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PubMed Journals Articles About "Tumor Microenvironment Confers MTOR Inhibitor Resistance Invasive Intestinal" - Page: 3 RSS

08:50 EDT 20th October 2018 | BioPortfolio

Tumor Microenvironment Confers MTOR Inhibitor Resistance Invasive Intestinal PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Tumor Microenvironment Confers MTOR Inhibitor Resistance Invasive Intestinal articles that have been published worldwide.

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Showing "Tumor microenvironment confers mTOR inhibitor resistance invasive intestinal" PubMed Articles 51–75 of 21,000+

Tumor microenvironment mediated by suppression of autophagic flux drives liver malignancy.

The physiological role of autophagy in the catabolic process of the body involves protein synthesis and degradation in homeostasis under normal and stressed conditions. In hepatocellular carcinoma (HCC), the role of tumor microenvironment (TME) has been concerned as the main issue in fighting against this deadly malignancy. During the last decade, the crosstalk between tumor cells and their TME in HCC extensively accumulated. However, a deeper knowledge for the actual function of autophagy in this interconn...


USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma.

Dysregulation of deubiquitination pathway is associated with poor prognosis in cancers such as hepatocellular carcinoma (HCC). The mammalian target of rapamycin, mTOR, has become an attractive cancer therapeutic target in HCC. However, whether and how aberrant expression of deubiquitination pathway regulates mTOR pathway has remained elusive. Here we report that ubiquitin-specific protease 10 (USP10) functions as a tumor suppressor which inhibits mTOR pathway by stabilizing PTEN and AMPKα in HCC cells. Mec...

Natural Hypoxia is Not a Limiting Factor in Evaluating the Novel Arylidene Derivative MLT-401 Against an In Vitro Colorectal Cancer Model.

Cancer cells in vivo develop resistance to many anti-tumor drugs. One known factor to influence such drug resistance is hypoxia, which is an important component of the tumor microenvironment. Standard cancer lines mostly do not exhibit a cellular hypoxic microenvironment and there is a paucity of information on the efficacy of lead molecules in both cellular- and environment-induced hypoxic conditions. Therefore, in the present study, we have evaluated the efficacy of the arylidene derivative MLT-401, a lea...


Nitric oxide signaling regulates tumor-induced intussusceptive-like angiogenesis.

Existing animal models for screening tumor angiogenic process have various setbacks that necessitate further investigations. In this study, we developed an ex-ovo egg yolk angiogenesis model to screen the angiogenic potency of tumor cells (HeLa and SiHa cell lines). The egg yolk angiogenesis assay was applied to study the nitric oxide (NO) influence on switching from sprouting angiogenesis (SA) to intussusceptive angiogenesis (IA) under tumor microenvironment. Morphological analysis and SA-like or IA-like m...

Inhibition of mTOR ameliorated bleomycin-induced pulmonary fibrosis by regulating epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) plays a pivotal role in idiopathic pulmonary fibrosis (IPF). In bleomycin-induced pulmonary fibrosis mice, we observed that inhibition of mTOR (mammalia target of rapamycin) attenuated IPF. Rapamycin suppressed the down-regulation of E-cadherin and up-regulation of fibronectin in bleomycin-induced pulmonary fibrosis mice. In addition, dual immunofluorescence staining for E-cadherin and fibronectin demonstrated that rapamycin pretreatment decreased the proportions of A...

Expression of combinatorial immunoglobulins in macrophages in the tumor microenvironment.

Recent evidence indicates the presence of macrophage subpopulations that express the TCRαβ in chronic inflammatory diseases such as tuberculosis and atherosclerosis and in the tumor microenvironment. Here, we demonstrate that a second subpopulation of macrophages expresses rearranged heavy and light chain immunoglobulins. We identify immunoglobulin expression in human and murine monocytes, in ex vivo differentiated macrophages and macrophages from the tumor microenvironment of five randomly selected disti...

Double-sided effect of tumor microenvironment on platelets targeting nanoparticles.

The cancer cells and stromal cells in tumor microenvironment secrete cytokines and recruit "homing" cells (macrophage, lymphocytes, platelets, etc.). Platelets can interact with tumor microenvironment and specifically aggregate at tumor sites. Surprising, we observed different "homing" effects of activated platelets in breast cancer model and pancreatic cancer model which is highly related with the blood supply of tumors. Besides, platelets targeting magnetic nanoparticles (MNPs) can home to breast cancer b...

Reduced menin expression impairs rapamycin effects as evidenced by an increase in mTORC2 signaling and cell migration.

Mammalian target of rapamycin (mTOR) is a master regulator of various cellular responses by forming two functional complexes, mTORC1 and mTORC2. mTOR signaling is frequently dysregulated in pancreatic neuroendocrine tumors (PNETs). mTOR inhibitors have been used in attempts to treat these lesions, and prolonged progression free survival has been recorded. If this holds true also for the multiple endocrine neoplasia type 1 (MEN1) associated PNETs is yet unclear. We investigated the relationship between expre...

