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https://www.readbyqxmd.com/read/28743736/sfpq-a-multifunctional-nuclear-protein-regulates-the-transcription-of-pde3a
#1
Dong Keun Rhee, Steven C Hockman, Sun-Kyung Choi, Yong-Eun Kim, Chungoo Park, Vincent C Manganiello, Kee Kwang Kim
Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation. However, the molecular mechanisms that regulate PDE3A gene expression remain largely unknown. In this study, we investigated the transcriptional regulation of PDE3A , and found that the splicing factor proline and glutamine rich (SFPQ) protein modulated PDE3A mRNA levels. Multiple transcription start sites (TSS1, 2, and 3) were identified within the first exon of PDE3A using 5'-rapid amplification of cDNA ends (RACE)...
July 25, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28743635/molecular-imaging-in-drug-development-update-and-challenges-for-radiolabeled-antibodies-and-nanotechnology
#2
REVIEW
Ilaria Colombo, Marta Overchuk, Juan Chen, Raymond M Reilly, Gang Zheng, Stephanie Lheureux
Despite the significant advancement achieved in understanding the molecular mechanisms responsible for cancer transformation and aberrant proliferation, leading to novel targeted cancer therapies, significant effort is still needed to "personalize" cancer treatment. Molecular imaging is an emerging field that has shown the ability to characterize in vivo the molecular pathways present at the cancer cell level, enabling diagnosis and personalized treatment of malignancies. These technologies, particularly SPECT and PET also permit the development of novel radiotheranostic probes, which provide capabilities for diagnosis and treatment with the same agent...
July 22, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28741662/molecular-breakdown-a-comprehensive-view-of-anaplastic-lymphoma-kinase-alk-rearranged-non-small-cell-lung-cancer
#3
Ka-Won Noh, Mi-Sook Lee, Seung Eun Lee, Ji-Young Song, Hyun-Tae Shin, Yu Jin Kim, Doo Yi Oh, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Young Mog Shim, Jae Ill Zo, Jhingook Kim, Woong-Yang Park, Se-Hoon Lee, Yoon-La Choi
Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how Echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors...
July 25, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28736756/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#4
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart Lung Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016 in Bethesda Maryland to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
June 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28734944/triple-negative-breast-cancer-next-generation-sequencing-for-target-identification
#5
REVIEW
Jonathan D Marotti, Francine B de Abreu, Wendy A Wells, Gregory J Tsongalis
Our ability to now study disease at the most fundamental molecular level has led to a reclassification of human cancers into numerous subtypes that vary in disease progression and response to therapy. Like most solid tumors, breast cancer is a heterogeneous disease with considerable variation in histological and biological features. Triple negative breast cancer (TNBC) is a subtype of breast cancer in which estrogen receptor and progesterone receptor are not expressed, and human epidermal growth factor receptor 2 is not amplified or overexpressed...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28725634/ip3-receptor-mediated-calcium-signaling-and-its-role-in-autophagy-in-cancer
#6
REVIEW
Elzbieta Kania, Gemma Roest, Tim Vervliet, Jan B Parys, Geert Bultynck
Calcium ions (Ca(2+)) play a complex role in orchestrating diverse cellular processes, including cell death and survival. To trigger signaling cascades, intracellular Ca(2+) is shuffled between the cytoplasm and the major Ca(2+) stores, the endoplasmic reticulum (ER), the mitochondria, and the lysosomes. A key role in the control of Ca(2+) signals is attributed to the inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), the main Ca(2+)-release channels in the ER. IP3Rs can transfer Ca(2+) to the mitochondria, thereby not only stimulating core metabolic pathways but also increasing apoptosis sensitivity and inhibiting basal autophagy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28721903/clinical-advances-of-hypoxia-activated-prodrugs-in-combination-with-radiation-therapy
#7
REVIEW
Ishna N Mistry, Matthew Thomas, Ewen D D Calder, Stuart J Conway, Ester M Hammond
With the increasing incidence of cancer worldwide, the need for specific, effective therapies is ever more urgent. One example of targeted cancer therapeutics is hypoxia-activated prodrugs (HAPs), also known as bioreductive prodrugs. These prodrugs are inactive in cells with normal oxygen levels but in hypoxic cells (with low oxygen levels) undergo chemical reduction to the active compound. Hypoxia is a common feature of solid tumors and is associated with a more aggressive phenotype and resistance to all modes of therapy...
