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Development and characterization of liposomal formulations for rapamycin delivery and investigation of their antiproliferative effect on MCF7 cells

Rouf, M.A. | Vural, I. | Renoir, J.M. | Hincal, A.A.

Article | 2009 | Journal of Liposome Research19 ( 4 ) , pp.322 - 331

Rapamycin (Sirolimus) is a macrolide lactone with antifungal, immunosuppressant, and antiproliferative actions. The mechanism of rapamycin action involves the inhibition of mTOR and subsequent cytostasis. Rapamycin also prevents angiogenesis in tumors and can prevent cancer cells' resistance to other chemotherapeutic agents. However, very poor water solubility, bioavailability, only slight solubility in acceptable parenteral excipients, chemical instability, and major sequestration (95%) of free rapamycin into the erythrocytes have prevented its development as an anticancer drug. To address these problems, it was attempted to develo . . .p liposomal rapamycin delivery systems in this study. Conventional and pegylated liposomes were prepared with various lipid and cholesterol ratios. They were then characterized; these liposomes contained 0.680.90mg of rapamycin per milliliter of liposome suspension. Having suitable particle size, these liposomes successfully retained the entrapped drug. Both types of liposomes were found to be effective; however, conventional liposomes showed better antiproliferative activity against MCF-7 cells than pegylated liposomes. But, pegylated liposome showed better stability than conventional liposomes. In conclusion, the enhanced permeability and retention effercts of tumors should provide the opportunity for pegylated liposomal rapamycin to be applied as an intravenous drug-delivery system for targeted delivery to cancer cells, avoiding the major sequestration of free rapamycin into the erythrocytes Daha fazlası Daha az

Regulation of signaling pathways by Ampelopsin (Dihydromyricetin) in different cancers: exploring the highways and byways less travelled

Fayyaz, S. | Qureshi, M.Z. | Alhewairini, S.S. | Avnioglu, S. | Attar, Rukset | Sabitaliyevich, U.Y. | Pawlak-Adamska, E.

Article | 2019 | Cellular and molecular biology (Noisy-le-Grand, France)65 ( 7 ) , pp.15 - 20

Ampelopsin or Dihydromyricetin is gradually emerging as a high-quality natural product because of its ability to modulate wide-ranging signaling pathways. Ampelopsin (Dihydromyricetin) has been reported to effectively modulate growth factor receptor (VEGFR2 and PDGFRß) mediated signaling,  TRAIL/TRAIL-R pathway, JAK/STAT and mTOR-driven signaling in different cancers. Ampelopsin (Dihydromyricetin) has also been shown to exert inhibitory effects on the versatile regulators which trigger EMT (Epithelial-to-Mesenchymal Transition). Findings obtained from in-vitro studies are encouraging and there is a need to comprehensively analyze ho . . .w Ampelopsin (Dihydromyricetin) inhibits tumor growth in different cancer models. Better knowledge of efficacy of Ampelopsin (Dihydromyricetin) in tumor bearing mice will be helpful in maximizing its translational potential Daha fazlası Daha az

Recent updates on true potential of an anesthetic agent as a regulator of cell signaling pathways and non-coding RNAs in different cancers: Focusing on the brighter side of propofol

Farooqi, A.A. | Adylova, A. | Sabitaliyevich, U.Y. | Attar, Rukset | Sohail, M.I. | Yilmaz, S.

Review | 2020 | Gene737 , pp.15 - 20

There has always been a quest to search for synthetic and natural compounds having premium pharmacological properties and minimum off-target and/or side effects. Therefore, in accordance with this approach, scientists have given special attention to the molecules having remarkable ability to target oncogenic protein network, restore drug sensitivity and induce apoptosis in cancer cells. The mechanisms through which general anesthetics modulated wide-ranging deregulated cell signaling pathways and non-coding RNAs remained unclear. However, rapidly accumulating experimentally verified evidence has started to resolve this long-standing . . . mystery and a knowledge about these important molecular targets has surfaced and how these drugs act at the molecular level is becoming more understandable. In this review we have given special attention to available evidence related to ability of propofol to modulate Wnt/ß-catenin, JAK/STAT and mTOR-driven pathway. Excitingly, great strides have been made in sharpening our concepts related to potential of propofol to modulate non-coding RNAs in different cancers. Collectively, these latest findings offer interesting, unexplored opportunities to target deregulated signaling pathways to induce apoptosis in drug-resistant cancers. © 2020 Elsevier B.V Daha fazlası Daha az

Genotoxic effects of PCB 52 and PCB 77 on cultured human peripheral lymphocytes

Sandal, S. | Yılmaz, B. | Carpenter, D.O.

