arm B versus 45.5% in arm A (P =.05). This difference might be attributed in part to better salvage regimens after relapse in arm B compared with arm A. We conclude that 200 mg/m(2) melphalan is a less toxic and at least as effective conditioning regimen when compared with 8 Gy total body irradiation with 140 mg/m(2) melphalan. This regimen should be considered as the standard of care before autologous stem cell transplantation in multiple myeloma.
UI - 11901667
AU - Speer SA; Semenza JC; Kurosaki T; Anton-Culver H
TI - Risk factors for acute myeloid leukemia and multiple myeloma: a combination of GIS and case-control studies.
SO - J Environ Health 2002 Mar;64(7):9-16; quiz 35-6
AD - Epidemiology Division, Department of Medicine, University of California, Irvine, 224 Irvine Hall, Irvine, CA 92697-7550, USA.
Risk factors for acute myeloid leukemia (AML) and multiple myeloma (MM) include exposure to toxic chemicals present in tobacco smoke, as well as to emissions from industrial operations and petroleum refinery waste dumps. The study reported here identified these risk factors among case patients and control patients in Orange County, California, from 1984 to 1993 and determined the significance of the risk factors in the study population. A case-control study was performed for 604 cases of AML and 643 cases of MM; there were 7,112 control subjects who had colon cancer. The model included the variables smoking history, occupational history, and residence in a census tract with a petroleum refinery waste dump. A geographic information system (GIS) analysis also was performed to correlate the incidence of AML and MM with proximity to the six dump sites that received large amounts of petroleum refinery waste. Current smokers were found to be at an increased risk of AML with an odds ratio of 2.0. Laborer/equipment cleaners and transportation workers/movers were at risk of AML with odds ratios of 3.5 and 2.4, respectively. Construction/resource extraction workers were at risk of MM with an odds ratio of 2.8. GIS analysis determined that the risk for MM was 1.6 cases per mile for 10 or more years of residence near a large chemical dump. The authors were able to identify census tracts with a high incidence of AML and MM, and to perform distance analysis using a statistical measure of spatial randomness. The case-control study identified occupational and lifestyle risk factors for AML and MM that were not apparent from census-tract-level data.
UI - 11961205
AU - Miller WH Jr
TI - Molecular targets of arsenic trioxide in malignant cells.
SO - Oncologist 2002;7 Suppl 1():14-9
AD - Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital and McGill University Department of Oncology, Montreal, Quebec, Canada. Wmiller@ldi.jgh.mcgill.ca
Arsenic trioxide (As2O3; ATO) has considerable efficacy in the treatment of relapsed acute promyelocytic leukemia (APL), inducing partial differentiation and promoting apoptosis of malignant promyelocytes. Although initial studies focused on the role of the characteristic APL fusion protein, PML-RARalpha, in mediating response to ATO, subsequent investigations have revealed that ATO acts on numerous intracellular targets. ATO broadly affects signal transduction pathways and causes a wide range of alterations leading to apoptosis. Key mediators of sensitivity to ATO-induced apoptosis include intracellular glutathione and hydrogen peroxide (H2O2). The loss of inner mitochondrial membrane potential is also an important step in ATO-mediated cell killing. Cellular and physiologic pathways affected by ATO provide some clues as to the mechanisms for the biologic effects of ATO. Recent research has shown that hematologic cancers other than APL and solid tumors derived from several tissue types may be responsive to monotherapy or combination therapy with ATO. A better understanding of the mechanisms of action of ATO may help guide the use of ATO for the treatment of a wide variety of malignancies and allow its potential in cancer therapy to be fully realized.
UI - 11961206
AU - Hussein MA
TI - Nontraditional cytotoxic therapies for relapsed/refractory multiple myeloma.
