Charlie Norwood VA Medical Center

About: Charlie Norwood VA Medical Center is a healthcare organization based out in Augusta, Georgia, United States. It is known for research contribution in the topics: Autophagy & Kidney. The organization has 349 authors who have published 490 publications receiving 16360 citations. The organization is also known as: Augusta VA Medical Center.

CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype.

Abstract: // Amy V. Paschall 1, 2, 3 , Dafeng Yang 1, 3 , Chunwan Lu 1, 3 , Priscilla S. Redd 1, 2, 3 , Jeong-Hyeon Choi 2 , Christopher M. Heaton 3 , Jeffrey R. Lee 3 , Asha Nayak-Kapoor 2, 3 , Kebin Liu 1, 2, 3 1 Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA 2 Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA 3 Charlie Norwood VA Medical Center, Augusta, GA 30904, USA Correspondence to: Kebin Liu, email: Kliu@augusta.edu Keywords: CD133, CD24, colon cancer stem cells, 5-Fluorouracil Received: January 14, 2016 Accepted: September 12, 2016 Published: September 21, 2016 ABSTRACT The chemotherapeutic agent 5-Fluorouracil (5-FU) is the most commonly used drug for patients with advanced colon cancer. However, development of resistance to 5-FU is inevitable in almost all patients. The mechanism by which colon cancer develops 5-FU resistance is still unclear. One recently proposed theory is that cancer stem-like cells underlie colon cancer 5-FU resistance, but the phenotypes of 5-FU-resistant colon cancer stem cells are still controversial. We report here that 5-FU treatment selectively enriches a subset of CD133 + colon cancer cells in vitro . 5-FU chemotherapy also increases CD133 + tumor cells in human colon cancer patients. However, sorted CD133 + colon cancer cells exhibit no increased resistance to 5-FU, and CD133 levels exhibit no correlation with colon cancer patient survival or cancer recurrence. Genome-wide analysis of gene expression between sorted CD133 + colon cancer cells and 5-FU-selected colon cancer cells identifies 207 differentially expressed genes. CD24 is one of the genes whose expression level is lower in the CD133 + and 5-FU-resistant colon cancer cells as compared to CD133 + and 5-FU-sensitive colon cancer cells. Consequently, CD133 + CD24 lo cells exhibit decreased sensitivity to 5-FU. Therefore, we determine that CD133 + CD24 lo phenotype defines 5-FU-resistant human colon cancer stem cell-like cells.

β-Arrestin-2 Counters CXCR7-Mediated EGFR Transactivation and Proliferation.

Abstract: The atypical 7-transmembrane chemokine receptor, CXCR7, transactivates the EGFR leading to increased tumor growth in several tumor types. However, the molecular mechanism of CXCR7 ligand–independent EGFR transactivation is unknown. We used cDNA knock-in, RNAi and analysis of mitogenic signaling components in both normal prostate epithelial cells and prostate cancer cells to decipher the proliferation-inducing mechanism of the CXCR7–EGFR interaction. The data demonstrate that CXCR7-induced EGFR transactivation is independent of both the release of cryptic EGFR ligands (e.g., AREG/amphiregulin) and G-protein–coupled receptor signaling. An alternate signaling mechanism involving β-arrestin-2 (ARRB2/β-AR2) was examined by manipulating the levels of β-AR2 and analyzing changes in LNCaP cell growth and phosphorylation of EGFR, ERK1/2, Src, and Akt. Depletion of β-AR2 in LNCaP cells increased proliferation/colony formation and significantly increased activation of Src, phosphorylation of EGFR at Tyr-1110, and phosphorylation/activation of ERK1/2 compared with that with control shRNA. Moreover, β-AR2 depletion downregulated the proliferation suppressor p21. Stimulation of β-AR2–expressing cells with EGF resulted in rapid nuclear translocation of phosphorylated/activated EGFR. Downregulation of β-AR2 enhanced this nuclear translocation. These results demonstrate that β-AR2 is a negative regulator of CXCR7/Src/EGFR–mediated mitogenic signaling. Implications: This study reveals that β-AR2 functions as a tumor suppressor, underscoring its clinical importance in regulating CXCR7/EGFR–mediated tumor cell proliferation. Mol Cancer Res; 14(5); 493–503. ©2016 AACR . This article is featured in Highlights of This Issue, [p. 409][1] [1]: /lookup/volpage/14/409?iss=5

