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Carcinoma-Associated Fibroblasts

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https://www.readbyqxmd.com/read/28526414/a-novel-sirt1-inhibitor-4bb-induces-apoptosis-in-hct116-human-colon-carcinoma-cells-partially-by-activating-p53
#1
Ananga Ghosh, Amrita Sengupta, Guru Pavan Kumar Seerapu, Ali Nakhi, E V Venkat Shivaji Ramarao, Navneet Bung, Gopalakrishnan Bulusu, Manojit Pal, Devyani Haldar
The NAD+-dependent protein deacetylase SIRT1 has emerged as an important target for epigenetic therapeutics of colon cancer as its increased expression is associated with cancer progression. Additionally, SIRT1 represses p53 function via deacetylation, promoting tumor growth. Therefore, inhibition of SIRT1 is of great therapeutic interest for the treatment of colon cancer. Here, we report discovery of a novel quinoxaline based small molecule inhibitor of human SIRT1, 4bb, investigated its effect on viability of colon cancer cells and molecular mechanism of action...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28525898/ginsenoside-rg3-inhibits-the-senescence-of-prostate-stromal-cells-through-down-regulation-of-interleukin-8-expression
#2
Yanfei Peng, Ran Zhang, Lingfei Kong, Yongmei Shen, Da Xu, Fang Zheng, Jianwei Liu, Qian Wu, Bona Jia, Ju Zhang
Senescent stromal cells support the development of prostate cancer and are considered potential therapeutic targets. This research evaluated the regulatory effects of ginsenoside Rg3 on the senescence of prostatic stromal cells pre-incubated in medium supplemented with 0.5% fetal bovine serum. The results revealed that ginsenoside Rg3 decreased the number of stromal cells positively stained with a senescent cell marker (senescence-associated β-galactosidase). Ginsenoside Rg3 also increased the viability of stromal cells and promoted cell cycle transition from G0/G1 to S phase, as well as inhibited the carcinoma-associated fibroblast-like phenotype in prostate stromal cells, through the up-regulation of smooth muscle cell markers SM22 and smooth muscle myosin heavy chain...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523716/cd44-fibroblasts-increases-breast-cancer-cell-survival-and-drug-resistance-via-igf2bp3-cd44-igf2-signalling
#3
Yonglei Liu, Conghui Yu, Yonggang Wu, Xiangjun Sun, Quanping Su, Cuiping You, Hongwu Xin
CD44, a cell adhesion protein, involves in various process in cancer such as cell survival and metastasis. Most researches on CD44 in cancer focus on cancer cells. Recently, it is found that CD44 expression is high in fibroblasts of tumour microenvironment. However, its role in communication between fibroblasts and breast cancer cells is seldom known. In this study, CD44-positive (CD44(+) Fbs) and CD44-negative carcinoma-associated fibroblasts (CD44(-) Fbs) were isolated and cocultured with breast cancer cells for analysis of cell survival and drug resistance...
May 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28518141/caf-secreted-cxcl1-conferred-radioresistance-by-regulating-dna-damage-response-in-a-ros-dependent-manner-in-esophageal-squamous-cell-carcinoma
#4
Hongfang Zhang, Jing Yue, Zhenzhen Jiang, Rongjing Zhou, Ruifei Xie, Yiping Xu, Shixiu Wu
Five-year survival rate of esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is <20%. Our study aimed to investigate whether cancer-associated fibroblasts (CAFs), one major component of tumor microenvironment, were involved in tumor radioresistance in ESCC. By use of human chemokine/cytokine array, human chemokine CXCL1 was found to be highly expressed in CAFs compared with that in matched normal fibroblasts. Inhibition of CXCL1 expression in CAFs significantly reversed CAF-conferred radioresistance in vitro and in vivo...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28506312/pathomimetic-avatars-reveal-divergent-roles-of-microenvironment-in-invasive-transition-of-ductal-carcinoma-in-situ
#5
Mansoureh Sameni, Dora Cavallo-Medved, Omar E Franco, Anita Chalasani, Kyungmin Ji, Neha Aggarwal, Arulselvi Anbalagan, Xuequn Chen, Raymond R Mattingly, Simon W Hayward, Bonnie F Sloane
BACKGROUND: The breast tumor microenvironment regulates progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). However, it is unclear how interactions between breast epithelial and stromal cells can drive this progression and whether there are reliable microenvironmental biomarkers to predict transition of DCIS to IDC. METHODS: We used xenograft mouse models and a 3D pathomimetic model termed mammary architecture and microenvironment engineering (MAME) to study the interplay between human breast myoepithelial cells (MEPs) and cancer-associated fibroblasts (CAFs) on DCIS progression...
