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https://www.readbyqxmd.com/read/29454008/temozolomide-affects-extracellular-vesicles-released-by-glioblastoma-cells
#1
Gwennan André-Grégoire, Nicolas Bidère, Julie Gavard
Glioblastoma multiforme (GBM) is the most aggressive primary tumour within the brain as well as the most common and lethal cerebral cancer, mainly because of treatment failure. Indeed, tumour recurrence is inevitable and fatal in a short period of time. Glioblastoma stem-like cells (GSCs) are thought to participate in tumour initiation, expansion, resistance to treatments, including to the alkylating chemotherapeutic agent temozolomide, and relapse. Here, we assessed whether extracellular vesicles (EVs) released by GSCs could disseminate factors involved in resistance mechanisms...
February 14, 2018: Biochimie
https://www.readbyqxmd.com/read/29453896/the-anti-malarial-mefloquine-inhibits-nf-%C3%AE%C2%BAb-signaling-and-induces-apoptosis-in-colorectal-cancer-cells
#2
Xin Xu, Jun Wang, Kunkun Han, Shaoyan Li, Feng Xu, Yili Yang
The NF-κB signaling pathway is activated in many colorectal cancer (CRC) cells and in the tumor microenvironment, which plays a critical role in cancer initiation, development, and response to therapies. We found in the present study that the widely used antimalarial drug mefloquine was a NF-κB inhibitor that blocked the activation of IκBα kinase, leading to the reduction of IκBα degradation, decrease of p65 phosphorylation, and suppressed expression of NF-κB target genes in colorectal cancer cells. We also found that mefloquine induced growth arrest and apoptosis of colorectal cancer cells harboring phosphorylated p65 in culture and mice...
February 17, 2018: Cancer Science
https://www.readbyqxmd.com/read/29453601/immunohistochemical-biomarkers-in-pituitary-pathology
#3
REVIEW
Sylvia L Asa, Ozgur Mete
Pituitary pathology is one area of endocrine pathology that is highly dependent on immunohistochemistry. There is a wide range of disorders that occur in and around the sella turcica, and the distinction of tumor-like lesions from neoplasms requires careful evaluation. The diagnosis, prognosis, and predictive features of neoplasms in the sellar region are all dependent on the application and interpretation of biomarkers of cell differentiation, hormonal activity, subcellular morphology, and proliferation. As in hematopathology, the number of biomarkers has increased dramatically and continues to increase...
February 16, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29453322/the-mtor-targets-4e-bp1-2-restrain-tumor-growth-and-promote-hypoxia-tolerance-in-pten-driven-prostate-cancer
#4
Mei Ding, Theodorus H van der Kwast, Ravi N Vellanki, Warren D Foltz, Trevor D McKee, Nahum Sonenberg, Pier Paolo Pandolfi, Marianne Koritzinsky, Bradly G Wouters
The mTOR signaling pathway is a central regulator of protein synthesis and cellular metabolism in response to the availability of energy, nutrients, oxygen, and growth factors. mTOR activation leads to phosphorylation of multiple downstream targets including the eukaryotic initiation factor 4E (eIF4E) binding proteins-1 and -2 (EIF4EBP1/4E-BP1 and EIF4EBP2/4E-BP2). These binding proteins inhibit protein synthesis, but are inactivated by mTOR to stimulate cell growth and metabolism. However, the role of these proteins in the context of aberrant activation of mTOR, which occurs frequently in cancers through loss of PTEN or mutational activation of the PI3K/AKT pathway, is unclear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452949/estimation-of-the-effectiveness-ratio-%C3%AE-%C3%AE-for-resistant-cancer-cells-in-u87mg-human-glioblastoma
#5
Perla Marmolejo-León, Erika Patricia Azorín-Vega, Nallely Jiménez-Mancilla, Héctor Javier Mendoza-Nava, Eleni Mitsoura, Benjamín Pineda, Eugenio Torres-García
Glioblastoma contains self-renewing, tumorigenic cancer stem-like cells that contribute to tumor initiation and therapeutic resistance. The aim of this research was to estimate and compare the effectiveness ratio (α/β) of stem-like cells and differentiated glioma cells derived from the U87MG glioblastoma cell line. Cell survival experiments were obtained in a dose range of 0-20 Gy (13.52 ± 0.09 Gy/h) as a hyperfractionationated accelerated radiotherapy scheme. Biochemical characterization of the post-irradiated cells was performed by flow cytometry analysis and the percentage of stem-like cells that resisted irradiation was determined by the CD133 expression...
