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https://www.readbyqxmd.com/read/29212028/non-canonical-hedgehog-signaling-is-a-positive-regulator-of-the-wnt-pathway-and-is-required-for-the-survival-of-colon-cancer-stem-cells
#1
Joseph L Regan, Dirk Schumacher, Stephanie Staudte, Andreas Steffen, Johannes Haybaeck, Ulrich Keilholz, Caroline Schweiger, Nicole Golob-Schwarzl, Dominik Mumberg, David Henderson, Hans Lehrach, Christian R A Regenbrecht, Reinhold Schäfer, Martin Lange
Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs). To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH)-positive CSCs...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29182983/mammospheres-of-hormonal-receptor-positive-breast-cancer-diverge-to-triple-negative-phenotype
#2
Mafalda Laranjo, Maria João Carvalho, Tânia Costa, André Alves, Rui Caetano Oliveira, João Casalta-Lopes, Patrícia Cordeiro, Filomena Botas, Ana Margarida Abrantes, Artur Paiva, Carlos Oliveira, Maria Filomena Botelho
OBJECTIVES: This study aimed to characterize mammospheres from hormonal receptor (HR) positive and triple-negative breast cancer (TNBC), hypothesizing a differential profile of CSC and differentiation markers, and a stemness enrichment when successive sphere forming-protocols are performed. METHODS: Breast cancer cells MCF-7 and HCC1806 were submitted to sphere-forming protocols. The first sphere generation (MS1) was cultured in adherent conditions (G1). This procedure was repeated and generations of mammospheres (MS1, MS2, and MS3) and sphere-derived cells in adherent conditions (G1, G2, and G3) were obtained...
November 25, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29175597/delivery-of-nf-%C3%AE%C2%BAb-shrna-using-carbamate-mannose-modified-pei-for-eliminating-cancer-stem-cells
#3
Xiyu Ke, Chuan Yang, Wei Cheng, Yi Yan Yang
The presence of cancer stem cells (CSCs) is one of the main reasons that cause cancer relapse and metastasis. In this study, NF-κB shRNA was delivered to target CSCs using carbamate-mannose modified PEI (CMP) as a non-viral gene vector. The polymer was synthesized by blocking primary amine groups of branched PEI (10kDa) through nucleophilic addition between PEI and protected mannose-functionalized cyclic carbonate, followed by mannose deprotection. CMP/control shRNA nanocomplexes showed lower cytotoxicity and higher transfection efficiency in 4 T1 murine breast cancer cells than unmodified PEI/control shRNA nanocomplexes...
November 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29170132/high-aldh-activity-defines-ovarian-cancer-stem-like-cells-with-enhanced-invasiveness-and-emt-progress-which-are-responsible-for-tumor-invasion
#4
Yiying Li, Tong Chen, Jie Zhu, Haiyan Zhang, Hua Jiang, Hong Sun
Epithelial ovarian cancer (EOC) is highly metastatic and current therapeutics are unsatisfactory. Cancer stem/stem-like cells (CSCs/CSCLs) represent a rare population of undifferentiated oncogenic cells responsible for tumor initiation and maintenance. We identified ovarian cancer ALDH(high) (aldehyde dehydrogenase) population could perform not only strengthened CSCLs properties embodied in colony-formation, CSCs-markers expression, and tumorigenesis in vivo, but also a greater invasive capacity with advanced EMT progress and anti-apoptosis compared with ALDH(low) cells...
November 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29162985/cbfa2t2-is-associated-with-a-cancer-stem-cell-state-in-renal-cell-carcinoma
#5
Du-Chu Chen, You-De Liang, Liang Peng, Yi-Ze Wang, Chun-Zhi Ai, Xin-Xing Zhu, Ya-Wei Yan, Yasmeen Saeed, Bin Yu, Jingying Huang, Yuxin Gao, Jiaqi Liu, Yi-Zhou Jiang, Min Liu, Demeng Chen
Background: Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80-90% of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment. Methods: OncoLnc was used as a tool for interactively exploring survival correlations. Gene manipulation and expression analysis were carried out using siRNA, RT-PCR and Western blotting...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29155365/targeting-aldh2-with-disulfiram-copper-reverses-the-resistance-of-cancer-cells-to-microtubule-inhibitors
#6
Nan-Nan Wang, Li-Hui Wang, Yi Li, Shi-Yuan Fu, Xue Xue, Li-Na Jia, Xiang-Zhong Yuan, Ya-Ting Wang, Xing Tang, Jing-Yu Yang, Chun-Fu Wu
Disulfiram (DSF) in combination with copper (Cu) has been reported to override drug resistance in cancer cells, and DSF combined with chemotherapy based on the microtubule inhibitor vinorelbine appears to prolong survival in non-small cell lung cancer patients. Here, we investigated the mechanisms underlying these findings. DSF/Cu reversed the microtubule inhibitor resistance in A549/Taxol and KB/VCR cells in vitro, and had anti-tumor effects in A549/Taxol and KB/VCR xenograft mice. DSF/Cu and DSF reduced the cancer stem cell (CSC) characteristics of drug-resistant A549/Taxol and KB/VCR cells, including sphere formation, colony generation and migration, and DSF/Cu was more effective than DSF alone...
