Z. Ahmed, A. Nasir, M. S. Shaikh, T. Moatter, A. Rasheed
{"title":"Therapeutic Targets and Signaling Pathways for Diagnosis of Myeloma","authors":"Z. Ahmed, A. Nasir, M. S. Shaikh, T. Moatter, A. Rasheed","doi":"10.5772/INTECHOPEN.81751","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.81751","url":null,"abstract":"Multiple myeloma (MM) is a malignancy of plasma cells that not only shows different clinical behavior but also depicts heterogeneous groups at molecular level. The prognosis of the disease has been dramatically changed with the arrival of new drugs in the past few years. In this context of better therapeutic agents, there are important challenges for accurate evaluation of patients by better prognostic and predictive tools. Transcriptomic studies have largely added to decipher MM heterogeneity, dividing MM patients into different subgroups according to prognosis. Micro-arrays and more recently RNA sequen- cing have helped in evaluating coding and non-coding genes, mutations, unique transcriptome convertors and different splicing events giving new information concerning biology, outcome and treatment options. Initial data from gene expression profiling studies have also pointed out genes that predict prognosis, i.e., CSK1-B, and can deliver phar- macogenomics and biologic vision into the pathophysiology, targeted treatment, and future direction. Importantly, we suggest that all prospective studies and clinical trials now accept genetic testing and risk stratification of MM patients. In this review, we discuss the part and effect of gene expression profiling in myeloma.","PeriodicalId":171832,"journal":{"name":"Update on Multiple Myeloma","volume":"125 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115884612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Management of Multiple Myeloma in Developing Countries","authors":"O. Nwabuko","doi":"10.5772/INTECHOPEN.76500","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.76500","url":null,"abstract":"Multiple myeloma (MM) is one of the commonest hematological malignancies of public health importance especially in low-income countries (LICs) of Sub-Saharan Africa. The two major challenges in the management of MM in developing countries are in the diagnosis and treatment. It poses diagnostic dilemma to physicians, especially orthopedic surgeons, because of the skeletal related events (SREs). Lack of modern equipment for diagnosis is a key player in late diagnosis of MM, and the management follows a palliative approach in the region. There is a gross inadequacy in the palliative care of MM in developing countries. The definitive treatment still remains melphalan-prednisone (MP) combination regimen as against the standard bortezomib-lenalidomide-dexamethasone (RVD) triplet regimen used in developed countries. Stem cell transplantation is still a far cry in the treatment of MM in the region due to its high cost and unavailability in the region. About 7.6% of MM patients survive up to 5 years postdiagnosis in LICs. This is below estimated 5 years postdiagnosis overall survival of 44.9% recorded by SEER cancer statistics review of 1975–2007 in the USA. This chapter highlights management and some of the diagnostic and therapeutic challenges encountered by people living with MM in developing countries.","PeriodicalId":171832,"journal":{"name":"Update on Multiple Myeloma","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132286213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Rudzianskiene, V. Rudžianskas, R. Dambrauskienė, R. Gerbutavičius
{"title":"The Role of Radiology and Radiotherapy for Multiple Myeloma","authors":"M. Rudzianskiene, V. Rudžianskas, R. Dambrauskienė, R. Gerbutavičius","doi":"10.5772/INTECHOPEN.75397","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75397","url":null,"abstract":"Skeletal-related events occur in 80% of patients with multiple myeloma (MM). Osteoporosis, osteoclastic destructions, pathological fractures of the bone, spinal cord and compression can impair patients’ quality of life and reduce survival. Many imaging techniques can be used for the detection of MM bone lesions. Many clinical studies suggest modern imaging techniques for their greater sensitivity. Radiotherapy is a treatment of choice for solitary plasmacytoma of the bone and extramedullary plasmacytomas. However, radiation treatment of MM can be used as a palliative approach for uncontrolled pain, impending pathological fractures and in the cases of spinal cord compression. Radiotherapy induces analgesic effect in 75–100% of patients and promotes a recalcification in 40–60%. In patients with spinal cord compression, radiation therapy is given along with dexamethasone, and up to half of patients may experience improvement. It is well known that pain perception, response to analgesics and pain relief effect of radiotherapy are quite different for multiple myeloma patients. Clinical, laboratory and genetic factors may influence the pain perception and analgesic effect of radiotherapy. Side effects of radiation are generally mild, are limited to the radiotherapy site and can be predicted.","PeriodicalId":171832,"journal":{"name":"Update on Multiple Myeloma","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122367118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Resistance Mechanisms to Novel Therapies in Myeloma","authors":"C. Wallington-Beddoe, D. Coghlan","doi":"10.5772/INTECHOPEN.77004","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.77004","url":null,"abstract":"The number of novel therapies for the treatment of multiple myeloma (MM) is rapidly increasing with proteasome inhibitors, immunomodulatory agents and monoclonal antibodies being the most well-known therapeutic classes whilst histone deacetylase inhibitors, selective inhibitors of nuclear export and CAR-T cells amongst others also being actively investigated. However, in parallel with the development and application of these novel myeloma therapies is the emergence of novel mechanisms of resistance, many of which remain elusive, particularly for more recently developed agents. Whilst resistance mecha- nisms have been best studied for proteasome inhibitors, particularly Bortezomib, class effects do not universally apply to all proteasome inhibitors, and within-class differences in efficacy, toxicity and resistance mechanisms have been observed. Immunomodulatory agents share the common cellular target cereblon and thus resistance patterns relate to cereblon expression and its pathway components. However, the cell surface antigens to which monoclonal antibodies are directed means these agents frequently exhibit unique within-class differences in clinical efficacy and resistance patterns. Despite the progres sive biological elucidation of resistance mechanisms to these novel therapies, attempts to specifically exploit these processes lag considerably behind and until such approaches become available, resistance to these therapies will remain a concern.","PeriodicalId":171832,"journal":{"name":"Update on Multiple Myeloma","volume":"113 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132039418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Ria, Antonio Giovanni Solimando, A. Melaccio, AzzurraSportelli, A. Vacca
