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)

Primary non-Hodgkin's lymphoma of the testis (PTL) accounts for about 9% of testicular neoplasms and 1-2% of all non-Hodgkin's lymphomas. It is the most common testicular malignancy in elder men. Anecdotal reports associated PTL development with trauma, chronic orchitis, cryptorchidism, or filariasis exist, but no case-control studies have confirmed their etiologic significance. Diffuse large B-cell lymphoma (DLBCL) is the most common histotype in primary forms; aggressive histologies, especially Burkitt's lymphoma, are prevalent in cases of secondary involvement of testis. The most common clinical presentation is a unilateral painless scrotal swelling, sometimes with sharp scrotal pain or hydrocele. Systemic B symptoms are present in 25-41% of patients with advanced stage. Less frequently, abdominal pain, and ascites can be seen in patients with involvement of retroperitoneal lymph nodes. Bilateral testicular involvement is detected in up to 35% of patients. Although good results with doxorubicin-containing chemotherapy, followed or not by radiotherapy, have been reported, a high proportion of patients with stage I-II diseases experience aggressive relapses, and patients with advanced disease have a very poor prognosis. PTL has a propensity to disseminate to other extranodal organs, including the controlateral testis, CNS, skin, Waldeyer's ring, lung, pleura, and soft tissue. Orchidectomy followed by R-CHOP combination, with CNS prophylaxis, and prophylactic irradiation of the contralateral testis is the recommended first-line treatment for patients with limited disease. Management of patients with advanced or relapsed disease should follow the worldwide recommendations for nodal DLBCL.
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PMID:Primary testicular lymphoma. 1796 36

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and the most common type of non-Hodgkin lymphoma. Despite recent advances in treatment, less than 50% of the patients are cured with current multiagent chemotherapy. Abnormal NF-kappaB activity not only contributes to tumor development but also renders cancer cells resistant to chemotherapeutic agents. Identifying and targeting signaling molecules that control NF-kappaB activation in cancer cells may thus yield more effective therapy for DLBCL. Here, we show that while overexpression of protein kinase C-associated kinase (PKK) activates NF-kappaB signaling in DLBCL cells, suppression of PKK expression inhibits NF-kappaB activity in these cells. In addition, we show that NF-kappaB activation induced by B cell-activating factor of tumor necrosis factor family (BAFF) in DLBCL cells requires PKK. Importantly, we show that knockdown of PKK impairs the survival of DLBCL cells in vitro and inhibits tumor growth of xenografted DLBCL cells in mice. Suppression of PKK expression also sensitizes DLBCL cells to treatment with chemotherapeutic agents. Together, these results indicate that PKK plays a pivotal role in the survival of human DLBCL cells and represents a potential target for DLBCL therapy.
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PMID:Protein kinase C-associated kinase is required for NF-kappaB signaling and survival in diffuse large B-cell lymphoma cells. 1802 52

The World Health Organization classification was used to conduct an analysis of geographic, age, sex, and lesion primarily biopsied/resected distribution of 2260 lymphoid neoplasms diagnosed during 2001-2006 throughout Japan. B-cell neoplasms accounted for 65% of all lymphoid neoplasms, T/natural killer (T/NK)-cell neoplasms for 25% and Hodgkin lymphoma for 7%. The most common type was diffuse large B-cell lymphoma (DLBCL, 33%), followed by follicular lymphoma (18%), and adult T-cell leukemia/lymphoma (ATLL, 10%). The high rate of 18% for follicular lymphoma was similar to that in Western countries (11-33%). T/NK-cell neoplasms accounted for a higher percentage of lymphoid neoplasms in Kyushu (30%) and Okinawa (38%) compared with other areas of Japan (18-20%). Among T/NK-cell neoplasms, ATLL was the most common type in Okinawa (54%) and Kyushu (59%). Extranodal NK/T cell lymphoma was the second most common type of T/NK-cell neoplasms in Okinawa (15%). This epidemiological study shows that the distribution patterns of malignant lymphoma differ especially in Kyushu and Okinawa, the endemic area of human T-cell leukemia/lymphoma virus type 1.
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PMID:Distribution of malignant lymphoma in Japan: analysis of 2260 cases, 2001-2006. 1825 81