August 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28718806/the-inhibitory-activity-of-luzonicosides-from-the-starfish-echinaster-luzonicus-against-human-melanoma-cells
#8
Olesya S Malyarenko, Sergey A Dyshlovoy, Alla A Kicha, Natalia V Ivanchina, Timofey V Malyarenko, Bokemeyer Carsten, von Amsberg Gunhild, Valentin A Stonik, Svetlana P Ermakova
Malignant melanoma is the most dangerous form of skin cancer, with a rapidly increasing incidence rate. Despite recent advances in melanoma research following the approval of several novel targeted and immuno-therapies, the majority of oncological patients will ultimately perish from the disease. Thus, new effective drugs are still required. Starfish steroid glycosides possess different biological activities, including antitumor activity. The current study focused on the determination of the in vitro inhibitory activity and the mechanism of action of cyclic steroid glycosides isolated from the starfish Echinaster luzonicus-luzonicoside A (LuzA) and luzonicoside D (LuzD)-in human melanoma RPMI-7951 and SK-Mel-28 cell lines...
July 18, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28718367/hbxip-suppression-reduces-cell-proliferation-and-migration-and-its-overexpression-predicts-poor-prognosis-in-non-small-cell-lung-cancer
#9
Yixuan Wang, Nan Li, Shuanlong Che, Tiefeng Jin, Junjie Piao, Shuangping Liu, Zhenhua Lin
Emerging evidence has demonstrated that the high expression of HBXIP has been correlated with many cancers. With evaluation of the functional role of HBXIP in non-small-cell lung cancer, the primary aim of this study is to investigate the correlation between HBXIP expression and the prognosis of non-small-cell lung cancer patients. The protein levels of HBXIP were detected using western blotting in non-small-cell lung cancer cells. Cell proliferation and migration assays were measured to evaluate the function of HBXIP in non-small-cell lung cancer cells...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28717401/novel-therapeutic-strategies-in-the-treatment-of-triple-negative-breast-cancer
#10
REVIEW
Karima Oualla, Heba M El-Zawahry, Banu Arun, James M Reuben, Wendy A Woodward, Heba Gamal El-Din, Bora Lim, Nawfel Mellas, Naoto T Ueno, Tamer M Fouad
Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is defined by negative estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Treating patients with TNBC remains clinically challenging, as patients are not candidates for endocrine or HER2-directed therapy. As a result, chemotherapy with traditional agents such as anthracyclines and taxanes remains the only available option with moderate success. Recent discoveries have revealed that TNBC is a heterogeneous disease at the clinical, histological and molecular levels...
July 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28716051/mir-380-5p-mediated-repression-of-tep1-and-tspyl5-interferes-with-telomerase-activity-and-favours-the-emergence-of-an-alt-like-phenotype-in-diffuse-malignant-peritoneal-mesothelioma-cells
#11
Graziella Cimino-Reale, Paolo Gandellini, Francesca Santambrogio, Marta Recagni, Nadia Zaffaroni, Marco Folini
BACKGROUND: Understanding the molecular/cellular underpinnings of diffuse malignant peritoneal mesothelioma (DMPM), a fatal malignancy with limited therapeutic options, is of utmost importance for the fruitful management of the disease. In this context, we previously found that telomerase activity (TA), which accounts for the limitless proliferative potential of cancer cells, is prognostic for disease relapse and cancer-related death in DMPM patients. Consequently, the identification of factors involved in telomerase activation/regulation may pave the way towards the development of novel therapeutic interventions for the disease...
