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https://www.readbyqxmd.com/read/29454091/anlotinib-inhibits-angiogenesis-via-suppressing-the-activation-of-vegfr2-pdgfr%C3%AE-and-fgfr1
#1
Binyan Lin, Xiuming Song, Dawei Yang, Dongsheng Bai, Yuyuan Yao, Na Lu
Tumor cells recruit vascular endothelial cells and circulating endothelial progenitor cells to form new vessels to support their own growth and metastasis. VEGF, PDGF-BB and FGF-2 are three major pro-angiogenic factors and applied to promote angiogenesis. In this research, we demonstrated that anlotinib, a potent multi-tyrosine kinases inhibitor (TKI), showed a significant inhibitory effect on VEGF/PDGF-BB/FGF-2-induced angiogenesis in vitro and in vivo. Wound healing assay, chamber directional migration assay and tube formation assay indicated that anlotinib inhibited VEGF/PDGF-BB/FGF-2-induced cell migration and formation of capillary-like tubes in endothelial cells...
February 14, 2018: Gene
https://www.readbyqxmd.com/read/29453759/systemic-treatment-of-patients-with-advanced-unresectable-hepatocellular-carcinoma-emergence-of-therapies
#2
REVIEW
Weijing Sun, Roniel Cabrera
To date, sorafenib, a multiple tyrosine kinase inhibitor, is the only systemic agent approved by the FDA in the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Several other tyrosine kinase-inhibiting agents have been investigated in the first-line setting, either alone (sunitinib, brivanib, linifanib, and lenvatinib) or in combination with sorafenib (erlotinib and doxorubicin) in phase 3 trials. However, none of these studies demonstrated an improvement in survival over sorafenib...
February 17, 2018: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/29453608/chemopreventive-action-of-imatinib-a-tyrosine-kinase-inhibitor-in-the-regulation-of-angiogenesis-and-apoptosis-in-rat-model-of-lung-cancer
#3
Kulvinder Kumar, Preety Ghanghas, S N Sanyal
The present study explored the events of angiogenesis and apoptosis in 7,12-dimethyl benz(a)anthracene (DMBA)-induced lung cancer in rat and its chemoprevention with Imatinib, a receptor tyrosine kinase inhibitor. Further, it includes lipopolysaccharide (LPS) mediating inflammation along with DMBA for the promotion of lung carcinogenesis. The animals received a single intratracheal instillation of DMBA (20 mg/kg body weight) in olive oil and LPS (0.6 mg/kg body weight) to induce tumors in 16 weeks. Besides morphology and histology of the lung tissues, RT-PCR, western blots, and immunofluorescence were performed for the expression of apoptotic and angiogenic proteins...
February 16, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29453318/integration-of-distinct-shca-signaling-complexes-promotes-breast-tumor-growth-and-tyrosine-kinase-inhibitor-resistance
#4
Jacqueline R Ha, Ryuhjin Ahn, Harvey W Smith, Valerie Sabourin, Steven Hėbert, Eduardo Cepeda Cañedo, Young Kyuen Im, Claudia Kleinman, William J Muller, Josie Ursini-Siegel
The commonality between most phospho-tyrosine signaling networks is their shared use of adaptor proteins to transduce mitogenic signals. ShcA (SHC1) is one such adaptor protein that employs two phospho-tyrosine binding domains (PTB and SH2) and key phospho-tyrosine residues to promote mammary tumorigenesis. Receptor tyrosine kinases (RTKs), such as ErbB2, engage the ShcA PTB domain to promote breast tumorigenesis by engaging Grb2 downstream of the ShcA tyrosine phosphorylation sites to activate AKT/mTOR signaling...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452665/novel-agents-for-relapsed-and-refractory-follicular-lymphoma
#5
REVIEW
Chan Yoon Cheah, Nathan H Fowler
Follicular lymphoma is one of the most common non-Hodgkin's lymphomas. Although current frontline regimens are associated with high response rates, most patients still relapse. When progression is discovered, re-establishing the diagnosis and ruling out transformation in paramount. The outcomes following relapse have been improving due to the activity and increasing availability of novel agents with various mechanisms of action. Despite these advances, single agent activity is limited and the disease remains incurable in the majority of cases...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29451857/micrornas-as-predictive-biomarkers-of-response-to-tyrosine-kinase-inhibitor-therapy-in-metastatic-renal-cell-carcinoma
#6
Julia Kovacova, Alexandr Poprach, Tomas Buchler, William C Cho, Ondrej Slaby
Renal cell carcinoma (RCC) accounts for 2%-3% of all malignant tumours. The first-choice treatment in metastatic RCC (mRCC) patients is tyrosine kinase inhibitors (TKIs). Although TKIs may prolong survival of the treated patients who are not primary resistant, almost all of them will eventually develop secondary resistance to the treatment after a progression-free period. To predict treatment response, thus, we need efficient biomarkers for rational indication of TKIs in mRCC. MicroRNAs (miRNAs) not only play important roles in the pathogenesis of many cancers, including RCC but also have been shown to serve as promising diagnostic, prognostic and predictive biomarkers in various cancers...
