Search results for: bone cancer

Authors: Elyas Palantei, Dewiani, Farid Armin, Ardiansyah

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High precision of printed microwave sensor utilized for sensing and monitoring the potential breast cancer existed in women breast tissue was optimally computed. The single element of UWB printed sensor that successfully modeled through several numerical optimizations was multiple fabricated and incorporated with woman bra to form the spherical sensors array. One sample of UWB microwave sensor obtained through the numerical computation and optimization was chosen to be fabricated. In overall, the spherical sensors array consists of twelve stair patch structures, and each element was individually measured to characterize its electrical properties, especially the return loss parameter. The comparison of S11 profiles of all UWB sensor elements is discussed. The constructed UWB sensor is well verified using HFSS programming, CST programming, and experimental measurement. Numerically, both HFSS and CST confirmed the potential operation bandwidth of UWB sensor is more or less 4.5 GHz. However, the measured bandwidth provided is about 1.2 GHz due to the technical difficulties existed during the manufacturing step. The configuration of UWB microwave sensing and monitoring system implemented consists of 12 element UWB printed sensors, vector network analyzer (VNA) to perform as the transceiver and signal processing part, the PC Desktop/Laptop acting as the image processing and displaying unit. In practice, all the reflected power collected from whole surface of artificial breast model are grouped into several numbers of pixel color classes positioned on the corresponding row and column (pixel number). The total number of power pixels applied in 2D-imaging process was specified to 100 pixels (or the power distribution pixels dimension 10x10). This was determined by considering the total area of breast phantom of average Asian women breast size and synchronizing with the single UWB sensor physical dimension. The interesting microwave imaging results were plotted and together with some technical problems arisen on developing the breast sensing and monitoring system are examined in the paper.

Keywords: UWB sensor, UWB microwave imaging, spherical array, breast cancer monitoring, 2D-medical imaging

Procedia PDF Downloads 189

Authors: Huang Wei-Yi

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Objective: This article explores the intensive care nursing experience of a terminal lung cancer patient who received palliative care after tracheal intubation. The patient was nearing death, and the family experienced sadness and grief as they faced the patient’s deteriorating condition and impending death. Methods: The patient was diagnosed with lung cancer in 2018 and received chemotherapy and radiation therapy with regular outpatient follow-ups. Due to brain metastasis and recent poor pain control and treatment outcomes, the patient was admitted to the intensive care unit (ICU), where the tracheal tube was removed, and palliative care was initiated. During the care period, a holistic assessment was conducted, addressing the physical, psychological, social, and spiritual aspects of care. Medical records were reviewed, interviews and family meetings were held, and a comprehensive assessment was carried out by the critical care team in collaboration with the palliative care team. The primary nursing issues identified included pain, ineffective breathing patterns, fear of death, and altered tissue perfusion. Results: Throughout the care process, the palliative care nurse, along with the family, utilized listening, caring, companionship, pain management, essential oil massage, distraction, and comfortable positioning to alleviate the patient’s pain and breathing difficulties. The use of Morphine 6mg in 0.9% N/S 50ml IV drip q6h reduced the FLACC pain score from 6 to 3. The patient’s respiratory rate improved from 28 breaths/min to 18-22 breaths/min, and sleep duration increased from 4 to 7 uninterrupted hours. The holistic palliative care approach, coupled with the involvement of the palliative care team, facilitated expressions of gratitude, apologies, and love between the patient and family. Visiting hours were extended, and with the nurse’s assistance, these moments were recorded and shared with the patient’s consent, providing cherished memories for the family. The patient’s end-of-life experience was thus improved, and the family was able to find peace. This case also served to promote the concept of palliative care, ensuring that more patients and families receive high-quality nursing care. Conclusion: When caring for terminal patients, collaboration with the palliative care team, including social workers, clergy, psychologists, and nutritionists, is essential. Involving the family in decision-making and providing opportunities for closeness and expressions of gratitude improve personalized care and enhance the patient's quality of life. Upon transferring to the ward, the patient’s hemodynamic stability was maintained, including SBP 110-130 mmHg, respiratory rate 20-22 breaths/min, and pain score <3. The patient was later discharged and transitioned to home hospice care for ongoing support.

Keywords: intensive care, lung cancer, palliative care, ICU

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Authors: Nkechi V. Enwuru, Bullum Nkeki, Elizabeth A. Adekoya, Olumide A. Adebesin, Rebecca F. Peters, Victoria A. Aikhomu, Mendie E. U.

