scholarly journals Comparison of osteoclastogenesis and local invasiveness of ameloblastoma and keratocystic odontogenic tumor

2018 ◽  
Vol 12 (01) ◽  
pp. 036-042
Author(s):  
Natheer H. Al-Rawi ◽  
Ammar K. Al-Siraj ◽  
Ahlam H. Majeed
Keyword(s):  
Matrix Metalloproteinase ◽  
Stromal Cells ◽  
Nuclear Factor Kappa B ◽  
The Other ◽  
Matrix Metalloproteinase 2 ◽  
Keratocystic Odontogenic Tumor ◽  
Nuclear Factor ◽  
Significant Expression ◽  
Type Ab ◽  
Keratocystic Odontogenic Tumors

Abstract: Objectives The aim of this study was to compare the expression of receptor-activated nuclear factor kappa B (RANK) with its ligand (RANKL) and matrix metalloproteinase-2 (MMP2) in solid/multicystic ameloblastomas (ABs) and keratocystic odontogenic tumors (KOTs). Materials and Methods: The expression of MMP2, RANK, and RANKL molecules was evaluated in 13 ABs and 14 KOTs by immunohistochemistry. The expressions were calculated in the odontogenic epithelial cells as well as the stromal cells. Results: Odontogenic epithelia of AB expressed MMP2, RANK, and RANKL significantly higher than that of KOTs (P < 0.05). The expression of MMP2, RANK, and RANKL was highest in plexiform subtype (79.9%, 81.08%, and 65.1%, respectively). KOTs without daughter epithelia nests expressed both MMP2 and RANK the least (56.06% and 47.5%, respectively). Stromal cells, on the other hand, expressed similar MMP2 pattern in odontogenic epithelia of both AB and KOT. RANKL was expressed weaker in the stromal cells of both lesions. Conclusion: Invasive biological and osteolytic behaviors of both lesions were evaluated in this study. It was found to be more in AB than keratocystic odontogenic. A significant expression of MMP2, RANK, and RANKL in both KOTs associated with microcyst and plexiform type AB as well.

L-Tetrahydropalmatine Inhibits the Progression of Glioblastoma Tumor by Suppressing the Extracellular-Signal-Regulated Kinase/Nuclear Factor-Kappa B Signaling Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 164-171
Author(s):  
Feng Xue ◽  
Tingting Chen
Keyword(s):  
Glioblastoma Multiforme ◽  
Nuclear Factor Kappa B ◽  
Matrix Metalloproteinase 2 ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Extracellular Signal ◽  
Apoptosis Protein ◽  
Endothelial Growth Factor

Glioblastoma multiforme is the most common malignancy of central nervous system. Herein we have evaluated the effect of L-tetrahydropalmatine, an isoquinoline alkaloid, on the tumor growth both in vivo and in vitro using C6 glioblastoma multiforme cells and BALB/c mice injected subcutaneously with C6/luc2 cells. The results of these studies show that L-tetrahydropalmatine exhibited cytotoxic effect on C6 glioblastoma multiforme cells, suppressed nuclear factor-kappa B activity, suppressed the levels of tumor-linked proteins such as matrix metalloproteinase-2/9, Cyclin-D1, vascular endothelial growth factor, and X-linked inhibitor of apoptosis protein via ERK/nuclear factor-kappa B cascade. Further, L-tetrahydropalmatine inhibited the cell migration and invasion properties of C6 cells, and also suppressed the tumor weight and volume in mice. Immunohistochemical staining of tumor tissues suggested that L-tetrahydropalmatine inhibited the extracellular-signal-regulated kinase/nuclear factor-kappa B cascade and suppressed the levels of Cyclin-D1; matrix metalloproteinase-2/9; X-linked inhibitor of apoptosis protein; and vascular endothelial growth factor, and also the progression and growth of glioblastoma multiforme in mice. In summary, L-tetrahydropalmatine inhibits the ERK/nuclear factor-kappa B cascade, decreases the tumor volume, and inhibits the proteins responsible for tumor growth both in vivo and in vitro.

