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

Fibrin deposits were observed in the involved lymph nodes and/or spleens of 15 patients with Hodgkin's disease by specific immunofluorescence and by electron microscopy. Two basic patterns of fibrin deposition were observed: 1) intercellular deposits, chiefly associated with nonneoplastic-appearing lymphoid cells and 2) deposits associated with the collagen fibers of young connective tissue. In addition, coarse fibrin deposits were observed in areas of necrosis, presumably a non-specific finding. Fibronectin was also observed in intercellular areas, but staining was less intense than for fibrin. Fibrin deposits were also observed in 3 of 6 cases of non-Hodgkin's lymphoma, indicating that the finding is not an exclusive feature of Hodgkin's disease. The pathogenesis and possible significance of fibrin deposition in Hodgkin's disease are related to earlier observations of activation of the coagulation system on neoplasia and cell-mediated immunity and to the possible role of fibrin, fibronectin, and their breakdown products in angiogenesis and fibroplasia.
 ...
PMID:Fibrin deposits in Hodgkin's disease. 704 53

Hepatocyte growth factor (HGF)/scatter factor (SF) is the ligand for a tyrosine kinase cell surface receptor encoded by the MET protooncogene (c-MET). HGF/SF can induce proliferation and motility in epithelial cells and promotes invasion of carcinoma cells and NIH3T3 fibroblasts transfected with both HGF/SF and c-MET genes. Our results show that HGF/ SF and c-MET also play a role in adhesion and invasion of human lymphoma cells. c-MET mRNA is expressed in hemopoietic cells, such as hemopoietic progenitor cells (CD34+ cells) in bone marrow (BM) and mobilized peripheral blood, immature B cells in cord blood and BM, and germinal center B-centroblasts. In normal peripheral blood B cells, which are c-MET-, c-MET expression was induced by PMA, ConA, HGF/ SF, and Epstein-Barr virus (EBV) infection. Using immunohistochemistry, we detected c-MET on the cell surface of large activated centroblasts in lymph nodes from patients with B-non-Hodgkin's lymphoma and Hodgkin's disease. In the latter group, c-MET expression correlated well with the presence of EBV. Because HGF/SF and c-MET promote metastasis of carcinoma cells, we studied the effects of c-MET stimulation by HGF/SF of B-lymphoma cells on properties relevant for metastasis, ie, adhesion, migration, and invasion. HGF/SF stimulated adhesion of the c-MET+ B-cell lines to the extracellular matrix molecules fibronectin (FN) and collagen (CN) in a dose dependent manner. However, adhesion to laminin was not affected by HGF/SF. Adhesion to FN was mediated by beta 1-integrins alpha 4 beta 1 (VLA4) and alpha 5 beta 1 (VLA5) since blocking antibodies against beta 1- (CD29), alpha 4-(CD49d), or alpha 5- (CD49e) integrin subunits, completely reversed the effect of HGF/SF. Furthermore, HGF/SF induced adhesion was abrogated by addition of genistein, which blocks protein tyrosine kinases, including c-MET. Addition of HGF/SF resulted in a sixfold increase in migration of c-MET B-lymphoma cells through Matrigel, compared to medium alone. In rat fibroblast cultures, HGF/SF doubled the number of c-MET+ B-lymphoma cells that invaded the fibroblast monolayer. In these adhesion, migration and invasion assays HGF/SF had no effect on c-MET- cell lines. In conclusion, c-MET is expressed or can be induced on immature, activated, and certain malignant B cells. HGF/SF increased adhesion of c-MET+ B-lymphoma cells to FN and CN, mediated via beta 1-integrins alpha 4 beta 1 and alpha 5 beta 1, and furthermore promoted migration and invasion.
 ...
PMID:Hepatocyte growth factor/scatter factor promotes adhesion of lymphoma cells to extracellular matrix molecules via alpha 4 beta 1 and alpha 5 beta 1 integrins. 902 31

