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1
Asbagh, Layka Abbasi Doymaz Fuat. "Investigating the role of zoledronic acid on interleukin-6 cytokine expression in prostate cancer cell lines/." [s.l.]: [s.n.], 2006. http://library.iyte.edu.tr/tezlerengelli/master/biyoteknoloji/T000552.pdf.
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Palmer, Jodie. "The IL-6 type cytokine family in prostate cancer." Monash University, Centre for Functional Genomics and Human Disease, 2003. http://arrow.monash.edu.au/hdl/1959.1/9441.
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Sanford, Daniel C. "C/EBP delta expression and function in prostate cancer biology." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1141421403.
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MacManus, Christopher Francis. "Characterisation of Interleukin-8 signalling in prostate cancer cells : implications for disease progression." Thesis, Queen's University Belfast, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426688.
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Kroon, Paula. "Importance of the IL-6/STAT3 signalling pathway in prostate cancer stem cells." Thesis, University of York, 2012. http://etheses.whiterose.ac.uk/3714/.
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Prostate cancer is the most diagnosed cancer in men in the Western world. Currently, most treatments are directed towards an androgen receptor-expressing cell, which encompasses the majority of prostate tumours. Unfortunately, the tumour recurs in the majority of patients. This recurrence is thought to arise due to the presence of a rare population of prostate cancer stem cells. These cells are also hypothesized to be responsible for tumour initiation, maintenance, recurrence and metastasis. It is therefore important to develop novel therapies to target these tumour-initiating cells. Interleukin-6 (IL-6) is a pro-inflammatory cytokine, which is involved in the regulation of a multitude of cellular functions, including proliferation, apoptosis, and differentiation. IL-6 and the associated JAK-STAT signalling pathway have been implicated in the development and progression of a variety of tumours, including prostate cancer. In this study we have demonstrated that these stem-like cells, selected from primary prostate cancer cultures have elevated IL-6 levels and express the IL-6 receptor, suggesting that these cells are constitutively active. Targeting IL-6, and downstream activation of STAT3, resulted in a significant decrease in colony forming ability of these stem-like cells. Moreover, treatment with a small molecule inhibitor of STAT3 resulted in a modest inhibition of tumour growth, with a significant increase in the proportion of CD24+ luminal cells. Whilst the impact on established tumours was modest, LLL12 abolished tumour initiation, suggesting that activation of STAT3, through IL-6, is important for the maintenance of the undifferentiated stem-like cells within prostate tumours. Targeting the JAK-STAT signalling pathway in this cell population might result in a more durable response to current standard of care therapies.
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Soori, Mehrnoosh. "Neuroendocrine differentiation of prostate cancer cells a survival mechanism during early stages of metastatic colonization of bone /." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 105 p, 2009. http://proquest.umi.com/pqdweb?did=1654490661&sid=6&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Basel, Dennis [Verfasser]. "Antagonizing autocrine Interleukin-6 receptor signaling inhibits prostate cancer growth in bone / Dennis Basel." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2018. http://d-nb.info/1170876900/34.
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O'Brien, John D. "The Effect of Small Organic Compounds on Triple Negative Breast Cancer Cells." Ohio University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1344436677.
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Dang, David. "LYSOPHOSPHATIDIC ACID IS A MEDIATOR OF INTERLEUKIN-6 PRODUCTION IN OVARIAN CANCER CELLS." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1907.
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Lysophosphatidic acid (LPA) is a naturally occurring bioactive lysophospholipid that mediates a broad range of cellular processes such as cell proliferation, survival, migration and invasion. LPA also plays a potential role in human oncogenesis as suggested by elevated expression of its receptors and its producing enzymes in malignant tissues. In the current study, we demonstrated that LPA is a potent mediator of interleukin-6 (IL-6) production in ovarian cancer. IL-6 is a pleiotropic cytokine which is thought to be an important mediator of ovarian cancer development and progression. Here, we demonstrated that IL-6 levels are indeed increased in the plasma of ovarian cancer patients as compared to normal women. The IL-6 concentrations in ascites of ovarian cancer patients are even higher than those present in the plasma samples. These results suggest that increased IL-6 are expressed and secreted by ovarian cancer cells, forming a gradient from the ascites to the blood. Ovarian cancer cells indeed produce IL-6 in culture. However, when these cells are starved in serum-free medium, they cease producing IL-6, suggesting that IL-6 is not constitutively expressed, but rather in response to exogenous factors present in serum. We showed that IL-6 expression is not driven by peptide growth factors such as insulin-like growth factor I or epidermal growth factor. Instead, IL-6 expression is most potently induced by the lysophospholipid growth factor LPA. Treatment of ovarian cancer cells with LPA leads to transcriptional activation of the IL-6 gene promoter through activation of the NF-kB and C/EBP transcription factors. LPA also induces tyrosine phosphorylation and activation of Stat-3, a well known intracellular effector of IL-6. However, blockade of IL-6 with a neutralizing antibody only slightly reduced Stat-3 phosphorylation in response to LPA, suggesting that LPA may induce Stat-3 directly or through secondary mediators other than IL-6. Together, these studies demonstrate the role of LPA in regulation of IL-6 production and the underlying mechanism in ovarian cancer.