{"title":"Angiogenesis and Antiangiogenesis in Multiple Myeloma","authors":"R. Ria, Antonio Giovanni Solimando, A. Melaccio, AzzurraSportelli, A. Vacca","doi":"10.5772/INTECHOPEN.76931","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.76931","url":null,"abstract":"Multiple myeloma progression is characterized by a dense interaction between cancer cells and bone marrow microenvironment. The interactions of myeloma cells with various stromal cells and extracellular matrix components are the main regulator of the biological processes that underlie the progression of the disease and of the classic symptomatology correlated. The bone marrow of myeloma patients has recognized autocrine and paracrine loops that regulate multiple signaling pathways and the malignant phenotype of plasma cells. One of the pivotal biological processes which are responsible for myeloma progression is the formation of new vessels from existing ones, known as angiogenesis. It represents a constant hallmark of disease progression and a characteristic feature of the active phase of the disease. Near angiogenesis, other two ancestral processes were active in the bone marrow: vasculogenesis and vasculogenic mimicry. These processes are mediated by the angiogenic cytokines, interleukins, and inflammatory cytokines directly secreted by plasma cells and stromal cells. Neovascularization is also mediated by direct interaction between plasma cells and the various components of bone marrow microenvironment. The observation of the increased bone marrow angiogenesis in multiple myeloma and its correlation with disease activity and overall survival led to consider angiogenesis as a new target in the treatment of multiple myeloma.","PeriodicalId":171832,"journal":{"name":"Update on Multiple Myeloma","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127395445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hematopoietic Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Therapies","authors":"K. Al-Anazi","doi":"10.5772/INTECHOPEN.79999","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.79999","url":null,"abstract":"Multiple myeloma is the second commonest hematologic malignancy. It is characterized by neoplastic proliferation of a single clone of plasma cells in the bone marrow producing a monoclonal immunoglobulin and ultimately causing various complications and organ dysfunction. Over the last 10 years, management of multiple myeloma has dramatically changed due to the introduction of several novel therapies that have improved the disease outcome and prognosis, as well as the quality of life of patients with myeloma due to their safety, tolerability and efficacy. Additionally, the widespread utilization of autologous hematopoietic stem cell transplantation, which is still the standard of care for transplant-eligible patients, and the implementation of new therapeutic strategies such as drug combinations in addition to consolidation and maintenance therapies have resulted in further improvements in response rates and survival in patients with multiple myeloma. This book chapter will be an update on the novel therapies and the recent treatment strategies in myeloma. The role of stem cell treatments in the era of novel therapies will be discussed thoroughly.","PeriodicalId":171832,"journal":{"name":"Update on Multiple Myeloma","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127849119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Ríos-Tamayo, D. Rodríguez, Y.L. Chang Chan, María José Sánchez Pérez
{"title":"Epidemiology of Multiple Myeloma","authors":"R. Ríos-Tamayo, D. Rodríguez, Y.L. Chang Chan, María José Sánchez Pérez","doi":"10.5772/INTECHOPEN.75396","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75396","url":null,"abstract":"Multiple myeloma is a heterogeneous hematological malignancy in which epidemiol- ogy plays an increasingly important role. In recent years, an unprecedented intensive research, including both clinical and molecular epidemiology, has deepened the knowl- edge about its pathogenesis, risk factors, and prognostic factors, leading also to the approval of new drugs. Although the etiology remains largely unknown, among the con- firmed risk factors, only obesity and the exposure to certain carcinogens are potentially preventable. Familial myeloma and occupational myeloma are topics of great interest. Most population-based cancer registries show a stable incidence or only a slight trend to increase. The diagnostic delay should be avoided as much as possible. Mortality rates, including early mortality, are progressively decreasing, although infection remains the leading cause of mortality. The outcome in terms of overall survival and health-related quality of life has remarkably improved, joining the group of potentially curable malignancies. Nowadays the clinical scenario is challenging. Clinical and epidemiological vari- ables of interest should be standardized in clinical records. Patients should be included in a population-based registry network. The clinical coordination of a multidisciplinary team in a specialized unit is needed in order to maximize the outcome of every patient.","PeriodicalId":171832,"journal":{"name":"Update on Multiple Myeloma","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124280331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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