Evaluation of MMP-2, MMP-9, TIMP-1, TIMP-2, NGAL and MMP-9/NGAL complex in urine and sera from patients with bladder cancer

Ricci, Serena; Bruzzese, Dario; Carlo, Angelina Di

doi:10.3892/ol.2015.3558

Cited by 36 publications

(24 citation statements)

References 25 publications

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“…TIMP1 is an inhibitor of matrix metalloproteinases, a matrix‐degrading enzyme that facilitates tumor cell dissemination . Urinary TIMP1 was found to be a predictor of cancers, such as renal carcinoma, bladder cancer, and pancreatic malignancies . GRP78 expressed on the surface of tumor cells is associated with proliferation and metastasis .…”

Section: Resultsmentioning

confidence: 99%

Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

Zhang

Meng

et al. 2019

Cancer Medicine

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Background Patients with primary and metastatic brain cancer have an extremely poor prognosis, mostly due to the late diagnosis of disease. Urine, which lacks homeostatic mechanisms, is an ideal biomarker source that accumulates early and highly sensitive changes to provide information about the early stage of disease. Methods A rat model mimicking the local tumor growth process in the brain was established with intracerebral Walker 256 (W256) cell injection. Urine samples were collected on days 3, 5, and 8 after injection, and then analyzed by liquid chromatography coupled with tandem mass spectrometry. Results In the intracerebral W256 model, no obvious clinical manifestations or abnormal magnetic resonance imaging (MRI) signals were found on days 3 or 5; at these time points, 9 proteins were changed significantly in the urine of all eight tumor rats. On day 8, when tumors were detected by MRI, 25 differential proteins were identified, including 10 that have been reported to be closely related to brain metastasis or primary tumors. The differential urinary proteome was compared with those from the subcutaneous W256 model and the intracerebral C6 model. Few differential proteins overlapped, and specific differential protein patterns were observed among the three models. Conclusions These findings demonstrate that early changes in the urine proteome can be detected in the intracerebral W256 model. The urinary proteome can reflect the difference when tumor cells with different growth characteristics are inoculated into the brain and when identical tumor cells are inoculated into different areas, specifically, the subcutis and the brain.

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Section: Resultsmentioning

confidence: 99%

Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

Zhang

Meng

et al. 2019

Cancer Medicine

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“…The present study agrees with previous studies that proved higher MMP-2 to TIMP-2 ratio (MMP-2/TIMP-2) in cancer patients than in controls. [20] MMPs could have a significant impact on angiogenesis in malignant tumors via activation of proangiogenic factors, [20] as well as the generation of angiogenesis inhibitors as endostatin and angiostatin. A higher ratio indicates an imbalance between MMPs and their inhibitors and this promote metastasis through remodeling of ECM.…”

Section: Discussionmentioning

confidence: 99%

MMP‐2 and MMP‐9 as prognostic markers for the early detection of urinary bladder cancer

Fouad

Salem

Ellakwa

et al. 2018

J Biochem & Molecular Tox

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The present study assessed protein and gene expression levels of tissue inhibitor of metalloproteinase‐2 (TIMP‐2), matrix metalloproteinase‐2 (MMP‐2), and MMP‐9 in urine and blood samples of 50 patients with bladder carcinoma. The expression of TIMP‐2, MMP‐2, and MMP‐9 levels with tumor stage and grade was also assessed. Results showed that the expression levels of MMP‐2 and MMP‐9 in both blood and urine were significantly elevated in group 1 when compared with groups 2 and 3 healthy subjects. The discriminatory ability in the diagnosis of bladder carcinoma of MMP‐2 and MMP‐9 expression was confirmed by receiver operating characteristic curve analysis that revealed a sensitivity and specificity of 100%. MMP‐2 and MMP‐9 levels were not correlated with grade or stage of the tumor. With respect to TIMP‐2 blood and urine levels, results showed a significant decrease in gene expression levels in bladder carcinoma group, whereas, TIMP‐2 protein showed a significant increase in bladder carcinoma.

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“…The degradation of the extracellular matrix (ECM) and basement membrane are crucial steps in SCLC cancer invasion and metastasis, and the proteolytic enzymes (MMPs) including MMP-2 and MMP-9 are strongly associated with this process (25). TIMP-2 is the selective inhibitor of MMPs (26). Therefore, we next measured the secretion changes of MMP-2, MMP-9 and TIMP-2 from H446 cells after doxycycline treatment by performing ELISA assay.…”

Section: Discussionmentioning

confidence: 99%

New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer

Wang

Zhao

Liu

et al. 2016

International Journal of Oncology

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Abstract. Small cell lung cancer (SCLC) remains one of the most aggressive tumors with a poor prognosis. The clinical outcome of SCLC patients has reached its plateau with the existing standard treatment and thus new therapies are urgently required. Accumulating evidences have indicated that doxycycline, a commonly used antibiotic, has antitumor activity against several malignancies. However, whether doxycycline has antitumor activity in SCLC and its underlying mechanisms remain unclear. Our investigation demonstrated that doxycycline could significantly inhibit the proliferation and colony formulation of SCLC cells (p<0.05). Furthermore, both Hoechst 33258 dye staining and TUNEL assays indicated that doxycycline could induce remarkable apoptosis of H446 cells in a concentration-dependent manner. RT-PCR and western blot assays proved that apoptosis induction effect of doxycycline was achieved via inducing the expression of caspase-3 and bax, as well as attenuating the expression of survivin and bcl-2. Moreover, the wound healing assay and Transwell assay indicated that doxycycline could significantly suppress the migration and invasion of H446 cells in a concentration-dependent manner (p<0.05). ELISA assay proved that the inhibitory effect of doxycycline on the migration and invasion of H446 cells was achieved via decreasing the secretion of MMP-2, MMP-9 and VEGF, as well as increasing the secretion of TIMP-2. Taken together, doxycycline dose-dependently suppressed the proliferation, colony formulation, migration and invasion of SCLC cells, as well as induced apoptosis. These findings encourage further investigations on the potential of doxycycline as a candidate drug for the treatment of SCLC. IntroductionLung cancer remains the most common cause of cancer-related death worldwide, and was responsible for 1.56 million deaths annually, as of 2012 (1). The main primary types are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Compared with NSCLC, SCLC has a more aggressive behavior due to its higher proliferative index and tends to spread in its early stages. Combination chemotherapy, generally platinumbased plus etoposide or irinotecan, is the mainstay first-line treatment for metastatic SCLC patients (2,3). Despite the initial sensitivity, the long-term outcomes of the majority of SCLC patients remain poor due to early relapse and acquired resistance (2). In addition, the vast majority of patients with SCLC fail to respond to tyrosine-kinase inhibitors against the epidermal growth factor receptor (EGFR) (4). Except for topotecan, few treatment options then remain (2,5,6). Therefore, it is urgent to develop novel and more effective therapeutic drugs for the treatment of SCLC patients. Doxycycline (DOXY) is a member of the tetracycline family of antibiotics in widespread clinical use. Accumulating evidence has suggested that doxycycline has antitumor activity against several kinds of malignancies. It has been reported that doxycycline has anti-metastatic activity and cytotoxicity in melanoma ...

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Evaluation of MMP-2, MMP-9, TIMP-1, TIMP-2, NGAL and MMP-9/NGAL complex in urine and sera from patients with bladder cancer

Cited by 36 publications

References 25 publications

Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

Dynamic urinary proteomic analysis in a Walker 256 intracerebral tumor model

MMP‐2 and MMP‐9 as prognostic markers for the early detection of urinary bladder cancer

New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer

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