Comparisons between Tethyan Anorthosite-bearing Ophiolites and Archean Anorthosite-bearing Layered Intrusions: Implications for Archean Geodynamic Processes

Elucidating the petrogenesis and geodynamic setting(s) of anorthosites in Archean layered intrusions and Tethyan ophiolites has significant implications for crustal evolution and growth throughout Earth history. Archean anorthosite-bearing layered intrusions occur on every continent. Tethyan ophiolites occur in Europe, Africa, and Asia. In this contribution, the field, petrographic, petrological, and geochemical characteristics of 100 Tethyan anorthosite-bearing ophiolites and 155 Archean anorthosite-bearing layered intrusions are compared. Tethyan anorthosite-bearing ophiolites range from Devonian to Paleocene in age, are variably composite, contain anorthosites with highly calcic (An44-100) plagioclase and magmatic amphibole. These ophiolites formed predominantly at convergent plate margins, with some forming in mid-ocean ridge, continental rift, and mantle plume settings. The predominantly convergent plate margin tectonic setting of Tethyan anorthosite-bearing ophiolites is indicated by negative Nb and Ti anomalies and magmatic amphibole. Archean anorthosite-bearing layered intrusions are Eoarchean to Neoarchean in age, have megacrystic anorthosites with highly calcic (An20-100) plagioclase and magmatic amphibole and are interlayered with gabbros and leucogabbros and intrude pillow basalts. These Archean layered intrusions are interpreted to have predominantly formed at convergent plate margins, with the remainder forming in mantle plume, continental rift, oceanic plateau, post-orogenic, anorogenic, mid-ocean ridge, and passive continental margin settings. These layered intrusions predominantly crystallized from hydrous Ca- and Al-rich tholeiitic magmas. The field, petrographic and geochemical similarities between Archean and Tethyan anorthosites indicate that they were produced by similar geodynamic processes mainly in suprasubduction zone settings. We suggest that Archean anorthosite-bearing layered intrusions and spatially associated greenstone belts represent dismembered subduction-related Archean ophiolites

Investigation of anticancer mechanism of oleuropein via cell cycle and apoptotic pathways in SH-SY5Y neuroblastoma cells.

Neuroblastoma is one of the most common types of pediatric tumors that can spread quickly in neuronal tissues. Oleuropein which is active compound of olive leaves, belongs to polyphenols group and has antioxidant, anti-microbial, anti-inflammatory, anti-hypertensive and anti-carcinogenic effects. The aim of the study is to determine the therapeutic effects of oleuropein on cell proliferation, invasion, colony formation, cell cycle and apoptotic mechanisms in SH-SY5Y neuroblastoma cell line under in vitro conditions. The effect of oleuropein on cell viability was determined by XTT method. 84 cell cycle control and 84 apoptosis related genes were evaluated by RT-PCR. Effects of oleuropein on apoptosis were researched by TUNEL assay. Protein expressions were determined by western blot analysis. Effects of oleuropein on cell invasion, colony formation and migration were detected by matrigel-chamber, colony formation assay and wound-healing assay, respectively. IC50 value of oleuropein in SH-SY5Y cells was detected as 350 μM at 48th hours. It is determined that oleuropein causes cell cycle arrest by down-regulating of CylinD1,CylinD2,CyclinD3,CDK4,CDK6 and up-regulating of p53 and CDKN2A, CDKN2B, CDKN1A gene expressions. Oleuropein also induces apoptosis by inhibiting of Bcl-2 and activating of Bax,caspase-9 and caspase-3 gene expressions. Apoptotic cell ratio was found 36.4 ± 3.27% in oleuropein dose group. Oleuropein decreased invasion in SH-SY5Y cells and suppressed colony numbers in ratio of 53.6 ± 4.71%.Our results demonstrated that oleuropein can be a therapeutic agent in the treatment of neuroblastoma

Assessment of the anticancer mechanism of ferulic acid via cell cycle and apoptotic pathways in human prostate cancer cell lines.

