Abstract：
:Despite the development of more effective therapies for multiple myeloma (MM) over the past decade, nearly all patients will eventually experience disease relapse and require further therapy. Designing the next generation of therapies for relapsed and refractory disease will depend on understanding the complex molecular pathogenesis of MM and mechanisms of resistance. Oncogenomic studies have identified many potential therapeutic targets and have led to emerging models of the multistep molecular pathogenesis of MM. The key to overcoming resistance may depend on interrupting the complex interactions between MM cells and the bone microenvironment. Direct interaction between MM cells and bone marrow cells activates pleiotropic signaling pathways that mediate growth, survival, and migration of MM cells as well as resistance to chemotherapy (known as cell adhesion-mediated drug resistance). The bone marrow also secretes growth factors and cytokines that maintain MM cells and inhibit apoptosis. Therefore, successful therapeutic strategies must target not only the MM plasma cell but also the bone microenvironment. The benefit of immunomodulatory drugs such as thalidomide and lenalidomide and the proteasome inhibitor bortezomib in relapsed/refractory MM is related to their ability to target both. Novel agents and combination strategies are building on the success of these agents and targeting synergistic pathways.
journal_name
Semin Hematoljournal_title
Seminars in hematologyauthors
Siegel DSdoi
10.1053/j.seminhematol.2012.05.005subject
Has Abstractpub_date
2012-07-01 00:00:00pages
S3-15eissn
0037-1963issn
1532-8686pii
S0037-1963(12)00039-Xjournal_volume
49 Suppl 1pub_type
杂志文章abstract：:Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder in which the patient's immune system reacts with a platelet autoantigen(s) resulting in thrombocytopenia due to immune-mediated platelet destruction and/or suppression of platelet production. Platelet membrane proteins, for reasons that are unclea...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2007.11.002
更新日期：2007-10-01 00:00:00
abstract：:The rationale for modulation of multidrug resistance (MDR) by inhibitors of the multidrug transporter, P-glycoprotein (P-gp) includes the following: (1) P-gp is expressed by human cancers, either at diagnosis or after failure of chemotherapy; (2) P-gp expression at diagnosis has been associated with a poor prognosis i...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1997-10-01 00:00:00
abstract：:Thrombus forms on catheters and other indwelling synthetic materials. Systemic heparin infusion decreases, but does not eliminate thrombus formation. The day is approaching when systemic heparinization may no longer be indicated to suppress catheter thrombogenesis. Passivation of catheters by heparin immobilization is...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1991-10-01 00:00:00
abstract：:In the era of modern communication, the physician and patient relationship has evolved to include an entirely new dimension-social media. This new dimension offers several opportunities for patient education, research and its dissemination, and professional development for health care providers; it can also serve as a...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2017.07.003
更新日期：2017-10-01 00:00:00
abstract：:There are now more than 25 million volunteer donors registered worldwide for patients in need of a life-saving hematopoietic cell transplant to cure blood disorders. Although a human leukocyte antigen (HLA)-matched donor remains the preferred stem cell source for transplantation, the use of a donor with limited HLA mi...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2016.07.003
更新日期：2016-10-01 00:00:00
abstract：:Recombinant activated factor VII (rFVIIa) is being increasingly used to treat bleeding associated with a variety of non-hemophilic coagulopathic indications, and its mechanism of action in these areas is under active investigation. Numerous studies have shown that FVIIa binds with low affinity to activated platelets; ...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2008.03.013
更新日期：2008-04-01 00:00:00
abstract：:Imatinib (Gleevec) (formerly STI571) is an orally bioavailable rationally developed inhibitor of the tyrosine kinases Bcr-Abl, Kit, and platelet-derived growth factor receptor (PDGFR). In 4 years of clinical development, more than 12,000 patients have been treated in the clinical development program. Imatinib was firs...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/shem.2003.50037
更新日期：2003-04-01 00:00:00
abstract：:Thrombosis is a common and potentially serious complication of immune-mediated heparin-induced thrombocytopenia (HIT). Discontinuation of heparin is a simple and important maneuver in patients with suspected HIT. Unfortunately, thrombosis often occurs even in those patients in whom heparin was discontinued because of ...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1998-10-01 00:00:00
abstract：:Anemia is frequently diagnosed in patients with cancer and its treatment is an important clinical problem. The deficiency in red blood cells (RBCs) can be a debilitating problem, and anemia correlates with poor performance status, deteriorates quality of life, and may negatively influence the prognosis of cancer patie...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2007.04.004
更新日期：2007-07-01 00:00:00
abstract：:Imatinib mesylate (Gleevec, Novartis Pharmaceuticals Corp, East Hanover, NJ; Glivec, Novartis Pharma AG, Basel, Switzerland), a signal transduction inhibitor with preferential effects against the tyrosine kinase activity of the protein product of the ABL proto-oncogene, induced hematologic responses in >or=90% of pati...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/shem.2002.36927
更新日期：2002-10-01 00:00:00
abstract：:From work particularly In the last two decades of the century, the cell populations forming blood cells can now be purified and cultured clonally so that blood cell formation can be analyzed in vitro. A large number of specific regulators of this process have been identified and mass-produced in recombinant form. Thre...
