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https://www.readbyqxmd.com/read/28522590/notch-inhibitor-pf-03084014-inhibits-hepatocellular-carcinoma-growth-and-metastasis-via-suppression-of-cancer-stemness-due-to-reduced-activation-of-notch1-stat3
#1
Chuan Xing Wu, Aimin Xu, Cathy C Zhang, Peter Olson, Lin Chen, Terence K Lee, Tan To Cheung, Chung Mau Lo, Xiao Qi Wang
Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma (HCC), indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084014 in HCC. HCC spherical cells (stem-like cancer cells), a sphere-derived orthotopic tumor model and one patient-derived xenograft (PDX) model were used in our experiment. We demonstrated that PF-03084014 inhibited the self-renewal and proliferation of cancer stem cells...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28499452/current-status-and-perspectives-of-patient-derived-xenograft-models-in-cancer-research
#2
REVIEW
Yunxin Lai, Xinru Wei, Shouheng Lin, Le Qin, Lin Cheng, Peng Li
Cancers remain a major public health problem worldwide, which still require profound research in both the basic and preclinical fields. Patient-derived xenograft (PDX) models are created when cancerous cells or tissues from patients' primary tumors are implanted into immunodeficient mice to simulate human tumor biology in vivo, which have been extensively used in cancer research. The routes of implantation appeared to affect the outcome of PDX research, and there has been increasing applications of patient-derived orthotopic xenograft (PDOX) models...
May 12, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28494180/intra-arterial-administration-of-tumor-targeting-salmonella-typhimurium-a1-r-regresses-a-cisplatin-resistant-relapsed-osteosarcoma-in-a-patient-derived-orthotopic-xenograft-pdox-mouse-model
#3
Kentaro Igarashi, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Scott D Nelson, Sarah M Dry, Yunfeng Li, Jane Yanagawa, Tara A Russell, Arun S Singh, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Previously, a patient-derived orthotopic xenograft (PDOX) model was established with a lung metastasis from an osteosarcoma patient which developed after adjuvant cisplatinum (CDDP) treatment. In this model, we previously demonstrated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared to CDDP. In the previous report, osteosarcoma tissue was implanted orthotopically in the distal femur of mice which were randomized into the following groups when tumor volume reached approximately 100 mm(3): On day 14 after initiation of treatment, all but CDDP treatments significantly inhibited tumor growth compared to untreated control: control (G1): 793...
May 11, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28472820/clinical-value-of-r-spondins-in-triple-negative-and-metaplastic-breast-cancers
#4
F Coussy, F Lallemand, S Vacher, A Schnitzler, W Chemlali, M Caly, A Nicolas, S Richon, D Meseure, R El Botty, L De-Plater, L Fuhrmann, T Dubois, S Roman-Roman, V Dangles-Marie, E Marangoni, I Bièche
BACKGROUND: RSPO ligands, activators of the Wnt/β-catenin pathway, are overexpressed in different cancers. The objective of this study was to investigate the role of RSPOs in breast cancer (BC). METHODS: Expression of RSPO and markers of various cancer pathways were measured in breast tumours and cell lines by qRT-PCR. The effect of RSPO on the Wnt/β-catenin pathway activity was determined by luciferase assay, western blotting, and qRT-PCR. The effect of RSPO2 inhibition on proliferation was determined by using RSPO2 siRNAs...
