Search results for: breast cancer

Authors: David C. Boettiger, Tracy Kuo Lin, Maram Almansour, Mariam M. Hamza, Reem Alsukait, Christopher H. Herbst, Nada Altheyab, Ayman Afghani, Faisal Kattan

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Background The number of people aged greater than 65 years per 100 people aged 20–64 years is expected to almost double in The Kingdom of Saudi Arabia (KSA) between 2020 and 2030. We therefore aimed to quantify the growing non-communicable disease (NCD) burden in KSA between 2020 and 2030, and the impact this will have on the national health budget. Methods Ten priority NCDs were selected: ischemic heart disease, stroke, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease, dementia, depression, osteoarthritis, colorectal cancer, and breast cancer. Age- and sex-specific prevalence was projected for each priority NCD between 2020 and 2030. Treatment coverage rates were applied to the projected prevalence estimates to calculate the number of patients incurring treatment costs for each condition. For each priority NCD, the average cost-of-illness was estimated based on published literature. The impact of changes to our base-case model in terms of assumed disease prevalence, treatment coverage, and costs of care, coming into effect from 2023 onwards, were explored. Results The prevalence estimates for colorectal cancer and stroke were estimated to almost double between 2020 and 2030 (97% and 88% increase, respectively). The only priority NCD prevalence projected to increase by less than 60% between 2020 and 2030 was for depression (22% increase). It is estimated that the total cost of managing priority NCDs in KSA will increase from USD 19.8 billion in 2020 to USD 32.4 billion in 2030 (an increase of USD 12.6 billion or 63%). The largest USD value increases were projected for osteoarthritis (USD 4.3 billion), diabetes (USD 2.4 billion), and dementia (USD 1.9 billion). In scenario analyses, our 2030 projection for the total cost of managing priority NCDs varied between USD 29.2 billion - USD 35.7 billion. Conclusions Managing the growing NCD burden in KSA’s aging population will require substantial healthcare spending increases over the coming years.

Keywords: aging, non communicable disease, costs, Saudi Arabia

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Authors: Mohammad Mohammadi, Mohammad Pashmchi

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Background: Malnutrition commonly develops and worsens following gastric cancer surgery, particularly after discharge, which is associated with adverse outcomes. Former studies have primarily focused on patients during their hospital stay period, and there is limited evidence regarding the recommendation of nutritional interventions for patients after discharge from the hospital following gastric cancer surgery. This review is aimed to evaluate the efficiency of post-discharge dietary counseling with oral nutritional supplements (ONS), and dietary counseling alone on post-surgical nutritional outcomes in patients undergoing gastric cancer surgery. Methods: The four databases of Embase, PubMed, web of science, and google scholar were searched up to November 2022 for relevant randomized controlled trials. The Cochrane Collaboration’s assessment tool for randomized trials was used to evaluate the quality of studies. Results: Compared to patients who only received dietary counseling, patients who received both dietary counseling and ONS had considerably higher SMI, BMI, and less weight loss and sarcopenia occurrence rate. The patients who had received dietary counseling and ONS had significantly lower risk of chemotherapy intolerance. No differences in the readmission rate between the two groups was found. In terms of the quality of life, concomitant dietary advice and ONS significantly was associated with lower appetite loss and fatigue rate, but there was no difference in the other outcomes between the two groups. Conclusions: Post-discharge dietary advice with ONS following gastric cancer surgery may improve skeletal muscle maintenance, nutritional outcomes, quality of life variables, and chemotherapy tolerance. This evidence supports the recommendation of post-discharge dietary advice with ONS for patients who underwent gastric cancer surgery.

Keywords: gastric cancer surgery, oral nutritional supplements, malnutrition, gastric cancer

Procedia PDF Downloads 51

Authors: Siva Chander Chabattula, Piyush Kumar Gupta, Debashis Chakraborty, Rama Shanker Verma

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Green nanoparticles have gotten a lot of attention because of their potential applications in tissue regeneration, bioimaging, wound healing, and cancer therapy. The physical and chemical methods to synthesize metal oxide nanoparticles have an environmental impact, necessitating the development of an environmentally friendly green strategy for nanoparticle synthesis. In this study, we used Annona muricata plant leaf extract to synthesize Zinc Oxide nanoparticles (Am-ZnO NPs), which were evaluated using UV/Visible spectroscopy, FTIR spectroscopy, X-Ray Diffraction, DLS, and Zeta potential. Nanoparticles had an optical absorbance of 355 nm and a net negative surface charge of ~ - 2.59 mV. Transmission Electron Microscope characterizes the Shape and size of the nanoparticles. The obtained Am-ZnO NPs are biocompatible and hemocompatible in nature. These nanoparticles caused an anti-cancer therapeutic effect in MIA PaCa2 and MOLT4 cancer cells by inducing oxidative stress, and a change in mitochondrial membrane potential leads to programmed cell death. Further, we observed a reduction in the size of lung cancer spheroids (act as tumor micro-environment) with doxorubicin as a positive control.

Keywords: Biomaterials, nanoparticle, anticancer activity, ZnO nanoparticles

Procedia PDF Downloads 172

Authors: Maximiliano Guerra, Lexi Frankel, Amalia D. Ardeljan, Sarah Ghali, Diya Kohli, Omar M. Rashid.