journal_title：Seminars in hematology
pub_type： 历史文章,杂志文章,评审
doi：
更新日期：1999-10-01 00:00:00
abstract：:Comprehensive study of the major chromosomal/molecular abnormalities in children and adults with acute lymphoblastic leukemia (ALL) has demonstrated prognostic utility for many of these anomalies, to the extent that cytogenetic and molecular genetic evaluations are now required for optimal clinical management of newly...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1016/s0037-1963(00)90018-0
更新日期：2000-10-01 00:00:00
abstract：:Though peripheral T-cell lymphoma (PTCL) is an area of significant unmet therapeutic need, a number of new treatment options are available for patients, especially those with relapsed or refractory disease. A plethora of drugs are now in development for PTCL, but drugs that truly target novel disease biology are notic...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2010.01.014
更新日期：2010-04-01 00:00:00
abstract：:Although often overlooked, the life of the patient with severe hemophilia is characterized by both intermittent and chronic pain. Bleeds into joints and muscles cause extensive pressure on sensory nerves and, following recurrent bleeds, joint destruction, and synovial reaction is accompanied by constant pains that are...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2005.11.024
更新日期：2006-01-01 00:00:00
abstract：:Macrocytic anemia, defined as a mean cell volume (MCV) ≥100 fL in adults, has a narrow differential diagnosis that requires evaluation of the peripheral blood smear as well as additional laboratory testing taken in conjunction with clinical information that includes patient history and physical examination findings. T...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2015.06.001
更新日期：2015-10-01 00:00:00
abstract：:High-dose chemoradiotherapy with allogeneic bone marrow or peripheral blood stem cell transplantation (SCT) is a potentially curative treatment for advanced or poor-prognosis hematological malignancies. This procedure was initially considered as a means to deliver supralethal doses of chemotherapy and radiation for th...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/shem.2002.30909
更新日期：2002-01-01 00:00:00
abstract：:Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Denmark) induces hemostasis in life- and limb-threatening bleeds and in major surgery of hemophilia A and B patients, regardless of inhibitor titer. A total of more than 6,500 patients have been treated, and NovoSeven has been administered in more than...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1016/s0037-1963(01)90147-7
更新日期：2001-10-01 00:00:00
abstract：:This report suggests modest changes in the criteria used for the diagnosis of ET and allows tentative recommendations concerning therapy. As outlined in Table I, we believe that absent stainable marrow iron does not necessarily indicate iron deficiency in these patients and that the serum ferritin and RBC mean corpusc...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1997-01-01 00:00:00
abstract：:The immunomodulatory drug (IMiD) lenalidomide is a more potent immunomodulator than thalidomide with respect to its effects on cytokine modulation and increased T-cell proliferation. Of all the IMiDs, clinical trial data are most mature for lenalidomide. In phase I studies, dose-limiting toxicities of lenalidomide wer...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2005.10.004
更新日期：2005-10-01 00:00:00
abstract：:The past decade has seen improvements in overall survival (OS) for patients with the two most common lymphoma histologies: diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). In FL, at least four independent datasets have confirmed these survival improvements. The monoclonal antibody rituximab has sign...