Soluble isoforms of various adhesion molecules have recently been found in the circulation, but the physiologic effects of such molecules are still unconfirmed. Our earlier study suggests that the serum level of the 70- to 80-kDa form of CD44 (sCD44) parallels the clinical treatment response in patients with lymphoma. In the present study we investigated the origin and the function of sCD44 in non-Hodgkin's lymphoma. Both peripheral blood and tumor lymphocytes were able to shed soluble CD44 in cell culture. In a SCID mouse model, transplanted Burkitt lymphoma (Namalwa) cells transfected with human CD44 shed soluble CD44. In binding studies sCD44 was able to adhere to hyaluronate and fibronectin, and moreover, sCD44 was able to block the binding of hyaluronate to CD44 on the cell surface and to block the binding of lymphocytes to high endothelial venules, suggesting that sCD44 retains its biological activity although it does not contain the cytoplasmic tail. In conclusion, sCD44 is biologically active and is at least partially shed by lymphoma cells in non-Hodgkin's lymphoma patients.
 ...
PMID:Origin and function of circulating CD44 in non-Hodgkin's lymphoma. 905 39

The feasibility of ex vivo expansion of hematopoietic progenitors selected from leukapheresis products of patients treated for multiple myeloma (MM) was studied and compared with progenitor expansions from patients with nodular non-Hodgkin's lymphoma (NHL) or healthy donors. After positive selection, CD34+ cells from leukapheresis products of 4 MM and 5 NHL patients and CD34+ cells from bone marrow (BM) of 3 healthy donors were grown in IMDM plus 12.5% horse serum, 12.5% fetal calf serum, IL-1alpha, IL-3, IL-6, SCF, GM-CSF, G-CSF (10 ng/ml each), and EP (4 UI/ml). Outputs of CD34+ cell cultures from MM and NHL patients were similar. Day 14 mean increases in CD34+, CFU-GM, and total cell numbers were, respectively, 5.3-fold, 19.8-fold, and 1173-fold for MM patients and 4.3-fold, 15.6-fold, and 1659-fold for NHL patients, with at least 40% of day 14 cells being of granulocytic lineage. Patient CD34+ cell culture output was found to be related to the CFU-GM/CD34+ cell ratio of selected CD34+ cells, not to underlying pathology. When the initial CFU-GM/CD34+ cell ratio was above 0.025, MM and NHL CD34+ cell culture outputs were always above 1000-fold. Moreover, in all but one CD34+ cell culture, the use of fibronectin (FN)-coated dishes improved CFU-GM and total cell expansion. In patient CD34+ cultures carried out in FN-coated dishes, mean day 14 CFU-GM and total cell outputs were increased, respectively, 2.1-fold and 1.9-fold. We conclude that if the CFU-GM/CD34+ cell ratio is sufficient (>0.025), ex vivo expansion of hematopoietic progenitors from CD34+ cells selected from leukapheresis products is possible for both MM and NHL patients and that using FN-coated flasks is a simple and reliable way to improve both CFU-GM and total cell output.
 ...
PMID:Ex vivo expansion of hematopoietic progenitors from CD34+ cells selected from leukapheresis products of lymphoma and myeloma patients: feasibility and enhancement by fibronectin. 911 56