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Introduction/Background: Haemophilus influenzae is present as a commensal organism in the nasopharynx of most healthy adults from where it can spread to cause both systemic and respiratory tract infection. Pathogenic properties of this bacterium as well as defects in host defense may result in the spread of these bacteria throughout the body. This can result in a proinflammatory state and colonization particularly in the lungs. Recent studies have failed to determine a link between H. Influenzae colonization and prostate cancer, despite previous research demonstrating the presence of proinflammatory states in preneoplastic and neoplastic prostate lesions. Given these contradictory findings, the primary goal of this study was to evaluate the correlation between H. Influenzae infection and the incidence of prostate cancer. Methods: To evaluate the incidence of Haemophilus influenzae infection and the development of prostate cancer in the future we used data provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. We were afforded access to this database by Holy Cross Health, Fort Lauderdale for the express purpose of academic research. Standard statistical methods were employed in this study including Pearson’s chi-square tests. Results: Between January 2010 and December 2019, the query was analyzed and resulted in 13, 691 patients in both the control and C. difficile infected groups, respectively. The two groups were matched by age range and CCI score. In the Haemophilus influenzae infected group, the incidence of prostate cancer was 1.46%, while the incidence of the prostate cancer control group was 4.56%. The observed difference in cancer incidence was determined to be a statistically significant p-value (< 2.2x10^-16). This suggests that patients with a history of C. difficile have less risk of developing prostate cancer (OR 0.425, 95% CI: 0.382 - 0.472). Treatment bias was considered, the data was analyzed and resulted in two groups matched groups of 3,208 patients in both the infected with H. Influenzae treated group and the control who used the same medications for a different cause. Patients infected with H. Influenzae and treated had an incidence of prostate cancer of 2.49% whereas the control group incidence of prostate cancer was 4.92% with a p-value (< 2.2x10^-16) OR 0.455 CI 95% (0.526 -0.754), proving that the initial results were not due to the use of medications. Conclusion: The findings of our study reveal a statistically significant correlation between H. Influenzae infection and a decreased incidence of prostate cancer. Our findings suggest that prior infection with H. Influenzae may confer some degree of protection to patients and reduce their risk for developing prostate cancer. Future research is recommended to further characterize the potential role of Haemophilus influenzae in the pathogenesis of prostate cancer.

Keywords: Haemophilus Influenzae, incidence, prostate cancer, risk.

Procedia PDF Downloads 171

Authors: Peri Harish Kumar, Sai Sharan Dwarka, Tajbinder Singh Bains, Suneet John Joseph, Chaitanya Kiran, Sambhu Dutta, Sarah Makram, Mohamed Sayed Zaazouee, Alaa Ahmed Elshanbary

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Objective: To identify cancer and non-cancer causes of death in hepatocellular carcinoma (HCC) patients over different time periods after diagnosis and to compare the mortality risk of each cause in HCC patients with the general population. Methods: In this retrospective cohort study, data of 67,637 HCC patients from 1975 to 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. We investigated the association between different causes of death and the following variables: age, race, tumor stage at diagnosis, and treatment (surgery, chemotherapy, and radiotherapy); each according to the periods of <1 year, 1-5 years, 5-10 years, and >10 years following the diagnosis. Standardized mortality ratios (SMRs) and their 95% confidence intervals (CIs) were calculated for cancer and non-cancer deaths in each of the mentioned periods following diagnosis. Results: Data of 67,637 patients, of whom 50,571 patients died during the follow-up period, were analyzed. Most deaths were due to HCC itself (35,535, 70.3%), followed by other cancers (3,983, 7.9%). Common causes of non-cancer mortality included infectious and parasitic diseases including HIV (2,823 patients, SMR=105.68, 95% CI: 101.82-109.65), chronic liver disease (2,719 patients, SMR=76.56, 95% CI: 73.71,79.5), and heart diseases (1,265 patients, SMR=2.26, 95% CI: 2.14-2.39), with higher mortality risk in HCC patients than in the general population. Conclusion: Cancers stand for most deaths in patients with HCC. Besides, infectious, and parasitic diseases including HIV represent the commonest non-cancer cause of mortality.

Keywords: hepatocellular carcinoma, seer, causes of death, mortality

Procedia PDF Downloads 53

Authors: Pei-Fan Mu

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Background: Lung cancer is the most common cancer with the highest mortality rate. Patients with lung cancer under chemotherapy treatment experience life-threatening uncertainty. This study was based on the broaden-and-build theory using intentionality reflection of the body and internalization of positive prioritization strategies to enhance positive emotions of patients with lung cancer. Purpose: The purpose of this study was to use a quasi-experimental research design to examine the effectiveness of the enhancing positive emotion program. Method: Data were collected from a medical center in Taiwan. Fifty-four participants with lung cancer were recruited. Thirty participants were in the experiential group receiving the two weeks program. The content of the program includes awareness and understanding of the symptom experience, co-existing with illness and establishing self-identity, cognitive-emotion adjustment and establishing a new body schema, and symptom management to reach spiritual well-being. Twenty-four participants were in the control group receiving regular nursing care. Baseline, one month later and two months later, programmed measurements of symptoms of distress, positive emotion, and psychological well-being. Results: These two weeks of enhancing the positive emotion program resulted in a significantly improved positive emotion score for the experimental group compared to the control group. The findings of this study indicated that the positive emotion had significant differences between the two groups. There were no differences in symptom distress between the two groups. Discussion: The findings indicated that the enhancing positive emotion program could help patients enhance their life-threatening facing conditions.

Keywords: positive emotion, lung cancer, experimental design, symptom distress

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Authors: Dujrudee Chinwong, Chanida Prompantakorn, Ubonphan Chaichana, Surarong Chinwong

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Objective: Understanding the university students’ perceptions on smoking caused lung cancer based on the Health Belief Model should help health care providers in assisting them to quit smoking. Thus, this study aimed to investigate the University students’ health belief in smoking behaviors caused lung cancer, which based on the Health Belief Model. Methods: Data were collected from voluntary participants using a self-administered questionnaire. Participants were students studying at a University in northern Thailand who were current smokers; they were selected using snowball sampling. Results: Of 361 students, 84% were males; 78% smoked not more than 10 cigarettes a day; 68% intended to quit smoking. Our findings, based on the health belief model, showed that 1) perceived susceptibility: participants strongly believed that if they did not stop smoking, they were at high risk of lung cancer (88%); 2) perceived severity: they strongly believed that they had a high chance of death from lung cancer if they continued smoking (84%); 3) perceived benefits: they strongly believed that quitting smoking could reduce the chance of developing lung cancer; 4) perceived barriers of quitting smoking: they strongly believed in the difficulty of quitting smoking because it needed a high effort and strong intention (69%); 5) perceived self-efficacy: however, they strongly believed that they can quit smoking right away if they had a strong intention to quit smoking (70%); 6) cues to action: they strongly believed in the support of parents (85%) and lovers (78%) in helping them to quit smoking. Further, they believed that limitation on smoking area in the University and smoking cessation services provided by the University can assist them to quit smoking. Conclusion: The Health Belief Model helps us to understand students’ smoking behaviors caused lung cancer. This could lead to designing a smoking cessation program to assist students to quit smoking.

