Search results for: cancer risks
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3841

Search results for: cancer risks

3331 Immunoliposomes Conjugated with CD133 Antibody for Targeting Melanoma Cancer Stem Cells

Authors: Chuan Yin

Abstract:

Cancer stem cells (CSCs) represent a subpopulation of cancer cells that possess the characteristics associated with normal stem cells. CD133 is a phenotype of melanoma CSCs responsible for melanoma metastasis and drug resistance. Although adriamycin (ADR) is commonly used drug in melanoma therapy, but it is ineffective in the treatment of melanoma CSCs. In this study, we constructed CD133 antibody conjugated ADR immunoliposomes (ADR-Lip-CD133) to target CD133+ melanoma CSCs. The results showed that the immunoliposomes possessed a small particle size (~150 nm), high drug encapsulation efficiency (~90%). After 72 hr treatment on the WM266-4 melanoma tumorspheres, the IC50 values of the drug formulated in ADR-Lip-CD133, ADR-Lip (ADR liposomes) and ADR are found to be 24.42, 57.13 and 59.98 ng/ml respectively, suggesting that ADR-Lip-CD133 was more effective than ADR-Lip and ADR. Significantly, ADR-Lip-CD133 could almost completely abolish the tumorigenic ability of WM266-4 tumorspheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. It is noteworthy that ADR-Lip-CD133 could selectively kill CD133+ melanoma CSCs of WM266-4 cells both in vitro and in vivo. ADR-Lip-CD133 represent a potential approach in targeting and killing CD133+ melanoma CSCs.

Keywords: cancer stem cells, melanoma, immunoliposomes, CD133

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3330 Association of Clostridium difficile Infection and Bone Cancer

Authors: Daniela Prado, Lexi Frankel, Amalia Ardeljan, Lokesh Manjani, Matthew Cardeiro, Omar Rashid

Abstract:

Background: Clostridium difficile (C. diff) is a gram-positive bacterium that is known to cause life-threatening diarrhea and severe inflammation of the colon. It originates as an alteration of the gut microbiome and can be transmitted through spores. Recent studies have shown a high association between the development of C. diff in cancer patients due to extensive hospitalization. However, research is lacking regarding C. diff’s association in the causation or prevention of cancer. The objective of this study was to therefore assess the correlation between Clostridium difficile infection (CDI) and the incidence of bone cancer. Methods: This retrospective analysis used data provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with C. diff using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale, for the purpose of academic research. Standard statistical methods were used. Results: Between January 2010 and December 2019, the query was analyzed and resulted in 78863 patients in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bone cancer was 659 patients (0.835%) in the C. diff group compared to 1941 patients (2.461%) in the control group. The difference was statistically significant by a P-value < 2.2x10^-16 with an odds ratio (OR)= 0.33 (0.31-0.37) with a 95% confidence interval (CI). Treatment for CDI was analyzed for both C. diff infected and noninfected populations. 91 out of 16,676 (0.55%) patients with a prior C. diff infection and treated with antibiotics were compared to the control group were 275 out of 16,676 (1.65%) patients with no history of CDI and received antibiotic treatment. Results remained statistically significant by P-value <2.2x10-16 with an OR= 0.42 (0.37, 0.48). and a 95% CI. Conclusion: The study shows a statistically significant correlation between C. diff and a reduced incidence of bone cancer. Further evaluation is recommended to assess the potential of C. difficile in reducing bone cancer incidence.

Keywords: bone cancer, colitis, clostridium difficile, microbiome

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3329 2D and 3D Breast Cancer Cells Behave Differently to the Applied Free Palbociclib or the Palbociclib-Loaded Nanoparticles

Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

Abstract:

Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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3328 Serum 25-Hydroxyvitamin D Levels in Korean Breast Cancer Patients

Authors: Sung Yong Kim, Byung Joo Song

Abstract:

Background: Circulating 25-hydroxyvitamin D (25(OH)D) levels has been considered to be inversely related to breast cancer development, recurrence risk, and mortality. Mean vitamin D levels in Korean population is lower than western countries due to higher incidence of lactose intolerance and lower exposure to sunlight. The purpose of this study was to assess incidence of 25(OH)D deficiency at diagnosis and after adjuvant chemotherapy and to investigate the correlation serum 25(OH)D levels with clinicopathologic features. Methods: From December 2011 to October 2012, 280 breast cancer patients seen at a single tertiary cancer center were enrolled. Serum 25(OH)D was measured at the time of surgery and after completion of adjuvant chemotherapy. Statistical analyses used chi-square test, Fisher's exact test, t-test, and ANOVA. Results: Mean serum 25(OH)D was 18.5 ng/ml. The 25(OH)D levels were deficient (<20 ng/ml) in 190 patients (67.9%), insufficient (20-29 ng/ml) in 51 patients(18.2%), and sufficient (30-150 ng/ml) in 39 patients(13.9%). A notable decrease in 25(OH)D concentration was observed(p<0.001) after chemotherapy but was not related to chemotherapy regimens. It was found significant lower 25(OH)D levels at winter season(from October to March, p=0.030). Subjects with invasive carcinoma (IDC or ILC) had significantly lower circulating levels of 25(OH)D than those with ductal carcinoma in situ(DCIS) (p=0.010). Patients with larger tumor size tends to have lower serum 25(OH)D but there were no statistical significance. Conclusions: Most of the breast cancer patients showed deficient or insufficient serum 25(OH)D concentration. Incidence of vitamin D deficiency was higher in invasive carcinoma than DCIS. Serum 25(OH)D levels were decreased after chemotherapy. Consideration should be given to the supplement of vitamin D to those patients.

