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drug resistant AND tumor

Han-Wei Lin, Ying-Cheng Chiang, Nai-Yun Sun, Yu-Li Chen, Chi-Fang Chang, Yi-Jou Tai, Chi-An Chen, Wen-Fang Cheng
The role of chitinase-3-like protein 1 (CHI3L1) in ovarian cancer and the possible mechanisms were elucidated. CHI3L1 is a secreted glycoprotein and associated with inflammation, fibrosis, asthma, extracellular tissue remodeling and solid tumors. Our previous study showed CHI3L1 could be a potential prognostic biomarker for epithelial ovarian cancer and protect cancer cells from apoptosis. Therefore, clinical data and quantitation of CHI3L1 of ovarian cancer patients, tumor spheroid formation, side-population assays, Aldefluor and apoptotic assays, ELISA, RT-PCR, immunoblotting, and animal experiments were performed in two ovarian cancer cells lines, OVCAR3 and CA5171, and their CHI3L1-overexpressing and knockdown transfectants...
August 18, 2018: Endocrine-related Cancer
Seema C Parte, Surinder K Batra, Sham S Kakar
BACKGROUND: Ovarian cancer is a complicated malady associated with cancer stem cells (CSCs) contributing to 238,700 estimated new cases and 151,900 deaths per year, worldwide. CSCs comprise a tiny fraction of tumor-bulk responsible for cancer recurrence and eventual mortality. CSCs or tumor initiating cells are responsible for self-renewal, differentiation and proliferative potential, tumor initiation capability, its progression, drug resistance and metastatic spread. Although several biomarkers are implicated in these processes, their distribution within the ovary and association with single cell type has neither been established nor demonstrated across ovarian tumor developmental stages...
August 18, 2018: Journal of Ovarian Research
Kelly M Kreitzburg, Samuel C Fehling, Charles N Landen, Tracy L Gamblin, Rebecca B Vance, Rebecca C Arend, Ashwini A Katre, Patsy G Oliver, Robert C A M van Waardenburg, Ronald D Alvarez, Karina J Yoon
Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States. Although most patients respond to frontline therapy, virtually all patients relapse with chemoresistant disease. This study addresses the hypothesis that carboplatin or tamoxifen + FTY720, a sphingosine analogue, will minimize or circumvent drug-resistance in ovarian cancer cells and tumor models. In vitro data demonstrate that FTY720 sensitized two drug-resistant (A2780. cp20, HeyA8. MDR) and two high-grade serous ovarian cancer cell lines (COV362, CAOV3) to carboplatin, a standard of care for patients with ovarian cancer, and to the selective estrogen receptor modulator tamoxifen...
August 15, 2018: Cancer Letters
Yunfei Zhang, Ping Huang, Xuewen Liu, Yuchen Xiang, Te Zhang, Yezi Wu, Jiaxin Xu, Zhiting Sun, Weiguo Zhen, Liang Zhang, Yuan Si, Ying Liu
The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) indicates poor prognosis and promotes EMT and metastasis. EMT, a crucial cellular process that occurs during cancer progression and metastasis, has been reported to promote drug resistance in several previous studies. Consequently, ongoing research has been focused on exploring therapeutic options for preventing EMT to delay or reverse drug resistance. Polyphyllin I (PPI) is a natural component extracted from Paris polyphylla that displays anti-cancer properties...
July 26, 2018: Journal of Pharmacological Sciences
Shima Aliebrahimi, Shideh Montasser Kouhsari, Seyed Shahriar Arab, Amir Shadboorestan, Seyed Nasser Ostad
Receptor tyrosine kinases (RTKs) are pharmaceutically attractive targets due to their fundamental role in tumor formation. The hallmark of pancreatic cancer is its high mortality rate attributed to the existence of cancer stem cell (CSC) subpopulations which result in therapy resistance and recurrence. c-Met is a known pancreatic CSC marker that belongs to the family of RTKs. To surmount the hurdles related to ligand-independent c-Met activation, we aimed to elucidate the inhibitory mechanisms of withaferin A (WA) and carnosol (CA) as two hit phytochemicals against c-Met kinase domain...