July 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28715732/proteasome-inhibitor-induced-cleavage-of-hsp90-is-mediated-by-ros-generation-and-caspase-10-activation-in-human-leukemic-cells
#12
Sangkyu Park, Jeong-A Park, Hwanmin Yoo, Han-Bum Park, Younghee Lee
Heat shock protein 90 (HSP90) is a molecular chaperone that supports the stability of client proteins. The proteasome is one of the targets for cancer therapy, and studies are underway to use proteasome inhibitors as anti-cancer drugs. In this study, we found that HSP90 was cleaved to a 55kDa protein after treatment with proteasome inhibitors including MG132 in leukemia cells but was not cleaved in other tissue-derived cells. HSP90 has two major isoforms (HSP90α and HSP90β), and both were cleaved by MG132 treatment...
July 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28714416/application-of-kinase-inhibitors-for-anti-aging-intervention
#13
Mercedes Cano, Antonio Ayala, Francesco Marotta, Sandro Argüelles
Protein phosphorylation, mediated by protein kinases, has important physiological and pathological implications in our lives . Targeting kinase is one of the most interesting of the emerging topics in the pharmaceutical industry, especially since there is a focus on cancer therapy. Given that kinases may be involved in the aging process the focus will be on using the kinase inhibitor for anti-aging intervention to enhance healthspan and increase longevity. In this review , we will summarize: (i) the impact of the phosphoproteomic approach to elucidate molecular mechanisms of diseases; (ii) importance of the drug discovery approach for targeting kinases; (iii) the dysregulation of Janus kinase (JAK) / signal-transducing adapter molecules (STAT) and p70 ribosomal protein S6 kinase (S6Ks) pathway in aging and the age-related process; (iv) the epidemiological studies available in order to see whether a correlation between JAK/STAT and S6Ks mRNA expression levels exist in cancer and in patient outcome; (v) finally, we will show selected inhibitors of these kinases approved by the US Food and Drug Administration (FDA)...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28711565/new-aspects-of-molecular-imaging-in-prostate-cancer
#14
Francesco Ceci, Paolo Castellucci, Juliano J Cerci, Stefano Fanti
Nowadays several new imaging modalities are available for investigating prostate cancer (PCa) such as magnet resonance imaging (MRI) in the form of whole body MRI and pelvic multiparametric MRI and positron emission tomography (PET) using choline as radiotracers. Nevertheless, these modalities proved sub-optimal accuracy for detecting PCa metastases, particularly in the recurrence setting. A new molecular probe targeting the prostate specific membrane antigen (PSMA) has been recently developed for PET imaging...
July 12, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28708785/y-box-binding-protein-1-promotes-epithelial-mesenchymal-transition-invasion-and-metastasis-of-cervical-cancer-via-enhancing-the-expressions-of-snail
#15
Tianyun Pang, Min Li, Ye Zhang, Weiwei Yong, Haixian Kang, Yunhong Yao, Xinrong Hu
OBJECTIVE: Y box-binding protein 1 (YB-1) is a potent oncogenic protein. How it regulates Snail in most tumors including cervical cancer is unknown. This article is to study if YB-1 plays a role in cervical cancer via regulating the expression of Snail. METHODS: Immunohistochemical staining of YB-1, Snail, and E-cadherin (E-cad) was performed on tissue specimens including 35 cases of chronic cervicitis (as a control), 35 cases of cervical intraepithelial neoplasm (CIN) I, 35 cases of CIN II/III, 28 cases of unmetastatic cervical squamous cell carcinoma, and 19 cases of metastatic cervical squamous cell carcinoma...
July 13, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28707679/anaplastic-thyroid-carcinoma-from-clinicopathology-to-genetics-and-advanced-therapies
#16
REVIEW
Eleonora Molinaro, Cristina Romei, Agnese Biagini, Elena Sabini, Laura Agate, Salvatore Mazzeo, Gabriele Materazzi, Stefano Sellari-Franceschini, Alessandro Ribechini, Liborio Torregrossa, Fulvio Basolo, Paolo Vitti, Rossella Elisei
Anaplastic thyroid carcinoma (ATC) is a rare malignancy, accounting for 1-2% of all thyroid cancers. Although rare, ATC accounts for the majority of deaths from thyroid carcinoma. ATC often originates in a pre-existing thyroid cancer lesion, as suggested by the simultaneous presence of areas of differentiated or poorly differentiated thyroid carcinoma. ATC is characterized by the accumulation of several oncogenic alterations, and studies have shown that an increased number of oncogenic alterations equates to an increased level of dedifferentiation and aggressiveness...
