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https://www.readbyqxmd.com/read/29033852/activation-of-casein-kinase-ii-by-gallic-acid-induces-bik-bax-bak-mediated-er-ca-ros-dependent-apoptosis-of-human-oral-cancer-cells
#1
Meng-Liang Lin, Shih-Shun Chen
Induction of the generation of endoplasmic reticulum (ER) calcium (Ca(++))-mediated reactive oxygen species (ROS) by gallic acid (GA) has been implicated in the mitochondrial apoptotic death of human oral cancer (OC) cells, but the molecular mechanism by which GA causes ER Ca(++) release of OC cells to undergo cell death remains unclear. Here, we report that GA-induced phosphorylation of B-cell lymphoma 2 (BCL-2)-interacting killer (BIK) (threonine (Thr) 33/Serine (Ser) 35) and p53 (Ser 15 and Ser 392), Bcl-2-associated x protein (BAX)/BCL-2 antagonist killer 1 (BAK) oligomerization on the ER and mitochondria, rising of cytosolic Ca(+)(+) and ROS, cytochrome c (Cyt c) release from the mitochondria, Ψm loss, and apoptosis were suppressed in cells co-treated with a specific inhibitor of casein kinase II (CK II) (4,5,6,7-tetrabromobenzotriazole)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29022645/the-significance-of-trip11-and-t3-signaling-pathway-in-renal-cancer-progression-and-survival-of-patients
#2
Piotr Popławski, Agnieszka Piekiełko-Witkowska, Alicja Nauman
INTRODUCTION: TRIP11 is a multifunctional protein localizing either to Golgi apparatus, acting as a golgin, or in the nucleus, acting as coactivator of transcription mediated by thyroid hormone receptor (THR) and hypoxia induced factor (HIF). Triiodothyronine (T3) regulates nuclear localization of TRIP11 by inducing its phosphorylation. The exact mechanism of this regulation unknown. The expressions of THR and HIF are disturbed in various cancers, including renal cell cancer (RCC). In this study we aimed to analyze: 1) the mechanism of T3-dependent subcellular localization of TRIP11; 2) the significance of TRIP11 and T3 signaling pathway in RCC progression...
October 12, 2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/29017516/identification-of-a-rac-akt-like-gene-in-leishmania-parasites-as-a-putative-therapeutic-target-in-leishmaniasis
#3
Rubén E Varela-M, Rodrigo Ochoa, Carlos E Muskus, Antonio Muro, Faustino Mollinedo
BACKGROUND: Leishmaniasis is one of the world's most neglected diseases caused by at least 20 different species of the protozoan parasite Leishmania. Although new drugs have become recently available, current therapy for leishmaniasis is still unsatisfactory. A subgroup of serine/threonine protein kinases named as related to A and C protein kinases (RAC), or protein kinase B (PKB)/AKT, has been identified in several organisms including Trypanosoma cruzi parasites. PKB/AKT plays a critical role in mammalian cell signaling promoting cell survival and is a major drug target in cancer therapy...
October 10, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28969692/role-of-protein-kinases-ck1%C3%AE-and-ck2-in-multiple-myeloma-regulation-of-pivotal-survival-and-stress-managing-pathways
#4
REVIEW
Sabrina Manni, Marilena Carrino, Francesco Piazza
Multiple myeloma (MM) is a malignant tumor of transformed plasma cells. MM pathogenesis is a multistep process. This cancer can occur de novo (rarely) or it can develop from monoclonal gammopathy of undetermined significance (most of the cases). MM can be asymptomatic (smoldering myeloma) or clinically active. Malignant plasma cells exploit intrinsic and extrinsic bone marrow microenvironment-derived growth signals. Upregulation of stress-coping pathways is also instrumental to maintain MM cell growth. The phylogenetically related Ser/Thr kinases CSNK1A1 (CK1α) and CSNK2 (CK2) have recently gained a growing importance in hematologic malignancies arising both from precursors and from mature blood cells...
October 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28951560/therapeutic-targeting-of-ck2-in-acute-and-chronic-leukemias
#5
REVIEW
F Buontempo, J A McCubrey, E Orsini, M Ruzzene, A Cappellini, A Lonetti, C Evangelisti, F Chiarini, C Evangelisti, J T Barata, A M Martelli
CK2 is a ubiquitously expressed, constitutively active Ser/Thr protein kinase, which is considered the most pleiotropic protein kinase in the human kinome. Such a pleiotropy explains the involvement of CK2 in many cellular events. However, its predominant roles are stimulation of cell growth and prevention of apoptosis. High levels of CK2 mRNA and protein are associated with CK2 pathological functions in human cancers. Over the last decade, basic and translational studies have provided evidence of CK2 as a pivotal molecule driving the growth of different blood malignancies...
