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https://www.readbyqxmd.com/read/29346317/liposomal-tricurin-a-synergistic-combination-of-curcumin-epicatechin-gallate-and-resveratrol-repolarizes-tumor-associated-microglia-macrophages-and-eliminates-glioblastoma-gbm-and-gbm-stem-cells
#1
Sumit Mukherjee, Juliet N E Baidoo, Samay Sampat, Andrew Mancuso, Lovena David, Leah S Cohen, Shuiqin Zhou, Probal Banerjee
Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12-15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM): 32:8:100 (termed 32 μM+ TriCurin)...
January 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29341112/conditionally-reprogrammed-cells-crc-methodology-does-not-allow-the-in-vitro-expansion-of-patient-derived-primary-and-metastatic-lung-cancer-cells
#2
Giovanni Sette, Valentina Salvati, Ilenia Giordani, Emanuela Pillozzi, Denise Quacquarini, Enrico Duranti, Francesca De Nicola, Matteo Pallocca, Maurizio Fanciulli, Mario Falchi, Roberto Pallini, Ruggero De Maria, Adriana Eramo
Availability of tumor and non-tumor patient-derived models would promote the development of more effective therapeutics for Non Small Cell Lung Cancer (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology demonstrated exceptional potential for the expansion of epithelial cells from patient tissues. However, the possibility to expand patient-derived lung cancer cells using CRC protocols is controversial. Here, we used CRC approach to expand cells from non-tumoral and tumor biopsies of patients with primary or metastatic NSCLC as well as pulmonary metastases of colorectal or breast cancers...
January 17, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29332467/is-hippocampal-avoidance-during-whole-brain-radiotherapy-risky-for-patients-with-small-cell-lung-cancer-hippocampal-metastasis-rate-and-associated-risk-factors
#3
Esra Korkmaz Kirakli, Ozgur Oztekin
OBJECTIVES: Hippocampal avoidance during whole-brain radiotherapy is performed to prevent neural stem cell injury causing neurocognitive dysfunction. Nevertheless, the estimated risk of metastases in hippocampal avoidance area in small-cell lung cancer is unknown. The current study aimed to characterize the metastatic distribution within the brain relative to the hippocampus, estimate the incidence of hippocampal metastasis in patients with small-cell lung cancer, and identify clinical and radiographic variables that may be associated with the risk of hippocampal avoidance area metastasis...
December 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29330809/analysis-of-hypoxia-and-the-hypoxic-response-in-tumor-xenografts
#4
Nuray Böğürcü, Sascha Seidel, Boyan K Garvalov, Till Acker
Solid tumors are often characterized by insufficient oxygen supply (hypoxia), as a result of inadequate vascularization, which cannot keep up with the rapid growth rate of the tumor. Tumor hypoxia is a negative prognostic and predictive factor and is associated with a more aggressive phenotype in various tumor entities. Activation of the hypoxic response in tumors, which is centered around the hypoxia-inducible transcription factors (HIFs), has been causally linked to neovascularization, increased radio- and chemoresistance, altered cell metabolism, genomic instability, increased metastatic potential, and tumor stem cell characteristics...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29328867/glioma-stem-cell-niches-in-human-glioblastoma-are-periarteriolar
#5
Vashendriya V V Hira, Diana A Aderetti, Cornelis J F van Noorden
Survival of primary brain tumor (glioblastoma) patients is seriously hampered by glioma stem cells (GSCs) that are distinct therapy-resistant self-replicating pluripotent cancer cells. GSCs reside in GSC niches, which are specific protective microenvironments in glioblastoma tumors. We have recently found that GSC niches are hypoxic periarteriolar, whereas in most studies, GSC niches are identified as hypoxic perivascular. The aim of this review is to critically evaluate the literature on perivascular GSC niches to establish whether these are periarteriolar, pericapillary, perivenular, and/or perilymphatic...
