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https://www.readbyqxmd.com/read/28535649/-cancer-associated-fibroblasts-regulate-the-chemoresistance-of-lung-cancer-cell-line-a549-via-sdf-1-secretion
#1
F Zou, Z H Zhang, Y T Zhang, J Q Zhao, X L Zhang, C L Wen, X Y Song, W M Zhou
Objective: To investigate whether cancer-associated- fibroblasts (CAF), the key component of tumor microenvironment, regulate the chemoresistant capacity of lung cancer cell line A549 through SDF-1 secretion. Methods: Primary cell isolation techniques was used to isolate cancer-associated-fibroblasts from lung cancer patients. MTT assay was applied to determine the proliferation and chemoresistance of A549 cells. Quantative PCR was used to detect the mRNA changes of Bcl-xL. Western blotting was used to detect the protein expression of Bcl-xL...
May 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28535350/activation-of-phenyl-4-2-oxo-3-alkylimidazolidin-1-yl-benzenesulfonates-prodrugs-by-cyp1a1-as-new-antimitotics-targeting-breast-cancer-cells
#2
Sébastien Fortin, Xavier Charest-Morin, Vanessa Turcotte, Coraline Lauvaux, Jacques Lacroix, Marie-France Côté, Stéphane Gobeil, Rene C-Gaudreault
Prodrug-mediated utilization of the cytochrome P450 (CYP) 1A1 to obtain the selective release of potent anticancer products within cancer tissues is a promising approach in chemotherapy. We herein report the rationale, preparation, biological evaluation and mechanism of action of phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs), that are antimicrotubule prodrugs activated by CYP1A1. Although PAIB-SOs are inert in most cells tested, they are highly cytocidal towards several human breast cancer cells, including hormone-independent and chemoresistant types...
May 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28534989/enhanced-cancer-stem-cell-properties-of-a-mitotically-quiescent-subpopulation-of-p75ntr-positive-cells-in-esophageal-squamous-cell-carcinoma
#3
Hirofumi Kojima, Tomoyuki Okumura, Tetsuji Yamaguchi, Takeshi Miwa, Yutaka Shimada, Takuya Nagata
Mitotically quiescent cancer stem cells (CSCs) possess higher malignant potential than other CSCs, indicating their higher contribution to therapeutic resistance than that of other CSCs. In esophageal squamous cell carcinoma (ESCC), p75 neurotrophin receptor (p75NTR) is expressed in a candidate CSC population showing high tumorigenicity and chemoresistance. In the present study, we isolated and characterized quiescent CSCs population in ESCC based on p75NTR expression and cell cycle status. Expression of p75NTR and Ki-67 in ESCC cell lines (KYSE cells) and surgically resected ESCC specimens was detected by performing immunocytochemical analysis...
May 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534965/cucurbitacin%C3%A2-b-induces-autophagy-and-apoptosis-by-suppressing-cip2a-pp2a-mtorc1-signaling-axis-in-human-cisplatin-resistant-gastric-cancer-cells
#4
Xuewen Liu, Chao Duan, Juanli Ji, Te Zhang, Xiaoning Yuan, Yunfei Zhang, Wenjing Ma, Jingyuan Yang, Linsen Yang, Zhiguo Jiang, Huiliang Yu, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of tumors including gastric cancer (GC). Mammalian target of rapamycin complex 1 (mTORC1) over-activation is detected in GC and many other cancers. Previous study found that CIP2A/mTORC1 controls cell growth and autophagy through direct association. CIP2A plays an 'oncogenic nexus' in several cancer types to participate in the tumorigenic transformation and chemoresistance. In the present study, we investigated whether Cucurbitacin B (CuB), a natural compound found in Cucurbitaceae, can be used in cisplatin (DDP)-resistant human GC cell line SGC7901/DDP...