Keywords: breast neoplasms, vitamin D, Korean population, breast cancer

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3327 Poor Medical Waste Management (MWM) Practices and Its Risks to Human Health and the Environment

Authors: Babanyara Y. Y., Ibrahim D. B., Garba T., Bogoro A. G., Abubakar, M. Y.

Abstract:

Medical care is vital for our life, health, and well-being. However, the waste generated from medical activities can be hazardous, toxic, and even lethal because of their high potential for diseases transmission. The hazardous and toxic parts of waste from healthcare establishments comprising infectious, medical, and radioactive material as well as sharps constitute a grave risks to mankind and the environment, if these are not properly treated/disposed or are allowed to be mixed with other municipal waste. In Nigeria, practical information on this aspect is inadequate and research on the public health implications of poor management of medical wastes is few and limited in scope. Findings drawn from Literature particularly in the third world countries highlights financial problems, lack of awareness of risks involved in MWM, lack of appropriate legislation and lack of specialized MWM staff. The paper recommends how MWM practices can be improved in medical facilities.

Keywords: environmental pollution, infectious, management, medical waste, public health

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3326 Role of P53 Codon 72 Polymorphism and miR-146a Rs2910164 Polymorphism in Breast Cancer

Authors: Marjan Moradi fard, Hossein Rassi, Masoud Houshmand

Abstract:

Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from Khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.

Keywords: breast cancer, miR-146a rs2910164 polymorphism, p53 codon 72 polymorphism, tumors, pathology reports

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3325 Study of Environmental Impact

Authors: Houmame Benbouali

Abstract:

The risks, in general, exist in any project; one can hardly carry out a project without taking risks. The hydraulic works are rather complex projects in their design, realization and exploitation, and are often subjected at the multiple risks being able to influence with their good performance, and can have an negative impact on their environment. The present study was carried out to quote the impacts caused by purification plant STEP Chlef on the environment, it aims has studies the environmental impacts during construction and when designing this STEP, it is divided into two parts: The first part results from a research task bibliographer which contain three chapters (-cleansing of water worn-general information on water worn-proceed of purification of waste water). The second part is an experimental part which is divided into four chapters (detailed state initial-description of the station of purification-evaluation of the impacts of the project analyzes measurements and recommendations).

Keywords: treatment plant, waste water, waste water treatment, environmental impact

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3324 Right Ventricular Dynamics During Breast Cancer Chemotherapy in Low Cardiovascular Risk Patients

Authors: Nana Gorgiladze, Tamar Gaprindashvili, Mikheil Shavdia, Zurab Pagava

Abstract:

Introduction/Purpose Chemotherapy is a common treatment for breast cancer, but it can also cause damage to the heart and blood vessels. This damage, known as cancer therapy-related cardiovascular toxicity (CTR-CVT), can increase the risk of heart failure and death in breast cancer patients. The left ventricle is often affected by CTR-CVT, but the right ventricle (RV) may also be vulnerable to CTR-CVT and may show signs of dysfunction before the left ventricle. The study aims to investigate how the RV function changes during chemotherapy for breast cancer by using conventional echocardiographic and global longitudinal strain (GLS) techniques. By measuring the GLS strain of the RV, researchers tend to detect early signs of CTR-CVT and improve the management of breast cancer patients. Methods The study was conducted on 28 women with low cardiovascular risk who received anthracycline chemotherapy for breast cancer. Conventional 2D echocardiography (LVEF, RVS’, TAPSE) and speckle-tracking echocardiography (STE) measurements of the left and right ventricles (LVGLS, RVGLS) were used to assess cardiac function before and after chemotherapy. All patients had normal LVEF at the beginning of the study. Cardiotoxicity was defined as a new LVEF reduction of 10 percentage points to an LVEF of 40-49% and/or a new decline in GLS of 15% from baseline, as proposed by the most recent cardio-oncology guideline. ResultsThe research found that the LVGLS decreased from -21.2%2.1% to -18.6%2.6% (t-test = -4.116; df = 54, p=0.001). The change in value LV-GLS was 2.6%3.0%. The mean percentage change of the LVGLS was 11,6%13,3%; p=0.001. Similarly, the right ventricular global longitudinal strain (RVGLS) decreased from -25.2%2.9% to -21.4%4.4% (t-test = -3.82; df = 54, p=0.001). The RV-GLS value of change was 3.8%3.6%. Likewise, the percentage decrease of the RVGLS was 15,0%14,3%, p=0.001.However, the measurements of the right ventricular systolic function (RVS) and tricuspid annular plane systolic excursion (TAPSE) were insignificant, and the left ventricular ejection fraction ( LVEF) remained unchanged.