February 16, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29451485/-the-roles-of-mast-cells-in-radiation-induced-damage-are-still-an-enigma
#7
Fabien Milliat, Agnès François
Mast cells are immune cells that mature within the host tissue. The acquired phenotype is dictated by the tissue microenvironment, giving rise to diverse tissue-dependent phenotypes and functions. The lack of cellular models reflecting phenotypes found in vivo and important differences between human and rodent mast cells are obstacles to the understanding of their exact role in several pathophysiological processes. Studies published over the past few years showed that mast cells' role lies far beyond their involvement in allergy and anaphylaxis...
February 2018: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/29451277/tivozanib-a-new-treatment-option-for-renal-cell-carcinoma
#8
L Saes, F A L M Eskens
Tivozanib is a tyrosine kinase inhibitor that targets all vascular endothelial growth factor receptors (VEGFRs), causing inhibition of angiogenesis. It has recently been approved by the European Medicines Agency (EMA) for first-line treatment of adult patients with advanced renal cell carcinoma (RCC) and for adult patients who are VEGFR and mammalian target of rapamycin (mTOR) pathway inhibitor-naive, following disease progression after one prior treatment with cytokine therapy for advanced RCC. This review will focus on mechanisms of action, early drug development and results of published and ongoing clinical trials of tivozanib...
November 2017: Drugs of Today
https://www.readbyqxmd.com/read/29450702/establishment-and-characterization-of-the-ncc-ss1-c1-synovial-sarcoma-cell-line
#9
Fusako Kito, Rieko Oyama, Yoko Takai, Marimu Sakumoto, Kumiko Shiozawa, Zhiwei Qiao, Takenori Uehara, Akihiko Yoshida, Akira Kawai, Tadashi Kondo
Synovial sarcoma is an aggressive mesenchymal malignancy characterized by unique gene fusions. Tissue culture cells are essential tools for further understanding tumorigenesis and anti-cancer drug development; however, only a limited number of well-characterized synovial sarcoma cell lines exist. Thus, the objective of this study was to establish a patient-derived synovial sarcoma cell line. We established a synovial sarcoma cell line from tumor tissue isolated from a 72-year-old female patient. Prepared cells were analyzed for the presence of gene fusions by fluorescence in situ hybridization, RT-PCR, and karyotyping...
February 15, 2018: Human Cell
https://www.readbyqxmd.com/read/29449840/c-abl-twist1-epigenetically-dysregulate-inflammatory-responses-during-mycobacterial-infection-by-co-regulating-bone-morphogenesis-protein-and-mir27a
#10
Kasturi Mahadik, Praveen Prakhar, R S Rajmani, Amit Singh, Kithiganahalli Narayanaswamy Balaji
Mycobacteria propelled modulation of host responses is of considerable interest in the face of emerging drug resistance. Although it is known that Abl tyrosine kinases affect entry and persistence of mycobacteria, mechanisms that couple c-Abl to proximal signaling pathways during immunity are poorly understood. Loss-of-function of c-Abl through Imatinib, in a mouse model of tuberculosis or RNA interference, identified bone morphogenesis protein (BMP) signaling as its cellular target. We demonstrate that c-Abl promotes mycobacterial survival through epigenetic modification brought about by KAT5-TWIST1 at Bmp loci...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29449681/secondary-philadelphia-chromosome-acquired-during-therapy-of-acute-leukemia-and-myelodysplastic-syndrome
#11
Habibe Kurt, Lan Zheng, Hagop M Kantarjian, Guilin Tang, Farhad Ravandi-Kashani, Guillermo Garcia-Manero, Zimu Gong, Hesham M Amin, Sergej N Konoplev, Mark J Routbort, Xin Han, Wei Wang, L Jeffery Medeiros, Shimin Hu
The Philadelphia chromosome resulting from t(9;22)(q34;q11.2) or its variants is a defining event in chronic myeloid leukemia. It is also observed in several types of de novo acute leukemia, commonly in B lymphoblastic leukemia, and rarely in acute myeloid leukemia, acute leukemia of ambiguous lineage, and T lymphoblastic leukemia. Acquisition of the Philadelphia chromosome during therapy of acute leukemia and myelodysplastic syndrome is rare. We reported 19 patients, including 11 men and 8 women with a median age of 53 years at initial diagnosis...
