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PubMed Journals Articles About "Tumor Microenvironment Confers MTOR Inhibitor Resistance Invasive Intestinal" RSS

23:49 EST 10th December 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 1–25 of 21,000+

Aberrant modulation of ribosomal protein S6 phosphorylation confers acquired resistance to MAPK pathway inhibitors in BRAF-mutant melanoma.

BRAF and MEK inhibitors have shown remarkable clinical efficacy in BRAF-mutant melanoma; however, most patients develop resistance, which limits the clinical benefit of these agents. In this study, we found that the human melanoma cell clones, A375-DR and A375-TR, with acquired resistance to BRAF inhibitor dabrafenib and MEK inhibitor trametinib, were cross resistant to other MAPK pathway inhibitors. In these resistant cells, phosphorylation of ribosomal protein S6 (rpS6) but not phosphorylation of ERK or p...


Comment on ' Role of platelet-rich fibrin on intestinal anastomosis wound healing in a rat'.

Platelet-rich fibrin (PRF) is indeed a promising treatment modality for healing promotion and acceleration. Are there, however, any disadvantages or contraindications regarding its safety when applied on intestinal anastomosis after tumor excision? The regenerative effect of PRF in a malignant microenvironment, deserves further experimental investigation and large-scale prospective randomized clinical trials, that could provide an indication of the extent to which the tumor cell instructs its microenvironme...

Collagen type I induces EGFR-TKI resistance in EGFR-mutated cancer cells via mTOR activation through Akt-independent pathway.

Primary resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a serious problem in lung adenocarcinoma patients harboring EGFR mutations. The aim of this study was to examine whether and how collagen type I (Col I), the most abundantly deposited matrix in tumor stroma, affects EGFR-TKI sensitivity in EGFR mutant cells. We evaluated the EGFR-TKI sensitivity of EGFR mutated cancer cells cultured with Col I. Changes in the activation of downstream signaling molecules of EGFR ...


Polarization and distribution of tumor-associated macrophages and COX-2 expression in basal cell carcinoma of the ocular adnexae.

Basal cell carcinoma (BCC) is a locally invasive skin tumor which can be subdivided into a circumscribed nodular and an invasive fibrosing subtype. There is increasing evidence that macrophages play an important role in interacting between tumor cells and their microenvironment, thereby affecting not only the invasive potential but also the patients' prognosis. Thus, we wanted to compare these two BCC variants with regard to tumor-related inflammation, COX-2 expression, distribution and polarization of tumo...

Role of extracellular matrix and microenvironment in regulation of tumor growth and LAR-mediated invasion in glioblastoma.

The cellular dispersion and therapeutic control of glioblastoma, the most aggressive type of primary brain cancer, depends critically on the migration patterns after surgery and intracellular responses of the individual cancer cells in response to external biochemical cues in the microenvironment. Recent studies have shown that miR-451 regulates downstream molecules including AMPK/CAB39/MARK and mTOR to determine the balance between rapid proliferation and invasion in response to metabolic stress in the har...

Modeling three-dimensional invasive solid tumor growth in heterogeneous microenvironment under chemotherapy.

A systematic understanding of the evolution and growth dynamics of invasive solid tumors in response to different chemotherapy strategies is crucial for the development of individually optimized oncotherapy. Here, we develop a hybrid three-dimensional (3D) computational model that integrates pharmacokinetic model, continuum diffusion-reaction model and discrete cell automaton model to investigate 3D invasive solid tumor growth in heterogeneous microenvironment under chemotherapy. Specifically, we consider t...

Mevalonate pathway blockage enhances the efficacy of mTOR inhibitors with the activation of retinoblastoma protein in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common malignancy of kidney and remains largely intractable once it recurs after resection. mTOR inhibitors have been one of the mainstays used against recurrent RCC; however, there has been a major problem of the resistance to mTOR inhibitors, and thus new combination treatments with mTOR inhibitors are required. We here retrospectively showed that regular use of antilipidemic drug statins could provide a longer progression free survival (PFS) in RCC patients prescrib...

Mechanisms of acquired resistance to rapalogs in metastatic renal cell carcinoma.

