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https://www.readbyqxmd.com/read/28107584/targeting-of-tumor-growth-and-angiogenesis-underlies-the-enhanced-antitumor-activity-of-lenvatinib-in-combination-with-everolimus
#1
Masahiro Matsuki, Yusuke Adachi, Yoichi Ozawa, Takayuki Kimura, Taisuke Hoshi, Kiyoshi Okamoto, Osamu Tohyama, Kaoru Mitsuhashi, Atsumi Yamaguchi, Junji Matsui, Yasuhiro Funahashi
The combination of lenvatinib-a multiple receptor tyrosine kinase (RTK) inhibitor-plus everolimus-a mammalian target of rapamycin (mTOR) inhibitor-significantly improved clinical outcomes versus everolimus monotherapy in a phase 2 clinical study of metastatic renal cell carcinoma (RCC). Here, we investigated potential mechanisms underlying the antitumor activity of the combination treatment in preclinical RCC models. Lenvatinib plus everolimus showed greater antitumor activity than either monotherapy in 3 human RCC xenograft mouse models (A-498, Caki-1, and Caki-2)...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28106614/study-of-intrapatient-variability-and-reproducibility-of-quantitative-tumor-perfusion-parameters-evaluated-with-dynamic-contrast-enhanced-ultrasonography
#2
Nathalie Lassau, Bénédicte Coiffier, Laura Faivre, Baya Benatsou, Sophie Bidault, Elizabeth Girard, Bernard Asselain, Stéphanie Pitre-Champagnat, Serge Koscielny
OBJECTIVES: Dynamic contrast-enhanced (DCE) ultrasonography (US) is a functional imaging technique enabling quantitative assessment of solid tumor perfusion in metastatic patients treated with antiangiogenic therapies.The objective of this prospective single-center study was to evaluate in real-life conditions (in routine clinical practice) the intrapatient variability and reproducibility of DCE-US parameters. MATERIALS AND METHODS: Each patient provided written informed consent and had 2 DCE-US examinations (preprandial and postprandial) at baseline, day 15, and 1 month after treatment initiation...
January 18, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28106169/inhibition-of-nucks-facilitates-corneal-recovery-following-alkali-burn
#3
Ming-Wai Poon, Dan Jiang, Peng Qin, Yuelin Zhang, Beiying Qiu, Sumit Chanda, Vinay Tergaonkar, Qing Li, Ian Y Wong, Zhendong Yu, Hung-Fat Tse, David S H Wong, Qizhou Lian
Corneal wound healing involves a complex cascade of cytokine-controlled cellular events, including inflammatory and angiogenesis responses that are regulated by transcriptional chromatin remodeling. Nuclear Ubiquitous Casein and cyclin-dependent Kinase Substrate (NUCKS) is a key chromatin modifier and transcriptional regulator of metabolic signaling. In this study, we investigated the role of NUCKS in corneal wound healing by comparing its effects on corneal alkali burn in NUCKS knockout (NKO) and NUCKS wild-type (NWT) mice...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105204/combining-fisetin-and-ionizing-radiation-suppresses-the-growth-of-mammalian-colorectal-cancers-in-xenograft-tumor-models
#4
Jyh-Der Leu, Bo-Shen Wang, Shu-Jun Chiu, Chun-Yuan Chang, Chien-Chih Chen, Fu-Du Chen, Shiirevnyamba Avirmed, Yi-Jang Lee
Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vivo effects of fisetin on tumor growth remain unclear...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28103739/newer-medical-therapies-for-metastatic-soft-tissue-sarcoma
#5
Akash Tiwari, Vineet Govinda Gupta, Sameer Bakhshi
Metastatic/advanced soft tissue sarcoma has a poor prognosis and conventionally, treatment options have been limited. In recent years, this area has been a rich ground for research with many new drugs being approved and several more in the pipeline. With multiple new treatment options available, it is vital to keep up pace with this rapidly changing field. Areas covered: Recent data regarding use of novel agents in advanced soft tissue sarcoma is reviewed with a focus on clinical applicability. The goal is to guide the clinician into choosing appropriate lines of therapy for the individual patient in light of recent availability of multiple new treatment options...
