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Targeted cancer therapy molecular level

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https://www.readbyqxmd.com/read/28088556/regulation-of-docetaxel-sensitivity-in-prostate-cancer-cells-by-hsa-mir-125a-3p-via-modulation-of-mta1-signaling
#1
Jian-Zhou Liu, Feng-Yan Yin, Chang-You Yan, Hui Wang, Xiao-Hui Luo
OBJECTIVE: To identify the potential down-stream targets of hsa-miR-125a-3p, a mature form of miR-125a, during the pathogenesis of chemoresistance in prostate cancer (PCa). METHODS: Expression levels of hsa-miR-125a-3p was assessed in chemoresistant PCa tissues and experimentally-established chemoresistant cells using quantitative RT-PCR (qRT-PCR). The effect of hsa-miR-125a-3p knockdown or hsa-miR-125a-3p overexpression on the Dox-induced cell death was evaluated using apoptosis ELISA in chemosensitive PC-3 cells or in chemoresistant PC-3 cells (PC-3R)...
January 11, 2017: Urology
https://www.readbyqxmd.com/read/28088493/apoptosis-induced-by-the-methanol-extract-of-salvia-miltiorrhiza-bunge-in-non-small-cell-lung-cancer-through-pten-mediated-inhibition-of-pi3k-akt-pathway
#2
Yin-Tao Ye, Wei Zhong, Pei Sun, Dong Wang, Chen Wang, Li-Min Hu, Jun-Qiang Qian
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies have reported that the active component tanshinones displayed a variety of biological activities: antithrombous, antiplatelet aggregation, antioxidant and antitumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated...
January 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28087598/bayesian-network-inference-modeling-identifies-trib1-as-a-novel-regulator-of-cell-cycle-progression-and-survival-in-cancer-cells
#3
Rina Gendelman, Heming Xing, Olga K Mirzoeva, Preeti Sarde, Christina Curtis, Heidi Feiler, Paul McDonagh, Joe W Gray, Iya Khalil, W Michael Korn
Molecular networks governing cellular responses to targeted therapies are complex dynamic systems with non-intuitive behaviors. Here we applied a novel computational strategy to infer probabilistic causal relationships between network components based on gene expression. We constructed a model comprised of an ensemble of networks using multidimensional data from cell line models of cell cycle arrest caused by inhibition of MEK1/2. Through simulation of reverse-engineered Bayesian network modeling, we generated predictions of G1-S transition...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28087315/assessing-light-independent-effects-of-hypericin-on-cell-viability-ultrastructure-and-metabolism-in-human-glioma-and-endothelial-cells
#4
Veronika Huntosova, Marta Novotova, Zuzana Nichtova, Lucia Balogova, Maria Maslanakova, Dana Petrovajova, Katarina Stroffekova
Cell exposure to light-independent effects of photosensitizers (PS) used in PDT is clinically relevant when PS affect the pro-apoptotic cascade.In many malignant cells, Hypericin (Hyp) has PS displayed light-dependent anti-proliferative and cytotoxic effects with no cytotoxicity in the dark. Recent studies have shown that Hyp also exhibited light-independent cytotoxic effects in a wide range of concentrations. The molecular mechanisms underlying Hyp light-independent (dark) toxicity may be due to its interaction with different molecules at the Hyp accumulation sites including mitochondria, and these mechanisms are not understood in detail...
