Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary cardiac lymphomas (PCLs), involving solely heart and/or pericardium at presentation, are rare events. They are frequently recognized at autopsy and generally carry a poor prognosis due either to a delay in the diagnosis or to infiltration of heart structures. We report here on two patients with large B-cell PCL. One is a 52-year-old man who presented with multiple cardiac tumors infiltrating mainly the right atrium and the inter-atrial septum. Diagnosis was established by ultrasound-assisted transesophageal biopsy of the intra-atrial multilobated tumor mass. He was treated with Rituximab-implemented high-dose sequential (R-HDS) chemotherapy followed by autologous peripheral blood stem cell transplantation, attaining complete response. He had no evidence of disease 24 months from onset. The second patient was a 70-year-old woman who presented with pericardial tamponade and low-output cardiac failure. Despite prompt pericadiocentesis and chemotherapy with cyclophosphamide and vincristine, she died 2 weeks later. Postmortem examination revealed large B-cell lymphoma proliferation confined to the heart. Whether primitive heart localizations represent an independent prognostic factor, and what specific measures should be adopted in patients with this rare presentation is the subject of the present report and review of the literature.
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PMID:Primary cardiac lymphoma: report of two cases occurring in immunocompetent subjects. 1516 Sep 56

Generally, there is a significantly lower risk of lymphoma relapse following allogeneic than after autologous stem cell transplant. Factors contributing to this lower risk of relapse include an absence of the use of ablative conditioning, with a tumor-free graft, and the generation of a graft-vs.-tumor (GVT) immune response. Allogeneic transplantation, however, has the possibility of graft-vs.-host disease (GVHD). The use of autologous and conventional allogeneic hematopoietic stem cell transplantation (HSCT) in follicular lymphoma, diffuse large cell lymphoma, chronic lymphocytic leukemia and multiple myeloma is discussed. Due to a 1-year transplant-related mortality of 30-40% and complications caused by GVHD, conventional, myeloablative, allogeneic transplantation is a high-risk option for low-grade lymphoproliferative disorders. Novel applications of allogeneic HSCT are described that take advantage of a GVT effect while reducing the risk of GVHD. Minimally myelotoxic pretransplant conditioning regimens allow host antigen-presenting cells to persist, enabling presentation of host minor histocompatibility antigens to donor T cells, causing a GVT response. Although complications may arise due to GVHD, non-myeloablative HSCT can be offered to patients previously ineligible for conventional high-dose treatment. A protocol developed in Seattle using a low-dose total body irradiation (TBI)-based conditioning regimen with immunosuppression using mycophenolate mofetil in combination with cyclosporin has been used in a multicenter trial. To overcome the problem of graft rejection fludarabine was later added to the protocol. A second protocol from a smaller trial used a preparative, conventional-dose regimen of fludarabine, given with cyclophosphamide. Rituximab was also given to provide synergistic action with the chemotherapy to enhance tumor control in the early post-transplant period to allow time for the establishment of the GVT effect. Following transplantation, GVHD prophylaxis was given using tacrolimus with methotrexate. A trial of a further variation of allogeneic HSCT, tandem auto/allo transplants, is described. First, high-dose therapy with autologous PBSC rescue was used to cytoreduce the disease. This was followed by a reduced-intensity or non-myeloablative allogeneic graft. This procedure was devised to take advantage of high-dose therapy and allogeneic HSCT. Results for non-myeloablative allogeneic HSCT are particularly promising in low-grade NHL and the GVT effect may augment response and delay or prevent relapse. However, for aggressive disease, non-myeloablative regimens are only indicated for patients with minimal disease, as the non-myeloablative regimens are unable to control the tumor before the generation of a GVT effect, and/or lack the ability to control rapidly proliferating disease. Patients with relapsed disease may require a higher-dose regimen or tandem transplant approach.
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PMID:Graft-vs.-lymphoma effect in various histologies of non-Hodgkin's lymphoma. 1520 32

Allogeneic hematopoietic cell transplantation (HCT) was originally developed as a form of rescue from high-dose chemoradiotherapy, which is given both to eradicate malignancy and provide sufficient immunosuppression for allogeneic engraftment. The first attempts of allogeneic HCT in humans met with little success. However, a better understanding of the complexities of the human leukocyte antigen (HLA) system has allowed selecting compatible sibling donors, and the development of postgrafting immunosuppressive regimens has helped prevent serious graft-versus-host disease, thereby changing the role of allogeneic HCT from a desperate therapeutic maneuver to a curative treatment modality for many patients with malignant hematological diseases. In addition, the establishment of large registries of HLA-typed volunteers has permitted finding suitable unrelated donors for many patients without family donors. Further advances in the immunogenetics of HLA, especially typing by molecular techniques, have improved results after unrelated HCT, which have begun resembling those obtained with HLA-identical sibling grafts, at least in young patients. Important advances have also been made in the prevention and treatment of infectious complications and in other areas of supportive care. Since the late seventies, it has been recognized that allogeneic immunocompetent cells transplanted with the stem cells, or arising from them, mediated therapeutic anti-tumor effects independent of the action of the high-dose therapy, termed graft-versus-tumor (GVT) effects. This has prompted the recent development of non-myeloablative conditioning regimens for allogeneic HCT that have opened the way to include elderly patients and those with comorbid conditions. Remaining challenges include further advances in the prevention and treatment of both severe graft-versus-host disease and infections. Also, progress in adoptive transfer of T cells with relative tumor specificity and disease-targeted therapy with agents such as Imatinib, Rituximab or radiolabeled monoclonal antibodies would make allogeneic HCT even more effective.
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PMID:Allogeneic hematopoietic cell transplantation as treatment for hematological malignancies: a review. 1554 4

