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

Monoclonal antibodies that selectively bind to pancreatic tumors may be useful in the therapy and diagnosis of pancreatic carcinoma. In this study we have examined the tumor localization of radioiodinated DU-PAN 1, a mouse monoclonal antibody that is selective for a human pancreatic cancer-associated antigen. After radiolabeling, both DU-PAN 1 intact monoclonal antibody and F(ab')2 fragments retained immunoreactivity and showed high affinity for the pancreatic tumor cell line CA13 in vitro. Paired-label biodistribution studies in nude mice bearing CA13 s.c. xenografts were performed. Mice received both 131I-labeled DU-PAN 1 immunoglobulin G2a or F(ab')2 fragment and 125I-labeled mouse myeloma immunoglobulin G2a or F(ab')2 fragment. Tumor uptake for 5-micrograms doses of DU-PAN 1 immunoglobulin ranged from 4.8 to 11.83% injected dose/g. Tumor uptake values for mice given 5-micrograms doses of DU-PAN 1 F(ab')2 ranged from 3.9 to 6.9% injected dose/g. Tumor uptakes of the respective myeloma controls were lower in all cases when compared with the DU-PAN 1 preparations. Tumor localization indices for 5-micrograms doses of DU-PAN 1 immunoglobulin were 3.0 and 24 h and 2.9 at 48 h. For 5-micrograms doses of DU-PAN 1 F(ab')2, tumor localization indices were 29.9 at 24 h and 90.0 at 48 h. In most cases, tumor:normal tissue ratios were greater than 3 at all time points, indicative of tumor selectivity for both DU-PAN 1 preparations, but the ratios were considerably higher using the DU-PAN 1 F(ab')2. The F(ab')2 fragment thus displays better tumor localization characteristics when compared with the intact immunoglobulin. Protein doses of DU-PAN 1 F(ab')2 of between 5 and 10 micrograms gave the best localization, although protein doses of up to 100 micrograms could be administered before apparent tumor saturation was seen.
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PMID:Radiolocalization of human pancreatic tumors in athymic mice by monoclonal antibody DU-PAN 1. 222 57

Patients with myeloma relapsing after tandem transplant have a poor survival and treatment options are limited. The role of additional salvage transplant procedures for these patients is unknown. To evaluate the benefit and identify prognostic factors, the outcome of 76 consecutive patients with recurrent myeloma after tandem transplant receiving salvage transplants (ST) was analyzed. Prior to ST, 23 patients (30%) had shown chemosensitive response to preceding salvage chemotherapy: two complete remissions (CR); eight near CRs (nCR: only immunofixation positive); 13 partial remissions (PR >or=75% reduction in M protein). Fifty received an autologous transplant, 22 a sibling-matched allogeneic transplant, and four a matched-unrelated allogeneic transplant. Overall response after ST was 59%: eight CRs (11%); 14 nCRs (18%); 23 PRs (30%). Overall survival (OS) at 2 years was 19%; 2 year event-free survival rate (EFS) 7%. On univariate analysis for survival, only pre-transplant chemosensitive relapse (P < 0.05), serum albumin >3 g/dl (P = 0.001), normal LDH (P = 0.04), and long interval between the second transplant and relapse/progression were significant beneficial factors. In a Cox proportional hazard model, chemosensitive relapse, and albumin >3 g/dl were significant for better OS: hazard ratio (HR) 1.4, 1.7, respectively, while normal LDH, and absence of CA13 were significant for better EFS: HR 1.8, 1.7, respectively. Patients with albumin >3 g/dl who had chemosensitive disease before ST (n = 16) had a median survival of 16 months, compared to 7 months (n = 34) and 2 months (n = 26) for patients with only one (n = 34) or no favorable prognostic factors (n = 28), respectively (P < 0.001). Their survival at 2 years post-ST was 43%, 17% and 11%, respectively. Our study suggests further transplantation should only be considered in the setting of a clinical trial in patients with favorable prognostic factors.
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PMID:Transplantation as salvage therapy for high-risk patients with myeloma in relapse. 1247 79

To identify a correlation between metaphase cytogenetics and relapse after reduced intensity conditioning (RIC) allotransplant for patients with multiple myeloma, data on 60 patients (median age 52) who received grafts from a sibling (n = 49) or unrelated donor (n = 11) were analyzed. Fifty-three patients (88%) showed chromosomal abnormalities (CA) before the allotransplant, including 42 with abnormalities involving 13q (CA13). Twenty-two patients (41%) relapsed post-allotransplant at a median of 165 days. Of these, 11 patients showed abnormal cytogenetics at the time of post-allotransplant relapse at a median of 167 days. Of 54 patients who developed graft-versus-host disease, relapse occurred in 19 of 48 patients (43%) with CA present before RCI allotransplant, versus 1 of 6 without CA (17%) (P = 0.06). Loss of CA before RIC allotransplant and disease status > PR after RIC allotransplant were significantly associated with a lower risk of post-allotransplant relapse with cytogenetic abnormalities; 5.2 vs 36%, and 18 vs 53%, (both P < 0.05), respectively. The current data suggests that myeloma associated with persistent clonal cytogenetic abnormalities is an entity which most likely escapes the effects of a graft versus myeloma activity, maybe because of acquisition of resistance to immunologic manipulations.
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PMID:Clonal cytogenetic changes and myeloma relapse after reduced intensity conditioning allogeneic transplantation. 1643 20