Studies on genetic changes underlying prostate cancer and the possible signaling pathways are getting increased day by day, and new treatment methods are being searched for. The aim of the present study is to investigate the effects of ferulic acid (FA), a phenolic compound, on cell cycle, apoptosis, invasion, and colony formation in the PC-3 and LNCaP prostate cancer cells. The effect of FA on cell viability was determined via a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method. Total RNA was isolated with Tri Reagent. Expression of 84 genes for both cell cycle and apoptosis separately was evaluated by reverse transcriptase PCR (RT-PCR). Protein expressions were evaluated by Western blot analysis. Furthermore, apoptotic effects of FA were observed with terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) assay. Effects of FA on cell invasion and colony formation were determined using Matrigel chamber and colony assay, respectively. The half maximal inhibitory concentration (IC50) dose of FA was found to be 300 μM in PC-3 cells and 500 μM in LNCaP cells. According to RT-PCR results, it was observed that FA inhibited cell proliferation by increasing the gene expressions of ATR, ATM, CDKN1A, CDKN1B, E2F4, RB1, and TP53 and decreasing the gene expressions of CCND1, CCND2, CCND3, CDK2, CDK4, and CDK6 in PC-3 cells. On the other hand, it was seen that FA suppressed cell proliferation by increasing in the gene expressions of CASP1, CASP2, CASP8, CYCS, FAS, FASLG, and TRADD and decreasing in the gene expressions of BCL2 and XIAP in LNCaP cells. In this study, protein expression of CDK4 and BCL2 genes significantly decreased in these cells. It could induce apoptosis in PC-3 and LNCaP cells. Also, it was observed that FA suppressed the invasion in PC-3 and LNCaP cells. Moreover, it suppressed the colony formation. In conclusion, it has been observed that FA may lead to cell cycle arrest in PC-3 cells while it may cause apoptosis in LNCaP cells

Determination of O⁶-methylguanine DNA methyltransferase promoter methylation in non-small cell lung cancer.

Aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of the tumor-related genes including DNA repair genes. The objective of this study was to determine the frequency of promoter methylation of the O⁶-methylguanine DNA methyltransferase (MGMT) gene as a DNA repair gene in nonsmall cell lung cancer (NSCLC) and to analyze the correlation with clinicopathological parameters including age, gender, smoking status, histological subtype, and clinical stage. Eighty patients with NSCLC were included in this study. The analysis of DNA methylation was performed on formalin-fixed, paraffin-embedded lung cancer tissues. Following DNA isolation and bisulfite treatment, DNA methylation was analyzed by methylation-specific real-time polymerase chain reaction. MGMT promoter methylation was detected in 51 of 80 (64%) NSCLC patients. There was a significant correlation between MGMT methylation and tumor stage (p = 0.01). The frequencies of the promoter methylation of MGMT gene in smokers and older patients were higher than in their counterparts. In conclusion, the present study provides strong evidence for a higher frequency of promoter methylation of the MGMT gene in NSCLC, indicating that it is a common event during the carcinogenesis of NSCLC

The determination of relationship between "excision repair cross-complementing group 1" (ERCC1) gene T19007C and C8092A single nucleotide polymorphisms and clinicopathological parameters in non-small cell lung cancer.

DNA repair plays a key role in prevention of carcinogenesis and one of the most important DNA repair mechanisms is nucleotide excision repair (NER) pathway. This pathway includes a number of genes such as excision repair cross-complementing group 1 (ERCC1) gene which are responsible for the 5' incision of damaged DNA. A reduced DNA repair capacity associated with ERCC1 mRNA level has been observed in lung carcinogenesis. Two single nucleotide polymorphisms (SNPs) in ERCC1 gene, T19007C (rs11615) and C8092A (rs3212986), reportedly predict to affect the mRNA of ERCC1 in non-small cell lung cancer (NSCLC). To examine the role of two common SNPs in ERCC1 gene further, we conducted this study where 80 cases histopatologically diagnosed as NSCLC were genotyped. Genomic DNA was extracted from formalin-fixed, paraffin embedded tissues and two SNPs were analyzed using real-time PCR. The distributions of TT, TC, and CC genotypes of the T19007C SNP were 40, 44 and 16%, respectively. Significantly increased frequency of the patients carrying at least one 19007C allele was observed in early stage compared to advanced stage (P=0.002). And also, the frequency of TC and CC genotypes significantly increased in younger patients compared to older patients (P=0.035). Regarding C8092A SNP, the distribution of CC, CA, and AA genotypes was 38, 51 and 11%, respectively. There was no significant difference in the genotype distribution between C8092A SNP and clinicopathological parameters. This study indicated that harboring at least one 19007C allele may have protective effect in NSCLC

Expression of ERCC1 and its clinicopathological correlations in non-small cell lung cancer.