July 14, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28705714/aristeromycin-and-dznep-cause-growth-inhibition-of-prostate-cancer-via-induction-of-mir-26a
#17
Noriko Uchiyama, Yukiya Tanaka, Tomohiro Kawamoto
Most prostate cancers initially respond to androgen deprivation therapy, but then progress from androgen-dependent to androgen-independent prostate cancers. In the present study, a differential cytotoxicity screen of hormone-resistant prostate cancer LNCaP-hr cells and the parental LNCaP-FGC cells against normal MRC5 fibroblast cells, identified a small molecule compound, Aristeromycin (a derivative of 3-deazaneplanocin A (DZNeP)). The molecular target was shown to be S-adenosylhomocysteine hydrolase (AHCY), which catalyzes reversible hydrolysis of S-adenosylhomocysteine (SAH) to adenosine and L-homocysteine...
July 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28701709/psma-expression-by-microvasculature-of-thyroid-tumors-potential-implications-for-psma-theranostics
#18
Andrey Bychkov, Usanee Vutrapongwatana, Supatporn Tepmongkol, Somboon Keelawat
Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer epithelium, making it a promising target for molecular imaging and therapy. Recently, several studies found unexpected PSMA radiotracer uptake by thyroid tumors, including radioiodine-refractory (RAIR) cancers. PSMA expression was reported in tumor-associated endothelium of various malignancies, however it has not been systematically addressed in thyroid tumors. We found that PSMA was frequently expressed in microvessels of thyroid tumors (120/267), but not in benign thyroid tissue...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698581/gtse1-promotes-cell-migration-and-invasion-by-regulating-emt-in-hepatocellular-carcinoma-and-is-associated-with-poor-prognosis
#19
Xiaojuan Wu, Hongbo Wang, Yifan Lian, Lubiao Chen, Lin Gu, Jialiang Wang, Yanlin Huang, Meihai Deng, Zhiliang Gao, Yuehua Huang
G2 and S phase-expressed-1 (GTSE1) regulates G1/S cell cycle transition. It was recently reported to be overexpressed in certain human cancers, but its significance and mechanism(s) in hepatocellular carcinoma (HCC) remain unknown. Here, we showed preferential GTSE1 upregulation in human HCC tissues and cell lines that positively correlated with Ki67. GTSE1 knockdown by short hairpin RNA resulted in deficient colony-forming ability and depleted capabilities of HCC cells to migrate and invade. Conversely, exogenous GTSE1 overexpression enhanced colony formation and stimulated HCC cell migration and invasion...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697344/muc1-and-hif-1alpha-signaling-crosstalk-induces-anabolic-glucose-metabolism-to-impart-gemcitabine-resistance-to-pancreatic-cancer
#20
Surendra K Shukla, Vinee Purohit, Kamiya Mehla, Venugopal Gunda, Nina V Chaika, Enza Vernucci, Ryan J King, Jaime Abrego, Gennifer D Goode, Aneesha Dasgupta, Alysha L Illies, Teklab Gebregiworgis, Bingbing Dai, Jithesh J Augustine, Divya Murthy, Kuldeep S Attri, Oksana Mashadova, Paul M Grandgenett, Robert Powers, Quan P Ly, Audrey J Lazenby, Jean L Grem, Fang Yu, José M Matés, John M Asara, Jung-Whan Kim, Jordan H Hankins, Colin Weekes, Michael A Hollingsworth, Natalie J Sarkova, Aaron R Sasson, Jason B Fleming, Jennifer M Oliveto, Costas A Lyssiotis, Lewis C Cantley, Lyudmyla Berim, Pankaj K Singh
Poor response to cancer therapy due to resistance remains a clinical challenge. The present study establishes a widely prevalent mechanism of resistance to gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to glucose addiction in cancer cells and a corresponding increase in pyrimidine biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate (dCTP). Increased levels of dCTP diminish the effective levels of gemcitabine through molecular competition. We also demonstrate that MUC1-regulated stabilization of hypoxia inducible factor-1α (HIF-1α) mediates such metabolic reprogramming...
July 10, 2017: Cancer Cell
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