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Gage Brummer, Diana S Acevedo, Qingting Hu, Mike Portsche, Wei Fang, Min Yao, Brandon Zinda, Megan Myers, Nehemiah S Alvarez, Patrick Fields, Yan Hong, Fariba Behbod, Nikki Cheng
Ductal carcinoma in situ (DCIS) is the most common form of breast cancer, with 50,000 cases diagnosed every year in the United States. Over-treatment and under-treatment remain significant clinical challenges in patient care. Identifying key mechanisms associated with DCIS progression could uncover new biomarkers to better predict patient prognosis and improve guided treatment. Chemokines are small soluble molecules that regulate cellular homing through molecular gradients. CCL2-mediated recruitment of CCR2+ macrophages are a well-established mechanism for metastatic progression...
November 13, 2017: Molecular Cancer Research: MCR
Che-Yi Lin, Pei-Ling Hsieh, Yi-Wen Liao, Chih-Yu Peng, Ming-Yi Lu, Ching-Hsuan Yang, Cheng-Chia Yu, Chia-Ming Liu
Cancer recurrence and chemoresistance are two major obstacles to the treatment of oral squamous cell carcinomas (OSCC). And cancer stem cells (CSCs) have been found to possess tumor initiating, self-renewal and metastasis abilities, resulting in the relapse and chemoresistance of OSCC. In the present study, we investigated the anti-CSCs effect of berberine, a phenanthrene alkaloid isolated from the Berberis genus. Our results demonstrated that berberine dose dependently downregulated the oncogenicity in vitro, including ALDH1 activity, self-renewal property, and colony formation and invasion abilities as well as potentiated chemosensitivity of OSCC-CSCs...
October 6, 2017: Oncotarget
Yue Dong, Sebastian Ochsenreither, Chengxuan Cai, Andreas M Kaufmann, Andreas E Albers, Xu Qian
There is a lack of predictive biomarkers that can identify patients with head and neck squamous cell carcinoma (HNSCC) who will experience treatment failure and develop drug resistance, recurrence, and metastases. Cancer stem-like cells (CSC) were identified as a subset of cells within the tumor in a variety of solid tumors including HNSCC. CSC are considered the tumor-initiating population responsible for recurrence or metastasis and are associated with therapy resistance. This meta-analysis including fourteen studies with altogether 1258 patients updates and summarizes all relevant data on the impact of ALDH1+ CSC on the prognosis of HNSCC and its association with clinicopathological parameters...
2017: PloS One
T J Miller, M J McCoy, C Hemmings, M K Bulsara, B Iacopetta, C F Platell
Cancer stem-like cells are highly tumourigenic cells that can repopulate entire tumours after apparent successful treatment. Recent evidence suggests they interact with other cells in the tumour microenvironment, including immune cell subsets, to enhance their survival. The aim of this study was to determine whether the expression of immune cell markers in primary colon cancer impacts the prognostic significance of cancer stem-like cell marker expression. Immunohistochemistry was used to assess the expression of putative stem cell markers (ALDH1, CD44v6, CD133, Lgr5, SOX2) and immune cell related markers (CD3, CD8, FoxP3, PD-L1) in 104 patients with stage III colon cancer...
October 25, 2017: Pathology
Hsi-Wen Yeh, Szu-Shuo Lee, Chieh-Yu Chang, Chun-Mei Hu, Yuh-Shan Jou
Cellular metabolism of cancer cell is generally recognized to provide energy for facilitating tumor growth, but little is known about the aberrant metabolism in tumor progression and its prognostic value. Here, we applied integrated genomic approach to uncover the aberrant expression of metabolic enzymes in poorly-differentiated human hepatocellular carcinoma (HCC) for revealing targets against HCC malignancy. A total of 135 upregulated (22 are rate-limiting enzymes (RLEs)) and 362 down-regulated (77 are RLEs) metabolic genes were identified and associated with poor patient survival in large-cohorts of HCC patients in TCGA-LIHC and two other independent transcriptomic studies...