scholarly journals Differential Expression of Matrix Metalloproteinase-2 Expression in Disseminated Tumor Cells and Micrometastasis in Bone Marrow of Patients with Nonmetastatic and Metastatic Prostate Cancer: Theoretical Considerations and Clinical Implications—An Immunocytochemical Study

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Nigel P. Murray ◽  
Eduardo Reyes ◽  
Pablo Tapia ◽  
Leonardo Badínez ◽  
Nelson Orellana
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Matrix Metalloproteinase ◽  
Tumor Cells ◽  
Gleason Score ◽  
Stromal Cells ◽  
Disseminated Tumor Cells ◽  
Matrix Metalloproteinase 2 ◽  
Low Grade ◽  
Immunocytochemical Study

Matrix metalloproteinase-2 (MMP-2) is important in the dissemination and invasion of tumor cells and activates angiogenesis. We present an immunocytochemical study of MMP-2 expression in circulating prostate cells (CPCs), disseminated tumor cells (DTCs), and micrometastasis (mM) in bone marrow of men with prostate cancer. Methods and Patients. Tumor cells were identified with anti-PSA immunocytochemistry. Positive samples underwent processing with anti-MMP-2, its expression was compared with Gleason score, concordance of expression, and metastatic and nonmetastatic disease. Results. 215 men participated, CPCs were detected in 62.7%, DTCs in 62.2%, and mM in 71.4% in nonmetastatic cancer; in metastatic cancer all had CPCs, DTCs, and mM detected. All CPCs and DTCs expressed MMP-2; in mM MMP-2 expression was positively associated with increasing Gleason score. MMP-2 expression in CPCs and DTCs showed concordance. In low grade tumors, mM and surrounding stromal cells were MMP-2 negative, with variable expression in high grade tumors; in metastatic disease, both mM and stromal cells were MMP-2 positive. Conclusions. CPCs and DTCs are different from mM, with inhibition of MMP-2 expression in mM of low grade tumors. With disease progression, MMP-2 expression increases in both mM and surrounding stromal cells, with implications for the use of bisphosphonates or MMP-2 inhibitors.

scholarly journals Steps involved in activation of the complex of pro-matrix metalloproteinase 2 (progelatinase A) and tissue inhibitor of metalloproteinases (TIMP)-2 by 4-aminophenylmercuric acetate

1995 ◽  
Vol 308 (2) ◽  
pp. 645-651 ◽  
Author(s):  
Y Itoh ◽  
S Binner ◽  
H Nagase
Keyword(s):  
Matrix Metalloproteinase ◽  
Noncovalent Complex ◽  
The Other ◽  
Gelatinolytic Activity ◽  
Matrix Metalloproteinase 2 ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor ◽  
Sh Group ◽  
Inhibitory Domain ◽  
Interstitial Collagenase

Tissue inhibitor of metalloproteinases (TIMP)-2 forms a noncovalent complex with the precursor of matrix metalloproteinase 2 (proMMP-2, progelatinase A) through interaction of the C-terminal domain of each molecule. We have isolated the proMMP-2-TIMP-2 complex from the medium of human uterine cervical fibroblasts and investigated the processes involved in its activation by 4-aminophenylmercuric acetate (APMA). The treatment of the complex with APMA-activated proMMP-2 by disrupting the Cys73-Zn2+ interaction of the zymogen. This is triggered by perturbation of the proMMP-2 molecule, but not by the reaction of the SH group of Cys73 with APMA. The ‘activated’ proMMP-2 (proMMP-2*) formed a new complex with TIMP-2 by binding to the N-terminal inhibitory domain of the inhibitor without processing the propeptide. Thus the APMA-treated proMMP-2*-TIMP-2 complex exhibited no gelatinolytic activity. In the presence of a small amount of free MMP-2, however, proMMP-2* in the complex was converted into the 65 kDa MMP-2 by proteolytic attack of MMP-2, but the complex did not exhibit gelatinolytic activity. The gelatinolytic activity detected after APMA treatment was solely derived from the activation of free proMMP-2. The removal of the propeptide of the proMMP-2* bound to TIMP-2 was also observed by MMP-3 (stromelysin 1), but not by MMP-1 (interstitial collagenase). MMP-3 cleaved the Asn80-Tyr81 bond of proMMP-2*. On the other hand, when MMP-3 was incubated with the proMMP-2-TIMP-2 complex, it bound to TIMP-2 and rendered proMMP-2 readily activatable by APMA. These results indicate that the blockage of TIMP-2 of the complex with an active MMP is essential for the activation of proMMP-2 when it is complexed with TIMP-2.