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Champa, Zachary J. "Modulation of IL-6 and IL-8 Expression in Ovarian Cancer Cells by a Small OrganicCompound." Ohio University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1460987166.
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D’Anello, Laura <1980>. "Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2011. http://amsdottorato.unibo.it/3368/.
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Fletcher, Elise Virginia May. "Epidermal growth factor receptor inhibitor induces Interleukin-6 via NADPH oxidase enzymes in head and neck cancer cells." Thesis, University of Iowa, 2012. https://ir.uiowa.edu/etd/3454.
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The epidermal growth factor receptor (EGFR) is a tyrosine kinase cell surface receptor, belonging to the ErbB family of receptors, which functions to initiate downstream signaling pathways resulting in cellular proliferation, differentiation, migration, adhesion, and metastasis. EGFR is over expressed in numerous types of cancers including head and neck, breast, colon, lung, renal, and ovarian, and this overexpression of EGFR has been correlated with poor prognosis and survival rates specifically in head and neck squamous cell carcinoma (HNSCC). Due to the pro-oncogenic activity of EGFR (e.g. cell growth, angiogenesis, and metastasis), ameliorating the function of EGFR makes it an attractive target for chemotherapy. While clinical therapy with Erlotinib is quite successful, resistance to the chemotherapy agent is highly prevalent. To date, the molecular mechanism by which cancers become resistant to Erlotinib remains unclear. Here we show a novel pathway in head and neck carcinoma cell lines involving the up-regulation of NADPH oxidase enzymes (NOX) after Erlotinib treatment, which leads to an increased production of hydrogen peroxide and finally increased IL-6 production. The IL-6 axis has been proposed to play a definitive role in the long-term proliferation and survival of various cancers, and perturbation of this axis by Erlotinib may initiate pro-survival signals which render the cancers resistant to Erlotinib. Therefore, we put forth a model of multidrug therapy targeting NOX enzymes and/or IL-6 in combination with Erlotinib to counteract the potential drug-resistance mechanisms often observed in malignancy.
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Li, Wenzhao. "A homeobox protein, NKX6.1, up-regulates interleukin-6 expression for cell growth in basal-like breast cancer cells." Kyoto University, 2016. http://hdl.handle.net/2433/216184.
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Sullivan, Nicholas James. "Interleukin-6 as a Potential Mediator of Breast Cancer Progression and Non-Melanoma Skin Carcinogenesis." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1249493495.
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Zhang, Guitao, and 张贵焘. "Epstein-barr virus (EBV) infection and STAT3 activation in nasopharyngeal epithelial cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hdl.handle.net/10722/209213.
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The etiology of nasopharyngeal carcinoma (NPC) is based on intricate interactions among environmental factors, genetic susceptibility and Epstein-Barr virus (EBV) infection. Information concerning the role of EBV infection, particularly during the early stage of NPC development is poorly understood. Our laboratory has shown that stable infection of EBV could be achieved in immortalized epithelial cell lines which harbor genetic alterations and altered cell signaling pathway. In this study, these cell models were used to elucidate early events involved in EBV infection in premalignant nasopharyngeal epithelial cell models and their implications on development and progression of nasopharyngeal carcinoma.
The response of EBV-infected cells to a stromal inflammatory cytokine, interleukin-6 (IL-6), was examined. EBV infection and long-term propagation of EBV-infected nasopharyngeal epithelial cells confer enhanced sensitivity to STAT3 activation induced by IL-6. IL-6-induced STAT3 activation reinforced their malignant properties in nasopharyngeal epithelial cells and may play a role in the development of nasopharyngeal carcinoma. Furthermore, constitutive STAT3 activation was demonstrated to facilitate malignant transformation of EBV-infected premalignant nasopharyngeal epithelial cells to cancer cells, suggesting that EBV infection and STAT3 activation might synergistically promote the development of NPC. This study also provides support for the existence of a positive feedback loop of IL-6/STAT3/LMP in NP460hTert-EBV cells, which enhanced STAT3 activation in EBV-infected cells.