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Background: Probiotics are live microbial feed supplement beneficial for host. Probiotics and their postbiotic products have been used to prevent or treat various health conditions. However, the products cell viability is often low due to harsh conditions subjected during processing, handling, storage, and gastrointestinal transit. These strongly influence probiotics’ benefits; thus, viability is essential for probiotics to produce health benefits for the host. Microencapsulation is a promising technique with considerable effects on probiotic survival. The study is aimed to formulate a microencapsulated probiotic and evaluate its viability, antimicrobial efficacy, and cytotoxic activity of its postbiotic on the MCF-7 breast cancer cell line. Method: Human and animal raw milk were sampled for lactic acid bacteria. The isolated bacteria were identified using conventional and VITEK 2 systems. The identified lactic acid bacterium was encapsulated using spray-dried and extrusion methods. The free, encapsulated, and chitosan-coated encapsulated probiotics were tested for viability in simulated-gastric intestinal (SGI) fluid and different storage conditions at refrigerated (4oC) and room (25oC) temperatures. The disintegration time and weight uniformity of the spray-dried hard gelatin capsules were tested. The antimicrobial property of free and encapsulated probiotics was tested against enteric pathogenic isolates from antiretroviral therapy (ART) treated HIV-positive patients. The postbiotic of the free cells was extracted, and its cytotoxic effect on the MCF-7 breast cancer cell line was tested through an MTT assay. Result: The Lactobacillus plantarum was isolated from animal raw milk. Zero-size hard gelatin L. plantarum capsules with granules within a size range of 0.71–1.00 mm diameter was formulated. The disintegration time ranges from 2.14±0.045 to 2.91±0.293 minutes, while the average weight is 502.1mg. Simulated gastric solution significantly affected viability of both free and microcapsules. However, the encapsulated cells were more protected and viable due to impermeability in the microcapsules. Furthermore, the viability of free cells stored at 4oC and 25oC were less than 4 log CFU/g and 6 log CFU/g respectively after 12 weeks. However, the microcapsules stored at 4oC achieved the highest viability among the free and microcapsules stored at 25oC and the free cells stored at 4oC. Encapsulated cells were released in the simulated gastric fluid, viable and effective against the enteric pathogens tested. However, chitosan-coated calcium alginate encapsulated probiotics significantly inhibited Shigella flexneri, Candida albicans, and Escherichia coli. The Postbiotic Metabolites (PM) of L. plantarum produced a cytotoxic effect on the MCF-7 breast cancer cell line. The postbiotic showed significant cytotoxic activity similar to 5FU, a standard antineoplastic agent. The inhibition concentration of 50% growth (IC50) of postbiotic metabolite K3 is low and consistent with the IC50 of the positive control (Cisplatin). Conclusions: Lactobacillus plantarum postbiotic exhibited a cytotoxic effect on the MCF-7 breast cancer cell line and could be used as combined adjuvant therapy in breast cancer management. The microencapsulation technique protects the probiotics, improving their viability and delivery to the gastrointestinal tract. Chitosan enhances antibacterial efficacy; thus, chitosan-coated microencapsulated L. plantarum probiotics could be more effective and used as a combined therapy in HIV management of opportunistic enteric infection.

Keywords: probiotics, encapsulation, gastrointestinal conditions, antimicrobial effect, postbiotic, cytotoxicity effect

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Authors: Irfan Anjum Manarvi, Zahid Ali kaimkhani

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Predicting location of the fracture in human bones has been a keen area of research for the past few decades. A variety of tests for hardness, deformation, and strain field measurement have been conducted in the past; but considered insufficient due to various limitations. Researchers, therefore, have proposed further studies due to inaccuracies in measurement methods, testing machines, and experimental errors. Advancement and availability of hardware, measuring instrumentation, and testing machines can now provide remedies to these limitations. The human foot is a critical part of the body exposed to various forces throughout its life. A number of products are developed for using it for protection and care, which many times do not provide sufficient protection and may itself become a source of stress due to non-consideration of the delicacy of bones in the feet. A continuous strain or overloading on feet may occur resulting to discomfort and even fracture. Mechanical properties of Tarsals, Metatarsals, and phalanges are, therefore, the primary area of consideration for all such design applications. Hardness is one of the mechanical properties which are considered very important to establish the mechanical resistance behavior of a material against applied loads. Past researchers have worked in the areas of investigating mechanical properties of these bones. However, their results were based on a limited number of experiments and taking average values of hardness due to either limitation of samples or testing instruments. Therefore, they proposed further studies in this area. The present research has been carried out to develop a hardness map of the human foot by measuring micro hardness at various locations of these bones. Results are compiled in the form of distance from a reference point on a bone and the hardness values for each surface. The number of test results is far more than previous studies and are spread over a typical bone to give a complete hardness map of these bones. These results could also be used to establish other properties such as stress and strain distribution in the bones. Also, industrial engineers could use it for design and development of various accessories for human feet health care and comfort and further research in the same areas.

Keywords: tarsals, metatarsals, phalanges, hardness testing, biomechanics of human foot

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Authors: Sarah Elsayed Mohammed, Lamiaa Ahmed Ahmed, Mahmoud Mohammed Khattab

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Aim: The aim of the present study was to investigate whether combined nicorandil and bone marrow-derived mesenchymal stem cells (BMDMSC) treatment could offer an additional benefit in ameliorating isoproterenol (ISO)-induced heart failure in rats. Methods: ISO (85 and 170 mg/kg/day) was injected subcutaneously for 2 successive days, respectively. By day 3, electrocardiographic changes were recorded and serum was separated for determination of CK-MB level for confirmation of myocardial damage. Nicorandil (3 mg/kg/day) was then given orally with or without a single i.v. BMDMSC administration. Electrocardiography and echocardiography were recorded 2 weeks after beginning of treatment. Rats were then sacrificed and ventricles were isolated for estimation of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) contents, caspase-3 activity as well as inducible nitric oxide synthase (iNOS) and connexin-43 protein expressions. Moreover, histological analysis of myocardial fibrosis was performed and cryosections were done for estimation of homing of BMDMSC. Results: ISO induced a significant increase in ventricles/body weight ratio, left ventricular end diastolic (LVEDD) and systolic dimensions (LVESD), ST segment and QRS duration. Moreover, myocardial fibrosis as well as VEGF, TNF-α and TGF-β contents were significantly increased. On the other hand, connexin-43 protein expression was significantly decreased, while caspase-3 and iNOS protein expressions were significantly increased. Combined therapy provided additional improvement compared to cell treatment alone towards reducing cardiac hypertrophy, fibrosis and inflammation. Furthermore, combined therapy induced significant increase in angiogenesis and BMDMSC homing and prevented ISO induced changes in iNOS, connexin-43 and caspase-3 protein expressions. Conclusion: Combined nicorandil/BMDMSC treatment was superior to BMDMSC alone towards preventing ISO-induced heart failure in rats.

