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https://www.readbyqxmd.com/read/28345026/oncolytic-adenoviruses-armed-with-tumor-necrosis-factor-alpha-and-interleukin-2-enable-successful-adoptive-cell-therapy
#1
Riikka Havunen, Mikko Siurala, Suvi Sorsa, Susanna Grönberg-Vähä-Koskela, Michael Behr, Siri Tähtinen, João Manuel Santos, Pauliina Karell, Juuso Rusanen, Dirk M Nettelbeck, Anja Ehrhardt, Anna Kanerva, Akseli Hemminki
Adoptive cell therapy holds much promise in the treatment of cancer but results in solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) therapy of melanoma, but this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both of which are associated with toxicities. To improve and broaden the applicability of adoptive cell transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis factor alpha (TNF-α), or both...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28337965/knockdown-of-e2f3-inhibits-proliferation-migration-and-invasion-and-increases-apoptosis-in-glioma-cells
#2
Zhi-Gang Shen, Xiao-Zhou Liu, Chang-Xiu Chen, Jing-Min Lu
E2F3a as a member of E2F family is essential for cell division associated with the progressing of many cancers. Whereas, the biological effects of E2F3a on glioma is less understood. To investigate the functional mechanism of E2F3a in glioma, we examined the expression of E2F3a in glioma tissues and cell lines. We found that E2F3a was upregulated in glioma tissues compared with adjacent tissues and associated a poor survival time. E2F3a was highly expressed in glioma cell lines compared with normal HEB cell lines...
March 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28320735/the-retinoblastoma-homolog-rbr1-mediates-localization-of-the-repair-protein-rad51-to-dna-lesions-in-arabidopsis
#3
Sascha Biedermann, Hirofumi Harashima, Poyu Chen, Maren Heese, Daniel Bouyer, Kostika Sofroni, Arp Schnittger
The retinoblastoma protein (Rb), which typically functions as a transcriptional repressor of E2F-regulated genes, represents a major control hub of the cell cycle. Here, we show that loss of the Arabidopsis Rb homolog RETINOBLASTOMA-RELATED 1 (RBR1) leads to cell death, especially upon exposure to genotoxic drugs such as the environmental toxin aluminum. While cell death can be suppressed by reduced cell-proliferation rates, rbr1 mutant cells exhibit elevated levels of DNA lesions, indicating a direct role of RBR1 in the DNA-damage response (DDR)...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28302719/a-repressive-role-of-enhancer-of-zeste-homolog-2-in-11%C3%AE-hydroxysteroid-dehydrogenase-type-2-expression-in-human-placenta
#4
Rujuan Zuo, Xiaohui Liu, Wangsheng Wang, Wenjiao Li, Hao Ying, Kang Sun
The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which acts as a placental glucocorticoid barrier, is silenced in the cytotrophoblasts but substantially up-regulated during syncytialization. However, the repressive mechanism of 11β-HSD2 expression before syncytialization and how this repression is lifted during syncytialization remain mostly unresolved. Here we found that enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11β-HSD2 expression via trimethylation of histone H3 lysine 27 (H3K27me3) at the promoter of 11β-HSD2 gene...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28297760/-promoting-effect-of-cyclin-d1-overexpression-on-proliferation-and-epithelial-mesenchymal-transition-of-cervical-squamous-cell-carcinoma-siha-cells
#5
P Wang, S Liu, B Cheng, X Z Wu, S S Ding, L Xu, Y Liu, L Duan, S Z Sun
Objective: To study effects of cyclin D1 overexpression on the proliferation and differentiation of cervical squamous cell carcinoma SiHa cells and to investigate related signaling molecules. Methods: Primers were designed to amplify the full length of cyclin D1 gene and cyclin D1 gene was amplified by PCR for constructing pcDNA3.1 plasmid vector. The construct was then transfected into SiHa cells, and the cells with stable overexpression of cyclin D1 were established, cyclin D1 gene and protein expression were detected by RT-PCR and Western blot, respectively...