September 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28938604/inflammation-and-stem-markers-association-to-pim1-pim2-kinase-induced-tumors-in-breast-and-uterus
#6
Manuel-Pedro Jiménez-García, Antonio Lucena-Cacace, María-José Robles-Frías, Irene Ferrer, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28934754/cntn-1-enhances-chemoresistance-in-human-lung-adenocarcinoma-through-induction-of-epithelial-mesenchymal-transition-by-targeting-the-pi3k-akt-pathway
#7
Ruijie Zhang, Shenghua Sun, Fuyun Ji, Chun Liu, Hua Lin, Lihua Xie, Honghui Yang, Wenxiang Tang, Yan Zhou, Jianping Xu, Pei Li
BACKGROUND/AIMS: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. METHODS: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28903364/kif7-attenuates-prostate-tumor-growth-through-lkb1-mediated-akt-inhibition
#8
Kai Yau Wong, Jing Liu, Kwok Wah Chan
This study investigated kinesin family member 7 (KIF7) expression and function in prostate cancer (PCa). Our results showed that KIF7 was significantly downregulated in PCa, compared with normal, benign prostatic hyperplasia and prostate intraepithelial neoplasia tissues, partially through promoter hypermethylation. We further investigated the effects of KIF7 coiled coil (CC) domain and motor domain (MD) on PCa development in vitro and in vivo. Our results showed that KIF7-CC but not KIF7-MD significantly attenuated proliferation and colony formation, impeded migration and invasion, induced apoptosis and sensitized PCa cells to paclitaxel...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28887153/the-eya-phosphatase-its-unique-role-in-cancer
#9
REVIEW
Hengbo Zhou, Lingdi Zhang, Rebecca L Vartuli, Heide L Ford, Rui Zhao
The Eya proteins were originally identified as essential transcriptional co-activators of the Six family of homeoproteins. Subsequently, the highly conserved C-terminal domains of the Eya proteins were discovered to act as a Mg(2+)-dependent Tyr phosphatases, making Eyas the first transcriptional activators to harbor intrinsic phosphatase activity. Only two direct targets of the Eya Tyr phosphatase have been identified: H2AX, whose dephosphorylation directs cells to the DNA repair instead of the apoptotic pathway upon DNA damage, and ERβ, whose dephosphorylation inhibits its anti-tumor transcriptional activity...
September 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28842631/elucidation-of-dietary-polyphenolics-as-potential-inhibitor-of-microtubule-affinity-regulating-kinase-4-in-silico-and-in-vitro-studies
#10
Parvez Khan, Shafikur Rahman, Aarfa Queen, Saaliqa Manzoor, Farha Naz, Gulam Mustafa Hasan, Suaib Luqman, Jihoe Kim, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Microtubule affinity regulating kinase 4 (MARK4) is a Ser/Thr kinase belonging to AMPK-like family, has recently become an important drug target against cancer and neurodegenerative disorders. In this study, we have evaluated different natural dietary polyphenolics including rutin, quercetin, ferulic acid, hesperidin, gallic acid and vanillin as MARK4 inhibitors. All compounds are primarily binds to the active site cavity of MARK4. In silico observations were further complemented by the fluorescence-binding studies and isothermal titration calorimetry (ITC) measurements...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28834399/opioid-tripeptides-hybridized-with-trans-1-cinnamylpiperazine-as-proliferation-inhibitors-of-pancreatic-cancer-cells-in-two-and-three-dimensional-in%C3%A2-vitro-models
#11
Anna K Laskowska, Anna K Puszko, Piotr Sosnowski, Krzysztof Różycki, Piotr Kosson, Joanna Matalińska, Marek Durlik, Aleksandra Misicka
According to the World Health Organization, the mortality rate among patients with pancreatic cancer will increase in the upcoming years. Gemcitabine is the first choice for treatment of pancreatic malignancy, but increasing resistance to this drug is decreasing its overall efficacy. Studies on new therapies that target metabolic pathways, growth factor inhibitors, and tumor stroma or tumor stem cells are currently underway in many research groups. Herein we report the bioactive properties (cytotoxicity and hemolytic activity) of synthetic peptidomimetics containing an opioid tripeptide fragment (Tyr-R(1) -R(2) -; where R(1) is d-Ala or d-Thr, and R(2) is Phe or Trp) hybridized with trans-1-cinnamylpiperazine...
August 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28808378/rutamarin-an-active-constituent-from-ruta-angustifolia-pers-induced-apoptotic-cell-death-in-the-ht29-colon-adenocarcinoma-cell-line
#12
Shafinah Ahmad Suhaimi, Sok Lai Hong, Sri Nurestri Abdul Malek
BACKGROUND: Ruta angustifolia Pers. is a perennial herb that is cultivated worldwide, including Southeast Asia, for the treatment of various diseases as traditional medicine. OBJECTIVE: The purpose of the study was to identify an active principle of R. angustifolia and to investigate its effect on the HT29 cell death. MATERIALS AND METHODS: The methanol and fractionated extracts (hexane, chloroform, ethyl acetate, and water) of R. angustifolia Pers...
