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https://www.readbyqxmd.com/read/27910780/naringenin-ameliorates-doxorubicin-toxicity-and-hypoxic-condition-in-dalton-s-lymphoma-ascites-tumor-mouse-model-evidence-from-electron-paramagnetic-resonance-imaging
#1
Venkatesan Kathiresan, Swathika Subburaman, Arun Venkatesh Krishna, Mathivanan Natarajan, Gandhidasan Rathinasamy, Kumaresan Ganesan, Murugesan Ramachandran
Doxorubicin (DOX) is a well-known cytotoxic agent used extensively as a chemotherapeutic drug to eradicate a wide variety of human cancers. Reactive oxygen species (ROS)-mediated oxidative stress during DOX treatment can induce cardiac, renal, and hepatic toxicities, which can constrain its use as a potential cytotoxic agent. The present work investigates the antioxidant potential of naringenin (NAR) against DOXinduced toxicities of a Dalton's lymphoma ascites (DLA) tumor-bearing mouse model. Mice were randomized into four groups: a negative control, positive control, DOX (2...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27908206/the-role-of-mesenchymal-stem-cells-in-oncology-and-regenerative-medicine
#2
Maliha Khan, Syeda Ezze Rukhshan Adil, Amanda L Olson
Mesenchymal stem cells (MSCs) have long been used as therapeutic agents in disease affecting various organ systems. However, MSCs are fast emerging as promising anticancer agents which have the potential to treat a number of different cancer types, including glioblastoma and metastatic breast, ovarian and hepatic carcinoma. The ability of MSC to migrate directly into the tumor microenvironment and to produce IFN-α and -β makes this possible. However, the possibility of MSC undergoing either malignant transformation or transformation into protumorigenic fibroblasts currently limits their role in clinical use...
December 2, 2016: Future Oncology
https://www.readbyqxmd.com/read/27903529/angiocrine-bmp2-signaling-in-murine-liver-controls-normal-iron-homeostasis
#3
Philipp-Sebastian Koch, Victor Olsavszky, Friederike Ulbrich, Carsten Sticht, Alexandra Demory, Thomas Leibing, Thomas Henzler, Mathias Meyer, Johanna Zierow, Sven Schneider, Katja Breitkopf-Heinlein, Haristi Gaitantzi, Bradley Spencer-Dene, Bernd Arnold, Kay Klapproth, Kai Schledzewski, Sergij Goerdt, Cyrill Géraud
Microvascular endothelial cells (EC) display a high degree of phenotypic and functional heterogeneity among different organs. Organ-specific EC control their tissue microenvironment by angiocrine factors in health and disease. Liver sinusoidal EC (LSEC) are uniquely differentiated to fulfil important organ-specific functions in development, under homeostatic conditions, and in regeneration and liver pathology. Recently, Bmp2 has been identified by us as an organ-specific angiokine derived from LSEC. To study angiocrine Bmp2 signaling in the liver, we conditionally deleted Bmp2 in LSEC using EC subtype-specific Stab2-Cre mice...
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27900050/molecular-alterations-in-the-carcinogenesis-and-progression-of-hepatocellular-carcinoma-tumor-factors-and-background-liver-factors
#4
Yoshikuni Inokawa, Kenichi Inaoka, Fuminori Sonohara, Masamichi Hayashi, Mitsuro Kanda, Shuji Nomoto
Although hepatocellular carcinoma (HCC) is associated with poor prognosis worldwide, the molecular mechanisms underlying the carcinogenesis and progression of this disease remain unclear. Several tumor characteristics have previously been demonstrated to be prognostic factors of survival following hepatic resection, or the recurrence of HCC or other types of cancer. Comparisons of normal tissues and HCC tumor tissues have revealed the presence of numerous molecular alterations in HCC, including genetic and epigenetic mechanisms, particularly mutations in certain genes and DNA methylation in the promoter regions of tumor-suppressor genes...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27881141/analysis-of-epithelial-mesenchymal-transition-markers-in-the-histogenesis-of-hepatic-progenitor-cell-in-hbv-related-liver-diseases
#5
Wei Xu, Nong-Rong Wang, Hua-Feng Wang, Qiong Feng, Jun Deng, Zhi-Qiang Gong, Jian Sun, Xiao-Liang Lou, Xue-Feng Yu, Lv Zhou, Jin-Ping Hu, Xiao-Feng Huang, Xiao-Qing Qi, Yan-Juan Deng, Rui Gong, Yan Guo, Meng-Meng Wang, Jia-Cheng Xiao, Huan Deng
BACKGROUND: The origin and heterogeneity of hepatic progenitor cells (HPCs) remain unclear. This study aimed to investigate the involvement of epithelial-mesenchymal transition (EMT) in the histogenesis of HPCs. METHODS: Surgical liver specimens from patients with HBV-related hepatitis and cirrhosis were investigated with double immunofluorescence labeling to detect antigens associated with HPCs and EMT. Ductular reactions were subjected to quantitative reverse transcription PCR following isolation by laser capture microdissection...
