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https://www.readbyqxmd.com/read/29458164/structure-dependent-induction-of-apoptosis-by-hepatotoxic-pyrrolizidine-alkaloids-in-the-human-hepatoma-cell-line-heparg-single-versus-repeated-exposure
#1
Julia Waizenegger, Albert Braeuning, Markus Templin, Alfonso Lampen, Stefanie Hessel-Pras
Pyrrolizidine alkaloids (PA) are secondary plant compounds. PA intoxication in humans causes severe acute and chronic hepatotoxicity. However, the molecular mechanisms of PA hepatotoxicity in humans are not well understood yet. Therefore, we investigated cell death parameters in human HepaRG cells following either single (24 h) or repeated dose treatment (14 d) with structurally different PA of the retronecine (echimidine, senecionine), heliotridine (heliotrine), and otonecine type (senkirkine). After 24 h of exposure only retronecine-type PA were cytotoxic in HepaRG cells and induced apoptosis indicated by a loss of membrane asymmetry, disruption of the mitochondrial membrane potential, and increased pro-caspase and PARP cleavage...
February 16, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29458160/gambogic-acid-sensitizes-breast-cancer-cells-to-trail-induced-apoptosis-by-promoting-the-crosstalk-of-extrinsic-and-intrinsic-apoptotic-signalings
#2
Shengpeng Wang, Yingqi Xu, Chenyang Li, Hongxun Tao, Anqi Wang, Chenyu Sun, Zhangfeng Zhong, Xu Wu, Peng Li, Yitao Wang
Due to the ability of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) to induce cancer cell apoptosis selectively, TRAIL has attracted significant interest in the treatment of cancer. However, although TRAIL triggers apoptosis in a broad range of cancer cells, most primary cancers are often intrinsically TRAIL-resistant, or acquire resistance after TRAIL treatment, evocating new strategies to overcome TRAIL resistance. Gambogic acid (GA), an active constituent of Garcinia Hanburyi (Teng Huang in Chinese), has been applied for thousands of years for medicinal uses, however, the potential effect of GA in combating cancer resistance remains poorly investigated...
February 16, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29457657/semaphorin4a-and-h-ferritin-utilize-tim-1-on-human-oligodendrocytes-a-novel-neuro-immune-axis
#3
Brian Chiou, Elisabeth Lucassen, Michael Sather, Asha Kallianpur, James Connor
Deficiency of trophic factors relating to the survival of oligodendrocytes, combined with direct interactions with the immune system, are favored paradigms that are increasingly implicated in demyelinating diseases of the central nervous system. We and others have previously shown that Sema4A and H-ferritin interact through the T-cell immunoglobulin and mucin domain (Tim-2) receptor in mice. H-ferritin has been identified as the iron delivery protein for oligodendrocytes, whereas Sema4A causes a direct cytotoxic effect...
February 19, 2018: Glia
https://www.readbyqxmd.com/read/29456737/distinctive-profiles-of-tumor-infiltrating-immune-cells-and-association-with-intensity-of-infiltration-in-colorectal-cancer
#4
Yugang Wu, Lei Yuan, Qicheng Lu, Haiyan Xu, Xiaozhou He
Tumor-infiltrating immune cells are heterogeneous and consist of characteristic compartments, including T helper (Th)1 and regulatory T (Treg) cells that exhibit distinctive biological functions. The present study investigated the profile of infiltrating immune cells from surgically removed tumor tissues from patients with colorectal cancer. The characteristic transcription factors of Th1 and Th2 cells, Treg cells, Th17 cells and T follicular helper (Tfh) cells were analyzed. The results demonstrated that a marked increased number of Treg cells presented in tumor infiltrates when compared with non-tumor adjacent tissues...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456630/roles-of-eph-ephrin-bidirectional-signaling-in-central-nervous-system-injury-and-recovery
#5
Jin-Shan Yang, Hui-Xing Wei, Ping-Ping Chen, Gang Wu
Multiple cellular components are involved in the complex pathological process following central nervous system (CNS) injury, including neurons, glial cells and endothelial cells. Previous studies and neurotherapeutic clinical trials have assessed the molecular mechanisms that underlie neuronal cell death following CNS injury. However, this approach has largely failed to reduce CNS damage or improve the functional recovery of patients. Erythropoietin-producing human hepatocellular (Eph) receptors and ephrin ligands have attracted considerable attention since their discovery, due to their extensive distribution and unique bidirectional signaling between astrocytes and neurons...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29455984/hyaluronate-coating-enhances-the-delivery-and-biocompatibility-of-gold-nanoparticles
#6
Bedia Begum Karakocak, Jue Liang, Pratim Biswas, Nathan Ravi
For targeted delivery with nanoparticles (NPs) as drug carriers, it is imperative that the NPs are internalized into the targeted cell. Surface properties of NPs influence their interactions with cells. We examined the responses of retinal pigment epithelial cells, NIH 3T3 fibroblast cells, and Chinese hamster ovary cells to gold nanoparticles (Au NPs) in their nascent form as well as coated with end-thiolated hyaluronate (HS-HA). The grafting density of HS-HA on Au NPs was calculated based on total organic carbon measurements and thermal gravimetric analysis...