September 29, 2017: Oncotarget
Jae Hee Cho, Sun A Kim, Soo Been Park, Hee Man Kim, Si Young Song
Pancreatic cancer stem cells (CSCs) play a crucial role in tumorigenesis and chemoresistance of pancreatic ductal adenocarcinoma. Pancreatic adenocarcinoma up-regulated factor (PAUF), a novel secretory protein, has been shown to contribute to cancer progression and metastasis. Because the clinical relationship between PAUF and pancreatic CSCs is largely unknown, we investigated the associations between the functional role of PAUF and pancreatic CSCs. Pancreatic cancer sphere cultured from the CFPAC-1 cells showed elevated expression of PAUF and pluripotent stemness genes (Oct4, Nanog, Stat3, and Sox2), and the mRNA of PAUF were increased in CD44(+)CD24(+)ESA(+) pancreatic CSCs...
September 29, 2017: Oncotarget
Yoon-Jae Kim, Daeil Sung, Eunhye Oh, Youngkwan Cho, Tae-Min Cho, Lee Farrand, Jae Hong Seo, Ji Young Kim
Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Trastuzumab resistance is a multi-factorial phenomenon thought to arise from the presence of cancer stem cells and interactions between truncated p95HER2 and HER family members. Flubendazole (FLU) is a potent anthelmintic agent with an exceptional safety profile. Evidence also suggests that it can act as an anticancer agent in several cancer cell types. We sought to investigate the effect of FLU on apoptosis, HER2/Akt signaling, breast cancer stem cell (BCSC)-like properties and trastuzumab resistance in HER2-positive breast cancer cells...
November 1, 2017: Cancer Letters
Jun Wang, Cheng-Liang Yang, Li-Li Zou
As a cancer stem cell marker associated with tumorigenesis, aldehyde dehydrogenase 1 (ALDH1) has recently been identified in gliomas. However, an insufficient number of clinical studies have been published to demonstrate its prognostic significance in glioma. In the present study, a systematic meta-analysis was performed to comprehensively evaluate the correlation of ALDH1 with age, sex, the World Health Organization (WHO) grade, and overall survival (OS) in patients with glioma. A search of relevant publications was conducted to select eligible studies on this subject, and the pooled hazard ratios (HRs) and related risks (RRs) with 95% confidence intervals (95% CIs) were assessed...
November 2017: Molecular and Clinical Oncology
Lauren MacDonagh, Michael F Gallagher, Brendan Ffrench, Claudia Gasch, Eamon Breen, Steven G Gray, Siobhan Nicholson, Niamh Leonard, Ronan Ryan, Vincent Young, John J O'Leary, Sinead Cuffe, Stephen P Finn, Kenneth J O'Byrne, Martin P Barr
Non-small cell lung cancer (NSCLC) accounts for a large proportion of cancer deaths and is characterized by low treatment response rates and poor overall prognosis. In the absence of specific treatable mutations, cisplatin-based chemotherapy plays an important role in the treatment of this disease. Unfortunately, the development of resistance has become a major therapeutic challenge in the use of this cytotoxic drug. Elucidating the mechanisms underlying this resistance phenotype, may result in the development of novel agents that enhance sensitivity to cisplatin in lung cancer patients...
September 22, 2017: Oncotarget
Wenzhe Li, Huailei Ma, Jin Zhang, Ling Zhu, Chen Wang, Yanlian Yang
CD44/CD24 and ALDH1 are widely used cancer stem cell (CSC) markers in breast cancer. However, their expression is not always consistent even in the same subtype of breast cancer. Systematic comparison of their functions is still lacking. We investigated the expression of CD44, CD24 and ALDH1 in different subtypes of breast cancer cells, and explored their relationship with cancer progression. We defined a parameter CD44/CD24 ratio to present the expression level of CD44 and CD24 and found that high CD44/CD24 ratio and ALDH1(+) are both indicators for cancer malignancy, but play different functions during tumor progression...
