Search results for: epithelial ovarian cancers
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 588

Search results for: epithelial ovarian cancers

558 Multi-Omics Investigation of Ferroptosis-Related Gene Expression in Ovarian Aging and the Impact of Nutritional Intervention

Authors: Chia-Jung Li, Kuan-Hao Tsui

Abstract:

As women age, the quality of their oocytes deteriorates irreversibly, leading to reduced fertility. To better understand the role of Ferroptosis-related genes in ovarian aging, we employed a multi-omics analysis approach, including spatial transcriptomics, single-cell RNA sequencing, human ovarian pathology, and clinical biopsies. Our study identified excess lipid peroxide accumulation in aging germ cells, metal ion accumulation via oxidative reduction, and the interaction between ferroptosis and cellular energy metabolism. We used multi-histological prediction of ferroptosis key genes to evaluate 75 patients with ovarian aging insufficiency and then analyzed changes in hub genes after supplementing with DHEA, Ubiquinol CoQ10, and Cleo-20 T3 for two months. Our results demonstrated a significant increase in TFRC, GPX4, NCOA4, and SLC3A2, which were consistent with our multi-component prediction. We theorized that these supplements increase the mitochondrial tricarboxylic acid cycle (TCA) or electron transport chain (ETC), thereby increasing antioxidant enzyme GPX4 levels and reducing lipid peroxide accumulation and ferroptosis. Overall, our findings suggest that supplementation intervention significantly improves IVF outcomes in senescent cells by enhancing metal ion and energy metabolism and enhancing oocyte quality in aging women.

Keywords: multi-omics, nutrients, ferroptosis, ovarian aging

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557 Impact of Nutritional Status on the Pubertal Transition in a Sample of Egyptian School Girls

Authors: Nayera E. Hassan, Salah Mostafa, Hamed Elkhayat, Kalled Hassan Sewidan, Sahar A. El-Masry, Manal Mouhamed Ali, Mones M. Abu Shady

Abstract:

Pubertal growth is influenced by many factors including environmental and nutritional factors. Objective: To assess impact of nutritional status on pubertal staging, ovarian and uterine volumes among school girls. Method: Study was cross sectional and carried out on 1000 healthy school girls, aged 8-18 years selected randomly. They were categorized according to their ages into three groups: 8-12 years, 13-15 years and 16-18 years ±6 months, then according to their body mass index percentile to normal weight: (≥15-<85.), overweight (≥85-<95) and obese (≥95). All girls were subjected for physical, anthropometric (weight, height, body mass index), nutritional markers WAZ (weight/age Z score), HAZ (height/age Z score) and BMI-Z (body mass index Z score), pubertal assessment (Tanner stage) and pelvic transabdominal sonography (uterine and ovarian volumes). Results: Highly significant differences in ovarian and uterine volumes and nutritional markers (WAZ, HAZ and BMI-Z score) were detected among different grades of puberty in the two age groups (8-12 years, 13-15 years) coming in advance of obese girls (with increase of BMI); except HAZ in the second age group. Girls aged 16-18 years reached to final volume for the uterus and ovary with insignificant differences. Pubertal stage, ovarian and uterine sizes were highly significantly correlated with nutritional markers. Mean ages of onset: of puberty, menarche and complete puberty were, 11.65 + 1.84, 14.79 + 1.75 and 15.02 + 1.68 years respectively. Conclusion: Nutritional status has a crucial role in determining pubertal stage, ovarian and uterine volumes among Egyptian girls during the pubertal process.

Keywords: pubertal stage, nutritional markers, girls, ovarian and uterine volumes

Procedia PDF Downloads 435
556 Evaluation of Brca1/2 Mutational Status among Algerian Familial Breast Cancer

Authors: Arab M., Ait Abdallah M., Zeraoulia N., Boumaza H., Aoutia M., Griene L., Ait Abdelkader B.,

Abstract:

breast and ovarian cancer are respectively the first and fourth leading causes of cancer among women in Algeria. A family story of cancer in the most important risk factor, and in most cases of families with breast and /or ovarian cancer, the pattern of cancer family can be attributed to mutation in BRCA1/2genes. objectibes: the aim of our study in to investigate the spectrum of BRCA1/2 germiline mutation in familial breast and /or ovarian cancer and to determine the prevalence and the nature of BRCA1/2mutation in Algeria methods: we deremined the prevalence of BRCA1/2 mutation within a cohort of 161 probands selected according the eisinger score double stranded sanger sequencing of all coding exons of BRCA1/2including flanking intronic region were performed results: we identified a total of 23 distinct deleterious mutations (class5) 12 differents mutations in BRCA1(52%) and 11 in BRCA2(48%). 78% (18/23) were protein truncating and 22%(5/23) missens mutations.3 novel deleterious mutations have been identified, which have not been described in public mutation database. one new mutation were found in two unrelated patients. the overall mutation detection rate in our study is 28,5%(46/161).more over, an UVS c7783 located in BRCA2 is found in two unrelated probands and segregate in the 02 families/ conclusion: our results sugget of large spectrum of BRCA1/2 mutation in Algerian breast/ovarian cancer family. The nature and prevalence of BRCA1/2mutation in algerian families are ongoing in a larger study, 80 probands are to day under investigation. This study which may therefore identify the genetic particularity of Algerian breast /ovarian cancer.