Bortezomib Is Not Active in Patients with Relapsed Hodgkin’s Lymphoma: Results of a Prematurely Closed Phase II Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2477-2477 ◽  
Author(s):  
Sven Trelle ◽  
Orhan Sezer ◽  
Ralph Naumann ◽  
Mathias Rummel ◽  
Ulrich Keller ◽  
...  
Keyword(s):  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Nuclear Factor Kappa B ◽  
Phase Ii Study ◽  
The Other ◽  
Hodgkin's Lymphoma ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Heavily Pretreated ◽  
Pretreated Patients

Abstract Background: Hodgkin’s and Reed-Sternberg cells are known to be resistant to apoptosis due to over-expression of Nuclear Factor kappa-B (NF-κB). Bortezomib increases intracellular levels of Inhibitor of Nuclear Factor kappa-B (I-κB) which inhibits activation of NF-κB. Laboratory studies indicate that bortezomib has a strong antiproliferative activity in Hodgkin’s lymphoma derived cell lines. We aimed to investigate the activity of bortezomib given in combination with dexamethasone in patients with relapsed Hodgkin’s lymphoma (HL). Methods: This was a multicenter, two-stage phase II study. Patients (pts.) with relapsed HL received 1.3 mg/m2 bortezomib plus 20 mg dexamethasone on days 1, 4, 8, and 11 of a 3-weekly cycle for up to 8 cycles. Response and toxicity were evaluated using standard criteria (Cheson 1999, Lister 1989; NCI-CTC v3.0). Circulating proteasome concentration was measured using sandwich enzyme-linked immunosorbent assay. Sample size was calculated according to Simon’s optimal design with 12 pts in the first stage and 25 thereafter. At least one response in the first 12 pts was required to proceed to the second stage. Results: As pre-specified in the protocol twelve pts were entered in the first stage and are assessable for response. All pts were heavily pre-treated with a median of 3 prior therapies and all but one had received high-dose chemotherapy. Two pts prematurely discontinued the study treatment due to toxicities after 2 and 3 cycles respectively. Both had stable disease at their final evaluation. All of the other 10 pts had progressive disease. Nine of these prematurely discontinued the study treatment due to insufficient response after a median of 2 cycles (range: 2–5 cycles) and only 1 received all 8 cycles. Since no response was observed in the first 12 pts, the study was stopped after the first stage. Eleven patients were assessable for toxicity as of August 2006. Two of these experienced no toxicity > °I. The other 9 patients experienced at least 1 episode of a ≥ °II toxicity requiring some dose modifications, treatment delays, or discontinuation and 4 of these experienced °IV toxicity. Reported toxicities included thrombocytopenia (°II: 1 pat; °III: 1 pat; IV: 2 pat); lymphopenia (°III: 1 pat); febrile neutropenia (°IV: 1 pat); infection (°II: 2 pat); herpes zoster (°III: 1 pat); pain (°II: 2 pat); loss of appetite (°IV: 1 pat); cough (°III: 1 pat); epistaxis (°III: 1 pat); paralytic ileus (°IV: 1 pat); diarrhea (°III: 1 pat); and sleep disturbance (°III: 2 pat). Details on treatment administration and proteasome concentration will be presented as well as results of a meta-analysis of all available phase II studies of bortezomib in HL. Interpretation: Bortezomib in combination with dexamethasone is not active in heavily-pretreated patients with relapsed Hodgkin’s lymphoma. Furthermore, this treatment regimen possesses severe toxicities in heavily pre-treated Hodgkin’s patients. The use of bortezomib combined with dexamethasone is therefore discouraging in heavily pre-treated patients with HL. Further studies may only be justified with other combinations or less heavily pretreated patients.

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