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https://www.readbyqxmd.com/read/29786931/real-time-monitoring-of-prodrug-activation-by-direct-mode-of-chemiluminescence
#1
Doron Shabat, Samer Gnaim, Anna Scomparin, Sayantan Das, Ronit Satchi-Fainaro
The majority of theranostic prodrugs reported so far relay information through a fluorogenic response generated upon release of the active chemotherapeutic agent. A chemiluminescence detection mode offers significant advantages over fluorescence, mainly due to the superior signal-to-noise ratio of chemiluminescence. Here we report the design and synthesis of the first theranostic prodrug monitored by a chemiluminescence diagnostic mode. As a representative model we prepared a prodrug from the chemotherapeutic monomethyl auristatin E designed for activation by β-galactosidase...
May 22, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29786746/luteolin-induces-myelodysplastic-syndrome%C3%A2-derived-cell-apoptosis-via-the-p53%C3%A2-dependent-mitochondrial-signaling-pathway-mediated-by-reactive-oxygen-species
#2
Weimin Dong, Yan Lin, Yang Cao, Yue Liu, Xiaobao Xie, Weiying Gu
Luteolin, a common dietary flavonoid, induces the apoptosis of cells in several types of cancer. However, its role in myelodysplastic syndrome (MDS) and the potential underlying mechanisms remain to be elucidated. To evaluate the potential benefit and underlying mechanisms of luteolin in MDS cells, the viability of SKM‑1 cells and primary bone marrow (PBM) mononuclear cells from patients with intermediate‑ or high‑risk MDS were assessed using a Cell Counting Kit‑8 assay. The apoptotic features of cell morphology were assessed using Wright‑Giemsa staining, DNA fragmentation was analyzed by agarose gel electrophoresis, and the extent of apoptosis was quantified by flow cytometry (FCM)...
May 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786668/scf-c-kit-signaling-increased-mucin2-production-by-maintaining-atoh1-expression-in-mucinous-colorectal-adenocarcinoma
#3
Ping Shen, Shu Yang, Haimei Sun, Guilan Li, Bo Wu, Fengqing Ji, Tingyi Sun, Deshan Zhou
Mucinous colorectal adenocarcinoma (MCA) patients often a show high risk of malignant potential and a poorer survival rate. Given that the pathological feature and oncobiological characteristics of MCA are correlated with its abundant extracellular mucin2 (MUC2), we paid interest toward investigating the key factor that promotes MUC2 production exposure to highly-activated stem cell factor (SCF)/c-KIT signaling, which we believed to contribute to MCA formation. Long-term azoxymethane and dextran sodium sulfate treatment successfully induced MCA only in wild-type (WT) mice at week 37 and 43, while all c-kit loss-of-function mutant mice (Wadsm/m ) developed non-MCA...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786517/estrogen-receptor-%C3%AE-potential-target-for-therapy-in-adult-granulosa-cell-tumors
#4
Alessandra Ciucci, Gabriella Ferrandina, Floriana Mascilini, Flavia Filippetti, Giovanni Scambia, Gian Franco Zannoni, Daniela Gallo
OBJECTIVE: Adult granulosa cell tumor (AGCT) is a rare form of sex-cord stromal ovarian tumors. Due to their origin, AGCTs secrete estrogens, and thus, estrogen receptor (ER)-mediated signaling has been considered as a possible target for therapy. The aim of the present study was to get insights into estrogen receptor status and activity in AGCTs, as a strategy to provide molecular support for personalized hormonal treatments. METHODS: We evaluated by immunohistochemistry the expression of ERα, ERβ isoforms (i...
