Search results for: liver tumor
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1440

Search results for: liver tumor

840 Clinical Application of Mesenchymal Stem Cells for Cancer Therapy: A Review of Registered Clinical Trials

Authors: Tuong Thi Van Thuy, Dao Van Toan, Nguyen Duc Phuc

Abstract:

Mesenchymal stem cells (MSCs) were discovered in the 1970s with their unique properties of differentiation, immunomodulation, multiple secreting, and homing factors to injured organs. MSC-based therapies have emerged as a promising strategy for various diseases such as cancer, tissue regeneration, or immunologic/inflammatory-related diseases. This study evaluated the clinical application of MSCs for cancer therapy in trials registered on Clinical Trial as of July 2022. The results showed 40 clinical trials used MSCs in various cancer conditions. 62% of trials used MSCs for therapeutic purposes to minimize the side effects of cancer treatment. Besides, 38% of trials were focused on using MSCs as a therapeutic agent to treat cancer directly. Most trials (38/40) are ongoing phase I/II, and 2 are entering phase III. 84% of trials used allogeneic MSCs compared with 13% using autologous sources and 3% using both. 25/40 trials showed participants received a single dose of MSCs, while the most times were 12 times in a pancreatic cancer treatment trial. Conclusion: MSC-based therapy for cancer in clinical trials should be applied to (1) minimize the side effects of oncological treatments and (2) directly affect the tumor via selectively delivering anti-cancer payloads to tumor cells. Allogeneic MSCs are a priority selected in clinical cancer therapy.

Keywords: mesenchymal stem cells, MSC-based therapy, cancer condition, cancer treatment, clinical trials

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839 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma

Authors: Aoxue Yang, Weili Tian, Haikun Liu

Abstract:

Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

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838 Progress Towards Optimizing and Standardizing Fiducial Placement Geometry in Prostate, Renal, and Pancreatic Cancer

Authors: Shiva Naidoo, Kristena Yossef, Grimm Jimm, Mirza Wasique, Eric Kemmerer, Joshua Obuch, Anand Mahadevan

Abstract:

Background: Fiducial markers effectively enhance tumor target visibility prior to Stereotactic Body Radiation Therapy or Proton therapy. To streamline clinical practice, fiducial placement guidelines from a robotic radiosurgery vendor were examined with the goals of optimizing and standardizing feasible geometries for each treatment indication. Clinical examples of prostate, renal, and pancreatic cases are presented. Methods: Vendor guidelines (Accuray, Sunnyvale, Ca) suggest implantation of 4–6 fiducials at least 20 mm apart, with at least a 15-degree angular difference between fiducials, within 50 mm or less from the target centroid, to ensure that any potential fiducial motion (e.g., from respiration or abdominal/pelvic pressures) will mimic target motion. Also recommended is that all fiducials can be seen in 45-degree oblique views with no overlap to coincide with the robotic radiosurgery imaging planes. For the prostate, a standardized geometry that meets all these objectives is a 2 cm-by-2 cm square in the coronal plane. The transperineal implant of two pairs of preloaded tandem fiducials makes the 2 cm-by-2 cm square geometry clinically feasible. This technique may be applied for renal cancer, except repositioned in a sagittal plane, with the retroperitoneal placement of the fiducials into the tumor. Pancreatic fiducial placement via endoscopic ultrasound (EUS) is technically more challenging, as fiducial placement is operator-dependent, and lesion access may be limited by adjacent vasculature, tumor location, or restricted mobility of the EUS probe in the duodenum. Fluoroscopically assisted fiducial placement during EUS can help ensure fiducial markers are deployed with optimal geometry and visualization. Results: Among the first 22 fiducial cases on a newly installed robotic radiosurgery system, live x-ray images for all nine prostatic cases had excellent fiducial visualization at the treatment console. Renal and pancreatic fiducials were not as clearly visible due to difficult target access and smaller caliber insertion needle/fiducial usage. The geometry of the first prostate case was used to ensure accurate geometric marker placement for the remaining 8 cases. Initially, some of the renal and pancreatic fiducials were closer than the 20 mm recommendation, and interactive feedback with the proceduralists led to subsequent fiducials being too far to the edge of the tumor. Further feedback and discussion of all cases are being used to help guide standardized geometries and achieve ideal fiducial placement. Conclusion: The ideal tradeoffs of fiducial visibility versus the thinnest possible gauge needle to avoid complications needs to be systematically optimized among all patients, particularly in regards to body habitus. Multidisciplinary collaboration among proceduralists and radiation oncologists can lead to improved outcomes.

Keywords: fiducial, prostate cancer, renal cancer, pancreatic cancer, radiotherapy

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837 Expression of Hypoxia-Inducible Transmembrane Carbonic Anhydrases IX, Ca XII and Glut 1 in Ovarian Cancer

Authors: M. Sunitha, B. Nithyavani, Mathew Yohannan, S. Thiruvieni Balajji, M. A. Rathi, C. Arul Raj, P. Ragavendran, V. K. Gopalkrishnan

Abstract:

Establishment of an early and reliable biomarker for ovarian carcinogenesis whose expression can be monitored through noninvasive techniques will enable early diagnosis of cancer. Carbonic anhydrases (CA) isozymes IX and XII have been suggested to play a role in oncogenic processes. In von Hippel-Lindau (VHL)-defective tumors, the cell surface transmembrane carbonic anhydrase (CA) CA XI and CA XII genes are overexpressed because of the absence of pVHL. These enzymes are involved in causing a hypoxia condition, thereby providing an environment for metastasis. Aberrant expression of the facilitative glucose transporter GLUT I is found in a wide spectrum of epithelial malignancies. Studying the mRNA expression of CA IX, CA XII and Glut I isozymes in ovarian cancer cell lines (OAW-42 and PA-1) revealed the expression of these hypoxia genes. Immunohistochemical staining of carbonic anhydrases was also performed in 40 ovarian cancer tissues. CA IX and CA XII were expressed at 540 bp and 520 bp in OAW42, PA1 in ovarian cancer cell lines. GLUT-1 was expressed at 325bp in OAW 42, PA1 genes in ovarian cancer cell lines. Immunohistochemistry revealed high to moderate levels of expression of these enzymes. The immuostaining was seen predominantly on the cell surface membrane. The study concluded that these genes CA IX, CA XII and Glut I are expressed under hypoxic condition in tumor cells. From the present results expression of CA IX, XII and Glut I may represent potential targets in ovarian cancer therapy.