November 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29141533/targeting-cancer-stem-cells-and-non-stem-cancer-cells-the-potential-of-lipid-based-nanoparticles
#7
Ana Filipa Cruz, Nuno Andre Fonseca, Vera Moura, Sergio Simoes, Joao Nuno Moreira
Background Cancer stem cells (CSCs) have been described as a relevant contributor to tumorigenicity, metastasis, tumor recurrence and drug resistance, making this cell population a relevant target in solid tumors. METHODS: This has stimulated the development of different therapeutic strategies often targeting surface markers (CD44, epithelial cell adhesion molecule (EpCAM), aldehyde dehydrogenase (ALDH) and nucleolin) and/or signaling pathways that are aberrantly activated and contribute to CSCs proliferation and survival...
November 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29137351/microrna-200-associated-with-metastatic-breast-cancer-promotes-traits-of-mammary-luminal-progenitor-cells
#8
Lourdes Sánchez-Cid, Mònica Pons, Juan José Lozano, Nuria Rubio, Marta Guerra-Rebollo, Aroa Soriano, Laia Paris-Coderch, Miquel F Segura, Raquel Fueyo, Judit Arguimbau, Erika Zodda, Raquel Bermudo, Immaculada Alonso, Xavier Caparrós, Marta Cascante, Arash Rafii, Yibin Kang, Marian Martínez-Balbás, Stephen J Weiss, Jerónimo Blanco, Montserrat Muñoz, Pedro L Fernández, Timothy M Thomson
MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137219/functional-characterization-of-lysine-specific-demethylase-2-lsd2-kdm1b-in-breast-cancer-progression
#9
Lin Chen, Shauna N Vasilatos, Ye Qin, Tiffany A Katz, Chunyu Cao, Hao Wu, Nilgun Tasdemir, Kevin M Levine, Steffi Oesterreich, Nancy E Davidson, Yi Huang
Flavin-dependent histone demethylases govern histone H3K4 methylation and act as important chromatin modulators that are extensively involved in regulation of DNA replication, gene transcription, DNA repair, and heterochromatin gene silencing. While the activities of lysine-specific demethylase 1 (LSD1/KDM1A) in facilitating breast cancer progression have been well characterized, the roles of its homolog LSD2 (KDM1B) in breast oncogenesis are relatively less understood. In this study, we showed that LSD2 protein level was significantly elevated in malignant breast cell lines compared with normal breast epithelial cell line...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29121598/novel-c-terminal-heat-shock-protein-90-inhibitors-ku711-and-ku757-are-effective-in-targeting-head-and-neck-squamous-cell-carcinoma-cancer-stem-cells
#10
C Subramanian, K J Kovatch, M W Sim, G Wang, M E Prince, T E Carey, R Davis, B S J Blagg, M S Cohen
Advanced head and neck squamous cell carcinoma (HNSCC) remains a therapeutic challenge due to the development of therapy resistance. Several studies have implicated the development of cancer stem cells as a possible mechanism for therapy resistance in HNSCC. Heat shock protein 90's (Hsp90's) molecular chaperone function is implicated in pathways of resistance in HNSCC. Therefore, in the present study, we investigated the efficacy of novel C-terminal Hsp90 inhibitors (KU711 and KU757) in targeting HNSCC cancer stem cells (CSCs)...
