PI3K/mTOR Inhibitor VS-5584 Alters Expression of WNT Signaling Genes and Induces Apoptosis in Lung Adenocarcinoma Cells: In Vitro and In Silico Insight.

Lung cancer (LC) accounts for approximately 25% of all cancer cases, with 80-85% of these being non-small cell lung cancer (NSCLC). VS-5584 is a novel anti-cancer agent that specifically inhibits mTORC1/2 and class I PI3K isoforms. There is cross-talk between the PI3K-Akt-mTOR and WNT signaling pathways that are abnormally activated in NSCLC.

Evaluation of the effect of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) techniques on survival response in cell lines with a new radiobiological modeling.

Background: The optimal radiobiological model, which assesses the biological effects of novel radiotherapy techniques that concurrently modify multiple physical factors, has not yet been defined. This study aimed to investigate the impact of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) on cellular response in head and neck cancer and melanoma models.

Methods: Clonogenic analysis, DNA double-strand break analysis, apoptosis, and cell cycle analysis were performed on cancer stem cell models, cancer models, and normal tissue cell models to assess radiation sensitivity.

The lncRNA expression profile signature of leukemia stem cells is altered upon PI3K/mTOR inhibition: an and study.

Genetic and/or epigenetic alterations in hematopoietic stem cells (HSCs) contribute to leukemia stem cell (LSC) formation. We aimed to identify alterations in the lncRNA expression profile signature of LSCs upon inhibition of PI3K/Akt/mTOR signaling, which provides selective advantages to LSCs. We also aimed to elucidate the potential interaction networks and functions of differentially expressed lncRNAs (DELs).

The effects of PKI-402 on breast tumor models' radiosensitivity via dual inhibition of PI3K/mTOR.

Purpose: PI3K/Akt/mTOR pathway activation causes relapse and resistance after radiotherapy in breast cancer (BC). We aimed to radiosensitize BC cell lines to irradiation (IR) by PKI-402, a dual PI3K/mTOR inhibitor.

Methods: We performed cytotoxicity, clonogenicity, hanging drop, apoptosis and double-strand break detection, and phosphorylation of 16 essential proteins involved in the PI3K/mTOR pathway.

Methanol Extract in Combination with Ponatinib Shows Synergistic anti-Leukemic Activities on Chronic Myeloid Leukemia Cells.

is used in folk medicine due to its anti-inflammatory, antimicrobial, and antioxidant properties. Ponatinib, an effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML), has severe side effects. Thus, we aimed to determine a novel herbal combination therapy that might not only increase the anti-leukemic efficacy but also reduce the dose of ponatinib in targeting CML cells.

Comparative expression analysis of dasatinib and ponatinib-regulated lncRNAs in chronic myeloid leukemia and their network analysis.

LncRNAs are associated with malignancies with their tumor suppressor/oncogenic properties. Although many studies are conducted related to the mechanism of action for dasatinib and ponatinib in chronic myeloid leukemia (CML), their comparative effects on lncRNA expressions are largely unknown. Hence, we aimed to define the lncRNAs involved in the treatment of CML with dasatinib and ponatinib.

PI3K/mTOR dual-inhibition with VS-5584 enhances anti-leukemic efficacy of ponatinib in blasts and Ph-negative LSCs of chronic myeloid leukemia.

Ponatinib is used for advanced treatment of chronic myeloid leukemia (CML), although low doses to prevent side effects do not suppress survival pathways and eradicate leukemia stem cells (LSCs). We evaluated the potential of ponatinib and PI3K/mTOR dual-inhibitor VS-5584 combination (PoVS) therapy to increase the anti-leukemic effects of ponatinib and investigated the underlying mechanisms at the molecular level. We measured the cytotoxicities of ponatinib, VS-5584, and PoVS (CCK-8 assay), and used the median-effect equation for combination analyses.

The effect of caffeic acid phenethyl ester on cell cycle control gene expressions in breast cancer cells.

We aimed to find the effect of caffeic acid phenethyl ester (CAPE) on the expression profiles of cell cycle control genes in breast cancer cell line (MCF-7). The cytotoxic effect of CAPE on MCF-7 cell line was found with an XTT analysis. Total RNA was isolated from the cells exposed to IC dose and untreated control cells.