January 20, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28103683/simultaneous-targeting-of-npc1-and-vdac1-by-itraconazole-leads-to-synergistic-inhibition-of-mtor-signaling-and-angiogenesis
#6
Sarah A Head, Wei Q Shi, Eun Ju Yang, Benjamin A Nacev, Sam Y Hong, Kalyan K Pasunooti, Ruo-Jing Li, Joong Sup Shim, Jun O Liu
The antifungal drug itraconazole was recently found to exhibit potent antiangiogenic activity and has since been repurposed as an investigational anticancer agent. Itraconazole has been shown to exert its antiangiogenic activity through inhibition of the mTOR signaling pathway, but the molecular mechanism of action was unknown. We recently identified the mitochondrial protein VDAC1 as a target of itraconazole and a mediator of its activation of AMPK, an upstream regulator of mTOR. However, VDAC1 could not account for the previously reported inhibition of cholesterol trafficking by itraconazole, which was also demonstrated to lead to mTOR inhibition...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28101838/renal-consequences-of-preterm-birth
#7
REVIEW
Amelie Stritzke, Sumesh Thomas, Harish Amin, Christoph Fusch, Abhay Lodha
BACKGROUND: The developmental origin of health and disease concept identifies the brain, cardiovascular, liver, and kidney systems as targets of fetal adverse programming with adult consequences. As the limits of viability in premature infants have been pushed to lower gestational ages, the long-term impact of prematurity on kidneys still remains a significant burden during hospital stay and beyond. OBJECTIVES: The purpose of this study is to summarize available evidence, mechanisms, and short- and long-term renal consequences of prematurity and identify nephroprotective strategies and areas of uncertainty...
December 2017: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/28100829/a-mathematical-model-of-tumour-angiogenesis-growth-regression-and-regrowth
#8
Guillermo Vilanova, Ignasi Colominas, Hector Gomez
Cancerous tumours have the ability to recruit new blood vessels through a process called angiogenesis. By stimulating vascular growth, tumours get connected to the circulatory system, receive nutrients and open a way to colonize distant organs. Tumour-induced vascular networks become unstable in the absence of tumour angiogenic factors (TAFs). They may undergo alternating stages of growth, regression and regrowth. Following a phase-field methodology, we propose a model of tumour angiogenesis that reproduces the aforementioned features and highlights the importance of vascular regression and regrowth...
January 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28099112/science-to-practice-multiparametric-molecular-and-functional-us-imaging-goes-three-dimensional
#9
Fabian Kiessling
Although microbubbles can boost the diagnostic value of ultrasonography (US), they are not routinely applied in clinical tumor diagnosis. This can be explained by the limited reproducibility of US examinations and the fact that single or few recorded image sections may not be representative of the entire tumor. Three-dimensional (3D) US may help to overcome these limitations. Therefore, Wang and coworkers applied a 3D matrix transducer to monitor response of colon cancer xenografts to antiangiogenic therapy with functional and molecular US imaging...
February 2017: Radiology
https://www.readbyqxmd.com/read/28098886/novel-zinc-phthalocyanine-as-a-promising-photosensitizer-for-photodynamic-treatment-of-esophageal-cancer
#10
Weronika Kuzyniak, Jacob Schmidt, Wojciech Glac, Janine Berkholz, Gustav Steinemann, Björn Hoffmann, Eugeny A Ermilov, Ayşe Gül Gürek, Vefa Ahsen, Bianca Nitzsche, Michael Höpfner
Photodynamic therapy (PDT) has gathered much attention in the field of cancer treatment and is increasingly used as an alternative solution for esophageal cancer therapy. However, there is a constant need for improving the effectiveness and tolerability of the applied photosensitizers (PS). Here, we propose tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) as a promising PS for photodynamic treatment of esophageal cancer. ZnPc-induced phototoxicity was studied in two human esophageal cancer cell lines: OE-33 (adenocarcinoma) and Kyse-140 (squamous cell carcinoma)...
January 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28095300/knockdown-of-cxcl14-disrupts-neurovascular-patterning-during-ocular-development
#11
Ana F Ojeda, Ravi P Munjaal, Peter Y Lwigale
The C-X-C motif ligand 14 (CXCL14) is a recently discovered chemokine that is highly conserved in vertebrates and expressed in various embryonic and adult tissues. CXCL14 signaling has been implicated to function as an antiangiogenic and anticancer agent in adults. However, its function during development is unknown. We previously identified novel expression of CXCL14 mRNA in various ocular tissues during development. Here, we show that CXCL14 protein is expressed in the anterior eye at a critical time during neurovascular development and in the retina during neurogenesis...