February 14, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29449680/pd-l1-expression-in-inflammatory-myofibroblastic-tumors
#12
Tricia R Cottrell, Anh T Duong, Christopher D Gocke, Haiying Xu, Aleksandra Ogurtsova, Janis M Taube, Deborah A Belchis
Inflammatory myofibroblastic tumor is a rare mesenchymal tumor occurring at many anatomic sites, with a predilection for children and young adults. Often indolent, they can be locally aggressive and can metastasize, resulting in significant morbidity and mortality. Therapeutic options are often limited. The identification of underlying kinase mutations has allowed the use of targeted therapy in a subset of patients. Unfortunately, not all tumors harbor mutations and resistance to tyrosine kinase inhibitor therapy is a potential problem...
February 15, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29449645/egfr-pi3k-pdk1-pathway-regulates-yap-signaling-in-hepatocellular-carcinoma-the-mechanism-and-its-implications-in-targeted-therapy
#13
Hongwei Xia, Xinyu Dai, Huangfei Yu, Sheng Zhou, Zhenghai Fan, Guoqing Wei, Qiulin Tang, Qiyong Gong, Feng Bi
The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449529/gambogenic-acid-inhibits-fibroblast-growth-factor-receptor-signaling-pathway-in-erlotinib-resistant-non-small-cell-lung-cancer-and-suppresses-patient-derived-xenograft-growth
#14
Linfeng Xu, Xiaoxiao Meng, Naihan Xu, Wenwei Fu, Hongsheng Tan, Li Zhang, Qianjun Zhou, Jianan Qian, Shiwei Tu, Xueting Li, Yuanzhi Lao, Hongxi Xu
Erlotinib resistance causes a high degree of lethality in non-small-cell lung cancer (NSCLC) patients. The high expression and activation of several receptor tyrosine kinases, such as JAK/STAT3, c-Met, and EGFR, play important roles in drug resistance. The development of tyrosine kinase inhibitors is urgently required in the clinic. Our previous study found that Gambogenic acid (GNA), a small molecule derived from the traditional Chinese medicine herb gamboge, induced cell death in several NSCLC cell lines through JAK/STAT3 inhibition...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449326/fatty-acid-synthase-mediates-egfr-palmitoylation-in-egfr-mutated-non-small-cell-lung-cancer
#15
Azhar Ali, Elena Levantini, Jun Ting Teo, Julian Goggi, John G Clohessy, Chan Shuo Wu, Leilei Chen, Henry Yang, Indira Krishnan, Olivier Kocher, Junyan Zhang, Ross A Soo, Kishore Bhakoo, Tan Min Chin, Daniel G Tenen
Metabolic reprogramming is widely known as a hallmark of cancer cells to allow adaptation of cells to sustain survival signals. In this report, we describe a novel oncogenic signaling pathway exclusively acting in mutated epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) with acquired tyrosine kinase inhibitor (TKI) resistance. Mutated EGFR mediates TKI resistance through regulation of the fatty acid synthase (FASN), which produces 16-C saturated fatty acid palmitate. Our work shows that the persistent signaling by mutated EGFR in TKI-resistant tumor cells relies on EGFR palmitoylation and can be targeted by Orlistat, an FDA-approved anti-obesity drug...