January 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29313411/inhibition-of-wnt-ctnnb1-signaling-upregulates-sqstm1-and-sensitizes-glioblastoma-cells-to-autophagy-blockers
#6
Mireia Nager, Marta Crespí Sallán, Anna Visa, Charumathi Pushparaj, Maria Santacana, Anna Macià, Andrée Yeramian, Carles Cantí, Judit Herreros
WNT-CTNN1B signaling promotes cancer cell proliferation and stemness. Furthermore, recent evidence indicates that macroautophagy/autophagy regulates WNT signaling. Here we investigated the impact of inhibiting WNT signaling on autophagy in glioblastoma (GBM), a devastating brain tumor. Inhibiting TCF, or silencing TCF4 or CTNNB1/β-catenin upregulated SQSTM1/p62 in GBM at transcriptional and protein levels and, in turn, autophagy. DKK1/Dickkopf1, a canonical WNT receptor antagonist, also induced autophagic flux...
January 9, 2018: Autophagy
https://www.readbyqxmd.com/read/29312541/energy-metabolism-in-glioblastoma-stem-cells-ppar%C3%AE-a-metabolic-adaptor-to-intratumoral-microenvironment
#7
Alessia Fidoamore, Loredana Cristiano, Chiara Laezza, Renato Galzio, Elisabetta Benedetti, Benedetta Cinque, Andrea Antonosante, Michele d'Angelo, Vanessa Castelli, Maria Grazia Cifone, Rodolfo Ippoliti, Antonio Giordano, Annamaria Cimini
Glioblastoma (GB), the most-common cancer in the adult brain, despite surgery and radio/ chemotherapy, is to date almost incurable. Many hypoxic tumors, including GB, show metabolic reprogramming to sustain uncontrolled proliferation, hypoxic conditions and angiogenesis. Peroxisome Proliferator-activated Receptors (PPAR), particularly the α isotype, have been involved in the control of energetic metabolism. Herein, we characterized patient-derived GB neurospheres focusing on their energetic metabolism and PPARα expression...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29310447/phosphorylation-de-phosphorylation-in-specific-sites-of-tumor-suppressor-wwox-and-control-of-distinct-biological-events
#8
Shenq-Shyang Huang, Nan-Shan Chang
Abnormal differentiation and growth of hematopoietic stem cells cause the development of hematopoietic diseases and hematopoietic malignancies. However, the molecular events underlying leukemia development are not well understood. In our recent study, we have demonstrated that calcium ionophore and phorbol ester force the differentiation of T lymphoblastic leukemia. The event involves a newly identified IκBα/WWOX/ERK signaling, in which WWOX is Ser14 phosphorylated. Additional evidence also reveals that pS14-WWOX is involved in enhancing cancer progression and metastasis and facilitating neurodegeneration...
January 1, 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29282720/revealing-the-glioma-cancer-stem-cell-interactome-one-niche-at-a-time
#9
Daniel J Silver, Justin D Lathia
Glioblastoma cancer stem cells (CSCs) are insidious. They extensively infiltrate brain tissue, resist radio- and chemotherapy, and are thought to represent the ultimate drivers of disease progression. New research has identified CD109, a GPI-anchored protein, on a population of perivascular CSCs. Interrogation of primary human tumor tissue suggests a role for CD109-expressing CSCs in the progression from low- to high-grade glioma, and animal modeling reveals a critical role for CD109 in the maintenance of the GBM CSC phenotype...
December 27, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29280516/suppression-of-stat3-nh2-terminal-domain-chemosensitizes-medulloblastoma-cells-by-activation-of-protein-inhibitor-of-activated-stat3-via-de-repression-by-microrna-21
#10
Sutapa Ray, Don W Coulter, Shawn D Gray, Jason A Sughroue, Shrabasti Roychoudhury, Erin M McIntyre, Nagendra K Chaturvedi, Kishor K Bhakat, Shantaram S Joshi, Timothy R McGuire, John G Sharp
Medulloblastoma (MB) is a malignant pediatric brain tumor with poor prognosis. Signal transducers and activators of transcription-3 (STAT3) is constitutively activated in MB where it functions as an oncoprotein, mediating cancer progression and metastasis. Here, we have delineated the functional role of activated STAT3 in MB, by using a cell permeable STAT3-NH2 terminal domain inhibitor (S3-NTDi) that specifically perturbs the structure/function of STAT3. We have implemented several biochemical experiments using human MB tumor microarray (TMA) and pediatric MB cell lines, derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/SHH tumors...