Keywords: cardiotoxicity, chemotherapy, GLS, right ventricle

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3323 Utilization of Cervical Cancer Screening Among HIV Infected Women in Nairobi, Kenya

Authors: E. Njuguna, S. Ilovi, P. Muiruri, K. Mutai, J. Kinuthia, P. Njoroge

Abstract:

Introduction: Cervical cancer is the commonest cause of cancer-related morbidity and mortality among women in developing countries in Sub Saharan Africa. Screening for cervical cancer in all women regardless of HIV status is crucial for the early detection of cancer of the cervix when treatment is most effective in curing the disease. It is particularly more important to screen HIV infected women as they are more at risk of developing the disease and progressing faster once infected with HPV (Human Papilloma Virus). We aimed to determine the factors affecting the utilization of cervical cancer screenings among HIV infected women above 18 years of age at Kenyatta National Hospital (KNH) Comprehensive Care Center (CCC). Materials and Methods: A cross-sectional mixed quantitative and qualitative study involving randomly and purposefully selected HIV positive female respectively was conducted. Qualitative data collection involved 4 focus group discussions of eligible female participants while quantitative data were acquired by one to one interviewer administered structured questionnaires. The outcome variable was the utilization of cervical cancer screening. Data were entered into Access data base and analyzed using Stata version 11.1. Qualitative data were analyzed after coding for significant clauses and transcribing to determine themes arising. Results: We enrolled a total of 387 patients, mean age (IQ range) 40 years (36-44). Cervical cancer screening utilization was 46% despite a health care provider recommendation of 85%. The screening results were reported as normal in 72 of 81 (88.9%) and abnormal 7 of 81(8.6%) of the cases. Those who did not know their result were 2 of 81(2.5%). Patients were less likely to utilize the service with increasing number of years attending the clinic (OR 0.9, 95% CI 0.86-0.99, p-value 0.02), but more likely to utilize the service if recommendation by a staff was made (OR 10, 95% CI 4.2-23.9, p<0.001), and if cervical screening had been done before joining KNH CCC (OR 2.9, 95% CI 1.7-4.9, p < 0.001). Similarly, they were more likely to rate the services on cervical cancer screening as good (OR 5.0, 95% CI 1.7-3.4, p <0.001) and very good (OR 8.1, 95% CI 2.5-6.1, p<0.001) if they had utilized the service. The main barrier themes emerging from qualitative data included fear of screening due to excessive pain or bleeding, lack of proper communication on screening procedures and increased waiting time. Conclusions: Utilization of cervical cancer screening services was low despite health care recommendation. Patient socio-demographic characteristics did not influence whether or not they utilized the services, indicating the important role of the health care provider in the referral and provision of the service.

Keywords: cervical, cancer, HIV, women, comprehensive care center

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3322 Biomarkers for Rectal Adenocarcinoma Identified by Lipidomic and Bioinformatic

Authors: Patricia O. Carvalho, Marcia C. F. Messias, Laura Credidio, Carlos A. R. Martinez

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Lipidomic strategy can provide important information regarding cancer pathogenesis mechanisms and could reveal new biomarkers to enable early diagnosis of rectal adenocarcinoma (RAC). This study set out to evaluate lipoperoxidation biomarkers, and lipidomic signature by gas chromatography (GC) and electrospray ionization-qToF-mass spectrometry (ESI-qToF-MS) combined with multivariate data analysis in plasma from 23 RAC patients (early- or advanced-stages cancer) and 18 healthy controls. The most abundant ions identified in the RAC patients were those of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) while those of lisophosphatidylcholine (LPC), identified as LPC (16:1), LPC (18:1) and LPC (18:2), were down-regulated. LPC plasmalogen containing palmitoleic acid (LPC (P-16:1)), with highest VIP score, showed a low tendency in the cancer patients. Malondialdehyde plasma levels were higher in patients with advanced cancer (III/IV stages) than in the early stages groups and the healthy group (p<0.05). No differences in F2-isoprostane levels were observed between these groups. This study shows that the reduction in plasma levels of LPC plasmalogens associated to an increase in MDA levels may indicate increased oxidative stress in these patients and identify the metabolite LPC (P-16:1) as new biomarkers for RAC.

