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https://www.readbyqxmd.com/read/28639950/reactive-oxygen-species-generation-and-increase-in-mitochondrial-copy-number-new-insight-into-the-potential-mechanism-of-cytotoxicity-induced-by-aurora-kinase-inhibitor-azd1152-hqpa
#1
Ali Zekri, Yashar Mesbahi, Samad Ghanizadeh-Vesali, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Aurora-B kinase overexpression plays important roles in the malignant progression of prostate cancer (PCa). AZD1152-HQPA, as an inhibitor of Aurora-B, has recently emerged as a promising agent for cancer treatment. In this study, we aimed to investigate the effects of AZD1152-HQPA on reactive oxygen species (ROS) generation and mitochondrial function in PCa. We used AZD1152-HQPA (Barasertib), a highly potent and selective inhibitor of Aurora-B kinase. The effects of AZD1152-HQPA on cell viability, DNA content, cell morphology, and ROS production were studied in the androgen-independent PC-3 PCa cell line...
June 21, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28639399/tp73-as1-promotes-breast-cancer-cell-proliferation-through-mir-200a-mediated-tfam-inhibition
#2
Jia Yao, Feng Xu, Danhua Zhang, Wenjun Yi, Xianyu Chen, Gannong Chen, Enxiang Zhou
P73 antisense RNA 1T (TP73-AS1 or PDAM) is a long non-coding RNA, which can regulate apoptosis through regulation of p53 signaling-related anti-apoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in breast cancer (BC) growth and the underlying mechanism remain unclear so far. In the present study, the effect of TP73-AS1 in BC cell lines and clinical tumor samples was detected so as to reveal its role and function. In the present study, TP73-AS1 was specifically upregulated in BC tissues and BC cell lines and was correlated to a poorer prognosis in patients with BC...
June 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28635633/new-insights-in-thyroid-cancer-and-p53-family-proteins
#3
REVIEW
Livia Manzella, Stefania Stella, Maria Stella Pennisi, Elena Tirrò, Michele Massimino, Chiara Romano, Adriana Puma, Martina Tavarelli, Paolo Vigneri
Thyroid cancers are common endocrine malignancies that comprise tumors with different clinical and histological features. Indeed, papillary and follicular thyroid cancers are slow-growing, well-differentiated tumors, whereas anaplastic thyroid cancers are undifferentiated neoplasias that behave much more aggressively. Well-differentiated thyroid carcinomas are efficiently cured by surgery and radioiodine, unlike undifferentiated tumors that fail to uptake radioactive iodine and are usually resistant to chemotherapy...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28630419/iscador-qu-inhibits-doxorubicin-induced-senescence-of-mcf7-cells
#4
T Srdic-Rajic, J F Santibañez, K Kanjer, N Tisma-Miletic, M Cavic, D Galun, M Jevric, N Kardum, A Konic-Ristic, T Zoranovic
Chemotherapy in patients with inoperable or advanced breast cancer inevitably results in low-dose exposure of tumor-cell subset and senescence. Metabolically active senescent cells secrete multiple tumor promoting factors making their elimination a therapeutic priority. Viscum album is one of the most widely used alternative anti-cancer medicines facilitating chemotherapy tolerance of breast cancer patients. The aim of this study was to model and investigate how Viscum album extracts execute additive anti-tumor activity with low-dose Dox using ER + MCF7 breast cancer cells...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28617799/p53-and-tap63-participate-in-the-recombination-dependent-pachytene-arrest-in-mouse-spermatocytes
#5
Marina Marcet-Ortega, Sarai Pacheco, Ana Martínez-Marchal, Helena Castillo, Elsa Flores, Maria Jasin, Scott Keeney, Ignasi Roig
To protect germ cells from genomic instability, surveillance mechanisms ensure meiosis occurs properly. In mammals, spermatocytes that display recombination defects experience a so-called recombination-dependent arrest at the pachytene stage, which relies on the MRE11 complex-ATM-CHK2 pathway responding to unrepaired DNA double-strand breaks (DSBs). Here, we asked if p53 family members-targets of ATM and CHK2-participate in this arrest. We bred double-mutant mice combining a mutation of a member of the p53 family (p53, TAp63, or p73) with a Trip13 mutation...
