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https://www.readbyqxmd.com/read/28230988/design-and-synthesis-of-novel-cyclic-amine-benzimidazoles-for-the-treatment-of-pancreatic-cancer
#1
Vibha Pathak, Corinne Elizabeth Augelli-Szafran, Han-Xun Wei, Yonghe Li, Patsy G Oliver, Wenyan Lu, Donald J Buchsbaum, Mark J Suto
Wnt/beta-Catenin signaling pathway has a very important role in pancreatic ductal adenocarcinoma (PDAC) initiation and progression. This signaling pathway has been implicated in angiogenesis, maintenance of resistant CICs (cancer-initiating cells), metastasis, regulation of cell cycle, apoptosis and chemoresistance. We investigated the activity of a chemical series of phenyl benzimidazoles, small molecule inhibitors of Wnt signaling in LRP6-expressing HEK 293 cells against PDAC cells. Several benzimidazoles were designed, synthesized and screened under adherent and CIC conditions...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28228254/control-of-mitochondrial-remodeling-by-the-atpase-inhibitory-factor-1%C3%A2-unveils-a-pro-survival-relay-via-opa1
#2
Danilo Faccenda, Junji Nakamura, Giulia Gorini, Gurtej K Dhoot, Mauro Piacentini, Masusuke Yoshida, Michelangelo Campanella
The ubiquitously expressed ATPase inhibitory factor 1 (IF1) is a mitochondrial protein that blocks the reversal of the F1Fo-ATPsynthase, preventing dissipation of cellular ATP and ischemic damage. IF1 suppresses programmed cell death, enhancing tumor invasion and chemoresistance, and is expressed in various types of human cancers. In this study, we examined its effect on mitochondrial redox balance and apoptotic cristae remodeling, finding that, by maintaining ATP levels, IF1 reduces glutathione (GSH) consumption and inactivation of peroxiredoxin 3 (Prx3) during apoptosis...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228232/hormone-receptor-expression-profile-of-low-grade-serous-ovarian-cancers
#3
Marianna Buttarelli, Floriana Mascilini, Gian Franco Zannoni, Alessandra Ciucci, Enrica Martinelli, Flavia Filippetti, Giovanni Scambia, Gabriella Ferrandina, Daniela Gallo
OBJECTIVE: Low-grade serous ovarian carcinomas (LGSOCs) are a histological subtype of epithelial ovarian tumors, accounting for fewer than 5% of all cases of ovarian carcinoma. Due to the chemoresistant nature of this subtype a search for more effective systemic therapies is actively ongoing, hormonal therapy showing some degree of activity in this clinical setting. The present study ought to investigate the hormone receptor status of LGSOCs, as a strategy to provide molecular support for patient-tailored hormonal treatments...
February 20, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28223127/multidrug-resistance-in-glioblastoma-stem-like-cells-role-of-the-hypoxic-microenvironment-and-adenosine-signaling
#4
REVIEW
Daniel Uribe, Ángelo Torres, José Dellis Rocha, Ignacio Niechi, Carlos Oyarzún, Luis Sobrevia, Rody San Martín, Claudia Quezada
Glioblastoma multiforme (GBM) is considered the most common and aggressive tumour of the central nervous system and is characterized for being highly chemoresistant. This property is mainly due to the activation of Multiple Drug Resistance (MDR) mechanisms that protect cancer cells from structurally and morphologically different drugs. Overexpression and increased ABC transporters activity is one of the most important MDR mechanisms at the clinical level, and both its expression and activity are elevated in GBM cells...