Charles Bonnet Syndrome: A Review of the Literature

Abstract: Charles Bonnet syndrome (CBS) commonly occurs in older adults with visual impairments, particularly those with age-related macular degeneration It is characterized by complex visual hallucinations in individuals without mental disorders The authors explore diagnostic criteria, demographic characteristics, clinical features, theories of pathogenesis, and management options for people who are diagnosed with CBS ********** A substantial number of older adults without mental disorders but with age-related visual impairments experience formed visual hallucinations that are due to a condition known as Charles Bonnet syndrome (CBS; Teunisse et al, 1999) CBS is particularly common in people with agerelated macular degeneration (AMD) (Kahn, Shahid, Thurlby, Yates, & Moore, 2008; Lannon et al, 2006) and has been reported in persons with diabetic retinopathy (Holroyd, Rabins, Finkelstein, & Lavrisha, 1994; Teunisse, Cruysberg, Verbeek, & Zitman, 1995; Teunisse, Zitman, Cruysberg, Hoefnagels, & Verbeek, 1996), glaucoma (Nesher, Nesher, Epstein, & Assia, 2001), and cataract (Teunisse, Zitman, & Raes, 1994; Teunisse et al, 1995) Historically, visual hallucinations have been associated with the negative stigma of mental disorders Menon, Rahman, Menon, and Dutton (2003) stated that individuals who grasp the unreality of the visual hallucinations may be disturbed by the possibility of imminent insanity, and because of their fears, they may be reluctant to discuss their experiences with physicians or allied professionals It is important for clinicians and those in allied professions to be knowledgeable about CBS in order to avoid misdiagnoses and consequent unsuitable therapies or recommendations It has been suggested that informing a client that the hallucinations are not a result of mental illness may have a therapeutic effect (Lannon et al, 2006; Menon et al, 2003; Nadarajah, 1998) Origin of CBS In 1936, Georges de Morsier, a neurologist, coined the eponym Charles Bonnet syndrome in recognition of Charles Bonnet, who was a Swiss naturalist, philosopher, and biologist Bonnet had documented the experiences with visual hallucinations in 1769 of his 89-year-old grandfather, Charles Lullin, who had cataracts Lullin was fully aware that the hallucinations were not real because the images of buildings and landscapes would spontaneously appear, disappear, and increase or decrease in size (Hedges, 2007) Lullin was further convinced of the unreal nature of the images because they never made noise He reported seeing people, buildings, carriages, and birds Bonnet, like his grandfather, experienced visual hallucinations early in his life because of deteriorating vision (Hedges, 2007; Menon et al, 2003) De Morsier defined CBS as visual hallucinations that occur in older people with otherwise intact mental functioning, but unlike Charles Bonnet, did not emphasize that visual impairment is a possible cause of the visual hallucinations (Hedges, 2007; Menon et al, 2003) The discrepancy regarding the inclusion or not of visual impairment as part of the CBS diagnosis has resulted in a vagueness of diagnostic criteria that has led to the assumption that the condition is rare (Teunisse et al, 1996) Diagnostic criteria Various criteria exist for diagnosing CBS (Menon et al, 2003; Terao, 2002) Schultz and Melzack (1991) described previously identified core features of CBS hallucinations as (1) a clear state of mind, (2) normal perception, (3) the absence of additional auditory or olfactory hallucinations, (4) the absence of other unusual sensations, (5) the absence of control over hallucinations, and (6) the disappearance of hallucinations upon closing the eyes They believed that an additional requirement should be the presence of reduced vision Teunisse et al (1995) isolated CBS from other psychiatric disorders by requiring the hallucinations to be (1) complex, repetitive, and persistent; (2) with full or partial insight, meaning awareness that the hallucinations are not real; (3) with no additional delusions; and (4) present in the absence of additional hallucinations in the other senses …

Amyloid β-peptide 1-42 modulates the proliferation of mouse neural stem cells: upregulation of fucosyltransferase IX and notch signaling.

Abstract: Amyloid β-peptides (Aβs) aggregate to form amyloid plaques, also known as senile plaques, which are a major pathological hallmark of Alzheimer’s disease (AD). Aβs are reported to possess proliferation effects on neural stem cells (NSCs); however, this effect remains controversial. Thus, clarification of their physiological function is an important topic. We have systematically evaluated the effects of several putative bioactive Aβs (Aβ1–40, Aβ1–42, and Aβ25–35) on NSC proliferation. Treatment of NSCs with Aβ1–42 significantly increased the number of those cells (149 ± 10 %). This was not observed with Aβ1–40 which did not have any effects on the proliferative property of NSC. Aβ25–35, on the other hand, exhibited inhibitory effects on cellular proliferation. Since cell surface glycoconjugates, such as glycolipids, glycoproteins, and proteoglycans, are known to be important for maintaining cell fate determination, including cellular proliferation, in NSCs and they undergo dramatic changes during differentiation, we examined the effect of Aβs on a number of key glycoconjugate metabolizing enzymes. Significantly, we found for the first time that Aβ1–42 altered the expression of several key glycosyltransferases and glycosidases, including fucosyltransferase IX (FUT9), sialyltransferase III (ST-III), glucosylceramide ceramidase (GLCC), and mitochondrial sialidase (Neu4). FUT9 is a key enzyme for the synthesis of the Lewis X carbohydrate epitope, which is known to be expressed in stem cells. Aβ1–42 also stimulated the Notch1 intracellular domain (NICD) by upregulation of the expression of Musashi-1 and the paired box protein, Pax6. Thus, Aβ1–42 upregulates NSC proliferation by modulating the expression of several glycogenes involved in Notch signaling.