Myeloma

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Myeloma

  • cell myeloma
  • diagnosed multiple myeloma
  • multiple myeloma
  • plasma cell myeloma
  • refractory multiple myeloma
  • refractory myeloma

  • Terms modified by Myeloma

  • myeloma cell
  • myeloma cell line
  • myeloma growth
  • myeloma patient
  • myeloma plasma cell

  • Selected Abstracts


    Hematological malignancies in the island of Sardinia, 1974,1993: age and sex distributions and temporal changes in incidence

    HEMATOLOGICAL ONCOLOGY, Issue 3 2004
    G. Broccia
    Abstract We have collected, by an active retrospective survey, all the cases of hematologic malignancies (HM) newly diagnosed during the time period 1974,1993 in the resident population of Sardinia. Diagnosis was deemed valid, after consultation of clinical records, in more than 90% of the 7264 collected cases. The number of newly diagnosed cases by year more than doubled during the 20-year period investigated. This striking increase can be only partially accounted for by ageing of population. Indeed, age-specific and age-adjusted rates of most of HM increased during this period, although Hodgkin Disease (HD), Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) were notable exceptions. The observed increase in rates is likely, in a large part, to be fictitious, due to easier access to a health care system, which in the meantime, improved its diagnostic efficiency. This was particularly evident for Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) and some others myelo- and lympho-proliferative disorders, but its relevance declined after 1984,1989. A likely true increase in occurrence was evidenced for Non-Hodgkin Lymphomas (NHL) and similarly, although to a lesser extent and more doubtful, for Myelodysplasias (MDS) and Acute Myeloid Leukemia (AML). At the end of the studied period each type of HM presented age and sex distributions and age-adjusted rates that show only minor differences from those reported for other western countries. No argument emerged to suggest that any genetic peculiarities of the Sardinian population might have affected the occurrence of HM. The confounding effects of improved diagnostic efficiency have prevented a reliable assessment of influence on incidences of environmental and socio-economic changes that, in relatively recent times, have occurred in Sardinia. Copyright © 2005 John Wiley & Sons, Ltd. [source]


    Role of the Bone Marrow Microenvironment in Multiple Myeloma,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2002
    G. David Roodman M.D., Ph.D.
    Abstract On June 26,27, 2001, the Sixth Research Roundtable in Multiple Myeloma, entitled "The Role of the Bone Microenvironment in Multiple Myeloma," was held and focused on the biology of cell-to-cell interactions, the mediators of bone disease, and novel treatment strategies for myeloma. Studies on cell-cell interactions showed that vascular cell adhesion molecule 1, expressed by local endothelial and stromal cells, binds to tumor cell surface integrins in which expression may be increased by tumor cell-derived chemokines such as macrophage inflammatory protein (MIP) 1,. These adhesive interactions increase production and release of vascular endothelial growth factor (VEGF). Studies on myeloma bone disease showed the ligand for receptor activator of nuclear transcription factor-,B (RANKL) was expressed on tumor cells and stromal cells associated with myeloma cells and was critical for osteoclast-induced osteolysis. Blockade of RANKL suppressed osteoclast maturation, bone resorption, and tumor development. Bisphosphonates, in addition to reducing osteoclast mobility and inducing osteoclast apoptosis, also decreased tumor cell adhesion to stroma. Immunomodulatory drugs such as thalidomide analogues targeted these tumor cell-stromal cell interactions, blocking both secretion of cytokines and activation of intracellular signaling pathways required for tumor survival and growth. These agents induced tumor cell apoptosis, decreased neovascularization, and potentiated natural killer cell activity. The proteasome inhibitor PS-341 also prevented expression of adhesion molecules and cytokines and triggered tumor cell apoptosis, even in drug-resistant cell lines, while showing minimal activity in healthy cells. In addition, potential therapeutic agents under investigation, which included RANKL antagonists, protein prenylation inhibitors, and osteoblast growth factors, were discussed. [source]