Keywords: ovarian cancer, carbonic anhydrase IX, XII, Glut I, tumor markers

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836 Protective Effects of Urtica dioica Seed Extract in Aflatoxicosis: Histopathological and Biochemical Findings

Authors: Ahmet Uyar, Zabit Yener, Abdulahad Dogan

Abstract:

(1). The ameliorative potential and antioxidant capacity of an extract of Urtica dioica seeds (UDS) were investigated using histopathological changes in liver and kidney of broiler, measuring serum marker enzymes, antioxidant defence systems and lipid peroxidation (malondialdehyde (MDA)) content in various tissues of broilers exposed to aflatoxin (AF). (2). A total of 32 broilers were divided randomly into 4 groups: control, UDS extract-treated, AF-treated and AF+UDS extract-treated. Broilers in control and UDS extract-treated groups were fed on a diet without AF. The AF-treated group and AF+UDS extract-treated groups were treated with an estimated 1 mg total AF/kg feed. The AF+UDS extract groups received in addition 30 ml UDS extract/kg diet for 21 days. (3). The AF-treated group had significantly decreased body weight gain when compared to the other groups. (4). Biochemical analysis showed a small increase in the concentrations of serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase and lactate dehydrogenase in the AF-treated group compared to that of the control group, whereas concentrations of these enzymes were decreased in the AF+UDS group compared to that of the AF-treated group. (5). Administration of supplementary UDS extract helped restore the AF-induced increase in MDA and reduced the antioxidant system towards normality, particularly in the liver, brain, kidney and heart. Hepatorenal protection by UDS extracts was further supported by the almost normal histology in AF +UDS extract-treated group as compared to the degenerative changes in the AF-treated broilers. (6). It was concluded that UDS extract has a protective hepatorenal effect in broilers affected by aflatoxicosis, probably acting by promoting the antioxidative defence systems.

Keywords: aflatoxicosis, biochemistry, broiler, histopathology, Urtica dioica seed extract

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835 Identification of Natural Liver X Receptor Agonists as the Treatments or Supplements for the Management of Alzheimer and Metabolic Diseases

Authors: Hsiang-Ru Lin

Abstract:

Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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834 Hsa-miR-329 Functions as a Tumor Suppressor through Targeting MET in Non-Small Cell Lung Cancer

Authors: Cheng-Cao Sun, Shu-Jun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, De-Jia Li

Abstract:

MicroRNAs (miRNAs) act as key regulators of multiple cancers. Hsa-miR-329 (miR-329) functions as a tumor suppressor in some malignancies. However, its role on lung cancer remains poorly understood. In this study, we investigated the role of miR-329 on the development of lung cancer. The results indicated that miR-329 was decreased in primary lung cancer tissues compared with matched adjacent normal lung tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-329 in lung cancer cell lines substantially repressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibiting cyclin D1, cyclin D2, and up-regulatiing p57(Kip2) and p21(WAF1/CIP1). In addition, miR-329 promoted NSCLC cell apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-329 inhibited cellular migration and invasiveness through inhibiting matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene MET was revealed to be a putative target of miR-329, which was inversely correlated with miR-329 expression. Furthermore, down-regulation of MET by siRNA performed similar effects to over-expression of miR-329. Collectively, our results demonstrated that miR-329 played a pivotal role in lung cancer through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic MET.

Keywords: hsa-miRNA-329(miR-329), MET, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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833 Effects of Dietary Protein and Lipid Levels on Growth and Body Composition of Juvenile Fancy Carp, Cyprinus carpio var. Koi

Authors: Jin Choi, Zahra Aminikhoei, Yi-Oh Kim, Sang-Min Lee

Abstract:

A 4 × 2 factorial experiment was conducted to determine the optimum dietary protein and lipid levels for juvenile fancy carp, Cyprinus carpio var. koi. Eight experimental diets were formulated to contain four protein levels (200, 300, 400, and 500 g kg-1) with two lipid levels (70 and 140 g kg-1). Triplicate groups of fish (initial weight, 12.1±0.2 g fish-1) were hand-fed the diets to apparent satiation for 8 weeks. Weight gain, daily feed intake, feed efficiency ratio and protein efficiency ratio were significantly (P < 0.0001) affected by dietary protein level, but not by dietary lipid level (P > 0.05). Weight gain and feed efficiency ratio tended to increase as dietary protein level increased up to 400 and 500 g kg-1, respectively. Daily feed intake of fish decreased with increasing dietary protein level and that of fish fed diet contained 500 g kg-1 protein was significantly lower than other fish groups. The protein efficiency ratio of fish fed 400 and 500 g kg-1 protein was lower than that of fish fed 200 and 300 g kg-1 protein. Moisture, crude protein and crude lipid contents of muscle and liver were significantly affected by dietary protein, but not by dietary lipid level (P > 0.05). The increase in dietary lipid level resulted in an increase in linoleic acid in liver and muscle paralleled with a decrease in n-3 highly unsaturated fatty acids content in muscle of fish. In considering these results, it was concluded that the diet containing 400 g kg-1 protein with 70 g kg-1 lipid level is optimal for growth and efficient feed utilization of juvenile fancy carp.