SO - Oncologist 2002;7 Suppl 1():20-9
AD - Cleveland Clinic Myeloma Research Program, Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, USA. firstname.lastname@example.org
Multiple myeloma remains an incurable disease, with median survival rates of 4-6 years even with aggressive, high-dose chemotherapy, bone marrow transplantation, and intensive supportive care. Additionally, multiple myeloma is primarily a disease of the elderly, many of whom cannot tolerate aggressive chemotherapy. Thus, newer treatments with good safety profiles are needed to improve the quality of responses and, hopefully, to translate into prolonged progression and overall survival. The pathophysiology of multiple myeloma is complex, involving many pathways and interactions among cytokines, adhesion molecules, angiogenesis, and mechanisms of resistance, which, taken together, provide multiple targets for novel therapeutic modalities. Agents currently under investigation for treating multiple myeloma include thalidomide and its successors, PS-341, and arsenic trioxide. Thalidomide and immunomodulatory drugs both exhibit activity against multiple myeloma by affecting different levels of the immune system. PS-341 is a proteasome inhibitor that halts the cell cycle, resulting in apoptosis; it also inhibits a key transcription factor and may have antiangiogenic activity. Arsenic trioxide activates multicellular mechanisms to induce apoptosis, inhibit angiogenesis, and stimulate immune responses. Preclinical and early clinical data suggest that combination regimens should be pursued, given the different mechanisms of action of these compounds on the immune system and their non-overlapping toxicities at low dosages.
UI - 12072017
AU - Bayer-Garner IB; Smoller BR
TI - AL amyloidosis is not present as an incidental finding in cutaneous biopsies of patients with multiple myeloma.
SO - Clin Exp Dermatol 2002 May;27(3):240-2
AD - Department of Pathology, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Multiple myeloma (MM) is a monoclonal B-cell neoplasm characterized by autonomous proliferation of immunoglobulin-secreting plasma cells that are capable of synthesizing amyloidogenic light chains resulting in AL amyloidosis. Clinically occult AL amyloid deposition may occur in up to 31% of patients with MM. The prognosis of combined amyloidosis and MM is improving with new therapeutic options. Thus it is imperative that patients with MM be screened for amyloidosis. Sixty-six consecutive skin biopsies from patients with MM and the diagnosis of graft vs. host disease (GVHD) were stained with Congo red and assessed for the presence of amyloid deposition. Twelve cases that had amyloid deposition in other tissue and had a cutaneous biopsy were also stained with Congo red and assessed for the presence of amyloid deposition. None of the 66 biopsies of GVHD, and none of the 12 cases that had documented amyloid deposition in other tissue showed evidence of amyloid deposition in the cutaneous biopsies. In the absence of specific cutaneous manifestations of amyloidosis, it is unlikely that amyloidogenic light chain deposition in the skin would be found. Type I collagen may appear similar to amyloid, both by light microscopy and fluorescence, after staining with Congo red. Thus care must be taken not to confuse type I collagen autofluorescence with positivity for amyloid when assessing skin biopsies stained with Congo red.
UI - 12060120
AU - Zojer N; Schuster-Kolbe J; Assmann I; Ackermann J; Strasser K; Hubl W;
TI - Drach J; Ludwig H Chromosomal aberrations are shared by malignant plasma cells and a small fraction of circulating CD19+ cells in patients with myeloma and monoclonal gammopathy of undetermined significance.
SO - Br J Haematol 2002 Jun;117(4):852-9
AD - First Department of Internal Medicine and Medical Oncology, Wilhelminenspital, University of Vienna, Montleartstrasse 37, 1160 Vienna, Austria.
In the present study, we aimed to identify distinct structural and numerical chromosomal aberrations in peripheral blood B cells of patients with myeloma and monoclonal gammopathy of undetermined significance (MGUS), which reflect changes thought to occur at different stages of the disease process. Peripheral blood from 12 patients with multiple myeloma and three patients with MGUS was investigated for the occurrence of retinoblastoma-1 gene deletions, p53 gene deletions and numerical aberrations demonstrated previously to be present in the patients' bone marrow CD138+ cells. By combining immunocytochemical staining for light chains and interphase fluorescence in situ hybridization (FISH), aberrant light-chain +ve cells were detected in the circulating CD19+ cell fraction. Each kind of chromosomal change present in the myeloma tumour cells was found to be shared by a small fraction of CD19+ cells (0.1-1.8%; median 0.36%, n = 6). In one MGUS patient, aberrant cells could be identified with a frequency of 0.34% within the CD19-sorted cell fraction. Clonotypic cells were detected with a frequency of 0.01-0.07% of peripheral blood nucleated cells by m-RNA in situ hybridization with patient-specific probes in three investigated patients. These results provide evidence that the circulating clonotypic B cells are closely related to the malignant plasma cells in myeloma and MGUS.
UI - 12060125
AU - Sahara N; Takeshita A; Shigeno K; Fujisawa S; Takeshita K; Naito K;
TI - Ihara M; Ono T; Tamashima S; Nara K; Ohnishi K; Ohno R Clinicopathological and prognostic characteristics of CD56-negative multiple myeloma.