January 11, 2018: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/29452720/evaluation-of-the-biological-activities-of-the-il-15-superagonist-complex-alt-803-following-intravenous-versus-subcutaneous-administration-in-murine-models
#6
Bai Liu, Monica Jones, Lin Kong, Terra Noel, Emily K Jeng, Sixiang Shi, Christopher G England, Sarah Alter, Jeffrey S Miller, Weibo Cai, Peter R Rhode, Hing C Wong
ALT-803 is a fusion protein complex consisting of an interleukin (IL)-15 superagonist and a dimeric IL-15 receptor alpha sushi domain IgG1 Fc fusion protein. When administered to mice, ALT-803 is capable of inducing natural killer (NK) and CD8 + T cell proliferation and activation, and effectively promoting potent anti-tumor responses. Currently, ALT-803 is in clinical trials for treatment of various solid tumors and hematological malignancies. In the initial phase of these clinical studies, intravenous (iv) injection was used according to the route used in pre-clinical efficacy studies...
February 13, 2018: Cytokine
https://www.readbyqxmd.com/read/29452350/extra-virgin-olive-oil-contains-a-metabolo-epigenetic-inhibitor-of-cancer-stem-cells
#7
Bruna Corominas-Faja, Elisabet Cuyàs, Jesús Lozano-Sánchez, Sílvia Cufí, Sara Verdura, Salvador Fernández-Arroyo, Isabel Borrás-Linares, Begoña Martin-Castillo, Ángel G Martin, Ruth Lupu, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Vicente Micol, Jorge Joven, Antonio Segura-Carretero, Javier A Menendez
Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target sub-populations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC...
February 14, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29452146/the-hippo-yap1-pathway-interacts-with-fgfr1-signaling-to-maintain-stemness-in-lung-cancer
#8
Tingting Lu, Ziming Li, Ying Yang, Wenxiang Ji, Yongfeng Yu, Xiaomin Niu, Qingyu Zeng, Weiliang Xia, Shun Lu
The Hippo pathway plays a critical role in organ size control, tissue homeostasis and tumor genesis through its key transcription regulator Yes-associated protein1 (YAP1), but the mechanism underlying its role in lung cancer is unclear. We hypothesized that YAP1 influences FGFR1 signaling to maintain cancer stem-like cell (CSC) properties in FGFR1-amplified lung cancer. In support of this, our data confirms that expression levels of YAP1 are positively associated with those of FGFR1 in clinical lung carcinoma samples as measured by real-time PCR, western blot, and immunohistochemistry (IHC) staining...
February 13, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29451897/selective-identification-of-somatic-mutations-in-pancreatic-cancer-cells-through-a-combination-of-next-generation-sequencing-of-plasma-dna-using-molecular-barcodes-and-a-bioinformatic-variant-filter
#9
Yoji Kukita, Kazuyoshi Ohkawa, Ryoji Takada, Hiroyuki Uehara, Kazuhiro Katayama, Kikuya Kato
The accuracy of next-generation sequencing (NGS) for detecting tumor-specific mutations in plasma DNA is hindered by errors introduced during PCR/sequencing, base substitutions caused by DNA damage, and pre-existing mutations in normal cells that are present at a low frequency. Here, we performed NGS of genes related to pancreatic cancer (comprising 2.8 kb of genomic DNA) in plasma DNA (average 4.5 ng) using molecular barcodes. The average number of sequenced molecules was 900, and the sequencing depth per molecule was 100 or more...
2018: PloS One
https://www.readbyqxmd.com/read/29450259/hand-assisted-laparoscopic-partial-nephrectomy-for-large-renal-carcinoma-with-succinate-dehydrogenase-deficiency
#10
Ann Buhl Bersang, Sarah Bube, Mikkel Fode, Nessn H Azawi
Background: Germline mutations in succinate dehydrogenase (SDH) are associated with multifocal cancers: pituitary gland tumors, pheochromocytomas, paragangliomas, gastrointestinal stromal tumors, and renal-cell carcinomas (RCCs). SDH-deficient renal-cell carcinoma (SDH-RCC) was first identified in 2004 as an inherited kidney cancer with mutations in the SDH gene. SDH consists of A, B, C, and D units. Mutation in the SDHB gene is the most common mutation in SDH-deficient RCCs. Case Presentation: We report a case of a 51-year-old healthy man diagnosed with SDHB germline mutation and RCCs...