Keywords: BRCA1/2 mutations, hereditary breast cancer, algerian women, prvalence

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555 Endometrioma Ethanol Sclerotherapy

Authors: Lamia Bensissaid

Abstract:

Goals: Endometriosis affects 6 to 10% of women of childbearing age. 17 to 44% of them have ovarian endometriomas. Medical and surgical treatments represent the two therapeutic axes with which PMA can be associated. Laparoscopic intraperitoneal ovarian cystectomy is described as the reference technique in the management of endometriomas by learned societies (CNGOF, ESHRE, NICE). However, it leads to a significant short-term reduction in the AMH level and the number of antral follicles, especially in cases of bilateral cystectomy, large cyst size or cystectomy after recurrence. Often, the disease is at an advanced stage with several surgical patients. Most have adhesions, which increase the risk of surgical complications and suboptimal resection and, therefore recurrence of the cyst. These results led to a change of opinion towards a conservative approach. Sclerotherapy is an old technique which acts by fibrinoid necrosis. It consists of injecting a sclerosing agent into the cyst cavity. Results : Recurrence was less than 15% for a 12-month follow-up; these rates are comparable to those of surgery. It does not seem to have a negative impact on ovarian reserve, but this is not sufficiently evaluated. It has an advantage in IVF pregnancy rates compared to cystectomy, particularly in cases of recurrent endometriomas. It has the advantages: · To be done on an outpatient basis. · To be inexpensive. · To avoid sometimes difficult and iterative surgery: · To allow an increase in pregnancy rates and the preservation of the ovarian reserve compared to iterative surgery. · of great interest in cases of bilateral endometriomas (kissing ovaries) or recurrent endometriomas. Conclusions: Ethanol sclerotherapy could be a good alternative to surgery.

Keywords: Endometrioma, Sclerotherapy, infertility, Ethanol

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554 Forecasting Cancers Cases in Algeria Using Double Exponential Smoothing Method

Authors: Messis A., Adjebli A., Ayeche R., Talbi M., Tighilet K., Louardiane M.

Abstract:

Cancers are the second cause of death worldwide. Prevalence and incidence of cancers is getting increased by aging and population growth. This study aims to predict and modeling the evolution of breast, Colorectal, Lung, Bladder and Prostate cancers over the period of 2014-2019. In this study, data were analyzed using time series analysis with double exponential smoothing method to forecast the future pattern. To describe and fit the appropriate models, Minitab statistical software version 17 was used. Between 2014 and 2019, the overall trend in the raw number of new cancer cases registered has been increasing over time; the change in observations over time has been increasing. Our forecast model is validated since we have good prediction for the period 2020 and data not available for 2021 and 2022. Time series analysis showed that the double exponential smoothing is an efficient tool to model the future data on the raw number of new cancer cases.

Keywords: cancer, time series, prediction, double exponential smoothing

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553 Umbilical Cord-Derived Cells in Corneal Epithelial Regeneration

Authors: Hasan Mahmud Reza

Abstract:

Extensive studies of the human umbilical cord, both basic and translational, over the last three decades have unveiled a plethora of information. The cord lining harbors at least two phenotypically different multipotent stem cells: mesenchymal stem cells (MSCs) and cord lining epithelial stem cells (CLECs). These cells exhibit a mixed genetic profiling of both embryonic and adult stem cells, hence display a broader stem features than cells from other sources. We have observed that umbilical cord-derived cells are immunologically privileged and non-tumorigenic by animal study. These cells are ethically acceptable, thus provides a significant advantage over other stem cells. The high proliferative capacity, viability, differentiation potential, and superior harvest of these cells have made them better candidates in comparison to contemporary adult stem cells. Following 30 replication cycles, these cells have been observed to retain their stemness, with their phenotype and karyotype intact. Transplantation of bioengineered CLEC sheets in limbal stem cell-deficient rabbit eyes resulted in regeneration of clear cornea with phenotypic expression of the normal cornea-specific epithelial cytokeratin markers. The striking features of low immunogenicity protecting self along with co-transplanted allografts from rejection largely define the transplantation potential of umbilical cord-derived stem cells.

Keywords: cord lining epithelial stem cells, mesenchymal stem cell, regenerative medicine, umbilical cord

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552 Induction of Hsp70 and Antioxidant Status in Porcine Granulosa Cells in Response to Deoxynivalenol and Zearalenone Exposure in vitro

Authors: Marcela Capcarova, Adriana Kolesarova, Marina Medvedova, Peter Petruska, Alexander V. Sirotkin

Abstract:

The aim of this study was to determine the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS) and accumulation of Hsp70 in porcine ovarian granulosa cells after deoxynivalenol (DON) and zearalenone (ZEA) exposure in vitro. Porcine ovarian granulosa cells were incubated with DON/ZEA administrations as follows: group A (10/10 ng/mL), group B (100/100 ng/mL), group C (1000/1000 ng/mL), and the control group without any additions for 24h. In this study mycotoxins developed stress reaction of porcine ovarian granulosa cells and increased accumulation of Hsp70 what resulted in increasing activities of SOD and GPx in groups with lower doses of mycotoxins. High dose of DON and ZEA had opposite effect on GPx activity than the lower doses. Slight increase in TAS of porcine granulosa cells was observed after mycotoxins exposure. These results contribute towards the understanding of cellular stress and its response.

Keywords: deoxynivalenol, zearalenone, antioxidants, Hsp70, granulosa cells

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551 Effect of Z-VAD-FMK on in Vitro Viability of Dog Follicles

Authors: Leda Maria Costa Pereira, Maria Denise Lopes, Nucharin Songsasen

Abstract:

Mammalian ovaries contain thousands of follicles that eventually degenerate or die after culture in vitro. Caspase-3 is a key enzyme that regulating cell death. Our objective was to examine the influence of anti-apoptotic drug Z-VAD-FMK (pan-caspase inhibitor) on in vitro viability of dog follicles within the ovarian cortex. Ovaries were obtained from prepubertal (age, 2.5–6 months) and adult (age, 8 months to 2 years) bitches and ovarian cortical fragments were recovered. The cortices were then incubated on 1.5% (w/v) agarose gel blocks within a 24-wells culture plate (three cortical pieces/well) containing Minimum Essential Medium Eagle - Alpha Modification (Alpha MEM) supplemented with 4.2 µg/ml insulin, 3.8 µg/ml transferrin, 5 ng/ml selenium, 2 mM L-glutamine, 100 µg/mL of penicillin G sodium, 100 µg/mL of streptomycin sulfate, 0.05 mM ascorbic acid, 10 ng/mL of FSH and 0.1% (w/v) polyvinyl alcohol in humidified atmosphere of 5% CO2 and 5% O2. The cortices were divided in six treatment groups: 1) 10 ng/mL EGF (EGF V0); 2) 10 ng/mL of EGF plus 1 mM Z-VAD-FMK (EGF V1); 3) 10 ng/mL of EGF and 10 mM Z-VAD-FMK (EGF V10); 4) 1 mM Z-VAD-FMK; 5) 10 mM Z-VAD-FMK and (6) no EGF and Z-VAD-FMK supplementation. Ovarian follicles within the tissues were processed for histology and assessed for follicle density, viability (based on morphology) and diameter immediately after collection (Control) or after 3 or 7 days of in vitro incubation. Comparison among fresh and culture treatment group was performed using ANOVA test. There were no differences (P > 0.05) in follicle density and viability among different culture treatments. However, there were differences in this parameter between culture days. Specifically, culturing tissue for 7 days resulted in significant reduction in follicle viability and density, regardless of treatments. We found a difference in size between culture days when these follicles were cultured using 10 mM Z-VAD-FMK or 10 ng/mL EGF (EGF V0). In sum, the finding demonstrated that Z-VAD-FMK at the dosage used in the present study does not provide the protective effect to ovarian tissue during in vitro culture. Future studies should explore different Z-VAD-FMK dosages or other anti-apoptotic agent, such as surviving in protecting ovarian follicles against cell death.

Keywords: anti apoptotic drug, bitches, follicles, Z-VAD-FMK

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550 Policy to Improve in vitro Fertilization Outcome in Women with Poor Ovarian Response: Frozen Embryo Transfer (ET) of Accumulated Vitrified Embryos vs. Frozen ET of Accumulated Vitrified Embryos plus Fresh ET

Authors: Hwang Kwon

Abstract:

Objective: To assess the efficacy of embryo transfer (ET) of accumulated vitrified embryos and compare pregnancy outcomes between ET of thawed embryos following accumulation of vitrified embryos (frozen ET) and ET of fresh and thawed frozen embryos following accumulation of vitrified embryos (fresh ET + frozen ET). Study design: Patients were poor ovarian responders defined according to the Bologna criteria as well as a subgroup of women whose previous IVF-ET cycle through controlled ovarian stimulation (COS) yielded one or no embryos. Sixty-four frozen ETs were performed following accumulation of vitrified embryos (ACCE )(ACCE Frozen) and 51 fresh + frozen ETs were performed following accumulation of vitrified embryos (ACCE Fresh + Frozen). Positive βhCG rate, clinical pregnancy rate, ongoing pregnancy rate, and good quality embryos (%, ±SD) were compared between two groups. Results: There were more good quality embryos in the ACCE Fresh + Frozen group than in the ACCE Frozen group: 60±34.7 versus 42.9±28.9, respectively (p=0.03). Positive βhCG rate [18/64(28.2%) vs. 13/51(25.5%); p=0.75] and clinical pregnancy rate [12/64 (18.8%) vs. 11/51 (10.9%); p=0.71] were comparable between the two groups. Conclusion: Accumulation of vitrified embryos is an effective method in patients with poor ovarian response who fulfill the Bologna criteria. Pregnancy outcomes were comparable between the two groups.

Keywords: accumulation of embryos, frozen embryo transfer, poor responder, Bologna criteria

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549 Diagnosis of Gingivitis Based on Correlations of Laser Doppler Data and Gingival Fluid Cytology

Authors: A. V. Belousov, Yakushenko

Abstract:

One of the main problems of modern dentistry is development a reliable method to detect inflammation in the gums on the stages of diagnosis and assessment of treatment efficacy. We have proposed a method of gingival fluid intake, which successfully combines accessibility, excluding the impact of the annoying and damaging the gingival sulcus factors and provides reliable results (patent of RF№ 2342956 Method of gingival fluid intake). The objects of the study were students - volunteers of Dentistry Faculty numbering 75 people aged 20-21 years. Cellular composition of gingival fluid was studied using microscope "Olympus CX 31" (Japan) with the calculation of epithelial leukocyte index (ELI). Assessment of gingival micro circulation was performed using the apparatus «LAKK–01» (Lazma, Moscow). Cytological investigation noted the highly informative of epithelial leukocyte index (ELI), which demonstrated changes in the mechanisms of protection gums. The increase of ELI occurs during inhibition mechanisms of phagocytosis and activation of epithelial desquamation. The cytological data correlate with micro circulation indicators obtained by laser Doppler flowmetry. We have identified and confirmed the correlations between parameters laser Doppler flowmetry and data cytology gingival fluid in patients with gingivitis.

Keywords: gingivitis, laser doppler flowmetry, gingival fluid cytology, epithelial leukocyte index (ELI)

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548 The Relationship between Size of Normal and Cystic Bovine Ovarian Follicles with Follicular Fluid Levels of Nitric Oxide and Estradiol

Authors: Hamidreza Khodaei, Behnaz Mahdavi, Leila Karshenas

Abstract:

