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The current study assessed the decision-making process before surgery in prostate cancer patients. A structured telephone interview was conducted by an independent third party in 162 consecutive patients who underwent surgery for prostate cancer. Responders revealed that details regarding diagnosis and treatment alternatives were withheld from a significant number of patients. Radiation and active surveillance were presented as alternative options to surgery in 57 (39%) and 20 (14%) of responders, respectively. Twenty-six (18%) patients reported not being informed regarding potential surgical side effects. Patients were not active participants in critical aspects of decision making in 61 (42%) of the cases. Being inadequately informed and more frequent visits to the urologist appeared to make decisions more difficult. Treatment regret was reported by 23 (16%) of the patients who underwent surgery and was more common when the patient was not involved in the decision or was inadequately informed. As such, shared decision making should replace paternalism when managing patients with localized prostate cancer in urologic practice.

The current study assessed the decision-making process before surgery in prostate cancer patients. A structured telephone interview was conducted by an independent third party in 162 consecutive patients who underwent surgery for prostate cancer. Responders revealed that details regarding diagnosis and treatment alternatives were withheld from a significant number of patients. Radiation and active surveillance were presented as alternative options to surgery in 57 (39%) and 20 (14%) of responders, respectively. Twenty-six (18%) patients reported not being informed regarding potential surgical side effects. Patients were not active participants in critical aspects of decision making in 61 (42%) of the cases. Being inadequately informed and more frequent visits to the urologist appeared to make decisions more difficult. Treatment regret was reported by 23 (16%) of the patients who underwent surgery and was more common when the patient was not involved in the decision or was inadequately informed. As such, shared decision making should replace paternalism when managing patients with localized prostate cancer in urologic practice. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate the effect of kinesiophobia on daily and sport activities. We compared Tampa scale of Kinesiophobia (TSK) with Tagner Activity score (TAS). We hypothesized that high level of Tampa scale of Kinesiophobia decreases Tagner Activity score. Materyal Methods:A total of 50 patients, with Anterior cruciate ligament (ACL) reconstruction surgery from January 2010 and December 2016 were included in this study. The patients completed the Lysholm Knee, TAS and TSK questionnaires postoperatively. KT-1000 arthrometer at 30 degrees knee flexion performed for both knees. The TSK score was compared with TAS and Lyshman knee score. Results:Mean age was 29.6 (18-50). Minimum follow-up was 12 months. Twenty of 50 patients (%40) had meniscal tears. The TAShad negative and significant correlation with TSK. Higher TSKled to lower TASand lower TSKled to higher TAS.There was no difference in Lysholm and TAS compared to TSKin patient with or without meniscal tear.Conclusion Our study showed that knee functions are not the only indicator to return preinjury daily and sport activities. Kinesiophobia may also play a significant role even if the Lyshman knee score is higher. The patients with Anterior cruciate ligamentinjury must be warned about the kinesiophobia. In our opinion, all the patients with Anterior cruciate ligamentruptures should have a kinesiophobia test. The patients who have high rate of kinesiophobia preoperatively, shouldhave a psychotherapy postoperatively in addition to their physical therapy.

Objective: Green Fluorescent Protein (GFP) has been used as a marker of gene expression and a single cell marker in living organisms in cell biology studies. The important areas that GFP is used are expression levels of different genes in different organisms by inserting GFP in these genes and as a marker in living cells. In this study, we tried to optimize transfection of mesenchymal stem cells, (MSCs) used for regeneration of damaged tissues in animals, by GFP containing plasmid vector by which MSCs can be followed in vivo. Material and Methods: To this aim, phM-GFP plasmid vector carrying GFP gene and effectene transfection reagent were used. Result: The data revealed that twice transfection of MSCs resulted in higher expression of GFP for longer times as compared to once transfected MSCs. On the other hand, leaving the chemical transfection agents in the medium induced apoptosis after a while. Conclusion: As a conclusion we suggest the transfection of MSCs twice with 48 hours interval and removal of transfection agents after 8 hours which removed toxic and apoptotic effects of the chemicals. [ABSTRACT FROM AUTHOR]

