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https://www.readbyqxmd.com/read/28813415/cdk4-6-inhibition-triggers-anti-tumour-immunity
#1
Shom Goel, Molly J DeCristo, April C Watt, Haley BrinJones, Jaclyn Sceneay, Ben B Li, Naveed Khan, Jessalyn M Ubellacker, Shaozhen Xie, Otto Metzger-Filho, Jeremy Hoog, Matthew J Ellis, Cynthia X Ma, Susanne Ramm, Ian E Krop, Eric P Winer, Thomas M Roberts, Hye-Jung Kim, Sandra S McAllister, Jean J Zhao
Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamental drivers of the cell cycle and are required for the initiation and progression of various malignancies. Pharmacological inhibitors of CDK4/6 have shown significant activity against several solid tumours. Their primary mechanism of action is thought to be the inhibition of phosphorylation of the retinoblastoma tumour suppressor, inducing G1 cell cycle arrest in tumour cells. Here we use mouse models of breast carcinoma and other solid tumours to show that selective CDK4/6 inhibitors not only induce tumour cell cycle arrest, but also promote anti-tumour immunity...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28812991/the-retinoblastoma-rb-tumor-suppressor-pushing-back-against-genome-instability-on-multiple-fronts
#2
REVIEW
Renier Vélez-Cruz, David G Johnson
The retinoblastoma (RB) tumor suppressor is known as a master regulator of the cell cycle. RB is mutated or functionally inactivated in the majority of human cancers. This transcriptional regulator exerts its function in cell cycle control through its interaction with the E2F family of transcription factors and with chromatin remodelers and modifiers that contribute to the repression of genes important for cell cycle progression. Over the years, studies have shown that RB participates in multiple processes in addition to cell cycle control...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28807343/anisometric-cell-lipoma-insight-from-a-case-series-and-review-of-the-literature-on-adipocytic-neoplasms-in-survivors-of-retinoblastoma-suggest-a-role-for-rb1-loss-and-possible-relationship-to-fat-predominant-fat-only-spindle-cell-lipoma
#3
Abbas Agaimy
The term "anisometric cell lipoma" (ACL) has been proposed recently by Evans for a lipoma variant characterized by striking variation in size and shape of adipocytes but little or no cytological atypia. One patient with multiple ACL had a history of retinoblastoma. The current study analyzed six patients with ACL (4 males and two females aged 34 to 87years; median, 58); all seen in consultation. Five patients presented with solitary and one with multiple subcutaneous masses measuring 5 to 9cm (median, 7.5cm)...
August 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28806945/tumor-microenvironment-conditions-alter-akt-and-na-h-exchanger-nhe1-expression-in-endothelial-cells-more-than-hypoxia-alone-implications-for-endothelial-cell-function-in-cancer
#4
A K Pedersen, J Mendes Lopes de Melo, N Mørup, K Tritsaris, S F Pedersen
BACKGROUND: Chronic angiogenesis is a hallmark of most tumors and takes place in a hostile tumor microenvironment (TME) characterized by hypoxia, low nutrient and glucose levels, elevated lactate and low pH. Despite this, most studies addressing angiogenic signaling use hypoxia as a proxy for tumor conditions. Here, we compared the effects of hypoxia and TME conditions on regulation of the Na(+)/H(+) exchanger NHE1, Ser/Thr kinases Akt1-3, and downstream effectors in endothelial cells...
August 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28803391/mutational-analysis-of-the-rb1-gene-and-the-inheritance-patterns-of-retinoblastoma-in-jordan
#5
Yacoub A Yousef, Abdelghani Tbakhi, Maysa Al-Hussaini, Ibrahim AlNawaiseh, Ala Saab, Amal Afifi, Maysa Naji, Mona Mohammad, Rasha Deebajah, Imad Jaradat, Iyad Sultan, Mustafa Mehyar
Retinoblastoma (RB) is a childhood cancer developing in the retina due to RB1 pathologic variant. Herein we are evaluating the oncogenic mutations in the RB1 gene and the inheritance patterns of RB in the Jordanian patients. In this prospective study, the peripheral blood of 50 retinoblastoma patients was collected, genomic DNA was extracted, mutations were identified using Quantitative multiplex PCR (QM-PCR), Allele-specific PCR, Next Generation Sequencing analysis, and Sanger sequencing. In this cohort of 50 patients, 20(40%) patients had unilateral RB and 30(60%) were males...
