Search results for: gastric cancer surgery

Authors: Cuneyt Yucelbas, Seral Ozsen, Sule Yucelbas, Gulay Tezel

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Due to the fact that there exist only a small number of complex systems in artificial immune system (AIS) that work out nonlinear problems, nonlinear AIS approaches, among the well-known solution techniques, need to be developed. Gaussian function is usually used as similarity estimation in classification problems and pattern recognition. In this study, diagnosis of breast cancer, the second type of the most widespread cancer in women, was performed with different distance calculation functions that euclidean, gaussian and gaussian-euclidean hybrid function in the clonal selection model of classical AIS on Wisconsin Breast Cancer Dataset (WBCD), which was taken from the University of California, Irvine Machine-Learning Repository. We used 3-fold cross validation method to train and test the dataset. According to the results, the maximum test classification accuracy was reported as 97.35% by using of gaussian-euclidean hybrid function for fold-3. Also, mean of test classification accuracies for all of functions were obtained as 94.78%, 94.45% and 95.31% with use of euclidean, gaussian and gaussian-euclidean, respectively. With these results, gaussian-euclidean hybrid function seems to be a potential distance calculation method, and it may be considered as an alternative distance calculation method for hard nonlinear classification problems.

Keywords: artificial immune system, breast cancer diagnosis, Euclidean function, Gaussian function

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Authors: Sean Yao Zu Kong, Khong Yik Chew

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Introduction: We described a case report of the successful use of advanced surgical techniques in a patient with recurrent breast cancer who underwent a wide resection including the hemi-sternum, clavicle, multiple ribs, and a lobe of the lung due to tumor involvement. This extensive resection exposed critical structures, requiring a creative approach to reconstruction. To address this complex chest wall reconstruction, a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap were successfully utilized. The use of a free vascularized bone flap allowed for rapid osteointegration and resistance against osteoradionecrosis after adjuvant radiation, while a four-zone tram flap allowed for reconstruction of both the chest wall and breast mound. Although limited recipient vessels made free flaps challenging, the free fibula flap served as both a bony reconstruction and vascular conduit, supercharged with the distal peroneal artery and veins of the peroneal artery from the fibula graft. Our approach highlights the potential of advanced surgical techniques to improve outcomes in complex cases of chest wall reconstruction in patients with recurrent breast cancer, which is becoming increasingly relevant as breast cancer incidence rates increases. Case presentation: This report describes a successful reconstruction of a patient with recurrent breast cancer who required extensive resection, including the anterior chest wall, clavicle, and sternoclavicular joint. Challenges arose due to the loss of accessory muscles and the non-rigid rib cage, which could lead to compromised ventilation and instability. A free fibula osteocutaneous flap and a four-zone TRAM flap with vascular supercharging were utilized to achieve long-term stability and function. The patient has since fully recovered, and during the review, both flaps remained viable, and chest mound reconstruction was satisfactory. A planned nipple/areolar reconstruction was offered pending the patient’s decision after adjuvant radiotherapy. Conclusion: In conclusion, this case report highlights the successful use of innovative surgical techniques in addressing a complex case of recurrent breast cancer requiring extensive resection and radical reconstruction. Our approach, utilized a combination of a free fibula flap and a 4-zone rectus abdominis musculocutaneous flap, demonstrates the potential for advanced techniques in chest wall reconstruction to minimize complications and ensure long-term stability and function. As the incidence of breast cancer continues to rise, it is crucial that healthcare professionals explore and utilize innovative techniques to improve patient outcomes and quality of life.

Keywords: free fibula flap, rectus abdominis musculocutaneous flap, post-adjuvant radiotherapy, reconstructive surgery, malignancy

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Authors: Catarina Grande, Barbara Mota

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The main goal of the present study was to understand the impact of childhood cancer on the quality of life of survivors and the extent to which oncologic disease affects the functionality and participation of survivors at the present time, compared to the time of diagnosis. Six survivors of pediatric cancer participated in the study. Participants were interviewed using a semi-structured interview, adapted from two instruments present in the literature - QALY and QLACS - and piloted through a previous study. This study is based on a qualitative approach using content analysis, allowing the identification of categories and subcategories. Subsequently, the correspondence between the units of meaning and the codes in the International Classification of Functioning, Disability, and Health for Children and Young, which contributed to a more detailed analysis of the impact on the quality of life of survivors in relation to the domains under study. The results showed significant changes between the moment of diagnosis and the present moment, concretely at the microsystem of the survivor. Regarding functionality and participation, the results show that the functions of the body are the most affected domain, emphasizing the emotional component that currently has a greater impact on the quality of life of survivors. The present study allowed identifying a set of codes for the development of a CIF-CJ core set for pediatric cancer survivors. He also indicated the need for future studies to validate and deepen these issues.

