Search results for: breast cancer cell lines

Authors: Hamsa T. Tayeb, Mohammad A. Arafah, Dana M. Bakheet, Duaa M. Khalaf, Agnieszka Tarnoska, Nduna Dzimiri

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Background: CYP2D6 is a member of the cytochrome P450 mixed-function oxidase system. The enzyme is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, especially in breast cancer and psychiatric therapy. Different phenotypes have been described displaying alleles that lead to a complete loss of enzyme activity, reduced function (poor metabolizers – PM), hyperfunctionality (ultrarapid metabolizers–UM) and therefore drug intoxication or loss of drug effect. The prevalence of these variants may vary among different ethnic groups. Furthermore, the xTAG system has been developed to categorized all patients into different groups based on their CYP2D6 substrate metabolization. Aim of the study: To determine the prevalence of the different CYP2D6 variants in our population, and to evaluate their clinical relevance in personalized medicine. Methodology: We used the Luminex xMAP genotyping system to sequence 305 Saudi individuals visiting the Blood Bank of our Institution and determine which polymorphisms of CYP2D6 gene are prevalent in our region. Results: xTAG genotyping showed that 36.72% (112 out of 305 individuals) carried the CYP2D6_*2. Out of the 112 individuals with the *2 SNP, 6.23% had multiple copies of *2 SNP (19 individuals out of 305 individuals), resulting in an UM phenotype. About 33.44% carried the CYP2D6_*41, which leads to decreased activity of the CYP2D6 enzyme. 19.67% had the wild-type alleles and thus had normal enzyme function. Furthermore, 15.74% carried the CYP2D6_*4, which is the most common nonfunctional form of the CYP2D6 enzyme worldwide. 6.56% carried the CYP2D6_*17, resulting in decreased enzyme activity. Approximately 5.73% carried the CYP2D6_*10, consequently decreasing the enzyme activity, resulting in a PM phenotype. 2.30% carried the CYP2D6_*29, leading to decreased metabolic activity of the enzyme, and 2.30% carried the CYP2D6_*35, resulting in an UM phenotype, 1.64% had a whole-gene deletion CYP2D6_*5, thus resulting in the loss of CYP2D6 enzyme production, 0.66% carried the CYP2D6_*6 variant. One individual carried the CYP2D6_*3(B), producing an inactive form of the enzyme, which leads to decrease of enzyme activity, resulting in a PM phenotype. Finally, one individual carried the CYP2D6_*9, which decreases the enzyme activity. Conclusions: Our study demonstrates that different CYP2D6 variants are highly prevalent in ethnic Saudi Arabs. This finding sets a basis for informed genotyping for these variants in personalized medicine. The study also suggests that xTAG is an appropriate procedure for genotyping the CYP2D6 variants in personalized medicine.

Keywords: CYP2D6, hormonal breast cancer, pharmacogenetics, polymorphism, psychiatric treatment, Saudi population

Procedia PDF Downloads 573

Authors: Michael Eickermann, Juergen Junk

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The Western honey (Apis mellifera) is threatened by a number of parasites, especially the devastating Varroa mite (Varroa destructor) is responsible for a high level of mortality over winter, e.g., in Europe and USA. While the use of synthetic pesticides or organic acids has been preferred so far to control this parasite, breeding strategies for less susceptible honey bees are in early stages. Hygienic behavior can be an important tool for controlling Varroa destructor. Worker bees with a high level of this behavior are able to detect infested brood in the cells under the wax lid during pupation and remove them out of the hive. The underlying processes of this behavior are only partly investigated, but it is for sure that hygienic behavior is heritable and therefore, can be integrated into commercial breeding lines. In a first step, breeding lines with a high level of phenotypic hygienic behavior have been identified by using a bioassay for accurate assessment of this trait in a long-term national breeding program in Luxembourg since 2015. Based on the artificial infestation of nucleus colonies with 150 phoretic Varroa destructor mites, the level of phenotypic hygienic behavior was detected by counting the number of mites in all stages, twelve days after infestation. A nucleus with a high level of hygienic behavior was overwintered and used for breeding activities in the following years. Artificial insemination was used to combine different breeding lines. Buckfast lines, as well as Carnica lines, were used. While Carnica lines offered only a low increase of hygienic behavior up to maximum 62.5%, Buckfast lines performed much better with mean levels of more than 87.5%. Some mating ends up with a level of 100%. But even with a level of 82.5% Varroa mites are not able to reproduce in the colony anymore. In a final step, a nucleus with a high level of hygienic behavior were build up to full colonies and located at two places in Luxembourg to build up a drone congregation area. Local beekeepers can bring their nucleus to this location for mating the queens with drones offering a high level of hygienic behavior.