Nitric oxide (NO) is a small fast acting neurotransmitter, which is synthesized From L-arginine by nitric oxide synthase. Studies show that NO affects a wide range of reproductive functions. Steroidal hormones synthesis, LH surge during ovulation, follicular growth and ovulation are all affected by NO. Therefore, the objective of this study was to evaluate the relationship between NO and estradiol (E2) production in ovarian follicles and cysts in bovines. Two experiment groups were formed and serum and follicular fluid levels Of NO and estradiol (E2) was measured. In the first group, follicular fluids were obtained from 30 slaughtered cows. Follicles were divided into three groups according to follicular diameter: Small follicles, <5 mm, medium-sized follicles, 5 to 10 mm, and large follicles, >10 mm. 30 follicles were randomly selected within each group. Blood samples were obtained via jugular vein. NO concentrations in blood and ovarian follicular fluids were measured by Griess reaction method and radio-immunoassay respectively. In the second group: 12 cows in follicular phase and with cystic follicles were selected and a cystic follicle was obtained from each. NO and E2 levels were measured as done for the first experiment group. The data were analyzed by SAS software using ANOVA and Duncan’s test. NO concentrations of follicular fluids from large follicles were significantly higher than those of the medium and small-sized ones. There were significant differences in the concentrations of nitrite and nitrate (Stable metabolites of NO) between large and cystic follicles, with extremely low NO and high E2 levels in cystic follicles (p<0.01).The results suggest that paracrine effects of NO may play an important role in the control of ovarian follicle growth and development of cystic follicles in bovines. It seems that NO dictates its effects through inhibition of ovarian steroidal synthesis.

Keywords: nitric oxide, estradiol, cystic follicle, cow, oogenesis, oocyte maturation, follicular fluid

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547 Smart Coating for Enhanced Corneal Healing via Delivering Progranulin

Authors: Dan Yan, Yunuo Zhang, Yuhan Huang, Weijie Ouyang

Abstract:

The cornea serves as a vital protective barrier for the eye; however, it is prone to injury and damage that can disrupt corneal epithelium and nerves, triggering inflammation. Therefore, understanding the biological effects and molecular mechanisms involved in corneal wound healing and identifying drugs targeting these pathways is crucial for researchers in this field. This study aimed to investigate the therapeutic potential of progranulin (PGRN) in treating corneal injuries. Our findings demonstrated that PGRN significantly enhanced corneal wound repair by accelerating corneal re-epithelialization and re-innervation. In vitro experiments with cultured epithelial cells and trigeminal ganglion cells further revealed that PGRN stimulated corneal epithelial cell proliferation and promoted axon growth in trigeminal ganglion cells. Through RNA-sequencing (RNA-seq) analysis and other experimental techniques, we discovered that PGRN exerted its healing effects by modulating the Wnt signaling pathway, which played a critical role in repairing epithelial cells and promoting axon regeneration in trigeminal neurons. Importantly, our study highlighted the anti-inflammatory properties of PGRN by inhibiting the NF-κB signaling pathway, leading to decreased infiltration of macrophages. In conclusion, our findings underscored the potential of PGRN in facilitating corneal wound healing by promoting corneal epithelial cell proliferation, trigeminal ganglion cell axon regeneration, and suppressing ocular inflammation. These results suggest that PGRN could potentially expedite the healing process and improve visual outcomes in patients with corneal injuries.

Keywords: cornea, wound healing, progranulin, corneal epithelial cells, trigeminal ganglion cells

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546 Development and Pre-clinical Evaluation of New ⁶⁴Cu-NOTA-Folate Conjugates for PET Imaging of Folate Receptor-Positive Tumors

Authors: Norah Al Hokbany, Ibrahim Al Jammaz, Basem Al Otaibi, Yousif Al Malki, Subhani M. Okarvi

Abstract:

Objective: The folate receptor is over-expressed in a wide variety of human tumors. Conjugates of folate have been shown to be selectively taken up by tumor cells via the folate receptor. In an attempt to develop new folate radiotracers with favorable biochemical properties for detecting folate receptor-positive cancers. Methods: we synthesized ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugates using a straightforward and simple one-step reaction. Radiochemical yields were greater than 95% (decay-corrected) with a total synthesis time of less than 20 min. Results: Radiochemical purities were always greater than 98% without high-performance liquid chromatography (HPLC) purification. These synthetic approaches hold considerable promise as a rapid and simple method for ⁶⁴Cu-folate conjugate preparation with high radiochemical yield in a short synthesis time. In vitro tests on the KB cell line showed that significant amounts of the radio conjugates were associated with cell fractions. Bio-distribution studies in nude mice bearing human KB xenografts demonstrated a significant tumor uptake and favorable bio-distribution profile for ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugate. The uptake in the tumors was blocked by the excess injection of folic acid, suggesting a receptor-mediated process. Conclusion: These results demonstrate that the ⁶⁴Cu-NOTAM-folate conjugate may be useful as a molecular probe for the detection and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis, as well as monitoring tumor response to treatment.

Keywords: folate, receptor, tumor imaging, ⁶⁴Cu-NOTA-folate, PET

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545 Screening Active Components in YPFS for Regulating Initiative Key Factors in Allergic Inflammation

Authors: Dandan Shen, Hui-zhu Wang, Xi Yu, LiLi Gui, Xiao Wei, Xiao-yan Jiang, Da-wei Wang, Min Hong

Abstract:

Yu-ping-feng-san (YPFS) is a clinical medicine for asthma and other allergic diseases, but the mechanism of YPFS on relapse of allergy is unclear. Currently, people come to realize the epithelial cells(EC) play a key role in stimulating and regulating local immune response. The study of thymic stromal lymphopoietin(TSLP derived from EC provides an important evidence that the EC can regulate immune response to stimulate allergic response. In this study, we observed the effect of YPFS on TSLP in vivo and in vitro. We established a method by using bronchial epithelial cells (16HBE) for screening potential bioactive components by HPLC-MS in YPFS and then analyzed the components in serum containing YPFS by UPLC-MS. The results showed that YPFS could decrease TSLP protein level in OVA-sensitized mice and 16HBE cells. Five components combing with the 16HBE cells were both detected in the serum.

