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https://www.readbyqxmd.com/read/28619760/fbw7-dependent-mcl-1-degradation-mediates-the-anticancer-effect-of-hsp90-inhibitors
#1
Jingshan Tong, Shuai Tan, Zaneta Nikolovska-Coleska, Jian Yu, Fangdong Zou, Lin Zhang
Heat shock protein 90 (Hsp90) is widely overexpressed in cancer cells and necessary for maintenance of malignant phenotypes. Hsp90 inhibition induces tumor cell death through degradation of its client oncoproteins, and has shown promises in preclinical studies. However, the mechanism by which Hsp90 inhibitors kill tumor cells is not well understood. Biomarkers associated with differential sensitivity and resistance to Hsp90 inhibitors remain to be identified. In this study, we found that colorectal cancer (CRC) cells containing inactivating mutations of FBW7, a tumor suppressor and E3 ubiquitin ligase, are intrinsically insensitive to Hsp90 inhibitors...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28618944/demethoxycurcumin-in-combination-with-ultraviolet-radiation-b-induces-apoptosis-through-the-mitochondrial-pathway-and-caspase-activation-in-a431-and-hacat-cells
#2
Yong Xin, Qian Huang, Pei Zhang, Wen Wen Guo, Long Zhen Zhang, Guan Jiang
Photodynamic therapy is widely used in the clinical treatment of tumors, especially skin cancers. It has been reported that the photosensitizer curcumin, in combination with ultraviolet radiation B, induces HaCaT cell apoptosis, and this effect may be due to the activation of caspase pathways. In this study, we examined the photodynamic effects of demethoxycurcumin, a more stable analogue of curcumin, to determine whether it could induce apoptosis in skin cancer cells. We investigated the effects of a combination of ultraviolet radiation B and demethoxycurcumin on apoptotic cell death in A431 and HaCaT cells and determined the molecular mechanism of action...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28617441/concomitant-epigenetic-targeting-of-lsd1-and-hdac-synergistically-induces-mitochondrial-apoptosis-in-rhabdomyosarcoma-cells
#3
Tinka Haydn, Eric Metzger, Roland Schuele, Simone Fulda
The lysine-specific demethylase 1 (LSD1) is overexpressed in several cancers including rhabdomyosarcoma (RMS). However, little is yet known about whether or not LSD1 may serve as therapeutic target in RMS. We therefore investigated the potential of LSD1 inhibitors alone or in combination with other epigenetic modifiers such as histone deacetylase (HDAC) inhibitors. Here, we identify a synergistic interaction of LSD1 inhibitors (i.e., GSK690, Ex917) and HDAC inhibitors (i.e., JNJ-26481585, SAHA) to induce cell death in RMS cells...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28615943/the-use-of-functional-epirubicin-liposomes-to-induce-programmed-death-in-refractory-breast-cancer
#4
Lei Liu, Li-Min Mu, Yan Yan, Jia-Shuan Wu, Ying-Jie Hu, Ying-Zi Bu, Jing-Ying Zhang, Rui Liu, Xue-Qi Li, Wan-Liang Lu
Currently, chemotherapy is less efficient in controlling the continued development of breast cancer because it cannot eliminate extrinsic and intrinsic refractory cancers. In this study, mitochondria were modified by functional epirubicin liposomes to eliminate refractory cancers through initiation of an apoptosis cascade. The efficacy and mechanism of epirubicin liposomes were investigated on human breast cancer cells in vitro and in vivo using flow cytometry, confocal microscopy, high-content screening system, in vivo imaging system, and tumor inhibition in mice...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28615299/ormeloxifene-suppresses-prostate-tumor-growth-and-metastatic-phenotypes-via-inhibition-of-oncogenic-%C3%AE-catenin-signaling-and-emt-progression
#5
Bilal Bin Hafeez, Aditya Ganju, Mohammed Sikander, Vivek K Kashyap, Zubair Bin Hafeez, Neeraj Chauhan, Shabnam Malik, Andrew E Massey, Manish K Tripathi, Fathi T Halaweish, Nadeem Zafar, Man M Singh, Murali M Yallapu, Meena Jaggi, Subhash C Chauhan
Ormeloxifene (ORM), is a clinically approved selective estrogen receptor modulator, which has also shown excellent anti-cancer activity, thus it can be an ideal repurposing pharmacophore. Herein, we report therapeutic effects of ORM on prostate cancer (PrCa) and elucidate a novel molecular mechanism of its anti-cancer activity. ORM treatment inhibited epithelial to mesenchymal transition (EMT) process as evident by repression of N-cadherin, Slug, Snail, and vimentin, MMPs (MMP2 and MMP3), β-catenin/TCF-4 transcriptional activity, and induced the expression of pGSK3β...
