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Transferrin AND cancer

David M Kingsley, Cassandra L Roberge, Alena Rudkouskaya, Denzel E Faulkner, Margarida Barroso, Xavier Intes, David T Corr
3D multicellular aggregates, and more advanced organotypic systems, have become central tools in recent years to study a wide variety of complex biological processes. Most notably, these model systems have become mainstream within oncology (multicellular tumor spheroids) and regenerative medicine (embryoid bodies) research. However, the biological behavior of these in vitro tissue surrogates is extremely sensitive to their aggregate size and geometry. Indeed, both of these geometrical parameters are key in producing pathophysiological gradients responsible for cellular and structural heterogeneity, replicating in vivo observations...
February 15, 2019: Acta Biomaterialia
Ai Kohata, P K Hashim, Kou Okuro, Takuzo Aida
Transferrin (Tf) is known to induce transcytosis, which is a consecutive endocytosis/exocytosis event. We developed a Tf-appended nanocaplet (Tf NC⊃siRNA) for the purpose of realizing siRNA delivery into deep tissues and RNA interference (RNAi) subsequently. For obtaining Tf NC⊃siRNA, a macromonomer (Az Gu) bearing multiple guanidinium ion (Gu+ ) units, azide (N3 ) groups, and trityl (Trt)-protected thiol groups in the main chain, side chains, and termini, respectively, was newly designed. Because of a multivalent Gu+ -phosphate salt-bridge interaction, Az Gu can adhere to siRNA along its strand...
February 6, 2019: Journal of the American Chemical Society
Zar Chi Soe, Jun Bum Kwon, Raj Kumar Thapa, Wenquan Ou, Hanh Thuy Nguyen, Milan Gautam, Kyung Taek Oh, Han-Gon Choi, Sae Kwang Ku, Chul Soon Yong, Jong Oh Kim
In this study, a transferrin (Tf )-conjugated polymeric nanoparticle was developed for the targeted delivery of the chemotherapeutic agent doxorubicin (Dox) in order to overcome multi-drug resistance in cancer treatment. Our objective was to improve Dox delivery for producing significant antitumor efficacy in Dox-resistant (R) breast cancer cell lines with minimum toxicity to healthy cells. The results of our experiments revealed that Dox was successfully loaded inside a transferrin (Tf )-conjugated polymeric nanoparticle composed of poloxamer 407 (F127) and 123 (P123) (Dox/F127 & P123-Tf ), which produced nanosized particles (~90 nm) with a low polydispersity index (~0...
February 1, 2019: Pharmaceutics
Xiaoliang Xie, Yaqin He, Hai Li, Dong Yu, Li Na, Ting Sun, Dong Zhang, Xinrong Shi, Yuhan Xia, Tao Jiang, Shikuo Rong, Shaoqi Yang, Xiaoqiang Ma, Guangxian Xu
OBJECTIVE: The aim of the present study was to investigate the effects of prebiotics (containing fructooligosaccharides, xylooligosaccharides, polydextrose, and resistant dextrin) intake on immune function and intestinal microbiota structure in perioperative patients with colorectal cancer (CRC). METHODS: A randomized, double-blind, no-treatment parallel control clinical trial involving 140 perioperative patients (90 men and 50 women, aged 40-75 y) with CRC was performed...
November 29, 2018: Nutrition
Emily A Wyatt, Mark E Davis
HER2-targeted therapies effectively control systemic disease, but their efficacy against brain metastases is hindered by their low penetration of the blood-brain and blood-tumor barriers (BBB and BTB). We investigate brain uptake and antitumor efficacy of transferrin receptor (TfR)-targeted, therapeutic nanoparticles designed to transcytose the BBB/BTB in three murine models. Two known models involving intracranial (IC) or intracardiac (ICD) injection of human breast cancer cells were employed, as was a third model developed here involving intravenous (IV) injection of the cells to form whole-body tumors that eventually metastasize to the brain...