Keywords: TSLP, bronchial epithelial cells, cell-binding, drug-containing serum

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544 Induction of Cytotoxicity and Apoptosis in Ovarian Cancer Cell Line (CAOV-3) by an Isoquinoline Alkaloid Isolated from Enicosanthellum pulchrum (King) Heusden

Authors: Noraziah Nordin, Najihah Mohd Hashim, Nazia Abdul Majid, Mashitoh Abdul Rahman, Hamed Karimian, Hapipah Mohd Ali

Abstract:

Enicosanthellum pulchrum belongs to family Annonaceae is also known as family of 'mempisang' in Malaysia. Liriodenine was isolated by prep-HPLC method. This method was first technique used for the isolation of this compound. The structure of the liriodenine was elucidated by 1D and 2D spectroscopy techniques. Liriodenine was tested on ovarian cancer cells line (CAOV-3) for MTT, AO/PI and cytotoxicity 3 assays. The MTT assay was performed to determine the cytotoxicity effect of lirodenine on CAOV-3 cells. The morphological changes on CAOV-3 cells were observed by AO/PI assay for the early and late stage of apoptosis, as well as necrosis. Meanwhile, the measurement of cell loss, nuclear morphology, DNA content, cell membrane permeability, mitochondrial membrane potential changes and cytochrome c release from mitochondria were detected through cytotoxicity 3 assay. The IC50 results showed liriodenine inhibits the growth of CAOV-3 cells after 24 h of treatment at 10.25 ± 1.06 µg/mL. After 48 and 72 h of treatments, the IC50 values were decreased to 7.65 ± 0:07 and 6.35 ± 1.62 µg/mL, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies with increasing time of treatment from 24 to 72 h. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with liriodenine, resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated the capability of liriodenine as a promising anticancer agent, particularly on human ovarian cancer.

Keywords: Enicosanthellum pulchrum, ovarian cancer, apoptosis, cytotoxicity

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543 Role of Bariatric Surgery in Polycystic Ovarian Syndrome &Infertility

Authors: Ahuja Ashish, Nain Prabhdeep Singh

Abstract:

Introduction: Polycystic ovarian syndrome(PCOS) is the most common endocrine disorder among women of reproductive age.Pcos encompasses a broad spectrum of signs&symptoms of ovary dysfunction,obesity,blood pressure,insulin resistance & infertility. Bariatric Surgery can be an effective means of weight loss in Pcos & curing infertility. Materials and Methods: 15 female patients were enrolled in the study from 2012-2014.66%(n=10) were in age group of 20-25 years,33%(n=5) were in age group of 25-33 years who underwent. Bariatric surgery in form of Laproscopic sleeve Gastrectomy(LSG)& Roux-en-Y gastric bypass. LSG 73%(n=11), RYGB26% (n=4). Results: There was a significant improvement in obesity (60% excess weight loss)over 1 year after bariatric surgery, in 12 patients there was gross improvement in restoration of menstrual cycle who had irregular menstrual cycle. In 80% patients the serum insulin level showed normal value. Over two years 8 patients become pregnant. Conclusions: 1)Obese women with Pcos maybe able to conceive after Bariatric Surgery. 2) Women with Pcos should only consider bariatric surgery if they were already considering it for other reasons to treat obesity, blood pressure & other co-morbid conditions.

Keywords: obesity, bariatric surgery, polycystic ovarian syndrome, infertility

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542 Quercetin and INT3 Inhibits Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition in MCF7 Breast Cancer Cells

Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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541 Anterior Segment Optical Coherence Tomography Study of Cornea and Tear Film Parameters in Juvenile Systemic Lupus Erythematous Patients

Authors: Mohamed Salah El-Din Mahmoud, Ahmed Hamed, Asmaa Anwar Mohamed

Abstract:

Purpose: To study the tear film parameters, total corneal thickness (CT), corneal epithelial thickness and, corneal power in Juvenile systemic lupus erythematosus (JSLE) patients compared to age-matched controls using anterior segment optical coherence tomography (AS-OCT). Methods: This was a cross-sectional study. Study participants were divided into 2 groups: Group A: 75 eyes of JSLE patients, Group B: 75 eyes of healthy controls. Tear meniscus height (TMH), tear meniscus depth (TMD), and tear meniscus area (TMA) were the lower tear meniscus parameters that were measured. The corneal power, CT, and epithelial thickness were all determined automatically. Results: In the JSLE group, the range of age was 10 to 15 years while the control group was 11 to 16 years. TMH, TMA, and TMD were 527.7±46.8, 0.059±0.015 and 343.3±59.9 respectively in JSLE group while 525.4±44.6, 0.058±0.011 and 340.6±58.0 respectively in control group without significant difference (p-value<0.001). The corneal power was 43.3±0.55 in the JSLE while 43.2±0.54 in the control group without significant difference (p-value= 0.407). CT was 551.1±13.5 in JSLE group while 551.2±15.3 in control group without significant difference (p-value= 0.982). Epithelial thickness was 52.66±1.35 in the JSLE group while 52.60±1.36 in the control group without significant difference (p-value= 0.765). Conclusion: We demonstrated no significant difference in tear meniscus dimensions, CT, epithelial thickness, and corneal power in the JSLE patients compared to age-matched controls using AS-OCT.

Keywords: tear film, ASOCT, JSLE, pachymetry, corneal thickness

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540 Circadian Disruption in Polycystic Ovary Syndrome Model Rats

Authors: Fangfang Wang, Fan Qu

Abstract:

Polycystic ovary syndrome (PCOS), the most common endocrinopathy among women of reproductive age, is characterized by ovarian dysfunction, hyperandrogenism and reduced fecundity. The aim of this study is to investigate whether the circadian disruption is involved in pathogenesis of PCOS in androgen-induced animal model. We established a rat model of PCOS using single subcutaneous injection with testosterone propionate on the ninth day after birth, and confirmed their PCOS-like phenotypes with vaginal smears, ovarian hematoxylin and eosin (HE) staining and serum androgen measurement. The control group rats received the vehicle only. Gene expression was detected by real-time quantitative PCR. (1) Compared with control group, PCOS model rats of 10-week group showed persistently keratinized vaginal cells, while all the control rats showed at least two consecutive estrous cycles. (2) Ovarian HE staining and histological examination showed that PCOS model rats of 10-week group presented many cystic follicles with decreased numbers of granulosa cells and corpora lutea in their ovaries, while the control rats had follicles with normal layers of granulosa cells at various stages of development and several generations of corpora lutea. (3) In the 10-week group, serum free androgen index was notably higher in PCOS model rats than controls. (4) Disturbed mRNA expression patterns of core clock genes were found in ovaries of PCOS model rats of 10-week group. Abnormal expression of key genes associated with circadian rhythm in ovary may be one of the mechanisms for ovarian dysfunction in PCOS model rats induced by androgen.

