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Cancer regulatory

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https://www.readbyqxmd.com/read/28433812/the-perlecan-interacting-growth-factor-progranulin-regulates-ubiquitination-sorting-and-lysosomal-degradation-of-sortilin
#1
Ryuta Tanimoto, Chiara Palladino, Shi-Qiong Xu, Simone Buraschi, Thomas Neill, Leonard G Gomella, Stephen C Peiper, Antonino Belfiore, Renato V Iozzo, Andrea Morrione
Despite extensive clinical and experimental studies over the past decades, the pathogenesis and progression to the castration-resistant stage of prostate cancer remains largely unknown. Progranulin, a secreted growth factor, strongly binds the heparin-sulfate proteoglycan perlecan, and counteracts its biological activity. We established that progranulin acts as an autocrine growth factor and promotes prostate cancer cell motility, invasion, and anchorage-independent growth. Progranulin was overexpressed in prostate cancer tissues vis-à-vis non-neoplastic tissues supporting the hypothesis that progranulin may play a key role in prostate cancer progression...
April 20, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28432789/probing-protein-flexibility-reveals-a-mechanism-for-selective-promiscuity
#2
Nicolas A Pabon, Carlos J Camacho
Many eukaryotic regulatory proteins adopt distinct bound and unbound conformations, and use this structural flexibility to bind specifically to multiple partners. However, we lack an understanding of how an interface can select some ligands, but not others. Here, we present a molecular dynamics approach to identify and quantitatively evaluate the interactions responsible for this selective promiscuity. We apply this approach to the anti-cancer target PD-1 and its ligands PD-L1 and PD-L2. We discover that while unbound PD-1 exhibits a hard-to-drug hydrophilic interface, conserved specific triggers encoded in the cognate ligands activate a promiscuous binding pathway that reveals a flexible hydrophobic binding cavity...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432593/talking-about-breast-cancer-which-symptoms-and-treatment-side-effects-are-important-to-patients-with-advanced-disease
#3
Anna Niklasson, Jean Paty, Anna Rydén
BACKGROUND: Patients' experience of symptoms and associated treatment is an increasingly important consideration in both regulatory and health technology assessments, and can inform treatment decisions. OBJECTIVE: This study aimed to gain insight directly from patients with advanced breast cancer about which symptoms and treatment side effects are important to them. METHODS: Women with locally advanced or metastatic breast cancer were interviewed individually by trained interviewers, using a semi-structured interview guide...
April 21, 2017: Patient
https://www.readbyqxmd.com/read/28432279/il-35-induces-n2-phenotype-of-neutrophils-to-promote-tumor-growth
#4
Jiu-Ming Zou, Jian Qin, Yong-Chao Li, Yu Wang, Dong Li, Yu Shu, Chao Luo, Shan-Shan Wang, Gang Chi, Fang Guo, Gui-Mei Zhang, Zuo-Hua Feng
IL-35 is an immunosuppressive cytokine and exerts regulatory effects on T cells, B cells, macrophages and dendritic cells. Neutrophils are important innate immune cells that play key roles in tumor development. The effect of IL-35 on neutrophils remains unknown. Here, we report that IL-35 can induce N2 neutrophil polarization (protumor phenotype) by increasing G-CSF and IL-6 production, and promote neutrophil infiltration into tumor microenvironment. The sustained expression of IL-35 could promote chronic inflammation to augment the proangiogenic and immunosuppressive function of neutrophils...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28432260/dual-histone-reader-zmynd8-inhibits-cancer-cell-invasion-by-positively-regulating-epithelial-genes
#5
Moitri Basu, Isha Sengupta, Wasim Khan, Dushyant Kumar Srivastava, Partha Chakrabarti, Siddhartha Roy, Chandrima Das
Enhanced migratory potential and invasiveness of cancer cells attribute crucially.in cancer progression. These phenotypes are achieved by precise alteration of invasion-associated genes through local epigenetic modifications which are recognized by a class of proteins termed as chromatin reader. ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a key component of transcription regulatory network, has been recently shown to be a novel reader of H3.1K36Me2/H4K16Ac marks. Through differential gene expression analysis upon silencing this chromatin reader, we identified a subset of genes involved in cell proliferation and invasion/migration regulated by ZMYND8...
