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https://www.readbyqxmd.com/read/29454280/8-chrysoeriol-as-a-potential-bcl-2-inhibitor-triggers-apoptosis-of-sw1990-pancreatic-cancer-cells
#1
Yiwen Zhang, Zhimei Li, Qiuxia Min, Abulizi Palida, Yiyuan Zhang, Ruotian Tang, Lixia Chen, Hua Li
8-Chrysoeriol, a bioactive flavanoid, was firstly identified to bind directly to BCL-2 as BH3 mimetics by structure-based virtual ligand screening. And 3D docking model revealed the molecular basis of 8-Chrysoeriol targeting to BCL-2. The interaction between 8-Chrysoeriol and BCL-2 was further confirmed using Microscale Thermophoresis (MST) technique. Meanwhile, high expression level of antiapoptotic protein BCL-2 was detected in SW1990 pancreatic cancer cells and 8-Chrysoeriol showed obvious proapoptosis effect against SW1990 in vitro...
February 2, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29454038/dendritic-cells-as-cancer-therapeutics
#2
REVIEW
Christian E Bryant, Sarah Sutherland, Benjamin Kong, Michael S Papadimitrious, Derek N J Hart
The ability of immune therapies to control cancer has recently generated intense interest. This therapeutic outcome is reliant on T cell recognition of tumour cells. The natural function of dendritic cells (DC) is to generate adaptive responses, by presenting antigen to T cells, hence they are a logical target to generate specific anti-tumour immunity. Our understanding of the biology of DC is expanding, and they are now known to be a family of related subsets with variable features and function. Most clinical experience to date with DC vaccination has been using monocyte-derived DC vaccines...
February 14, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29453900/downregulation-of-reticulocalbin-1-differentially-facilitates-apoptosis-and-necroptosis-in-human-prostate-cancer-cells
#3
Xiaofei Liu, Nianzhao Zhang, Dawei Wang, Deyu Zhu, Quan Yuan, Xiulei Zhang, Lilin Qian, Huanmin Niu, Yi Lu, Guijie Ren, Keli Tian, Huiqing Yuan
Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca 2+ -binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with Cyclin B, not Cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively...
February 17, 2018: Cancer Science
https://www.readbyqxmd.com/read/29453896/the-anti-malarial-mefloquine-inhibits-nf-%C3%AE%C2%BAb-signaling-and-induces-apoptosis-in-colorectal-cancer-cells
#4
Xin Xu, Jun Wang, Kunkun Han, Shaoyan Li, Feng Xu, Yili Yang
The NF-κB signaling pathway is activated in many colorectal cancer (CRC) cells and in the tumor microenvironment, which plays a critical role in cancer initiation, development, and response to therapies. We found in the present study that the widely used antimalarial drug mefloquine was a NF-κB inhibitor that blocked the activation of IκBα kinase, leading to the reduction of IκBα degradation, decrease of p65 phosphorylation, and suppressed expression of NF-κB target genes in colorectal cancer cells. We also found that mefloquine induced growth arrest and apoptosis of colorectal cancer cells harboring phosphorylated p65 in culture and mice...
February 17, 2018: Cancer Science
https://www.readbyqxmd.com/read/29453833/ketamine-induces-apoptosis-in-lung-adenocarcinoma-cells-by-regulating-the-expression-of-cd69
#5
Xuhui Zhou, Peihong Zhang, Wei Luo, Lei Zhang, Rong Hu, Yu Sun, Hong Jiang
Ketamine, an anesthetic, analgesic, or sedative, is widely used for the treatment of cancer pain. Recently, ketamine has been also reported to be tumor repressor for inhibiting proliferation, invasion, and migration, and inducing apoptosis in many cancers. However, whether ketamine can induce the apoptosis of lung adenocarcinoma (LUAD) and which downstream molecular mediates its function remain largely unknown. A LUAD cell line A549 was incubated with ketamine at 0, 1, 10, and 100 μmol/L for 24 h. Trypan blue staining was used to detect the cell viability...
