292 research outputs found
HLA associated invariant chain gene expression in human B cell neoplasia.
No full textThe expression of the gene encoding the HLA-DR associated invariant chain (In-gene) in human B lymphocytes was analyzed by determining the level of invariant chain, mRNA in peripheral blood and bone marrow cells of several patients affected by hematological malignancies. In B cell neoplasms representative of different stages of B lymphocyte differentiation, In-gene activation was an early event that may occur in pre-B cells before immunoglobulin gene transcripts are detectable. The highest level of invariant chain mRNA were observed at an intermediate maturation stage corresponding to sIg, Ia, and B1 positive peripheral blood lymphocytes. At the terminal stage of B lymphocyte differentiation, the In-gene was turned off. In leukemic cell populations, the pattern of temporal activation of the In-gene corresponded to the pattern of activation of the genes encoding the HLA-DR alpha and beta chain
High-dose chemotherapy with hematopoietic stem cell transplantation for patients with advanced multiple myeloma
No full textBlood stem cell collections after mobilization with combination chemotherapy containing ifosfamide followed by G-CSF in multiple myeloma
No full textHigh-dose chemotherapy with autologous peripheral blood stem cell transplantation is the standard treatment of patients with multiple myeloma today. In this study we used a combination mobilizing chemotherapy containing ifosfamide with G-CSF before stem cell collection. The chemotherapy regimen consisted of ifosfamide (2,500 mg/m(2) days 1-3), epirubicin (100 mg/m(2) day 1) and etoposide (150 mg/m2 days 1-3) followed by G-CSF (5 mug/kg from day 5). In 30 younger patients (median age 51 years; range 41-60 years) who received the IEV regimen in 100% dosage, a median of 11.15 x 10(6) CD34(+) cells/kg (range 0-44.60 x 10(6) CD34(+) cells/kg) was collected. In 22 elder patients (median age 64 years; range 59-72 years) similar collection results were obtained with a median of 10.82 x 10(6) CD34(+) cells/kg (range 0.99-42.22 x 10(6) CD34(+) cells/kg) after the IEV regimen in 75% dosage. The pretreatment chemotherapy cycles before mobilization were fewer in elder patients with a median of 0 cycles (range 0-7 cycles) compared with younger patients with a median of 4 cycles (range 0-7 cycles). These collection results were favorable and allowed to support a tandem transplantation procedure in younger and elder patients in 97 and 95%, respectively. In the majority of patients, the hematological toxicity of IEV was of WHO grade 3/4. The extramedullary toxicity was mild to moderate and there were only few cases (5-10%) of relevant nephrotoxicity or neurotoxicity associated with the application of ifosfamide. Copyright (C) 2003 S. Karger AG, Basel
HLA DR associated invariant chain is highly expressed in chronic lymphocytic leukemia.
No full textTotal RNA extracted from peripheral blood lymphocytes of a patient with B-cell chronic lymphocytic leukemia (CLL) and the poly (A+) RNA was purified. A cDNA library was constructed and approximately 4,000 clones were screened in order to identify genes preferentially expressed in CLL. A relatively low repetition frequency characterizes the majority of the abundant mRNA species present in CLL lymphocytes. One clone, corresponding to the mRNA encoding the HLA-DR-associated invariant chain, was selected and its expression was examined in different leukemic cell populations and in normal tissues. DNA-RNA hybridization studies showed that the invariant chain mRNA (In-mRNA) is detectable in RNA preparations from human blood cells and their precursors, whereas no In-mRNA is found in several other tissues examined. Among various normal and leukemic leukocyte populations, the highest levels of In-mRNA are found in CLL. Therefore, a role of In-chain mRNA as a marker of CLL is proposed. Our data support a relationship between high levels of invariant chain mRNA and the out of cycle condition of CLL peripheral blood lymphocytes
Alteration and abnormal expression of the c myc oncogene in human multiple myeloma.