May 15, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28504692/mint3-mediated-l1cam-expression-in-fibroblasts-promotes-cancer-cell-proliferation-via-integrin-%C3%AE-5%C3%AE-1-and-tumour-growth
#6
H J Nakaoka, Z Tanei, T Hara, J S Weng, A Kanamori, T Hayashi, H Sato, A Orimo, K Otsuji, K Tada, T Morikawa, T Sasaki, M Fukayama, M Seiki, Y Murakami, T Sakamoto
Fibroblasts are some of the major cells in tumour tissues that influence tumour progression and drug resistance. However, our understanding on fibroblast-mediated tumour malignancy remains incomplete. Munc18-1-interacting protein 3 (Mint3) is known as an activator of hypoxia-inducible factor-1 (HIF-1) even during normoxia in cancer cells, macrophages and fibroblasts. Although Mint3 promotes ATP production via glycolysis by activating HIF-1 in cancer cells and macrophages, the biological role of Mint3-mediated HIF-1 activation in fibroblasts remains unclear...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28484082/temporal-and-spatial-changes-of-cells-positive-for-stem-like-markers-in-different-compartments-and-stages-of-human-colorectal-adenoma-carcinoma-sequence
#7
Guanglin Cui, Gang Xu, Li Zhu, Zhigang Pang, Wei Zheng, Zhenfeng Li, Aping Yuan
Considerable evidence supports the idea that stem-like cells may play an essential role during the development of colorectal cancer (CRC). To accomplish this aim, we use immunohistochemistry (IHC) and double IHC with different potential stem-like markers, anti-musashi (Msi), anti-CD133, anti- LGR5 and anti-ALDH1 to examine the presentation of stem-like cells in different compartments including adenoma/CRC epithelium, transitional crypts and tumor stroma in colorectal adenoma and CRC. The results showed that cells positive for stem-like markers were remarkably increased in number and frequently observed in the adenoma/CRC epithelium, transitional crypts and tumor stroma...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28483948/high-affinity-internalizing-human-scfv-fc-antibody-for-targeting-fgfr1-overexpressing-lung-cancer
#8
Aleksandra Sokolowska-Wedzina, Grzegorz Chodaczek, Julia Chudzian, Aleksandra Borek, Malgorzata Zakrzewska, Jacek Otlewski
Targeted delivery of anti-cancer drugs using antibodies specific for tumor-associated antigens represents one of the most important approaches in current immuno-oncology research. Fibroblast growth factor receptor 1 (FGFR1) has been demonstrated to be a high-frequency targetable oncogene specific for smoking-associated lung cancers, present in over 20% of lung squamous cell carcinoma cases. This report describes the generation of a potent, fully human antibody fragment in scFv-Fc format efficiently targeting FGFR1...
May 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28475003/the-primary-growth-of-laryngeal-squamous-cell-carcinoma-cells-in-vitro-is-effectively-supported-by-paired-cancer-associated-fibroblasts-alone
#9
Mei Wang, Chunping Wu, Yu Guo, Xiaojuan Cao, Wenwei Zheng, Guo-Kang Fan
Most primarily cultured laryngeal squamous cell carcinoma cells are difficult to propagate in vitro and have a low survival rate. However, in our previous work to establish a laryngeal squamous cell carcinoma cell line, we found that laryngeal cancer-associated fibroblasts appeared to strongly inhibit the apoptosis of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In this study, we investigated whether paired laryngeal cancer-associated fibroblasts alone can effectively support the growth of primarily cultured laryngeal squamous cell carcinoma cells in vitro...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28473196/in-vitro-evaluation-of-the-potential-toxic-effects-of-palladium-nanoparticles-on-fibroblasts-and-lung-epithelial-cells
#10
I Iavicoli, M Farina, L Fontana, D Lucchetti, V Leso, C Fanali, V Cufino, A Boninsegna, K Leopold, R Schindl, D Brucker, A Sgambato
Palladium nanoparticles have been increasingly used in catalytic processes, wastewater treatment, electronics, and biomedicine. However, recent evidence proved that these nanoparticles are able to induce adverse effects both in in vitro and in vivo models. Nevertheless, molecular mechanisms underlying the toxic effects are still poorly understood. Therefore, this study aimed to investigate the potential toxicological mechanisms of palladium nanoparticles assessing their effects on normal diploid rat fibroblast and lung carcinoma human epithelial cell lines...