January 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28093334/in-vitro-antitumor-and-antiangiogenic-effects-of-bothropoidin-a-metalloproteinase-from-bothrops-pauloensis-snake-venom
#12
Denise de Oliveira Guimarães, Daiana Silva Lopes, Fernanda Van Petten Vasconcelos Azevedo, Sarah Natalie Gimenes, Makswell Almeida Silva, David Collares Achê, Mário Sérgio Rocha Gomes, Lara Vecchi, Luiz Ricardo Goulart, Kelly Aparecida Geraldo Yoneyama, Renata Santos Rodrigues, Veridiana de Melo Rodrigues
Breast cancer is a highly malignant carcinoma and remains the second leading cause of mortality among women. The antitumor effects of metalloproteinases and disintegrins from snake venom on various types of cancer cells have been investigated. In this study, we evaluated the antitumor and antiangiogenic effects on MDA-MB-231 human breast cancer cells and endothelial cells induced by Bothropoidin, a disintegrin-like metalloproteinase isolated from Bothrops pauloensis snake venom. At 24h after treatment at 100μg/mL, Bothropoidin exerted a moderate cytotoxic effect of 30% on MDA-MB-231 versus 10% cytotoxicity against MCF10A (a non-tumorigenic breast cell line), a significant difference that suggests a possible preference by this protein for targets in cancer cells...
January 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28093298/metronomic-chemotherapy-using-orally-active-carboplatin-deoxycholate-complex-to-maintain-drug-concentration-within-a-tolerable-range-for-effective-cancer-management
#13
Foyez Mahmud, Seung Woo Chung, Farzana Alam, Jeong Uk Choi, Seong Who Kim, In-San Kim, Sang Yoon Kim, Dong Soo Lee, Youngro Byun
Metronomic chemotherapy has translated into favorable toxicity profile and capable of delaying tumor progression. Despite its promise, conventional injectable chemotherapeutics are not meaningful to use as metronomic for personalized therapy in long-term cancer treatments due to its frequent administration. This study aims to exploit the benefits of the oral application of carboplatin as metronomic therapy for non-small cell lung cancer (NSCLC). We developed an orally active carboplatin by physical complexation with a deoxycholic acid (DOCA)...
January 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28093280/metronomics-in-the-neoadjuvant-and-adjuvant-treatment-of-breast-cancer
#14
Elisabetta Munzone, Marco Colleoni
The concept of metronomic chemotherapy (MC) has evolved from a descriptive preclinical phenomenon encompassing inhibition of angiogenesis to a clinically validated treatment concept involving multiple potential mechanisms of action. Clinicians are progressively more incline to consider MC as a component of mainstream medical oncology practice in advanced breast cancer. However, more recently MC has been tested even in the adjuvant/neoadjuvant setting, taking the opportunity to obtain tumor specimens and blood samples, in order to identify tumor-specific or patient-specific biomarkers for personalizing treatments...
January 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28088233/successful-recovery-from-a-subclavicular-ulcer-caused-by-lenvatinib-for-thyroid-cancer-a-case-report
#15
Morimasa Kitamura, Tomomasa Hayashi, Chiaki Suzuki, Shigeru Hirano, Ichiro Tateya, Yo Kishimoto, Koichi Omori
BACKGROUND: There are currently no effective therapeutic methods for locally recurrent, metastatic, or progressive radioactive iodine (RAI)-refractory differentiated thyroid cancer. However, multitargeted tyrosine kinase inhibitors (TKIs) such as lenvatinib or sorafenib have been approved for patients with RAI-refractory differentiated thyroid cancer as a second targeted therapy, and these agents can prolong patient survival. However, several cases have been reported that TKIs have caused fatal complications such as fistula formation or bleeding...