One of the studies on new drug delivery and release systems that has increased in recent years is the study using plasmonic nanoparticles. In this study, polydopamine nanoparticles (PDOP NPs), which contribute to photothermal drug release by near infrared radiation (NIR), were decorated with gold nanoparticles (AuNPs) to utilize their plasmonic properties, and a core-satellite-like system was formed. With this approach, epirubicin (EPI)-loaded PDOP NPs were prepared by utilizing the plasmonic properties of AuNPs. Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD) methods were used to evaluate the structural properties of these particles. The release behavior of the prepared structures in acidic (pH 5.0) and neutral (pH 7.4) environments based on the ON/OFF approach was also examined. The biocompatibility properties of the particles were evaluated on mouse fibroblast (L929) and anticancer activities on neuroblastoma (SH-SY5Y) cells. The effects of prepared EPI-loaded particles and laser-controlled drug release on ROS production, genotoxicity, and apoptosis were also investigated in SH-SY5Y cells. With the calculated combination index (CI) value, it was shown that the activity of EPI-loaded AuNP@PDOP NPs increased synergistically with the ON/OFF-based approach. The developed combination approach is considered to be remarkable and promising for further evaluation before clinical use., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/aim/aim: SARS-CoV-2 disease was announced as a pandemic by The World Health Organization in early 2020. It is still threatening the world population. Here, we aimed to produce hyperimmune sera that contain immunoglobulin G and F(ab')2 fragments sourced from horse antibodies as an urgent response to the pandemic., Materials and Methods: SARS-CoV-2 was produced and inactivated with three different methods [formaldehyde (FA), formaldehyde, and binary ethylene amine (FA + BEI), and heat treatment]. After in vitro inactivation control, immunogens were mixed with Freund’s adjuvant, thereafter horses (n: 2 for FA, 4 for FA + BEI, 2 for heat inactivation) and New Zealand rabbits (n: 6 for FA, 6 fo r FA + BEI, 6 for heat inactivation) were immunized four times. Neutralizing antibody levels of the sera were measured at the 4th, 6th, and 8th weeks. When the antibodies were detected at the peak level, plasma was collected from horses and hyperimmune sera procured after the purification process., Results: Horses and rabbits produced highly neutralizing antibodies against the SARS-CoV-2 in FA and FA + BEI inactivation groups, foreign proteins were removed effectively after purification., Conclusion: This study presents a profitable practice to develop specific antisera in horses against SARS-CoV-2 for emergency and low-cost response. In further studies, new purification methods can be used to increase the efficiency of the final product., Competing Interests: The authors have no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy. Paclitaxel (taxol), a diterpenoid pseudoalkaloid isolated from the shells of Taxus brevifolia, is the first taxane derivative used in the clinic for cancer treatment. Poly (lactic-co-glycolic acid) (PLGA) is one of the most successfully used biodegradable polymers for drug delivery which has a minimum systemic toxicity. This study aimed to evaluate the cytotoxicity and genotoxicity of paclitaxel nanoencapsulated with PLGA. Cytotoxic effects were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and genotoxic effects were determined by single cell gel electrophoresis (Comet) method in human neuroblastoma cells (SH-SY5Y). According to our results, the viability of cells treated with concentrations higher than 10 nM of free paclitaxel and paclitaxel loaded PLGA nanoparticles for 48 and 72 h was found lower than 50%. Additionally, DNA damage increased with the increase of nanoparticle dose when the cells exposed to paclitaxel loaded PLGA nanoparticles for 24, 48 and 72 h. It can be concluded that PLGA nanoparticles can be considered as a biocompatible carrier system for drug delivery and might be promising agent against neuroblastoma., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Platinum-based chemotherapy in non-small cell lung cancer (NSCLC) has been demonstrated as a promising approach by many researchers. However, due to low bioavailability and several side effects, drug targeting to lungs by intravenous administration is not a common route of administration., Objective: In this study, oxaliplatin loaded polycaprolactone (PCL) nanoparticles were prepared to overcome the limitations of the drug. 3 3 factorial design was used to evaluate the combined effect of the selected variables on the nanoparticle characteristics and to optimize oxaliplatin loaded PCL nanoparticles., Methods: The factorial design was used to study the influence of three different independent variables on the response of nanoparticle particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. The cellular uptakes of oxaliplatin loaded nanoparticles with different molecular weights of PCL were evaluated. Moreover, optimized nanoparticles were evaluated for their efficacy in non-small lung cancer using the SK-MES-1 cell line., Results: In factorial design, it is found that the homogenization speed and surfactant ratio represented the main factors influencing particle size and PDI and did not seem to depend on the PCL ratio. While the cytotoxicity of free oxaliplatin and oxaliplatin loaded nanoparticles were similar in low drug doses (2.5 and 25 μg/mL), the cytotoxicity of oxaliplatin loaded nanoparticles on SK-MES-1 cell was found higher in higher doses (p < 0.05). Moreover, oxaliplatin nanoparticles formulated with different molecular weights of PCL did not show significant differences in cellular uptake in 1 h and 2 h. However, the uptake of PCL 80000 NPs was found significantly greater than free oxaliplatin at 4 h (p < 0.05)., Conclusion: Hence, the development of oxaliplatin loaded PCL nanoparticles can be a useful approach for effective NSCLC therapy. Development, optimization and in vitro evaluation of oxaliplatin loaded nanoparticles in non-small cell lung cancer.

