Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anaplastic large cell lymphomas (ALCLs) represent a heterogeneous group of malignant lymphoproliferative diseases. Most of the cases are of T-cell line with a loss of cell surface receptors but with a production of cytotoxic cytoplasmatic granules--immunohistochemically (IHC) positive perforin, granzyme B, and TIA-1. The diagnostics of ALCL is based on morphological findings and results of IHC, which further stratify ALCLs to basic immunophenotypes according to ALK (anaplastic lymphoma kinase) protein expression--ALCL CD30+ ALK+ and ALCL CD30+ ALK+. The morphological investigations are supplemented by karyotyping and/or by a demonstration of breakpoint at 2p23 harboring ALK gene (FISH), and by molecular detection of chimeric genes characteristic of ALK+ lymphomas (NPM-ALK, ATIC-ALK, TPM3-ALK, TFG-ALK, and some even rarer rearrangements). Molecular diagnostics is important in monitoring minimal residual disease. As some of the characteristic molecular changes were demonstrated in healthy individuals and in Hodgkin's disease by quantitative PCR, the validation of these findings demands further studies. ALK protein positive ALCLs affect patients in age categories up to the third decade, whereas ALK protein negative cases occur in older patients with an average age of 60 years. Both subgroups of lymphomas are aggressive but ALK+ lymphomas react well to systemic treatment, and have a more favorable prognosis. Primary skin ALCLs belong to a group of T-cell lymphoproliferative diseases of the skin and have, in the majority of cases, a favorable course without generalization.
 ...
PMID:[Anaplastic large-cell lymphoma: review]. 1463 6

We used 3'-minor groove binder (MGB) technology to develop consensus fluorogenically labeled probes of the immunoglobulin heavy-chain (IgH) gene for detecting minimal residual disease (MRD) in B-cell non-Hodgkin lymphoma (B-NHL). Sequence data from 59 patients with B-NHLs revealed a narrow consensus region as a result of somatic hypermutations and variable VH usage, indicating that it would be difficult to design ordinary non-MGB probes. MGB probes, characterized by shorter length but higher melting temperature, are more suitable for this situation than ordinary non-MGB probes. In fact, the present data indicated that about 20% more cases were detectable with MGB probes (34/59, 57.6%) than with the non-MGB probes (23/59, 39.0%) designed by Donovan et al. MGB technology is useful for the design of consensus fluorogenically labeled probes of the IgH gene for detecting MRD.
 ...
PMID:Short consensus probes with 3'-minor groove binder of the immunoglobulin heavy-chain gene for real-time quantitative PCR in B-cell non-Hodgkin lymphomas. 1503 98

Approximately 15% of all cases of childhood classical Hodgkin's disease (HD) express CD20, a B-cell marker associated with immunoglobulin heavy chain rearrangements. Immunoglobulin heavy chain rearrangements in Reed-Sternberg cells could be used to assess minimal residual disease (MRD), as was shown with immunoglobulin heavy chain patient-specific primers (PSPs) in non-Hodgkin's lymphoma. The aim of this study was to analyze pediatric HD for future design of immunoglobulin heavy chain PSP for MRD detection. DNA was extracted from paraffin-embedded tissue from unstained slides of 8 pediatric CD20+ nodular sclerosis HD cases and 10 CD20-nodular sclerosis HD cases. Immunoglobulin heavy chain polymerase chain reaction and sequencing were performed on 16 of 18 cases, which had adequate DNA for further analysis. Sequence analysis from 3 cases (19% of HD cases) demonstrated unique V(D)J regions, which could potentially be used to design PSP. Unique PSPs could be used to assess MRD in advanced-stage HD specimens. Future studies should focus on improved detection and analysis of more cases to identify appropriate specimens in assessing clinical implications of MRD detection.
 ...
PMID:Assessing immunoglobulin heavy chain rearrangements in pediatric CD20-positive and CD20-negative classic Hodgkin's disease. 1563 94

