Publications by authors named "Kenneth Ndebele"

Although colorectal cancer (CRC) treatment has seen a remarkable improvement in the recent years, many patients will develop metastasis due to the resistance of cancer cells to chemotherapeutics. Targeting mechanisms driving the resistance of CRC cells to treatment would significantly reduce cases of metastasis and death. Induction of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a direct target of the Wnt/β-catenin signaling pathway, might promote resistance of CRC cells to treatment via activation of anti-apoptotic pathways and induction of the multidrug resistance (MDR1) membrane transporter that pumps drugs out of the cells.

View Article and Find Full Text PDF

Background: Arsenic trioxide (ATO) is highly effective in the treatment of patients with acute promyelocytic leukemia (APL). It is a chemotherapeutic agent that has been shown to induce apoptosis in several tumor cell lines. However, research into its effects on colon carcinoma cells is still very limited.

View Article and Find Full Text PDF

Precision in redox signaling is attained through posttranslational protein modifications such as oxidation of protein thiols. The peroxidase peroxiredoxin 1 (PRDX1) regulates signal transduction through changes in thiol oxidation of its cysteines. We demonstrate here that PRDX1 is a binding partner for the tumor suppressive transcription factor FOXO3 that directly regulates the FOXO3 stress response.

View Article and Find Full Text PDF

Background: Lung cancer is one of the most lethal and common cancers in the world, causing up to 3 million deaths annually. The chemotherapeutic drugs that have been used in treating lung cancer include cisplatin-pemetrexed, cisplastin-gencitabinoe, carboplatin-paclitaxel and crizotinib. Arsenic trioxide (ATO) has been used in the treatment of acute promyelocytic leukemia.

View Article and Find Full Text PDF

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is largely incurable due to late diagnosis. Superior early detection biomarkers are critical to improving PDAC survival and risk stratification.

Experimental Design: Optimized meta-analysis of PDAC transcriptome datasets identified and validated key PDAC biomarkers.

View Article and Find Full Text PDF

Glioblastoma is the most common brain tumor in adults in which recurrence has been attributed to the presence of cancer stem cells in a hypoxic microenvironment. On the basis of tumor formation in vivo and growth type in vitro, two published microarray gene expression profiling studies grouped nine glioblastoma stem-like (GS) cell lines into one of two groups: full (GSf) or restricted (GSr) stem-like phenotypes. Aquaporin-1 (AQP1) and aquaporin-4 (AQP4) are water transport proteins that are highly expressed in primary glial-derived tumors.

View Article and Find Full Text PDF

Induced pluripotent stem cells (IPS) are an artificially derived type of pluripotent stem cell, showing many of the same characteristics as natural pluripotent stem cells. IPS are a hopeful therapeutic model; however there is a critical need to determine their response to environmental toxins. Effects of arsenic on cells have been studied extensively; however, its effect on IPS is yet to be elucidated.

View Article and Find Full Text PDF

Glioblastoma multiforme (GBM) is the most aggressive brain cancer with a median survival of 1-2 years. The treatment of GBM includes surgical resection, radiation and chemotherapy, which minimally extends survival. This poor prognosis necessitates the identification of novel molecular targets associated with glioblastoma.

View Article and Find Full Text PDF

The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels.

View Article and Find Full Text PDF

Inorganic arsenic is a known environmental toxicant and carcinogen of global public health concern. Arsenic is genotoxic and cytotoxic to human keratinocytes. However, the biological pathways perturbed in keratinocytes by low chronic dose inorganic arsenic are not completely understood.

View Article and Find Full Text PDF

Arsenic trioxide, the trade name Trisenox, is a drug used to treat acute promyleocytic leukemia (APL). Studies have demonstrated that arsenic trioxide slows cancer cells growth. Although arsenic influences numerous signal-transduction pathways, cell-cycle progression, and/or apoptosis, its apoptotic mechanisms are complex and not entirely delineated.

View Article and Find Full Text PDF

Endogenous estrogens have dramatic and differential effects on classical endocrine organ and proliferation. Xenoestrogens are environmental estrogens that have endocrine impact, acting as both estrogen agonists and antagonists, but whose effects are not well characterized. In this investigation we sought to delineate effects of xenoestrogens.

View Article and Find Full Text PDF

Lung cancer is the second leading deadly cancer in United States. In 2007, the United States reported 213,380 new lung cancer diagnoses and 160,390 deaths caused by lung cancer. Retinoic acid and retinyl esters are the oxidized and storage forms of vitamin A in the body.

View Article and Find Full Text PDF

The bodys elemental/ metal loads are known to exert essential influence in maintaining normal and abnormal metabolism leading to eventual pathology of some forms of cancer phenotypes. Accumulation of potentially toxic or nonessential trace metals has been observed but not highly noted as an active factor in toxicogenesis and in the development of many diseases including cancers. The compositional balance and distribution of trace metals in various body tissues are essential key players in homeostasis in life.

View Article and Find Full Text PDF

Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) initiate pathways of cell death in which caspase activation is mediated either directly (without mitochondrial amplification), or indirectly via the release of apoptogenic factors from mitochondria. Phospholipid scramblases (PLS) are enzymes that play a key role in cellular function by inducing bidirectional movement of membrane lipids. Changes in mitochondrial membrane lipids, cardiolipin, are critical for mediating apoptotic response in many cell-types.

View Article and Find Full Text PDF

Participation of diverse organelles in the intracellular signalling that follows CD95/Fas receptor ligation encompasses a series of subcellular changes that are mandatory for, or even bolster, the apoptotic cascade. In the present study, we analysed the role of endocytosis in the propagation of cell death signalling after CD95/Fas engagement in type II cells (CEM cells). We show that this receptor-ligand interaction triggers endocytosis independently of any caspase activation.

View Article and Find Full Text PDF

In Eastern cultures, such as India, it is traditionally recommended that women but not men cover their heads while working in the scorching sun. The purpose of this pilot study was to determine whether there was any scientific basis for this cultural tradition. We examined the differential cytotoxic effects of ultraviolet A light (UVA) on an established T cell line treated with female and male sex hormones.

View Article and Find Full Text PDF

Endogenous estrogens are known to modulate several components of immune response, including interleukin-2 (IL-2) production. IL-2 is a cytokine that plays an important role in adaptive immune responses. These responses may be modulated by xenoestrogens such as coumestrol, bisphenol A (BPA), DDT, and TCDD.

View Article and Find Full Text PDF

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to have selective antitumor activity. TRAIL induces ubiquitous pathways of cell death in which caspase activation is mediated either directly or via the release of apoptogenic factors from mitochondria; however, the precise components of the mitochondrial signaling pathway have not been well defined. Notably, mitochondria constitute an important target in overcoming resistance to TRAIL in many types of tumors.

View Article and Find Full Text PDF

Apoptosis of vascular endothelial cells is associated with the regression of angiogenesis. Endostatin is a potential anti-angiogenic drug, but the effects of endostatin on apoptotic machinery in endothelial cells largely remain unclear. In the present study, human endostatin was expressed in E.

View Article and Find Full Text PDF

The effects of static electromagnetic fields (SEFs) on MG-63, a human osteoblast cell-line, were investigated. We examined proliferation, proline uptake and gene expression in an SEF approximately 1/728th the intensity of those previously reported. Cells were placed within an SEF apparatus (average field intensity of 0.

View Article and Find Full Text PDF