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https://www.readbyqxmd.com/read/29353230/a-model-of-dormant-emergent-metastatic-breast-cancer-progression-enabling-exploration-of-biomarker-signatures
#1
Amanda M Clark, Manu Kumar, Sarah Wheeler, Carissa Young, Raman Venkataramanan, Donna Stolz, Linda Griffith, Douglas A Lauffenburger, Alan Wells
Breast cancer mortality predominantly results from dormant micrometastases that emerge as fatal outgrowths years after initial diagnosis. In order to gain insights concerning factors associated with emergence of liver metastases, we recreated spontaneous dormancy in an all-human ex vivo hepatic microphysiological system (MPS). Seeding this MPS with small numbers (<0.05% by cell count) of the aggressive MDA-MB-231 breast cancer cell line, two populations formed: actively proliferating ('growing'; EdU+), and spontaneously quiescent ('dormant'; EdU-)...
January 20, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29352988/stat3-as-a-promising-chemoresistance-biomarker-associated-with-the-cd44-high-cd24-low-aldh-bcscs-like-subset-of-the-triple-negative-breast-cancer-tnbc-cell-line
#2
Milene Pereira Moreira, Letícia da Conceição Braga, Geovanni Dantas Cassali, Luciana Maria Silva
The cancer stem cell (CSC) concept is currently employed to explain the mechanism of multidrug resistance that is implicated in the reduced efficacy of many chemotherapeutic agents, consequently leading to metastatic spread and disease relapse. We searched for potential predictive markers of doxorubicin (DOX) resistance in breast cancer stem cells (BCSCs) of the BT-549 human triple-negative breast cancer (TNBC) cell line classified as a claudin-low subtype. In this study, we show that BT-549 presents a BCSCs-like subset determined by a CD44+/high/CD24-/low/ALDH1+ phenotype...
January 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29352223/zeb1-confers-chemotherapeutic-resistance-to-breast-cancer-by-activating-atm
#3
Xiang Zhang, Zhen Zhang, Qing Zhang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Guosheng Ren, Shuang Yang
Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351753/mesenchymal-stem-cells-show-functional-defect-and-decreased-anti-cancer-effect-after-exposure-to-chemotherapeutic-drugs
#4
Chinnapaka Somaiah, Atul Kumar, Renu Sharma, Amit Sharma, Trishna Anand, Jina Bhattacharyya, Damodar Das, Sewali Deka Talukdar, Bithiah Grace Jaganathan
BACKGROUND: Mesenchymal stem cells (MSC) are used for several therapeutic applications to improve the functions of bone, cardiac, nervous tissue as well as to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the non-hematopoietic stromal cells of the bone marrow and are important for the maintenance of normal hematopoiesis. Chemotherapeutic drugs used for treatment of leukemia extensively damage the stromal cells and alter their gene expression profiles. METHODS: We determined the changes in adipogenic, osteogenic differentiation, phenotypic and gene expression in MSC during treatment with chemotherapeutic drugs cytarabine, daunorubicin and vincristine...
January 19, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29350904/nanoplatform-assembled-from-a-cd44-targeted-prodrug-and-smart-liposomes-for-dual-targeting-of-tumor-microenvironment-and-cancer-cells
#5
Yaqi Lv, Chaoran Xu, Xiangmei Zhao, Chenshi Lin, Xin Yang, Xiaofei Xin, Li Zhang, Chao Qin, Xiaopeng Han, Lei Yang, Wei He, Lifang Yin
The tumor microenvironment (TME) plays a critical role in tumor initiation, progression, invasion and metastasis. Therefore, a therapy that combines chemotherapeutic drugs with a TME modulator could be a promising route for cancer treatment. This paper reports a nanoplatform self-assembled from a hyaluronic acid (HA)-paclitaxel (PTX) (HA-PTX) prodrug and marimastat (MATT)-loaded thermosensitive liposomes (LTSLs) (MATT-LTSLs) for the dual targeting of the TME and cancer cells. Interestingly, the prodrug HA-PTX can self-assemble on both positively and negatively charged liposomes, forming hybrid nanoparticles (HNPs, 100 nm)...
January 19, 2018: ACS Nano
https://www.readbyqxmd.com/read/29350902/hierarchically-self-assembled-supramolecular-host-guest-delivery-system-for-delivery-of-chemotherapeutics-to-drug-resistant-cancer-tumours
#6
Hongwei Cheng, Xiaoshan Fan, Xiaoyuan Wang, Enyi Ye, Xian Jun Loh, Zibiao Li, Yun-Long Wu
In this report, a new star-like copolymer -CD-g-(PNIPAAm-b-POEGA)x consisting of a -CD core, grafted with temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(oligo(ethylene glycol) acrylate) (POEGA) in a block copolymer of the arms, was used to deliver chemotherapeutics to drug resistant cancer tumours. The first step of the self-assembly process involves the encapsulation of chemotherapeutics through host-guest inclusion complexation between the -cyclodextrin cavity and the anti-cancer drug...
