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https://www.readbyqxmd.com/read/29623068/nuclear-insulin-like-growth-factor-binding-protein-3-as-a-biomarker-in-triple-negative-breast-cancer-xenograft-tumors-effect-of-targeted-therapy-and-comparison-with-chemotherapy
#1
Sohel M Julovi, Janet L Martin, Robert C Baxter
Triple-negative breast cancer (TNBC) typically has a worse outcome than other breast cancer subtypes, in part owing to a lack of approved therapeutic targets or prognostic markers. We have previously described an oncogenic pathway in basal-like TNBC cells, initiated by insulin-like growth factor binding protein-3 (IGFBP-3), in which the epidermal growth factor receptor (EGFR) is transactivated by sphingosine-1-phosphate (S1P) resulting from sphingosine kinase (SphK)-1 activation. Oncogenic IGFBP-3 signaling can be targeted by combination treatment with the S1P receptor modulator and SphK inhibitor, fingolimod, and the EGFR kinase inhibitor, gefitinib (F + G)...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29608021/curcumin-enhances-the-anti-cancer-effects-of-paris-saponin-ii-in-lung-cancer-cells
#2
Shuli Man, Lili Zhang, Jingxia Cui, Li Yang, Long Ma, Wenyuan Gao
OBJECTIVES: To investigate the synergistic mechanisms of Paris Saponin II (PSII) and Curcumin (CUR) in lung cancer. MATERIALS AND METHODS: The combination changed the cellular uptake of CUR and PSII, apoptosis, cell cycle arrest and cytokine levels were analysed on different lung cancer cells. RESULTS: The combination displayed a synergistic anti-cancer effect through promoting the cellular uptake of CUR on different lung cancer cells. Hoechst H33258 staining and FACS assay indicated that the combination of PSII and CUR induced cell cycle arrest and apoptosis...
April 2, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29603395/peptidyl-prolyl-cis-trans-isomerase-pin1-regulates-withaferin-a-mediated-cell-cycle-arrest-in-human-breast-cancer-cells
#3
Suman K Samanta, Joomin Lee, Eun-Ryeong Hahm, Shivendra V Singh
We have reported previously that withaferin A (WA) prevents breast cancer development in mouse mammary tumor virus-neu (MMTV-neu) transgenic mice, but the mechanism is not fully understood. Unbiased proteomics of the mammary tumors from control- and WA-treated MMTV-neu mice revealed downregulation of peptidyl-prolyl cis/trans isomerase (Pin1) protein by WA administration. The present study extends these findings to elucidate the role of Pin1 in cancer chemopreventive mechanisms of WA. The mammary tumor level of Pin1 protein was lower by about 55% in WA-treated rats exposed to N-methyl-N-nitrosourea, compared to control...
March 30, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29572229/the-mda-9-syntenin-igf-1r-stat3-axis-directs-prostate-cancer-invasion
#4
Swadesh K Das, Anjan K Pradhan, Praveen Bhoopathi, Sarmistha Talukdar, Xue-Ning Shen, Devanand Sarkar, Luni Emdad, Paul B Fisher
Although prostate cancer (PCa) is clinically manageable during several stages of progression, survival is severely compromised once cells invade and metastasize to distant organs. Comprehending the pathobiology of invasion is required for developing efficacious targeted therapies against metastasis. Based on bioinformatics data, we predicted an association of melanoma differentiation associated gene-9 (syntenin, or syndecan binding protein (SDCBP)) in PCa progression. Using tissue samples from various Gleason stage PCa patients with adjacent normal tissue, a series of normal prostate and PCa cell lines (with differing tumorigenic/metastatic properties), mda-9/syntenin manipulated variants (including loss-of-function and gain-of-function cell lines), and CRISPR/Cas9 stable MDA-9/syntenin knockout cells, we now confirm the relevance of and dependence on MDA-9/syntenin in PCa invasion...
March 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29527422/cellular-prion-protein-and-%C3%AE-synuclein-overexpression-in-ls-174t-colorectal-cancer-cell-drives-endothelial-proliferation-to-differentiation-switch
#5
Sing-Hui Ong, Kai-Wey Goh, Cornelius Kwang-Lee Chieng, Yee-How Say
Background: Tumor-induced angiogenesis is an imperative event in pledging new vasculature for tumor metastasis. Since overexpression of neuronal proteins gamma-synuclein (γ-Syn) and cellular prion protein (PrPC ) is always detected in advanced stages of cancer diseases which involve metastasis, this study aimed to investigate whether γ-Syn or PrPC overexpression in colorectal adenocarcinoma, LS 174T cells affects angiogenesis of endothelial cells, EA.hy 926 (EA). Methods: EA cells were treated with conditioned media (CM) of LS 174T-γ-Syn or LS 174T-PrP, and their proliferation, invasion, migration, adhesion and ability to form angiogenic tubes were assessed using a range of biological assays...
