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Carcinoma-Associated Fibroblasts

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https://www.readbyqxmd.com/read/28334808/downregulation-of-pathways-implicated-in-liver-inflammation-and-tumorigenesis-of-glycogen-storage-disease-type-ia-mice-receiving-gene-therapy
#1
Goo-Young Kim, Joon Hyun Kwon, Jun-Ho Cho, Lisa Zhang, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated...
March 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28326574/tumour-epithelial-and-stromal-characteristics-of-hepatocellular-carcinomas-with-abundant-fibrous-stroma-fibrolamellar-versus-scirrhous-hepatocellular-carcinoma
#2
Young-Joo Kim, Hyungjin Rhee, Jeong Eun Yoo, Venancio A F Alves, Gi Jeong Kim, Hye Min Kim, Paulo Herman, Aline Chagas, Haeryoung Kim, Young Nyun Park
AIMS: The scirrhous variant of hepatocellular carcinoma (S-HCC) and fibrolamellar HCC (FL-HCC) are less common subtypes of HCC that are characterised by abundant fibrous stroma. Here, we aimed to investigate differences in the tumour microenvironment and the tumour epithelial cell characteristics of S-HCC and FL-HCC. METHODS AND RESULTS: Whole tissue sections of 17 S-HCCs and 9 FL-HCCs were subjected to immunohistochemical stains for K7, K19, EpCAM, CD56/NCAM, CD163, CD68, pSTAT3, FAP, CCN2 and Ki-67...
March 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28314267/induced-pluripotent-stem-cell-related-genes-contribute-to-de-differentiation-in-oral-squamous-cell-carcinoma
#3
Daisuke Takeda, Takumi Hasegawa, Takeshi Ueha, Eiji Iwata, Risa Harada, Akiko Sakakibara, Teruya Kawamoto, Tsutomu Minamikawa, Yoshitada Sakai, Takahide Komori
BACKGROUND/AIM: Cancer stem cells are suspected to contribute to malignancy in tumors. Hypoxia affects cell differentiation and induces stem-cell-like characteristics in malignancies. Induced pluripotency was demonstrated in mouse fibroblasts by reprogramming with four transcriptional factors: Oct3/4, Sox2, c-Myc, and Klf4. Conversely, oncogenic transformations frequently express transcriptional factors and Nanog. Therefore, cancer cells present some similarities with induced pluripotent stem (iPS) cells...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28288874/loss-of-exosomal-mir-320a-from-cancer-associated-fibroblasts-contributes-to-hcc-proliferation-and-metastasis
#4
Zhuochao Zhang, Xiao Li, Wei Sun, Shuqiang Yue, Jingyue Yang, Junjie Li, Ben Ma, Jianlin Wang, Xisheng Yang, Meng Pu, Bai Ruan, Ge Zhao, Qike Huang, Lin Wang, Kaishan Tao, Kefeng Dou
Cancer-associated fibroblasts (CAFs) play a pivotal role in regulating tumour progression. Therefore, understanding how CAFs communicate with hepatocellular carcinoma (HCC) is crucial for HCC therapy. Recently, exosomes have been considered an important "messenger" between cells. In this study, we performed microRNA (miRNA) sequencing of exosomes derived from CAFs and corresponding para-cancer fibroblasts (PAFs) of HCC patients. We found a significant reduction in the miR-320a level in CAF-derived exosomes...
March 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28273155/tumor-stroma-with-senescence-associated-secretory-phenotype-in-steatohepatitic-hepatocellular-carcinoma
#5
Jee San Lee, Jeong Eun Yoo, Haeryoung Kim, Hyungjin Rhee, Myoung Ju Koh, Ji Hae Nahm, Jin Sub Choi, Kee-Ho Lee, Young Nyun Park
Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC), a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP) were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs)...