Elevated levels of IL-6Rα expression were observed in EBV-infected NP460hTert cells compared with uninfected cells and were largely responsible for the enhanced sensitivity of IL-6-induced STAT3 activation in these cells. High expression level of IL-6Rα could amplify IL-6 signaling in nasopharyngeal epithelial cells to promote growth proliferation in NP460hTert cells and increase the growth rate of xenografted NPC cells in immune-suppressed animals, suggesting that IL-6Rα overexpression may play a role of contributing to the development of nasopharyngeal carcinoma. The serum concentrations of both IL-6 and sIL-6R were also higher in NPC patients than healthy individuals and may have prognostic values to predict clinical outcome and disease progression in NPC patients.
In conclusion, these data support the hypothesis that EBV infection under inflammatory environment may activate aberrant gene expressions and cell signaling to facilitate malignant transformation. The inflammatory cytokine, IL-6, may mediate the role of EBV infection in the development of NPC.<br>published_or_final_version<br>Anatomy<br>Doctoral<br>Doctor of Philosophy
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Isaac, Jared. "Studies of Protein S-nitrosylation in Prostate Cancer focused on Integrin Alpha 6, Proliferating Cell Nuclear Antigen and Estrogen Receptor Beta." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1342543634.
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Schröder, Anne [Verfasser]. "Inhibition of the IL-6/STAT3 signaling pathway for therapeutic intervention in prostate carcinogenesis and cancer cell differentiation / Anne Schröder." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2013. http://d-nb.info/1037106776/34.
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Chien, Yu-Ju, and 簡玉如. "Interleukin-6 Overexpression Enhances Anti-apoptosis Effects in Human Prostate Cancer LNCaP Cells." Thesis, 1999. http://ndltd.ncl.edu.tw/handle/62086975863489477352.
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碩士<br>國立臺灣大學<br>毒理學研究所<br>87<br>As the dietary habits in Taiwan occidentalizing, the incidence of prostate cancer elevated dramatically. According to the reports about the statistic of cancer in Taiwan from the Department of Health, prostate cancer had been included in the 10 major death causes of cancer disease.
Interleukin-6﹝IL-6﹞is a pleiotropic cytokine, it was initially identified as a regulator of immune and inflammatory response. Recent studies suggested that it played a diversified role in the growth, differentiation, and death of different tumor cells, including prostate carcinoma cells. In current clinical observations, high IL-6 level was recognized to be associated with the progression of prostate cancer, and was thought in relation with the drug resistance of prostate cancer patients in practice.
In the present study, we intend to explore whether IL-6 was involved in drug resistant mechanism of prostate cancer. To address this issue, we choose LNCaP, an androgen-dependent prostate cancer cell line, as the cell model. Then we respectively transfected an empty plasmid pcDNA3 and pCMVFIL-6, which contains full-length IL-6 cDNA, into LNCaP WT cell. After G418 long-term selection, we found that the LNCaP IL-6 transfectants were differentiated along with neuroendocrine-like phenotype. Otherwise, we also found that LNCaP IL-6 transfectants had lower proliferation rate, became insensitive to androgen-stimulated cellular growth, and had better tumorgenicity.
In apoptosis assay, LNCaP IL-6 transfectants are resistant to apoptosis induced by topotecan, doxorubicin, and UV treatment as compared to LNCaP neo control cells. To study the possible mechanism of IL-6-induced anti-apoptosis effect, we pretreat MEK-1 inhibitor PD98059 and PI3 kinase inhibitor LY294002, then we found that the anti-apoptosis effect could be partially removed by LY294002 pretreatment. Forther more, the phosphorylation level of PI3 kinase subunit, p85, increased in LNCaP IL-6 transfectants, and could be down-regulated by LY294002 pretreatment.
Therefore, we thought that PI3 kinase plays an imortant role in the anti-apoptosis signal transduction of IL-6 in prostate cancer cell line LNCaP.
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Li, Pei-Chi, and 李培齊. "Cdk5 involves interleukin-6-induced phosphorylation of serine727 STAT3, serine81 AR, and AR activation in prostate cancer cells." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/09251440627061400234.
