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Retinoblastoma

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https://www.readbyqxmd.com/read/28447713/tetramethylpyrazine-mediated-regulation-of-cxcr4-in-retinoblastoma-is-sensitive-to-cell-density
#1
Nandan Wu, Lijun Xu, Ying Yang, Na Yu, Zhang Zhang, Pei Chen, Jing Zhang, Mingjun Tang, Meng Yuan, Jian Ge, Keming Yu, Jing Zhuang
Retinoblastoma is the most common ocular tumor in children, and it causes extensive damage. Current treatment options for retinoblastoma include surgery, chemotherapy, radiotherapy and cryotherapy. However, the majority of chemotherapy medicines cause complications and side effects that lead to severe impairment of patient health. Previous studies have reported that tetramethylpyrazine (TMP), which is an extract of the Chinese herbal medicine Chuanxiong, reduces the risk of multidrug resistance in chemotherapy and inhibits the proliferation and metastasis of various types of cancer cells...
March 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28446612/cdk4-is-degraded-by-apc-c-in-mitosis-and-reaccumulates-in-early-g1-phase-to-initiate-a-new-cell-cycle-in-hela-cells
#2
Huabo Chen, Xiaowei Xu, Guopeng Wang, Boyan Zhang, Gang Wang, Guangwei Xin, Junjun Liu, Qing Jiang, Hongyin Zhang, Chuanmao Zhang
CDK4 regulates G1-S phase transition in mammalian cell cycle by phosphorylating retinoblastoma family proteins. However, the mechanism underlying the regulation of CDK4 activity is not fully understood. Here, we show that CDK4 protein is degraded by APC/C during metaphase-anaphase (M-A) transition in HeLa cells, whereas its main regulator cyclin D1 remains intact but is sequestered in cytoplasm. CDK4 protein reaccumulates in the following G1 phase, and shuttles between the nucleus and the cytoplasm to facilitate the nuclear import of cyclin D1...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28445974/lowered-expression-of-microrna-125a-5p-in-human-hepatocellular-carcinoma-and-up-regulation-of-its-oncogenic-targets-sirtuin-7-matrix-metalloproteinase-11-and-c-raf
#3
Nicola Coppola, Giorgio de Stefano, Marta Panella, Lorenzo Onorato, Valentina Iodice, Carmine Minichini, Nicola Mosca, Luisa Desiato, Nunzia Farella, Mario Starace, Giulia Liorre, Nicoletta Potenza, Evangelista Sagnelli, Aniello Russo
Human microRNA-125a-5p (miR-125a) is expressed in most tissues where it downregulates the expression of membrane receptors or intracellular transductors of mitogenic signals, thus limiting cell proliferation. Expression of this miRNA generally increases with cell differentiation whereas it is downregulated in several types of tumors, such as breast, lung, ovarian, gastric, colon, and cervical cancers, neuroblastoma, medulloblastoma, glioblastoma, and retinoblastoma. In this study, we focused on hepatocellular carcinoma and used real-time quantitative PCR to measure miR-125a expression in 55 tumor biopsies and in matched adjacent non-tumor liver tissues...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445155/retinoblastoma-cells-activate-the-akt-pathway-and-are-vulnerable-to-the-pi3k-mtor-inhibitor-nvp-bez235
#4
Chencheng Xie, Matthew J Freeman, Huarui Lu, Xiaohong Wang, Colleen L Forster, Aaron L Sarver, Timothy C Hallstrom
Retinoblastoma is a pediatric cancer of the retina most often caused by inactivation of the retinoblastoma (RB1) tumor suppressor gene. We previously showed that Rb1 loss cooperates with either co-activating the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, or co-deleting Pten, to initiate retinoblastoma tumors in mice. The objectives of this study were to determine if the AKT pathway is activated in human retinoblastomas and the extent that anti-PI3K therapy induces apoptosis in retinoblastoma cells, alone or in combination with the DNA damaging drugs carboplatin and topotecan...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443472/mir-26a-downregulates-retinoblastoma-in-colorectal-cancer
#5
