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Cancer Treatment and Research

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https://www.readbyqxmd.com/read/27696269/waldenstrom-macroglobulinemia-genomic-aberrations-and-treatment
#1
Prashant Kapoor, Stephen M Ansell, Esteban Braggio
Waldenström macroglobulinemia (WM) is a rare, indolent, and monoclonal immunoglobulin M-associated lymphoplasmacytic disorder with unique clinicopathologic characteristics. Over the past decade, remarkable progress has occurred on both the diagnostic and therapeutic fronts in WM. A deeper understanding of the disease biology emanates from the seminal discoveries of myeloid differentiation primary response 88 (MYD88) L265P somatic mutation in the vast majority of cases and C-X-C chemokine receptor, type 4, mutations in about a third of patients...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696268/immunoglobulin-light-chain-systemic-amyloidosis
#2
Angela Dispenzieri, Giampaolo Merlini
Immunoglobulin light chain amyloidosis (AL) is a rare, complex disease caused by misfolded free light chains produced by a usually small, indolent plasma cell clone. Effective treatments exist that can alter the natural history, provided that they are started before irreversible organ damage has occurred. The cornerstones of the management of AL amyloidosis are early diagnosis, accurate typing, appropriate risk-adapted therapy, tight follow-up, and effective supportive treatment. The suppression of the amyloidogenic light chains using the cardiac biomarkers as guide to choose chemotherapy is still the mainstay of therapy...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696267/bone-disease-in-multiple-myeloma
#3
Homare Eda, Loredana Santo, G David Roodman, Noopur Raje
Bone involvement represented by osteolytic bone disease (OBD) or osteopenia is one of the pathognomonic and defining characteristics of multiple myeloma (MM). Nearly 90 % of patients with MM develop osteolytic bone lesions, frequently complicated by skeletal-related events (SRE) such as severe bone pain, pathological fractures, vertebral collapse, hypercalcemia, and spinal cord compression. All of these not only result in a negative impact on quality of life but also adversely impact overall survival. OBD is a consequence of increased osteoclast (OC) activation along with osteoblast (OB) inhibition, resulting in altered bone remodeling...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696266/transplantation-for-multiple-myeloma
#4
Yogesh S Jethava, Frits van Rhee
Multiple myeloma is a disorder characterized by accumulation of malignant plasma cells in the bone marrow, hypercalcemia, monoclonal protein, and end organ damage. Recently newer generation proteosome inhibitors, monoclonal antibodies and novel agents have been approved by FDA, which is undoubtedly increasing life expectancy of the patients. However, hematopoietic stem cell transplantation still remains the cornerstone of the treatment. In this chapter, we are discussing the autologous stem cell transplant, allogeneic stem cell transplant and total therapy trials with outcomes...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696265/role-of-the-immune-response-in-disease-progression-and-therapy-in-multiple-myeloma
#5
Susan J Lee, Ivan Borrello
Multiple myeloma (MM) is a hematologic cancer derived from malignant plasma cells within the bone marrow. Unlike most solid tumors, which originate from epithelial cells, the myeloma tumor is a plasma cell derived from the lymphoid cell lineage originating from a post-germinal B-cell. As such, the MM plasma cell represents an integral component of the immune system in terms of both antibody production and antigen presentation, albeit not efficiently. This fundamental difference has significant implications when one considers the implications of immunotherapy...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696264/treatment-of-mm-upcoming-novel-therapies
#6
Sagar Lonial
Treatment for myeloma has dramatically changed over the past decade, as has overall survival, due in large part to the development of new targeted agents. While proteasome inhibitors and immunomodulatory agents have contributed to improved outcomes, additional new options remain an unmet medical need. Classes of emerging agents include those targeting epigenetics, such as histone deacetylase inhibitors, monoclonal antibodies, and other emerging targets, such as kinesin spindle protein (KSP) inhibitors, cyclin dependent kinase (CDK) inhibitors, and nuclear protein export inhibitors...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696263/treatment-of-relapsed-refractory-multiple-myeloma
#7
Paola Neri, Nizar J Bahlis, Claudia Paba-Prada, Paul Richardson