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碩士<br>國立中興大學<br>生命科學系所<br>101<br>Prostate cancer is the most common type of cancer in men and ranks the second place in cancer-related deaths. Signal transducers and activators of transcription 3 (STAT3), which is constitutively activated in a wide variety of human cancers, in-cluding prostate cancer. STAT3 contains a DNA binding, a transactivation, and a SH2 domain, and is activated by tyrosine 705 (Y705) phosphorylation which re-sults in homodimerization through SH2-phosphotyrosyl interaction and transloca-tion into the nucleus, where it binds to promoter transactivating downstream genes. In addition to Y705 phosphorylation, phosphorylation of another conserved STAT3 residue, Serine 727 (S727), has also been documented to activate STAT3 signaling. In LNCaP cells, a prostate cancer cell line, which expresses AR and is androgen-dependent, Interleukin-6 (IL-6), a cytokine, can activate the androgen receptor and promotes proliferation. Previous studies have shown the cross talk between STAT3 and AR showing that IL-6 activates the androgen receptor in a STAT3 dependent manner. Here, we find that IL-6 stimulates S727 phosphoryla-tion of STAT3, and further more upregulates AR expression, especially Serine 81 (S81) phosphorylate. On the other hand, our lab previous data shown that Cdk5 enables phosphorylation of AR at S81 site through direct biochemical interaction and, therefore, results in the stabilization of AR proteins. The positive regulations of Cdk5-AR on cell growth are also determined in vitro and in vivo. Cdk5 also can positively regulates S727 phosphorylation and promotes prostate cancer cell pro-liferation. In the present study, we found S727 of STAT3 activation plays a critical role for S81-AR phosphorylation, to promote AR stabilize its protein level, and causes accumulation of AR protein into nuclear localization and subsequent tran-scription activation. We also found that mutant S727-STAT3 (S727A) increased the association of AR and Mdm2, which is turn induced AR degradation through proteasome-mediated pathway, resulting in AR protein expression decrease. Moreover, IL-6 induced Tyrosine 15 (Y15) phosphorylation of Cdk5, and which was inhibited by AG490. We also found that mutant Y15-Cdk5 (Y15F) reduced both of S727-STAT3 and S81-AR phosphorylation, resulting decrease STAT3-AR interaction. These finding demonstrate that IL-6 induces S727-STAT3 and further to activate AR protein through S81 phosphorylation site, as well as, Cdk5 also in-volved in the IL-6 stimulated pathway.
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Liao, Chih-Kang, and 廖致綱. "Chemoresistant Mechanism of Interleukin-8 in Docetaxel-Resistant Prostate Cancer Cells." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/05821397661199501597.
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碩士<br>高雄醫學大學<br>生物化學研究所<br>101<br>Hormone therapy for hormone-sensitive prostate cancer patients slows down the growth of the cancer for few years but it will finally turn into castration-resistant prostate cancer (CRPC). The chemotherapeutic agent docetaxel has been used as a prostate chemotherapy drug for years. Significant outcome has been observed in CRPC patients, but for the most part them will ultimately get docetaxel resistant cancer. Without any widely-used or promoted clinical drug for docetaxel resistant patients, to find the mechanism behind the drug resistance has become imperative and of utmost importance. In our previous studies, we found that the docetaxel resistant cell line PC/DX expresses a higher Interleukin-8 (IL-8) mRNA level than its parental androgen-insensitive prostate cancer cell line (AIPC) PC-3. In order to further this finding, we were hoping to confirm that IL-8 plays a role in docetaxel resistance and to locate the possible mechanism behind it. At the start, we constructed another docetaxel resistant cell lines DU/DX from DU145. This higher IL-8 secretion cell line expressed a 43.3 times stronger docetaxel resistant ability than the DU145. Treating DU145 and PC-3 with docetaxel induced IL-8 cell secretion. We also showed that IL-8 plays a role in drug resistance by treating both DU145 and PC-3 with a recombinant IL-8 and knocking down an innate IL-8. Considerable IL-8 expression DU145 stable clones we constructed in this study also displayed higher docetaxel resistance ability. We also proved that NF-κB and AP-1 are transcription factors of AIPC cell lines by transfecting IL-8 promoter which contains different mutated transcription factors binding sites into AIPC cells, and detecting with Luciferase reporter assay. An over-expressed p-EGFR protein was observed in DU/DX cell lines, corresponding to former research of PC/DX done in our lab. To make sure that EGFR had some relations to IL-8, we treated DU145 and PC-3 with EGF. A more highly secreted IL-8 and stronger IL-8 promoter activity were observed while the EGF was binding to these cells. To simulate the more highly secreted IL-8 appearance in the DU/DX cell line, we treated DU145 and PC-3 with a recombinant IL-8. We found that the recombinant IL-8 stimulating cell expressed higher p-EGFR and p-AKT both in DU145 and PC-3 with a time dependence, which corresponded to circumstances in DU/DX and IL-8 stable clones. In this study, we have proved the role of IL-8 in docetaxel resistance and found the possible pathway activated by IL-8 in AIPC cell lines. These results may modestly provide a new aspect of the role of cytokines in multiple drug resistance and views to aid future research.
