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https://www.readbyqxmd.com/read/28719746/structure-activity-study-of-ghrelin-1-8-resulting-in-high-affinity-fluorine-bearing-ligands-for-the-ghrelin-receptor
#1
Carlie L Charron, Jin-Qiang 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...
July 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28718440/selective-targeting-of-rsk-isoforms-in-cancer
#2
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
#3
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...
July 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28715648/tumor-suppressor-candidate-2-tusc2-fus-1-and-human-cancers
#4
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
https://www.readbyqxmd.com/read/28699701/rictor-regulates-the-vasculogenic-mimicry-of-melanoma-via-the-akt-mmp-2-9-pathway
#5
Xingmei Liang, Ran Sun, Xiulan Zhao, Yanhui Zhang, Qiang Gu, Xueyi Dong, Danfang Zhang, Junying Sun, Baocun Sun
Vasculogenic mimicry (VM)-positive melanomas are usually associated with poor prognosis. Rictor, the key component of the rapamycin-insensitive complex of mTOR (mTORC2), is up-regulated in several cancers, especially in melanomas with poor prognosis. The aim of this study was to investigate the role of Rictor in the regulation of VM and the mechanism underlying this possible regulation. VM channels were found in 35 of 81 tested melanoma samples and high Rictor expression correlated with VM structures. Moreover, Kaplan-Meier survival curves indicated that VM structures and high Rictor expression correlated with shorter survival in patients with melanoma...
July 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28692035/role-of-integrin-linked-kinase-in-regulating-the-protein-stability-of-the-muc1-c-oncoprotein-in-pancreatic-cancer-cells
#6
H-L Huang, H-Y Wu, P-C Chu, I-L Lai, P-H Huang, S K Kulp, S-L Pan, C-M Teng, C-S Chen
MUC1-C overexpression has been associated with the progression of pancreatic tumors by promoting the aggressive and metastatic phenotypes. As MUC1 is a STAT3 target gene, STAT3 plays a major role in regulating MUC1-C expression. In this study, we report an alternative mechanism by which integrin-linked kinase (ILK) post-transcriptionally modulates the expression of MUC1-C by maintaining its protein stability in pancreatic cancer cells. We found that ILK acts in concert with STAT3 to facilitate IL-6-mediated upregulation of MUC1-C; ILK depletion was equally effective as STAT3 depletion in abolishing IL-6-induced MUC1-C overexpression without disturbing the phosphorylation or cellular distribution of STAT3...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28677687/topk-modulates-tumour-specific-radiosensitivity-and-correlates-with-recurrence-after-prostate-radiotherapy
#7
Giacomo Pirovano, Thomas M Ashton, Katharine J Herbert, Richard J Bryant, Clare L Verrill, Lucia Cerundolo, Francesca M Buffa, Remko Prevo, Iona Harrap, Anderson J Ryan, Valentine Macaulay, William G McKenna, Geoff S Higgins
BACKGROUND: Tumour-specific radiosensitising treatments may enhance the efficacy of radiotherapy without exacerbating side effects. In this study we determined the radiation response following depletion or inhibition of TOPK, a mitogen-activated protein kinase kinase family Ser/Thr protein kinase that is upregulated in many cancers. METHODS: Radiation response was studied in a wide range of cancer cell lines and normal cells using colony formation assays. The effect on cell cycle progression was assessed and the relationship between TOPK expression and therapeutic efficacy was studied in a cohort of 128 prostate cancer patients treated with radical radiotherapy...
July 4, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28671058/dual-roles-of-pin1-in-cancer-development-and-progression
#8
Hyeong-Jun Han, Bu Young Choi, Young-Joon Surh
Pin 1 is a unique peptidyl-prolyl cis/trans isomerase (PPIase) that catalyzes the cis/trans isomerization of peptidyl-prolyl peptide bonds of its substrate proteins by binding to their specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs. This alters the conformation of target proteins and consequently affects their stability, intracellular localization, and/or biological functions. The abnormal overexpression of Pin1 is observed in some malignancies, which is associated with cancer cell proliferation, migration and invasion...
July 3, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28655918/the-role-of-set-i2pp2a-in-canine-mammary-tumors
#9
Satoru Kake, Shunya Tsuji, Shuhei Enjoji, Sayaka Hanasaki, Hiroshi Hayase, Ryotaro Yabe, Yuiko Tanaka, Takayuki Nakagawa, Hao-Ping Liu, Shih-Chieh Chang, Tatsuya Usui, Takashi Ohama, Koichi Sato
Canine mammary tumor is the most common neoplasm in female dogs, and it has generated considerable attention as a translational model for human breast cancer. Ser/Thr protein phosphatase 2A (PP2A) plays a critical role as a tumor suppressor, and SET/I2PP2A, the endogenous inhibitory protein of PP2A, binds directly to PP2A and suppresses its phosphatase activity. Here, we investigated the role of SET in the tumorigenic growth in canine mammary tumor as well as in the sensitivity of tumors to existing therapeutics...
