Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cast nephropathy is a severe complication of multiple myeloma. Binding of filtered monoclonal light chains (LC) with Tamm-Horsfall glycoprotein (THP) triggers heterotypic aggregation of these two proteins to form casts in the distal nephron of the kidney. To localize the LC binding site on THP, human THP was deglycosylated and underwent limited trypsin digestion in the presence or absence of a nephrotoxic LC known to bind THP. A 29.6-kD band was protected from trypsin digestion by the addition of LC. NH2-terminal amino acid sequence and amino acid analyses revealed this band was located between the 6th and 287th amino acid residues of THP. Six peptides located within this 29.6-kD fragment were synthesized and used as potential inhibitors of binding or aggregation of five different nephrotoxic LCs with THP. Peptide AHWSGHCCL (from amino acid 225 to 233) completely inhibited binding and aggregation of these proteins. Optimal inhibition required a cystine residue in this peptide. Truncation experiments demonstrated the entire sequence was necessary for ideal inhibition and the histidine residue explained the effects of pH on binding. These studies provided a basis for further study of LC-THP interaction and a potential approach toward the prevention of cast nephropathy.
 ...
PMID:Localization of a single binding site for immunoglobulin light chains on human Tamm-Horsfall glycoprotein. 904 77

Optimal methods of stem cell mobilization in multiple myeloma are undefined, and contaminating clonotypic cells could contribute to disease recurrence. A phase 2 trial of intravenous melphalan (60 mg/m2) and granulocyte colony-stimulating factor (G-CSF) (10 microg/kg/d) for mobilization was performed. To enhance reliability, contamination was assessed with 2 sensitive methods, immunoglobulin light and heavy chain variable region patient-specific limiting-dilution polymerase chain reaction (PCR). We evaluated 29 stem cell components (SCCs) from 15 patients; for 9 SCCs, only VL PCR was used because of light chain disease or technical problems with VH primers. For 20 SCCs, VL and VH PCR results were highly correlated (r2 = 0.93, P <.01), with 35% (7 of 20) having identical estimates. VH PCR gave significantly higher estimates for 8-and VL PCR for 5-SCCs, supporting the utility of using 2 methods. Estimated clonotypic contamination per SCC was 0.0009% (range, 0%-0.1%) or 0.5 x 10(4) clonotypic cells per kilogram (range, 0-41.2 x 10(4)/kg), and contamination correlated with CD34+ cells collected (r2 = 0.42, P <.01). Melphalan-mobilized SCCs contain minimal clonotypic contamination.
 ...
PMID:Melphalan-mobilized blood stem cell components contain minimal clonotypic myeloma cell contamination. 1264 34

Radiotherapy is an established treatment for metastatic bone pain. It may be delivered as a localised low dose treatment for localised bone pain or systemically for more widespread symptoms using hemibody external beam radiotherapy or intravenous bone-seeking radioisotopes. Bisphosphonates have been shown to reduce morbidity from bone metastases when given to patients with asymptomatic disease from myeloma and primary breast and prostate cancers. They also reduce metastatic bone pain in these sites. In the absence of randomised data comparing radiotherapy with bisphosphonates in the same clinical setting, comparison of the response rates from individual trials of the two modalities suggests that the overall pain response in all tumour types from radiotherapy is around 80% compared to a similar rate in myeloma with bisphosphonates but only 40% in solid tumours. Optimal use of the two modalities requires further investigation but since they have different dose limiting toxicities their incorporation in a combined modality approach to metastatic bone pain is rational using the concepts of additive effect and spatial co-operation in which bisphosphonates provide background control alongside acute pain relief using radiotherapy. They are also an important alternative for bone pain where radiation tolerance has been reached or radiotherapy is not readily available.
 ...
PMID:Bisphosphonates and radiation therapy for palliation of metastatic bone disease. 1292 72