Keywords: health belief model, lung cancer, smoking, Thailand

Procedia PDF Downloads 274

Authors: Daniel Nigusse Tollosa, Erica James, Alexis Hurre, Meredith Tavener

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Introduction: Lifestyle behaviours such as healthy diet, regular physical activity and maintaining a healthy weight are essential for cancer survivors to improve the quality of life and longevity. However, there is no study that synthesis cancer survivor’s adherence to healthy lifestyle recommendations. The purpose of this review was to collate existing data on the prevalence of adherence to healthy behaviours and produce the pooled estimate among adult cancer survivors. Method: Multiple databases (Embase, Medline, Scopus, Web of Science and Google Scholar) were searched for relevant articles published since 2007, reporting cancer survivors adherence to more than two lifestyle behaviours based on the WCRF/AICR recommendations. The pooled prevalence of adherence to single and multiple behaviours (operationalized as adherence to more than 75% (3/4) of health behaviours included in a particular study) was calculated using a random effects model. Subgroup analysis adherence to multiple behaviours was undertaken corresponding to the mean survival years and year of publication. Results: A total of 3322 articles were generated through our search strategies. Of these, 51 studies matched our inclusion criteria, which presenting data from 2,620,586 adult cancer survivors. The highest prevalence of adherence was observed for smoking (pooled estimate: 87%, 95% CI: 85%, 88%) and alcohol intake (pooled estimate 83%, 95% CI: 81%, 86%), and the lowest was for fiber intake (pooled estimate: 31%, 95% CI: 21%, 40%). Thirteen studies were reported the proportion of cancer survivors (all used a simple summative index method) to multiple healthy behaviours, whereby the prevalence of adherence was ranged from 7% to 40% (pooled estimate 23%, 95% CI: 17% to 30%). Subgroup analysis suggest that short-term survivors ( < 5 years survival time) had relatively a better adherence to multiple behaviours (pooled estimate: 31%, 95% CI: 27%, 35%) than long-term ( > 5 years survival time) cancer survivors (pooled estimate: 25%, 95% CI: 14%, 36%). Pooling of estimates according to the year of publication (since 2007) also suggests an increasing trend of adherence to multiple behaviours over time. Conclusion: Overall, the adherence to multiple lifestyle behaviors was poor (not satisfactory), and relatively, it is a major concern for long-term than the short-term cancer survivor. Cancer survivors need to obey with healthy lifestyle recommendations related to physical activity, fruit and vegetable, fiber, red/processed meat and sodium intake.

Keywords: adherence, lifestyle behaviours, cancer survivors, WCRF/AICR

Procedia PDF Downloads 159

Authors: E. Abustam, M. Yusuf, M. I. Said

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One of functional properties of the meat is decrease of water holding capacity (WHC) during rigor mortis. At the time of pre-rigor, WHC is higher than post-rigor. The decline of WHC has implication to the other functional properties such as decreased cooking lost and yields resulting in lower elasticity and compactness of processed meat product. In many cases, the addition of phosphate in the meat will increase the functional properties of the meat such as WHC. Furthermore, liquid smoke has also been known in increasing the WHC of fresh meat. For food safety reasons, liquid smoke in the present study was used as a substitute to phosphate in production of chicken nuggets. This study aimed to know the effect of substitution of phosphate with liquid smoke on the quality of nuggets made from post-rigor chicken thigh and breast. The study was arranged using completely randomized design of factorial pattern 2x3 with three replications. Factor 1 was thigh and breast parts of the chicken, and factor 2 was different levels of liquid smoke in substitution to phosphate (0%, 50%, and 100%). The thigh and breast post-rigor broiler aged 40 days were used as the main raw materials in making nuggets. Auxiliary materials instead of meat were phosphate, liquid smoke at concentration of 10%, tapioca flour, salt, eggs and ice. Variables measured were flexibility, shear force value, cooking loss, elasticity level, and preferences. The results of this study showed that the substitution of phosphate with 100% liquid smoke resulting high quality nuggets. Likewise, the breast part of the meat showed higher quality nuggets than thigh part. This is indicated by high elasticity, low shear force value, low cooking loss, and a high level of preference of the nuggets. It can be concluded that liquid smoke can be used as a binder in making nuggets of chicken post-rigor.

Keywords: liquid smoke, nugget quality, phosphate, post-rigor

Procedia PDF Downloads 217

Authors: L. Lamola, E. Manolas, A. Krause

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Background: The incidence of childhood cancer incidence is increasing gradually in low-middle income countries, such as South Africa. Globally, there is an extensive range of familial- and hereditary-cancer syndromes, where underlying germline variants increase the likelihood of developing cancer in childhood. Next-Generation Sequencing (NGS) technologies have been key in determining the occurrence and genetic contribution of germline variants to paediatric cancer development. We aimed to design and evaluate a candidate gene panel specific to inherited cancer-predisposing genes to provide a comprehensive insight into the contribution of germline variants to childhood cancer. Methods: 32 paediatric patients (aged 0-18 years) diagnosed with a malignant tumour were recruited, and biological samples were obtained. After quality control, DNA was sequenced using an ion Ampliseq 50 candidate gene panel design and Ion Torrent S5 technologies. Sequencing variants were called using Ion Torrent Suite software and were subsequently annotated using Ion Reporter and Ensembl's VEP. High priority variants were manually analysed using tools such as MutationTaster, SIFT-INDEL and VarSome. Putative identified candidates were validated via Sanger Sequencing. Results: The patients studied had a variety of cancers, the most common being nephroblastoma (13), followed by osteosarcoma (4) and astrocytoma (3). We identified 10 pathogenic / likely pathogenic variants in 10 patients, most of which were novel. Conclusions: According to the literature, we expected ~10% of our patient population to harbour pathogenic or likely pathogenic germline variants, however, we reported about 3 times (~30%) more than we expected. Majority of the identified variants are novel; this may be because this is the first study of its kind in an understudied South African population.

