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Kinase targeting and clear cell carcinoma

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https://www.readbyqxmd.com/read/29911113/survival-outcomes-for-advanced-kidney-cancer-patients-in-the-era-of-targeted-therapies
#1
Arpit Rao, Charles Wiggins, Richard C Lauer
Background: Advanced renal cell carcinoma (RCC) results in over 14,000 deaths each year in the United States alone. The therapeutic landscape for advanced RCC changed dramatically with the approval of tyrosine kinase inhibitors (TKI) between 2006 and 2012. A large-scale analysis of survival trends has not been performed in the TKI era to determine their impact on outcomes for advanced RCC patients. Methods: The Surveillance, Epidemiology and End-Results (SEER) database was queried for adult patients with advanced RCC diagnosed between 2000 and 2013...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29902078/leukemia-inhibitory-factor-receptor-suppresses-the-metastasis-of-clear-cell-renal-cell-carcinoma-through-negative-regulation-of-the-yes-associated-protein
#2
Chengyong Lei, Shidong Lv, Hongyi Wang, Chuan Liu, Qiliang Zhai, Shanci Wang, Guixing Cai, Dingheng Lu, Zhen Sun, Qiang Wei
The role of leukemia inhibitory factor receptor (LIFR), which is important in the signal transduction of the interleukin-6 cytokine family, is still undefined in clear cell renal cell carcinoma (ccRCC). Thus, we examined the function and mechanism of LIFR in ccRCC. Low LIFR expression correlated with a poor prognosis and an aggressive tumor phenotype. Moreover, integrated LIFR DNA and mRNA analysis revealed that promoter methylation and copy number variation contributed to the reduced LIFR expression. LIFR knockdown increased 786-O and Caki-2 cell invasion and migration...
June 14, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29901626/curcumin-induces-endoplasmic-reticulum-stress-associated-apoptosis-in-human-papillary-thyroid-carcinoma-bcpap-cells-via-disruption-of-intracellular-calcium-homeostasis
#3
Li Zhang, Xian Cheng, Shichen Xu, Jiandong Bao, Huixin Yu
BACKGROUND: Thyroid cancer is the most common endocrine tumor. Our previous studies have demonstrated that curcumin can induce apoptosis in human papillary thyroid carcinoma BCPAP cells. However, the underlined mechanism has not been clearly elucidated. Endoplasmic reticulum (ER) is a major organelle for synthesis, maturation, and folding proteins as well as a large store for Ca. Overcoming chronically activated ER stress by triggering pro-apoptotic pathways of the unfolded protein response (UPR) is a novel strategy for cancer therapeutics...
June 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29900041/neurotensin-il-8-pathway-orchestrates-local-inflammatory-response-and-tumor-invasion-by-inducing-m2-polarization-of-tumor-associated-macrophages-and-epithelial-mesenchymal-transition-of-hepatocellular-carcinoma-cells
#4
Pei Xiao, Xinxin Long, Lijie Zhang, Yingnan Ye, Jincheng Guo, Pengpeng Liu, Rui Zhang, Junya Ning, Wenwen Yu, Feng Wei, Jinpu Yu
We previously demonstrated that neurotensin (NTS) induces local inflammation and promotes tumor invasion in hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms are not clear. In this study, positive correlations between NTS and interleukin (IL)-8 were identified at both the mRNA and protein levels in 71 fresh HCC tissues and 100 paraffin-embedded HCC tissues. Furthermore, significant correlations were determined among the co-expression of NTS and IL-8, infiltration of inflammatory cells and enhanced epithelial-mesenchymal transition (EMT) of HCC cells...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29894497/imaging-c-met-expression-using-18f-labeled-binding-peptide-in-human-cancer-xenografts
#5
Weihua Li, Hongqun Zheng, Jiankai Xu, Shaodong Cao, Xiuan Xu, Peng Xiao
OBJECTIVES: c-Met is a receptor tyrosine kinase shown inappropriate expression and actively involved in progression and metastasis in most types of human cancer. Development of c-Met-targeted imaging and therapeutic agents would be extremely useful. Previous studies reported that c-Met-binding peptide (Met-pep1, YLFSVHWPPLKA) specifically targets c-Met receptor. Here, we evaluated 18F-labeled Met-pep1 for PET imaging of c-Met positive tumor in human head and neck squamous cell carcinoma (HNSCC) xenografted mice...