    Thalidomide-associated neuropathy in multiple myeloma

    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004
    S Morino
    Thalidomide is a neurotoxic immunomodulating agent currently used in Multiple Myeloma (MM). We prospectively evaluated the frequency and characteristics of peripheral neuropathy in a continuous series of 25 patients (13 M, 12 F; age 38,60, median 55 yrs) treated with thalidomide for MM. Patients underwent a neurological and neurophysiological evaluation before starting thalidomide therapy and monthly throughout duration of treatment. Sixteen patients (5 M, 11 F) developed neurophysiological characteristics of axonal sensitive damage and/or clinical peripheral neuropathy with distal sensory symptoms; treatment duration ranged between 95 and 572 days (median 298) in patients with neuropathy, and 49,264 days (median 162) in patients without neuropathy; the total amount of thalidomide taken ranged between 26 and 169 g (median 83 g) for patients with neuropathy and 13,170 g (median 51 g) for those without. In four patients, ENG alterations appeared before clinical symptoms, while in two patients they were not followed by clinical symptoms. In the remaining three patients, clinical symptoms preceded neurophysiological alterations. Age at onset of MM, disease duration before thalidomide therapy was started, total dose, duration of therapy and previous treatments were not correlated with neuropathy (multivariate logistic regression analysis). Female gender was a risk factor for developing neuropathy (OR 7.7). [source]


    Eradication of Multiple Myeloma and Breast Cancer Cells by TH9402-mediated Photodynamic Therapy: Implication for Clinical Ex Vivo Purging of Autologous Stem Cell Transplants,

    PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2000
    N. Brasseur
    ABSTRACT High-dose chemotherapy combined with autologous transplantation using bone marrow or peripheral blood-derived stem cells (PBSC) is now widely used in the treatment of hematologic malignancies as well as some solid tumors like breast cancer (BC). However, some controversial results were recently obtained in the latter case. The presence of malignant cells in the autograft has been associated with the recurrence of the disease, and purging procedures are needed to eliminate this risk. The aim of this study was to evaluate the potential of the photosensitizer 4,5-dibromorhodamine methyl ester (TH9402), a dibrominated rhodamine derivative, to eradicate multiple myeloma (MM) and BC cell lines, while sparing more than 50% of normal pluripotential blood stem cells from healthy volunteers. The human BC MCF-7 and T-47D and MM RPMI 8226 and NCI-H929 cell lines were used to optimize the photodynamic purging process. Cell concentration and the cell suspension thickness as well as the dye and light doses were varied in order to eventually treat 1,2 L of apheresis. The light source consisted of two fluorescent scanning tubes emitting green light centered about 515 nm. The cellular uptake of TH9402 was measured during the incubation and washout periods and after photodynamic treatment (PDT) using spectrofluorometric analysis. The limiting dilution assay showed that an eradication rate of more than 5 logs is obtained when using a 40 min incubation with 5,10 ,M dye followed by a 90 min washout period and a light dose of 5,10 J/cm2 (2.8 mW/cm2) in all cell lines. Agitating the 2 cm thick cell suspension containing 20 ◊ 106 cells/mL during PDT was essential for maximal photoinactivation. Experiments on mobilized PBSC obtained from healthy volunteers showed that even more drastic purging conditions than those found optimal for maximal eradication of the malignant cell lines were compatible with a good recovery of hematopoietic progenitors cells. The absence of significant toxicity towards normal hematopoietic stem cells, combined with the 5 logs eradication of cancer cell lines induced by this procedure suggests that TH9402 offers an excellent potential as an ex vivo photodynamic purging agent for autologous transplantation in MM and BC treatment. [source]


    Myeloma in monozygotic twin

    BRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2006
    Robert J. Cutting
    No abstract is available for this article. [source]


    Diagnosis and Management of Multiple Myeloma

    BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2002
    Scott A. Ely
    No abstract is available for this article. [source]


    Thalidomide for the Treatment of Refractory Multiple Myeloma: Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical Outcome

    CANCER SCIENCE, Issue 9 2002
    Tsunayuki Kakimoto
    Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2,4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (,2.0 ,g/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P=0.025), but not in non-responders (P=0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide. [source]


    Lack of Ku80 Alteration in Multiple Myeloma

    CANCER SCIENCE, Issue 4 2002
    Miyuki Kato
    Chromosomal rearrangement involving the immunoglobulin gene locus, as a result of marked chromosomal instability, is the hallmark of human multiple myeloma (MM) cells. Since Ku80 plays a key role in the non-homologous end-joining (NHEJ) system, we investigated whether Ku80 alteration contributes to this genetic instability by examining its status in 16 MM cell lines. Our study demonstrated a lack of Ku80 alterations at the protein, mRNA and gene level in 15 out of the 16 cell lines. Only the U266 cell line carried a missense mutation of Ser335Leu in one allele of the cDNA. Six marrow samples derived from myeloma patients also did not show any aberrant Ku80 protein, in terms of size. Accordingly, Ku80 alteration is unlikely to be involved in MM, in disagreement with a previous study reporting frequent presence of a 69-kD Ku80 variant (Ku86v) with reduced DNA binding activity in MM cells. [source]


