Search results for: squamous cell skin cancer

Authors: Duygu Yüksel Deniz, Memet Vezir Kahraman, Serap Erdem Kuruca, Mediha Süleymanoğlu

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Our first aim was to synthesize Hydroxy Apatite (HAP) and then modify its surface by adding 4-Vinylbenzene boronic acid (4-VBBA). The characterization was done by FT-IR. By adding Polyvinyl alcohol (PVA) to 4- VBBA-HAP, we obtained a suitable electrospinning solution. PVA solution which was also modified by using alkoxy silanes, in order to prevent the scaffolds from being damaged by aqueous cell medium, was added. Keratin was dissolved and then added into the electrospinning solution. Keratin containing 4-VBBA- HAP/PVA composite was used to fabricate nanofiber scaffolds with the simultaneous UV-reactive electrospinning technique. The structural characterization was done by FT-IR. Thermal gravimetric analysis was also performed by using TGA. The morphological characterization was determined by SEM analyses. Our second aim was to create a scaffold where cells could grow. With this purpose, suitable nanofibers were choosen according to their SEM analysis. Keratin containing nanofibers were seeded with 3T3, ECV and SAOS cells and their cytotoxicity and cell proliferation were investigated by using MTT assay. After cell culturing process morphological characterization was determined by SEM analyses. These scaffolds were designed to be nontoxic biomaterials. Here, a comparision was made between keratin containing 3T3, ECV and SAOS seeded nanofiber scaffolds and the results were presented and discussed.

Keywords: cell culture, keratin, nanofibers, UV-reactive electrospinning

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Authors: Arati Inamdar, Siddharth Bhattacharyya, Kester Haye

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Collision tumors are rare entities characterized by neoplasms of two different cell populations with distinct separating boundaries. Such tumors could be benign, malignant, or a combination of both. The exact mechanism of origin for collision tumors is predicted to be tumor heterogeneity or concurrent occurrence of neoplasm in the same organ. We present two cases of plasmacytoma presenting as a collision tumor, one with a tumor of hematological origin and another with a non-hematological origin, namely Chronic Lymphocytic Leukemia and Adenocarcinoma of the colon, respectively. The immunohistochemical stains and flowcytometry analysis performed on the specimens aided incorrect diagnosis. Interestingly, neoplastic cells of plasmacytoma in the first case demonstrated strong cytokeratin along with weak Epithelial Specific Antigen/ Epithelial cell adhesion molecule Monoclonal Antibody (MOC31) positivity, indicating that the tumor may influence the microenvironment of the tumor in the vicinity. Furthermore, the next-generation sequencing studies performed on the specimen with plasmacytoma and chronic lymphocytic lymphoma demonstrated BReast CAncer gene (BRCA2) and Tumor Necrosis Factor Alpha Induced Protein 3 (TNFAIP3) as a disease associated variants suggestive of risk for multiple tumors including collision tumors. Our reports highlight the unique collision tumors involving plasmacytoma, which have never been reported previously, as well as provide necessary insights about the underline genetic aberrations and tumor heterogeneity through sequencing studies and allow clonality assessment for subsequent tumors.

Keywords: BRCA2, collision tumor, chronic lymphocytic leukemia, plasmacytoma

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Authors: Scott Nielsen, Luca Longanesi, Chris Chuck

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Palm oil is obtained from the flesh and kernel of the fruit of oil palms and is the most productive and inexpensive oil crop. The global demand for palm oil is approximately 75 million metric tonnes, a 29% increase in global production of palm oil since 2016. This expansion of oil palm cultivation has resulted in mass deforestation, vast biodiversity destruction and increasing net greenhouse gas emissions. One possible alternative is to produce a saturated oil, similar to palm, from microbes such as oleaginous yeast. The yeasts can be cultured on sugars derived from second-generation sources and do not compete with tropical forests for land. One highly promising oleaginous yeast for this application is Metschnikowia pulcherrima. However, recent techno-economic modeling has shown that cell lysis and standard lipid extraction are major contributors to the cost of the oil. Typical cell disruption techniques to extract either single cell oils or proteins have been based around bead-beating, homogenization and acid lysis. However, these can have a detrimental effect on lipid quality and are energy-intensive. In this study, a vortex separator, which produces high sheer with minimal energy input, was investigated as a potential low energy method of lysing cells. This was compared to four more traditional methods (thermal lysis, acid lysis, alkaline lysis, and osmotic lysis). For each method, the yeast loading was also examined at 1 g/L, 10 g/L and 100 g/L. The quality of the cell disruption was measured by optical cell density, cell counting and the particle size distribution profile comparison over a 2-hour period. This study demonstrates that the vortex separator is highly effective at lysing the cells and could potentially be used as a simple apparatus for lipid recovery in an oleaginous yeast process. The further development of this technology could potentially reduce the overall cost of microbial lipids in the future.

