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P53 -apoptosis

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https://www.readbyqxmd.com/read/29777905/coupling-of-the-polyamine-and-iron-metabolism-pathways-in-the-regulation-of-proliferation-mechanistic-links-to-alterations-in-key-polyamine-biosynthetic-and-catabolic-enzymes
#1
Darius J R Lane, Dong-Hun Bae, Aritee R Siafakas, Yohan Suryo Rahmanto, Lina Al-Akra, Patric J Jansson, Robert A Casero, Des R Richardson
Many biological processes result from the coupling of metabolic pathways. Considering this, proliferation depends on adequate iron and polyamines, and although iron-depletion impairs proliferation, the metabolic link between iron and polyamine metabolism has never been thoroughly investigated. This is important to decipher, as many disease states demonstrate co-dysregulation of iron and polyamine metabolism. Herein, for the first time, we demonstrate that cellular iron levels robustly regulate 13 polyamine pathway proteins...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777397/telomeres-and-telomerase-during-human-papillomavirus-induced-carcinogenesis
#2
REVIEW
Anna Pańczyszyn, Ewa Boniewska-Bernacka, Grzegorz Głąb
Human papillomaviruses (HPVs) belong to a small spherical virus family and are transmitted through direct contact, most often through sexual behavior. More than 200 types of HPV are known, a dozen or so of which are classified as high-risk viruses (HR HPV) and may contribute to the development of cervical cancer. HPV is a small virus with a capsid composed of L1 and L2 proteins, which are crucial for entry to the cell. The infection begins at the basal cell layer and progresses to involve cells from higher layers of the cervical epithelium...
May 18, 2018: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29777149/stretching-reduces-tumor-growth-in-a-mouse-breast-cancer-model
#3
L Berrueta, J Bergholz, D Munoz, I Muskaj, G J Badger, A Shukla, H J Kim, J J Zhao, H M Langevin
There is growing interest in developing non-pharmacological treatments that could boost natural defenses against cancer and contribute to primary and secondary cancer prevention. Recent studies have shown that gentle daily stretching for 10 minutes can reduce local connective tissue inflammation and fibrosis. Because mechanical factors within the stroma can influence the tumor microenvironment, we hypothesized that stretching would reduce the growth of tumors implanted within locally stretched tissues and tested this hypothesis in a mouse orthotopic breast cancer model...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29776635/molecular-diagnostics-in-esophageal-and-gastric-neoplasms-2018-update
#4
REVIEW
Muhammad Zulfiqar, Martin H Bluth, Amarpreet Bhalla
Esophageal cancer (EC) is rapidly increasing in incidence in the United States. Genetic changes associated with the development of EC involve the p16, p53, and APC genes. Human epidermal growth factor 2 (HER-2) overexpression is seen in gastroesophageal junction carcinoma and a subset gastric carcinoma (GC). Interestingly, up to 50% cases of GC are related to Helicobacter pylori infection and up to 16% are related to EBV infection. Microsatellite instability is observed in up to 39% of GC and cell free nucleic acid analysis provides additional opportunities for diagnosis and prognosis of disease...
June 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29775997/improved-acmg-compliant-in-silico-prediction-of-pathogenicity-for-missense-substitutions-encoded-by-tp53-variants
#5
Cristina Fortuno, Paul A James, Erin L Young, Bing Feng, Magali Olivier, Tina Pesaran, Sean V Tavtigian, Amanda B Spurdle
Clinical interpretation of germline missense variants represents a major challenge, including those in the TP53 Li-Fraumeni syndrome gene. Bioinformatic prediction is a key part of variant classification strategies. We aimed to optimize the performance of the Align-GVGD tool used for p53 missense variant prediction, and compare its performance to other bioinformatic tools (SIFT, PolyPhen-2) and ensemble methods (REVEL, BayesDel). Reference sets of assumed pathogenic and assumed benign variants were defined using functional and/or clinical data...
May 18, 2018: Human Mutation
https://www.readbyqxmd.com/read/29775409/transactivation-domain-of-p53-regulates-dna-repair-and-integrity-in-human-ips-cells
#6
Ramaswamy Kannappan, Saidulu Mattapally, Pooja A Wagle, Jianyi Zhang
The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human iPS cells has never been studied. p53-TAD was knocked out in iPS cells using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD KO cells were characterized by: accelerated proliferation, decreased population doubling time, and unaltered Bcl2, BBC3, IGF1R, Bax and altered Mdm2, p21, and PIDD transcripts expression. In p53-TAD KO cells p53 regulated DNA repair proteins XPA, DNA polH and DDB2 expression were found to be reduced compared to p53-WT cells...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29775073/diffuse-gliomas-for-nonneuropathologists-the-new-integrated-molecular-diagnostics
#7
Sunhee C Lee
Diffuse gliomas comprise the bulk of "brain cancer" in adults. The recent update to the 4th edition of the World Health Organization's classification of tumors of the central nervous system reflects an unprecedented change in the landscape of the diagnosis and management of diffuse gliomas that will affect all those involved in the management and care of patients. Of the recently discovered gene alterations, mutations in the Krebs cycle enzymes isocitrate dehydrogenases (IDHs) 1 and 2 have fundamentally changed the way the gliomas are understood and classified...