    Current Awareness in Hematological Oncology

    HEMATOLOGICAL ONCOLOGY, Issue 2 2008
    Article first published online: 28 MAY 200
    In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Reviews; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]


    Current Awareness in Hematological Oncology

    HEMATOLOGICAL ONCOLOGY, Issue 4 2003
    Article first published online: 15 JAN 200
    In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]


    Current Awareness in Hematological Oncology

    HEMATOLOGICAL ONCOLOGY, Issue 4 2002
    Article first published online: 5 DEC 200
    In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]


    Current Awareness in Hematological Oncology

    HEMATOLOGICAL ONCOLOGY, Issue 3 2002
    Article first published online: 29 AUG 200
    In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]


    Current Awareness in Hematological Oncology

    HEMATOLOGICAL ONCOLOGY, Issue 4 2001
    Article first published online: 17 DEC 200
    In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]


    Thalidomide for the treatment of multiple myeloma

    CONGENITAL ANOMALIES, Issue 3 2004
    Yutaka Hattori
    ABSTRACT Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and anti-inflammatory effects. Recent studies have also demonstrated that thalidomide has antineoplastic activity via an antiangiogenic mechanism. Observations in the late 1990s that the microenvironment in the bone marrow plays a role in tumor progression in multiple myeloma provided an impetus to use thalidomide for the treatment of this disease. It is known that thalidomide monotherapy is effective in one-third of refractory cases, and in combination with glucocorticoids and/or antineoplastic drugs, thalidomide provides a response rate of more than 50%. Thus, thalidomide therapy is considered a standard approach for the treatment of relapsed and refractory myeloma. The exact mechanism of the antimyeloma effect of thalidomide is not yet clearly understood. Anti-angiogenic effects, direct activity in tumor cells such as the induction of apoptosis or G1 arrest of the cell cycle, the inhibition of growth factor production, the regulation of interactions between tumor and stromal cells, and the modulation of tumor immunity have been considered as possible mechanisms. In addition to its teratogenicity, the adverse effects of thalidomide have been general symptoms such as somnolence and headache, peripheral neuropathy, constipation, skin rash, and other symptoms. Although these adverse effects are generally reversible and mild, grade 3 and 4 toxicities such as peripheral neuropathy, deep venous thrombosis, neutropenia, and toxic dermal necrosis have occasionally been reported. The application of thalidomide therapy in patients with multiple myeloma is being broadened to include not only cases of refractory myeloma, but also previously untreated cases, as well as for maintenance therapy after hematopoietic stem cell transplantation and for the treatment of other hematological diseases. The safe use of this drug will depend on the establishment of diagnostic and treatment guidelines. In addition, the establishment of a nation-wide regulation system is urgently needed in Japan. [source]


    Multiparameter immunophenotyping by flow cytometry in multiple myeloma: The diagnostic utility of defining ranges of normal antigenic expression in comparison to histology,

    CYTOMETRY, Issue 4 2010
    Elisa Cannizzo
    Abstract Background: Numerous studies have reported on the immunophenotype of plasma cells (PCs) in monoclonal gammopathy of undetermined significance (MGUS) and in plasma cell myeloma (PCM), but very few have examined the immunophenotype of normal PCs. In this study, an objective definition of normal range of expression for each antigen was found on normal control PCs. Using these new ranges of normal expression (new method) is different from using a static 20% of PCs cut-off for all antigens as described in the literature (traditional method). These newly calculated normal ranges for each antigen were applied to our data, and compared to histologic and immunohistochemical findings. Methods: Bone marrow samples from 46 patients with PC neoplasms and 15 normal controls were studied. A minimum of 100 PC were analyzed for each patient and control sample. An 8-color staining method was applied to study the immunophenotype of PCs, using a BD FACSCanto II. Results: By the new ranges of normality calculated in this study it was determined that different antigens have different level of expression on polyclonal PCs. CD19 correlated with histology by both the traditional and new methods, but had superior correlation by the new method. Conclusions: This report is the first 8-color immunophenotypic study of PCM in which a "range of normal expression" for each antigen is defined. This is a critical step to help distinguish between a normal and neoplastic PC immunophenotype and discern which antigens are of diagnostic importance. © 2010 Clinical Cytometry Society [source]


    Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders,

    CYTOMETRY, Issue 4 2010
    Bruno Paiva
    Abstract In recent years, multiparameter flow cytometry (MFC) immunophenotyping has become mandatory in the clinical management of hematological malignancies, both for diagnostic and monitoring purposes. Multiple myeloma (MM) and other clonal plasma cell-related (PC) disorders should be no exception to this paradigm, but incorporation of immunophenotypic studies in the management of patients with PC disorders is still far from being routinely established in many diagnostic flow cytometry laboratories. For clonal PC disorders, MFC is of clear and established clinical relevance in: (1) the differential diagnosis between MM and other PC-related disorders; (2) the identification of high-risk MGUS and smoldering MM; (3) minimal residual disease investigation after therapy; additionally it may also be useful for (4) the definition of prognosis-associated antigenic profiles; and (5) the identification of new therapeutic targets. In this article, we review the clinical value of MFC in the study of PC disorders, with specific emphasis in those areas where consensus exists on the need to incorporate MFC into routine evaluation of MM and other clonal PC-related disorders. © 2010 Clinical Cytometry Society [source]


    Increased immature hematopoietic progenitor cells CD34+/CD38dim in myelodysplasia

    CYTOMETRY, Issue 2 2006
    Mariela B. Monreal
    Abstract Background Myelodysplastic syndromes (MDS) are clonal disorders affecting hematopoietic progenitor cells (HPC). Despite the relevance of clonal CD34+ cells in developing MDS, only few studies analyze the phenotype of this cell population. The aim of this study was to evaluate phenotypic changes on HPC in MDS that could reflect abnormalities in the differentiation process of stem cells. Methods We analyzed the expression of CD38 and HLA-DR on CD34+ cells by flow cytometry in 36 patients with MDS, as well as in healthy donors (n = 12) and patients with other hematological disorders: non-Hodgkin lymphomas and multiple myeloma, both in complete remission (CR) (n = 32); acute lymphoblastic leukemia in CR (n = 17); de novo acute myeloblastic leukemia (AML) at diagnosis (n = 22) and in CR (n = 37); and AML secondary to MDS at diagnosis (n = 19). Cases with available karyotype were grouped according to the International Prognostic Scoring System (IPSS). Results Compared to normal BM, the fraction of immature HPC, characterized as CD34+bright, intermediate FSC/SSC, and CD38dim, was significantly increased in high risk MDS and secondary AML, but not in low risk MDS, (P , 0.001, P = 0.03, and P = 0.7). De novo AML showed decreased immature HPC. High numbers of immature HPC correlated with higher IPSS risk groups (P = 0.05) and showed significant impact on disease progression (P = 0.03). Conclusion Our study confirms that evaluation of CD38 expression pattern on HPC is an easy and reproducible test that allows evaluating the immature subset of progenitor cells. Increased immature HPC in high risk MDS and secondary AML may reflect blocked differentiation of CD34+ cells in these diseases. © 2006 International Society for Analytical Cytology [source]


    Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytology

    CYTOPATHOLOGY, Issue 3 2010
    U. Handa
    U. Handa, S. Chhabra and H. Mohan Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytology Objective:, Plasma cell tumours represent autonomous proliferation of plasma cells and can manifest as multiple myeloma, monoclonal gammopathy of undetermined significance, variants of plasma cell myeloma or plasmacytoma. Methods:, We report 12 cases of plasma cell tumours, which were initially diagnosed as plasmacytoma on fine needle aspiration cytology (FNAC). The patients were further subjected to bone marrow examination, serum electrophoresis, urine examination for Bence,Jones proteins, and x-ray examination of the skeleton. Results:, The cytological smears from all cases were cellular and showed numerous plasma cells in varying degrees of maturity. Subsequent to investigations, five cases were labelled as multiple myeloma with secondary extramedullary plasmacytoma, three as solitary bone plasmacytoma and two as primary extramedullary plasmacytoma. In the remaining two cases, bone marrow and urine examination findings were not available, so a conclusive diagnosis of multiple myeloma or solitary plasmacytoma could not be made. Conclusion:, The study highlights the role of FNAC in the diagnosis of plasma cell tumours. Subsequent work-up and follow-up of these patients is important to rule out the presence of multiple myeloma. [source]


    Disseminated subcutaneous nocardiosis caused by Nocardia farcinica diagnosed by FNA biopsy and 16S ribosomal gene sequencing

