Search results for: pancreatic cancer
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2157

Search results for: pancreatic cancer

1227 Bacteriological Spectrum and Resistance Patterns of Common Clinical Isolates from Infections in Cancer Patients

Authors: Vivek Bhat, Rohini Kelkar, Sanjay Biswas

Abstract:

Introduction: Cancer patients are at increased risk of bacterial infections. This may due to the disease process itself, the effect of chemotherapeutic drugs or invasive procedures such as catheterization. A wide variety of bacteria including some emerging pathogens are increasingly being reported from these patients. The incidence of multidrug-resistant organisms particularly in the Gram negative group is also increasing, with higher resistance rates seen to cephalosporins, β-lactam/β-lactam inhibitor combinations, and the carbapenems. This study documents the bacteriological spectrum of infections and their resistance patterns in cancer patients. Methods: This study includes all bacterial isolates recovered from infections cancer patients over a period of 18 months. Samples included Blood cultures, Pus/wound swabs, urine, tissue biopsies, body fluids, catheter tips and respiratory specimens such as sputum and bronchoalveolar lavage (BAL). All samples were processed in the microbiology laboratory as per standard laboratory protocols. Organisms were identified to species level and antimicrobial susceptibility testing was performed manually by the disc diffusion technique or in the Vitek-2 (Biomereux, France) instrument. Interpretations were as per Clinical laboratory Standards Institute (CLSI) guidelines. Results: A total of 1150 bacterial isolates were cultured from 884 test samples during the study period. Of these 227 were Gram-positive and 923 were Gram-negative organisms. Staphylococcus aureus (99 isolates) was the commonest Gram-positive isolate followed by Enterococcus (79) and Gr A Streptococcus (30). Among the Gram negatives, E. coli (304), Pseudomonas aeruginosa (201) and Klebsiella pneumoniae (190) were the most common. Of the Staphylococcus aureus isolates 27.2% were methicillin resistant. Only 5.06% enterococci were vancomycin resistant. High rates of resistance to cefotaxime and ciprofloxacin were seen amongst E. coli (84.8% & 83.55%) and Klebsiella pneumoniae (71 & 62.1%) respectively. Resistance to carbapenems (meropenem) was high at 70% in Acinetobacter spp.; however all isolates were sensitive to colistin. Among the aminoglycosides, amikacin retained good efficacy against Escherichia coli (82.9%) and Pseudomonas aeruginosa (78.1%). Occasional isolates of emerging pathogens such as Chryseobacterium indologens, Roseomonas, and Achromobacter xyloxidans were also recovered. Conclusion: The common infections in cancer patients include respiratory, wound, tract infections and sepsis. The commonest isolates include Staphylococcus aureus, Enterococci, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. There is a high level of resistance to the commonly used antibiotics among Gram-negative organisms.

Keywords: bacteria, resistance, infection, cancer

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1226 A Prospective Review of Axillary Drainage in Axillary Lymph Node Dissection in Breast Conservation Cancer Surgery

Authors: Ruqayya Naheed Khan, Romaisa Shamim, Awais Amjad Malik, Awais Naeem, Amina Iqbal Khan, Asad Parvaiz

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Objective: Patients undergoing axillary lymph node dissection (ALND) for metastatic lymph nodes in our hospital usually have drains placed in their axilla for a period of 6-10 days. We evaluated the post-op course of patients who underwent breast conservation surgery (BCS) along with ALND. Methods: A prospective cohort study was conducted at Shaukat Khanam Memorial Cancer Hospital from April 2017 to August 2017 including all lymph node positive breast cancer patients undergoing BCS with ALND. Patients were divided into two groups. Group A had no axillary drain while in Group B a drain was placed in axilla. Results: A total of 76 patients were included. 41 patients were included in group A and 35 patients in Group B. Median number of LNs dissected in group A was 17 and in group B was 15 (p value 0.443). Median operative time in group A was 84 min and in group B was 79 min (p value 0.223). Median hospital stay in both groups was 1 day (p value 0.78). At 2 weeks all patients in group A developed seroma as compared to none in group B (p value < 0.001). 3 of these patients in group A required aspiration of seroma due to pressure effects. Rest were managed conservatively. At 6 weeks only 50% patients had a seroma radiologically in Group A as compared to 33% in group B (p value 0.023). No intervention was required in any patients at week 6. QOL at 2 weeks was much better in Group A (7/41 patients had unsatisfactory response) as compared to group B (10/31 had unsatisfactory response). Results were statistically significant (p value 0.045). However, there wasn’t much difference in QOL at 6 weeks. Only 1 patient in group A had an unsatisfactory response. Average pain score at 2 weeks was similar in both groups (4.2 v/s 4.1 p value 0.73). Infection was seen in 1 patient in each group at 2 weeks (p value 0.668) and in only 1 patient in group A at 6 weeks (p value 0.067). Conclusion: We conclude from our study that there isn’t much difference in drain and no drain group in terms of wound infection and pain scores. No drain group is however associated with a better QOL in early post-op period.

Keywords: axillary drainage, axillary lymph node dissection, breast cancer, no drain in axilla

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1225 Synthesis and Cytotoxic Activity of New Quinazolinone-Based Compounds against Human Breast Cancer Cell Line MCF-7

Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Maryam Hajrezaie, Nazia Abdul Majid, Mahmood Ameen Abdulla, Hapipah Mohd Ali

Abstract:

In the current study, we prepared two new quinazoline schiff bases through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The chemical structures of both newly synthesized compounds (1 and 2) were confirmed by FT-IR and X-ray crystallography studies. The cytotoxic effect of compounds was investigated against MCF-7 human breast cancer cells. MTT results showed that (1) and (2) decreased the viability of MCF-7 cells in a time-dependent manner, exhibiting an IC50 value of 3.23 ± 0.28 µg/mL and 3.41 ± 0.34 µg/mL, respectively, after a 72-hours treatment period. In contrast, they did not show significant anti-proliferative effect towards MCF-10A normal breast cells and WRL-68 normal liver cells. We found a perturbation in mitochondrial membrane potential and increased cytochrome c release from the mitochondria to the cytosol, suggesting an activation of apoptosis by compounds, which was confirmed by activation of the initiator caspase-9 and the executioner caspases-3/7. (1) was also able to trigger extrinsic pathway via activation of caspase-8 and inhibition of NF-κB translocation. The acute toxicity test showed no toxicity effect of the compounds in rats. Our results showed that the selected synthesized compounds are highly potent to induce apoptosis in MCF-7 cells via either intrinsic or extrinsic mitochondrial pathway.

