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Akciğer Kanseri Kök Hücrelerinde Naked İfadesinin Düzenlenmesinde Histon Modifikasyonlarının Rolünün Araştırılması
(2020) Ulukaya, Engin; Sapancı, Selin; Bozkurt, Süreyya; Aztopal, Nazlıhan
Epigenetik değişiklikler, geleneksel tedaviye dirençten sorumlu tutulan kanser kök hücrelerin (KKH) özelliklerinin düzenlenmesinde anahtar bir role sahiptir. Bu hücrelerde, Wnt/ ß-katenin sinyalizasyonunun yeniden/aşırı aktive olduğu ve sürecin epigenetik mekanizmalar tarafından düzenlendiği bilinmektedir. Dolayısıyla, ilgili epigenetik düzenekleri hedefleyen yaklaşımlarla KKH?lerinin terapötik olarak hedeflenebildiği gösterilmiştir. Özellikle, yolağı inaktif durumda tutan ana düzenleyicilerin aktivitesinin epigenetik modifikasyonlar aracılığıyla baskılanması kötü prognoz ile ilişkilendirilmektedir. Bu nedenle, proje önerisi kapsamında, akciğer kanseri KKH?lerinde epigenetik inhibitörlerle manipülasyon sonrası Wnt/ß-katenin sinyal yolağının negatif düzenleyici bileşeni Naked (NKD1 ve NKD2) düzeylerinde değişimin araştırılması ve sürece katkı sağlayan ilgili histon modifikasyonlarının belirlenmesi amaçlanmıştır. Öncelikli olarak, parental H1299 hücre soyu (H1299/P) içindeki KKH sayısı göreceli olarak arttırıldı (propagasyon, H1299/S) ve KKH?lere karakteristik yüzey belirteci oranları akım sitometri ile gösterildi. Ardından, histon demetilaz inhibitörü /DZNep ile ön tedavi uygulanan hücreler histon deasetilaz inhibitörü/TSA ile muamele edildi ve sitotoksik etki araştırıldı. İnhibitörlerin tek başlarına toksik etki sergilemedikleri dozların (0.1-0.25 uM) kombine kullanımında güçlü sitotoksik etki saptandı. H1299/S?in agresif karakteri ile ilişkili olarak NKD2?nin gen ve protein düzeylerinde azalma olduğu ve kombinasyon uygulaması sonrası ifadesinin yeniden düzenlendiği (artış) RT-PCR ve western blotting ile gösterildi. Wnt/ ß-katenin sinyal yolağı aktivitesi, EMT süreci ve ?stemness? ilişkili değişiklikler western blotting ile araştırıldı. NKD2 ifadesinde artışın Wnt/ ß-katenin sinyal yolağının inaktivasyonu ve agresif karakterin baskılanmasına katkı sağladığı belirlendi. Kombinasyon uygulaması sonrası global histon modifikasyon profili ELISA ile değerlendirildi ve NKD2 promotor bölgelerinde ilgili histon işaretlerinin değişimi ChIP yöntemi ile araştırıldı. Transkripsiyonel baskılanma ile ilişkili histon işareti H3K9me3 düzeylerinde gözlenen azalma ile NKD2 düzeylerindeki artış arasında doğrudan bir ilişki olmadığı saptandı. Bu kombinasyon tedavisinin, KKH?leri hedeflemedeki başarısının yeni ve umut verici bir epigenetiik tedavi seçeneği olarak kullanılabileceği öngörüsüyle ileri analizlerinin yapılması gerektiği sonucuna varılmıştır.
Anticancer potential of albumin bound wnt/beta-catenin pathway inhibitor niclosamide in breast cancer cells
(WILEY, 2021) Arı, Ferda; Erkısa Genel, Merve; Pekel, Gonca; Ertürk, Elif; Büyükköroğlu, Gülay; Ulukaya, Engin
Albumin-based nanoparticle transport systems (nab-technology) are a new strategy in cancer treatment and we aimed to increase the effectiveness of Niclosamide using this technology. Niclosamide was bound with bovine serum albumin (BSA) by desolvation to yield nanoparticle albumin-bound Niclosamide (nab-Niclo). Nab-Niclo anticancer activity was assessed by proliferation, apoptosis and DNA damage analyses on breast cancer cells. The results implied that nab-Niclo was a more potent agent in the inhibition of cell viability than free Niclosamide and albumin. Flow cytometry analysis show that nab-Niclo triggered apoptosis by caspase and mitochondriadependent pathways in cells and nab-Niclo enhances apoptosis by induce DNA damage in cells. Overall results of this study showed that the nanoparticle form of Niclosamide is effective for breast cancer treatment, presenting a new treatment strategy that can be safe and effective for breast cancer patients.