Keywords: biomarkers, lipidomic, plasmalogen, rectal adenocarcinoma

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3321 Biological Activities of Flaxseed Peptides (Linusorbs)

Authors: Youn Young Shim, Ji Hye Kim, Jae Youl Cho, Martin J. T. Reaney

Abstract:

Flaxseed (Linum usitatissimum L.) is gaining popularity in the food industry as a superfood due to its health-promoting properties. The flax plant synthesizes an array of biologically active cyclic peptides or linusorbs (LOs, a.k.a. cyclolinopeptides) from three or more ribosome-derived precursors. [1–9-NαC]-linusorb B3 and [1–9-NαC]-linusorb B2, suppress immunity, induce apoptosis in human epithelial cancer cell line (Calu-3) cells, and inhibit T-cell proliferation, but the mechanism of LOs action is unknown. Using gene expression analysis in nematode cultures and human cancer cell lines, we have observed that LOs exert their activity, in part, through induction of apoptosis. Specific LOs’ properties include: 1) distribution throughout the body after flaxseed consumption; 2) induce heat shock protein (HSP) 70A production as an indicator of stress and address the issue in Caenorhabditis elegans (exposure of nematode cultures to [1–9-NαC]-linusorb B3 induced a 30% increase in production of the HSP 70A protein); 3) induce apoptosis in Calu-3 cells; and 4) modulate regulatory genes in microarray analysis. These diverse activities indicate that LOs might induce apoptosis in cancer cells or act as versatile platforms to deliver a variety of biologically active molecules for cancer therapy.

Keywords: flaxseed, linusorb, cyclic peptide, orbitides, heat shock protein, apoptosis, anti-cancer

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3320 Tocilizumab Suppresses the Pro-carcinogenic Effects of Breast Cancer-associated Fibroblasts Through Inhibition of the STAT3/AUF1 Pathway

Authors: Naif Al-Jomah, Falah H Al-Mohanna, Abdelilah Aboussekhra

Abstract:

Active breast cancer-associated fibroblasts (CAFs), the most influential cells in breast tumor microenvironment, express/secrete high levels of the proinvasive/metastatic interleukin-6 (IL-6). Therefore, we have tested here the effect of the IL-6 receptor (IL-6R) inhibitor tocilizumab (TCZ; Actemra) on different active breast CAFs. We have shown that TCZ potently and persistently suppresses the expression of various CAF biomarkers, namely α-SMA, SDF-1 as well as the STAT3 pathway and its downstream target AUF1. TCZ also inhibited the proliferation, migration and invasion abilities of active breast CAF cells. Additionally, TCZ repressed the ability of CAF cells in promoting epithelial-to-mesenchymal transition, and enhancing the migratory/invasive and proliferative capacities of breast cancer cells in vitro. Importantly, these findings were confirmed in orthotopic humanized breast tumors in mice. Furthermore, TCZ suppressed the expression of the pro-angiogenic factor VEGF-A and its transactivator HIF-1α in CAF cells, and consequently inhibited the angiogenic-promoting effect of active CAFs both in vitro and in orthotopic tumor xenografts. These results indicate that inhibition of the IL-6/STAT3/AUF1 pathway by TCZ can normalize active breast CAFs and suppress their paracrine pro-carcinogenic effects, which paves the way toward development of specific CAF-targeting therapy, badly needed for more efficient breast cancer treatments.

Keywords: angiogenesis, interleukin-6, paracrine, cancer-associated fibroblasts

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3319 Analysis of Saudi Breast Cancer Patients’ Primary Tumors using Array Comparative Genomic Hybridization

Authors: L. M. Al-Harbi, A. M. Shokry, J. S. M. Sabir, A. Chaudhary, J. Manikandan, K. S. Saini

Abstract:

Breast cancer is the second most common cause of cancer death worldwide and is the most common malignancy among Saudi females. During breast carcinogenesis, a wide-array of cytogenetic changes involving deletions, or amplification, or translocations, of part or whole of chromosome regions have been observed. Because of the limitations of various earlier technologies, newer tools are developed to scan for changes at the genomic level. Recently, Array Comparative Genomic Hybridization (aCGH) technique has been applied for detecting segmental genomic alterations at molecular level. In this study, aCGH was performed on twenty breast cancer tumors and their matching non-tumor (normal) counterparts using the Agilent 2x400K. Several regions were identified to be either amplified or deleted in a tumor-specific manner. Most frequent alterations were amplification of chromosome 1q, chromosome 8q, 20q, and deletions at 16q were also detected. The amplification of genetic events at 1q and 8q were further validated using FISH analysis using probes targeting 1q25 and 8q (MYC gene). The copy number changes at these loci can potentially cause a significant change in the tumor behavior, as deletions in the E-Cadherin (CDH1)-tumor suppressor gene as well as amplification of the oncogenes-Aurora Kinase A. (AURKA) and MYC could make these tumors highly metastatic. This study validates the use of aCGH in Saudi breast cancer patients and sets the foundations necessary for performing larger cohort studies searching for ethnicity-specific biomarkers and gene copy number variations.