SO - Br J Haematol 2002 Jun;117(4):882-5
AD - Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, 431-3192 Japan. email@example.com
We analysed CD56 expression in 70 patients with multiple myeloma (MM) to determine its clinicopathological and prognostic significance. Fifty-five (79%) patients were CD56+. CD56- patients (n = 15) had higher beta2 microglobulin levels and a higher incidence of extramedullary disease, Bence Jones protein, renal insufficiency and thrombocytopenia than CD56+ patients. Their myelomas more frequently had a plasmablastic morphology. Overall survival was significantly lower in CD56- than CD56+ patients (22 vs 63 months, P = 0.0002). We conclude that CD56- MM is a discrete entity associated with more aggressive disease. The higher incidence of plasmablastic cases suggested that CD56- MM may develop from a less mature plasma cell than CD56+ MM.
UI - 12060127
AU - Gonzalez-Fraile MI; Garcia-Sanz R; Mateos MV; Balanzategui A; Gonzalez
TI - M; Vaquez L; San Miguel JF Methylenetetrahydrofolate reductase genotype does not play a role in multiple myeloma pathogenesis.
SO - Br J Haematol 2002 Jun;117(4):890-2
AD - Servicio de Hematologia, Hospital Clinico Universitario de Salamanca, Centro de Investigacion del Cancer (CIC), Paseo de San Vicente 58-182, 37007 Salamanca, Spain.
Methylenetetrahydrofolate reductase (MTHFR) plays an important role in carcinogenesis. A decreased incidence of cancer has been reported in the presence of MTHFR 677TT, 1298AC and 1298CC polymorphic variants. We have analysed the MTHFR genotype in 107 multiple myeloma (MM) patients and 86 controls. The MM and control polymorphisms frequencies were: 34% and 48% for 677CC, 53% and 41% for 677CT, 12% and 11% for 677TT; 36% and 43% for 1298AA, 51% and 44% for 1298AC; and 12% and 13% for 1298CC respectively. No statistically significant differences were observed. In addition, no differences were seen according to MM stage, presence of p16 gene hypermethylation or response to treatment.
UI - 12171498
AU - Yin H; Alhasan N; Ciervo A; Zinterhofer L
TI - Soft tissue amyloidoma with features of plasmacytoma: a case report and review.
SO - Arch Pathol Lab Med 2002 Aug;126(8):969-71
AD - Department of Pathology, Monmouth Medical Center, Long Branch, NJ 07740, USA.
Soft tissue amyloidoma is rare, and soft tissue amyloidoma associated with plasmacytoma and without evidence of systemic amyloidosis is even more rare. We report a case of soft tissue amyloidoma associated with an apparently localized monoclonal proliferation of plasma cells (plasmacytoma).
UI - 12173037
AU - Mitsiades CS; Mitsiades N; Poulaki V; Schlossman R; Akiyama M; Chauhan
TI - D; Hideshima T; Treon SP; Munshi NC; Richardson PG; Anderson KC Activation of NF-kappaB and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications.
SO - Oncogene 2002 Aug 22;21(37):5673-83
AD - Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, MA 02115, USA.
Interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) promote the proliferation of multiple myeloma (MM) cells and protect them against dexamethasone (Dex)-induced apoptosis. We have previously shown that Apo2 ligand/TNF-Related apoptosis inducing ligand (Apo2L/TRAIL) induces apoptosis of MM cells, including cells either sensitive or resistant to Dex and cytotoxic drugs, and overcomes the growth and survival effect of IL-6; conversely, NF-kappaB transcriptional activity attenuates their Apo2L/TRAIL-sensitivity. In the current study, we demonstrate that IGF-1 stimulates sustained activation of NF-kappaB and Akt; induces phosphorylation of the FKHRL-1 Forkhead transcription factor; upregulates a series of intracellular anti-apoptotic proteins including FLIP, survivin, cIAP-2, A1/Bfl-1, and XIAP; and decreases Apo2L/TRAIL-sensitivity of MM cells. In contrast, IL-6 does not cause sustained NF-kappaB activation, induces less pronounced Akt activation and FKHRL-1 phosphorylation than IGF-1, and increases the expression of only survivin. Forced overexpression of constitutively active Akt in MM-1S cells reduced their sensitivity to Apo2L/TRAIL and to doxorubicin (Doxo). In contrast, the Akt inhibitor IL-6-Hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate induced cell death of both Dex- and Doxo-sensitive and -resistant cells; opposed the protective effect of constitutive Akt activity against Apo2L/TRAIL; and abrogated the NF-kappaB activation, increase of anti-apoptotic proteins and protection against Apo2L/TRAIL induced by IGF-1. These findings therefore define an important role of the Akt pathway in modulating tumor cell responsiveness to Apo2L/TRAIL, delineate molecular mechanisms for the survival effects of IGF-1, and characterize differential pathophysiologic sequelae of IGF-1 vs IL-6 on MM cells. Importantly, they provide the basis for future clinical trials in MM combining conventional or novel agents with strategies designed to neutralize IGF-1.