Keywords: Africa, genetics, germline-variants, paediatric-cancer

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Authors: Cassandra Springate, Alexandra Furber, Jack E. Hines

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Objectives: To create an evidence map of the cost-utility studies available with non-small cell lung cancer patients, and identify the geographical settings and interventions used. Methods: Using the Disease, Study Type, and Model Type filters in heoro.com we identified all cost-utility studies published between 1960 and 2017 with patients with non-small cell lung cancer. These papers were then indexed according to pre-specified categories. Results: Heoro.com identified 89 independent publications, published between 1995 and 2017. Of the 89 papers, 74 were published since 2010, 28 were from the USA, and 35 were from Europe, 16 of which were from the UK. Other publications were from China and Japan (13), Canada (9), Australia and New Zealand (4), and other countries (8). Fifty-nine studies included a chemotherapy intervention, of which 23 included erlotinib or gefitinib, 21 included pemetrexed or docetaxel, others included nivolumab (3), pembrolizumab (2), crizotinib (2), denosumab (2), necitumumab (1), and bevacizumab (1). Also, 19 studies modeled screening, staging, or surveillance strategies. Conclusions: The cost-utility studies found for NSCLC most commonly looked at the effectiveness of different chemotherapy treatments, with some also evaluating the addition of screening strategies. Most were also conducted with patient data from the USA and Europe.

Keywords: cancer, cost-utility, economic model, non-small cell lung cancer

Procedia PDF Downloads 128

Authors: Meral Tuncbilek, Duygu Sac, Irem Durmaz, Rengul Cetin Atalay

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Nucleoside analogs are a pharmacologically diverse family that includes cytotoxic compounds, antiviral agents, and immunosuppressive molecules. Purine nucleoside derivatives such as fludarabine, cladribine, and pentostatin are significant drugs used in chemotherapy for the treatment of solid tumors and hematological malignancies. In this study, we synthesized novel purine ribonucleoside analogs containing a 4-(4-substituted phenylsulfonyl) piperazine in the substituent at N6- and O-substituted sulfonyl group at 5’-position as putative cytotoxic agents. The newly obtained compounds were then characterized for their cytotoxicity in human cancer cell lines. The 5’, 6-disubstituted 9-(β-D-ribofuranosyl)purine derivatives (44-67) were readily obtained from commercially available inosine in seven steps in very cost effective synthesis approach. The newly synthesized compounds were first evaluated for their anti-tumor activities against human liver (Huh7), colon (HCT116) and breast (MCF7) carcinoma cell lines. The IC50 values were in micromolar concentrations with 5’, 6-disubstituted purine nucleoside derivatives. Time-dependent IC50 values for each molecule were also calculated in comparison with known cytotoxic agents Camptothecin (CPT), 5-Fluorouracil (5-FU), Cladribine, Pentostatine and Fludarabine. N6-(4-trifluoromethyl phenyl) / N6-(4-bromophenyl) and 5’-O-(4-methoxybenzene sulfonyl) / 5’-O-(benzenesulfonyl) derivatives 54, 64 displayed the best cytotoxic activity with IC50 values of 8.8, 7 µM against MCF7 cell line. The N6-(4-methylphenyl) analog 50 was also very active (IC50= 10.7 μM) against HCT116 cell line. Furthermore, compound 64 had a better cytotoxic activity than the known cell growth inhibitors 5-FU and Fludarabine on Huh7 (1.5 vs 30.7, 29.9 μM for 5-FU and Fludarabine).

Keywords: cytotoxic activity, Huh7, HCT116, MCF7, nucleoside, synthesis

Procedia PDF Downloads 213

Authors: Christian Skowronski, Andrew Shanholtzer, Brent Yelton, Muayad Almahariq, Daniel J. Krauss

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Prostate cancer has the third highest incidence rate and is the second leading cause of cancer death for men in the United States. Of the diagnostic tools available for intermediate-risk prostate cancer, magnetic resonance imaging (MRI) provides superior soft tissue delineation serving as a valuable tool for both diagnosis and treatment planning. Currently, there is minimal data regarding the practical utility of MRI for evaluation of intermediate-risk prostate cancer. As such, the National Comprehensive Cancer Network’s guidelines indicate MRI as optional in intermediate-risk prostate cancer evaluation. This project aims to elucidate whether MRI affects radiation treatment decisions for intermediate-risk prostate cancer. This was a retrospective study evaluating 210 patients with intermediate-risk prostate cancer, treated with definitive radiotherapy at our institution between 2019-2020. NCCN risk stratification criteria were used to define intermediate-risk prostate cancer. Patients were divided into two groups: those with pretreatment prostate MRI, and those without pretreatment prostate MRI. We compared the use of external beam radiotherapy, brachytherapy alone, brachytherapy boost, and androgen depravation therapy between the two groups. Inverse probability of treatment weighting was used to match the two groups for age, comorbidity index, American Urologic Association symptoms index, pretreatment PSA, grade group, and percent core involvement on prostate biopsy. Wilcoxon Rank Sum and Chi-squared tests were used to compare continuous and categorical variables. Of the patients who met the study’s eligibility criteria, 133 had a prostate MRI and 77 did not. Following propensity matching, there were no differences between baseline characteristics between the two groups. There were no statistically significant differences in treatments pursued between the two groups: 42% vs 47% were treated with brachytherapy alone, 40% vs 42% were treated with external beam radiotherapy alone, 18% vs 12% were treated with external beam radiotherapy with a brachytherapy boost, and 24% vs 17% received androgen deprivation therapy in the non-MRI and MRI groups, respectively. This analysis suggests that pretreatment MRI does not significantly impact radiation therapy or androgen deprivation therapy decisions in patients with intermediate-risk prostate cancer. Obtaining a pretreatment prostate MRI should be used judiciously and pursued only to answer a specific question, for which the answer is likely to impact treatment decision. Further follow up is needed to correlate MRI findings with their impacts on specific oncologic outcomes.