May 18, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29774995/-study-on-the-relationship-between-mct-1-and-p53-in-laryngeal-squamous-cell-carcinoma
#8
Y B Wang, O Xu, R J Zhang, C G Shan
Objective: The aim of this study is to investigate the expression and clinical significance of monocarboxylate transporter 1 (MCT-1) and p53 in laryngeal squamous cell carcinoma (LSCC). Method: Immunohistochemical staining of MCT-1 and p53 was carried out in 41 cases of laryngeal squamous cell carcinoma embedded in paraffin, and the relationship between positive expression and clinicopathological data was evaluated. All data were analyzed by SPSS software (Windows version 21.0). Result: In normal mucosa p53 expression was absent; while, the basal "stem cell" layer is highly enriched in MCT-1...
June 5, 2017: Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery
https://www.readbyqxmd.com/read/29774132/natural-products-a-hope-for-glioblastoma-patients
#9
REVIEW
Raghupathy Vengoji, Muzafar A Macha, Surinder K Batra, Nicole A Shonka
Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774100/differential-proteomic-profile-of-leukemic-cd34-progenitor-cells-from-chronic-myeloid-leukemia-patients
#10
Maria Rosaria Ricciardi, Valentina Salvestrini, Roberto Licchetta, Simone Mirabilii, Mattia Forcato, Gabriele Gugliotta, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Massimo Lemoli, Agostino Tafuri
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774081/g9a-stimulates-crc-growth-by-inducing-p53-lys373-dimethylation-dependent-activation-of-plk1
#11
Jie Zhang, Yafang Wang, Yanyan Shen, Pengxing He, Jian Ding, Yi Chen
Rationale: G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. Methods: The role of Plk1 in G9a aberrant CRC was determined by performing different in vitro and in vivo assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a...
2018: Theranostics
https://www.readbyqxmd.com/read/29773584/mechanisms-in-endocrinology-cell-cycle-regulation-in-adrenocortical-carcinoma
#12
Sofia Pereira, Mariana P Monteiro, Isabelle Bourdeau, Andre Lacroix, Duarte Pignatelli
Adrenocortical carcinomas are rather rare endocrine tumors that often have a poor prognosis. The reduced survival rate associated with these tumors is due to their aggressive biological behavior, combined with the scarcity of effective treatment options that are currently available. The recent identification of the genomic alterations present in ACC have provided further molecular mechanisms to develop consistent strategies for the diagnosis, prevention of progression and treatment of advanced ACCs. Taken together, molecular and genomic advances could be leading the way to develop personalized medicine in ACCs similarly to similar developments in lung or breast cancers...
May 17, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29771771/a-therapeutic-strategy-for-resectable-pancreatic-cancer-based-on-risk-factors-of-early-recurrence
#13
Hiroshi Kurahara, Kosei Maemura, Yuko Mataki, Masahiko Sakoda, Satoshi Iino, Yota Kawasaki, Takaaki Arigami, Shinichiro Mori, Yuko Kijima, Shinichi Ueno, Hiroyuki Shinchi, Shoji Natsugoe
OBJECTIVES: The aim of this study was to identify risk factors for early recurrence and assess the prognostic benefit of neoadjuvant therapy (NAT) for resectable pancreatic cancer. METHODS: Patients with radiographically resectable pancreatic cancer according to the National Comprehensive Cancer Network guidelines were enrolled. We regarded recurrence within 6 months after surgery as early recurrence. RESULTS: This study involved 115 patients (80 who underwent upfront surgery and 35 who received NAT)...