Keywords: fibrosis, isoproterenol, mesenchymal stem cells, nicorandil

Procedia PDF Downloads 523

Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

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Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

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Authors: H. N. Alyaseen, S. E. Alalawi, T. Cordoba, É. Delisle, C. Cordoba, A. Odobescu

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Sternal dehiscence is defined as the persistent separation of sternal bones that are often complicated with mediastinitis. Etiologies that lead to sternal dehiscence vary, with cardiovascular and thoracic surgeries being the most common. Early diagnosis in susceptible patients is crucial to the management of such cases, as they are associated with high mortality rates. A recent meta-analysis of more than four hundred thousand patients concluded that deep sternal wound infections were the leading cause of mortality and morbidity in patients undergoing cardiac procedures. Long-term complications associated with sternal dehiscence include increased hospitalizations, cardiac infarctions, and renal and respiratory failures. Numerous osteosynthesis methods have been described in the literature. Surgical materials offer enough rigidity to support the sternum and can be flexible enough to allow physiological breathing movements of the chest; however, these materials fall short when managing patients with extensive bone loss, osteopenia, or general poor bone quality, for such cases, flaps offer a better closure system. Early utilization of flaps yields better survival rates compared to delayed closure or to patients treated with sternal rewiring and closed drainage. The utilization of pectoralis major flaps, rectus abdominus, and latissimus muscle flaps have all been described in the literature as great alternatives. Flap selection depends on a variety of factors, mainly the size of the sternal defect, infection, and the availability of local tissues. Free fibular flaps are commonly harvested flaps utilized in reconstruction around the body. In cases regarding sternal reconstruction with free fibular flaps, the literature exclusively discussed the flap applied vertically to the chest wall. We present a different technique applying the free fibular triple barrel flap oriented in a transverse manner, in parallel to the ribs. In our experience, this method could have enhanced results and improved prognosis as it contributes to the normal circumferential shape of the chest wall.

Keywords: sternal dehiscence, management, free fibular flaps, novel surgical techniques

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Authors: A. A. Dehpour, B. Eslami, S. Rezaie, S. F. Hashemian, F. Shafie, M. Kiaie

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The aims of study were investigation on chemical composition essential oil and the effect of extract of Coronilla varia on antimicrobial and cytotoxicity activity. The essential oils of Coronilla varia is obtained by hydrodistillation and analyzed by (GC/MS) for determining their chemical composition and identification of their components. Antibacterial activity of plant extract was determined by disc diffusion method. The effect of hydroalcolic extracts from Cornilla varia investigated on MCF7 cancer cell line by MTT assay. The major components were Caryophyllene Oxide (60.19%), Alphacadinol (4.13%) and Homoadantaneca Robexylic Acid (3.31%). The extracts from Coronilla varia had interesting activity against Proteus mirabilis in the concentration of 700 µg/disc and did not show any activity against Staphylococus aureus, Bacillus subtillis, Klebsiella pneumonia and Entrobacter cloacae. The positive control, Ampicillin, Chloramphenicol and Cenphalothin had shown zone of inhibition resistant all bacteria. Corohilla varia ethanol extract could inhibit the proliferation of MCF7 cell line in RPMI 1640 medium. IC50 5(mg/ml) was the optimum concentration of extract from Coronilla varia inhibition of cell line growth. The MCF7 cancer cell line and Proteus mirabilis were more sensitive to Coronilla varia ethanol extract.

Keywords: Coronilla varia, essential oil, antibacterial, anticancer, hela cell line

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Authors: Renu Pattanshetty

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The aim of this narrative review is to highlight the impact of menopause on osteoporosis and weight gain. The review also aims to summarize physiotherapeutic strategies to combat the same.A thorough literature search was conducted using electronic databases like MEDline, PUBmed, Highwire Press, PUBmed Central for English language studies that included search terms like menopause, osteoporosis, obesity, weight gain, exercises, physical activity, physiotherapy strategies from the year 2000 till date. Out of 157 studies that included metanalyses, critical reviews and randomized clinical trials, a total of 84 were selected that met the inclusion criteria. Prevalence of obesity is increasing world - wide and is reaching epidemic proportions even in the menopausal women. Prevalence of abdominal obesity is almost double than that general obesity with rates in the US with 65.5% in women ages 40-59 years and 73.8 in women aged 60 years or more. Physical activities and exercises play a vital role in prevention and treatment of osteoporosis and weight gain related to menopause that aim to boost the general well-being and any symptoms brought about by natural body changes. Endurance exercises lasting about 30 minutes /day for 5 days/ week has shown to decrease weight and prevent weight gain. In addition, strength training with at least 8 exercises of 8-12 repetitions working for whole body and for large muscle groups has shown to result positive outcomes. Hot flashes can be combatted through yogic breathing and relaxation exercises. Prevention of fall strategies and resistance training are key to treat diagnosed cases of osteoporosis related to menopause. One to three sets with five to eight repetitions of four to six weight bearing exercises have shown positive results. Menopause marks an important time for women to evaluate their risk of obesity and osteoporosis. It is known fact that bone benefit from exercises are lost when training is stopped, hence, practicing bone smart habits and strict adherence to recommended physical activity programs are recommended which are enjoyable, safe and effective.

Keywords: menopause, osteoporosis, obesity, weight gain, exercises, physical activity, physiotherapy strategies

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Authors: Maha Azzam, Mahmoud Gabr, Mahmoud Zakaria, Ayman Refaie, Amani Ismail, Sherry Khater, Sylvia Ashamallah, Mohamed Ghoniem

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Evidence was provided that human bone marrow-derived mesenhymal stem cells (HBM-MSCs) could be differentiated to form insulin-producing cells (IPCs). Transplantation of these cells was able to cure chemically-induced diabetes in nude mice. The efficacy of these cells to control diabetes in large animals was carried out to evaluate the sufficient number of cells needed/Kg body weight and to determine the functional longevity in vivo. Materials/Methods: Ten male mongrel dogs weighing 15-20 Kg were used in this study. Diabetes was chemically-induced in 7 dogs by a mixture of alloxan and streptozotocin. Three non-diabetic served as normal controls. Differentiated HBM-MSCs (5 million/Kg) were encapsulated in theracyte capsules and transplanted beneath the rectus sheath. Each dog received 2 capsules. One dog died 4 days postoperative from inhalation pneumonia. The remaining 6 dogs were followed up for 6-18 months. Results: Four dogs became normoglycemic within 6-8 weeks with normal glucose tolerance curves providing evidence that the transplanted cells were glucose-sensitive and insulin-responsive. In the remaining 2 dogs, fasting blood glucose was reduced but did not reach euglycemic levels. The sera of all transplanted dogs contained human insulin and c-peptide but negligible levels of canine insulin. When the HBM-MSCs loaded capsules were removed, rapid return of diabetic state was noted. The harvested capsules were examined by immunofluorescence. IPCs were seen and co-expression of with c-peptide was confirmed. Furthermore, all the pancreatic endocrine genes were expressed by the transplanted cells. Conclusions: This study provided evidence that theracyte capsules could protect the xenogenic HBM-MSCs from the host immune response. This is an important issue when clinical stem cell therapy is considered for definitive treatment for T1DM.