Nerve agents (NA) are chemical warfare munitions and their exposure causes a progressive inhibition of acetylcholinesterase (AChE). This inhibition causes NA-induced brain damage in central nervous system (CNS). Oximes reactivate AChE in both the peripheral nervous system and the CNS. Transport of the oxime across the blood-brain barrier (BBB) in the existed therapeutic concentrations at the brain parenchyma determines the effectiveness of antidote therapy on respiratory depression and NA-induced brain damage. However, oximes could not cross the BBB in therapeutic concentrations. The aim of this study was to load AChE reactivator obidoxime chloride to PLGA and PEG-b-PLGA nanoparticles and to improve the BBB transport of the molecule. Brain microvascular endothelial cells were used as the BBB model. 79.3 ± 4.2% of obidoxime was released from PLGA nanoparticles and 88.2 ± 4.4% of obidoxime was released from PEG-b-PLGA nanoparticles within 24 h. It was found that PEG-b-PLGA nanoparticles were ideal drug carrier because of its low tissue toxicity, few side effects, and controllable drug release profile. Transport efficiency of obidoxime across the BBB is a major challenge in the prevention of the CNS, the effectiveness of NA poisoning and new strategies like using obidoxime-loaded PEG-b-PLGA nanoparticles could overcome this challenge for the management of NA-induced brain damage., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Multidrug resistance (MDR) is the most common problem of inadequate therapeutic response in tumor cells. Many trials has been developed to overcome drug efflux by P-glycoprotein (P-gp). For instance, co-administration of a number of drugs called chemosensitizers or MDR modulators with a chemotherapeutic agent to inhibit drug efflux. But for optimal synergy, the drug and inhibitor combination may need to be temporally colocalized in the tumor cells. In this study, we encapsulated the Ver and Dox in PLGA nanoparticles to inhibit the P-gp drug efflux in breast cancer. Moreover, the effect of either Dox solution (Dox S ), Dox nanoparticles (Dox NP ), Dox S  + Ver S , Dox NP  + Ver S , Dox NP  + Ver NP or Dox-Ver NP was evaluated. It was found that co administration of Dox NP with Ver NP (70.76%) showed similar cellular uptake of Dox to Dox/Ver combination solution (70.62%). However it is observed that Dox NP  + Ver NP has the highest apoptotic activity (early apoptotic 13.52 ± 0.06%, late apoptotic 53.94 ± 0.15%) on human breast adenocarcinoma (MCF 7) cells. Hence, it is suggested that Dox NP  + Ver NP is a promising administration for tumor therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Published by Elsevier B.V. on behalf of King Saud University.)