2018: PloS One
https://www.readbyqxmd.com/read/29805677/tudor-staphylococcal-nuclease-regulates-the-expression-and-biological-function-of-alkylglycerone-phosphate-synthase-via-nuclear-factor-%C3%AE%C2%BAb-and-microrna-127-in-human-glioma-u87mg-cells
#6
Yongqiang Zhang, Jun Jia, Ying Li, Yan-Ge Chen, Huan Huang, Yang Qiao, Yu Zhu
Glioma is one of the malignant tumor types detrimental to human health; therefore, it is important to find novel targets and therapeutics for this tumor. The downregulated expression of Tudor-staphylococcal nuclease (SN) and alkylglycerone phosphate synthase (AGPS) can decrease cancer malignancy, and the overexpression of them can the increase viability and migration potential of various tumor cell types; however, the role of AGPS in the proliferation and migration of glioma, and the association of Tudor-SN and AGPS in human glioma is not clear...
June 2018: Oncology Letters
https://www.readbyqxmd.com/read/29765173/hemodiafiltration-and-plasma-levels-of-axitinib-in-a-patient-with-metastatic-renal-clear-cell-carcinoma
#7
Jindrich Kopecky, Alena Ticha, Hana Janeckova, Melichar Bohuslav
BACKGROUND: The standard treatment for metastatic renal cancer is based on vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTor) inhibitors. Compared to other advanced tumors, the treatment of renal cancer is highly affected by impaired renal function; therefore, patients with severe renal insufficiency, including patients on hemodialysis, are generally excluded from clinical trials. CASE REPORT: In the present manuscript we present the case of a renal cancer patient who underwent bilateral nephrectomy and received two lines of treatment...
May 15, 2018: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/29728723/pushing-the-limits-of-immune-related-response-a-case-of-extreme-pseudoprogression
#8
Alvin S Wong, Yee-Liang Thian, Jeevesh Kapur, Cheng-Nang Leong, Patrick Kee, Chun-Tsu Lee, Martin B Lee
The advent of immune checkpoint targeted immunotherapy has seen a spectrum of immune-related phenomena in both tumor responses and toxicities. We describe a case of pseudoprogression that pushes the limits of immune-related response criteria and challenges the boundaries and definitions set by trial protocols. A middle-aged man with conventional clear cell renal cell carcinoma (RCC) had received multiple prior systemic treatments including vascular endothelial growth factor receptor tyrosine kinase inhibitors, as well as multiple surgeries and radiotherapy treatments...
May 4, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29721182/crosstalk-between-akt-signaling-and-cold-shock-proteins-in-mediating-invasive-cell-phenotypes
#9
Raphael Hohlfeld, Sabine Brandt, Anja Bernhardt, Xenia Gorny, Daniel Schindele, Burkhard Jandrig, Martin Schostak, Berend Isermann, Jonathan A Lindquist, Peter R Mertens
Cold shock proteins are up-regulated by cellular stress and orchestrate inflammatory responses, cell proliferation, and differentiation. Enhanced cold shock protein expression promotes malignant cell transformation; up-regulation is detected in most cancers and associated with poor prognosis. Akt1, a serine/threonine kinase, is a potent oncogene, which activates pro-proliferative and anti-apoptotic signaling pathways, and phosphorylates the cold shock domain. Unexpectedly, chicken-YB-1 abrogates PI3K-Akt-dependent oncogenic cell transformation in embryonic fibroblasts...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720560/targeting-the-mevalonate-pathway-suppresses-vhl-deficient-cc-rcc-through-a-hif-dependent-mechanism
#10
Jordan M Thompson, Alejandro Alvarez, Monika K Singha, Matthew W Pavesic, Quy H Nguyen, Luke J Nelson, David A Fruman, Olga V Razorenova
Clear Cell Renal Cell Carcinoma (CC-RCC) is a devastating disease with limited therapeutic options available for advance stages. The objective of this study was to investigate HMG-CoA Reductase inhibitors, also known as statins, as potential therapeutics for CC-RCC. Importantly, treatment with statins was found to be synthetically lethal with the loss of the von Hippel-Lindau (VHL) tumor suppressor gene, which occurs in 90% of CC-RCC driving the disease. This effect has been confirmed in three different CC-RCC cell lines with three different lipophilic statins...