Keywords: diabetes, mesenchymal stem cells, dogs, Insulin-producing cells

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Authors: Alvaro L. Ronco

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Background and purpose: Although our country is a developing one, it has a typical Western meat-rich dietary style. Based on estimates of heme and nonheme iron contents in representative foods, we carried out the present epidemiologic study, with the aim of accurately analyzing dietary iron and its role on CRC risk. Subjects/methods: Patients (611 CRC incident cases and 2394 controls, all belonging to public hospitals of our capital city) were interviewed through a questionnaire including socio-demographic, reproductive and lifestyle variables, and a food frequency questionnaire of 64 items, which asked about food intake 5 years before the interview. The sample included 1937 men and 1068 women. Controls were matched by sex and age (± 5 years) to cases. Food-derived nutrients were calculated from available databases. Total dietary iron was calculated and classified by heme or nonheme source, following data of specific Dutch and Canadian studies, and additionally adjusted by energy. Odds Ratios (OR) and 95% confidence intervals were calculated through unconditional logistic regression, adjusting for relevant potential confounders (education, body mass index, family history of cancer, energy, infusions, and others). A heme/nonheme (H/NH) ratio was created and the interest variables were categorized into tertiles, for analysis purposes. Results: The following risk estimations correspond to the highest tertiles. Total iron intake showed no association with CRC risk neither among men (OR=0.83, ptrend =.18) nor among women (OR=1.48, ptrend =.09). Heme iron was positively associated among men (OR=1.88, ptrend < .001) and for the overall sample (OR=1.44, ptrend =.002), however, it was not associated among women (OR=0.91, ptrend =.83). Nonheme iron showed an inverse association among men (OR=0.53, ptrend < .001) and the overall sample (OR=0.78, ptrend =.04), but was not associated among women (OR=1.46, ptrend =.14). Regarding H/NH ratio, risks increased only among men (OR=2.12, ptrend < .001) but lacked of association among women (OR=0.81, ptrend =.29). Conclusions. We have observed different types of associations between CRC risk and high dietary heme, nonheme and H/NH iron ratio. Therefore, the source of the available iron might be of importance as a link to colorectal carcinogenesis, perhaps pointing to reconsider the animal/plant proportions of this vital mineral within diet. Nevertheless, the different associations observed for each sex, demand further studies in order to clarify these points.

Keywords: chelation, colorectal cancer, heme, iron, nonheme

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Authors: Corina Muscurel, Irina Stoian, Laura Gaman, Valeriu Atanasiu

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Chronic inflammation predisposes cells to neoplastic transformation and is associated with angiogenesis. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) give rise to anti-inflammatory metabolites and decrease some inflammatory cytokines. The aim of the study was to analyze the effect of n-3 PUFAs intake on patients with tumors in early-stage (without regional or distant metastasis). There were two groups of patients: one group with colon tumors and one group with lung tumors. All patients took for 60 days daily supplements from fish-oil containing 600 mg eicosapentaenoic acid and 400 mg docosahexaenoic acid. The plasma markers were evaluated before and after PUFAs intake: ceruloplasmin (using p-phenylenediamine oxidase method), plasma total thiol groups (using dithiobis-nitrobenzoic acid method) and CEA (carcinoembryonic antigen using electrochemiluminescent immunoassay). The results reflect ceruloplasmin decrease (p < 0.05), plasma total thiol groups increase (not statistically significant) and CEA decrease (p < 0.05) after n-3 PUFAs intake. Conclusions: n-3 PUFAs intake is favorable in premalignant lesions or in early tumor stage and dietary fish-oil has anti-inflammatory effects and can contribute to reduce cancer progression.

Keywords: cancer, fish-oil, inflammation, n-3 polyunsaturated fatty acids

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Authors: Abdul Hafeez, Samiya Shehzadi

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This research paper presents a different approach towards eco-friendly textile design by developing a sustainable composite fabric from orange peel for ladies' undergarments. The research focuses on utilizing orange peel to develop a unique orange leather/composite (fabric) through a process involving heating, extracting, and subsequent sun-drying to obtain the composite. The sustainable composite fabric shows properties that are favorable to the development of environmentally friendly undergarments, which not only offer UV protection but also possess healing properties for the skin. Through comprehensive testing and analysis, it has been determined that the orange peel composite fabric has zero harmful effects on the skin, making it a safe and desirable material for intimate wear. Furthermore, the research suggests that the orange peel composite fabric has the potential to reduce the rate of cancer cell growth. While the exact mechanisms and factors contributing to this effect require further investigation, the initial findings indicate promising aspects of the fabric in terms of potential cancer-preventive properties. Research contribution to the field of sustainable textile design by introducing a usual and eco-friendly approach utilizing orange peel waste. This work opens up avenues for further exploration and development of innovative materials that are both sustainable and beneficial for human health.

