Read by QxMD icon Read

Hypoxia and metastasis

Hung-Yi Liu, Tanja Greene, Tsai-Yu Lin, Camron S Dawes, Murray Korc, Chien-Chi Lin
: The complex network of biochemical and biophysical cues in the pancreatic desmoplasia not only presents challenges to the fundamental understanding of tumor progression, but also hinders the development of therapeutic strategies against pancreatic cancer. Residing in the desmoplasia, pancreatic stellate cells (PSCs) are the major stromal cells affecting the growth and metastasis of pancreatic cancer cells by means of paracrine effects and extracellular matrix protein deposition. PSCs remain in a quiescent/dormant state until they are 'activated' by various environmental cues...
October 18, 2016: Acta Biomaterialia
Maud-Emmanuelle Gilles, Federica Maione, Mélissande Cossutta, Gilles Carpentier, Laure Caruana, Sylvia Di Maria, Claire Houppe, Damien Destouches, Ksenya Shchors, Christopher Prochasson, Fabien Mongelard, Simona Lamba, Alberto Bardelli, Philippe Bouvet, Anne Couvelard, José Courty, Enrico Giraudo, Ilaria Cascone
Pancreatic cancer is a highly aggressive tumor, mostly resistant to the standard treatments. Nucleolin (NCL) is overexpressed in cancers and its inhibition impairs tumor growth. Herein we showed that NCL was overexpressed in human specimens of pancreatic ductal adenocarcinoma (PDAC) and that the overall survival significantly increased in patients with low levels of NCL. The NCL antagonist N6L strongly impaired the growth of primary tumors and liver metastasis in an orthotopic mouse model of PDAC (mPDAC). Similar anti-tumor effect of N6L has been observed in a highly angiogenic mouse model of pancreatic neuroendocrine tumor RIP-Tag2...
October 17, 2016: Cancer Research
Seung Yun Lee, Mee Ja Park, Hye Kyung Lee, Hyun Jin Son, Chang Nam Kim, Joo Heon Kim, Dong Wook Kang
Background: Thymosin β4 is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinico-pathologic implications of thymosin β4 expression in human colorectal carcinomas (CRCs). Materials and Methods: We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin β4 expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series...
October 16, 2016: Journal of Pathology and Translational Medicine
Prabhu Thirusangu, V Vigneshwaran, T Prashanth, B R Vijay Avin, Vikas H Malojirao, H Rakesh, Shaukath Ara Khanum, Riaz Mahmood, B T Prabhakar
Hypoxia is a feature of all solid tumours, contributing to tumour progression. Activation of HIF-1α plays a critical role in promoting tumour angiogenesis and metastasis. Since its expression is positively correlated with poor prognosis for cancer patients, HIF-1α is one of the most convincing anticancer targets. BP-1T is a novel antiproliferative agent with promising antiangiogenic effects. In the present study, the molecular mechanism underlying cytotoxic/antiangiogenic effects of BP-1T on tumour/non-tumour angiogenesis was evaluated...
October 14, 2016: Angiogenesis
Ivana Jochmanova, Karel Pacak
Dysregulated metabolism is one of the key characteristics of cancer cells. The most prominent alterations are present during regulation of cell respiration, which leads to a switch from oxidative phosphorylation to aerobic glycolysis. This metabolic shift results in activation of numerous signaling and metabolic pathways supporting cell proliferation and survival. Recent progress in genetics and metabolomics has allowed us to take a closer look at the metabolic changes present in pheochromocytomas (PHEO) and paragangliomas (PGL)...
October 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Nuh N Rahbari, Dmitriy Kedrin, Joao Incio, Hao Liu, William W Ho, Hadi T Nia, Christina M Edrich, Keehoon Jung, Julien Daubriac, Ivy Chen, Takahiro Heishi, John D Martin, Yuhui Huang, Nir Maimon, Christoph Reissfelder, Jurgen Weitz, Yves Boucher, Jeffrey W Clark, Alan J Grodzinsky, Dan G Duda, Rakesh K Jain, Dai Fukumura
The survival benefit of anti-vascular endothelial growth factor (VEGF) therapy in metastatic colorectal cancer (mCRC) patients is limited to a few months because of acquired resistance. We show that anti-VEGF therapy induced remodeling of the extracellular matrix with subsequent alteration of the physical properties of colorectal liver metastases. Preoperative treatment with bevacizumab in patients with colorectal liver metastases increased hyaluronic acid (HA) deposition within the tumors. Moreover, in two syngeneic mouse models of CRC metastasis in the liver, we show that anti-VEGF therapy markedly increased the expression of HA and sulfated glycosaminoglycans (sGAGs), without significantly changing collagen deposition...