April 15, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29455675/the-function-and-therapeutic-targeting-of-anaplastic-lymphoma-kinase-alk-in-non-small-cell-lung-cancer-nsclc
#7
REVIEW
Brandon Golding, Anita Luu, Robert Jones, Alicia M Viloria-Petit
Lung cancer is the leading cause of death by cancer in North America. A decade ago, genomic rearrangements in the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase were identified in a subset of non-small cell lung carcinoma (NSCLC) patients. Soon after, crizotinib, a small molecule ATP-competitive ALK inhibitor was proven to be more effective than chemotherapy in ALK-positive NSCLC patients. Crizotinib and two other ATP-competitive ALK inhibitors, ceritinib and alectinib, are approved for use as a first-line therapy in these patients, where ALK rearrangement is currently diagnosed by immunohistochemistry and in situ hybridization...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455665/pten-ptenp1-regulating-the-regulator-of-rtk-dependent-pi3k-akt-signalling-new-targets-for-cancer-therapy
#8
REVIEW
Nahal Haddadi, Yiguang Lin, Glena Travis, Ann M Simpson, Eileen M McGowan, Najah T Nassif
Regulation of the PI-3 kinase (PI3K)/Akt signalling pathway is essential for maintaining the integrity of fundamental cellular processes, cell growth, survival, death and metabolism, and dysregulation of this pathway is implicated in the development and progression of cancers. Receptor tyrosine kinases (RTKs) are major upstream regulators of PI3K/Akt signalling. The phosphatase and tensin homologue (PTEN), a well characterised tumour suppressor, is a prime antagonist of PI3K and therefore a negative regulator of this pathway...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455652/expression-regulation-and-targeting-of-receptor-tyrosine-kinases-in-esophageal-squamous-cell-carcinoma
#9
REVIEW
Manoj Kumar Kashyap, Omar Abdel-Rahman
Esophageal cancer is one of the most common types of cancer, which is a leading cause of cancer-related death worldwide. Based on histological behavior, it is mainly of two types (i) Esophageal squamous cell carcinoma (ESCC), and (ii) esophageal adenocarcinoma (EAD or EAC). In astronomically immense majority of malignancies, receptor tyrosine kinases (RTKs) have been kenned to play a consequential role in cellular proliferation, migration, and metastasis of the cells. The post-translational modifications (PTMs) including phosphorylation of tyrosine (pY) residue of the tyrosine kinase (TK) domain have been exploited for treatment in different malignancies...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29454648/foxp3-renders-activated-human-regulatory-t-cells-resistant-to-restimulation-induced-cell-death-by-suppressing-sap-expression
#10
Gil Katz, Kelsey Voss, Toria F Yan, Yong Chan Kim, Robert L Kortum, David W Scott, Andrew L Snow
Restimulation-induced cell death (RICD) is an apoptotic program that regulates effector T cell expansion, triggered by repeated stimulation through the T cell receptor (TCR) in the presence of interleukin-2 (IL-2). Although CD4+ regulatory T cells (Tregs) consume IL-2 and experience frequent TCR stimulation, they are highly resistant to RICD. Resistance in Tregs is dependent on the forkhead box P3 (FOXP3) transcription factor, although the mechanism remains unclear. T cells from patients with X-linked lymphoproliferative disease (XLP-1), that lack the adaptor molecule SLAM-associated protein (SAP), are also resistant to RICD...