January 14, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28087600/sunitinib-stimulates-expression-of-vegfc-by-tumor-cells-and-promotes-lymphangiogenesis-in-clear-cell-renal-cell-carcinomas
#16
Maeva Dufies, Sandy Giuliano, Damien Ambrosetti, Audrey Claren, Papa Diogop Ndiaye, Michalis Mastri, Walid Moghrabi, Lindsay S Cooley, Marc Ettaiche, Emmanuel Chamorey, Julien Parola, Valerie Vial, Marilena Lupu-Plesu, Jean-Christophe Bernhard, Alain Ravaud, Delphine Borchiellini, Jean Marc Ferrero, Andreas Bikfalvi, John M L Ebos, Khalid S A Khabar, Renaud Grepin, Gilles Pagès
Sunitinib is an antiangiogenic therapy given as a first-line treatment for renal cell carcinoma (RCC). While treatment improves progression-free survival, most patients relapse. We hypothesized that patient relapse can stem from the development of a lymphatic network driven by the production of the main growth factor for lymphatic endothelial cells, vascular endothelial growth factor C (VEGFC). In this study, we found that sunitinib can stimulate VEGFC gene transcription and increase VEGFC mRNA half-life. Additionally, sunitinib activated p38 MAP kinase, which resulted in the upregulation/activity of HuR and inactivation of tristetraprolin, two AU-rich-element binding proteins...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28081548/serum-ldh-predicts-benefit-from-bevacizumab-beyond-progression-in-metastatic-colorectal-cancer
#17
Federica Marmorino, Lisa Salvatore, Cecilia Barbara, Giacomo Allegrini, Lorenzo Antonuzzo, Gianluca Masi, Fotios Loupakis, Beatrice Borelli, Silvana Chiara, Maria Chiara Banzi, Emanuela Miraglio, Domenico Amoroso, Francesco Dargenio, Andrea Bonetti, Angelo Martignetti, Myriam Paris, Daniela Tomcikova, Luca Boni, Alfredo Falcone, Chiara Cremolini
BACKGROUND: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. METHODS: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28078994/modulation-of-tumour-related-signaling-pathways-by-natural-pentacyclic-triterpenoids-and-their-semisynthetic-derivatives
#18
Andrey V Markov, Evgeniya B Logashenko, Marina A Zenkova
Pentacyclic triterpenoids are a large class of natural isoprenoids that are widely biosynthesized in higher plants. These compounds are potent anticancer agents that exhibit antiproliferative, antiangiogenic, antiinflammatory and proapoptotic activities. Although their effects on multiple pathways have been reported, unifying mechanisms of action have not yet been established. To date, a huge number of semisynthetic derivatives have been synthesized in different laboratories on the basis of triterpenoid scaffolds, and many have been assayed for their biological activities...
January 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28059847/angiogenic-and-antiangiogenic-markers-for-prediction-and-risk-classification-of-preeclampsia
#19
Amol K Malshe, Baha M Sibai
Preeclampsia is a pregnancy-specific hypertensive disorder with multisystem involvement and is a significant cause of obstetric morbidity and mortality worldwide. A major issue in the treatment of preeclampsia stems from its still significant rates of misclassification and misdiagnosis. Angiogenic factors have been speculated as a possible diagnostic modality due to a perceived imbalance in angiogenesis in preeclampsia. Factors currently studied include soluble fms-like protein kinase 1 and placental growth factor...
January 4, 2017: Clinical Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28056463/soluble-ve-cadherin-in-metastatic-breast-cancer-an-independent-prognostic-factor-for-both-progression-free-survival-and-overall-survival
#20
Pauline Rochefort, Sylvie Chabaud, Jean-Yves Pierga, Olivier Tredan, Etienne Brain, François-Clément Bidard, Camille Schiffler, Helena Polena, Abir Khalil-Mgharbel, Isabelle Vilgrain, Thomas Bachelot
BACKGROUND: Patients with metastatic breast cancer (MBC) represent a heterogeneous group, with large differences in outcomes from individual patients. VE-cadherin, an endothelial-specific cadherin, was shown to promote tumour proliferation and angiogenesis. Soluble VE-cadherin has been recently associated to breast cancer progression. This study was designed to investigate the prognosis significance of soluble VE-cadherin in hormone-refractory MBC. METHODS: Between 2004 and 2007, 150 patients with a fully documented history of hormone-refractory MBC were included in the prospective SEMTOF study...
January 5, 2017: British Journal of Cancer
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