Background: Compared to polymeric nanoparticles prepared using non-lipid surfactants, lecithin addition forms larger nanoparticles and exhibits higher drug loading and the stability of nanoparticles can be conferred by adding Vitamin E Polyethylene Glycol Succinate (TPGS) into the formulation., Aim: The aim of this study is to prepare Gemcitabine (Gem) loaded lecithin/PLGA nanoparticles. Moreover, the effect of TPGS and sodium cholate (SK) on the preparation of lecithin/PLGA nanoparticles was compared., Methods: It was found that while PC addition into PLGATPGS nanoparticles formed larger particles (251.3± 6.0 nm for Gem-PLGATPGS NPs and 516,9 ± 3.9 nm for Gem-PLGA-PCTPGS NPs), the particle size of PLGASK nanoparticles was not affected by lecithin addition (p>0.05;)., Results: In cytotoxicity studies, it was found that the SK-MES-1 cell inhibition rates of Gem-PLGATPGS NPs, Gem-PLGA-PCTPGS NPs, Gem-PLGASK NPs, Gem-PLGA-PCSK NPs were similar with free Gem (p>0.05;). In cytotoxicity studies, it was found that the encapsulation into nanoparticles did not change the cytotoxicity of the drug. However, higher cellular uptake has been observed when the lecithin was used in the preparation of PLGA nanoparticles., Conclusion: Compared with free Gem, the Gem-loaded nanoparticles enhanced the uptake of the drug by SK-MES-1 cells which can increase the effect of gemcitabine for non-small cell lung cancer therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The tumor microenvironment is fundamental to cancer progression, and the influence of its mechanical properties is increasingly being appreciated. Tamoxifen has been used for many years to treat estrogen-positive breast cancer. Here we report that tamoxifen regulates the level and activity of collagen cross-linking and degradative enzymes, and hence the organization of the extracellular matrix, via a mechanism involving both the G protein-coupled estrogen receptor (GPER) and hypoxia-inducible factor-1 alpha (HIF-1A). We show that tamoxifen reduces HIF-1A levels by suppressing myosin-dependent contractility and matrix stiffness mechanosensing. Tamoxifen also downregulates hypoxia-regulated genes and increases vascularization in PDAC tissues. Our findings implicate the GPER/HIF-1A axis as a master regulator of peri-tumoral stromal remodeling and the fibrovascular tumor microenvironment and offer a paradigm shift for tamoxifen from a well-established drug in breast cancer hormonal therapy to an alternative candidate for stromal targeting strategies in PDAC and possibly other cancers., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

The mechanical properties of the tumor microenvironment are emerging as attractive targets for the development of therapies. Tamoxifen, an agonist of the G protein-coupled estrogen receptor (GPER), is widely used to treat estrogen-positive breast cancer. Here, we show that tamoxifen mechanically reprograms the tumor microenvironment through a newly identified GPER-mediated mechanism. Tamoxifen inhibits the myofibroblastic differentiation of pancreatic stellate cells (PSCs) in the tumor microenvironment of pancreatic cancer in an acto-myosin-dependent manner via RhoA-mediated contractility, YAP deactivation, and GPER signaling. This hampers the ability of PSCs to remodel the extracellular matrix and to promote cancer cell invasion. Tamoxifen also reduces the recruitment and polarization to the M2 phenotype of tumor-associated macrophages. Our results highlight GPER as a mechanical regulator of the tumor microenvironment that targets the three hallmarks of pancreatic cancer: desmoplasia, inflammation, and immune suppression. The well-established safety of tamoxifen in clinics may offer the possibility to redirect the singular focus of tamoxifen on the cancer cells to the greater tumor microenvironment and lead a new strategy of drug repurposing., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Normal myoepithelial cells (MECs) play an important tumour-suppressor role in the breast but display an altered phenotype in ductal carcinoma in situ (DCIS), gaining tumour-promoter functions. Matrix metalloproteinase-8 (MMP-8) is expressed by normal MECs but is lost in DCIS. This study investigated the function of MMP-8 in MECs and the impact of its loss in DCIS., Methods: Primary normal and DCIS-associated MECs, and normal (N-1089) and DCIS-modified myoepithelial (β6-1089) cell lines, were used to assess MMP-8 expression and function. β6-1089 lacking MMP-8 were transfected with MMP-8 WT and catalytically inactive MMP-8 EA, and MMP-8 in N-1089 MEC was knocked down with siRNA. The effect on adhesion and migration to extracellular matrix (ECM), localisation of α6β4 integrin to hemidesmosomes (HD), TGF-β signalling and gelatinase activity was measured. The effect of altering MEC MMP-8 expression on tumour cell invasion was investigated in 2D and 3D organotypic models., Results: Assessment of primary cells and MEC lines confirmed expression of MMP-8 in normal MEC and its loss in DCIS-MEC. Over-expression of MMP-8 WT but not MMP-8 EA in β6-1089 cells increased adhesion to ECM proteins and reduced migration. Conversely, knock-down of MMP-8 in N-1089 reduced adhesion and increased migration. Expression of MMP-8 WT in β6-1089 led to greater localisation of α6β4 to HD and reduced retraction fibre formation, this being reversed by MMP-8 knock-down in N-1089. Over-expression of MMP-8 WT reduced TGF-β signalling and gelatinolytic activity. MMP-8 knock-down enhanced TGF-β signalling and gelatinolytic activity, which was reversed by blocking MMP-9 by knock-down or an inhibitor. MMP-8 WT but not MMP-8 EA over-expression in β6-1089 reduced breast cancer cell invasion in 2D and 3D invasion assays, while MMP-8 knock-down in N-1089 enhanced cancer cell invasion. Staining of breast cancer cases for MMP-8 revealed a statistically significant loss of MMP-8 expression in DCIS with invasion versus pure DCIS (p = 0.001)., Conclusions: These data indicate MMP-8 is a vital component of the myoepithelial tumour-suppressor function. It restores MEC interaction with the matrix, opposes TGF-β signalling and MMP-9 proteolysis, which contributes to inhibition of tumour cell invasion. Assessment of MMP-8 expression may help to determine risk of DCIS progression.

