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Colon Treatment Resistance Stem like

Agnieszka Kotlarz, Małgorzata Przybyszewska, Paweł Swoboda, Jacek Neska, Joanna Miłoszewska, Monika Anna Grygorowicz, Andrzej Kutner, Sergiusz Markowicz
Conventional cytotoxic drugs preferentially eliminate differentiated cancer cells but spare relatively more resistant stem-like cancer cells capable to initiate recurrence. Due to cancer cell plasticity, the stem-like phenotype can be also acquired by cancer cells refractory to treatment with cytotoxic drugs. We investigated whether drugs inhibiting receptor tyrosine kinases could be used to target human colon cancer cells initiating cancer regrowth following conventional cytotoxic treatment. The moderately differentiated cell line HT-29 and poorly differentiated cell line HCT-116 were exposed to 5-fluorouracil (5-FU)...
February 14, 2019: Journal of Steroid Biochemistry and Molecular Biology
Thi Thinh Nguyen, Trong Thuan Ung, Nam Ho Kim, Young Do Jung
Bile acids (BAs) are cholesterol derivatives synthesized in the liver and then secreted into the intestine for lipid absorption. There are numerous scientific reports describing BAs, especially secondary BAs, as strong carcinogens or promoters of colon cancers. Firstly, BAs act as strong stimulators of colorectal cancer (CRC) initiation by damaging colonic epithelial cells, and inducing reactive oxygen species production, genomic destabilization, apoptosis resistance, and cancer stem cells-like formation. Consequently, BAs promote CRC progression via multiple mechanisms, including inhibiting apoptosis, enhancing cancer cell proliferation, invasion, and angiogenesis...
November 6, 2018: World Journal of Clinical Cases
Alexandra Soler, Laure Cayrefourcq, Thibault Mazard, Anna Babayan, Pierre-Jean Lamy, Said Assou, Eric Assenat, Klaus Pantel, Catherine Alix-Panabières
Circulating tumor cells (CTCs) are important clinical indicators for prognosis and treatment efficacy. However, CTC investigation is hampered by their low number, making the establishment of permanent CTC lines very challenging. We derived and characterized nine CTC lines using blood samples from a patient with metastatic colorectal cancer collected before and after chemotherapy and targeted therapy, and during cancer progression. These cell lines displayed an intermediate epithelial/mesenchymal phenotype, stem-cell like characteristics, angiogenesis potential, an osteomimetic signature and the capacity to escape from the immune system...
October 29, 2018: Scientific Reports
Xiao-Yun Li, Xiao-Feng Liao, Hong-Bo Wang, Jian Zhang
Despite improvements in the development of drugs for the treatment of cancer, drug resistance remains a major obstacle. In colon cancer, following an initially promising response, patients develop drug resistance, which impacts the efficacy and halts the response of cancerous cells towards drugs. In the present study, a phosphatase and tensin homolog (PTEN) knockdown model of LS180 cells, doxorubicin-resistant models of LS180 cells as well as doxorubicin-resistant LS180 (PTEN) knockdown model were established...
November 2018: Oncology Letters
Szu-Yuan Wu, Yan-Jiun Huang, Yew-Min Tzeng, Chi-Ying F Huang, Michael Hsiao, Alexander T H Wu, Tse-Hung Huang
BACKGROUND: Drug resistance represents a major challenge for treating patients with colon cancer. Accumulating evidence suggests that Insulin-like growth factor (IGF)-associated signaling promotes colon tumorigenesis and cancer stemness. Therefore, the identification of agents, which can disrupt cancer stemness signaling, may provide improved therapeutic efficacy. METHODS: Mimicking the tumor microenvironment, we treated colon cancer cells with exogenous IGF1. The increased stemness of IGF1-cultured cells was determined by ALDH1 activity, side-population, tumor sphere formation assays...
September 25, 2018: Cancers
Sara Soltanian, Helia Riahirad, Athareh Pabarja, Elham Jafari, Behjat Kalantari Khandani
PURPOSE: There is a lot of evidence suggesting that a small subset of cancer cells resistant to conventional chemotherapy and radiotherapy and known as cancer stem cells (CSCs) is responsible for promoting metastasis and cancer relapse. Therefore, targeting and eliminating the CSCs could lead to higher survival rates and a better quality of life. In comparison with conventional chemical drugs that may not be effective against CSCs, phytochemicals are strong anti-CSCs agents. The current study examines the effect of 5-fluorouracil plus oxaliplatin (FOLFOX) as a common chemotherapy drug on colorectal cancer as well as the influence of Cinnamic acid (CINN) as a plant-derived phytochemical on colon cancer stem-like cells in HT-29 adenocarcinoma cell line...
September 12, 2018: Daru: Journal of Faculty of Pharmacy, Tehran University of Medical Sciences
Yong-Qing Liu, Shi-Kang Wang, Qing-Qing Xu, Hui-Qing Yuan, Yan-Xia Guo, Qian Wang, Feng Kong, Zhao-Min Lin, De-Qing Sun, Rong-Mei Wang, Hong-Xiang Lou
Acquired docetaxel-resistance of prostate cancer (PCa) remains a clinical obstacle due to the lack of effective therapies. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic triterpenic acid isolated from the fragrant gum resin of the Boswellia serrata tree, which has shown intriguing antitumor activity against human cell lines established from PCa, colon cancer, malignant glioma, and leukemia. In this study, we examined the effects of AKBA against docetaxel-resistant PCa in vitro and in vivo as well as its anticancer mechanisms...