August 12, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28802717/chronic-d609-treatment-interferes-with-cell-cycle-and-targets-the-expression-of-olig2-in-glioma-stem-like-cells
#6
Haviryaji S G Kalluri, John S Kuo, Robert J Dempsey
Glioma Stem-like Cells (GSCs) isolated from patient derived tumors have high metabolic activity and survive in the absence of exogenous growth factors. We recently demonstrated that acute D609 (Tricyclodecan-9-yl-xanthogenate), a PC-PLC inhibitor with anti-oxidative property, can decrease the ATP content & GADD45β protein in GSCs cultured without growth factors, but not in the presence of growth factors. In this study we examined the effect of chronic D609 treatment on GSCs cultured in complete medium containing growth factors...
August 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28800675/discovery-and-pharmacological-characterisation-of-a-novel-series-of-highly-selective-inhibitors-of-cyclin-dependent-kinases-4-and-6-as-anticancer-agents
#7
Solomon Tadesse, Laychiluh Bantie, Khamis Tomusange, Mingfeng Yu, Saiful Islam, Nataliya Bykovska, Benjamin Noll, Ge Zhu, Peng Li, Frankie Lam, Malika Kumarasiri, Robert Milne, Shudong Wang
BACKGROUND AND PURPOSE: Cyclin D dependent kinases 4 and 6 (CDK4/6) are crucial regulators of the G1 to S phase transition of the cell cycle, and are actively pursued as therapeutic targets in cancer targets. We sought to discover a novel series of orally bioavailable, and highly selective small molecule inhibitors of CDK4/6. EXPERIMENTAL APPROACH: The discovery of pharmacological inhibitors and optimisation for potency, selectivity and drug properties were achieved by iterative chemical synthesis, biochemical screening against a panel of kinases, cell-based assays measuring cellular viability, cell cycle distribution, induction of apoptosis, and the level of retinoblastoma tumour suppressor protein (Rb) phosphorylation and E2 factor (E2F) regulated gene expression, and in vitro biopharmaceutical and in vivo pharmacokinetic profiling...
August 11, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28798814/editorial-childhood-cancer-in-sub-saharan-africa
#8
EDITORIAL
Donald Maxwell Parkin, Cristina Stefan
Measurement of incidence rates of childhood cancer in Africa is difficult. The study 'Cancer of Childhood in sub Saharan Africa' [Stefan C, Bray F, Ferlay J, Parkin DM and Liu B (2017) Cancer of Childhood in sub-Saharan Africaecancer11(755)] brings together results from 16 population-based registries which, as members of the African Cancer Registry Network (AFCRN), have been evaluated as achieving adequate coverage of their target population. The cancers are classified according to the third revision of the International Classification of Childhood Cancer (ICCC-3) and recorded rates in Africa are compared with those in childhood populations in the UK, France, and the USA...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28798812/clinical-epidemiological-and-therapeutic-profile-of-patients-with-a-retinoblastoma-diagnosis-experience-in-the-costa-rica-national-children-s-hospital-oncology-unit-from-january-2009-to-december-2015
#9
Jennie Chen Lo, Carlos Rodríguez, Rigoberto Monestel, Arnoldo Zúñiga
INTRODUCTION: Retinoblastoma represents only 3% of paediatric cancers, but it is the most prevalent intraocular tumour in this population. It develops in the retina as a primitive neuroectodermal tumour that affects development during gestation. The tumour presents in two different forms depending on whether or not it expresses a genetic modification. For patients diagnosed at preschool age, 75% are unilateral non-hereditary cases. While enucleation is the preferred treatment for advanced stages of the tumour, other modalities, such as systemic and intraocular chemotherapy, radiotherapy and local treatments with thermotherapy, cryotherapy, and brachytherapy can be used to try to preserve the eye...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28798482/retinoblastoma-protein-rb-links-hypoxia-to-altered-mechanical-properties-in-cancer-cells-as-measured-by-an-optical-tweezer