May 2, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29707125/the-hnf-1%C3%AE-usp28-claspin-pathway-upregulates-dna-damage-induced-chk1-activation-in-ovarian-clear-cell-carcinoma
#11
Fuminori Ito, Chiharu Yoshimoto, Yuki Yamada, Tamotsu Sudo, Hiroshi Kobayashi
Transcription factor hepatocyte nuclear factor 1-beta (HNF-1β) enhances checkpoint kinase 1 (Chk1) activation and promotes G2/M cell cycle progression in ovarian clear cell carcinoma (CCC) following exposure to diverse genotoxic agents including bleomycin. However, the underlying mechanism leading to checkpoint activation of HNF-1β still remains largely unknown. To clarify the effects of HNF-1β on cell cycle checkpoints, human CCC cell lines were transfected with siRNAs targeting HNF-1β, Claspin , USP28, or a control vector...
April 3, 2018: Oncotarget
https://www.readbyqxmd.com/read/29685880/integrative-kinome-profiling-identifies-mtorc1-2-inhibition-as-treatment-strategy-in-ovarian-clear-cell-carcinoma
#12
Joseph J Caumanns, Katrien Berns, G Bea A Wisman, Rudolf S N Fehrmann, Tushar Tomar, Harry Klip, Gert Jan Meersma, E Marielle Hijmans, Annemiek Gennissen, Evelien W Duiker, Desiree Weening, Hiroaki Itamochi, Roelof Jc Kluin, An K L Reyners, Michael J Birrer, Helga B Salvesen, Ignace Vergote, Els Van Nieuwenhuysen, James D Brenton, Elena I Braicu, Jolanta Kupryjanczyk, Beata Spiewankiewicz, Lorenza Mittempergher, Rene Bernards, Ate G J van der Zee, Steven de Jong
PURPOSE: Advanced stage ovarian clear cell carcinoma (OCCC) is unresponsive to conventional platinum-based chemotherapy. Frequent alterations in OCCC include deleterious mutations in the tumor suppressor ARID1A and activating mutations in the PI3K subunit PIK3CA. In this study, we aimed to identify currently unknown mutated kinases in OCCC patients and test druggability of downstream affected pathways in OCCC models. EXPERIMENTAL DESIGN: In a large set of OCCC patients (n=124), the human kinome (518 kinases) and additional cancer related genes were sequenced and copy number alterations were determined...
April 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29663364/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#13
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29645088/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#14
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 12, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29554941/when-tyrosine-kinase-inhibitor-sunitinib-can-be-discontinued-in-metastatic-renal-cell-carcinoma-to-pancreas-a-case-report
#15
Yassir Sbitti, Adil Debbagh, Khaoula Slimani, Mohamed Mahi, Hassan Errihani, Mohamed Ichou
BACKGROUND: Long-term survival with durable response remains possible in the area of targeted therapies. Discontinuation of sunitinib could improve quality of life and reduce treatment costs in metastatic renal cell carcinoma with long-term disease stabilization. We discuss a case of successful interruption of antiangiogenic therapy in a patient with persisting evidence of metastases. The discontinuation of antiangiogenic therapy seems to be an option, even in indolent oligo-metastatic renal cell carcinoma with long disease stabilization before sunitinib...