May 1, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28467965/intratumoral-acidosis-fosters-cancer-induced-bone-pain-through-the-activation-of-the-mesenchymal-tumor-associated-stroma-in-bone-metastasis-from-breast-carcinoma
#11
Gemma Di Pompo, Silvia Lemma, Lorenzo Canti, Nadia Rucci, Marco Ponzetti, Costantino Errani, Davide Maria Donati, Shonagh Russell, Robert Gillies, Tokuhiro Chano, Nicola Baldini, Sofia Avnet
Cancer-induced bone pain (CIBP) is common in patients with bone metastases (BM), significantly impairing quality of life. The current treatments for CIBP are limited since they are often ineffective. Local acidosis derived from glycolytic carcinoma and tumor-induced osteolysis is only barely explored cause of pain. We found that breast carcinoma cells that prefer bone as a metastatic site have very high extracellular proton efflux and expression of pumps/ion transporters associated with acid-base balance (MCT4, CA9, and V-ATPase)...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465475/down-regulation-of-mir-29b-in-carcinoma-associated-fibroblasts-promotes-cell-growth-and-metastasis-of-breast-cancer
#12
Yonglei Liu, Jingling Zhang, Xiangjun Sun, Quanping Su, Cuiping You
Carcinoma associated fibroblasts (CAFs) play important roles in breast cancer development and progression. Recent studies show that microRNAs (miRNAs) are the main regulators in CAFs. MiR-29b is one of the significant down-regulated miRNAs in CAFs from the miRNA screening. The role of miR-29b in the interaction between CAFs and breast cancer is still unclear. In the present study, we investigated the effects of CAFs on breast cancer cell proliferation and metastasis regulated by miR-29b. We found that fibroblasts activated by co-cultured breast cancer cells produced higher levels of some chemokines like CCL11, CXCL14, which accelerated breast cancer cell growth and induced drug resistance and metastasis...
April 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28464583/-advances-in-immunotherapy-of-pancreatic-ductal-adenocarcinoma
#13
J Q Yang, T Wei, Y W Chen, X L Bai, T B Liang
The morbidity of pancreatic ductal adenocarcinoma (PDAC) has been increasing over years, while the treatment efficacy and prognosis of PDAC remain far from satisfying. The newly-ermerged tumor immunotherapy has not only made lots of breakthroughs in various malignancies, but also brought an opportunity to the treatment of pancreatic cancer.PDAC immunotherapies, mainly including vaccine therapy, adoptive T cell thanfer therapy, checkpoint blockade therapy, have achieved a certain effect, however, the clinical outcomes have not been satisfactory...
