Search results for "Cause"

Abstract C75: Overcoming KRAS/LKB1 mutant NSCLC resistance to BET bromodomain inhibitors with gemcitabine or Mcl-1 inhibition

2015

Abstract The purpose of our study was to define a method and mechanism for overcoming the resistance of clinically relevant KRAS-mutant/LKB1-deficient NSCLC cells to the BET-bromodomain inhibitor JQ1. LKB1 (Serine/threonine kinase 11) is mutated with loss of function in conjunction with mutated KRAS in 7-10% of NSCLC. Importantly, KRAS-mutant/LKB1-deficiency is associated with tumor aggressiveness and poor survival in human patients as well as in genetically engineered mouse models. Indeed, although the BET bromodomain inhibitor JQ1 dramatically reduces tumor volume in KRAS mutant mice, it has little effect in KRAS-mutant/LKB1-deficient mice. BET bromodomain proteins are chromatin readers t…

Abstract 857: Metal oxide nanoparticles as adjuvant for radiation therapy

2018

Abstract Background: Radiation therapy comprises a fundamental component of modern tumor treatment. Unfortunately, its success is limited by the development of radiation resistances. The emerging field of nanotechnology offers great opportunities for diagnosing, imaging, as well as treating cancer. Metal oxide nanoparticles in particular zinc oxide nanoparticles (ZnO-NP) have been shown to display a selective cytotoxic effect on tumor cells via a yet unknown mechanism. Most likely the generation of reactive oxygen species (ROS), breakdown of mitochondria and DNA damage are involved. The success of radiation therapy equally relies on the generation of ROS, which develop their cytotoxic poten…

Identification and expansion of human colon-cancer-initiating cells

2007

Colon carcinoma is the second most common cause of death from cancer. The isolation and characterization of tumorigenic colon cancer cells may help to devise novel diagnostic and therapeutic procedures. Although there is increasing evidence that a rare population of undifferentiated cells is responsible for tumour formation and maintenance, this has not been explored for colorectal cancer. Here, we show that tumorigenic cells in colon cancer are included in the high-density CD133+ population, which accounts for about 2.5% of the tumour cells. Subcutaneous injection of colon cancer CD133+ cells readily reproduced the original tumour in immunodeficient mice, whereas CD133- cells did not form …

Genetic structure in the paleoendemic and endangered Petagnaea gussonei (Spreng.) Rauschert (Saniculoideae, Apiaceae) and implications for its conser…

2012

Our investigation aims to understand the genetic structure and evolutionary history of Petagnaea gussonei, an ancient and endangered species belonging to the Saniculoideae subfamily (Apiaceae). It is paleoendemic to Sicily, with a small number of populations in the Nebrodi Mountains. A total of seven chloroplast microsatellite repeat loci and 12 AFLP primer combinations were used to screen 115 individuals corresponding to 17 populations. The ratio of seed to pollen flow was also calculated using the modified Ennos equation. A relatively high level of genetic diversity was detected with AFLPs (e.g., 0.045 < H < 0.278), and a moderate variation was also found using cpSSRs (0 < Hk < 0.667). Tw…

Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

2021

International audience; Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress. This leads to insulin resistance …

The lignan, (-)-sesamin reveals cytotoxicity toward cancer cells: pharmacogenomic determination of genes associated with sensitivity or resistance.

2013

(-)-Sesamin is a lignan present in sesam oil and a number of medicinal plants. It exerts various pharmacological effects, such as prevention of hyperlipidemia, hypertension, and carcinogenesis. Moreover, (-)-sesamin has chemopreventive and anticancer activity in vitro and in vivo. Multidrug resistance (MDR) of tumors leads to fatal treatment outcome in many patients and novel drugs able to kill multidrug-resistant cells are urgently needed. P-glycoprotein (MDR1/ABCB1) is the best known ATP-binding cassette (ABC) drug transporter mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. We found that the mRNA expressions of ABCB1 and ABCB5 were not related to the 50% inhibi…

Pharmacogenomic Characterization of Cytotoxic Compounds from Salvia officinalis in Cancer Cells.

2015

Salvia officinalis is used as a dietary supplement with diverse medicinal activity (e.g. antidiabetic and antiatherosclerotic effects). The plant also exerts profound cytotoxicity toward cancer cells. Here, we investigated possible modes of action to explain its activity toward drug-resistant tumor cells. Log10IC50 values of two constituents of S. officinalis (ursolic acid, pomolic acid) were correlated to the expression of ATP-binding cassette (ABC) transporters (P-glycoprotein/ABCB1/MDR1, MRP1/ABCC1, BCRP/ABCG2) and epidermal growth factor receptor (EGFR) or mutations in RAS oncogenes and the tumor suppressor gene TP53 of the NCI panel of cell lines. Gene expression profiles predicting se…

CitA/CitB Two-Component System Regulating Citrate Fermentation in Escherichia coli and Its Relation to the DcuS/DcuR System In Vivo

2011

ABSTRACT Citrate fermentation by Escherichia coli requires the function of the citrate/succinate antiporter CitT ( citT gene) and of citrate lyase ( citCDEFXG genes). Earlier experiments suggested that the two-component system CitA/CitB, consisting of the membrane-bound sensor kinase CitA and the response regulator CitB, stimulates the expression of the genes in the presence of citrate, similarly to CitA/CitB of Klebsiella pneumoniae . In this study, the expression of a chromosomal citC-lacZ gene fusion was shown to depend on CitA/CitB and citrate. CitA/CitB is related to the DcuS/DcuR two-component system which induces the expression of genes for fumarate respiration in response to C 4 -di…

S1/3 The stator stalk of Escherichia coli ATP synthase

2008

Annual cycles of apoptosis, DNA strand breaks, heat shock proteins, and metallothionen isoforms in dab (Limanda limanda): influences of natural facto…

2013

The present study was undertaken to investigate the influence of natural and anthropogenic stressors on the induction of apoptosis, metallothionein (MT) isoforms, heat shock proteins and DNA strand breaks in the marine flatfish dab (Limbanda limanda) Seasonal changes and possible physiological influences were evaluated over a 1-year period at a fixed location northwest of Helgoland in the German Bight. These results were compared with data from sampling sites in the North Sea and the Baltic Sea. Annual cycles could be observed for all parameters except for Cd. The data revealed that changes in biomarker are not only linked to physiological processes related to reproduction but also to facto…