Design, synthesis, cytotoxic activity, and apoptosis inducing effects of 4- and N-substituted benzoyltaurinamide derivatives.

In this study, a group of 4-substituted benzoyltaurinamide derivatives were designed, synthesized, and investigated for their anticancer activity against three cancer cell lines and one nontumorigenic cell line by MTT assay. Among the final compounds, methoxyphenyl derivatives 14, 15, 16 were found to be effective against all the tested cancerous cell lines with promising selectivity. The most active compounds were further evaluated to determine the molecular mechanism of their anticancer activity by using western blot assay and the Annexin V-FITC/PI test.

The Evaluation of Effect of Aurora Kinase Inhibitor CCT137690 in Melanoma and Melanoma Cancer Stem Cell.

Background: Dysregulation of the cell cycle is one of the main causes of melanomagenesis. Genomewide studies showed that the expression of Aurora -A and -B significantly has been upregulated in melanoma. However, there is no FDA approved drug targeting aurora kinases in the treatment of melanoma.

Effect of CCT137690 on long non-coding RNA expression profiles in MCF-7 and MDA-MB-231 cell lines.

Long non-coding RNAs (lncRNAs) are involved in a range of biological processes, such as cellular differentiation, migration, apoptosis, invasion, proliferation, and transcriptional regulation. The aberrant expression of lncRNAs plays a significant role in several cancer types. Aurora kinases are increasingly expressed in various malignancies; accordingly, the inhibition of these enzymes may represent a novel approach for the treatment of various cancers.

Investigation of the synergistic effects of paclitaxel and herbal substances and endemic plant extracts on cell cycle and apoptosis signal pathways in prostate cancer cell lines.

Paclitaxel, which isolated from Taxus brevifolia, is recently started to be used against prostate cancer treatment and it is a very effective compound against cancer. In this study, we aimed to test the synergistic effect of two plant active compounds (sulphoraphane (SFN) and silymarin (SILY)) and several endemic plant species from Turkey (such as Phlomis leucophracta, Rubia davisiana, Alkanna tinctoria), which are known to have anticarcinogenic effect on androgen-independent PC3 and DU145, and androgen-dependent VCaP prostate cancer cell lines, with paclitaxel on the expression of cell cycle signaling and apoptosis regulator genes. Herbal substances and endemic herbal extracts were combined with Paclitaxel drug.

The current clinical and geographical situation of cutaneous leishmaniasis based on species identification in Turkey.

Leishmaniases are a group of vector-borne diseases caused by the members of Leishmania genus, and there are three main clinical forms of the infection as visceral, cutaneous, and mucocutaneous. Cutaneous leishmaniasis is a growing public health problem in Turkey due to increasing detection of autochthonous cases caused by L. major and L.

The effect of ICRT-3 on Wnt signaling pathway in head and neck cancer.

The effect of Wnt pathway in head and neck cancer could not be elucidated, even though the aberrant Wnt signaling plays a key role in the development of many types of cancer. The inhibitor of β-catenin responsive transcription (ICRT-3) blocks the Wnt signaling pathway by binding to β-catenin, which is a coactivator of the Wnt signaling pathway and a promising agent for inhibiting aberrant signaling. In our study, we aimed to evaluate the effect of ICRT-3 on the cytotoxicity, apoptosis, cell cycle progression, migration, and gene expressions in head and neck cancer stem cell (HNCSC) and hypopharynx cancer.

Analysis of long non-coding RNA (lncRNA) expression in hepatitis B patients.

Long non-coding RNAs (lncRNAs) have been implicated in numerous biological processes, including epigenetic regulation, cell-cycle control, and transcriptional/translational regulation of gene expression. Differential expression of lncRNAs and disruption of the regulatory processes are recognized as critical steps in cancer development. The role of lncRNAs in hepatitis B virus (HBV) infection is not well understood.

Antileukemic effect of paclitaxel in combination with metformin in HL-60 cell line.

Acute promyelocytic leukemia (APL) is a subtype of AML that is a mixture of hematological malignancy, characterized by a specific translocation t(15;17). The using of all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) or chemotherapeutic agents or both of these agents, composes main treatment strategy of APL. While it is possible to achieve success in treatment of low-risk APL with current treatment regimens, such success is not mentioned in high-risk APL.

Comparative effect of imatinib and ponatinib on autophagy and miRNome in chronic myeloid leukemia.