We have previously reported on the ex vivo generation of cytotoxic effector cells, termed cytokine-induced killer (CIK) cells, that have both in vitro and in vivo antitumor activity in murine models. We now report on our efforts for the large-scale expansion of CIK cells and also present preliminary results from a phase I clinical trial. Nine patients with advanced Hodgkin disease (n = 7) and non-Hodgkin lymphoma (n = 2), all of whom had relapsed after an autologous transplantation, were treated with escalating doses of CIK cells (3 patients at each dose level of 1 x 10(9) , 5 x 10(9) , or 1 x 10(10) cells). The CIK cells were produced by culturing unselected cells from steady-state apheresis products with interferon gamma, OKT3, and interleukin 2. After 21 days in culture, with the addition of fresh media and interleukin 2 every 3 to 4 days, the median culture was 97% viable (range, 61%-100%), 98% CD3 + (range, 66%-99%), 76% CD8 + (range, 27%-96%), 23% CD4 + (range, 6%-78%), 20% CD3 + CD56 + (range, 8%-58%), and <1% CD16 + 56 + (range, 0.2%-7.7%). The CD3 + CD56 + cells have previously been shown to exhibit the most cytotoxic activity. The absolute number of CD3 + CD56 + cells typically expanded 290-fold (range, 3- to 4000-fold) under these culture conditions. In vitro cytotoxic activity was measured against a human B-cell tumor line (OCI-Ly8). At a 40:1 effector-target cell ratio, CIK cells killed 32% (range, 2%-69%) of the target cells. A total of 21 infusions were administered to 9 patients. The number of CIK cells infused ranged from 1.0 x 10(9) to 1.0 x 10(10) per treatment. Toxicity was minimal, and there were no immediate adverse reactions to the infusions. Two patients had partial responses, and 2 patients had stabilization of disease: 1 for more than 18 months. Considering that these were heavily pretreated patients with advanced hematologic malignancies, we believe that CIK cells expanded in this fashion may have utility for the treatment of high-risk patients with evidence of minimal residual disease after autologous transplantation.
 ...
PMID:A phase I trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma. 1574 36

A comparison of flow cytometry (FC) and bone marrow biopsy (BMB) to evaluate bone marrow infiltration was made in 114 patients suffering from B-cell non-Hodgkin's lymphomas (NHLs; 51 at diagnosis, 63 during post-therapy follow-up). The following parameters were indicative of bone marrow infiltration: altered surface k/l ratio; specific immunophenotypic pattern in particular NHLs (CLL, mantle cell lymphoma, hairy cell leukemia). FC and BMB agreed in 89.5% of cases (i.e. both showed 48 positive and 54 negative cases). In discordant cases (7.9%) and in cases not evaluable by FC (2.6%) IgH rearrangement and bcl-1 gene expression, both evaluated by PCR methods, were used to detect bone marrow infiltration with higher precision. These results show that a more complex analysis of bone marrow is needed to diagnose bone marrow infiltration, particularly in samples with minimal residual disease.
 ...
PMID:[Bone marrow infiltration in B-cell non-Hodgkin's lymphomas: comparison between flow cytometry and bone marrow biopsy]. 1607 57

In Hodgkin's lymphoma (HL), PET imaging should be performed in all patients, particularly in stage I or II disease where change in staging will alter management. For aggressive Non-Hodgkin's lymphoma (NHL), PET imaging is valuable to provide a baseline for response evaluation. For indolent NHL, it is concluded that PET imaging is not generally indicated. For HL, a negative FDG-PET scan is highly indicative of long-term, disease-free survival and is particularly useful in the presence of residual CT mass. For aggressive NHL, a positive FDG-PET scan is predictive of disease persistence or recurrence. There is a significant incidence of false-negative FDG-PET scans, which in most cases means minimal residual disease that cannot be detected by the current instrumentation. For both NHL and aggressive HL, early assessment of response appears to be predictive of long-term outcome. Optimal time of FDG-PET scan during therapy needs to be determined. For indolent NHL, the high rate of false-negative FDG-PET scans raises questions to its clinical role in response evaluation. FDG-PET and PET-CT improve primary staging and restaging of lymphomas. Metabolic imaging will be the standard technology for assessment of therapy with documented prognostic value. Imaging during therapy may be valuable to individualize therapeutic protocols and to define chemosensitivity of tumor tissue. Minimal residual disease cannot be detected with current imaging devices.
 ...
PMID:Role of PET in lymphoma. 1608 46

During the past two decades, flow-cytometric immunophenotyping of lymphocytes has evolved from a research technique into a routine laboratory diagnostic test. Extensive studies in healthy individuals resulted in detailed age-related reference values for different lymphocyte subpopulations in peripheral blood. This is an important tool for the diagnosis of hematological and immunological disorders. Similar, albeit less detailed, information is now available for other lymphoid organs, e.g., normal bone marrow, lymph nodes, tonsils, thymus and spleen. Flow-cytometric immunophenotyping forms the basis of modern classification of acute and chronic leukemias and is increasingly applied for initial diagnostic work-up of non-Hodgkin's lymphomas. Finally, with multiparameter flow cytometry, it is now possible to identify routinely and reliably low numbers of leukemia and lymphoma cells (minimal residual disease).
 ...
PMID:Flow-cytometric immunophenotyping of normal and malignant lymphocytes. 1677 21