February 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29453600/argininosuccinate-synthetase-1-ass1-loss-in-high-grade-neuroendocrine-carcinomas-of-the-urinary-bladder-implications-for-targeted-therapy-with-adi-peg-20
#6
Sounak Gupta, Divya Sahu, John S Bomalaski, Igor Frank, Stephen A Boorjian, Prabin Thapa, John C Cheville, Donna E Hansel
High-grade neuroendocrine carcinomas (HGNECs) of the urinary bladder encompass small cell (SCNEC) and large cell neuroendocrine carcinomas (LCNEC). Currently, recommended initial management is with systemic chemotherapy, followed by consolidative therapy with either radical cystectomy or radiotherapy in patients with localized disease. Nevertheless, survival in this setting remains poor. We therefore evaluated the potential to modify arginine metabolism as an alternative, targeted therapy approach in these carcinomas...
February 16, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29453361/heterogeneity-and-mutation-in-kras-and-associated-oncogenes-evaluating-the-potential-for-the-evolution-of-resistance-to-targeting-of-kras-g12c
#7
Vincent L Cannataro, Stephen G Gaffney, Carly Stender, Zi-Ming Zhao, Mark Philips, Andrew E Greenstein, Jeffrey P Townsend
Activating mutations in RAS genes are associated with approximately 20% of all human cancers. New targeted therapies show preclinical promise in inhibiting the KRAS G12C variant. However, concerns exist regarding the effectiveness of such therapies in vivo given the possibilities of existing intratumor heterogeneity or de novo mutation leading to treatment resistance. We performed deep sequencing of 27 KRAS G12-positive lung tumors to determine the prevalence of other oncogenic mutations within KRAS or within commonly mutated downstream genes that could confer resistance at the time of treatment...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29453321/inhibition-of-cd95-cd95l-signaling-with-apg101-prevents-invasion-and-enhances-radiation-therapy-for-glioblastoma
#8
Jonas Blaes, Carina M Thomé, Philipp-Niclas Pfenning, Petra Rübmann, Felix Sahm, Antje Wick, Theresa Bunse, Torsten Schmenger, Jaromir Sykora, Andreas von Deimling, Benedikt Wiestler, Christian Merz, Manfred Jugold, Uwe Haberkorn, Amir Abdollahi, Jürgen Debus, Christian Gieffers, Claudia Kunz, Martin Bendszus, Michael Kluge, Michael Platten, Harald Fricke, Wolfgang Wick, Dieter Lemke
CD95 (Fas/APO-1), a death receptor family member, activity has been linked to tumorigenicity in multiple cancers, including glioblastoma multiforme (GBM). A phase II clinical trial on relapsed glioblastoma patients demonstrated that targeted inhibition of CD95 signaling via the CD95 ligand (CD95L) binding and neutralizing Fc-fusion protein APG101 (asunercept) prolonged patient survival. While CD95 signaling may be relevant for multiple aspects of tumor growth, the mechanism of action of APG101 in glioblastoma is not clear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453314/ar-expression-in-breast-cancer-ctcs-associates-with-bone-metastases
#9
Nicola Aceto, Aditya Bardia, Ben S Wittner, Maria C Donaldson, Ryan O'Keefe, Amanda Engstrom, Francesca Bersani, Yu Zheng, Valentine Comaills, Kira Niederhoffer, Huili Zhu, Olivia MacKenzie, Toshi Shioda, Dennis Sgroi, Ravi Kapur, David T Ting, Beverly Moy, Sridhar Ramaswamy, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran
Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing (RNA-seq) was performed of circulating tumor cells (CTCs) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452958/brca1-mutation-spectrum-functions-and-therapeutic-strategies-the-story-so-far
#10
REVIEW
Babita Sharma, Raman Preet Kaur, Sonali Raut, Anjana Munshi
BRCA1 gene mutations account for about 25-28% of hereditary Breast Cancer as BRCA1 is included in the category of high penetrance genes. Except for few commonmutations, there is a heterogenous spectrum of BRCA1 mutations in various ethnic groups. 185AGdel and 5382ins Care the most common BRCA1 alterations (founder mutations) which have been identified in most of the population. This review has been compiled with an aim to consolidate the information on genetic variants reported in BRCA1 found in various ethnic groups, their functional implications if known; involvement of BRCA1 in various cellular pathways/processes and potential BRCA1 targeted therapies...