Keywords: sustainability, composite textiles, extracting, undergarments, eco-friendly, orange peels

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Authors: Aoxue Yang, Weili Tian, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

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Authors: Shenlun Chen, Leonard Wee

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Tumor grading is an essential reference for colorectal cancer (CRC) staging and survival prognostication. The widely used World Health Organization (WHO) grading system defines histological grade of CRC adenocarcinoma based on the density of glandular formation on whole slide images (WSI). Tumors are classified as well-, moderately-, poorly- or un-differentiated depending on the percentage of the tumor that is gland forming; >95%, 50-95%, 5-50% and <5%, respectively. However, manually grading WSIs is a time-consuming process and can cause observer error due to subjective judgment and unnoticed regions. Furthermore, pathologists’ grading is usually coarse while a finer and continuous differentiation grade may help to stratifying CRC patients better. In this study, a deep learning based automatic differentiation grading algorithm was developed and evaluated by survival analysis. Firstly, a gland segmentation model was developed for segmenting gland structures. Gland regions of WSIs were delineated and used for differentiation annotating. Tumor regions were annotated by experienced pathologists into high-, medium-, low-differentiation and normal tissue, which correspond to tumor with clear-, unclear-, no-gland structure and non-tumor, respectively. Then a differentiation prediction model was developed on these human annotations. Finally, all enrolled WSIs were processed by gland segmentation model and differentiation prediction model. The differentiation grade can be calculated by deep learning models’ prediction of tumor regions and tumor differentiation status according to WHO’s defines. If multiple WSIs were possessed by a patient, the highest differentiation grade was chosen. Additionally, the differentiation grade was normalized into scale between 0 to 1. The Cancer Genome Atlas, project COAD (TCGA-COAD) project was enrolled into this study. For the gland segmentation model, receiver operating characteristic (ROC) reached 0.981 and accuracy reached 0.932 in validation set. For the differentiation prediction model, ROC reached 0.983, 0.963, 0.963, 0.981 and accuracy reached 0.880, 0.923, 0.668, 0.881 for groups of low-, medium-, high-differentiation and normal tissue in validation set. Four hundred and one patients were selected after removing WSIs without gland regions and patients without follow up data. The concordance index reached to 0.609. Optimized cut off point of 51% was found by “Maxstat” method which was almost the same as WHO system’s cut off point of 50%. Both WHO system’s cut off point and optimized cut off point performed impressively in Kaplan-Meier curves and both p value of logrank test were below 0.005. In this study, gland structure of WSIs and differentiation status of tumor regions were proven to be predictable through deep leaning method. A finer and continuous differentiation grade can also be automatically calculated through above models. The differentiation grade was proven to stratify CAC patients well in survival analysis, whose optimized cut off point was almost the same as WHO tumor grading system. The tool of automatically calculating differentiation grade may show potential in field of therapy decision making and personalized treatment.

Keywords: colorectal cancer, differentiation, survival analysis, tumor grading

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Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

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Authors: Rajish Shil, Mohammad Ali Houri, Mohammad Milad Ismail, Fatimah Al Kaabi

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The clinical presentation of Primary hyperparathyroidism can vary from simple asymptomatic hypercalcemia to severe life-threatening hypercalcemic crisis with multi-organ dysfunction, which can be due to parathyroid adenoma or sometimes with malignant cancer. This cascade of clinical presentation can lead to a diagnostic and therapeutic challenge for treating the disease. We are presenting a case of severe hypercalcemic crisis due to parathyroid adenoma with an emphasis on early management, diagnosis, and interventions to prevent any lifelong complications and any permanent organ dysfunction. A 30 years old female with a history of primary Infertility, admitted to Al Ain Hospital critical care unit with Acute Severe Necrotizing Pancreatitis. She initially had a 1-month history of abdominal pain on and off, for which she was treated conservatively with no much improvement, and later on, she developed life-threatening severe pancreatitis, which required her to be admitted to the critical care unit. She was transferred from a private healthcare facility, where she was found to have a very high level of calcium up to 15mmol/L. She received systemic Zoledronic Acid, which lowered her calcium level transiently and later was increased again. She went on to develop multiple end-organ damages along with multiple electrolytes disturbances. She was found to have high levels of Parathyroid hormone, which was correlated with a parathyroid mass on the neck via radiological imaging. After a long course of medical treatment to lower the calcium to a near-normal level, parathyroidectomy was done, which showed parathyroid adenoma on histology. She developed hungry bone syndrome after the surgery and pancreatic pseudocyst after resolving of pancreatitis. She required aggressive treatment with Intravenous calcium for her hypocalcemia as she received zoledronic acid at the beginning of the disease. Later on, she was discharged on long term calcium and other electrolytes supplements. In patients presenting with hypercalcemia, it is prudent to investigate and start treatment early to prevent complications and end-organ damage from hypercalcemia and also to treat the primary cause of the hypercalcemia, with conscious follow up to prevent hypocalcemic complications after treatment. It is important to follow up patients with parathyroid adenomas for a long period in order to detect any recurrence of the tumor or to make sure if the primary tumor is either benign or malignant.

Keywords: hypercalcemia, pancreatitis, hypocalcemia, hyperparathyroidism

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Authors: Felipa de Mello-Sampayo

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The aim of this study is to undertake, from patient’s perspective, the timing and probability of using teledermatology, comparing it with a conventional referral system. The dynamic stochastic model’s main value-added consists of the concrete application to patients waiting for dermatology surgical intervention. Patients with low health level uncertainty must use teledermatology treatment as soon as possible, which is precisely when the teledermatology is least valuable. The results of the model were then tested empirically with the teledermatology network covering the area served by the Hospital Garcia da Horta, Portugal, links the primary care centers of 24 health districts with the hospital’s dermatology department via the corporate intranet of the Portuguese healthcare system. Health level volatility can be understood as the hazard of developing skin cancer and the trend of health level as the bias of developing skin lesions. The results of the survival analysis suggest that the theoretical model can explain the use of teledermatology. It depends negatively on the volatility of patients' health, and positively on the trend of health, i.e., the lower the risk of developing skin cancer and the younger the patients, the more presurgical teledermatology one expects to occur. Presurgical teledermatology also depends positively on out-of-pocket expenses and negatively on the opportunity costs of teledermatology, i.e., the lower the benefit missed by using teledermatology, the more presurgical teledermatology one expects to occur.