Keywords: cancer, participation, quality of life, survivor

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Authors: Shannon Hearney, Jeffrey Hoch

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While all cancers are costly to treat, pancreatic cancer is a notoriously costly and deadly form of cancer. Across the world there are a variety of treatment centers ranging from small clinics to large, high-volume hospitals as well as differing structures of payment and access. It has been noted that centers that treat a high volume of pancreatic cancer patients have higher quality of care, it is unclear if that care is cost-effective. In the US there is no clear consensus on the cost-effectiveness of high-volume centers for the surgical care of pancreatic cancer. Other European countries, like Finland and Italy have shown that high-volume centers have lower mortality rates and can have lower costs, there however, is still a gap in knowledge about these centers cost-effectiveness globally. This paper seeks to review the current literature in Europe and the US to gain a better understanding of the state of high-volume pancreatic surgical centers cost-effectiveness while considering the contextual differences in health system structure. A review of major reference databases such as Medline, Embase and PubMed will be conducted for cost-effectiveness studies on the surgical treatment of pancreatic cancer at high-volume centers. Possible MeSH terms to be included, but not limited to, are: “pancreatic cancer”, “cost analysis”, “cost-effectiveness”, “economic evaluation”, “pancreatic neoplasms”, “surgical”, “Europe” “socialized medicine”, “privatized medicine”, “for-profit”, and “high-volume”. Studies must also have been available in the English language. This review will encompass European scientific literature, as well as those in the US. Based on our preliminary findings, we anticipate high-volume hospitals to provide better care at greater costs. We anticipate that high-volume hospitals may be cost-effective in different contexts depending on the national structure of a healthcare system. Countries with more centralized and socialized healthcare may yield results that are more cost-effective. High-volume centers may differ in their cost-effectiveness of the surgical care of pancreatic cancer internationally especially when comparing those in the United States to others throughout Europe.

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

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Authors: Evelyn Marie Richmond, Andrew McBride, Chris Johnston, John Marley

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Background: Good quality patient information resources for orthognathic treatment help to reinforce information delivered during the initial consultation and help patients make informed decisions about their care. The Consultant Orthodontists and a Dental Core Trainee noted limited patient engagement with the British Orthodontic Society (BOS) 'Your Jaw Surgery' online resources and that the existing BOS patient information leaflet (PIL) could be customised and developed to meet local requirements. Aim: The quality improvement project (QIP) aimed to improve patients' understanding of orthognathic treatment by ensuring at least 90% of patients had read the new in-house patient information leaflet (PIL) and a minimum of 50% of patients had accessed the British Orthodontic Society (BOS) 'Your Jaw Surgery' online resources before attending the joint orthognathic multidisciplinary clinic by June 2023. Methods: The QIP was undertaken in the orthodontic department of the School of Dentistry, Belfast. Data was collected prospectively during a 6-month period from January 2023 to June 2023 over 3 Plan, Do, Study, Act (PDSA) cycles. Suitable patients were identified at consultant orthodontic new patient clinics. Following initial consultation for orthognathic treatment, patients were contacted to complete a patient questionnaire. Design: The change ideas were a poster with a QR code directing patients to the BOS 'Your Jaw Surgery' website in consultation areas and a new in-house PIL with a QR code directing patients to the BOS 'Your Jaw Surgery' website. Results: In PDSA cycle 1, 86.7% of patients were verbally directed to the BOS 'Your Jaw Surgery' website, and 53.3% accessed the online resources after their initial consultation. Although 100% of patients reported reading the existing PIL, only 64.3% felt it discussed the risks of orthognathic treatment in sufficient detail. By PDSA cycle 3, 100% of patients reported being directed to the BOS 'Your Jaw Surgery' website, however, only 58.3% engaged with the website. 100% of patients who read the new PIL felt that it discussed the risks of orthognathic treatment in sufficient detail. Conclusion: The slight improvement in access to the BOS 'Your Jaw Surgery' website shows that patients do not necessarily choose to access information online despite its availability. The uptake of the new PIL was greater than reported patient engagement with the BOS 'Your Jaw Surgery' website, which indicates patients still value written information despite the availability of online resources.