October 12, 2016: Science Translational Medicine
Chung-Wein Lee, Keith M Stantz
BACKGROUND: Tumor hypoxia is involved in every stage of solid tumor development: formation, progression, metastasis, and apoptosis. Two types of hypoxia exist in tumors-chronic hypoxia and acute hypoxia. Recent studies indicate that the regional hypoxia kinetics is closely linked to metastasis and therapeutic responses, but regional hypoxia kinetics is hard to measure. We propose a novel approach to determine the local pO2 by fusing the parameters obtained from in vivo functional imaging through the use of a modified multivariate Krogh model...
October 12, 2016: Biomedical Engineering Online
Cesar Sepúlveda, Iván Palomo, Eduardo Fuentes
The adenosine A2b receptor is a G-protein coupled receptor. Its activation occurs with high extracellular adenosine concentration, for example in inflammation or hypoxia. These conditions are generated in the tumor environment. Studies show that A2b receptor is overexpressed in various tumor lines and biopsies from patients with different cancers. This suggests that A2b receptor can be used by tumor cells to promote progression. Thus A2b participates in different events, such as angiogenesis and metastasis, besides exerting immunomodulatory effects that protect tumor cells...
October 8, 2016: Life Sciences
Katrin Gutsche, Elisa Randi, Volker Blank, Daniel Fink, Roland H Wenger, Cornelia Leo, Carsten C Scholz
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Treatment options are limited and the mechanisms underlying its aggressiveness are poorly understood. Intermittent hypoxia (IH) causes oxidative stress and is emerging as important regulator of tumor metastasis. Vessels in IBC tumors have been shown to be immature, which is a primary cause of IH. We therefore investigated the relevance of IH for the modulation of gene expression in IBC cells in order to assess IH as potential regulator of IBC aggressiveness...
October 5, 2016: Free Radical Biology & Medicine
Li Ren, Yang Yu, Li Wang, Zhifeng Zhu, Rong Lu, Zhi Yao
Tumor cells craft microenvironment to overcome growth disadvantages and adjust to escape the immunosurveillance during tumorigenesis and metastasis. The evolving adaption to the changing microenvironment is exemplified by the development of strategies to deal with hypoxia resulted from fast proliferation of the tumor cells. In this study, we found that hypoxia hepatocellular carcinoma (HCC) cells recruited Regulatory T cells (Tregs) and expressed more Chemokine (C-C motif) ligand 28 (CCL28). Deletion of CCL28 inhibited Treg recruitment...
October 3, 2016: Oncotarget
Zhe Huang, Yong Feng
Cancer cell-derived exosomes have been actively released into the tumor microenvironment with pleiotropic roles in tumor growth and metastasis, including angiogenesis and immune modulation. However, the functions and underlying mechanisms of exosomes shed by colorectal cancer (CRC) cells under hypoxic conditions remains unknown. Here, we found that exosomes derived from hypoxic CRC cells promoted the proliferation and migration of endothelial cells. Suppression of exosome secretion through RAB27a knockdown in CRC cells inhibited exosomal induced proliferation and migration of endothelial cells...
October 5, 2016: Oncology Research
Shrikant Pradhan, Divyank Mahajan, Prabhjot Kaur, Namita Pandey, Chandresh Sharma, Tapasya Srivastava
Non-small cell lung cancer (NSCLC), comprising 85% of lung cancer cases, has been associated with resistance to chemo/radiotherapy. The hypoxic tumor micro-environment, where insufficient vasculature results in poor drug penetrance and sub-optimal chemotherapy in the tumor interiors contributes heavily to this resistance. Additionally, epigenetic changes in tumorigenic cells also change their response to different forms of therapy. In our study, we have investigated the effectiveness of a combination of cisplatin with scriptaid [a pan-Histone Deacetylase inhibitor (HDACi)] in a model that mimics the tumor microenvironment of hypoxia and sub-lethal chemotherapy...
September 30, 2016: Oncotarget
Jian-Li Gao, Yan-Mei Shui, Wei Jiang, En-Yi Huang, Qi-Yang Shou, Xin Ji, Bai-Cheng He, Gui-Yuan Lv, Tong-Chuan He
Hypoxic in the tumor mass is leading to the myeloproliferative-like disease (leukemoid reaction) and anemia of body, which characterized by strong extensive extramedullary hematopoiesis (EMH) in spleen. As the key transcription factor of hypoxia, hypoxia-inducible factor-1 (HIF-1) activates the expression of genes essential for EMH processes including enhanced blood cell production and angiogenesis. We found ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, inhibited growth of breast cancer both in vivo and in vitro...
September 30, 2016: Oncotarget
Jingli Hao, Peter Graham, Lei Chang, Jie Ni, Valerie Wasinger, Julia Beretov, Junli Deng, Wei Duan, Joseph Bucci, David Malouf, David Gillatt, Yong Li
Radioresistance is a major challenge for prostate cancer (CaP) metastasis and recurrence after radiotherapy. This study aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant (RR) subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. PC-3RR and PC-3 xenograft tumors were established and differential protein expression profiles from two groups of xenografts were analyzed using liquid chromatography tandem-mass spectrometry...
