Search results for: larynx cancer

Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

Abstract:

Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

Procedia PDF Downloads 364

Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

Abstract:

Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

Procedia PDF Downloads 217

Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

Abstract:

Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

Procedia PDF Downloads 128

Authors: Anne-Loes K. Warps, Rob A. E. M. Tollenaar, Pieter J. Tanis, Jan Willem T. Dekker

Abstract:

Anastomotic leakage after colorectal cancer surgery remains a severe complication. Early diagnosis and treatment are essential to prevent further adverse outcomes. In the literature, it has been suggested that earlier reintervention is associated with better survival, but anastomotic leakage can occur with a highly variable time interval to index surgery. This study aims to evaluate the time-interval between rectal cancer resection with primary anastomosis creation and reoperation, in relation to short-term outcomes, stratified for the use of a defunctioning stoma. Methods: Data of all primary rectal cancer patients that underwent elective resection with primary anastomosis during 2013-2019 were extracted from the Dutch ColoRectal Audit. Analyses were stratified for defunctioning stoma. Anastomotic leakage was defined as a defect of the intestinal wall or abscess at the site of the colorectal anastomosis for which a reintervention was required within 30 days. Primary outcomes were new stoma construction, mortality, ICU admission, prolonged hospital stay and readmission. The association between time to reoperation and outcome was evaluated in three ways: Per 2 days, before versus on or after postoperative day 5 and during primary versus readmission. Results: In total 10,772 rectal cancer patients underwent resection with primary anastomosis. A defunctioning stoma was made in 46.6% of patients. These patients had a lower anastomotic leakage rate (8.2% vs. 11.6%, p < 0.001) and less often underwent a reoperation (45.3% vs. 88.7%, p < 0.001). Early reoperations (< 5 days) had the highest complication and mortality rate. Thereafter the distribution of adverse outcomes was more spread over the 30-day postoperative period for patients with a defunctioning stoma. Median time-interval from primary resection to reoperation for defunctioning stoma patients was 7 days (IQR 4-14) versus 5 days (IQR 3-13 days) for no-defunctioning stoma patients. The mortality rate after primary resection and reoperation were comparable (resp. for defunctioning vs. no-defunctioning stoma 1.0% vs. 0.7%, P=0.106 and 5.0% vs. 2.3%, P=0.107). Conclusion: This study demonstrated that early reinterventions after anastomotic leakage are associated with worse outcomes (i.e. mortality). Maybe the combination of a physiological dip in the cellular immune response and release of cytokines following surgery, as well as a release of endotoxins caused by the bacteremia originating from the leakage, leads to a more profound sepsis. Another explanation might be that early leaks are not contained to the pelvis, leading to a more profound sepsis requiring early reoperations. Leakage with or without defunctioning stoma resulted in a different type of reinterventions and time-interval between surgery and reoperation.

Keywords: rectal cancer surgery, defunctioning stoma, anastomotic leakage, time-interval to reoperation

Procedia PDF Downloads 138

Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

Abstract:

Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. 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. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

Procedia PDF Downloads 472

Authors: Amira ben Hassine, A. Valverde, V. Serafín, C. Muñoz-San Martín, M. Garranzo-Asensio, M. Gamella, R. Barderas, M. Pedrero, N. Raouafi, S. Campuzano, P. Yáñez-Sedeño, J. M. Pingarrón

Abstract:

This work describes the development of a dual electrochemical immunosensing platform for accurate determination of two target proteins, IL-13 Receptor α2 (IL-13Rα2) and E-cadherin (E-cad). The proposed methodology is based on the use of sandwich immunosensing approaches (involving horseradish peroxidase-labeled detector antibodies) implemented onto magnetic microbeads (MBs) and amperometric transduction at screen-printed dual carbon electrodes (SPdCEs). The magnetic bioconjugates were captured onto SPdCEs and the amperometric transduction was performed using the H2O2/hydroquinone (HQ) system. Under optimal experimental conditions, the developed bio platform demonstrates linear concentration ranges of 1.0–25 and 5.0-100 ng mL-1, detection limits of 0.28 and 1.04 ng mL-1 for E-cad and IL-13Rα2, respectively, and excellent selectivity against other non-target proteins. The developed immuno-platform also offers a good reproducibility among amperometric responses provided by nine different sensors constructed in the same manner (Relative Standard Deviation values of 3.1% for E-cad and 4.3% for IL-13Rα2). Moreover, obtained results confirm the practical applicability of this bio-platform for the accurate determination of the endogenous levels of both extracellular receptors in colon cancer cells (both intact and lysed) with different metastatic potential and serum and tissues from patients diagnosed with colorectal cancer at different grades. Interesting features in terms of, simplicity, speed, portability and sample amount required to provide quantitative results, make this immuno-platform more compatible than conventional methodologies with the clinical diagnosis and prognosis at the point of care.