June 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28596495/association-of-p73-polymorphisms-with-susceptibilities-of-cervical-carcinoma-a-meta-analysis
#6
Xianghua Liang, Bingxiang Chen, Jianxin Zhong
OBJECTIVE: The relation between P73 gene polymorphism and cervical cancer has not been determined. At present, we utilized a meta-analysis method to elucidate the association between P73 and cervical cancer. RESULTS: The present study included 635 patients with cervical cancer and 998 cancer-free control subjects. Using meta-analysis, we found a significant association of P73 genetic polymorphism with cervical cancer in a recessive model [OR = 0.91, 95% CI: 0.84-0...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28576884/mdm2-is-required-for-survival-and-growth-of-p53-deficient-cancer-cells
#7
Kyle Feeley, Clare M Adams, Ramkrishna Mitra, Christine M Eischen
p53 deletion prevents the embryonic lethality of normal tissues lacking Mdm2, suggesting that cells can survive without Mdm2 if p53 is also absent. Here we report evidence challenging this view, with implications for therapeutically targeting Mdm2. Deletion of Mdm2 in T cell lymphomas or sarcomas lacking p53 induced apoptosis and G2 cell cycle arrest, prolonging survival of mice with these tumors. p53(-/-) fibroblasts showed similar results, indicating that the effects of Mdm2 loss extend to pre-malignant cells...
June 2, 2017: Cancer Research
https://www.readbyqxmd.com/read/28565861/global-methylation-and-promoter-specific-methylation-of-the-p16-socs-1-e-cadherin-p73-and-shp-1-genes-and-their-expression-in-patients-with-multiple-myeloma-during-active-disease-and-remission
#8
Déborah Martínez-Baños, Beatríz Sánchez-Hernández, Guadalupe Jiménez, Georgina Barrera-Lumbreras, Olga Barrales-Benítez
Tumor suppressor gene promoter CpG island methylation is a well-recognized mechanism in cancer pathogenesis, but its role in multiple myeloma (MM) is controversial. The present study investigated the methylation status and expression of P16, suppressor of cytokine signaling 1 (SOCS-1), P73, E-cadherin and Src homology region 2 domain-containing phosphatase 1 (SHP-1), as well as global methylation in patients with MM during active disease and remission. Bone marrow samples were obtained from 43 patients at the Multiple Myeloma Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (Mexico City, Mexico) during active disease and remission...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28555173/efficacy-and-molecular-mechanisms-of-differentiated-response-to-the-aurora-and-angiogenic-kinase-inhibitor-enmd-2076-in-preclinical-models-of-p53-mutated-triple-negative-breast-cancer
#9
Anastasia A Ionkina, John J Tentler, Jihye Kim, Anna Capasso, Todd M Pitts, Karen A Ryall, Rebekah R Howison, Peter Kabos, Carol A Sartorius, Aik Choon Tan, S Gail Eckhardt, Jennifer R Diamond
PURPOSE: Triple-negative breast cancer (TNBC) is a subtype associated with poor prognosis and for which there are limited therapeutic options. The purpose of this study was to evaluate the efficacy of ENMD-2076 in p53-mutated TNBC patient-derived xenograft (PDX) models and describe patterns of terminal cell fate in models demonstrating sensitivity, intrinsic resistance, and acquired resistance to ENMD-2076. EXPERIMENTAL DESIGN: p53-mutated, TNBC PDX models were treated with ENMD-2076 and evaluated for mechanisms of sensitivity or resistance to treatment...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28551631/aberration-of-p73-promoter-methylation-in-chondrosarcoma
#10
Pei Liu, Cassandra Garbutt, Francis J Hornicek, Fuyun Liu, Zhenfeng Duan
BACKGROUND: p73 is a tumor-suppressor gene with significant homology to p53. Abnormal promoter methylation of p73 is present in different types of cancer. However, the promoter methylation status of p73 in chondrosarcoma (CS) is unknown. MATERIALS AND METHODS: p73 promoter methylation status was evaluated by quantitative polymerase chain reaction (PCR), p73 protein expression by western blot, and the relationship between p73 methylation and clinical data was analyzed...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28543759/abrus-agglutinin-promotes-irreparable-dna-damage-by-triggering-ros-generation-followed-by-atm-p73-mediated-apoptosis-in-oral-squamous-cell-carcinoma
#11
Niharika Sinha, Prashanta Kumar Panda, Prajna Paramita Naik, Durgesh Nandini Das, Subhadip Mukhopadhyay, Tapas K Maiti, Muthu K Shanmugam, Arunachalam Chinnathambi, M E Zayed, Sulaiman Ali Alharbi, Gautam Sethi, Rajesh Agarwal, Sujit K Bhutia
Oral cancer, a type of head and neck cancer, is ranked as one of the top most malignancies in India. Herein, we evaluated the anticancer efficacy of Abrus agglutinin (AGG), a plant lectin, in oral squamous cell carcinoma. AGG selectively inhibited cell growth, and caused cell cycle arrest and mitochondrial apoptosis through a reactive oxygen species (ROS)-mediated ATM-p73 dependent pathway in FaDu cells. AGG-induced ROS accumulation was identified as the major mechanism regulating apoptosis, DNA damage and DNA-damage response, which were significantly reversed by ROS scavenger N-acetylcysteine (NAC)...
