Luteolin induces oxidative stress and apoptosis via dysregulating the cytoprotective Nrf2-Keap1-Cul3 redox signaling in metastatic castration-resistant prostate cancer cells.

Background: The treatment of metastatic castration-resistant prostate cancer (mCRPC) is still challenging clinically. Due to the refractor and highly metastatic phenotype of mCRPC, novel therapy strategies need to be investigated. Luteolin, a promising anticancer agent with various biological targets in many cancer types, also has a pro-oxidant effect that selectively triggers ROS and apoptosis.

Association between the apoptotic effect of Cabazitaxel and its pro-oxidant efficacy on the redox adaptation mechanisms in prostate cancer cells with different resistance phenotypes.

Redox adaptation causes poor prognosis by adapting cancer cells to excessive oxidative stress. Previously, we introduced an oxidative stress-resistant metastatic prostate cancer (mPC) model (LNCaP-HPR) that redox adaptation reduced the effect of Cabazitaxel (Cab), the last taxane-derivative for metastatic castration-resistant PC (mCRPC). Whereas, we investigated for the first time whether there is an association between the altered apoptotic effect and pro-oxidant efficacy of Cab on the redox adaptation in PC cells with different phenotypes, including LNCaP mPC, LNCaP-HPR, C4-2 mCRPC, and RWPE-1 cells.

The regulatory effect of cabazitaxel on epithelial-mesenchymal transition in metastatic prostate cancer.

Introduction: : Epithelial-mesenchymal transition (EMT) is a critical mechanism that promotes cancer cells to metastasis. Therefore, EMT regulation has become an important target in anticancer therapy approaches in recent years. However, in metastatic prostate cancer (PC), the EMT regulatory effect has not fully understood for cabazitaxel (Cbx), a third line taxane-based chemotherapeutic for metastatic castration-resistant PC.

Correlation between Ubiquitin E3 Ligases (s) and Heat Shock Protein 90 in Breast Cancer Patients.

Background: Breast cancer is a heterogeneous disease and differences in the expression levels of the ER, PR, and HER2 the triplet of established biomarkers used for clinical decision-making have been reported among breast cancer patients. Furthermore, resistance to anti-estrogen and anti-HER2 therapies emerges in a considerable rate of breast cancer patients, and novel drug therapies are required. Several anomalous signaling pathways have been known in breast cancer have been known; heat shock protein 90 (HSP90) is one of the most plenty proteins in breast cells.

An in vitro redox adaptation model for metastatic prostate cancer: Establishing, characterizing and Cabazitaxel response evaluating.

Little is known about the redox-adapted cancer cells for understanding their pharmacologically targetable features and chemotherapeutic responses. Thus, we present the first in vitro redox adaptation model for metastatic prostate cancer (mPC), LNCaP-hydrogen peroxide resistant (LNCaP-HPR), with enhanced oxidative stress resistance accompanying poor Cabazitaxel response. After establishing, the cells were characterized by comparing the viability, death, oxidative stress, total glutathione (GSH) levels and the mRNA and protein levels of the redox-sensitive transcription factors responsible for the adaptation, Nrf-2, NF-κB and HIF-1α.

Identification of CHEK2 germline mutations in BRCA1/2 and PALB2 negative breast and ovarian cancer patients.

Introduction: The CHEK2 gene is known to be an important signal transducer involved in DNA repair, apoptosis, or cell cycle arrest in response to DNA damage. The mutations in this gene have been associated with a wide range of cancers, both sporadic and hereditary. Germline CHEK2 mutations are linked to an increased risk of breast cancer.

Investigation of VHL gene associated with miR-223 in clear cell renal cell carcinoma.

Background: Clear cell type renal cell carcinoma (ccRCC) is the most common renal cell carcinoma (RCC). In this study, we examined the expressions of VHL and miR-223 in ccRCC patients׳ tissues to investigate the possible role in the development of ccRCC.

Methods And Results: This study collected five expression profiles (GSE36139, GSE3, GSE73731, GSE40435, and GSE26032) from Gene Omnibus Data.

The expression and prognostic value of miR-146a and miR-155 in Turkish patients with multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory, autoimmune demyelinating, and neurodegenerative disorder of the central nervous system. Interactions between environmental factors, predisposition genes, and determining genes appear to be involved in its etiology. Epigenetic mechanisms such as microRNA-mediated gene regulation can determine the susceptibility and severity of autoimmune diseases.