January 2019: Bioengineering & Translational Medicine
Jiayan Lang, Xiao Zhao, Xiuchao Wang, Ying Zhao, Yiye Li, Ruifang Zhao, Keman Cheng, Yao Li, Xuexiang Han, Xiaowei Zheng, Hao Qin, Marzieh Geranpayehvaghei, Jian Shi, Gregory J Anderson, Jihui Hao, He Ren, Guangjun Nie
Rapidly growing cancer cells exhibit a strong dependence on iron for their survival. Thus, iron-removing drugs, iron chelators, have potential applications in cancer treatment. Deferoxamine (DFO) is an efficient iron chelator, but its short circulation half-life and ability to induce hypox-ia-inducible factor 1α (HIF1α) overexpression restricts its use as an antitumor agent. In the present study, we first found that a pattern of iron-related protein expression favoring higher intracellular iron closely correlates with shorter overall and relapse-free survival in pancreatic cancer patients...
January 24, 2019: ACS Nano
Yi Chai, Feng Tan, Sumin Ye, Feixiang Liu, Qiaoling Fan
Osteoporosis (OP) is an age-related disease, and osteoporotic fracture is one of the major causes of disability and mortality in elderly patients (>70 years old). As the pathogenesis and molecular mechanism of OP remain unclear, the identification of disease biomarkers is important for guiding research and providing therapeutic targets. In the present study, core genes and microRNAs (miRNAs) associated with OP were identified. Differentially expressed genes (DEGs) between human mesenchymal stem cell specimens from normal osseous tissues and OP tissues were detected using the GEO2R tool of the Gene Expression Omnibus database and Morpheus...
January 2019: Oncology Letters
Xiaofeng Xu, Tao Liu, Jun Wu, Yijin Wang, Ying Hong, Huaijun Zhou
Cervical cancer is one of the most prevalent gynecologic malignancies and has remained an intractable cancer over the past decades. We analyzed the aberrant expression patterns of cervical cancer using RNA-Seq data from The Cancer Genome Atlas (TCGA). A total of 3352 differently expressed genes (DEGs) were identified in 306 cervical cancer samples compared with 3 control samples, with 1401 genes upregulated and 1951 downregulated. Under Kaplan-Meier analysis, 76 out of these DEGs with a significantly different survival rate between patients with high and low expression groups were picked out and uploaded to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, which identified a transferrin receptor (TFRC)-involved HIF-1 signaling pathway (p < 0...
January 17, 2019: Cancer Gene Therapy
Zheng Zhang, Jingrong Yang, Qingqing Min, Chenjie Ling, Debabrata Maiti, Jiaying Xu, Liqiang Qin, Kai Yang
Hypoxic microenvironments in the solid tumor play a negative role in radiotherapy. Holo-lactoferrin (holo-Lf) is a natural protein, which acts as a potential ligand of transferrin receptor (TfR). In this work, an anticancer drug, doxorubicin (Dox)-loaded liposome-holo-Lf nanocomposites, is developed for tumor targeting and imaging guided combined radiochemotherapy. Dox-loaded liposome-holo-Lf (Lf-Liposome-Dox) nanocomposites exhibit significant cellular uptake likely owing to the TfR receptor-mediated targeting accumulation of Lf-Liposome-Dox nanocomposites...
January 15, 2019: Small
Grzegorz Mariusz Sukiennicki, Wojciech Marciniak, Magdalena Muszyńska, Piotr Baszuk, Satish Gupta, Katarzyna Białkowska, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Marcin Lener, Sandra Pietrzak, Tomasz Gromowski, Karolina Prajzendanc, Alicja Łukomska, Piotr Waloszczyk, Janusz Zenon Wójcik, Rodney Scott, Jan Lubiński, Anna Jakubowska
BACKGROUND: Lung cancer is the most common adult malignancy accounting for the largest proportion of cancer related deaths. Iron (Fe) is an essential trace element and is a component of several major metabolic pathways playing an important role in many physiological processes. In this study we evaluated the association between Fe concentration in serum, iron metabolism parameters and genetic variaton in 7 genes involved in iron metabolism and anti-oxidative processes with the incidence of lung cancer in Poland...
