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Gilotrif (afatinib) Research

07:06 EST 14th December 2018 | BioPortfolio

A Multi-functional Vector for delivery of Genome Editing Plasmid Targeting β-Catenin to Re-modulate Cancer Cell Properties.

Accurate and efficient delivery of genome editing plasmids to targeted cells is of critical importance in genome editing. Herein, we prepared a multifunctional delivery vector with combination of ligand-mediated selectivity and peptide mediated transmembrane function to effectively deliver plasmids to targeted cancerous cells. In the delivery system, the CRISPR-Cas9 plasmid is combined with protam...

Dasatinib is preferentially active in the activated B-cell subtype of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, with at least one-third of its patients relapsing after treatment with the current chemotherapy regimen, R-CHOP. By gene expression profiling, patients with DLBCL can be categorized into two clinically relevant subtypes: activated B-cell (ABC) and germinal center B-cell (GCB) DLBCL. Patients with the ABC subtype have a poorer progno...

Induction of apoptosis in MDA-MB-231 breast cancer cells by a PARP1-targeting PROTAC small molecule.

Poly (ADP-ribose) polymerase-1 (PARP1) is a major member of the PARP superfamily that is involved in DNA damage signalling and other important cellular processes. Here we report the development of a small molecule targeting PARP1 based on the PROTAC strategy. In the MDA-MB-231 cell line, the representative compound 3 can induce significant PARP1 cleavage and programmed cell death.

Black Lung Resurgence Raises New Challenges for Coal Country Physicians.

GEP100/ARF6 regulates VEGFR2 signaling to facilitate high glucose induced epithelial-mesenchymal transition and cell permeability in RPE cells.

Cell permeability and epithelial-mesenchymal transition (EMT) was found to be enhanced in diabetic retinopathy, and the aim of this study was to investigate the underlying mechanism.

Artemisinin and its derivatives: a potential treatment for leukemia.

Artemisinin (ART) and its derivatives are one of the most important classes of antimalarial agents, originally derived from a Chinese medicinal plant called Artemisia annua L. Beyond their outstanding antimalarial and antischistosomal activities, ART and its derivatives also possess both in-vitro and in-vivo activities against various types of cancer. Their anticancer effects range from initiation...

Aurora kinase B inhibitor barasertib (AZD1152) inhibits glucose metabolism in gastric cancer cells.

Barasertib is a highly selective Aurora kinase B (AURKB) inhibitor and has been widely applied in a variety of cancer cells to investigate the regulatory function of AURKB. However, the effect of barasertib on glucose metabolism in gastric cancer (GC) remains illustrated. Here, barasertib was identified to effectively reduce glucose uptake and lactate production in GC cells in a dose-dependent and...

Cannabis-related cognitive impairment: a prospective evaluation of possible influences on patients with cancer during chemotherapy treatment as a pilot study.

In patients with cancer, the use of medical cannabis has increased significantly during the recent years. There is evidence that cannabis consumption may affect cognitive performance; however, this potential effect has not been investigated prospectively in patients with cancer to date. We aimed to evaluate the effect of cannabis consumption on cognitive abilities as well as on symptom relief in p...

Differential Gene Expression in Erlotinib-treated Fibroblasts.

Therapies targeting the epidermal growth factor receptor (EGFR) result in a painful rash, the most common and debilitating toxicity among patients with non-small cell lung cancer (NSCLC) who take EGFR tyrosine kinase inhibitor (TKI) therapy; however, predicting the development and the severity of the rash is difficult.

An elderly man with gastric cancer, Saint's triad and Heyde's syndrome.

This case study describes a 71-year-old man with signet-ring cell gastric adenocarcinoma and malignant sigmoidal polyp; and typical features of Saint's triad and Heyde syndrome. He had digestive bleeding, two types of hernia, diverticulosis, arterial hypertension, malignant polyp, and antecedent of smoking, lung tuberculosis, and surgical correction of aortic valve stenosis. There is a hypothetica...

Screen for modulators of atonal homolog 1 gene expression using notch pathway-relevant gene transcription based cellular assays.

Atonal homolog 1 (Atoh1) is a basic helix-loop-helix 9 (bHLH) transcription factor acting downstream of Notch and is required for the differentiation of sensory hair cells in the inner ear and the specification of secretory cells during the intestinal crypt cell regeneration. Motivated by the observations that the upregulation of Atoh1 gene expression, through genetic manipulation or pharmacologic...

Point-of-care lung ultrasound for the detection of pulmonary manifestations of malaria and sepsis: An observational study.

Patients with severe malaria or sepsis are at risk of developing life-threatening acute respiratory distress syndrome (ARDS). The objective of this study was to evaluate point-of-care lung ultrasound as a novel tool to determine the prevalence and early signs of ARDS in a resource-limited setting among patients with severe malaria or sepsis.

Recent advances in pediatric non-Hodgkin lymphoma. Report on a retrospective single-center cohort and review of the literature.

Classification, staging and treatment response criteria of pediatric NHL have been revised. Long-term survival reaches ~90% at the expense of severe acute toxicities. The outcome of refractory and relapsed cases is poor. The small number of patients hinders introduction of targeted therapies. Here we summarize principles and perspectives of pediatric NHL supported by results of a retrospective cli...