Keywords: orthognathic surgery, patient information resources, quality improvement project, risks

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Authors: Munish Saroch, Amit Saini

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Introduction: Many children with congenital malformation of inner ear have undergone cochlear implant (CI) surgery. The results for cochlear implant surgery in these children are very encouraging and provide a ray of hope for these patients. Objective: The main objective of this presentation is to prove that even in Mondini’s deformity Minimal incision cochlear implantation improves cosmesis, reduces post-operative infection and earliest switch on of device. Methods: We report a case of two-year-old child suffering from Mondini’s deformity who underwent CI with minimal incision cochlear implantation (MICI). MICI has been developed with the aims of reducing the impact of surgery on the patient without any preoperative shaving of hairs. Results: Patient after surgery with MICI showed better looking postauricular scar, low post-operative morbidity in comparison to conventional wider access approach and hence earliest switch on of device (1st post operative day). Conclusion: We are of opinion that MICI is safe and successful in Mondini’s deformity.

Keywords: CI, Cochlear Implant, MICI, Minimal Incision Cochlear Implantation, HL, Hearing Loss, HRCT, High Resolution Computer Tomography, MRI, Magnetic resonance imaging, SCI, Standard cochlear implantation

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Authors: Reuben Mugisha, Stella Bakibinga

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The cervical cancer burden is a global threat, but more so in low income settings where more than 85% of mortality cases occur due to lack of sufficient screening programs. There is consequently a lack of early detection of cancer and precancerous cells among women. Studies show that 3% to 35% of deaths could have been avoided through early screening depending on prognosis, disease progression, environmental and lifestyle factors. In this study, a systematic literature review is undertaken to understand potential barriers and facilitators as documented in previous studies that focus on the application of telehealth in cervical cancer screening programs for early detection of cancer and precancerous cells. The study informs future studies especially those from low income settings about lessons learned from previous studies and how to be best prepared while planning to implement telehealth for cervical cancer screening. It further identifies the knowledge gaps in the research area and makes recommendations. Using a specified selection criterion, 15 different articles are analyzed based on the study’s aim, theory or conceptual framework used, method applied, study findings and conclusion. Results are then tabulated and presented thematically to better inform readers about emerging facts on barriers and facilitators to telehealth implementation as documented in the reviewed articles, and how they consequently lead to evidence informed conclusions that are relevant to telehealth implementation for cervical cancer screening. Preliminary findings of this study underscore that use of low cost mobile colposcope is an appealing option in cervical cancer screening, particularly when coupled with onsite treatment of suspicious lesions. These tools relay cervical images to the online databases for storage and retrieval, they permit integration of connected devices at the point of care to rapidly collect clinical data for further analysis of the prevalence of cervical dysplasia and cervical cancer. Results however reveal the need for population sensitization prior to use of mobile colposcopies among patients, standardization of mobile colposcopy programs across screening partners, sufficient logistics and good connectivity, experienced experts to review image cases at the point-of-care as important facilitators to the implementation of mobile colposcope as a telehealth cervical cancer screening mechanism.

Keywords: cervical cancer screening, digital technology, hand-held colposcopy, knowledge-sharing

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Authors: Dimitra V. Peristeri, Hussameldin M. Nour, Amiya Ahsan, Sameh Abogabal, Krishna K. Singh, Muhammad Shafique Sajid

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Introduction: The use of optimal skin antiseptic agents for the prevention of surgical site infection (SSI) is of critical importance, especially during abdominal surgical procedures. Alcohol-based chlorhexidine gluconate (CHG) and aqueous-based povidone-iodine (PVI) are the two most common skin antiseptics used nowadays. The objective of this article is to evaluate the effectiveness of alcohol-based CHG versus aqueous-based PVI used for skin preparation before abdominal surgery to reduce SSIs. Methods: Standard medical databases such as MEDLINE, Embase, Pubmed, and Cochrane Library were searched to find randomised, controlled trials (RCTs) comparing alcohol-based CHG skin preparation versus aqueous-based PVI in patients undergoing abdominal surgery. The combined outcomes of SSIs were calculated using an odds ratio (OR) with 95% confidence intervals (95% CI). All data were analysed using Review Manager (RevMan) Software 5.4, and the meta-analysis was performed with a random effect model analysis. Results: A total of 11 studies, all RCTs, were included (n= 12072 participants), recruiting adult patients undergoing abdominal surgery. In the random effect model analysis, the use of alcohol-based CHG in patients undergoing abdominal surgery was associated with a reduced risk of SSI compared to aqueous-based PVI (OR: 0.84; 95% CI [0.74, 0.96], z= 2.61, p= 0.009). Conclusion: Alcohol-based CHG may be more effective for preventing the risk of SSI compared to aqueous-based PVI agents in abdominal surgery. The conclusion of this meta-analysis may add a guiding value to reinforce current clinical practice guidelines.