July 2017: Pharmacognosy Magazine
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
#13
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/28765625/blood-testis-barrier-integrity-depends-on-pin1-expression-in-sertoli-cells
#14
Rabia Islam, Heein Yoon, Bong-Soo Kim, Han-Sol Bae, Hye-Rim Shin, Woo-Jin Kim, Won-Joon Yoon, Yun-Sil Lee, Kyung Mi Woo, Jeong-Hwa Baek, Hyun-Mo Ryoo
The conformation and function of a subset of serine and threonine-phosphorylated proteins are regulated by the prolyl isomerase Pin1 through isomerization of phosphorylated Ser/Thr-Pro bonds. Pin1 is intensely expressed in Sertoli cells, but its function in this post mitotic cell remains unclear. Our aim was to investigate the role of Pin1 in the Sertoli cells. Lack of Pin1 caused disruption of the blood-testis barrier. We next investigated if the activin pathways in the Sertoli cells were affected by lack of Pin1 through immunostaining for Smad3 protein in testis tissue...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28753556/inflammation-and-stem-markers-association-to-pim1-pim2-kinase-induced-tumors-in-breast-and-uterus
#15
Manuel-Pedro Jiménez-García, Antonio Lucena-Cacace, María-José Robles-Frías, Irene Ferrer, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28744811/evidence-of-vanillin-binding-to-camkiv-explains-the-anti-cancer-mechanism-in-human-hepatic-carcinoma-and-neuroblastoma-cells
#16
Huma Naz, Mohd Tarique, Parvez Khan, Suaib Luqman, Shahzaib Ahamad, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Human calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a member of Ser/Thr kinase family, and is associated with different types of cancer and neurodegenerative diseases. Vanillin is a natural compound, a primary component of the extract of the vanilla bean which possesses varieties of pharmacological features including anti-oxidant, anti-inflammatory, anti-bacterial and anti-tumor. Here, we have investigated the binding mechanism and affinity of vanillin to the CAMKIV which is being considered as a potential drug target for cancer and neurodegenerative diseases...
July 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28719746/structure-activity-study-of-ghrelin-1-8-resulting-in-high-affinity-fluorine-bearing-ligands-for-the-ghrelin-receptor
#17
Carlie L Charron, Jinqiang Hou, Mark S McFarland, Savita Dhanvantari, Michael S Kovacs, Leonard G Luyt
The ghrelin receptor, also known as the growth hormone secretagogue receptor 1a (GHS-R1a), is a G-protein-coupled receptor that is differentially expressed in healthy tissue and several cancers, including prostate, testicular, and ovarian. Selectively targeting the ghrelin receptor using fluorine-18 tagged entities would allow localization and visualization of ghrelin receptor expressing carcinomas using PET imaging. The endogenous ligand ghrelin, a 28 amino acid peptide with 3.1 nM affinity, has poor in vivo stability...
September 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28718440/selective-targeting-of-rsk-isoforms-in-cancer
#18
REVIEW
Kimberly A Casalvieri, Christopher J Matheson, Donald S Backos, Philip Reigan
The p90 ribosomal S6 kinase family (RSK1-4) is a group of highly conserved Ser/Thr kinases that act as downstream effectors of the Ras/Raf/MEK/ERK signaling pathway. The RSKs phosphorylate a range of substrates involved in transcription, translation, cell cycle regulation, and cell survival. Although the RSKs have a high degree of sequence homology, their functional differences in cancer are of great interest. Current RSK inhibitors target more than one RSK isoform, and this may limit their efficacy as anticancer agents...
April 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28716524/the-e3-ligase-hectd3-promotes-esophageal-squamous-cell-carcinoma-escc-growth-and-cell-survival-through-targeting-and-inhibiting-caspase-9-activation
#19
Yi Li, Xiaowei Wu, Lin Li, Yongshuo Liu, Chengshan Xu, Dan Su, Zhihua Liu
Apoptosis resistance is an acquired hallmark of cancer cells and many factors can contribute to the tumor cell apoptosis resistance. In this study, we demonstrated that HECTD3, overexpressed in human esophageal squamous cell carcinoma (ESCC), confers cells resistance to cisplatin-induced apoptosis and promotes cancer cell survival. HECTD3 can bind and ubiquitinate caspase-9, which leads to inhibiting caspase-9 oligomerization and association with Apaf-1, and results in suppressing caspase-9 activation and inhibiting apoptosis...
September 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28715648/tumor-suppressor-candidate-2-tusc2-fus-1-and-human-cancers
#20
Tadas Rimkus, Sherona Sirkisoon, Alexandra Harrison, Hui-Wen Lo
Tumor suppressor candidate 2 (TUSC2, also known as FUS1) was identified in 2000 as a candidate tumor suppressor gene located in a region on chromosome 3p21.3 that is homozygously deleted in some lung and breast cancers. The deletion is rare in lung and breast cancers, but is frequent in malignant pleural mesothelioma. Evidence to date indicates that TUSC2 behaves as a tumor suppressor in lung cancer; however, its role as a tumor suppressor for other tumor types has not been fully established. Loss of TUSC2 expression at the mRNA and protein levels has been reported in various cancers...
May 2017: Discovery Medicine
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