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Targeted cancer therapy molecular level

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https://www.readbyqxmd.com/read/29792166/the-pdgfr%C3%AE-erk1-2-pathway-regulates-cdcp1-expression-in-triple-negative-breast-cancer
#1
Luca Forte, Federica Turdo, Cristina Ghirelli, Piera Aiello, Patrizia Casalini, Marilena Valeria Iorio, Elvira D'Ippolito, Patrizia Gasparini, Roberto Agresti, Beatrice Belmonte, Gabriella Sozzi, Lucia Sfondrini, Elda Tagliabue, Manuela Campiglio, Francesca Bianchi
BACKGROUND: CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels. METHODS: The expression of CDCP1, PDGFRβ and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines...
May 23, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29786517/estrogen-receptor-%C3%AE-potential-target-for-therapy-in-adult-granulosa-cell-tumors
#2
Alessandra Ciucci, Gabriella Ferrandina, Floriana Mascilini, Flavia Filippetti, Giovanni Scambia, Gian Franco Zannoni, Daniela Gallo
OBJECTIVE: Adult granulosa cell tumor (AGCT) is a rare form of sex-cord stromal ovarian tumors. Due to their origin, AGCTs secrete estrogens, and thus, estrogen receptor (ER)-mediated signaling has been considered as a possible target for therapy. The aim of the present study was to get insights into estrogen receptor status and activity in AGCTs, as a strategy to provide molecular support for personalized hormonal treatments. METHODS: We evaluated by immunohistochemistry the expression of ERα, ERβ isoforms (i...
May 18, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29785118/traditional-chinese-medicine-astragalus-polysaccharide-enhanced-antitumor-effects-of-the-angiogenesis-inhibitor-apatinib-in-pancreatic-cancer-cells-on-proliferation-invasiveness-and-apoptosis
#3
Jun Wu, Jing Wang, Qiang Su, Wei Ding, Teng Li, Junxian Yu, Bangwei Cao
Background: Traditional chemotherapy and molecular targeted therapy have shown modest effects on the survival of patients with pancreatic cancer. The current study aimed to investigate the antitumor effects of apatinib, Astragalus polysaccharide (APS), and the combination of both the drugs in pancreatic cancer cells and further explore the molecular mechanisms in vitro. Materials and methods: Expression of vascular endothelial growth factor receptor-2 (VEGFR-2) in human pancreatic cancer cell lines ASPC-1, PANC-1, and SW1990 was detected by Western blotting...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29781537/microrna-508-suppresses-epithelial-mesenchymal-transition-migration-and-invasion-of-ovarian-cancer-cells-through-the-mapk1-erk-signaling-pathway
#4
Lan Hong, Yifeng Wang, Wangsheng Chen, Shuying Yang
Ovarian cancer (OC) is the sixth most common cancer in women worldwide. Despite advances in detection and therapies, it still represents the most lethal gynecologic malignancy in the industrialized countries. Unfortunately, the molecular events that lead to the development of this highly aggressive disease remain largely unknown. The study explored the ability of microRNA-508 (miR-508) to influence proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in OC cells. We quantified the level of miR-508 cancer tissues with corresponding adjacent normal tissues collected from 84 patients with OC...
May 21, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29778566/lung-squamous-cell-carcinoma-cells-express-non-canonically-glycosylated-igg-that-activates-integrin-fak-signaling
#5
Jingshu Tang, Jingxuan Zhang, Yang Liu, Qinyuan Liao, Jing Huang, Zihan Geng, Weiyan Xu, Zhengzuo Sheng, Gregory Lee, Youhui Zhang, Jinfeng Chen, Liang Zhang, Xiaoyan Qiu
It is increasingly recognized that many human carcinomas express immunoglobulin (Ig) molecules that are distinct from B-cell-derived Ig and play important roles in cancer initiation, progression, and metastasis. However, the molecular mechanisms underlying the functions of cancer-derived Ig remain elusive. Here, we report that lung squamous cell carcinoma (LSCC) cells frequently express high levels of cancer IgG (CIgG) that is specifically recognized by a monoclonal antibody RP215. RP215 recognizes CIgG via a novel epitope that involves an N-glycan modification at a non-consensus site within the CH 1 domain...