2018: Journal of Endourology Case Reports
https://www.readbyqxmd.com/read/29450136/initiative-action-of-tumor-associated-macrophage-during-tumor-metastasis
#11
REVIEW
Saroj Singh, Neesha Mehta, Jiang Lilan, Meen Bahadur Budhthoki, Fu Chao, Li Yong
Tumor-associated macrophages (TAMs) are a significant component of the microenvironment of any solid tumors in the majority of cancers, associated with unfavorable prognosis. TAMs emerge as attractive targets for therapeutic strategies aimed at reprogramming their protumor phenotype into an effective antitumor activity. In this review article, we present an overview of mechanisms responsible for TAMs recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance...
June 2017: Biochimie Open
https://www.readbyqxmd.com/read/29449731/mixed-malignant-mullerian-tumor-with-neuroendocrine-features-in-an-irradiated-uterus-for-cervical-carcinoma-a-unique-association-a-morphological-immunohistochemisty-and-ultrastructural-study
#12
V G Vellone, B Spina, F Grillo, P Calamaro, F Sarocchi, P Sala, S Ferrero, E Fulcheri
Chemo-radiation represents an effective therapy for carcinoma of the uterine cervix. The endometrium may however receive a consistent dose of mutagenic radiations and patients may have an increased risk of secondary malignancies. Endometrial mixed malignant mullerian tumor (MMMT) is a rare, highly aggressive disease, and neuroendocrine features are even rarer. A 68 years old woman underwent radio-chemotherapy for a squamous cell carcinoma of the cervix. Follow up was uneventful until, eight years after radio-chemotherapy, imaging exams detected a diffuse enlargement of the uterine body...
December 2017: Pathologica
https://www.readbyqxmd.com/read/29449696/snail-regulates-bmp-and-tgf%C3%AE-pathways-to-control-the-differentiation-status-of-glioma-initiating-cells
#13
Laia Caja, Kalliopi Tzavlaki, Mahsa S Dadras, E-Jean Tan, Gad Hatem, Naga P Maturi, Anita Morén, Lotta Wik, Yukihide Watanabe, Katia Savary, Masood Kamali-Moghaddan, Lene Uhrbom, Carl-Henrik Heldin, Aristidis Moustakas
Glioblastoma multiforme is a brain malignancy characterized by high heterogeneity, invasiveness, and resistance to current therapies, attributes related to the occurrence of glioma stem cells (GSCs). Transforming growth factor β (TGFβ) promotes self-renewal and bone morphogenetic protein (BMP) induces differentiation of GSCs. BMP7 induces the transcription factor Snail to promote astrocytic differentiation in GSCs and suppress tumor growth in vivo. We demonstrate that Snail represses stemness in GSCs. Snail interacts with SMAD signaling mediators, generates a positive feedback loop of BMP signaling and transcriptionally represses the TGFB1 gene, decreasing TGFβ1 signaling activity...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29449559/downregulation-of-srebp-inhibits-tumor-growth-and-initiation-by-altering-cellular-metabolism-in-colon-cancer
#14
Yang-An Wen, Xiaopeng Xiong, Yekaterina Y Zaytseva, Dana L Napier, Emma Vallee, Austin T Li, Chi Wang, Heidi L Weiss, B Mark Evers, Tianyan Gao
Sterol regulatory element-binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression of genes required for the synthesis of fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c, and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are derived from a single gene through the use of alternative transcription start sites. Here we investigated the role of SREBP-mediated lipogenesis in regulating tumor growth and initiation in colon cancer...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449538/downregulation-of-perk-activity-and-eif2%C3%AE-serine-51-phosphorylation-by-mtor-complex-1-elicits-pro-oxidant-and-pro-death-effects-in-tuberous-sclerosis-deficient-cells
#15
Jothilatha Krishnamoorthy, Clara Tenkerian, Jyotsana Gupta, Nour Ghaddar, Shuo Wang, Cedric Darini, Kirk A Staschke, Abhishek Ghosh, Valentina Gandin, Ivan Topisirovic, Arnold S Kristof, Maria Hatzoglou, George Simos, Antonis E Koromilas
Oxidative stress determines cell fate through several mechanisms, among which regulation of mRNA translation by the phosphorylation of the alpha (α) subunit of the translation initiation factor eIF2α at serine 51 (eIF2αP) plays a prominent role. Increased eIF2αP can contribute to tumor progression as well as tumor suppression. While eIF2αP is increased in most cells to promote survival and adaptation to different forms of stress, we demonstrate that eIF2αP is reduced in tuberous sclerosis complex 2 (TSC2)-deficient cells subjected to oxidative insults...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449169/interaction-of-the-wnt-%C3%AE-catenin-and-ras-erk-pathways-involving-co-stabilization-of-both-%C3%AE-catenin-and-ras-plays-important-roles-in-the-colorectal-tumorigenesis
#16
REVIEW
Sang-Kyu Lee, Jeong-Ha Hwang, Kang-Yell Choi
Cancer development is usually driven by multiple genetic and molecular alterations rather than by a single defect. In the human colorectal cancer (CRC), series of mutations of genes are involved in the different stages of tumorigenesis. For example, adenomatous polyposis coli (APC) and KRAS mutations have been known to play roles in the initiation and progression of the tumorigenesis, respectively. However, many studies indicate that mutations of these two genes, which play roles in the Wnt/β-catenin and RAS-extra-cellular signal regulated kinase (ERK) pathways, respectively, cooperatively interact in the tumorigenesis in several different cancer types including CRC...