Keywords: agiculture, artificial insemination, honey bee, varroa destructor

Procedia PDF Downloads 138

Authors: Ossama Abdelmotaal, Olfat Shaker, Tarek Salman, Lamiaa Nabeel, Mostafa Shabayek

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Colorectal Cancer (CRC) is an important worldwide health problem. Colonoscopy is used in detecting CRC suffer from drawbacks where colonoscopy is an invasive method. This study validates easier and less time-consuming techniques to evaluate the usefulness of detecting miRNA-21, miRNA-215 and miRNA-378 in the sera of colorectal cancer patients as new diagnostic tools. This study includes malignant (Colo Rectal Cancer patients, n= 64)) and healthy (n=27) groups. The studied groups were subjected to colonoscopic examination and estimation of miRNA-21, miRNA-215 and miRNA-378 in sera by RT-PCR. miRNA-21 showed the statistically significantly highest median fold change. miRNA-378 showed statistically significantly lower value (Both showed over-expression). miRNA-215 showed the statistically significantly lowest median fold change (It showed down-regulation). Overall the miRNA (21-215 and 378) appear to be promising method of detecting CRC and evaluating its stages.

Keywords: colorectal cancer, miRNA-21, miRNA-215, miRNA-378

Procedia PDF Downloads 303

Authors: Ashraf Mohammadzadeh, Ahmad Shah Farhat, Azin Vaezi, Aradokht Vaezi

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Background & Aim: Preterm infants born at less than 34 weeks postconceptional age are not as neurologically mature as their term counterparts and thus have difficulty coordinating sucking, swallowing and breathing. As a result, they are traditionally gavage fed until they are able to oral feed successfully. The aim of study was to evaluate comparative effect of orogastric and breast feeding on oxygen saturation in very low birth weight infant (<1500gm). Patients and Methods: In this clinical trial all babies admitted in the Neonatal Research Center of Imamreza Hospital, Mashhad during a 4 months period were elected. Criteria for entrance to study included birth weight ≤ 1500 grams, exclusive breastfeeding, having no special problem after 48 hours, receivinge only routine care and intake of milk was 100cc/kg/day. Each neonate received two rounds of orogastric and breast feeding in the morning and in the afternoon, during which mean oxygen saturation was measured by pulse-oxymetry. During the study the heart rate and temperature of the neonates were monitored, and in case of hypothermia, bradycardia(less than 100 per minute) or apnea the feeding was discontinued and the study was repeated the following day. Data analysis was carried out using SPSS. Results: Fifty neonates were studied. The average birth weight was 1267.20±165.42 grams and average gestational age was 31.81±1.92 and female/male ratio was 1.2. There was no significant statistical difference in arterial oxygen saturation in orogastric and breast feeding in the morning and in the afternoon. (p=0.16 in the morning and p=0.6 in the afternoon). There was no complication of apnea, hypothermia or bradycardia. Conclusion: There was no significant statistical difference between the two methods in arterial oxygen saturation. It seems that oral feeding (which is a natural route) and skin contact between the mother and neonate causes a strong emotional bonding between the two and brings about better social adaptation for the neonate. Also shorter period of stay in hospital is more preferred, and breast feeding should be started at the earliest possible time after birth.

Keywords: Very low birth weight (V.L.B.W), O2 Saturation, Breast Feeding, Tube Feeding

Procedia PDF Downloads 87

Authors: Sadegh Abebi

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There are problems with estimating time of product process of products, especially when there is variable serving time, like control stage. These problems will cause overestimation of process time. Layout constraints, reworking constraints and inflexible product schedule in multi product lines, needs a precise planning to reduce volume in particular situation of line stock. In this article, by analyzing real queue systems with layout constraints and by using concepts and principles of Markov chain in queue theory, a hybrid model has been presented. This model can be a base to assess queue systems with probable parameters of service. Here by presenting a case study, the proposed model will be described. so, production lines of a home application manufacturer will be analyzed.

Keywords: Queuing theory, Markov Chain, layout, line balance

Procedia PDF Downloads 626

Authors: W. J. Zhang, Y. Q. Du, M. L. Wang

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Noninvasive diagnostics of diseases via breath analysis has attracted considerable scientific and clinical interest for many years and become more and more promising with the rapid advancement in nanotechnology and biotechnology. The volatile organic compounds (VOCs) in exhaled breath, which are mainly blood borne, particularly provide highly valuable information about individuals’ physiological and pathophysiological conditions. Additionally, breath analysis is noninvasive, real-time, painless and agreeable to patients. We have developed a wireless sensor array based on single-stranded DNA (ssDNA)-decorated single-walled carbon nanotubes (SWNT) for the detection of a number of physiological indicators in breath. Eight DNA sequences were used to functionalize SWNT sensors to detect trace amount of methanol, benzene, dimethyl sulfide, hydrogen sulfide, acetone and ethanol, which are indicators of heavy smoking, excessive drinking, and diseases such as lung cancer, breast cancer, cirrhosis and diabetes. Our tests indicated that DNA functionalized SWNT sensors exhibit great selectivity, sensitivity, reproducibility, and repeatability. Furthermore, different molecules can be distinguished through pattern recognition enabled by this sensor array. Thus, the DNA-SWNT sensor array has great potential to be applied in chemical or bimolecular detection for the noninvasive diagnostics of diseases and health monitoring.