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults, accounting for nearly 40% of all non-Hodgkin's lymphomas. As cell proliferation is essential for tumor growth, analysis of the cell cycle might give additional information on tumor progression. Although markers distinctive for cell-cycle regulation in DLBCL have been addressed, less attention has been paid to cyclin H in DLBCL with respect to its prognostic and potential therapeutic implications. Cyclin H occurs as a component of the cyclin H/Cdk 7/Mat 1 complex. Cyclin H is also a substrate of protein kinase 2, a ubiquitously expressed serine/threonine protein kinase required for cell viability and cell-cycle progression. We evaluated the expression of cyclin H by immunohistochemistry in 301 DLBCLs in a tissue microarray format. Validation was done by performing quantitative real-time polymerase chain reaction and Western blotting experiments for cyclin H. We studied the relationship between cyclin H expression in comparison to other cyclins (A, B1, D1, D3, and E) and the proliferation marker Ki-67. Reduced or absent cyclin H expression was seen in 14.5% of the DLBCL cases. Interestingly, reduced or absent cyclin H expression was correlated with lower expression of proliferation marker Ki-67 (P < .0001), cyclin B1 (P = .0001), cyclin D3 (P = .0007), and cyclin E (P < .0001). Reduced or absent cyclin H expression was significantly associated with poor overall survival, in both the univariate (P = .0286) and multivariate analysis with International Prognostic Index (P = .0180). Our study demonstrates the independent prognostic value of cyclin H expression in DLBCL and proposes its use as a prognostic marker.
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PMID:Reduced or absent cyclin H expression is an independent prognostic marker for poor outcome in diffuse large B-cell lymphoma. 1840 Feb 56

Diffuse large B-cell lymphomas (DLBCL) are neoplasms of transformed mature B cells, accounting for approximately 10% of non-Hodgkin lymphomas (NHL) of childhood. Increasing evidence indicates that DLBCL are composed of biologically distinct subsets. Clinical features of children with DLBCL differ from those with other NHL entities, e.g. by a lower frequency of bone-marrow and central nervous system involvement. Treatment strategies originally designed for Burkitt lymphoma appear to be efficacious for children with DLBCL. However, children with primary mediastinal large B-cell lymphoma may need a more specific treatment approach, given their inferior outcome in recent studies. The addition of the monoclonal anti-CD20 antibody rituximab to standard CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy improved outcome of adults with DLBCL significantly. However, preliminary data suggest differences between DLBCL of children and adults concerning cell of origin, genetic abnormalities and responsiveness to current treatments. Thus, the potential role of monoclonal antibodies in the treatment of children with DLBCL remains to be determined. The availability of new methodological tools, such as gene expression profiling, will greatly enhance our insights into the biology of childhood DLBCL and its similarities and disparities compared to adult DLBCL. Furthermore, these tools may enable a more risk-adapted and rationally targeted subtype-specific therapy in the future.
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PMID:Recent advances in the understanding and management of diffuse large B-cell lymphoma in children. 1853 79

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although some patients can be cured by current therapies, novel agents are needed to further improve outcomes. We hypothesized that Src tyrosine kinase inhibition by dasatinib may have antilymphoma effects. Here, we demonstrate that dasatinib inhibits cell growth through G(1)-S blockage in five of seven DLBCL cell lines at clinically achievable concentrations. Compared to resting B cells, DLBCL has increased tyrosine phosphorylation activities. As expected, dasatinib inhibits phosphorylation of several Src family kinase members. However, this inhibition occurs in all cell lines regardless of their proliferative response to the drug. In contrast, the activity of two downstream signaling molecules, Syk and phospholipase Cgamma2 (PLCgamma2), are well correlated with cell line sensitivity to dasatinib, suggesting that these molecules are crucial in mediating the proliferation of activated lymphoma cells. Furthermore, dasatinib inhibits B-cell receptor signaling in primary lymphoma cells. Together, our findings not only show dasatinib as a potentially useful therapy for DLBCL but also provide insights into the pathogenesis of the lymphoma. The results further suggest the possibility of using Syk and PLCgamma2 as biomarkers to predict dasatinib therapeutic response in prospective clinical trials.
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PMID:Tyrosine kinase inhibition in diffuse large B-cell lymphoma: molecular basis for antitumor activity and drug resistance of dasatinib. 1859 45

Primary mediastinal large B-cell lymphoma (PMLCL) is an aggressive non-Hodgkin lymphoma with distinct clinical and gene expression profiles. Outcomes of salvage chemotherapy and autologous stem cell transplantation (ASCT) for relapsed or refractory disease (RR) have not been well characterised. We retrospectively identified 180 consecutive RR patients (37 PMLCL and a control group of 143 DLBCL) that underwent salvage chemotherapy. The overall response rate (ORR) to salvage chemotherapy (25% vs. 48%, p = 0.01) and 2-year OS after diagnosis of RR disease (15% vs. 34%, p = 0.018) was inferior in PMLCL patients. The 2-year post-ASCT OS (67% PMLCL vs. 53%, p = 0.78) and PFS (57% PMLCL vs. 36%, p = 0.64) were similar. RR PMLCL had an inferior ORR and survival compared with DLBCL but chemosensitive PMLCL and DLBCL patients have similar outcomes post-ASCT. Strategies for PMLCL should focus on identifying poor risk patients to test novel induction and salvage strategies.
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PMID:Salvage chemotherapy and autologous stem cell transplantation are inferior for relapsed or refractory primary mediastinal large B-cell lymphoma compared with diffuse large B-cell lymphoma. 1860 22