May 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28534517/prolonged-exposure-to-extracellular-lumican-restrains-pancreatic-adenocarcinoma-growth
#5
X Li, Y Kang, D Roife, Y Lee, M Pratt, M R Perez, B Dai, E J Koay, J B Fleming
We previously demonstrated that pancreatic stellate cells within pancreatic ductal adenocarcinoma (PDAC) stroma secrete lumican and its presence is associated with prolonged survival of patients with localized PDAC. Here, we observed that extracellular lumican decreases PDAC tumour cell growth in xenograft and syngeneic orthotopic animal models, and induces growth inhibition of low-passage human PDAC cells in a species-specific manner. PDAC cells grown in variant culture conditions and exposed to extracellular lumican display typical characterizations of cancer cell in a quiescent state, such as growth inhibition, apoptosis, G0/G1 arrest and chemoresistance...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534505/proteomic-identification-of-erp29-as-a-key-chemoresistant-factor-activated-by-the-aggregating-p53-mutant-arg282trp
#6
Y Zhang, Y Hu, J-L Wang, H Yao, H Wang, L Liang, C Li, H Shi, Y Chen, J-Y Fang, J Xu
Mutation of the TP53 gene represents a prevalent genetic alteration in human cancers, and a subset of p53 mutants may form amyloid-like aggregates that contribute to the gain of oncogenic functions (GOFs) and chemoresistance. Here we identify the pathways that may mediate the aggregation-associated GOF by using combined proteomic analysis and genome-wide recruitment profiling. Mass spectrometry revealed activation of unfolded protein response (UPR) pathway and upregulation of endoplasmic reticulum protein 29 (ERp29) in (R282W)TP53-expressing cells that were exposed to cisplatin stress...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28532411/aldehyde-dehydrogenase-2-2-knock-in-mice-show-increased-reactive-oxygen-species-production-in-response-to-cisplatin-treatment
#7
Jeewon Kim, Che-Hong Chen, Jieying Yang, Daria Mochly-Rosen
BACKGROUND: The aldehyde dehydrogenase (ALDH) enzyme family metabolizes and detoxifies both exogenous and endogenous aldehydes. Since chemotherapeutic agents, such as cisplatin, generate cytotoxic aldehydes and oxidative stress, and chemoresistant cancer cells express high levels of ALDH enzymes, we hypothesized that different ALDH expression within cells may show different chemosensitivity. ALDH2 has the lowest Km for acetaldehyde among ALDH isozymes and detoxifies acetaldehydes in addition to other reactive aldehydes, such as 4-hydroxy-nonenal, malondialdehyde and acrolein produced from lipid peroxidation by reactive oxygen species (ROS)...
May 22, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28530221/micu1-drives-glycolysis-and-chemoresistance-in-ovarian-cancer
#8
Prabir K Chakraborty, Soumyajit Banerjee Mustafi, Xunhao Xiong, Shailendra Kumar Dhar Dwivedi, Vasyl Nesin, Sounik Saha, Min Zhang, Danny Dhanasekaran, Muralidharan Jayaraman, Robert Mannel, Kathleen Moore, Scott McMeekin, Da Yang, Rosemary Zuna, Kai Ding, Leonidas Tsiokas, Resham Bhattacharya, Priyabrata Mukherjee
Cancer cells actively promote aerobic glycolysis to sustain their metabolic requirements through mechanisms not always clear. Here, we demonstrate that the gatekeeper of mitochondrial Ca(2+) uptake, Mitochondrial Calcium Uptake 1 (MICU1/CBARA1) drives aerobic glycolysis in ovarian cancer. We show that MICU1 is overexpressed in a panel of ovarian cancer cell lines and that MICU1 overexpression correlates with poor overall survival (OS). Silencing MICU1 in vitro increases oxygen consumption, decreases lactate production, inhibits clonal growth, migration and invasion of ovarian cancer cells, whereas silencing in vivo inhibits tumour growth, increases cisplatin efficacy and OS...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529925/targeting-lung-cancer-stem-cells-research-and-clinical-impacts
#9
REVIEW
Norashikin Zakaria, Nazilah Abdul Satar, Noor Hanis Abu Halim, Siti Hawa Ngalim, Narazah Mohd Yusoff, Juntang Lin, Badrul Hisham Yahaya
Lung cancer is the most common cancer worldwide, accounting for 1.8 million new cases and 1.6 million deaths in 2012. Non-small cell lung cancer (NSCLC), which is one of two types of lung cancer, accounts for 85-90% of all lung cancers. Despite advances in therapy, lung cancer still remains a leading cause of death. Cancer relapse and dissemination after treatment indicates the existence of a niche of cancer cells that are not fully eradicated by current therapies. These chemoresistant populations of cancer cells are called cancer stem cells (CSCs) because they possess the self-renewal and differentiation capabilities similar to those of normal stem cells...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28529574/knockdown-of-stmn1-enhances-osteosarcoma-cell-chemosensitivity-through-inhibition-of-autophagy