May 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/28454334/taxotere-induced-elevated-expression-of-il8-in-carcinoma-associated-fibroblasts-of-breast-invasive-ductal-cancer
#14
Yingliang Li, Guohua Rong, Hua Kang
Breast cancer is the most common malignant tumor in women worldwide, and accounts for an estimated 29% of new cases and 15% of cancer-associated mortalities each year. Invasive ductal carcinoma represents 70-80% of all breast cancer cases, which are responsible for the majority of breast cancer fatalities. Though great progress has been made in understanding the tumorigenesis and development of breast cancer, problems surrounding treatment persist. It was previously reported that carcinoma-associated fibroblasts (CAFs) may be closely associated with chemotherapy resistance...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454283/targeting-of-growth-factors-in-the-treatment-of-hepatocellular-carcinoma-the-potentials-of-polysaccharides
#15
Xuan Wang, Jieyu Ding, Yuanyuan Feng, Lingling Weng, Guangqiang Zhao, Jianfeng Xiang, Minguang Zhang, Dongwei Xing
Hepatocellular carcinoma (HCC) has become a leading cause of cancer-associated mortality worldwide and is thus of great concern. Although various chemotherapeutic drugs are currently used for the treatment of HCC, severe side effects associated with these treatments have prompted interest in novel therapies, including the use of certain biological macromolecules such as polysaccharides. Several studies have shown that polysaccharides have anticancer and antiproliferative effects on HCC. Vascular endothelial growth factor, transforming growth factor β, epidermal growth factor and fibroblast growth factor may be effective targets for polysaccharides and may modulate tumor growth and immunity through increasing the expression levels of cytokines...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#16
Changhoon Yoo, Jihoon Kang, Deokhoon Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Seung-Mo Hong, Jung Jin Hwang, Seong-Yun Jeong, Shin Hwang, Ki-Hun Kim, Young-Joo Lee, Klaus P Hoeflich, Oleg Schmidt-Kittler, Stephen Miller, Eun Kyung Choi
BACKGROUND: The fibroblast growth factor receptor 4 (FGFR4) pathway is an essential regulatory component of bile acid synthesis, and its relationship with hepatocellular carcinoma (HCC) has been reported. We investigated the gene expression and clinical significance of FGFR4 and related pathways in intrahepatic cholangiocarcinoma (iCCA). RESULTS: The median age was 56 years (range 30-78) and 34 patients (74%) were male. Six patients (13%) had hepatitis B virus infection, with or without liver cirrhosis...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430665/p2x7-receptor-and-nlrp3-inflammasome-activation-in-head-and-neck-cancer
#17
Ju Young Bae, Sang-Woo Lee, Yong-Hwan Shin, Jong-Ho Lee, Jeong Won Jahng, Kyungpyo Park
In this study, we investigated purinergic receptor P2X7 and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome expressions, and their role in head and neck cancer. We found upregulation of purinergic receptor P2X7 and all NLRP3 inflammasome components in biopsied head and neck squamous cell carcinoma tissues. Similarly, the expression of purinergic receptor P2X7, apoptosis-associated speck-like protein containing CARD, and pro-form caspase 1 in A253 cells derived from epidermoid carcinoma were highly upregulated in comparison to normal Human Salivary Gland cell line...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428709/disruption-of-the-tweak-fn14-pathway-prevents-5-fluorouracil-induced-diarrhea-in-mice
#18
Takuhito Sezaki, Yuki Hirata, Teruki Hagiwara, Yuki I Kawamura, Tadashi Okamura, Rieko Takanashi, Kenta Nakano, Miwa Tamura-Nakano, Linda C Burkly, Taeko Dohi
AIM: To clarify the roles of TWEAK and its receptor Fn14 in 5-fluorouracil (5-FU)-induced diarrhea. METHODS: Diarrhea was induced in wild-type (WT), Fn14 knockout (KO), and IL-13 receptor (IL-13R)α1 KO BALB/c mice using a single injection of 5-FU. Histological analysis, cytokine analysis, and flow cytometry was performed on ileal tissues and cells. Murine colon carcinoma-bearing mice were co-treated with an anti-TWEAK antibody and 5-FU. Embryonic fibroblast response to cytokines was also analyzed...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28428708/indoleamine-2-3-dioxygenase-as-a-potential-prognostic-marker-and-immunotherapeutic-target-for-hepatocellular-carcinoma
#19
REVIEW
Kashif Asghar, Asim Farooq, Bilal Zulfiqar, Muhammad Usman Rashid
Tumor cells induce an immunosuppressive microenvironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28418447/association-of-oral-cavity-and-oropharyngeal-cancer-biomarkers-in-surgical-drain-fluid-with-patient-outcomes
#20
Amy Anne D Lassig, Anne M Joseph, Bruce R Lindgren, Bevan Yueh
Importance: Survival rates for head and neck cancer have been relatively stable for several decades. Individualized prognostic indicators are needed to identify patients at risk for poorer outcomes. Objective: To determine whether biomarker levels in surgical drain fluid of patients with head and neck cancer are associated with poor cancer outcomes. Design, Setting, and Participants: This prospective cohort study enrolled patients with squamous cell carcinoma (SCC) of the oral cavity and oropharynx who required surgical treatment from April 1, 2011, to February 1, 2016, at a tertiary or academic care center...
April 13, 2017: JAMA Otolaryngology—Head & Neck Surgery
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