Keywords: Quinazoline Schiff base, apoptosis, MCF-7 human breast cancer cell line, caspase, NF-κB translocation

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1224 Thoughts Regarding Interprofessional Work between Nurses and Speech-Language-Hearing Therapists in Cancer Rehabilitation: An Approach for Dysphagia

Authors: Akemi Nasu, Keiko Matsumoto

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Rehabilitation for cancer requires setting up individual goals for each patient and an approach that properly fits the stage of cancer when putting into practice. In order to cope with the daily changes in the patients' condition, the establishment of a good cooperative relationship between the nurses and the physiotherapists, occupational therapists, and speech-language-hearing therapists (therapists) becomes essential. This study will focus on the present situation of the cooperation between nurses and therapists, especially the speech-language-hearing therapists, and aim to elucidate what develops there. A semi-structured interview was conducted targeted at a physical therapist having practical experience in working in collaboration with nurses. The contents of the interview were transcribed and converted to data, and the data was encoded and categorized with sequentially increasing degrees of abstraction to conduct a qualitative explorative factor analysis of the data. When providing ethical explanations, particular care was taken to ensure that participants would not be subjected to any disadvantages as a result of participating in the study. In addition, they were also informed that their privacy would be ensured and that they have the right to decline to participate in the study. In addition, they were also informed that the results of the study would be announced publicly at an applicable nursing academic conference. This study has been approved following application to the ethical committee of the university with which the researchers are affiliated. The survey participant is a female speech-language-hearing therapist in her forties. As a result of the analysis, 6 categories were extracted consisting of 'measures to address appetite and aspiration pneumonia prevention', 'limitation of the care a therapist alone could provide', 'the all-inclusive patient- supportive care provided by nurses', 'expand the beneficial cooperation with nurses', 'providing education for nurses on the swallowing function utilizing videofluoroscopic examination of swallowing', 'enhancement of communication including conferences'. In order to improve the team performance, and for the teamwork competency necessary for the provision of safer care, mutual support is essential. As for the cooperation between nurses and therapists, this survey indicates that the maturing of the cooperation between professionals in order to improve nursing professionals' knowledge and enhance communication will lead to an improvement in the quality of the rehabilitation for cancer.

Keywords: cancer rehabilitation, nurses, speech-language-hearing therapists, interprofessional work

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1223 The Role of Intraluminal Endoscopy in the Diagnosis and Treatment of Fluid Collections in Patients With Acute Pancreatitis

Authors: A. Askerov, Y. Teterin, P. Yartcev, S. Novikov

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Introduction: Acute pancreatitis (AP) is a socially significant problem for public health and continues to be one of the most common causes of hospitalization of patients with pathology of the gastrointestinal tract. It is characterized by high mortality rates, which reaches 62-65% in infected pancreatic necrosis. Aims & Methods: The study group included 63 patients who underwent transluminal drainage (TLD) fluid collection (FC). All patients were performed transabdominal ultrasound, computer tomography of the abdominal cavity and retroperitoneal organs and endoscopic ultrasound (EUS) of the pancreatobiliary zone. The EUS was used as a final diagnostic method to determine the characteristics of FC. The indications for TLD were: the distance between the wall of the hollow organ and the FC was not more than 1 cm, the absence of large vessels on the puncture trajectory (more than 3 mm), and the size of the formation was more than 5 cm. When a homogeneous cavity with clear, even contours was detected, a plastic stent with rounded ends (“double pig tail”) was installed. The indication for the installation of a fully covered self-expanding stent was the detection of nonhomogeneous anechoic FC with hyperechoic inclusions and cloudy purulent contents. In patients with necrotic forms after drainage of the purulent cavity, a cystonasal drainage with a diameter of 7Fr was installed in its lumen under X-ray control to sanitize the cavity with a 0.05% aqueous solution of chlorhexidine. Endoscopic necrectomy was performed every 24-48 hours. The plastic stent was removed in 6 month, the fully covered self-expanding stent - in 1 month after the patient was discharged from the hospital. Results: Endoscopic TLD was performed in 63 patients. The FC corresponding to interstitial edematous pancreatitis was detected in 39 (62%) patients who underwent TLD with the installation of a plastic stent with rounded ends. In 24 (38%) patients with necrotic forms of FC, a fully covered self-expanding stent was placed. Communication with the ductal system of the pancreas was found in 5 (7.9%) patients. They underwent pancreaticoduodenal stenting. A complicated postoperative period was noted in 4 (6.3%) cases and was manifested by bleeding from the zone of pancreatogenic destruction. In 2 (3.1%) cases, this required angiography and endovascular embolization a. gastroduodenalis, in 1 (1.6%) case, endoscopic hemostasis was performed by filling the cavity with 4 ml of Hemoblock hemostatic solution. The combination of both methods was used in 1 (1.6%) patient. There was no evidence of recurrent bleeding in these patients. Lethal outcome occurred in 4 patients (6.3%). In 3 (4.7%) patients, the cause of death was multiple organ failure, in 1 (1.6%) - severe nosocomial pneumonia that developed on the 32nd day after drainage. Conclusions: 1. EUS is not only the most important method for diagnosing FC in AP, but also allows you to determine further tactics for their intraluminal drainage.2. Endoscopic intraluminal drainage of fluid zones in 45.8% of cases is the final minimally invasive method of surgical treatment of large-focal pancreatic necrosis. Disclosure: Nothing to disclose.