Anticancer Potential of Albumin Bound Wnt/β-Catenin Pathway Inhibitor Niclosamide in Breast Cancer Cells
(John Wiley and Sons Inc, 2021) Arı, Ferda; Erkısa, Merve; Pekel, Gonca; Ertürk, Elif; Büyükkoroğlu, Gülay; Ulukaya, Engin
Albumin-based nanoparticle transport systems (nab-technology) are a new strategy in cancer treatment and we aimed to increase the effectiveness of Niclosamide using this technology. Niclosamide was bound with bovine serum albumin (BSA) by desolvation to yield nanoparticle albumin-bound Niclosamide (nab-Niclo). Nab-Niclo anticancer activity was assessed by proliferation, apoptosis and DNA damage analyses on breast cancer cells. The results implied that nab-Niclo was a more potent agent in the inhibition of cell viability than free Niclosamide and albumin. Flow cytometry analysis show that nab-Niclo triggered apoptosis by caspase and mitochondria-dependent pathways in cells and nab-Niclo enhances apoptosis by induce DNA damage in cells. Overall results of this study showed that the nanoparticle form of Niclosamide is effective for breast cancer treatment, presenting a new treatment strategy that can be safe and effective for breast cancer patients. © 2021 Wiley-VCH GmbH.
Assessment of oxidative stress effects in serum determined by FT-IR spectroscopy in cholangiocarcinoma patients
(AMG Transcend Association, 2023) Bulut, Huri; Tarhan, Nevzat; Büyük, Melek; Serin, Kürşat Rahmi; Ulukaya, Engin; Depciuch, Joanna; Parlinska-Wojtan, Magdalena; Güleken, Zozan
Cholangiocarcinoma (CCA) is a heterogeneous malignant tumor containing intrahepatic and extrahepatic bile ducts and gallbladder carcinoma. Mostly diagnosed at an advanced stage with a <5% cure chance. Early-stage diagnosis may increase the number of patients who reach curative treatment. Fourier Transform InfraRed (FT-IR) spectroscopy was used to detect chemical changes in serum collected from CCA patients vs. healthy individuals. The study aims to correlate the FTIR spectra with biochemical indices such as TAS, TOS, OSI, and total protein levels. Decreased TAS and increased TOS, OSI, and total protein levels in CCA patients vs. healthy individuals were found. FTIR spectra showed higher absorbance of the peaks corresponding to C–O and bending vibration of C–O–H groups in CCA patients, while more CH2 functional groups than lipids could be seen in the FTIR spectra of controls serum. PLS analysis showed IR ranges of 1500 cm-1 to 1700 cm-1, and 2700 cm-1 to 3000 cm-1 were able to distinguish between CCA from controls, respectively. PCA confirmed this, while HCA did not differentiate between CCA and those without the disease. Lipids and some functional groups changes caused by oxidative stress can be applied to predict CCA by using FTIR spectroscopy. © 2022 by the authors.