Understanding patterns of etiologic commonality and heterogeneity for non-Hodgkin lymphomas may illuminate lymphomagenesis. We present the first systematic comparison of risks by lymphoma subtype for a broad range of putative risk factors in a population-based case-control study, including diffuse large B-cell (DLBCL; N = 416), follicular (N = 318), and marginal zone lymphomas (N = 106), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; N = 133). We required at least 2 of 3 analyses to support differences in risk: (1) polytomous logistic regression, (2) homogeneity tests, or (3) dichotomous logistic regression, analyzing all 7 possible pairwise comparisons among the subtypes, corresponding to various groupings by clinical behavior, genetic features, and differentiation. Late birth order and high body mass index (>/= 35) kg/m(2)) increased risk for DLBCL alone. Autoimmune conditions increased risk for marginal zone lymphoma alone. The tumor necrosis factor G-308A polymorphism (rs1800629) increased risks for both DLBCL and marginal zone lymphoma. Exposure to certain dietary heterocyclic amines from meat consumption increased risk for CLL/SLL alone. We observed no significant risk factors for follicular lymphoma alone. These data clearly support both etiologic commonality and heterogeneity for lymphoma subtypes, suggesting that immune dysfunction is of greater etiologic importance for DLBCL and marginal zone lymphoma than for CLL/SLL and follicular lymphoma.
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PMID:Etiologic heterogeneity among non-Hodgkin lymphoma subtypes. 1879 28

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and it is recognized to constitute a heterogenous group of neoplasms. It can be divided into germinal center B-cell-like (GCB) and non-GCB subgroups. The aim of the present study was to evaluate the utility of immunophenotype subgrouping of DLBCL in a cohort of multi-ethnic Asian patients. A total of 84 reconfirmed de novo DLBCL were immunostained for the expression of CD10, BCL-2, BCL-6 and multiple myeloma-1. Thirty-three (39.3%) had the GCB phenotype, and the remainder (60.7%), the non-GCB phenotype. The results concur with most reports using a similar method of stratification. Forty-five patients had complete demographic and phenotype studies and 42 patients did not have rituximab treatment and had sufficient data for survival rate analysis. Similar to other studies, patients with combined low and low-intermediate International Prognostic Index score had better overall survival (P = 0.006). But patients with GCB phenotype did not have better prognosis, and BCL-2 expression was not associated with better prognosis. The expression of BCL-6 was associated with lower overall survival rate (P = 0.038). No apparent difference in overall and disease-free survival was noted between patients with GCB and non-GCB disease. BCL-6 expression by tumor cells appears to be associated with poorer prognosis.
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PMID:Clinical relevance of CD10, BCL-6 and multiple myeloma-1 expression in diffuse large B-cell lymphomas in Malaysia. 1880 Oct 72

The female genital tract is rarely the primary site for hematologic malignancies; however, secondary involvement of this anatomic site is common. Primary lymphomas of the gynecologic tract are reported to represent less than 1% of extranodal non-Hodgkin lymphomas (NHL), and the majority of them being B-cell in origin. Diffuse large B-cell lymphoma is the most common subtype, whereas primary extraosseus plasmacytoma of the genital tract is rare.If clinically not suspected, these rare tumors pose a diagnostic challenge both for clinicians and pathologists. Clinical symptoms are often nonspecific and mimic other more common gynecologic malignancies such as squamous cell carcinoma of the cervix or endometrial adenocarcinoma. Although cervico-vaginal (Pap) smear is the primary screening method for cervical squamous cell carcinoma and its precursors, it is far less sensitive for detection of other primary or metastatic malignancies. In this review, we present three cases of hematologic gynecologic malignancies, two cases of primary NHL, and a case of acute myeloid leukemia with relapse as a pelvic mass, all of which were diagnosed on a liquid-based Pap test. In addition, we discuss the morphologic features of differential diagnostic entities of these rare tumors on conventional and liquid-based preparations.
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PMID:Hematologic malignancies of the female genital tract diagnosed on liquid-based Pap test: Cytomorphologic features and review of differential diagnoses. 1897 27


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