Keywords: palm oil substitute, metschnikowia pulcherrima, cell disruption, cell lysis

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Authors: Adel Dalilottojari, Bahman Delalat, Frances J. Harding, Michaelia P. Cockshell, Claudine S. Bonder, Nicolas H. Voelcker

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Endothelial Progenitor Cell (EPC) based therapies continue to be of interest to treat ischemic events based on their proven role to promote blood vessel formation and thus tissue re-vascularisation. Current strategies for the production of clinical-grade EPCs requires the in vitro isolation of EPCs from peripheral blood followed by cell expansion to provide sufficient quantities EPCs for cell therapy. This study aims to examine the use of different biomolecules to significantly improve the current strategy of EPC capture and expansion on collagen type I (Col I). In this study, four different biomolecules were immobilised on a surface and then investigated for their capacity to support EPC capture and proliferation. First, a cell microarray platform was fabricated by coating a glass surface with epoxy functional allyl glycidyl ether plasma polymer (AGEpp) to mediate biomolecule binding. The four candidate biomolecules tested were Col I, collagen type II (Col II), collagen type IV (Col IV) and vascular endothelial growth factor A (VEGF-A), which were arrayed on the epoxy-functionalised surface using a non-contact printer. The surrounding area between the printed biomolecules was passivated with polyethylene glycol-bisamine (A-PEG) to prevent non-specific cell attachment. EPCs were seeded onto the microarray platform and cell numbers quantified after 1 h (to determine capture) and 72 h (to determine proliferation). All of the extracellular matrix (ECM) biomolecules printed demonstrated an ability to capture EPCs within 1 h of cell seeding with Col II exhibiting the highest level of attachment when compared to the other biomolecules. Interestingly, Col IV exhibited the highest increase in EPC expansion after 72 h when compared to Col I, Col II and VEGF-A. These results provide information for significant improvement in the capture and expansion of human EPC for further application.

Keywords: biomolecules, cell microarray platform, cell therapy, endothelial progenitor cells, high throughput screening

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Authors: Andriy Fedorenko

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Background Early closure of the open abdomen is a priority after damage control laparotomy to prevent retraction of fascial layers and prevent hernia formation that requires definitive repair at a later stage. This substantially reduces the complications associated with ventral hernia formation for up to a year after initial surgery. TopClosure® is an innovative method that employs stress-relaxation and mechanical creep for skin stretching. Its use enables the primary closure of large abdominal wall defects and mitigates large ventral hernia formation. Materials and Methods A 7-year-old girl presented with severe blast injury. She underwent initial laparotomy in a facility within the conflict zone and was transferred in a state of septic shock to our facility for further care. Her abdominal injuries included liver lacerations, multiple perforations of the transverse colon and ileum, and a 8x16cm oblique abdominal wall defect. Further damage control laparotomy was performed with primary suture of the colon and ileum and temporary closure of the abdomen using a Bagota bag. Twelve hours later, negative pressure wound therapy (NPWT) was applied to the abdominal wound after relook laparotomy. Five days later, TopClosure® was applied to the lower part of the wound incorporating NPWT to the upper wound. Results The patient suffered leak from the colonic suture line and required relaparotomy. TopClosure® abdominal closure was achieved after every laparotomy. Conclusion TopClosure® utilizes the viscoelastic properties of the skin achieving full closure of the abdominal wall (including the fascia and skin),eliminating the need for prolonged NPWT, skin graft, and delayed ventral hernia repair surgery.