Bioassay-guided isolation of cytotoxic compounds from chrysophthalmum montanum (DC.) boiss
(Pergamon-Elsevier Science Ltd, 2019) Ayaz, Fatma; Küçükkboyacı, Nurgün; Gören, Nezhun; Çalış, İhsan; Aydınlık, Şeyma; Ulukaya, Engin; Duman, Hayri; Choudhary, Muhammad Iqbal
Bioassay-guided isolation of the 80% methanol extract of the aerial parts of Chrysophthalmum montanum (DC.) Boiss. (Asteraceae) led to the isolation of four known guaianolide-type sesquiterpene lactones, 6 alpha-acetoxy-4 alpha-hydroxy-113H-guaia-9.11(13)-dien-12.8a-olide (1), 6 alpha-acetoxy-4 alpha-hydroxy-9 beta.10 beta-epoxy-1 beta H-guaia-11(13)-en12.8 alpha-olide (2), 4 alpha,6 alpha-dihydroxy-1 beta H,5 alpha,7 alpha H-guaia-9(10),11(13)-dien-12,8 alpha-olide (3), and (4 alpha,5 alpha,8 beta,10 beta)-4,10-dihydroxy-1,11(13)-guaidien-12,8-olide (4), along a steroidal glycoside mixture (5a and 5b). The structures of the compounds were identified on the basis of spectroscopic data. Among them, 2, 4 and a steroidal glycoside mixture were obtained from C. montanum for the first time. All isolates were also first time assayed for in vitro cytotoxicities against four human cancer cell lines, i.e. breast (MCF-7, MDA-MB 231), colon (FIT-29), and lung (PC3). Among the isolates, 1-3 showed significant inhibitory effect on the proliferation of cancer cells with viability ranging from 6.86 to 26.51%, while steroidal glycoside mixture showed no cytotoxicity, except against HT-29 (viability 61.99%). Compound 4 exhibited strong and selective cell growth inhibition against HT-29 with viability 20.99% and was identified as a promising compound with high selectivity between cancer cells and normal human lung cells (SEAS-2B), especially against HT-29 (IC50 = 12.2 pg/mL) compared to that of cisplatin. These results suggested that 4 is worthy of further study to determine its cytotoxicity mechanisms.
Cancer stem cells : root of the evil
(Begell House Inc., 2019) Erkısa Genel, Merve; Karakaş Zeybek, Didem; Ulukaya, Engin
Cancer stem cells (CSCs) have been one of the most attractive research areas over the last two decades due to their important roles in aggressive tumor behaviors. Although CSCs are usually a small subpopulation of tumors (less than 0.1%), these cells determine the fate of cancer patients because of their roles in poor prognoses. Accumulating evidence has shown that CSCs are the major responsible cell population in tumor development, growth, metastasis, and therapy resistance. The self-renewal and differentiation capacity of CSCs contribute to the initiation and maintenance of tumor growth. Several reports indicate that CSCs share numerous molecular characteristics with mesenchymal cells, so CSCs are accepted as leading players in metastasis. In addition, these cells possess a higher intrinsic resistance to chemotherapies and radiotherapies than bulk cancer cells. Therefore, therapeutic approaches in recent years have focused on effectively targeting CSCs. Here, we have reviewed the current literature on the resistant mechanisms of CSCs, their roles in metastasis, and the roles of non-coding RNAs in the regulation of aggressive CSC characteristics and novel therapy approaches against CSCs. © 2019 Begell House, Inc.
Chloroquine used in combination with chemotherapy synergistically suppresses growth and angiogenesis in vitro and in vivo
(Int Inst Anticancer Research, 2018) Gürel-Gürevin, Ebru; Kıyan, Hülya Tuba; Esener, Osman Behzat Burak; Aydınlık, Şeyma; Üvez, Ayça; Ulukaya, Engin; Dimas, Konstantinos; Armutak, Elif İlkay
Background: The inhibition of autophagy using pharmacological inhibitors such as chloroquine may be an effective strategy to overcome chemotherapy or resistance to anti-angiogenic therapy. Materials and Methods: The cytotoxic effect of doxorubicin (0.1-1 mu M), chloroquine (0.25-32 ,mu M) and their combination were investigated by employing ATP assay in human umbilical vein endothelial cells (HUVECs). The effect of doxorubicin and chloroquine combination was also measured using tube formation assay on Matrigel. The anti-angiogenic activities of doxorubicin (2.5 mu g/pellet) and chloroquine (15 mu g/pellet), their combination, and standards (50 mu g/pellet) were tested in vivo using the chick embryo chorioallantoic membrane (CAM) assay. Results: The combination of doxorubicin and chloroquine significantly had a stronger anti-angiogenic effect than the positive control (+/-)-thalidomide and doxorubicin alone in the CAM assay and in vitro tube-formation assay. Conclusion: Chloroquine enhanced the anti-angiogenic effect of doxorubicin on CAM at the tested concentrations.