Keywords: electrochemistry, mmunosensors, biosensors, E-cadherin, IL-13 receptor α2, cancer colorectal

Procedia PDF Downloads 137

Authors: Ammar Asma, Bouafia Nabiha, Dhahri Meriem, Ben Cheikh Asma, Ezzi Olfa, Chafai Rim, Njah Mansour

Abstract:

Despite recent advances in treatment of the lung cancer patients, the prognosis remains poor. Information is limited regarding health related quality of life (QOL) status of advanced lung cancer patients. The purposes of this study were: to assess patient reported symptom burden, to measure their QOL, and to identify determinant factors associated with QOL. Materials/Methods: A cross sectional study of 60 patients was carried out from over the period of 03 months from February 1st to 30 April 2016. Patients were recruited in two department of health care: Pneumology department in a university hospital in Sousse and an oncology unit in a University Hospital in Kairouan. Patients with advanced stage (III and IV) of lung cancer who were hospitalized or admitted in the day hospital were recruited by convenience sampling. We used a questionnaire administrated and completed by a trained interviewer. This questionnaire is composed of three parts: demographic, clinical and therapeutic information’s, QOL measurements: based on the SF-36 questionnaire, Symptom’s burden measurement using the Lung Cancer Symptom Scale (LCSS). To assess Correlation between symptoms burden and QOL, we compared the scores of two scales two by two using the Pearson correlation. To identify factors influencing QOL in Lung cancer, a univariate statistical analysis then, a stepwise backward approach, wherein the variables with p< 0.2, were carried out to determine the association between SF-36 scores and different variables. Results: During the study period, 60 patients consented to complete symptom and quality of life questionnaires at a single point time (72% were recruited from day hospital). The majority of patients were male (88%), age ranged from 21 to 79 years with a mean of 60.5 years. Among patients, 48 (80%) were diagnosed as having non-small cell lung carcinoma (NSCLC). Approximately, 60 % (n=36) of patients were in stage IV, 25 % in stage IIIa and 15 % in stage IIIb. For symptom burden, the symptom burden index was 43.07 (Standard Deviation, 21.45). Loss of appetite and fatigue were rated as the most severe symptoms with mean scores (SD): 49.6 (25.7) and 58.2 (15.5). The average overall score of SF36 was 39.3 (SD, 15.4). The physical and emotional limitations had the lowest scores. Univariate analysis showed that factors which influence negatively QOL were: married status (p<0.03), smoking cessation after diagnosis (p<0.024), LCSS total score (p<0.001), LCSS symptom burden index (p<0.001), fatigue (p<0.001), loss of appetite (p<0.001), dyspnea (p<0.001), pain (p<0.002), and metastatic stage (p<0.01). In multivariate analysis, unemployment (p<0.014), smoking cessation after diagnosis (p<0.013), consumption of analgesic (p<0.002) and the indication of an analgesic radiotherapy (p<0.001) are revealed as independent determinants of QOL. The result of the correlation analyses between total LCSS scores and the total and individual domain SF36 scores was significant (p<0.001); the higher total LCSS score is, the poorer QOL is. Conclusion: A built in support of lung cancer patients would better control the symptoms and promote the QOL of these patients.

Keywords: quality of life, lung cancer, metastasis, symptoms burden

Procedia PDF Downloads 381

Authors: Herlin Vallejo, Jhon Osorio

Abstract:

Quality is a concept that has gained importance in different scenarios over time, especially in the area of health. The nursing staff is one of the actors that contributes most to the care process and the satisfaction of the users in the evaluation of quality. However, until now, there are few tools to measure the quality of care in specialized performance scenarios. Patients receiving ambulatory cancer treatments can face various problems, which can increase their level of distress, so improving the quality of outpatient care for cancer patients should be a priority for oncology nursing. The experience of the patient in relation to the care in these services has been little investigated. The purpose of this study was to understand the perception that patients have about quality care in outpatient chemotherapy services. A qualitative, exploratory, descriptive study was carried out in 9 patients older than 18 years, diagnosed with cancer, who were treated at the Institute of Cancerology, in outpatient chemotherapy rooms, with a minimum of three months of treatment with curative intention and which had given your informed consent. The total of participants was determined by the theoretical saturation, and the selection of these was for convenience. Unstructured interviews were conducted, recorded and transcribed. The analysis of the information was done under the technique of content analysis. Three categories emerged that reflect the perception that patients have regarding quality care: patient-centered care, care with love and effects of care. Patients highlighted situations that show that care is centered on them, incorporating elements of patient-centered care from the institutional, infrastructure, qualities of care and what for them, in contrast, means inappropriate care. Care with love as a perception of quality care means for patients that the nursing staff must have certain qualities, perceive caring with love as a family affair, limits on care with love and the nurse-patient relationship. Quality care has effects on both the patient and the nursing staff. One of the most relevant effects was the confidence that the patient develops towards the nurse, besides to transform the unreal images about cancer treatment with chemotherapy. On the other hand, care with quality generates a commitment to self-care and is a facilitator in the transit of oncological disease and chemotherapeutic treatment, but from the perception of a healing transit. It is concluded that care with quality from the perception of patients, is a construction that goes beyond the structural issues and is related to an institutional culture of quality that is reflected in the attitude of the nursing staff and in the acts of Care that have positive effects on the experience of chemotherapy and disease. With the results, it contributes to better understand how quality care is built from the perception of patients and to open a range of possibilities for the future development of an individualized instrument that allows evaluating the quality of care from the perception of patients with cancer.