Keywords: breath analysis, diagnosis, DNA-SWNT sensor array, noninvasive

Procedia PDF Downloads 348

Authors: Harish Rajak, Kamlesh Raghuwanshi

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Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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Authors: Olfat Shaker, Miriam Wadie, Reham Ali, Ayman Yosry

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Colorectal cancer (CRC) is a major cause of mortality and morbidity and accounts for over 9% of cancer incidence worldwide. Silent information regulator 2 homolog 1 (SIRT1) gene is located in the nucleus and exert its effects via modulation of histone and non-histone targets. They function in the cell via histone deacetylase (HDAC) and/or adenosine diphosphate ribosyl transferase (ADPRT) enzymatic activity. The aim of this work was to study the relationship between SIRT1 polymorphism and its protein level in colorectal cancer patients in comparison to control cases. This study includes 2 groups: thirty healthy subjects (control group) & one hundred CRC patients. All subjects were subjected to: SIRT-1 serum level was measured by ELISA and gene polymorphisms of rs12778366, rs375891 and rs3740051 were detected by real time PCR. For CRC patients clinical data were collected (size, site of tumor as well as its grading, obesity) CRC patients showed high significant increase in the mean level of serum SIRT-1 compared to control group (P<0.001). Mean serum level of SIRT-1 showed high significant increase in patients with tumor size ≥5 compared to the size < 5 cm (P<0.05). In CRC patients, percentage of T allele of rs12778366 was significantly lower than controls, CC genotype and C allele C of rs 375891 were significantly higher than control group. In CRC patients, the CC genotype of rs12778366, was 75% in rectosigmoid and 25% in cecum & ascending colon. According to tumor size, the percentage of CC genotype was 87.5% in tumor size ≥5 cm. Conclusion: serum level of SIRT-1 and T allele, C allele of rs12778366 and rs 375891 respectively can be used as diagnostic markers for CRC patients.

Keywords: CRC, SIRT1, polymorphisms, ELISA

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Authors: Jovana Bogojeski, Dusan Cocic, Nenad Jankovic, Angelina Petrovic

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Kinetically-inert transition metal complexes, such as Rh(III) and Os(III) complexes, attract increasing attention as leading scaffolds for the development of potential pharmacological agents due to their inertness and stability. Therefore, we have designed and fully characterized a few novel rhodium(III) and osmium(III) complexes with a tridentate nitrogen−donor chelate system. For some complexes, the crystal X-ray structure analysis was performed. Reactivity of the newly synthesized complexes towards small biomolecules, such as L-methionine (L-Met), guanosine-5’-monophosphate (5’-GMP), and glutathione (GSH) has been examined. Also, the reactivity of these complexes towards the DNA/RNA (Ribonucleic acid) duplexes was investigated. Obtained results show that the newly synthesized complexes exhibit good affinity towards the studied ligands. Results also show that the complexes react faster with the RNA duplex than with the DNA and that in the DNA duplex reaction is faster with 15mer GG than with the 22mer GG. The UV-Vis (Ultraviolet-visible spectroscopy) is absorption spectroscopy, and the EB (Ethidium bromide) displacement studies were used to examine the interaction of these complexes with CT-DNA and BSA (Bovine serum albumin). All studied complex showed good interaction ability with both the DNA and BSA. Furthermore, the DFT (Density-functional theory) calculation and docking studies were performed. The impact of the metal complex on the cytotoxicity was tested by MTT assay (a colorimetric assay for assessing cell metabolic activity) on HCT-116 lines (human colon cancer cell line). In addition, all these tests were repeated in the presence of several water-soluble biologically active ionic liquids. Attained results indicate that the ionic liquids increase the activity of the investigated complexes. All obtained results in this study imply that the introduction of different spectator ligand can be used to improve the reactivity of rhodium(III) and osmium(III) complexes. Finally, these results indicate that the examined complexes show reactivity characteristics needed for potential anti-tumor agents, with possible targets being both the DNA and proteins. Every new contribution in this field is highly warranted due to the current lack of clinically used Metallo-based alternatives to cisplatin.

Keywords: biomolecules, ionic liquids, osmium(III), rhodium(III)

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Authors: Mukesh K., Siddiqui A. K., Abbas H., Gupta R.