Combination of histone deacetylase inhibitor with Cu(II) 5,5- diethylbarbiturate complex induces apoptosis in breast cancer stem cells: a promising novel approach
(2021) Erkısa Genel, Merve; Aztopal, Nazlıhan; Ertürk, Elif; Ulukaya, Engin; Yılmaz, Veysel Turan; Ari, Ferda
Background: Cancer stem cells (CSC) are subpopulation within the tumor that acts a part in the initiation, progression, recurrence, resistance to drugs and metastasis of cancer. It is well known that epigenetic changes lead to tumor formation in cancer stem cells and show drug resistance. Epigenetic modulators and /or their combination with different agents have been used in cancer therapy. Objective: In our study we scope out the effects of combination of a histone deacetylases inhibitor, valproic acid (VPA), and Cu(II) complex [Cu(barb-?N)(barb-?2N,O)(phen-?N,N')]·H2O] on cytotoxicity/apoptosis in a stem-cell enriched population (MCF-7s) obtained from parental breast cancer cell line (MCF-7). Methods: Viability of the cells was measured by the ATP assay. Apoptosis was elucidated via the assessment of caspase-cleaved cytokeratin 18 (M30 ELISA) and a group of flow cytometry analysis (caspase 3/7 activity, phosphatidylserine translocation by annexin V-FITC assay, DNA damage and oxidative stress) and 2',7'-dichlorofluorescein diacetate staining. Results: The VPA combined with Cu(II) complex showed anti proliferative activity on MCF-7s cells in a dose- and time-dependently. Treatment with combination of 2.5 mM VPA and 3.12 ?M Cu(II) complex induces oxidative stress in a time-dependent manner, as well as apoptosis that is evidenced by the increase in caspase 3/7 activity, positive annexin-V-FITC, and increase in M30 levels. Conclusion: The results suggest that the combination therapy induces apoptosis following increased oxidative stress, thereby making it a possible promising therapeutic strategy that further analysis is required.
Cytotoxic and apoptotic effects of the combination of palladium (II) 5,5-diethylbarbiturate complex with bis(2-pyridylmethyl)amine and curcumin on non small lung cancer cell lines
(Pergamon-Elsevier Science Ltd, 2017) Tunç, Duygu; Dere, Egemen; Karakaş, Didem; Cevatemre, Buse; Yılmaz, Veysel Turan; Ulukaya, Engin
Metal-based chemotherapeutics such as cisplatin are widely used treatment of lung cancer which is the major cause of cancer-related mortality worldwide. Recent studies demonstrated that novel metal-based compounds have strong cytotoxic activity in a similar way as cisplatin. Therefore, metal-based compounds have been synthesized and investigated in order to determine their cytotoxic activities. It has been also reported curcumin, which has been derived from turmeric plant, has powerful cytotoxic effect on various cancer cell lines. In the light of these data, it has been investigated the cytotoxic effects of combination of curcumin (0.78-100 mu M) and palladium (II) 5,5-diethylbarbiturate complex with bis(2-pyridylmethyl)amine [Pd(II) complex] (0.39-50 mu M) against non small lung cancer cell lines, A549 and H1299. It has been found that combination of Pd(II) complex and curcumin enhanced the cytotoxic activity and apoptotic cell death at 48 h, compared to single use of each agent, only in H1299 cell line (combination index <1). Apoptosis was evident by annexin v staining positivity, increased caspase 3/7 activity and the presence of pyknotic nuclei. Pro-apoptotic genes of TNFRSFIOA and HRK were found to be involved in apoptotic cell death. In conclusion, the application of this combination may be regarded as a novel and effective approach for the treatment of lung cancer due to its promising cytotoxic and apoptotic effect. (C) 2017 Elsevier Ltd. All rights reserved.
