Yıldırım, Gazi | Attar, Rukset | Fıçıcıoğlu, Cem | Karateke, Ateş | Özkan, Ferda | Kılıç, Ertuğrul | Yeşildağlar, Narter

Other | 2009 | Journal of the Turkish-German Gynecological Association10 ( 4 ) , pp.199 - 204

Amaç: Kombine letrozol ve melatonin tedavisinin cerrahi olarak indüklenmiş endometriosis üzerindeki etkisini belirlemek. Gereç ve Yöntemler: Bu prospektif randomize kontrollü bir deneysel çalışma olarak dizayn edildi ve Yeditepe Üniversitesi Deneysel Hayvanlar Araştırma Merkezinde (YUDETAM) gerçekleştirildi. Cerrahi olarak endometriosis oluşturulmuş 17 tane nulligravida dişi Wistar – Hannover albino rat kullanıldı. Ratlara homolog uterin boynuz inokülasyonu yapılarak endometriosis oluşturuldu ve iki hafta aralar ile dört operasyon yapıldı. Endometriosis indüksiyonu ilk operasyonda yapıldı. İki haftalık östradiol tedavisini takiben i . . .kinci operasyon yapıldı. Sonra östrojen kesildi ve çalışma grubuna ilaç başlandı. Takip eden iki haftanın sonunda üçüncü operasyon yapılarak endometriyal odaklar üzerinde ilaçların etkinliği araştırıldı. Üçüncü operasyondan sonra bütün ilaçlar kesildi ve östrojen tekrar başlandı. Iki haftalık östrojen tedavisinin ardından tüm ratlara ötanazi yapıldı ve rekürrens oranlarına bakıldı. Bulgular: Kontrol grubunda tedavinin başında lezyonların volüm ortalaması 93.631.7 mm3 idi. Östradiol tedavisi kesildikten sonra 85.023.8 mm3 (P0.31) boyutlarına indi ve rekürrens zamanı 119.729.4 mm3’ e çıktı (P0.02). Östradiol kesildikten sonra histopatalojik skorda anlamlı bir düşüş gözlendi (p0.04) fakat rekürrens zamanı tedavi öncesi boyutlarına ulaştı. LM grubunda lezyonların volümü tedavi grubunda anlamlı bir şekilde düştü (82.821.0 mm3 ve 15.78.0 mm3). Rekürrens zamanı ortalama volüm 43.931.8 mm3 olarak hesaplandı (p0.002). Histopatolojik skor ise tedavi öncesi tedavi sonrası ve rekürrens zamanlarında sırası ile 2.30.1, 2.00.2 ve 2.20.3 idi. Sonuç: Çalışmamızda Letrozol ve Melatonin endometriotik lezyonların boyutlarında gerileme oratya çıkarırken, histopatolojik skorlarda değişikliğe yol açmadı. Objective: To determine the effects of the combination of letrozole and melatonin on surgically induced endometriosis. Material and Methods: This prospective, randomized, controlled, experimental study was carried out at Yeditepe University Experimental Research Center (YUDETAM). Female non-pregnant, 17 nulligravid Wistar - Hannover albino rats with surgically induced endometriosis were used in this study. Endometriosis was induced by using homologous uterine horn transplantation in the rats. Four operations were performed on each rat. The induction of endometriosis was performed in the first operation. After two weeks of estradiol treatment the second operation was performed and endometriotic lesions were evaluated. Estrogen was then discontinued and in the study groups medications were started. During two weeks the rats were given medications and the third operation was performed for the assessment of the effects of the medications on the endometriotic foci. Then all the medications were stopped and estrogen was started again. Two weeks later all the rats were euthanized and recurrence of endometriosis was evaluated. Results: The sum of the lesion volumes in the control group was 93.6±31.7 mm3 at the end of the second week. After the cessation of estradiol it decreased to 85.0±23.8 mm3 (P0.31) and increased to 119.7±29.4 mm3 at the sixth week (P0.02). A significant reduction in histopathologic scores were seen after cessation of the estradiol (p0.04). At the end of the sixth week, histopathological scores reached the pretreatment values. In the letrozole and melatonin group the sum of the lesion volumes decreased significantly after the treatment (82.8±21.0 mm3 and 15.7±8.0 mm3 respectively). At the end of the sixth week, the mean volume was calculated as 43.9±31.8 mm3 (p0.002). Histopathologic scores were 2.3±0.1, 2.0±0.2 and 2.2±0.3 at the end of the second, fourth and sixth weeks, respectively, in the letrozole and melatonin group. Conclusions: Letrozole and melatonin caused a significant regression in lesion volumes; however, histopathological scores of endometriotic lesions did not change significantly Daha fazlası Daha az