Keywords: magnetic resonance imaging, prostate cancer, definitive radiotherapy, gleason score 7

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Authors: S. Nikpour, S. Vahidi, H. Haghani

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Introduction: Exercise has mental and physical health benefits for patients with advanced stage cancer who actively receive chemotherapy, yet little is known about patients’ levels of interest in becoming more active or their confidence in increasing their activity level. Methods and materials: A convenience sample of 200 patients with advanced-stage cancer who were receiving chemotherapy completed self-report measures assessing physical activity level, mood, and quality-of-life variables. Qualitative data on patient-perceived benefits of, and barriers to, physical activity also were collected, coded by independent raters, and organized by predominant themes. Results: Current physical activity level, physical activity outcome expectations, and positive mood were significantly associated with self-efficacy. Fatigue was the most frequently listed barrier to physical activity; improved physical strength and health were the most commonly listed benefits. Participants identified benefits related to both general health and cancer-symptom management that were related to exercise. 59.5% of participants reported that they were seriously planning to increase or maintain their physical activity level, and over 40% reported having interest in receiving an intervention to become more active. Conclusion: These results suggested that many advanced-stage cancer patients who receive chemotherapy are interested in maintaining or increasing their physical activity level and in receiving professional support for exercise. In addition, these individuals identified general health and cancer-specific benefits of, and barriers to, physical activity. Future research will investigate how these findings may be incorporated into physical activity interventions for advanced-stage oncology patients receiving medical treatment.

Keywords: physical activity, cancer, self-efficacy

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Authors: V. Naga Sravan Kumar Varma, H. G. Shivakumar

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The aim of the study was to develop dual sensitive poly (N-isopropylacrylamide-co-acrylic acid) (PNA) nanogels(NGs) and studying its applications for Anti-Cancer therapy. NGs were fabricated by free radical polymerization using different amount of N-isopropylacrylamide and acrylic acid. A study for polymer composition over the effect on LCST in different pH was evaluated by measuring the absorbance at 500nm using UV spectrophotometer. Further selected NG’s were evaluated for change in hydrodynamic diameters in response to pH and temperature. NGs which could sharply respond to low pH value of cancer cells at body temperature were loaded with Fluorouracil (5-FU) using equilibrium swelling method and studied for drug release behaviour in different pH. A significant influence of NGs polymer composition over pH dependent LCST was observed. NGs which were spherical with an average particle size of 268nm at room temperature, shrinked forming an irregular shape when heated above to their respective LCST. 5FU loaded NGs did not intervene any difference in pH depended LCST behaviour of NGs. The in vitro drug release of NGs exhibited a pH and thermo-dependent control release. The cytoxicity study of blank carrier to MCF7 cell line showed no cytotoxicity. The results indicated that PNA NGs could be used as a potential drug carrier for anti-cancer therapy.

Keywords: pH and thermo-sensitive, nanogels, P(NIPAM-co-AAc), anti-cancer, 5-FU

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Authors: Deirdre Mc Grath, Joanne Reid

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Background: Ovarian cancer is the leading cause of mortality among gynaecologic cancers in developed countries and the seventh most common cancer worldwide with nearly 240,000 women diagnosed each year. Although it is recognized engaging in exercise results in positive health care outcomes, women with ovarian cancer are reluctant to participate. No evidence currently exists focusing on how to successfully implement an exercise intervention program for patients with ovarian cancer, using a realist approach. There is a requirement for the implementation of exercise programmes within the oncology health care setting as engagement in such interventions has positive health care outcomes for women with ovarian cancer both during and following treatment. Aim: To co-design the implementation of an exercise intervention for women following treatment for ovarian cancer. Methods: This study is a realist evaluation using quantitative and qualitative methods of data collection and analysis. Realist evaluation is well-established within the health and social care setting and has in relation to this study enabled a flexible approach to investigate how to optimise implementation of an exercise intervention for this patient population. This single centre study incorporates three stages in order to identify the underlying contexts and mechanisms which lead to the successful implementation of an exercise intervention for women who have had treatment for ovarian cancer. Stage 1 - A realist literature review. Stage 2 -Co-design of the implementation of an exercise intervention with women following treatment for ovarian cancer, their carer’s, and health care professionals. Stage 3 –Implementation of an exercise intervention with women following treatment for ovarian cancer. Evaluation of the implementation of the intervention from the perspectives of the women who participated in the intervention, their informal carers, and health care professionals. The underlying program theory initially conceptualised before and during the realist review was developed further during the co-design stage. The evolving program theory in relation to how to successfully implement an exercise for these women is currently been refined and tested during the final stage of this realist evaluation which is the implementation and evaluation stage. Results: This realist evaluation highlights key issues in relation to the implementation of an exercise intervention within this patient population. The underlying contexts and mechanisms which influence recruitment, adherence, and retention rates of participants are identified. Conclusions: This study will inform future research on the implementation of exercise interventions for this patient population. It is anticipated that this intervention will be implemented into practice as part of standard care for this group of patients.