December 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29259700/neuroprotective-effects-of-human-umbilical-cord-derived-mesenchymal-stem-cells-on-periventricular-leukomalacia-like-brain-injury-in-neonatal-rats
#11
Chikako Morioka, Motohiro Komaki, Atsuko Taki, Izumi Honda, Naoki Yokoyama, Kengo Iwasaki, Sachiko Iseki, Tomohiro Morio, Ikuo Morita
Background: Periventricular leukomalacia (PVL) is a type of multifactorial brain injury that causes cerebral palsy in premature infants. To date, effective therapies for PVL have not been available. In this study, we examined whether mesenchymal stem cells (MSCs) possess neuroprotective property in a lipopolysaccharide (LPS)-induced neonatal rat PVL-like brain injury. Methods: Human umbilical cord-derived MSCs (UCMSCs) were used in this study. Four-day-old rats were intraperitoneally injected with LPS (15 mg/kg) to cause the PVL-like brain injury and were treated immediately after the LPS-injection with UCMSCs, conditioned medium prepared from MSCs (UCMSC-CM) or interferon-gamma (IFN-γ)-pretreated MSC (IFN-γ-UCMSC-CM)...
2017: Inflammation and Regeneration
https://www.readbyqxmd.com/read/29251326/isoliquiritigenin-inhibits-the-proliferation-and-induces-the-differentiation-of-human-glioma-stem-cells
#12
Yuliang Lin, Hongjun Sun, Ying Dang, Zhiyun Li
Glioma stem cells (GSCs) have been proven to be resistant to various therapeutic strategies, such as temozolomide chemotherapy and radiotherapy, leading to glioma recurrence. Isoliquiritigenin (ISL), a menber of the flavonoids isolated from liquorice has been found to be a potent stimulator of cell differentiation and has potential application for treating various types of cancer including human brain glioma. However, the antitumor activity of ISL on GSCs and the signaling pathway underlying its therapeutic effects are poorly understood...
February 2018: Oncology Reports
https://www.readbyqxmd.com/read/29246166/inhibition-of-egr1-inhibits-glioma-proliferation-by-targeting-ccnd1-promoter
#13
Dian-Gang Chen, Bo Zhu, Sheng-Qing Lv, Hongfan Zhu, Jinliang Tang, Changlin Huang, Qingrui Li, Pu Zhou, Dong-Lin Wang, Guang-Hui Li
BACKGROUND: Gliomas are the most common primary tumors in central nervous system. The prognosis of the patients with glioma is poor regardless of the development of therapeutic strategies. Its aggressive behavior mainly depends on the potent ability of proliferation. The transcription factor EGR1 (early growth response 1) is a member of a zinc finger transcription factor family which plays an essential role in cell growth and proliferation. METHODS: EGR1 expression levels in 39 glioma tissues and 10 normal brain tissues were tested by RT-qPCR and Western-blotting...
December 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29246031/a-molecular-view-of-the-radioresistance-of-gliomas
#14
REVIEW
Xuetao Han, Xiaoying Xue, Huandi Zhou, Ge Zhang
Gliomas originate from glial cells and are the most frequent primary brain tumors. High-grade gliomas occur ∼4 times more frequently than low-grade gliomas, are highly malignant, and have extremely poor prognosis. Radiotherapy, sometimes combined with chemotherapy, is considered the treatment of choice for gliomas and is used after resective surgery. Despite great technological improvements, the radiotherapeutic effect is generally limited, due to the marked radioresistance exhibited by gliomas cells, especially glioma stem cells (GSCs)...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29245920/nampt-overexpression-induces-cancer-stemness-and-defines-a-novel-tumor-signature-for-glioma-prognosis
#15
Antonio Lucena-Cacace, Daniel Otero-Albiol, Manuel P Jiménez-García, Javier Peinado-Serrano, Amancio Carnero
Gliomas are the most prevalent primary malignant brain tumors associated with poor prognosis. NAMPT, a rate-limiting enzyme that boosts the nicotinamide adenine dinucleotide (NAD) regeneration in the salvage pathway, is commonly expressed in these tumors. NAD metabolism is required to maintain tissue homeostasis. To maintain metabolism, cancer cells require a stable NAD regeneration circuit. However, high levels of NAD confer resistance to therapy to these tumors, usually treated with Temozolomide (TMZ). We report that NAMPT overexpression in glioma cell lines increases tumorigenic properties controlling stem cell pathways and enriching the cancer-initiating cell (CIC) population...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29239688/compromising-asymmetric-stem-cell-division-in-drosophila-central-brain-revisiting-the-connections-with-tumorigenesis
#16
Ana Carmena
Asymmetric cell division (ACD) is an essential process during development for generating cell diversity. In addition, a more recent connection between ACD, cancer and stem cell biology has opened novel and highly intriguing venues in the field. This connection between compromised ACD and tumorigenesis was first demonstrated using Drosophila neural stem cells (neuroblasts, NBs) more than a decade ago and, over the past years, it has also been established in vertebrate stem cells. Here, focusing on Drosophila larval brain NBs, and in light of results recently obtained in our lab, we revisit this connection emphasizing two main aspects: 1) the differences in tumor suppressor activity of different ACD regulators and 2) the potential relevance of environment and temporal window frame for compromised ACD-dependent induction of tumor-like overgrowth...