March 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28293272/multiple-molecular-interactions-redundantly-contribute-to-rb-mediated-cell-cycle-control
#6
Michael J Thwaites, Matthew J Cecchini, Srikanth Talluri, Daniel T Passos, Jasmyne Carnevale, Frederick A Dick
BACKGROUND: The G1-S phase transition is critical to maintaining proliferative control and preventing carcinogenesis. The retinoblastoma tumor suppressor is a key regulator of this step in the cell cycle. RESULTS: Here we use a structure-function approach to evaluate the contributions of multiple protein interaction surfaces on pRB towards cell cycle regulation. SAOS2 cell cycle arrest assays showed that disruption of three separate binding surfaces were necessary to inhibit pRB-mediated cell cycle control...
2017: Cell Division
https://www.readbyqxmd.com/read/28289097/human-cytomegalovirus-v-cdk-ul97-phosphorylates-and-inactivates-the-retinoblastoma-protein-related-p107-and-p130-proteins
#7
Satoko Iwahori, Angie C Umaña, Halena R VanDeusen, Robert F Kalejta
The human cytomegalovirus (HCMV)-encoded viral cyclin-dependent kinase (v-CDK) UL97 phosphorylates the retinoblastoma (Rb) tumor suppressor. Here we identify the other Rb family members p107 and p130 as novel targets of UL97. UL97 phosphorylates p107 and p130 thereby inhibiting their ability to repress the E2F-responsive E2F1 promoter. As with Rb, this phosphorylation, and the rescue of E2F-responsive transcription, is dependent on the L1 LXCXE motif in UL97 and its interacting clefts on p107 and p130. Interestingly, UL97 does not induce the disruption of all p107-E2F or p130-E2F complexes, as it does to Rb-E2F complexes...
March 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28270497/neopalana-neoadjuvant-palbociclib-a-cyclin-dependent-kinase-4-6-inhibitor-and-anastrozole-for-clinical-stage-2-or-3-estrogen-receptor-positive-breast-cancer
#8
Cynthia X Ma, Feng Gao, Jingqin Luo, Donald W Northfelt, Matthew P Goetz, Andres Forero, Jeremy Hoog, Michael J Naughton, Foluso Ademuyiwa, Rama Suresh, Karen S Anderson, Julie Margenthaler, Rebecca Aft, Timothy J Hobday, Timothy Moynihan, William Gillanders, Amy Cyr, Timothy J Eberlein, Tina Hieken, Helen Krontiras, Zhanfang Guo, Michelle Lee, Nicholas C Spies, Zachary L Skidmore, Obi L Griffith, Malachi Griffith, Shana Thomas, Caroline Bumb, Kiran Vij, Cynthia Huang Bartlett, Maria Koehler, Hussam Al-Kateb, Souzan Sanati, Matthew J Ellis
PURPOSE: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the anti-proliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. EXPERIMENTAL DESIGN: Eligible patients with clinical stage II/III ER+/HER2- breast cancer received anastrozole 1mg daily for 4 weeks (cycle 0) (with goserelin if premenopausal), followed by adding palbociclib (125mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67>10%, in which case patients went off study due to inadequately response...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28270228/e2f8-a-direct-target-of-mir-144-promotes-papillary-thyroid-cancer-progression-via-regulating-cell-cycle
#9
Jing Sun, Run Shi, Sha Zhao, Xiaona Li, Shan Lu, Hemei Bu, Xianghua Ma, Chuan Su
BACKGROUND: Thyroid cancer is the most common malignancy of endocrine system, and papillary thyroid cancer (PTC) is the most common subtype. E2F8, a novel identified E2F family member, was reported to associate with progression of several human cancers, however, its clinical significance and biological role in PTC remain unknown. METHODS: E2F8 or miR-144 expression profiles in PTC tissues were obtained from The Cancer Genome Atlas (TCGA) datasets, and the correlation of E2F8 expression with clinicopathological features was analyzed in a cohort PTC patients...