Eduardo López-Urrutia, Jossimar Coronel-Hernández, Verónica García-Castillo, Carlos Contreras-Romero, Antonio Martínez-Gutierrez, Diana Estrada-Galicia, Luis Ignacio Terrazas, César López-Camarillo, Hector Maldonado-Martínez, Nadia Jacobo-Herrera, Carlos Pérez-Plasencia
MicroRNAs are non-coding short RNAs that target the 3' untranslated region of messenger RNAs (mRNAs) and lead to their degradation or to translational repression. Several microRNAs have been designated as oncomirs, owing to their regulating tumor suppressor genes. Interestingly, a few of them have been found to target multiple genes whose simultaneous suppression contributes to the development of a tumoral phenotype. Here, we have showed that miR-26a is overexpressed in colorectal cancer data obtained from TCGA Research Network and in human colon cancer pathological specimens; moreover, an orthotopic in vivo model of colon cancer showed overexpression of miR-26a, while Rb1 expression inversely correlated to miR-26a in TCGA Research Network data, pathological samples, and the in vivo model...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28440424/therapeutic-potential-of-the-antidiabetic-drug-metformin-in-small-bowel-adenocarcinoma
#6
Taiga Chiyo, Kiyohito Kato, Hisakazu Iwama, Shintaro Fujihara, Koji Fujita, Tomoko Tadokoro, Kyoko Ohura, Eri Samukawa, Yoshimi Yamana, Nobuya Kobayashi, Tae Matsunaga, Noriko Nishiyama, Maki Ayaki, Tatsuo Yachida, Asahiro Morishita, Hideki Kobara, Hirohito Mori, Tsutomu Masaki
Small bowel adenocarcinoma (SBAC) accounts for 3% of all gastrointestinal tract tumors and approximately 0.5% of all cancer cases. Recent studies have indicated that the use of metformin, one of the most commonly prescribed antidiabetic drugs, is associated with a better prognosis for certain malignant diseases. However, there have been no reports on the effect of metformin in SBAC. In the present study, we evaluated the effect of metformin on human SBAC cell proliferation in vitro and in vivo and identified the microRNAs (miRNAs) associated with its antitumor effects...
April 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28439018/conservation-and-divergence-of-c-terminal-domain-structure-in-the-retinoblastoma-protein-family
#7
Tyler J Liban, Edgar M Medina, Sarvind Tripathi, Satyaki Sengupta, R William Henry, Nicolas E Buchler, Seth M Rubin
The retinoblastoma protein (Rb) and the homologous pocket proteins p107 and p130 negatively regulate cell proliferation by binding and inhibiting members of the E2F transcription factor family. The structural features that distinguish Rb from other pocket proteins have been unclear but are critical for understanding their functional diversity and determining why Rb has unique tumor suppressor activities. We describe here important differences in how the Rb and p107 C-terminal domains (CTDs) associate with the coiled-coil and marked-box domains (CMs) of E2Fs...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28435935/proliferative-vitreoretinopathy-in-treated-retinoblastoma
#8
Cindy S Hwang, Pia R Mendoza, Jill R Wells, Hans E Grossniklaus, G Baker Hubbard
OBJECTIVE: To evaluate the clinical and histopathologic characteristics of patients who develop proliferative vitreoretinopathy after retinoblastoma treatment. DESIGN: Retrospective review of three cases of proliferative vitreoretinopathy (PVR) that developed after successful treatment of retinoblastoma from 2003 to 2015. SUBJECTS: Three patients with treated retinoblastoma who developed severe PVR and required enucleation. METHODS: Review of clinical charts, fundus drawings, Ret-Cam 3 images, and histopathology specimens...
March 2017: Ophthalmol Retina
https://www.readbyqxmd.com/read/28432176/a-phase-i-study-of-the-cdk4-6-inhibitor-ribociclib-lee011-in-pediatric-patients-with-malignant-rhabdoid-tumors-neuroblastoma-and-other-solid-tumors
#9
Birgit Geoerger, Franck Bourdeaut, Steven G DuBois, Matthias Fischer, James I Geller, Nicholas G Gottardo, Aurélien Marabelle, Andrew D J Pearson, Shakeel Modak, Thomas Cash, Giles W Robinson, Marlyane Motta, Alessandro Matano, Suraj G Bhansali, Jason R Dobson, Sudha Parasuraman, Susan N Chi
Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off)...
