Fingolimod sensitizes EGFR wild ‑type non‑small cell lung cancer cells to lapatinib or sorafenib and induces cell cycle arrest.

Fingolimod sensitizes EGFR wild‑type non‑small cell lung cancer cells to lapatinib or sorafenib and induces cell cycle arrest. Oncol Rep. 2019 May 02;: Authors: Ota K, Okuma T, Lorenzo A, Yokota A, Hino H, Kazama H, Moriya S, Takano N, Hiramoto M, Miyazawa K Abstract Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase and mutations in this gene are major drivers of lung cancer development. EGFR tyrosine kinase inhibitors (TKIs) are standard first‑line therapies for patients with advanced non‑small cell lung cancer (NSCLC) with activating EGFR mutations, but are not effective in patients with wild‑type EGFR. In the present study, the cytotoxic effects of various TKIs against EGFR were investigated in wild‑type NSCLC cells as single treatments or in combination with Fingolimod (FTY720), which has been approved for treating multiple sclerosis and has cytotoxic effects against several tumor cell lines. It was found that the combined treatment with TKIs lapatinib (Lap) or sorafenib (Sor) and FTY720 synergistically suppressed the viability of the NSCLC cell lines A549 and H596. Additionally, FTY720 inhibited lysosomal acidification and suppressed autophagy flux. Immunoblotting and reverse transcription‑quantitative polymerase chain reaction showed that FTY720 combined with Lap or Sor, enhanced endoplasmic reticulum (ER) stress loading and cell cycle arrest in A549 cells. The enhancement of ER stress loading and cell cycle arrest ...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

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Publication date: Available online 20 July 2019Source: Seminars in Cancer BiologyAuthor(s): Nancy A. Espinoza-Sánchez, Martin GötteAbstractOver the past few decades, understanding how tumor cells evade the immune system and their communication with their tumor microenvironment, has been the subject of intense investigation, with the aim of developing new cancer immunotherapies. The current therapies against cancer such as monoclonal antibodies against checkpoint inhibitors, adoptive T-cell transfer, cytokines, vaccines, and oncolytic viruses have managed to improve the clinical outcome of the patients. However,...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
DiscussionWe estimated higher risks of ALL in the offspring of women with pregestational diabetes. These results are consistent with previous findings and compatible with a role of prenatal glycaemic environment in childhood cancer aetiology.
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 20 July 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Ashlynn L.Z. Lee, Chuan Yang, Shujun Gao, James L. Hedrick, Yi Yan YangAbstractProlonged vaccine release enables gradual immunostimulation, providing long-term immunity. Herein, Vitamin E- PEG-Vitamin E triblock ‘ABA’ hydrogel, which is formed through physical cross-linking of flower-shaped micelles and can reside in vivo for>17 weeks, was employed for delivery of cancer preventive vaccines to provide sustained anticancer immunity. Mice vaccinated with hydrogel formulations produced a sign...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research
Publication date: Available online 20 July 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Samaneh Kabirian-Dehkordi, Mounira Chalabi-Dchar, Hichem C Mertani, Dominique Le Guellec, Bernard Verrier, Jean-Jacques Diaz, Masoud A. Mehrgardi, Philippe BouvetAbstractG-rich oligonucleotide, AS1411, has been shown to interact with nucleolin and to inhibit cancer cell proliferation and tumor growth. This antiproliferative action is increased when AS1411 is conjugated to different types of nanoparticles. However, the molecular mechanisms are not known. In this work, we show in several cell lines that optimiz...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research
Publication date: Available online 20 July 2019Source: NeurocomputingAuthor(s): Yan Li, Lu Wang, Jiayu Zhou, Jieping YeAbstractThere are many major diseases that remain incurable, such as cancer and Alzheimer’s disease (AD). Therefore, the prevention for these diseases has more impact than diagnosis and treatment. Survival analysis aims at predicting the time of occurrence of specific events of interest. It can be used to identify patients of high risk, which helps healthcare system effectively allocate limited medical resources. In many real-world applications, such as healthcare analysis, a lot of datasets are coll...
Source: Neurocomputing - Category: Neuroscience Source Type: research
ConclusionsAt-risk smokers in Virginia, particularly those living in rural areas with high smoking rates, do not have adequate recommended LDCT coverage. More screening centers are needed to care for the high number of rural smokers at risk for lung cancer.
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Publication date: August 2019Source: The Annals of Thoracic Surgery, Volume 108, Issue 2Author(s): Bryan M. Burt, Duy Nguyen, Shawn S. Groth, Nihanth Palivela, R. Taylor Ripley, Konstantinos I. Makris, Farhood Farjah, Lorraine Cornwell, Nader N. MassarwehBackgroundMinimally invasive thymectomy (MIT) has demonstrated improved short-term outcomes compared with open thymectomy (OT). Although adoption of MIT for thymoma is increasing, oncologic outcomes have not been well characterized.MethodsThis was a retrospective cohort study of adult patients from the National Cancer Database who underwent MIT or OT for Masaoka stage I to...
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroinfla...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Abstract Overall, NSCLC has a poor 5-year survival and new therapeutic approaches are urgently needed. ERBB-addicted NSCLC that have become resistant to ERBB inhibitors are often refractory to additional therapeutic interventions. The sphingosine-1-phosphate receptor modulator fingolimod (FTY720), approved for the treatment of multiple sclerosis, synergized with the NSCLC therapeutic pemetrexed to kill NSCLC and ovarian cancer cells. This occurred in lung cancer cells expressing mutated K-RAS, mutated ERBB1, or in NSCLC cells resistant to afatinib (an ERBB1/2/4 inhibitor). This drug combination appeared to use ove...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
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