Keywords: fancy carp, dietary protein, dietary lipid, Cyprinus carpio, fatty acid

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832 Green Synthesis of Silver Nanoparticles with Aqueous Extract of Moringa oleifera Lam Leaves and Its Ameliorative Effect on Benign Prostatic Hyperplasia in Wistar Rat

Authors: Rotimi Larayetana, Yahaya Abdulrazaq, Oladunni O. Falola, Abayomi Ajayi

Abstract:

The aim of this study was to perform green synthesis of silver nanoparticles (AgNPs) with the aqueous extract of Moringa oleifera Lam (M oleifera) leaves and determine its effects on benign prostatic hyperplasia in Wistar rats. Silver nitrate (AgNO₃) solution was reduced using the aqueous extract of Moringa oleifera Lam leaves, the resultant biogenic AgNPs were characterized by Fourier transformed infrared spectrophotometric, SEM, TEM and X-ray diffraction analysis. Animal experiments involved thirty (30) adult male Wistar rats randomly divided into five groups (A to E; n ₌ 5). Group A received only subcutaneous injection of olive oil daily while the other groups got 3 mg/kg/daily of testosterone propionate (TP) subcutaneously plus 50 mg/kg/daily of AgNPs intraperitoneally (B), 3 mg/kg/daily of TP plus 25 mg/kg/daily of AgNPs (C), 3 mg/kg/daily of TP only (D) and 25 mg/kg/daily of AgNPs only (E). The animals were sacrificed after 14 days, and the prostate gland, liver, and kidney were processed for histological analysis. Phytochemical screening and GC-MS analysis were performed to determine the composition of the M oleifera extract used. Biogenic AgNPs with an average diameter of 23 nm were synthesized. Biogenic AgNPs ameliorated hormone-induced prostate enlargement, and the inhibition of prostatic hypertrophy could be due to the presence of a significant amount of plant fatty acids and phytosterols in the aqueous extract of M oleifera extract. However, the administration of biogenic AgNPs at higher doses impacted negatively on the cytoarchitecture of the liver. Green synthesis of AgNPs with the aqueous extract of Moringa oleifera might be beneficial for the treatment of BPH.

Keywords: benign prostatic hyperplasia, biogenic synthesis, Moringa oleifera, silver nanoparticles, testosterone

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831 Hexane Extract of Thymus serpyllum L.: GC-MS Profile, Antioxidant Potential and Anticancer Impact on HepG2 (Liver Carcinoma) Cell Line

Authors: Salma Baig, Bakrudeen Ali Ahmad, Ainnul Hamidah Syahadah Azizan, Hapipah Mohd Ali, Elham Rouhollahi, Mahmood Ameen Abdulla

Abstract:

Free radical damage induced by reactive oxygen species (ROS) contributes to etiology of many chronic diseases, cancer being one of them. Recent studies have been successful in ROS targeted therapies via antioxidants using mouse models in cancer therapeutics. The present study was designed to scrutinize anticancer activity, antioxidant activity of 5 different extracts of Thymus serpyllum in MDA-MB-231, MCF-7, HepG2, HCT-116, PC3, and A549. Identification of the phytochemicals present in the most active extract of Thymus serpyllum was conducted using gas chromatography coupled with mass spectrophotometry and antioxidant activity was measured by using DPPH radical scavenging and FRAP assay. Anticancer impact of the extract in terms of IC50 was evaluated using MTT cell viability assay. Results revealed that the hexane extract showed the best anticancer activity in HepG2 (Liver Carcinoma Cell Line) with an IC50 value of 23 ± 0.14 µg/ml followed by 25 µg/ml in HCT-116 (Colon Cancer Cell Line), 30 µm/ml in MCF-7 (Breast Cancer Cell Line), 35 µg/ml in MDA-MB-231 (Breast Cancer Cell Line), 57 µg/ml in PC3 (Prostate Cancer Cell Line) and 60 µg/ml in A549 (Lung Carcinoma Cell Line). GC-MS profile of the hexane extract showed the presence of 31 compounds with carvacrol, thymol and thymoquione being the major compounds. Phenolics such as Vitamin E, terpinen-4-ol, borneol and phytol were also identified. Hence, here we present the first report on cytotoxicity of hexane extract of Thymus serpyllum extract in HepG2 cell line with a robust anticancer activity with an IC50 of 23 ± 0.14 µg/ml.

Keywords: Thymus serpyllum L., hexane extract, GC-MS profile, antioxidant activity, anticancer activity, HepG2 cell line

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830 Optimization of Culture Conditions of Paecilomyces tenuipes, Entomopathogenic Fungi Inoculated into the Silkworm Larva, Bombyx mori

Authors: Sunghee Nam

Abstract:

Entomopathogenic fungi is a Cordyceps species that is isolated from dead silkworm and cicada. Fungi on cicadas were described in old Chinese medicinal books and from ancient times, vegetable wasps and plant worms were widely known to have active substance and have been studied for pharmacological use. Among many fungi belonging to the genus Cordyceps, Cordyceps sinensis have been demonstrated to yield natural products possessing various biological activities and many bioactive components. Generally, It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. Due to their commercial and economic importance, the demand for Cordyceps has been rapidly increased. However, a supply of Cordyceps specimen could not meet the increasing demand because of their sole dependence on field collection and habitat destruction. Because it is difficult to obtain many insect hosts in nature and the edibility of host insect needs to be verified in a pharmacological aspect. Recently, this setback was overcome that P. tenuipes was able to be cultivated in a large scale using silkworm as host. Pharmacological effects of P. tenuipes cultured on silkworm such as strengthening immune function, anti-fatigue, anti-tumor activity and controlling liver etc. have been proved. They are widely commercialized. In this study, we attempted to establish a method for stable growth inhibition of P. tenuipes on silkworm hosts and an optimal condition for synnemata formation. To determine optimum culturing conditions, temperature and light conditions were varied. The length and number of synnemata was highest at 25℃ temperature and 100~300 lux illumination. On an average, the synnemata of wild P. tenuipes measures 70 ㎜ in length and 20 in number; those of the cultured strain were relatively shorter and more in number. The number of synnemata may have increased as a result of inoculating the host with highly concentrated conidia, while the length may have decreased due to limited nutrition per individual. It is not able that changes in light illumination cause morphological variations in the synnemata. However, regulation of only light and temperature could not produce stromata like perithecia, asci, and ascospores.