    DIAGNOSTIC CYTOPATHOLOGY, Issue 4 2008
    Ronald M. Angeles M.D.
    Abstract Nocardia is an infrequent but significant cause of infections in the immunocompromised host. Clinical syndromes are varied and ranges from pulmonary, disseminated, cutaneous, and CNS involvement. Here we describe a case of disseminated subcutaneous nodules in a patient with multiple myeloma caused by Nocardia farcinica. The diagnosis was made by FNA biopsy which revealed gram positive filamentous bacilli in background of acute inflammation on smears. This was confirmed by 16S ribosomal gene sequencing. Prompt identification of N. farcinica is important because of its intrinsic resistance to broad spectrum cephalosporins and high risk of dissemination. Diagn. Cytopathol. 2008;36:266,269. © 2008 Wiley-Liss, Inc. [source]


    A rare case of multiple myeloma initially presenting with pseudoachalasia

    DISEASES OF THE ESOPHAGUS, Issue 6 2009
    Georgia Lazaraki
    SUMMARY Pseudoachalasia is a rare clinical entity with clinical, radiographic, and manometric features often indistinguishable from achalasia. Primary adenocarcinomas arising at the gastroesophageal junction or a tumor of the distal esophagus are the most frequent causes of pseudoachalasia. Rarely, processes other than esophagogastric cancers including chronic idiopathic intestinal pseudo-obstruction, amyloidosis, sarcoidosis, Chagas' disease, vagotomy, antireflux surgery, pancreatic pseudocysts, von Recklinghausen's neuroinomatosis, gastrointestinal stromal tumor, and other malignancies and rare genetic syndromes, may lead to the development of pseudoachalasia. Secondary achalasia is extremely rare, with less than 100 cases reported in the literature so far. Gastrointestinal manifestations in primary or secondary amyloidosis include abdominal pain, diarrhea, constipation, malabsorption, obstruction, motility disturbance, intestinal infarction, perforation, and hemorrhage; however, gastrointestinal tract involvement is asymptomatic in most instances. We present here a rare case of multiple myeloma initially presenting with dysphagia because of esophageal amyloidosis and manometric findings typical of achalasia. [source]


    The histone deacetylase inhibitor MS-275 induces p21WAF1/Cip1 expression in human Hep3B hepatoma cells

    DRUG DEVELOPMENT RESEARCH, Issue 2 2007
    Haiyuan Zhang
    Abstract MS-275 is a novel synthetic benzamide derivative histone deacetylase (HDAC) inhibitor, that has demonstrated antiproliferative activity in a variety of in vitro human cancer cell lines including breast, colon, lung, myeloma, ovary, pancreas, prostate, and leukemia. Currently, little information is available concerning the effects of MS-275 on liver cancer cells. In the current study, MS-275 was found to have potent actions against human hepatoma Hep3B cells including inhibition of cell proliferation and induction of apoptosis. MS-275 selectively up-regulated a cyclin-dependent kinase inhibitor, p21WAF1/Cip1 without alteration of p27WAF1. Expression of p21WAF1/Cip1 is considered to play a pivotal role in Hep3B cell growth arrest and induction of apoptosis. Induction of p21WAF1/Cip1 expression was accompanied by an accumulation of acetylated histones H3 and H4 associated specifically with p21WAF1/Cip1 gene. ChIP analysis revealed remarkable alterations in protein components bound to the promoter region of p21WAF1/Cip1 gene in response to MS-275 treatment. These included the degradation of HDAC1, HDAC3, and c-Myc, and as well as increased p300 and RNA polymerase II. The selective effect of MS-275 on the up-regulation of the p21WAF1/Cip1 gene whose expression was suppressed in the hepatoma cancer cell line indicated that it would be a very attractive approach in clinical liver cancer therapy. Drug Dev Res 68:61,70, 2007. © 2007 Wiley-Liss, Inc. [source]


    Nonsecretory multiple myeloma in a horse

    EQUINE VETERINARY EDUCATION, Issue 11 2007
    A. J. Morton
    First page of article [source]


    Management of multiple myeloma

    EUROPEAN JOURNAL OF CANCER CARE, Issue 1 2008
    B. SIROHI mbbs, dch
    No abstract is available for this article. [source]


    Patients' health beliefs and coping prior to autologous peripheral stem cell transplantation