New nephelometric immunoassays specific for free immunoglobulin light chains (FLCs) improve detection of monoclonal proteins (M-protein). Initial studies with FLC have focused on multiple myeloma and amyloidosis. The goal of this study was to evaluate the frequency of monoclonal serum FLC in patients with other B-cell malignancies. Frozen sera from 226 patients with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) were tested for M-protein by the serum FLC assay and compared with standard protein electrophoresis (PEL) and immunofixation (IF). Overall, 24% (54/226) of samples had a detectable M-protein with 63% of these (34/54) FLC-positive. In 35% (19/54), the M-protein was only detectable by FLC analysis. Of the 208 NHL patients, 22% (46/208) had a detectable M-protein. Also, 13% (27/208) were positive for FLC and 16% (33/208) had a detectable M-protein by PEL/IF. Twenty-eighty percent (13/46) of NHL patients with M-proteins were detectable only by FLC analysis. Within NHL, the highest incidences of FLC presence were in patients with mantle cell (36%) and small lymphocytic (24%). Among CLL patients, 44% had an M-protein with 39% detected by FLC and 11% detected by PEL/IF. Notably, in 6 of 8 CLL patients, the M-protein was only detectable by the FLC method. Serum FLC can be detected in a substantial fraction of patients with NHL/CLL, and the FLC technique improves detection of M-proteins when combined with standard PEL/IF. Future studies are warranted to elucidate the role of serum FLC as biomarkers of disease, for monitoring of minimal residual disease, and as a prognostic factor for response and survival.
 ...
PMID:Serum-free light chain-a new biomarker for patients with B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia. 1738 97

Mantle cell lymphoma (MCL) accounts for 3-10% of all non-Hodgkin's lymphomas, with median overall survival not exceeding 3-4 years. Rituximab in combination with the Hyper-CVAD regimen appears the most promising regimen; thus, we adopted it as a first-line treatment strategy in a series of 24 patients. In addition to evaluation of clinical success of the regimen, we investigated a possible role of polymorphism in IgG Fc receptors, FCgammaRIIIa and FCgammaRIIa. The frequencies of FCgammaRIIIa-158 were as follows: V/V=4/24 (17%); V/F=16/24 (66%); F/F=4/24 (17%). Those of the FCgammaRIIa-131 polymorphism were H/H=11/24 (46%), H/R=9/24 (37%), R/R=4/24 (17%). The overall response rate was 62.5%, with 33% of complete responses (CRs) after four cycles of R-Hyper-CVAD. Two-year progression-free survival (PFS) was 78% for 158V/V patients vs 75% for cases carrying phenylalanine (p=0.88). When the FCgammaRIIa polymorphism was assessed, the 2-year PFS was 82% for 131H/H patients vs 75% for those carrying arginine (p=0.26). Eighty-three percent of cases achieved Polymerase Chain Reaction (PCR)-negativity: the progression rate was significantly influenced by the minimal residual disease clearance, with 12% progression in the subgroup of PCR-negative cases versus 67% progression in PCR-positive cases (p=0.008). The achievement of PCRnegativity was not significantly influenced by FCgammaR polymorphisms. Results confirm that rituximab plus Hyper-CVAD is an effective regimen for the induction of prolonged remission in patients with aggressive MCL and suggest that rituximab efficacy is independent of the FCgammaR polymorphisms.
 ...
PMID:The efficacy of rituximab plus Hyper-CVAD regimen in mantle cell lymphoma is independent of FCgammaRIIIa and FCgammaRIIa polymorphisms. 1759 28

Non-Hodgkin's lymphomas (NHL) represent a heterogenous group of diseases including low, intermediate and high grade histological subtypes. Most entities are sensitive to chemotherapy and radiotherapy. However, most relapsed patients are incurable with conventional treatment. The major reason for unsatisfactory long-term results in NHL is tumour cells that persist after standard treatment. New sensitive techniques have been developed to detect occult lymphoma cells. These cells might be eradicated by new immunotherapeutic agents with different modes of action, such as cytokines or antibody-based agents. In NHL, most experience has been accumulated with interferon-alpha, which seems to be effective against minimal residual disease (MRD). The experience with interleukin-2 and interleukin-3 is less convincing. Monoclonal antibodies have been used in their native form, or conjugated with radioisotopes or toxins to selectively destroy lymphoma cells. Such immunotoxins and radioisotope-coupled antibodies have shown promising results in early clinical trials, and are now being evaluated in patients with smaller tumour burdens.
 ...
PMID:Non-Hodgkin's Lymphoma: A Review of Immunotherapeutic Approaches to Treatment. 1802 May 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>