January 10, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28079144/igf-ir-cooperates-with-er%C3%AE-to-inhibit-breast-cancer-cell-aggressiveness-by-regulating-the-expression-and-localisation-of-ecm-molecules
#5
Nikolaos A Afratis, Panagiotis Bouris, Spyros S Skandalis, Hinke A Multhaupt, John R Couchman, Achilleas D Theocharis, Nikos K Karamanos
IGF-IR is highly associated with the behaviour of breast cancer cells. In ERα-positive breast cancer, IGF-IR is present at high levels. In clinical practice, prolonged treatment with anti-estrogen agents results in resistance to the therapy with activation of alternative signaling pathways. Receptor Tyrosine Kinases, and especially IGF-IR, have crucial roles in these processes. Here, we report a nodal role of IGF-IR in the regulation of ERα-positive breast cancer cell aggressiveness and the regulation of expression levels of several extracellular matrix molecules...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078663/inhibition-of-hsp90-exerts-anti-tumor-effect-on-angiosarcoma-involvement-of-vegf-signaling-pathway
#6
S Yamada-Kanazawa, I Kajihara, S Fukushima, M Jinnin, M Masuzawa, M Masuzawa, Y Amoh, D Hoshina, R Abe, H Ihn
BACKGROUND: Angiosarcoma is a rare malignant neoplasm derived from endothelial cells and its prognosis is poor because advanced angiosarcoma is resistant to standard chemotherapy, and new therapies are urgently needed. Heat shock protein 90 (HSP90) has been identified as a molecular chaperone that regulates various cancer-related proteins. Numerous clinical trials are testing the effectiveness of HSP90 inhibitors in various types of malignancies. OBJECTIVES: To investigate the role of HSP90 in the pathogenesis of angiosarcoma and whether inhibition of HSP90 may have anti-tumor activity...
January 12, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28077300/pharmacological-strategies-to-target-oncogenic-kras-signaling-in-pancreatic-cancer
#7
REVIEW
Hsiao-Ching Chuang, Po-Hsien Huang, Samuel K Kulp, Ching-Shih Chen
The clear importance of mutated KRAS as a therapeutic target has driven the investigation of multiple approaches to inhibit oncogenic KRAS signaling at different molecular levels. However, no KRAS-targeted therapy has reached the clinic to date, which underlies the intrinsic difficulty in developing effective, direct inhibitors of KRAS. Thus, this article provides an overview of the history and recent progress in the development of pharmacological strategies to target oncogenic KRAS with small molecule agents...
January 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28076324/poly-c-binding-protein-1-mediates-drug-resistance-in-colorectal-cancer
#8
Jiani Guo, Changli Zhu, Kangqun Yang, Jin Li, Nan Du, Mingzhu Zong, Jianwei Zhou, Jingdong He
Oxaliplatin (L-OHP) is standard treatment for colorectal cancer. However, resistance to L-OHP often leads to treatment failure or cancer relapse. Understanding of the mechanism underlying L-OHP resistance is important to overcome the resistance and improve colorectal cancer treatment. This study aimed to identify new proteins that mediates L-OHP resistance in colorectal cancer and elucidate their mode of function. HT-29 cells were exposed to gradually increased concentration of L-OHP to select L-OHP resistant HT-29/L-OHP cell line...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28069826/endostatin-inhibits-androgen-independent-prostate-cancer-growth-by-suppressing-nuclear-receptor-mediated-oxidative-stress
#9
Joo Hyoung Lee, Minsung Kang, Hong Wang, Gurudatta Naik, James A Mobley, Guru Sonpavde, W Timothy Garvey, Victor M Darley-Usmar, Selvarangan Ponnazhagan
Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28069687/adaptive-resistance-of-melanoma-cells-to-raf-inhibition-via-reversible-induction-of-a-slowly-dividing-de-differentiated-state
#10
Mohammad Fallahi-Sichani, Verena Becker, Benjamin Izar, Gregory J Baker, Jia-Ren Lin, Sarah A Boswell, Parin Shah, Asaf Rotem, Levi A Garraway, Peter K Sorger
Treatment of BRAF-mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use live-cell imaging, single-cell analysis, and molecular profiling to show that exposure of tumor cells to RAF/MEK inhibitors elicits a heterogeneous response in which some cells die, some arrest, and the remainder adapt to drug. Drug-adapted cells up-regulate markers of the neural crest (e.g., NGFR), a melanocyte precursor, and grow slowly...
January 9, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28061880/phospho-akt-overexpression-is-prognostic-and-can-be-used-to-tailor-the-synergistic-interaction-of-akt-inhibitors-with-gemcitabine-in-pancreatic-cancer
#11
Daniela Massihnia, Amir Avan, Niccola Funel, Mina Maftouh, Anne van Krieken, Carlotta Granchi, Rajiv Raktoe, Ugo Boggi, Babette Aicher, Filippo Minutolo, Antonio Russo, Leticia G Leon, Godefridus J Peters, Elisa Giovannetti
BACKGROUND: There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and cells, and investigated molecular mechanisms influencing the therapeutic potential of Akt inhibition in combination with gemcitabine. METHODS: Phospho-Akt expression was evaluated by immunohistochemistry in tissue microarrays (TMAs) with specimens tissue from radically-resected patients (n = 100)...
