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https://www.readbyqxmd.com/read/29119271/rnr1-s-role-in-telomere-elongation-cannot-be-replaced-by-rnr3-a-role-beyond-dntps
#1
REVIEW
André Maicher, Martin Kupiec
Telomeres, the nucleoprotein complexes at the end of eukaryotic chromosomes, protect them from degradation and ensure the replicative capacity of cells. In most human tumors and in budding yeast, telomere length is maintained by the activity of telomerase, an enzyme that adds dNTPs according to an internal RNA template. The dNTPs are generated with the help of the ribonucleotide reductase (RNR) complex. We have recently generated strains lacking the large subunit of RNR, Rnr1, which were kept viable by the expression of RNR complexes containing the Rnr1 homolog, Rnr3...
November 8, 2017: Current Genetics
https://www.readbyqxmd.com/read/29112018/tumor-budding-and-pdc-grade-are-stage-independent-predictors-of-clinical-outcome-in-mismatch-repair-deficient-colorectal-cancer
#2
Éanna Ryan, Yi Ling Khaw, Ben Creavin, Robert Geraghty, Elizabeth J Ryan, David Gibbons, Ann Hanly, Sean T Martin, P Ronan O'Connell, Desmond C Winter, Kieran Sheahan
Mismatch repair deficient (dMMR) colorectal cancer (CRC) despite its association with poor histologic grade often has improved prognosis compared with MMR proficient CRC. Tumor budding and poorly differentiated clusters (PDCs) may predict metastatic potential of colorectal adenocarcinoma (CRC). In addition, their assessment may be more reproducible than the evaluation of other histopathologic parameters. Therefore, we wished to determine their potential as prognostic indicators in a cohort of dMMR CRC patients relative to histologic grade...
November 3, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29109268/syntenin-mediates-src-function-in-exosomal-cell-to-cell-communication
#3
Naga Sailaja Imjeti, Kerstin Menck, Antonio Luis Egea-Jimenez, Celine Lecointre, Frederique Lembo, Habib Bouguenina, Ali Badache, Rania Ghossoub, Guido David, Serge Roche, Pascale Zimmermann
The cytoplasmic tyrosine kinase SRC controls cell growth, proliferation, adhesion, and motility. The current view is that SRC acts primarily downstream of cell-surface receptors to control intracellular signaling cascades. Here we reveal that SRC functions in cell-to-cell communication by controlling the biogenesis and the activity of exosomes. Exosomes are viral-like particles from endosomal origin that can reprogram recipient cells. By gain- and loss-of-function studies, we establish that SRC stimulates the secretion of exosomes having promigratory activity on endothelial cells and that syntenin is mandatory for SRC exosomal function...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29100315/low-bub1-expression-is-an-adverse-prognostic-marker-in-gastric-adenocarcinoma
#4
David Stahl, Martin Braun, Andrew J Gentles, Philipp Lingohr, Adeline Walter, Glen Kristiansen, Ines Gütgemann
Gastric adenocarcinomas are associated with a poor prognosis due to the fact that the tumor has often metastasized by the time of diagnosis and prognostic markers are urgently needed to tailor treatment. We examined the expression of the mitotic spindle checkpoint protein BUB1 (budding uninhibited by benzimidazoles 1) and Ki-67 protein expression by immunohistochemistry in 218 patients with primary gastric adenocarcinomas. Tumors with low frequency of BUB1 expression were associated with larger tumor size (pT) (p < 0...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29052910/cell-proliferation-is-associated-with-intensity-of-tumor-budding-in-oral-squamous-cell-carcinoma
#5
Helvécio Marangon Junior, Priscila Laiza Rubim Leão, Victória Vasconcellos Moreira Melo, Ângela Braga Caixeta, Paulo Eduardo Alencar Souza, Maria Cássia Ferreira de Aguiar, Martinho Campolina Rebello Horta
BACKGROUND: Tumor budding is a morphological marker of cancer invasion, defined as the presence of isolated or small clusters of neoplastic cells at the tumor invasive front. This study aimed to evaluate the association between intensity of tumor budding and cell proliferation in oral squamous cell carcinoma (OSCC). METHODS: Immunohistochemistry was employed in 163 OSCC samples to detect the cell proliferation marker Ki-67 and multi-cytokeratin (to identify OSCC cells in tumor budding evaluation)...