August 31, 2018: Acta Pharmacologica Sinica
Donghyeok Kim, Bo-Hyun Choi, In-Geun Ryoo, Mi-Kyoung Kwak
Aldehyde dehydrogenase 1A1 (ALDH1A1) is one of cancer stem cell (CSC) markers, and high ALDH1 expression has been related to drug resistance and facilitated tumor growth. In this study, we investigated the potential involvement of nuclear factor erythroid 2-like 2 (NFE2L2/NRF2) in CSC-like properties of ALDH-high ovarian CSCs. Our experimental system, ALDH1A1-high (ALDH-H) subpopulation, was isolated and stabilized using doxorubicin-resistant ovarian cancer A2780 cells. ALDH-H exerted CSC-like properties such as drug resistance, colony/sphere formation, and enhanced tumor growth along with high levels of CSCs markers compared to ALDH1A1-low (ALDH-L)...
August 30, 2018: Cell Death & Disease
Mao-Hua Cai, Xiao-Gang Xu, Shi-Li Yan, Ze Sun, Yin Ying, Bai-Kui Wang, Yue-Xing Tu
BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent malignancies in the world and developed drug resistance has represented one of the most challenging tasks for management. The current therapeutic regimens may select and enrich cancer stem-like cells (CSCs) resulting in the increased resistance against treatment, metastatic potential and mortality. Regorafenib is a multi-kinase inhibitor, an FDA-approved last-of-line treatment for patients with chemo-refractory metastatic CRC...
July 13, 2018: Journal of Experimental & Clinical Cancer Research: CR
Pengfei Su, Yong Yang, Guoxin Wang, Xiaowu Chen, Yongle Ju
Resistance to conventional chemotherapeutic agents, including irinotecan (CPT‑11), 5-fluorouracil and capecitabine is a major cause for therapeutic failure in patients with colorectal cancer (CRC). Increasing evidence has demonstrated that cancer cells exhibiting stem cell-like characteristics are associated with the development of resistance to chemotherapeutic agents. As a plant polyphenol, curcumin has been demonstrated to have the ability to ameliorate resistance of CRC to chemotherapeutic agents, but the associations among curcumin, cancer stem cells (CSCs) and chemoresistance of CRC remain unclear...
September 2018: International Journal of Oncology
Cindy Slater, Jo-Anne De La Mare, Adrienne Lesley Edkins
The cancer stem cell (CSC) theory implicates a small subpopulation of cells with stem-like properties, which is responsible for tumour initiation, development and metastasis. The unique biological and functional characteristics of CSCs, widely associated with treatment resistance, indicate an association between metastasis and stemness. It was hypothesised that metastatic cell lines may be enriched in CSCs and that this would correlate with a more resistant tumour. In the present study, the SW480 and SW620 paired cell lines derived from a colon adenocarcinoma and its lymph node metastasis, respectively were compared as an in vitro model of cancer progression...
June 2018: Oncology Letters
Vandana Venkatesh, Raghu Nataraj, Gopenath S Thangaraj, Murugesan Karthikeyan, Ashok Gnanasekaran, Shanmukhappa B Kaginelli, Gobianand Kuppanna, Chandrashekrappa Gowdru Kallappa, Kanthesh M Basalingappa
Cancer stem cells (CSCs) have been defined as cells within tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. CSCs have been increasingly identified in blood cancer, prostate, ovarian, lung, melanoma, pancreatic, colon, brain and many more malignancies. CSCs have slow growth rate and are resistant to chemotherapy and radiotherapy that lead to the failure of traditional current therapy. Eradicating the CSCs and recurrence, is promising aspect for the cure of cancer...
2018: Stem Cell Investigation
Xingxing Kang, Wanling Zhang, Xunchao Cai, Tong Zhu, Yarong Xue, Changhong Liu
Biocontrol bacteria that can act like a "vaccine", stimulating plant resistance to pathogenic diseases, are still not fully elucidated. In this study, an endophytic bacterium, Bacillus velezensis CC09, labeled with green fluorescent protein, was tested for its colonization, migration, and expression of genes encoding iturin A synthetase within wheat tissues and organs as well as for protective effects against wheat take-all and spot blotch diseases. The results showed that strain CC09 not only formed biofilm on the root surface but was also widely distributed in almost every tissue, including the epidermis, cortex, and xylem vessels, and even migrated to stems and leaves, resulting in 66...