2018: PeerJ
https://www.readbyqxmd.com/read/29474865/trajectories-of-plasma-igf-1-igfbp-3-and-their-ratio-in-the-mayo-clinic-study-of-aging
#6
Alexandra M V Wennberg, Clinton E Hagen, Ronald C Petersen, Michelle M Mielke
Insulin-like growth factor 1 (IGF-1) has been associated with osteoporosis, cardiovascular disease, cancer, neurodegenerative diseases, and mortality in middle and older aged adults. Cross-sectionally, IGF-1 decreases with age and levels of IGF-1 are markedly different between individuals. However, little is known about intra-individual trajectories of IGF-1. We examined baseline and serial measures of plasma total IGF-1, IGF binding protein (IGFBP)-3, and their ratio, which is a proxy for bioavailable IGF-1, among 1618 adults, aged 50-95, enrolled in the Mayo Clinic Study of Aging...
February 20, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29473153/serum-insulin-like-growth-factor-i-and-insulin-like-growth-factor-binding-protein-3-in-relation-to-terminal-duct-lobular-unit-involution-of-the-normal-breast-in-caucasian-and-african-american-women-the-susan-g-komen-tissue-bank
#7
Hannah Oh, Ruth M Pfeiffer, Roni T Falk, Hisani N Horne, Jackie Xiang, Michael Pollak, Louise A Brinton, Anna Maria V Storniolo, Mark E Sherman, Gretchen L Gierach, Jonine D Figueroa
Lesser degrees of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini/TDLU, are associated with elevated breast cancer risk. In rodent models, the insulin-like growth factor (IGF) system regulates involution of the mammary gland. We examined associations of circulating IGF measures with TDLU involution in normal breast tissues among women without precancerous lesions. Among 715 Caucasian and 283 African American (AA) women who donated normal breast tissue samples to the Komen Tissue Bank between 2009 to 2012 (75% premenopausal), serum concentrations of IGF-I and binding protein (IGFBP)-3 were quantified using enzyme-linked immunosorbent assay...
February 22, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29456350/recurrent-glioblastomas-exhibit-higher-expression-of-biomarkers-with-stem-like-properties
#8
B N Nandeesh, Sharmistha Naskar, Arun H Shashtri, A Arivazhagan, Vani Santosh
Background: Despite advances in the treatment of glioblastoma (GBM), the prognosis of patients continues to remain dismal. This unfavorable prognosis is mainly attributed to the tumor's propensity for progression and recurrence, which in turn is due to the highly aggressive nature of the persisting GBM cells that actively egress from the main tumor mass into the surrounding normal brain tissue. Such a recurrent tumor described to have a more malignant potential is highly invasive and resistant to current therapies, probably due to increased stemness and preferential selection of therapy-resistant clones of tumor cells...
January 2018: Journal of Neurosciences in Rural Practice
https://www.readbyqxmd.com/read/29439316/correlation-of-igfbp-6-expression-with-apoptosis-and-migration-of-colorectal-carcinoma-cells
#9
Fei Qiu, Wei Gao, Bin Wang
Colorectal cancer (CRC) is one of the most common malignant tumors in digestive tract. Previous study found close correlation between insulin-like growth factor binding proteins (IGFBPs) and occurrence of multiple tumors. This study aims to analyze the effects of IGFBP6 on the apoptosis and migration of tumor cells, and to investigate underlying mechanism. HCT-116 or SW480 cell was cultured with 1.0 mg/l, 10 mg/l and 100 mg/l IGFBP-6. MTT assay was employed to test the proliferation activity of tumor cells after differential treatment...
February 2, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29383334/effects-of-toremifene-a-selective-estrogen-receptor-modulator-on-spontaneous-and-stimulated-gh-secretion-igf-i-and-igf-binding-proteins-in-healthy-elderly-subjects
#10
Ferdinand Roelfsema, Rebecca J Yang, Paul Y Takahashi, Dana Erickson, Cyril Y Bowers, Johannes D Veldhuis
Context: Estrogens amplify spontaneous and stimulated growth hormone (GH) secretion, whereas they diminish GH-dependent insulin-like growth factor (IGF)-I in a dose-dependent manner. Selective estrogen receptor modulators (SERMs), including tamoxifen and toremifene, are widely adjunctively used in breast and prostate cancer. Although some endocrine effects of tamoxifen are known, few data are available for toremifene. Objective: To explore sex-dependent effects of toremifene on spontaneous 10-hour overnight GH secretion, followed by GH-releasing hormone-ghrelin stimulation...