Keywords: topclosure, abdominal wall defect, hernia, damage control

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Authors: Wooseok Byon, Eunyoung Kim, Junseong Kwon, Byung Joo Song, Chan Heun Park

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Purpose: 18F Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a noninvasive imaging modality that can identify nodal metastases in women with primary breast cancer. The aim of this study was to compare the accuracy of FDG-PET with MRI and sonography scanning to determine axillary lymph node status in patients with breast cancer undergoing sentinel lymph node biopsy or axillary lymph node dissection. Patients and Methods: Between January and December 2012, ninety-nine patients with breast cancer and clinically negative axillary nodes were evaluated. All patients underwent FDG-PET, MRI, ultrasound followed by sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Results: Using axillary lymph node assessment as the gold standard, the sensitivity and specificity of FDG-PET were 51.4% (95% CI, 41.3% to 65.6%) and 92.2% (95% CI, 82.7% to 97.4%) respectively. The sensitivity and specificity of MRI and ultrasound were 57.1% (95% CI, 39.4% to 73.7%), 67.2% (95% CI, 54.3% to 78.4%) and 42.86% (95% CI, 26.3% to 60.7%), 92.2% (95% CI, 82.7% to 97.4%). Stratification according to hormone receptor status showed an increase in specificity when negative (FDG-PET: 42.3% to 77.8%, MRI 50% to 77.8%, ultrasound 34.6% to 66.7%). Also, positive HER2 status was associated with an increase in specificity (FDG-PET: 42.9% to 85.7%, MRI 50% to 85.7%, ultrasound 35.7% to 71.4%). Conclusions: The sensitivity and specificity of FDG-PET compared with MRI and ultrasound was high. However, FDG-PET is not sufficiently accurate to appropriately identify lymph node metastases. This study suggests that FDG-PET scanning cannot replace histologic staging in early-stage breast cancer, but might have a role in evaluating axillary lymph node status in hormone receptor negative or HER-2 overexpressing subtypes.

Keywords: axillary lymph node metastasis, FDG-PET, MRI, ultrasound

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Authors: Jyoti Srivastava, Sandhya S. Kaushik, Mallika Tewari, Hari S. Shukla

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Little information is available about the development of psychological well being over time among women who have been undergoing treatment for breast cancer. The aim of this study was to identify the trajectories of depression anxiety and stress among women with early-stage breast cancer. Of the 48 Indian women with newly diagnosed early-stage breast cancer recruited from surgical oncology unit, 39 completed an interview and were assessed for depression anxiety and stress (Depression Anxiety Stress Scale-DASS 21) before their first course of chemotherapy (baseline) and follow up interviews at 3, 6 and 9 months thereafter. Growth mixture modeling was used to identify distinct trajectories of Depression Anxiety and Stress symptoms. Logistic Regression analysis was used to evaluate the characteristics of women in distinct groups. Most women showed mild to moderate level of depression and anxiety (68%) while normal to mild level of stress (71%). But one in 11 women was chronically anxious (9%) and depressed (9%). Young age, having a partner, shorter education and receiving chemotherapy but not radiotherapy might characterize women whose psychological symptoms remain strong nine months after diagnosis. By looking beyond the mean, it was found that several socio-demographic and treatment factors characterized the women whose depression, anxiety and stress level remained severe even nine months after diagnosis. The results suggest that support provided to cancer patients should have a special focus on a relatively small group of patient most in need.

Keywords: psychological well being, growth mixture modeling, logistic regression analysis, socio-demographic factors

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Authors: Tefera Worku Mekonnen, Hiseh Chih Tsai

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Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR) based tumor targeted 4.5 (4.5G) poly(amidoamine) dendrimer-cisplatin nanocomplex (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs have been examined by FTIR, X-ray diffraction, Raman, and X-ray photoelectron spectroscopy. The conjugation of cisplatin (Cis-pt) with 4.5GDP was confirmed using carbon NMR. The tumor-specific 4.5GDP-Cis-pt NC provided ~45% and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed when the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NP was biocompatible in different cell lines, even at a high concentration (200 µg mL−1). In contrast, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL−1) significantly increased the cytotoxicity against the cancer cells, which is dose-dependent on the concentration of AC-IO-Ova NPs. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, the efficiency of anticancer cells may be further assisted by induction of an innate immune response via M1 macrophage polarization due to the presence of AC-IO-Ova NPs. We provide a better synergestic chemoimmunotherapeutic strategy to enhance the efficiency of anticancer of cisplatin via chemotherapeutic agent 4.5GDP-Cis-pt NC and induction of proinflammatory cytokines to stimulate innate immunity through AC-IO-Ova NPs against tumors.