May 18, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29786427/diallyl-trisulfide-induces-apoptosis-of-human-papillary-thyroid-carcinoma-bcpap-cells-through-activating-mapk-signaling-pathway
#5
Jie Pan, Li Zhang, Shichen Xu, Xian Cheng, Huixin Yu, Jiandong Bao, Rong-Rong Lu
This study aimed to elucidate the potential effects of diallyl trisulfide (DATS) on human papillary thyroid carcinoma BCPAP cells and its underling mechanisms. DATS is one of the organosulfur compounds which derived from garlic. In this study, we demonstrated that compared to the solvent control, DATS treatment at concentrations of 5, 10 and 20 μΜ decreased cell survival rate of BCPAP cells to 84.51 ± 2.67%, 57.16 ± 1.18%, 41.22 ± 1.19% respectively. DATS also caused cell cycle arrest at G0/G1 phase and the proportion of cells arrested in G0/G1 phase rose from 68...
May 22, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29786110/multi%C3%A2-layered-prevention-and-treatment-of-chronic-inflammation-organ-fibrosis-and-cancer-associated-with-canonical-wnt-%C3%AE-%C3%A2-catenin-signaling-activation-review
#6
Masaru Katoh
β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulators (BCL9, BCL9L, CREBBP/CBP, EP300/p300, FOXM1, MED12, SMARCA4/BRG1 and TCF/LEF). Gain‑of‑function CTTNB1 mutations are detected in bladder cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer and uterine cancer, whereas loss‑of‑function CTNNB1 mutations are also detected in human cancer...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786075/tp53-gain-of-function-mutation-promotes-inflammation-in-glioblastoma
#7
Seok Won Ham, Hee-Young Jeon, Xiong Jin, Eun-Jung Kim, Jun-Kyum Kim, Yong Jae Shin, Yeri Lee, Se Hoon Kim, Seon Yong Lee, Sunyoung Seo, Min Gi Park, Hye-Mi Kim, Do-Hyun Nam, Hyunggee Kim
Glioblastoma (GBM), the most severe and common brain tumor in adults, is characterized by multiple somatic mutations and aberrant activation of inflammatory responses. Immune cell infiltration and subsequent inflammation cause tumor growth and resistance to therapy. Somatic loss-of-function mutations in the gene encoding tumor suppressor protein p53 (TP53) are frequently observed in various cancers. However, numerous studies suggest that TP53 regulates malignant phenotypes by gain-of-function (GOF) mutations...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29786073/integrin-%C3%AE-6%C3%AE-4-src-akt-signaling-induces-cellular-senescence-by-counteracting-apoptosis-in-irradiated-tumor-cells-and-tissues
#8
Seung Hee Jung, Minyoung Lee, Hyun A Park, Hyung Chul Lee, Donghee Kang, Hyun Jung Hwang, Chanho Park, Dong-Min Yu, Yu Ri Jung, Mi-Na Hong, Yong-Nyun Kim, Heon Joo Park, Young-Gyu Ko, Jae-Seon Lee
Cellular senescence refers to an irreversible growth arrest that is triggered by various intrinsic and extrinsic stresses. Many recent studies have demonstrated that cellular senescence plays a crucial role in the regression of tumors exposed to ionizing radiation (IR), but the underlying mechanism remains unknown. Here we show that the activation of integrin β4 is essential for IR-induced cellular senescence. IR treatment results in the phosphorylation of integrin β4 at tyrosine residue 1510, leading to activation of the integrin α6β4-Src-AKT signaling pathway...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785943/-roles-and-molecular-mechanisms-of-hypoxia-inducible-factors-in-renal-cell-carcinoma
#9
Jun Xia Zou, Ke Chen
Renal cancer is a common urologic malignancy. However, the therapeutic options for metastatic renal cancer patients are limited. Hypoxia (low oxygen) is a fundamental microenvironmental determinant of solid tumor pathophysiology. Recent data from molecular and clinical studies indicate that hypoxia-inducible factors (HIFs) play critical roles in the development and progress of renal cell carcinoma (RCC). The HIF transcription factor family is a type of heterodimeric transcription factor consisting of HIF-α and HIF-β subunits and can transcriptionally activate genes that mediate the hypoxic response...