May 4, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28467965/intratumoral-acidosis-fosters-cancer-induced-bone-pain-through-the-activation-of-the-mesenchymal-tumor-associated-stroma-in-bone-metastasis-from-breast-carcinoma
#5
Gemma Di Pompo, Silvia Lemma, Lorenzo Canti, Nadia Rucci, Marco Ponzetti, Costantino Errani, Davide Maria Donati, Shonagh Russell, Robert Gillies, Tokuhiro Chano, Nicola Baldini, Sofia Avnet
Cancer-induced bone pain (CIBP) is common in patients with bone metastases (BM), significantly impairing quality of life. The current treatments for CIBP are limited since they are often ineffective. Local acidosis derived from glycolytic carcinoma and tumor-induced osteolysis is only barely explored cause of pain. We found that breast carcinoma cells that prefer bone as a metastatic site have very high extracellular proton efflux and expression of pumps/ion transporters associated with acid-base balance (MCT4, CA9, and V-ATPase)...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28450156/microrna-7-impairs-autophagy-derived-pools-of-glucose-to-suppress-pancreatic-cancer-progression
#6
Dian-Na Gu, Ming-Jie Jiang, Zhu Mei, Juan-Juan Dai, Chen-Yun Dai, Chi Fang, Qian Huang, Ling Tian
Pancreatic cancer commonly addicts to aerobic glycolysis, and abnormally activates autophagy to adapt the stringent metabolic microenvironment. microRNA-7 (miR-7) was supposed to modulate various gastrointestinal cancer progression. We wonder whether miR-7 could destroy the reprogrammed metabolic homeostasis in pancreatic cancer via modulating the level of autophagy, and further affect tumor proliferation and survival. Herein, we first reported that pancreatic cancer could take advantage of autophagy as a survival strategy to provide essential glucose required for glycolysis metabolism...
April 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28446252/ring-finger-protein-43-associates-with-gastric-cancer-progression-and-attenuates-the-stemness-of-gastric-cancer-stem-like-cells-via-the-wnt-%C3%AE-catenin-signaling-pathway
#7
Yunhe Gao, Aizhen Cai, Hongqing Xi, Jiyang Li, Wei Xu, Yanmei Zhang, Kecheng Zhang, Jianxin Cui, Xiaosong Wu, Bo Wei, Lin Chen
BACKGROUND: Ring finger protein 43 (RNF43) is a member of the transmembrane E3 ubiquitin ligase family that was originally found in stem cells and plays important roles in tumor formation and progression. Our previous study indicated that RNF43 might be a tumor suppressor protein in gastric cancer. Given its antagonistic relationship with leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), one of the gastric cancer stem cell markers, investigation of the potential role of RNF43 in gastric stem cancer cells is necessary...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28446206/cooperation-of-neurotrophin-receptor-trkb-and-her2-in-breast-cancer-cells-facilitates-brain-metastases
#8
Cecilia Choy, Khairul I Ansari, Josh Neman, Sarah Hsu, Matthew J Duenas, Hubert Li, Nagarajan Vaidehi, Rahul Jandial
BACKGROUND: Patients with primary breast cancer that is positive for human epidermal growth factor receptor 2 (Her2+) have a high risk of developing metastases in the brain. Despite gains with systemic control of Her2+ disease using molecular therapies, brain metastases remain recalcitrant to therapeutic discovery. The clinical predilection of Her2+ breast cancer cells to colonize the brain likely relies on paracrine mechanisms. The neural niche poses unique selection pressures, and neoplastic cells that utilize the brain microenvironment may have a survival advantage...
April 26, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28435028/antagonistic-effects-of-p53-and-hif1a-on-microrna-34a-regulation-of-ppp1r11-and-stat3-and-hypoxia-induced-epithelial-to-mesenchymal-transition-in-colorectal-cancer-cells
#9
Huihui Li, Matjaz Rokavec, Longchang Jiang, David Horst, Heiko Hermeking
BACKGROUND & AIMS: In colorectal tumors, hypoxia causes resistance to therapy and promotes metastasis. Loss of the tumor suppressor p53 (encoded by TP53) provides cancer cells with a selective advantage under conditions of hypoxia, but little is known about the mediators of this effect. METHODS: Isogenic CRC cell lines with different TP53 genotypes were placed under conditions of hypoxia. We examined the effects on levels and activity of microRNA-34 a (MIR34A) in CRC cells...