October 20, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29050261/alpha-linolenic-acid-stabilizes-hif-1-%C3%AE-and-downregulates-fasn-to-promote-mitochondrial-apoptosis-for-mammary-gland-chemoprevention
#6
Subhadeep Roy, Atul Kumar Rawat, Shreesh Raj Sammi, Uma Devi, Manjari Singh, Swetlana Gautam, Rajnish Kumar Yadav, Jitendra Kumar Rawat, Lakhveer Singh, Mohd Nazam Ansari, Abdulaziz S Saeedan, Rakesh Pandey, Dinesh Kumar, Gaurav Kaithwas
Alpha linolenic acid is an essential polyunsaturated fatty acid and is reported to have the anti-cancer potential with no defined hypothesis or mechanism/s. Henceforth present study was in-quested to validate the effect of alpha linolenic acid on mitochondrial apoptosis, hypoxic microenvironment and de novo fatty acid synthesis using in-vitro and in-vivo studies. The IC50 value of alpha linolenic acid was recorded to be 17.55μM against ER+MCF-7 cells. Treatment with alpha linolenic acid was evident for the presence of early and late apoptotic signals along with mitochondrial depolarization, when studied through acridine orange/ethidium bromide and JC-1 staining...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29044503/clinical-significance-of-programmed-cell-death-ligand-1-expression-and-the-immune-microenvironment-at-the-invasive-front-of-colorectal-cancers-with-high-microsatellite-instability
#7
Shotaro Korehisa, Eiji Oki, Makoto Iimori, Yu Nakaji, Mototsugu Shimokawa, Hiroshi Saeki, Shinji Okano, Yoshinao Oda, Yoshihiko Maehara
Immunotherapy is reportedly effective in colorectal cancers (CRCs) with high microsatellite instability (MSI-H); however, the specific cell types that respond to immune checkpoint therapy are unclear. Herein, we aimed to examine the expression of programmed cell death-ligand 1 (PD-L1) and related proteins in MSI-H and microsatellite-stable (MSS) CRCs to investigate the immune microenvironment at the tumor's invasive front. The MSI status was retrospectively assessed in 499 patients undergoing surgical resection of primary CRC; of these, 48 were classified as MSI-H...
October 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29040282/colorectal-carcinoma-tumour-budding-and-podia-formation-in-the-xenograft-microenvironment
#8
Friedrich Prall, Claudia Maletzki, Maja Hühns, Mathias Krohn, Michael Linnebacher
Tumour budding and podia formation are well-appreciated in surgical pathology as an aggressive invasion phenotype of colorectal carcinoma cells that is attained in the microenvironment of the invasive margin. In this study, we addressed how tumour budding and podia formation feature in xenografts. Primary colorectal carcinomas (N = 44) of various molecular types (sporadic standard type, high-degree microsatellite-unstable, CpG island methylator phenotype) were transplanted subcutaneously into T and B cell-deficient NSG mice, making possible immunohistochemistry with routine surgical pathology antibodies...
2017: PloS One
https://www.readbyqxmd.com/read/29036423/invasive-micropapillary-carcinoma-component-is-an-independent-prognosticator-of-poorer-survival-in-stage-iii-colorectal-cancer-patients
#9
Hiroki Kitagawa, Masanori Yoshimitsu, Mayumi Kaneko, Yuta Ibuki, Manabu Emi, Toshihiko Kohashi, Hidenori Mukaida, Hiroo Matsuura, Hiroki Ohge, Hideki Ohdan, Naoki Hirabayashi
Background: Invasive micropapillary carcinoma (IMPC) is an aggressive variant of adenocarcinoma found in several organs. Recent studies showed that IMPC in colorectal cancer leads to poorer prognosis than conventional colorectal cancer; however, the influence of IMPC on outcomes remains unclear. The present study aimed to identify the clinicopathological characteristics of colorectal cancers with IMPCs, and to evaluate the prognostic significance of IMPCsper se. Methods: We retrospectively analyzed data from 837 patients with colorectal cancer who underwent surgical treatment...
September 21, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28986696/progression-level-of-extracapsular-spread-and-tumor-budding-for-cervical-lymph-node-metastasis-of-oscc
#10
Shin-Ichi Yamada, Mitsunobu Otsuru, Souichi Yanamoto, Takumi Hasegawa, Hitoshi Aizawa, Takahiro Kamata, Nobuhiro Yamakawa, Tomoyuki Kohgo, Akira Ito, Yuri Noda, Chihoko Hirai, Tetsuya Kitamura, Masaya Okura, Tadaaki Kirita, Michihiro Ueda, Tetsuro Yamashita, Yoshihide Ota, Takahide Komori, Masahiro Umeda, Hiroshi Kurita
OBJECTIVES: The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined. PATIENTS AND METHODS: The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis...