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Background: General Anesthesia is a standard for breast onco-surgery. The issue of postoperative pain and the occurrence of nausea and vomiting has prompted the quest for a superior methodology with fewer complications. Over the recent couple of years, paravertebral block (PVB) has acquired huge fame either in combination with GA or alone for anesthetic management. In this study, we aim to evaluate the efficacy of morphine and clonidine as an adjunct to ropivacaine in a paravertebral block in breast cancer patients undergoing modified radical mastectomy. Methods: In this study, total 90 patients were divided into three groups (30 each) on the basis of computer-generated randomization. Group C (Control): Paravertebral block with 0.25% ropivacaine (19ml) and 1 ml saline; Group M- Paravertebral block with 0.25% ropivacaine(19ml) + 20 microgram/kg body weight morphine; Group N: Paravertebral block with 0.25% ropivacaine(19ml) +1.0 microgram/kg body weight clonidine. The postoperative pain intensity was recorded using the visual analog scale (VAS) and Sedation was observed by the Ramsay Sedation score (RSS). Results: The VAS was similar at 0hr, 2hr and 4 hr in the postoperative period among all the groups. There was a significant (p=0.003) difference in VAS from 6 hr to 20 hr in the postoperative period among the groups. A significant (p<0.05) difference was observed among the groups at 8 hr to 20 hr). The first requirement of analgesia was significantly (p=0.001) higher in Group N (7.70±1.74) than in Group C (4.43±1.43) and Group M (7.33±2.21). Conclusion: The morphine in the paravertebral block provides better postoperative analgesia. The consumption of rescue analgesia was significantly reduced in the morphine group as compared to the clonidine group. The procedure also proved to be safe as no complication was encountered in the paravertebral block in our study.

Keywords: ropivacaine, morphine, clonidine, paravertebral block

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Authors: Bouzaki Mohammed Moustafa, Benyoucef Boumediene, Benouaz Tayeb, Benhamou Amina

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The ambient temperature and the defects density in the Hetero-junction with Intrinsic Thin layers solar cells (HIT) strongly influence their performances. In first part, we presented the bands diagram on the front/back simulated solar cell based on a-Si: H / c-Si (p)/a-Si:h. In another part, we modeled the following layers structure: ZnO/a-Si:H(n)/a-Si:H(i)/c-Si(p)/a-Si:H(p)/Ag where we studied the effect of the ambient temperature and the defects density in the gap of the crystalline silicon layer on the performance of the heterojunction solar cell with intrinsic layer (HIT).

Keywords: heterojunction solar cell, solar cell performance, bands diagram, ambient temperature, defect density

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Authors: Firas Gerges, Frank Y. Shih

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Malignant melanoma, known simply as melanoma, is a type of skin cancer that appears as a mole on the skin. It is critical to detect this cancer at an early stage because it can spread across the body and may lead to the patient's death. When detected early, melanoma is curable. In this paper, we propose a deep learning model (convolutional neural networks) in order to automatically classify skin lesion images as malignant or benign. Images underwent certain pre-processing steps to diminish the effect of the normal skin region on the model. The result of the proposed model showed a significant improvement over previous work, achieving an accuracy of 97%.

Keywords: deep learning, skin cancer, image processing, melanoma

Procedia PDF Downloads 150

Authors: Hyo-Min Kim, Seokjin Ham, Mi-Joung Yoo, Minseon Kim, Tae-Young Roh

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The gastrointestinal (GI) tract of most animals, including murine, is highly compartmentalized epithelia which also provide distinct different functions of its own tissue. Nevertheless, these epithelia share certain characteristics that enhance immune responses to infections and maintain the barrier function of the intestine. GI tract epithelia also undergo regeneration not only in homeostatic conditions but also in a response to the damage. A full turnover of the murine gastrointestinal epithelium occurs every 4-5 day, a process that is regulated and maintained by a minor population of Lgr5+ adult stem cell that commonly conserved in the bottom of crypts through GI tract. Maintenance of the stem cell is somehow regulated by epigenetic factors according to recent studies. Chromatin vacancy, remodelers, histone variants and histone modifiers could affect adult stem cell fate. In this study, Lgr5-EGFP reporter mouse was used to take advantage of exploring the epigenetic dynamics among Lgr5 positive mutual stem cell in GI tract. Cells were isolated by fluorescence-activated cell sorting (FACS), gene expression levels, chromatin accessibility changes and histone modifications were analyzed. Some notable chromatin structural related epigenetic variants were detected. To identify the overall cell-cell interaction inside the stem cell niche, an extensive genome-wide analysis should be also followed. According to the results, nevertheless, we expected a broader understanding of cellular niche maintaining stem cells and epigenetic barriers through conserved stem cell in GI tract. We expect that our study could provide more evidence of adult stem cell plasticity and more chances to understand each stem cell that takes parts in certain organs.