Keywords: skin preparation, surgical site infection, chlorhexidine, skin antiseptics

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Authors: Shekoufeh Behdad, Amirhossein Yadegari, Leila Ghodrati, Saman Yadegari

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Context: Preoperative anxiety is a common psychological reaction experienced by all patients undergoing surgery. It can have negative effects on the patient's well-being and even impact surgical outcomes. Therefore, finding effective interventions to reduce preoperative anxiety is important in improving patient care. Research Aim: The aim of this study is to compare the effects of oral administration of zaleplon (5 mg) and alprazolam (0.5 mg) on preoperative anxiety levels in women undergoing gynecological abdominal surgery. Methodology: This study is a double-blind, randomized clinical trial conducted after receiving approval from the university's ethics committee and obtaining written informed consent from the patients. The night before the surgery, patients were randomly assigned to receive either 0.5 mg of alprazolam or 5 mg of zaleplon orally. Anxiety levels, measured using a 10-cm visual analog scale, and hemodynamic variables (blood pressure and heart rate) were assessed before drug administration and on the morning of the operation after the patient entered the pre-operation room. Findings: The study found that there were no significant differences in mean anxiety levels or hemodynamic variables before and after administration of either drug in both groups (P value > 0.05). This suggests that both 0.5 mg of alprazolam and 5 mg of zaleplon effectively reduce preoperative anxiety in women undergoing abdominal surgery without serious side effects. Theoretical Importance: This study contributes to the understanding of the effectiveness of alprazolam and zaleplon in reducing preoperative anxiety. It adds to the existing literature on pharmacological interventions for anxiety management, specifically in the context of gynecological abdominal surgery. Data Collection: Data for this study were collected through the assessment of anxiety levels using a visual analog scale and measuring hemodynamic variables, including systolic, diastolic, and mean arterial blood pressures, as well as heart rate. These measurements were taken before drug administration and on the morning of the surgery. Analysis Procedures: Statistical analysis was performed to compare the mean anxiety levels and hemodynamic variables before and after drug administration in the two groups. The significance of the differences was determined using appropriate statistical tests. Questions Addressed: This study aimed to answer the question of whether there are differences in the effects of alprazolam and zaleplon on preoperative anxiety levels in women undergoing gynecological abdominal surgery. Conclusion: The oral administration of both 0.5 mg of alprazolam and 5 mg of zaleplon the night before surgery effectively reduces preoperative anxiety in women undergoing abdominal surgery. These findings have important implications for the management of preoperative anxiety and can contribute to improving the overall surgical experience for patients.

Keywords: zaleplon, alprazolam, premedication, abdominal surgery

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Authors: Seema Dutt Bandhu, Yashi Bansal, Tania Moudgil, Barinder Kaur

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Introduction: Scleral perforation during the passage of suture needle is a known complication of strabismus surgery. The present study was conducted to evolve a safe and easy technique of passing the suture needle through the sclera. A scleral tunnel was created with a 26-guage needle through which the suture needle was passed. The rest of the steps of strabismus surgery were carried out as usual. Material and Methods: After taking clearance from the Institutional Ethics Committee, an interventional study was carried out on twenty patients. The scleral tunnel technique was performed on the patients of strabismus after taking written informed consent. Before passing the suture needle through the sclera during strabismus surgery, a tunnel through approximately half the thickness of the sclera was created with the help of a bent 26-gauge needle. The suture needle was then passed through this tunnel. Rest of the steps of the surgery were carried out in the conventional manner. In a control group of same number of patients, the surgery was performed in the conventional method. Both the groups were followed up for any complications. Ease of passing suture and surgeons’ satisfaction with the technique was noted on a 10-point Likert scale. Results: None of the patients in either group suffered from any complications. Four surgeons participated in the study. The average Likert scale score of the surgeons for satisfaction with the technique was 4.5 on a scale of 5. The score for ease of passage of suture needle was 5 on a score of 5. Discussion: Scleral perforation during passing the sutures through the sclera is a known complication of strabismus surgery. Incidence reported is 7.8% It occurs due to inappropriate engagement of the scleral tissue or passage of the suture needle along a wrong axis during the process of passing the suture needle. The needle track technique eases the passage of passing the suture needle through the sclera as the engagement of the scleral tissue can be done with greater control with a 26-guage needle. The surgeons have reported that they are highly satisfied with the technique and they have reported that the technique eased the passage of the suture needle through the sclera.