Keywords: polycystic ovary syndrome, androgen, animal model, circadian disruption

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539 Targeted Photodynamic Therapy for Intraperitoneal Ovarian Cancer, A Way to Stimulate Anti-Tumoral Immune Response

Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

Abstract:

Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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538 Real Time PCR Analysis of microRNA Expression in Oral Cancer

Authors: Karl Kingsley

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Many mechanisms are involved in the control of cellular differentiation and growth, which are often dysregulated in many cancers. Many distinct pathways are involved in these mechanisms of control, including deoxyribonuclease (DNA) methyltransferase and histone deacetylase (HDAC) activation that controls both genetic and epigenetic modifications and micro ribonucleic acid (RNA) expression. Less is known about the expression of DNA methyltransferase (DNMT) and HDAC in oral cancers and the effect on microRNA expression. The primary objective of this study was to evaluate the expression of DNMT and HDAC family members in oral cancer and the concomitant expression of cancer-associated microRNAs. Using commercially available oral cancers, including squamous cell carcinoma (SCC)-4, SCC-9, SCC-15, and SCC-25, RNA was extracted and screened for DNMT, HDAC, and microRNA expression using highly-specific primers and quantitative polymerase chain reaction (qPCR). These data revealed low or absent expression of DNMT-1, which is associated with cellular differentiation but increased expression of DNMT-3a and DNMT-3b in all SCC cell lines compared with normal non-cancerous cell controls. In addition, no expression of HDAC1 and HDAC2 expression was found among the normal, non-cancerous cells but was highly expressed in each of the SCC cell lines examined. Differential expression of oncogenic and cancer-associated microRNAs was also observed among the SCC cell lines, including miR-21, miR-133, miR-149, miR-155, miR-365, and miR-720. These findings also appeared to vary according to observed growth rates among these cells. These data may be the first to demonstrate the expression and association between HDAC and DNMT3 family members among oral cancers. In addition, the differential expression of these epigenetic modifiers may be associated with the expression of specific microRNAs in these cancers, which have not previously been observed to the best of the author's knowledge. In addition, some associations and relationships may exist between the expression of these biomarkers and the rates of growth and proliferation, which may suggest that these expression patterns might represent potentially useful biomarkers to determine tumor aggressiveness and other phenotypic behaviors among oral cancers.

Keywords: oral cancer, DNA methyltransferase, histone deacetylase, microRNA

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537 Efficacy and Safety of Updated Target Therapies for Treatment of Platinum-Resistant Recurrent Ovarian Cancer

Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

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536 Novel Steviosides Analogs Induced Apoptosis in Breast Cancers

Authors: Ahmed Malki

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Breast cancer has been identified as the most lethal form of cancer today. In our study, we designed and screened 16 steviosides derivatives for their cytotoxic activities in MCF-7human breast cancer cells and normal MCF-12a cells. Our data indicated that steviosides derivatives 9 and 15 decreased cell proliferation and induced apoptosis in MCF-7 breast cancer cells more thannormal breast cells epithelial cells. Flow cytometric analysis showed that both steviosides, derivatives 9 and 15 arrested the MCF-7 cells in G1 phase, which is further confirmed by the increased expression level of p21. Moreover, both steviosides derivatives increased caspase-9 activity, and the induction of apoptosis was significantly reduced after treating cells with caspase-9 inhibitor LEHD-CHO. Both steviosides derivatives increased Caspase 3 activities and induced Parp-1 cleavage in H1299 cells. Based on previous results, we have identified two novel steviosides derivatives which provoked apoptosis in breast cancer cells by arresting cells in G1 phase and increasing caspase-9 and caspase-3 activities which merits further development and investigations.

Keywords: steviosides, breast cancer, p53, cell cycle

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535 Role of Dedicated Medical Social Worker in Fund Mobilisation and Economic Evaluation in Ovarian Cancer: Experience from a Tertiary Referral Centre in Eastern India

Authors: Aparajita Bhattacharya, Mousumi Dutta, Zakir Husain, Dionne Sequeira, Asima Mukhopadhyay