Keywords: nursing care, oncology service hospital, quality management, qualitative studies

Procedia PDF Downloads 137

Authors: Arezoo Fallahi, Fateme Aslibigi, Parvaneh Taymoori, Babak Nematshahrbabaki

Abstract:

Background and Aims: Cancer of the cervix, one of cancer-related death, is the second most common cancer in women worldwide. It develops over time but it is one of the most preventable types of cancer and there is the available proper screening program for its preventing. Since Pap smear test is vital to prevent and control of disease but women do not accomplish it regularly. Therefore, this study was aimed to explore women's needs referring to health care centers for doing Pap smear test. Material and methods: In this study, an inductive qualitative method with content analysis approach was used. This survey was done in varamin city (is located capital of Iran) in year 2014. Through the purposive sampling 15 women's view of point referring to health care centers of for doing Pap smear test was surveyed. Inclusion criteria were: 20-50 years old married women, having experience Pap smear test and attendance to participate in the Study. Recorded semi- structured interviews were typed and analyzed through of content analysis method. To obtain trustworthiness and rigor of the data, the criteria of credibility, dependability, confirmability and transferability was used. Results: During the data analysis, four main categories of “role of health care team”, “role of organizations”, “social support” and “policies and administration system” were developed. The participants emphasized on making motivational rules and coordination among organizations to do behaviors related to women health. Conclusion: The findings of study showed that doing Pap smear test are attributed to appropriate and intimate interactions with health professionals, family support, encouraging legislation and policies and coordination and notification of organizations. Therefore, designers and stockholders of policies and health system should more consider to growth and involve other organizations toward women's health.

Keywords: qualitative approach, pap smear test, women, health care centers

Procedia PDF Downloads 496

Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

Abstract:

Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

Procedia PDF Downloads 356

Authors: Grzegorz Raniszewski, Zbigniew Kolacinski, Lukasz Szymanski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza

Abstract:

One of the most promising area for carbon nanotubes (CNTs) application is medicine. One of the most devastating diseases is cancer. Carbon nanotubes may be used as carriers of a slowly released drug. It is possible to use of electromagnetic waves to destroy cancer cells by the carbon nanotubes (CNTs). In our research we focused on thermal ablation by ferromagnetic carbon nanotubes (Fe-CNTs). In the cancer cell hyperthermia functionalized carbon nanotubes are exposed to radio frequency electromagnetic field. Properly functionalized Fe-CNTs join the cancer cells. Heat generated in nanoparticles connected to nanotubes warm up nanotubes and then the target tissue. When the temperature in tumor tissue exceeds 316 K the necrosis of cancer cells may be observed. Several techniques can be used for Fe-CNTs synthesis. In our work, we use high-temperature methods where arc-discharge is applied. Low-temperature systems are microwave plasma with assisted chemical vapor deposition (MPCVD) and hybrid physical-chemical vapor deposition (HPCVD). In the arc discharge system, the plasma reactor works with a pressure of He up to 0,5 atm. The electric arc burns between two graphite rods. Vapors of carbon move from the anode, through a short arc column and forms CNTs which can be collected either from the reactor walls or cathode deposit. This method is suitable for the production of multi-wall and single-wall CNTs. A disadvantage of high-temperature methods is a low purification, short length, random size and multi-directional distribution. In MPCVD system plasma is generated in waveguide connected to the microwave generator. Then containing carbon and ferromagnetic elements plasma flux go to the quartz tube. The additional resistance heating can be applied to increase the reaction effectiveness and efficiency. CNTs nucleation occurs on the quartz tube walls. It is also possible to use substrates to improve carbon nanotubes growth. HPCVD system involves both chemical decomposition of carbon containing gases and vaporization of a solid or liquid source of catalyst. In this system, a tube furnace is applied. A mixture of working and carbon-containing gases go through the quartz tube placed inside the furnace. As a catalyst ferrocene vapors can be used. Fe-CNTs may be collected then either from the quartz tube walls or on the substrates. Low-temperature methods are characterized by higher purity product. Moreover, carbon nanotubes from tested CVD systems were partially filled with the iron. Regardless of the method of Fe-CNTs synthesis the final product always needs to be purified for applications in medicine. The simplest method of purification is an oxidation of the amorphous carbon. Carbon nanotubes dedicated for cancer cell thermal ablation need to be additionally treated by acids for defects amplification on the CNTs surface what facilitates biofunctionalization. Application of ferromagnetic nanotubes for cancer treatment is a promising method of fighting with cancer for the next decade. Acknowledgment: The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013

Keywords: arc discharge, cancer, carbon nanotubes, CVD, thermal ablation

Procedia PDF Downloads 449

Authors: Ghada Esheba, Ghadeer Aldoobi, Salwa Almalk, Abrar Alshareef, Eman Al-khairi, Eman Yaseen

Abstract:

Background: In Saudi Arabia, ovarian cancer ranked seventh among female population and is the most common female genital tract malignancy after endometrial cancer. A slight increase in the incidence of ovarian cancer was observed from 2001–2008. Makkah, Riyadh, and the eastern region of Saudi Arabia had the highest incidence rate ratio for the number of ovarian cancer cases (1). Differentiating metastatic adenocarcinomas from primary ovarian carcinomas, especially those of endometrioid and mucinous type is clinically significant and a challenge for clinicians and pathologists, yet the distinction has important therapeutic and prognostic implications. Aim: To clarify the most important histopathological criteria to differentiate between primary ovarian surface epithelial tumors especially mucinous and endometrioid subtypes, and metastatic adenocarcinoma and to evaluate the value of a panel of antibodies consisting of CK7, CK20, and CDX-2 in the distinction between primary ovarian surface epithelial tumors and metastatic adenocarcinoma. Material and methods: This study was carried out on 26 cases of primary ovarian surface epithelial neoplasms and 14 cases of metastatic ovarian adenocarcinoma. All cases were studied immunohistochemically using CK7, CK20, and CDX-2. Results: All cases of primary ovarian adenocarcinoma were positive for CK7. 25% and 58% of mucinous borderline mucinous tumor and mucinous carcinoma respectively were positive for CK20. Only 42% of mucinous carcinoma were positive for CDX-2. All cases of endometrioid carcinomas were negative for both CK20 and CDX-2. All cases of metastatic adenocarcinoma from the colon were negative for CK7 and positive for CK20 and CDX-2. Conclusions: CK7 is an important positive marker for primary ovarian tumors, while CK20 and CDX-2 are useful markers for colorectal carcinoma metastatic to the ovary. Caution should be taken as primary ovarian mucinous tumors may stain positive for CK20, CDX-2, or both, however, they usually exhibit a focal pattern of reactivity.

Keywords: adenoma, endometrioid, malignancy, ovarian

Procedia PDF Downloads 232

Authors: Kasi Viswanadh Matte, Abhisheh Kumar Mehata, M.S. Muthu

Abstract:

Brest cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol succinate 1000 conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted and targeted nanoparticles were found to be in the range of 126-186 nm and 74-78% respectively. In-vitro, MDA-MB-231 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional nanoparticles. The IC50 values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than DocelTM. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than DocelTM, and after i.v administration, non-targeted and targeted nanoparticle achieved 3.48 and 5.94 times prolonged half-life in comparison to DocelTM. The area under the curve (AUC), relative bioavailability (FR) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles compared to DocelTM. Further, histopathology results of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney compared to DocelTM.

Keywords: breast cancer, HER-2 receptor, targeted nanomedicine, chitosan, TPGS

Procedia PDF Downloads 240

Authors: Philippa Sambevski

Abstract:

Breast cancer is the most common cancer diagnosed in Australian women. The incidence of breast cancer for Aboriginal and Torres Strait Islander (ATSI) women is lower than for non-indigenous women. However, the mortality rate for ATSI women is higher. The participation rate of ATSI women in BreastScreen Australia is below the general population. In this thematic literature review, the author collates viable strategies to increase breast screening rates among culturally and linguistically diverse individuals and provide culturally competent care. Barriers to accessing BreastScreen for ATSI women include language or communication limits, isolation, and a lack of culturally sensitive information. Culturally competent strategies require healthcare workers with an appropriate cultural and social background, clear messages, and the embedding of cultural respect within healthcare organisations. Cultural safety is determined by partnering with local indigenous groups, recognising the consumer experience, and allowing people to raise their concerns. The corresponding academic poster identifies strategies for healthcare workers to provide culturally competent care in a BreastScreen setting.

Keywords: breast screen, closing the gap, Australia, cultural safety, Aboriginal and Torres Strait Islander

Procedia PDF Downloads 113

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

Abstract:

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

Keywords: anticancer, Artocarpus kemando, ovarian cancer, cytotoxicity

Procedia PDF Downloads 551

Authors: Ibtissem El Ouar, Cornelia Braicu, Dalila Naimi, Alexendru Irimie, Ioana Berindan-Neagoe

Abstract:

Helix aspersa, 'the garden snail' is a big land snail widely found in the Mediterranean countries, it is one of the most consumed species in the west of Algeria. It is commonly used in zootherapy to purify blood and to treat cardiovascular diseases and liver problems. The aim of our study is to investigate, the antitumor activity of an aqueous extract from Helix aspersa prepared by the traditional method on Hs578T; a triple negative breast cancer cell line. Firstly, the free radical scavenging activity of H. aspersa extract was assessed by measuring its capability for scavenging the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), as well as its ability to reduce ferric ion by the FRAP assay (ferric reducing ability). The cytotoxic effect of H. aspersa extract against Hs578T cells was evaluated by the MTT test (3-(4,5- dimethylthiazl-2-yl)-2,5- diphenyltetrazolium bromide)) while the mode of cell death induced by the extract has been determined by fluorescence microscopy using acredine orange/ethidium bromide (AO/EB) probe. The level of TNFα has also measured in cell medium by ELISA method. The results suggest that H. aspersa extract has an antioxidant activity, especially at high concentrations, it can reduce DPPH radical and ferric ion. The MTT test shows that H. aspersa extract has a great cytotoxic effect against breast cancer cells, the IC50 value correspond of the dilution 1% of the crude extract. Moreover, the AO/EB staining shows that TNFα induced necrosis is the main form of cell death induced by the extract. In conclusion, the present study may open new perspectives in the search for new natural anticancer drugs.