Keywords: optimization of culture conditions of paecilomyces tenuipes, entomopathogenic fungi optimization of culture conditions of paecilomyces tenuipes, entomopathogenic fungi silkworm larva, bombyx mori

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829 MCD-017: Potential Candidate from the Class of Nitroimidazoles to Treat Tuberculosis

Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

Abstract:

New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

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828 An Analytical Study on the Effect of Chronic Liver Disease Severity and Etiology on Lipid Profiles

Authors: Thinakar Mani Balusamy, Venkateswaran A. R., Bharat Narasimhan, Ratnakar Kini S., Kani Sheikh M., Prem Kumar K., Pugazhendi Thangavelu, Arun Murugan, Sibi Thooran Karmegam, Radhakrishnan N., Mohammed Noufal, Amit Soni

Abstract:

Background and Aims: The liver is integral to lipid metabolism, and a compromise in its function leads to perturbations in these pathways. In this study, we hope to determine the correlation between CLD severity and its effect on lipid parameters. We also look at the etiology-specific effects on lipid levels. Materials and Methods: This is a retrospective cross-sectional analysis of 250 patients with cirrhosis compared to 250 healthy age and sex-matched controls. Severity assessment of CLD using MELD and Child-Pugh scores was performed and etiological details collected. A questionnaire was used to obtain patient demographic details and lastly, a fasting lipid profile (Total, LDL, HDL cholesterol, Triglycerides and VLDL) was obtained. Results: All components of the lipid profile declined linearly with increasing severity of CLD as determined by MELD and Child-Pugh scores. Lipid levels were clearly lower in CLD patients as compared to healthy controls. Interestingly, preliminary analysis indicated that CLD of different etiologies had differential effects on Lipid profiles. This aspect is under further analysis. Conclusion: All components of the lipid profile were definitely lower in CLD patients as compared to controls and demonstrated an inverse correlation with increasing severity. The utilization of this parameter as a prognosticating aid requires further study. Additionally, preliminary analysis indicates that various CLD etiologies appear to have specific effects on the lipid profile – a finding under further analysis.

Keywords: CLD, cholesterol, HDL, LDL, lipid profile, triglycerides, VLDL

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827 A Case Study on Utility of 18FDG-PET/CT Scan in Identifying Active Extra Lymph Nodes and Staging of Breast Cancer

Authors: Farid Risheq, M. Zaid Alrisheq, Shuaa Al-Sadoon, Karim Al-Faqih, Mays Abdulazeez

Abstract:

Breast cancer is the most frequently diagnosed cancer worldwide, and a common cause of death among women. Various conventional anatomical imaging tools are utilized for diagnosis, histological assessment and TNM (Tumor, Node, Metastases) staging of breast cancer. Biopsy of sentinel lymph node is becoming an alternative to the axillary lymph node dissection. Advances in 18-Fluoro-Deoxi-Glucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT) imaging have facilitated breast cancer diagnosis utilizing biological trapping of 18FDG inside lesion cells, expressed as Standardized Uptake Value (SUVmax). Objective: To present the utility of 18FDG uptake PET/CT scans in detecting active extra lymph nodes and distant occult metastases for breast cancer staging. Subjects and Methods: Four female patients were presented with initially classified TNM stages of breast cancer based on conventional anatomical diagnostic techniques. 18FDG-PET/CT scans were performed one hour post 18FDG intra-venous injection of (300-370) MBq, and (7-8) bed/130sec. Transverse, sagittal, and coronal views; fused PET/CT and MIP modality were reconstructed for each patient. Results: A total of twenty four lesions in breast, extended lesions to lung, liver, bone and active extra lymph nodes were detected among patients. The initial TNM stage was significantly changed post 18FDG-PET/CT scan for each patient, as follows: Patient-1: Initial TNM-stage: T1N1M0-(stage I). Finding: Two lesions in right breast (3.2cm2, SUVmax=10.2), (1.8cm2, SUVmax=6.7), associated with metastases to two right axillary lymph nodes. Final TNM-stage: T1N2M0-(stage II). Patient-2: Initial TNM-stage: T2N2M0-(stage III). Finding: Right breast lesion (6.1cm2, SUVmax=15.2), associated with metastases to right internal mammary lymph node, two right axillary lymph nodes, and sclerotic lesions in right scapula. Final TNM-stage: T2N3M1-(stage IV). Patient-3: Initial TNM-stage: T2N0M1-(stage III). Finding: Left breast lesion (11.1cm2, SUVmax=18.8), associated with metastases to two lymph nodes in left hilum, and three lesions in both lungs. Final TNM-stage: T2N2M1-(stage IV). Patient-4: Initial TNM-stage: T4N1M1-(stage III). Finding: Four lesions in upper outer quadrant area of right breast (largest: 12.7cm2, SUVmax=18.6), in addition to one lesion in left breast (4.8cm2, SUVmax=7.1), associated with metastases to multiple lesions in liver (largest: 11.4cm2, SUV=8.0), and two bony-lytic lesions in left scapula and cervicle-1. No evidence of regional or distant lymph node involvement. Final TNM-stage: T4N0M2-(stage IV). Conclusions: Our results demonstrated that 18FDG-PET/CT scans had significantly changed the TNM stages of breast cancer patients. While the T factor was unchanged, N and M factors showed significant variations. A single session of PET/CT scan was effective in detecting active extra lymph nodes and distant occult metastases, which were not identified by conventional diagnostic techniques, and might advantageously replace bone scan, and contrast enhanced CT of chest, abdomen and pelvis. Applying 18FDG-PET/CT scan early in the investigation, might shorten diagnosis time, helps deciding adequate treatment protocol, and could improve patients’ quality of life and survival. Trapping of 18FDG in malignant lesion cells, after a PET/CT scan, increases the retention index (RI%) for a considerable time, which might help localize sentinel lymph node for biopsy using a hand held gamma probe detector. Future work is required to demonstrate its utility.