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Jiang, Wen-Sheng, and 江■笙. "The Role of Interleukin-6 in the Mechanism of Apopotosis of Prostate Cancer Cell Lines." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/26899298244150509084.
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碩士<br>國立臺灣大學<br>毒理學研究所<br>86<br>As the change of dietary habit in Taiwan , the incidence of prostate cancerin
creases dramatically . According to the reports of the Department of Healthabo
ut cancer statistic in Taiwan that the postate cancer was included in ten mior
causes of death in cancer diseases . IL-6 is one kind of cytokine in relation
to drug resistance in prostate cancer proved in clinical practice currently .
But it is still not clear about the role of IL-6 in prostate cancer cell lines
to regulate drug resistance . In this experiment , we compared the growth ra
te of cell and its ability to secrete IL-6 of PC-3 (one human cell line of pro
state cancer) , incubated in complete medium with in serum free medium , at f
irst . Then having both conditions treated with anti-cancer drugs . We di
sclosed that, the cell line in complete medium had faster growth rate , more s
ecretion of IL-6 , and it had drug resistance . By the previous series of stud
ies , apoptosiscan be induced when prostate cancer cell line was treated with
low dose b-lapachone . We found that treating PC-3 cell line with b-lapachone
had such results as (1) the phenomenon of Go/G1 stoppage . (2) DNA ladder . (3
) sub G1 peak in cell cycle analysis which is thought as apoptotic peak . (4)
DNA condensation showed by flouromicroscopy . We also used trypan blue exclusi
onmethod and flow cytometer to analysis the cells which was treated b-lapachon
e with or without IL-6 . We get the conclusion that when treat PC-3 cells with
b-lapachone , IL-6 can lower the cytotoxicity of b-lapachone . Besides , thea
mount of BCL-xL protein increased when prostate cancer cell line PC-3 was trea
ted with IL-6 and the amounnt of BAD protein was decreased . It will blockthe
process of anti-apoptosis caused by IL-6 if BCL-xL anti-sense was added . We a
lso showed that overexpression STAT3 can express anti-apoptosis against b-lapa
chone . Therefore , the signal transduction of IL-6 in prostate cancercell lin
e PC-3 is through STAT3 and PI 3-k . IL-6 get the ability of anti-apoptosis by
these pathway .
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(9189491), Paula Cooper. "The Impacts of Inflammation on Adult Prostate Stem Cells." Thesis, 2020.
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<p>Adult prostate stem cells (PSC) are a rare epithelial progenitor population in the prostate. While essential for normal homeostasis, they have also been implicated in hyperplasia and cancer initiation. While studies have shown that inflammatory growth factors and cytokines can fuel stem cell expansion, the impact of inflammation on PSC is not well understood. To study the impact of inflammation on the prostate, the Ratliff laboratory developed the Prostate Ovalbumin Expressing Transgenic 3 (POET3), an inducible mouse model of abacterial T cell mediated prostate inflammation, which functions as a model for human autoimmune prostatitis. Previous studies using the POET3 demonstrated that inflammation increased proliferation and differentiation of PSC enrichments. Based on these findings, it was speculated that inflammation impacts prostate stem cells to enhance mechanisms of survival, possibly as a means of tissue protection.</p><p>Since androgen receptor (AR) signaling is the major driver of cellular differentiation and survival in the prostate, it was further hypothesized that inflammation promotes AR signaling in the PSC. To address this hypothesis, PSC and their resulting organoids from inflamed and non-inflamed (naïve) POET3 mice as well as human patient samples were assessed for AR and its signaling components.</p><p>These data were expanded by single cell mRNA sequencing using Fluidigm’s C1 platform, which revealed changes in stem cell populations, differential expression of interleukin 1 alpha (IL-1⍺) and its signaling components, and upregulation of various genes associated with immune regulation. Thus, experiments described herein probed the impacts of inflammation on AR, IL-1⍺, and T cell regulatory abilities in the PSC.</p>The results of these studies indicate that indeed, inflammation increases PSC survival. Inhibition of IL-1⍺ via inflammation-mediated up-regulation of IL-1 receptor antagonist (IL-1RA) promotes AR signaling, resulting in proliferation, differentiation, and AR target gene expression which can be modulated by Enzalutamide (a clinical AR inhibitor). Furthermore, PSC from inflamed mice are able to suppress cytotoxic T cell function in <i>ex vivo</i> assays. These studies set the foundation for new ways to treat proliferative diseases of the prostate by targeting IL-1⍺, AR, and immune regulation in the PSC.