May 23, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28535906/the-effects-of-curcumin-on-proliferation-apoptosis-invasion-and-nedd4-expression-in-pancreatic-cancer
#12
Jingna Su, Xiuxia Zhou, Xuyuan Yin, Lixia Wang, Zhe Zhao, Yingying Hou, Nana Zheng, Jun Xia, Zhiwei Wang
Pancreatic cancer (PC) is one of the most fatal cancers worldwide. The incidence and death rates are still increasing for PC. Curcumin is the biologically active diarylheptanoid constituent of the spice turmeric, which exerts its anticancer properties in various human cancers including PC. In particular, accumulating evidence has proved that curcumin targets numerous therapeutically important proteins in cell signaling pathways. The neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) is an E3 HECT ubiquitin ligase and is frequently over-expressed in various cancers...
May 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28533173/targeting-human-telomerase-rna-component-using-antisense-oligonucleotide-induces-rapid-cell-death-and-increases-ato-induced-apoptosis-in-apl-cells
#13
Leila Asghari-Kia, Davood Bashash, Ava Safaroghli-Azar, Majid Momeny, Mohsen Hamidpour, Seyed H Ghaffari
The impressive advances carried out in designing pharmacological strategies with the aim of telomerase inhibition in cancers emerged a consensus that telomerase-targeted therapies could be exciting prospect in repertoire of future cancer strategies. The results of the present study indicated that targeting telomerase using an oligonucleotide-based molecule against human telomerase RNA template (hTR ASODN) reduced the survival rate of NB4 cells and induced a caspase-3-dependent apoptosis. Our finding was even noticeable in the synergistic experiments, where we found an enhanced reduction in the viability of the cells after short-term treatment with ATO in combination with the inhibitor...
May 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28527972/genetic-and-epigenetic-alterations-in-meningiomas
#14
REVIEW
Vasiliki Galani, Evangeli Lampri, Anna Varouktsi, George Alexiou, Antigoni Mitselou, Athanasios P Kyritsis
Meningiomas originate from the arachnoid layer of the meninges and divided histologically into three grades: benign (grade I), atypical (grade II), and malignant meningiomas (grade III). Genetic alterations in grade I meningiomas include frequent deletions of chromosomal locus 22q12 and NF2 gene mutations and uncommon somatic SMARCB1 and SMARCE1gene mutations; In grade II meningiomas, chromosomal losses occur on 1p, 22q, 14q, 18q, 10, and 6q, and gains on 20q, 12q, 15q, 1q, 9q, and 17q; In grade III meningiomas, losses have been recognized on 6q, 10, and 14q and alterations of PTEN, CDKN2A and CDKN2B genes...