February 18, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28222068/inhibition-of-cdk5-induces-cell-death-of-tumor-initiating-cells
#5
Melanie M Mandl, Siwei Zhang, Melanie Ulrich, Elisa Schmoeckel, Doris Mayr, Angelika M Vollmar, Johanna Liebl
BACKGROUND: Tumour-initiating cells (TICs) account for chemoresistance, tumour recurrence and metastasis, and therefore represent a major problem in tumour therapy. However, strategies to address TICs are limited. Recent studies indicate Cdk5 as a promising target for anti-cancer therapy and Cdk5 has recently been associated with epithelial-mesenchymal transition (EMT). However, a role of Cdk5 in TICs has not been described yet. METHODS: Expression of Cdk5 in human cancer tissue was analysed by staining of a human tissue microarray (TMA)...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28219181/-immunotherapy-for-head-and-neck-squamous-cell-carcinoma
#6
J Chen, M Chen, H T Wu
Head and neck squamous cell carcinoma(HNSCC) is the sixth most common malignancies of human beings. The prognosis of advanced HNSCC is poor despite improvements in traditional treatment strategies including surgery, chemotherapy, and radiotherapy. Cancer immunotherapy is the use of the immune system to treat cancer, which provides a sustained antitumor reaction but an absense of chemoresistance. Cancer immunotherapy is becoming the forth treatment strategy towards cancer. Therefore, we reviewed the current state of immunotherapy for HNSCC...
February 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28217977/mir-506-enhances-the-sensitivity-of-human-colorectal-cancer-cells-to-oxaliplatin-by-suppressing-mdr1-p-gp-expression
#7
Hui Zhou, Changwei Lin, Yi Zhang, Xiuzhong Zhang, Chong Zhang, Pengbo Zhang, Xingwang Xie, Zeqiang Ren
OBJECTIVES: Chemoresistance development represents a major obstacle to the successful treatment of colorectal cancer (CRC). The aim of this study was to elucidate the mechanism by which miR-506 reverses oxaliplatin chemoresistance in CRC. METHODS: In this study, miR-506 levels were measured in 74 patients with colon cancer via quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). We subsequently analysed the relationship between miR-506 expression and CRC patient survival via the Kaplan-Meier method...
February 19, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28216370/targeting-autophagy-in-cancer-stem-cells-as-an-anticancer-therapy
#8
Yuanyuan Lei, Dan Zhang, Jin Yu, Hui Dong, Jianwei Zhang, Shiming Yang
Cancer stem cells (CSCs), which comprise a small proportion of total cancer cells, have special capacities for self-renewal, differentiation and tumor formation. Currently, CSCs are regarded as the major cause of the failure in anticancer therapy, such as chemoresistance and/or radioresistance, tumor recurrence and metastasis. Autophagy, a process of cellular self-digestion and response to stress, has a role in tumor formation and progression, and it may play a dual role in CSCs-related resistance to anticancer therapy...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28214878/mirna-26a-contributes-to-the-acquisition-of-malignant-behaviors-of-doctaxel-resistant-lung-adenocarcinoma-cells-through-targeting-ezh2
#9
Jing Chen, Yuejuan Xu, Leilei Tao, Yan Pan, Kai Zhang, Rui Wang, Long-Bang Chen, Xiaoyuan Chu
BACKGROUND/AIMS: Accumulating evidence revealed that microRNAs (miRNAs) have been demonstrated as critical molecules in tumor development and progression. MiR-26a, located in a fragile chromosomal region associated with various human cancer, has been reported to be involved in regulating various cellular process, such as proliferation, apoptosis and invasion through targeting multiple oncogene. Docetaxel-mediated chemotherapy has been applied in improving the survival and prognosis of patients with advanced lung adenocarcinoma (LAD)...