Comparison of Clinical and Molecular Wnt and SHH Subgroups in Medulloblastoma Tumor Cases.

Aim: To determine the Wnt and SHH subtypes at the molecular level, and to compare them clinically by examining the changes in CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression in the medulloblastoma of a Turkish population determined according to patient selection criteria. In this context, the clinical distinction between Wnt and SHH groups are realized by considering the age, gender, survival time, location of the lesion, and radiological features of the patients.

Material And Methods: Molecular separation was performed by RT-PCR analysis of CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression changes.

c.1905 + 1G>A Promotes Fluoropyrimidine-Induced Anemia, a Prognostic Factor in Disease-Free Survival, in Colorectal Cancer.

In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase ( gene variant, c.1905 + 1G>A, leads to intolerance to fluoropyrimidines.

Evaluation of the Clinical Features Accompanied by the Gene Mutations: The 2 Novel PSEN1 Variants in a Turkish Early-onset Alzheimer Disease Cohort.

Introduction: Early-onset Alzheimer disease (EOAD) is an earlier Alzheimer disease form which is characterized by the mutations in the amyloid precursor protein, presenilin-1/2 (PSEN1/2), and triggering receptor expressed on myeloid cells 2 (TREM2). However, it is still necessary to report mutational screening in multiethnic groups to improve the genetic background of EOAD due to the variant classification challenge.

Methods: We performed targeted sequencing for the amyloid precursor protein, PSEN1, PSEN2, and TREM2 genes in 74 patients and 1 family diagnosed with EOAD.

NEAT1 Is a Novel Oncogenic LncRNA and Correlated with miR-143 in Pediatric Oligodendrogliomas.

Introduction: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for <1% of pediatric brain tumors.

The Anticancer Effect of Methanol Extract by miRNAs' Re-regulation: An Study on Human Malignant Melanoma Cells.

Alternative and natural therapies are needed for malignant melanoma (MM), the most deadly skin cancer type due to chemotherapy's limited effect. In the present study, we evaluated the anticancer potentials of methanol and water extracts (IVM and IVW) on MM cells, A2058 and MeWo, and normal fibroblasts. After the chromatographic and antioxidant activity analysis, their antiproliferative effects were determined with the increasing doses for 24-72 h.

Association between the anticancer efficacy of cabazitaxel and toll-like receptor 4 mediating signaling pathways in metastatic castration-resistant prostate cancer cells.

Background: We evaluated the effect of cabazitaxel (CAB) as a third-line taxane on Toll-like receptor 4 (TLR4)-mediated signaling pathways, especially NF-κB activity, in metastatic castration-resistant prostate cancer (mCRPC) cells.

Methods: CAB cytotoxicity was determined by WST-1 assay. To assess the relationship between CAB efficacy and TLR4 signaling pathways, RT-PCR, western blot and immunofluorescence analysis were performed.

Contribution of functional dopamine D2 and D3 receptor variants to motor and non-motor symptoms of early onset Parkinson's disease.

In the present study, we focused on investigating the contribution of functional dopamine D2 and D3 receptor variants to motor and/or non-motor symptoms of early onset Parkinson's disease (EOPD). Three functional single nucleotide polymorphisms (SNPs), DRD3 rs6280, DRD2 rs2283265 and DRD2 rs1076560, were genotyped in 128 Turkish EOPD patients and then, statistical analysis was conducted for the potential impacts of SNPs on clinical parameters. All three SNPs were found to be statistically significant in terms of PD-related pain: DRD3 [rs6280; risk allele "T" for pain; p = 0.

Inhibitory Effects of Leaf Extract on Mesenchymal Transition Mechanism in Glioblastoma Cells.

Background: Glioblastoma (GB) is the most aggressive form of brain tumor. Despite the current treatment methods, the survival rate of patients is very low. Therefore, there is a need to develop new therapeutic agents.

Talazoparib nanoparticles for overcoming multidrug resistance in triple-negative breast cancer.

Herein, we investigated efflux pumps-mediated talazoparib-resistance in the treatment of triple-negative breast cancer (TNBC). Furthermore, we produced a novel talazoparib-solid lipid nanoparticles (SLNs) and then explored in vitro therapeutic efficacy of talazoparib-SLNs to overcome talazoparib-resistance in TNBC cells. Talazoparib-SLNs formulation was produced and then characterized.