December 14, 2017: Fly
https://www.readbyqxmd.com/read/29228586/targeting-intercellular-adhesion-molecule-1-prolongs-survival-in-mice-bearing-bevacizumab-resistant-glioblastoma
#17
Yuji Piao, Verlene Henry, Ningyi Tiao, Soon Young Park, Juan Martinez-Ledesma, Jian Wen Dong, Veerakumar Balasubramaniyan, John F de Groot
Intercellular cell adhesion molecule 1 (ICAM-1; also known as CD54) is overexpressed in bevacizumab-resistant glioblastoma. In the present study, we tested our hypothesis that highly expressed ICAM-1 mediates glioblastoma's resistance to antiangiogenic therapy. We validated ICAM-1 overexpression in tumors resistant to antiangiogenic therapy using real-time polymerase chain reaction, immunohistochemistry, and Western blotting. We also detected ICAM1 expression in most glioma stem cells (GSCs). We investigated the mechanism of ICAM-1 overexpression after bevacizumab treatment and found that ICAM-1 protein expression was markedly increased in a time-dependent manner in GSC11 and GSC17 cells under hypoxic conditions in vitro...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228563/riluzole-a-potential-therapeutic-intervention-in-human-brain-tumor-stem-like-cells
#18
Swetlana Sperling, Thiha Aung, Sabine Martin, Veit Rohde, Milena Ninkovic
A small subpopulation of tumor stem-like cells has the capacity to initiate tumors and mediate radio- and chemoresistance in diverse cancers hence also in glioblastoma (GBM). It has been reported that this capacity of tumor initiation in the brain is mainly dependent on the body's nutrient supply. This population of so-called brain tumor initiating or brain tumor stem-like cells (BTSCs) is able to extract nutrients like glucose with a higher affinity. Riluzole, a drug approved for treating amyotrophic lateral sclerosis (ALS), was reported to possess anticancer properties, affecting the glutamate metabolism...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222306/therapy-of-primary-cns-lymphoma-role-of-intensity-radiation-and-novel-agents
#19
REVIEW
Andrés José María Ferreri
Primary central nervous system (CNS) lymphomas represent a subgroup of malignancies with specific characteristics, an aggressive course, and unsatisfactory outcome in contrast with other lymphomas comparable for tumor burden and histological type. Despite the high sensitivity to conventional chemotherapy and radiotherapy, remissions are frequently short lasting. Treatment efficacy is limited by several factors, including the biology and microenvironment of this malignancy and the "protective" effect of the blood-brain barrier, which limits the access of most drugs to the CNS...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29218080/whether-cd44-is-an-applicable-marker-for-glioma-stem-cells
#20
Hsiao-Han Wang, Chen-Chieh Liao, Nan-Haw Chow, Lynn Ling-Huei Huang, Jih-Ing Chuang, Kuo-Chen Wei, Jyh-Wei Shin
Glioblastoma multiforme (GBM) is one of the most malignant and aggressive brain tumors with great amount of hyaluronan (HA) secretion and CD44 overexpression (HA receptor). CD44 has been suggested as a cancer stem cells (CSCs) marker. However, several clinical studies have indicated that CD44low glioma cell exhibit CSCs traits. Additionally, our previous study indicated that more CD44 expression was associated with a better prognosis in GBM patients. To determine whether CD44 is an appropriate marker of glioma stem cells (GSCs), we manipulated CD44 expression using intrinsic (CD44 knockdown, CD44kd) and extrinsic (HA supplement, HA+) methods...
2017: American Journal of Translational Research
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