NF-κB signaling activation via increases in BRD2 and BRD4 confers resistance to the bromodomain inhibitor I-BET151 in U937 cells.

Novel epigenetic therapies targeting bromodomain and extra-terminal (BET) family proteins have shown therapeutic efficacy in diverse hematologic malignancies and solid cancers. However, the mechanism of resistance remains poorly understood. In the present study, we evaluated the mechanism of resistance to the BET inhibitor I-BET151 and its signaling pathway to overcome resistance in U937 cells. Treatment with 10 μM I-BET151 significantly induced growth inhibition, apoptosis, and cell cycle modulation, incl...

Presence of stromal cells in a bioengineered tumor microenvironment alters glioblastoma migration and response to STAT3 inhibition.

Despite the increasingly recognized importance of the tumor microenvironment (TME) as a regulator of tumor progression, only few in vitro models have been developed to systematically study the effects of TME on tumor behavior in a controlled manner. Here we developed a three-dimensional (3D) in vitro model that recapitulates the physical and compositional characteristics of Glioblastoma (GBM) extracellular matrix (ECM) and incorporates brain stromal cells such as astrocytes and endothelial cell precursors. ...

Outcomes associated with mammalian target of rapamycin (mTOR) inhibitors in heart transplant recipients: A meta-analysis.

Data evaluating mTOR inhibitor use heart transplant (HT) patients comes from relatively small studies and controversy exists regarding their specific role. We performed a meta-analysis of randomized trials to evaluate the efficacy and safety of mTOR inhibitors in HT patients.

Essential Function of Mec1, the Budding Yeast ATM/ATR Checkpoint-Response Kinase, in Protein Homeostasis.

Unlike most checkpoint proteins, Mec1, an ATM/ATR kinase, is essential. We utilized mec1-4, a missense allele (E2130K) that confers diminished kinase activity, to interrogate the question. Unbiased screen for genetic interactors of mec1-4 identified numerous genes involved in proteostasis. mec1-4 confers sensitivity to heat, an amino acid analog, and Htt103Q, an aggregation-prone model peptide of Huntingtin. Oppositely, mec1-4 confers resistance to cycloheximide, a translation inhibitor. In response to heat...

Correlation Of Immune Cells And Cytokines In The Tumor Microenvironment With Elevated Neutrophil-To-Lymphocyte Ratio In Blood: An Analysis Of Muscle-Invasive Bladder Cancer.

We investigated the relationship between Neutrophil-to-lymphocyte ratio (NLR) and the quantities of neutrophil elastase, CD3, Foxp3, and CD204 in tumor-infiltrating cells and circulating cytokines (IL-2, -6, -8, 17a, and TGF-β) in muscle-invasive bladder cancer. IL-6 and IL-8 levels showed a significant correlation with NLR in blood and Foxp3+ cells around the tumor. After co-culture of peripheral blood cells with bladder cancer cell lines, the induction of regulatory T cell (Treg) was higher in T24 whose ...

Inhibition of autophagy potentiated the anti-tumor effects of VEGF and CD47 bispecific therapy in glioblastoma.

Glioblastoma, characterized by extensive microvascular proliferation and invasive tumor growth, is one of the most common and lethal malignancies in adults. Benefits of the conventional anti-angiogenic therapy were only observed in a subset of patients and limited by diverse relapse mechanism. Fortunately, recent advances in cancer immunotherapy have offered new hope for patients with glioblastoma. Herein, we reported a novel dual-targeting therapy for glioblastoma through simultaneous blockade of VEGF and ...

Lenvatinib in the management of metastatic renal cell carcinoma: a promising combination therapy?

To date, results of combination therapy studies have shown no meaningful clinical benefit over monotherapy and an unacceptably high degree of toxicity in the treatment of metastatic renal cell carcinoma (RCC), with the exception of a combination of immune-checkpoint inhibitors and the association of lenvatinib with everolimus. Lenvatinib is a potent multi-targeted tyrosine kinase inhibitor that targets VEGFR pathways. Everolimus inhibits primarily mTORC1 complex, a downstream effecter of the intracellular P...

mTOR mediates a mechanism of resistance to chemotherapy and defines a rational combination strategy to treat KRAS-mutant lung cancer.

Oncogenic KRAS mutations comprise the largest subset of lung cancer defined by genetic alterations, but in the clinic no targeted therapies are available that effectively control mutational KRAS activation. Consequently, patients with KRAS-driven tumors are routinely treated with cytotoxic chemotherapy, which is often transiently effective owing to development of drug resistance. In this study, we show that hyperactivated mammalian target of rapamycin (mTOR) pathway is a characteristic hallmark of KRAS-muta...

The prognostic impact of differentiation at the invasive front of biliary tract cancer.