High-dose therapy and autologous stem cell transplantation (HDT-ASCT) have significantly improved survival in multiple myeloma (MM). However, patients are not cured, responses are variable and only about 40% of patients achieve a complete response (CR). Optimal timing of the procedure and knowledge of the relapse kinetics may assist physicians when they consider this therapeutic modality for their patients. We analyzed myeloma tumor burden and kinetics before and after HDT-ASCT in a cohort of 265 patients. Disease burden was estimated from serial M-spike measurements and the data fitted to the Gompertz function to determine the general parameters for all patients. Functions that couple disease burden and kinetics with time to progression (TTP) were derived and used to determine the optimal timing of transplantation. Patients who achieve CR with the first episode of HDT-ASCT should not be routinely offered tandem transplantation but carefully monitored and transplanted at an optimal disease burden. If CR is not achieved with a first trial of HDT-ASCT, the probability of CR after a tandem second trial is approximately 10%. TTP after tandem transplants (with its higher associated mortality) cannot be superior to TTP achieved with optimally timed serial transplants. Individualized HDT-ASCT for patients with MM is possible and may optimize results.
 ...
PMID:In vivo and in silico studies on single versus multiple transplants for multiple myeloma. 1735 86

We previously showed that at least 5/mm(3) hematopoietic progenitor cells (HPCs) could be used as a marker for initiating autologous blood stem cell collection (ABSCC). However, the timing of efficient ABSCC following mobilization is still to be determined. We conducted a prospective, randomized comparison of 5/mm(3) versus 50/mm(3) peripheral blood (PB) HPCs as a surrogate marker to initiate efficient ABSCC. Forty-five consecutive patients, 26 with multiple myeloma (MM) and 19 with non-Hodgkin's lymphoma (NHL), were enrolled between October 2004 and October 2006. Chemotherapy was cyclophosphamide 4 g/m(2) for MM and ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), with or without Rituximab, for NHL. Circulating HPCs were monitored daily with the Sysmex SE9000 automated hematology analyzer, and harvested CD34+ cells were counted by flow cytometry. ABSCC was initiated when HPC levels reached at least 5/mm(3) (HPC5 group) or 50/mm(3) (HPC50 group). The median number of harvested CD34+ cells was 15.0 x 10(6)/kg and 21.0 x 10(6)/kg in the HPC5 and HPC50 groups, respectively (P = 0.23). Optimal collection (>5 x 10(6) CD34+ cells/kg) in a single session (day 1) was attained in 15 HPC5 patients (63%) and in 14 HPC50 patients (67%), and targeted collection of 5 x 10(6) CD34+ cells/kg was achieved in 100 and 95% of HPC5 and HPC50 patients, respectively (P = 0.47), with a median number of 1 apheresis in both groups (P = 0.58). There were no between group differences in optimal collection rate on day 1, median number of aphereses to achieve optimal collection, and overall optimal collection rate. HPC > or = 5/mm(3) and > or =50/mm(3) are both reliable indices for the timing of ABSCC.
 ...
PMID:A randomized comparison of peripheral blood hematopoietic progenitor cell level of 5/mm3 versus 50/mm3 as a surrogate marker to initiate efficient autologous blood stem cell collection. 1788 17

Bisphosphonate-associated osteonecrosis of the jaw (BON) is mainly observed in patients with multiple myeloma, and to a lesser extent in breast and prostate cancer patients receiving intravenous treatment with potent bisphosphonates. The incidence of BON increases with the duration of bisphosphonate therapy and with the potency of the used bisphosphonate. BON usually develops after tooth extraction or other oral surgery, and has proven difficult to treat. Optimal dental hygiene should be ensured prior to treatment initiation where possible, and once bisphosphonate treatment is instituted, oral surgery should be avoided if possible.
 ...
PMID:[Bisphosphonate-associated osteonecrosis of the jaw in patients with multiple myeloma]. 1933 Sep 57