April 20, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28414297/tumor-penetrating-peptide-enhances-transcytosis-of-silicasome-based-chemotherapy-for-pancreatic-cancer
#10
Xiangsheng Liu, Paulina Lin, Ian Perrett, Joshua Lin, Yu-Pei Liao, Chong Hyun Chang, Jinhong Jiang, Nanping Wu, Timothy Donahue, Zev Wainberg, Andre E Nel, Huan Meng
Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal; however, some improvement in overall survival has been achieved with the introduction of nanocarriers that deliver irinotecan or paclitaxel. Although it is generally assumed that nanocarriers rely principally on abnormal leaky vasculature for tumor access, a transcytosis transport pathway that is regulated by neuropilin-1 (NRP-1) has recently been reported. NRP-1-mediated transport can be triggered by the cyclic tumor-penetrating peptide iRGD...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28376210/estrogen-receptor-%C3%AE-as-a-therapeutic-target-in-breast-cancer-stem-cells
#11
Ran Ma, Govindasamy-Muralidharan Karthik, John Lövrot, Felix Haglund, Gustaf Rosin, Anne Katchy, Xiaonan Zhang, Lisa Viberg, Jan Frisell, Cecilia Williams, Stig Linder, Irma Fredriksson, Johan Hartman
Background: Breast cancer cells with tumor-initiating capabilities (BSCs) are considered to maintain tumor growth and govern metastasis. Hence, targeting BSCs will be crucial to achieve successful treatment of breast cancer. Methods: We characterized mammospheres derived from more than 40 cancer patients and two breast cancer cell lines for the expression of estrogen receptors (ERs) and stem cell markers. Mammosphere formation and proliferation assays were performed on cells from 19 cancer patients and five healthy individuals after incubation with ER-subtype selective ligands...
March 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28371798/mutual-regulation-of-tumour-vessel-normalization-and-immunostimulatory-reprogramming
#12
Lin Tian, Amit Goldstein, Hai Wang, Hin Ching Lo, Ik Sun Kim, Thomas Welte, Kuanwei Sheng, Lacey E Dobrolecki, Xiaomei Zhang, Nagireddy Putluri, Thuy L Phung, Sendurai A Mani, Fabio Stossi, Arun Sreekumar, Michael A Mancini, William K Decker, Chenghang Zong, Michael T Lewis, Xiang H-F Zhang
Blockade of angiogenesis can retard tumour growth, but may also paradoxically increase metastasis. This paradox may be resolved by vessel normalization, which involves increased pericyte coverage, improved tumour vessel perfusion, reduced vascular permeability, and consequently mitigated hypoxia. Although these processes alter tumour progression, their regulation is poorly understood. Here we show that type 1 T helper (TH1) cells play a crucial role in vessel normalization. Bioinformatic analyses revealed that gene expression features related to vessel normalization correlate with immunostimulatory pathways, especially T lymphocyte infiltration or activity...
April 13, 2017: Nature
https://www.readbyqxmd.com/read/28368402/sox2-is-not-required-for-melanomagenesis-melanoma-growth-and-melanoma-metastasis-in-vivo
#13
V Cesarini, E Guida, F Todaro, S Di Agostino, V Tassinari, S Nicolis, R Favaro, S Caporali, P M Lacal, E Botti, A Costanzo, P Rossi, E A Jannini, S Dolci
Melanoma is a dangerous form of skin cancer derived from the malignant transformation of melanocytes. The transcription factor SOX2 is not expressed in melanocytes, however, it has been shown to be differentially expressed between benign nevi and malignant melanomas and to be essential for melanoma stem cell maintenance and expansion in vitro and in xenograft models. By using a mouse model in which BRaf(V600E) mutation cooperates with Pten loss to induce the development of metastatic melanoma, we investigated if Sox2 is required during the process of melanomagenesis, melanoma growth and metastasis and in the acquisition of resistance to BRAF inhibitors (BRAFi) treatments...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28362858/3-bromopyruvate-and-buthionine-sulfoximine-effectively-kill-anoikis-resistant-hepatocellular-carcinoma-cells
#14
Minjong Lee, Ara Jo, Seulki Lee, Jong Bin Kim, Young Chang, Joon Yeul Nam, Hyeki Cho, Young Youn Cho, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Yoon Jun Kim
BACKGROUND & AIMS: Acquisition of anoikis resistance is a prerequisite for metastasis in hepatocellular carcinoma (HCC). However, little is known about how energy metabolism and antioxidant systems are altered in anoikis-resistant (AR) HCC cells. We evaluated anti-tumor effects of a combination treatment of 3-bromopyruvate (3-BP) and buthionine sulfoximine (BSO) in AR HCC cells. METHODS: We compared glycolysis, reactive oxygen species (ROS) production, and chemoresistance among Huh-BAT, HepG2 HCC cells, and the corresponding AR cells...