UI - 12151702
AU - Gonen C; Oksuzoglu B; Yalcin S
TI - Abdominal pain in a diabetic myeloma patient with cirrhosis.
SO - Postgrad Med J 2002 Jun;78(920):375, 379
AD - Department of Internal Medicine, Hacettepe University, Samanpazari, 06100 Ankara, Turkey.
UI - 12100137
AU - Mitterbauer M; Kalhs P; Keil F; Prinz E; Moser K; Mannhalter C;
TI - Mitterbauer G; Brugger S; Gisslinger H; Lechner K; Greinix HT Continuous complete clinical and molecular remission in two patients with refractory lymphoid malignancies after autografting followed by allogeneic stem cell transplantation with reduced intensity conditioning.
SO - Br J Haematol 2002 Jul;118(1):132-5
AD - Department of Medicine I, Bone Marrow Transplantation, University Hospital of Vienna, Vienna, Austria. Margit.Mitterbauer@akh-wien.ac.at
We present a 60-year-old patient with primary refractory non-Hodgkin's lymphoma and a 58-year-old patient with multiple myeloma with relapse after first autologous stem cell transplantation (ASCT), who underwent ASCT followed by allogeneic stem cell transplantation (alloSCT) with reduced intensity conditioning consisting of fludarabine and a single dose of total body irradiation. For graft-versus-host disease prophylaxis cyclosporine and mycophenolate mofetyl were given. Complete donor chimaerism was observed on d 28 after SCT. Both patients achieved sustained complete haematological and molecular remission of the immunoglobulin kappa light chain (Igkappa) rearrangement and are alive and well 17 and 16 months after SCT respectively.
UI - 12100143
AU - Frassanito MA; Cusmai A; Piccoli C; Dammacco F
TI - Manumycin inhibits farnesyltransferase and induces apoptosis of drug-resistant interleukin 6-producing myeloma cells.
SO - Br J Haematol 2002 Jul;118(1):157-65
AD - Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
Interleukin 6 (IL-6) is an important survival and growth factor for myeloma cells and exerts its effects by activating several transduction pathways, including the Ras cascade. As farnesylation of the activated Ras oncogene product by protein farnesyltransferase (FTase) is a critical step for Ras functional activity, FTase has emerged as a potential target for the development of new anti-cancer agents. Based on our previous demonstration that IL-6-producing myeloma cells are refractory to drug-induced apoptosis, we have analysed the effect of manumycin, a natural FTase inhibitor, on IL-6-producing myeloma cells resistant to Fas-, dexamethasone- and doxorubicin-induced apoptosis. Treatment of myeloma cells with manumycin prevented cell proliferation and induced apoptosis. Western blotting experiments demonstrated that this effect was related to inhibition of the post-translational Ras processing.Further analysis showed that manumycin-induced apoptosis involved caspase-3. Activation of caspase-3, in fact, was observed in 6 h-treated myeloma cells expressing Apo 2.7 antigen, the marker of early apoptosis, whereas their treatment with cell-permeable DEVD-fmk, that irreversibly inhibits caspase-3 activity, prevented their apoptosis. Over-expression of caspase-3 was also demonstrated by reverse transcription-polymerase chain reaction. Finally, over-expression of Bcl-2 and its homologue Bcl-xL was observed in manumycin-treated cells as well as in control myeloma cells, implying that the Bcl-2 family is not involved. FTase inhibitors may thus be proposed as a potential pharmacological weapon, as they block the Ras pathway and induce the apoptosis of drug-resistant IL-6-producing myeloma cells.
UI - 12100153
AU - Martin A; Garcia-Sanz R; Hernandez J; Blade J; Suquia B; Fernandez-Calvo
TI - J; Gonzalez M; Mateo G; Orfao A; San Miguel JF Pamidronate induces bone formation in patients with smouldering or indolent myeloma, with no significant anti-tumour effect.