May 15, 2018: Pancreas
https://www.readbyqxmd.com/read/29771335/loss-of-fragile-x-protein-fmrp-impairs-homeostatic-synaptic-downscaling-through-tumor-suppressor-p53-and-ubiquitin-e3-ligase-nedd4-2
#14
Kwan Young Lee, Kathryn A Jewett, Hee Jung Chung, Nien-Pei Tsai
Synaptic scaling allows neurons to homeostatically readjust synaptic strength upon chronic neural activity perturbations. Although altered synaptic scaling has been implicated to underlie imbalanced brain excitability in neurological disorders such as autism spectrum disorders and epilepsy, the molecular dysregulation and restoration of synaptic scaling in those diseases have not been demonstrated. Here, we showed that the homeostatic synaptic downscaling is absent in the hippocampal neurons of Fmr1 KO mice, the mouse model of the most common inherited autism, Fragile X Syndrome (FXS)...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29770483/melatonin-modulates-dysregulated-circadian-clocks-in-mice-with-diethylnitrosamine-induced-hepatocellular-carcinoma
#15
Diana I Sánchez, Bárbara González-Fernández, Irene Crespo, Beatriz San-Miguel, Marcelino Álvarez, Javier González-Gallego, María Jesús Tuñón
Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long-term diseases including hepatocellular carcinoma (HCC). Melatonin has been reported to alleviate promotion and progression of HCC, but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p.) once a week for 8 weeks. Melatonin was given at 5 or 10 mg/kg/day i...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29769552/a-comprehensive-bioinformatics-analysis-on-multiple-gene-expression-omnibus-datasets-of-nonalcoholic-fatty-liver-disease-and-nonalcoholic-steatohepatitis
#16
Shanzhou Huang, Chengjun Sun, Yuchen Hou, Yunhua Tang, Zebin Zhu, Zhiheng Zhang, Yixi Zhang, Linhe Wang, Qiang Zhao, Mao-Gen Chen, Zhiyong Guo, Dongping Wang, Weiqiang Ju, Qi Zhou, Linwei Wu, Xiaoshun He
Fatty liver disease is one of the leading causes of chronic damage in western countries. Approximately 25% of adults in the United States have fatty livers in the absence of excessive alcohol consumption, a condition termed nonalcoholic fatty liver disease (NAFLD). Little is known about the prevalence and genetic background of NAFLD or the factors that determine its development. In this study, we used the Gene-Cloud of Biotechnology Information bioinformatics platform to carry out a comprehensive bioinformatics analysis identifying differentially expressed genes (DEGs), key biological processes and intersecting pathways...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768261/n-cadherin-attenuates-high-glucose-induced-nucleus-pulposus-cell-senescence-through-regulation-of-the-ros-nf-%C3%AE%C2%BAb-pathway
#17
Gang Hou, Huiqing Zhao, Haijun Teng, Pei Li, Wenbin Xu, Junbin Zhang, Lulu Lv, Zhiliang Guo, Li Wei, Hui Yao, Yichun Xu
BACKGROUND/AIMS: Diabetes mellitus (DM) is a potential etiology of disc degeneration. N-cadherin (N-CDH) helps maintain the cell viability, cell phenotype and matrix biosynthesis of nucleus pulposus (NP) cells. Here, we mainly aimed to investigate whether N-CDH can attenuate high glucose-induced NP cell senescence and its potential mechanism. METHODS: Rat NP cells were cultured in a base culture medium and base culture medium with a 0.2 M glucose concentration. Recombinant lentiviral vectors were used to enhance N-CDH expression in NP cells...
May 11, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29767452/adenoma-of-colorectal-laterally-spreading-tumor-non-granular-type-with-biological-phenotypic-features-similar-to-cancer
#18
Kengo Nagai, Yoshito Hayashi, Keiichiro Honma, Akihiko Sakatani, Shunsuke Yoshii, Tetsuji Fujinaga, Akira Maekawa, Yoshiki Tsujii, Satoshi Hiyama, Shinichiro Shinzaki, Kenji Watabe, Hideki Iijima, Masahiko Tsujii, Tsunekazu Mizushima, Eiichi Morii, Tetsuo Takehara
BACKGROUND AND AIM: Colorectal laterally spreading tumors (LST) are morphologically subdivided into granular (LST-G) and non-granular (LST-NG) categories. We aimed to elucidate the differences in oncogenic characteristics between the two types. METHODS: LST resected by endoscopic submucosal dissection and surgery from March 2009 to May 2017 were examined for p53-positivity, Ki-67 labeling index (LI), microvessel density, degree of fibrosis, intensities of inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT), and expression of acid mucins...
May 16, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29767261/inhibition-of-mek-erk-stat3-signaling-in-oleuropein-treatment-inhibits-myocardial-ischemia-reperfusion
#19
Hong-Xu Jin, Yun-Hu Zhang, Ruo-Nan Guo, Su-Nuan Zhao
Studies have shown that oleuropein has antifungal, anti‑inflammatory, antiviral, antioxidant, anticancer and hypoglycemic functions. TTC solution staining was used to measure myocardial infarction size. A commercial kit was used to measure lactate dehydrogenase (LDH), creatinine kinase‑MB (CK‑MB), tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β), IL 6, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and catalase levels. Western blot analysis was used to measure p53, p-MEK p-ERK and p‑IκBα protein expression...
May 11, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29766825/anti-glioma-effects-of-caffeic-acid-phenethyl-ester-and-dasatinib-combination-therapy-in-an-in-vivo-rat-glioma-model
#20
Henah Balkhi, Ehtishamul Haq, Taseen Guler, Syed Sana
BACKGROUND: Caffeic acid phenethyl ester and Dasatinib in combination, when used in congruous proportions and durations, present an antitumor potential for glioma in vitro, suggesting a high therapeutic potential for glioma treatment. OBJECTIVE: In the present study, we addressed the question whether CAPE and Dasatinib target multiple pathways involved in tumor growth, proliferation and development on an in vivo rat model of glioma. METHODS: Expression analysis of proteins thought to be mediating proliferation, cell motility, angiogenesis, and invasion was carried out to delineate the antineoplastic action of CAPE and Dasatinib...
May 15, 2018: Anti-cancer Agents in Medicinal Chemistry
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