2017: PloS One
https://www.readbyqxmd.com/read/28341788/discovery-and-pharmacological-characterization-of-jnj-42756493-erdafitinib-a-functionally-selective-small-molecule-fgfr-family-inhibitor
#15
Timothy P S Perera, Eleonora Jovcheva, Laurence Mevellec, Jorge Vialard, Desiree De Lange, Tinne Verhulst, Caroline Paulussen, Kelly Van De Ven, Peter King, Eddy Freyne, David C Rees, Matthew Squires, Gordon Saxty, Martin Page, Ron Gilissen, Christopher W Murray, George Ward, Neil T Thompson, David R Newell, Na Cheng, Liang Xie, Jennifer Yang, Suso J Platero, Jayaprakash D Karkera, Christopher Moy, Patrick Angibaud, Sylvie Laquerre, Matthew V Lorenzi
Fibroblast growth factor (FGF) signaling plays critical roles in key biological processes ranging from embryogenesis to wound healing and has strong links to several hallmarks of cancer. Genetic alterations in FGF receptor (FGFR) family members are associated with increased tumor growth, metastasis, angiogenesis and decreased survival. JNJ-42756493, erdafitinib, is an orally active small molecule with potent tyrosine kinase inhibitory activity against all four FGFR family members and selectivity versus other highly related kinases...
March 24, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28330676/stromal-gene-expression-is-predictive-for-metastatic-primary-prostate-cancer
#16
Fan Mo, Dong Lin, Mandeep Takhar, Varune Rohan Ramnarine, Xin Dong, Robert H Bell, Stanislav V Volik, Kendric Wang, Hui Xue, Yuwei Wang, Anne Haegert, Shawn Anderson, Sonal Brahmbhatt, Nicholas Erho, Xinya Wang, Peter W Gout, James Morris, R Jeffrey Karnes, Robert B Den, Eric A Klein, Edward M Schaeffer, Ashley Ross, Shancheng Ren, S Cenk Sahinalp, Yingrui Li, Xun Xu, Jun Wang, Jian Wang, Martin E Gleave, Elai Davicioni, Yinghao Sun, Yuzhuo Wang, Colin C Collins
BACKGROUND: Clinical grading systems using clinical features alongside nomograms lack precision in guiding treatment decisions in prostate cancer (PCa). There is a critical need for identification of biomarkers that can more accurately stratify patients with primary PCa. OBJECTIVE: To identify a robust prognostic signature to better distinguish indolent from aggressive prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: To develop the signature, whole-genome and whole-transcriptome sequencing was conducted on five PCa patient-derived xenograft (PDX) models collected from independent foci of a single primary tumor and exhibiting variable metastatic phenotypes...