Keywords: acute pancreatitis, fluid collection, endoscopy surgery, necrectomy, transluminal drainage

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1222 Breast Cancer as a Response to Distress in Women with or without a History of Precancerous Breast Disease

Authors: Viacheslav Sushko, Viktor Sushko

Abstract:

Pre-cancerous breast diseases are pathological changes that precede the appearance of adenocarcinoma. The most common benign breast disease is mastopathy. We examined the life and disease history of 114 women aged 58-69 who were diagnosed with adenocarcinoma of the breast at different stages of development. They filled out the Reeder Scale to determine the level of stress. The results of the study revealed that 62 of them had mastopathy at the age of 30-45 years old. These women refused surgical treatment for mastopathy. Five to six years before their diagnosis of adenocarcinoma of the mammary gland, 84 women had experienced severe stress (death of a beloved close relative, torture accompanied by rape, prolonged stay in extreme conditions (under bombardment and bombardment). In the assessment of data from completed Reeder scales, 114 women had a high level of mental stress, with a score from 1-1.72. The 84 women who suffered from severe stress showed overeating or a significant decrease in food intake, insomnia, apathy, increased irritability and restlessness, loss of interest in sexual relationships, forgetfulness, difficulty in performing routine work, prolonged uncontrollable headaches, unexplained fatigue, heart pain, reduced capacity for work. In conclusion, it is important to provide psychotherapy for breast cancer patients as the diagnosis, and the different stages of treatment are very stressful. It is also advisable to see a psychiatrist at an early stage and prevent distress and treat precancerous breast disease.

Keywords: breast cancer, distress, mastopathy, severe stress

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1221 Heterogenous Dimensional Super Resolution of 3D CT Scans Using Transformers

Authors: Helen Zhang

Abstract:

Accurate segmentation of the airways from CT scans is crucial for early diagnosis of lung cancer. However, the existing airway segmentation algorithms often rely on thin-slice CT scans, which can be inconvenient and costly. This paper presents a set of machine learning-based 3D super-resolution algorithms along heterogeneous dimensions to improve the resolution of thicker CT scans to reduce the reliance on thin-slice scans. To evaluate the efficacy of the super-resolution algorithms, quantitative assessments using PSNR (Peak Signal to Noise Ratio) and SSIM (Structural SIMilarity index) were performed. The impact of super-resolution on airway segmentation accuracy is also studied. The proposed approach has the potential to make airway segmentation more accessible and affordable, thereby facilitating early diagnosis and treatment of lung cancer.

Keywords: 3D super-resolution, airway segmentation, thin-slice CT scans, machine learning

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1220 Analysis of Expression Data Using Unsupervised Techniques

Authors: M. A. I Perera, C. R. Wijesinghe, A. R. Weerasinghe

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his study was conducted to review and identify the unsupervised techniques that can be employed to analyze gene expression data in order to identify better subtypes of tumors. Identifying subtypes of cancer help in improving the efficacy and reducing the toxicity of the treatments by identifying clues to find target therapeutics. Process of gene expression data analysis described under three steps as preprocessing, clustering, and cluster validation. Feature selection is important since the genomic data are high dimensional with a large number of features compared to samples. Hierarchical clustering and K Means are often used in the analysis of gene expression data. There are several cluster validation techniques used in validating the clusters. Heatmaps are an effective external validation method that allows comparing the identified classes with clinical variables and visual analysis of the classes.

Keywords: cancer subtypes, gene expression data analysis, clustering, cluster validation

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1219 Combined Treatment of Estrogen-Receptor Positive Breast Microtumors with 4-Hydroxytamoxifen and Novel Non-Steroidal Diethyl Stilbestrol-Like Analog Produces Enhanced Preclinical Treatment Response and Decreased Drug Resistance

Authors: Sarah Crawford, Gerry Lesley

Abstract:

This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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1218 Evaluation and Risk Assessment of Heavy Metals Pollution Using Edible Crabs, Based on Food Intended for Human Consumption

Authors: Nayab Kanwal, Noor Us Saher

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The management and utilization of food resources is becoming a big issue due to rapid urbanization, wastage and non-sustainable use of food, especially in developing countries. Therefore, the use of seafood as alternative sources is strongly promoted worldwide. Marine pollution strongly affects marine organisms, which ultimately decreases their export quality. The monitoring of contamination in marine organisms is a good indicator of the environmental quality as well as seafood quality. Monitoring the accumulation of chemical elements within various tissues of organisms has become a useful tool to survey current or chronic levels of heavy metal exposure within an environment. In this perspective, this study was carried out to compare the previous and current levels (Year 2012 and 2014) of heavy metals (Cd, Pb, Cr, Cu and Zn) in crabs marketed in Karachi and to estimate the toxicological risk associated with their intake. The accumulation of metals in marine organisms, both essential (Cu and Zn) and toxic (Pb, Cd and Cr), natural and anthropogenic, is an actual food safety issue. Significant (p>0.05) variations in metal concentrations were found in all crab species between the two years, with most of the metals showing high accumulation in 2012. For toxicological risk assessment, EWI (Estimated weekly intake), Target Hazard quotient (THQ) and cancer risk (CR) were also assessed and high EWI, Non- cancer risk (THQ < 1) showed that there is no serious threat associated with the consumption of shellfish species on Karachi coast. The Cancer risk showed the highest risk from Cd and Pb pollution if consumed in excess. We summarize key environmental health research on health effects associated with exposure to contaminated seafood. It could be concluded that considering the Pakistan coast, these edible species may be sensitive and vulnerable to the adverse effects of environmental contaminants; more attention should be paid to the Pb and Cd metal bioaccumulation and to toxicological risks to seafood and consumers.

Keywords: cancer risk, edible crabs, heavy metals pollution, risk assessment

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1217 Pattern Of Polymorphism SLC22A1 Gene In Children With Diabetes Mellitus Type 2

Authors: Elly Usman, S. Dante, Diah Purnamasari

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Type 2 diabetes mellitus ( T2DM ) is a syndrome characterized by a state of increased blood sugar levels due to chronic disorders of insulin secretion by pancreatic beta cells and insulin action or a combination of both. The organic cation transporter 1, encoded by the SLC22A1 gene, responsible for the uptake of the antihyperglycemic drug, metformin, in the hepatocyte. We assessed whether a genetic variation in the SLC22A1 gene was associated with the glucose - lowering effect of metformin. Method case study research design. Samples are children with type 2 diabetes mellitus who meet the inclusion criteria. The results proportions SLC22A1 gene polymorphisms in children with diabetes mellitus type 2 amounted to 52.04 % at position 400T/C, there is one heterozygous and one at position 595T/C Conclusion The presence of SLC22A1 gene polymorphisms in children with diabetes mellitus type 2.