Cytotoxic and genotoxic effects of an endemic plant of Turkey salvia kronenburgii on breast cancer cell lines
(Wolters Kluwer Medknow Publications, 2019) Çebi, Ayşegül; Akgün, Egemen; Çelikler, Serap; Fırat, Mehmet; Özel, Mustafa Zafer; Ulukaya, Engin; Arı, Ferda
Context: The natural products derived from plants are the important sources that can be used for breast cancer treatment. Salvia species and their derived products were recommended as potential antitumor substances. Aim: The potential cytotoxic and genotoxic effects of Salvia kronenburgii have been investigated on breast cancer cell lines, MCF-7 and MDA-MB-231. Materials and Methods: Determination of chemical compounds of S. kronenburgii was done using a gas chromatography coupled to time-of-flight mass spectrometry system and a dual-stage commercial thermal desorption injector. Growth inhibition of the S. kronenburgii was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and ATP viability assays. The cell death mode was detected by fluorescent dyes. Genotoxic effect of S. kronenburgii was measured by comet assay. Results: S. kronenburgii showed antiproliferative effect in a dose-dependent manner on MCF-7 and MDA-MB-231 cell lines by inducing apoptosis-like cell death. The pyknotic cell nuclei were observed at the cell lines in response to S. kronenburgii. Furthermore, significant increase was shown in genetic damage index and frequencies in the damaged cells. Conclusion: S. kronenburgii might be a promising natural source for cancer therapy. Further experiments need to be done in vivo to understand of the anticancer effects of this plant.
Cytotoxic effect of conyza canadensis (L.) cronquist on human lung cancer cell lines
(Turkish Pharmacists Assoc, 2016) Ayaz, Fatma; Sarımahmut, Mehmet; Küçükboyacı, Nurgün; Ulukaya, Engin
Asteraceae family plants are receiving great attention because they have potential anticancer activity. Therefore, in this study, the cytotoxic effect of Conyza canadensis (L.) Cronquist (Asteraceae) were tested against human lung adenocarcinoma cell lines (A549 and H1299) for the first time. Cytotoxic effect of the n-hexane, chloroform, n-butanol and remaining water (R-H2O) extracts fractioned from the methanol extracts of the aerial parts and roots of C. canadensis was investigated using Sulforhodamine B (SRB) assay and percent (%) viability was measured. The results indicate that the extracts of C. canadensis have cytotoxic activities on these cells in a dose-dependent manner. The root extracts exhibited relatively higher cytotoxic effects than the aerial parts of the plant. The most active extract was found to be n-hexane extract of the roots with IC50 values 94.73 and 84.85 mu g/mL on A549 and H1299 cell lines, respectively. These results suggest that C. canadensis exhibits moderate cytotoxic effect in lung cancer cells. This might be taken into account in its use for therapeutic purposes.
Cytotoxic platinum(II) complexes derived from saccharinate and phosphine ligands: synthesis, structures, DNA cleavage, and oxidative stress-induced apoptosis
(Springer, 2020) İçsel, Ceyda; Yılmaz, Veysel T.; Cevatemre, Buse; Aygün, Muhittin; Ulukaya, Engin
A series of the structurally related platinum(II) saccharinate (sac) complexes with alkylphenylphosphines, namely cis-[Pt(sac)(2)(PPh2Me)(2)]center dot DMSO (1), cis-[Pt(sac)(2)(PPhMe2)(2)] (2), cis-[Pt(sac)(2)(PPh2Et)(2)] (3), and cis-[Pt(sac)(2)(PPhEt2)(2)]center dot 2DMSO (4), were synthesized and fully characterized; their structures were determined by X-ray crystallography. All the complexes were investigated for their anticancer potentials on three human cancer cells including A549 (lung), MCF-7 (breast), and HCT116 (colon) in addition to a noncancerous human bronchial epithelial cells (BEAS-2B). Specifically, 1 and 3 showed significant cytotoxic effects against MCF-7 and HCT116 cell lines in comparison to cisplatin, and were considered as the most potent ones in the series. The cytotoxic complexes were found to cleave DNA efficiently. In addition, the binding interactions of the complexes with DNA were confirmed by enzyme inhibition and molecular docking studies. Complexes 1 and 3 were capable of inducing apoptosis and arrested the cell cycle at the DNA synthesis (S) phase in MCF-7 cells. Furthermore, 1 and 3 caused the excessive generation of reactive oxygen species (ROS), leading to mitochondrial dysfunction and double-strand DNA breaks.