November 24, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27878234/prometastatic-mechanisms-of-caf-mediated-emt-regulation-in-pancreatic-cancer-cells
#6
Tao Shan, Shuo Chen, Xi Chen, Wan Run Lin, Wei Li, Jiancang Ma, Tao Wu, Hong Ji, Yiming Li, Xijuan Cui, Ya'an Kang
Tumor metastasis are accompanied by the EMT (epithelial-mesenchymal transition)-MET (mesenchymal-epithelial transition) two-step process. In this study, we investigated the importance of cancer associated fibroblasts (CAF) in the process. First, the primary cultures of isolated pancreatic CAF, fibroblasts of normal pancreatic tissues (NF), and normal hepatic stellate cells (HSF) were identified and verified via the expression of α-SMA and vimentin. Using an indirect three-dimensional co-culture model, the morphological changes were observed by light microscopy and laser scanning confocal microscopy...
November 23, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27864114/lipopolysaccharide-promotes-tumorigenicity-of-hepatic-progenitor-cells-by-promoting-proliferation-and-blocking-normal-differentiation
#7
Xiao-Yong Li, Xue Yang, Qiu-Dong Zhao, Zhi-Peng Han, Lei Liang, Xiao-Rong Pan, Jing-Ni Zhu, Rong Li, Meng-Chao Wu, Li-Xin Wei
Hepatic progenitor cells (HPCs) are bipotential stem cells that can differentiate into mature hepatocytes or biliary epithelial cells (BECs). They are thought to be involved in repair of liver injury and the incidence of hepatic carcinoma. Their physiology is closely associated with the microenvironment where they reside. Lipopolysaccharide (LPS), an important component of the hepatic pathological microenvironment, is stored in the liver and affects many types of cells in various hepatosis. HPCs may also be influenced by LPS...
November 15, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27853640/high-throughput-t-cell-receptor-sequencing-reveals-distinct-repertoires-between-tumor-and-adjacent-non-tumor-tissues-in-hbv-associated-hcc
#8
Yunqing Chen, Ying Xu, Miaoxian Zhao, Yu Liu, Mingxing Gong, Cantao Xie, Hongkai Wu, Zhanhui Wang
T lymphocytes, which recognize antigen peptides through specific T cell receptors (TCRs), play an important role in the human adaptive immune response. TCR diversity is closely associated with host immune response and cancer prognosis. Although tumor-infiltrating T lymphocytes have implications for tumor prognosis, few studies have performed a detailed characterization of TCR diversity in both tumor and non-tumor tissues in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Here, we performed high-throughput sequencing of the TCRβ chain complementarity determining region 3 (CDR3) of liver-infiltrating T cells from 48 HBV-associated HCC patients...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27853186/activated-hepatic-stellate-cells-play-pivotal-roles-in-hepatocellular-carcinoma-cell-chemoresistance-and-migration-in-multicellular-tumor-spheroids
#9
Yeonhwa Song, Se-Hyuk Kim, Kang Mo Kim, Eun Kyung Choi, Joon Kim, Haeng Ran Seo
Most Hepatocellular carcinoma (HCC) are resistant to conventional chemotherapeutic agents and remain an unmet medical need. Recently, multiple studies on the crosstalk between HCC and their tumor microenvironment have been conducted to overcome chemoresistance in HCC. In this study, we formed multicellular tumor spheroids (MCTS) to elucidate the mechanisms of environment-mediated chemoresistance in HCC. We observed that hepatic stellate cells (HSCs) in MCTS significantly increased the compactness of spheroids and exhibited strong resistance to sorafenib and cisplatin relative to other types of stromal cells...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27831558/ripk1-protects-from-tnf-%C3%AE-mediated-liver-damage-during-hepatitis
#10
Aveline Filliol, Claire Piquet-Pellorce, Jacques Le Seyec, Muhammad Farooq, Valentine Genet, Catherine Lucas-Clerc, John Bertin, Peter J Gough, Marie-Thérèse Dimanche-Boitrel, Peter Vandenabeele, Mathieu Jm Bertrand, Michel Samson
Cell death of hepatocytes is a prominent characteristic in the pathogenesis of liver disease, while hepatolysis is a starting point of inflammation in hepatitis and loss of hepatic function. However, the precise molecular mechanisms of hepatocyte cell death, the role of the cytokines of hepatic microenvironment and the involvement of intracellular kinases, remain unclear. Tumor necrosis factor alpha (TNF-α) is a key cytokine involved in cell death or survival pathways and the role of RIPK1 has been associated to the TNF-α-dependent signaling pathway...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27830548/fetal-liver-stem-progenitor-cell-transplantation-a-model-to-study-tissue-mass-replacement-and-cell-based-therapies