February 1, 2018: Journal of the Endocrine Society
https://www.readbyqxmd.com/read/29344663/adeno-associated-virus-type-2-mediated-gene-transfer-of-a-short-hairpin-rna-targeting-human-igfbp-2-suppresses-the-proliferation-and-invasion-of-mda-mb-468-cells
#11
Chao Gao, Ru-Song Zhang, Nan Zheng, Chen Wang
Adeno-associated virus 2 (AAV2) is prepotent in the biological treatment of breast tumor because of its low pathogenicity and immunogenicity. Our previous study demonstrated that insulin‑like growth factor‑binding protein 2 (IGFBP‑2) was highly expressed in patients with breast metastasis. In the present study, the effects of recombinant AAV2 on the growth and metastasis of breast cancer cells were determined in vitro, and in vivo. rAAV2-ZsGreen-shRNA-scramble and rAAV2‑ZsGreen‑shRNA‑hIGFBP‑2 were used to transfect MDA‑MB‑468, and MCF‑10A cells respectively, and observed that these virus could not penetrate the normal human breast epithelia MCF‑10A cell line...
January 16, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29321953/matrix-metalloproteinase-1-facilitates-msc-migration-via-cleavage-of-igf-2-igfbp2-complex
#12
Shou P Guan, Alan T L Lam, Jennifer P Newman, Kevin L M Chua, Catherine Y L Kok, Siao T Chong, Melvin L K Chua, Paula Y P Lam
The specific mechanism underlying the tumor tropism of human mesenchymal stem cells (MSCs) for cancer is not well defined. We previously showed that the migration potential of MSCs correlated with the expression and protease activity of matrix metalloproteinase (MMP)-1. Furthermore, highly tumor-tropic MSCs expressed higher levels of MMP-1 and insulin-like growth factor (IGF)-2 than poorly migrating MSCs. In this study, we examined the functional roles of IGF-2 and MMP-1 in mediating the tumor tropism of MSCs...
January 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29321818/ews-fli-1-creates-a-cell-surface-microenvironment-conducive-to-igf-signaling-by-inducing-pappalysin-1
#13
Panneerselvam Jayabal, Peter J Houghton, Yuzuru Shiio
Ewing sarcoma is an aggressive cancer of bone and soft tissue in children with poor prognosis. It is characterized by the chromosomal translocation between EWS and an Ets family transcription factor, most commonly FLI-1. EWS-FLI-1 fusion accounts for 85% of Ewing sarcoma cases. EWS-FLI-1 regulates the expression of a number of genes important for sarcomagenesis, can transform NIH3T3 and C3H10T1/2 cells, and is necessary for proliferation and tumorigenicity of Ewing sarcoma cells, suggesting that EWS-FLI-1 is the causative oncoprotein...
November 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29217518/enhancement-of-mammary-tumour-growth-by-igfbp-3-involves-impaired-t-cell-accumulation
#14
Tiffany Scully, Carolyn D Scott, Sue M Firth, Lisa M Sedger, John E Pintar, Stephen M Twigg, Robert C Baxter
Epidemiological studies show an association between obesity and poor breast cancer prognosis. We previously demonstrated that global IGFBP-3 deficiency, in IGFBP-3-null mice, resulted in a 50% reduction in mammary tumour growth over 3 weeks relative to tumours in wild-type (WT) C57BL/6 mice. This growth reduction was ameliorated by high fat feeding-induced obesity. This study aimed to examine how IGFBP-3 promotes tumour growth by influencing the immune tumour microenvironment in healthy and obese mice. Syngeneic EO771 cells, which lack detectable IGFBP-3 expression, were grown as orthotopic tumours in WT and IGFBP-3-null C57BL/6 mice placed on either a control chow or a high-fat diet (HFD), and examined by quantitative PCR and immunohistochemistry...
February 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29208357/differential-expression-of-igfbps-in-laron-syndrome-derived-lymphoblastoid-cell-lines-potential-correlation-with-reduced-cancer-incidence
#15
Lina Somri, Rive Sarfstein, Lena Lapkina-Gendler, Karthik Nagaraj, Zvi Laron, Leon A Bach, Haim Werner
Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is a growth disorder that results from mutation of the GH-receptor (GHR) gene leading to congenital insulin-like growth factor-1 (IGF-1) deficiency. Recent epidemiological studies have shown that LS patients are protected from cancer development. Genome-wide profiling identified genes and signaling pathways that are differentially represented in LS patients, and that may contribute to cancer protection. The present study was aimed at evaluating the hypothesis that IGF binding proteins (IGFBPs) are differentially expressed in LS, most probably as a result of low circulating levels of IGF-1...