2019: PloS One
Marina A Naves, Angelica E Graminha, Legna C Vegas, Liany Luna-Dulcey, João Honorato, Antonio C S Menezes, Alzir A Batista, Marcia R Cominetti
The triple negative breast cancer subtype (TNBC) is highly aggressive, metastatic and corresponds to 15-20% of diagnosed cases. TNBC treatment is hampered because these cells usually do not respond to hormonal therapy and develop resistance to chemotherapeutic drugs. On the other hand, the severe side effects of cisplatin represent an obstacle for its clinical use. Ruthenium (Ru)-based complexes have emerged as promising antitumor and antimetastatic substitutes for cisplatin. In this study, we demonstrated the effects of a Ru/biphosphine complex, containing gallic acid (GA) as a ligand, [Ru(GA)(dppe)2]PF6, hereafter called Ru(GA), on a TNBC cell line, comparing to the effects in a non-tumor breast cell line...
January 11, 2019: Molecular Pharmaceutics
Hanh Thuy Nguyen, Zar Chi Soe, Kwan Yeol Yang, Cao Dai Phung, Lan Thi-Trinh Nguyen, Jee-Heon Jeong, Sung Giu Jin, Han-Gon Choi, Sae Kwang Ku, Chul Soon Yong, Jong Oh Kim
Porous palladium (Pd) nanoparticles have garnered great research attention due to their potential anticancer activity and photothermal effect. In this study, a transferrin-conjugated pH-sensitive platform (Tf-PPP), comprising porous Pd nanoparticles (PdNPs) and paclitaxel (PTX), was successfully developed for combined chemo-phototherapy. Tf-PPPs have a small size of 164.6 ± 8.7 nm, PDI of 0.278 ± 0.029, and negative charge (-13.2 ± 1.8 mV). Poly(acrylic acid)-poly(ethylene oxide) (PAA-PEO), a pH sensitive polymer, was used to achieve pH-dependent drug release from nanoparticles...
January 3, 2019: Colloids and Surfaces. B, Biointerfaces
María Jesús Laso-Morales, Roser Vives, Andrea Vallejo-Tarrat, Novella Caló, Anna Valle-Beltran, Caridad Pontes
BACKGROUND: Patients with colorectal cancer (CRC) often present with associated anaemia which is usually present at the time of diagnosis and is aggravated during the postoperative period due to blood loss during the surgery process. Several guidelines advocate for the treatment of postoperative anaemia in these patients in order to prevent complications and allogeneic blood transfusions. However, there are no publications to shed light on the effectiveness of intravenous iron (IVI) administration after CRC surgery and the optimal dose and regimen...
January 7, 2019: Trials
Madeline Neiveyans, Rana Melhem, Christophe Arnoult, Thomas Bourquard, Marta Jarlier, Muriel Busson, Adrien Laroche, Martine Cerutti, Martine Pugnières, David Ternant, Nadège Gaborit, Thierry Chardès, Anne Poupon, Valérie Gouilleux-Gruart, Andre Pèlegrin, Marie-Alix Poul
Targeting transferrin receptor 1 (TfR1) with monoclonal antibodies is a promising therapeutic strategy in cancer as tumor cells often overexpress TfR1 and show increased iron needs. We have re-engineered six anti-human TfR1 single-chain variable fragment (scFv) antibodies into fully human scFv2 -Fcγ1 and IgG1 antibodies. We selected the more promising candidate (H7), based on its ability to inhibit TfR1-mediated iron-loaded transferrin internalization in Raji cells (B-cell lymphoma). The H7 antibody displayed nanomolar affinity for its target in both formats (scFv2 -Fcγ1 and IgG1), but cross-reacted with mouse TfR1 only in the scFv2 -Fc format...
January 3, 2019: MAbs
Sirirat Boondireke, Michèle Léonard, Alain Durand, Benjamas Thanomsub Wongsatayanon
The cytotoxicity of monomyristin (MM), a monoacylglycerol, was investigated against cervical cancer cells (HeLa) and two normal cells (Vero and endometrial epithelial cells). MM exhibited cytotoxicity specifically to HeLa cells and not against normal cells except at the highest investigated doses (> 500 μg/mL). MM was showed to increase apoptotic dead cells by intrinsic mitochondrial pathway. To overcome the poor water solubility of MM and increase its efficacy against HeLa cells, MM was encapsulated into dextran-covered polylactide (PLA) nanoparticles (NPs)...