May 20, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29785773/molecular-tension-probes-to-investigate-the-mechanopharmacology-of-single-cells-a-step-toward-personalized-mechanomedicine
#10
Kornelia Galior, Victor Pui-Yan Ma, Yang Liu, Hanquan Su, Nusaiba Baker, Reynold A Panettieri, Cherry Wongtrakool, Khalid Salaita
Given that dysregulation of mechanics contributes to diseases ranging from cancer metastasis to lung disease, it is important to develop methods for screening the efficacy of drugs that target cellular forces. Here, nanoparticle-based tension sensors are used to quantify the mechanical response of individual cells upon drug treatment. As a proof-of-concept, the activity of bronchodilators is tested on human airway smooth muscle cells derived from seven donors, four of which are asthmatic. It is revealed that airway smooth muscle cells isolated from asthmatic donors exhibit greater traction forces compared to the control donors...
May 22, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29785726/t2-hypointense-rim-of-breast-mass-lesions-on-magnetic-resonance-images-radiologic-pathologic-correlation
#11
Kazuaki Nakashima, Takayoshi Uematsu, Takashi Sugino, Kaoru Takahashi, Seiichirou Nishimura, Yukiko Tadokoro, Tomomi Hayashi
We investigated the radiologic-pathologic correlation of a strong hypointense rim on T2-weighted images (T2-hypo-rim) surrounding breast mass lesions and evaluated its clinical significance. We retrospectively reviewed 3503 consecutive breast magnetic resonance imaging (MRI) examinations. The T2-hypo-rim was defined as a border of strong hypointensity compared with the fat signal on fat-suppressed T2-weighted images. Detected lesions with T2-hypo-rim were classified as a solid or cystic mass with MRI and correlated with histopathologic findings...
May 21, 2018: Breast Journal
https://www.readbyqxmd.com/read/29785403/immunotherapy-for-hepatocellular-carcinoma-current-advances-and-future-expectations
#12
REVIEW
Yingjun Xie, Yien Xiang, Jiyao Sheng, Dan Zhang, Xiaoxiao Yao, Yongsheng Yang, Xuewen Zhang
Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29785244/more-than-just-an-immunosuppressant-the-emerging-role-of-fty720-as-a-novel-inducer-of-ros-and-apoptosis
#13
REVIEW
Teruaki Takasaki, Kanako Hagihara, Ryosuke Satoh, Reiko Sugiura
Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29785126/impact-of-targeting-transforming-growth-factor-%C3%AE-2-with-antisense-ot-101-on-the-cytokine-and-chemokine-profile-in-patients-with-advanced-pancreatic-cancer
#14
Osmond J D'Cruz, Sanjive Qazi, Larn Hwang, Kevin Ng, Vuong Trieu
Background: Overexpression of the cytokine - transforming growth factor-beta 2 (TGF-β2) - has been implicated in the malignant progression of pancreatic cancer (PAC). OT-101 (trabedersen) is an antisense oligodeoxynucleotide designed to target the human TGF-β2 mRNA. In a Phase I/II study, OT-101 treatment with subsequent chemotherapy was characterized by outstanding overall survival (OS) in patients with PAC. Objective: This study sought to identify 1) co-regulated sets of cyto-/chemokines; 2) potential mechanisms that link TGF-β receptor type 2 receptor inhibition that may result in the induction of a cytokine storm; and 3) predictive biomarkers for OS outcome in OT-101-treated patients with PAC...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29785121/association-between-angiogenesis-and-cytotoxic-signatures-in-the-tumor-microenvironment-of-gastric-cancer
#15
Yi Feng, Ying Dai, Zhihua Gong, Jia-Nan Cheng, Longhui Zhang, Chengdu Sun, Xianghua Zeng, Qingzhu Jia, Bo Zhu
Background: A suppressive immune microenvironment and pathological angiogenesis are hallmarks of gastric cancer. Theoretically, immune checkpoint inhibitors (ICIs) stimulate pre-primed neoantigen-specific T cells, and antiangiogenic agents then facilitate their infiltration into the tumor niche by promoting vascular normalization. Currently, the interconnections of these two phenotypes and their relevance to the tumor microenvironment (TME) have not been fully characterized in gastric cancer...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29785118/traditional-chinese-medicine-astragalus-polysaccharide-enhanced-antitumor-effects-of-the-angiogenesis-inhibitor-apatinib-in-pancreatic-cancer-cells-on-proliferation-invasiveness-and-apoptosis