Objective: To evaluate the cytotoxicity and mineralization effects of TEGDMA in human dental pulp cells (hDPCs) under hypoxic and normoxic culture conditions., Design: Cell viability was evaluated using XTT assay after incubation periods of 24, 48, or 72h. The expression of mineralization-related genes (osteonectin, osteopontin, dentin sialophosphoprotein, collagen type 1) and heme oxygenase 1 (HO-1) was assessed by quantitative real-time polymerase chain reaction at 24 and 72h., Results: In XTT assay, viability was higher in 0.3, 1, 2, 4, and 5mM groups in the presence of 21% O 2 after 24h (p<0.05). Additionally, while 0.3, 1, 2mM groups had higher cell viability in the presence of 21% O 2 after 48h (p<0.05), in 3mM groups cell viability was higher under 3% O 2 than 21% O 2 after both 24 and 48h (p<0.05). 1-3mM groups had higher cell viability under 3% O 2 after 72h (p<0.05). There was no difference between 4 and 5mM groups with regards to cell viability after 48 or 72h (p>0.05). In the gene expression study, TEGDMA-treated hDPCs showed lower mineralization potential in the presence of 3% than with 21% O 2 (p<0.05). hDPCs revealed higher HO 1 expression in 0.3 and 1mM groups under hypoxic than under normoxic conditions after a 72-h time period (p<0.001)., Conclusions: Hypoxic conditions increased cell survival in accordance with the culture period but inhibited the odontoblastic differentiation of hDPCs treated with TEGDMA., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The hallmark of pancreatic ductal adenocarcinoma (PDAC) is abundant desmoplasia, which is orchestrated by pancreatic stellate cells (PSCs) and accounts for the majority of the stroma surrounding the tumour. Healthy PSCs are quiescent, but upon activation during disease progression, they adopt a myofibroblast-contractile phenotype and secrete and concomitantly reorganise the stiff extracellular matrix (ECM). Transforming growth factor β (TGF-β) is a potent activator of PSCs, and its activation requires spatiotemporal organisation of cellular and extracellular cues to liberate it from an inactive complex with latent TGF-β binding protein (LTBP). Here we study the mechanical activation of TGF-β by PSCs in vitro by investigating LTBP-1 organisation with fibrillar fibronectin and show that all trans-retinoic acid (ATRA), which induces PSC quiescence, down-regulates the ability of PSCs to mechanically organise LTBP-1 and activate TGF-β through a mechanism involving myosin II dependent contractility. Therefore, ATRA inhibits the ability of PSCs to mechanically release active TGF-β, which might otherwise act in an autocrine manner to sustain PSCs in an active state and a tumour-favouring stiff microenvironment.

Extracellular matrix (ECM) remodelling is integral to numerous physiological and pathological processes in biology, such as embryogenesis, wound healing, fibrosis and cancer. Until recently, most cellular studies have been conducted on 2D environments where mechanical cues significantly differ from physiologically relevant 3D environments, impacting cellular behaviour and masking the interpretation of cellular function in health and disease. We present an integrated methodology where cell-ECM interactions can be investigated in 3D environments via ECM remodelling. Monitoring and quantification of collagen-I structure in remodelled matrices, through designated algorithms, show that 3D matrices can be used to correlate remodelling with increased ECM stiffness observed in fibrosis. Pancreatic stellate cells (PSCs) are the key effectors of the stromal fibrosis associated to pancreatic cancer. We use PSCs to implement our methodology and demonstrate that PSC matrix remodelling capabilities depend on their contractile machinery and β1 integrin-mediated cell-ECM attachment., (© 2016. Published by The Company of Biologists Ltd.)