May 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777906/reduced-rar-%C3%AE-gene-expression-in-benzo-a-pyrene-induced-lung-cancer-mice-is-upregulated-by-dotap-lipo-atra-treatment
#6
S Viswanathan, V M Berlin Grace
Molecular targeted therapy for specific genes is an emerging research. Retinoic Acid Receptor (RAR-β) is a key tumor suppressor which is found to be lost drastically during much cancer progression. We hence, analyzed the expression level of RAR-β gene during B(a)P induced lung cancer development in mice and studied the lung cancer targeted action of All Trans Retinoic Acid (ATRA) in DOTAP liposomal formulation. The effect of its treatment on lung cancer was determined by histopathological analysis. RAR-β gene expression was assessed by RT-PCR and qPCR...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29774123/the-association-of-human-endogenous-retrovirus-h-long-terminal-repeat-associating-protein-2-hhla2-expression-with-gastric-cancer-prognosis
#7
Masataka Shimonosono, Takaaki Arigami, Shigehiro Yanagita, Daisuke Matsushita, Yasuto Uchikado, Yuko Kijima, Hiroshi Kurahara, Yoshiaki Kita, Shinichiro Mori, Ken Sasaki, Itaru Omoto, Kosei Maemura, Yoshikazu Uenosono, Sumiya Ishigami, Shoji Natsugoe
Currently, immune checkpoint blockade against members of the B7/CD28 family is being used as a new molecular-targeted therapy, in patients with unresectable advanced or recurrent gastric cancer. Although human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a novel molecule of the B7/CD28 family, the clinical impact of its expression remains uncertain in gastric cancer. Consequently, we examined HHLA2 expression in blood specimens from patients with gastric cancer, and investigated the relationship between its expression and clinicopathological factors to assess its potential power as a prognostic blood predictor...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29771460/targeting-prostate-cancer-prostate-specific-membrane-antigen-based-diagnosis-and-therapy
#8
REVIEW
Till Wüstemann, Uwe Haberkorn, John Babich, Walter Mier
The high incidence rates of prostate cancer (PCa) raise demand for improved therapeutic strategies. Prostate tumors specifically express the prostate-specific membrane antigen (PSMA), a membrane-bound protease. As PSMA is highly overexpressed on malignant prostate tumor cells and as its expression rate correlates with the aggressiveness of the disease, this tumor-associated biomarker provides the possibility to develop new strategies for diagnostics and therapy of PCa. Major advances have been made in PSMA targeting, ranging from immunotherapeutic approaches to therapeutic small molecules...
May 17, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29768576/recent-advances-and-perspectives-in-cancer-drug-design
#9
Luma G Magalhaes, Leonardo L G Ferreira, Adriano D Andricopulo
Cancer is one of the leading causes of death worldwide. With the increase in life expectancy, the number of cancer cases has reached unprecedented levels. In this scenario, the pharmaceutical industry has made significant investments in this therapeutic area. Despite these efforts, cancer drug research remains a remarkably challenging field, and therapeutic innovations have not yet achieved expected clinical results. However, the physiopathology of the disease is now better understood, and the discovery of novel molecular targets has refreshed the expectations of developing improved treatments...
May 14, 2018: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29767260/rnai%C3%A2-mediated-downregulation-of-asparaginase%C3%A2-like-protein-1-inhibits-growth-and-promotes-apoptosis-of-human-cervical-cancer-line-siha
#10
Xiao-Feng Lv, Han-Qing Hong, Ling Liu, Shi-Hong Cui, Chen-Chen Ren, Hong-Yu Li, Xiao-An Zhang, Lin-Dong Zhang, Tian-Xiang Wei, Jin-Jin Liu, Wen-Ying Xing, Han Fu, Shu-Jun Yan
Asparaginase like 1 (ASRGL1) protein belongs to the N‑terminal nucleophile group, cleaving the isoaspartyl‑dipeptides and L‑asparagine by adding water. It tends to be overexpressed in cancerous tumors including ovarian cancer and breast tumors. The present study assessed the potential ability of ASRGL1 as a molecular target in gene‑based cervical cancer treatment. The protein expression level of ASRGL1 was determined in paraffin‑embedded tumor specimen by immunohistochemistry. Additionally, in order to assess the activity of ASRGL1 during the process of cervical cancer cell multiplication, ASRGL1‑short hairpin (sh) RNA‑expressing lentivirus was established, which was used to infect SiHa cells...