Fıçıcıoğlu, Cem | Kumbak, Banu | Akcin, Oya | Attar, Rukset | Yıldırım, Gazi | Tecellioğlu, Nihan | Yeşildağlar, Narter

Other | 2009 | Journal of the Turkish-German Gynecological Association10 ( 3 ) , pp.132 - 136

Amaç: Folikül sıvısı içindeki sitokinlerin ve nitrik oksitin matur oosit gelişimi üzerindeki etkisi tartışmalıdır. Bu çalışmanın amacı, tüp bebek tadavisi alan hastaların folikül sıvısı (FF) ve serumunda (S) interlökinleri IL-1?, IL-6, IL-8, IL-12, tümor nekrozis faktör (TNF)-? ve NO düzeylerini saptamak ve bunların başarı ile ilişkisini araştırmaktır. Gereç ve Yöntemler: Bir üniversite hastanesinin tüp bebek merkezinde retrospektif çalışma planlandı. 85 kadın çalışmaya dahil edildi. IL-1?, IL-6, IL-8, IL-12, tümor nekrozis faktör (TNF)-? düzeyleri ELISA ile, NO düzeyleri ise nitrat/nitrit kolorometrik assay ile saptandı. Bulgular: . . .Gebe kalan ve kalamayan kadınların S ve FF sitokin ve NO konsantrasyonları arasında fark bulunamadı. Sonuç: Serum ve folüküler sıvı IL-1?, IL-6, IL-8, IL-12, tümör nekrozis faktör (TNF)-? ve NO düzeyleri tüp bebek tedavilerinde başarıyı predikte etmez. Objective: The role of cytokines and nitric oxide (NO) in ovarian folliculogenesis and the development of mature and fertilizable oocytes is controversial. The aim of this study is to determine the concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-α and NO in the follicular fluid (FF) and blood serum (S) of patients undergoing assisted reproductive treatment (ART) and to investigate whether these cytokines could be used as a predictive parameter for ART outcome. Material and Methods: A retrospective clinical study was performed at a university hospital including a total of 85 women who underwent ART. FF and serum samples were collected at the time of oocyte retrieval and measured for interleukin (IL)-1β, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-α by the enzyme-linked immunosorbant assay (ELISA) technique, using commercially available kits and NO by the nitrate/nitrite colorimetric assay. The results were compared between the women who became pregnant and those who did not following ART. Results: No significant difference was found in the FF and blood serum concentrations of the cytokines and NO between pregnant and non-pregnant women. Conclusion: Follicular fluid and blood serum concentrations of IL-1β, IL-6, IL-8, IL-12, TNF-α and NO do not predict pregnancy achievement following ART Daha fazlası Daha az

Shahwar, D. | Iqbal, M.J. | Nisa, M.-U. | Todorovska, M. | Attar, Rukset | Sabitaliyevich, U.Y. | Xu, B.

Review | 2019 | International Journal of Molecular Sciences20 ( 8 ) , pp.132 - 136

Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression . . . of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers. © 2019 by the authors. Licensee MDPI, Basel, Switzerland Daha fazlası Daha az

Farooqi, A.A. | Wang, Z. | Hasnain, S. | Attar, Rukset | Aslam, A. | Mansoor, Q. | Ismail, M.