February 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28212584/hyaluronic-acid-serum-albumin-conjugate-based-nanoparticles-for-targeted-cancer-therapy
#10
Ravit Edelman, Yehuda G Assaraf, Inna Levitzky, Tal Shahar, Yoav D Livney
Multiple carcinomas including breast, ovarian, colon, lung and stomach cancer, overexpress the hyaluronic acid (HA) receptor, CD44. Overexpression of CD44 contributes to key cancer processes including tumor invasion, metastasis, recurrence, and chemoresistance. Herein, we devised novel targeted nanoparticles (NPs) for delivery of anticancer chemotherapeutics, comprised of self-assembling Maillard reaction-based conjugates of HA and bovine serum albumin (BSA). HA served as the hydrophilic block, and as the ligand for actively targeting cancer cells overexpressing CD44...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212536/targeting-the-stress-oncoprotein-ledgf-p75-to-sensitize-chemoresistant-prostate-cancer-cells-to-taxanes
#11
Leslimar Ríos-Colón, Christina K Cajigas-Du Ross, Anamika Basu, Catherine Elix, Ivana Alicea-Polanco, Tino W Sanchez, Vinodh Radhakrishnan, Chien-Shing Chen, Carlos A Casiano
Prostate cancer (PCa) is associated with chronic prostate inflammation resulting in activation of stress and pro-survival pathways that contribute to disease progression and chemoresistance. The stress oncoprotein lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, promotes cellular survival against environmental stressors, including oxidative stress, radiation, and cytotoxic drugs. Furthermore, LEDGF/p75 overexpression in PCa and other cancers has been associated with features of tumor aggressiveness, including resistance to cell death and chemotherapy...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211885/the-novel-bmi-1-inhibitor-ptc596-downregulates-mcl-1-and-induces-p53-independent-mitochondrial-apoptosis-in-acute-myeloid-leukemia-progenitor-cells
#12
Y Nishida, A Maeda, M J Kim, L Cao, Y Kubota, J Ishizawa, A AlRawi, Y Kato, A Iwama, M Fujisawa, K Matsue, M Weetall, M Dumble, M Andreeff, T W Davis, A Branstrom, S Kimura, K Kojima
Disease recurrence is the major problem in the treatment of acute myeloid leukemia (AML). Relapse is driven by leukemia stem cells, a chemoresistant subpopulation capable of re-establishing disease. Patients with p53 mutant AML are at an extremely high risk of relapse. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of AML stem cells. Here we studied the effects of a novel small molecule inhibitor of BMI-1, PTC596, in AML cells. Treatment with PTC596 reduced MCL-1 expression and triggered several molecular events consistent with induction of mitochondrial apoptosis: loss of mitochondrial membrane potential, BAX conformational change, caspase-3 cleavage and phosphatidylserine externalization...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28210897/upregulated-single-stranded-dna-binding-protein-1-induces-cell-chemoresistance-to-cisplatin-in-lung-cancer-cell-lines
#13
Xiang Zhao, Rong He, Yu Liu, Yongkai Wu, Leitao Kang
Cisplatin and its analogues are widely used as anti-tumor drugs in lung cancer but many cisplatin-resistant lung cancer cases have been identified in recent years. Single-stranded DNA-binding protein 1 (SSDBP1) can effectively induce H69 cell resistance to cisplatin in our previous identification; thus, it is necessary to explore the mechanism underlying the effects of SSDBP1-induced resistance to cisplatin. First, SSDBP1-overexpressed or silent cell line was constructed and used to analyze the effects of SSDBP1 on chemoresistance of lung cancer cells to cisplatin...
February 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28210099/study-of-polymorphisms-in-the-tp53-and-rb1-genes-in-children-with-retinoblastoma-in-northern-mexico
#14
Edwin J Anaya-Pava, Jesús Nares-Cisneros, Rubén I Cárdenas-Hernández, Yolanda Jaramillo-Rodríguez, Graciela Zambrano-Galván
PURPOSE: To determine the frequency and association of polymorphisms in the TP53 and RB1 genes with clinical characteristics in a group of children with retinoblastoma (RB) in northern Mexico. METHODS: A prospective, longitudinal, and analytical study of 11 patients diagnosed with RB was conducted. Endpoint PCR and high-resolution real-time PCR were performed. Chi-square and Student t tests were used to evaluate associations between variables. Allelic frequencies, as well as genotypic and Hardy-Weinberg equilibriums, were evaluated using Guo and Thompson's method...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28209618/the-stat3-mirna-92-wnt-signaling-pathway-regulates-spheroid-formation-and-malignant-progression-in-ovarian-cancer