    EUROPEAN JOURNAL OF CANCER CARE, Issue 2 2007
    E. FRICK md
    The aim of this study was to determine the associations between health locus of control (LoC), causal attributions and coping in tumour patients prior to autologous peripheral blood stem cell transplantation. Patients completed the Questionnaire of Health Related Control Expectancies, the Questionnaire of Personal Illness Causes (QPIC), and the Freiburg Questionnaire of Coping with Illness. A total of 126 patients (45% women; 54% suffering from a multiple myeloma, 29% from non-Hodgkin lymphomas, and 17% from other malignancies) participated in the study. Cluster analysis yielded four LoC clusters: ,fatalistic external', ,powerful others', ,yeah-sayer' and ,double external'. Self-blaming QPIC items were positively correlated with depressive coping, and ,fate or destiny' attributions with religious coping (P < 0.001). The highest scores were found for ,active coping' in the LoC clusters ,powerful others' and ,yeah-sayer'. External LoC and an active coping style prevail before undergoing autologous peripheral blood stem cell transplantation, whereas the depressive coping is less frequent, associated with self-blaming causal attributions. Health beliefs include causal and control attributions, which can improve or impair the patient's adjustment. A mixture between internal and external attributions seems to be most adaptive. [source]


    Delayed complete remission in a patient with multiple myeloma

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2008
    R. Ria
    Abstract We report a strikingly positive, late response to bortezomib in conjunction with pegylated liposomal doxorubicin in a 79-year old woman with multiple myeloma (MM). The patient obtained a partial remission after eight courses of therapy and a complete remission about 10 months after the end of therapy. This delayed complete remission may be similar to the spontaneous regression reported for other malignancies such as melanoma or lymphoma. We postulate that the immune response and a persistent anti-angiogenic effect of bortezomib could well explain the delayed complete remission in our patient. [source]


    First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2010
    Thomas Lund
    Abstract Objectives:, The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naÔve, previously untreated patients with myeloma. Methods:, Twenty newly diagnosed patients received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also studied in vitro. Results:, Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro bortezomib induced osteoblast proliferation and differentiation. Differentiation but not proliferation was inhibited by glucocorticoid treatment. Conclusions:, Bortezomib used as first-line treatment significantly increased collagen deposition in patients with multiple myeloma and osteolytic lesions, but the addition of a glucocorticoid to the treatment transiently inhibited the positive effect of bortezomib, suggesting that bortezomib may result in better healing of osteolytic lesions when used without glucocorticoids in patients that have obtained remission with a previous therapy. The potential bone-healing properties of single-agent bortezomib are currently being explored in a clinical study in patients who have undergone high-dose therapy and autologous stem cell transplantation. [source]


    Therapeutic approaches for newly diagnosed multiple myeloma patients in the era of novel drugs

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010
    Fortunato Morabito
    Abstract The treatment of newly diagnosed multiple myeloma (MM) has evolved rapidly over recent years. The availability of new effective drugs with novel mechanisms of action, such as thalidomide, lenalidomide and bortezomib in the last decade, has resulted in a new scenario expected to impact favorably on the outcome of patients with MM. The introduction of new drugs in the treatment of patients eligible for autologous stem cell transplantation (ASCT) has allowed for a significant increase of complete response rate with a positive impact on progression-free survival. In patients not eligible for ASCT, randomized trials have shown that both thalidomide and bortezomib when combined with melphalan and prednisone (MP) are superior to MP and are now considered the standard of care. Ongoing trials are assessing whether MP plus lenalidomide or the combination of lenalidomide plus dexamethasone should be considered an attractive treatment option, while additional studies are needed to determine the role of routine maintenance or consolidation therapy with these new drugs. This new therapeutic armamentarium in light of adequate prophylaxis and supportive care allows clinicians to greatly improve the survival perspectives for both young and elderly patients. In this review, we report updated data for the front-line therapy of MM, examining the role of new drugs either when administered as induction therapy before ASCT in younger patients or when combined with alkylating agents for the treatment of older patients. The most relevant articles on therapy of MM published from November 1982 to January 2010 (selected through PubMed), and recent meeting abstracts were used as sources for this review. [source]


