Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several reports recently found that patients with B cell non-Hodgkin's lymphoma (NHL) had a higher carrier rate of hepatitis B surface antigen (HBsAg). The current study aimed to examine the hepatitis B virus (HBV) infection status of NHL patients in Taiwan, an HBV-endemic area. Serum HBV and serum hepatitis C virus were measured in 471 NHL patients and 1,013 non-lymphoma cancer patients enrolled between February 2000 and March 2007. Furthermore, nested polymerase chain reaction of HBV-DNA was used to examine the sera from selected patients in these two populations and healthy volunteers for the presence of occult HBV infection. The infection rates (as indicated by the rates of HBsAg and occult HBV) were compared between different groups. There was a higher incidence of HBV infection in B cell NHL patients (23.5%), especially patients with diffuse large B lymphoma, than solid tumor patients (15.6%, P = 0.001). Among HbsAg-negative patients, those with B cell NHL had a higher prevalence of occult HBV infection (6%) than those with non-lymphoma solid tumors and healthy volunteers, 0% and 0.9%, respectively (P = 0.005). B cell NHL patients, even HBsAg-negative B cell NHL patients, but not T cell NHL patients, have a higher incidence of HBV infection than patients with solid tumors. Our findings support the etiologic role of HBV infection in B cell NHL.
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PMID:High prevalence of occult hepatitis B virus infection in patients with B cell non-Hodgkin's lymphoma. 1832 83

B cells play a critical role in the pathogenesis of rheumatoid arthritis (RA) and other autoimmune diseases. Recently, a number of biologic agents that target B cells have been tested as therapies for these conditions. These agents either deplete B cells, by targeting cell-surface antigens such as CD20, or block B cell function, for example by inhibiting the activity of B cell survival factors such as BLyS. Of this group of agents, the first in clinical use has been rituximab, a chimeric monoclonal antibody that depletes B cells by binding to the CD20 cell-surface antigen. Initially introduced as a treatment for non-Hodgkin's lymphoma, rituximab is now approved for the treatment of RA. In this review we explore the rationale behind B cell-targeted therapy, highlight the results of clinical trials with rituximab in RA and other autoimmune diseases, and describe other emerging therapies directed at B cells.
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PMID:B cell-targeted therapy in autoimmune disease: rationale, mechanisms, and clinical application. 1860 33

Antibodies directed against B cells are in use for the treatment of non-Hodgkin's lymphoma and autoimmune disorders. The B-cell-restricted surface antigen CD79b, a signaling component of the B-cell receptor, has been shown as a promising antibody target in mouse efficacy models of systemic lupus erythematosus. Anti-CD79b antibody-drug conjugates (ADC), cytotoxic drugs linked through specialized chemical linkers to antibodies, are effective in mouse xenograft models of non-Hodgkin's lymphoma. We were interested in evaluating the systemic effects of anti-CD79b antibodies and ADCs in normal animals as a step toward the development of these molecules as therapeutics. As we were unable to identify any cell surface binding anti-human CD79b antibodies that were cross-reactive to other species, we developed an antibody to cynomolgus monkey (Macaca fascicularis) CD79b (anti-cyCD79b). The anti-cynomolgus antibody, anti-cyCD79b (10D10), and the maytansine (tubulin inhibitor)-conjugated ADC, anti-cyCD79b (10D10)-MCC-DM1, were administered to cynomolgus monkeys at approximately 30 mg/kg (6,000 microg DM1/m(2)) for two doses 3 weeks apart. Anti-cyCD79b and anti-cyCD79b-MCC-DM1 resulted in peripheral blood B-cell depletion of approximately 65% and approximately 94%, respectively. In addition, anti-cyCD79b-MCC-DM1 resulted in near-complete absence of splenic germinal centers, an observation supporting an effect on dividing B cells. Both molecules were well tolerated, with minimal findings for the antibody and findings for the ADC limited to the lymphoid and hematopoietic systems, liver, and peripheral nerves. These preclinical data suggest that targeting CD79b with antibodies or ADCs may provide safe and effective therapies for B-cell malignancies and autoimmune diseases.
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PMID:In vivo effects of targeting CD79b with antibodies and antibody-drug conjugates. 1980 77

This prospective study was conducted to find the effective vaccination schedule against hepatitis B virus (HBV) infection for children with hematological malignancies. Sixty patients ages 2-15 years old with hematological malignancies on chemotherapy, negative for hepatitis B surface antigen (HBsAg) and never vaccinated for HBV before, were vaccinated with 40 microg of vaccine at 0, 1 and 2 months. Antibody titers were measured 6 weeks after administration of last dose. Out of the 60 children enrolled, 5 died during the course of treatment and 4 dropped out before completion, leaving 51 for final analysis. More than 70% exhibited protective levels of antibodies (> 10 mIU/ml) against hepatitis B virus. There were no significant effects of age or sex on the antibody response, although antibodies were higher among girls (90.9%) than boys (65%). Patients with non-Hodgkin's lymphoma were found to exhibit a better antibody response than leukemic children (p = 0.024). Children with hematological cancers should be vaccinated with an escalated regimen of the vaccine.
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PMID:Escalated regimen of hepatitis B vaccine in childhood hematological malignancies while on chemotherapy. 2057 42

