scholarly journals Mesenchymal stem/stromal cells in cancer therapy

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tianxia Lan ◽  
Min Luo ◽  
Xiawei Wei
Keyword(s):  
Signal Transduction ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Translational Medicine ◽  
Signal Transduction Pathways ◽  
Published Data ◽  
Efficacy And Safety ◽  
Therapeutic Mechanisms ◽  
Tumor Homing ◽  
Special Relevance

AbstractThe multipotent mesenchymal stem/stromal cells (MSCs), initially discovered from bone marrow in 1976, have been identified in nearly all tissues of human body now. The multipotency of MSCs allows them to give rise to osteocytes, chondrocytes, adipocytes, and other lineages. Moreover, armed with the immunomodulation capacity and tumor-homing property, MSCs are of special relevance for cell-based therapies in the treatment of cancer. However, hampered by lack of knowledge about the controversial roles that MSC plays in the crosstalk with tumors, limited progress has been made with regard to translational medicine. Therefore, in this review, we discuss the prospects of MSC-associated anticancer strategies in light of therapeutic mechanisms and signal transduction pathways. In addition, the clinical trials designed to appraise the efficacy and safety of MSC-based anticancer therapies will be assessed according to published data.

The signal transduction pathways via protease activated receptor-1 (PAR-1) in human decidual stromal cells

2015 ◽  
Vol 112 ◽  
pp. 128
Author(s):  
Kaori Goto ◽  
Fumiko Kawabe ◽  
Yasushi Kawano ◽  
Takafumi Utsunomiya ◽  
Hisashi Narahara
Keyword(s):  
Signal Transduction ◽  
Stromal Cells ◽  
Signal Transduction Pathways ◽  
Protease Activated Receptor 1

scholarly journals Characterization of Signal Transduction Pathways in Human Bone Marrow Endothelial Cells

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2253-2259 ◽  
Author(s):  
Zhong-Ying Liu ◽  
Ramesh K. Ganju ◽  
Jian-Feng Wang ◽  
Karin Schweitzer ◽  
Babette Weksler ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
T Antigen ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Signal Transduction Pathways ◽  
Stimulation Of

Human bone marrow endothelial cells immortalized with the T antigen of SV40 (TrHBMEC) have previously been characterized by us with regard to their properties that are similar to primary marrow endothelial cells and their utility as a model system. We now report that TrHBMEC express a recently discovered signal transduction molecule termed RAFTK (related adhesion focal tyrosine kinase), also called Pyk2 or CAK-β. RAFTK, the second member of the focal adhesion kinase (FAK) family, is known to be activated in response to calcium flux in neuronal cells and integrin stimulation in megakaryocytes and B cells. We have studied the effects of cytokines on RAFTK activation in TrHBMEC. Treatment of TrHBMEC with the vascular endothelial growth factor (VEGF ), as well as the VEGF-related protein (VRP), the recently identified ligand for the FLT-4 receptor, resulted in enhanced tyrosine phosphorylation of RAFTK. Similar changes in RAFTK phosphorylation were observed upon stimulation of TrHBMEC with basic fibroblast growth factor (bFGF ) or oncostatin M (OSM). Stimulation of these cells with growth factors also resulted in an increase in RAFTK activity and the c-Jun NH2 -terminal kinase (JNK). RAFTK coimmunoprecipitated with the cytoskeletal protein paxillin through its C-terminal proline-rich domain in TrHBMEC. These results suggest that, in marrow endothelium, activation of RAFTK by VEGF, VRP, OSM, and bFGF represents a new element in the signal transduction pathways used by these growth factors and likely acts to coordinate signaling from their surface receptors to the cytoskeleton, thereby modulating cell growth and function.

scholarly journals Therapeutic Efficacy and Safety of Lenvatinib for Unresectable Hepatocellular Carcinoma Beyond Progression with Sorafenib