January 8, 2018: Current Problems in Cancer
https://www.readbyqxmd.com/read/29452859/evaluation-of-liquid-biopsies-for-detection-of-emerging-mutated-genes-in-metastatic-colorectal-cancer
#11
Hiroyasu Furuki, Takeshi Yamada, Goro Takahashi, Takuma Iwai, Michihiro Koizumi, Seiichi Shinji, Yasuyuki Yokoyama, Kohki Takeda, Nobuhiko Taniai, Eiji Uchida
BACKGROUND: Detection of gene mutations is important for planning molecular targeted therapy. Although most gene mutations are concordant between primary colon cancers and their liver metastases, new mutations can emerge in metastases. The liquid biopsy is a newly developed, gene analytic method to detect mutations in metastatic tumors. In this prospective study, we evaluated the applicability of liquid biopsies in the detection of mutations in primary and metastatic tumors. METHODS: We included 22 patients with liver metastases from colorectal cancer and extracted DNA from primary colorectal tumors, metastatic liver tumors, and peripheral blood (liquid biopsy)...
February 2, 2018: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29452772/metabolic-and-lipidomic-reprogramming-in-renal-cell-carcinoma-subtypes-reflects-regions-of-tumor-origin
#12
Elke Schaeffeler, Florian Büttner, Anna Reustle, Verena Klumpp, Stefan Winter, Steffen Rausch, Pascale Fisel, Jörg Hennenlotter, Stephan Kruck, Arnulf Stenzl, Judith Wahrheit, Denise Sonntag, Marcus Scharpf, Falko Fend, Abbas Agaimy, Arndt Hartmann, Jens Bedke, Matthias Schwab
BACKGROUND: Renal cell carcinoma (RCC) consists of prognostic distinct subtypes derived from different cells of origin (eg, clear cell RCC [ccRCC], papillary RCC [papRCC], and chromophobe RCC [chRCC]). ccRCC is characterized by lipid accumulation and metabolic alterations, whereas data on metabolic alterations in non-ccRCC are limited. OBJECTIVE: We assessed metabolic alterations and the lipid composition of RCC subtypes and ccRCC-derived metastases. Moreover, we elucidated the potential of metabolites/lipids for subtype classification and identification of therapeutic targets...
February 13, 2018: European Urology Focus
https://www.readbyqxmd.com/read/29452455/complex-hur-function-in-pancreatic-cancer-cells
#13
REVIEW
Jonathan R Brody, Dan A Dixon
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with dismal patient outcomes. The underlying core genetic drivers of disease have been identified in human tumor specimens and described in genetically engineered mouse models. These genetic drivers of PDAC include KRAS signaling, TP53 mutations, and genetic loss of the SMAD4 tumor suppressor protein. Beyond the known mutational landscape of PDAC genomes, alternative disrupted targets that extend beyond conventional genetic mutations have been elusive and understudied in the context of PDAC cell therapeutic resistance and survival...
February 16, 2018: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/29452346/beyond-second-line-therapy-in-patients-with-metastatic-colorectal-cancer-a-systematic-review
#14
D Arnold, G W Prager, A Quintela, A Stein, S Moreno, N Mounedji, J Taieb
Background: The optimal chemotherapeutic regimen for use beyond the second-line for patients with metastatic colorectal cancer (mCRC) remains unclear. Materials and methods: We systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the efficacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC...
February 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29452344/overexpression-of-blm-promotes-dna-damage-and-increased-sensitivity-to-platinum-salts-in-triple-negative-breast-and-serous-ovarian-cancers
#15
N J Birkbak, Y Li, S Pathania, A Greene-Colozzi, M Dreze, C Bowman-Colin, Z Sztupinszki, M Krzystanek, M Diossy, N Tung, P D Ryan, J E Garber, D P Silver, J D Iglehart, Z C Wang, D Szuts, Z Szallasi, A L Richardson
Background: Platinum based therapy is an effective treatment for a subset of triple negative breast cancer and ovarian cancer patients. In order to increase response rate and decrease unnecessary use, robust biomarkers that predict response to therapy are needed. Patients and methods: We performed an integrated genomic approach combining differential analysis of gene expression and DNA copy number in sensitive compared to resistant triple negative breast cancers in two independent neoadjuvant cisplatin treated cohorts...
February 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29452272/ph-sensitive-doxorubicin-conjugated-prodrug-micelles-with-charge-conversion-for-cancer-therapy
#16
Boxuan Ma, Weihua Zhuang, Yanan Wang, Rifang Luo, Yunbing Wang
Intelligent drug delivery systems with prolonged circulation time, reduced drug leakage in blood, target site-triggered drug release and endosomal escape are attractive and ideal for malignant tumor therapy. Herein, doxorubicin (DOX)-conjugated smart polymeric micelles based on 4-carboxy benzaldehyde-grafted poly (L-lysine)-block-poly (methacryloyloxyethyl phosphorylcholine) (PLL(CB/DOX)-b-PMPC) copolymer are prepared. DOX and electronegative 4-carboxy benzaldehyde are conjugated to the PLL block via an imine linkage and as a result, the drug loaded micelles exhibited the pH-triggered charge-conversion property and accelerated drug release at tumor pH...