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Chang, Hsi-Wen, and 張喜雯. "Molecular role of EGFR and interleukin-8 related migration in docetaxel-resistant prostate cancer cells." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/41113753848072293683.
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碩士<br>高雄醫學大學<br>醫學研究所碩士班<br>105<br>In clinical, docetaxel is used in the first-line treatment for patients with castration‑resistant prostate cancer （CRPC）, significantly extended overall survival of patients. However, the treatment is usually limited when gradual development of docetaxel-resistance. It has become imperative and important to find the mechanism of the docetaxel-resistance in prostate cancer. In previous studies have suggested that epidermal growth factor receptor （EGFR） and Interleukin-8 （IL-8） are required for prostate cancer progression and drug resistance. The molecular mechanism of how EGFR and IL-8 mediated migration in prostate cancer cells is still elusive. Thus, this study was aimed to investigate the molecular mechanisms of EGFR and IL-8 regulated migration in the docetaxel-resistant prostate cancer cells and to search the possible therapeutic strategies for docetaxel-resistant metastatic CRPC in future. We have established PC3 docetaxel-resistant cell line (PC/DX), PC/DX25 maintain in 25 nM docetaxel. We found that PC/DX25 metastatic developed faster than PC3 cellls, and expressed the higher protein levels of EGFR, IL-8 and CXCR1 than PC3 and Immortalized prostate cells. In this study, the cell migration, protein levels of EGFR, p-EGFR(Y1068), IL-8, NF-κB p65 and Epithelial-Mesenchymal Transition (EMT) were induced by the treatment with EGF and IL-8 recombinant proteins. In contrast, the cell migration, protein levels of EGFR, IL-8, NF-κB p65 and EMT were inhibited by the treatment with EGFR and IL-8 siRNA. And we also found that nuclear p-p38 was inhibited by the treatment with EGFR siRNA. Interestingly, the PC3 cells were induced EGFR and IL-8 protein levels by the treatment with docetaxel. We also found that treated the PC3 cells with docetaxel induced IL-8 promoter activative and IL-8 cytokine secretion. These results suggest that EGFR and IL-8 have key roles in regulation of the migration of docetaxel-resistant prostate cancer cells, and molecular mechanism of cell migration EGFR/p-EGFR（Y1068）/NF-κB p65/IL-8 signaling pathway. Our study revealed EGFR and IL-8 signaling pathway regulated cell migration in docetaxel-resistant prostate cancer cells, and suggested that combined EGFR and IL-8 inhibitor with docetaxel may used to treatment for prevention of potential drug-resistance and metastasis.
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Chuang, Chia-Hua, and 莊家驊. "IL-6 increases VEGF expression through regulating p35 expression and CDK5 activity in prostate cancer cells." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/68283069748947586083.
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Luo, Yun-Li, and 羅勻里. "Identify REST-targeting LincRNAs that are Essential for IL-6 induced Neuroendocrine Differentiation of Prostate Cancer cells." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/jaqwpz.
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碩士<br>國立陽明大學<br>微生物及免疫學研究所<br>105<br>The central dogma of molecular biology is that DNA is transcribed into messenger RNAs, then being the template for protein synthesis. The next-generation sequencing (NGS) technology revealed that there are a lot of long non-coding RNAs (lncRNAs) across the human genome. LncRNAs, is used to be thought as a “transcription noise” are now believed as functional components of transcriptome and play an important role in a variety of biological process. Lots of studies have revealed that lncRNAs were dysregulation in different cancers. As a result, lncRNAs are becoming potential targets for the therapy and biomarkers for diagnosis and prognosis. As a result, researches are contributed to find relation between tumor and lncRNAs.
A major cancer that give rise to death in male population is prostate cancer (PCa). The therapeutic treatment of PCa is hampered by its relapse from the successful androgen-deprivation therapy (ADT) and become the castration-resistant prostate cancer (CRPC). There are many mechanisms related to the development of CRPC. Among them, neuroendocrine differentiation (NED) of PCa cells into neuroendocrine-like (NE-like) cells is considered to be one of the root causes of CRPC. In previous studies, androgen-deprivation, IL-6, and hypoxia have been shown to induce NED of PCa cells. The development of NE-like cell depends on a complicated network of transcriptional reprogramming. Recent studies show that repressor element-1 silencing transcription factor (REST), a transcriptional repressor that is significantly reduced in CRPC tumors, plays a key regulator for inducing NED in PCa cells. In addition, these treatments also contribute to the induction of autophagy during NED of the PCa cell. As a result we try to find out the lncRNAs as the potential biomarkers and the therapeutic target for CRPC.