2020 ◽  
Author(s):  
Tetsu Tomonari ◽  
Yasushi Sato ◽  
Hironori Tanaka ◽  
Takahiro Tanaka ◽  
Yasuteru Fujino ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
Array Analysis ◽  
Third Line ◽  
Protein Array Analysis ◽  
Third Line Treatment

AbstractBackground & AimsThe efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line treatment of LEN, investigated the sensitivity of SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and their signal transduction pathway by protein array analysis.MethodsWe retrospectively enrolled 57 unresectable HCC patients. Radiologic responses in 53 patients were evaluated by modified Response Evaluation Criteria in Solid Tumors. Active signal transduction pathways in cells were identified by protein array analysis, including 1205 proteins.ResultsPatients comprised 34 tyrosine kinase inhibitor (TKI)-naive (first-line), nine SOR-intolerant (second-line), and ten resistant to regorafenib (third-line). Objective response rates (ORRs) were 61.8% (21/34) in TKI-naive, 33.3% (3/9) in second-line, and 20.0% (2/10) in third-line groups. The overall survival (OS) and the progression free survival (PFS) in the first-line was significantly longer than those in third-line group (p<0.05). Patients with better liver functional reserve (Child score, ALBI grade) exhibited higher ORR and longer OS. LEN was well-tolerated as second/third-line treatment. The IC50 value of LEN against PLC/PRF5-R2 cells (30 μM) was significantly higher than that against PLC/PRF5 cells (6.4 μM). LEN inhibited significantly more signal transduction pathways related to FRS2, a crucial FGFR downstream molecule, in PLC/PRF5 than PLC/PRF5-R2 cells.ConclusionsLEN was active and safe as a second/third-line treatment for unresectable HCC. LEN seems to be more effective for HCC patients with better hepatic reserve function or before TKI-resistance is acquired because of partial cross-resistance to SOR.

Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma beyond progression of sorafenib treatment: A real-world evidence and in vitro assessment with protein phosphorylation array.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 485-485
Author(s):  
Yasushi Sato ◽  
Tetsu Tomonari ◽  
Hironori Tanaka ◽  
Takahiro Tanaka ◽  
Akihiro Hirao ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Array Analysis ◽  
Third Line ◽  
Protein Array Analysis ◽  
Third Line Treatment

485 Background: No information is available on the efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy. We evaluated the characteristics and the therapeutic efficacy and safety of LEN as a second- and third-line treatment as well as first- treatment for unresectable HCC patients in clinical settings. Moreover, to rationalize these clinical findings in vitro, we assessed the anti-tumor activity of LEN on SOR-resistant cell line and performed a comprehensive phosphorylated protein array analysis associated with 377 signal transduction pathways using SOR-resistant and parental HCC cells. Methods: We retrospectively enrolled 51 unresectable HCC patients. Radiologic responses in 41 patients were evaluated by modified RECIST. Active signal transduction pathways in the cells were identified by protein array analysis, including 1205 proteins. Results: The evaluated patients comprised 25 TKI-naive (first- line), 7 intolerant to SOR (second-line), and 9 patients resistant to regorafenib (third-line). The ORRs were 64% in first-line, 42.8% in second-line, and 22.2% in third-line groups (first-line vs. third-line p< 0.05). The OS in the first-line was significantly longer than that in third-line group ( p< 0.05). Patients with better liver functional reserve (Child score, ALBI grade) exhibited higher ORR and longer OS. LEN was well-tolerated in the second/third-line treatment. The IC50 value of LEN against PLC/PRF5-R2 (30 μM) was significantly higher than that against PLC/PRF5 (6.4 μM). LEN significantly inhibited more signal transduction pathways related to FRS2, a crucial FGFR downstream molecule, in PLC/PRF5 than in PLC/PRF5-R2 cells. Conclusions: Our study indicates that LEN was active and safe in the second/third-line treatment for unresectable HCC. LEN seems more effective for HCC patients with better hepatic reserve function, or before TKI-resistance is acquired because of the partial cross-resistance to SOR.

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