June 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28610850/dietary-myo-inositol-deficiency-decreased-the-growth-performances-and-impaired-intestinal-physical-barrier-function-partly-relating-to-nrf2-jnk-e2f4-and-mlck-signaling-in-young-grass-carp-ctenopharyngodon-idella
#6
Shuang-An Li, Wei-Dan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
In this study, we investigated the effects of dietary myo-inositol on the growth and intestinal physical barrier functions of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (221.83 ± 0.84 g) were fed six diets containing graded levels of myo-inositol (27.0, 137.9, 286.8, 438.6, 587.7 and 737.3 mg/kg) for 10 weeks. After the growth trial, fish were challenged with Aeromonas hydrophila for 14 days. The results indicated that compared with optimal myo-inositol levels, myo-inositol deficiency (27...
June 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28609843/knockdown-of-anril-aggravates-h2o2-induced-injury-in-pc-12-cells-by-targeting-microrna-125a
#7
Ran Li, Fei Yin, Ying-Ying Guo, Kun-Chi Zhao, Qing Ruan, Ying-Mei Qi
Spinal cord injury (SCI) is a devastating and common neurological disorder which causes local oxidative damage. The study aimed to investigate the underlying role of ANRIL in H2O2-induced cell injury of rat PC-12 cells. Cell injury was evaluated on the basis of cell viability, migration, invasion and apoptosis. The effect of ANRIL on H2O2-induced cell injury was estimated after cell transfection. Then, the interaction between ANRIL and miR-125a was explored by qRT-PCR and estimation of cell injury. Predicted by TargetScan, the possible target gene of miR-125a was verified...
June 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28596644/highlights-of-multiple-myeloma-at-the-annual-meeting-of-american-society-of-hematology-2016
#8
REVIEW
Nidhi Tandon, Shaji K Kumar
This review discusses the landmark studies in the field of multiple myeloma (MM) which were presented at American society of hematology annual meeting, 2016. There were contrary results from two large phase III trials (one from US and one from Europe) that evaluated the role of additional interventions like tandem autologous transplant (ASCT) and consolidation after induction therapy followed by ASCT in newly diagnosed MM (NDMM) patients, but there were critical differences between the two studies. Novel agents like carfilzomib and ixazomib proved to be of benefit when used as induction and post ASCT consolidation and maintenance in NDMM...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28590547/geraniin-suppresses-ovarian-cancer-growth-through-inhibition-of-nf-%C3%AE%C2%BAb-activation-and-downregulation-of-mcl-1-expression
#9
Xue Wang, Zhuo Chen, Xiao Li, Zheng-Kui Jiang, Yan-Qiu Zhao, Feng-Feng Ping
This study investigated the anticancer effects of geraniin on ovarian cancer cells and the signaling pathways involved. Ovarian cancer cells were treated with different concentrations of geraniin for 48 h and examined for viability, apoptosis, mitochondrial membrane depolarization, and gene expression. Xenograft tumor studies were performed to determine the anticancer activity of geraniin in vivo. Geraniin significantly decreased cancer cell viability in a concentration-dependent fashion. Geraniin significantly triggered apoptosis, which was accompanied by loss of mitochondrial membrane potential and increased cytochrome c release and caspsase-3 activity...
June 7, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28587170/the-combination-of-arginine-deprivation-and-5-fluorouracil-improves-therapeutic-efficacy-in-argininosuccinate-synthetase-negative-hepatocellular-carcinoma
#10
Angkana Thongkum, Chunjing Wu, Ying-Ying Li, Medhi Wangpaichitr, Panida Navasumrit, Varabhorn Parnlob, Thaniya Sricharunrat, Vajarabhongsa Bhudhisawasdi, Mathuros Ruchirawat, Niramol Savaraj
Argininosuccinate synthetase (ASS), a key enzyme to synthesize arginine is down regulated in many tumors including hepatocellular carcinoma (HCC). Similar to previous reports, we have found the decrease in ASS expression in poorly differentiated HCC. These ASS(-) tumors are auxotrophic for arginine. Pegylated arginine deiminase (ADI-PEG20), which degrades arginine, has shown activity in these tumors, but the antitumor effect is not robust and hence combination treatment is needed. Herein, we have elucidated the effectiveness of ADI-PEG20 combined with 5-Fluorouracil (5-FU) in ASS(-)HCC by targeting urea cycle and pyrimidine metabolism using four HCC cell lines as model...