Keywords: breast cancer, molecular biology, ecology, environment

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3318 Modeling Salam Contract for Profit and Loss Sharing

Authors: Dchieche Amina, Aboulaich Rajae

Abstract:

Profit and loss sharing suggests an equitable sharing of risks and profits between the parts involved in a financial transaction. Salam is a contract in which advance payment is made for goods to be delivered at a future date. The purpose of this work is to price a new contract for profit and loss sharing based on Salam contract, using Khiyar Al Ghabn which is an agreement of choice in case of misrepresent facts.

Keywords: Islamic finance, shariah compliance, profi t and loss sharing, derivatives, risks, hedging, salam contract

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3317 Sequential Release of Dual Drugs Using Thermo-Sensitive Hydrogel for Tumor Vascular Inhibition and to Enhance the Efficacy of Chemotherapy

Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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3316 Dual Drug Piperine-Paclitaxel Nanoparticles Inhibit Migration and Invasion in Human Breast Cancer Cells

Authors: Monika Verma, Renuka Sharma, B. R. Gulati, Namita Singh

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In combination therapy, two chemotherapeutic agents work together in a collaborative action. It has appeared as one of the promising approaches to improve anti-cancer treatment efficacy. In the present investigation, piperine (P-NPS), paclitaxel (PTX NPS), and a combination of both, piperine-paclitaxel nanoparticle (Pip-PTX NPS), were made by the nanoprecipitation method and later characterized by PSA, DSC, SEM, TEM, and FTIR. All nanoparticles exhibited a monodispersed size distribution with a size of below 200 nm, zeta potential ranges from (-30-40mV) and a narrow polydispersity index (>0.3) of the drugs. The average encapsulation efficiency was found to be between 80 and 90%. In vitro release of drugs for nanoparticles was done spectrophotometrically. FTIR and DSC results confirmed the presence of the drug. The Pip-PTX NPS significantly inhibit cell proliferation as compared to the native drugs nanoparticles in the breast cancer cell line MCF-7. In addition, Pip-PTX NPS suppresses cells in colony formation and soft gel agar assay. Scratch migration and Transwell chamber invasion assays revealed that combined nanoparticles reduce the migration and invasion of breast cancer cells. Morphological studies showed that Pip-PTX NPS penetrates the cells and induces apoptosis, which was further confirmed by DNA fragmentation, SEM, and western blot analysis. Taken together, Pip-PTX NPS inhibits cell proliferation, anchorage dependent and anchorage independent cell growth, reduces migration and invasion, and induces apoptosis in cells. These findings support that combination therapy using Pip-PTX NPS represents a potential approach and could be helpful in the future for breast cancer therapy.

Keywords: piperine, paclitaxel, breast cancer, apoptosis

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3315 A Microfluidic Biosensor for Detection of EGFR 19 Deletion Mutation Targeting Non-Small Cell Lung Cancer on Rolling Circle Amplification

Authors: Ji Su Kim, Bo Ram Choi, Ju Yeon Cho, Hyukjin Lee

Abstract:

Epidermal growth factor receptor (EGFR) 19 deletion mutation gene is over-expressed in carcinoma patient. EGFR 19 deletion mutation is known as typical biomarker of non-small cell lung cancer (NSCLC), which one section in the coding exon 19 of EGFR is deleted. Therefore, there have been many attempts over the years to detect EGFR 19 deletion mutation for replacing conventional diagnostic method such as PCR and tissue biopsy. We developed a simple and facile detection platform based on Rolling Circle Amplification (RCA), which provides highly amplified products in isothermal amplification of the ligated DNA template. Limit of detection (~50 nM) and a faster detection time (~30 min) could be achieved by introducing RCA.

Keywords: EGFR19, cancer, diagnosis, rolling circle amplification (RCA), hydrogel

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3314 Human Health Risks Assessment of Particulate Air Pollution in Romania

Authors: Katalin Bodor, Zsolt Bodor, Robert Szep

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The particulate matter (PM) smaller than 2.5 μm are less studied due to the limited availability of PM₂.₅, and less information is available on the health effects attributable to PM₁₀ in Central-Eastern Europe. The objective of the current study was to assess the human health risk and characterize the spatial and temporal variation of PM₂.₅ and PM₁₀ in eight Romanian regions between the 2009-2018 and. The PM concentrations showed high variability over time and spatial distribution. The highest concentration was detected in the Bucharest region in the winter period, and the lowest was detected in West. The relative risk caused by the PM₁₀ for all-cause mortality varied between 1.017 (B) and 1.025 (W), with an average 1.020. The results demonstrate a positive relative risk of cardiopulmonary and lung cancer disease due to exposure to PM₂.₅ on the national average 1.26 ( ± 0.023) and 1.42 ( ± 0.037), respectively.