By using bioinformatics analysis of transcriptome profiles of IL-6 treatment, REST knockdown LNCaP cell, and utilizing the NONCODEv4 database to extract the Fragments Per Kilobase of transcript per Million mapped read (FPKM) of all lncRNAs from our RNA-seq data using the condition of FPKM>1; 1.5-fold up-regulated, 12,330 up-regulated lncRNAs. Here, I focus on identifying the long intergenic non-coding RNAs (lincRNAs), a sub-population of lncRNAs that located at genome loci between coding genes. For this purpose, lincRNAs were selected from the 12,330 lncRNAs and overlapped with the Lincode siRNA Library (GE Dharmacon). 177 lincRNAs were found and used to perform a small scale siRNA knockdown screening. Among them, there are 15 lincRNAs were necessary to IL-6-induced NED of LNCaP cells. Besides, we also use LNCaP-eGFP-LC3 to check whether it reduces the autophagy and then inhibit the NED. Finally, I focus on SEPSECS-AS1 which has the strongest inhibition of IL-6 induced NED in our screening result and it reduces the activation of autophagy during IL-6 induce NED as well.
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Chen, Yu Hsi, and 陳郁羲. "Understanding the function and regulatory mechanism of interleukin-6 in human prostate and bladder cancer." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/09033249802949306649.
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碩士<br>長庚大學<br>生物醫學研究所<br>99<br>IL-6 regulates many physiological and pathological mechanisms, such as inflammation and immune response, bone metabolism, etc., IL-6 is discovered in many cancers, like prostate cancer, breast, bladder, kidney and brain tumors. It is also known that IL-6 plays an important role for androgen-independent prostate cancer which is the most cause of death of prostate cancer. Study also pointed out that compare with localized prostate cancer, advance prostate cancer patients have higher levels of IL-6 secretion into blood, and cachectic patients IL-6 secreted higher than non-cachectic patients is IL-6 regulates prostate cancer development, proliferation, survival and other gene expression. Results from 3H-thymidine incorporation assay and cell invasion assay revealed that IL-6 promotes cell proliferation and ability of invasion of prostate carcinoma cells, but inhibits bladder carcinoma cells. Xenografts animal studies suggested the same results. In our studies, we found IL-6 is related with mAcon, HO-1, GDF15, CD82/KAI, NDrg1 and Maspin gene expression through JAK/STAT3, MAPK and PI3K/Akt pathway. NFB inhibitors, celastrol and curcumin, has been effectively used in the treatment of immune diseases and cancers. It could inhibit IKKphosphorylation which may effect the IL-6 gene expression through NFB signalling pathway and delay prostate cancer progression. And other antioxidant, luteolin, which can delay prostate carcinoma cells growth through inhibits JAK/STAT3 activation. Our results provide the notion of function of IL-6 of prostate and bladder carcinoma cells.
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(9759410), Janelle Weslyn Salameh. "The Development of Targeted Cytokine-based Gene Therapies for Treating Prostate Cancer Bone Metastases." Thesis, 2020.
Find full textAbstract:
Prostate cancer (PCa) bone metastases have been reported in ~90% of patients with advanced disease. Bone metastases disrupt tissue homeostasis and weaken the skeleton, resulting in an increased risk of bone fractures and morbidity. Specifically, PCa cells disrupt the crosstalk between critical cells within the tumor/bone microenvironment (osteoblasts, osteoclasts, and immune cells), and utilize this effector-rich environment for cancer survival and growth. Therefore, a key therapeutic objective in malignant skeletal disease management is to eliminate tumors while restoring bone homeostasis. Current treatments include palliative radiotherapy, chemotherapy, or anti-RANK treatments, all of which have considerable side effects such as osteonecrosis of the jaw or enhanced tumor invasion. There remains a critical gap in therapies than can reduce tumor burden and simultaneously restore bone homeostasis. To address this gap, our work explores emerging gene therapy approaches for treating skeletal malignancies by utilizing multifunctional cytokine-based agents that can simultaneously combat tumor growth and promote bone regeneration.<div><br></div><div>We hypothesize that rationally designed cytokine-based gene therapies that can be secreted from skeletal muscle and targeted to the bone/tumor microenvironment, could effectively reduce tumor growth and restore bone cell homeostasis. To test this hypothesis, we adopted two strategies: 1) a second-generation targeted IL-27 cytokine, and 2) a de novodesign of a cytokine-like therapeutic agent (Propeptide) that includes anti-tumorigenic and pro-osteogenic domains. Both strategies share modules with overlapping therapeutic functions, rendering them complementary in their therapeutic application. In this work, we examined the proof of principle for propeptide gene therapy in muscle cells (in vitro models) and assessed the therapeutic efficacy of our cytokine-based biologics in reducing prostate tumor growth and rebalancing bone cell proliferation and differentiation. Our studies resulted in a propeptide construct representative of a cytokine structure comprised of a bundle of helices that we were able to express in cells. Additionally, our work demonstrated the targeting and anti-tumor efficacy of our therapeutic cytokines in cancer and bone cell models. Ultimately, this will provide the framework for innovative peptide and cytokine-based therapeutics that target and treat both the tumor metastases and bone. This approach will facilitate improvement of morbidity and quality of life of prostate cancer patients with bone metastases and could be applicable to other diseases with bone/tumor pathologies. <br><div><br></div></div>
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Chun-HuaHung and 洪君樺. "The study of glycosylation pattern on secreted interleukin-6 and its biological functions in lung cancer cells." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/e54354.