July 25, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Huixing Deng, Geng Qianqian, Ji Ting, Yang Aimin
microRNAs (miRNAs) have been implicated to play critical roles in non-small celllung cancer (NSCLC) progression and participate in the regulation of drug resistance during cancer chemotherapy. However, the underlying molecular mechanism of how miR-539 modulates the chemosensitivity to cisplatin (DDP) in NSCLC cells remains largely unknown. In this study, we found that miR-539 was significantly downregulated in DDP-resistant cell lines (A549/DDP and H1299/DDP). Overexpression of miR-539 enhanced the sensitivity of DDP-resistant NSCLC cells to DDP by suppressing cell proliferation, causing cell cycle arrest, inducing apoptosis, repressing invasion and migration...
July 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yifan Liu, Eun Ju Yang, Baoyuan Zhang, Zhengqiang Miao, Changjie Wu, Junfang Lyu, Kaeling Tan, Terence Chuen Wai Poon, Joong Sup Shim
PTEN is a tumor suppressor found mutated in many cancers. From a synthetic lethality drug screen with PTEN-isogenic colorectal cancer cells, we found that mutant-PTEN cells were resistant to dual inhibitors of FLT3 and aurora kinase-A, including KW2449 and ENMD-2076. KW2449 significantly reduced the viability of wildtype-PTEN cells causing apoptosis, while little effect was observed in mutant-PTEN counterparts. Transcriptome profiling showed that members of PI3K-AKT signaling pathway were strongly changed in cells after KW2449 treatment, indicating a potential role of the pathway in drug resistance...
August 14, 2018: Cancer Letters
Jeanne A Hardy
Kinase inhibitors are effective cancer therapies. Unfortunately, drug resistance emerges in response to kinase inhibition leading to loss of drug efficacy. In this issue of Cell Chemical Biology, Peh et al. (2018) demonstrate that caspase activators effectively delay onset of resistance to kinase inhibitors and are excellent co-therapeutics for a number of tumor types.
August 16, 2018: Cell Chemical Biology
Rekha Pal, Ning Wei, Nan Song, Shaoyu Wu, Rim S Kim, Ying Wang, Patrick G Gavin, Peter C Lucas, Ashok Srinivasan, Carmen J Allegra, Samuel A Jacobs, Soonmyung Paik, John C Schmitz, Katherine L Pogue-Geile
Molecular subtypes of colorectal tumors are associated with prognosis and prediction for treatment benefit from chemotherapy. The purpose of this study was two-fold: 1) to determine the association of colorectal (CRC) molecular subtypes with response to targeted therapies in pre-clinical models and 2) to identify treatments for CRC stem-like subtype because these tumors are associated with a very poor patient prognosis. Eleven CRC cell lines were classified into molecular subtypes and tested for their response to pan-ERBB, MEK, and ERK inhibitors as single agents and in combination...
2018: PloS One
Xuan Sun, Robert C G Martin, Qianqian Zheng, Russell Farmer, Harshul Pandit, Xuanyi Li, Kevin Jacob, Jian Suo, Yan Li
BACKGROUND: With a less than 5% overall survival rate, esophageal adenocarcinoma (EAC) is one of the leading causes of death in the United States. Epithelial cell adhesion molecule (EpCAM) is a cancer stem cell (CSC) marker that is expressed in various epithelial carcinomas, including EAC. Accumulating evidence indicates that CSC subpopulations can initiate cancer development and, in addition, drive metastasis, recurrence and drug resistance. It has also been reported that EpCAM up-regulation in EAC may lead to an aggressive behavior and, thus, an adverse clinical outcome...