October 6, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28986220/two-mutations-in-mitochondrial-atp6-gene-of-atp-synthase-related-to-human-cancer-affect-ros-calcium-homeostasis-and-mitochondrial-permeability-transition-in-yeast
#11
Katarzyna Niedzwiecka, Renata Tisi, Sara Penna, Malgorzata Lichocka, Danuta Plochocka, Roza Kucharczyk
The relevance of mitochondrial DNA (mtDNA) mutations in cancer process is still unknown. Since the mutagenesis of mitochondrial genome in mammals is not possible yet, we have exploited budding yeast S. cerevisiae as a model to study the effects of tumor-associated mutations in the mitochondrial MTATP6 gene, encoding subunit 6 of ATP synthase, on the energy metabolism. We previously reported that four mutations in this gene have a limited impact on the production of cellular energy. Here we show that two mutations, Atp6-P163S and Atp6-K90E (human MTATP6-P136S and MTATP6-K64E, found in prostate and thyroid cancer samples, respectively), increase sensitivity of yeast cells both to compounds inducing oxidative stress and to high concentrations of calcium ions in the medium, when Om45p, the component of porin complex in outer mitochondrial membrane (OM), was fused to GFP...
October 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28969025/identification-of-genes-and-pathways-in-nasopharyngeal-carcinoma-by-bioinformatics-analysis
#12
Fang Chen, Congxiang Shen, Xiaoqi Wang, Huigang Wang, Yanhui Liu, Chaosheng Yu, Jieyu Lv, Jingjing He, Zhong Wen
Nasopharyngeal carcinoma is a metastatic malignant tumor originating from nasopharyngeal epithelium. Lacking or nonspecific symptoms of patients with early stage nasopharyngeal carcinoma have significantly reduced the accuracy of diagnosing and predicting nasopharyngeal carcinoma development. This study aimed to identify gene signatures of nasopharyngeal carcinoma and uncover potential mechanisms. Two gene expression profiles (GSE12452 and GSE13597) containing 56 nasopharyngeal carcinoma samples and 13 normal control samples were analyzed to identify the differentially expressed genes...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968818/deletions-at-slc18a1-increased-the-risk-of-crc-and-lower-slc18a1-expression-associated-with-poor-crc-outcome
#13
Dandan Zhang, Zhenli Li, Xiaohong Xu, Dan Zhou, Shunli Tang, Xiaoyang Yin, Fangying Xu, Hui Li, Yuan Zhou, Tao Zhu, Hong Deng, Shuai Zhang, Qiong Huang, Jing Wang, Wei Yin, Yimin Zhu, Maode Lai
Copy number variations (CNVs) contribute to the development of colorectal cancer (CRC). We conducted a two-stage association study to identify CNV risk loci for CRC. We performed a gene-based rare CNV study on 694 sporadic CRC and 1641 controls using Illumina Human-OmniExpress-12v1.0 BeadChips, and further replicated in 934 CRC cases and 2680 controls for risk CNVs by using TaqMan Copy Number Assay. Tumor buddings, cancer cells in the center of primary tumor and normal intestinal epithelial cells were captured using laser capture microdissection (LCM) and were assayed using AffymetrixGeneChip® Human Genome U133 Plus 2...
October 26, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28962043/a-novel-ability-of-endocytoscopy-to-diagnose-histological-grade-of-differentiation-in-t1-colorectal-carcinomas
#14
Tomoya Sako, Shin-Ei Kudo, Hideyuki Miyachi, Kunihiko Wakamura, Kenta Igarashi, Masashi Misawa, Yuichi Mori, Toyoki Kudo, Takemasa Hayashi, Atsushi Katagiri, Fumio Ishida, Takeshi Azuma, Haruhiro Inoue, Shigeharu Hamatani
Background and study aims Endocytoscopic images closely resemble histopathology. We assessed whether endocytoscopy could be used to determine T1 colorectal cancer histological grade. Patients and methods Endocytoscopic images of 161 lesions were divided into three types: tubular gland lumens, unclear gland lumens, and fused gland formations on endocytoscopy (FGFE). We retrospectively compared endocytoscopic findings with histological grade in the resected specimen superficial layer, and examined the incidence of risk factors for lymph node metastasis...