September 30, 2016: Oncotarget
Daniele M Gilkes
Most solid tumors contain regions of hypoxia in which increased cell proliferation promotes increased oxygen consumption and the condition is further exacerbated as cancer cells become localized far from a functional blood vessel, further decreasing the oxygen supply. An important mechanism that promotes cell adaptation to hypoxic conditions is the expression of hypoxia-inducible factors (HIFs). Hypoxia-inducible factors transcriptionally regulate many genes involved in the invasion and metastasis of breast cancer cells...
September 30, 2016: International Journal of Molecular Sciences
Angélica Morales, Sumiko Morimoto, Felipe Vilchis, Natsuko Taniyama, Claudia J Bautista, Carlos Robles, Enrique Bargalló
Vascular endothelial growth factor (VEGF) is important in the growth and metastasis of cancer cells. In 2001, another angiogenic factor, endocrine gland-derived VEGF (EG-VEGF), was characterized and sequenced. EG-VEGF activity appears to be restricted to endothelial cells derived from endocrine glands. At the molecular level, its expression is regulated by hypoxia and steroid hormones. Although VEGF and EG-VEGF are structurally different, they function in a coordinated fashion. Since the majority of mammary tumors are hormone-dependent, it was hypothesized that EG-VEGF would be expressed in these tumors, and therefore, represent a potential target for anti-angiogenic therapy...
October 2016: Oncology Letters
Takahiro Kuchimaru, Tomoya Suka, Keisuke Hirota, Tetsuya Kadonosono, Shinae Kizaka-Kondoh
The ubiquitin-proteasome system (UPS) is a selective protein degradation system that plays a critical role in many essential biological processes by regulating the existence of various cellular proteins. The target proteins of UPS are recognized and tagged with polyubiquitin chains by E3 ubiquitin ligases, which have high substrate-specific activities. Here we present a novel injectable imaging probe POL-N that can detect the UPS-regulated hypoxia-inducible factor (HIF) activity in vivo. Because the luciferase is fused to the E3 ligase-recognition domain of the HIF-1α, POL-N is intact only in the HIFα-overexpressing cells, that is, HIF-active cells, generating signals via an intramolecular bioluminescence resonance energy transfer (BRET) between luciferase and a near-infrared (NIR) fluorescent dye at the C-terminal end of the probe...
October 4, 2016: Scientific Reports
Shi Chen, Jiang-Zhi Chen, Jia-Qiang Zhang, Hui-Xin Chen, Mao-Lin Yan, Long Huang, Yi-Feng Tian, Yan-Lin Chen, Yao-Dong Wang
The epithelial-mesenchymal transition (EMT) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) development and progression. TWIST activated by intra-tumoral hypoxia functions to promote the EMT. We hypothesized that TWIST and the downstream gene pathway could mediate PDAC progression under hypoxia. Therefore, 90 PDAC tissue specimens were immunostained for TWIST and other proteins. Pancreatic cancer cell lines were used for in vitro experiments and nude mice were used to confirm the in vivo data...
September 28, 2016: Cancer Letters
Anna Bagnato, Laura Rosanò
Metastatization is a complex multistep process requiring fine-tuned regulated cytoskeleton re-modeling, mediated by the cross-talk of actin with interacting partners, such as the Rho GTPases. Our expanding knowledge of invadopodia, small invasive membrane protrusions composed of a core of F-actin, actin regulators and actin-binding proteins, and hotspots for secretion of extracellular matrix (ECM) proteinases, contributes to clarify critical steps of the metastatic program. Growth factor receptors and their intermediate signaling molecules, along with matrix adhesion and rigidity, pH and hypoxia, act as drivers of cytoskeleton changes and invadopodia formation...
October 3, 2016: Small GTPases
Chunying Wu, Xizhen Wang, Nicholas Tomko, Junqing Zhu, William R Wang, Jinle Zhu, Yanming Wang, Robert G Salomon
Angiogenesis is a fundamental process in the progression, invasion, and metastasis of tumors. Therapeutic drugs such as bevacizumab and ranibuzumab have thus been developed to inhibit vascular endothelial growth factor (VEFG)-promoted angiogenesis. While these anti-angiogenic drugs have been commonly used in the treatment of cancer, patients often develop significant resistance that limits the efficacy of anti-VEGF therapies to a short period of time. This is in part due to the fact that an independent pathway of angiogenesis exists, which is mediated by 2-(ω-carboxyethyl)pyrrole (CEP) in a TLR2 receptor-dependent manner that can compensate for inhibition of the VEGF-mediated pathway...
September 22, 2016: Anti-cancer Agents in Medicinal Chemistry
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"