November 6, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29110840/immunohistochemical-and-genetic-characteristics-of-lung-cancer-mimicking-organizing-pneumonia
#11
Tomohiro Ichikawa, Koichi Saruwatari, Sachiyo Mimaki, Masato Sugano, Keiju Aokage, Motohiro Kojima, Tomoyuki Hishida, Satoshi Fujii, Junji Yoshida, Takeshi Kuwata, Atsushi Ochiai, Kenji Suzuki, Masahiro Tsuboi, Koichi Goto, Katsuya Tsuchihara, Genichiro Ishii
INTRODUCTION: Lung cancer mimicking organizing pneumonia (LCOP) is a novel radiological entity of lung adenocarcinoma that could be misdiagnosed as inflammatory lesions. However, the characteristic biological and genetic features of LCOP are not fully clarified. MATERIALS AND METHODS: We used thin-section CT images to select cases of (LCOP) among surgically resected lung adenocarcinoma patients. We compared the clinicopathological characteristics and the immunophenotypes of LCOP (n=44) and other lepidic-predominant adenocarcinomas (non-LCOP, n=56)...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29106390/glycolysis-gatekeeper-pdk1-reprograms-breast-cancer-stem-cells-under-hypoxia
#12
F Peng, J-H Wang, W-J Fan, Y-T Meng, M-M Li, T-T Li, B Cui, H-F Wang, Y Zhao, F An, T Guo, X-F Liu, L Zhang, L Lv, D-K Lv, L-Z Xu, J-J Xie, W-X Lin, E W-F Lam, J Xu, Q Liu
Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH(+) subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival...
November 6, 2017: Oncogene
https://www.readbyqxmd.com/read/29091754/a-targetable-egfr-dependent-tumor-initiating-program-in-breast-cancer
#13
Paul Savage, Alexis Blanchet-Cohen, Timothée Revil, Dunarel Badescu, Sadiq M I Saleh, Yu-Chang Wang, Dongmei Zuo, Leah Liu, Nicholas R Bertos, Valentina Munoz-Ramos, Mark Basik, Kevin Petrecca, Jamil Asselah, Sarkis Meterissian, Marie-Christine Guiot, Atilla Omeroglu, Claudia L Kleinman, Morag Park, Jiannis Ragoussis
Therapies targeting epidermal growth factor receptor (EGFR) have variable and unpredictable responses in breast cancer. Screening triple-negative breast cancer (TNBC) patient-derived xenografts (PDXs), we identify a subset responsive to EGFR inhibition by gefitinib, which displays heterogeneous expression of wild-type EGFR. Deep single-cell RNA sequencing of 3,500 cells from an exceptional responder identified subpopulations displaying distinct biological features, where elevated EGFR expression was significantly enriched in a mesenchymal/stem-like cellular cluster...
October 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/29081945/thiophene-bridged-aldehydes-tbas-image-aldh-activity-in-cells-via-modulation-of-intramolecular-charge-transfer
#14
Santanu Maity, Corinne M Sadlowski, Jung-Ming George Lin, Che-Hong Chen, Li-Hua Peng, Eun-Soo Lee, Giri K Vegesna, Charles Lee, Se-Hwa Kim, Daria Mochly-Rosen, Sanjay Kumar, Niren Murthy
Aldehyde dehydrogenases (ALDHs) catalyze the oxidation of an aldehyde to a carboxylic acid and are implicated in the etiology of numerous diseases. However, despite their importance, imaging ALDH activity in cells is challenging due to a lack of fluorescent imaging probes. In this report, we present a new family of fluorescent probes composed of an oligothiophene flanked by an aldehyde and an electron donor, termed thiophene-bridged aldehydes (TBAs), which can image ALDH activity in cells. The TBAs image ALDH activity via a fluorescence sensing mechanism based on the modulation of intramolecular charge transfer (ICT) and this enables the TBAs and their ALDH-mediated oxidized products, thiophene-bridged carboxylates (TBCs), to have distinguishable fluorescence spectra...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29074539/nf-kb-promotes-ovarian-tumorigenesis-via-classical-pathways-supporting-proliferative-cancer-cells-and-alternative-pathways-supporting-aldh-cancer-stem-like-cells
#15
Carrie D House, Elizabeth Jordan, Lidia Hernandez, Michelle Ozaki, Jana M James, Marianne Kim, Michael J Kruhlak, Eric Batchelor, Fathi Elloumi, Margaret C Cam, Christina M Annunziata
Understanding the mechanisms supporting tumor-initiating cells (TIC) is vital to combat advanced stage recurrent cancers. Here we show that in advanced ovarian cancers NF-kB signaling via the RelB transcription factor supports TIC populations by directly regulating the cancer stem-like associated enzyme aldehyde dehydrogenase (ALDH). Loss of RelB significantly inhibited spheroid formation, ALDH expression and activity, chemoresistance, and tumorigenesis in subcutaneous and intrabursal mouse xenograft models of human ovarian cancer...