Excision Repair Cross-Complementing Group 1 (ERCC1) is an important DNA repair gene, playing critical role in nucleotide excision repair pathway and having a significant influence on genomic instability. Some studies support that ERCC1 might be a potential predictive and prognostic marker in non-small cell lung cancer (NSCLC). ERCC1 has also been shown to be a promising biomarker in NSCLC treated with a cisplatin-based regimen. Therefore, the determination of ERCC1 expression at DNA, mRNA and protein level in different stages of NSCLC is still an important topic in the cancer. Ninety-one formalin-fixed paraffin-embedded tumor samples histopathologically diagnosed as NSCLC were examined in this study. ERCC1 expression at protein level were scored by immunohistochemistry. The gene amplification and mRNA expression levels for ERCC1 were determined by real-time quantitative PCR. There was complete concordance among the three methods in 39 tumor samples (42.9%). A strong correlation was found between DNA amplification and mRNA expression (r=0.662) while there was no correlation between mRNA and protein assessment for ERCC1 expression (r=-0.013). ERCC1 expression at mRNA and DNA level (63.1 and 84.2%, respectively) in tumors at stage III was higher than at the other stages. In contrast, the protein expression at stage II and III (56.6 and 52.6%, respectively) of NSCLC was lower than that of tumors with stage I NSCLC. These results show that the mechanism by which ERCC1 expression might play a role in tumor behavior. This study was also confirmed that the appropriate validation and qualification in methods used for ERCC1 status were needed before its clinical application and implementation

Petrology of ultramafic to mafic cumulate rocks from the Göksun (Kahramanmaraş) ophiolite, southeast Turkey

The Göksun (Kahramanmaraş) ophiolite (GKO), cropping out in a tectonic window bounded by the Malatya metamorphic unit on both the north and south, is located in the EW-trending lower nappe zone of the southeast Anatolian orogenic belt (Turkey). It exhibits a complete oceanic lithospheric section and overlies the Middle Eocene Maden Group/Complex with a tectonic contact at its base. The ophiolitic rocks and the tectonically overlying Malatya metamorphic (continental) unit were intruded by I-type calc-alkaline Late Cretaceous granitoid (~81–84 Ma). The ultramafic to cumulates in the GKO are represented by wehrlite, plagioclase wehrlite, olivine gabbro and gabbro. The crystallization order for the cumulate rocks is as follows: olivine ± chromian spinel›clinopyroxene›plagioclase. The major and trace element geochemistry as well as the mineral chemistry of the ultramafic to mafic cumulate rocks suggest that the primary magma generating the GKO is compositionally similar to that observed in the modern island-arc tholeiitic sequences. The mineral chemistry of the ultramafic to mafic cumulates indicates that they were derived from a mantle source that was previously depleted by earlier partial melting events. The highly magnesian olivine (Fo77–83), clinopyroxene (Mg# of 82–90) and the highly Ca-plagioclase (An81–89) exhibit a close similarity to those, which formed in a supra-subduction zone (SSZ) setting. The field and the geochemical evidence suggest that the GKO formed as part of a much larger sheet of oceanic lithosphere, which accreted to the base of the Tauride active continental margin, including the İspendere, Kömürhan and the Guleman ophiolites. The latter were contemporaneous and genetically/tectonically related within the same SSZ setting during the closure of the Neotethyan oceanic basin (Berit Ocean) between the Taurides to the north and the Bitlis-Pütürge massif to the south during the Late Cretaceous. © 2019 China University of Geosciences (Beijing) and Peking UniversityGovernment Council on Grants, Russian Federation Firat University Scientific Research Projects Management Unit: MMF2002BAP41 YDABÇAG-199Y011Emilio Saccani, Laura Gaggero and anonymous reviewer are thanked for their constructive and very valuable comments that improved the quality of the paper. The authors would like to thank Fabio Capponi for performing XRF major and trace element analyses at Geneva (Switzerland) University. Dan Topa is thanked for his guidance during the microprobe analysis at Salzburg (Austria) University. This research was supported by TÜBİTAK ( YDABÇAG-199Y011 ) and the Çukurova University Scientific Research Projects ( MMF2002BAP41 ). OP acknowledges the Open Fund (GPMR201702) of State Key Lab of Geological Processes and Mineral Resources, China University of Geosciences, Wuhan. CI acknowledges subsidy by the Russian Government to support the Program of competitive growth of Kazan Federal University. Appendix