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Targeted cancer therapy molecular level

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https://www.readbyqxmd.com/read/28938160/nilotinib-enhances-tumor-angiogenesis-and-counteracts-vegfr2-blockade-in-an-orthotopic-breast-cancer-xenograft-model-with-desmoplastic-response
#1
Sara Zafarnia, Jessica Bzyl-Ibach, Igor Spivak, Yongping Li, Susanne Koletnik, Dennis Doleschel, Anne Rix, Sibylle Pochon, Isabelle Tardy, Seena Koyadan, Marc van Zandvoort, Moritz Palmowski, Fabian Kiessling, Wiltrud Lederle
Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-targeted therapies predominantly affect nascent, immature tumor vessels. Since platelet-derived growth factor receptor (PDGFR) blockade inhibits vessel maturation and thus increases the amount of immature tumor vessels, we evaluated whether the combined PDGFR inhibition by nilotinib and VEGFR2 blockade by DC101 has synergistic therapy effects in a desmoplastic breast cancer xenograft model. In this context, besides immunohistological evaluation, molecular ultrasound imaging with BR55, the clinically used VEGFR2-targeted microbubbles, was applied to monitor VEGFR2-positive vessels noninvasively and to assess the therapy effects on tumor angiogenesis...
September 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28936716/induction-of-reactive-oxygen-species-an-emerging-approach-for-cancer-therapy
#2
REVIEW
Zhengzhi Zou, Haocai Chang, Haolong Li, Songmao Wang
Reactive oxygen species (ROS), a group of ions and molecules, include hydroxyl radicals (·OH), alkoxyl radicals, superoxide anion (O2·-), singlet oxygen ((1)O2) and hydrogen peroxide (H2O2). Hydroxyl radicals and alkoxyl radicals are extremely and highly reactive species respectively. Endogenous ROS are mainly formed in mitochondrial respiratory chain. Low levels of ROS play important roles in regulating biological functions in mammalian cells. However, excess production of ROS can induce cell death by oxidative damaging effects to intracellular biomacromolecules...
September 21, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28933410/honey-and-cancer-current-status-and-future-directions
#3
REVIEW
Laura M Porcza, Claire Simms, Mridula Chopra
Cancer is a leading cause of death worldwide and poses a challenge to treatment. With overwhelming evidence of the role played by diet and lifestyle in cancer risk and prevention, there is a growing interest into the search for chemopreventative or chemotherapeutic agents derived from natural products. Honey is an important source of bioactive compounds derived from plants and recent years have seen an increased interest in its anticancer properties. This review examines the role of honey in targeting key hallmarks of carcinogenesis, including uncontrolled proliferation, apoptosis evasion, angiogenesis, growth factor signalling, invasion, and inflammation...
September 30, 2016: Diseases (Basel)
https://www.readbyqxmd.com/read/28928864/high-immunoreactivity-of-duox2-is-associated-with-poor-response-to-preoperative-chemoradiation-therapy-and-worse-prognosis-in-rectal-cancers
#4
Shih-Chun Lin, I-Wei Chang, Pei-Ling Hsieh, Ching-Yih Lin, Ding-Ping Sun, Ming-Jen Sheu, Ching-Chieh Yang, Li-Ching Lin, Hong-Lin He, Yu-Feng Tian
Purpose: Colorectal cancer is the third most common cancer and also the fourth most common cause of cancer mortality worldwide. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a documented database of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information, we recognized that DUOX2 was the most significantly up-regulated transcript among those related to cytokine and chemokine mediated signaling pathway (GO:0019221)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928842/significant-response-to-ramucirumab-monotherapy-in-chemotherapy-resistant-recurrent-alpha-fetoprotein-producing-gastric-cancer-a-case-report
#5
Yasuhiro Arakawa, Miho Tamura, Keisuke Aiba, Kazuhiko Morikawa, Daisuke Aizawa, Masahiro Ikegami, Masami Yuda, Katsunori Nishikawa
Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is a relatively rare type of gastric cancer characterized by a high incidence of liver and lymph node metastases, and a poor prognosis. Few advanced AFPGC cases treated successfully with conventional chemotherapy have been reported thus far. Although the development of molecular-targeted therapy has improved the prognosis of various types of cancer, there are currently no tailored therapies for AFPGC. In the present report, the case of a chemotherapy-resistant recurrent AFPGC patient who exhibited a significant response to ramucirumab monotherapy is presented...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927526/putative-biomarkers-for-cervical-cancer-snvs-methylation-and-expression-profiles