Note | 2015 | Asian Pacific Journal of Cancer Prevention16 ( 6 ) , pp.2575 - 2580

Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increas . . .ing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies Daha fazlası Daha az

Ficicioglu, C. | Attar, Rukset | Yildirim, G. | Cetinkaya, N.

Letter | 2010 | Taiwanese Journal of Obstetrics and Gynecology49 ( 2 ) , pp.211 - 213

[No abstract available]

Attar, Rukset | Attar, E.

Article | 2015 | Women's Health11 ( 5 ) , pp.653 - 664

Endometriosis is defined as the presence of endometrial gland and stroma outside the uterine cavity. It is an estrogen-dependent disease and is associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. The treatment of endometriosis is conservative or radical surgery, medical therapies or their combination. All currently used hormonally active treatments are effective in the treatment of endometriosis; however, the adverse effects of these hormonal treatments limit their long-term use. Moreover, recurrence rates are high after cessation of therapy, and the treatments have no benefit in endometriosis-associated . . .infertility. Therefore, researchers are working on new treatment modalities with improved side effects, mainly focusing on the molecular targets involved in etiopathogenesis of endometriosis. Here we summarized these novel treatments modalities. © 2015 Future Medicine Ltd Daha fazlası Daha az

Ozbey, U. | Attar, Rukset | Romero, M.A. | Alhewairini, S.S. | Afshar, B. | Sabitaliyevich, U.Y. | Farooqi, A.A.

Article | 2019 | Journal of Cellular Biochemistry120 ( 2 ) , pp.1060 - 1067

Wealth of information gleaned from decades of high-impact research work; scientists have disentangled the complicated web of versatile regulators that underlie cancer development and progression. Use of structural biology approaches and functional genomics have helped us to gain new insights into complex nature of cancer, and it is now clear that genetic/epigenetic mutations, overexpression of oncogenes, inactivation of tumor suppressors, loss of apoptosis, and versatility of protein binding partners have contributory roles in carcinogenesis and metastatic spread. It is becoming progressively more understandable that reprogramming o . . .f gene expression during and nontranscriptional changes during cancer development and progression are initiated and controlled by deregulated signal transduction cascades, all of which collectively create an incalculable complexity. Data obtained through preclinical and clinical trials revealed that alterations in the targeted oncogenes and other downstream, and parallel pathways played a central role in the development of resistance against different therapeutics. Phytochemicals have regained limelight, and different natural products are currently being tested for efficacy in preclinical studies. Apigenin, a plant-derived flavonoid has considerable pharmacological value and is reportedly involved in the regulation of different signaling cascades. In this review, we have attempted to summarize rapidly evolving understanding of molecular biologists and pharmacologists about the potential of apigenin in the regulation of deregulated signaling pathways in different cancers. We have emphasized on the regulation of WNT/ß-catenin and janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways. We also comprehensively discuss how apigenin restored apoptosis in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant cancers. The review also gives a snapshot of microRNAs (miRNAs) that regulate wide-ranging biological processes, and it is now clear that each miRNA can control hundreds of gene targets. Apigenin was noted to upregulate miR-520b and miR-101 in different cancers to inhibit tumor growth. Moreover, apigenin-induced apoptotic rate was significantly higher when used in combination with miR-423-5p inhibitors or miR-138 mimics. Better comprehension of linear and integrated signaling pathways will be helpful in effective therapeutic targeting of deregulated signaling pathways to inhibit/prevent cancer. © 2018 Wiley Periodicals, Inc Daha fazlası Daha az

Yıldırım, Gazi | Attar, Rukset | Fıçıcıoğlu, Cem | Karateke, Ateş | Çetinkaya, Nilüfer | Kumbak, Banu | Yeşildağlar, Narter

Other | 2009 | Journal of the Turkish-German Gynecological Association10 ( 1 ) , pp.57 - 58

…

Butt, G. | Attar, Rukset | Tabassum, S. | Aras, A. | Qadir, M.I. | Ozbey, U. | Farooqi, A.A.