We evaluated the gene expression profiles of human dental pulp cells exposed to iRoot BP using microarray after 24 and 72 h. The results were verified using quantitative reverse transcriptase PCR analysis. Of the 36,000 transcripts arrayed, 21 were up-regulated and 15 were down-regulated by more than two fold. The largest group of up-regulated genes included those involved in nucleobase-containing compound metabolic processes, cell communication, protein metabolic processes, developmental processes, and biological regulation. The largest groups of down-regulated genes were those involved in cell communication, development, and biological regulation processes. In conclusion, iRoot BP affects the expression of genes involved in different biological processes in human dental pulp cells. (J Oral Sci 58, 307-315, 2016).

Objective: Interleukin-18 (IL-18) is a cytokine that belongs to the IL-1 superfamily and is secreted by various immune and nonimmune cells. Evidence has shown that IL-18 has both anticancer and procancer effects. The aim of this study was to evaluate the relationship between IL-18 gene polymorphisms and susceptibility to chronic lymphocytic leukemias (CLL) and chronic myelogenous leukemias (CML) in Turkish patients., Materials and Methods: The frequencies of polymorphisms (rs61667799(G/T), rs5744227(C/G), rs5744228(A/G), and rs187238(G/C)) were studied in 20 CLL patients, 30 CML patients, and 30 healthy individuals. The genotyping was performed by polymerase chain reaction and DNA sequencing analysis., Results: Significant associations were detected between the IL-18 rs187238(G/C) polymorphism and chronic leukemia. A higher prevalence of the C allele was found in CML cases with respect to controls. The GC heterozygous and CC homozygous genotypes were associated with risk of CML when compared with controls. However, prevalence of the C allele was not significantly high in CLL cases with respect to controls. There was only a significant difference between the homozygous CC genotype of CLL patients and the control group; thus, it can be concluded that the CC genotype may be associated with the risk of CLL. Based on our data, there were no significant associations between the IL-18 rs61667799(G/T), rs5744227(C/G), or rs5744228(A/G) polymorphisms and CLL or CML., Conclusions: IL-18 gene promoter rs187238(G/C) polymorphism is associated with chronic leukemia in the Turkish population. However, due to the limited number of studied patients, these are preliminary results that show the association between -137G/C polymorphism and patients (CLL and CML). Further large-scale studies combined with haplotype and expression analysis are required to validate the current findings.

Background: The majority of Achillea species are the most important native economic plants of Anatolia. They include highly bioactive compounds, so they have therapeutic applications., Objective: In the present study, the aim was to investigate in vitro anti-oxidant, cytotoxic and pro-apoptotic effects of Achillea teretifolia Willd extracts (Turkish name: Beyaz civanperÇemi)., Materials and Methods: The anti-oxidant potential of the extracts was analyzed by the free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and total phenolic content methods. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to detect cytotoxicity of the extracts onhuman prostate cancer cell lines (DU145 and PC-3) and human gingival fibroblast (HGF) cells. mRNA expression levels of pro-apoptotic (bax, caspase-3) and anti-apoptotic (bcl-2) genes were measured by quantitative real-time polymerase chain reaction., Results: The results showed that extracts exhibited a remarkable DPPH scavenging activity, and total phenolic content of the methanol extract was higher than that of the water extract. As time and concentration were increased, the methanol extract exhibited a more powerful cytotoxic effect on prostate cancer cells. In prostate cancer cells, the levels of mRNA expression of the bax and caspase-3 genes were significantly up-regulated (P < 0.05), whereas the expression of bcl-2 was down-regulated (P < 0.05). In HGF cells, there were no cytotoxic effect and apoptosis induction triggered by the extracts., Conclusion: The methanol extract had more powerful anti-oxidant, cytotoxic and pro-apoptotic effects than the water extract. The extracts could be good anti-oxidant sources, and they might include anti-cancer compounds triggering the cytotoxicity and the apoptosis on prostate cancer cells.