Keywords: suture, scleral tunnel, strabismus, scleral perforation

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Authors: Maryam Zahedi Fard, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

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New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.

Keywords: antiproliferative effect, MCF-7 human breast cancer cell line, apoptosis, caspases

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Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

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As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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Authors: Fernanda F. Zimmermann, Beverley Burrell, Jennifer Jordan

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Introduction: Supportive care for people affected by cancer is recognised as a priority for research but yet there is little solid evidence of the effectiveness of psychological treatments for those with advanced cancer. The literature suggests that mindfulness-based interventions may be acceptable and beneficial for this population. This study aims to develop a mindfulness intervention to provide emotional support for advanced cancer population. The treatment package includes mindfulness meditation, developing an acceptance attitude and reflections on meaning in life. Methods: This study design is a one-group pre-post test with a mixed methods approach. Participants are recruited through public and private hospitals in Christchurch, NZ. Quantitative measures are the Acceptance and Action Questionnaire-II, Mindful Coping Scale and, the Meaning in Life Questionnaire. Qualitative semi-structured interviews enquire about emotional support before and after the diagnosis, participants’ thoughts about meaning in life, expectations and reflections on the mindfulness training. Qualitative data will be analysed using thematic analysis. Treatment consists of one to one 30 minutes session weekly for 4 weeks using a pre-recorded CD/podcast of the mindfulness training. This research is part of the presenter’s PhD study. Findings: This project is currently underway. The presenter will provide preliminary data on the acceptability of the mindfulness training package being delivered to participants along with the recruitment strategies. We anticipate that this novel treatment used as a self-management tool will reduce psychological distress and enable better coping for patients with advanced cancer.

Keywords: acceptance, cancer, meaning in life, mindfulness

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Authors: Chuan Yin

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

Keywords: cancer stem cells, melanoma, immunoliposomes, CD133

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

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

Keywords: bone cancer, colitis, clostridium difficile, microbiome

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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

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

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Authors: Marjan Moradi fard, Hossein Rassi, Masoud Houshmand

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

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

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Authors: Mihail Nagea, Olivera Lupescu, Elena Taina Avramescu, Cristina Patru

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Classical education of orthopedic surgeons involves lectures, self study, workshops and cadaver dissections, and sometimes supervised practical training within surgery, which quite seldom gives the young surgeons the feeling of being unable to apply what they have learned especially in surgical practice. The purpose of this paper is to present a different approach from the classical one, which enhances the practical skills of the orthopedic trainees and prepare them for future practice. The paper presents the content of the research project 2015-1-RO01-KA202-015230, ERASMUS+ VET ‘Collaborative learning for enhancing practical skills for patient-focused interventions in gait rehabilitation after orthopedic surgery’ which, using e learning as a basic tool , delivers to the trainees not only courses, but especially practical information through videos and case scenarios including gait analysis in order to build patient focused therapeutic plans, adapted to the characteristics of each patient. The outcome of this project is to enhance the practical skills in orthopedic surgery and the results are evaluated following the answers to the questionnaires, but especially the reactions within the case scenarios. The participants will thus follow the idea that any mistake within solving the cases might represent a failure of treating a real patient. This modern approach, besides using interactivity to evaluate the theoretical and practical knowledge of the trainee, increases the sense of responsibility, as well as the ability to react properly in real cases.

Keywords: interdisciplinary approach, gait analysis, orthopedic surgery, vocational training

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

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

Keywords: cardiotoxicity, chemotherapy, GLS, right ventricle

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

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

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

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

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

Keywords: biomarkers, lipidomic, plasmalogen, rectal adenocarcinoma

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

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

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

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

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

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

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

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

Keywords: breast cancer, molecular biology, ecology, environment

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Authors: Smita Lakhotia, C. Kew, S. H. M. Siraj, B. Chern

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Up to 50% of those with endometriosis may suffer from infertility due to either distorted pelvic anatomy/impaired oocyte release or inhibit ovum pickup and transport, altered peritoneal function, endocrine and anovulatory disorders, including LUF, impaired implantation, progesterone resistance or decreased levels of cellular immunity. The dilemma continues as to whether the surgery or IVF is the optimal management for such recurrent endometriomas. The core question is whether surgery adds anything of value for infertile women with recurrent endometriosis or not. Complete and detailed information on risks and benefits of treatment alternatives must be offered to patients, giving a realistic estimate of chances of success of repetitive surgery and of multiple IVF cycles in order to allow unbiased choices between different possible optionsAn individualized treatment plan should be developed taking into account patient age, duration of infertility, previous pregnancies and specific clinical conditions and wish.