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder of unknown etiology and characterized by various clinical manifestations and multiple organ involvement. It has been reported in association with POEMS syndrome and can progress to Kaposi's sarcoma or malignant lymphoma. The disease runs a more aggressive course and a poor prognosis. Optimal therapies have not been well established up to now. We here reported a case of rare MCD complicated with multiple myeloma who received bortezomib and achieved very good remission. To our knowledge, this is the first report on MCD in the setting of multiple myeloma with good response to bortezomib.
 ...
PMID:Treatment of multicentric Castleman's Disease accompanying multiple myeloma with bortezomib: a case report. 1940 Sep 35

Multiple myeloma (MM) is an incurable disease, and the goal of therapy is to prolong survival. Newer therapies (thalidomide, lenalidomide, and bortezomib) have contributed to the recent improvements in survival. Optimal integration of these newer therapies into standard practice may be aided by better methods of risk stratification. Supplementation of existing risk stratification methods with new prognostic information, such as cytogenetic data and gene expression profiles, may improve prognostication and help to identify appropriate treatment. The advent of newer therapies has also prompted a reassessment of traditional endpoints and goals of therapy, such as complete response. While complete response correlates with survival in some cases, the correlation is not consistent across all treatment regimens and patient groups, and is therefore not always the most appropriate goal of therapy. With the aim of prolonging survival, trials are currently evaluating newer therapies as long-term maintenance therapy or as prevention therapy for patients with smouldering myeloma. Given that these patients are often asymptomatic and free of clinically active disease, success in this setting depends highly on long-term tolerability of these agents. The available evidence suggests that their adverse event profiles are distinct, predictable, and manageable with careful monitoring and intervention as appropriate. Treatment of MM should therefore be tailored to the individual patient based on the goals of therapy, patient condition, expected adverse events, and patient preference.
 ...
PMID:Optimising patient outcomes in myeloma. 2047 87

Multiple myeloma remains a fatal plasma cell malignancy. However, new insights into the disease biology and immunology have identified molecular mechanisms, underling functional interactions between plasma cells and the bone marrow microenvironment that have become molecular targets of so-called "new drugs" such as thalidomide, lenalidomide, and bortezomib. Recently, the combinations of new drugs with melphalan and prednisone in elderly patients, and with autologous stem cell transplantation in induction and/or maintenance schedules in younger patients have significantly prolonged overall survival. Optimal combinations and timing are a matter of debate. Moreover, management of side effects is a key clinical target to improve long-term quality of life. Many randomized phase III studies are currently in progress to address these issues. Whether these new advancements in myeloma treatment will eventually translate into a long chronic phase or a monoclonal gammopathy of undetermined significance-like status for the majority of patients remains, however, still unanswered.
Clin Lymphoma Myeloma Leuk 2011 Jun
PMID:Management of myeloma: an Italian perspective. 2203 55

Optimal glycosylation with respect to the efficacy, serum half-life time, and immunogenic properties is essential in the generation of therapeutic antibodies. The glycosylation pattern can be affected by several different parameters during the manufacture of antibodies and may change significantly over cultivation time. Fast and robust methods for determination of the glycosylation patterns of therapeutic antibodies are therefore needed. We have recently presented an efficient method for the determination of glycans on therapeutic antibodies using a microfluidic CD platform for sample preparation prior to matrix-assisted laser-desorption mass spectrometry analysis. In the present work, this method is applied to analyse the glycosylation patterns of three commercially available therapeutic antibodies and one intended for therapeutic use. Two of the antibodies produced in mouse myeloma cell line (SP2/0) and one produced in Chinese hamster ovary (CHO) cells exhibited similar glycosylation patterns but could still be readily differentiated from each other using multivariate statistical methods. The two antibodies with most similar glycosylation patterns were also studied in an assessment of the method's applicability for quality control of therapeutic antibodies. The method presented in this paper is highly automated and rapid. It can therefore efficiently generate data that helps to keep a production process within the desired design space or assess that an identical product is being produced after changes to the process.
 ...
PMID:Discrimination between glycosylation patterns of therapeutic antibodies using a microfluidic platform, MALDI-MS and multivariate statistics. 2270 37


<< Previous 1 2 3 4 5 Next >>