scholarly journals CNTO 530 functions as a potent EPO mimetic via unique sustained effects on bone marrow proerythroblast pools

Blood ◽  
2009 ◽  
Vol 113 (20) ◽  
pp. 4955-4962 ◽  
Author(s):  
Pradeep Sathyanarayana ◽  
Estelle Houde ◽  
Deborah Marshall ◽  
Amy Volk ◽  
Dorie Makropoulos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Epoetin Alfa ◽  
Akt Activation ◽  
Sustained Effects ◽  
Primary Bone ◽  
Clinical Conditions ◽  
Kinetics Of ◽  
P70s6k Activation ◽  
Primary Bone Marrow

Abstract Anemia as associated with numerous clinical conditions can be debilitating, but frequently can be treated via administration of epoetin-alfa, darbepoietin-alfa, or methoxy-PEG epoetin-beta. Despite the complexity of EPO-EPO receptor interactions, the development of interesting EPO mimetic peptides (EMPs) also has been possible. CNTO 530 is one such novel MIMETIBODY Fc-domain dimeric EMP fusion protein. In a mouse model, single-dose CNTO 530 (unlike epoetin-alfa or darbepoietin-alfa) bolstered red cell production for up to 1 month. In 5-fluorouracil and carboplatin-paclitaxel models, CNTO 530 also protected against anemia with unique efficiency. These actions were not fully accounted for by half-life estimates, and CNTO 530 signaling events therefore were studied. Within primary bone marrow erythroblasts, kinetics of STAT5, ERK, and AKT activation were similar for CNTO 530 and epoetin-alfa. p70S6K activation by CNTO 530, however, was selectively sustained. In vivo, CNTO 530 uniquely stimulated the enhanced formation of PODXLhighCD71high (pro)erythroblasts at frequencies multifold above epoetin-alfa or darbepoietin-alfa. CNTO 530 moreover supported the sustained expansion of a bone marrow–resident KitnegCD71highTer119neg progenitor pool. Based on these distinct erythropoietic and EPOR signaling properties, CNTO 530 holds excellent promise as a new EPO mimetic.

scholarly journals Long-Term Remission of Primary Bone Marrow Diffuse Large B-Cell Lymphoma Treated with High-Dose Chemotherapy Rescued byIn VivoRituximab-Purged Autologous Stem Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Hiroshi Kazama ◽  
Masanao Teramura ◽  
Kentaro Yoshinaga ◽  
Akihiro Masuda ◽  
Toshiko Motoji
Keyword(s):  
Bone Marrow ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
Primary Bone ◽  
Primary Bone Marrow ◽  
Large B Cell

Primary bone marrow diffuse large B-cell lymphoma (DLBCL) is a rare type of extranodal lymphoma with poor prognosis. Here, we report a case of primary bone marrow DLBCL successfully treated with high-dose chemotherapy and rescued byin vivorituximab-purged autologous stem cells. A 39-year-old woman visited our hospital because of anemia. Bone marrow examination revealed a large B-cell lymphoma invasion. An18F-fluorodeoxyglucose positron emission tomography scan revealed disseminated bone marrow uptake without evidence of dissemination at other sites. These findings led to a diagnosis of primary bone marrow DLBCL. Our patient underwent R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy and achieved complete remission. Subsequently, she received high-dose chemotherapy with anin vivorituximab-purged autologous stem cell transplant. Seven years have passed since the transplantation, and she remains in remission. This suggests that transplantation of anin vivorituximab-purged autograft is a promising strategy for primary bone marrow DLBCL.

scholarly journals Primary Bone Marrow B-Cell Lymphoma Undetected by Multiple Imaging Modalities That Initially Presented with Hypercalcemia

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Jin Sae Yoo ◽  
Juwon Kim ◽  
Hyeong Ju Kwon ◽  
Jung Soo Lim
Keyword(s):  
Computed Tomography ◽  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
Hematologic Malignancy ◽  
B Cell Lymphoma ◽  
Severe Hypercalcemia ◽  
Multiple Imaging ◽  
Primary Bone ◽  
Primary Bone Marrow