February 15, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29449091/adjuvant-therapies-in-nonmetastatic-renal-cell-carcinoma-a-review-of-the-literature
#16
REVIEW
Marco Bandini, Ariane Smith, Michele Marchioni, Raisa S Pompe, Tristan F Martel, Luca Cindolo, Francesco Montorsi, Shahrokh F Shariat, Alberto Briganti, Anil Kapoor, Umberto Capitanio, Pierre I Karakiewicz
To conduct a review of literature on adjuvant therapy in nonmetastatic renal-cell carcinoma (nmRCC) treated with nephrectomy and to describe the efficacy of adjuvant agents on cancer control outcomes. A review of the literature was performed in January 2018 to identify all studies evaluating adjuvant therapy in patients with nmRCC treated with nephrectomy using PubMed, Embase, Medline, and Cochrane Library databases. The following keywords were used: adjuvant therapy, renal-cell carcinoma, nonmetastatic, targeted molecular therapy, kidney cancer...
February 2, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29448857/therapy-free-remission-in-chronic-myeloid-leukemia-possible-mechanism
#17
Robert Peter Gale, Andreas Hochhaus
Chronic myeloid leukemia (CML) can be cured using tyrosine kinase-inhibitors (TKIs) when cure is defined as achieving a life-expectancy similar or even better than sex- and age-matched persons without CML. Most deaths in persons with CML are now from non-leukemia-related causes including heart disease, diabetes other cancers and stroke. Contrary to expectation, 40-50 percent of persons with CML treated for a few years with TKIs and who achieve a deep molecular response can stop TKI-therapy without leukemia recurrence for several years, some possibly indefinitely...
February 15, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29448845/a-systematic-review-of-economic-evaluations-of-tyrosine-kinase-inhibitors-of-vascular-endothelial-growth-factor-receptors-mammalian-target-of-rapamycin-inhibitors-and-programmed-death-1-inhibitors-in-metastatic-renal-cell-cancer
#18
Panagiotis Petrou
The therapeutic categories of Tyrosine Kinase Inhibitors of Vascular Endothelial Growth Factor Receptors, mammalian target of rapamycin inhibitors and Programmed Death-1 inhibitors have transformed the treatment of metastatic renal cell cancer. Nevertheless, this comes at an increased cost, in tandem with similar fiscal pressures in the broader oncology sector, which may jeopardize the sustainability of health systems. Areas covered To this direction, the economic evaluation of these agents is essential for rational and efficient resource allocation...
February 16, 2018: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/29448300/identification-of-preoperative-factors-associated-with-outcomes-following-surgical-management-of-intra-abdominal-recurrent-or-metastatic-gist-following-neoadjuvant-tyrosine-kinase-inhibitor-therapy
#19
Christina L Roland, Brian K Bednarski, Kelsey Watson, Keila E Torres, Janice N Cormier, Wei-Lien Wang, Alexander J Lazar, Neeta Somaiah, Kelly K Hunt, Barry W Feig
BACKGROUND: The role of surgical resection in the treatment of patients with metastatic/recurrent gastrointestinal stromal tumors (GIST) is unclear. The aim of this study was to identify preoperative factors associated with oncologic outcomes for recurrent/metastatic GIST after tyrosine kinase inhibitor (TKI) therapy. METHODS: We identified 107 patients with metastatic or recurrent GIST treated with TKIs and surgical resection (2002-2012). Patients that underwent palliative or incomplete resection were excluded...
February 15, 2018: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/29447132/role-of-gpcr-mu-opioid-receptor-tyrosine-kinase-epidermal-growth-factor-crosstalk-in-opioid-induced-hyperalgesic-priming-type-ii
#20
Dionéia Araldi, Luiz F Ferrari, Jon D Levine
Repeated stimulation of mu-opioid receptors (MORs), by an MOR-selective agonist DAMGO induces type II priming, a form of nociceptor neuroplasticity, which has 2 components: opioid-induced hyperalgesia (OIH) and prolongation of prostaglandin-E2 (PGE2)-induced hyperalgesia. We report that intrathecal antisense knockdown of the MOR in nociceptors, prevented the induction of both components of type II priming. Type II priming was also eliminated by SSP-saporin, which destroys the peptidergic class of nociceptors...
January 11, 2018: Pain
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