Keywords: recurrent endometriosis, infertility, oocyte release, pregnancy

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Authors: Anil Bhandari, Imran Khan Pathan, Peeyush K. Sharma, Rakesh K. Patel, Suresh Purohit

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The purpose of this study was to prepare time and pH dependent release tablets of Ayurvedic Churna formulation and evaluate their advantages as colon targeted drug delivery system. The Vidangadi Churna was selected for this study which contains Embelin and Gallic acid. Embelin is used in Helminthiasis as therapeutic agent. Embelin is insoluble in water and unstable in gastric environment so it was formulated in time and pH dependent tablets coated with combination of two polymers Eudragit L100 and ethyl cellulose. The 150mg of core tablet of dried extract and lactose were prepared by wet granulation method. The compression coating was used in the polymer concentration of 150mg for both the layer as upper and lower coating tablet was investigated. The results showed that no release was found in 0.1 N HCl and pH 6.8 phosphate buffers for initial 5 hours and about 98.97% of the drug was released in pH 7.4 phosphate buffer in total 17 hours. The in vitro release profiles of drug from the formulation could be best expressed first order kinetics as highest linearity (r2= 0.9943). The results of the present study have demonstrated that the time and pH dependent tablets system is a promising vehicle for preventing rapid hydrolysis in gastric environment and improving oral bioavailability of Embelin and Gallic acid for treatment of Helminthiasis.

Keywords: embelin, gallic acid, Vidangadi Churna, colon targeted drug delivery

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Authors: Haile F. Darge, Hsieh C. Tsai

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

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

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

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

Keywords: piperine, paclitaxel, breast cancer, apoptosis

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Authors: Parag Katira, Frederika Rentzeperis, Zuzanna Nowicka, Giada Fiandaca, Thomas Veith, Jack Farinhas, Noemi Andor

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Resource limitations shape the outcome of competitions between genetically heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. A whole-genome duplication (WGD) transforms a diploid cell into a tetraploid one and has been detected in 28-56% of human cancers. If a tetraploid subclone expands, it consistently does so early in tumor evolution, when cell density is still low, and competition for nutrients is comparatively weak – an observation confirmed for several tumor types. WGD+ cells need more resources to synthesize increasing amounts of DNA, RNA, and proteins. To quantify resource limitations and how they relate to ploidy, we performed a PAN cancer analysis of WGD, PET/CT, and MRI scans. Segmentation of >20 different organs from >900 PET/CT scans were performed with MOOSE. We observed a strong correlation between organ-wide population-average estimates of Oxygen and the average ploidy of cancers growing in the respective organ (Pearson R = 0.66; P= 0.001). In-vitro experiments using near-diploid and near-tetraploid lineages derived from a breast cancer cell line supported the hypothesis that DNA content influences Glucose- and Oxygen-dependent proliferation-, death- and migration rates. To model how subpopulations with variable DNA content compete in the resource-limited environment of the human brain, we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time: stiffness, Oxygen, phosphate, glucose, vasculature, dead cells, migrating cells and proliferating cells of various DNA content, and treat conditions such as radiotherapy and chemotherapy. Well-established Fokker-Planck partial differential equations govern the distribution of resources and cells across voxels. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We performed whole genome sequencing (WGS) of four surgical specimens collected during the 1ˢᵗ and 2ⁿᵈ surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the two surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29, respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. The S3MB domain was initiated from 4mm³ voxels of the MNI space. T1 post and T2 flair scan acquired after the 1ˢᵗ surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2ⁿᵈ surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate (0.70 vs. 0.49), but a lower Glucose-dependent death rate (0.47 vs. 1.42). These differences resulted in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions and could help pave the way to therapeutic strategies that mimic prognostically favorable environments.

Keywords: tumor evolution, intra-tumor heterogeneity, whole-genome doubling, mathematical modeling

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

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

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

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