Clinicopathologic features and genetic characteristics of the BRCA1/2 mutation in Turkish breast cancer patients.

The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with breast carcinoma. In this study, a total of 603 breast cancer subjects from Turkey were screened for BRCA1/BRCA2 mutations using HDA and Sanger sequencing. In the present study, 21 BRCA1 and BRCA2 pathogenic variants were detected in 30 patients and BRCA1/2 mutations were significantly associated with a family history of breast/ovarian cancer.

Long noncoding RNA MALAT1 may be a prognostic biomarker in IDH1/2 wild-type primary glioblastomas.

Primary glioblastoma (GB) is the most aggressive type of brain tumors. While mutations in isocitrate dehydrogenase (IDH) genes are frequent in secondary GBs and correlate with a better prognosis, most primary GBs are IDH wild-type. Recent studies have shown that the long noncoding RNA metastasis associated lung adenocarcinoma transcript-1 (MALAT1) is associated with aggressive tumor phenotypes in different cancers.

Talazoparib Loaded Solid Lipid Nanoparticles: Preparation, Characterization and Evaluation of the Therapeutic Efficacy In vitro.

Objective: In the present work, we report for the first time the therapeutic potential of talazoparib (BMN 673)-SLNs for the treatment of BRCA1 deficient Triple Negative Breast Cancer (TNBC). BMN 673-SLNs were produced by hot-homogenization technique and then characterized.

Methods: The cytotoxic and apoptotic effects of BMN 673-SLNs compared with BMN 673 were determined on HCC1937BRCA1-/-, HCC1937-R resistant TNBC and MCF-10A control cell lines.

Investigation of new treatment option for hepatocellular carcinoma: a combination of sorafenib with usnic acid.

Objectives: Sorafenib (SOR) is an orally administered molecular targeted agent in the systemic chemotherapy of hepatocellular carcinoma (HCC). However, the partial response of SOR is limited due to its adverse side effect and high heterogeneity and resistant phenotype of HCC. In the current study, we investigated synergistic effects of SOR and usnic acid (UA) on HCC cell lines including HepG2 and SNU-449, and a normal cell line, HUVEC.

Synergistic effects of hormone therapy drugs and usnic acid on hormone receptor-positive breast and prostate cancer cells.

The aim of this study was to investigate the combined effects of usnic acid (UA) and Tamoxifen (Tam) or Enzalutamide (Enz) on hormone receptor-positive breast and prostate cancer (BC and PC), respectively. The antiproliferative and apoptotic effects of Tam or Enz alone and in combination with UA on MCF7 and LNCaP cancer cells were detected. The results of the WST-1 assay indicated that UA was a promising anticancer compound that significantly enhanced the effectiveness of hormone therapy drugs compared with each drug alone (combination index < 1).

BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile.

The objective of the present study was to elucidate the effect of BMN 673 (talozoparib) on BRCA1 mutant (HCC1937) and wild-type (MDA-MB-231) triple negative breast cancer (TNBC). The in vitro cytotoxicity results indicated that BMN 673 had considerable inhibitory effects on HCC1937 and MDA-MB-231 cell lines by inducing apoptosis, multicaspase activity, G2/M arrest, and altering the expression levels of apoptosis-related genes (P < 0.01).

RNA-based markers in biopsy cores with atypical small acinar proliferation: Predictive effect of T2E fusion positivity and MMP-2 upregulation for a subsequent prostate cancer diagnosis.

Background: Atypical small acinar proliferation (ASAP) is a precursor lesion of prostate cancer (PC), and PC develops from this suspicious focus or an unsampled malignant gland nearby. However, PC-related molecular alterations that could guide the timing of repeat biopsies and help monitor PC risk in ASAP-diagnosed patients have not been investigated. The purpose of this study was to first investigate the expression of seven different PC-related RNAs that included serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG) gene (TMPRSS2-ERG, T2E) fusion, alpha-methylacyl-CoA racemase (AMACR), kallikrein related peptidase 3 (KLK3), androgen receptor (AR), prostate cancer specific antigen 3 (PCA3), and matrix metalloproteinases (MMP)-2 and 9.