No full textStructural alterations of the c-myc oncogene in humanBurkitt’s lymphoma and mouse plasmacytoma suggest thatthis oncogene is involved in several B cell neoplasms. This report describes alterations in the c-myc locus with concomitant elevated expression of mRNA in the tumor cells of two of 37 patients withmultiple myeloma. In one case. somatic cell hybrid studies revealed that the cloned rearranged DNA was entirelyderived from chromosome 8. thus indicating a novel mechanismof c-myc activation different from that in Burkitt’slymphoma. Seven other patients exhibited five- to 12-foldoverexpression of c-myc RNA when compared with normalmarrow cells. Elevated mRNA expression in about onefourth of our patients suggests that the c-myc oncogenehas a pathogenetic role in the evolution of multiple myeloma
A multicenter phase II trial of 4'-iodo-4'deoxydoxorubicin in primary amyloidosis (AL)
No full textINTRODUCTION: 4'-Iodo-4'-deoxydoxorubicin (IDOX) has been reported to bind to and lead to the catabolism of amyloid deposits. A multicenter study attempted to develop a dosing schedule to confirm those results.
METHODS: Patients with biopsy-proven amyloidosis were required to have a cardiac ejection fraction > 50%, ventricular septal thickness 1,500 per microL, and platelets > 100,000 per microL. IDOX was administered intravenously over 1 hour at a dose of 15 mg per m2 once a week for 4 consecutive weeks. This therapy was repeated every 3 months up to 4 times.
RESULTS: Twenty-five previously treated and 15 untreated patients with primary amyloidosis (AL) received therapy. Fifteen patients had > 3 g of protein per day in the urine. Eleven patients had an ejection fraction < 60%. One, 2, 3, 4, and 5 organ systems were involved in 22, 10, 4, 3, and 1 patient, respectively. The median time between diagnosis and initiation of IDOX was 17.4 months. There were 6 responses (15%). Twelve of the patients have died
CONCLUSION: IDOX administered in this protocol was insufficiently active at the current dose
Epidemiology and pathophysiology of cancer-associated thrombosis
No full textVenous thromboembolism (VTE) is a common complication in patients with malignant disease. First recognised by Bouillard in 1823 and later described by Trousseau in 1844, multiple studies have since provided considerable evidence for a clinical association between VTE and cancer. Across all cancers, the risk for VTE is elevated 7-fold; in certain malignancies, the risk for VTE may be increased up to 28-fold. Venous thromboembolism is the second leading cause of death in patients with cancer; among survivors, complications commonly include recurrent VTE and post-thrombotic syndrome, and (more rarely) chronic thromboembolic pulmonary hypertension, which are costly, and have a profound impact on the patient's quality of life. Tumour cells can activate blood coagulation through multiple mechanisms, including production of procoagulant, fibrinolytic, and proaggregating activities, release of proinflammatory and proangiogenic cytokines, and interacting directly with host vascular and blood cells (e.g., endothelial cells, leukocytes, and platelets) through adhesion molecules. Increasing evidence suggests that elements of the haemostatic system also have a direct role in eliciting or enhancing angiogenesis, cell survival, and metastasis. Despite the problem posed by VTE in the setting of cancer, it is evident that a significant number of oncologists do not recognise the link between cancer, its treatment, and thrombogenesis. On 22 May 2009, a group of UK-based physicians met in London, UK, to evaluate recent data on cancer thrombosis. This article (1 of 4) briefly reviews key data on the epidemiology and pathophysiology of VTE as a context for a discussion and consensus statement developed by meeting attendees, on the implications of this information for UK clinical practice
Letter to the Editor. IgM-expressing Waldenstrom's macroglobulinemia tumor cells reveal a potential for isotype switch events in vivo
No full textPrognostic markers and criteria to initiate therapy in Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia.
No full textMIxed cryoglobulinemia with an IgMk monoclonal component: new biological and molecular features
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