Keywords: axillary lymph nodes, breast cancer staging, fluorodeoxyglucose positron emission tomography/computed tomography, lymph nodes

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826 Assessing the Correlation between miR-141 Expression, Common K-Ras Gene Mutations, and Their Impact on Prognosis in Colorectal Cancer Tissue of Iranian Patients

Authors: Shima Behzadi

Abstract:

Background: In many human malignant tumors, microRNA expression is aberrant. This study investigates miR-141 as a prognostic marker in colorectal cancer with K-Ras mutation. Materials and methods: In this case-control study, 100 patients, mostly over the age of 50, who were diagnosed with colorectal cancer were selected. The pathology department of the Mostoufi Pathobiology and Genetics Laboratory in Tehran confirmed the presence of colorectal cancer in samples of paraffin-embedded colon tissue. The case group was composed of patients with codon 12 and 13 mutations in exon 2 of the K-Ras gene, while tumor samples of individuals without these mutations in exon 2 of the K-Ras gene were selected as the control group, with patient consent. The changes in the expression of miR-141 were examined in both groups. Results: The study found that 20% of the patients tested positive for codon 12 mutation, and 10% of patients had codon 13 mutation. As a result, in 30 cases, there was a higher level of miR-141 expression. The miR-141 gene expression level in K-Ras positive tumor samples was 1.5 times higher than its expression level in K-Ras negative samples. This increase in expression was statistically significant, with a p-value of less than 0.001, indicating that the observed results are highly statistically significant. Conclusion: The study revealed that the incidence of typical K-Ras gene mutations among the colorectal cancer patients in the sample matches the national average in Iran. Additionally, the expression of miR-141 can serve as a useful biomarker to aid in the prognosis of colorectal cancer.

Keywords: colorectal cancer, K-Ras gene, miR-141 marker, real time PCR, electrophoresis

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825 Oil and Proteins of Sardine (Sardina Pilchardus) Compared with Casein or Mixture of Vegetable Oils Improves Dyslipidemia and Reduces Inflammation and Oxidative Stress in Hypercholesterolemic and Obese Rats

Authors: Khelladi Hadj Mostefa, Krouf Djamil, Taleb-Dida Nawel

Abstract:

Background: Obesity results from a prolonged imbalance between energy intake and energy expenditure, as depending on basal metabolic rate. Oils and proteins from sea have important therapeutic (such as obesity and hypercholesterolemia) and antioxidant effects. Sardine are a widely consumed fish in the Mediterranean region. Its consumption provides humans with various nutrients such as oils (rich in omega 3 plyunsaturated fatty acids)) and proteins. Methods: Sardine oil (SO) and sardine proteins (SP) were extracted and purified. Mixture of vegetable oils (olive-walnut-sunflower) were prepared from oils produced in Algeria. Eighteen wistar rats are fed a high fat diet enriched with 1% cholesterol for 30 days to induce obesity and hypercholesterolemia. The rats are divided into 3 groups. The first group consumes 20% sardine protein combined with 5% sardine oil (38% SFA (saturated fatty acids), 31% MIFA (monounsaturated fatty acids) and 31% PIFA (polyunsaturated fatty acids)) (SPso). The second group consumes 20% sardine protein combined with 5% of a mixture of vegetable oils (VO) containing 13% SFA, 58% MIFA and 29% PIFA (PSvo), and the third group consuming 20% casein combined with 5% of the mixture of vegetable oils and serves as a semi-synthetic reference (CASvo). Body weights and glycaemia are measured weekly After 28 days of experimentation, the rats are sacrificed, the blood and the liver removed. Serum assays of total cholesterol (TC) and triglycerides (TG) were performed by enzymatic colorimetric methods. Evaluation of lipid peroxidation was performed by assaying thiobarbituric acid reactive species (TBARS) and hydroperoxides values. The protein oxidation was performed by assaying carbonyl derivatives values. Finally, evaluation of antioxidant defense is made by measuring the activity of antioxidant enzymes, the superoxide dismutase (SOD) and the catalase (CAT).Results: After 28 days, the body weight (BW) of the rats increased significantly in SPso and SPvo groups compared to CAS group, by +11% and 7%, respectively. Cholesterolemia (TC) increased significantly in the SPso and SPvo groups compared to the CAS group (P<0.01), while triglyceridemia (TG) decreased significantly in the SPso group compared to SPvo and CAS groups (P<0.01). Albumin (marker of inflammation) increased in the PSs group compared to SPvo and CAS groups by +35% and +13%, respectively. The serum TBARS levels are -40% lower in SPso group compared to SPvo group, and they are -80% and -76% lower in SPso compared to SPvo and CAS groups, respectively. The level of carbonyls derivatives in the serum and liver are significantly reduced in the SPso group compared to the SPvo and CAS groups. Superoxide dismutase (SOD) activity decreased in liver of SPso group compared to SPvo group (P<0.01). While that of CAT is increased in liver tissue of SPso group compared to SPvo group (P<0.01). Conclusion: Sardine oil combined with sardine protein has a hypotriglyceridemic effect, reduces body weight, attenuates inflammation and seems to protect against lipid peroxidation and protein oxidation and increases antioxidant defense in hypercholesterolemic and obese rats. This could be in favor of a protective effect against obesity and cardiovascular diseases.

Keywords: rat, obesity, hypercholesterolemia, sardine protein, sardine oil, vegetable oils mixture, lipid peroxidation, protein oxidation, antioxidant defense

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824 Restless Leg Syndrome as the Presenting Symptom of Neuroendocrine Tumor

Authors: Mustafa Cam, Nedim Ongun, Ufuk Kutluana

Abstract:

Introduction: Restless LegsSyndrome (RLS) is a common, under-recognized disorder disrupts sleep and diminishes quality of life (1). The most common conditions highly associated with RLS include renalfailure, iron and folic acid deficiency, peripheral neuropathy, pregnancy, celiacdisease, Crohn’sdiseaseandrarelymalignancy (2).Despite a clear relation between low peripheral iron and increased prevalence and severity of RLS, the prevalence and clinical significance of RLS in iron-deficientanemic populations is unknown (2). We report here a case of RLS due to iron deficiency in the setting of neuroendocrinetumor. Report of Case: A 35 year-old man was referred to our clinic with general weakness, weight loss (10 kg in 2 months)and 2-month history of uncomfortable sensations in his legs with urge to move, partially relieved by movement. The symptoms were presented very day, worsening in the evening; the discomfort forced the patient to getup and walk around at night. RLS was severe, with a score of 22 at the International RLS ratingscale. The patient had no past medical history. The patient underwent a complete set of blood analyses and the following ab normal values were found (normal limitswithinbrackets): hemoglobin 9.9 g/dl (14-18), MCV 70 fL (80-94), ferritin 3,5 ng/mL (13-150). Brain and spinemagnetic resonance imaging was normal. The patient consultated with gastroenterology clinic and gastointestinal systemendoscopy was performed for theetiology of the iron deficiency anemia. After the gastricbiopsy, results allowed us to reach the diagnosis of neuroen docrine tumor and the patient referred to oncology clinic. Discussion: The first important consideration from this case report is that the patient was referred to our clinic because of his severe RLS symptoms dramatically reducing his quality of life. However, our clinical study clearly demonstrated that RLS was not the primary disease. Considering the information available for this patient, we believe that the most likely possibility is that RLS was secondary to iron deficiency, a very well-known and established cause of RLS in theliterature (3,4). Neuroendocrine tumors (NETs) are rare epithelial neoplasms with neuroendocrine differentiation that most commonly originate in the lungs and gastrointestinal tract (5). NETs vary widely in their clinical presentation; symptoms are often nonspecific and can be mistaken for those of other more common conditions (6). 50% of patients with reported disease stage have either regional or distant metastases at diagnosis (7). Accurate and earlier NET diagnosis is the first step in shortening the time to optimal care and improved outcomes for patients (8). The most important message from this case report is that RLS symptoms can sometimes be thesign of a life-threatening condition. Conclusion: Careful and complete collection of clinical and laboratory data should be carried out in RLS patients. Inparticular, if RLS onset coincides with weight loss and iron deficieny anemia, gastricendos copy should be performed. It is known about that malignancy is a rare etiology in RLS patients and to our knowledge; it is the first case with neuro endocrine tumor presenting with RLS.

Keywords: neurology, neuroendocrine tumor, restless legs syndrome, sleep

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823 High-Dose-Rate Brachytherapy for Cervical Cancer: The Effect of Total Reference Air Kerma on the Results of Single-Channel and Tri-Channel Applicators

Authors: Hossain A., Miah S., Ray P. K.

Abstract:

Introduction: Single channel and tri-channel applicators are used in the traditional treatment of cervical cancer. Total reference air kerma (TRAK) and treatment outcomes in high-dose-rate brachytherapy for cervical cancer using single-channel and tri-channel applicators were the main objectives of this retrospective study. Material and Methods: Patients in the radiotherapy division who received brachytherapy, chemotherapy, and external radiotherapy (EBRT) using single and tri-channel applicators were the subjects of a retrospective cohort study from 2016 to 2020. All brachytherapy parameters, including TRAK, were calculated in accordance with the international protocol. The Kaplan Meier method was used to analyze survival rates using a log-rank test. Results and Discussions: Based on treatment times of 15.34 (10-20) days and 21.35 (6.5-28) days, the TRAK for the tri-channel applicator was 0.52 cGy.m² and for the single-channel applicator was 0.34 cGy.m². Based on TRAK, the rectum, bladder, and tumor had respective Pearson correlations of 0.082, 0.009, and 0.032. The 1-specificity and sensitivity were 0.70 and 0.30, respectively. At that time, AUC was 0.71. The log-rank test showed that tri-channel applicators had a survival rate of 95% and single-channel applicators had a survival rate of 85% (p=0.565). Conclusions: The relationship between TRAK and treatment duration and Pearson correlation for the tumor, rectum, and bladder suggests that TRAK should be taken into account for the proper operation of single channel and tri-channel applicators.

Keywords: single-channel, tri-channel, high dose rate brachytherapy, cervical cancer

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822 Molecular Portraits: The Role of Posttranslational Modification in Cancer Metastasis

Authors: Navkiran Kaur, Apoorva Mathur, Abhishree Agarwal, Sakshi Gupta, Tuhin Rashmi

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Aim: Breast cancer is the most common cancer in women worldwide, and resistance to the current therapeutics, often concurrently, is an increasing clinical challenge. Glycosylation of proteins is one of the most important post-translational modifications. It is widely known that aberrant glycosylation has been implicated in many different diseases due to changes associated with biological function and protein folding. Alterations in cell surface glycosylation, can promote invasive behavior of tumor cells that ultimately lead to the progression of cancer. In breast cancer, there is an increasing evidence pertaining to the role of glycosylation in tumor formation and metastasis. In the present study, an attempt has been made to study the disease associated sialoglycoproteins in breast cancer by using bioinformatics tools. The sequence will be retrieved from UniProt database. A database in the form of a word document was made by a collection of FASTA sequences of breast cancer gene sequence. Glycosylation was studied using yinOyang tool on ExPASy and Differential genes expression and protein analysis was done in context of breast cancer metastasis. The number of residues predicted O-glc NAc threshold containing 50 aberrant glycosylation sites or more was detected and recorded for individual sequence. We found that the there is a significant change in the expression profiling of glycosylation patterns of various proteins associated with breast cancer. Differential aberrant glycosylated proteins in breast cancer cells with respect to non-neoplastic cells are an important factor for the overall progression and development of cancer.

Keywords: breast cancer, bioinformatics, cancer, metastasis, glycosylation

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821 Study of the Protective Effects of Summer Savory against Multiple Organ Damage Induced by Lead Acetate in Rats

Authors: Bassant M. M. Ibrahim, Doha H. Abou Baker, Ahmed Abd Elghafour

Abstract:

Excessive exposure to heavy metals contributes to the occurrence of deleterious health problems that affect vital organs like the brain, liver, kidneys, and heart. The use of natural products that have antioxidant capabilities may contribute to the protection of these organs. In the present study, the essential oil of summer savory (Satureja hortensis) was used to evaluate its protective effects against lead acetate induced damaging effect on rats’ vital organs, due to its high contents of carvacrol, y-terpinene, and p-cymene. Forty female Wister Albino rats were classified into five equal groups, the 1st served as normal group, the 2nd served as positive control group was given lead acetate (60 mg/kg) intra-peritoneal (IP), the third to fifth groups were treated with calcium disodium (EDTA) as chelating agent and summer savory essential oil in doses of (50 and 100mg/kg) respectively. All treatments were given IP concomitant with lead acetate for ten successive days. At the end of the experiment duration electrocardiogram (ECG), an open field test for the evaluation of psychological state, rotarod test as for the evaluation of locomotor coordination ability as well as anti-inflammatory and oxidative stress biomarkers in serum and histopathology of vital organs were performed. The investigations in this study show that the protective effect of high dose of summer savory essential oil is more than the low dose and that the essential oil of summer savory is a promising agent that can contribute to the protection of vital organs against the hazardous damaging effects of lead acetate.