April 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28432112/reduction-of-severe-visual-loss-and-complications-following-intra-arterial-chemotherapy-iac-for-refractory-retinoblastoma
#10
M Ashwin Reddy, Zishan Naeem, Catriona Duncan, Fergus Robertson, Jane Herod, Adam Rennie, Alki Liasis, Dorothy Ann Thompson, Mandeep Sagoo
BACKGROUND: Intra-arterial chemotherapy (IAC) for retinoblastoma has been documented as causing visual loss and ocular motility problems. A lack of safety data has precluded its acceptance in all centres. METHODS: Retrospective cohort study of patients with retinoblastoma from 2013 to 2015 who had a healthy foveola and relapsed following systemic chemotherapy. All required IAC. The correlation of complications with doses of melphalan +/- topotecan used and putative catheterisation complications was assessed...
April 21, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28431342/discovery-of-tetrahydrocarbazoles-as-dual-perk-and-prb-inhibitors
#11
Mahesh R Kulkarni, Madhav S Mane, Usha Ghosh, Rajiv Sharma, Nitin P Lad, Ankita Srivastava, Asha Kulkarni-Almeida, Prashant S Kharkar, Vijay M Khedkar, Shivaji S Pandit
The extracellular signal-regulated kinase (ERK) is one of the most important molecular targets for cancer that controls diverse cellular processes such as proliferation, survival, differentiation and motility. Similarly, the Rb (retinoblastoma protein) is a tumor suppressor protein and its function is to prevent excessive cell growth by inhibiting cell cycle progression. When the cell is ready to divide, pRb is phosphorylated, becomes inactive and allows cell cycle progression. Herein, we discovered a new series of tetrahydrocarbazoles as dual inhibitors of pERK and pRb phosphorylation...
March 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28421271/-hereditary-bone-tumors
#12
D Baumhoer
Hereditary bone tumors are rare and result from mutations affecting cell cycle regulation (e.g. retinoblastoma syndrome/RB1 and Li-Fraumeni syndrome/TP53, Gardner syndrome/APC), energy metabolism (enchondromatosis/IDH1/2), complex signaling cascades (multiple hereditary exostoses/EXT1/2) and DNA integrity (Rothmund-Thomson/RECQL4, Werner/WRN and Bloom syndromes/BLM). The majority of syndromes are incompletely understood and can lead to multiple benign tumors, of which some might undergo secondary malignant transformation over time (enchondromatosis: enchondromas, multiple hereditary exostoses: osteochondromas, Gardner syndrome: osteomas) or bone sarcomas, primarily osteosarcomas as primary (Li-Fraumeni, Rothmund-Thomson, Werner and Bloom syndromes) or secondary manifestation (retinoblastoma syndrome) of the disease...
April 18, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28420213/folate-decorated-nanomicelles-loaded-with-a-potent-curcumin-analogue-for-targeting-retinoblastoma
#13
Hashem Alsaab, Rami M Alzhrani, Prashant Kesharwani, Samaresh Sau, Sai Hs Boddu, Arun K Iyer
The aim of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using a promising anticancer agent, curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used as a targeting moiety to enhance the targeting and bioavailability of CDF. For this purpose, amphiphilic poly(styrene-co-maleic acid)-conjugated-folic acid (SMA-FA) was synthesized and utilized to improve the aqueous solubility of a highly hydrophobic, but very potent anticancer compound, CDF, and its targeted delivery to folate overexpressing cancers...
April 18, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28415600/the-value-of-mri-in-evaluating-the-efficacy-and-complications-with-the-treatment-of-intra-arterial-chemotherapy-for-retinoblastoma
#14
Shuxian Chen, Xunda Ji, Ming Liu, Zhengrong Xia, Hui Zheng, Qiufeng Yin, He Wang, Yuhua Li
Retinoblastoma is the most common intraocular malignant tumor of childhood. Intra-arterial chemotherapy (IAC) is a recently popularized technique used for the treatment of retinoblastoma, to decrease mortality, increase preservation of the eye, and prevent blindness. Along with the extensive use of IAC, it is important to apply noninvasive examination methods to assess the activity of the tumor and the risk factors for disease dissemination without histopathological confirmation. There are few studies that have assessed the value of magnetic resonance imaging (MRI) in evaluating the efficacy and complications of IAC for retinoblastoma...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401291/the-human-retinoblastoma-susceptibility-gene-rb1-an-evolutionary-story-in-primates
#15
Maria C Viana, William C Tavares, Ayslan C Brant, Mariana Boroni, Héctor N Seuánez
The tumor suppressor gene RB1 (Human Retinoblastoma Susceptibility Gene) plays a prominent role in normal development, gene transcription, DNA replication, repair, and mitosis. Its complete biallelic dysfunction in retinoblasts is the main cause of retinoblastoma in the human. Although this gene has been evolutionary conserved, comparisons between the reference and human RB1 coding region with its counterparts in 19 non-human primates showed 359 sites where nucleotide replacements took place during the radiation of these species...