October 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/29073729/eugenol-potentiates-cisplatin-anti-cancer-activity-through-inhibition-of-aldh-positive-breast-cancer-stem-cells-and-the-nf-%C3%AE%C2%BAb-signaling-pathway
#16
Syed S Islam, Ibtehaj Al-Sharif, Ahlam Sultan, Amer Al-Mazrou, Adnane Remmal, Abdelilah Aboussekhra
Triple-negative breast tumors are very aggressive and contain relatively high proportion of cancer stem cells, and resistant to chemotherapeutic drugs including cisplatin. To overcome these limitations, we combined eugenol, a natural polyphenolic molecule with cisplatin to normalize cisplatin mediated toxicity and potential drug resistance. Interestingly, the combination treatment provided significantly greater cytotoxic and pro-apoptotic effects as compared to treatment with eugenol or cisplatin alone on several triple-negative breast cancer cells both in vitro and in vivo...
October 26, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29065820/recent-advances-in-antabuse-disulfiram-the-importance-of-its-metal-binding-ability-to-its-anticancer-activity
#17
Maricela Viola-Rhenals, Kush Rohit Patel, Laura Jaimes-Santamaria, Guojun Wu, Jinbao Liu, Q Ping Dou
Disulfiram (DSF, also called tetraethylthiuram disulphide), a disulfide derivative of N,N-diethyldithiocarbamate (DEDTC), is an antialcoholism drug that is currently being repurposed as a promising anticancer drug. DSF has been investigated in many studies, including in vitro, in vivo, preclinical and clinical. Various mechanisms have been proposed to be responsible for the cytotoxic effect of DSF on cancer cells. DSF is a pro-drug which is converted to its metabolite DEDTC in human body. A complex of DEDTC with a metal ion [usually Cu(II) or Zn(II)] could be responsible for the anticancer activity of DSF in breast, prostate, glioblastoma, lung, melanoma, cervical, colorectal cancers as well as myeloma and leukemia...
October 23, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29050299/exostosin-1-regulates-cancer-cell-stemness-in-doxorubicin-resistant-breast-cancer-cells
#18
Sarala Manandhar, Chang-Gu Kim, Sun-Hee Lee, Soo Hyun Kang, Nikita Basnet, You Mie Lee
Cancer stem cells (CSCs) are associated with cancer recurrence following radio/chemotherapy owing to their high resistance to therapeutic intervention. In this study, we investigated the role of exostoxin 1 (EXT1), an endoplasmic reticulum (ER)-residing type II transmembrane glycoprotein, in cancer cell stemness. DNA microarray analysis revealed that doxorubicin-resistant MCF7/ADR cells have high levels of EXT1 expression compared to its parental cell line, MCF7. These cells showed significantly higher populations of CSCs and larger populations of aldehyde dehydrogenase (ALDH(+)) and CD44(+)/CD24(-)cells, as compared to MCF7 cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049740/phenotypic-plasticity-in-uveal-melanoma-is-not-restricted-to-a-tumor-subpopulation-and-is-unrelated-to-cancer-stem-cell-characteristics
#19
Rachel E Doherty, Karen Sisley, David W Hammond, Ian G Rennie, Neil A Cross
Purpose: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and approximately half of those diagnosed will die of metastasis. This study investigates whether UM progression is driven by a subpopulation of stem-like cells, termed "cancer stem cells" (CSCs). Methods: Expression of postulated stem cell markers aldehyde dehydrogenase (ALDH), CD44, and CD133 was analyzed in UM cell lines and primary UM short-term cultures (STCs) established from tumor samples...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29048400/cd10-aldh-cells-are-the-sole-cisplatin-resistant-component-of-a-novel-ovarian-cancer-stem-cell-hierarchy
#20
Brendan Ffrench, Claudia Gasch, Karsten Hokamp, Cathy Spillane, Gordon Blackshields, Thamir Mahmoud Mahgoub, Mark Bates, Louise Kehoe, Aoibhinn Mooney, Ronan Doyle, Brendan Doyle, Dearbhaile O'Donnell, Noreen Gleeson, Bryan T Hennessy, Britta Stordal, Ciaran O'Riain, Helen Lambkin, Sharon O'Toole, John J O'Leary, Michael F Gallagher
It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CSC hierarchies and chemoresistance in an ovarian cancer model. Using a single cell-based approach to CSC discovery and validation, we report a novel, four-component CSC hierarchy based around the markers cluster of differentiation 10 (CD10) and aldehyde dehydrogenase (ALDH)...
October 19, 2017: Cell Death & Disease
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