journal_title：Seminars in hematology
pub_type：
doi：10.1053/j.seminhematol.2008.02.005
更新日期：2008-04-01 00:00:00
abstract：:From a computational perspective, Bayesian methods can be viewed as a natural extension of familiar confidence intervals and significance tests, which sheds light on their meaning. This viewpoint shows that no special software is required to compute Bayesian results, leaving the distinctions between conventional and B...
journal_title：Seminars in hematology
pub_type： 杂志文章
doi：10.1053/j.seminhematol.2008.04.004
更新日期：2008-07-01 00:00:00
abstract：:In both normal and abnormal vascular biology, platelet-leukocyte-RBC-EC adhesive and functional interactions appear to play a significant role. The clinical hallmarks of the TTP/HUS syndromes, including prominent platelet aggregation and thrombi without prominent soluble coagulation system activation along with microa...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1997-04-01 00:00:00
abstract：:Hydroxyurea (HU) is the first widely used treatment to have an impact on the severity of disease in adult patients with sickle cell anemia, but limited data are available for younger patients or those with variant genotypes. We reviewed 324 months of experience with HU in 16 patients from 5.3 to 18.4 years of age trea...
journal_title：Seminars in hematology
pub_type： 临床试验,杂志文章
doi：
更新日期：1997-07-01 00:00:00
abstract：:Acute myeloid leukemia (AML) is a complex and heterogeneous disease with distinct age-associated genomic and epigenomic alterations. A large number of somatic karyotypic and molecular alterations have been identified in AML to date; however, very few predict outcome or identify potential therapeutic targets. Here we d...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2013.09.003
更新日期：2013-10-01 00:00:00
abstract：:Mantle cell lymphoma (MCL) has only recently been recognized as a separate biologically defined lymphoma entity. Due to its low incidence, many reports on clinical prognostic factors are limited by small patient numbers. The MCL International Prognostic Index (MIPI) was developed using data of more than 400 patients t...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2011.06.001
更新日期：2011-07-01 00:00:00
abstract：:The introduction of chimeric antigen receptor (CAR) T-cell therapy in acute lymphoblastic leukemia (ALL) has dramatically altered the landscape of treatment options available to children and adults with ALL. With complete remission induction rates exceeding 70% in most trials and FDA approval of one CD19 CAR T-cell co...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2020.07.002
更新日期：2020-07-01 00:00:00
abstract：:Familial thrombosis has long been considered as an autosomal dominant trait, caused by a dominant gene defect with a reduced penetrance for the disease. Recently, this view has changed and today familial thrombophilia is considered as a complex genetic disorder caused by the segregation of two or more gene defects (kn...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：
更新日期：1997-07-01 00:00:00
abstract：:Antibody-mediated rejection (AMR) is a major risk factor for graft loss following kidney transplantation. Traditional anti-humoral therapies provide suboptimal therapy and they do not deplete plasma cells, which are the source of antibody production. Proteasome inhibitors (PI) have been shown to deplete both transform...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2012.04.008
更新日期：2012-07-01 00:00:00
abstract：:This phase I trial of idarubicin (IDA) was conducted in 32 patients with acute leukemia and chronic myelogenous leukemia (CML) in blastic crisis (CML/BC) who either had failed to achieve a complete remission (CR) after initial induction therapy or had relapsed after CR. IDA was administered at dosages ranging from an ...
journal_title：Seminars in hematology
pub_type： 临床试验,杂志文章,评审
doi：
更新日期：1996-10-01 00:00:00
abstract：:Anemia of chronic disease (ACD) or inflammation may be secondary to infections, autoimmune disorders, chronic renal failure, or malignancies. It is characterized by an immune activation with an increase in inflammatory cytokines and resultant increase in hepcidin levels. In addition, inappropriate erythropoietin level...
journal_title：Seminars in hematology
pub_type： 杂志文章,评审
doi：10.1053/j.seminhematol.2013.06.006
更新日期：2013-07-01 00:00:00