Survival outcomes of patients with Multiple Myeloma (MM) have improved over the last decade due to the introduction of novel agents such as the immunomodulatory drugs thalidomide, lenalidomide (Len) and pomalidomide, and the proteasome inhibitors bortezomib (BTZ) and carfilzomib [1, 2]. However, despite these major advances, MM remains largely incurable and almost all patients relapse and require additional therapy [3]. The successful introduction of next generation novel agents including oral proteasome inhibitors, deacetylase inhibitors, and especially monoclonal antibodies as part of immunotherapy promises to further improve outcome...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696262/management-of-transplant-eligible-patients-with-newly-diagnosed-multiple-myeloma
#8
Jacob Laubach, Shaji Kumar
Treatment approaches for newly diagnosed myeloma have changed considerably during the past decade, along with a better understanding of the disease heterogeneity. Availability of new drug classes such as proteasome inhibitors and immunomodulatory drugs, and use of these drugs in combinations have led to higher response rates and deeper responses in the vast majority of patients with newly diagnosed myeloma. In addition to improved efficacy, these regimens are tolerated better than those with conventional chemotherapy drugs, which have reduced the early mortality seen in MM, while allowing for successful stem cell collection in patients undergoing stem cell transplant consolidation...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696261/treatment-of-newly-diagnosed-elderly-multiple-myeloma
#9
Guillemette Fouquet, Francesca Gay, Eileen Boyle, Sara Bringhen, Alessandra Larocca, Thierry Facon, Xavier Leleu, Antonio Palumbo
Multiple myeloma (MM) is a disease of the elderly, with a median age at diagnosis of approximately 70 years old, and more than 30 % of patients aged >75 years. This latter and very elderly population is going to significantly rise in the near future given the increase in life expectancy in Western countries, and, most importantly, global health status of elderly patients is improving, justifying appropriate treatments. Changes in treatment paradigm from the old melphalan-prednisone regimen used since the 1970s to its use as a backbone in a nontransplant setting since the late 1990s have highlighted different subgroups in elderly MM...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696260/multiple-myeloma-minimal-residual-disease
#10
Bruno Paiva, Ramón García-Sanz, Jesús F San Miguel
Assessment of minimal residual disease (MRD) is becoming standard diagnostic care for potentially curable neoplasms such as some acute leukemias as well as chronic myeloid and lymphocytic leukemia. Although multiple myeloma (MM) remains as an incurable disease, around half of the patients achieve complete remission (CR), and recent data suggests increasing rates of curability with "total-therapy-like" programs. This landscape is likely to be improved with the advent of new antibodies and small molecules. Therefore, conventional serological and morphological techniques have become suboptimal for sensitive evaluation of highly effective treatment strategies...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696259/targeting-the-bone-marrow-microenvironment
#11
Michele Moschetta, Yawara Kawano, Klaus Podar
Unprecedented advances in multiple myeloma (MM) therapy during the last 15 years are predominantly based on our increasing understanding of the pathophysiologic role of the bone marrow (BM) microenvironment. Indeed, new treatment paradigms, which incorporate thalidomide, immunomodulatory drugs (IMiDs), and proteasome inhibitors, target the tumor cell as well as its BM microenvironment. Ongoing translational research aims to understand in more detail how disordered BM-niche functions contribute to MM pathogenesis and to identify additional derived targeting agents...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696258/role-of-endothelial-cells-and-fibroblasts-in-multiple-myeloma-angiogenic-switch
#12
Domenico Ribatti, Angelo Vacca
Multiple myeloma (MM) mainly progresses in bone marrow (BM). Therefore, signals from the BM microenvironment are thought to play a critical role in maintaining plasma cell growth, migration, and survival. Reciprocal positive and negative interactions between plasma cells and microenvironmental cells, including endothelial cells (ECs) and fibroblasts may occur. The BM neovascularization is a constant hallmark of MM, and goes hand in hand with progression to leukemic phase. Microenvironmental factors induce MMECs and fibroblasts to become functionally different from monoclonal gammopathy of undetermined significance (MGUS) ECs (MGECs), i...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696257/epigenetics-in-multiple-myeloma
#13
Siobhan V Glavey, Salomon Manier, Antonio Sacco, Karma Salem, Yawara Kawano, Juliette Bouyssou, Irene M Ghobrial, Aldo M Roccaro
Multiple myeloma is characterized by clonal proliferation of plasma cells within the bone marrow resulting in anemia, lytic bone lesions, hypercalcemia, and renal impairment. Despite advanced in our understanding of this complex disease in recent years, it is still considered an incurable malignancy. This is, in part, due to the highly heterogenous genomic and phenotypic nature of the disease, which is to date incompletely understood. It is clear that a deeper level of knowledge of the biological events underlying the development of these diseases is needed to identify new targets and generate effective novel therapies...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696256/genomic-aberrations-in-multiple-myeloma