April 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28431404/upregulation-of-microrna-125b-by-g-csf-promotes-metastasis-in-colorectal-cancer
#6
Xinghua Zhang, Xiao Ma, Huaying An, Changqing Xu, Wenjo Cao, Wei Yuan, Jie Ma
Although there are reports of miR-125b being dysregulated in colorectal cancer (CRC) and associated with CRC progression, little is known about its intrinsic regulatory mechanisms. Here we detected the expression of miR-125b in CRC tissues, subsequently investigated the effect of miR-125b on the proliferation, apoptosis, cell cycle and metastasis on CRC cells. Our results showed that the expression of miR-125b was significantly decreased in CRC tissues comparing to adjacent tissues. However, with the stimulation of Granulocyte colony-stimulating factor (G-CSF), which was highly expressed in CRC tissues, the expression of miR-125b could be improved...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431272/specific-microrna-mrna-regulatory-network-of-colon-cancer-invasion-mediated-by-tissue-kallikrein-related-peptidase-6
#7
Earlphia Sells, Ritu Pandey, Hwudaurw Chen, Bethany A Skovan, Haiyan Cui, Natalia A Ignatenko
Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC) patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein subfamily of peptidase S1 family serine proteases, has been reported in CRC and is associated with low patient survival rates and poor disease prognosis. We knocked down KLK6 expression in HCT116 colon cancer cells to determine the significance of KLK6 expression for metastatic dissemination and to identify the KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer...
April 18, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28431241/akt-pkb-signaling-navigating-the-network
#8
REVIEW
Brendan D Manning, Alex Toker
The Ser and Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of AKT, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28430655/a-study-on-the-anti-tumor-mechanism-of-total-flavonoids-from-radix-tetrastigmae-against-additional-cell-line-based-on-cox-2-mediated-wnt-%C3%AE-catenin-signaling-pathway
#9
Li Qinglin, Xin Wenxiu, Zhong Like, Fangluo, Cao Gang, Huang Ping
This study is to explore the effect of total flavonoids from Radix Tetrastigmae (TF) against hepatic cancer and discuss the acting mechanism. Proliferation of HepG2 cells was promoted by PGE2 and Butaprost. Using AH6809 as the positive control, the inhibitory effect of TF on additional cell line was detected through a CCK-8 assay, the apoptosis rate was detected by flow cytometry, and the nuclear morphology of cells were observed by Hochest33258 staining. Then PCR was applied to determine the mRNA expression...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430641/the-regulation-of-%C3%AE-catenin-activity-and-function-in-cancer-therapeutic-opportunities
#10
REVIEW
Shuang Shang, Fang Hua, Zhuo-Wei Hu
Wnt/β-catenin signaling is an evolutionarily conserved and versatile pathway that is known to be involved in embryonic development, tissue homeostasis and a wide variety of human diseases. Aberrant activation of this pathway gives rise to the accumulation of β-catenin in the nucleus and promotes the transcription of many oncogenes such as c-Myc and CyclinD-1. As a result, it contributes to carcinogenesis and tumor progression of several cancers, including colon cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer and ovarian cancer...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430604/signal-transducing-adaptor-protein-2-promotes-generation-of-functional-long-term-memory-cd8-t-cells-by-preventing-terminal-effector-differentiation
#11
Daisuke Muraoka, Naohiro Seo, Tae Hayashi, Chisaki Hyuga-Amaike, Kana Okamori, Isao Tawara, Naozumi Harada, Hiroshi Shiku
Long-surviving memory CD8+ T cells generated by stimulation with appropriate tumor-associated antigens are the most aggressive and persistent tumoricidal effectors. In this event of memory CD8+ T cell development, the signal transducer and activator of transcription (STAT) proteins function as the crucial intracellular signaling molecules, but the regulatory mechanism of STATs in CD8+ T cells is not fully understood. In this study, we report for the first time, by using murine vaccination models, that signal-transducing adaptor protein-2 (STAP2) maintains the cytotoxicity of long-lived memory CD8+ T cells by controlling a STAT3/suppressor of cytokine signaling 3 (SOCS3) cascade...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430586/epidermal-growth-factor-receptor-egfr-a-rising-star-in-the-era-of-precision-medicine-of-lung-cancer
#12
REVIEW
Xiaomin Liu, Ping Wang, Caiyan Zhang, Zhongliang Ma
Lung cancer is a leading cause of cancer mortality worldwide. In tumors, the important role of noncoding RNA regulatory networks has been more and more reveal. EGFR has been identified as an oncogenic driver of NSCLC, especially activating mutations EGFR and its inhibition with specific TKIs can generate dramatic tumor responses. Studies have shown that EGFR plays significant roles in the progression of NSCLC. Subset analysis of the small proportion of patients with EGFR-mutant lung cancer showed a disease-free survival benefit, but was underpowered to detect a survival advantage...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#13