Monoclonal antibodies (mAbs) therapies have been introduced to the many kinds of malignancies. Rituximab (Rituxan), a chimeric anti-CD20 monoclonal antibody, has improved clinical outcome in the patients with B cell non-Hodgkin's lymphoma (NHL) as a single agent as well as combination with chemotherapies including CHOP and stem cell transplantation. The efficacy has been reported in the patients with follicular lymphoma as well as aggressive NHL. The expression of CD20 should be confirmed by immunopathological staining or flow cytometry before the treatment. Gemtuzumab ozogamicin (Mylotarg), calicheamicin conjugates of anti-CD33 mAb, has been introduced in the treatment of AML. CD33 is not expressed by immature pluripotent stem cells even though expressed on myeloid progenitor cells. Mylotarg is internalized via CD33, however, detouched calicheamicin might be pumped out by multi-drug resistant related p glycoprotains (p-gp). The expression of CD33 and p-gp should be analyzed by flow cytometry before the treatment. We should give another caution to tumor-lysis syndrome and veno-occlusive disease.
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PMID:[Monoclonal antibody therapy and laboratory medicine]. 1565 71

We report a 78 year old male with prostatism, that was subjected to a prostate biopsy. The pathological study showed a microvascular lymphocytic infiltration. Four months later, the patients presented with reduced alertness, cough, dyspnea, fever and elevation of lactic dehydrogenase and erythrocyte sedimentation rate. Chest and abdominal CAT scans, bone marrow aspirate, protein electrophoresis and prostate specific antigen were normal. A re-evaluation of prostate biopsy showed an intravascular lymphoid infiltration, positive for CD45 and CD20, compatible with the diagnosis of intravascular lymphoma. Chemotherapy was started, but it was not tolerated by the patient and the response was partial. Therefore, treatment with monoclonal antibodies anti CD20 (Rituximab) was started. The tumor had a complete and prolonged (24 months) remission after the treatment
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PMID:[Intravascular lymphoma treated with anti CD20 monoclonal antibodies. Report of one case]. 1569 4

Lymphomatoid granulomatosis is a rare Epstein-Barr virus (EBV)-positive-B-cell lymphoproliferative disorder. Treatment options include corticosteroids, antiviral therapy, interferon-alpha and chemotherapy. However, long-term prognosis is poor and no therapeutic standard has been established yet. In a 21-year-old woman, a biopsy of mediastinal mass revealed lymphomatoid granulomatosis. Combined therapy with valganciclovir and interferon-alpha proved ineffective. In view of the CD20 expression of the tumor cells, monotherapy with rituximab was intiated. After 3 months a complete remission was achieved. Rituximab was continued for another 6 months with subsequent consolidation radiotherapy. This is the first report of an enduring complete remission (20 months) of a non-CNS lymphomatoid granulomatosis treated with rituximab.
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PMID:Successful treatment of mediastinal lymphomatoid granulomatosis with rituximab monotherapy. 1731 66

Rituximab, a chimeric Ab directed against CD20, induces apoptosis in targeted cells. Although the majority of B cell malignancies express the CD20 Ag, only approximately 50% of patients will respond to single-agent rituximab. The available data suggest that a decreased CD20 expression could account for the lack of response observed in some patients treated with rituximab. Despite the potential critical role of CD20 in the biology of B cell malignancies, the mechanisms controlling its expression are poorly understood. We evaluated the effect of the immune modulator agent bryostatin-1 on the expression of CD20 in non-Hodgkin's lymphoma cells. Using the B cell lines, DB and RAMOS, as well as tumor cells derived from a chronic lymphocytic leukemia patient, we demonstrated that bryostatin-1 enhanced the expression of both CD20 mRNA and protein. The enhanced expression of CD20 was associated with increased transcriptional activity of the CD20 gene, whereas the stability of CD20 mRNA was not affected. The effect of bryostatin-1 on CD20 expression in non-Hodgkin's lymphoma cells was mediated through the MAPK kinase/ERK signal transduction pathway and involved protein kinase C, but was independent of p38 MAPK and was insensitive to dexamethasone. Cells pretreated with bryostatin-1 were more susceptible to the proapoptotic effect of anti-CD20 Ab. Overall, these data demonstrate for the first time that ERK phosphorylation is required for the up-regulated expression of CD20 on B cell malignancies. The findings also suggest that bryostatin-1 and rituximab could be a valuable combined therapy for B cell malignancies.
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PMID:Enhanced expression of CD20 in human tumor B cells is controlled through ERK-dependent mechanisms. 1594 91

