Search results for " tumor"

Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells

2013

Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth an…

Lovastatin stimulates p75 TNF receptor (TNFR2) expression in primary human endothelial cells

2005

HMG-CoA reductase inhibitors (statins) exert pleiotropic physiological effects. Among others they attenuate cellular responses to genotoxic and inflammatory stress. We investigated the effect of lovastatin on the expression level of TNF receptors (TNFR) in primary human endothelial cells (HUVEC). ELISA, FACS and immunocytochemical analyses show that lovastatin selectively increases the cell surface expression of TNFR2 without affecting the expression level of TNFR1. This effect of lovastatin is independent from inhibition of cell-cycle progression since cells both in G1- and G2-phase showed elevated levels of TNFR2 after lovastatin treatment. To analyze the physiological relevance of lovast…

Delivery of siHIF‐1α to Reconstruct Tumor Normoxic Microenvironment for Effective Chemotherapeutic and Photodynamic Anticancer Treatments

2021

The tumor hypoxic microenvironment not only induces genetic and epigenetic changes in tumor cells, immature vessels formation for oxygen demand, but also compromises the efficiency of therapeutic interventions. On the other hand, conventional therapeutic approaches which kill tumor cells or destroy tumor blood vessels to block nutrition and oxygen supply usually facilitate even harsher microenvironment. Thus, simultaneously relieving the strained response of tumor cells and blood vessels represents a promising strategy to reverse the adverse tumor hypoxic microenvironment. In the present study, an integrated amphiphilic system (RSCD) is designed based on Angiotensin II receptor blocker cand…

Cytotoxicity of natural products and derivatives toward MCF-7 cell monolayers and cancer stem-like mammospheres

2015

Abstract Although cancer stem-like cells (CSCs) are rare, they can enter a non-proliferative or dormant state and resist therapy. Furthermore, quiescent CSCs are responsible for metastases that can appear after curative surgical treatment of a primary tumor. Because of drug resistance of CSCs, the development of novel therapies is urgently required that specifically target CSCs. Purpose The aim of the present study was to investigate the potential of a panel of natural products and derivatives to inhibit CSC-enriched mammospheres of MCF-7 breast cancer cells. Methods CD44high/CD24low cells were identified by flow cytometry and maintained as mammospheres. As a control, we used two clinically…

Natural Killer Group 2D Ligand Depletion Reconstitutes Natural Killer Cell Immunosurveillance of Head and Neck Squamous Cell Carcinoma

2017

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive tumor originating from the epithelial lining of the upper aero-digestive tract accounting for 300,000 annual deaths worldwide due to failure of current therapies. The natural killer group 2D (NKG2D) receptors on natural killer (NK) cells and several T cell subsets play an important role for immunosurveillance of HNSCC and are thus targeted by tumor immune evasion strategies in particular by shedding of various NKG2D ligands (NKG2DLs). Based on plasma and tumor samples of 44 HNSCC patients, we found that despite compositional heterogeneity the total plasma level of NKG2DLs correlates with NK cell inhibitio…

Cancer-Initiating Cells from Colorectal Cancer Patients Escape from T Cell-Mediated Immunosurveillance In Vitro through Membrane-Bound IL-4

2014

Abstract Cancer-initiating cells (CICs) that are responsible for tumor initiation, propagation, and resistance to standard therapies have been isolated from human solid tumors, including colorectal cancer (CRC). The aim of this study was to obtain an immunological profile of CRC-derived CICs and to identify CIC-associated target molecules for T cell immunotherapy. We have isolated cells with CIC properties along with their putative non-CIC autologous counterparts from human primary CRC tissues. These CICs have been shown to display “tumor-initiating/stemness” properties, including the expression of CIC-associated markers (e.g., CD44, CD24, ALDH-1, EpCAM, Lgr5), multipotency, and tumorigenic…

Descriptive study on subjective experience of genetic testing with respect to relationship, family planning and psychosocial wellbeing among women wi…

2021

AbstractBackgroundDue to increased risk of endometrial and ovarian cancer, women belonging to known Lynch Syndrome (LS) families are recommended to undergo germline testing. Current practice in Finland is to offer counselling to women with pathogenic variant and advocate risk-reducing surgery (RRS) after completion of childbirth. The present study aimed to clarify the impacts of positive germline testing on family planning and reproductive decisions of these women, which are relatively unknown.MethodsSeventy-nine carriers of germline MMR gene pathogenic variant (path_MMR)were identified from the Finnish LS Registry as having genetic testing performed before the age of 45 years and not havin…

Proteomic profiling of vesicles released by 8701-bc cells

2008

8701-BC cells were shown to release “membrane vesicles” playing a role in tumor progression mechanisms. On the other hand, production of “exosomes”, smaller vesicles known to be involved in immune response activation, had not been revealed. The first goal of this study was to separate different vesicle populations from 8701-BC cell conditioned medium. To this aim, the medium was differentially centrifuged. Western analysis revealed that the 15,000xg pelletted fraction contains β1-integrin, which had been shown to be clustered in membrane vesicles shed by 8701-BC cells, but not Hsc70, a protein found in exosomes. On the contrary, Hsc70 is detectable while β1-integrin is not present in the fr…

The E3 Ubiquitin Ligase MID1 Catalyzes Ubiquitination and Cleavage of Fu

2014

Sonic Hedgehog (SHH)-GLI signalling plays an important role during embryogenesis and in tumorigenesis. The survival and growth of several types of cancer depend on autonomously activated SHH-GLI signalling. A protein complex containing the ubiquitin-ligase MID1 and protein phosphatase 2A (PP2A) regulates the nuclear localization and transcriptional activity of GLI3, a transcriptional effector molecule of SHH, in cancer cell lines with autonomously activated SHH signalling. However, the exact molecular mechanisms that mediate the interaction between MID1 and GLI3 remained unknown. Here, we show that MID1 catalyses the ubiquitination and proteasomal cleavage of the GLI3-regulator Fu. Our data…

Liquid biopsy in colorectal carcinoma: the search for potential prognostic and predictive biomarkers

Background: Liquid biopsy is considered a repeatable, non-invasive and dynamic tool. It could be able to recover from liquid samples (expecially blood)) cancer-specific informations (miRNAs, circulating-free DNA (cfDNA), circulating tumor DNA (ctDNA) and exosomes) by overcoming the limitations associated with traditional tissue biopsy. Aim: to investigate the potential prognostic and predictive role of blood cancer-related biomarkers such as cfDNA or ctDNA and exosomal DNA in colorectal cancer (CRC) patients. Results: cfDNA or ctDNA and exosomal DNA could have a potential applicability in CRC management. New generation technologies are able to identify clinically relevant genomic alteration…