August 16, 2018: Cellular Oncology (Dordrecht)
Austin B Henslee, Timothy A Steele
Background: Aggressive natural killer cell leukemia is a devastating disease, with an average patient survival time of less than 2 months following diagnosis. Due to P-glycoprotein-mediated resistance of the tumor cells most forms of chemotherapy are of limited efficacy, therefore new treatment strategies are needed. Statin drugs have recently been found to inhibit the growth of various tumor cell types. Methods: We investigated the effects of statin drug-mediated mevalonate pathway inhibition on cell proliferation, tumor-induced cytotoxicity, cell cycle progression and ERK MAP kinase signal transduction pathway activation...
2018: Biomarker Research
Fen Wang, Yuanfang Zhu, Shanyu Fang, Shuya Li, Sisun Liu
Ovarian cancer is the leading cause of mortality resulting from gynecologic cancer. A common anti-ovarian tumor drug is cisplatin; however, repeated use of cisplatin causes severe resistance and leads to poor long-term survival rate in ovarian cancer patients. Recently, it was reported that lanthanum chloride (LaCl3 ) may inhibit tumor growth and induce apoptosis in certain cancer cells. In the present study, the effect of LaCl3 on ovarian cancer was determined in vivo and in vitro . A cisplatin-sensitive human ovarian cancer cell line, COC1, was used in the current study...
August 2018: Experimental and Therapeutic Medicine
Shih-Shen Lin, Chih-Yu Peng, Yi-Wen Liao, Ming-Yung Chou, Pei-Ling Hsieh, Cheng-Chia Yu
MiRNAs have been recognized as crucial components in carcinogenesis, but whether miR-1246 affects the cancer stemness and drug resistance in oral squamous cell carcinoma (OSCC) has not been fully understood and its downstream targets still need to be unraveled. In the present work, we employed miRNAs RT-PCR analysis to evaluate the expression of miR-1246 in tumor tissues and oral cancer stem cells (OCSC). Stemness phenotypes, including self-renewal, migration, invasion, colony formation capacities, and in vivo oncogenicity of oral cancer cells following transfected with miR-1246 inhibitors or mimics were examined...
August 16, 2018: Cancers
Yeongseon Byeon, Jeong-Won Lee, Wahn Soo Choi, Ji Eun Won, Ga Hee Kim, Min Gi Kim, Tae In Wi, Jae Myeong Lee, Tae Heung Kang, In Duk Jung, Young-Jae Cho, Hyung Jun Ahn, Byung Cheol Shin, Young Joo Lee, Anil K Sood, Hee Dong Han, Yeong-Min Park
Chemotherapy is commonly used in the treatment of ovarian cancer, yet most ovarian cancers harbor inherent resistance or develop acquired resistance. Therefore, novel therapeutic approaches to overcome chemoresistance are required. In this study, we developed a hyaluronic acid-labeled poly(d,l-lactide-co-glycolide) nanoparticle (HA-PLGA-NP) encapsulating both paclitaxel (PTX) and focal adhesion kinase (FAK) siRNA as a selective delivery system against chemoresistant ovarian cancer. The mean size and zeta potential of the HA-PLGA-NP were 220 nm and -7...
August 16, 2018: Cancer Research
Sjors M Kas, Julian de Ruiter, Eva Schut, Lorenzo Bombardelli, Ellen Wientjens, Anne Paulien Drenth, Renske de Korte-Grimmerink, Sunny Mahakena, Chris Phillips, Paul D Smith, Sjoerd Klarenbeek, Koen van de Wetering, Anton Berns, Lodewyk F A Wessels, Jos Jonkers, Koen Schipper
In human cancers, fibroblast growth factor receptor (FGFR) signaling is frequently hyperactivated by deregulation of FGF ligands or by activating mutations in the FGFR receptors such as gene amplifications, point mutations and gene fusions. As such, FGFR inhibitors are considered an attractive therapeutic strategy for patients with mutations in FGFR family members. We previously identified Fgfr2 as a key driver of invasive lobular carcinoma (ILC) in an in vivo insertional mutagenesis screen using the Sleeping Beauty (SB) transposon system...