#6
REVIEW
Maria de Fátima Senra Cardoso, Carlos Henrique Madeiros Castelletti, José Luiz de Lima-Filho, Danyelly Bruneska Gondim Martins, José António Couto Teixeira
Cervical cancer is primarily caused by Human papillomavirus (HPV) infection, but other factors such as smoking habits, co-infections and genetic background, can also contribute to its development. Although this cancer is avoidable, it is the fourth most frequent type of cancer in females worldwide and can only be treated with chemotherapy and radical surgery. There is a need for biomarkers that will enable early diagnosis and targeted therapy for this type of cancer. Therefore, a systems biology pipeline was applied in order to identify potential biomarkers for cervical cancer, which show significant reports in three molecular aspects: DNA sequence variants, DNA methylation pattern and alterations in mRNA/protein expression levels...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28926138/tnfaip8-regulates-hippo-pathway-through-interacting-with-lats1-to-promote-cell-proliferation-and-invasion-in-lung-cancer
#7
Yong Han, ZhongPing Tang, Yue Zhao, Qingchang Li, Enhua Wang
TNFAIP8 is associated with prognosis of several human malignancies. However, the molecular mechanism of TNFAIP8 in lung cancer remains unknown. In our study, we found TNFAIP8 could enhance TEAD luciferase activity and inhibits the activity of Hippo pathway. TNFAIP8 also increased cyclin D1, CDK6 and decreased p27 in lung cancer cells. In addition, TNFAIP8 increased total YAP protein and promoted nuclear localization of YAP. More importantly, YAP depletion blocked the role of TNFAIP8 on cell cycle-related proteins and TEAD luciferase activity, revealing that TNFAIP8 regulates Hippo pathway in a YAP-dependend manner...
September 19, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28925878/genistein-induces-alterations-of-epigenetic-modulatory-signatures-in-human-cervical-cancer-cells
#8
Madhumitha Kedhari Sundaram, Mohammad Zeeshan Ansari, Abdullah Al Mutery, Maryam Ashraf, Reem Nasab, Sheethal Rai, Naushad Rais, Arif Hussain
Introduction Epidemiological studies indicate that diet rich in fruits and vegetables are associated with decreased cancer risk thereby indicating that dietary polyphenols can be potential chemo-preventive agents. The reversible nature of epigenetic modifications makes them a favorable target for cancer prevention. Polyphenols have been shown to reverse aberrant epigenetic patterns by targeting the regulatory enzymes, DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). In vitro and in silico studies of DNMTs and HDACs were planned to examine genistein's role as a natural epigenetic modifier in human cervical cancer cells, HeLa...
September 18, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28911087/an-antisense-oligonucleotide-targeting-tgf-%C3%AE-2-inhibits-lung-metastasis-and-induces-cd86-expression-in-tumor-associated-macrophages
#9
I Huber-Ruano, C Raventós, I Cuartas, C Sánchez-Jaro, A Arias, J L Parra, K Wosikowski, M Janicot, J Seoane
Background: The transforming growth factor (TGF)-β pathway is a well-described inducer of immunosuppression and can act as an oncogenic factor in advanced tumors. Several preclinical and clinical studies show that the TGF-β pathway can be considered a promising molecular target for cancer therapy. The human genome has three TGF-β isoforms and not much is known about the oncogenic response to each of the isoforms. Here, we studied the antitumor response to ISTH0047, a recently developed locked nucleic acid-modified antisense oligonucleotide targeting TGF-β2...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28895563/characteristics-and-clinical-significance-of-histological-variants-of-bladder-cancer
#10
REVIEW
Marco Moschini, David D'Andrea, Stephan Korn, Yasin Irmak, Francesco Soria, Eva Compérat, Shahrokh F Shariat
In the past 10 years evidence for the clinical relevance of variant histology in urinary bladder cancer has been increasing. This increase has resulted in new classifications of urothelial cancers by the WHO in 2016, highlighting the importance of an accurate morphological description of pathological specimens for the therapeutic management of patients with bladder cancer. The rising awareness of the importance of an accurate pathological report manifests itself in the increasing prevalence of reporting of variant histology in daily practice...