October 23, 2017: Scientific Reports
Tung Yuan Wang, Cheng-Chia Yu, Pei-Ling Hsieh, Yi-Wen Liao, Chuan-Hang Yu, Ming-Yung Chou
Cancer stem cells (CSCs) have been identified to exert tumor-initiating ability, resulting in the recurrence, metastasis and chemoresistance of oral squamous cell carcinomas. In the present study, we showed that GMI, an immunomodulatory protein from Ganoderma microsporum, induc ed a cytotoxic effect in oral carcinomas stem cells (OCSCs). Treatment of GMI dose-dependently inhibited the expression of CSC markers, including ALDH1 activity and CD44 positivity. Moreover, GMI suppressed the self-renewal property, colony formation, migration, and invasion abilities as well as potentiated chemo-sensitivity in OCSCs...
September 19, 2017: Oncotarget
Qudeer Ahmed Abdul, Byung Pal Yu, Hae Young Chung, Hyun Ah Jung, Jae Sue Choi
Epigenetics oftenly described as the heritable changes in gene expression independent of changes in DNA sequence. Various environmental factors such as nutrition-dietary components, lifestyle, exercise, physical activity, toxins, and other contributing factors remodel the genome either in a constructive or detrimental way. Since epigenetic changes are reversible and nutrition is one of the many epigenetic regulators that modify gene expression without changing the DNA sequence, dietary nutrients and bioactive food components contribute to epigenetic phenomena either by directly suppressing DNA methylation or histone catalyzing enzymes or by changing the availability of substrates required for enzymatic reactions...
October 17, 2017: Archives of Pharmacal Research
Yuka Nozaki, Shoma Tamori, Masahiro Inada, Reika Katayama, Hiromi Nakane, Osamu Minamishima, Yuka Onodera, Makoto Abe, Shota Shiina, Kei Tamura, Daichi Kodama, Keiko Sato, Yasushi Hara, Ryo Abe, Ryoko Takasawa, Atsushi Yoshimori, Nariyoshi Shinomiya, Sei-Ichi Tanuma, Kazunori Akimoto
c-Met is a receptor-type tyrosine kinase, which is involved in a wide range of cellular responses such as proliferation, motility, migration and invasion. It has been reported to be overexpressed in various cancers. However, the role of c-Met in breast cancer stem cells (CSCs) still remains unclear. We herein, show that c-Met expression is significantly elevated in Basal-like type of breast cancer in comparison with other subtypes. High expression of c-Met strongly correlated with the expression of two CSC markers, ALDH1A3 and CD133 in breast cancers...
July 2017: Genes & Cancer
Takeharu Imai, Naohide Oue, Yuji Yamamoto, Ryuichi Asai, Naohiro Uraoka, Kazuhiro Sentani, Kazuhiro Yoshida, Wataru Yasui
Esophageal squamous cell carcinoma (ESCC) is one of the most common human cancers. We previously reported that KIFC1 is involved in gastric cancer pathogenesis and that KIFC1 plays an important role in gastric cancer spheroid colony formation. However, the significance of KIFC1 in ESCC has not been examined. In the present study, we analyzed the expression and distribution of KIFC1 in 132 ESCC cases by immunohistochemistry. In contrast to weak or no staining of KIFC1 in non-neoplastic mucosa, ESCC tissue showed stronger, more extensive KIFC1 staining...
September 12, 2017: Pathology, Research and Practice
Fatma Senel, Tuba Dilay Kökenek Unal, Hatice Karaman, Mevlüde Inanç, Aynur Aytekin
Purpose: To determine expression levels of CD44 and ALDH1/2, known cancer stem cell (CSC) markers, in stomach adenocarcinomas and assess relationships with clinicopathologic parameters and prognosis. Methods: Eighty patients diagnosed with gastric cancer between the years 2011-2015 were included in this study of clinicopathologic characteristics, postoperative prognostic indexes and stem cell marker CD44 and ALDH1/2 expression in paraffin-embedded tumour sections analyzed immunohistochemically. Clinicopathologic parameters were evaluated using the chi-square test and t-test...