February 12, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29454638/testosterone-levels-and-prostate-cancer-prognosis-systematic-review-and-meta-analysis
#11
REVIEW
Mélanie Claps, Fausto Petrelli, Orazio Caffo, Vito Amoroso, Elisa Roca, Alessandra Mosca, Francesca Maines, Sandro Barni, Alfredo Berruti
Androgen receptor is the major driver of and testosterone the natural growth factor of prostate cancer (PC). Studies exploring the relationship among circulating testosterone levels, PC aggressiveness, and patient prognosis showed contradictory results. We performed a comprehensive literature search for studies reporting the independent relationship between serum testosterone and prognosis of PC patients. Meta-analyses using random effects models were conducted to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs)...
February 2, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29454061/activation-of-nlrx1-mediated-autophagy-accelerates-the-ototoxic-potential-of-cisplatin-in-auditory-cells
#12
Haiyan Yin, Qianqian Yang, Zhixin Cao, Hongrui Li, Zhaoyan Yu, Guodong Zhang, Gaoying Sun, Rongjun Man, Haibo Wang, Jianfeng Li
To date, the mechanism (s) underlying the cisplatin-elicited ototoxicity has not been elucidated fully. Nucleotide-binding domain and leucine-rich-repeat-containing family member ×1 (NLRX1), a cytoplasmic pattern recognition receptor, is tightly related to mitochondrial function, reactive oxygen species (ROS) production, and autophagy. In this work, autophagy alteration, NLRX1 expression, ROS generation and cell injury were investigated correspondingly by immunofluorescence staining, western-blot, TEM, flow cytometry and MTT in HEI-OC1 cells of both NLRX1 overexpression and silencing in response to cisplatin stimulus...
February 14, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29453963/significance-of-spread-through-air-spaces-in-resected-pathological-stage-i-lung-adenocarcinoma
#13
Gouji Toyokawa, Yuichi Yamada, Tetsuzo Tagawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND: Spread through air spaces (STAS) is a recently described invasive pattern of lung cancer, which spreads within air spaces beyond the edge of the main tumor. In the current study, we investigated the significance of STAS in patients with pathological stage I adenocarcinoma. METHODS: STAS was assessed in a total of 276 patients with resected pathological stage I adenocarcinoma. STAS was classified as either no STAS, low STAS (1-4 single cells or clusters of STAS), or high STAS (≥5 single cells or clusters of STAS) using a 20x objective and a 10x ocular lens...
February 14, 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29453321/inhibition-of-cd95-cd95l-signaling-with-apg101-prevents-invasion-and-enhances-radiation-therapy-for-glioblastoma
#14
Jonas Blaes, Carina M Thomé, Philipp-Niclas Pfenning, Petra Rübmann, Felix Sahm, Antje Wick, Theresa Bunse, Torsten Schmenger, Jaromir Sykora, Andreas von Deimling, Benedikt Wiestler, Christian Merz, Manfred Jugold, Uwe Haberkorn, Amir Abdollahi, Jürgen Debus, Christian Gieffers, Claudia Kunz, Martin Bendszus, Michael Kluge, Michael Platten, Harald Fricke, Wolfgang Wick, Dieter Lemke
CD95 (Fas/APO-1), a death receptor family member, activity has been linked to tumorigenicity in multiple cancers, including glioblastoma multiforme (GBM). A phase II clinical trial on relapsed glioblastoma patients demonstrated that targeted inhibition of CD95 signaling via the CD95 ligand (CD95L) binding and neutralizing Fc-fusion protein APG101 (asunercept) prolonged patient survival. While CD95 signaling may be relevant for multiple aspects of tumor growth, the mechanism of action of APG101 in glioblastoma is not clear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452998/resection-of-intrathoracic-paraganglioma-with-and-without-cardiopulmonary-bypass
#15
Carmelina Gurrieri, James J Butz, Toby N Weingarten, Irina Bancos, William F Young, Stephen D Cassivi, Sameh M Said, Travis J McKenzie, David W Barbara, Juraj Sprung
BACKGROUND: Intrathoracic paragangliomas (PGLs) are rare tumors. Approximately 50% originate from and around cardiac structures. METHODS: A retrospective review was made of the perioperative course of patients with intrathoracic PGL resection from 2000 through 2015 at Mayo Clinic in Rochester, Minnesota. RESULTS: Twenty-two patients underwent PGL resection. Sixteen patients (73%) had functioning tumors (11, noradrenergic; 4, mixed noradrenergic and dopaminergic; 1, dopaminergic)...