Keywords: brain, heart, kidneys, lead acetate, liver, protective, summer savory

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820 Mature Cystic Teratomas of Ovary: A Series of 19 Cases with Rare Malignant Transformation in Three

Authors: Parveen Kundu, Nitika Chawla, Ruchi Agarwal, Swaran Kaur

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Background: Mature cystic teratoma is a benign, most common tumor of the ovary occurring mostly in young and middle-aged females. This study consists of 19 cases of mature cystic teratomas which were received in the Department Of Pathology over a period of two years. There were malignant transformations observed in three cases, which makes it very important for pathologists to thoroughly examine the entire specimen of mature cystic teratomas. Material and Methods: Nineteen reported cases of mature cystic teratomas were received in Deptt. Of Pathology, BPS GMC Khanpur Kalan, Sonepat, over a two-year period from November 2020 to October 2022 and reviewed retrospectively. Data regarding age, size, laterality, gross, morphological features, and surgery performed were retrieved from pathological archives. Results: In our study, the most common age of presentation was the 20-40 year age group. The most common presenting complaint was fullness in the abdomen or abdominal distension. Four out of 19 cases studied cases presented with bilateral ovarian cysts. Tumor size ranged from 6 to 20 cm in diameter. In seven cases, cysts were greater than or equal to 10 cm in diameter. Three cases showed malignant transformation. Conclusion: It is very important to thoroughly examine the contralateral ovary to rule out bilateral presentation. A furthermost thorough examination is advised in tumors of size >10 cm and in tumors with solid areas to rule out any malignant transformation.

Keywords: teratoma, ovary, malignant, transformation

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819 Epstein-Barr Virus-associated Diseases and TCM Syndromes Types: In Search for Correlation

Authors: Xu Yifei, Le Yining, Yang Qingluan, Tu Yanjie

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Objective: This study aims to investigate the distribution features of Traditional Chinese Medicine (TCM) syndromes and syndrome elements in Epstein-Barr virus-associated diseases and then explores the relations between TCM syndromes or syndrome elements and laboratory indicators of Epstein-Barr virus-associated diseases. Methods: A cross-sectional study of 70 patients with EBV infection was described. We assessed the diagnostic information and laboratory indicators of these patients from Huashan Hospital Affiliated to Fudan University between November 2017 and July 2019. The disease diagnosis and syndrome differentiation were based on the diagnostic criteria of EBV-associated diseases and the theory of TCM respectively. Confidence correlation analysis, logistic regression analysis, cluster analysis, and the Sankey diagram were used to analyze the correlation between the data. Results: The differentiation of the 4 primary TCM syndromes in the collected patients was correlated with the indexes of immune function, liver function, inflammation, and anemia, especially the relationship between Qifen syndrome and high lactic acid dehydrogenase level. The common 11 TCM syndrome elements were associated with the increased CD3+ T cell rate, low hemoglobin level, high procalcitonin level, high lactic acid dehydrogenase level, and low albumin level. Conclusion: The changes in immune function indexes, procalcitonin, and liver function-related indexes in patients with EBV-associated diseases were consistent with the evolution law of TCM syndromes. This study provides a reference for judging the pathological stages of these kinds of diseases, predicting their prognosis, and guiding subsequent treatment strategies based on TCM syndrome type.

Keywords: EBV-associated diseases, traditional Chinese medicine syndrome, syndrome element, diagnostics

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818 Neuroblastoma in Children and the Potential Involvement of Viruses in Its Pathogenesis

Authors: Ugo Rovigatti

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Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

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817 Sphingosomes: Potential Anti-Cancer Vectors for the Delivery of Doxorubicin

Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain

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The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

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816 Tumour-Associated Tissue Eosinophilia as a Prognosticator in Oral Squamous Cell Carcinoma

Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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815 Molecular Characterization of Cysticercus tenuicolis of Slaughtered Livestock in Upper-Egypt Governorates

Authors: Mosaab A. Omara, Layla O. Elmajdoubb, Mohammad Saleh Al-Aboodyc, Ahmed ElSifyd, Ahmed O. Elkhtamd

Abstract:

The aim of this study is to present the molecular characterization of cysticercus tenuicolis of Taenia hydatigena from livestock isolates in Egypt, using the amplification of sequencing of the mt-CO1 gene. We introduce a detailed image of the Cysticercus tenuicolis infection in ruminant animals in Upper Egypt. Cysticercus tenuicolis inhabits such organs in ruminants as the omentum, viscera, and liver. In the present study, the infection rate of Cysticercus tenuicolis was found to be 16% and 19% in sheep and goat sample respectively. Firstly we report one larval stage of Taenia hydatigena detected in the camel liver in Egypt. Cysticercus tenuicolis infection manifested a higher prevalence in females than in males. Those above 2 years of age manifested a higher infection rate than younger animals. The preferred site for the infection was the omentum: a 70% preference in sheep and a 68% preference in goat samples. The molecular characterization using the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene of isolates from sheep, goats and camels corresponded to T. hydatigena. For this study, molecular characterizations of T. hydatigena were done for the first time in Egypt. Molecular tools are of great assistance in characterizing the Cysticercus tenuicolis parasite especially when the morphological character cannot be detected because the metacestodes are frequently confused with infection by the Hydatid cyst, especially when these occur in the visceral organs. In the present study, Cysticercus tenuicolis manifested high identity in the goat and sheep samples, while differences were found more frequently in the camel samples (10 pairbase). Clearly molecular diagnosis for Cysticercus tenuicolis infection significantly helps to differentiate it from such other metacestodes.