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Syu, Siang-Ci, and 徐湘琦. "2-phenylnaphthyridin-4-one derivatives repress Interleukin-6 induces an epithelial–mesenchymal transition phenotype in human breast cancer cells." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/06889737543737935494.
Full textAbstract:
碩士<br>中國醫藥大學<br>生物科技學系碩士班<br>99<br>Breast tumor interleukin-6 (IL-6) levels increase with tumor grade, and elevated serum IL-6 correlates with poor breast cancer patient survival. Epithelial–mesenchymal transition (EMT) phenotypes such as impaired E-cadherin expression or aberrant vimentin induction are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Despite this fact, few tumor microenvironment-derived extracellular signaling factors capable of provoking such a phenotypic transition have been identified. In this study, we showed that IL-6 exhibited an EMT phenotype characterized. Moreover, we report that the induction of an EMT by IL-6 results in the acquisition of mesenchymal traits and in the expression of cancer stem cells (CSCs) markers. Many beneficial properties have been attributed to 2-phenylnaphthyridin-4-one derivatives, including inhibition of tubulin polymerization etc. Here, we found that 2-phenylnaphthyridin-4-one derivatives could repress IL-6 induced EMT phenotype and cancer stem cell markers through repressing Jak2/STAT3 signaling pathway. LYF-11 also effectively inhibited IL6-induced decrease of E-cadherin and increase of vimentin via down-regulation of
phosphorylated Jak2 and STAT3. Briefly, our results suggest that a connection between IL-6 receptor activity and phospho-STAT3 protein expression, and suggest that LYF-11 is a potential compound for breast cancer therapy by targeting major components of Jak2/STAT3 signaling pathway.
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Bringman, Lauren R. "Specificity protein 1 induces the expression of angiomotin in response to IL-6/STAT3 activation to mediate YAP-dependent growth of breast cancer cells." Diss., 2016. http://hdl.handle.net/1805/12088.
Full textAbstract:
Indiana University-Purdue University Indianapolis (IUPUI)<br>Chronic inflammation is a major driver of tumor progression in over fifty
percent of breast cancers. Tumors activate inflammatory processes by secreting
factors that recruit and trigger inflammatory cells to release cytokines such as
Interleukin 6 (IL-6). IL-6 stimulates the activity of signal transducers and
activators of transcription 3 (STAT3), a transcription factor that has been
extensively studied for its role in promoting breast cancer. Recently,
downregulated HIPPO signaling was shown to drive the pro-growth effects of IL
6. Reduced HIPPO signaling allows for the nuclear translocation of
transcriptional co-activator yes associated protein (YAP), implicating IL-6 in the
co-activation of several transcription factors such as the TEADs that trigger pro
growth programs. While IL-6/STAT3 stimulation has been shown to increase
YAP activity, the mechanism driving this remains undocumented. The
Angiomotins (Amots) are adapters of the HIPPO pathway that directly bind and
regulate YAP activity. Molecular characterization of Amot transcriptional
regulation unexpectedly revealed a single promoter controlling the expression of
its two major isoforms: Amot 130 and Amot 80. Through immunofluorescent
analysis, this study found that total Amot levels were elevated across multiple
breast tumor subtypes and highest in samples with increased presence of
stromal inflammatory cells. Further, the induction of total Amot expression by IL
6 was found to be essential for YAP dependent growth of breast cancer cells. The activation of Amot transcription by IL-6 was found to be through Specificity
Protein 1 (Sp1), a transcription factor that is activated by STAT3. This work
connects the activation of YAP1 by IL-6/STAT3 through the elevation of Amot
expression by Sp1. Taken together, this explains a new avenue whereby breast
cancer cells acquire enhanced oncogenic properties in response to inflammatory signaling.