September 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
Guodong Xiao, Boxiang Zhang, Jinying Meng, Jichang Wang, Chongwen Xu, Shou-Ching Tang, Xiang Li, Jing Zhang, Rui Liang, Hong Ren, Xin Sun
Lung carcinoma tops the categories of cancer related motility, and has been treated as the main threat to human health. The functions and related mechanism of FBXW7 controlled lung cancer stem cells' signatures is barely unknown, and the miR-367 regulations of FBXW7 via Wnt signaling have not been explored. Cancer stem cells of either ALDH1+ or CD133+ phenotype were found to be referred to advanced stages in patients with NSCLC (non-small cell lung carcinoma). To study the roles of miR-367, we found greater miR-367 level or FBXW7 level was reserved in NSCLC than that of paired adjacent normal tissues, and their upregulations were positively correlated with Wnt signaling activation...
September 26, 2017: Cell Cycle
Zhiqiang Fu, Changhao Chen, Quanbo Zhou, Yinxue Wang, Yue Zhao, Xiaohui Zhao, Wenzhu Li, Shangyou Zheng, Huilin Ye, Lin Wang, Zhanghai He, Qing Lin, Zhihua Li, Rufu Chen
Our previous study demonstrated that long non-coding RNA (lncRNA) HOTTIP was maximally expressed in PDAC, and promoted cancer cell progression and epithelial to mesenchymal transition (EMT). Numerous studies indicated that lncRNAs or EMT supported cancer stem cells. However, the role of HOTTIP in pancreatic cancer stem cells (PCSCs) remains unclear. Here, we evaluated the role and mechanism of HOTTIP in PCSCs. First, we analyzed the relationship between HOTTIP expression and overall or disease-free survival in 90 patients with PDAC after radical resection...
September 22, 2017: Cancer Letters
Ming-Shao Tsai, Wen-Cheng Chen, Chia-Hsuan Lai, Yu-Yen Chen, Miao-Fen Chen
OBJECTIVES: Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and shown to identify cancer stem cells (CSC)-like cells. We aimed to investigate the significance of ALDH1 in oral squamous cell carcinoma (OSCC) and its correlation with DNMT3b and immune evasion in the present study. METHODS: We retrospectively analyzed the clinical outcomes of OSCC patients and examined its correlation with the levels of ALDH1 in tumors and circulating myeloid-derived suppressor cells (MDSCs) in the peripheral blood...
October 2017: Oral Oncology
Alysha K Croker, Mauricio Rodriguez-Torres, Ying Xia, Siddika Pardhan, Hon Sing Leong, John D Lewis, Alison L Allan
Previous studies indicate that breast cancer cells with high aldehyde dehydrogenase (ALDH) activity and CD44 expression (ALDH(hi)CD44⁺) contribute to metastasis and therapy resistance, and that ALDH1 correlates with poor outcome in breast cancer patients. The current study hypothesized that ALDH1 functionally contributes to breast cancer metastatic behavior and therapy resistance. Expression of ALDH1A1 or ALDH1A3 was knocked down in MDA-MB-468 and SUM159 human breast cancer cells using siRNA. Resulting impacts on ALDH activity (Aldefluor(®) assay); metastatic behavior and therapy response in vitro (proliferation/adhesion/migration/colony formation/chemotherapy and radiation) and extravasation/metastasis in vivo (chick choroiallantoic membrane assay) was assessed...
September 22, 2017: International Journal of Molecular Sciences
Yamei Pang, Jian Liu, Xiang Li, Yiwen Zhang, Boxiang Zhang, Jing Zhang, Ning Du, Chongwen Xu, Rui Liang, Hong Ren, Shou-Ching Tang, Xin Sun
The poor therapy response and poor prognosis of esophageal cancer has made it one of the most malignant carcinoma, and the complicated multidisciplinary treatment failed to achieve a long-term disease-free survival. To diagnose esophageal cancer at an earlier stage, and to improve the effect of anticancer therapy would improve the therapeutic efficacy. After retrospective analysis of the cancer samples of patients who received esophagectomy, we found the relevance between ratio of either ALDH1 or CD133-positive cancer stem cells and 2-year recurrence...
October 2017: International Journal of Oncology
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