Keywords: breast cancer, Helix aspersa, Hs578t cell line, necrosis

Procedia PDF Downloads 422

Authors: V. Veeraprathap, G. S. Harish, G. Narendra Kumar

Abstract:

Uncontrolled growth of abnormal cells in the lung in the form of tumor can be either benign (non-cancerous) or malignant (cancerous). Patients with Lung Cancer (LC) have an average of five years life span expectancy provided diagnosis, detection and prediction, which reduces many treatment options to risk of invasive surgery increasing survival rate. Computed Tomography (CT), Positron Emission Tomography (PET), and Magnetic Resonance Imaging (MRI) for earlier detection of cancer are common. Gaussian filter along with median filter used for smoothing and noise removal, Histogram Equalization (HE) for image enhancement gives the best results without inviting further opinions. Lung cavities are extracted and the background portion other than two lung cavities is completely removed with right and left lungs segmented separately. Region properties measurements area, perimeter, diameter, centroid and eccentricity measured for the tumor segmented image, while texture is characterized by Gray-Level Co-occurrence Matrix (GLCM) functions, feature extraction provides Region of Interest (ROI) given as input to classifier. Two levels of classifications, K-Nearest Neighbor (KNN) is used for determining patient condition as normal or abnormal, while Artificial Neural Networks (ANN) is used for identifying the cancer stage is employed. Discrete Wavelet Transform (DWT) algorithm is used for the main feature extraction leading to best efficiency. The developed technology finds encouraging results for real time information and on line detection for future research.

Keywords: artificial neural networks, ANN, discrete wavelet transform, DWT, gray-level co-occurrence matrix, GLCM, k-nearest neighbor, KNN, region of interest, ROI

Procedia PDF Downloads 153

Authors: M. Marjaneh, M. Y. Narazah, H. Shahrul

Abstract:

Array-based gene expression analysis is a powerful tool to profile expression of genes and to generate information on therapeutic effects of new anti-cancer compounds. Anti-apoptotic effect of thymoquinone was studied in MCF7 breast cancer cell line using gene expression profiling with cDNA micro array. The purity and yield of RNA samples were determined using RNeasyPlus Mini kit. The Agilent RNA 6000 Nano LabChip kit evaluated the quantity of the RNA samples. AffinityScript RT oligo-dT promoter primer was used to generate cDNA strands. T7 RNA polymerase was used to convert cDNA to cRNA. The cRNA samples and human universal reference RNA were labelled with Cy-3-CTP and Cy-5-CTP, respectively. Feature Extraction and GeneSpring software analysed the data. The single experiment analysis revealed involvement of 64 pathways with up-regulated genes and 78 pathways with down-regulated genes. The MAPK and p38-MAPK pathways were inhibited due to the up-regulation of PTPRR gene. The inhibition of p38-MAPK suggested up-regulation of TGF-ß pathway. Inhibition of p38 - MAPK caused up-regulation of TP53 and down-regulation of Bcl2 genes indicating involvement of intrinsic apoptotic pathway. Down-regulation of CARD16 gene as an adaptor molecule regulated CASP1 and suggested necrosis-like programmed cell death and involvement of caspase in apoptosis. Furthermore, down-regulation of GPCR, EGF-EGFR signalling pathways suggested reduction of ER. Involvement of AhR pathway which control cytochrome P450 and glucuronidation pathways showed metabolism of Thymoquinone. The findings showed differential expression of several genes in apoptosis pathways with thymoquinone treatment in estrogen receptor-positive breast cancer cells.

Keywords: cDNA microarray, thymoquinone, CARD16, PTPRR, CASP10

Procedia PDF Downloads 347

Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur

Abstract:

Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.

Keywords: withania somnifera, withaferin A, withanolides D, PKCα

Procedia PDF Downloads 146

Authors: L. Mallesha, P. Mallu, B. Veeresh

Abstract:

In the present study, 2, 6-diflurobenzohydrazide and 4-fluorophenylisothiocyanate were used as the starting materials to synthesize 5-phenyl-N3-(4-fluorophenyl)-4H-1, 2, 4-triazole-3, 4-diamine. Further, compound 5-phenyl-N3-(4-fluorophenyl)-4H-1, 2, 4-triazole-3,4-diamine reacted with fluoro substituted benzaldehydes to yield a series of Schiff bases. All the final compounds were characterized using IR, 1H NMR, 13C NMR, MS and elemental analyses. New compounds were evaluated for their antiproliferative effect using the MTT assay method against four human cancer cell lines (K562, COLO-205, MDA-MB231, and IMR-32) for the time period of 24 h. Among the series, few compounds showed good activity on all cell lines, whereas the other compounds in the series exhibited moderate activity.

Keywords: Schiff bases, MTT assay, antiproliferative activity, human cancer cell lines, 1, 2, 4-triazoles

Procedia PDF Downloads 372

Authors: Hacer Kobya Bulut, Ilknur Kahriman, Birsel C. Demirbag

Abstract:

Introduction and Purpose: The lives of children with cancer are affected by long term hospitalizations in a negative way due to complications arising from diagnosis or treatment. However, the children's parents are known to have difficulties in meeting their children’s needs and providing home care after cancer treatment or during remission process. Supporting these children and their parents by giving a planned discharge training starting from the hospital and home care leads to reducing hospital applications, hospitalizations, hospital costs, shortening the length of hospital stay and increasing the satisfaction of the children with cancer and their families. This study was conducted to investigate the status of children and their parents' unplanned application to hospital and re-hospitalization. Methods: The study was carried out with 65 children with hematological malignancy in 0-17 age group and their families in a hematology clinic and polyclinic of a university hospital in Trabzon. Data were collected with survey methodology between August-November, 2015 through face to face interview using numbers, percentage and chi-square test in the evaluation. Findings: Most of the children were leukemia (90.8%) and 49.2% had been ill over 13 months. Few of the parents (32.3%) stated that they had received discharge and home care training (24.6%) but most of them (69.2%) found themselves enough in providing home care. Very few parents (6.2%) received home care training after their children being discharged and the majority of parents (61.5%) faced difficulties in home care and had no one to call around them. The parents expressed that in providing care to their children with hematological malignance, they faced difficulty in feeding them (74.6%), explaining their disease (50.0%), giving their oral medication (47.5%), providing hygiene (43.5%) and providing oral care (39.3%). The question ‘What are the emergency situations in which you have to bring your children to a doctor immediately?' was replied as fever (89.2%), severe nausea and vomiting (87.7%), hemorrhage (86.2%) and pain (81.5%). The study showed that 50.8% of the children had unplanned applications to hospitals and 33.8% of them identified as unplanned hospitalization and the first causes of this were fever and pain. The study showed that the frequency of applications (%78.8) and hospitalizations (%81.8) was higher for boys and a statistically significant difference was found between gender and unplanned applications (X=4.779; p=0.02). Applications (48.5%) and hospitalizations (40.9%) were found lower for the parents who had received hospital discharge training, and a significant difference was determined between receiving training and unplanned hospitalizations (X=8.021; p=0.00). Similarly, applications (30.3%) and hospitalizations (40.9%) was found lower for the ones who had received home care training, and a significant difference was determined between receiving home care training and unplanned hospitalizations (X=4.758; p=0.02). Conclusion: It was found out that caregivers of children with cancer did not receive training related to home care and complications about treatment after discharging from hospital, so they faced difficulties in providing home care and this led to an increase in unplanned hospital applications and hospitalizations.

Keywords: cancer, children, unplanned application, unplanned hospitalization

Procedia PDF Downloads 268

Authors: Fernanda Rodriguez

Abstract:

Breast cancer is pervasive among women, and an increasing number of women are opting for a mastectomy: a medical operation in which one or both breasts are removed with the intention of treating or averting breast cancer. However, there is an emerging population of cancer survivors in European nations that, rather than attempting to reconstruct their breasts to resemble as much as possible ‘normal’ breasts, have turned to dress their scars with decorative tattoos. At a practical level, this study hopes to improve the support systems of these women by possibly providing professionals in the medical field, tattoo artists, and family members of cancer survivors with a deeper understanding of their motivations and decision-making processes for choosing an alternative restorative route - such as decorative tattoos - after their mastectomy. At an intellectual level, however, this study aims to narrow a gap in the academic field concerning the relationship between mastectomies and alternative methods of healing, such as decorative tattoos, as well as to broaden the understanding regarding meaning-making and the ‘normal’ feminine body. Thus, by means of semi-structured interviews and a phenomenological standpoint, this research set itself the goal to understand why do women who have undergone a mastectomy choose to dress their scars with decorative tattoos instead of attempting to regain ‘normalcy’ through breast reconstruction or 3D areola tattoos? The results obtained from the interviews with fifteen women showed that the disillusionment with one part of the other of breast restoration techniques had led these women to find an alternative form of healing that allows them not only to close a painful chapter of their life but also to regain control over their bodies after a period of time in which agency was taking away from them. Decorative post-mastectomy tattoos allow these women to grant their bodies with new meanings and produce their own interpretation of their feminine body and identity.

Keywords: alternative femininity, decorative mastectomy tattoos, gender embodiment, social stigmatization

Procedia PDF Downloads 120

Authors: Poonam Goswami

Abstract:

Background: The diagnosis of a serious illness like cancer can have an impact on a patient’s emotional well-being and may result in psychological symptoms, anxiety, depression, and loss of control. Advance care planning discussions ensure patients’ values and goals of care, including patients’ freedom to choose their place of death, are respected. Unfortunately, these discussions are often delayed and are not initiated early in patients’ cancer trajectory. As a result, patients’ wishes often remains unknown until the last phase of their life. Evidence suggests that many patients inappropriately receive aggressive treatment near the end of life, which does lead to higher resource utilization, decreased quality of life, and increased cost. Additionally, the novel coronavirus disease 2019 (COVID-19) pandemic challenged the health care systems worldwide and raised important ethical issues, especially regarding the potential need for rationing health care in the context of scarce resources and crisis capacity. The importance of goal concordant care is now even substantially important and is heightened in the context of this pandemic. Problem: Although there is growing evidence on the effects of the ACP on the completion of advanced directives, improved patient and family concordance for preferences for medical care, and receipt of care, there is still a lack of standardized ACP conversation strategies for patients with cancer. Methods: The Key concepts of ACP include (1) assessing patient and family readiness, (2) identifying a surrogate decision maker ( medical power of attorney), (3) exploring patient and family understanding of the disease and treatment options,(4) discussing the values and goals of care, and options for end-of-life care, (5) documenting patient preferences in the medical record, and (6) revisiting the discussions at every change in the treatment plan and /or change in clinical status, including at every hospitalization. Conclusion/Implication for practice: Advance Care Planning (ACP) and end-of-life (EOL) discussions are important for patients, families, and health care providers. Adopting the verbal and nonverbal communication strategies can help overcome the barriers to effective communication on these difficult discussions. ACP with goals of care discussions should not be delayed until the patient is hospitalized.