#10
S Khakshour, M P Labrecque, H Esmaeilsabzali, F J S Lee, M E Cox, E J Park, T V Beischlag
Hypoxia modulates actin organization via multiple pathways. Analyzing the effect of hypoxia on the biophysical properties of cancer cells is beneficial for studying modulatory signalling pathways by quantifying cytoskeleton rearrangements. We have characterized the biophysical properties of human LNCaP prostate cancer cells that occur in response to loss of the retinoblastoma protein (Rb) under hypoxic stress using an oscillating optical tweezer. Hypoxia and Rb-loss increased cell stiffness in a fashion that was dependent on activation of the extracellular signal-regulated kinase (ERK) and the protein kinase B (AKT)- mammalian target of rapamycin (MTOR) pathways...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790340/verteporfin-inhibits-growth-of-human-glioma-in-vitro-without-light-activation
#11
Ahmad Al-Moujahed, Katarzyna Brodowska, Tomasz P Stryjewski, Nikolaos E Efstathiou, Ioannis Vasilikos, Joanna Cichy, Joan W Miller, Evangelos Gragoudas, Demetrios G Vavvas
Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19)...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28780672/defective-splicing-of-the-rb1-transcript-is-the-dominant-cause-of-retinoblastomas
#12
Kamil J Cygan, Rachel Soemedi, Christy L Rhine, Abraham Profeta, Eileen L Murphy, Michael F Murray, William G Fairbrother
Defective splicing is a common cause of genetic diseases. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations with most mapping to the critical GT or AG nucleotides within the 5' and 3' splice sites. However, splicing mutations are underreported and the fraction of splicing mutations that compose all disease alleles varies greatly across disease gene. For example, there is a great excess (46%; ~threefold) of hereditary disease alleles that map to splice sites in RB1 that cause retinoblastoma...
August 5, 2017: Human Genetics
https://www.readbyqxmd.com/read/28780249/dermal-fat-graft-for-anophthalmic-socket-in-children-enucleated-for-retinoblastoma
#13
V Bosch-Canto, C Cruz, J C Ordaz-Favila
Retinoblastoma is the most frequent intraocular tumour in childhood. The definitive treatment is enucleation. The management of the anophthalmic socket consists in the use of a plastic implant. The problem is that they are expensive and they usually extrude. The use of dermal-fat grafts minimises the hemi-facial hypoplasia. They usually grow with the face, and help to expand the orbital bones, thus avoiding the psychological and physical consequences. OBJECTIVE: To determine if there is hemi-facial hypoplasia, using MRI images after the use of a dermal-fat implant in patients enucleated for RB...
August 2, 2017: Archivos de la Sociedad Española de Oftalmología
https://www.readbyqxmd.com/read/28772359/correction-ablating-all-three-retinoblastoma-family-members-in-mouse-lung-leads-to-neuroendocrine-tumor-formation
#14
Sara Lázaro, Miriam Pérez-Crespo, Ana Belén Enguita, Pilar Hernández, Jesús Martínez-Palacio, Marta Oteo, Julien Sage, Jesús M Paramio, Mirentxu Santos
No abstract text is available yet for this article.
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28770899/outcome-of-focal-treatment-to-residual-retinoblastoma-after-chemotherapy-experience-with-focal-treatment-of-retinoblastoma
#15
Sumbul Kashif, Kashif Muhammad, Nisar Siyal, Mohammed Idrees Adhi
We report a prospective case series on the anatomical, and functional outcomes, and complications of focal treatment of retinoblastoma to residual tumors in patients who had already received chemotherapy. We examined the patients of retinoblastoma under general anaesthesia with Ret Cam II. Patients with lesions from Group 1 to Group 5 of Reese Ellsworth classification at presentation. They were first given chemotherapy according to VEC (Vincristine, Etoposide and Carboplatin) protocol and then focal treatment...