June 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28586754/enantiomerically-pure-%C3%AE-dipeptide-derivative-induces-anticancer-activity-against-human-hormone-refractory-prostate-cancer-through-both-pi3k-akt-dependent-and-independent-pathways
#11
Mei-Ling Chan, Chia-Chun Yu, Jui-Ling Hsu, Wohn-Jenn Leu, She-Hung Chan, Lih-Ching Hsu, Shih-Ping Liu, Polina M Ivantcova, Özdemir Dogan, Stefan Bräse, Konstantin V Kudryavtsev, Jih-Hwa Guh
The use of peptides that target cancer cells and induce anticancer activities through various mechanisms is developing as a potential anticancer strategy. KUD983, an enantiomerically pure β-dipeptide derivative, displays potent activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells with submicromolar IC50. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB...
May 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28578655/potential-mechanisms-of-resistance-to-venetoclax-and-strategies-to-circumvent-it
#12
Stephen K Tahir, Morey L Smith, Paul Hessler, Lisa Roberts Rapp, Kenneth B Idler, Chang H Park, Joel D Leverson, Lloyd T Lam
BACKGROUND: Venetoclax (ABT-199), a first-in-class orally bioavailable BCL-2-selective inhibitor, was recently approved by the FDA for use in patients with 17p-deleted chronic lymphocytic leukemia who have received prior therapy. It is also being evaluated in numerous clinical trials for treating patients with various hematologic malignancies. As with any targeted cancer therapy, it is critically important to identify potential mechanisms of resistance, both for patient stratification and developing strategies to overcome resistance, either before it develops or as it emerges...
June 2, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28571773/dats-induces-trail-sensitization-of-human-glioma-cancer-cells-through-selective-er-stress-induction
#13
Jung Soon Hwang, Dae-Hee Lee, Ki Han Kwon
Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is a promising anticancer reagent for antitumor therapy. However, many cancer cells, including malignant glioma cells, tend to be resistant to TRAIL, due to repeat treat to cancer cells, highlighting the need for strategies to overcome TRAIL resistance. Here we present that in combination with diallyl trisulfide (DATS), exposure to TRAIL induced apoptosis in TRAIL-resistant glioma cells. Surprisingly, we found that subtoxic concentrations of DATS significantly potentiated TRAIL-induced cytotoxicity and apoptosis in glioma cells...
May 29, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28562341/combination-of-fe-cu-chelators-and-docosahexaenoic-acid-an-exploration-for-the-treatment-of-colorectal-cancer
#14
Nanhui Yu, Hong Zhu, Yuan Yang, Yiming Tao, Fengbo Tan, Qian Pei, Yuan Zhou, Xiangping Song, Qiurong Tan, Haiping Pei
Colorectal cancer (CRC) is one of the major causes of cancer deaths in the world. 5-fluorouracil (5-FU) -based chemotherapy is a common choice for patients with CRC; unfortunately, the benefit is rather limited due to the acquisition of drug resistance. Therefore, the alternative therapeutic strategies are required. The activation of autophagic mechanism was considered as the main cause of the acquisition of drug resistance in 5-FU treatment. Docosahexaenoic acid (DHA), a fatty acid, has been regarded as an efficient anticancer agent and can improve the drug resistance in conventional cancer therapy by a low basal level of autophagy in colon cancer cells...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28560500/synergistic-induction-of-apoptosis-by-combination-treatment-with-mesupron-and-auranofin-in-human-breast-cancer-cells
#15
Joo-Eun Lee, Yeo-Jung Kwon, Hyoung-Seok Baek, Dong-Jin Ye, Eunah Cho, Hyung-Kyoon Choi, Kyung-Soo Oh, Young-Jin Chun
Urokinase-type plasminogen activator (uPA) has been validated as a predictive or prognostic biomarker protein, and mesupron is considered the first-in-class anticancer agent to inhibit uPA activity in human breast cancer. In the present study, we showed that the synergism between mesupron and auranofin, a thioredoxin reductase inhibitor, for inducing of apoptosis in MCF-7 human breast cancer cells. Our results demonstrated that mesupron and auranofin significantly lead to inhibition of the cancer cells proliferation; cell cycle arrest at the G1/S phase of the cell cycle, and apoptosis as indicated by caspase 3 activation, poly(ADP-ribose) polymerase cleavage, and annexin V staining...