Keywords: cisplatin-release, iron oxide, ovalbumin, poly(amidoamine) dendrimer

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Authors: Alejandro Salicrup, Riacrdo Gelhman, Geetha Gopalakrishna

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The main aim of this session is to have a panel to discuss specific steps for the integration of traditional, complementary and alternative medicine (TCAM) with conventional oncology for enhancing treatment practices at the global level, specifically in low-and-middle-income-countries (LMICs). Concrete current and required programs for strengthening Integrative Oncology research in LMICs will also be discussed. Case Studies from Latin America, Asia, Europe and Africa will discuss and highlight 1) What is working regarding treatment practices in integrative oncology in their countries/regions providing concrete examples 2) What is not working on this integration for cancer treatment in their countries/regions with concrete examples and 3) What are the challenges and opportunities for research related to integrative oncology treatment. Discussion will include potential next steps and potential mechanisms to enhance global integrative oncology research aimed to enhance the use of TCAM therapies and strengthening cancer treatment in LMICs.

Keywords: global cancer treatment, integrative oncology research, low and middle income countries, traditional, complementary and alternative medicines

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Authors: Federico Cevoli

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Purinergic P2X7 receptors (P2X7R) are ligand-gated non-selective cation channels involved in several physiological and pathological processes. They are particularly promising pharmacological targets as they are present in an increasing number of different cells types. P2X7R activation is triggered following elevated concentrations of extracellular ATP, similarly to those observed in tissues injury, chronic inflammation and T-cell activation, as well as in the scrambling of phospholipids leading to membrane blebbing and apoptosis. Another hallmark of P2X7 is cell permeabilization, commonly known as “macropore” formation allowing the passage of nanometer-sized molecules up to 900Da. Recently, full-length P2X7 Cryo-EM structures revealed unique functional sites, including two cytoplasmic domains - the cytoplasmic "anchor" and "ballast". To date, the molecular units/complex by which P2X7R exerts its pathophysiological functions are unknown. Using custom-made cell-penetrating HIV-1 TAT peptides, we show for the first-time potential implications of P2X7 cytoplasmic anchor in the regulation of caspase3/7 activation as well as TNFα regulation.

Keywords: P2X7R, immunology, TAT-peptide, cell death

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Authors: Hannah Nagel, Hayley Lang, Albert Sole Guitart, Natasha Lean, Rachel Allavena, Cleide Sprohnie-Barrera, Alex Young

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Aggressive neoplasia of the hoof is a rare occurrence in horses and has been only sporadically described in the literature. In the few cases reported intra-hoof wall, aggressive neoplasia has been documented radiographically and has been described with variable imaging characteristics. These include a well-defined osteolytic area, a smoothly outlined semi-circular defect, an extensive draining tract beneath the hoof wall, as well as an additional large area of osteolysis or an extensive central lytic region. A 20-year-old Quarterhorse gelding and a 10-year-old Thoroughbred gelding were both presented for chronic reoccurring lameness in the left forelimb and left hindlimb, respectively. Both of the cases displayed radiographic lesions that have been previously described but also displayed osteoproliferative expansile regions of additional bone formation. Changes associated with hoof neoplasia are often non-specific due to the nature and capacity of bone to react to pathological insult, which is either to proliferate or be absorbed. Both cases depict and describe imaging findings seen on radiography, contrast radiography, computed tomography, and magnetic resonance imaging before reaching a histological diagnosis of malignant melanoma and squamous cell carcinoma. Although aggressive hoof wall neoplasia is rare, there are some imaging features which may raise our index of suspicion for an aggressive hoof wall lesion. This case report documents two horses with similar imaging findings who underwent multiple assessments, surgical interventions, and imaging modalities with a final diagnosis of malignant neoplasia.