#10
Zili Wang, Rongzhen He, Hansong Xia, Yu Wei, Song Wu
Chemoresistance is a major cause for the poor prognosis of osteosarcoma (OS) patients. However, our understanding of mechanisms underlying chemoresistance in OS are limited. The present study aimed to investigate the effect of stathmin 1 (STMN1) on paclitaxel-induced chemoresistance, as well as the underlying mechanism. Western blot analysis data revealed that the expression level of STMN1 was dramatically increased in OS cell lines (HOS, Saos-2, U-2OS and MG-63), when compared to normal osteoblast hFOB1.19 cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28528979/sensitization-of-breast-cancer-cells-to-paclitaxel-by-dichloroacetate-through-inhibiting-autophagy
#11
Minghao Wang, Cuiwei Liao, Ying Hu, Wenqin Pan, Jun Jiang
Chemotherapy is still the main adjuvant strategy in the treatment of cancer, however, chemoresistance is also frequently encountered. Autophagy inhibition has been widely accepted as a promising therapeutic strategy in cancer, while the lack of effective and specific autophagy inhibitors hinders its application. Here we found that dichloroacetate (DCA), a small molecule compound, could significantly inhibit the autophagy induced by Doxorubicin in breast cancer cells. And DCA markedly enhances Doxorubicin-induced breast cancer cell death and anti-proliferation in vitro...
May 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28528134/enhancing-tumor-cell-response-to-multidrug-resistance-with-ph-sensitive-quercetin-and-doxorubicin-conjugated-multifunctional-nanoparticles
#12
Cenk Daglioglu
Classical chemotherapy uses chemotherapeutic agents as a mainstay of anticancer treatment. However, the development of multidrug resistance to chemotherapy limits the effectiveness of current cancer treatment. Nanosized bioconjugates combining a chemotherapeutic agent with a pharmacological approach may improve the curative effect of chemotherapeutic agents. Herein I addressed this issue by describing the synthesis, and testing of, pH-responsive Fe3O4@SiO2(FITC)-BTN/QUR/DOX multifunctional nanoparticles. The particles were designed to modulate resistance-mediating factors and to potentiate the efficacy of DOX against chemoresistance...
May 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28527723/activation-of-nrf2-signaling-augments-vesicular-stomatitis-virus-oncolysis-via-autophagy-driven-suppression-of-antiviral-immunity
#13
David Olagnier, Rassin R Lababidi, Samar Bel Hadj, Alexandre Sze, Yiliu Liu, Sharadha Dayalan Naidu, Matteo Ferrari, Yuan Jiang, Cindy Chiang, Vladimir Beljanski, Marie-Line Goulet, Elena V Knatko, Albena T Dinkova-Kostova, John Hiscott, Rongtuan Lin
Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28526879/musashi-1-promotes-a-cancer-stem-cell-lineage-and-chemoresistance-in-colorectal-cancer-cells
#14
Guang-Yuh Chiou, Tzu-Wei Yang, Chi-Chou Huang, Chia-Ying Tang, Jung-Yi Yen, Ming-Chang Tsai, Hsuan-Yi Chen, Nurul Fadhilah, Chun-Che Lin, Yuh-Jyh Jong
Colorectal cancers (CRCs) are a critical health issue worldwide. Cancer stem cell (CSC) lineages are associated with tumour transformation, progression, and malignant transformation. However, how lineages are transformed and how chemoresistance is acquired by CRCs remain largely unknown. In this report, we demonstrated that the RNA-binding protein Musashi-1 enhanced the development of CD44(+) colorectal CSCs and triggered the formation of anti-apoptotic stress granules (SGs). Our results indicated that CD44(+) CSC lineage-specific induction of tumour malignancies was controlled by Musashi-1...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526769/tam-receptor-tyrosine-kinases-in-cancer-drug-resistance
#15
REVIEW
Mikaella Vouri, Sassan Hafizi
