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Angiogenesis and cancer therapy

Fleur M Ferguson, Nathanael S Gray
Receptor tyrosine kinase signalling pathways have been successfully targeted to inhibit proliferation and angiogenesis for cancer therapy. However, kinase deregulation has been firmly demonstrated to play an essential role in virtually all major disease areas. Kinase inhibitor drug discovery programmes have recently broadened their focus to include an expanded range of kinase targets and therapeutic areas. In this Review, we provide an overview of the novel targets, biological processes and disease areas that kinase-targeting small molecules are being developed against, highlight the associated challenges and assess the strategies and technologies that are enabling efficient generation of highly optimized kinase inhibitors...
March 16, 2018: Nature Reviews. Drug Discovery
Joao Incio, Jennifer A Ligibel, Daniel T McManus, Priya Suboj, Keehoon Jung, Kosuke Kawaguchi, Matthias Pinter, Suboj Babykutty, Shan M Chin, Trupti D Vardam, Yuhui Huang, Nuh N Rahbari, Sylvie Roberge, Dannie Wang, Igor L Gomes-Santos, Stefan B Puchner, Christopher L Schlett, Udo Hoffmman, Marek Ancukiewicz, Sara M Tolaney, Ian E Krop, Dan G Duda, Yves Boucher, Dai Fukumura, Rakesh K Jain
Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance to anti-VEGF therapy include the up-regulation of alternative angiogenic and proinflammatory factors. Obesity is associated with hypoxic adipose tissues, including those in the breast, resulting in increased production of some of the aforementioned factors. Hence, we hypothesized that obesity could contribute to anti-VEGF therapy's lack of efficacy. We found that BC patients with obesity harbored increased systemic concentrations of interleukin-6 (IL-6) and/or fibroblast growth factor 2 (FGF-2), and their tumor vasculature was less sensitive to anti-VEGF treatment...
March 14, 2018: Science Translational Medicine
Sarah Berndt, Mark E Issa, Gilles Carpentier, Muriel Cuendet
The effects of genistein on angiogenesis remain poorly understood. Some studies claim an antiangiogenic effect and others claim a pro-angiogenic one. Thus, the aim of this study was to determine if genistein may exhibit bivalent angiogenic effects. To address this question, genistein angiogenic modulatory effects were examined using an in vitro 3D angiogenesis model using human umbilical vein endothelial cells. In this model, a bivalent effect of genistein was demonstrated on sprouting angiogenesis, with angiogenic stimulation at low concentrations (0...
March 14, 2018: Planta Medica
Alfredo Perales-Puchalt, Jairo Perez-Sanz, Kyle K Payne, Nikolaos Svoronos, Michael J Allegrezza, Ricardo A Chaurio, Carmen Anadon, Joseph Calmette, Subir Biswas, Jessica A Mine, Tara Lee Costich, Logan Nickels, Jayamanna Wickramasinghe, Melanie R Rutkowski, Jose R Conejo-Garcia
Due to their cytotoxic activities, many anticancer drugs cause extensive damage to the intestinal mucosa and have antibiotic activities. Here, we show that cisplatin induces significant changes in the repertoire of intestinal commensal bacteria that exacerbate mucosal damage. Restoration of the microbiota through fecal-pellet gavage drives healing of cisplatin-induced intestinal damage. Bacterial translocation to the blood stream is correspondingly abrogated, resulting in a significant reduction in systemic inflammation, as evidenced by decreased serum IL-6 and reduced mobilization of granulocytes...
March 14, 2018: Journal of Leukocyte Biology
Javed Iqbal, Banzeer Ahsan Abbasi, Riffat Batool, Tariq Mahmood, Barkat Ali, Ali Talha Khalil, Sobia Kanwal, Sayed Afzal Shah, Riaz Ahmad
Breast cancer (BC) is a devastating disease in female around the world causing significant health care burden in both developed and developing countries. In many cases BC has shown resistance to chemotherapy, radiation and hormonal therapy. Development of new, cost effective, affordable treatment method is the need of hour. Chemical compounds isolated from plants are often biologically active and is attracting the attention of scientific community. Different in vitro and in vivo studies have shown a potential role in reducing the risk of cancer metastasis...
March 10, 2018: European Journal of Pharmacology
Natalia Pascuali, Leopoldina Scotti, Mariana Di Pietro, Gonzalo Oubiña, Diana Bas, María May, Antonio Gómez Muñoz, Patricia S Cuasnicú, Débora J Cohen, Marta Tesone, Dalhia Abramovich, Fernanda Parborell
STUDY QUESTION: Is ceramide-1-phosphate (C1P) an ovarian protective agent during alkylating chemotherapy? SUMMARY ANSWER: Local administration of C1P drastically reduces ovarian damage induced by cyclophosphamide (Cy) via protection of follicular reserve, restoration of hormone levels, inhibition of apoptosis and improvement of stromal vasculature, while protecting fertility, oocyte quality and uterine morphology. WHAT IS KNOWN ALREADY: Cancer-directed therapies cause accelerated loss of ovarian reserve and lead to premature ovarian failure (POF)...