2017: PloS One
https://www.readbyqxmd.com/read/28263980/an-fgfr-inhibitor-converts-the-tumor-promoting-effect-of-tgf-%C3%AE-by-the-induction-of-fibroblast-associated-genes-of-hepatoma-cells
#6
H-R Zhang, X-D Wang, X Yang, D Chen, J Hao, R Cao, X-Z Wu
Tumors consistently mimic wound-generating chronic inflammation; however, why they do not heal like wounds with fibrotic scars remains unknown. The components of the tumor microenvironment, such as transforming growth factor β (TGF-β) and fibroblast growth factors (FGFs), may account for this phenomenon. Tumor formation involves continuous activation of the FGF pathway, whereas the repair of tissue injury is a self-limiting process accompanied with controlled activation of the FGF pathway. In the tumor microenvironment TGF-β increases the secretion of FGFs, further promoting the malignant biological properties of tumors...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28260649/higher-serum-interleukin-17a-levels-as-a-potential-biomarker-for-predicting-early-disease-progression-in-patients-with-hepatitis-b-virus-associated-advanced-hepatocellular-carcinoma-treated-with-sorafenib
#7
Hyo Jung Cho, Soon Sun Kim, Ji Sun Nam, Min Jung Oh, Dae Ryong Kang, Jai Keun Kim, Jei Hee Lee, Bohyun Kim, Min Jae Yang, Jae Chul Hwang, Sun Gyo Lim, Sung Jae Shin, Kee Myung Lee, Byung Moo Yoo, Kwang Jae Lee, Sung Won Cho, Jae Youn Cheong
BACKGROUND: Although sorafenib is the only available drug with proven efficacy for patients with advanced hepatocellular carcinoma (HCC), the clinical efficacy of sorafenib is variable and unpredictable. The aim of the current study was to identify potential serum biomarkers predicting cancer progression and overall survival (OS) in patients with hepatitis B virus (HBV)-related advanced HCC treated with sorafenib. METHODS: Thirty-four patients with HBV-related advanced HCC (modified Union for International Cancer Control [UICC] stage IVa or IVb) treated with sorafenib for more than 4weeks were retrospectively enrolled...
March 2, 2017: Cytokine
https://www.readbyqxmd.com/read/28254435/il-6-and-pd-l1-blockade-combination-inhibits-hepatocellular-carcinoma-cancer-development-in-mouse-model
#8
Hu Liu, Jun Shen, Kai Lu
Limited efficacy of immune checkpoint inhibitors in hepatocellular carcinoma (HCC) was observed in clinical trials, thus prompting investigation into combination therapy. Interleukin-6 (IL-6) has important roles in modeling immune responses in cancers. Here, we hypothesized that IL-6 blockade would enhance antitumor immunity of HCC and synergize with anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor in treating HCC. The sources and immune modulating effects of IL-6 were investigated in HCC models...
February 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28247413/mesothelial-to-mesenchymal-transition-as-a-possible-therapeutic-target-in-peritoneal-metastasis-of-ovarian-cancer
#9
Angela Rynne-Vidal, Chi Lam Au-Yeung, José A Jiménez-Heffernan, María Luisa Pérez-Lozano, Lucía Cremades-Jimeno, Carmen Bárcena, Ignacio Cristóbal-García, Concepción Fernández-Chacón, Tsz Lun Yeung, Samuel C Mok, Pilar Sandoval, Manuel López-Cabrera
Peritoneal dissemination is the primary metastatic route of ovarian cancer (OvCa), often accompanied by accumulation of ascitic fluid. The peritoneal cavity is lined by mesothelial cells (MCs), which can convert into carcinoma-associated fibroblasts (CAFs) through mesothelial-to-mesenchymal transition (MMT). Here, we demonstrate that MCs isolated from ascitic fluid (AFMCs) of OvCa patients with peritoneal implants also undergo MMT and promote subcutaneous tumour growth in mice. RNA sequencing of AFMCs revealed that MMT-related pathways-including TGF-β signalling-are differentially regulated, and a gene signature was verified in peritoneal implants from OvCa patients...
March 1, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28223108/tenascin-c-is-a-prognostic-determinant-and-potential-cancer-associated-fibroblasts-marker-for-breast-ductal-carcinoma
#10
Zhaoting Yang, Weidong Ni, Chunai Cui, Longyun Fang, Yanhua Xuan
Tenascin C (TNC) is a key of extracellular matrix glycoprotein and highly express in numerous human malignancies. Herein, we attempted to clarify the clinicopathological significance of TNC as a prognostic determinant of breast ductal carcinoma. Then, we investigated TNC immunohistochemical expression in 150 breast ductal carcinomas and 27 normal breast tissue samples. Clinical relevance of TNC expression and the association TNC expression with other factors related to cancer-associated fibroblasts were also examined...