Receptor tyrosine kinases (RTK) are major regulators of key biological processes, including cell growth, survival, and differentiation, and were established early on as proto-oncogenes, with aberrant expression linked to tumor progression in many cancers. Therefore, RTKs have emerged as major targets for selective therapy with small-molecule inhibitors. However, despite improvements in survival rates, it is now apparent that the targeting of RTKs with selective inhibitors is only transiently effective, as the majority of patients eventually become resistant to therapy...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28526406/trastuzumab-emtansine-suppresses-the-growth-of-her2-positive-small-cell-lung-cancer-in-preclinical-models
#16
Osamu Morimura, Toshiyuki Minami, Takashi Kijima, Shohei Koyama, Tomoyuki Otsuka, Yuhei Kinehara, Akio Osa, Masayoshi Higashiguchi, Kotaro Miyake, Izumi Nagatomo, Haruhiko Hirata, Kota Iwahori, Takayuki Takimoto, Yoshito Takeda, Hiroshi Kida, Atsushi Kumanogoh
Overcoming chemoresistance is essential for achieving better prognoses in SCLC. Previously, we reported that HER2 is upregulated when HER2-positive SCLC cells acquire chemoresistance. HER2-upregulated cisplatin- or etoposide-resistant SCLC cells were sensitive to trastuzumab-mediated ADCC. However, irinotecan-resistant SCLC cells, such as SBC-3/SN-38, were refractory to trastuzumab despite high HER2 expression. To address this issue, we examined the antitumor efficacy of trastuzumab emtansine (T-DM1) on trastuzumab-resistant HER2-positive SCLC...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526069/xlf-mediated-nhej-activity-in-hepatocellular-carcinoma-therapy-resistance
#17
Sitian Yang, Xiao Qi Wang
BACKGROUND: DNA repair pathways are used by cancer cells to overcome many standard anticancer treatments, causing therapy resistance. Here, we investigated the role of XRCC4-like factor (XLF), a core member of the non-homologous end joining (NHEJ) repair pathway, in chemoresistance in hepatocellular carcinoma (HCC). METHODS: qRT-PCR analysis and western blotting were performed to detect expression levels of genes and proteins related to NHEJ. NHEJ repair capacity was assessed in vitro (cell-free) and in vivo by monitoring the activity of the NHEJ pathway...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28521472/cd117-expression-is-a-predictive-marker-for-poor-prognosis-in-patients-with-non-small-cell-lung-cancer
#18
Tomohiko Sakabe, Junya Azumi, Tomohiro Haruki, Yoshihisa Umekita, Hiroshige Nakamura, Goshi Shiota
Non-small cell lung cancer (NSCLC) accounts for >85% of incidences of lung cancer, for which the predicted 5-year survival rates are low and recurrence rates remain high. Although it has been reported that the patients with SCLC cells that possess the cluster of differentiation (CD) 117 marker exhibited poor prognosis and poor response to chemotherapy, no studies concerning the association of CD117 expression with prognosis of the patients with NSCLC have been reported. An in vitro study reportedly revealed that CD117-positive cell populations in NSCLC cell lines exhibited cancer stem cell (CSC) phenotypes including self-renewal and chemoresistance...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521444/microrna-330-inhibited-cell-proliferation-and-enhanced-chemosensitivity-to-5-fluorouracil-in-colorectal-cancer-by-directly-targeting-thymidylate-synthase
#19
Weidong Xu, Huayong Jiang, Fuli Zhang, Junmao Gao, Jun Hou
Colorectal cancer (CRC) is the third most common cancer in males and the second most common in females, worldwide. Currently, 5-fluorouracil (5-FU)-mediated chemotherapy is the adjuvant treatment for patients with CRC following surgical resection. However, a number of patients with CRC develop 5-FU resistance, which is a major challenge for the effective treatment of cancer. Therefore, it is important to investigate the molecular mechanisms underlying chemoresistance and the therapeutic treatments that may improve the treatment of CRC...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28517961/overcoming-chemoresistance-in-cancer-stem-cells-with-the-help-of-micrornas-in-colorectal-cancer
#20
Andrew Fesler, Shixiang Guo, Hua Liu, Ning Wu, Jingfang Ju
It has been recognized that acute resistance to chemotherapy mediated by post-transcriptional and translational control is crucial to influence response and survival in cancer treatment. Tumor cells are highly heterogeneous and have the ability to adapt a resistance phenotype through epigenetic regulations such as microRNAs. This poses a major challenge to the treatment of advanced stage colon cancer patients. Colon cancer stem cells have been identified as one of the major contributors to resistance of colon cancer to chemotherapy...
May 18, 2017: Epigenomics
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