June 2018: Molecular Plant-microbe Interactions: MPMI
Jason P W Carey, Cansu Karakas, Tuyen Bui, Xian Chen, Smruthi Vijayaraghavan, Yang Zhao, Jing Wang, Keith Mikule, Jennifer K Litton, Kelly K Hunt, Khandan Keyomarsi
PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients. Several of those patients exhibit intrinsic/acquired resistance mechanisms that limit efficacy of PARPi monotherapy. Here we show how the efficacy of PARPi in triple-negative breast cancers (TNBC) can be expanded by targeting MYC-induced oncogenic addiction. In BRCA-mutant/sporadic TNBC patients, amplification of the MYC gene is correlated with increased expression of the homologous DNA recombination enzyme RAD51 and tumors overexpressing both genes are associated with worse overall survival...
February 1, 2018: Cancer Research
H Was, J Czarnecka, A Kominek, K Barszcz, T Bernas, K Piwocka, B Kaminska
Colorectal cancer (CRC) is the second leading cause of death among cancer patients in the Northern countries. CRC can reappear a long time after treatment. Recent clinical studies demonstrated that, in response to chemotherapy, cancer cells may undergo stress-induced premature senescence (SIPS), which typically results in growth arrest. Nonetheless, these senescent cells were reported to divide in an atypical manner and thus contribute to cancer re-growth. Therefore, we examined if SIPS escape may follow treatment with chemotherapeutics used clinically: 5-fluorouracil (5-FU), oxaliplatin (OXA) and irinotecan (IRINO)...
January 2, 2018: Cancer Biology & Therapy
Paolo Luraghi, Viola Bigatto, Elia Cipriano, Gigliola Reato, Francesca Orzan, Francesco Sassi, Francesca De Bacco, Claudio Isella, Sara E Bellomo, Enzo Medico, Paolo M Comoglio, Andrea Bertotti, Livio Trusolino, Carla Boccaccio
Purpose: Patient-derived xenografts (" xenopatients ") of colorectal cancer metastases have been essential to identify genetic determinants of resistance to the anti-EGFR antibody cetuximab and to explore new therapeutic strategies. From xenopatients, a genetically annotated collection of stem-like cultures (" xenospheres ") was generated and characterized for response to targeted therapies. Experimental Design: Xenospheres underwent exome-sequencing analysis, gene expression profile, and in vitro targeted treatments to assess genetic, biological, and pharmacologic correspondence with xenopatients, and to investigate nongenetic biomarkers of therapeutic resistance...
February 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Koran S Harris, Bethany A Kerr
Metastatic or recurrent tumors are the primary cause of cancer-related death. For prostate cancer, patients diagnosed with local disease have a 99% 5-year survival rate; however, this 5-year survival rate drops to 28% in patients with metastatic disease. This dramatic decline in survival has driven interest in discovering new markers able to identify tumors likely to recur and in developing new methods to prevent metastases from occurring. Biomarker discovery for aggressive tumor cells includes attempts to identify cancer stem cells (CSCs)...
2017: Stem Cells International
Pei-Chi Hou, Yo-Hua Li, Shih-Chieh Lin, Shau-Chieh Lin, Jenq-Chang Lee, Bo-Wen Lin, Jing-Ping Liou, Jang-Yang Chang, Ching-Chuan Kuo, Yi-Min Liu, H Sunny Sun, Shaw-Jenq Tsai
Cancer stem-like cells (CSC) evolve to overcome the pressures of reduced oxygen, nutrients or chemically induced cell death, but the mechanisms driving this evolution are incompletely understood. Here, we report that hypoxia-mediated downregulation of the dual specificity phosphatase 2 (DUSP2) is critical for the accumulation of CSC in colorectal cancer. Reduced expression of DUSP2 led to overproduction of COX-2-derived prostaglandin E2 , which promoted cancer stemness via the EP2/EP4 signaling pathways. Genetic and pharmacological inhibition of PGE2 biosynthesis or signal transduction ameliorated loss-of-DUSP2-induced tumor growth and cancer stemness...
August 15, 2017: Cancer Research
Yong Yang, Guoxin Wang, Dajian Zhu, Yanfeng Huang, Yong Luo, Pengfei Su, Xiaowu Chen, Qian Wang
Inherent and acquired chemoresistance reduce the effectiveness of irinotecan in the treatment of metastatic colorectal cancer (CRC). However, the molecular mechanisms underlying this resistance process are still unclear. Twist1 is one of the master transcription factors of epithelial-mesenchymal transition (EMT). Our previous study indicated that Twist1 is overexpressed in colon cancer tissues, and demonstrated that Twist1 plays a crucial role in the chemoresistance of CRC. In the present study, we further investigated how Twist1 contribute to acquired resistance to irinotecan in colon cancer...
August 2017: International Journal of Oncology
Tse-Hung Huang, Szu-Yuan Wu, Yan-Jiun Huang, Po-Li Wei, Alexander Th Wu, Tsu-Yi Chao
Colon cancer is one of the most prevalent cancer types in developed countries. Metastasis and drug resistance are two contributing factors to the high mortality rate. Accumulating evidence suggest that cancer stem-like cells (CSCs) represents as a major contributor to these malignant features. Here, we identified and isolated colon cancer stem-like cells using side-population (SP) method from human colon cancer cell lines. SP colon cells demonstrate cancer stem-like cell properties including enhanced sphere-forming ability and resistance towards fluorouracil (5-FU)...
2017: American Journal of Cancer Research
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