September 12, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28892308/targeting-epidermal-growth-factor-receptor-co-dependent-signaling-pathways-in-glioblastoma
#11
Feng Liu, Paul S Mischel
The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase (RTK) that is critical for normal development and function. EGFR is also amplified or mutated in a variety of cancers including in nearly 60% of cases of the highly lethal brain cancer glioblastoma (GBM). EGFR amplification and mutation reprogram cellular metabolism and broadly alter gene transcription to drive tumor formation and progression, rendering EGFR as a compelling drug target. To date, brain tumor patients have yet to benefit from anti-EGFR therapy due in part to an inability to achieve sufficient intratumoral drug levels in the brain, cultivating adaptive mechanisms of resistance...
September 11, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28889753/silencing-of-bach1-inhibits-invasion-and-migration-of-prostate-cancer-cells-by-altering-metastasis-related-gene-expression
#12
Neda Shajari, Sadaf Davudian, Tohid Kazemi, Behzad Mansoori, Shima Salehi, Vahid Khaze Shahgoli, Dariush Shanehbandi, Ali Mohammadi, Pascal H G Duijf, Behzad Baradaran
BACKGROUND: Cancer lethality is mainly caused by metastasis. Therefore, understanding the nature of the genes involved in this process has become a priority. BACH1, a basic leucine zipper transcription factor, has been shown to transcriptionally regulate expression of a range of genes that are associated with breast cancer metastasis. However, the exact role and the underlying molecular mechanism of BACH1 in prostate cancer remain unclear. This study aims to explore the expression of BACH1 in prostate cancer tissues and the effect of BACH1 suppression on prostate cancer cell behavior...
September 11, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28882160/intrinsic-fluorescence-of-the-clinically-approved-multikinase-inhibitor-nintedanib-reveals-lysosomal-sequestration-as-resistance-mechanism-in-fgfr-driven-lung-cancer
#13
Bernhard Englinger, Sebastian Kallus, Julia Senkiv, Daniela Heilos, Lisa Gabler, Sushilla van Schoonhoven, Alessio Terenzi, Patrick Moser, Christine Pirker, Gerald Timelthaler, Walter Jäger, Christian R Kowol, Petra Heffeter, Michael Grusch, Walter Berger
BACKGROUND: Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells...
September 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28881780/pd-l1-a-novel-prognostic-biomarker-in-head-and-neck-squamous-cell-carcinoma
#14
Tim Müller, Martin Braun, Dimo Dietrich, Seher Aktekin, Simon Höft, Glen Kristiansen, Friederike Göke, Andreas Schröck, Johannes Brägelmann, Stefanie A E Held, Friedrich Bootz, Peter Brossart
BACKGROUND: The PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881732/oncogenic-secretory-clusterin-in-hepatocellular-carcinoma-expression-at-early-staging-and-emerging-molecular-target
#15
Wenjie Zheng, Min Yao, Qi Qian, Wenli Sai, Liwei Qiu, Junling Yang, Wei Wu, Zhizhen Dong, Dengfu Yao
Secretory clusterin (sCLU) is associated with hepatocellular carcinoma (HCC) progression by contributing to angiogenesis, chemoresistance, cell survival, and metastasis. However, the sCLU expression at early stage of HCC progression remains to be clarified. In this study, the alteration of sCLU oncogenicity was firstly evaluated in HCC- and their para-cancerous- tissues. The incidence of sCLU expression in HCC was significantly higher than that in their non-tumorous tissues at message RNA (mRNA) or protein level, gradually increasing with tumor-node-metastasis (TNM) staging...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877626/tumor-associated-macrophages-nanomedicine-and-imaging-the-axis-of-success-in-the-future-of-cancer-immunotherapy
#16
Saeid Zanganeh, Ryan Spitler, Gregor Hutter, Jim Q Ho, Mohan Pauliah, Morteza Mahmoudi
The success of any given cancer immunotherapy relies on several key factors. In particular, success hinges on the ability to stimulate the immune system in a controlled and precise fashion, select the best treatment options and appropriate therapeutic agents, and use highly effective tools to accurately and efficiently assess the outcome of the immunotherapeutic intervention. Furthermore, a deep understanding and effective utilization of tumor-associated macrophages (TAMs), nanomedicine and biomedical imaging must be harmonized to improve treatment efficacy...