August 16, 2018: Cancer Research
Jimmy Lee, Liang Leo Zhang, Wenjun Wu, Hui Guo, Yan Li, Madina Sukhanova, Girish Venkataraman, Hui Zhang, Mir Alikhan, Pin Lu, Ailin Guo, Natalie Galanina, Jorge Andrade, Michael L Wang, Y Lynn Wang
The BTK inhibitor ibrutinib has demonstrated a remarkable therapeutic effect in mantle cell lymphoma (MCL). However, approximately one-third of patients do not respond to the drug initially. To identify the mechanisms underlying primary ibrutinib resistance in MCL, we analyzed the transcriptome changes in ibrutinib-sensitive and ibrutinib-resistant cell lines on ibrutinib treatment. We found that MYC gene signature was suppressed by ibrutinib in sensitive but not resistant cell lines. We demonstrated that MYC gene was structurally abnormal and MYC protein was overexpressed in MCL cells...
August 28, 2018: Blood Advances
Shenglong Zhu, Ninghan Feng, Guangxiao Lin, Yuelin Tong, Xuan Jiang, Qin Yang, Shunhe Wang, Wei Chen, Zhao He, Yong Q Chen
BACKGROUND/AIMS: Rapamycin (Rp), the main mammalian target of rapamycin complex inhibitor, is a promising therapeutic agent for breast cancer. However, metabolic disorders and drug resistance reduce its efficacy. Epidemiological, clinical, and experimental studies have demonstrated that omega-3 polyunsaturated fatty acids (ω-3 PUFAs) significantly reduce the incidence and mortality of breast cancer and improve metabolic disorders. METHODS: Three breast cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Rp plus ω-3 PUFA treatment...
August 16, 2018: Cellular Physiology and Biochemistry
Chunlei Ge, Fang Wang, Chaochu Cui, Xiaodong Su, Kenneth Kin Wah To, Xiaokun Wang, Hui Zhang, Xin Song, Liwu Fu
BACKGROUND/AIMS: Multidrug resistance (MDR) induced by the ABC transporter subfamily B member 1 (ABCB1) and subfamilyG member 2 (ABCG2) limits successful cancer chemotherapy and no commercially available MDR modulator is used in the clinic. In the current study, we aimed to investigate the effects of PCI29732 on the enhancement of chemotherapeutic agents. METHODS: Cell cytotoxicity and reversal effect were measured with MTT assay. Additionally, flow cytometry was employed to detect the accumulation and efflux of the drugs...
August 16, 2018: Cellular Physiology and Biochemistry
Xiao Du, Shaoping Yin, Fang Zhou, Xu Du, Jianan Xu, Xiaochen Gu, Guangji Wang, Juan Li
Stimuli-responsive nanocarriers have demonstrated their potentials in optimizing chemotherapeutics and anticancer efficacy. In this study, a mixed micelle system (THSP) was prepared by combining reduction-sensitive hyaluronic acid-poly(lactide) (HA-ss-PLA) conjugates and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), with objective to achieve multiple functionalities of selective intracellular rapid release, active targeting capability and multidrug resistance reversal. The mixed micelle possessed desirable particle diameter of 124...
August 13, 2018: International Journal of Pharmaceutics
Zhiyi Shao, Yibo Li, Wenjie Dai, Hui Jia, Yingshi Zhang, Qiyu Jiang, Yantao Chai, Xiaojuan Li, Huiwei Sun, Ruichuang Yang, Yu Cao, Fan Feng, Yingjie Guo
Transcription factor E26 transformation specific sequence 1 (ETS-1) is a primary regulator in the metastasis of human cancer cells, especially hepatocellular carcinoma (HCC) cells; and it would affect the prognosis of HCC patients who received chemotherapies. However, the regulatory role of ETS-1 in the resistance of HCC cells to molecular-targeting agent remains poorly understood. In the present work, we demonstrate that high ETS-1 expression correlates with poor prognosis of advanced HCC patients received Sorafenib treatment...
August 13, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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