December 21, 2018: Colloids and Surfaces. B, Biointerfaces
You Ke, Cheng Xiang
Background: Thyroid cancer becomes the most common endocrine cancer with the greatest growing incidence in this decade. Sorafenib is a multikinase inhibitor for the treatment of progressive radioactive iodine-refractory differentiated thyroid cancer (DTC), while the off-target toxicity effect is usually inconvenient for patients taking. Methods: In this study, hollow mesoporous silica nanoparticles (HMSNs) with transferrin modification (Tf-HMSNs) were loaded with sorafenib (sora@Tf-HMSNs) to help targeted delivery of sorafenib...
2018: International Journal of Nanomedicine
Daniel Hauser, Manuela Estermann, Ana Milosevic, Lukas Steinmetz, Dimitri Vanhecke, Dedy Septiadi, Barbara Drasler, Alke Petri-Fink, Vincent Ball, Barbara Rothen-Rutishauser
Polydopamine can form biocompatible particles that convert light into heat. Recently, a protocol has been optimized to synthesize polydopamine/protein hybrid nanoparticles that retain the biological function of proteins, and combine it with the stimuli-induced heat generation of polydopamine. We have utilized this novel system to form polydopamine particles, containing transferrin (PDA/Tf). Mouse melanoma cells, which strongly express the transferrin receptor, were exposed to PDA/Tf nanoparticles (NPs) and, subsequently, were irradiated with a UV laser...
December 17, 2018: Nanomaterials
Li Zhang, Xiaoyu Zhu, Shijia Wu, Yazhou Chen, Shiming Tan, Yingjie Liu, Wenzheng Jiang, Jing Huang
Background: cis-Dichlorodiamineplatinum (CDDP) was one of the most common used drugs in clinic for cancer treatment. However, CDDP caused a variety of side effects. The abundant carboxyl groups on the surface of poly glutamic acid (PGA) could be modified with various kinds of targeted ligands. PGA delivery system loaded CDDP for cancer therapies possesses potential to overcome the side effects. Materials and methods: In this study, we constructed a safe and efficient anticancer drug delivery system PGA-Asp-maleimide-cisplatin-peptide complex (PAMCP), which was loaded with CDDP and conjugated with the transferrin receptor (TFR)-targeting peptide through a maleimide functional linker...
2018: International Journal of Nanomedicine
Attilio Marino, Enrico Almici, Simone Migliorin, Christos Tapeinos, Matteo Battaglini, Valentina Cappello, Marco Marchetti, Giuseppe de Vito, Riccardo Cicchi, Francesco Saverio Pavone, Gianni Ciofani
Major obstacles to the successful treatment of gliolastoma multiforme are mostly related to the acquired resistance to chemotherapy drugs and, after surgery, to the cancer recurrence in correspondence of residual microscopic foci. As innovative anticancer approach, low-intensity electric stimulation represents a physical treatment able to reduce multidrug resistance of cancer and to induce remarkable anti-proliferative effects by interfering with Ca2+ and K+ homeostasis and by affecting the organization of the mitotic spindles...
December 4, 2018: Journal of Colloid and Interface Science
Geetha Maniam, Chun-Wai Mai, Mohd Zulkefeli, Christine Dufès, Doryn Meam-Yee Tan, Ju-Yen Fu
Plant-derived phytonutrients have emerged as health enhancers. Tocotrienols from the vitamin E family gained high attention in recent years due to their multi-targeted biological properties, including lipid-lowering, neuroprotection, anti-inflammatory, antioxidant, and anticancer effects. Despite well-defined mechanism of action as an anti-cancer agent, their clinical use is hampered by poor pharmacokinetic profile and low oral bioavailability. Delivery systems based on nanotechnology were proven to be advantageous in elevating the delivery of tocotrienols to tumor sites for enhanced efficacy...
2018: Frontiers in Pharmacology
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