Keywords: cysticercus tenuicolis, its2, genetic, qena, molecular and taenia hydatigena

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814 Protective Effect of Celosia Argentea Leaf Extract on Cadmium Induced Toxicity and Oxidative Stress in Rats

Authors: Sulyman Abdulhakeem Olarewaju, S. O. Malomo, M. T. Yakubu, J. O. Akolade

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The ameliorative effect of Celosia argentea var. cristata leaf extract against cadmium (Cd) induced oxidative stress and toxicity in selected tissues of rats was investigated. Toxicity coupled with oxidative stress was induced in rats by oral administration of Cd (8 mg/kg b. wt). Preliminary quantitative phytochemical and in vitro antioxidant analyses showed that the methanolic extract of C. argentea leaves was constituted by polyphenols (5.72%), saponins (3.20%), tannins (0.65%) and cadenolides (0.006%). IC50 of 9800, 7406, and 45.04 μg/ml were recorded for inhibition of linoleic acid oxidation, 2, 2-diphenyl-1-picrylhydrazyl and hydrogen peroxide radicals respectively. Simultaneous administration of C. argentea leaf extract with Cd significantly attenuated Cd-induced elevation of serum enzyme markers such as aspartate and alanine transaminase, alkaline and acid phosphatase as well as γ-glutaryltransferase in a dose-dependent fashion, while their reduced level in the liver were significantly increased. Higher levels of enzymatic antioxidants; superoxide dismutase and catalase activities were observed in the liver, brain, kidney and testes of the Cd-induced rats treated with C. argentea extract, while lipid peroxidation expressed in malondialdehyde concentrations were lower when compared to values in rats administered Cd only. Other Cd-induced toxicity and stress markers in the serum viz. reduced uric acid and albumin levels as well as elevated total and unconjugated bilirubin were attenuated by the extract and their values compared favorably with those animals co-administered cadmium with ascorbic acid. Data from the study showed that oral administration of extract from the leaf C. argentea may ameliorate Cd-induced oxidative stress and toxicity in rats.

Keywords: toxicity, cadmium, celosia, antioxidants, oxidative stress

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813 Simulation Of A Renal Phantom Using the MAG 3

Authors: Ati Moncef

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We describe in this paper the results of a phantom of dynamics renal with MAG3. Our phantom consisted of (tow shaped of kidneys, 1 liver). These phantoms were scanned with static and dynamic protocols and compared with clinical data. in a normal conditions we use our phantoms it's possible to acquire a renal images when we can be compared with clinical scintigraphy. In conclusion, Renal phantom also can use in the quality control of a renal scintigraphy.

Keywords: Renal scintigraphy, MAG3, Nuclear medicine, Gamma Camera.

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812 Criteria for Assessing Prostate Structure after Proton Radiotherapy for Prostate Cancer

Authors: Kuplevatsky V., Kuplevatskay, Cherkashin M., Berezina N.

Abstract:

After 6 months, a violation of the differentiation of the structure of the gland due to edema in 100%. 20% retained signs of a tumor according to DWI/ADC data. By 12 months, the reduction in the size of the gland is 100%. In all cases, no diffusion restriction was observed. The study after 18 months showed no significant changes in all (100%) patients. In the study, 24 months after treatment, the size of the gland was stable in all cases (+/- up to 5%). Diffuse decrease in T2VI signals from peripheral zones, without signs of diffusion restriction in 100%. After 30 months, signs of recovery of adenomatous changes in the transient zone were revealed in 85%. After 36 and 42 months, the restoration of organ differentiation was observed in 93% of patients. In 4 patients, by the 48th month, signs of biochemical relapse were clinically noted. According to the MRI data, signs of a local relapse were revealed. After 48 months, there were signs of restoration of organ differentiation, which allowed the use of PI-RADS criteria. The study after 54 months showed no changes compared to the control. 60 months after treatment, 97% of patients showed a restoration of differentiation of the gland structure, which allows evaluating the organ according to PI-RADS criteria Conclusions: The beginning of restoration of the structure of the prostate gland began 24 months after proton radiation therapy, the PI-RADS criteria can be fully applied after 48 months of treatment. Control studies every 6 months without clinical signs of relapse are not advisable. Local control of the prostate tumor after proton radiation therapy was achieved in 95% of patients during the entire follow-up period ( 60 months).

Keywords: proton therapy, prostate cancer, MRI imaging, PI-RADS

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811 In vivo Iron Availability and Profile Lipid Composition in Anemic Rats Fed on Diets with Black Rice Bran Extract

Authors: Nurlaili E. P., Astuti M., Marsono Y., Naruki S.

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Iron is an essential nutrient with limited bioavailability. Nutritional anemia caused mainly by iron deficiency is the most recognized nutritional problem in both countries as well as affluent societies. Rice (Oryza sativa L.) has become the most important cereal crop for the improvement of human health due to the starch, protein, oil, and the majority of micronutrients, particularly in Asian countries. In this study, the iron availability and profile lipid were evaluated for the extracts from Cibeusi varieties (black rices) of ancient rice brans. Results: The quality of K, B, R, E diets groups shows the same effect on the growth of rats. This indicate that groups is as efficiently utilized by the body as E diets. Hematocrit and MCHC levels of rats fed K, B, R and E diets were not significantly (P< 0.05). MCV and MCH levels of rats K, B, R were significantly (P< 0.05) with E groups but rats K, B, R were not significantly (P< 0.05). The iron content in the serum of rats fed with K, B, R and E diets were not significantly (P< 0.05). The highest level of iron in the serum was founded in the B group. The iron content in the liver of rats fed with K, B, R and E diets were not significantly (P< 0.05). The highest level of iron in the liver was founded in the R group. HDL cholesterol levels were significantly (P< 0.05) between rats of fed B, E with K, R, but K and R were not significantly (P< 0.05). LDL cholesterol levels of rats fed K and E significantly (P< 0.05) with B and R. Conclusions: the bran of pigmented rice varieties has, with some exceptions, greater antioxidant and free-radical scavenging activities. The results also show that pigmented rice extracts acted as pro-oxidants in the lipid peroxidation assay, possibly by mechanisms described for the pro-oxidant activities of tocopherol and ascorbic. Pigmented rice bran extracts more effectively increases iron stores and reduces the prevalence of iron deficiency. And reduces cholesterol, TG and LDL cholesterol and increses HDL cholesterol.

Keywords: anemia, black rice bran extract, iron, profile lipid

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