Article | 2008 | Mutation Research - Genetic Toxicology and Environmental Mutagenesis654 ( 1 ) , pp.88 - 92

Polychlorinated biphenyls (PCBs) are known to be carcinogenic, but the mechanisms of this action are uncertain. Most, but not all, studies have concluded that PCBs are not directly mutagenic, and that much if not all of the carcinogenic activity resides in the fraction of the PCB mixture that contains congeners with dioxin-like activity. The present study was designed to determine genotoxic effects of an ortho-substituted, non-coplanar congener, 2,2',5,5'-tetrachlorobiphenyl (PCB 52), and a non-ortho-substituted coplanar congener with dioxin-like activity, 3,3',4,4'-tetrachlorobiphenyl (PCB 77) on cultured human peripheral lymphocyt . . .es. DNA damage was assessed by use of the comet assay (alkaline single-cell gel electrophoresis). After cell cultures were prepared, test groups were treated with different concentrations of PCB 52 (0.2 and 1 µM) and PCB 77 (1 and 10 µM) for 1 h at 37 °C in a humidified carbon dioxide incubator, and compared to a DMSO vehicle control group. The cells were visually classified into four categories on the basis of extent of migration such as undamaged (UD), low damage (LD), moderate damage (MD) and high damage (HD). The highest concentration of PCBs 52 and 77 significantly increased DNA breakage in human lymphocytes (p < 0.001). Our results indicate that both the non-coplanar PCB 52 and coplanar PCB 77 cause DNA damage, and that the ortho-substituted congener was significantly more potent than the dioxin-like coplanar congener. © 2008 Elsevier B.V. All rights reserved Daha fazlası Daha az

Citrus fruits and their bioactive ingredients: Leading four horsemen from front

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

Reliability and Validity of Turkish Version of the Caregiver Quality of Life Index Cancer Scale

Yakar, H.K. | Pinar, R.

Article | 2013 | Asian Pacific Journal of Cancer Prevention14 ( 7 ) , pp.4415 - 4419

Background: Measuring effects of cancer on family caregivers is important to develop methods which can improve their quality of life (QOL). Nevertheless, up to now, only a few tools have been developed to be used in this group. Among those, the Caregiver Quality of Life Index-Cancer Scale (CQOLC) has met minimum psychometric criteria in different populations in spite of conflicting results. The present study was conducted to evaluate reliability and validity of CQOLC among Turkish cancer family caregivers. Materials and Methods: The CQOLC was administered to 120 caregivers, along with Beck Depression Inventory (BDI), Medical Outcome . . .s Study MOS 36- Item Short Form Health Survey (SF-36), State-Trait Anxiety Inventory (STAI), and Multidimensional Scale of Perceived Social Support (MSPSS). Internal consistency and test-retest stability were used to investigate reliability. Construct validity was examined by using known group method, convergent, and divergent validity. For the known group method, we hypothesized that CQOLC scores would differ between depressed and non-depressed subjects. We investigated convergent validity by correlating scores for CQOLC with scores for other similar measures including SF-36 and STAI. The MSPSS was completed at the same time as CQOLC to provide divergent validity. Results: The values for internal consistency and test-retest correlation were 0.88 and 0.96, respectively. The CQOLC discriminated those who were depressed from those who were not. Convergent validity supported strong correlations between CQOLC scores and two main component scores (PCS, MCS) in SF-36 although there was a weak correlation between CQOLC and STAI scores. Regarding divergent validity, the correlation between CQOLC and MSPSS was in the low range, as expected. Conclusions: The Turkish CQOLC is a reliable and valid tool and it can be utilized to determine QOL of family caregivers Daha fazlası Daha az

A novel thiazolidine compound induces caspase-9 dependent apoptosis in cancer cells

Onen-Bayram, F.E. | Durmaz, I. | Scherman, D. | Herscovici, J. | Cetin-Atalay, R.