Keywords: teledermatology, wait time, uncertainty, opportunity cost, survival analysis

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Authors: Kamila Dus-Szachniewicz, Artur Bednarkiewicz, Katarzyna Gdesz-Birula, Slawomir Drobczynski

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In modern oncology hyperthermia (HT) is defined as a controlled tumor heating. HT treatment temperatures range between 40–48 °C and can selectively damage heat-sensitive cancer cells or limit their further growth, usually with minimal injury to healthy tissues. Despite many advantages, conventional whole-body and regional hyperthermia have clinically relevant side effects, including cardiac and vascular disorders. Additionally, the lack of accessibility of deep-seated tumor sites and impaired targeting micrometastases renders HT less effective. It is believed that above disadvantages can significantly overcome by the application of biofunctionalized microparticles, which can specifically target tumor sites and become activated by an external stimulus to provide a sufficient cellular response. In our research, the unique optical tweezers system have enabled capturing the silica microparticles, primary cells and tumor spheroids in highly controllable and reproducible environment to study the impact of localized heat stimulation on normal and pathological cell and within multicellular tumor spheroid. High throughput spheroid model was introduced to better mimic the response to HT treatment on tumors in vivo. Additionally, application of local heating of tumor spheroids was performed in strictly controlled conditions resembling tumor microenvironment (temperature, pH, hypoxia, etc.), in response to localized and nonhomogeneous hyperthermia in the extracellular matrix, which promotes tumor progression and metastatic spread. The lack of precise control over these well- defined parameters in basic research leads to discrepancies in the response of tumor cells to the new treatment strategy in preclinical animal testing. The developed approach enables also sorting out subclasses of cells, which exhibit partial or total resistance to therapy, in order to understand fundamental aspects of the resistance shown by given tumor cells in response to given therapy mode and conditions. This work was funded by the National Science Centre (NCN, Poland) under grant no. UMO-2017/27/B/ST7/01255.

Keywords: cancer spheroids, hyperthermia, microparticles, optical tweezers

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Authors: H. S. Niroshani, W. M. Ediri Arachchi, R. Tudugala, U. J. M. A. L. Jayasinghe, U. M. U. J. Jayasekara, P. B. Hewavithana

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Mammography is used as a screening tool for early diagnosis of breast cancer. It is also useful in refining the diagnosis of breast cancer either by assessment or work up after a suspicious area in the breast has been detected. In order to detect breast cancer accurately and at the earliest possible stage, the image must have an optimum contrast to reveal mass densities and spiculated fibrous structures radiating from them. In addition, the spatial resolution must be adequate to reveal the suffusion of micro calcifications and their shape. The above factors can be optimized by implementing an effective QA programme to enhance the accurate diagnosis of mammographic imaging. Therefore, the radiographer’s knowledge on QA is greatly instrumental in routine mammographic practice. The aim of this study was to assess the radiographer’s knowledge on Quality Assurance and Quality Control programmes in relation to mammographic procedures. A cross-sectional study was carried out among all radiographers working in each mammography setting in Sri Lanka. Pre-tested, anonymous self-administered questionnaires were circulated among the study population and duly filled questionnaires returned within a period of three months were taken into the account. The data on demographical information, knowledge on QA programme and associated QC tests, overall knowledge on QA and QC programmes were obtained. Data analysis was performed using IBM SPSS statistical software (version 20.0). The total response rate was 59.6% and the average knowledge score was 54.15±11.29 SD out of 100. Knowledge was compared on the basis of education level, special training of mammography, and the years of working experience in a mammographic setting of the individuals. Out of 31 subjects, 64.5% (n=20) were graduate radiographers and 35.5% (n=11) were diploma holders while 83.9% (n=26) of radiographers have been specially trained for mammography and 16.1% (n=5) have not been attended for any special training for mammography. It is also noted that 58.1% (n=18) of individuals possessed their experience of less than one year and rest 41.9% (n=13) of them were greater than that. Further, the results found that there is a significant difference (P < 0.05) in the knowledge of QA and overall knowledge on QA and QC programme in the categories of education level and working experience. Also, results imply that there was a significant difference (P < 0.05) in the knowledge of QC test among the groups of trained and non-trained radiographers. This study reveals that education level, working experience and the training obtained particularly in the field of mammography have a significant impact on their knowledge on QA and QC in mammography.

Keywords: knowledge, mammography, quality assurance, quality control

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Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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Authors: Mehmet Budak, Mehmet Fatih Ustundag

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Objectives: In this research, we studied the extent of exposure to physical violence and committing violence in patients diagnosed with schizophrenia in comparison to a control group consisting of patients with psychiatric diseases other than psychotic and mood disorders. Method: Between August 2019 and October 2019, a total of 100 hospitalized patients diagnosed with schizophrenia (clinically in remission, Brief Psychiatric Rate Scale < 30) were sequentially studied while undergoing inpatient treatment at Erenkoy Mental Health Training and Research Hospital. From the outpatient clinic, 50 patients with psychiatric disorders other than psychotic disorders or mood disorders were consecutively included as a control group. All participants were evaluated by the sociodemographic data that also questions the history of violence, physical examination, bilateral comparative hand, and forearm anterior-posterior and lateral radiography. Results: While 59% of patients with schizophrenia and 28% of the control group stated that they were exposed to physical violence at least once in a lifetime (p < 0,001); a defensive wound or fracture was detected in 29% of patients with schizophrenia and 2% of the control group (p < 0.001). On the other hand, 61% of patients diagnosed with schizophrenia, and 32% of the control group expressed that they committed physical violence at least once in a lifetime (p: 0.001). A self-destructive wound or fracture was detected in 53% of the patients with schizophrenia and 24% of the control group (p: 0,001). In the schizophrenia group, the rate of committing physical violence is higher in those with substance use compared to those without substance use (p:0.049). Also, wounds and bone fractures (boxer’s fracture) resulting from self-injury are more common in schizophrenia patients with substance use (p:0,002). In the schizophrenia group, defensive wounds and parry fractures (which are located in the hand, forearm, and arm usually occur as a result of a trial to shield the face against an aggressive attack and are known to be the indicators of interpersonal violence) are higher in those with substance use compared to those who do not (p:0,007). Conclusion: This study shows that exposure to physical violence and the rate of violence is higher in patients with schizophrenia compared to the control group. It is observed that schizophrenia patients who are stigmatized as being aggressive are more exposed to violence. Substance use in schizophrenia patients increases both exposure to physical violence and the use of physical violence. Physical examination and anamnesis that question violence are important tools to reveal the exposure to violence in patients. Furthermore, some specific bone fractures and wounds could be used to detect victimization even after plenty of time passes.