March 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28260085/roles-of-immune-inhibitory-molecule-b7-h4-in-cervical-cancer
#10
Sai Han, Yi Li, Jingjing Zhang, Lu Liu, Qian Chen, Qiuhong Qian, Shan Li, Youzhong Zhang
Recent studies have reported that the immune-regulatory protein B7-H4 is highly expressed in various types of cancer, but little is known concerning its roles in cervical cancer. In the present study, we investigated the expression of B7-H4 in human tissues and serum samples, and explored the effects of B7-H4 on proliferation, apoptosis, migration and invasion of cervical cancer cell lines, including SiHa and HeLa. We found that B7-H4 was mainly located in the cytoplasm of cervical cancer cells as determined by immunofluorescence staining...
March 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259945/rb-deficiency-accelerates-progression-of-carcinoma-of-the-urinary-bladder-in-vivo-and-in-vitro-through-inhibiting-autophagy-and-apoptosis
#11
Cheng-Yuan Wang, Zhi-Bin Xu, Jiang-Ping Wang, Yong Jiao, Bo Zhang
Urinary bladder cancer is known as a common cancer diagnosed across the world and results in significant mortality and morbidity rates among patients. The retinoblastoma (Rb) protein, as a main tumor suppressor, controls cellular responses to potentially oncogenic stimulation. Rb phosphorylation could disrupt E2F complex formation, resulting in diverse transcription factor dysfunction. In our study, we investigated how Rb is involved in controlling urinary bladder cancer progression. The results indicate that Rb expression is reduced in mice with urinary bladder tumor, and its suppression leads to urinary bladder cancer progression in vivo and in vitro...
February 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28240846/identification-of-a-low-frequency-missense-variant-in-e2f-transcription-factor-7-associated-with-colorectal-cancer-risk-in-a-chinese-population
#12
Ai Ye Guo, Kan Zhai, Jin Ling Xu, Jin Long Hu, Lan Gao
Background: Transcription factors regulate gene expression and play important role in tumor genesis. Especially, the E2F transcription factor family controls the cell cycle and regulate many tumor suppressors. Missense variants in E2F family genes, which change the amino acid sequence, may alter the capacity for DNA binding or the protein structure, leading to a functional alteration. Material and Methods: We here searched for missense variants in E2F transcription family genes (E2F1~E2F8) and identified two (rs2075995 for E2F2 and rs3829295 for E2F7) with minor allele frequencies >0...
January 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28211871/expression-level-is-a-key-determinant-of-e2f1-mediated-cell-fate
#13
Igor Shats, Michael Deng, Adam Davidovich, Carolyn Zhang, Jungeun S Kwon, Dinesh Manandhar, Raluca Gordân, Guang Yao, Lingchong You
The Rb/E2F network has a critical role in regulating cell cycle progression and cell fate decisions. It is dysfunctional in virtually all human cancers, because of genetic lesions that cause overexpression of activators, inactivation of repressors, or both. Paradoxically, the downstream target of this network, E2F1, is rarely strongly overexpressed in cancer. E2F1 can induce both proliferation and apoptosis but the factors governing these critical cell fate decisions remain unclear. Previous studies have focused on qualitative mechanisms such as differential cofactors, posttranslational modification or state of other signaling pathways as modifiers of the cell fate decisions downstream of E2F1 activation...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28203301/progress-with-palbociclib-in-breast-cancer-latest-evidence-and-clinical-considerations
#14
REVIEW
Andrea Rocca, Alessio Schirone, Roberta Maltoni, Sara Bravaccini, Lorenzo Cecconetto, Alberto Farolfi, Giuseppe Bronte, Daniele Andreis
Deregulation of the cell cycle is a hallmark of cancer, and research on cell cycle control has allowed identification of potential targets for anticancer treatment. Palbociclib is a selective inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6), which are involved, with their coregulatory partners cyclin D, in the G1-S transition. Inhibition of this step halts cell cycle progression in cells in which the involved pathway, including the retinoblastoma protein (Rb) and the E2F family of transcription factors, is functioning, although having been deregulated...