February 13, 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29452946/time-responsive-osteogenic-niche-of-stem-cells-a-sequentially-triggered-dual-peptide-loaded-alginate-hybrid-system-for-promoting-cell-activity-and-osteo-differentiation
#16
Zuyuan Luo, Siqi Zhang, Jijia Pan, Rui Shi, Hao Liu, Yalin Lyu, Xiao Han, Yan Li, Yue Yang, Zhixiu Xu, Yi Sui, En Luo, Yuanyuan Zhang, Shicheng Wei
The efficacy of stem cell-based bone tissue engineering has been hampered by cell death and limited fate control. A smart cell culture system with the capability of sequentially delivering multiple factors in specific growth stages, like the mechanism of the natural extracellular matrix modulating tissue formation, is attractive for enhancing cell activity and controlling cell fate. Here, a bone forming peptide-1 (BFP-1)-laden mesoporous silica nanoparticles (pep@MSNs) incorporated adhesion peptide, containing the arginine-glycine-aspartic acid (RGD) domain, modified alginate hydrogel (RA) system (pep@MSNs-RA) was developed to promote the activity and stimulate osteo-differentiation of human mesenchymal stem cells (hMSCs) in sequence...
February 10, 2018: Biomaterials
https://www.readbyqxmd.com/read/29452613/the-role-of-plasma-membrane-calcium-atpases-pmcas-in-neurodegenerative-disorders
#17
REVIEW
Parvana Hajieva, Marius W Baeken, Bernd Moosmann
Selective degeneration of differentiated neurons in the brain is the unifying feature of neurodegenerative disorders such as Parkinson's disease (PD) or Alzheimer's disease (AD). A broad spectrum of evidence indicates that initially subtle, but temporally early calcium dysregulation may be central to the selective neuronal vulnerability observed in these slowly progressing, chronic disorders. Moreover, it has long been evident that excitotoxicity and its major toxic effector mechanism, neuronal calcium overload, play a decisive role in the propagation of secondary neuronal death after acute brain injury from trauma or ischemia...
January 10, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29452280/sticholysin-ii-mediated-cytotoxicity-involves-the-activation-of-regulated-intracellular-responses-that-anticipates-cell-death
#18
Carmen Soto, Gretchen Bergado, Rancés Blanco, Tania Griñán, Hermis Rodríguez, Uris Ros, Fabiola Pazos, María Eliana Lanio, Ana María Hernández, Carlos Álvarez
Sticholysin II (StII) is a pore-forming toxin of biomedical interest that belongs to the actinoporin protein family. Sticholysins are currently under examination as an active immunomodulating component of a vaccinal platform against tumoral cells and as a key element of a nucleic acids delivery system to cell cytosol. These proteins form pores in the plasma membrane leading to ion imbalance and cell lysis. However, the intracellular mechanisms triggered by actinoporins upon binding to membranes and its consequences for cell death are barely understood...
February 13, 2018: Biochimie
https://www.readbyqxmd.com/read/29452205/impaired-cerebral-microcirculation-induced-by-ammonium-chloride-in-rats-is-due-to-cortical-adenosine-release
#19
Peter Nissen Bjerring, Esben Jannik Bjerrum, Fin Stolze Larsen
BACKGROUND: Liver failure results in hyperammonaemia, impaired regulation of cerebral microcirculation, encephalopathy and death. However, the key mediator that alters cerebral microcirculation remains unidentified. In this study we show that topical ammonium significantly increases periarteriolar adenosine tone on the brain surface of healthy rats and is associated with a disturbed microcirculation. METHODS: Cranial windows were prepared in anaesthetized Wistar rats...
February 13, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29452097/stimulation-of-trpv1-channels-activates-the-ap-1-transcription-factor
#20
Tobias M Backes, Oliver G Rössler, Xin Hui, Carsten Grötzinger, Peter Lipp, Gerald Thiel
Transient receptor potential vanilloid 1 (TRPV1) channels were originally described as the receptors of capsaicin, the main constituent of hot chili pepper. The biological functions of TRPV1 channels include pain sensation and inflammatory thermal hyperalgesia. Here, we show that stimulation of HEK293 cells expressing TRPV1 channels (H2C1 cells) with capsaicin or the TRPV1 ligand resiniferatoxin activated transcription mediated by the transcription factor AP-1. No cell death was occurring under these experimental conditions...
February 13, 2018: Biochemical Pharmacology
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