May 14, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29763624/the-gsk3-signaling-axis-regulates-adaptive-glutamine-metabolism-in-lung-squamous-cell-carcinoma
#11
Milica Momcilovic, Sean T Bailey, Jason T Lee, Michael C Fishbein, Daniel Braas, James Go, Thomas G Graeber, Francesco Parlati, Susan Demo, Rui Li, Tonya C Walser, Michael Gricowski, Robert Shuman, Julio Ibarra, Deborah Fridman, Michael E Phelps, Karam Badran, Maie St John, Nicholas M Bernthal, Noah Federman, Jane Yanagawa, Steven M Dubinett, Saman Sadeghi, Heather R Christofk, David B Shackelford
Altered metabolism is a hallmark of cancer growth, forming the conceptual basis for development of metabolic therapies as cancer treatments. We performed in vivo metabolic profiling and molecular analysis of lung squamous cell carcinoma (SCC) to identify metabolic nodes for therapeutic targeting. Lung SCCs adapt to chronic mTOR inhibition and suppression of glycolysis through the GSK3α/β signaling pathway, which upregulates glutaminolysis. Phospho-GSK3α/β protein levels are predictive of response to single-therapy mTOR inhibition while combinatorial treatment with the glutaminase inhibitor CB-839 effectively overcomes therapy resistance...
May 14, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29762048/theranostics-of-prostate-cancer-from-molecular-imaging-to-precision-molecular-radiotherapy-targeting-the-prostate-specific-membrane-antigen
#12
Harshad R Kulkarni, Aviral Singh, Thomas Langbein, Christiane Schuchardt, Dirk Mueller, Jingjing Zhang, Coline Lehmann, Richard P Baum
Alterations at the molecular level are a hallmark of cancer. Prostate cancer is associated with the overexpression of prostate specific membrane antigen (PSMA) in a majority of cases, predominantly in advanced tumors, increasing with the grade or Gleason's score. PSMA can be selectively targeted using radiolabelled PSMA ligands. These small molecules binding the PSMA can be radiolabelled with gamma-emitters like 99m Tc and 111 In or positron emitters like 68 Ga and 18 F for diagnosis as well as with their theranostic pairs such as 177 Lu (beta-emitter) or 225 Ac (alpha-emitter) for therapy...
May 15, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29760539/new-therapeutic-options-opened-by-the-molecular-classification-of-gastric-cancer
#13
REVIEW
Mihaela Chivu-Economescu, Lilia Matei, Laura G Necula, Denisa L Dragu, Coralia Bleotu, Carmen C Diaconu
Gastric cancer (GC) is one of the most lethal and aggressive cancers, being the third cause of cancer related death worldwide. Even with radical gastrectomy and the latest generation of molecular chemotherapeutics, the numbers of recurrence and mortality remains high. This is due to its biological heterogeneity based on the interaction between multiple factors, from genomic to environmental factors, diet or infections with various pathogens. Therefore, understanding the molecular characteristics at a genomic level is critical to develop new treatment strategies...
May 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29758299/autophagy-regulates-apoptosis-by-targeting-noxa-for-degradation
#14
Jingchao Wang, Danrui Cui, Shanshan Gu, Xiaoyu Chen, Yanli Bi, Xiufang Xiong, Yongchao Zhao
Apoptosis and autophagy mutually regulate various cellular physiological and pathological processes. The crosstalk between autophagy and apoptosis is multifaceted and complicated. Elucidating the molecular mechanism of their crosstalk will advance the therapeutic applications of autophagy for treating cancer and other diseases. NOXA, a BH3-only member of the BCL-2 family, was reported to induce apoptosis and promote autophagy. Here, we report that autophagy regulates apoptosis by targeting NOXA for degradation...
May 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29755129/molecular-mechanism-of-the-tp53-mdm2-ar-akt-signalling-network-regulation-by-usp12
#15
Urszula L McClurg, Nay C T H Chit, Mahsa Azizyan, Joanne Edwards, Arash Nabbi, Karl T Riabowol, Sirintra Nakjang, Stuart R McCracken, Craig N Robson
The TP53-MDM2-AR-AKT signalling network plays a critical role in the development and progression of prostate cancer. However, the molecular mechanisms regulating this signalling network are not completely defined. By conducting transcriptome analysis, denaturing immunoprecipitations and immunopathology, we demonstrate that the TP53-MDM2-AR-AKT cross-talk is regulated by the deubiquitinating enzyme USP12 in prostate cancer. Our findings explain why USP12 is one of the 12 most commonly overexpressed cancer-associated genes located near an amplified super-enhancer...