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Background: Tata Medical Centre (TMC), Kolkata is a major cancer referral centre in Eastern India and neighbouring countries providing state of the art facilities; however, it is a non-profit organisation with patients requiring to pay at subsidised rates. Although a system for social assessment and applying for governmental/ non-governmental (NGO) funds is in place, access is challenging. Amongst gynaecological cancers (GC), ovarian cancer (OC) is associated with the highest treatment cost; majority of which is required at the beginning when complex surgery is performed and funding arrangements cannot be made in time. We therefore appointed a dedicated Medical Social Worker (MSW) in 2016, supported by NGO for GC patients in order to assist patients/family members to access/avail these funds more readily and assist in economic evaluation for both direct and opportunity costs. Objectives: To reflect on our experience and challenges in collecting data on economic evaluation of cancer patients and compare success rates in achieving fund mobilization after introduction of MSW. Methods: A Retrospective survey. Patients with OC and their relatives were seen by the MSW during the initial outpatients department visit and followed though till discharge from the hospital and during follow-up visits. Assistance was provided in preparing the essential documents/paperwork/contacts for the funding agencies including both governmental (Chief-Minister/Prime-Minister/President) and NGO sources. In addition, a detailed questionnaire was filled up for economic assessment of direct/opportunity costs during the entire treatment and 12 months follow up period which forms a part of the study called HEPTROC (Health economic evaluation of primary treatment for ovarian cancer) developed in collaboration with economics departments of Universities. Results: In 2015, 102 patients were operated for OC; only 16 patients (15.68 %) had availed funding of a total sum of INR 1640000 through the hospital system for social assessment. Following challenges were faced by majority of the relatives: 1. Gathering important documents/proper contact details for governmental funding bodies and difficulty in following up the current status 3. Late arrival of funds. In contrast in 2016, 104 OC patients underwent surgery; the direct cost of treatment was significantly higher (median, INR 300000- 400000) compared to other GCs (n=274). 98/104 (94.23%) OC patients could be helped to apply for funds and 90/104(86.56%) patients received funding amounting to a total of INR 10897000. There has been a tenfold increase in funds mobilized in 2016 after the introduction of dedicated MSW in GC. So far, in 2017 (till June), 46/54(85.18%) OC patients applied for funds and 37/54(68.51%) patients have received funding. In a qualitative survey, all patients appreciated the role of the MSW who subsequently became the key worker for patient follow up and the chief portal for patient reported outcome monitoring. Data collection quality for the HEPTROC study was improved when questionnaires were administered by the MSW compared to researchers. Conclusion: Introduction of cancer specific MSW can expedite the availability of funds required for cancer patients and it can positively impact on patient satisfaction and outcome reporting. The economic assessment will influence fund allocation and decision for policymaking in ovarian cancer. Acknowledgement: Jivdaya Foundation Dallas, Texas.

Keywords: economic evaluation, funding, medical social worker, ovarian cancer

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534 Structure-Based Virtual Screening to Identify CLDN4 Inhibitors

Authors: Jayanthi Sivaraman

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Claudins are the important components of the tight junctions that play a key role in paracellular permeability. Among various members of Claudin family, Claudin 4 (CLDN4) is found to be overexpressed in ovarian, pancreatic carcinomas and other epithelial malignancies. Therefore, in this study, an attempt has been made to identify potent inhibitors for CLDN4 from the ZINC database using virtual screening, molecular docking and molecular dynamics simulations. A well refined molecular model of CLDN4 was built using Prime of Schrodinger v10.2(Template- PDB ID: 4P79). Approximately, 6 million compounds from ZINC database are subjected to high-throughput virtual screening (HTVS) against the active site of CLDN4. Molecular docking using GLIDE predicted ARG31, ASN142, ASP146 and ARG158 as critically important residues. Furthermore, three compounds from ZINC database (ZINC96331839, ZINC36533519 and ZINC75819394) showed highly promising ADME properties and binding affinity with stable conformation. The therapeutic efficiency of these lead compounds is evaluated and confirmed by in-vitro and in-vivo studies which leads to the development of novel anti-cancer drugs.

Keywords: ADME property, inhibitors, molecular docking, virtual screening

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533 Concanavaline a Conjugated Bacterial Polyester Based PHBHHx Nanoparticles Loaded with Curcumin for the Ovarian Cancer Therapy

Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

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In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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532 The Impact of Co-Administration of Phosphodiesterase-5 Inhibitor and Sodium Selenite on Ischemia/Reperfusion Injury in a Rat Ovary Model: Biochemical and Histopathologic Evaluation

Authors: Waleed Aly Sayed Ahmed, Eman Kishk, Tahani Shams

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Aim: To study the effects of co-administration of phosphodiesterase-5 inhibitor (PDE-5) and sodium selenite against the damage induced by ovarian ischemia-reperfusion in rats. Materials and Methods: A total of forty-two sexually mature, virgin, female rats were divided randomly into six groups of seven each: sham group (C), ischemia group (I), ischemia/reperfusion group (I/R), ischemia/reperfusion plus 1.4mg/kg sildenafil (I/R+S) group, ischemia/reperfusion plus 0.2mg/kg selenium (I/R+Se) group and ischemia/reperfusion plus combination of sildenafil and selenium (I/R+S+Se) group. In ischemia group (I), rats were exposed to ischemia for 3 hours (h). In ischemia/reperfusion group (I/R), rats were exposed to ischemia for 3 h followed by 6 h of reperfusion. Treated groups received 1.4mg/kg sildenafil or 0.2 mg/kg selenium or both 30 min before reperfusion. Both ovaries were surgically removed carefully. One ovary was examined for histopathological changes and the other was subject to biochemical analysis including malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx). Results: Assessment of ovarian tissue damage using a scoring system showed marked vascular congestion, interstitial edema, leukocyte infiltration, hemorrhage, and follicular degeneration in ischemia and ischemia/reperfusion groups. Tissue damage score for I, IR and all treated groups were significantly higher than those of the sham group (p<0.001), while tissue damage score decreased significantly in I/R+S and I/R+Se groups compared to I/R group (p<0.05), and notably, the difference was highly significant in I/R+S+Se group (p<0.001). There was significant increase in MDA levels and reduction in activities of CAT and GPx in I/R group compared to the sham group (p < 0.05). In I/R+S and I/R+Se groups, MDA was significantly decreased compared to the I/R group (p<0.05) and the difference was highly significant with co-administration of sildenafil and selenium (p<0.001). CAT and GPx were higher in all treated groups compared to I/R group (p<0.05). Conclusion: The co-administration of sildenafil citrate and selenium are highly protective against damage induced by ovarian ischemia/reperfusion in rats.