Keywords: adult stem cell, epigenetics, LGR5 stem cell, gastrointestinal tract

Procedia PDF Downloads 229

Authors: Saif Ullah, Guan Zailin, Xu Xianhao, He Zongdong, Wang Baoxi

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Assembly line balancing problem is aimed to divide the tasks among the stations in assembly lines and optimize some objectives. In assembly lines the workload on stations is different from each other due to different tasks times and the difference in workloads between stations can cause blockage or starvation in some stations in assembly lines. Buffers are used to store the semi-finished parts between the stations and can help to smooth the assembly production. The assembly line balancing and buffer sizing problem can affect the throughput of the assembly lines. Assembly line balancing and buffer sizing problems have been studied separately in literature and due to their collective contribution in throughput rate of assembly lines, balancing and buffer sizing problem are desired to study simultaneously and therefore they are considered concurrently in current research. Current research is aimed to maximize throughput, minimize total size of buffers in assembly line and minimize workload variations in assembly line simultaneously. A multi objective optimization objective is designed which can give better Pareto solutions from the Pareto front and a simple example problem is solved for assembly line balancing and buffer sizing simultaneously. Current research is significant for assembly line balancing research and it can be significant to introduce optimization approaches which can optimize current multi objective problem in future.

Keywords: assembly line balancing, buffer sizing, Pareto solutions

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Authors: Khalid Iqbal

Abstract:

This work presents a comparison of an anthropomorphic PRESAGE® dosimeter and radiochromic film measurements with a commercial treatment planning system to determine the feasibility of PRESAGE® for 3D dosimetry in breast IMRT. An anthropomorphic PRESAGE® phantom was created in the shape of a breast phantom. A five-field IMRT plan was generated with a commercially available treatment planning system and delivered to the PRESAGE® phantom. The anthropomorphic PRESAGE® was scanned with the Duke midsized optical CT scanner (DMOS-RPC) and the OD distribution was converted to dose. Comparisons were performed between the dose distribution calculated with the Pinnacle3 treatment planning system, PRESAGE®, and EBT2 film measurements. DVHs, gamma maps, and line profiles were used to evaluate the agreement. Gamma map comparisons showed that Pinnacle3 agreed with PRESAGE® as greater than 95% of comparison points for the PTV passed a ± 3%/± 3 mm criterion when the outer 8 mm of phantom data were discluded. Edge artifacts were observed in the optical CT reconstruction, from the surface to approximately 8 mm depth. These artifacts resulted in dose differences between Pinnacle3 and PRESAGE® of up to 5% between the surface and a depth of 8 mm and decreased with increasing depth in the phantom. Line profile comparisons between all three independent measurements yielded a maximum difference of 2% within the central 80% of the field width. For the breast IMRT plan studied, the Pinnacle3 calculations agreed with PRESAGE® measurements to within the ±3%/± 3 mm gamma criterion. This work demonstrates the feasibility of the PRESAGE® to be fashioned into anthropomorphic shape, and establishes the accuracy of Pinnacle3 for breast IMRT. Furthermore, these data have established the groundwork for future investigations into 3D dosimetry with more complex anthropomorphic phantoms.

Keywords: 3D dosimetry, PRESAGE®, IMRT, QA, EBT2 GAFCHROMIC film

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Authors: Lamis Naddaf, Yuval Tabach

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We identified missense genetic variants with the potential to enhance resistance against cancer. Such a field has not been widely explored as researchers tend to investigate the mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and have significant implications for improved risk estimation, diagnostics, prognosis, and even personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and selected the alleles that showed a correlation with the species’ cancer resistance. Interestingly, we found several amino acids that are more generally preferred (like the Proline) or avoided (like the Cysteine) by the resistant species. Furthermore, Cancer resistance in mammals and reptiles is significantly predicted by the number of the predicted protecting variants (PVs) a species has. Moreover, PVs-enriched-genes are enriched in pathways relevant to tumor suppression. For example, they are enriched in the Hedgehog signaling and silencing pathways, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are mostly more abundant in healthy people compared to cancer patients within different human races.

Keywords: cancer resistance, protecting variant, naked mole rat, comparative genomics

Procedia PDF Downloads 112

Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko

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During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.

Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity

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Authors: Vallisree Sivathanu, Kumaraswamidhas Lakshmi Annamalai, Trupti Ranjan Lenka

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We report a tandem solar cell model with Silicon as the bottom cell absorber material and Cu₂BaSn(S, Se)₄(CBTSSe) as absorber material for the top cell. As a first step, the top and bottom cells were modelled and validated by comparison with the experiment. Once the individual cells are validated, then the tandem structure is modelled with Indium Tin Oxide(ITO) as conducting layer between the top and bottom cells. The tandem structure yielded better open circuit voltage and fill factor; however, the efficiency obtained is 7.01%. The top cell and the bottom cells are investigated with the help of electron-hole current density, photogeneration rate, and external quantum efficiency profiles. In order to minimize the various loss mechanisms in the tandem solar cell, the material parameters are optimized within experimentally achievable limits. Initially, the top cell optimization was carried out; then, the bottom cell is optimized for maximizing the light absorption, and upon minimizing the current and photon losses in the tandem structure, the maximum achievable efficiency is predicted to be 19.52%.