March 19, 2017: European Urology
https://www.readbyqxmd.com/read/28302679/disrupting-androgen-receptor-signaling-induces-snail-mediated-epithelial-mesenchymal-plasticity-in-prostate-cancer
#17
Lu Miao, Lin Yang, Rui Li, Daniel Nava Rodrigues, Mateus Crespo, Jer-Tsong Hsieh, Wayne D Tilley, Johann S de Bono, Luke A Selth, Ganesh V Raj
Epithelial to mesenchymal plasticity (EMP) has been linked to metastasis, stemness, and drug resistance. In prostate cancer (PCa), EMP has been associated with both suppression and activation of androgen receptor (AR) signaling. Here we investigated the effect of the potent AR antagonist enzalutamide on EMP in multiple preclinical models of PCa and patient tissues. Enzalutamide treatment significantly enhanced the expression of EMP drivers (ZEB1, ZEB2, Snail, Twist, and FOXC2) and mesenchymal markers (N-cadherin, fibronectin, and vimentin) in PCa cells, enhanced PCa cell migration, and induced PCa transformation to a spindle, fibroblast-like morphology...
March 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28298340/pre-clinical-validation-of-a-selective-anti-cancer-stem-cell-therapy-for-numb-deficient-human-breast-cancers
#18
Daniela Tosoni, Sarah Pambianco, Blanche Ekalle Soppo, Silvia Zecchini, Giovanni Bertalot, Giancarlo Pruneri, Giuseppe Viale, Pier Paolo Di Fiore, Salvatore Pece
The cell fate determinant Numb is frequently downregulated in human breast cancers (BCs), resulting in p53 inactivation and an aggressive disease course. In the mouse mammary gland, Numb/p53 downregulation leads to aberrant tissue morphogenesis, expansion of the stem cell compartment, and emergence of cancer stem cells (CSCs). Strikingly, CSC phenotypes in a Numb-knockout mouse model can be reverted by Numb/p53 restoration. Thus, targeting Numb/p53 dysfunction in Numb-deficient human BCs could represent a novel anti-CSC therapy...
May 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28292941/preclinical-antitumor-efficacy-of-bay-1129980-a-novel-auristatin-based-anti-c4-4a-lypd3-antibody-drug-conjugate-for-the-treatment-of-non-small-cell-lung-cancer
#19
Jörg Willuda, Lars Linden, Hans-Georg Lerchen, Charlotte Kopitz, Beatrix Stelte-Ludwig, Carol Pena, Claudia Lange, Sven Golfier, Christoph Kneip, Patricia E Carrigan, Kirk Mclean, Joachim Schuhmacher, Oliver von Ahsen, Jörg Müller, Frank Dittmer, Rudolf Beier, Sherif El Sheikh, Jan Tebbe, Gabriele Leder, Heiner Apeler, Rolf Jautelat, Karl Ziegelbauer, Bertolt Kreft
C4.4A (LYPD3) has been identified as a cancer- and metastasis-associated internalizing cell surface protein that is expressed in non-small cell lung cancer (NSCLC), with particularly high prevalence in the squamous cell carcinoma (SCC) subtype. With the exception of skin keratinocytes and esophageal endothelial cells, C4.4A expression is scarce in normal tissues, presenting an opportunity to selectively treat cancers with a C4.4A-directed antibody-drug conjugate (ADC). We have generated BAY 1129980 (C4.4A-ADC), an ADC consisting of a fully human C4...
May 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28288874/loss-of-exosomal-mir-320a-from-cancer-associated-fibroblasts-contributes-to-hcc-proliferation-and-metastasis
#20
Zhuochao Zhang, Xiao Li, Wei Sun, Shuqiang Yue, Jingyue Yang, Junjie Li, Ben Ma, Jianlin Wang, Xisheng Yang, Meng Pu, Bai Ruan, Ge Zhao, Qike Huang, Lin Wang, Kaishan Tao, Kefeng Dou
Cancer-associated fibroblasts (CAFs) play a pivotal role in regulating tumour progression. Therefore, understanding how CAFs communicate with hepatocellular carcinoma (HCC) is crucial for HCC therapy. Recently, exosomes have been considered an important "messenger" between cells. In this study, we performed microRNA (miRNA) sequencing of exosomes derived from CAFs and corresponding para-cancer fibroblasts (PAFs) of HCC patients. We found a significant reduction in the miR-320a level in CAF-derived exosomes...
March 10, 2017: Cancer Letters
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