Keywords: phosphodiesterase-5 inhibitor, sildenafil, antioxidant, selenium, ovarian ischemia

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531 Studies on Induction of Cytotoxicity Through Apoptosis In Ovarian Cancer Cell Line (CAOV-3) by Chloroform Extract of Artocarpus Kemando Miq

Authors: Noor Shafifiyaz Mohd Yazid, Najihah Mohd Hashim, Hapipah Mohd Ali, Syam Mohan, Rosea Go

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Artocarpus kemando is a plant species from Moraceae family. This plant is used as household utensil by the local and the fruits are edible. The plants’ bark was used for the extraction process and yielded the chloroform crude extract which was used to screen for anticancer potential. The cytotoxic effect of the extract on CAOV-3 and WRL 68 cell lines were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assays. Qualitative AO/PI assay was performed to confirm the apoptosis and necrosis process. Meanwhile, the measurement of cell loss, nuclear morphology, DNA content, cell membrane permeability, mitochondrial membrane potential changes and cytochrome c release from mitochondria were detected through cytotoxicity 3 assay. In MTT assay, A. kemando inhibited 50% growth of CAOV-3 cells at 27.9 ± 0:03, 20.1± 0:03, 18.21± 0:04 µg/mL after 24, 48 and 72 hour, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with extract resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated A. kemando has potentially anticancer agent, particularly on human ovarian cancer.

Keywords: anticancer, Artocarpus kemando, ovarian cancer, cytotoxicity

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530 Correlation of Clinical and Sonographic Findings with Cytohistology for Diagnosis of Ovarian Tumours

Authors: Meenakshi Barsaul Chauhan, Aastha Chauhan, Shilpa Hurmade, Rajeev Sen, Jyotsna Sen, Monika Dalal

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Introduction: Ovarian masses are common forms of neoplasm in women and represent 2/3rd of gynaecological malignancies. A pre-operative suggestion of malignancy can guide the gynecologist to refer women with suspected pelvic mass to a gynecological oncologist for appropriate therapy and optimized treatment, which can improve survival. In the younger age group preoperative differentiation into benign or malignant pathology can decide for conservative or radical surgery. Imaging modalities have a definite role in establishing the diagnosis. By using International Ovarian Tumor Analysis (IOTA) classification with sonography, costly radiological methods like Magnetic Resonance Imaging (MRI) / computed tomography (CT) scan can be reduced, especially in developing countries like India. Thus, this study is being undertaken to evaluate the role of clinical methods and sonography for diagnosis of the nature of the ovarian tumor. Material And Methods: This prospective observational study was conducted on 40 patients presenting with ovarian masses, in the Department of Obstetrics and Gynaecology, at a tertiary care center in northern India. Functional cysts were excluded. Ultrasonography and color Doppler were performed on all the cases.IOTA rules were applied, which take into account locularity, size, presence of solid components, acoustic shadow, dopper flow etc . Magnetic Resonance Imaging (MRI) / computed tomography (CT) scans abdomen and pelvis were done in cases where sonography was inconclusive. In inoperable cases, Fine needle aspiration cytology (FNAC) was done. The histopathology report after surgery and cytology report after FNAC was correlated statistically with the pre-operative diagnosis made clinically and sonographically using IOTA rules. Statistical Analysis: Descriptive measures were analyzed by using mean and standard deviation and the Student t-test was applied and the proportion was analyzed by applying the chi-square test. Inferential measures were analyzed by sensitivity, specificity, negative predictive value, and positive predictive value. Results: Provisional diagnosis of the benign tumor was made in 16(42.5%) and of the malignant tumor was made in 24(57.5%) patients on the basis of clinical findings. With IOTA simple rules on sonography, 15(37.5%) were found to be benign, while 23 (57.5%) were found to be malignant and findings were inconclusive in 2 patients (5%). FNAC/Histopathology reported that benign ovarian tumors were 14 (35%) and 26(65%) were malignant, which was taken as the gold standard. The clinical finding alone was found to have a sensitivity of 66.6% and a specificity of 90.9%. USG alone had a sensitivity of 86% and a specificity of 80%. When clinical findings and IOTA simple rules of sonography were combined (excluding inconclusive masses), the sensitivity and specificity were 83.3% and 92.3%, respectively. While including inconclusive masses, sensitivity came out to be 91.6% and specificity was 89.2. Conclusion: IOTA's simple sonography rules are highly sensitive and specific in the prediction of ovarian malignancy and also easy to use and easily reproducible. Thus, combining clinical examination with USG will help in the better management of patients in terms of time, cost and better prognosis. This will also avoid the need for costlier modalities like CT, and MRI.

Keywords: benign, international ovarian tumor analysis classification, malignant, ovarian tumours, sonography

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529 Influence of JHA and Ecdysteroid on Reproduction in Dysdercus similis (Hemiptera: Pyrrhocoridae)

Authors: Versha Sharma

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Juvenile hormone analogue, fenoxycarb and ecdysterone, when applied at varying concentrations in the adult females of Dysdercus similis, in situ histochemical observations of treated ovarian and adipose tissues during the first gonotrophic cycle elicited drastic histomorphological changes in both tissues. The action and effect of both JHa and ecdysterone on ovarian development, vitellogenesis, the activity of follicular epithelium, chorion formation all were monitored in detail. SDS-PAGE electrophoretic analysis showed drastic downregulation on the protein profile of differently treated tissue samples. After exogenous JHa supply, resorption of the developing oocytes was also often noticed. Gradational decline and disappearance of different protein bands in treated both ovarian and adipose tissues noticed could be due to the depletion of specific metabolites essential for oocyte development and maturation. Natural products support both crop production and the environment that being effective in pest control, less toxic to non-target organisms and at the same time biodegradable. Hence, these could be utilized as an attractive alternative to the synthetic chemical insecticides for at least cotton bug pest management. Increasing IGR dosages is found to elicit both qualitative and quantitative depletion of protein metabolites and drastic histochemical changes in the gonads of the treated forms brought forth the production of a large number of immature mal-formed oocytes. Findings in greater detail could be discussed.

Keywords: juvenile hormone, ecdysone, P. picta, Dysdercus similis

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