Keywords: diabetes Mellitus type 2, metformin, organic cation transporter 1, pharmacogenomics

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1216 Performance of Visual Inspection Using Acetic Acid for Cervical Cancer Screening as Compared to HPV DNA Testingin Ethiopia: A Comparative Cross-Sectional Study

Authors: Agajie Likie Bogale, Tilahun Teklehaymanot, Getnet Mitike Kassie, Girmay Medhin, Jemal Haidar Ali, Nega Berhe Belay

Abstract:

Objectives: The aim of this study is to evaluate the performance of visual inspection using acetic acid compared with HPV DNA testing among women living with HIV in Ethiopia. Methods: Acomparative cross-sectional study was conducted to address the aforementioned objective. Data were collected from January to October 2021 to compare the performance of these two screening modalities. Trained clinicians collected cervical specimens and immediately applied acetic acid for visual inspection. The HPV DNA testing was done using Abbott m2000rt/SP by trained laboratory professionals in accredited laboratories. A total of 578 HIV positive women with age 25-49 years were included. Results: Test positivity was 8.9% using VIA and 23.3% using HPV DNA test. The sensitivity and specificity of the VIA test were 19.2% and 95.1%, respectively, while the positive and negative predictive values of the VIA test were 54.4% and 79.4%, respectively. The strength of agreement between the two screening methods was poor (k=0.184), and the area under the curve was 0.572. The burden of genetic distribution of high risk HPV16 was 3.8%, and mixed HPV16& other HR HPV was 1.9%. Other high risk HPV types were predominant in this study (15.7%). Conclusion: The high positivity result using HPV DNA testing compared with VIA, and low sensitivity of VIA are indicating that the implementation of HPV DNA testing as the primary screening strategy is likely to reduce cervical cancer cases and deaths of women in the country.

Keywords: cervical cancer screening, HPV DNA, VIA, Ethiopia

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1215 Difficulties in Providing Palliative Care in Rural India, West Bengal: Experience of an NGO

Authors: Aditya Manna

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Introduction: As in any developing countries state of West Bengal in India has a huge burden of cancer patients in advanced stage coming from rural area where awareness regarding the usefulness of palliative care in rather poor. Objective: Our goal is to give a pain free good quality of life in these advanced stage cancer patients. Objective of this study is to identify the main difficulties in achieving the above goal in a rural village setting in India. Method: Advanced cancer patients in need of palliative care in various villages in of rural India were selected for this study. Their symptoms and managements in that rural surroundings were evaluated by an NGO (under the guidance of a senior palliative care specialist) working in that area. An attempt was made to identify the main obstacles in getting proper palliative care in a rural setting. Results: Pain, fatigue are the main symptoms effecting these patients. In most patients pain and other symptoms control were grossly inadequate due to lack of properly trained manpower in the rural India. However regular homecare visits by a group of social workers were of immense help in the last few months of life. NGO team was well guided by a palliative care specialist. Conclusion: There is a wide gap of trained manpower in this filled in rural areas of India. Dedicated groups from rural area itself need encouragement and proper training, so that difficult symptoms can be managed locally along with necessary social and psychological support to these patients.

Keywords: palliative care, NGO, rural India, home care

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1214 Safety and Efficacy of Laparoscopic D2 Gastrectomy for Advanced Gastric Cancers Single Unit Experience

Authors: S. M. P Manjula, Ishara Amarathunga, Aryan Nath Koura, Jaideepraj Rao

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Background: Laparoscopic D2 Gastrectomy for non metastatic advanced Gastric cancer (AGC) has become a controversial topic as there are confronting ideas from experts in the field. Lack of consensus are mainly due to non feasibility of the dissection and safety and efficacy. Method: Data from all D2 Gastrectomies performed (both Subtotal and Total Gastrectomies) in our unit from 2009 December to 2013 December were retrospectively analysed. Computor database was prospectively maintained. Pathological stage two A (iiA) and above considered advanced Gastric cancers, who underwent curative intent D2 Gastrectomy were included for analysis(n=46). Four patients excluded from the study as peritoneal fluid cytology came positive for cancer cells and one patient exempted as microscopic resection margin positive(R1) after curative resection. Thirty day morbidity and mortality, operative time, lymph nodes harvest and survival (disease free and overall) analyzed. Results: Complete curative resection achieved in 40 patients. Mean age of the study population was 62.2 (32-88) and male to female ratio was 23: 17. Thirty day mortality (1/40) and morbidity (6/40). Average operative time 203.7 minutes (185- 400) and average lymphnodes harvest was 40.5 (18-91). Disease free survival of the AGC in this study population was 16.75 months (1-49). Average hospital stay was 6.8 days (3-31). Conclusion: Laparoscopic dissection is effective feasible and safe in AGC.

Keywords: laparoscopy, advanced gastric cancer, safety, efficacy

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1213 Postoperative Radiotherapy in Cancers of the Larynx: Experience of the Emir Abdelkader Cancer Center of Oran, about 89 Cases

Authors: Taleb Lotfi, Benarbia Maheidine, Allam Hamza, Boutira Fatima, Boukerche Abdelbaki