Keywords: fracture, physical violence, schizophrenia, substance use

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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Authors: Eashwar V. Somasundaram, Raoul R. Wadhwa, Jacob G. Scott

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The use of radiomics in measuring geometric properties of tumor images such as size, surface area, and volume has been invaluable in assessing cancer diagnosis, treatment, and prognosis. In addition to analyzing geometric properties, radiomics would benefit from measuring topological properties using persistent homology. Intuitively, features uncovered by persistent homology may correlate to tumor structural features. One example is necrotic cavities (corresponding to 2D topological features), which are markers of very aggressive tumors. We develop a data pipeline in R that clusters tumors images based on persistent homology is used to identify meaningful clinical distinctions between tumors and possibly new relationships not captured by established clinical categorizations. A preliminary analysis was performed on 16 Magnetic Resonance Imaging (MRI) breast tissue segments downloaded from the 'Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis' (I-SPY TRIAL or ISPY1) collection in The Cancer Imaging Archive. Each segment represents a patient’s breast tumor prior to treatment. The ISPY1 dataset also provided the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status data. A persistent homology matrix up to 2-dimensional features was calculated for each of the MRI segmentation. Wasserstein distances were then calculated between all pairwise tumor image persistent homology matrices to create a distance matrix for each feature dimension. Since Wasserstein distances were calculated for 0, 1, and 2-dimensional features, three hierarchal clusters were constructed. The adjusted Rand Index was used to see how well the clusters corresponded to the ER/PR/HER2 status of the tumors. Triple-negative cancers (negative status for all three receptors) significantly clustered together in the 2-dimensional features dendrogram (Adjusted Rand Index of .35, p = .031). It is known that having a triple-negative breast tumor is associated with aggressive tumor growth and poor prognosis when compared to non-triple negative breast tumors. The aggressive tumor growth associated with triple-negative tumors may have a unique structure in an MRI segmentation, which persistent homology is able to identify. This preliminary analysis shows promising results in the use of persistent homology on tumor imaging to assess the severity of breast tumors. The next step is to apply this pipeline to other tumor segment images from The Cancer Imaging Archive at different sites such as the lung, kidney, and brain. In addition, whether other clinical parameters, such as overall survival, tumor stage, and tumor genotype data are captured well in persistent homology clusters will be assessed. If analyzing tumor MRI segments using persistent homology consistently identifies clinical relationships, this could enable clinicians to use persistent homology data as a noninvasive way to inform clinical decision making in oncology.

Keywords: cancer biology, oncology, persistent homology, radiomics, topological data analysis, tumor imaging

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Authors: Ľudmila Ballová, Slavomír Kurhajec, Eva Petrovová, Jarmila Eftimová

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Angiogenesis, a formation of new blood vessels from a pre-existing vasculature, plays an important role in pathologic processes such as the growth and metastasis of tumours. Tumours cannot grow beyond a few millimetres without blood supply from the newly formed blood vessels from the host tissue, a process called tumour-induced angiogenesis. The successful research of antiangiogenic treatment of cancer has focused on nutraceuticals with angiogenesis-modulating properties. Berberine, as a major active component of the bark of Phellodendron amurense Rupr., has shown antitumour activity by intervening into different steps of carcinogenesis. The influence of ethanolic extract of Phellodendron amurese bark on the angiogenesis was tested in vivo on chick chorioallantoic membrane (CAM). The irritancy of the CAM after the application of the crude bark extract dissolved in normal saline (10 mg/mL) was investigated on embryonic day 7. No significant signs of the irritancy, such as vasoconstriction, hyperaemia, haemorrhage or coagulation were observed which indicates the harmless character of the extract. A significant reduction in vessel sprouting and higher percentage of avascular zone was observed in the case of CAM treated with the extract in comparison with non-treated CAM (control), which is a proof of the antiangiogenic potential of the extract. These results could contribute to the development of novel drugs for the treatment of cancer or other diseases, in which angiogenesis plays a significant role.

Keywords: angiogenesis, berberine, chorioallantoic membrane, irritancy, phellodendron amurense

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Authors: Philip Friedlander, John Rutledge, Jason Suh

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Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

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Authors: Alena O. Stepanova, Vera S. Chernonosova, Tatyana S. Godovikova, Konstantin A. Bulatov, Andrey Y. Patrushev, Pavel P. Laktionov