January 19, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29350534/discovery-of-tetrahydroisoquinoline-containing-cxcr4-antagonists-with-improved-in-vitro-admet-properties
#7
Eric J Miller, Edgars Jecs, Valarie M Truax, Brooke M Katzman, Yesim A Tahirovic, Robert J Wilson, Katie M Kuo, Michelle B Kim, Huy H Nguyen, Manohar T Saindane, Huanyu Zhao, Tao Wang, Chi S Sum, Mary Ellen Cvijic, Gretchen M Schroeder, Lawrence J Wilson, Dennis C Liotta
CXCR4 is a 7-transmembrane receptor expressed by hematopoietic stem cells and progeny, as well as by ≥ 48 different cancers types. CXCL12, the only chemokine ligand of CXCR4, is secreted within the tumor microenvironment, providing sanctuary for CXCR4+ tumor cells from immune surveillance and chemotherapeutic elimination by 1) stimulating pro-survival signaling and 2) recruiting CXCR4+ immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract and support CXCR4+ metastatic growths. Accordingly, CXCR4 antagonists can potentially obstruct CXCR4-mediated pro-survival signaling, recondition the CXCR4+ leukocyte infiltrate from immunosuppressive to immunoreactive, and inhibit CXCR4+ cancer cell metastasis...
January 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29350484/paraptosis-inducing-nanomedicine-overcomes-cancer-drug-resistance-for-a-potent-cancer-therapy
#8
Yongcun Zhou, Feiteng Huang, Ying Yang, Pingli Wang, Zhen Zhang, Yining Tang, Youqing Shen, Kai Wang
Most chemotherapeutic drugs and their nanomedicine formulations exert anticancer activity by inducing cancer cell apoptosis. However, cancer cells inherently have and acquire many antiapoptosis mechanisms, causing cancer drug resistance and poor prognoses in patients. Herein, a potent paraptosis-inducing nanomedicine is reported that causes quick nonapoptotic death of cancer cells, overcoming apoptosis-based resistance and effectively inhibiting drug-resistant tumor growth. The nanomedicine is composed of micelles made from an amphiphilic 8-hydroxyquinoline (HQ)-conjugate block copolymer with polyethylene glycol...
January 19, 2018: Small
https://www.readbyqxmd.com/read/29350175/update-on-the-nephrotoxicity-of%C3%A2-novel%C3%A2-anticancer-agents%C3%A2
#9
Eliezer Zachary Nussbaum, Mark A Perazella
Anticancer drug-induced kidney disease is a problem commonly encountered by nephrologists. The number of medications employed by oncologists causing acute and chronic kidney injury as well as electrolyte and acid-base disturbances has increased significantly over the past several decades. While conventional chemotherapeutic drugs induce a number of kidney lesions, emergence of very effective and well-tolerated targeted therapies and novel immunotherapies has increased the occurrence of drug-induced acute and chronic kidney injury in cancer patients...