Keywords: PM₂.₅, PM₁₀, relative risk, health effect

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3313 Cost and Benefits of Collocation in the Use of Biogas to Reduce Vulnerabilities and Risks

Authors: Janaina Camile Pasqual Lofhagen, David Savarese, Veronika Vazhnik

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The urgency of the climate crisis requires both innovation and practicality. The energy transition framework allows industry to deliver resilient cities, enhance adaptability to change, pursue energy objectives such as growth or efficiencies, and increase renewable energy. This paper investigates a real-world application perspective for the use of biogas in Brazil and the U.S.. It will examine interventions to provide a foundation of infrastructure, as well as the tangible benefits for policy-makers crafting law and providing incentives.

Keywords: resilience, vulnerability, risks, biogas, sustainability.

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3312 Automated Prediction of HIV-associated Cervical Cancer Patients Using Data Mining Techniques for Survival Analysis

Authors: O. J. Akinsola, Yinan Zheng, Rose Anorlu, F. T. Ogunsola, Lifang Hou, Robert Leo-Murphy

Abstract:

Cervical Cancer (CC) is the 2nd most common cancer among women living in low and middle-income countries, with no associated symptoms during formative periods. With the advancement and innovative medical research, there are numerous preventive measures being utilized, but the incidence of cervical cancer cannot be truncated with the application of only screening tests. The mortality associated with this invasive cervical cancer can be nipped in the bud through the important role of early-stage detection. This study research selected an array of different top features selection techniques which was aimed at developing a model that could validly diagnose the risk factors of cervical cancer. A retrospective clinic-based cohort study was conducted on 178 HIV-associated cervical cancer patients in Lagos University teaching Hospital, Nigeria (U54 data repository) in April 2022. The outcome measure was the automated prediction of the HIV-associated cervical cancer cases, while the predictor variables include: demographic information, reproductive history, birth control, sexual history, cervical cancer screening history for invasive cervical cancer. The proposed technique was assessed with R and Python programming software to produce the model by utilizing the classification algorithms for the detection and diagnosis of cervical cancer disease. Four machine learning classification algorithms used are: the machine learning model was split into training and testing dataset into ratio 80:20. The numerical features were also standardized while hyperparameter tuning was carried out on the machine learning to train and test the data. Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), and K-Nearest Neighbor (KNN). Some fitting features were selected for the detection and diagnosis of cervical cancer diseases from selected characteristics in the dataset using the contribution of various selection methods for the classification cervical cancer into healthy or diseased status. The mean age of patients was 49.7±12.1 years, mean age at pregnancy was 23.3±5.5 years, mean age at first sexual experience was 19.4±3.2 years, while the mean BMI was 27.1±5.6 kg/m2. A larger percentage of the patients are Married (62.9%), while most of them have at least two sexual partners (72.5%). Age of patients (OR=1.065, p<0.001**), marital status (OR=0.375, p=0.011**), number of pregnancy live-births (OR=1.317, p=0.007**), and use of birth control pills (OR=0.291, p=0.015**) were found to be significantly associated with HIV-associated cervical cancer. On top ten 10 features (variables) considered in the analysis, RF claims the overall model performance, which include: accuracy of (72.0%), the precision of (84.6%), a recall of (84.6%) and F1-score of (74.0%) while LR has: an accuracy of (74.0%), precision of (70.0%), recall of (70.0%) and F1-score of (70.0%). The RF model identified 10 features predictive of developing cervical cancer. The age of patients was considered as the most important risk factor, followed by the number of pregnancy livebirths, marital status, and use of birth control pills, The study shows that data mining techniques could be used to identify women living with HIV at high risk of developing cervical cancer in Nigeria and other sub-Saharan African countries.

Keywords: associated cervical cancer, data mining, random forest, logistic regression

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3311 IL-23, an Inflammatory Cytokine, Decreased by Shark Cartilage and Vitamin A Oral Treatment in Patient with Gastric Cancer

Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

Abstract:

Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

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3310 The Cost-Effectiveness of High-Volume Hospital’s Surgical Care for Pancreatic Cancer: Economic Evidence Reviewed

Authors: Shannon Hearney, Jeffrey Hoch

Abstract:

Pancreatic cancer is a notoriously costly and deadly form of cancer. Many types of treatment centers exist for patients to seek care from, including high-volume centers which have shown promise to provide the highest quality of care. While it may be true that this type of center provides the best care it is unclear if that care is cost-effective. Studies in the US have confirmed that high-volume hospitals do provide higher quality of care but have shown inconsistencies in the cost-effectiveness of that care. Other studies, like those from Finland have shown that high-volume centers had lower mortality and lower costs than low-volume centers. This paper thus seeks to review the current scientific literature to better understand if high-volume centers are cost-effective in delivering care in both a European setting and in the US. A review of major reference databases such as Medline, Embase and PubMed will be conducted for cost-effectiveness studies on the surgical treatment of pancreatic cancer at high-volume centers. Possible MeSH terms to be included, but not limited to, are: “pancreatic cancer”, “cost analysis”, “cost-effectiveness”, “economic evaluation”, “pancreatic neoplasms”, “surgical”, and “high-volume”. Studies must also have been available in the English language. This review will encompass European scientific literature, as well as those in the US. Based on our preliminary findings, we anticipate high-volume hospitals to provide better care at greater costs. We anticipate that high-volume hospitals may be cost-effective in different contexts depending on the national structure of a healthcare system. Countries with more centralized and socialized healthcare may yield results that are more cost-effective. High-volume centers may differ in their cost-effectiveness of the surgical care of pancreatic cancer internationally especially when comparing those in the United States to others throughout Europe.