July 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/28769987/anticancer-effects-of-sinocrassulosides-vi-vii-from-silene-viscidula-on-hela-cells
#16
Hang Chen, Qian Ma, Wei Xu, Wan-Ming Li, De-Zheng Yuan, Jia-Mei Wu, Yu-Shan Li, Jin Fang
Natural products are becoming increasingly important in chemoprevention and for cancer therapy. Silene viscidula (S. viscidula), a traditional Chinese herb, has long been used as an anti-inflammatory and neuroleptic agent. However, the anticancer activity of S. viscidula has remained unclear. In this study, 16 compounds were extracted from S. viscidula. Among those compounds, sinocrassulosides VI/VII, an inseparable isomer mixture, possess the strongest inhibitory activity on HeLa cells with the IC50 value of 2...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28763932/-the-progress-and-prospect-of-application-of-genetic-testing-technology-based-gene-detection-technology-in-the-diagnosis-and-treatment-of-hereditary-cancer
#17
J X He, Y F Jiang
Hereditary cancer is caused by specific pathogenic gene mutations. Early detection and early intervention are the most effective ways to prevent and control hereditary cancer. High-throughput sequencing based genetic testing technology (NGS) breaks through the restrictions of pedigree analysis, provide a convenient and efficient method to detect and diagnose hereditary cancer. Here, we introduce the mechanism of hereditary cancer, summarize, discuss and prospect the application of NGS and other genetic tests in the diagnosis of hereditary retinoblastoma, hereditary breast and ovarian cancer syndrome, hereditary colorectal cancer and other complex and rare hereditary tumors...
August 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/28757689/management-outcome-s-in-eyes-with-retinoblastoma-previously-inadequately-treated-with-systemic-chemotherapy-alone-without-focal-therapy
#18
Yacoub A Yousef, Rashed M Nazzal, Mohammed B Khalil, Rasha Deebajah, Mustafa Mehyar, Shatha Hajja, Mona Mohammad, Reem Al Jabary, Imad Jaradat, Iyad Sultan, Ibrahim Al Nawaiseh
OBJECTIVE: The objective of this study was to evaluate the outcome of management in eyes with intraocular retinoblastoma (RB) that had received inadequate initial therapy (chemotherapy without focal therapy) before eventually receiving necessary consolidation therapy at a tertiary referral center. METHODS: A retrospective observational case series of 30 eyes from 26 RB patients who had initially received systemic chemotherapy as a sole therapy. The main outcome measures were demographics, laterality, International Classification of RB (ICRB), treatments, tumor control, and survival...
May 2017: Oman Journal of Ophthalmology
https://www.readbyqxmd.com/read/28755959/an-open-label-single-arm-phase-ii-multicenter-study-of-the-safety-and-efficacy-of-cg0070-oncolytic-vector-regimen-in-patients-with-bcg-unresponsive-non-muscle-invasive-bladder-cancer-interim-results
#19
Vignesh T Packiam, Donald L Lamm, Daniel A Barocas, Andrew Trainer, Benjamin Fand, Ronald L Davis, William Clark, Michael Kroeger, Igor Dumbadze, Karim Chamie, A Karim Kader, Dominic Curran, John Gutheil, Arthur Kuan, Alex W Yeung, Gary D Steinberg
OBJECTIVES: CG0070 is a replication-competent oncolytic adenovirus that targets bladder tumor cells through their defective retinoblastoma pathway. Prior reports of intravesical CG0070 have shown promising activity in patients with high-grade non-muscle invasive bladder cancer (NMIBC) who previously did not respond to bacillus Calmette-Guérin (BCG). However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy...
July 26, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28748347/molecular-basis-of-pediatric-brain-tumors
#20
REVIEW
Alexia Klonou, Christina Piperi, Antonios N Gargalionis, Athanasios G Papavassiliou
Brain tumors emerge as the second commonest type of pediatric solid tumors following hematologic malignancies. Genomic profiling of low- and high-grade gliomas, ependymomas and medulloblastomas has revealed chromosomal abnormalities and specific gene mutations which have been associated with aberrant activation of crucial signal transduction pathways, including mitogen-activated protein kinase, mammalian target of rapamycin and retinoblastoma tumor suppressor signaling. Furthermore, pediatric high-grade gliomas are associated with chromatin remodeling defects and somatic histone gene mutations that affect prognosis...
July 26, 2017: Neuromolecular Medicine
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