January 19, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/29348889/metformin-and-temozolomide-a-synergic-option-to-overcome-resistance-in-glioblastoma-multiforme-models
#10
Silvia Valtorta, Alessia Lo Dico, Isabella Raccagni, Daniela Gaglio, Sara Belloli, Letterio S Politi, Cristina Martelli, Cecilia Diceglie, Marcella Bonanomi, Giulia Ercoli, Valentina Vaira, Luisa Ottobrini, Rosa Maria Moresco
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor survival. Cytoreduction in association with radiotherapy and temozolomide (TMZ) is the standard therapy, but response is heterogeneous and life expectancy is limited. The combined use of chemotherapeutic agents with drugs targeting cell metabolism is becoming an interesting therapeutic option for cancer treatment. Here, we found that metformin (MET) enhances TMZ effect on TMZ-sensitive cell line (U251) and overcomes TMZ-resistance in T98G GBM cell line...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348885/drug-resistance-in-doxorubicin-resistant-fl5-12-hematopoietic-cells-elevated-mdr1-drug-efflux-and-side-population-positive-and-decreased-bcl2-family-member-expression
#11
Linda S Steelman, Steve L Abrams, Peter Ruvolo, Vivian Ruvolo, Lucio Cocco, Stefano Ratti, Alberto M Martelli, Luca M Neri, Saverio Candido, Massimo Libra, James A McCubrey
Chemotherapeutic drug treatment can result in the emergence of drug-resistant cells. By culturing an interleukin-3 (IL-3)-dependent cell line, FL5.12 cells in the presence of the chemotherapeutic drug doxorubicin, we isolated FL/Doxo cells which are multi-drug resistant. Increased levels of drug efflux were detected in FL/Doxo cells which could be inhibited by the MDR1 inhibitor verapamil but not by the MRP1 inhibitor MK571. The effects of TP53 and MEK1 were examined by infection of FL/Doxo cells with retroviruses encoding either a dominant negative TP-53 gene (FL/Doxo+ TP53 (DN) or a constitutively-activated MEK-1 gene (FL/Doxo + MEK1 (CA)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348852/reduced-fbxw7-expression-in-pancreatic-cancer-correlates-with-poor-prognosis-and-chemotherapeutic-resistance-via-accumulation-of-mcl1
#12
Norihiro Ishii, Kenichiro Araki, Takehiko Yokobori, Dorgormaa Gantumur, Takahiro Yamanaka, Bolag Altan, Mariko Tsukagoshi, Takamichi Igarashi, Akira Watanabe, Norio Kubo, Yasuo Hosouchi, Hiroyuki Kuwano, Ken Shirabe
Pancreatic cancer is a highly malignant tumor type with poor outcomes, and elucidation of the mechanisms involved in cancer progression and therapeutic resistance is critical. FBXW7 is a key regulator of tumor malignant potential, and its substrate MCL1 regulates therapeutic resistance in human malignancies. Therefore, determination of the relevance of FBXW7 expression is critical for improving patient outcomes. In this study, we investigated the function and clinical significance of FBXW7 in pancreatic cancer...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348846/st6galnac1-plays-important-roles-in-enhancing-cancer-stem-phenotypes-of-colorectal-cancer-via-the-akt-pathway
#13
Tadashi Ogawa, Yoshihiko Hirohashi, Aiko Murai, Toshihiko Nishidate, Kenji Okita, Liming Wang, Yuzuru Ikehara, Tetsuta Satoyoshi, Akihiro Usui, Terufumi Kubo, Munehide Nakastugawa, Takayuki Kanaseki, Tomohide Tsukahara, Goro Kutomi, Tomohisa Furuhata, Koichi Hirata, Noriyuki Sato, Toru Mizuguchi, Ichiro Takemasa, Toshihiko Torigoe
Colorectal cancer (CRC) is a mortal disease due to treatment resistance, recurrence and distant metastasis. Emerging evidence has revealed that a small sub-population of cancer cells termed cancer stem cells (CSCs)/ cancer-initiating cells (CICs) is endowed with high levels of tumor-initiating ability, self-renewal ability and differentiation ability and is responsible for treatment resistance, recurrence and distant metastasis. Eradication of CSCs/CICs is essential to improve current treatments. However, the molecular mechanisms by which CSCs/CICs are maintained are still elusive...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348537/radionuclides-transform-chemotherapeutics-into-phototherapeutics-for-precise-treatment-of-disseminated-cancer
#14
Nalinikanth Kotagiri, Matthew L Cooper, Michael Rettig, Christopher Egbulefu, Julie Prior, Grace Cui, Partha Karmakar, Mingzhou Zhou, Xiaoxia Yang, Gail Sudlow, Lynne Marsala, Chantiya Chanswangphuwana, Lan Lu, LeMoyne Habimana-Griffin, Monica Shokeen, Xinming Xu, Katherine Weilbaecher, Michael Tomasson, Gregory Lanza, John F DiPersio, Samuel Achilefu
Most cancer patients succumb to disseminated disease because conventional systemic therapies lack spatiotemporal control of their toxic effects in vivo, particularly in a complicated milieu such as bone marrow where progenitor stem cells reside. Here, we demonstrate the treatment of disseminated cancer by photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting strategy and a contact-facilitated nanomicelle technology enabled highly selective delivery and co-localization of titanocene and radiolabelled fluorodeoxyglucose in disseminated multiple myeloma cells...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29348307/non-mammalian-models-of-multiple-endocrine-neoplasia-type-2
#15
REVIEW
Tirtha K Das, Ross L Cagan
Twenty-five years ago, RET was identified as the primary driver of multiple endocrine neoplasia type 2 (MEN2) syndrome. MEN2 is characterized by several transformation events including pheochromocytoma, parathyroid adenoma and, especially penetrant, medullary thyroid carcinoma (MTC). Overall, MTC is a rare but aggressive type of thyroid cancer for which no effective treatment currently exists. Surgery, radiation, radioisotope treatment and chemotherapeutics have all shown limited success, and none of these approaches have proven durable in advanced disease...