Purpose. We report a rare case of severe hypercalcemia that was ultimately diagnosed as primary bone marrow diffuse large B-cell lymphoma (BCL). Case Report. A 74-year-old male patient visited our hospital complaining of tenderness and swelling of the left knee caused by supracondylar fracture of the left distal femur. His initial blood tests showed a serum calcium level of 13.9 mg/dL, inorganic phosphorus of 4.34 mg/dL, and a serum creatinine level of 1.54 mg/dL. A serum assay of intact parathyroid hormone showed 5.24 pg/mL, and the patient’s serum 25(OH)D level was 22.33 ng/mL. To exclude malignancy, we performed imaging studies, including abdomen or chest computed tomography and positron emission tomography-computed tomography; however, no suspicious lesion was found, although the serum PTH-related peptide level was elevated at 4.0 pmol/L. A bone marrow biopsy was performed to identify any hidden hematologic malignancy. As a result, the pathology of bone marrow confirmed the presence of atypical lymphocytes that stained positive for the CD20 marker, which is consistent with BCL involving the bone marrow. Conclusion. This case highlights the importance of pursuing a thorough workup for rare underlying causes of hypercalcemia when parathyroid-related etiologies can be excluded.

scholarly journals Dexamethasone-induced plasminogen activator inhibitor-1 expression in human primary bone marrow adipocytes

2010 ◽  
Vol 31 (5) ◽  
pp. 281-286 ◽  
Author(s):  
Akira Hozumi ◽  
Makoto Osaki ◽  
Kazutaka Sakamoto ◽  
Hisataka Goto ◽  
Tatsuya Fukushima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Bone Marrow Adipocytes ◽  
Primary Bone ◽  
Activator Inhibitor ◽  
Primary Bone Marrow

scholarly journals Chidamide combined with ibrutinib improved the prognosis of primary bone marrow diffuse large B cell lymphoma

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052093605 ◽  
Author(s):  
Chen Tian ◽  
Zehui Chen ◽  
Yueyang Li
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Young Patients ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Chop Regimen ◽  
Large B Cell Lymphoma ◽  
Primary Bone ◽  
Primary Bone Marrow

Primary bone marrow diffuse large B cell lymphoma (DLBCL) is an independent pathologic type with a poor prognosis when treated with standard chemoimmunotherapy. Generally, rituximab-based high-dose chemotherapy regimens such as dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) can be administered to young patients, followed by autologous stem cell transplantation. For elderly patients, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen is well tolerated, but it is an insufficient induction therapy for this group. Herein, we reported an elderly patient diagnosed with primary bone marrow DLBCL, germinal center B-cell-like subtype. Considering tolerance, the R-CHOP regimen was administered. However, his disease progressed after two treatment cycles. Then, the rituximab, gemcitabine, dexamethasone, cisplatin, lenalidomide regimen was administered, but the patient still experienced disease progression. Subsequently, the histone deacetylase (HDAC) inhibitor chidamide and Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib were concurrently administered, and the patient achieved complete remission. We found that the response of primary bone marrow DLBCL to chemotherapy was poorer than that of de novo DLBCL. High-dose chemotherapy regimens such as DA-EPOCH should be administered to young patients in combination with rituximab. For elderly patients, new targeted drugs such as HDAC and BTK inhibitors appear to produce favorable outcomes.

scholarly journals Selenoproteome Identification in Inflamed Murine Primary Bone Marrow-Derived Macrophages by Nano-LC Orbitrap Fusion Tribrid Mass Spectrometry

2019 ◽  
Vol 30 (7) ◽  
pp. 1276-1283 ◽  
Author(s):  
Arvind M. Korwar ◽  
Ashley E. Shay ◽  
Venkatesha Basrur ◽  
Kevin Conlon ◽  
K. Sandeep Prabhu
Keyword(s):  
Mass Spectrometry ◽  
Bone Marrow ◽  
Primary Bone ◽  
Primary Bone Marrow
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