January 10, 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29448097/selective-degradation-of-bet-proteins-with-dbet1-a-proteolysis-targeting-chimera-potently-reduces-pro-inflammatory-responses-in-lipopolysaccharide-activated-microglia
#17
Kelly M DeMars, Changjun Yang, Carolina I Castro-Rivera, Eduardo Candelario-Jalil
Bromodomain and extraterminal (BET) proteins are essential to pro-inflammatory gene transcription. The BET family proteins, BRD2, BRD3, BRD4, and testis-specific BRDT, couple chromatin remodeling to gene transcription, acting as histone acetyltransferases, scaffolds for transcription complexes, and markers of histone acetylation. To initiate an inflammatory response, cells undergo de novo gene transcription requiring histone-modifying proteins to make DNA wrapped around histones more or less readily available to transcription complexes...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29448000/bone-marrow-derived-fibrocytes-promote-stem-cell-like-properties-of-lung-cancer-cells
#18
Atsuro Saijo, Hisatsugu Goto, Mayuri Nakano, Atsushi Mitsuhashi, Yoshinori Aono, Masaki Hanibuchi, Hirohisa Ogawa, Hisanori Uehara, Kazuya Kondo, Yasuhiko Nishioka
Cancer stem cells (CSCs) represent a minor population that have clonal tumor initiation and self-renewal capacity and are responsible for tumor initiation, metastasis, and therapeutic resistance. CSCs reside in niches, which are composed of diverse types of stromal cells and extracellular matrix components. These stromal cells regulate CSC-like properties by providing secreted factors or by physical contact. Fibrocytes are differentiated from bone marrow-derived CD14 + monocytes and have features of both macrophages and fibroblasts...
February 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29447458/e-cadherin-loss-accelerates-tumor-progression-and-metastasis-in-a-mouse-model-of-lung-adenocarcinoma
#19
Kerstin W Sinkevicius, Kelly J Bellaria, Juliana Barrios, Patrizia Pessina, Manav Gupta, Christine Fillmore Brainson, Roderick T Bronson, Carla F Kim
Metastatic disease is the primary cause of death of lung cancer patients, but the mouse models of lung adenocarcinoma do not accurately recapitulate the tumor microenvironment or metastatic disease observed in patients. In this study, we conditionally deleted E-cadherin in an autochthonous lung adenocarcinoma mouse model driven by activated oncogenic Kras and p53 loss. Loss of E-cadherin significantly accelerated lung adenocarcinoma progression and decreased survival of the mice. Kras;p53;E-cadherin mice had a 41% lung tumor burden, invasive grade 4 tumors, and a desmoplastic stroma just 8 weeks after tumor initiation...
February 15, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29447149/optimizing-homeostatic-cell-renewal-in-hierarchical-tissues
#20
Cesar Alvarado, Nicole A Fider, Helen J Wearing, Natalia L Komarova
In order to maintain homeostasis, mature cells removed from the top compartment of hierarchical tissues have to be replenished by means of differentiation and self-renewal events happening in the more primitive compartments. As each cell division is associated with a risk of mutation, cell division patterns have to be optimized, in order to minimize or delay the risk of malignancy generation. Here we study this optimization problem, focusing on the role of division tree length, that is, the number of layers of cells activated in response to the loss of terminally differentiated cells, which is related to the balance between differentiation and self-renewal events in the compartments...
February 15, 2018: PLoS Computational Biology
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