January 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28060554/current-molecular-and-genetic-aspects-of-pancreatic-cancer-the-role-of-metastasis-associated-proteins-mta-a-review
#12
Efstathios T Pavlidis, Theodoros E Pavlidis
: Purpose/aim: To focus on current molecular and genetic aspects and MTA proteins, since pancreatic cancer is a lethal malignant with poor prognosis. Early diagnosis is essential step, contributing to potential curative resection. MATERIALS AND METHODS: A PubMed search of relevant articles published up to August 2016 was performed to identify current information about pancreatic cancer regarding molecular biomarkers, with emphasis on carcinogenesis, novel therapeutic targets, and MTA proteins...
January 6, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/28058423/rapidly-cell-penetrating-and-reductive-milieu-responsive-nanoaggregates-assembled-from-an-amphiphilic-folate-camptothecin-prodrug-for-enhanced-drug-delivery-and-controlled-release
#13
Zhigang Xu, Meili Hou, Xiaoxiao Shi, Yong-E Gao, Peng Xue, Shiying Liu, Yuejun Kang
Accurate diagnosis and treatment based on small molecular prodrugs can enhance drug efficiency and reduce side-effects during cancer therapy. Herein, we report the preparation of a type of glutathione (GSH)-responsive small prodrug delivery system based on targeting folic acid (FA) and conjugating with the hydrophobic antitumor drug camptothecin (CPT) via disulfide bonds. The obtained prodrug is capable of high and precise drug loading (36.8 wt%) and can self-assemble into nanoaggregates with an average size of 46...
January 6, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28057486/mir-221-3p-targets-arf4-and-inhibits-the-proliferation-and-migration-of-epithelial-ovarian-cancer-cells
#14
Qihui Wu, Xiaolei Ren, Yimin Zhang, Xiaodan Fu, Yimin Li, Yulong Peng, Qing Xiao, Tong Li, Chunli Ouyang, Yixi Hu, Yu Zhang, Wenjuan Zhou, Wenguang Yan, Ke Guo, Wei Li, Yongbin Hu, Xiaojing Yang, Guang Shu, Haofan Xue, Zhangming Wei, Yonghong Luo, Gang Yin
Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. Although molecular diagnostic tools and targeted therapies have been developed over the past few decades, the survival rate is still rather low. Numerous researches suggest that some microRNAs (miRNAs) are key regulators of tumor progression. Among those miRNAs that has attracted much attention for their multiple roles in human cancers, the function of miR-221-3p in EOC has not been elucidated. Herein, we examined the expression of miR-221-3p in EOC patients and cell lines...
January 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28045433/functions-and-epigenetic-regulation-of-wwox-in-bone-metastasis-from-breast-carcinoma-comparison-with-primary-tumors
#15
REVIEW
Paola Maroni, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox). The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1) affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma...