Oral contraception and the risk of breast cancer. Review of the literature.

At present an estimated hundred millions of women worldwide use oral contraception, but the influence of hormonal contraception on carcinogenesis of breast is not fully understood. Previous studies of breast cancer risk show inconsistent findings - from zero elevation to approximately 30%-40% increase in risk. The beneficial effect on ovarian and endometrial cancer risk is apparent. In this litera...

Influence of HPV infection on cell cycle regulation in epithelial cell alterations of cervix uteri: Immunohistochemical and in situ hybridization observations.

The HPV16 E6 DNA incorporation into the cervical epithelial cell genome was determined. In addition, using p16, p21 and p27 protein immunohistochemistry, we intended to present how the normal cell cycle machinery was disturbed in cervical epithelial cells. In CIN1 the epithelial cells are transformed into koilocytes, p16 is not expressed. p21 is only visible over the parabasal cell layers, while p...

The Tyrosine Kinase Inhibitor TAS-115 Attenuates Bleomycin-Induced Lung Fibrosis in Mice.

The signaling pathways of growth factors including platelet-derived growth factor (PDGF) can be considered specific targets for overcoming the poor prognosis of idiopathic pulmonary fibrosis (IPF). Nintedanib, the recently approved multiple kinase inhibitor, has shown promising anti-fibrotic effects in IPF patients; however, its efficacy is still limited, and in some cases, treatment discontinuati...

Telomeres in Interstitial Lung Disease: The Short and the Long of It.

Telomeres are repetitive nucleotide sequences that cap linear chromosomes, thereby limiting progressive chromosomal shortening during cell replication. In conjunction with environmental factors, common single nucleotide polymorphisms and rare and ultra-rare telomere-related mutations are associated with accelerated telomere shortening resulting in organ dysfunction, including interstitial lung dis...

Phosphatidyl Inositol 3-Kinase (PI3K)-mTOR Inhibitor PKI-402 Inhibits Breast Cancer Induced Osteolysis.

Bone metastasis causes bone pain and pathological bone fracture in breast cancer patients with a serious complication. Previous studies have demonstrated that a novel phosphatidyl inositol 3-kinase (PI3K)-mTOR inhibitor PKI-402 suppressed the growth of breast cancer cells. However, the role of PKI-402 involved in osteolysis induced by breast cancer remains unclear. In this study, we showed that tr...

PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.

PARP inhibitors have shown promising clinical activities for patients with BRCA mutations and are changing the landscape of ovarian cancer treatment. However, the therapeutic mechanisms of action for PARP inhibition in the interaction of tumors with the tumor microenvironment and the host immune system remain unclear. We find that PARP inhibition by olaparib triggers robust local and systemic anti...

KLF4, A Gene Regulating Prostate Stem Cell Homeostasis, Is a Barrier to Malignant Progression and Predictor of Good Prognosis in Prostate Cancer.

There is a considerable need to identify those individuals with prostate cancer who have indolent disease. We propose that genes that control adult stem cell homeostasis in organs with slow turnover, such as the prostate, control cancer fate. One such gene, KLF4, overexpressed in murine prostate stem cells, regulates their homeostasis, blocks malignant transformation, and controls the self-renewal...

Myeloid-Derived Suppressor Cells Produce IL-10 to Elicit DNMT3b-Dependent IRF8 Silencing to Promote Colitis-Associated Colon Tumorigenesis.

IL-10 functions as a suppressor of colitis and colitis-associated colon cancer, but it is also a risk locus associated with ulcerative colitis. The mechanism underlying the contrasting roles of IL-10 in inflammation and colon cancer is unknown. We report here that inflammation induces the accumulation of CD11bGr1 myeloid-derived suppressor cells (MDSCs) that express high levels of IL-10 in colon t...

Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells.

Highly glycolytic cancer cells prevent intracellular acidification by excreting the glycolytic end-products lactate and H via the monocarboxylate transporters 1 (MCT1) and 4 (MCT4). We report that syrosingopine, an anti-hypertensive drug, is a dual MCT1 and MCT4 inhibitor (with 60-fold higher potency on MCT4) that prevents lactate and H efflux. Syrosingopine elicits synthetic lethality with metfor...

Drp1 Controls Effective T Cell Immune-Surveillance by Regulating T Cell Migration, Proliferation, and cMyc-Dependent Metabolic Reprogramming.

Mitochondria are key players in the regulation of T cell biology by dynamically responding to cell needs, but how these dynamics integrate in T cells is still poorly understood. We show here that the mitochondrial pro-fission protein Drp1 fosters migration and expansion of developing thymocytes both in vitro and in vivo. In addition, we find that Drp1 sustains in vitro clonal expansion and cM...

CDK Phosphorylation of Translation Initiation Factors Couples Protein Translation with Cell-Cycle Transition.

Protein translation in eukaryotes is cell-cycle dependent, with translation rates more robust in G1 phase of the cell cycle than in mitosis. However, whether the fundamental cell-cycle control machinery directly activates protein translation during the G1/S cell-cycle transition remains unknown. Using the early divergent eukaryote Trypanosoma brucei as a model organism, we report that the G1 cycli...

The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification.

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