BCR-ABL tyrosine kinase inhibitors (TKIs) are selective therapies for the patients with Chronic Myeloid Leukemia (CML). Imatinib and ponatinib have remarkable long-term efficacy on a major molecular response. Although TKI related induction of cytotoxicity and apoptosis have been clearly investigated in molecular levels, their comparative effect on autophagy and miRNome are largely unknown.

The effect of tomatine on metastasis related matrix metalloproteinase (MMP) activities in breast cancer cell model.

Breast cancer is one of the most common malignancies in women and metastasis is the cause of morbidity and mortality in patients. In the development of metastasis, the matrix metalloproteinase (MMP) family has a very important role in tumor development. MMP-2 and MMP-9 work together for extracellular matrix (ECM) cleavage to increase migration.

Dual Nuclear/Fluorescence Imaging Potantial of Zinc(II) Phthalocyanine in MIA PaCa-2 Cell Line.

Background And Objective: Pancreatic cancer is very common and difficult to diagnose in early stage. Imaging systems for diagnosing cancer have many disadvantages. However, combining different imaging modalities offers synergistic advantages.

Analysis of dysregulated long non-coding RNA expressions in glioblastoma cells.

Long non coding RNAs (lncRNAs) are associated with various biological roles such as embryogenesis, stem cell biology, cellular development and present specific tissue expression profiles. Aberrant expression of lncRNAs are thought to play a critical role in the progression and development of various cancer types, including gliomas. Glioblastomas (GBM) are common and malignant primary brain tumours.

Nuclear imaging potential and in vitro photodynamic activity of symmetrical and asymmetrical zinc phthalocyanines.

Photodynamic therapy (PDT) is based on exposing a light-sensitive material that has been localized in target tissues with visible light. In the current study, symmetric Zn(II) octaoctadodecylphthalocyanine (1) and the asymmetrically substituted hydroxyhexyloxy derivative (2) were examined as a multifunctional agent for tumour nuclear imaging and for PDT potential. Zn(II)Pc 1 and Zn(II)Pc 2 were radiolabelled with (131) I using an iodogen method with high efficiency (93.

Leishmaniasis in Turkey: first clinical isolation of Leishmania major from 18 autochthonous cases of cutaneous leishmaniasis in four geographical regions.

Objective: To report isolation of Leishmania major strains obtained from 18 Turkish autochthonous cutaneous leishmaniasis (CL) patients infected with L. major between 2011 and 2014.

Methods: Initial diagnosis relied on microscopy and culture in enriched medium, prepared by adding specific amounts of liver extract, protein and lipid sources to NNN medium.

Investigation of In vitro PDT Activities and In vivo Biopotential of Zinc Phthalocyanines Using (131)I Radioisotope.

Novel octylthio-containing asymmetrically substituted Zn(II) phthalocyanine (Zn(II)Pc1) and a symmetric derivative (Zn(II)Pc2) have been prepared to investigate the biological potential and ability to photosensitize singlet oxygen for photodynamic therapy applications. In this study, the singlet oxygen generation potential and in vitro photodynamic activities of these compounds have been tested. Both ZnPcs reveal to be very efficient singlet oxygen generators and promising PSs for PDT applications.

131I-Zn-Chlorophyll derivative photosensitizer for tumor imaging and photodynamic therapy.

In recent years, the photodynamic therapy studies have gained considerable attention as an alternative method to surgery, chemotherapy and radiotherapy which is commonly used to fight cancer. In this study, biological potentials of a benzyloxy bearing zinc(II) pheophorbide-a (Zn-PH-A) were investigated via in vivo and in vitro experiments. Zn-PH-A was labeled with (131)I with high efficiency (95.

Synergistic effect of ponatinib and epigallocatechin-3-gallate induces apoptosis in chronic myeloid leukemia cells through altering expressions of cell cycle regulatory genes.

Purpose: Ponatinib (P) has been used for the treatment of chronic myeloid leukemia (CML) and it is known that inhibition of BCR-ABL fusion protein by ponatinib induces apoptosis of CML cells. Epigallocatechin-3-gallate (EGCG), which is a polyphenol in green tea, induces apoptosis in different types of cancer cells. The purpose of this study was to determine the cytotoxic and apoptotic effects of ponatinib and EGCG combination in K562 CML cell line.