Keywords: ovarian cancer, exercise intervention, implementation, Co-design

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Authors: Adeline Fontvieille, Hugo Parent-Roberge, Marie-France Langlois, Tamas Fulop, Michel Pavic, Eleonor Riesco

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Introduction: Total lean body mass is reduced during cancer treatment. This loss is called cancer cachexia and is accompanied by a progressive loss of fat mass. In older adults, these body composition changes can have a larger impact on metabolic health, physical autonomy, and cancer survival. Although currently untreatable, exercise training could reduce these effects. Hence, the objective of this pilot study is to investigate if 12 weeks of exercise training during cancer treatment can mitigate the loss of muscle mass and fat mass in older adults. Methods: A total of 40 older adults (65-80 years) with an ongoing treatment for a curable cancer are currently recruited and randomised in two groups: 1) Combined training (EX, n=20) and 2) Control group (CON, n=20). All variables are measured before and after 12 weeks of intervention: Anthropometry (weight, height, body mass index), body composition (total fat mass, visceral adipose tissue, total and appendicular muscle mass; DXA), metabolic profile (HDL-C and LDL-C, triglycerides, glucose and insulin levels). Results: Preliminary analyses revealed no impact of exercise training on appendicular muscle mass (p=0,31) and fat mass (p=0,31). Furthermore, total body weight, waist circumference, HDL-cholesterol, LDL-cholesterol, glucose and insulin levels remained unchanged (all p ≥ 0.79) after 12 weeks of training. However, statistical analyses revealed that triglyceride levels slightly increased (p=0.03), irrespective of the group. Conclusion: Preliminary analyses did not reveal any impact of aerobic and resistance exercise training on body composition in oncogeriatric patients. Furthermore, exercise training seems not efficient to prevent the cancer treatment-related triglyceride levels increase.

Keywords: muscle mass, fat mass, metabolic profile, combined training, aging, cancer

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here, we report the definition of miR-346 as an oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.

Keywords: microRNA-346, miR-346, XPC, non-small cell lung cancer, oncogenesis

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Authors: Dmitry V. Pasynkov, Ivan A. Egoshin, Alexey A. Kolchev, Ivan V. Kliouchkin

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In most cases, typical cysts are easily recognized at ultrasonography. The specificity of this method for typical cysts reaches 98%, and it is usually considered as gold standard for typical cyst diagnosis. However, it is necessary to have all the following features to conclude the typical cyst: clear margin, the absence of internal echoes and dorsal acoustic enhancement. At the same time, not every breast cyst is typical. It is especially characteristic for protein-contained cysts that may have significant internal echoes. On the other hand, some solid lesions (predominantly malignant) may have cystic appearance and may be falsely accepted as cysts. Therefore we tried to develop the automatic method of cystic and solid breast lesions differentiation. Materials and methods. The input data were the ultrasonography digital images with the 256-gradations of gray color (Medison SA8000SE, Siemens X150, Esaote MyLab C). Identification of the lesion on these images was performed in two steps. On the first one, the region of interest (or contour of lesion) was searched and selected. Selection of such region is carried out using the sigmoid filter where the threshold is calculated according to the empirical distribution function of the image brightness and, if necessary, it was corrected according to the average brightness of the image points which have the highest gradient of brightness. At the second step, the identification of the selected region to one of lesion groups by its statistical characteristics of brightness distribution was made. The following characteristics were used: entropy, coefficients of the linear and polynomial regression, quantiles of different orders, an average gradient of brightness, etc. For determination of decisive criterion of belonging to one of lesion groups (cystic or solid) the training set of these characteristics of brightness distribution separately for benign and malignant lesions were received. To test our approach we used a set of 217 ultrasonic images of 107 cystic (including 53 atypical, difficult for bare eye differentiation) and 110 solid lesions. All lesions were cytologically and/or histologically confirmed. Visual identification was performed by trained specialist in breast ultrasonography. Results. Our system correctly distinguished all (107, 100%) typical cysts, 107 of 110 (97.3%) solid lesions and 50 of 53 (94.3%) atypical cysts. On the contrary, with the bare eye it was possible to identify correctly all (107, 100%) typical cysts, 96 of 110 (87.3%) solid lesions and 32 of 53 (60.4%) atypical cysts. Conclusion. Automatic approach significantly surpasses the visual assessment performed by trained specialist. The difference is especially large for atypical cysts and hypoechoic solid lesions with the clear margin. This data may have a clinical significance.

Keywords: breast cyst, breast solid lesion, differentiation, ultrasonography

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Authors: Jinfeng Zhang, Chun-Sing Lee

Abstract:

The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed for improving their drug loading capacities (typically less than 10%) and reducing their potential systemic toxicity. So development of alternative self-carried nanodrug delivery strategies without using any inert carriers is highly desirable. In this study, we developed a self-carried theranostic curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environment, with drug loading capacity higher than 78 wt.%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescent “OFF-ON” activation and real-time monitoring of Cur molecule release, showing its potential for cancer diagnosis. In vitro and in vivo experiments clearly show that therapeutic efficacy of the PEGylated Cur NPs is much better than that of free Cur. This self-carried theranostic strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and diagnosis.

Keywords: drug delivery, in vitro and in vivo cancer therapy, real-time monitoring, self-carried

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Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

Abstract:

Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: M. Chaichanyut, S. Tungjitkusolmun

Abstract:

This research is presented with microwave (MW) ablation by using the T-Prong monopole antennas. In the study, three-dimensional (3D) finite-element methods (FEM) were utilized to analyse: the tissue heat flux, temperature distributions (heating pattern) and volume destruction during MW ablation in liver cancer tissue. The configurations of T-Prong monopole antennas were considered: Three T-prong antenna, Expand T-Prong antenna and Arrow T-Prong antenna. The 3D FEMs solutions were based on Maxwell and bio-heat equations. The microwave power deliveries were 10 W; the duration of ablation in all cases was 300s. Our numerical result, heat flux and the hotspot occurred at the tip of the T-prong antenna for all cases. The temperature distribution pattern of all antennas was teardrop. The Arrow T-Prong antenna can induce the highest temperature within cancer tissue. The microwave ablation was successful when the region where the temperatures exceed 50°C (i.e. complete destruction). The Expand T-Prong antenna could complete destruction the liver cancer tissue was maximized (6.05 cm³). The ablation pattern or axial ratio (Widest/length) of Expand T-Prong antenna and Arrow T-Prong antenna was 1, but the axial ratio of Three T-prong antenna of about 1.15.