Background/aim: In this study, the in vitro and in vivo effectiveness of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE) in combination with bortezomib, a proteasome inhibitor, was explored in multiple myeloma (MM) cells., Materials and Methods: The cytotoxic effects of CAPE and bortezomib were determined by XTT cell proliferation assay. Apoptosis levels were analyzed with annexin V-fluorescein isothiocyanate, nuclear factor kappa beta (NF-κB) was analyzed with electrophoretic mobility-shift assay, and interleukin (IL)-6 levels were analyzed with enzyme-linked immunosorbent assay to evaluate CAPE's mechanism of action. To investigate the in vivo effectiveness of CAPE and bortezomib, an experimental plasmacytoma model was induced in BALB/c mice., Results: Increasing concentrations of CAPE and bortezomib decreased the proliferation of ARH-77 cells in a dose-dependent manner. With doses of CAPE IC50, a significant increase in apoptosis and a significant decrease in IL-6 levels were detected. The NF-κB DNA- binding activity decreased compared to the basal ARH-77 level. The administration of CAPE alone or in combination with bortezomib increased the rate of survival compared to the control group., Conclusion: We think that our study, which is the first to demonstrate the in vitro and in vivo effectiveness of the.combined use of CAPE and bortezomib, will be a pioneer for future human applications of CAPE in MM.

Objective: To investigate the in vitro antimicrobial potential of Thermopsis turcica Kit Tan, Vural & Küçüködük against periodontopathogenic bacteria, its antioxidant activity and cytotoxic effect on various cancer cell lines., Methods: In vitro antimicrobial activities of ethanol, methanol, ethyl acetate (EtAc), n-hexane and water extracts of Thermopsis turcica herb against periodontopathogenic bacteria, Aggregatibacter actinomycetemcomitans ATCC 29523 and Porphyromonas gingivalis ATCC 33277 were tested by agar well diffusion, minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Antioxidant properties of the extracts were evaluated by 1,1-diphenyl-2-picryl-hydrazyl radical scavenging activity and β-carotene bleaching methods. Amounts of phenolic contents of the extracts were also analysed by using the Folin-Ciocalteu reagent. Additionally, cytotoxic activity of the extracts on androgen-insensitive prostate cancer, androgen-sensitive prostate cancer, chronic myelogenous leukemia and acute promyelocytic leukemia human cancer cell lines were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Human gingival fibroblast cells were used as a control., Results: Our data showed that EtAc extract had the highest antimicrobial effect on Aggregatibacter actinomycetemcomitans (MIC: 1.562 mg/mL, MBC: 3.124 mg/mL) and Porphyromonas gingivalis (MIC: 0.781 mg/mL, MBC: 1.562 mg/mL). In antioxidant assays, EtAc extract exhibited also the highest radical scavenging activity [IC50=(30.0±0.3) µg/mL] and the highest inhibition [(74.35±0.30)%] against lineloic acide oxidation. The amount of phenolic content of it was also the highest [(162.5±1.2) µg/mg gallic acid]. In cytotoxic assay, only ethanol [IC50=(80.00±1.21) µg/mL] and EtAc extract [IC50=(70.0±0.9) µg/mL] were toxic on acute promyelocytic leukemia cells at 20-100 µg/mL (P<0.05). However, no toxic effect was observed on human gingival fibroblast cells., Conclusions: According to our findings, owing to its antioxidant and cytotoxic potential, EtAc extract might include anticancer agents for acute promyelocytic leukemia.

Modern medicinal agents currently available for treatment of cancers are very expensive, toxic, and less effective in treating some of the disease. Thus, one must investigate further in detail the agents derived from natural sources, such as grape seed, for the prevention and treatment of cancer and disease. In recent years interest of researchers has focused on grape seed and nowadays scientists have used extracts of grape seed to treat different health problems including cancer. We examined the cytotoxic effect of red grape seed extract (GSE) and its main compound resveratrol (RES) on different human cancer cell lines representing various solid tumors and hematological malignancies at the same time. Red GSE was prepared by using 1, 1, 1, 2- Tetrafluoroethane extraction method. Cytotoxicity of the extract and RES was evaluated by using trypan blue dye exclusion method and MTT assay. The results of our study show that GSE and RES have cytotoxic activities in varying degree in several cancer cell lines. There has not been any study evaluating the GES and RES in the same cell lines and in the same conditions. But, it is still needed to have more pre-clinical and laboratory studies to validate the usefulness of these agents either alone or in combination with existing therapy.