Keywords: CBTSSe, silicon, tandem, solar cell, device modeling, current losses, photon losses

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Authors: Valerie A. Conrade

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Introduction: A large body of literature suggests patients who complete fecal immunochemical testing (FIT) kits are likely to identify colorectal cancer sooner than those who do not complete FIT kits. Background: Patients who do not participate in preventative measures such as the FIT kit are at a higher risk of colorectal cancer growing unnoticed. The objective was to see if the method the principal investigator (PI) uses to educate clinical staff on the importance of FIT kit administration provides an increased amount of FIT kit dissemination to patients post clinical education. Methodologies: Data collection via manual tallies took place before and after the clinical staff was educated on the importance of FIT kits. Results: The results showed an increase in FIT kit dissemination post clinical staff education. Through enhanced instruction to the clinical staff regarding the importance of FIT kits, expanding their knowledge on preventative measures to detect colorectal cancer positively impacted nurses and, in turn, their patients.

Keywords: colon cancer, education, fecal immunochemical testing, nursing

Procedia PDF Downloads 138

Authors: Alireza Barari, Maryam Firoozi, Maryam Ebrahimzadeh, Romina Roohan Ardeshiri, Maryam Kamarloeei

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Background: The The purpose of this study was to evaluate the effect of six-week aerobic training and taxol consumption on interleukin 8 and Plasminogen Activator Inhibitor-1 (PAI-1) in mice with cervical cancer. Material and method: In this experimental study, 40 female C57 mice, eight weeks old, were randomly divided into 4 groups: cancer, cancer-taxol complement, cancer-training and cancer-training - taxol complement with 10 mice in each group. The implantation of cancerous tumors was performed under the skin of the upper pelvis. The training group completed the endurance training protocol, which included 3 sessions per week, 50 minutes per session, at a speed of 14-18 m/s for six weeks. A dose of 60 mg/ kg/day, a pure extract of Taxol was injected peritoneal Data were analyzed by t-test, One-way ANOVA and post hoc Bonferron's at the significant level P<0. 05. Results: The results showed that there was a significant difference between mean values of interleukin-8 (P < 0.05, F = 12.25) and the plasminogen activator inhibitor-1 (P < 0.05, P=0.10737) in four groups. A significance level of less than 0.05 in Tukey test for both variables also showed a significant difference between the "control" group and the complementary "exercise" group. Namely, six weeks of aerobic training, along with taxol, have a significant effect on the level of plasminogen activator inhibitor-1 and interleukin-8 mice with cervical cancer. Conclusion: Considering the effect of training on these variables, this type of exercise can be used as a complementary therapeutic approach along with other therapies for cervical cancer.

Keywords: cervical cancer, taxol, endurance training, interleukin 8, plasminogen activator inhibitor-1

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Authors: Haonan Hu, Shuge Lei, Dasheng Sun, Huabin Zhang, Kehong Yuan, Jian Dai, Jijun Tang

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This paper focuses on the classification task of breast ultrasound images and conducts research on the reliability measurement of classification results. A dual-channel evaluation framework was developed based on the proposed inference reliability and predictive reliability scores. For the inference reliability evaluation, human-aligned and doctor-agreed inference rationals based on the improved feature attribution algorithm SP-RISA are gracefully applied. Uncertainty quantification is used to evaluate the predictive reliability via the test time enhancement. The effectiveness of this reliability evaluation framework has been verified on the breast ultrasound clinical dataset YBUS, and its robustness is verified on the public dataset BUSI. The expected calibration errors on both datasets are significantly lower than traditional evaluation methods, which proves the effectiveness of the proposed reliability measurement.

Keywords: medical imaging, ultrasound imaging, XAI, uncertainty measurement, trustworthy AI

Procedia PDF Downloads 103

Authors: Andreea Molnar, Amalia Ardeljan, Lexi Frankel, Marissa Dallara, Brittany Nagel, Omar Rashid

Abstract:

Background: Escherichia coli is a gram-negative, facultative anaerobic bacteria that belongs to the family Enterobacteriaceae and resides in the intestinal tracts of individuals. E.Coli has numerous strains grouped into serogroups and serotypes based on differences in antigens in their cell walls (somatic, or “O” antigens) and flagella (“H” antigens). More than 700 serotypes of E. coli have been identified. Although most strains of E. coli are harmless, a few strains, such as E. coli O157:H7 which produces Shiga toxin, can cause intestinal infection with symptoms of severe abdominal cramps, bloody diarrhea, and vomiting. Infection with E. Coli can lead to the development of systemic inflammation as the toxin exerts its effects. Chronic inflammation is now known to contribute to cancer development in several organs, including the prostate. The purpose of this study was to evaluate the correlation between E. Coli and the incidence of prostate cancer. Methods: Data collected in this cohort study was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate patients infected with E.Coli infection and prostate cancer using the International Classification of Disease (ICD-10 and ICD-9 codes). Permission to use the database was granted by Holy Cross Health, Fort Lauderdale for the purpose of academic research. Data analysis was conducted through the use of standard statistical methods. Results: Between January 2010 and December 2019, the query was analyzed and resulted in 81, 037 patients after matching in both infected and control groups, respectively. The two groups were matched by Age Range and CCI score. The incidence of prostate cancer was 2.07% and 1,680 patients in the E. Coli group compared to 5.19% and 4,206 patients in the control group. The difference was statistically significant by a p-value p<2.2x10-16 with an Odds Ratio of 0.53 and a 95% CI. Based on the specific treatment for E.Coli, the infected group vs control group were matched again with a result of 31,696 patients in each group. 827 out of 31,696 (2.60%) patients with a prior E.coli infection and treated with antibiotics were compared to 1634 out of 31,696 (5.15%) patients with no history of E.coli infection (control) and received antibiotic treatment. Both populations subsequently developed prostate carcinoma. Results remained statistically significant (p<2.2x10-16), Odds Ratio=0.55 (95% CI 0.51-0.59). Conclusion: This retrospective study shows a statistically significant correlation between E.Coli infection and a decreased incidence of prostate cancer. Further evaluation is needed in order to identify the impact of E.Coli infection and prostate cancer development.

Keywords: E. Coli, prostate cancer, protective, microbiology

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Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

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Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

Procedia PDF Downloads 590

Authors: Karen Boaz, C. R. Charan

Abstract:

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

Procedia PDF Downloads 250

Authors: William Kelly, Sorelle Veigne, Xianhua Li, Zuyi Huang, Shyamsundar Subramanian, Eugene Schaefer

Abstract:

The ambr15™ bioreactor is a single-use microbioreactor for cell line development and process optimization. The ambr system offers fully automatic liquid handling with the possibility of fed-batch operation and automatic control of pH and oxygen delivery. With operating conditions for large scale biopharmaceutical production properly scaled down, micro bioreactors such as the ambr15™ can potentially be used to predict the effect of process changes such as modified media or different cell lines. In this study, gassing rates and dilution rates were varied for a semi-continuous cell culture system in the ambr15™ bioreactor. The corresponding changes to metabolite production and consumption, as well as cell growth rate and therapeutic protein production were measured. Conditions were identified in the ambr15™ bioreactor that produced metabolic shifts and specific metabolic and protein production rates also seen in the corresponding larger (5 liter) scale perfusion process. A Dynamic Flux Balance model was employed to understand and predict the metabolic changes observed. The DFB model-predicted trends observed experimentally, including lower specific glucose consumption when CO₂ was maintained at higher levels (i.e. 100 mm Hg) in the broth. A Computational Fluid Dynamic (CFD) model of the ambr15™ was also developed, to understand transfer of O₂ and CO₂ to the liquid. This CFD model predicted gas-liquid flow in the bioreactor using the ANSYS software. The two-phase flow equations were solved via an Eulerian method, with population balance equations tracking the size of the gas bubbles resulting from breakage and coalescence. Reasonable results were obtained in that the Carbon Dioxide mass transfer coefficient (kLa) and the air hold up increased with higher gas flow rate. Volume-averaged kLa values at 500 RPM increased as the gas flow rate was doubled and matched experimentally determined values. These results form a solid basis for optimizing the ambr15™, using both CFD and FBA modelling approaches together, for use in microscale simulations of larger scale cell culture processes.

Keywords: cell culture, computational fluid dynamics, dynamic flux balance analysis, microbioreactor

Procedia PDF Downloads 283

Authors: Meisam Omidi, M. Mirijalili, Mohammadmehdi Choolaei, Z. Sharifi, F. Haghiralsadat, F. Yazdian

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In this work, we have used arrays of micromechanical piezoresistive cantilever with different geometries to detect carcinoembryonic antigen (CEA), which is known as an important biomarker associated with various cancers such as the colorectal, lung, breast, pancreatic, and bladder cancer. The sensing principle is based on the surface stress changes induced by antigen–antibody interaction on the microcantilevers surfaces. Different concentrations of CEA in a human serum albumin (HSA) solution were detected as a function of the deflection of the beams. According to the experiments, it was revealed that microcantilevers have surface stress sensitivities in the order of 8 (mJ/m). This matter allows them to detect CEA concentrations as low as 3 ng/mL or 18 pM. This indicates the fact that the self-sensing microcantilever approach is beneficial for pathological tests.