De novo antineoplastic drug design to suppress head, neck and oral cancer using theoretical organic and biochemistry via comprehensive molecular docking and dynamics
(Asian pacific organization for cancer prevention, 2024) Agar, Soykan; Mokhtari, Mohaddeseh; Yanık, Muhammed; Akkurt, Barbaros; Ulukaya, Engin; Terzi, Rabia
Objective: A de novo antineoplastic drug was planned to suppress and modulate the Head, Neck, and Oral Cancer. Methods: Using the computational software tools including molecular docking, molecular dynamics (MD), and post-molecular dynamics bond contact analyses, it has been shown that the new drug called ‘’Innovative Head, Neck, and Oral Cancer Suppressor’’, or simply abbreviated as “IHNOCS” is very effective in terms of suppressing and co-modulating TGF-β and KRTAP2-3 together. Result: The drug suppresses the KRTAP2-3 protein activity while also holding onto TGF-β and modulating it to slow down and halt the metastasis. Conclusion: We have effectively created a novel medication using principles of theoretical chemistry, biochemistry, pharmaceutical chemistry and organic chemistry and organic chemistry to inhibit Head, Neck, and Oral Cancer. This medication should further undergo experimental testing in various stages, including in vitro, in vivo, and human clinical phases. It exhibits significant effectiveness in inhibiting the progression of cancer by simultaneously targeting TGF-β and KRTAP2-3, thereby impeding metastasis and suppressing the disease. This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License.
Development of a cysteine responsive chlorinated hemicyanine for image-guided dual phototherapy
(2022) Savani, Samira; Onbaşlı, Kübra; Gündüz, Eren; Aydındoğan, Eda; Erkısa, Merve; Muti, Abdullah; Khan, Minahil; Sennaroglu, Alphan; Ulukaya, Engin; Yağcı Acar, Havva; Kölemen, Safacan
A cysteine (Cys) activatable chlorinated hemicyanine (Cl-Cys) was introduced as a tumour selective image-guided dual phototherapy agent. Cl-Cys exhibited a significant turn on response in its near-IR emission signal and activated its singlet oxygen generation as well as photothermal conversion potentials upon reacting with Cys. The laser irradiation of Cl-Cys induced significant cell death in cancer cells with high Cys level, while it stayed deactivated and non-emissive in a healthy cell line. A profound synergistic PDT/PTT effect was observed at high doses. Remarkably, Cl-Cys marks the first ever example of Cys-responsive small organic-based therapeutic agent and holds a great promise to develop new activity-based photosensitizers for dual phototherapy action.
Development of near-infrared region luminescent N-acetyl-L-cysteine-coated Ag2S quantum dots with differential therapeutic effect
(Future Medicine Ltd, 2019) Buz, Pelin Turhan; Duman, Fatma Demir; Erkısa Genel, Merve; Demirci, Gözde; Arı, Ferda; Ulukaya, Engin; Acar, Havva Yağcı
Aim: N-acetyl-L-cysteine (NAC) is a free radical scavenger. We developed NAC-coated Ag2S (NAC-Ag2S) quantum dot (QD) as an optical imaging and therapeutic agent. Materials & methods: QDs were synthesized in water. Their optical imaging potential and toxicity were studied in vitro. Results: NAC-Ag2S QDs have strong emission, that is tunable between 748 and 840 nm, and are stable in biologically relevant media. QDs showed significant differences both in cell internalization and toxicity in vitro. QDs were quite toxic to breast and cervical cancer cells but not to lung derived cells despite the higher uptake. NAC-Ag2S reduces reactive oxygen species (ROS) but causes cell death via DNA damage and apoptosis. Conclusion: NAC-Ag2S QDs are stable and strong signal-generating theranostic agents offering selective therapeutic effects.