Keywords: horse, hoof, imaging, radiography, neoplasia

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Authors: Nishanth Venugopal Menon, Chuah Yon Jin, Samantha Phey, Wu Yingnan, Zhang Ying, Vincent Chan, Kang Yuejun

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Cell Migration is a vital phenomenon that the cells undergo in various physiological processes like wound healing, disease progression, embryogenesis, etc. Cell migration depends primarily on the chemical and physical cues available in the cellular environment. The chemical cue involves the chemokines secreted and gradients generated in the environment while physical cues indicate the impact of matrix properties like nanotopography and stiffness on the cells. Mesenchymal Stem Cells (MSCs) have been shown to have a role wound healing in vivo and its migration to the site of the wound has been shown to have a therapeutic effect. In the field of stem cell based tissue regeneration of bones and cartilage, one approach has been to introduce scaffold laden with MSCs into the site of injury to enable tissue regeneration. In this work, we have studied the combinatorial impact of the substrate physical properties on MSC migration. A microfluidic in vitro model was created to perform the migration studies. The microfluidic model used is a three compartment device consisting of two cell seeding compartments and one migration compartment. Four different PDMS substrates with varying substrate roughness, stiffness and hydrophobicity were created. Its surface roughness and stiffness was measured using Atomic Force Microscopy (AFM) while its hydrphobicity was measured from the water contact angle using an optical tensiometer. These PDMS substrates are sealed to the microfluidic chip following which the MSCs are seeded and the cell migration is studied over the period of a week. Cell migration was quantified using fluorescence imaging of the cytoskeleton (F-actin) to find out the area covered by the cells inside the migration compartment. The impact of adhesion proteins on cell migration was also quantified using a real-time polymerase chain reaction (qRT PCR). These results suggested that the optimal substrate for cell migration would be one with an intermediate level of roughness, stiffness and hydrophobicity. A higher or lower value of these properties affected cell migration negatively. These observations have helped us in understanding that different substrate properties need to be considered in tandem, especially while designing scaffolds for tissue regeneration as cell migration is normally impacted by the combinatorial impact of the matrix. These observations may lead us to scaffold optimization in future tissue regeneration applications.

Keywords: cell migration, microfluidics, in vitro model, stem cell migration, scaffold, substrate properties

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Authors: Jean Paul M. Milambo

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Purpose: Aromatase inhibitors (AIs) are indicated in the treatment of hormone-receptive breast cancer in postmenopausal women in various settings. Studies have shown cardiovascular events in some developed countries. To date the data is sparce for evidence-based recommendations in African clinical settings due to lack of cancer registries, capacity building and surveillance systems. Therefore, this study was conducted to assess the feasibility of HyBeacon® probe genotyping adjunctive to standard care for timely prediction and diagnosis of Aromatase inhibitors (AIs) associated adverse events in breast cancer survivors in Africa. Methods: Cross sectional study was conducted to assess the knowledge of POCT among six African countries using online survey and telephonically contacted. Incremental cost effectiveness ratio (ICER) was calculated, using diagnostic accuracy study. This was based on mathematical modeling. Results: One hundred twenty-six participants were considered for analysis (mean age = 61 years; SD = 7.11 years; 95%CI: 60-62 years). Comparison of genotyping from HyBeacon® probe technology to Sanger sequencing showed that sensitivity was reported at 99% (95% CI: 94.55% to 99.97%), specificity at 89.44% (95% CI: 87.25 to 91.38%), PPV at 51% (95%: 43.77 to 58.26%), and NPV at 99.88% (95% CI: 99.31 to 100.00%). Based on the mathematical model, the assumptions revealed that ICER was R7 044.55. Conclusion: POCT using HyBeacon® probe genotyping for AI-associated adverse events maybe cost effective in many African clinical settings. Integration of preventive measures for early detection and prevention guided by different subtype of breast cancer diagnosis with specific clinical, biomedical and genetic screenings may improve cancer survivorship. Feasibility of POCT was demonstrated but the implementation could be achieved by improving the integration of POCT within primary health cares, referral cancer hospitals with capacity building activities at different level of health systems. This finding is pertinent for a future envisioned implementation and global scale-up of POCT-based initiative as part of risk communication strategies with clear management pathways.