#11
Mladen I Yovchev, Michael Oertel
Liver transplantation is the only therapeutic treatment for patients with end-stage liver diseases. However, donor organ scarcity is the major limitation, and therefore, alternative strategies are urgently needed. The ultimate goal for successful cell-based therapies is the ability of transplanted cells to efficiently engraft and reconstitute injured liver mass. To evaluate the repopulation capacity of transplanted cells, it is essential to identify their specific characteristics, as well as to study the mechanism(s) Through which transplanted donor cells replace tissue mass in hepatic microenvironments, using well-established cell transplantation models...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27829276/biliary-carcinomas-pathology-and-the-role-of-dna-mismatch-repair-deficiency
#12
Vitor Werneck Krauss Silva, Gokce Askan, Tanisha D Daniel, Maeve Lowery, David S Klimstra, Ghassan K Abou-Alfa, Jinru Shia
The pathology of biliary carcinomas is diverse with different gross and histological features in tumors arising in the different segments of the biliary system. Various epidemiological risk factors, varied genetic makeup, and tissue microenvironment are contributory factors. As biliary tumors have been shown to be a part of the Lynch syndrome tumor spectrum, it is plausible to speculate that DNA mismatch repair (MMR) deficiency plays a role in biliary tumors. Literature data suggest that DNA MMR deficiency indeed occurs in these tumors, albeit infrequently with the reported frequencies (weighted for sample size) of high level microsatellite instability (MSI) being 5% each for gallbladder carcinoma and carcinoma of extra-hepatic bile ducts, and 10% each for intrahepatic cholangiocarcinoma and ampullary carcinoma...
October 2016: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/27811394/sympathetic-neurotransmitters-promote-the-process-of-recellularization-in-decellularized-liver-matrix-via-activating-the-il-6-stat3-pathway
#13
Xudong Wen, Hongbo Huan, Xiaojun Wang, Xuejiao Chen, Lili Wu, Yujun Zhang, Weihui Liu, Ping Bie, Feng Xia
Recellularized liver, as an approach for hepatic tissue engineering, is an effective alternative to orthotopic liver transplantation for end-stage hepatic failure. When compared with normal liver, recellularized liver has a disparity in hepatocyte viability and function, owing to the difficulty of fully simulating the microenvironment of liver. Although the sympathetic nervous system (SNS) is considered an important constituent of liver function, few studies have examined the effect of the SNS on hepatic tissue engineering...
November 4, 2016: Biomedical Materials
https://www.readbyqxmd.com/read/27805290/in-vitro-differentiated-hepatic-oval-like-cells-enhance-hepatic-regeneration-in-ccl4-induced-hepatic-injury
#14
Sana Javaid Awan, Maria Tayyab Baig, Faiza Yaqub, Asima Tayyeb, Gibran Ali
Hepatic oval cells are likely to be activated during advanced stage of liver fibrosis to reconstruct damaged hepatic tissue. However, their scarcity, difficulties in isolation, and in vitro expansion hampered their transplantation in fibrotic liver. This study was aimed to investigate the repair potential of in vitro differentiated hepatic oval-like cells in CCl4 -induced liver fibrosis. BMSCs and oval cells were isolated and characterized from C57BL/6 GFP(+) mice. BMSCs were differentiated into oval cells by preconditioning with HGF, EGF, SCF, and LIF and analyzed for the oval cells-specific genes...
November 2, 2016: Cell Biology International
https://www.readbyqxmd.com/read/27797969/role-of-the-microenvironment-in-liver-metastasis-from-pre-to-prometastatic-niches
#15
REVIEW
Pnina Brodt
Liver metastases remain a major barrier to successful management of malignant disease, particularly for cancers of the gastrointestinal tract but also for other malignancies, such as breast carcinoma and melanoma. The ability of metastatic cells to survive and proliferate in the liver is determined by the outcome of complex, reciprocal interactions between tumor cells and different local resident subpopulations, including the sinusoidal endothelium, stellate, Kupffer, and inflammatory cells that are mediated through cell-cell and cell-extracellular matrix adhesion and the release of soluble factors...