February 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29348080/squid-ink-polysaccharide-prevents-chemotherapy-induced-injury-in-the-testes-of-reproducing-mice
#16
Ping Luo, Hua-Zhong Liu, Xiao-Yan Le, Hui Du, Xin-Huang Kang
The present study was conducted to investigate the preventive effects of squid ink polysaccharides (SIP) on the damage of sperm and reproduction induced by cyclophosphamide that is most commonly used for treating clinically cancers. Male Kunming mice exposed to cyclophosphamide were administered with SIP and were sacrificed to determine sperm parameters, testicular antioxidant ability and reproductive capacity. Data indicated that cyclophosphamide caused obvious changes in mice such as significant reduction (P<0...
January 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29347215/optomechanical-proposal-for-monitoring-microtubule-mechanical-vibrations
#17
Sh Barzanjeh, V Salari, J A Tuszynski, M Cifra, C Simon
Microtubules provide the mechanical force required for chromosome separation during mitosis. However, little is known about the dynamic (high-frequency) mechanical properties of microtubules. Here, we theoretically propose to control the vibrations of a doubly clamped microtubule by tip electrodes and to detect its motion via the optomechanical coupling between the vibrational modes of the microtubule and an optical cavity. In the presence of a red-detuned strong pump laser, this coupling leads to optomechanical-induced transparency of an optical probe field, which can be detected with state-of-the art technology...
July 2017: Physical Review. E
https://www.readbyqxmd.com/read/29345906/prediction-of-hot-spots-at-myeloid-cell-leukemia-1-inhibitors-interface-using-energy-estimation-and-alanine-scanning-mutagenesis
#18
Parthiban Marimuthu, Kalaimathy Singaravelu
Myeloid cell leukemia 1 (Mcl1) is an anti-apoptotic protein that plays central role in apoptosis regulation. Also, Mcl1 has the potency to resist apoptotic cues resulting in up-regulation and cancer cell protection. A molecular probe that has the potential to specifically target Mcl1, and thereby provoke its down-regulatory activity is very essential. The aim of the current study is to probe the internal conformational dynamics of protein motions and potential binding mechanism in response to a series of picomolar range Mcl1 inhibitors using explicit-solvent molecular dynamics (MD) simulations...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29344837/evaluation-of-the-profile-and-mechanism-of-neurotoxicity-of-water-soluble-cu-p-4-pf6-and-au-p-4-pf6-p-thp-or-pta-anticancer-complexes
#19
C Ceresa, G Nicolini, S Semperboni, V Gandin, M Monfrini, F Avezza, P Alberti, A Bravin, M Pellei, C Santini, Guido Cavaletti
[Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp = tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I) and gold(I) water-soluble complexes characterized by high anticancer activity in a wide range of solid tumors, often able to overcome drug resistance of platinum-based compounds. For these reasons, they have been proposed as a valid alternative to platinum-based chemotherapeutic drugs (e.g., cisplatin and oxaliplatin). In vitro experiments performed on organotypic cultures of dorsal root ganglia (DRG) from 15-day-old rat embryos revealed that copper-based compounds were not neurotoxic even at concentrations higher than the IC50 obtained in human cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower concentration than IC50 in cancer cell lines...
January 17, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29344663/adeno-associated-virus-type-2-mediated-gene-transfer-of-a-short-hairpin-rna-targeting-human-igfbp-2-suppresses-the-proliferation-and-invasion-of-mda-mb-468-cells
#20
Chao Gao, Ru-Song Zhang, Nan Zheng, Chen Wang
Adeno-associated virus 2 (AAV2) is prepotent in the biological treatment of breast tumor because of its low pathogenicity and immunogenicity. Our previous study demonstrated that insulin‑like growth factor‑binding protein 2 (IGFBP‑2) was highly expressed in patients with breast metastasis. In the present study, the effects of recombinant AAV2 on the growth and metastasis of breast cancer cells were determined in vitro, and in vivo. rAAV2-ZsGreen-shRNA-scramble and rAAV2‑ZsGreen‑shRNA‑hIGFBP‑2 were used to transfect MDA‑MB‑468, and MCF‑10A cells respectively, and observed that these virus could not penetrate the normal human breast epithelia MCF‑10A cell line...
January 16, 2018: Molecular Medicine Reports
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