February 20, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28216578/tumor-microenvironment-a-paradigm-in-hepatocellular-carcinoma-progression-and-therapy
#11
REVIEW
Maryam Tahmasebi Birgani, Vinicio Carloni
Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers in the human population. Different etiological factors such as hepatitis B and C virus, alcohol and diabetes cause liver injury followed by inflammation, necrosis and hepatocytes proliferation. Continuous cycles of this destructive-regenerative process culminates in liver cirrhosis which is characterized by regenerating nodules that progress to dysplastic nodules and ultimately HCC. Despite its significance, there is only an elemental understanding of the pathogenetic mechanisms, and there are only limited therapeutic options...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207006/papillary-transitional-cell-bladder-carcinoma-and-systematized-epidermal-nevus-syndrome
#12
Adekemi Akingboye, Heather Schultz, Gina A Taylor
Epidermal nevus syndrome (ENS), also known as Solomon syndrome, is a rare neurocutaneous disorder defined by mosaicism. Epidermal nevus syndrome may be associated with a variety of systemic findings, several of which have been described in the literature, including but not limited to central nervous system abnormalities and internal malignancies. There is a paucity of reports of patients with both epidermal nevi and papillary transitional cell bladder carcinoma in the literature. We present a rare case of systematized epidermal nevi associated with development of papillary transitional cell bladder carcinoma in a young woman...
January 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28202677/cancer-associated-fibroblasts-modulate-growth-factor-signaling-and-extracellular-matrix-remodeling-to-regulate-tumor-metastasis
#13
REVIEW
Begum Erdogan, Donna J Webb
Cancer-associated fibroblasts (CAFs) are major components of the surrounding stroma of carcinomas that emerge in the tumor microenvironment as a result of signals derived from the cancer cells. Biochemical cross-talk between cancer cells and CAFs as well as mechanical remodeling of the stromal extracellular matrix (ECM) by CAFs are important contributors to tumor cell migration and invasion, which are critical for cancer progression from a primary tumor to metastatic disease. In this review, we discuss key paracrine signaling pathways between CAFs and cancer cells that promote cancer cell migration and invasion...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28193024/evaluating-tumor-associated-activity-of-extracellular-sulfatase-by-analyzing-naturally-occurring-substrate-in-tumor-microenvironment-of-hepatocellular-carcinoma
#14
Yue Yu, Hao Li, Yucai Yang, Yitao Ding, Zhaoxia Wang, Genxi Li
The progress of cancer is intimately connected with the activity of the extracellular matrix (ECM) enzymes. To evaluate the promoting effect of these enzymes on tumor development in a pathological biocontext, we propose in this work to analyze their natural substrates in the ECM. This strategy is demonstrated by studying heparan sulfate (HS), the substrate of ECM sulfatase, in the development of hepatocellular carcinoma (HCC). An assay is designed to study the abundance and sulfation of HS and to evaluate the interactions between HS and the growth factors, such as fibroblast growth factor 2 (FGF2)...
December 20, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28186989/inhibiting-dna-pkcs-in-a-non-homologous-end-joining-pathway-in-response-to-dna-double-strand-breaks
#15
Jun Dong, Tian Zhang, Yufeng Ren, Zhenyu Wang, Clifton C Ling, Fuqiu He, Gloria C Li, Chengtao Wang, Bixiu Wen
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a distinct factor in the non-homologous end-joining (NHEJ) pathway involved in DNA double-strand break (DSB) repair. We examined the crosstalk between key proteins in the DSB NHEJ repair pathway and cell cycle regulation and found that mouse embryonic fibroblast (MEF) cells deficient in DNA-PKcs or Ku70 were more vulnerable to ionizing radiation (IR) compared with wild-type cells and that DSB repair was delayed. γH2AX was associated with phospho-Ataxia-telangiectasia mutated kinase (Ser1987) and phospho-checkpoint effector kinase 1 (Ser345) foci for the arrest of cell cycle through the G2/M phase...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185819/expression-of-polysialic-acid-in-primary-laryngeal-squamous-cell-carcinoma
#16
Marko Klobučar, Sarah Visentin, Antonija Jakovčević, Mario Bilić, Lana Kovač-Bilić, Davorin Đanić, Krešimir Pavelić, Sandra Kraljević Pavelić
AIMS: Expression of polySia is associated with metastatic dissemination and progression of various malignant diseases. In particular, it may contribute to tumorigenesis by a negative modulatory effect on cellular signaling cascades responsible for cellular migration, differentiation and proliferation. In this study, we investigated the expression of polySia in primary metastatic and non-metastatic laryngeal squamous cell carcinoma (LSCC) tumor tissues and its potential impact on the LSCC progression...