July 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28526240/endocrine-actions-of-vitamin-d-in-skin-relevance-for-photocarcinogenesis-of-non-melanoma-skin-cancer-and-beyond
#15
REVIEW
Jörg Reichrath, Roman Saternus, Thomas Vogt
The skin represents a pivotal organ for the human body's vitamin D endocrine system, being both the site of ultraviolet (UV)-B-induced vitamin D synthesis and a target tissue for the pluripotent effects of 1,25(OH)2D3 and other biologically active vitamin D metabolites. As many other steroid hormones, 1,25(OH)2D3 exerts its effects via two independent signal transduction pathways: the classical genomic and the non-genomic pathway. While non-genomic effects of 1,25(OH)2D3 are in part exerted via effects on intracellular calcium, genomic effects are mediated by the vitamin D receptor (VDR)...
May 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28471195/-application-of-pla-method-for-detection-of-p53-p63-p73-complexes-in-situ-in-tumour-cells-and-tumour-tissue
#16
V Hrabal, M Nekulová, R Nenutil, J Holčaková, P J Coates, B Vojtěšek
BACKGROUND: PLA (proximity ligation assay) can be used for detection of protein-protein interactions in situ directly in cells and tissues. Due to its high sensitivity and specificity it is useful for detection, localization and quantification of protein complexes with single molecule resolution. One of the mechanisms of mutated p53 gain of function is formation of proten-protein complexes with other members of p53 family - p63 and p73. These interactions influences chemosensitivity and invasivity of cancer cells and this is why these complexes are potential targets of anti-cancer therapy...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28439015/mutant-p53-perturbs-dna-replication-checkpoint-control-through-topbp1-and-treslin
#17
Kang Liu, Fang-Tsyr Lin, Joshua D Graves, Yu-Ju Lee, Weei-Chin Lin
Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s). However, whether mutp53 directly perturbs the DNA replication checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which inhibits its ATR-activating function. Here we show that various contact and conformational mutp53s bypass Akt to induce TopBP1 oligomerization and attenuate ATR checkpoint response during replication stress...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28415779/relationship-of-p73-gene-polymorphism-and-additional-gene-smoking-and-gene-obesity-interaction-with-non-small-cell-lung-cancer-risk
#18
Qiuge Wu, Yan Shi, Lulu Ge, Dongbo Ma, Hui Zhang, Jing Wang
AIM: The aim of this study was to investigate the impact of G4C14-to-A4T14 polymorphism within P73 gene and additional interactions with current smoking and obesity on non-small cell lung cancer (NSCLC) risk in a Chinese population. RESULTS: Logistic regression analysis showed a significant association between genotypes of the AT allele in G4C14-to-A4T14 and decreased NSCLC risk. NSCLC risk was significantly lower in carriers of the G4C14-to-A4T14- AT allele than those with GC/GC genotype (AT/AT + GC/AT versus GC/GC), adjusted OR (95%CI) = 0...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415683/suppression-of-pkc-causes-oncogenic-stress-for-triggering-apoptosis-in-cancer-cells
#19
Suthakar Ganapathy, Bo Peng, Ling Shen, Tianqi Yu, Jean Lafontant, Ping Li, Rui Xiong, Alexandros Makriyannis, Changyan Chen
Gain of functional mutations in ras occurs in more than 30% of human malignancies and in particular 90% of pancreatic cancer. Mutant ras, via activating multiple effector pathways, not only promote cell growth or survival, but also apoptosis, depending upon cell types or circumstances. In order to further study the mechanisms of apoptosis induced by oncogenic ras, we employed the ras loop mutant genes and demonstrated that Akt functioned downstream of Ras in human pancreatic cancer or HPNE cells ectopically expressing mutated K-ras for the induction of apoptosis after the concurrent suppression of PKC α and β...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409295/metal-chelator-tpen-selectively-induces-apoptosis-in-k562-cells-through-reactive-oxygen-species-signaling-mechanism-implications-for-chronic-myeloid-leukemia
#20
Luisa Rojas-Valencia, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio
Chronic myeloid leukemia (CML) is a hematologic disorder characterized by the constitutive expression of BCR-ABL tyrosine kinase. Although successful implementation of tyrosine kinase inhibitors for the treatment of CML remain a traditional choice for molecularly targeted therapy, some patients present primary or secondary resistance to such therapy. Therefore, alternative therapeutic strategies are required to treat resistant CML cells. Accordingly, new anti-proliferative and/or pro-apoptotic compounds would be needed for clinical treatment...
June 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
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