    BSc2118 is a novel proteasome inhibitor with activity against multiple myeloma

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2010
    Jan Sterz
    Abstract Objectives:, The ubiquitin,proteasome system emerged as a new therapeutic target in cancer treatment. The purpose of this study was to elucidate the effects of the novel proteasome inhibitor BSc2118 on t(4;14) positive and negative multiple myeloma (MM) cells and normal peripheral blood mononuclear cells (PBMNC). Methods:, Human MM cell lines OPM-2, RPMI-8226, and U266 and primary MM cells from bone marrow aspirates were exposed to BSc2118. Cytotoxicity levels were evaluated using the MTT-test. BSc2118-induced apoptosis was analyzed by annexin-V assay. Further methods used included proteasomal activity determination, cell cycle analysis, western blot, and transcription factor assays. Results:, In OPM-2, RPMI-8226, U266 cell lines and primary MM cells, BSc2118 caused dose-dependent growth inhibitory effects. After 48 h, dose-dependent apoptosis occurred both in cell lines and primary myeloma cells irrespective of t(4;14). A significant G2-M cell cycle arrest occurred after 24 h. Furthermore, we observed a marked inhibition of intracellular proteasome activity, an increase in intracellular p21 levels, and an inhibition of NF-,B activation. The toxicity against PBMNC remained low, suggesting a broad therapeutic range of this agent. Conclusion:, Taken together, BSc2118 shows significant antimyeloma activity and may be considered as a promising agent in cancer drug development. [source]


    Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2010
    Meletios A. Dimopoulos
    Abstract Objectives:, Lenalidomide and dexamethasone (LenDex) is an active regimen for relapsed/refractory multiple myeloma (MM). However, there is limited data for the effect of LenDex on renal impairment (RI) and on renal reversibility. Patients & Methods:, Fifty consecutive patients with relapsed/refractory MM received LenDex in 28-d cycles. Median lines of previous therapies were 2 (range: 1,6). Lenalidomide was administered on days 1,21 according to creatinine clearance (CrCl), while dexamethasone was given at a dose of 40 mg on days 1,4 and 15,18 for the first four cycles and only on days 1,4 thereafter. Results:, Twelve patients (24%) had RI at baseline, defined as CrCl < 50 mL/min. Most patients were pretreated with either thalidomide or bortezomib and > 50% of them were refractory to both drugs. At least partial response was documented in 60.5% and 58% of patients with and without RI. Median progression-free survival (PFS) and overall survival (OS) for all patients was 9 and 16 months, respectively. RI was not associated with an inferior PFS or OS. There were no differences in the incidence of adverse events among patients with and without RI. Three of 12 patients with RI (25%) achieved complete renal response and two (16%) achieved minor renal response with LenDex. Conclusions:, We conclude that LenDex is an active treatment even in heavily pretreated MM. With dosing of lenalidomide according to renal function, LenDex can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in approximately 40% of patients with RI. [source]


    The proteasome inhibitor bortezomib inhibits FGF-2-induced reduction of TAZ levels in osteoblast-like cells

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2010
    Homare Eda
    Abstract Objectives:,Bortezomib (PS-341; Velcade‘), a proteasome inhibitor, is used as a therapeutic agent for multiple myeloma. Bortezomib has been shown to strongly induce osteoblast differentiation and elevate the levels of osteoblast-related differentiation markers in the serum of patients with myeloma. Bortezomib also reportedly increases the activity of the transcription factor, Runx2. However, the mechanism of action by which bortezomib-elevated Runx2 activity mediates osteoblast differentiation remains unclear. On the other hand, fibroblast growth factor 2 (FGF-2) is found at high levels in patients with multiple myeloma. We previously reported that FGF-2 reduces the levels of the transcriptional coactivator with PDZ-binding motif (TAZ). We therefore investigated the effects of bortezomib on TAZ protein levels in the presence of FGF-2. Methods: Osteoblastic MC3T3-E1 cells were treated with different concentrations of bortezomib in the presence or absence of FGF-2 and various biologic responses were investigated by immunoblotting, RT-PCR, quantitative PCR, and alizarin red staining. Results: We found that bortezomib inhibited FGF-2-induced reduction of TAZ levels through a pathway other than that used for proteasome inhibition, while maintaining TAZ function, which in turn, enhanced the expression of Runx2-transcribed osteogenic differentiation markers. Bortezomib also suppressed the antimineralization effect of FGF-2. Conclusions: These findings suggest that bortezomib inhibited FGF-2-induced reduction of TAZ and consequently stimulated osteogenic differentiation independently of proteasome inhibition. These findings may contribute to elucidate the osteolytic mechanism in multiple myeloma, and to the development of new drugs for multiple myeloma and other osteolytic diseases. [source]