The mechanistic target of rapamycin (mTOR) is an established therapeutic target in renal cell carcinoma (RCC). Mechanisms of secondary resistance to rapalog therapy in RCC have not been studied previously. We identified six patients with metastatic RCC who initially responded to mTOR inhibitor therapy and then progressed, and had pre-treatment and post-treatment tumor samples available for analysis. We performed deep whole exome sequencing on the paired tumor samples and a blood sample. Sequence data was an...

Stromal extracellular matrix is a microenvironmental cue promoting resistance to EGFR tyrosine kinase inhibitors in lung cancer cells.

The acquisition of resistance to EGFR tyrosine kinase inhibitors (TKIs) remains a critical problem in lung cancer clinic, but the underlying mechanisms have remained incompletely understood. Although the TKI-induced or -selected genetic changes are known to drive resistance, resistance also occurs in tumor cells without genetic changes through poorly-characterized processes. Here, we show that the extracellular matrix (ECM) from various components of the tumor microenvironment, including neighboring tumor c...

Altered cancer metabolism in mechanisms of immunotherapy resistance.

Many metabolic alterations, including the Warburg effect, occur in cancer cells that influence the tumor microenvironment, including switching to glycolysis from oxidative phosphorylation, using opportunistic modes of nutrient acquisition, and increasing lipid biosynthesis. The altered metabolic landscape of the tumor microenvironment can suppress the infiltration of immune cells and other functions of antitumor immunity through the production of immune-suppressive metabolites. Metabolic dysregulation in ca...

Bad Company: Microenvironmentally Mediated Resistance to Targeted Therapy in Melanoma.

This review will focus on the role of the tumor microenvironment (TME) in the development of drug resistance in melanoma. Resistance to mitogen-activated protein kinase inhibitors (MAPKi) in melanoma is observed months after treatment, a phenomenon that is often attributed to the incredible plasticity of melanoma cells but may also depend on the TME. The TME is unique in its cellular composition - it contains fibroblasts, immune cells, endothelial cells, adipocytes and amongst others. In addition, the TME p...

BRAF Splice Variant Resistance to RAF Inhibitor Requires Enhanced MEK Association.

Expression of aberrantly spliced BRAF V600E isoforms (BRAF V600E ΔEx) mediates resistance in 13%-30% of melanoma patients progressing on RAF inhibitors. BRAF V600E ΔEx confers resistance, in part, through enhanced dimerization. Here, we uncoupled BRAF V600E ΔEx dimerization from maintenance of MEK-ERK1/2 signaling. Furthermore, we show BRAF V600E ΔEx association with its substrate, MEK, is enhanced and required for RAF inhibitor resistance. RAF inhibitor treatment increased phosphorylation at serine 729...

Microenvironment signaling driving lymphomagenesis.

In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, drug resistance, and late progression/transformation. The purpose of this review is to outline the most recent findings regarding malignant B-cell niche composition and organization supporting direct and indirect tumor-promoting functions of lymphoma microenvironment.

Glioma stem cells reconstruct similar immunoinflammatory microenvironment in different transplant sites and induce malignant transformation of tumor microenvironment cells.

This study aimed to examine whether the different tumor-transplanted sites could construct a similar immunoinflammatory microenvironment and to investigate the interactions between tumor microenvironment cells.

Rapamycin-insensitive mechanistic target of rapamycin regulates basal and resistance exercise-induced muscle protein synthesis.

We investigated whether rapamycin-insensitive mechanistic target of rapamycin (mTOR) signaling plays a role in regulating resistance exercise-induced muscle protein synthesis. We used a rodent model of resistance exercise and compared the effect of rapamycin, an allosteric mTOR inhibitor, with the effect of AZD8055, an ATP-competitive mTOR kinase inhibitor. The right gastrocnemius muscle of male Sprague-Dawley rats age 11 wk was contracted isometrically via percutaneous electrical stimulation (100 Hz, 5 set...

Inducible SHP-2 activation confers resistance to imatinib in drug-tolerant chronic myeloid leukemia cells.

BCR-ABL kinase mutations, accounting for clinical resistance to tyrosine kinase inhibitor (TKI) such as imatinib, frequently occur in acquired resistance or in advanced phases of chronic myeloid leukemia (CML). Emerging evidence implicates a critical role for non-mutational drug resistance mechanisms underlying the survival of residual cancer 'persister' cells. Here, we utilized non-mutational imatinib-resistant K562/G cells to reveal SHP-2 as a resistance modulator of imatinib treatment response during the...