Article | 2012 | Bioorganic and Medicinal Chemistry20 ( 17 ) , pp.5094 - 5102

The forward chemogenomics strategy allowed us to identify a potent cytotoxic thiazolidine compound as an apoptosis-inducing agent. Chemical structures were designed around a thiazolidine ring, a structure already noted for its anticancer properties. Initially, we evaluated these novel compounds on liver, breast, colon and endometrial cancer cell lines. The compound 3 (ALC67) showed the strongest cytotoxic activity (IC50 ~5 µM). Cell cycle analysis with ALC67 on liver cells revealed SubG1/G1 arrest bearing apoptosis. Furthermore we demonstrated that cytotoxicity of this compound was due to the activation of caspase-9 involved apoptot . . .ic pathway, which is death receptor independent. © 2012 Elsevier Ltd. All rights reserved Daha fazlası Daha az

Maslinic acid as an effective anticancer agent

Lin, X. | Ozbey, U. | Sabitaliyevich, U.Y. | Attar, Rukset | Ozcelik, B. | Zhang, Y. | Farooqi, A.A.

Article | 2018 | Cellular and Molecular Biology64 ( 10 ) , pp.87 - 91

Maslinic acid (2?,3ß-dihydroxyolean-12-en-28-oic acid) is a naturally occurring pentacyclic triterpenic compound. Maslinic acid is gradually gaining attention as an excellent pharmacologically active product because of its premium biological properties. In this review we will focus on chemopreventive properties of Maslinic acid against different cancers. Seemingly, available data is limited and we have yet to unravel how Maslinic acid therapeutically targeted oncogenic cell signal transduction cascades in different cancers. Moreover, there are visible knowledge gaps about the ability of Maslinic acid to modulate oncogenic and tumor . . .suppressor microRNAs in various cancers. © 2018 by the C.M.B. Association Daha fazlası Daha az

Regulation of signal transduction cascades by Pterostilbenes in different cancers: Is it a death knell for oncogenic pathways

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

NEDD4 Family of E3 Ubiquitin Ligases in Breast Cancer: Spotlight on SMURFs, WWPs and NEDD4

Butt, G. | Yaylim, I. | Attar, Rukset | Aras, A. | Romero, M.A. | Qureshi, M.Z. | Farooqi, A.A.

Book Part | 2019 | Advances in Experimental Medicine and Biology1152 , pp.365 - 375

Massively parallel sequencing, genomic and proteomic technologies have provided near complete resolution of signaling landscape of breast cancer (BCa). NEDD4 family of E3-ubiquitin ligases comprises a large family of proteins particularly, SMURFs (SMURF1, SMURF2), WWPs and NEDD4 which are ideal candidates for targeted therapy. However, it is becoming progressively more understandable that SMURFs and NEDD4 have “split-personalities”. These molecules behave dualistically in breast cancer and future studies must converge on detailed identification of context specific role of these proteins in BCa. Finally, we provide scattered clues of . . . regulation of SMURF2 by oncogenic miRNAs, specifically considering longstanding questions related to regulation of SMURF1 and WWPs by miRNAs in BCa. SMURFS, WWPs and NEDD4 are versatile regulators and represent a fast-growing field in cancer research and better understanding of the underlying mechanisms will be helpful in transition of our knowledge from a segmented view to a more conceptual continuum. © 2019, Springer Nature Switzerland AG Daha fazlası Daha az

Tumor infiltrating lymphocytes in ovarian cancer

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

Use of hematopoietic stem cells in obstetrics and gynecology

Attar, Rukset | Attar, E.

Review | 2008 | Transfusion and Apheresis Science38 ( 3 ) , pp.245 - 251

Stem cells can be used in different areas of obstetrics and gynecology. Adult stem cells are specialized cells found within many tissues of the body where they function in tissue homeostasis and repair. In vitro they have been shown to differentiate into a wide variety of cell types. Hematopoietic stem cells (HSC) have been used to set up therapeutic strategies for the treatment of gynecological solid tumors such as ovarian cancer. Stem cells can be used for prenatal transplantation and in utero gene therapy. Also stem cells can be used in infertility and IVF for research and treatment. © 2008 Elsevier Ltd. All rights reserved.

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