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Introduction and purpose of the study: This is a retrospective single-center study with an analytical aim to determine the prognostic factors for relapse in patients treated with radiotherapy after total laryngectomy with lymph node dissection for laryngeal cancer at the Emir Abdelkader cancer center in Oran (Algeria). Material and methods: During the study period from January 2014 to December 2018, eighty-nine patients (n=89) with squamous cell carcinoma of the larynx were treated with postoperative radiotherapy. Relapse-free survival was studied in the univariate analysis according to pre-treatment criteria using Kaplan-Meier survival curves. We performed a univariate analysis to identify relapse factors. Statistically significant factors have been studied in the multifactorial analysis according to the Cox model. Results and statistical analysis: The average age was 62.7 years (40-86 years). It was a squamous cell carcinoma in all cases. Postoperatively, the tumor was classified as pT3 and pT4 in 93.3% of patients. Histological lymph node involvement was found in 36 cases (40.4%), with capsule rupture in 39% of cases, while the limits of surgical excision were microscopically infiltrated in 11 patients (12.3%). Chemotherapy concomitant with radiotherapy was used in 67.4% of patients. With a median follow-up of 57 months (23 to 104 months), the probabilities of relapse-free survival and five-year overall survival are 71.2% and 72.4%, respectively. The factors correlated with a high risk of relapse were locally advanced tumor stage pT4 (p=0.001), tumor site in case of subglottic extension (p=0.0003), infiltrated surgical limits R1 (p=0.001), l lymph node involvement (p=0.002), particularly in the event of lymph node capsular rupture (p=0.0003) as well as the time between surgery and adjuvant radiotherapy (p=0.001). However, in the subgroup analysis, the major prognostic factors for disease-free survival were subglottic tumor extension (p=0.001) and time from surgery to adjuvant radiotherapy (p=0.005). Conclusion: Combined surgery and postoperative radiation therapy are effective treatment modalities in the management of laryngeal cancer. Close cooperation of the entire cervicofacial oncology team is essential, expressed during a multidisciplinary consultation meeting, with the need to respect the time between surgery and radiotherapy.

Keywords: laryngeal cancer, laryngectomy, postoperative radiotherapy, survival

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1212 Metastatic Papillary Thyroid Carcinoma in Pleural Effusion- A Very Rare Case

Authors: Mohammed A. Abutalib

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Papillary thyroid carcinoma (PTC) accounts for the most common type of thyroid cancer, a well-differentiated type. PTC is featured by biologically low-grade and less aggressive tumors with a survival rate of 10 years in most of the diagnosed cases. PTC can be presented with the involvement of cervical lymph nodes in about 50% of the patients, yet the distant spread is very uncommon. Herein, we discussed an early 50-year-old male patient with a history of PTC that presented to the emergency department complaining of shortness of breath and a radiological finding of hydrothorax. Cytologic examination, together with immune-histochemical staining and molecular studies of pleural effusion aspiration, concluded the definitive diagnosis of metastatic papillary thyroid carcinoma in the pleural space. PTC seldom causes metastatic niches in the pleural space, and this is a rare clinical presentation; nevertheless, a differential diagnosis of thyroid metastasis needs to be excluded.

Keywords: thyroid cancer, malignant pleural effusion, cytology aspiration, papillary thyroid carcinoma

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1211 Effects of Starvation, Glucose Treatment and Metformin on Resistance in Chronic Myeloid Leukemia Cells

Authors: Nehir Nebioglu

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Chemotherapy is widely used for the treatment of cancer. Doxorubicin is an anti-cancer chemotherapy drug that is classified as an anthracycline antibiotic. Antitumor antibiotics consist of natural products produced by species of the soil fungus Streptomyces. These drugs act in multiple phases of the cell cycle and are known cell-cycle specific. Although DOX is a precious clinical antineoplastic agent, resistance is also a problem that limits its utility besides cardiotoxicity problem. The drug resistance of cancer cells results from multiple factors including individual variation, genetic heterogeneity within a tumor, and cellular evolution. The mechanism of resistance is thought to involve, in particular, ABCB1 (MDR1, Pgp) and ABCC1 (MRP1) as well as other transporters. Several studies on DOX-resistant cell lines have shown that resistance can be overcome by an inhibition of ABCB1, ABCC1, and ABCC2. This study attempts to understand the effects of different concentration levels of glucose treatment and starvation on the proliferation of Doxorubicin resistant cancer cells lines. To understand the effect of starvation, K562/Dox and K562 cell lines were treated with 0, 5 nM, 50 nM, 500 nM, 5 uM and 50 uM Dox concentrations in both starvation and normal medium conditions. In addition to this, to interpret the effect of glucose treatment, different concentrations (0, 1 mM, 5 mM, 25 mM) of glucose were applied to Dox-treated (with 0, 5 nM, 50 nM, 500 nM, 5 uM and 50 uM) K562/Dox and K652 cell lines. All results show significant decreasing in the cell count of K562/Dox, when cells were starved. However, while proliferation of K562/Dox lines decrease is associated with the increasingly applied Dox concentration, K562/Dox starved ones remain at the same proliferation level. Thus, the results imply that an amount of K562/Dox lines gain starvation resistance and remain resistant. Furthermore, for K562/Dox, there is no clear effect of glucose treatment in terms of cell proliferation. In the presence of a moderate level of glucose (5 mM), proliferation increases compared to other concentration of glucose for each different Dox application. On the other hand, a significant increase in cell proliferation in moderate level of glucose is only observed in 5 uM Dox concentration. The moderate concentration level of Dox can be examined in further studies. For the high amount of glucose (25 mM), cell proliferation levels are lower than moderate glucose application. The reason could be high amount of glucose may not be absorbable by cells. Also, in the presence of low amount of glucose, proliferation is decreasing in an orderly manner of increase in Dox concentration. This situation can be explained by the glucose depletion -Warburg effect- in the literature.