Keywords: advance care planning, end of life, cancer, global, pandemic

Procedia PDF Downloads 129

Authors: Yu-Wen Lin, Li-Ni Liu

Abstract:

Introduction: Fatigue is the most common symptoms experienced by cancer patients undergoing chemotherapy. Patients receiving anticancer therapies develop a higher proportion of fatigue compared with patients who do not receive anticancer therapies. Fatigue has significant impacts on quality of life, daily activities, mood status, and social behaviors. A warm-water footbath (WWF) at 41℃ promotes circulation and removes metabolites resulting in improving sleep and relieving fatigue. The aim of this study is to determine the effectiveness of WWF for relieving fatigue with cancer patients undergoing chemotherapy. Materials and Methods: This is a single-center, prospective, quasi-experimental design study in the oncology ward in Taiwan. Participants in this study were assigned to WWF group as experimental group and standard care group as a control group by purposive sampling. In the WWF group, the participants were asked to soak their feet in 42-43℃ water 15 minutes for consecutive 6 days at one day before chemotherapy. Each participant was evaluated for fatigue level by the Taiwanese version of the Brief Fatigue Inventory (BFI-T). BFI-T was completed for consecutive 8 days of the study. The primary outcome was compared the BFI-T score of WWF group to the standard care group. Results: There were 60 participants enrolled in this study. Thirty participants were assigned to WWF group and 30 participants were assigned to standard care group. Both groups have comparable characteristic. The BFI-T scores of both groups were increased associated with the days of chemotherapy. The highest BFI-T scores of both groups were on the day 4 of chemotherapy. The BFI-T scores of both groups were decreased since day 5 and significantly decreased in WWF group on day 5 compared to standard care group (4.17 vs. 5.7, P ＜ .05). At the end of the study the fatigue at its worse were significantly decreased in WWF group (2.33 vs. 4.37, P ＜ .001). There was no adverse event reported in this study. Conclusion: WWF is an easy, safe, non-invasive, and relatively inexpensive nursing intervention for improving fatigue of cancer patients undergoing chemotherapy. In summary, this study shows the WWF is a simple complementary care method, and it is effective for improving and relieving fatigue in a short time. Through improving fatigue is a way to enhance the quality of life which is important for cancer patients undergoing chemotherapy. Larger prospective randomized controlled trial and long-term effectiveness and outcomes of WWF should be performed to confirm this study.

Keywords: chemotherapy, warm-water footbath, fatigue, Taiwanese version of the brief fatigue inventory

Procedia PDF Downloads 142

Authors: Badawia Ibrahim, Iman Hussein, Samar El Sheikh, Fatma Abou Elkasem, Hazem Abo Ismael

Abstract:

Background: Response of breast carcinoma to neoadjuvant chemotherapy (NAC) varies regarding many factors including hormonal receptor status. Breast cancer is a heterogenous disease with different outcomes, hence a need arises for new markers predicting the outcome of NAC especially for the triple negative group when estrogen, progesterone receptors and Her2/neu are negative. FOXP3 is a promising target with unclear role. Aim: To examine the value of FOXP3 expression in locally advanced triple negative breast cancer tumoral cells as well as tumor infiltrating lymphocytes (TILs) and to elucidate its relation to the extent of NAC response. Material and Methods: Forty five cases of immunohistochemically confirmed to be triple negative breast carcinoma were evaluated for NAC (Doxorubicin, Cyclophosphamide AC x 4 cycles + Paclitaxel x 12 weeks, patients with ejection fraction less than 60% received Taxotere or Cyclophosphamide, Methotrexate, Fluorouracil CMF) response in both tumour and lymph nodes status according to Miller & Payne's and Sataloff's systems. FOXP3 expression in tumor as well as TILs evaluated in the pretherapy biopsies was correlated with NAC response in breast tumor and lymph nodes as well as other clinicopathological factors. Results: Breast tumour cells showed FOXP3 positive cytoplasmic expression in (42%) of cases. High FOXP3 expression percentage was detected in (47%) of cases. High infiltration by FOXP3+TILs was detected in (49%) of cases. Positive FOXP3 expression was associated with negative lymph node metastasis. High FOXP3 expression percentage and high infiltration by FOXP3+TILs were significantly associated with complete therapy response in axillary lymph nodes. High FOXP3 expression in tumour cells was associated with high infiltration by FOXP3+TILs. Conclusion: This result may provide evidence that FOXP3 marker is a good prognostic and predictive marker for triple negative breast cancer (TNBC) indicated for neoadjuvant chemotherapy and can be used for stratifications of TNBC cases indicated for NAC. As well, this study confirmed the fact that the tumour cells and the surrounding microenvironment interact with each other and the tumour microenvironment can influence the treatment outcomes of TNBC.