The mechanisms of maintenance of residual lymphoma in bone marrow during chemotherapy are currently not well understood. Previous studies have shown that primary lymphoma cells obtained from histologically negative bone marrow of non-Hodgkin's lymphoma (NHL) patients grew in long-term bone marrow cultures primarily in association with bone marrow stromal cells. Furthermore, the interaction of NHL patient cells with bone marrow stromal cells inhibited their spontaneous apoptosis. The current studies were designed to characterize the components of the heterotypic interaction between lymphoma cells and bone marrow stromal cells as well as to probe the consequences of this interaction as it pertains to the potential survival of minimal numbers of lymphoma cells during chemotherapy. Cellular adhesion assays performed in the presence of either neutralizing antibodies to VCAM- or the alpha and beta subunit of VLA-4 resulted in >95%, 82% and 35% inhibition of lymphoma cell line adhesion to the bone marrow stromal line MS-5, respectively. Modulation of VLA-4 affinity by the 8A2 antibody resulted in enhanced secondary adhesion at 24 and 72 hours to either cellular fibronectin (65% and 65%) or MS-5 cells (60% and 55%), superceding levels obtained using untreated lymphoma cells (<20%). The bone marrow stromal cells induced a chemoprotective effect for adherent lymphoma cells over a 3-log dose range of vincristine, resulting in a 2-log increase in the ED50 at day 6 of culture. The failure of glutaraldehyde fixed stromal cells to induce a chemoprotective effect demonstrated that viable bone marrow stromal cells were necessary. Similarly, lymphoma/stromal cell conditioned medium also failed to provide a survival advantage. These data demonstrated that viable bone marrow stromal cells possessed the ability to actively inhibit the apoptotic pathways of intimately adherent lymphoma cells and this potentially contributes to their survival during chemotherapy.
 ...
PMID:VLA-4 mediated adhesion to bone marrow stromal cells confers chemoresistance to adherent lymphoma cells. 1142 35

Recent studies have identified that thyroid hormone receptor-interacting protein 6 (TRIP6) is implicated in tumorigenesis. However, the functional role of TRIP6 in non-Hodgkin's lymphoma (NHL) has never been elucidated. In this study, we demonstrated that TRIP6 is reversely correlated with the clinical outcomes of NHL patients. Western blot and immunohistochemical analysis revealed that TRIP6 expression is lower in indolent lymphoma than in progressive lymphoma. Kaplan-Meier survival curves indicated that the upregulation of TRIP6 is significantly associated with poor overall survival. Moreover, patients with higher expression of TRIP6 are prone to shorter time to recurrence. Furthermore, we also found that TRIP6 can promote the proliferation of NHL cells via regulating cell cycle progression. In addition, adhesion of lymphoma cells to fibronectin (FN) decreased TRIP6 expression, which led to the upregulation of nuclear p27(Kip1) expression by decreasing phosphorylation of p27(Kip1) at T157. Importantly, overexpression of TRIP6 can reverse cell adhesion-mediated drug resistance (CAM-DR) phenotype in NHL. In summary, these results suggest that TRIP6 is a novel prognostic indicator for NHL patients and may shed new insights into the important role of TRIP6 in cancer development.
...
PMID:Overexpression of TRIP6 promotes tumor proliferation and reverses cell adhesion-mediated drug resistance (CAM-DR) via regulating nuclear p27(Kip1) expression in non-Hodgkin's lymphoma. 2629 25

Casein kinase 2 interacting protein-1 (CKIP-1; also known as PLEKHO1) is involved in regulating many processes such as cell proliferation, differentiation and apoptosis. CKIP-1 also plays an important role in many types of cancer, such as colon, breast cancer and human osteosarcoma. In the present study, we found that CKIP-1 was reversely associated with the proliferation of non-Hodgkin's lymphoma (NHL) and cell adhesion mediated drug resistance (CAM-DR). We demonstrated that knockdown of CKIP-1 promoted the proliferation of NHL cells through interacting with Akt and suppressing Akt phosphorylation. In addition, adhesion of lymphoma cells to fibronectin or stroma cells (HS-5 cells) decreased CKIP-1 expression, which led to the upregulation of Akt phosphorylation. Importantly, we showed that the phosphorylation of Akt was correlated with CAM-DR phenotype in NHL cells. Taken together, the present study shed new light on the molecular mechanism of CAM-DR in NHL and targeting CKIP-1 may be a novel therapeutic target for NHL.
 ...
PMID:Silencing of CKIP-1 promotes tumor proliferation and cell adhesion-mediated drug resistance via regulating AKT activity in non-Hodgkin's lymphoma. 2784 Sep 70