Keywords: drug resistance, cancer cells, chemotherapy, doxorubicin

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1210 The Experiences and Needs of Mothers’ of Children With Cancer in Coping With the Child's Disease

Authors: Maarja Karbus, Elsbet Lippmaa, Kadri Kööp, Mare Tupits

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Aim: The aim is to describe the experiences and needs of mothers of children with cancer in coping with the child's illness. Background: Cancer affects different life areas. Especially if it is a child, in this case the whole family is involved. Loved ones are mentally affected, there are limitations, and life changes need to be made to make the whole treatment regimen and recovery as comfortable as possible. Also, the whole process is expensive and time consuming. The research is part of a larger project that covers the experiences and needs of parents of children with chronic illness and coping strategies related to the child's illness. Design: Qualitative, empirical, descriptive research. Method: Semi-structured interviews were used to collect data and inductive content analysis was used to analyze the data. The interviews were conducted in the autumn of 2020, 5 respondents participated in the research. Results and Conclusions: The research revealed that the mothers' experiences of coping with a child's disease included health-related experiences, material aspects, changes in lifestyle, support systems and contact with professionals. Regarding the organizational and material aspects of life, the subjects presented experiences with economic problems, adaptation of changes in lifestyle, access to information and changes in the treatment process. With regard to health, the respondents identified experiences with the mother's physical and mental health and experiences with the health of an ill child. The experience of different support systems was related to the support of family, friends, acquaintances, various organizations and specialists. Experiences with specialist support included experiences with family relationships and positive and negatiive experiences with staff. The mothers' needs in dealing with the child's disease included the mother's emotional needs, the support of other family members, and the need for various support systems and services. The needs of coping with the child were the need for understanding, support, confidence, the need to be strong and courageous, the need to ignore one's own needs, and the need for personal time and rest. The needs of other family members included the needs of an ill child and the need to pay attention to other children in the family. The needs of different supporters and services were related to different helpers and different services.

Keywords: cancer, mother, coping, child, need, experience, illness

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1209 Factors Associated with Mammography Screening Behaviors: A Cross-Sectional Descriptive Study of Egyptian Women

Authors: Salwa Hagag Abdelaziz, Naglaa Fathy Youssef, Nadia Abdellatif Hassan, Rasha Wesam Abdelrahman

Abstract:

Breast cancer is considered as a substantial health concern and practicing mammography screening [MS] is important in minimizing its related morbidity. So it is essential to have a better understanding of breast cancer screening behaviors of women and factors that influence utilization of them. The aim of this study is to identify the factors that are linked to MS behaviors among the Egyptian women. A cross-sectional descriptive design was carried out to provide a snapshot of the factors that are linked to MS behaviors. A convenience sample of 311 women was utilized and all eligible participants admitted to the Women Imaging Unit who are 40 years of age or above, coming for mammography assessment, not pregnant or breast feeding and who accepted to participate in the study were included. A structured questionnaire was developed by the researchers and contains three parts; Socio-demographic data; Motivating factors associated with MS; and association between MS and model of behavior change. The analyzed data indicated that most of the participated women (66.6 %) belonged to the age group of 40-49.A high proportion of participants (58.1%) of group having previous MS influenced by their neighbors to practice MS, whereas 32.7 % in group not having previous MS were influenced by family members which indicated significant differences (P <0.05). Doctors and media are shown to be the least influence of others to practice MS. Women with intention to have a future mammogram had higher OR (1.404) for practicing MS compared with women with no intention. Further studies are needed to examine the relation between Trans-theoretical Model [TTM] and practicing MS.

Keywords: breast cancer, mammography, screening behaviors, morbidity

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1208 Giant Filiform Polyposis in a Patient with Ulcerative Colitis Mimicking Colorectal Cancer

Authors: Godwin Dennison, Edwin Cooper, George Theobald, Richard Dalton

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We report an unusual case of giant filiform polyposis in a patient with ulcerative colitis, causing a large stricture in the colon. A 62-year-old man was referred to the Bowel Cancer Screening Programme with a positive Faecal Immunochemical Test (FIT). He was known to have UC for 30 years. A CT scan showed a 9 cm stricture in the transverse colon suspicious of malignancy. A colonoscopy was attempted three times, and biopsies confirmed features of ulcerative colitis. A laparoscopic assisted transverse colectomy (Left hemicolectomy) was performed, and the histology revealed giant filiform polyposis. This should be considered in a UC patient presenting with signs of obstruction mimicking a carcinoma. Whilst it is a benign condition, because of the size of the lesion, it often causes obstruction, and surgery is indicated to relieve symptoms.

Keywords: giant inflammatory polyposis, filiform polyposis, ulcerative colitis, inflammatory bowel disease

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1207 Contrast Enhancement of Masses in Mammograms Using Multiscale Morphology

Authors: Amit Kamra, V. K. Jain, Pragya

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Mammography is widely used technique for breast cancer screening. There are various other techniques for breast cancer screening but mammography is the most reliable and effective technique. The images obtained through mammography are of low contrast which causes problem for the radiologists to interpret. Hence, a high quality image is mandatory for the processing of the image for extracting any kind of information from it. Many contrast enhancement algorithms have been developed over the years. In the present work, an efficient morphology based technique is proposed for contrast enhancement of masses in mammographic images. The proposed method is based on Multiscale Morphology and it takes into consideration the scale of the structuring element. The proposed method is compared with other state-of-the-art techniques. The experimental results show that the proposed method is better both qualitatively and quantitatively than the other standard contrast enhancement techniques.

Keywords: enhancement, mammography, multi-scale, mathematical morphology

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1206 Identification of Breast Anomalies Based on Deep Convolutional Neural Networks and K-Nearest Neighbors

Authors: Ayyaz Hussain, Tariq Sadad

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Breast cancer (BC) is one of the widespread ailments among females globally. The early prognosis of BC can decrease the mortality rate. Exact findings of benign tumors can avoid unnecessary biopsies and further treatments of patients under investigation. However, due to variations in images, it is a tough job to isolate cancerous cases from normal and benign ones. The machine learning technique is widely employed in the classification of BC pattern and prognosis. In this research, a deep convolution neural network (DCNN) called AlexNet architecture is employed to get more discriminative features from breast tissues. To achieve higher accuracy, K-nearest neighbor (KNN) classifiers are employed as a substitute for the softmax layer in deep learning. The proposed model is tested on a widely used breast image database called MIAS dataset for experimental purposes and achieved 99% accuracy.