September 2017: Immunotherapy
https://www.readbyqxmd.com/read/28875010/anti-apoptotic-effects-of-osteopontin-via-the-up-regulation-of-akt-mtor-%C3%AE-catenin-loop-in-acute-myeloid-leukemia-cells
#17
Mahdi Zahed Panah, Mohsen Nikbakht, Seyed Mehdi Sajjadi, Shahrbano Rostami, Amir Hossein Norooznezhad, Hosein Kamranzadeh Fumani, Ardeshir Ghavamzadeh, Saeed Mohammadi
Background: The conventional chemotherapeutic regimens which applied for treatment of acute myeloid leukemia (AML) mostly target tumor bulk but not leukemic stem cells (LSCs). Aberrant expression or activation of mediators such as osteopontin (OPN) or PI3K/PTEN/Akt/mTOR pathway plays a key role in making prone to develop leukemia. Preventing or treating cancer by curcumin (CUR) has been suggested recently. CUR induces apoptosis and growth inhibition through various mechanisms in leukemic cells. In present study, we tried to measure the toxic response in vitro to CUR for evaluation ofchangesin cell viability, survival and molecular-mediated resistance in primary AML cells...
April 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28864615/prostate-specific-membrane-antigen-ligands-for-imaging-and-therapy
#18
Matthias Eiber, Wolfgang P Fendler, Steven P Rowe, Jeremie Calais, Michael S Hofman, Tobias Maurer, Sarah M Schwarzenboeck, Clemens Kratowchil, Ken Herrmann, Frederik L Giesel
The prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PC) cells. Therefore, the targeting of PSMA has become increasingly important over the last decade. Glu-urea-based PSMA ligands used for both imaging and radioligand therapy are the mainstays of the current success. For PET imaging, both (68)Ga- and (18)F-labeled agents have been successfully translated to clinical applications. Mainly retrospective cohort studies have shown a high value in the setting of biochemical recurrence, with high detection rates even in the presence of low prostate-specific antigen levels...
September 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28862319/breakthroughs-in-modern-cancer-therapy-and-elusive-cardiotoxicity-critical-research-practice-gaps-challenges-and-insights
#19
REVIEW
Ping-Pin Zheng, Jin Li, Johan M Kros
To date, five cancer treatment modalities have been defined. The three traditional modalities of cancer treatment are surgery, radiotherapy, and conventional chemotherapy, and the two modern modalities include molecularly targeted therapy (the fourth modality) and immunotherapy (the fifth modality). The cardiotoxicity associated with conventional chemotherapy and radiotherapy is well known. Similar adverse cardiac events are resurging with the fourth modality. Aside from the conventional and newer targeted agents, even the most newly developed, immune-based therapeutic modalities of anticancer treatment (the fifth modality), e...
September 1, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28861770/economic-considerations-in-the-use-of-novel-targeted-therapies-for-lung-cancer-review-of-current-literature
#20
Hamzeh Albaba, Charles Lim, Natasha B Leighl
Lung cancer remains the leading cause of cancer-related death and economic burden worldwide. Despite the heavy toll of lung cancer, multiple new advances have improved patient outcomes, largely through precision medicine and targeted therapy. The associated rising economic burden however may impact the uptake of novel therapeutic agents in lung cancer, thereby limiting patient access. This article identifies and reviews economic evaluations of targeted agents in lung cancer in the era of precision medicine...
August 31, 2017: PharmacoEconomics
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