March 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28180998/the-prognostic-value-and-pathobiological-significance-of-glasgow-microenvironment-score-in-gastric-cancer
#17
Zhi-Hua Zhou, Cheng-Dong Ji, Jiang Zhu, Hua-Liang Xiao, Hai-Bin Zhao, You-Hong Cui, Xiu-Wu Bian
PURPOSE: To evaluate the prognostic value and pathobiological significance of Glasgow microenvironment score (GMS), a parameter based on tumor stroma percentage and inflammatory cell infiltration, in gastric cancer. METHODS: A total of 225 cases of gastric cancer were histologically reviewed, and GMS was evaluated for each case. The association between GMS and patients' survival was investigated. Then the relationship between GMS and mismatch repair (MMR) status, Epstein-Barr virus (EBV) infection were determined using immunohistochemistry (IHC) and in situ hybridization, and the expression of PD1/PD-L1 was examined...
February 8, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28178689/malignant-ascites-derived-exosomes-promote-proliferation-and-induce-carcinoma-associated-fibroblasts-transition-in-peritoneal-mesothelial-cells
#18
Mingtian Wei, Tinghan Yang, Xiangzheng Chen, Yangping Wu, Xiangbing Deng, Wanbin He, Jinliang Yang, Ziqiang Wang
Malignant ascites-derived exosomes have been demonstrated to participate in tumor metastasis. In peritoneal metastasis, normal mesothelial cells (MCs) can be converted into carcinoma-associated fibroblasts (CAFs) by mesothelial-mesenchymal transition (MMT). Herein, we evaluated the effect of malignant ascites-derived exosomes on peritoneal MCs in vitro and in vivo experiments to determine whether exosomes could educate MCs and contribute to peritoneal metastasis.Under the treatment of ascites-derived exosomes, peritoneal MCs showed increased ability to proliferate and migrate...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178651/stromal-fibroblasts-present-in-breast-carcinomas-promote-tumor-growth-and-angiogenesis-through-adrenomedullin-secretion
#19
Zohra Benyahia, Nadège Dussault, Mylène Cayol, Romain Sigaud, Caroline Berenguer-Daizé, Christine Delfino, Asma Tounsi, Stéphane Garcia, Pierre-Marie Martin, Kamel Mabrouk, L'Houcine Ouafik
Tumor- or cancer-associated fibroblasts (TAFs or CAFs) are active players in tumorigenesis and exhibit distinct angiogenic and tumorigenic properties. Adrenomedullin (AM), a multifunctional peptide plays an important role in angiogenesis and tumor growth through its receptors calcitonin receptor-like receptor/receptor activity modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). We show that AM and AM receptors mRNAs are highly expressed in CAFs prepared from invasive breast carcinoma when compared to normal fibroblasts...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178124/anaplastic-thyroid-carcinoma-and-foscarnet-use-in-a-multitarget-treatment-documented-by-18f-fdg-pet-ct-a-case-report
#20
Elisa Giannetta, Andrea M Isidori, Cosimo Durante, Cira Di Gioia, Flavia Longo, Vincenzo Tombolini, Nadia Bulzonetti, Chiara Graziadio, Riccardo Pofi, Daniele Gianfrilli, Antonella Verrienti, Raffaella Carletti, Sebastiano Filetti, Andrea Lenzi, Alberto Baroli
RATIONALE: The case reported the rapid remission of disease recurrence achieved adding foscarnet, a DNA polymerase inhibitor that interacts with fibroblast growth factor 2, to low molecular weight heparin and sunitinib for the first time in a patient with an anaplastic thyroid cancer (ATC). PATIENT CONCERNS: A 65-year-old woman with a multinodular goiter referred for a rapid enlargement of a nodule. Histological examination revealed an ATC with a little area of papillary thyroid cancer (PTC)...
February 2017: Medicine (Baltimore)
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