May 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29752474/checkpoint-suppressor-1-suppresses-transcriptional-activity-of-er%C3%AE-and-breast-cancer-cell-proliferation-via-deacetylase-sirt1
#16
Zhaowei Xu, Yangyang Yang, Bowen Li, Yanan Li, Kangkai Xia, Yuxi Yang, Xiahui Li, Miao Wang, Shujing Li, Huijian Wu
Breast cancer is a highly heterogeneous carcinoma in women worldwide, but the underlying mechanisms that account for breast cancer initiation and development have not been fully established. Mounting evidence indicates that Checkpoint suppressor 1 (CHES1) is tightly associated with tumorigenesis and prognosis in many types of cancer. However, the definitive function of CHES1 in breast cancer remains to be explored. Here we showed that CHES1 had a physical interaction with estrogen receptor-α (ERα) and repressed the transactivation of ERα in breast cancer cells...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29751615/the-maxi-k-bk-channel-antagonist-penitrem-a-as-a-novel-breast-cancer-targeted-therapeutic
#17
Amira A Goda, Abu Bakar Siddique, Mohamed Mohyeldin, Nehad M Ayoub, Khalid A El Sayed
Breast cancer (BC) is a heterogeneous disease with different molecular subtypes. The high conductance calcium-activated potassium channels (BK, Maxi-K channels) play an important role in the survival of some BC phenotypes, via membrane hyperpolarization and regulation of cell cycle. BK channels have been implicated in BC cell proliferation and invasion. Penitrems are indole diterpene alkaloids produced by various terrestrial and marine Penicillium species. Penitrem A ( 1 ) is a selective BK channel antagonist with reported antiproliferative and anti-invasive activities against multiple malignancies, including BC...
May 11, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29748372/traf1-is-critical-for-regulating-the-braf-mek-erk-pathway-in-non-small-cell-lung-carcinogenesis
#18
Qiushi Wang, Ge Gao, Tianshun Zhang, Ke Yao, Hanyong Chen, Mi Hee Park, Hiroyuki Yamamoto, Keke Wang, Weiya Ma, Margarita Malakhova, Ann M Bode, Zigang Dong
Tumor necrosis factor receptor (TNFR)-associated factor 1 (TRAF1) is a unique TRAF protein that can interact directly or indirectly with multiple TNFR family members, regulatory proteins, kinases, and adaptors that contribute to its diverse functions in specific tissues. However, the role of TRAF1 in non-small cell lung cancer (NSCLC) remains unknown. In this study, we report that TRAF1 is overexpressed in human lung cancer cells and tissues. TRAF1 expression level inversely correlated with patient survival probability...
May 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29748184/dual-suppressive-effect-of-microrna-34a-on-the-foxm1-eef2-kinase-axis-regulates-triple-negative-breast-cancer-growth-and-invasion
#19
Recep Bayraktar, Cristina Ivan, Emine Bayraktar, Pinar Kanlikilicer, Nashwa Kabil, Nermin Kahraman, Hamada Ahmed Mokhlis, Didem Karakas, Cristian Rodriguez-Aguayo, Ahmet Arslan, Jianting Sheng, Stephen Tc Wong, Gabriel Lopez-Berestein, George A Calin, Bulent Ozpolat
Purpose - Recent studies indicated that dysregulation of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) is involved in pathogenesis of various human cancers. However, the molecular mechanisms underlying miR-34a are not fully understood in triple-negative breast cancer (TNBC). Experimental Design- We performed  in vitro  functional assays on TNBC cell lines to investigate the role of miR-34a in FOXM1/eEF2K signaling axis. TNBC tumor xenograft models were used for in vivo therapeutic delivery of miR-34a...
May 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29747487/diagnostic-significance-of-p38-isoforms-p38%C3%AE-p38%C3%AE-p38%C3%AE-p38%C3%AE-in-head-and-neck-squamous-cell-carcinoma-comparative-serum-level-evaluation-and-design-of-novel-peptide-inhibitor-targeting-the-same
#20
Vishal Sahu, Lokesh Nigam, Vertica Agnihotri, Abhishek Gupta, Shashank Shekhar, Naidu Subbarao, Suman Bhaskar, Sharmistha Dey
Purpose: The p38 mitogen-activated protein kinase (MAPKs) play a crucial role in the production of pro-inflammatory cytokines and over-expression of it increase cytokines which promote cancer. Among four isoforms, p38α has been well studied in head and neck squamous cell carcinoma (HNSCC) and other cancers as a therapeutic target.p38δ has recently emerged as a potential disease-specific drug target. Elevated serum p38α level in HNSCC was reported earlier from our lab. This study aims to estimate the levels of p38 MAPK-isoforms in the serum of HNSCC and design peptide inhibitor targeting the same...
May 9, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
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