March 9, 2018: Human Reproduction
Thais Roque, Laurent Risser, Veerle Kersemans, Sean Smart, Danny Allen, Paul Kinchesh, Stuart Gilchrist, Ana L Gomes, Julia A Schnabel, Michael A Chappell
Predicting tumor growth and its response to therapy remains a major challenge in cancer research and strongly relies on tumor growth models. In this paper, we introduce, calibrate, and verify a novel image-driven reaction-diffusion model of avascular tumor growth. The model allows for proliferation, death and spread of tumor cells, and accounts for nutrient distribution and hypoxia. It is constrained by longitudinal time series of dynamic contrast-enhancement-MRI images. Tumor specific parameters are estimated from two early time points and used to predict the spatio-temporal evolution of the tumor volume and cell densities at later time points...
March 2018: IEEE Transactions on Medical Imaging
Przemysław Janas, Iwona Kucybała, Małgorzata Radoń-Pokracka, Hubert Huras
Telocytes are emerging cell population localized in the stroma of numerous organs, characterized by a distinctive morphology - small cell body with very long, slender prolongations, termed telopodes. Those cells can be found in the whole female reproductive system: in the vagina, uterus, oviducts and ovaries, mammary glands and also in the placenta. In our review, we aim at complete and transparent revision of the current knowledge of telocytes' localization and function, enriched by the analysis of the possible future direction of development of their clinical applications...
March 13, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Wen-Jie Lu, Wen Peng, Qian-Qian Sun, Yong-Huai Li, Bo Chen, Luo-Ting Yu, You-Zhi Xu, Si-Ying Wang, Ying-Lan Zhao
Arresting cell cycle has been one of the most common approaches worldwide in cancer therapy. Specifically, arresting cells in the G2/M phase is a promising therapeutic approach in the battle against lung cancer. In the present study, we demonstrated the anticancer activities and possible mechanism of compound #2714, which can prompt G2/M phase arrest followed by cell apoptosis induction in Lewis lung carcinoma LL/2 cells. In vitro, #2714 significantly inhibited LL/2 cell viability in a concentration- and time-dependent manner while exhibiting few toxicities on non-cancer cells...
December 2018: Cell Death Discovery
Pravin Bhattarai, Sadaf Hameed, Zhifei Dai
Angiogenesis is a normal physiological remodeling process initiated at the time of embryonic development and lessened with the progress of time. Nevertheless, continuous activation of stringent signaling pathways and proangiogenic factors during tumorigenesis (a pathological condition) instigates serious vessel abnormalities eliciting severe therapeutic inefficiency. In principle, systemic delivery of robust antiangiogenic drugs often fails to reach these abnormal tumor vessels depicting poor pharmacokinetics, biodistribution profiles and adverse side effects in vivo...
March 12, 2018: Nanoscale
Jeng-Ting Chen, Chien-Chun Liu, Jau-Song Yu, Hung-Hsuan Li, Ming-Chih Lai
Hypoxia is associated with poor prognosis in most solid tumors due to its multiple effects on therapy resistance, angiogenesis, apoptotic resistance, and tumor invasion/metastasis. Here we used a comprehensive omics profiling to investigate hypoxia-regulated gene expression in HCT116 colon cancer cells. Quantitative analyses of proteome and secretome were performed in HCT116 cells cultured under hypoxic or normoxic conditions. A total of 5700 proteins were quantified in proteome analysis and 722 proteins were quantified in secretome analysis...
March 7, 2018: Journal of Proteomics
Min Zhou, Xinjian Liu, Zonghai Li, Qian Huang, Fang Li, Chuan-Yuan Li
Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy, or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 also has non-apoptotic roles such as promotion of tumor relapse and tumor angiogenesis. Therefore, the roles of caspase-3 in tumor progression remains to be defined clearly. In this study, we established caspase-3 knockout (KO) colon cancer cell lines by use of the CRISPR technology...
March 10, 2018: International Journal of Cancer. Journal International du Cancer
Da Yeon Kim, Seok Yun Jung, Yeon Ju Kim, Songhwa Kang, Ji Hye Park, Seung Taek Ji, Woong Bi Jang, Shreekrishna Lamichane, Babita Dahal Lamichane, Young Chan Chae, Dongjun Lee, Joo Seop Chung, Sang-Mo Kwon
Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions...