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28429652/atypical-regulators-of-wnt-%C3%AE-catenin-signaling-as-potential-therapeutic-targets-in-hepatocellular-carcinoma
#14
Jianxiang Chen, Muthukumar Rajasekaran, Kam M Hui
Hepatocellular carcinoma is one of the most common causes of cancer-related death worldwide. Hepatocellular carcinoma development depends on the inhibition and activation of multiple vital pathways, including the Wnt signaling pathway. The Wnt/β-catenin pathway lies at the center of various signaling pathways that regulate embryonic development, tissue homeostasis and cancers. Activation of the Wnt/β-catenin pathway has been observed frequently in hepatocellular carcinoma. However, activating mutations in β-catenin, Axin and Adenomatous Polyposis Coli only contribute to a portion of the Wnt signaling hyper-activation observed in hepatocellular carcinoma...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28429331/the-correlation-of-cd19%C3%A2-%C3%A2-cd24%C3%A2-%C3%A2-cd38%C3%A2-%C3%A2-b-cells-and-other-clinicopathological-variables-with-the-proportion-of-circulating-tregs-in-breast-cancer-patients
#15
Mohammad Kazzem Gheybi, Shokrollah Farrokhi, Mohammad Reza Ravanbod, Afshin Ostovar, Valiollah Mehrzad, Pardis Nematollahi
BACKGROUND: T regulatory cells (Tregs) are known to negatively control immune response. The frequency of these cells was inversely correlated with clinical outcomes of breast cancer. CD19(+)CD24(hi)CD38(hi) cells also play a critical role in inflammation and autoimmune disease. However, their function in tumor immune response is less studied. In this study we aimed to determine the role of CD19(+)CD24(hi)CD38(hi) cells and some other clinicopathological variables in increasing the proportion of Tregs in breast cancer patients...
April 20, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28429073/urinary-extracellular-vesicles-a-promising-shortcut-to-novel-biomarker-discoveries
#16
REVIEW
Karina Barreiro, Harry Holthofer
Proteomic and genomic techniques have reached full maturity and are providing unforeseen details for the comprehensive understanding of disease pathologies at a fraction of previous costs. However, for kidney diseases, many gaps in such information remain to inhibit major advances in the prevention, treatment and diagnostics of these devastating diseases, which have enormous global impact. The discovery of ubiquitous extracellular vesicles (EV) in all bodily fluids is rapidly increasing the fundamental knowledge of disease mechanisms and the ways in which cells communicate with distant locations in processes of cancer spread, immunological regulation, barrier functions and general modulation of cellular activity...
April 20, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28429008/anticancer-effects-of-novel-resveratrol-analogues-on-human-ovarian-cancer-cells
#17
Daniele Vergara, Stefania De Domenico, Andrea Tinelli, Eleonora Stanca, Loretta L Del Mercato, Anna M Giudetti, Pasquale Simeone, Nicola Guazzelli, Marco Lessi, Chiara Manzini, Angelo Santino, Fabio Bellina, Michele Maffia
Resveratrol, a naturally occurring phytoalexin, has long been known to play an important regulatory role in key functions in cell physiology. This multifunctional role of resveratrol is explained by its ability to interact with several targets of various cell pathways. In the recent past, synthetic chemical modifications have been made in an attempt to enhance the biological effects of resveratrol, including its anti-cancer properties. In this study, we investigated the molecular mechanisms of action of novel trans-restricted analogues of resveratrol in which the C-C double bond of the natural derivative has been replaced by diaryl-substituted imidazole analogues...
April 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28428790/nanoparticle-interactions-with-the-immune-system-clinical-implications-for-liposome-based-cancer-chemotherapy
#18
Ninh M La-Beck, Alberto A Gabizon
The development of stable and long-circulating liposomes provides protection of the drug cargo from degradation and increases tumor drug delivery, leading to the design of liposome formulations with great potential in cancer therapy. However, despite the sound pharmacologic basis, many liposomal as well as other nanoparticle-based drug formulations have failed to meet regulatory criteria for approval. The question that arises is whether we have missed key liposome-host interactions that can account for the gap between the major pharmacologic advantages in preclinical studies and the modest impact of the clinical effects in humans...
2017: Frontiers in Immunology
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/28428286/a-genetic-analysis-of-the-caenorhabditis-elegans-detoxification-response
#20
Tetsunari Fukushige, Harold E Smith, Johji Miwa, Michael W Krause, John A Hanover
Oxidative damage contributes to human diseases of aging including diabetes, cancer, and cardiovascular disorders. Reactive oxygen species resulting from xenobiotic and endogenous metabolites are sensed by a poorly understood process, triggering a cascade of regulatory factors and leading to the activation of the transcription factor Nrf2 (SKN-1 in Caenorhabditis elegans). Nrf2/SKN-1 activation promotes the induction of the Phase II detoxification system that serves to limit oxidative stress. We have extended a previous C...
April 19, 2017: Genetics
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