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Lymphoma
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Sarah J Vinnicombe, Rodney J Hicks
The development of antibody therapies has revolutionized the treatment of NHL and the immunological subtype is a critical consideration, particularly for B-cell lymphomas, which express a variety of surface antigens. Rituximab is a chimeric monoclonal antibody against CD20, expressed in more than 95% of B-cell tumours. It can be used as a single agent in indolent NHL, including FL, and as single-agent maintenance therapy for FL, it may prolong time to first chemotherapy. It is additive with chemotherapy and patients with high-grade disease are treated with combined rituximab and anthracycline-containing chemotherapy such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). R-CHOP is standard treatment for DLBCL, but for FL, rituximab and bendamustine may be more efficacious (42). A revised IPI (R-IPI) has been shown to be more prognostic in the rituximab era (43).
Involvement of Dopamine with Various Cancers
Published in Nira Ben-Jonathan, Dopamine, 2020
B-cell lymphomas have several subtypes, including diffuse large B cell lymphoma, follicular lymphoma, Burkitt lymphoma, and mantle cell lymphoma [20,21]. Normal and malignant human B lymphocytes were examined for expression of DA pathway components and for cytostatic responses to DA and related compounds [22]. DA in the micromolar range rapidly arrested the proliferation of both normal and malignant lymphocytes. L-Dopa and apomorphine also showed antiproliferative activity. With the exception of D4R, all other DAR subtypes were variably expressed in normal and neoplastic B cells, as was DAT. The authors concluded that the impact of DA on lymphocytes provides an opportunity for therapeutic intervention in B cell neoplasia and other lymphoproliferative disorders. Another study reported that addition of DA to cultured Burkitt lymphoma cells (Raji, Namalwa, Daudi, and Jijoye) caused a rapid and an extensive cell death, while a myeloma cell line, SKO, was unresponsive [23]. Additions of fetal calf serum or supernatant from cultures of Raji or T24 bladder carcinoma cells partially counteracted the effect of DA, suggesting that DA acted by inhibiting the production of unidentified endocrine/autocrine factors.
B Cells and Humoral Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
In mice, CD5+ cells produce mainly interleukin-10 and transforming growth factor-β, while CD5− cells secrete predominantly interleukin-6. These B cell subsets further differ with respect to antigen specificities, and Ig variable gene usage. CD5+ B cells are thought to have an important role in autoimmunity, and also frequently become malignant; more than 90% of chronic lymphocytic leukemias, and 60% of B cell lymphomas are CD5+. CD5+ cells are able to proliferate largely independently of antigen stimulation and T cell regulation. Interleukin-10 may play an autocrine role in this process. This may underlie the tendency toward the malignant phenotype in CD5+ cells.
DDX3: a relevant therapeutic target for lymphoma?
Published in Expert Opinion on Therapeutic Targets, 2022
Marion Lacroix, Hugues Beauchemin, Tarik Möröy
Finally, it is conceivable that the combination of established drug treatments for B lymphoma with DDX3 inhibitors could prove beneficial. The current treatments for B cell lymphoma include standard chemotherapeutic agents (cyclophosphamide, vincristine, methotrexate, doxorubicin, and cytarabine), although some targeted therapies have shown success (Rituximab). Previous reports indicated that simultaneous inhibition of DDX3 and PARP1 shows synergistic effects on cell growth and tumorigenicity; or even that DDX3 inhibition causes radiosensitization on breast cancer cells [14,15]. It is therefore possible that a combination of DDX3 inhibitors with standard treatments for B malignancies may be beneficial and improve disease outcomes. If such combinations permit to reduce chemotherapy doses and lower toxicity, the risk of secondary cancers arising later in life as seen in pediatric patients with B lymphoma may be mitigated. However, a better understanding of DDX3 mechanistic role in B cells is necessary to assess which therapeutic combination could be beneficial.
Large pancreatic mass with chylous ascites
Published in Baylor University Medical Center Proceedings, 2020
Madhuri Badrinath, Ajay Tambe, Rachana Mandru, Sheikh Saleem, David Heisig
Fine-needle aspiration of the mass was performed. Microscopic examination revealed numerous small and large lymphoid cells, with irregular nuclear membrane contours, in a background of pancreatic acinar cells. Immunohistochemical stains showed lymphoid cells strongly positive for CD20 and a few scattered cells stained with CD5 (Figure 2). These findings were consistent with possible B-cell lymphoma. A positron emission tomography-CT scan showed the pancreatic mass associated with metabolically active inguinal, aortocaval, juxtadiaphragmatic, and inframammary lymphadenopathy (Figure 3a). The low-level fluorodeoxyglucose activity of ascites was suggestive of malignant ascites. The patient underwent a diagnostic laparoscopic biopsy of the mass confirming the diagnosis of B-cell lymphoma of germinal center origin positive for CD10, BCL6, BCL2, and CD45. Fluorescence in situ hybridization analysis showed no evidence of double- or triple-hit lymphoma. The patient received six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and tolerated it well. A follow-up positron emission tomography-CT scan showed that the pancreatic mass reduced in size to 10 × 5 cm without areas of new or worsening lymphoma (Figure 3b).
Therapeutic potential of PI3K signaling in distinct entities of B-cell lymphoma
Published in Expert Review of Hematology, 2019
Ramona Wullenkord, Birte Friedrichs, Tabea Erdmann, Georg Lenz
B-cell lymphomas represent a heterogeneous group of lymphoproliferative malignancies arising from B-lymphocytes at different stages of differentiation. They account for roughly 4% of all cancers [1]. Based on their clinical behavior, B-cell lymphomas can be divided into indolent and aggressive entities [2]. Indolent lymphomas are normally characterized by a low proliferation rate of tumor cells and a relatively good prognosis. However, they are still considered as not curable with currently available therapeutic means, except stage I disease, which might be cured by radiation therapy. They represent one third of all lymphoma entities and include among others follicular lymphoma (FL), small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL), marginal zone lymphoma (MZL) and lymphoplasmacytic lymphoma with or without Waldenström’s macroglobulinemia (LPL) [2]. Aggressive lymphomas are regularly characterized by a high proliferation rate of tumor cells and frequently need to be treated immediately. They represent a biologically highly heterogeneous group of lymphoid malignancies with variable clinical features, divergent molecular alterations and significant differences in therapeutic responsiveness. Diffuse large B-cell lymphoma (DLBCL) represents the most common entity of aggressive lymphoma which accounts for roughly 30–40% of all newly diagnosed lymphomas. Other common entities, however less frequent, include mantle cell lymphoma (MCL), follicular lymphoma grade 3B (FL 3B) as well as transformed follicular lymphoma (tFL) [2].