Keywords: breast cancer, diagnosis, point of care, South Africa, aromatase inhibitors

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Authors: Sara Ataei, Molouk Hadjibabaie, Shirinsadat Badri, Amirhossein Moslehi, Iman Karimzadeh, Ardeshir Ghavamzadeh

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Purpose: To assess the pattern and probable risk factors for moderate and major drug–drug interactions in a referral hematology-oncology ward in Iran. Methods: All patients admitted to hematology–oncology ward of Dr. Shariati Hospital during a 6-month period and received at least two anti-cancer or non-anti-cancer medications simultaneously were included. All being scheduled anti-cancer and non-anti-cancer medications both prescribed and administered during ward stay were considered for drug–drug interaction screening by Lexi-Interact On- Desktop software. Results: One hundred and eighty-five drug–drug interactions with moderate or major severity were detected from 83 patients. Most of drug–drug interactions (69.73 %) were classified as pharmacokinetics. Fluconazole (25.95 %) was the most commonly offending medication in drug–drug interactions. Interaction of sulfamethoxazole-trimethoprim with fluconazole was the most common drug–drug interaction (27.27 %). Vincristine with imatinib was the only identified interaction between two anti-cancer agents. The number of administered medications during ward stay was considered as an independent risk factor for developing a drug–drug interaction. Conclusions: Potential moderate or major drug–drug interactions occur frequently in patients with hematological malignancies or related diseases. Performing larger standard studies are required to assess the real clinical and economical effects of drug–drug interactions on patients with hematological and non-hematological malignancies.

Keywords: drug–drug interactions, hematology–oncology ward, hematological malignancies

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Authors: Amit Kumar Baghel, Sisir Kumar Nayak

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The proposed metamaterial design help to increase the radiation efficiency at 2.9 GHz by reducing the side and back lobes by making the phase difference of the waves emerging from the phase center of the horn antenna same after passing through metamaterial array. The unit cell of the metamaterial is having concentric ring structure made of copper of 0.035 mm thickness on both sides of FR4 sheet. The inner ring diameter is kept as 3 mm, and the outer ring diameters are changed according to the path and tramission phase difference of the unit cell from the phase center of the antenna in both the horizontal and vertical direction, i.e., in x- and y-axis. In this case, the ring radius varies from 3.19 mm to 6.99 mm with the respective S21 phase difference of -62.25° to -124.64°. The total phase difference can be calculated by adding the path difference of the respective unit cell in the array to the phase difference of S21. Taking one of the unit cell as the reference, the total phase difference between the reference unit cell and other cells must be integer multiple of 360°. The variation of transmission coefficient S21 with the ring radius is greater than -6 dB. The array having 5 x 5 unit cell is kept inside the pyramidal horn antenna (L X B X H = 295.451 x 384.233 x 298.66 mm3) at a distance of 36.68 mm from the waveguide throat. There is an improvement in side lobe level in E-plane by 14.6 dB when the array is used. The front to back lobe ration is increased by 1 dB by using the array. The proposed antenna with metamaterial array can be used in beam shaping for wireless power transfer applications.

Keywords: metamaterial, side lobe level, front to back ratio, beam forming

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Authors: Harish K. Chandrawanshi, Mithun S. Rajput, Neelima Choure, Purnima Dey Sarkar, Shailesh Jain

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The present research study aimed to fabricate and evaluate biodegradable nanoparticles of aromatase inhibitor letrozole, intended for breast cancer therapy. Letrozole loaded poly(D,L-lactide-co-glycolide acid) nanoparticles were prepared by solvent evaporation method using dichlorometane as solvent (oil phase) and polyvinyl alcohol (PVA) as aqueous phase. Prepared nanoparticles were characterized by particle size, infrared spectra, drug loading efficiency, drug entrapment efficiency and in vitro release and also evaluated for in vivo anticancer activity. The high speed homogenizer was used to produce stable nanoparticles of mean size range 198.35 ± 0.04 nm with high entrapment efficiency (69.86 ± 2.78%). Percentage of drug and homogenization speed significantly influenced the particle size, entrapment efficiency and release (p<0.05). The nanoparticles show significant in vivo anticancer activity against Ehrlich ascites carcinoma in mice. The significant system sustained the release of letrozole drug effectively and further investigation could exhibit its potential usefulness in breast cancer therapy.