February 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28197540/an-rb-insensitive-to-cdk-regulation
#15
Manel Joaquin, Eulàlia de Nadal, Francesc Posas
The N-term phosphorylation of Retinoblastoma (RB) by the p38 stress-activated protein kinase (SAPK) makes RB insensitive to cyclin-dependent kinase (CDK)-Cyclin inhibition, which enhances the transcriptional repression of E2F-driven promoters and delays tumor cell growth. This novel mechanism of RB regulation opens up a window for developing new cancer drug treatments for tumors harboring high CDK-Cyclin activity and a wild-type RB gene.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28193232/peg10-overexpression-induced-by-e2f-1-promotes-cell-proliferation-migration-and-invasion-in-pancreatic-cancer
#16
Yun-Peng Peng, Yi Zhu, Ling-Di Yin, Jing-Jing Zhang, Ji-Shu Wei, Xian Liu, Xin-Chun Liu, Wen-Tao Gao, Kui-Rong Jiang, Yi Miao
BACKGROUND: Overexpression of paternally expressed gene-10 (PEG10) is known to promote the progression of several carcinomas, however, its role in pancreatic cancer (PC) is unknown. We investigated the expression and function of PEG10 in PC. METHODS: PEG10 expression and correlation with PC progression was assessed in cancerous tissues and paired non-cancerous tissues. Further, the role of PEG10 in PC cell progression and the underlying mechanisms were studied by using small interfering RNA (Si-RNA)...
February 13, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28184930/resveratrol-enhances-the-radiosensitivity-of-nasopharyngeal-carcinoma-cells-by-downregulating-e2f1
#17
Yuhui Tan, Xianli Wei, Wenyin Zhang, Xiaolan Wang, Kun Wang, Biaoyan Du, Jianyong Xiao
Identification of safe, effective radiosensitizing agents is urgently needed to improve the outcome of radiotherapy in nasopharyngeal cancer (NPC). In this study, we assessed the ability of the polyphenol resveratrol to act as a radiosensitizer in vitro and in vivo. CNE-1 cells were treated with 50 µM resveratrol for 24 h, then irradiated. E2F transcription factor 1 (E2F1) was stably knocked down and overexpressed using lentiviruses. A xenograft model of NPC was established in nude mice using CNE-1 cells...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28174135/a-system-of-recurrent-neural-networks-for-modularising-parameterising-and-dynamic-analysis-of-cell-signalling-networks
#18
S Samarasinghe, H Ling
In this paper, we show how to extend our previously proposed novel continuous time Recurrent Neural Networks (RNN) approach that retains the advantage of continuous dynamics offered by Ordinary Differential Equations (ODE) while enabling parameter estimation through adaptation, to larger signalling networks using a modular approach. Specifically, the signalling network is decomposed into several sub-models based on important temporal events in the network. Each sub-model is represented by the proposed RNN and trained using data generated from the corresponding ODE model...
February 4, 2017: Bio Systems
https://www.readbyqxmd.com/read/28165337/a-mouse-model-of-mycn-driven-retinoblastoma-reveals-mycn-independent-tumor-reemergence
#19
Nan Wu, Deshui Jia, Breanna Bates, Ryan Basom, Charles G Eberhart, David MacPherson
The most frequent focal alterations in human retinoblastoma are mutations in the tumor-suppressor gene retinoblastoma (RB) and amplification of the oncogene MYCN. Whether MYCN overexpression drives retinoblastoma has not been assessed in model systems. Here, we have shown that Rb inactivation collaborates strongly with MYCN overexpression and leads to retinoblastoma in mice. Overexpression of human MYCN in the context of Rb inactivation increased the expression of MYC-, E2F-, and ribosome-related gene sets, promoted excessive proliferation, and led to retinoblastoma with anaplastic changes...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28158315/a-dual-transcriptional-reporter-and-cdk-activity-sensor-marks-cell-cycle-entry-and-progression-in-c-elegans
#20
Lotte M van Rijnberk, Suzanne E M van der Horst, Sander van den Heuvel, Suzan Ruijtenberg
Development, tissue homeostasis and tumor suppression depend critically on the correct regulation of cell division. Central in the cell division process is the decision whether to enter the next cell cycle and commit to going through the S and M phases, or to remain temporarily or permanently arrested. Cell cycle studies in genetic model systems could greatly benefit from visualizing cell cycle commitment in individual cells without the need of fixation. Here, we report the development and characterization of a reporter to monitor cell cycle entry in the nematode C...
2017: PloS One
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