#14
Salomon Manier, Karma Salem, Siobhan V Glavey, Aldo M Roccaro, Irene M Ghobrial
Multiple myeloma (MM) is a genetically complex disease. The past few years have seen an evolution in cancer research with the emergence of next-generation sequencing (NGS), enabling high throughput sequencing of tumors-including whole exome, whole genome, RNA, and single-cell sequencing as well as genome-wide association study (GWAS). A few inherited variants have been described, counting for some cases of familial disease. Hierarchically, primary events in MM can be divided into hyperdiploid (HDR) and nonhyperdiploid subtypes...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696255/vision-statement-for-multiple-myeloma-future-directions
#15
Kenneth C Anderson
There has been great progress in the management and patient outcome in multiple myeloma due to the use of novel agents including immunomodulatory drugs and proteasome inhibitors; nonetheless, novel agents remain an urgent need. The three promising Achilles heals or vulnerabilities to be targetted in novel therapies include: protein degradation by the ubiquitin proteasome or aggresome pathways; restoring autologous antimyeloma immunity; and targeting aberrant biology resulting from constitutive and ongoing DNA damage in tumour cells...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27696254/mgus-and-smoldering-multiple-myeloma-diagnosis-and-epidemiology
#16
María-Victoria Mateos, Ola Landgren
Monoclonal gammopathy of undetermined significance (MHUS) is characterized by the presence of a serum M-protein less than 3 g/dL, less than 10 % clonal plasma cells in the bone marrow, and the absence of myeloma-defining event. Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence of ≥3 g/dL serum M-protein and/or 10-60 % bone marrow plasma cell infiltration with no myeloma-defining event. The risk of progression to multiple myeloma (MM) requiring therapy varies greatly for individual patients, but it is uniform and 1 % per year for MGUS, while higher (10 % per year) and not uniform for SMM patients...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27535400/small-cell-lung-cancer
#17
Erica B Bernhardt, Shadia I Jalal
Small cell lung cancer (SCLC) is an aggressive cancer of neuroendocrine origin, which is strongly associated with cigarette smoking. Patients typically present with a short duration of symptoms and frequently (60-65 %) with metastatic disease. SCLC is a heterogeneous disease including extremely chemosensitive and chemoresistant clones. For this reason, a high percentage of patients respond to first-line chemotherapy but rapidly succumb to the disease. SCLC is generally divided into two stages, limited and extensive...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27535399/multidisciplinary-care
#18
Megan E Daly, Jonathan W Riess
Optimal multidisciplinary care of the lung cancer patient at all stages should encompass integration of the key relevant medical specialties, including not only medical, surgical, and radiation oncology, but also pulmonology, interventional and diagnostic radiology, pathology, palliative care, and supportive services such as physical therapy, case management, smoking cessation, and nutrition. Multidisciplinary management starts at staging and tissue diagnosis with pathologic and molecular phenotyping, extends through selection of a treatment modality or modalities, management of treatment and cancer-related symptoms, and to survivorship and end-of-life care...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27535398/management-of-lung-cancer-in-the-elderly
#19
Archana Rao, Namita Sharma, Ajeet Gajra
Lung cancer is the leading cause of cancer-associated mortality in the USA. The median age at diagnosis of lung cancer is 70 years, and thus, about one-half of patients with lung cancer fall into the elderly subgroup. There is dearth of high level of evidence regarding the management of lung cancer in the elderly in the three broad stages of the disease including early-stage, locally advanced, and metastatic disease. A major reason for the lack of evidence is the underrepresentation of elderly in prospective randomized clinical trials...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27535397/palliative-care-in-lung-cancer
#20
Arvind M Shinde, Azadeh Dashti
Lung cancer is the most common cancer worldwide and is the leading cause of cancer death for both men and women in the USA. Symptom burden in patients with advanced lung cancer is very high and has a negative impact on their quality of life (QOL). Palliative care with its focus on the management of symptoms and addressing physical, psychosocial, spiritual, and existential suffering, as well as medically appropriate goal setting and open communication with patients and families, significantly adds to the quality of care received by advanced lung cancer patients...
2016: Cancer Treatment and Research
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