#16
Jun Wu, Jing Wang, Qiang Su, Wei Ding, Teng Li, Junxian Yu, Bangwei Cao
Background: Traditional chemotherapy and molecular targeted therapy have shown modest effects on the survival of patients with pancreatic cancer. The current study aimed to investigate the antitumor effects of apatinib, Astragalus polysaccharide (APS), and the combination of both the drugs in pancreatic cancer cells and further explore the molecular mechanisms in vitro. Materials and methods: Expression of vascular endothelial growth factor receptor-2 (VEGFR-2) in human pancreatic cancer cell lines ASPC-1, PANC-1, and SW1990 was detected by Western blotting...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29785050/the-tumor-suppressor-dlc1-inhibits-cancer-progression-and-oncogenic-autophagy-in-hepatocellular-carcinoma
#17
Hui-Ta Wu, Cheng-Rong Xie, Jie Lv, He-Qiang Qi, Fei Wang, Sheng Zhang, Qin-Liang Fang, Fu-Qiang Wang, Yu-Yan Lu, Zhen-Yu Yin
Downregulation of deleted in liver cancer 1 (DLC1) is associated with poor prognosis of various cancers, but its functional mechanisms in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the roles of DLC1 in tumor progression and autophagy of HCC. We found that DLC1 was frequently downregulated in HCC tissues. Underexpression of DLC1 correlated with AFP level, vascular invasion, poor differentiation, and poor prognosis. In vitro assays revealed that DLC1 not only suppressed the proliferation, migration, and invasion of HCC cells, but also inhibited autophagy of HCC cells...
May 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29784973/significance-of-prohibitin-domain-family-in-tumorigenesis-and-its-implication-in-cancer-diagnosis-and-treatment
#18
Jie Yang, Bin Li, Qing-Yu He
Prohibitin (PHB) was originally isolated and characterized as an anti-proliferative gene in rat liver. The evolutionarily conserved PHB gene encodes two human protein isoforms with molecular weights of ~33 kDa, PHB1 and PHB2. PHB1 and PHB2 belong to the prohibitin domain family, and both are widely distributed in different cellular compartments such as the mitochondria, nucleus, and cell membrane. Most studies have confirmed differential expression of PHB1 and PHB2 in cancers compared to corresponding normal tissues...
May 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29784917/clonal-analysis-of-notch1-expressing-cells-reveals-the-existence-of-unipotent-stem-cells-that-retain-long-term-plasticity-in-the-embryonic-mammary-gland
#19
Anna M Lilja, Veronica Rodilla, Mathilde Huyghe, Edouard Hannezo, Camille Landragin, Olivier Renaud, Olivier Leroy, Steffen Rulands, Benjamin D Simons, Silvia Fre
Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12...
May 21, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29784906/the-anti-cancer-activity-of-an-andrographolide-analogue-functions-through-a-gsk-3%C3%AE-independent-wnt-%C3%AE-catenin-signaling-pathway-in-colorectal-cancer-cells
#20
Somrudee Reabroi, Rungnapha Saeeng, Nittaya Boonmuen, Teerapich Kasemsuk, Witchuda Saengsawang, Kanoknetr Suksen, Weiming Zhu, Pawinee Piyachaturawat, Arthit Chairoungdua
The Wnt/β-catenin signaling pathway plays a key role in the progression of human colorectal cancers (CRCs) and is one of the leading targets of chemotherapy agents developed for CRC. The present study aimed to investigate the anti-cancer effects and molecular mechanisms of 19-O-triphenylmethyl andrographolide (RS-PP-050), an andrographolide analogue and determine its activity in the Wnt/β-catenin pathway. RS-PP-050 was found to potently inhibit the proliferation and survival of HT-29 CRC cells. It induces cell cycle arrest and promotes apoptotic cell death which was associated with the activation of PARP-1 and p53...
May 21, 2018: Scientific Reports
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