April 2018: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/29165552/what-happened-to-the-igf-binding-proteins
#16
Leon A Bach
Insulinlike growth factor (IGF) binding proteins (IGFBPs) 1 to 6 are high-affinity regulators of IGF activity. They generally inhibit IGF actions by preventing binding to the IGF-I receptor but can also enhance their actions under some conditions. Posttranslational modifications such as glycosylation and phosphorylation modulate IGFBP properties, and IGFBP proteolysis results in IGF release. IGFBPs have more recently been shown to have IGF-independent actions. A number of mechanisms are involved, including modulation of other growth factor pathways, nuclear localization and transcriptional regulation, interaction with the sphingolipid pathway, and binding to non-IGF biomolecules in the extracellular space and matrix, on the cell surface and intracellularly...
February 1, 2018: Endocrinology
https://www.readbyqxmd.com/read/29163706/igfbp-4-expression-is-adversely-associated-with-lung-cancer-prognosis
#17
Yang Xiao, Shan Zhu, Wen Yin, Xiaofan Liu, Yi Hu
Insulin-like growth factor binding protein-4 (IGFBP-4) was reported to be associated with prognosis in several types of cancer; however, to the best of our knowledge, whether it is correlated with lung cancer has yet to be reported. In the present study, 102 pairs of lung cancer tissues and surrounding non-cancerous tissues (SNCTs) were collected. The IGFBP-4 levels in tissues were detected with immunohistochemistry. The relevance of IGFBP-4 to the survival of patients was assessed. The IGFBP-4 gene was knocked down, and its function in the proliferation of lung cancer cells was measured...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29163372/hyperglycemia-promotes-tmprss2-erg-gene-fusion-in-prostate-cancer-cells-via-upregulating-insulin-like-growth-factor-binding-protein-2
#18
Jeff M P Holly, Jessica Broadhurst, Rehanna Mansor, Amit Bahl, Claire M Perks
Background: Epidemiologic evidence shows that obesity is associated with a greater risk of aggressive prostate cancer (PCa) and PCa-specific mortality and this is observed mainly in men with the TMPRSS2-ERG gene fusion. Obesity is often associated with comorbid conditions such as type 2 diabetes and hyperglycemia: we investigated whether some of the exposures associated with disturbed metabolism can also affect the frequency of this gene fusion. Methods: Fusion was induced in LNCaP PCa cells in normal or high levels of glucose, with or without insulin-like growth factor binding protein-2 (IGFBP-2) silenced or the presence of insulin-like growth factor-1 (IGF-I), insulin, or epidermal growth factor (EGF)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29157747/multiplex-proximity-ligation-assay-to-identify-potential-prognostic-biomarkers-for-improved-survival-in-locally-advanced-pancreatic-cancer-patients-treated-with-stereotactic-body-radiation-therapy
#19
Avani D Rao, Yufei Liu, Rie von Eyben, Charles C Hsu, Chen Hu, Lauren M Rosati, Arti Parekh, Kendall Ng, Amy Hacker-Prietz, Lei Zheng, Timothy M Pawlik, Daniel A Laheru, Elizabeth M Jaffee, Matthew J Weiss, Dung T Le, Ralph H Hruban, Ana De Jesus-Acosta, Christopher L Wolfgang, Amol K Narang, Daniel T Chang, Albert C Koong, Joseph M Herman
PURPOSE: To explore seromarker levels for associations with outcomes in locally advanced pancreatic cancer (LAPC) patients who received chemotherapy and stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Serum from LAPC patients in 2 prospective trials of hypofractionated SBRT (5-6.6 Gy × 5) was collected before SBRT. Proximity ligation assay quantified the expression levels of 36 pancreatic cancer-specific candidate seromarkers: Axl, BMP2, CA 125, CA 19-9, CEA, CXCL-1/6/9/10, EGFR, Gas6, Her2, IGF-2, IGFBP-2/3/7, IL-6/6Ra/7/8/12, mesothelin, MMP-1/2/3/7, osteopontin, PDGFRa, PDK1, PF4, RegIV, SPARC, TGF-β, VEGF-A/D, and YKL40...
February 1, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29123408/the-matrix-metalloproteinase-and-insulin-like-growth-factor-system-in-oral-cancer-a-prospective-clinical-study
#20
Eik Schiegnitz, Peer W Kämmerer, Holger Schön, Christoph Gülle, Manfred Berres, Keyvan Sagheb, Bilal Al-Nawas
Aim: The absence of reliable single serum biomarkers for oral premalignant lesion (OPL) and oral squamous cell carcinoma (OSCC) limits early diagnosis, monitoring of advanced disease, and prediction of prognosis. Methods: In this prospective study, serum levels of matrix metalloproteinase (MMP)-2, MMP-3, MMP-13, insulin-like growth factor (IGF)-1, and IGF-binding protein (IGFBP)-3 were measured in 81 untreated OSCC patients, 49 healthy subjects, and 75 individuals with OPLs, and correlated with clinicopathological parameters...
2017: OncoTargets and Therapy
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