#15
Min-Wei Chen, Shu-Ting Yang, Ming-Hsien Chien, Kuo-Tai Hua, Chin-Jui Wu, Sheng-Mou Hsiao, Hao Lin, Michael Hsiao, Jen-Liang Su, Lin-Hung Wei
Ovarian cancer spheroids constitute a metastatic niche for transcoelomic spread that also engenders drug resistance. Spheroid-forming cells express active STAT3 signaling and display stem cell-like properties that may contribute to ovarian tumor progression. In this study, we show that STAT3 is hyperactivated in ovarian cancer spheroids and that STAT3 disruption in this setting is sufficient to relieve chemoresistance. In an NSG murine model of human ovarian cancer, STAT3 signaling regulated spheroid formation and self-renewal properties, whereas STAT3 attenuation reduced tumorigenicity...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28208648/n-butylidenephthalide-regulated-tumor-stem-cell-genes-ezh2-axl-and-reduced-its-migration-and-invasion-in-glioblastoma
#16
Ssu-Yin Yen, Hong-Meng Chuang, Mao-Hsuan Huang, Shinn-Zong Lin, Tzyy-Wen Chiou, Horng-Jyh Harn
Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20-21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28206956/nf-%C3%AE%C2%BAb1-c-rel-and-elk1-inhibit-mir-134-expression-leading-to-tab1-upregulation-in-paclitaxel-resistant-human-ovarian-cancer
#17
Ting Shuang, Min Wang, Yingying Zhou, Cong Shi, Dandan Wang
The mechanism by which the transcription factors inhibit the miRNA expression in ovarian cancer chemoresistance is unclear. The present study investigated the mechanism underlying the transcriptional repression of miR-134 in chemoresistant serous epithelial ovarian cancer. The results demonstrate that NF-κB1, c-Rel, and ELK1 are involved as transcription factors in repressing miR-134 expression in paclitaxel-resistant ovarian cancer cells. Knockdown of these transcription factors led to increased miR-134 expression, resulting in increased apoptosis and inhibition of proliferation in SKOV3-TR30 cells...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28204832/anti-proliferative-effect-of-jesridonin-on-paclitaxel-resistant-ec109-human-esophageal-carcinoma-cells
#18
Cong Wang, Liubin Guo, Saiqi Wang, Junwei Wang, Yongmei Li, Yinhui Dou, Ran Wang, Hongge Shi, Yu Ke, Hongmin Liu
Chemoresistance to anticancer drugs is a major obstacle in the efforts to develop a successful treatment strategy for esophageal squamous carcinoma (ESCC). Thus, the exploration of new drugs and treatment strategies for combating resistance are of utmost importance. In this study, we investigated the antitumor drug resistance activity of Jesridonin, a new ent-kaurene diterpenoid, and its possible mechanisms of action using the resistant cancer cell line, EC109/Taxol. MTT assay revealed that Jesridonin had similar IC50 values against EC109 paclitaxel-sensitive cells and drug-resistant EC109/Taxol cells in vitro...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28203521/down-regulation-of-mir-26b-induces-cisplatin-resistance-in-nasopharyngeal-carcinoma-by-repressing-jag1
#19
Lei Shi, Wei Yin, Zhiyu Zhang, Guanggang Shi
Therapy against nasopharyngeal carcinoma (NPC) is hurdled by chemoresistance. Recent studies found that microRNA (miRNA) are important regulators of cancer resistance. In this study, we aimed to explore the role and mechanism of miR-26b in regulating NPC cisplatin (CDDP) resistance. Real-time PCR was used to evaluate miR-26b levels in CDDP-resistant and CDDP-sensitive NPC cells, as well as human NPC tissues. MiR-26b was ectopically overexpressed in CDDP-resistant cells, followed by monitoring changes in cell viability and apoptosis...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28203090/exploring-targeted-therapy-of-osteosarcoma-using-proteomics-data
#20
Parunya Chaiyawat, Jongkolnee Settakorn, Apiruk Sangsin, Pimpisa Teeyakasem, Jeerawan Klangjorhor, Aungsumalee Soongkhaw, Dumnoensun Pruksakorn
Despite multimodal therapeutic treatments of osteosarcoma (OS), some patients develop resistance to currently available regimens and eventually end up with recurrent or metastatic outcomes. Many attempts have been made to discover effective drugs for improving outcome; however, due to the heterogeneity of the disease, new therapeutic options have not yet been identified. This study aims to explore potential targeted therapy related to protein profiles of OS. In this review of proteomics studies, we extracted data on differentially expressed proteins (DEPs) from archived literature in PubMed and our in-house repository...
2017: OncoTargets and Therapy
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