Keywords: breast cancer, DCNN, KNN, mammography

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1205 Timing of Ileostomy Closure Following Rectal Cancer Surgery at an Australian Regional Hospital

Authors: Tedman Cheuk-Yiu Chau, Xavier Harvey, Hung Nguyen

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Defunctioning ileostomies are frequently used as an adjunct to low anterior resection in the surgical treatment of rectal cancer. Despite reducing the rate of clinically relevant anastomotic leak, the burden of defunctioning ileostomy is significant, with up to two-thirds of patients reporting stoma-related morbidity. International data have demonstrated an increased risk of bowel dysfunction and lower quality of life in patients with delayed closure (greater than six months post-surgery). While timely reversal is safe and cost-effective, the time to the reversal in Australian and New Zealand public hospitals is not described in the published literature. Thus, it is important to assess the current timeliness of ileostomy closure in the Australian regional context and examine the reasons for the delay. A retrospective analysis of ileostomy closure in Launceston General Hospital (LGH) patients treated with low/ultra low anterior resection for rectal cancer between 2012 and 2019 was undertaken. 94 cases of rectal adenocarcinoma undergoing ultralow anterior resection were examined over the years between 2012-2019. Amongst these, 21 cases (22.3%) were not reversed due to disease progress, death prior to reversal, or surgical complication. Demographics, disease status, surgical technique, and hospital inpatient events of these cases were examined. An average waiting time of 213.2 days was noted. Reasons for the delay include non-specified/prolonged hospital waiting time (54%), delayed or complicated chemotherapy course (13%), surgical complication (11%), advanced age, and frailty(5%). Complication of a delayed ileostomy reversal includes post-operation ileus and the development of an incisional hernia. We conclude that a delayed reversal of ileostomy can contribute to a higher incidence of stoma-related co-morbidities and contribute to a longer hospital stay and therefore use of public hospital resources.

Keywords: anterior resection, colorectal surgery, ileostomy reversal, rectal cancer

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1204 Pleomorphic Dermal Sarcoma: A Management Challenge

Authors: Mona Nada, Fahmy Fahmy

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Background: Pleomorphic dermal sarcoma is a rare form of skin cancer affecting cutaneous layer and, in some cases associated with recurrence and metastasis, very commonly to seen in elderly patient affecting the area of head and neck. Pleomorphic dermal sarcoma rises in ultraviolet light exposed areas. The symptoms and severity of this kind of skin cancer varies according to histological factors. The differentiation of Pleomorphic dermal sarcoma needs extensive immunohistochemistry, as the diagnosis depends mainly on exclusion to rule out other malignancy like poorly differentiated squamous cell carcinoma, melanoma, angiosarcoma and leiomyosarcoma. Objective: assessing the management of Pleomorphic dermal sarcoma in our unit and compared to the updated guidelines. Design: Retrospective study Collection of patient data from medical records at countess of Chester plastic surgery unit of the last 5 years, all histologically confirmed Pleomorphic dermal sarcoma (2017-2023). Data were collected confirmed to be Pleomorphic dermal sarcoma were included in the study. The data collected: clinical description of the lesions at first presentation, operation time, multidisciplinary team discussion, plan, referral as well as second operation and investigation done. With comparison of histological examination, immunohistochemistry staining, the excision and rate of recurrence. Results: data collected N19 from (2017-2023) showed the disease predominantly affecting males and the lesion mainly in head and neck, the diagnosis needed extensive immunohistochemistry to differentiate between other malignancy. recurrence present in numbers of the cases which managed after multidisciplinary team discussion either by excision or radiotherapy. Conclusion: Pleomorphic dermal sarcoma is a rare malignancy which needs more understanding and avoid missing as it is aggressive form of skin cancer, there is a chance of metastasis and recurrence which makes it very important to understand the process of development of the cancer and frequent review of the management guidelines.

Keywords: pleomorphic dermal sarcoma, recurrence, radiotherapy, surgical

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1203 Significant Factor of Magnetic Resonance for Survival Outcome in Rectal Cancer Patients Following Neoadjuvant Combined Chemotherapy and Radiation Therapy: Stratification of Lateral Pelvic Lymph Node

Authors: Min Ju Kim, Beom Jin Park, Deuk Jae Sung, Na Yeon Han, Kichoon Sim

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Purpose: The purpose of this study is to determine the significant magnetic resonance (MR) imaging factors of lateral pelvic lymph node (LPLN) on the assessment of survival outcomes of neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with mid/low rectal cancer. Materials and Methods: The institutional review board approved this retrospective study of 63 patients with mid/low rectal cancer who underwent MR before and after CRT and patient consent was not required. Surgery performed within 4 weeks after CRT. The location of LPLNs was divided into following four groups; 1) common iliac, 2) external iliac, 3) obturator, and 4) internal iliac lymph nodes. The short and long axis diameters, numbers, shape (ovoid vs round), signal intensity (homogenous vs heterogenous), margin (smooth vs irregular), and diffusion-weighted restriction of LPLN were analyzed on pre- and post-CRT images. For treatment response using size, lymph node groups were defined as group 1) short axis diameter ≤ 5mm on both MR, group 2) > 5mm change into ≤ 5mm after CRT, and group 3) persistent size > 5mm before and after CRT. Clinical findings were also evaluated. The disease-free survival and overall survival rate were evaluated and the risk factors for survival outcomes were analyzed using cox regression analysis. Results: Patients in the group 3 (persistent size >5mm) showed significantly lower survival rates than the group 1 and 2 (Disease-free survival rates of 36.1% and 78.8, 88.8%, p < 0.001). The size response (group 1-3), multiplicity of LPLN, the level of carcinoembryonic antigen (CEA), patient’s age, T and N stage, vessel invasion, perineural invasion were significant factors affecting disease-free survival rate or overall survival rate using univariate analysis (p < 0.05). The persistent size (group 3) and multiplicity of LPLN were independent risk factors among MR imaging features influencing disease-free survival rate (HR = 10.087, p < 0.05; HR = 4.808, p < 0.05). Perineural invasion and T stage were shown as independent histologic risk factors (HR = 16.594, p < 0.05; HR = 15.891, p < 0.05). Conclusion: The persistent size greater than 5mm and multiplicity of LPLN on both pre- and post-MR after CRT were significant MR factors affecting survival outcomes in the patients with mid/low rectal cancer.