Keywords: cost-effectiveness analysis, economic evaluation, pancreatic cancer, scientific literature review

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3309 Curcumin Nanomedicine: A Breakthrough Approach for Enhanced Lung Cancer Therapy

Authors: Shiva Shakori Poshteh

Abstract:

Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.

Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery

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3308 Exhaled Breath Condensate in Lung Cancer: A Non-Invasive Sample for Easier Mutations Detection by Next Generation Sequencing

Authors: Omar Youssef, Aija Knuuttila, Paivi Piirilä, Virinder Sarhadi, Sakari Knuutila

Abstract:

Exhaled breath condensate (EBC) is a unique sample that allows studying different genetic changes in lung carcinoma through a non-invasive way. With the aid of next generation sequencing (NGS) technology, analysis of genetic mutations has been more efficient with increased sensitivity for detection of genetic variants. In order to investigate the possibility of applying this method for cancer diagnostics, mutations in EBC DNA from lung cancer patients and healthy individuals were studied by using NGS. The key aim is to assess the feasibility of using this approach to detect clinically important mutations in EBC. EBC was collected from 20 healthy individuals and 9 lung cancer patients (four lung adenocarcinomas, four 8 squamous cell carcinoma, and one case of mesothelioma). Mutations in hotpot regions of 22 genes were studied by using Ampliseq Colon and Lung cancer panel and sequenced on Ion PGM. Results demonstrated that all nine patients showed a total of 19 cosmic mutations in APC, BRAF, EGFR, ERBB4, FBXW7, FGFR1, KRAS, MAP2K1, NRAS, PIK3CA, PTEN, RET, SMAD4, and TP53. In controls, 15 individuals showed 35 cosmic mutations in BRAF, CTNNB1, DDR2, EGFR, ERBB2, FBXW7, FGFR3, KRAS, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, and TP53. Additionally, 45 novel mutations not reported previously were also seen in patients’ samples, and 106 novel mutations were seen in controls’ specimens. KRAS exon 2 mutations G12D was identified in one control specimen with mutant allele fraction of 6.8%, while KRAS G13D mutation seen in one patient sample showed mutant allele fraction of 17%. These findings illustrate that hotspot mutations are present in DNA from EBC of both cancer patients and healthy controls. As some of the cosmic mutations were seen in controls too, no firm conclusion can be drawn on the clinical importance of cosmic mutations in patients. Mutations reported in controls could represent early neoplastic changes or normal homeostatic process of apoptosis occurring in lung tissue to get rid of mutant cells. At the same time, mutations detected in patients might represent a non-invasive easily accessible way for early cancer detection. Follow up of individuals with important cancer mutations is necessary to clarify the significance of these mutations in both healthy individuals and cancer patients.

Keywords: exhaled breath condensate, lung cancer, mutations, next generation sequencing

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3307 Data Science in Military Decision-Making: A Semi-Systematic Literature Review

Authors: H. W. Meerveld, R. H. A. Lindelauf

Abstract:

In contemporary warfare, data science is crucial for the military in achieving information superiority. Yet, to the authors’ knowledge, no extensive literature survey on data science in military decision-making has been conducted so far. In this study, 156 peer-reviewed articles were analysed through an integrative, semi-systematic literature review to gain an overview of the topic. The study examined to what extent literature is focussed on the opportunities or risks of data science in military decision-making, differentiated per level of war (i.e. strategic, operational, and tactical level). A relatively large focus on the risks of data science was observed in social science literature, implying that political and military policymakers are disproportionally influenced by a pessimistic view on the application of data science in the military domain. The perceived risks of data science are, however, hardly addressed in formal science literature. This means that the concerns on the military application of data science are not addressed to the audience that can actually develop and enhance data science models and algorithms. Cross-disciplinary research on both the opportunities and risks of military data science can address the observed research gaps. Considering the levels of war, relatively low attention for the operational level compared to the other two levels was observed, suggesting a research gap with reference to military operational data science. Opportunities for military data science mostly arise at the tactical level. On the contrary, studies examining strategic issues mostly emphasise the risks of military data science. Consequently, domain-specific requirements for military strategic data science applications are hardly expressed. Lacking such applications may ultimately lead to a suboptimal strategic decision in today’s warfare.