Review | 2017 | Cellular and Molecular Biology63 ( 12 ) , pp.5 - 10

Interdisciplinary research has revolutionized the field of medicine and we have witnessed exponential increase in the high-impact research in past few decades. However, the road to this burgeoning research field is obstacle-ridden because of intratumor heterogeneity, loss of apoptosis and dysregulation of spatio-temporally controlled signaling pathways. Ground-breaking findings obtained through genetic, genomic and proteomic studies have considerably improved our concepts related to the complexity of protein network and excitingly, discovery of miRNAs has added another layer of intricacy to quantitatively regulated gene networks. In . . . this review, we chronicle the milestone achievements and discuss how Pterostilbenes effectively regulated different cellular pathways. We have provided detailed mechanistic insights related to regulation of JAK-STAT signaling, Notch pathway, Wnt mediated intracellular signaling by pterostilbene. Underlying mechanisms about regulation of PI3K/AKT and MAPK pathways by pterostilbene in different cancers. Regulation of Metastasis-associated protein 1 (MTA1) proteins and Human telomerase reverse transcriptase (hTERT) in cancer cells by pterostilbene. Pterostilbene has also been reported to modulate the expression of various oncogenic and tumor suppressor microRNAs in cancer cells. Better and sharper comprehension of the concepts associated with the modes of action of pterostilbene in different cancers will be useful in identification of cancers which can be efficiently targeted by pterostilbene. © 2017 by the C.M.B. Association Daha fazlası Daha az

Attar, Rukset | Yıldırım, Gazi | İnan, Yücel | Kızılkale, Özge | Karateke, Ateş

Article | 2013 | Journal of the Turkish-German Gynecological Association14 ( 4 ) , pp.242 - 245

Tek taraflı kapalı vajen ve aynı tarafta böbrek agenezisi ile birlikte di- delfik uterus nadir görülen bir durumdur. Genellikle menarj sonrasın- da görülen pelvik ağrı, dismenore, karın hacminde artış veya tek ta- raflı hematokolposa bağlı olarak ele gelen kitle şeklinde ortaya çıkar. Bu yazıda özellikle adet sırasında ortaya çıkan pelvik ağrı ve düzensiz adet kanaması şikayetleri ile başvuran 13 yaşındaki bir kız çocuğunun olgusunu sunduk. Hastaya pelvik ultrasonografi ve manyetik rezonans (MR) incelemesi yapıldı. Tek taraflı kapalı vajen ve aynı tarafta böb- rek agenezisi ile birlikte didelfik uterus tanısı konuldu. Tanı ve tedavi . . . amaçlı laparotomi yapıldı. İki ayrı hemiuterus, iki serviks ve sağ tarafta hematometra ve hematokolpos ile aynı tarafta böbrek agenezi tesbit edildi. Vaginal septum tamamen çıkartıldı ve Strassmann metroplas- tisi yapıldı. Ameliyat sonrasında hastanın bütün şikayetleri geçti ve bulguları tamamen kayboldu. Anatomik yapılardaki farklılığa, şikayet- lerin özgün olmamasına ve değişik şekillerde ortaya çıkmasına bağlı olarak bu konjenital anomalinin tanısı ve tedavisi güçtür. Dönemsel karın ağrısı ve abdominopelvik kitle ile başvuran bir kadında mutlaka bu bozuklukların da olabileceği düşünülmelidir. (J Turkish-German Gynecol Assoc 2013; 14: 242-5) Didelphic uterus with obstructed hemivagina and ipsilateral renal agenesis is a rare condition. It usually presents with pelvic pain fol- lowing the menarche, dysmenorrhoea, and an increase in abdomi- nal volume or a palpable mass due to unilateral haematocolpos. We present the case of a 13-year-old girl who referred with recurrent pel- vic pain, mainly at the time of menses, and irregular menstrual cycle complaints in this report. The patient underwent ultrasonography and magnetic resonance (MR) imaging of the pelvis was performed. The diagnosis was uterus didelphys with obstructed hemivagina and ipsi- lateral renal agenesia. Laparotomy was performed for diagnosis and treatment purposes. Two separated hemiuteri and two cervices with hematometra and hematocolpos on the right side and ipsilateral renal agenesis were detected. The vaginal septum was excised completely and Strassman metroplasty was performed. Her complaints were re- solved and she was absolutely asymptomatic after surgery. Diagnosis and management of this congenital anomaly is challenging due to the complexity of the anatomic structures, nonspecific complaints, and heterogenic presentation. These anomalies must always be consid- ered while working-up female patients presenting with episodic ab- dominal pain and abdominopelvic mass. (J Turkish-German Gynecol Assoc 2013; 14: 242-5) Key words Daha fazlası Daha az