Keywords: rectal cancer, MRI, lymph node, combined chemoradiotherapy

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1202 Chemopreventive Efficacy Of Cdcl2(C14H21N3O2) in Rat Colon Carcinogenesis Model Using Aberrant Crypt Foci (ACF) as Endpoint Marker

Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia AbdulMajid, Maryam Zahedifard

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Colon cancer is one of the most prevalent cancers in the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. New schiff based compounds are reported to exhibit a wide spectrum of biological activities of therapeutic importance. To evaluate inhibitory properties of CdCl2(C14H21N3O2) complex on colonic aberrant crypt foci, five groups of 7-week-old male rats were used. Control group was fed with 10% Tween 20 once a day, cancer control group was intra-peritoneally injected with 15 mg/kg Azoxymethan, drug control group was injected with 15 mg/kg azoxymethan and 5-Flourouracil, experimental groups were fed with 2.5 and 5 mg/kg CdCl2(C14H21N3O2) compound each once a day. Administration of compound were found to be effectively chemoprotective. Andrographolide suppressed total colonic ACF formation up to 72% to 74%, respectively, when compared with control group. The results also showed a significant increase in glutathione peroxidase, superoxide dismutase, catalase activities and a decrease in malondialdehyde level. Immunohistochemical staining demonstrated down-regulation of PCNA protein. According to the Western blot comparison analysis, COX-2 and Bcl2 is up-regulated whilst the Bax is down-regulated. according to these data, this compound plays promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, Schiff based compound, aberrant crypt foci (ACF), immunohistochemical staining

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1201 Thermodynamic and Immunochemical Studies of Antibody Biofunctionalized Gold Nanoparticles Mediated Photothermal Ablation in Human Liver Cancer Cells

Authors: Lucian Mocan, Flaviu Tabaran, Teodora Mocan, Cristian Matea, Cornel Iancu

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We present method of Gold Nanoparticle enhanced laser thermal ablation of HepG2 cells (Human hepatocellular liver carcinoma cell line), based on a simple gold nanoparticle carrier system, such as serum albumin (BSA), and demonstrate its selective therapeutic efficacy. Hyperspectral, contrast phase, and confocal microscopy combined immunochemical staining were used to demonstrate the selective internalization of HSA-GNPs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. We examined the ability of laser-activated carbon nanotubes to induce Hsp70 expression using confocal microscopy. Hep G2 cells heat-shocked (laser activated BSA-GNPs) to 42°C demonstrated an up-regulation of Hsp70 compared with control cells (BSA-GNPs treated cells without laser), which showed no detectable constitutive expression of Hsp70. We observed a time-dependent induction in Hsp70 expression in Hep G2 treated with BSA-GNPs and LASER irradiated. The post-irradiation apoptotic rate of HepG2 cells treated with HSA-GNPs ranged from 88.24% (for 50 mg/L) at 60 seconds, while at 30 minute the rate increased to 92.34% (50 mg/L). These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

Keywords: gold nanoparticles, liver cancer, albumin, laser irradiation

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1200 New Targets Promoting Oncolytic Virotherapy

Authors: Felicia Segeth, Florian G. Klein, Lea Berger, Andreas Kolk, Per S. Holm

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The entry of oncolytic viruses (OVs) into clinical application opens groundbreaking changes in current and future treatment regimens. However, despite their potent anti-cancer activity in vitro, clinical studies revealed limitations of OVs as monotherapy. The same applies to CDK 4/6 inhibitors (CDK4/6i) targeting cell cycle as well as bromodomain and extra-terminal domain inhibitors (BETi) targeting gene expression. In this study, the anti-tumoral effect of XVir-N-31, an YB-1 dependent oncolytic adenovirus, was evaluated in combination with Ribociclib, a CDK4/6i, and JQ1, a BETi. The head and neck squamous cell carcinoma (HNSCC) cell lines Fadu, SAS, and Cal-33 were used. DNA replication and gene expression of XVir-N-31 was measured by RT-qPCR, protein expression by western blotting, and cell lysis by SRB assays. Treatment with CDK4/6i and BETi increased viral gene expression, viral DNA replication, and viral particle formation. The data show that the combination of oncolytic adenovirus XVir-N-31 with CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore, additional molecular analyses on this subject demonstrate that the positive transcription elongation factor P-TEFb plays a decisive role in this regard, indicating an influence of the combinational therapy on gene transcription control. The combination of CDK4/6i & BETi and XVir-N-31 is an attractive strategy to achieve substantial cancer cell killing and is highly suitable for clinical testing.

Keywords: adenovirus, BET, CDK4/6, HNSCC, P-TEFb, YB-1

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1199 Bereavement Risk Assessment of Family Caregivers of Patients with Cancer: Relationship between Bereavement Risk and Post-Loss Psychological Distress

Authors: Tomohiro Uchida, Noriaki Satake, Toshimichi Nakaho, Akira Inoue, Hidemitsu Saito

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In this study, we assessed the bereavement risk of family caregivers of patients with cancer. In the palliative care unit of Tohoku University Hospital, we conducted a family psychoeducation session to support the family caregivers of patients with cancer. A total of 50 participants (8 males and 42 females; mean age = 62.98 years, SD = 11.10) were assessed after the session for bereavement risk using the Japanese version of the Bereavement Risk Assessment Tool (BRAT-J). According to the BRAT-J scores, eight participants were considered to be having no known risk (Level 1), seventeen had minimal risk (Level 2), twenty had a low risk (Level 3), four had a moderate risk (Level 4), and one had a high risk (Level 5). Of these participants, seven participants had completed the follow-up postal survey that assessed their psychological distress (the Kessler Psychological Distress Scale: K6) to compare the bereavement risk. According to the K6 scores, three-fourth of the individuals, who were considered to be at Level 3 on the BRAT-J, scored higher than the cutoff point (>10) for the detection of depressive disorder. On the other hand, one-third of the individuals, who were considered to be at Level 2 on the BRAT-J, scored higher than the cutoff point. Therefore, it appears that the BRAT-J can predict the likelihood of difficulties or complications in bereaved family caregivers. This research was approved by the Ethics Committee of Tohoku University Graduate School of Medicine and Tohoku University Hospital.

Keywords: palliative care, family caregivers, bereavement risk, BRAT, post-loss psychological distress

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1198 Long Non-Coding RNAs Mediated Regulation of Diabetes in Humanized Mouse

Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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