June 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28653224/acquisition-of-anoikis-resistance-promotes-alterations-in-the-ras-erk-and-pi3k-akt-signaling-pathways-and-matrix-remodeling-in-endothelial-cells
#10
Ana Paula de Sousa Mesquita, Silvana de Araújo Lopes, Paulo Castanho A Pernambuco Filho, Helena B Nader, Carla Cristina Lopes
Anoikis is a programmed cell death induced upon cell detachment from extracellular matrix. Anoikis resistance is a critical mechanism in tumor metastasis. Cancer cells deregulate and adapt their metabolism to survive in the absence of adhesion, spreading metastases to distant organs. These adaptations include abnormal regulation of growth factor receptors activating prosurvival signaling pathways, such as the Ras/ERK and PI3K/Akt pathways, and extracellular matrix remodeling, leading to metastasis by an increase of invasiveness and inhibiting anoikis...
June 26, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28639054/a-strong-relationship-between-oral-squamous-cell-carcinoma-and-dna-repair-genes
#11
Hakan Avci, Arzu Ergen, Elif Sinem Bireller, Baris Ertugrul, Bedia Cakmakoglu
Single nucleotide polymorphisms of DNA repair genes alter protein function and modulate DNA repair efficiency in various cancers. The X-ray repair cross-complementing group (XRCC) is responsible for the repair of DNA base damage and single-strand breaks. The aim of our study was to investigate the association of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms with the susceptibility to develop oral squamous cell carcinoma (OSCC) in Turkish subjects. One hundred eleven patients with OSCC and 148 healthy controls were recruited for the study...
June 21, 2017: Biochemical Genetics
https://www.readbyqxmd.com/read/28619086/patterns-of-venous-thromboembolism-risk-in-patients-with-localized-colorectal-cancer-undergoing-adjuvant-chemotherapy-or-active-surveillance-an-observational-cohort-study
#12
Jakob Michael Riedl, Florian Posch, Angelika Bezan, Joanna Szkandera, Maria Anna Smolle, Thomas Winder, Christopher H Rossmann, Renate Schaberl-Moser, Martin Pichler, Michael Stotz, Herbert Stöger, Armin Gerger
BACKGROUND: Venous thromoboembolism (VTE) is a frequent and burdensome complication of metastatic colorectal cancer (CRC). However, the epidemiology of VTE in patients with localized CRC after surgery in curative intent is incompletely understood. In this single-center observational cohort study, we investigate patterns of VTE risk in localized CRC, and define its relationship with baseline risk factors, adjuvant chemotherapy and CRC recurrence. METHODS: Five-hundred-sixteen patients with stage II/III CRC were included retrospectively at the time of surgery, and followed until the occurrence of VTE, CRC recurrence, or death (median age = 65...
June 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28580709/early-ovariectomy-reveals-the-germline-encoding-of-natural-anti-a-and-tn-cross-reactive-immunoglobulin-m-igm-arising-from-developmental-o-galnac-glycosylations-germline-encoded-natural-anti-a-tn-cross-reactive-igm
#13
Peter Arend
While native blood group A-like glycans have not been demonstrated in prokaryotic microorganisms as a source of human "natural" anti-A isoagglutinin production, and metazoan eukaryotic N-acetylgalactosamine O-glycosylation of serine or threonine residues (O-GalNAc-Ser/Thr-R) does not occur in bacteria, the O-GalNAc glycan-bearing ovarian glycolipids, discovered in C57BL/10 mice, are complementary to the syngeneic anti-A-reactive immunoglobulin M (IgM), which is not present in animals that have undergone ovariectomy prior to the onset of puberty...
July 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28577130/gemcitabine-cisplatin-treatment-induces-concomitant-sertad1-cdkn2b-and-gadd45a-modulation-and-cellular-changes-in-bladder-cancer-cells-regardless-of-the-site-of-tp53-mutation
#14
Glenda Nicioli da Silva, Leandro Toshio Filoni, Maria Cecília Salvadori, Daisy Maria Fávero Salvadori
Simultaneous use of cisplatin (CIS) and gemcitabine (GEN) for treating bladder cancer has increased because of their complementary effects. However, the molecular mechanisms underlying the activities of these two antineoplastic drugs are not fully known. Here, molecular biology techniques and microscopy were used to investigate transcriptomic and morphological changes in low and high-grade urinary bladder transitional carcinoma cell lines [RT4 - wild type TP53; 5637 - two TP53 mutations, one in codon 72 (Arg-Pro) and other in codon 280 (Arg-Thr) and T24 - in-frame deletion of tyrosine 126 in the TP53 allele] simultaneously treated with CIS/GEN...