The invasive front of tumor can provide prognostic information in many cancers. We investigated the prognostic morphological factors at the invasive front including tumor differentiation (Dif) and tumor budding (Bud) in biliary tract cancer (BTC).

miR-338 modulates proliferation and autophagy by PI3K/AKT/mTOR signaling pathway in cervical cancer.

Cervical cancer (CC) is a malignant solid tumor, which is one of the main causes of morbidity and mortality in women. Given that autophagy is an important factor promoting tumor progression, we aim to investigate the functional role of miR-338 in autophagy and proliferation of cervical cancer. In our study, expression of miR-338 was validated by quantitative RT-PCR in 30 paired cervical cancer tissues and normal tissues. We performed MTT, colony formation and cell cycle assay to explore the effect of miR-33...

Dual gene deficient models of Apc mouse in assessing molecular mechanisms of intestinal carcinogenesis.

The Apc mouse, carrying an inactivated allele of the adenomatous polyposis coli (Apc) gene, is a widely used animal model of human colorectal tumorigenesis. While crossed with other gene knockout or knock-in mice, these mice possess advantages in investigation of human intestinal tumorigenesis. Intestinal tumor pathogenesis involves multiple gene alterations; thus, various double gene deficiency models could provide novel insights into molecular mechanisms of tumor biology, as well as gene-gene interactions...

Prevalence of NS5A resistance associated variants in NS5A inhibitor treatment failures and an effective treatment for NS5A-P32 deleted hepatitis C virus in humanized mice.

Patients with chronic hepatitis C virus (HCV) infection who have failed to respond to direct-acting antiviral (DAA) treatment often acquire drug resistance-associated variants (RAVs). The NS5A-P32 deletion (P32del) RAV confers potent resistance to NS5A inhibitors; therefore, patients who acquire this deletion are likely to fail to respond to DAA re-treatment. We investigated the prevalence of N55A-P32del in patients who failed to respond to prior NS5A inhibitor treatment using direct sequencing and analyzed...

Role of AMP activated protein kinase signaling pathway in intestinal development of mammals.

Intestinal tract is an important digestive organ, which takes on the functions of nutrient absorption, bile and metabolic waste excretion. Impaired intestinal barrier function might lead to inflammatory and intestinal diseases. Structure and function of intestinal tract is closely related to differentiation and development of intestinal cells. Differentiation and development of intestinal cells are coordinated and regulated via signaling pathways such as adenosine monophosphate-activated protein kinase (AMP...

Long noncoding RNA growth arrest-specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR-dependent manner.

Malignant glioma is a severe type of brain tumor with a grim prognosis. The occurrence of resistance compromises the efficacy of chemotherapy for glioma. Long noncoding RNA growth arrest-specific 5 (GAS5) has recently become an attractive target for cancer therapy by regulating cell growth, invasion, and migration. Nevertheless, its role in glioma chemoresistance remains elusive. In the current study, the expression of GAS5 was decreased in glioma cell lines, and lower levels of GAS5 were observed in U138 a...

Tumor Oxygenation and Hypoxia-Inducible-Factor-1 Functional Inhibition via a Reactive-Oxygen-Species Responsive Nanoplatform for Enhancing Radiation Therapy and Abscopal Effects.

Hypoxia, and hypoxia-inducible factor-1 (HIF-1), can induce tumor resistance to radiation therapy. To overcome hypoxia-induced radiation resistance, recent studies have described nano-systems to improve tumor oxygenation for immobilizing DNA damage and simultaneously initiate oxygen-dependent HIF-1α degradation. However, HIF-1α degradation is incomplete during tumor oxygenation treatment alone. Therefore, tumor oxygenation combined with residual HIF-1 functional inhibition is crucial to optimizing therape...

Tumor-associated neutrophils suppress pro-tumoral IL-17+ γδ T cells through induction of oxidative stress.

Interleukin 17 (IL-17)-producing γδ T cells (γδ17 T cells) have been recently found to promote tumor growth and metastasis formation. How such γδ17 T-cell responses may be regulated in the tumor microenvironment remains, however, largely unknown. Here, we report that tumor-associated neutrophils can display an overt antitumor role by strongly suppressing γδ17 T cells. Tumor-associated neutrophils inhibited the proliferation of murine CD27- Vγ6+ γδ17 T cells via induction of oxidative stress, ther...

Functional Role of microRNAs in the Progression of Breast Ductal Carcinoma in situ.

microRNAs (miRNAs) are small RNAs that influence gene expression by targeting messenger RNAs (mRNAs). Depending on the function of their target genes, miRNAs may regulate the expression of oncogenes and tumor suppressors, thereby contributing to the promotion or inhibition of tumor progression. Ductal carcinoma in situ (DCIS), although often diagnosed as breast cancer, is a potential precursor to invasive ductal carcinoma. Many of the genetic events required for the invasive progression of DCIS occur at the...


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