May 31, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28557543/impaired-mitochondrial-microbicidal-responses-in-chronic-obstructive-pulmonary-disease-macrophages
#16
Martin A Bewley, Julie A Preston, Mohammed Mohasin, Helen M Marriott, Richard C Budd, Julie Swales, Paul Collini, David R Greaves, Ruth W Craig, Christopher E Brightling, Louise E Donnelly, Peter J Barnes, Dave Singh, Steven D Shapiro, Moira K B Whyte, David H Dockrell
RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by impaired clearance of pulmonary bacteria. OBJECTIVES: The effect of COPD on alveolar macrophage (AM) microbicidal responses was investigated. METHODS: Alveolar macrophages (AMs) were obtained from bronchoalveolar lavage from healthy donors or COPD patients and challenged with opsonized serotype 14 Streptococcus pneumoniae. Cells were assessed for apoptosis, bactericidal activity and mitochondrial reactive oxygen species (mROS) production...
May 30, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28555524/ellipticine-inhibits-the-proliferation-and-induces-apoptosis-in-rheumatoid-arthritis-fibroblast-like-synoviocytes-via-the-stat3-pathway
#17
Hui-Long Wen, Guang Yang, Qi-Rong Dong
OBJECTIVE: Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is an alkaloid isolated from Apocyanaceae plants. This study was designed to investigate the effects of ellipticine on the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). METHODS: RA-FLSs were exposed to different concentrations of ellipticine (i.e., 0.5, 1, 2, 4 and 8 μM) for 24-72h and measured for viability, proliferation and apoptosis...
May 30, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28545562/the-inhibition-of-fgf-receptor-1-activity-mediates-sorafenib-antiproliferative-effects-in-human-malignant-pleural-mesothelioma-tumor-initiating-cells
#18
Alessandra Pattarozzi, Elisa Carra, Roberto E Favoni, Roberto Würth, Daniela Marubbi, Rosa Angela Filiberti, Luciano Mutti, Tullio Florio, Federica Barbieri, Antonio Daga
BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer, characterized by rapid progression and high mortality. Persistence of tumor-initiating cells (TICs, or cancer stem cells) after cytotoxic drug treatment is responsible for tumor relapse, and represents one of the main reasons for the poor prognosis of mesothelioma. In fact, identification of the molecules affecting TIC viability is still a significant challenge. METHODS: TIC-enriched cultures were obtained from 10 human malignant pleural mesotheliomas and cultured in vitro...
May 25, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28545465/an-increase-in-long-non-coding-rna-pandar-is-associated-with-poor-prognosis-in-clear-cell-renal-cell-carcinoma
#19
Yi Xu, Yanyue Tong, Jianyong Zhu, Zhangming Lei, Lijun Wan, Xiuwen Zhu, Feng Ye, Liping Xie
BACKGROUND: Nearly 30% of clear cell renal cell carcinoma (ccRCC) patients present with metastasis at the time of diagnosis, and the prognosis for these patients is poor. Therefore, novel potential prognostic biomarkers and therapeutic targets for ccRCC could be helpful. Emerging evidence indicates that lncRNAs play important roles in cancer tumorigenesis and could be used as potential biomarkers or therapeutic targets. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) is a relatively novel lncRNA that plays an important role in the development of multiple cancers...
May 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28537899/nras-mutations-in-cutaneous-t-cell-lymphoma-ctcl-sensitize-tumors-towards-treatment-with-the-multikinase-inhibitor-sorafenib
#20
Michael K Kießling, Jan P Nicolay, Tabea Schlör, Claus-Detlev Klemke, Dorothee Süss, Peter H Krammer, Karsten Gülow
Therapy of cutaneous T cell lymphoma (CTCL) is complicated by a distinct resistance of the malignant T cells towards apoptosis that can be caused by NRAS mutations in late-stage patients. These mutations correlate with decreased overall survival, but sensitize the respective CTCL cells towards MEK-inhibition-induced apoptosis which represents a promising novel therapeutic target in CTCL. Here, we show that the multi-kinase inhibitor Sorafenib induces apoptosis in NRAS-mutated CTCL cells. CTCL cell lines and to a minor extent primary T cells from Sézary patients without NRAS mutations are also affected by Sorafenib-induced apoptosis suggesting a sensitizing role of NRAS mutations for Sorafenib-induced apoptosis...
May 7, 2017: Oncotarget
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