September 29, 2017: Endoscopy
https://www.readbyqxmd.com/read/28938483/varying-susceptibility-of-the-female-mammary-gland-to-in-utero-windows-of-bpa-exposure
#15
Andrea R Hindman, Xiaokui Molly Mo, Hannah L Helber, Claire E Kovalchin, Nanditha Ravichandran, Alina R Murphy, Abigail M Fagan, Pamela M St John, Craig J Burd
In utero exposure to the endocrine disrupting compound bisphenol A (BPA) is known to disrupt mammary gland development and increase tumor susceptibility in rodents. It is unclear whether different periods of in utero development might be more susceptible to BPA exposure. We exposed pregnant CD-1 mice to BPA at different times during gestation that correspond to specific milestones of in utero mammary gland development. The mammary glands of early-life and adult female mice, exposed in utero to BPA, were morphologically and molecularly (estrogen receptor-α and Ki67) evaluated for developmental abnormalities...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28932085/novel-predictors-for-lymph-node-metastasis-in-submucosal-invasive-colorectal-carcinoma
#16
Kwangil Yim, Daeyoun David Won, In Kyu Lee, Seong-Taek Oh, Eun Sun Jung, Sung Hak Lee
AIM: To evaluate a novel grading system to predict lymph node metastasis (LNM) in patients with submucosal invasive colorectal carcinoma (SICRC). METHODS: We analyzed the associations between LNM and various clinicopathological features in 252 patients with SICRC who had undergone radical surgery at the Seoul Saint Mary's hospital between 2000 and 2015. RESULTS: LNM was observed in 31 patients (12.3%). The depth and width of the submucosal invasion, lymphatic invasion, tumor budding, and the presence of poorly differentiated clusters (PDCs) were significantly associated with the incidence of LNM...
August 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28926609/developmental-expression-of-membrane-type-4-matrix-metalloproteinase-mt4-mmp-mmp17-in-the-mouse-embryo
#17
María José Blanco, Iván Rodríguez-Martín, Ana I R Learte, Cristina Clemente, María Gregoria Montalvo, Motoharu Seiki, Alicia G Arroyo, Cristina Sánchez-Camacho
Matrix metalloproteinases (MMPs) constitute a large group of endoproteases that play important functions during embryonic development, tumor metastasis and angiogenesis by degrading components of the extracellular matrix. Within this family, we focused our study on Mt4-mmp (also called Mmp17) that belongs to a distinct subset that is anchored to the cell surface via a glycosylphosphatidylinositol (GPI) moiety and with the catalytic site exposed to the extracellular space. Information about its function and substrates is very limited to date, and little has been reported on its role in the developing embryo...
2017: PloS One
https://www.readbyqxmd.com/read/28915717/p53-p63-and-p73-in-the-wonderland-of-s-cerevisiae
#18
REVIEW
Olivier Billant, Marc Blondel, Cécile Voisset
Since its discovery in 1979, p53 has been on the forefront of cancer research. It is considered a master gene of cancer suppression and is found mutated in around 50% of all human tumors. In addition, the progressive identification of p53-related transcription factors p63 and p73 as well as their multiple isoforms have added further layers of complexity to an already dense network. Among the numerous models used to unravel the p53 family mysteries, S. cerevisiae has been particularly useful. This seemingly naive model allows the expression of a functional human p53 and thus the assessment of p53 intrinsic transcriptional activity...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915237/dna-replication-stress-restricts-ribosomal-dna-copy-number
#19
Devika Salim, William D Bradford, Amy Freeland, Gillian Cady, Jianmin Wang, Steven C Pruitt, Jennifer L Gerton
Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28881767/transgenic-overexpression-of-nanogp8-in-the-mouse-prostate-is-insufficient-to-initiate-tumorigenesis-but-weakly-promotes-tumor-development-in-the-hi-myc-mouse-model
#20
Bigang Liu, Shuai Gong, Qiuhui Li, Xin Chen, John Moore, Mahipal V Suraneni, Mark D Badeaux, Collene R Jeter, Jianjun Shen, Rashid Mehmood, Qingxia Fan, Dean G Tang
This project was undertaken to address a critical cancer biology question: Is overexpression of the pluripotency molecule Nanog sufficient to initiate tumor development in a somatic tissue? Nanog1 is critical for the self-renewal and pluripotency of ES cells, and its retrotransposed homolog, NanogP8 is preferentially expressed in somatic cancer cells. Our work has shown that shRNA-mediated knockdown of NanogP8 in prostate, breast, and colon cancer cells inhibits tumor regeneration whereas inducible overexpression of NanogP8 promotes cancer stem cell phenotypes and properties...
August 8, 2017: Oncotarget
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