Keywords: breast cancer, FOXP3 expression, prediction of neoadjuvant chemotherapy effect, triple negative

Procedia PDF Downloads 274

Authors: Paul J Yazaki, Michael Bouvet, John Shively

Abstract:

Surgery for solid gastrointestinal (GI) cancers such as pancreatic, colorectal, and gastric adenocarcinoma remains the mainstay of curative therapy. Complete resection of the primary tumor with negative margins (R0 resection), its draining lymph nodes, and distant metastases offers the optimal surgical benefit. Real-time fluorescence guided surgery (FGS) promises to improve GI cancer outcomes and is rapidly advancing with tumor-specific antibody conjugated fluorophores that can be imaged using near infrared (NIR) technology. Carcinoembryonic Antigen (CEA) is a non-internalizing tumor antigen validated as a surface tumor marker expressed in >95% of colorectal, 80% of gastric, and 60% of pancreatic adenocarcinomas. Our humanized anti-CEA hT84.66-M5A (M5A) monoclonal antibody (mAb)was conjugated with the NHS-IRDye800CW fluorophore and shown it can rapidly and effectively NIRoptical imageorthotopically implanted human colon and pancreatic cancer in mouse models. A limitation observed is that these NIR-800 dye conjugated mAbs have a rapid clearance from the blood, leading to a narrow timeframe for FGS and requiring high doses for effective optical imaging. We developed a novel antibody-fluorophore conjugate by incorporating a PEGylated sidearm linker to shield or mask the IR800 dye’s hydrophobicity which effectively extended the agent’s blood circulation half-life leading to increased tumor sensitivity and lowered normal hepatic uptake. We hypothesized that our unique anti-CEA linked to the fluorophore, IR800 by PEGylated sidewinder, M5A-SW-IR800 will become the next generation optical imaging agent, safe, effective, and widely applicable for intraoperative image guided surgery in CEA expressing GI cancers.

Keywords: optical imaging, anti-CEA, cancer, fluorescence-guided surgery

Procedia PDF Downloads 147

Authors: Seemab Safdar, Shazia Fatima, Ahmad Qureshy, M. Adnan Saeed, M. Faheem

Abstract:

Background: Thyroid cancer has 586,000 cases per year worldwide, and this translates to 3% of all tumor diagnoses. 90% of the cases fall under differentiated thyroid carcinoma (DTC), which includes follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC). During their illness, 10% of patients develop distant metastases, and two-thirds of them develop resistance to radioactive iodine (RAI) treatment. It has been shown that in some circumstances, like DTC with high TG levels and negative 131I whole-body scintigraphy (TENIS), [18F] FDG-PET-CT is an effective imaging technique. This study determines the role of [18F] FDG-PET-CT in the treatment of TENIS patients. Methods: 16 patients (n = 12 female; 4 males, age 45 ± 15 years) with histologically proven thyroid cancer (Differentiated and poorly differentiated) and high TG with negative iodine scans were included in this prospective study from January 2024 to June 2024. They underwent scanning in state-of-the-art (GE Discovery MI) [18F] FDG-PET-CT for re-staging or diagnostics of recurrent disease using a standardized protocol. All DTC subtypes and PDTC were included. The referring physicians completed standardized questionnaires both before and after PET-CT to prospectively determine the examination's effect on clinical decision-making. Patient outcomes were measured by analysis of medical records. Moreover, after PET-CT, a change in the pre-PET-CT planned therapies was documented in 32% of cases and additional invasive diagnostic procedures could be waived in 37.5 % of cases. TG levels under TSH stimulation were significantly higher in patients showing PET-CT metastases compared to patients without such findings (68.75%). Results: Without PET-CT, physicians referring to the doctors had not established a complete treatment plan for 45% of patients with thyroid carcinoma. 12/16 patients showed FDG avidity in cervical lymph nodes that were not Iodine avid previously, 2 patients had FDG avid disease in the lungs. In the process, PET-CT helped plan patient management and created a clear plan for treatment in 68.75% of patients. Conclusions: This study confirms that [18F] FDG-PET-CT used in a routine clinical setting has a very important impact on the management of patients with thyroid cancer when TG levels are persistently high in the presence of negative Iodine Scans by initiating treatments and replacing additional imaging and invasive tests.

Keywords: PET-CT, TENIS, role, FDG

Procedia PDF Downloads 14

Authors: Jawad Alzeer

Abstract:

Natural products are well recognized as sources of drugs in several human ailments. To investigate the impact of variable extraction techniques on the cytotoxic effects of medicinal plant extracts, 5 well-known medicinal plants from Palestine were extracted with 90% ethanol, 80% methanol, acetone, coconut water, apple vinegar, grape vinegar or 5% acetic acid. The resulting extracts were screened for cytotoxic activities against three different cancer cell lines (B16F10, MCF-7, and HeLa) using a standard resazurin-based cytotoxicity assay and Nile Blue A as the positive control. Highly variable toxicities and tissue sensitivity were observed, depending upon the solvent used for extraction. Acetone consistently gave lower extraction yields but higher cytotoxicity, whereas other solvent systems gave much higher extraction yields with lower cytotoxicity. Interestingly, coconut water was found to offer a potential alternative to classical organic solvents; it gave consistently highest extraction yields, and in the case of S. officinalis L., highly toxic extracts towards MCF-7 cells derived from human breast cancer. These results demonstrate how the cytotoxicity of plant extracts can be inversely proportional to the yield, and that solvent selection plays an important role in both factors.

Keywords: plant extract, natural products, anti cancer drug, cytotoxicity

Procedia PDF Downloads 454

Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

Abstract:

A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

Procedia PDF Downloads 95

Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

Procedia PDF Downloads 98