Overexpression of c-Myc and inactivation of p53 are hallmarks of human Burkitt's lymphomas. We had previously showed that transduction of murine p53-null bone marrow cells with a Myc-encoding retrovirus is sufficient for B lymphomagenesis. To address the role of Myc in tumor sustenance, we generated lymphomas induced by the Myc-estrogen receptor fusion protein (MycER). Engrafted hosts were continuously treated with the ER ligand 4-hydroxytamoxifen (4-OHT) to allow tumor formation. Subsequent inactivation of MycER via 4-OHT deprivation resulted in tumor stasis but only partial regression. At the cellular level, dormant neoplastic lymphocytes withdrew from mitosis and underwent further B-cell differentiation. Concomitantly, they up-regulated genes involved in lymphocyte proliferation and survival, most notably interleukin 10 receptor alpha (IL10Ralpha) and CD20, the target for antibody therapy with Rituxan. We found that overexpression of IL10Ralpha affords significant proliferative advantages and in 4-OHT-deprived animals correlates with eventual tumor relapse. Both dormant and relapsing tumors maintain IL10Ralpha expression suggesting that they might be sensitive to emerging drugs targeting the IL-10 pathway. Up-regulation of CD20 following Myc inactivation was also observed in immortalized human lymphocytes. Importantly, in this system, Myc(OFF)CD20(HIGH) cells were more prone to Rituxan-induced apoptosis than Myc(ON)CD20(MED). Thus, targeting Myc, while moderately effective on its own, shapes the phenotype of dormant neoplastic cells and sensitizes them to adjuvant molecular therapies.
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PMID:Inactivation of Myc in murine two-hit B lymphomas causes dormancy with elevated levels of interleukin 10 receptor and CD20: implications for adjuvant therapies. 1595 95

Epstein-Barr virus (EBV) is a ubiquitous viral pathogen in humans that has a unique ability to immortalize B-cells. In immunosuppressed individuals, EBV can produce non-neoplastic lymphoproliferative disorders involving various organs. We describe a case report of EBV-associated lymphoproliferative disorder in an immunocompetent 14-year-old male. The case provides a description of EBV-associated lymphoproliferation affecting the upper and lower respiratory tract. The massive submucosal infiltration of B-cells in the lingual tonsils, trachea, and bronchi produced near-complete airway obstruction resulting in tracheotomy. Neither surgical reduction of lingual tonsils nor treatment with steroids was of benefit. An extensive evaluation for immunodeficiency and neoplasia was normal. Treatment with rituximab, an anti-CD20 antibody, resulted in near-complete resolution of the infiltrative process, sufficient to allow decannulation. Rituximab is a treatment option for the rare occurrence of non-neoplastic, EBV-associated, lymphoproliferative disorders.
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PMID:Lymphoproliferative disorder of the airway of an adolescent without immunodeficiency. 1596 76

Expression of the complement-regulatory proteins (CRP) CD46, CD55 and CD59 represents a strategy used by tumor cells to evade complement-dependent cell cytoxicity stimulated by monoclonal antibodies. We have isolated two single-chain variable fragments (scFv) to CD55 and CD59 from a human phage-display library and from these scFv we have produced two miniantibodies (MB), MB-55 (against CD55) and MB-59 (against CD59), containing the human hinge-CH2-CH3 domains of IgG1. The specificity of the two MB for the corresponding CRP was assessed by ELISA using purified CD46, CD55 and CD59. MB-55 and MB-59 neutralized the inhibitory activity of CD55 and CD59, respectively, restoring the complement-mediated lysis of sheep and guinea pig erythrocytes that was otherwise inhibited by the two CRP. FACS analysis revealed binding of MB-55 and MB-59 to the lymphoma cell line Karpas 422. The two MB induced a two-fold increase in the complement-dependent killing of these cells stimulated by Rituximab, a chimeric anti-CD20 monoclonal antibody. Transfection of HEK293T cells with vectors encoding MB-55 or MB-59 markedly reduced the expression of CD55 and CD59. We conclude that the human antibodies MB-55 and MB-59 may represent a therapeutic tool to increase the complement-dependent killing activity of Rituximab in the treatment of non-Hodgkin's lymphoma.
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PMID:Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59. 1597 Dec 70


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