Accumulation of multiple mutations in vivo confers cross-resistance to new and existing integrase inhibitors.

Bictegravir (BIC) and cabotegravir (CAB) are the latest available HIV integrase inhibitors in clinical trials. The combination of major integrase inhibitor substitutions G140S/Q148H has been shown to confer high-level resistance to the approved integrase inhibitors raltegravir (RAL) and elvitegravir (EVG) but not necessarily dolutegravir (DTG). We assayed recombinant viruses made from patient-derived RNA extracts for resistance phenotype for a panel of viruses containing G140S/Q148H with additional accessor...

Complex interplay between tumor microenvironment and cancer therapy.

Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within and around the tumor mass. The TME is highly dynamic and its importance in different stages of cancer progression has been well recognized. A growing body of evidence suggests that TME also plays pivotal roles in cancer treatment responses. TME is significantly remodeled upon cancer therapies, and such change either enhances the responses or induces drug resistance. Given the importance of TME in tumor progre...

Correction: Both HIV-Infected and Uninfected Cells Express TRAILshort, Which Confers TRAIL Resistance upon Bystander Cells within the Microenvironment.

High collagen density augments mTOR-dependent cancer stem cells in ERα+ mammary carcinomas, and increases mTOR-independent lung metastases.

Metastatic estrogen receptor alpha positive (ERα+) cancers account for most breast cancer mortality. Cancer stem cells (CSCs) and dense/stiff extracellular matrices are implicated in aggression and therapy resistance. We examined this interplay and response to mTOR inhibition using ERα+ adenocarcinomas from NRL-PRL females in combination with Col1a1 (mCol1a1) mice, which accumulate collagen-I around growing tumors. Orthotopic transplantation of tumor cells to mCol1a1 but not wildtype hosts resulted in str...

Exosomes Function in Tumor Immune Microenvironment.

Immune cells and mesenchymal stem/stromal cells are the major cellular components in tumor microenvironment that actively migrate to tumor sites by sensing "signals" released from tumor cells. Together with other stromal cells, they form the soil for malignant cell progression. In the crosstalk between tumor cells and its surrounded microenvironment, exosomes exert multiple functions in shaping tumor immune responses. In tumor cells, their exosomes can lead to pro-tumor immune responses, whereas in immune c...

Durable response to anti-PD-1 immunotherapy in epithelioid angiomyolipoma: a report on the successful treatment of a rare malignancy.

Malignant angiomyolipoma is an uncommon tumor of the class of perivasciular epithelioid cell neoplasms (PEComas). These tumors are characteristically driven by deleterious mutations in the tumor suppressors TSC1 and TSC2, whose gene products typically act to inhibit mTOR. There are several cases of malignant angiomyolipoma which exhibit transient responses to mTOR inhibitors, forming the basis of current practice guidelines in malignant PEComa. However the tumors ultimately acquire resistance, and there is ...

RANKL-induced c-Src activation contributes to conventional anti-cancer drug resistance and dasatinib overcomes this resistance in RANK-expressing multiple myeloma cells.

The survival and growth of multiple myeloma (MM) cells are facilitated by cell-cell interactions with bone marrow stromal cells and the bone marrow microenvironment. These interactions induce de novo drug resistance known as cell adhesion-mediated drug resistance. Our previous results recently revealed that the receptor activator of NF-κB (RANK) ligand (RANKL), which is expressed by bone marrow stromal cells, contributes to anti-cancer drug resistance through the activation of various signaling molecules a...

β7 integrins contribute to intestinal tumor growth in mice.

The gut homing receptor integrin α4β7 is essential for the migration of pro-inflammatory T cells into the gut mucosa. Since intestinal neoplasia has been associated with chronic inflammation, we investigated whether interfering with gut-homing affects intestinal tumorigenesis. Using chemically induced and spontaneous intestinal tumor models we showed that lack of β7 integrin significantly impairs tumor growth without affecting tumor frequencies, with a mild translatable effect on overall survival. This c...

PD-L1 in tumor microenvironment mediates resistance to oncolytic immunotherapy.


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