April 11, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28401192/evasion-of-targeted-cancer-therapy-through-stem-cell-like-reprogramming
#16
Kristine M Wadosky, Leigh Ellis, David W Goodrich
Prostate cancer variants expressing alternative lineage markers appear at relapse from antiandrogen therapy. We show that loss of the retinoblastoma (RB1) and tumor protein 53 (TP53) genes drives expression of stem cell reprogramming factors, lineage plasticity, and antiandrogen resistance. Epigenetic manipulation restores antiandrogen sensitivity-suggesting an approach for treating lethal prostate cancers.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28399338/genetics-and-molecular-diagnostics-in-retinoblastoma-an-update
#17
Sameh E Soliman, Hilary Racher, Chengyue Zhang, Heather MacDonald, Brenda L Gallie
Retinoblastoma is the prototype genetic cancer: in one or both eyes of young children, most retinoblastomas are initiated by biallelic mutation of the retinoblastoma tumor suppressor gene, RB1, in a developing retinal cell. All those with bilateral retinoblastoma have heritable cancer, although 95% have not inherited the RB1 mutation. Non-heritable retinoblastoma is always unilateral, with 98% caused by loss of both RB1 alleles from the tumor, whereas 2% have normal RB1 in tumors initiated by amplification of the MYCN oncogene...
March 2017: Asia-Pacific Journal of Ophthalmology
https://www.readbyqxmd.com/read/28398584/genomic-profiles-of-low-grade-murine-gliomas-evolve-during-progression-to-glioblastoma
#18
Mark Vitucci, David M Irvin, Robert S McNeill, Ralf S Schmid, Jeremy M Simon, Harshil D Dhruv, Marni B Siegel, Andrea M Werneke, Ryan E Bash, Seungchan Kim, Michael E Berens, C Ryan Miller
Background: Gliomas are diverse neoplasms with multiple molecular subtypes. How tumor-initiating mutations relate to molecular subtypes as these tumors evolve during malignant progression remains unclear. Methods: We used genetically engineered mouse models, histopathology, genetic lineage tracing, expression profiling, and copy number analyses to examine how genomic tumor diversity evolves during the course of malignant progression from low- to high-grade disease...
April 7, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28397259/patient-understanding-of-genetic-information-influences-reproductive-decision-making-in-retinoblastoma
#19
A Foster, L Boyes, L Burgess, S Carless, V Bowyer, H Jenkinson, M Parulekar, J Ainsworth, J Hungerford, Z Onadim, M Sagoo, E Rosser, M A Reddy, T Cole
Retinoblastoma is the most common malignant tumour of the eye in childhood, with nearly all bilateral tumours and around 17-18% of unilateral tumours due to an oncogenic mutation in the RB1 gene in the germline. Genetic testing in all cases enables accurate risk assessment and optimal clinical management for the affected individual, siblings, and future offspring. We carried out the first UK-wide audit of understanding of genetic testing in individuals with retinoblastoma. A total of 292 individuals aged 16-45 years were included...
April 11, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28396848/update-on-the-treatment-of-metastatic-squamous-non-small-cell-lung-cancer-in-new-era-of-personalized-medicine
#20
REVIEW
Sara Victoria Soldera, Natasha B Leighl
Despite advances in molecular characterization and lung cancer treatment in recent years, treatment options for patients diagnosed with squamous cell carcinoma of the lung (SCC) remain limited as actionable mutations are rarely detected in this subtype. This article reviews potential molecular targets and associated novel agents for the treatment of advanced SCC in the era of personalized medicine. Elements of various pathways including epidermal growth factor receptor, PI3KCA, fibroblast growth factor receptor, retinoblastoma, cyclin-dependent kinases, discoidin domain receptor tyrosine kinase 2, and mesenchymal-to-epithelial transition may play pivotal roles in the development of SCC and are under investigation for drug development...
2017: Frontiers in Oncology
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