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Trauma and arthrosis, not to mention cartilage destruction in overweight and elders put hyaline cartilage lesion among the most frequent diseases of locomotor system. These problems combined with low regeneration potential of the cartilage make regeneration of articular cartilage a high-priority task of tissue engineering. Many types of matrices, the procedures of their installation and autologous chondrocyte implantation protocols were offered, but certain aspects including adhesion of the implant with surrounding cartilage/bone, prevention of the ossification and fibrosis were not resolved. Simplification and acceleration of the procedures resulting in restoration of normal cartilage are also required. We have demonstrated that human chondroblasts can be successfully cultivated at the surface of electrospun scaffolds and produce extracellular matrix components in contrast to chondroblasts grown in homogeneous hydrogels. To restore cartilage we offer to use stacks of electrospun scaffolds fixed with photopolymerized solution of prepared from gelatin and chondroitin-4-sulfate both modified by glycidyl methacrylate and non-toxic photoinitator Darocur 2959. Scaffolds were prepared from nylon 6, polylactide-co-glicolide and their mixtures with modified gelatin. Illumination of chondroblasts in photopolymerized solution using 365 nm LED light had no effect on cell viability at compressive strength of the gel less than0,12 MPa. Stacks of electrospun scaffolds provide good compressive strength and have the potential for substitution with cartilage when biodegradable scaffolds are used. Vascularization can be prevented by introduction of biostable scaffolds in the layers contacting the subchondral bone. Studies of two-component materials (2-3 sheets of electrospun scaffold) implanted in the knee-joints of rabbits and fixed by photopolymerization demonstrated good crush resistance, biocompatibility and good adhesion of the implant with surrounding cartilage. Histological examination of the implants 3 month after implantation demonstrates absence of any inflammation and signs of replacement of the biodegradable scaffolds with normal cartilage. The possibility of intraoperative population of the implants with autologous cells is being investigated.

Keywords: chondroblasts, electrospun scaffolds, hyaline cartilage, photopolymerized gel

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Authors: Malgorzata J. Rybak-Smith, Benedicte Thiebaut, Simon Johnson, Peter Bishop, Helen E. Townley

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Gadolinium doped titania (TiO2:Gd) nanoparticles (NPs) can be activated by X-ray radiation to generate Reactive Oxygen Species (ROS), which can be effective in killing cancer cells. As such, treatment with these NPs can be used to enhance the efficacy of conventional radiotherapy. Incorporation of the NPs in to tumour tissue will permit the extension of radiotherapy to currently untreatable tumours deep within the body, and also reduce damage to neighbouring healthy cells. In an attempt to find a fast and scalable method for the synthesis of the TiO2:Gd NPs, the use of Flame Spray Pyrolysis (FSP) was investigated. A series of TiO2 NPs were generated with 1, 2, 5 and 7 mol% gadolinium dopant. Post-synthesis, the TiO2:Gd NPs were silica-coated to improve their biocompatibility. Physico-chemical characterisation was used to determine the size and stability in aqueous suspensions of the NPs. All analysed TiO2:Gd NPs were shown to have relatively high photocatalytic activity. Furthermore, the FSP synthesized silica-coated TiO2:Gd NPs generated enhanced ROS in chemico. Studies on rhabdomyosarcoma (RMS) cell lines (RD & RH30) demonstrated that in the absence of irradiation all TiO2:Gd NPs were inert. However, application of TiO2:Gd NPs to RMS cells, followed by irradiation, showed a significant decrease in cell proliferation. Consequently, our studies showed that the X-ray-activatable TiO2:Gd NPs can be prepared by a high-throughput scalable technique to provide a novel and affordable anticancer therapy.

Keywords: cancer, gadolinium, ROS, titania nanoparticles, X-ray

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Authors: Xuechun Kan, Dongdong Li, Fan Li, Peidang Liu

Abstract:

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with a poor prognosis, and radiotherapy is one of the main treatment methods. However, due to the obvious resistance of tumor cells to radiotherapy, high dose of ionizing radiation is required during radiotherapy, which causes serious damage to normal tissues near the tumor. Therefore, how to improve radiotherapy resistance and enhance the specific killing of tumor cells by radiation is a hot issue that needs to be solved in clinic. Recent studies have shown that silver-based nanoparticles have strong radiosensitization, and silver nanoclusters (AgNCs) also provide a broad prospect for tumor targeted radiosensitization therapy due to their ultra-small size, low toxicity or non-toxicity, self-fluorescence and strong photostability. Aptamer 5TR1 is a 25-base oligonucleotide aptamer that can specifically bind to mucin-1 highly expressed on the membrane surface of TNBC 4T1 cells, and can be used as a highly efficient tumor targeting molecule. In this study, AgNCs were synthesized by DNA template based on 5TR1 aptamer (NC-T5-5TR1), and its role as a targeted radiosensitizer in TNBC radiotherapy was investigated. The optimal DNA template was first screened by fluorescence emission spectroscopy, and NC-T5-5TR1 was prepared. NC-T5-5TR1 was characterized by transmission electron microscopy, ultraviolet-visible spectroscopy and dynamic light scattering. The inhibitory effect of NC-T5-5TR1 on cell activity was evaluated using the MTT method. Laser confocal microscopy was employed to observe NC-T5-5TR1 targeting 4T1 cells and verify its self-fluorescence characteristics. The uptake of NC-T5-5TR1 by 4T1 cells was observed by dark-field imaging, and the uptake peak was evaluated by inductively coupled plasma mass spectrometry. The radiation sensitization effect of NC-T5-5TR1 was evaluated through cell cloning and in vivo anti-tumor experiments. Annexin V-FITC/PI double staining flow cytometry was utilized to detect the impact of nanomaterials combined with radiotherapy on apoptosis. The results demonstrated that the particle size of NC-T5-5TR1 is about 2 nm, and the UV-visible absorption spectrum detection verifies the successful construction of NC-T5-5TR1, and it shows good dispersion. NC-T5-5TR1 significantly inhibited the activity of 4T1 cells and effectively targeted and fluoresced within 4T1 cells. The uptake of NC-T5-5TR1 reached its peak at 3 h in the tumor area. Compared with AgNCs without aptamer modification, NC-T5-5TR1 exhibited superior radiation sensitization, and combined radiotherapy significantly inhibited the activity of 4T1 cells and tumor growth in 4T1-bearing mice. The apoptosis level of NC-T5-5TR1 combined with radiation was significantly increased. These findings provide important theoretical and experimental support for NC-T5-5TR1 as a radiation sensitizer for TNBC.

Keywords: 5TR1 aptamer, silver nanoclusters, radio sensitization, triple-negative breast cancer

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