Keywords: liver cancer, T-Prong antenna, finite element, microwave ablation

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

Abstract:

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

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

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Authors: Salvador Garcia Bernal, Chi Zheng, Keqi Zhang, Lei Mao

Abstract:

Circulating Tumor Cells (CTC) is used to detect tumoral cell metastases using blood samples of patients with cancer (lung, breast, etc.). Using an immunofluorescent method a three channel image (Red, Green, and Blue) are obtained. These set of images usually overpass the 11 x 30 M pixels in size. An aided tool is designed for imaging cell analysis to segmented and identify the tumorous cell based on the three markers signals. Our Method, it is cell-based (area and cell shape) considering each channel information and extracting and making decisions if it is a valid CTC. The system also gives information about number and size of tumor cells found in the sample. We present results in real-life samples achieving acceptable performance in identifying CTCs in short time.

Keywords: Circulating Tumor Cells (CTC), cell analysis, immunofluorescent, medical image analysis

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Authors: Shu-Pin Huang, Pai-Chi Teng, Hao-Han Chang, Chia-Hsin Liu, Yung-Lun Lin, Shu-Chi Wang, Hsin-Chih Yeh, Chih-Pin Chuu, Jiun-Hung Geng, Li-Hsin Chang, Wei-Chung Cheng, Chia-Yang Li

Abstract:

The emergence of immune checkpoint inhibitors (ICIs) targeting proteins like PD-1 and PD-L1 has changed the treatment paradigm of bladder cancer. However, not all patients benefit from ICIs, with some experiencing early death. There's a significant need for biomarkers associated with the PD-1 pathway in bladder cancer. Current biomarkers focus on tumor PD-L1 expression, but a more comprehensive understanding of PD-1-related biology is needed. Our study has developed a seven-gene risk score panel, employing a comprehensive bioinformatics strategy, which could serve as a potential prognostic and predictive biomarker for bladder cancer. This panel incorporates the FYN, GRAP2, TRIB3, MAP3K8, AKT3, CD274, and CD80 genes. Additionally, we examined the relationship between this panel and immune cell function, utilizing validated tools such as ESTIMATE, TIDE, and CIBERSORT. Our seven-genes panel has been found to be significantly associated with bladder cancer survival in two independent cohorts. The panel was also significantly correlated with tumor infiltration lymphocytes, immune scores, and tumor purity. These factors have been previously reported to have clinical implications on ICIs. The findings suggest the potential of a PD-1 pathway-based transcriptomic panel as a prognostic and predictive biomarker in bladder cancer, which could help optimize treatment strategies and improve patient outcomes.

Keywords: bladder cancer, programmed cell death protein 1, prognostic biomarker, immune checkpoint inhibitors, predictive biomarker

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Authors: Deirdre Mc Grath, Joanne Reid

Abstract:

Background: Ovarian cancer is the leading cause of mortality among gynaecologic cancers in developed countries and the seventh most common cancer worldwide, with nearly 240,000 women diagnosed each year. Although it is recognized engaging in exercise results in positive health care outcomes, women with ovarian cancer are reluctant to participate. No evidence currently exists focusing on how to successfully implement an exercise intervention program for patients with ovarian cancer, using a realist approach. There is a requirement for the implementation of exercise programmes within the oncology health care setting as engagement in such interventions has positive health care outcomes for women with ovarian cancer both during and following treatment. Aim: To co-design the implementation of an exercise intervention for women following treatment for ovarian cancer. Methods: This study is a realist evaluation using quantitative and qualitative methods of data collection and analysis. Realist evaluation is well-established within the health and social care setting and has, in relation to this study, enabled a flexible approach to investigate how to optimise implementation of an exercise intervention for this patient population. This single centre study incorporates three stages in order to identify the underlying contexts and mechanisms which lead to the successful implementation of an exercise intervention for women who have had treatment for ovarian cancer. Stage 1 - A realist literature review. Stage 2 -Co-design of the implementation of an exercise intervention with women following treatment for ovarian cancer, their carer’s, and health care professionals. Stage 3 –Implementation of an exercise intervention with women following treatment for ovarian cancer. Evaluation of the implementation of the intervention from the perspectives of the women who participated in the intervention, their informal carers, and health care professionals. The underlying programme theory initially conceptualised before and during the realist review was developed further during the co-design stage. The evolving programme theory in relation to how to successfully implement an exercise for these women is currently been refined and tested during the final stage of this realist evaluation which is the implementation and evaluation stage. Results: This realist evaluation highlights key issues in relation to the implementation of an exercise intervention within this patient population. The underlying contexts and mechanisms which influence recruitment, adherence, and retention rates of participants are identified. Conclusions: This study will inform future research on the implementation of exercise interventions for this patient population. It is anticipated that this intervention will be implemented into practice as part of standard care for this group of patients.

Keywords: exercise, ovarian cancer, co-design, implementation

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Authors: Conor Mccartney, Mark Lee

Abstract:

Background: An essential component in ambulatory breast augmentation surgery is good analgesia. The demographic undergoing this operation is usually fit, low risk with few comorbidities. These patients do not require long-term hospitalization and do not want to spend excessive time in the hospital for financial reasons. Opiate analgesia can have significant side effects such as nausea, vomiting and sedation. Reducing volumes of postoperative opiates allows faster ambulation and discharge from day surgery. We have developed two targeted nerve blocks that can be applied by the operating surgeon in a matter of seconds under direct vision, not requiring imaging. Anecdotally we found that these targeted nerve blocks reduced opiate requirements and allowed accelerated discharge and faster return to normal activities. This was then tested in a prospective randomized, double-blind trial. Methods: 20 patients were randomized into saline (n = 10) or Ropivicaine adrenaline solution (n = 10). The operating surgeon and anesthetist were blinded to the solution. All patients were closely followed up and morphine equivalents were accurately recorded. Follow-up pain scores were recorded using the Overall Benefit of Analgesia pain questionnaire. Findings: The Ropivicaine nerve blocks significantly reduced opiate requirements postoperatively (p<0.05). Pain scores were significantly decreased in the study group (p<0.05). There were no side effects attributable to the nerve blocks. Conclusions: Intraoperative targeted nerve blocks significantly reduce postoperative opiate requirements in breast augmentation surgery. This results in faster recovery and higher patient satisfaction.