Differential of cholangiocarcinoma disease using Raman spectroscopy combined with multivariate analysis
(2022) Depciuch, Joanna; Parlinska-Wojtan, Magdalena; Serin, Kürşat Rahmi; Bulut, Huri; Ulukaya, Engin; Tarhan, Nevzat; Güleken, Zozan
Cholangiocarcinoma (CCA) is a type of cancer, which 5-year survival is lower than 20 %, and which is detected mostly in advanced stage of the disease. Unfortunately, there are no diagnostic tools, which could show changes in the body indicating the development of the disease. Therefore, in this study, we investigate Raman spectroscopy as a promising analytical tool in medical diagnostics and as a method, which would allow to distinguish between healthy patients and patients suffering from cholangiocarcinoma. The obtained Raman spectra showed, that lower intensities of peaks corresponding to amino acids and proteins, as well as higher intensities of peaks originating from lipids vibrations were observed in healthy individuals in comparison with cancer patients. Moreover, Partial Last Square (PLS), Principal Component Analysis (PCA) and Hierarchical Component Analysis (HCA) of Raman spectra indicate that the ranges between 800 cm-1 and 1800 cm-1, 3477 cm-1 -3322 cm-1 and 1394 cm-1 -1297 cm-1 allow to distinguish cancer patients from healthy ones. The obtained results showed, that Raman spectroscopy is a good candidate, to become in future one of the diagnostic tools of Cholangiocarcinoma.
DNA damage response inhibitors in cholangiocarcinoma: current progress and perspectives
(PubMed, 2022) Anichini, Giulia; Ulukaya, Engin; Marra, Fabio; Raggi, Chiara; Geyik, Öykü Gönül
Cholangiocarcinoma (CCA) is a poorly treatable type of cancer and its incidence is dramatically increasing. The lack of understanding of the biology of this tumor has slowed down the identification of novel targets and the development of effective treatments. Based on next generation sequencing profiling, alterations in DNA damage response (DDR)-related genes are paving the way for DDR-targeting strategies in CCA. Based on the notion of synthetic lethality, several DDR-inhibitors (DDRi) have been developed with the aim of accumulating enough DNA damage to induce cell death in tumor cells. Observing that DDRi alone could be insufficient for clinical use in CCA patients, the combination of DNA-damaging regimens with targeted approaches has started to be considered, as evidenced by many emerging clinical trials. Hence, novel therapeutic strategies combining DDRi with patient-specific targeted drugs could be the next level for treating cholangiocarcinoma.
Dual inhibition of Wnt/beta-catenin signaling and histone deacetylation as a new strategy to eliminate breast cancer stem cells by augmentation of apoptosis
(Wiley, 2018) Aztopal, Nazlıhan; Erkısa Genel, Merve; Arı, Ferda; Dere, E.; Ulukaya, Engin
[No Abstract Available]
The effect of NOTCH, IL-1 and LEPTIN (NILCO) inhibition in xenograft colorectal cancer
(Wiley, 2019) Özyurt, R.; Erkasap, N.; Özkurt, M.; Erkasap, S.; Ulukaya, Engin; Dimas, K.
Questions: Studies in various cancer tissues have shown that Notch, IL-1 and leptin interaction (NILCO) play a role in the proliferation, migration and expression of proangogenic molecules. It has been suggested that VEGF/VEGFR2 gene expression in angiogenesis may increase by NILCO and may contribute significantly to tumor development. However, there is no any comprehensive molecular study of the relationship between NILCO pathway and cancer development in colon tissue. For this purpose, we studied the effect of NILCO and related angiogenic/proinflammatory molecules on xenograft colorectal cancer (CRC).
Effects of exosomes on major pathways promote tumor formation and progression
(Bentham Science, 2021) Köse, Mehmet Emin; Aydın, Beste; Geyik, Caner; Gönül Geyik, Öykü; Ulukaya, Engin
Exosomal vesicles enclose and carry a broad range of biological molecules, such as nucleic acids, lipids, and proteins, and transfer them between cells. In cancer, cells being mentioned could be neighbors in the same tumor microenvironment communicating with each other, or they could be localized at distant sites of the body, enabling suitable conditions for metastasis. Either way, it is a concrete fact that cells under physiological or pathological conditions make crosstalk via exosomal secretion. This review looks at the relation between exosomal cargo and mechanisms of cancer through recent research.

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