March 20, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29549930/pyrvinium-sensitizes-clear-cell-renal-cell-carcinoma-response-to-chemotherapy-via-casein-kinase-1%C3%AE-dependent-inhibition-of-wnt-%C3%AE-catenin
#16
Long Cui, Juan Zhao, Jingjing Liu
BACKGROUND: Aberrant Wnt/β-catenin activation has been shown to play essential roles in cancer, including renal cell carcinoma (RCC). In this work, we demonstrate that Wnt/β-catenin inhibition by a Food and Drug Administration-approved drug, pyrvinium, effectively targets clear cell RCC and enhances chemotherapy agent's efficacy. MATERIALS AND METHODS: We performed in vitro cell culture assays and in vivo xenograft tumor model to evaluate the effects of pyrvinium alone and its combination with paclitaxel, and analyzed the underlying mechanism(s) of pyrvinium's action in RCC...
March 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29531214/lasp1-promotes-nasopharyngeal-carcinoma-progression-through-negatively-regulation-of-the-tumor-suppressor-pten
#17
Qingzu Gao, Lihua Tang, Ling Wu, Kaitao Li, Hui Wang, Weidong Li, Juan Wu, Mingyi Li, Shuang Wang, Liang Zhao
LIM and SH3 protein 1 (LASP1) enhances tumor growth and metastasis in various cancers, but its role in nasopharyngeal carcinoma (NPC) remains unclear. Herein, we investigated the role of LASP1 in NPC and explored the underlying mechanisms in NPC. Clinically, overexpression of LASP1 is associated with tumor metastasis and poor prognosis of NPC patients. Gain-of-function and loss-of-function assays showed that LASP1 promoted NPC cell proliferation, metastasis, and invasion in vitro and in vivo. Mechanistically, we observed clear co-localization between LASP1 and PTEN in NPC cells...
March 12, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29527128/crosstalk-between-vegfr-and-other-receptor-tyrosine-kinases-for-tki-therapy-of-metastatic-renal-cell-carcinoma
#18
REVIEW
Yongchang Lai, Zhijian Zhao, Tao Zeng, Xiongfa Liang, Dong Chen, Xiaolu Duan, Guohua Zeng, Wenqi Wu
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and is frequently accompanied by the genetic features of von Hippel-Lindau (VHL) loss. VHL loss increases the expression of hypoxia-inducible factors (HIFs) and their targets, including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF). The primary treatment for metastatic RCC (mRCC) is molecular-targeted therapy, especially anti-angiogenic therapy...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29502423/systemic-administration-of-sirna-with-anti-hb-egf-antibody-modified-lipid-nanoparticles-for-the-treatment-of-triple-negative-breast-cancer
#19
Ayaka Okamoto, Tomohiro Asai, Yusuke Hirai, Kosuke Shimizu, Hiroyuki Koide, Tetsuo Minamino, Naoto Oku
Triple-negative breast cancer is one of the intractable cancers that are not sensitive to treatment with existing molecular-targeted drugs. Recently, there has been much interest in RNA interference-mediated treatment of triple-negative breast cancer. In the present study, we have developed lipid nanoparticles encapsulating siRNA (LNP-siRNA) decorated with an Fab' antibody against heparin-binding EGF-like growth factor (αHB-EGF LNP-siRNA). αHB-EGF LNP-siRNA targeting polo-like kinase 1 (PLK1) was prepared and evaluated for its anticancer effect using MDA-MB-231 human triple-negative breast cancer cells overexpressing HB-EGF on their cell surface...
April 2, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29487224/second-line-treatment-landscape-for-renal-cell-carcinoma-a-comprehensive-review
#20
REVIEW
Nizar M Tannir, Sumanta K Pal, Michael B Atkins
The management of advanced clear-cell renal cell carcinoma has steadily improved over the past decade with the introduction of antiangiogenic and targeted therapies. Recently, three new therapies have been approved for use as second-line options that further advance the treatment armamentarium: nivolumab, a monoclonal antibody targeting the programmed cell death receptor; cabozantinib, a small-molecule tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR), MET, and AXL; and lenvatinib, a small-molecule TKI of VEGF and fibroblast growth factor receptors that is used in combination with everolimus, an inhibitor of the mechanistic target of rapamycin...
May 2018: Oncologist
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