March 2018: Korean Journal of Physiology & Pharmacology
Madelon Q Wentink, Henk M W Verheul, Arjan W Griffioen, Kenneth A Schafer, Susan McPherson, Richard J Early, Hans J van der Vliet, Tanja D de Gruijl
INTRODUCTION: Vascular endothelial growth factor (VEGF) is pivotal in tumor angiogenesis and therapies targeting the VEGF axis are widely used in the clinic for the treatment of cancer. We have developed a therapeutic vaccine targeting human (h)VEGF165 . hVEGF26-104 /RFASE is based on the truncated protein hVEGF26-104 as antigen formulated in an oil-in-water emulsion containing the sulpholipopolysaccharide RFASE as adjuvant. Here we describe the toxicity and immunogenicity of this therapeutic vaccine in cynomolgus monkeys...
March 5, 2018: Vaccine
Jingjing Qu, Yongchang Zhang, Xue Chen, Haiyan Yang, Chunhua Zhou, Nong Yang
Angiogenesis and its role in the growth and development of non-small cell lung cancer (NSCLC) metastases has become an increasing clinical problem. Vascular endothelial growth factor (VEGF) plays a key role in advanced NSCLC. To some extent, anti-angiogenic therapies acquired some efficacy in combination with chemotherapy, target therapy and immunotherapy. However, the reliable clinical benefit obtained with these drugs is still questionable and often quantitatively limited. In this review, the authors highlight the data obtained from first-line, second-line, epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) target therapy and immunotherapy in NSCLC patients who are treated with anti-angiogenic molecules in advanced NSCLC...
February 9, 2018: Oncotarget
Jiulong Zhang, Chunrong Yang, Shuang Pan, Menghao Shi, Jie Li, Haiyang Hu, Mingxi Qiao, Dawei Chen, Xiuli Zhao
Mitochondrial-targeting therapy was considered to be a promising approach for the efficient treatment of cancer while positive charge induced nonspecific cytotoxicity severely limits its application. To overcome this drawback, a novel mitochondria targeted conjugate triphenylphosphine-docetaxel (TD) has been synthesized successfully and incorporated it into liposomes (EPSLP/TD), which possessed excellent pH-sensitive characteristic, EphA 10 mediated active targetability as well as mitochondria-targeting capability...
November 2018: Drug Delivery
Weili Liang, Shasha Song, Yintao Xu, Huiying Li, Huantao Liu
Breast cancer is a common malignant tumor in women. It has been suggested that a type of microcirculation pattern that does not rely on host microvascular endothelial cells known as vasculogenic mimicry (VM) may contribute to the poor effect of anti‑angiogenesis treatment on some patients with breast cancer. However, the formation and regulatory mechanism of VM in breast cancer are unclear and still require further investigation. The present study examined whether decreasing the expression of zinc finger E‑box binding homeobox (ZEB1) using siRNA can inhibit the formation of VM in Triple Negative Breast Cancer (TNBC), and its specific function and molecular mechanism...
March 5, 2018: Molecular Medicine Reports
N Garmpis, C Damaskos, A Garmpi, E Spartalis, E Kalampokas, T Kalampokas, G-A Margonis, D Schizas, N Andreatos, A Angelou, A Lavaris, A Athanasiou, K G Apostolou, M Spartalis, Z Damaskou, A Daskalopoulou, E Diamantis, K Tsivelekas, A Alavanos, S Valsami, M M Moschos, A Sampani, A Nonni, E A Antoniou, D Mantas, G Tsourouflis, K Markatos, K Kontzoglou, D Perrea, N Nikiteas, A Kostakis, D Dimitroulis
OBJECTIVE: Endometrial cancer is increasingly prevalent in western societies and affects mainly postmenopausal women; notably incidence rates have been rising by 1.9% per year on average since 2005. Although the early-stage endometrial cancer can be effectively managed with surgery, more advanced stages of the disease require multimodality treatment with varying results. In recent years, endometrial cancer has been extensively studied at the molecular level in an attempt to develop effective therapies...
February 2018: European Review for Medical and Pharmacological Sciences
S Di Martino, C Acierno, A Licito
No abstract text is available yet for this article.
February 2018: European Review for Medical and Pharmacological Sciences
Marianne Yardley, Lars Gullestad, Kari Nytrøen
One of the most important prognostic factors in heart failure patients is physical capacity. Patients with very poor physical performance and otherwise eligible, may be listed as candidates for heart transplantation (HTx). After such surgery, life-long immunosuppression therapy is needed to prevent rejection of the new heart. The dark side of immunosuppression is the increased risk of infections, kidney failure, cancer and advanced atherosclerosis (cardiac allograft vasculopathy), with the two latter conditions as the main causes of later mortality...
February 24, 2018: World Journal of Transplantation
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