February 13, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29451980/tri-layer-polymeric-shells-containing-magnetite-nanocarrier-mediated-lcs-1-delivery-for-synthetic-lethal-therapy-of-blm-defective-colorectal-cancer-cells
#17
Anuradha Gupta, Anas Ahmad, Hardeep Singh, Sharanjeet Kaur, Neethu K M, Md Meraj Ansari, Govindasamy Jayamurugan, Rehan Khan
Synthetic lethality is a molecular targeted therapy for selective killing of cancer cells. We exploited a lethal interaction between Superoxide dismutase1 inhibition and Bloom syndrome gene product (BLM) defect for the treatment of colorectal cancer (CRC) cells (HCT 116) with lung cancer screen-1 (LCS-1) loaded customized nanocarrier. LCS-1 has poor aqueous solubility. To overcome its limitations, customized nanocarrier (NC), composed of magnetite core coated with three polymeric shells namely, aminocellulose, branched poly(amidoamine) and paraben-PEG, was developed for encapsulating LCS-1...
February 16, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29451745/detection-of-ros1-positive-non-small-cell-lung-cancer-on-cytological-specimens-using-immunocytochemistry
#18
Tatjana Vlajnic, Spasenija Savic, Audrey Barascud, Betty Baschiera, Michel Bihl, Bruno Grilli, Michelle Herzog, Julien Rebetez, Lukas Bubendorf
BACKGROUND: Rearrangements of the ROS1 oncogene are found in 1% to 2% of non-small cell lung cancers (NSCLC) and are regarded as mutually exclusive oncogenic driver mutations. Since the approval of targeted therapy for ROS1-positive NSCLC, ROS1 testing has become a part of the diagnostic routine. Fluorescence in situ hybridization (FISH), optionally selected for by immunohistochemistry on histological material, is a common practice for the detection of ROS1 rearrangements. However, NSCLC often is diagnosed by cytology alone, requiring predictive marker testing on cytological specimens...
February 16, 2018: Cancer Cytopathology
https://www.readbyqxmd.com/read/29451577/an-upconversion-nanoplatform-with-extracellular-ph-driven-tumor-targeting-ability-for-improved-photodynamic-therapy
#19
Fujin Ai, Na Wang, Xiaoman Zhang, Tianying Sun, Qi Zhu, Wei Kong, Feng Wang, Guangyu Zhu
Upconversion nanoparticles (UCNPs) are widely utilized for photodynamic therapy (PDT) due to their specific upconverting luminescence that utilizes near infrared (NIR) light to excite photosensitizers (PSs) for PDT. The efficiency of UCNP-based PDT will be improved if the cancer-targeting property of nanomedicine is enhanced. Herein, we employed the pH low insertion peptide (pHLIP), a cancer-targeting moiety, to functionalize an 808 nm excited UCNP-based nanoplatform that has a minimized over-heating effect to perform PDT...
February 16, 2018: Nanoscale
https://www.readbyqxmd.com/read/29451575/functionalized-cu-3-bis-3-nanoparticles-for-dual-modal-imaging-and-targeted-photothermal-photodynamic-therapy
#20
Yanke Wang, Dongdong Cai, Huixia Wu, Yu Fu, Yang Cao, Yingjian Zhang, Dongmei Wu, Qiwei Tian, Shiping Yang
Multifunctional nano-biomaterials with the integration of diagnostic and therapeutic functions have shown great promise in improving the efficacy of cancer therapy. Herein, a new nanoplatform based on functionalized Cu 3 BiS 3 nanoparticles (NPs) is fabricated for tumour-targeted combination phototherapy. The as-synthesized hydrophobic Cu 3 BiS 3 NPs are modified with DSPE-PEG/DSPE-PEG-NH 2 , followed by the conjugation of the photosensitizer chlorin e6 (Ce6) and the target ligand folic acid (FA). The introduced Ce6 can further form a chelate complex with Gd 3+ ...
February 16, 2018: Nanoscale
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