Keywords: data science, decision-making, information superiority, literature review, military

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3306 The Effects of Metformin And PCL-sorafenib Nanoparticles Co-treatment on MCF-7 Cell Culture Model of Breast Cancer

Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

Abstract:

Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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3305 Discovery of New Inhibitors for Colorectal Cancer Treatment

Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

Abstract:

Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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3304 Weight Gain After Total Thyroidectomy

Authors: Yong Seong Kim, Seongbin Hong, So Hun Kim, Moonsuk Nam

Abstract:

Background: Patients who undergo thyroidectomy due to thyroid cancer often complain weight gain, although they are on suppressive thyroid hormone treatment. The aim of this study is to know whether thyroid cancer patients gain the weight after thyroidectomy and weight change is dependent on estrogen state or use of rhTSH. Material and Method: We performed a retrospective chart review of subjects receiving medical care at an academic medical center. Two hundred two patients who underwent total thyroidectomy were included. As a control group, patients with thyroid nodule and euthyroidism were matched for age, gender, menopausal status. The weight changes occurring over first one year and thyroid function were assessed. Results: Mean age was 51±12 years and patients was composed with 38% of premenopausal, 15 % perimenopausal women, 37% of postmenopausal women and 20% of men. Patients with thyroid cancer gained 2.2 kg during the first year. It’ was not significantly different with control. However, weigh change in perimenopausal and post menopausal women gained more weight than control (P <0.05). Age, baseline body weight and weight gain were not correlated. Discussion: Patient who had undergone thyroidectomy gained more weight than their control, especially in peri- and postmenopausal women. Patients in this age should be monitored for their weight carefully.

Keywords: weight gain, thyroidectomy, thyroid cancer, weight chance

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3303 Oncological and Antiresorptive Treatment of Breast Cancer: Dental Assessment and Risk of MRONJ Development

Authors: Magdalena Korytowska, Gunnar Lengstrand, Cecilia Larsson Wexell

Abstract:

Background: Breast cancer (BC) is the most common cancer among women worldwide, and cases are continuing to increase in Sweden. Bone is the most common metastatic site in breast cancer patients, where > 65-75% of women with advanced breast cancer develop bone metastases during their disease. To prevent the skeletal-related events of metastases (e.g., pathological fractures, bone loss, cancer-induced bone pain, and hypercalcemia bone), two different classes of antiresorptive medications (AR), bisphosphonate and denosumab are typically administered every 3 to 4 weeks. Since 2015, adjuvant bisphosphonate treatment has been used every six months for three to five years in postmenopausal women for the prevention of skeletal metastases and improved survival. Methods: A case-control study was conducted to test the hypotheses that patients treated with high-dose AR are at higher risk of developing MRONJ than breast cancer patients with adjuvant bisphosphonate treatment at a lower dose. Medical and odontological data was collected between 2015-2020. Assessment of oral health and dental care before and during oncological treatment took place at the specialist clinic for Orofacial medicine linked to the specific hospital. Results: In total, 220 patients were included, 101 patients in the high-dose group and 119 patients in the adjuvant BP-treatment group. MRONJ was diagnosed in 13 patients (14%) in the high-dose group. The mandible was affected in most of the cases (84.6%), with a mean duration of high-dose treatment of 19.7 months. In 46.2% of cases, no dental cause of MRONJ could be identified. Overall, estrogen receptor-positive (ER+) BC was the most representative type in 172 patients (78.2%). However, this was 83.9% in the high-dose cases group. The most used drug was denosumab. Twenty-five patients (26.9%) switched their medication from ZOL to denosumab during their oncological treatment. Patients with ER+ breast cancer were reported in 88 patients (87.8%) in the adjuvant group that was treated with ZOL. Conclusions: MRONJ was diagnosed only in the high-dose AR group. Dental assessment and care of patients in the adjuvant group should be considered, with a recommendation to potentially prolong ZOL treatment from 3 to 5 years, with concomitant use of hormonal therapy in patients diagnosed with ER+ breast cancer to prevent bone loss induced by oncological treatment. A new referral for dental assessment is very important in the case of bone metastases when treatment with high dose AR will be required since it is associated with a higher risk of MRONJ.

Keywords: antiresorptive therapy, breast cancer, dental care, MRONJ

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3302 Contracting Strategies to Foster Industrial Symbiosis Implementation

Authors: Robin Molinier

Abstract:

Industrial symbiosis (I.S) deals with the exchange of waste materials, fatal energy and utilities as resources for production. While it brings environmental benefits from resource conservation its economic profitability is one of the main barriers to its implementation. I.S involves several actors with their own objectives and resources so that each actor must be satisfied by ex-ante arrangements to commit toward investments and transactions. Regarding I.S Transaction cost economics helps to identify hybrid forms of governance for transactions governance due to I.S projects specificities induced by the need for customization (asset specificity, non-homogeneity). Thus we propose a framework to analyze the best contractual practices tailored to address I.S specific risks that we identified as threefold (load profiles and quality mismatch, value fluctuations). Schemes from cooperative game theory and contracting management are integrated to analyze value flows between actors. Contractual guidelines are then proposed to address the identified risks and to split the value for a set of I.S archetypes drawn from actual experiences.

Keywords: contracts, economics, industrial symbiosis, risks

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