SO - Br J Haematol 2002 Jul;118(1):239-42
AD - Hospital Universitario de Salamanca, Salamanca, Spain.
Twelve patients with smouldering or indolent multiple myeloma (MM) received 12 courses of intravenous pamidronate as a single agent to evaluate both the antitumour and bone metabolism effects. One patient achieved minor response, eight had stable disease, and three - all indolent MM - showed disease progression. Serum interleukin 6 (IL-6), IL-1beta and Oncostatin-M remained stable throughout the study, while tumour necrosis factor-alpha increased. Bone density significantly increased after four and 12 courses compared with baseline. Markers for bone resorption and bone formation decreased with treatment. These results suggest that pamidronate treatment reduces bone turnover in smouldering or indolent MM, but has no significant antitumour effect.
UI - 11503969
AU - Shinagawa A; Kojima H; Kobayashi T; Kawada K; Nagasawa T
TI - Lupus anticoagulant-like activity observed in a dimeric lambda protein produced by myeloma cells.
SO - Int J Hematol 2001 Jun;73(4):526-31
AD - Division of Hematology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
We report here a lupus anticoagulant (LA)-like activity observed in a 45-year-old man with Bence-Jones protein (BJP) lambda-type multiple myeloma. This patient showed no clinical symptoms of thrombosis or bleeding diathesis. Laboratory examination on admission showed mild anemia, prolongation of activated partial thromboplastin time (APTT) (APTT, 56.2 seconds; control, 29.1 seconds), normal prothrombin time, normal thrombin time, and massive proteinuria (2.3 g/d). The mix test with normal plasma showed the presence of circulating anticoagulant. Based on the assumption that the lambda-type BJP may have been responsible for the prolongation of APTT, we purified the BJP from the patient's urine using column works. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting showed that the purified protein was a 48-kd homodimer of immunoglobulin lambda-chains. Addition of the purified dimeric lambda-type BJP to the normal plasma prolonged both APTT and dilute Russell's viper venom time (DRVVT) in a dose-dependent manner, and the negatively charged phospholipid-dependent prothrombinase activity was significantly inhibited in the presence of this protein. Furthermore, both the prolongation of DRVVT and the inhibition of the prothrombinase activity were almost completely abrogated under the condition of high ionic strength. These findings collectively suggest that the dimeric lambda-type BJP showed LA-like activity via the mechanism of ionic charge.
UI - 11594523
AU - Shimizu K; Nagura E; Hirabayashi N; Wakita A; Takeyama H; Sao H; Nitta
TI - M; Kawashima K; Saito H Posttreatment nadir M-protein level is a stronger discriminator of survival following plateau attainment than is percent reduction in M-protein in patients with IgG myeloma.
SO - Int J Hematol 2001 Aug;74(2):205-8
AD - Department of Medicine, Nagoya City Higashi General Hospital, Nagoya, Japan.
We conducted a retrospective study of patients with IgG or IgA myeloma who attained plateau to evaluate the relationships between survival and posttreatment nadir M-protein levels and between survival and the response to treatment evaluated by the percent reduction in M-protein. Of the 127 patients comprising 92 IgG and 35 IgA myeloma patients with disease stages II or III, 51 (40.2%) attained plateau. For IgG myeloma patients who attained plateau, survival time was not affected by the percent reduction in M-protein (median survival, 59.5 months for responding patients versus 54.4 months for nonresponding patients, P = .6910). Posttreatment nadir M-protein level, however, did affect survival time (median survival, 61.2 months for <3000 mg/dL versus 25.7 months for >3000 mg/dL, P = .0439). These findings suggest that the posttreatment nadir M-protein level is a stronger discriminator of survival following plateau attainment than the percent reduction of M-protein in patients with IgG myeloma.
UI - 12149193
AU - Zangari M; Siegel E; Barlogie B; Anaissie E; Saghafifar F; Fassas A;
TI - Morris C; Fink L; Tricot G Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy.
SO - Blood 2002 Aug 15;100(4):1168-71
AD - Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, AR, USA. firstname.lastname@example.org
Ten percent of newly diagnosed myeloma patients treated with any type of chemotherapy develop deep venous thrombosis (DVT). Thalidomide has proven activity in refractory multiple myeloma (MM), and although single-agent thalidomide has minimal prothrombogenic activity, its combination with cytotoxic chemotherapy is associated with a significantly increased risk of DVT. We analyzed the inci
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