Farooqi, A.A. | Khalid, S. | Tahir, F. | Sabitaliyevich, U.Y. | Yaylim, I. | Attar, Rukset | Xu, B.

Article | 2018 | Food and Chemical Toxicology119 , pp.98 - 105

Research over decades has progressively explored pharmacological actions of bitter gourd (Momordica charantia). Biologically and pharmacologically active molecules isolated from M. charantia have shown significant anti-cancer activity in cancer cell lines and xenografted mice. In this review spotlight was set on the bioactive compounds isolated from M. charantia that effectively inhibited cancer development and progression via regulation of protein network in cancer cells. We summarize most recent high-quality research work in cancer cell lines and xenografted mice related to tumor suppressive role-play of M. charantia and its bioac . . .tive compounds. Although M. charantia mediated health promoting, anti-diabetic, hepatoprotective, anti-inflammatory effects have been extensively investigated, there is insufficient information related to regulation of signaling networks by bioactive molecules obtained from M. charantia in different cancers. M. charantia has been shown to modulate AKT/mTOR/p70S6K signaling, p38MAPK-MAPKAPK-2/HSP-27 pathway, cell cycle regulatory proteins and apoptosis-associated proteins in different cancers. However, still there are visible knowledge gaps related to the drug targets in different cancers because we have not yet developed comprehensive understanding of the M. charantia mediated regulation of signal transduction pathways. To explore these questions, experimental platforms are needed that can prove to be helpful in getting a step closer to personalized medicine. © 2018 Elsevier Lt Daha fazlası Daha az

Gasparri, M.L. | Attar, Rukset | Palaia, I. | Perniola, G. | Marchetti, C. | Di Donato, V. | Panici, P.B.

Article | 2015 | Asian Pacific Journal of Cancer Prevention16 ( 9 ) , pp.3635 - 3638

Several improvements in ovarian cancer treatment have been achieved in recent years, both in surgery and in combination chemotherapy with targeting. However, ovarian tumors remain the women's cancers with highest mortality rates. In this scenario, a pivotal role has been endorsed to the immunological environment and to the immunological mechanisms involved in ovarian cancer behavior. Recent evidence suggests a loss of the critical balance between immune-activating and immune-suppressing mechanisms when oncogenesis and cancer progression occur. Ovarian cancer generates a mechanism to escape the immune system by producing a highly sup . . .pressive environment. Immune-activated tumor infiltrating lymphocytes (TILs) in ovarian tumor tissue testify that the immune system is the trigger in this neoplasm. The TIL mileau has been demonstrated to be associated with better prognosis, more chemosensitivity, and more cases of optimal residual tumor achieved during primary cytoreduction. Nowadays, scientists are focusing attention on new immunologically effective tumor biomarkers in order to optimize selection of patients for recruitment in clinical trials and to identify relationships of these biomarkers with responses to immunotherapeutics. Assessing this point of view, TILs might be considered as a potent predictive immunotherapy biomarker Daha fazlası Daha az