Keywords: breast augmentation, nerve block, postoperative recovery, opiate analgesia, inter pectoral block, sub serratus block

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Authors: Zixuan Zhao, Lingbin Du, Le Wang, Youqing Wang, Yi Yang, Jingjun Chen, Hengjin Dong

Abstract:

Objectives: Few results from public attitudes for lung cancer screening are available both in China and abroad. This study aimed to identify preferred lung cancer screening modalities in a Chinese population and predict uptake rates of different modalities. Materials and Methods: A discrete choice experiment questionnaire was administered to 392 Chinese individuals aged 50–74 years who were at high risk for lung cancer. Each choice set had two lung screening options and an option to opt-out, and respondents were asked to choose the most preferred one. Both mixed logit analysis and stepwise logistic analysis were conducted to explore whether preferences were related to respondent characteristics and identify which kinds of respondents were more likely to opt out of any screening. Results: On mixed logit analysis, attributes that were predictive of choice at 1% level of statistical significance included the screening interval, screening venue, and out-of-pocket costs. The preferred screening modality seemed to be screening by low-dose computed tomography (LDCT) + blood test once a year in a general hospital at a cost of RMB 50; this could increase the uptake rate by 0.40 compared to the baseline setting. On stepwise logistic regression, those with no endowment insurance were more likely to opt out; those who were older and housewives/househusbands, and those with a health check habit and with commercial endowment insurance were less likely to opt out from a screening programme. Conclusions: There was considerable variance between real risk and self-perceived risk of lung cancer among respondents, and further research is required in this area. Lung cancer screening uptake can be increased by offering various screening modalities, so as to help policymakers further design the screening modality.

Keywords: lung cancer, screening, China., discrete choice experiment

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Authors: Qi LI, Xu Lin, Nengming Lin

Abstract:

Objective: The aim of this study was to investigate the role of desmocollin 2 (DSC2) protein in the proliferation, migration and drug resistance of lung cancer cells. Method: CCK-8 assays and colony formation assays were used to evaluate the effect of dsc2 regulation on cancer cell viability and colony formation. Transwell assays and wound healing assays were also performed. Cell flow double staining was used to detect the apoptosis rate of cells with DSC2, which was added cisplatin. Western blot assay was used to detect cell cycle, PI3k/Akt and apoptosis-related proteins. Results: Our data showed that dsc2 is upregulated in clinical lung cancer tissues compared with pericarcinomatous tissues, and it is differentially expressed in lung cancer cell lines. The down-regulation of dsc2 in A549 and H358 lung cancer cells significantly suppressed the cell proliferation, metastasis, and motility. In contrast, the opposite effects were observed in overexpression of dsc2 both in H23 and PC9 cell lines. In addition to lung adenocarcinoma cell lines, we also examined its expression in lung squamous cell lines, such as H226. Western blotting showed that dsc2 could reduce the level of phosphorylated Akt (Ser 473) and p-mTOR. Thus, it is speculated that dsc2 up-regulation promotes proliferation and invasiveness through activation of the PI3K/AKT pathway. Also, knockdown of dsc2 in A549 and H226 could significantly decreased in the levels of cyclinB and wee1 protein. Additionally, flow cytometry showed that dsc2 knockdown combined with cisplatin could significantly enhance cell apoptosis rate. Conclusion: These data suggest that dsc2 promotes the proliferation and migration of lung cancer cells in vitro. Also, the results suggested that dsc2 could affect the cell cycle and apoptosis of lung cells. Furthermore, knockdown of dsc2 could sensitize cisplatin in both lung adenocarcinoma and lung squamous cell lines. Thus we suggested that dsc2 can be used as a therapeutic target for lung cancer.

Keywords: desmocollin 2, cisplatin, lung cancer, PI3K/AKT, lung squamous cell

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Authors: Dong-Gyu Leem, Ji-Sun Shin, Sang Yoon Choi, Kyung-Tae Lee

Abstract:

In this study, we focused on the anti-proliferative effects of panaxydol, a C17 polyacetylenic compound derived from Panax ginseng roots, against various human cancer cells. We treated with panaxydol to various cancer cells and panaxydol treatment was found to significantly inhibit the proliferation of human lung cancer cells (A549) and human pancreatic cancer cells (AsPC-1 and MIA PaCa-2), of which AsPC-1 cells were most sensitive to its treatment. DNA flow cytometric analysis indicated that panaxydol blocked cell cycle progression at the G1 phase in A549 cells, which accompanied by a parallel reduction of protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E. CDK inhibitors (CDKIs), such as p21CIP1/WAF1 and p27KIP1, were gradually upregulated after panaxydol treatment at the protein levels. Furthermore, panaxydol induced the activation of p53 in A549 cells. In addition, panaxydol also induced apoptosis of AsPC-1 and MIA PaCa-2 cells, as shown by accumulation of subG1 and apoptotic cell populations. Panaxydol triggered the activation of caspase-3, -8, -9 and the cleavage of poly (ADP-ribose) polymerase (PARP). Reduction of mitochondrial transmembrane potential by panaxydol was determined by staining with dihexyloxacarbocyanine iodide. Furthermore, panaxydol suppressed the levels of anti-apoptotic proteins, XIAP and Bcl-2, and increased the levels of proapoptotic proteins, Bax and Bad. In addition, panaxydol inhibited the activation of Akt and extracellular signal-regulated kinase (ERK) and activated the p38 mitogen-activated protein kinase kinase (MAPK). Our results suggest that panaxydol is an anti-tumor compound that causes p53-mediated cell cycle arrest and apoptosis via mitochondrial apoptotic pathway in various cancer cells.

Keywords: apoptosis, cancer, G1 arrest, panaxydol

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