January 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28039457/tumor-associated-macrophages-promote-prostate-cancer-migration-through-activation-of-the-ccl22-ccr4-axis
#16
Aerken Maolake, Kouji Izumi, Kazuyoshi Shigehara, Ariunbold Natsagdorj, Hiroaki Iwamoto, Suguru Kadomoto, Yuta Takezawa, Kazuaki Machioka, Kazutaka Narimoto, Mikio Namiki, Wen-Jye Lin, Guzailinuer Wufuer, Atsushi Mizokami
Previous studies have found that tumor-associated macrophages (TAMs) promote cancer progression. We previously reported that TAMs promote prostate cancer metastasis via activation of the CCL2-CCR2 axis. The CCR4 (receptor of CCL17 and CCL22) expression level in breast cancer was reported to be associated with lung metastasis. The aim of this study was to elucidate the role of CCR2 and CCR4 in prostate cancer progression. CCR2 and CCR4 were expressed in human prostate cancer cell lines and prostate cancer tissues...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039357/key-survival-factor-mcl-1-correlates-with-sensitivity-to-combined-bcl-2-bcl-xl-blockade
#17
Michelle Williams, Linus Lee, Donna J Hicks, Meghan M Joly, David Elion, Bushra Rahman, Courtney McKernan, Violeta Sanchez, Justin M Balko, Thomas Stricker, Monica Valeria Estrada, Rebecca S Cook
: An estimated 40,000 deaths will be attributed to breast cancer in 2016, underscoring the need for improved therapies. Evading cell death is a major hallmark of cancer, driving tumor progression and therapeutic resistance. To evade apoptosis, cancers use anti-apoptotic Bcl-2 proteins to bind to and neutralize apoptotic activators, such as Bim. Investigation of anti-apoptotic Bcl-2 family members in clinical breast cancer datasets, revealed greater expression and more frequent gene amplification of MCL1 as compared to BCL2 or BCL2L1 (Bcl-xL) across three major molecular breast cancer subtypes, Luminal (A and B), HER2-enriched, and Basal-like...
December 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28034805/cd133-confers-cancer-stem-like-cell-properties-by-stabilizing-egfr-akt-signaling-in-hepatocellular-carcinoma
#18
Jae-Woo Jang, Yeonhwa Song, Se-Hyuk Kim, Jin-Sun Kim, Kang Mo Kim, Eun Kyung Choi, Joon Kim, Haeng Ran Seo
Hepatocellular carcinoma (HCC) is the seventh most common malignant tumor and the third leading cause of cancer-related death in the world. Cancer stem cells (CSCs) are small subpopulation of cells within tumors that drive chemoresistance and tumor recurrence in various cancers. We characterized CSCs in primary HCC and identified CD133 as a CSC surface marker. CD133(+) HCC cells displayed more stem cell-like properties, tumor spheroid-forming ability, chemoresistance, migration ability, and tumorigenic capacity than CD133(-) HCC cells...
December 27, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28028181/rybp-expression-is-regulated-by-klf4-and-sp1-and-is-related-to-hepatocellular-carcinoma-prognosis
#19
Qiaojiajie Zhao, Weihua Cai, Xuan Zhang, Shuo Tian, Junwen Zhang, Haibo Li, Congcong Hou, Xiaoli Ma, Hong Chen, Bingren Huang, Deng Chen
The expression of Ring1 and YY1 binding protein (RYBP) is reduced in several human cancers, but the molecular mechanism(s) have remained elusive. In this study, we used human HCC cell lines and tissue specimens to study the mechanism, and herein report several new findings. First, we cloned and characterized the basal promoter region of the human rybp gene. We found that the decreased RYBP expression in HCC tissues was not due to promoter sequence variation/polymorphisms or CpG dinucleotide methylation. We identified two transcription factors, KLF4 and Sp1, which directly bind the promoter region of rybp to respectively induce and suppress rybp transcription...
December 27, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28026860/pioglitazone-together-with-imatinib-in-chronic-myeloid-leukemia-a-proof-of-concept-study
#20
Philippe Rousselot, Stéphane Prost, Joelle Guilhot, Lydia Roy, Gabriel Etienne, Laurence Legros, Aude Charbonnier, Valérie Coiteux, Pascale Cony-Makhoul, Francoise Huguet, Emilie Cayssials, Jean-Michel Cayuela, Francis Relouzat, Marc Delord, Heriberto Bruzzoni-Giovanelli, Laure Morisset, François-Xavier Mahon, François Guilhot, Philippe Leboulch
BACKGROUND: We recently reported that peroxisome proliferator-activated receptor γ agonists target chronic myeloid leukemia (CML) quiescent stem cells in vitro by decreasing transcription of STAT5. Here in the ACTIM phase 2 clinical trial, we asked whether pioglitazone add-on therapy to imatinib would impact CML residual disease, as assessed by BCR-ABL1 transcript quantification. METHODS: CML patients were eligible if treated with imatinib for at least 2 years at a stable daily dose, having yielded major molecular response (MMR) but not having achieved molecular response 4...
December 27, 2016: Cancer
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