Keywords: micromechanical biosensors, carcinoembryonic antigen (CEA), surface stress

Procedia PDF Downloads 472

Authors: Giuliano Raimondo, Jörg Wangemann, Peer Drechsel

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In systems development involving Fuel Cells generators, it is important to have from an early stage of the project a dynamic model for the electrical behavior of the stack to be shared between involved development parties. It allows independent and early design and tests of fuel cell related power electronic. This paper presents an empirical Fuel Cell system model derived from characterization tests on a real system. Moreover, it is illustrated how the obtained model is used to build and validate a real-time Fuel Cell system emulator which is used for aerospace electrical integration testing activities.

Keywords: fuel cell, modelling, real time emulation, testing

Procedia PDF Downloads 337

Authors: Omer Ibrahim Abdallh Omer

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Cancer patients often face complex medication regimens, leading to challenges in treatment adherence and clinical outcomes. Pharmacist-led medication therapy management (MTM) has emerged as a potential solution to optimize medication use and improve patient outcomes in oncology settings. In this prospective intervention study, we aimed to evaluate the impact of pharmacist-led MTM on treatment adherence and clinical outcomes among cancer patients. Participants were randomized to receive either pharmacist-led MTM or standard care, with assessments conducted at baseline and follow-up visits. Pharmacist interventions included medication reconciliation, adherence counseling, and personalized care plans. Our findings reveal that pharmacist-led MTM significantly improved medication adherence rates and clinical outcomes compared to standard care. Patients receiving pharmacist interventions reported higher satisfaction levels and perceived value in pharmacist involvement in their cancer care. These results underscore the critical role of pharmacists in optimizing medication therapy and enhancing patient-centered care in oncology settings. Integration of pharmacist-led MTM into routine cancer care pathways holds promise for improving treatment outcomes and quality of life for cancer patients.

Keywords: cancer, medications adherence, medication therapy management, pharmacist

Procedia PDF Downloads 64

Authors: Monisha Edirisooriya, Wilma Jack, Dominique Twelves, Jennifer Royds, Fiona Scott, Nicola Mason, Arran Turnbull, J. Michael Dixon

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Introduction: Excision biopsy has been the investigation of choice for patients presenting with pathological axillary lymphadenopathy without a breast abnormality. Core biopsy of nodes can provide sufficient tissue for diagnosis and has advantages in terms of morbidity and speed of diagnosis. This study evaluates the diagnostic accuracy of core biopsy in patients presenting with axillary lymphadenopathy. Methods: Between 2009 and 2019, 165 patients referred to the Edinburgh Breast Unit had a total of 179 axillary lymph node core biopsies. Results: 152 (92%) of the 165 initial core biopsies were deemed to contain adequate nodal tissue. Core biopsy correctly established malignancy in 75 of the 78 patients with haematological malignancy (96%) and in all 28 patients with metastatic carcinoma (100%) and correctly diagnosed benign changes in 49 of 57 (86%) patients with benign conditions. There were no false positives and no false negatives. In 67 (85.9%) of the 78 patients with hematological malignancy, there was sufficient material in the first core biopsy to allow the pathologist to make an actionable diagnosis and not ask for more tissue sampling prior to treatment. There were no complications of core biopsy. On follow up, none of the patients with benign cores has been shown to have malignancy in the axilla and none with lymphoma had their initial disease incorrectly classified. Conclusions: This study shows that core biopsy is now the investigation of choice for patients presenting with axillary lymphadenopathy even in those suspected as having lymphoma.

Keywords: core biopsy, excision biopsy, axillary lymphadenopathy, non-breast malignancy

Procedia PDF Downloads 242

Authors: Meenu Mehta, Munish Garg

Abstract:

The use of oral anticancer drugs from AYUSH system of medicine is widely increased among the society due to their low cost, enhanced efficacy, increased patient preference, lack of inconveniences related to infusion and they provide an opportunity to develop chronic treatment regimens. However, oral delivery of these drugs usually laid down by the limited bioavailability of the drug, which is associated with a wide variation. As most of the cytotoxic agents have a narrow therapeutic window and are dosed at or near the maximum tolerated dose, a wide variability in the bioavailability can negatively affect treatment result. It is estimated that 40% of active substances are poorly soluble in water. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations. There are several techniques reported in literature. Among all these Self Emulsifying Drug Delivery System (SEDDS) has gained more attention due to enhanced oral bio-availability enabling a reduction in dose. Thus, SEDDS anticancer drugs will have the increased bioavailability and efficacy. These dosage form will provide societal benefit in a cost-effective manner as compared to other oral dosage forms. Present study reflects on the formulation strategies as SEDDS for oral anticancer agents of AYUSH system for enhanced bioavailability with proven efficacy by cancer cell lines.

Keywords: anticancer agents, AYUSH system, bioavailability, SEDDS

Procedia PDF Downloads 306