Hepatitis B virus (HBV) reactivation is a well-recognized complication that occurs in lymphoma patients who undergo chemotherapy. Only very few cases of HBV reactivation in patients with isolated antibody against hepatitis B surface antigen (anti-HBs) have been reported. We present a case of a 78-year-old woman diagnosed with diffuse large B cell non-Hodgkin's lymphoma who only displayed a positive anti-HBs, as the single possible marker of occult HBV infection, before starting therapy. She was treated with several chemotherapeutic regimens (including rituximab) for disease relapses during 3 years. Forty days after the last cycle of chemotherapy, she presented with jaundice, markedly elevated serum aminotransferase levels, and coagulopathy. HBV serology showed positivity for HBsAg, anti-HBc and anti-HBs. HBV DNA was positive. Antiviral treatment with entecavir was promptly initiated, but the patient died from liver failure. A review of the literature of HBV reactivation in patients with detectable anti-HBs levels is discussed.
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PMID:Fatal hepatitis B reactivation treated with entecavir in an isolated anti-HBs positive lymphoma patient: a case report and literature review. 2282 72

Radioimmunotherapy (RIT) has demonstrated efficacy with acceptable toxicity leading to approval in non-Hodgkin's lymphoma, but has been slower to develop for the treatment of advanced solid tumors. Prostate cancer (PC) represents a good candidate for RIT based upon high exposure to circulating antibodies at common disease sites with a specific, highly expressed cell-surface antigen of prostate-specific membrane antigen. Four phase I and II trials utilizing (177)Lu- or (90)Y-J591 have been reported. Long-term toxicity and chemotherapy administration was analyzed. As expected, the only serious toxicity observed was myelosuppression. Grade 4 thrombocytopenia occurred in 33.3% without significant hemorrhage and grade 4 neutropenia occurred in 17.3% with 0.07% febrile neutropenia. Nearly all subjects (97.3%) recovered to grade 0 or 1 platelets and all had complete neutrophil recovery. The majority (81.3%) received chemotherapy at any time, with 61.3% receiving chemotherapy following RIT. Ten subjects underwent bone marrow biopsies at some point in their disease course following RIT for low counts; all had diffuse PC infiltration without evidence of myelodysplasia or leukemia. As expected, myelosuppression occurs following therapeutic doses of RIT for men with metastatic castration-resistant PC. However, toxicity is predictable and self-limited, with the majority of patients who do not refuse able to receive cytotoxic chemotherapy following RIT.
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PMID:Bone marrow recovery and subsequent chemotherapy following radiolabeled anti-prostate-specific membrane antigen monoclonal antibody j591 in men with metastatic castration-resistant prostate cancer. 2398 81

Hybrid nanomaterials composed of synthetic and biological building blocks possess high potential for the design of nanomedicines. The use of self-assembling nanomaterials as "bio-mimics" may trigger cellular events and result in new therapeutic effects. Motivated by this rationale, we designed a therapeutic platform that mimics the mechanism of immune effector cells to cross-link surface receptors of target cells and induce apoptosis. This platform was tested against B-cell lymphomas that highly express the surface antigen CD20. Here, two nanoconjugates were synthesized: (1) an anti-CD20 Fab' fragment covalently linked to a single-stranded morpholino oligonucleotide (MORF1), and (2) a linear polymer of N-(2-hydroxypropyl)methacrylamide (HPMA) grafted with multiple copies of the complementary oligonucleotide MORF2. We show that the two conjugates self-assemble via MORF1-MORF2 hybridization at the surface of CD20(+) malignant B-cells, which cross-links CD20 antigens and initiates apoptosis. When tested in a murine model of human non-Hodgkin's lymphoma, the two conjugates, either administered consecutively or as a premixture, eradicated cancer cells and produced long-term survivors. The designed therapeutics contains no small-molecule cytotoxic compounds and is immune-independent, aiming to improve over chemotherapy, radiotherapy and immunotherapy. This therapeutic platform can be applied to cross-link any noninternalizing receptor and potentially treat other diseases.
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PMID:Cell surface self-assembly of hybrid nanoconjugates via oligonucleotide hybridization induces apoptosis. 2430 67

Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin's lymphoma which is confined to the central nervous system and may also affect intraocular structures. Despite high initial rates of response to methotrexate-based chemotherapy, more than 50% of patients will experience relapse and about 10% have disease that is refractory to chemotherapy. Outcome in patients who fail treatment is very poor, and therefore new therapeutic approaches that may increase the rate of complete response and the proportion of durable remission are sought. Based on the pivotal role that anti-CD20 therapy now plays in the treatment outcome of aggressive systemic B-cell lymphomas, a similar approach is commonly being adapted for PCNSL despite the lack of evidence for its effectiveness. This review examines the current status and level of evidence for the use of monoclonal antibodies against the CD20 surface antigen, which is present on normal and malignant B-cells in PCNSL. The review covers both systemic and local (intracerebrospinal fluid or intravitreal) administration of CD20 monoclonal antibodies in PCNSL. In addition, it scrutinizes the response criteria commonly reported for evaluation of treatment outcome. The importance of differentiating unconfirmed complete response from partial response is outlined and the lack of consensus on response criteria for atypical imaging presentations of PCNSL is delineated.
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PMID:Primary central nervous system lymphoma: current state of anti-CD20 therapy and appraisal of reported response criteria. 2472 53


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