June 2, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28530534/biological-evaluation-of-99mtc-hynic-edda-tricine-ser-3-d4-peptide-for-tumor-targeting
#15
Ziba Kazemi, Mona Haddad Zahmatkesh, Seyed Mohammad Abedi, Seyed Jalal Hosseinimehr
BACKGROUND: D4 small peptide (Leu-Ala-Arg-Leu-Leu-Thr) was selected as an appropriate agent for specific targeting of epidermal growth factor receptor (EGFR). OBJECTIVE: The aim of study was to investigate the 99mTc-labeled D4 peptide for non small cell lung tumor targeting. METHOD: HYNIC-(Ser)3-D4 peptide was labeled with 99mTc using mixture of tricine and ethylenediamine diacetic acid (EDDA) as co-ligands. The in vitro cellular uptake of radiolabebled peptide was evaluated by blocking test on human non small lung cancer (A-549) cell line and its biodistribution was evaluated in A-549 xenografted nude mice...
May 19, 2017: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/28510570/bag-1-as-a-biomarker-in-early-breast-cancer-prognosis-a-systematic-review-with-meta-analyses
#16
E S Papadakis, T Reeves, N H Robson, T Maishman, G Packham, R I Cutress
BACKGROUND: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28488246/potential-coordination-role-between-o-glcnacylation-and-epigenetics
#17
REVIEW
Donglu Wu, Yong Cai, Jingji Jin
Dynamic changes of the post-translational O-GlcNAc modification (O-GlcNAcylation) are controlled by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and the glycoside hydrolase O-GlcNAcase (OGA) in cells. O-GlcNAcylation often occurs on serine (Ser) and threonine (Thr) residues of the specific substrate proteins via the addition of O-GlcNAc group by OGT. It has been known that O-GlcNAcylation is not only involved in many fundamental cellular processes, but also plays an important role in cancer development through various mechanisms...
May 9, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28486685/inhibition-of-ser-thr-phosphatase-ppm1d-induces-neutrophil-differentiation-in-hl-60-cells
#18
Rui Kamada, Fuki Kudoh, Fumihiko Yoshimura, Keiji Tanino, Kazuyasu Sakaguchi
Protein phosphatase Magnesium-dependent 1, Delta (PPM1D) is a wild-type p53-inducible Ser/Thr phosphatase that acts as a negative regulator of the p53 tumor suppressor. Gene amplification and overexpression of PPM1D have been reported in various cancers including leukemia and neuroblastoma. Therefore, PPM1D is a promising target in cancer therapy. It has been reported that PPM1D knockout mice exhibit neutrophilia in blood and show a defective immune response. Here, we found that inhibition of PPM1D induced neutrophil differentiation of human promyelocytic leukemia cell line HL-60...
May 9, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28477117/studies-of-atm-kinase-activity-using-engineered-atm-sensitive-to-atp-analogues-atm-as
#19
Masato Enari, Yuko Matsushima-Hibiya, Makoto Miyazaki, Ryo Otomo
Ataxia-telangiectasia mutated (ATM) protein is a member of the phosphatidylinositol 3-phosphate kinase (PI3-K)-related protein kinase (PIKK) family and is implicated in the initiation of signaling pathways following DNA double strand breaks (DSBs) elicited by exposure to ionizing irradiation (IR) or radiomimetic compounds. Loss of function of the ATM gene product results in the human genetic disorder ataxia-telangiectasia (A-T) characterized by neurodegeneration, immunodeficiency, genomic instability, and cancer predisposition...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28476656/defining-the-role-of-the-rsk-isoforms-in-cancer
#20
REVIEW
Thibault Houles, Philippe P Roux
The 90kDa ribosomal S6 kinase (RSK) family is a group of Ser/Thr protein kinases (RSK1-4) that function downstream of the Ras/mitogen-activated protein kinase (MAPK) signalling pathway. RSK regulates many substrates involved in cell survival, growth, and proliferation, and as such, deregulated RSK activity has been associated with multiple cancer types. RSK expression and activity are dysregulated in several malignancies, including breast, prostate, and lung cancer, and available evidence suggests that RSK may be a promising cancer therapeutic target...
May 2, 2017: Seminars in Cancer Biology
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