October 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27797146/innovative-technologies-in-nanomedicines-from-passive-targeting-to-active-targeting-from-controlled-pharmacokinetics-to-controlled-intracellular-pharmacokinetics
#16
Yusuke Sato, Yu Sakurai, Kazuaki Kajimoto, Takashi Nakamura, Yuma Yamada, Hidetaka Akita, Hideyoshi Harashima
Nanomedicines promise to extend drug therapy from small molecular compounds to proteins/nucleic acids/genes. Multifunctional envelope-type nanodevices (MENDs) have been developed for delivering such molecules to the site of action. The YSK-MEND contains new types of pH-responsive cationic lipids to efficiently deliver siRNA to hepatocytes via receptor-mediated endocytosis and use in treating hepatitis C and B in model mice. The RGD ligand is introduced to target tumor endothelial cells (TEC) and RGD-MEND is able to send siRNA to TEC to regulate the function of tumor microenvironments...
October 31, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27796316/ductular-reaction-on-a-chip-microfluidic-co-cultures-to-study-stem-cell-fate-selection-during-liver-injury
#17
Amranul Haque, Pantea Gheibi, Gulnaz Stybayeva, Yandong Gao, Natalie Torok, Alexander Revzin
Liver injury modulates local microenvironment, triggering production of signals that instruct stem cell fate choices. In this study, we employed a microfluidic co-culture system to recreate important interactions in the liver stem cell niche, those between adult hepatocytes and liver progenitor cells (LPCs). We demonstrate that pluripotent stem cell-derived LPCs choose hepatic fate when cultured next to healthy hepatocytes but begin biliary differentiation program when co-cultured with injured hepatocytes. We connect this fate selection to skewing in production of hepatocyte growth factor (HGF) and transforming growth factor (TGF)-β1 caused by injury...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27780972/developmental-origins-of-nafld-a-womb-with-a-clue
#18
REVIEW
Stephanie R Wesolowski, Karim C El Kasmi, Karen R Jonscher, Jacob E Friedman
Changes in the maternal environment leading to an altered intrauterine milieu can result in subtle insults to the fetus, promoting increased lifetime disease risk and/or disease acceleration in childhood and later in life. Particularly worrisome is that the prevalence of NAFLD is rapidly increasing among children and adults, and is being diagnosed at increasingly younger ages, pointing towards an early-life origin. A wealth of evidence, in humans and non-human primates, suggests that maternal nutrition affects the placenta and fetal tissues, leading to persistent changes in hepatic metabolism, mitochondrial function, the intestinal microbiota, liver macrophage activation and susceptibility to NASH postnatally...
October 26, 2016: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27760163/role-of-pxr-in-hepatic-cancer-its-influences-on-liver-detoxification-capacity-and-cancer-progression
#19
Deepak Kotiya, Bharti Jaiswal, Sampa Ghose, Rachna Kaul, Kasturi Datta, Rakesh K Tyagi
The role of nuclear receptor PXR in detoxification and clearance of xenobiotics and endobiotics is well-established. However, its projected role in hepatic cancer is rather illusive where its expression is reported altered in different cancers depending on the tissue-type and microenvironment. The expression of PXR, its target genes and their biological or clinical significance have not been examined in hepatic cancer. In the present study, by generating DEN-induced hepatic cancer in mice, we report that the expression of PXR and its target genes CYP3A11 and GSTa2 are down-regulated implying impairment of hepatic detoxification capacity...
2016: PloS One
https://www.readbyqxmd.com/read/27738324/the-type-i-insulin-like-growth-factor-regulates-the-liver-stromal-response-to-metastatic-colon-carcinoma-cells
#20
Maria Celia Fernandez, Roni Rayes, Boram Ham, Ni Wang, France Bourdeau, Simon Milette, Martin Lllemann, Nigel Bird, Ali Majeed, Jun Xu, Tatiana Kisselova, Pnina Brodt
Hepatic stellate cells (HSC) play a major role in initiating the liver fibrogenic (wounding) response of the liver and can also orchestrate a pro-metastatic microenvironment in the liver in response to invading cancer cells. Here we explored the role of the hepatic stellate cells in colon carcinoma liver metastasis with emphasis on the contribution of the insulin-like growth factor (IGF) axis to their activation and function. To this end, we used mice with a Tamoxifen inducible liver IGF-I deficiency. We found that in mice with a sustained IGF-I deficiency, recruitment and activation of HSC into tumor-infiltrated areas of the liver were markedly diminished, resulting in decreased collagen deposition and reduced tumor expansion...
October 12, 2016: Oncotarget
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