Keywords: breast cancer/therapy, letrozole, nanoparticles, PLGA

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Authors: Anna Bak-Klimek, Emily Spencer, Siew Lee, Karen Campbell, Wendy McInally

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Background & Significance: Over half of Teenagers and Young Adults (TYAs) say that they experience psychological distress after cancer diagnosis and TYAs with cancer are at higher risk of developing distress compared to other age groups. Despite this there are no age-appropriate interventions to help TYAs manage distress and there is a lack of conceptual understanding of what causes distress in this population group. This makes it difficult to design a targeted, developmentally appropriate intervention. This review aims to identify the key determinants of distress in TYAs affected by cancer and to propose an integrative model of cancer-related distress for TYAs. Method: A literature search was performed in Cochrane Database of Systematic Reviews, MEDLINE, PsycINFO, CINAHL, EMBASE and PsycArticles in May-June, 2022. Quantitative literature was systematically reviewed on the relationship between psychological distress experienced by TYAs affected by cancer and a wide range of factors i.e. individual (demographic, psychological, developmental, and clinical factors) and contextual (social/environmental) factors. Evidence was synthesized and correlates were categorized using the Biopsychosocial Model. The full protocol is available from PROSPERO (CRD42022322069) Results: Thirty eligible quantitative studies met criteria for the review. A total of twenty-six studies were cross-sectional, three were longitudinal and one study was a case control study. The evidence on the relationship between the socio-demographic, illness and treatment-related factors and psychological distress is inconsistent and unclear. There is however consistent evidence on the link between psychological factors and psychological distress. For instance, the use of cognitive and defence coping, negative meta-cognitive beliefs, less optimism, a lack of sense of meaning and lower resilience levels were significantly associated with higher psychological distress. Furthermore, developmental factors such as poor self-image, identity issues and perceived conflict were strongly associated with higher distress levels. Conclusions: The current review suggests that psychological and developmental factors such as ineffective coping strategies, poor self-image and identity issues may play a key role in the development of psychological distress in TYAs affected by cancer. The review proposes a Positive Developmental Psychology Model of Distress for Teenagers and Young Adults affected by cancer. The review highlights that implementation of psychological interventions that foster optimism, improve resilience and address self-image may result in reduced distress in TYA’s with cancer.

Keywords: cancer, determinant, psychological distress, teenager and young adult, theoretical model

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Authors: Kriyapa lairungruang, Arunporn Itharat

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Limonia acidissima L. (LA) (Common name: wood apple, Thai name: ma-khwit) is a medicinal plant which has long been used in Thai traditional medicine. Its bark is used for treatment of diarrhea, abscess, wound healing and inflammation and it is also used in oral cancer. Thus, this research aimed to investigate antioxidant and cytotoxic activities of the LA bark extracts produced by various extraction methods. Different extraction procedures were used to extract LA bark for biological activity testing: boiling in water, maceration with 95% ethanol, maceration with 50% ethanol and water boiling of each the 95% and the 50% ethanolic residues. All extracts were tested for antioxidant activity using DPPH radical scavenging assay, cytotoxic activity against human laryngeal epidermoid carcinoma (HEp-2) cells and human oral epidermoid carcinoma (KB) cells using sulforhodamine B (SRB) assay. The results found that the 95% ethanolic extract of LA bark showed the highest antioxidant activity with EC50 values of 29.76±1.88 µg/ml. For cytotoxic activity, the 50% ethanolic extract showed the best cytotoxic activity against HEp-2 and KB cells with IC50 values of 9.55±1.68 and 18.90±0.86 µg/ml, respectively. This study demonstrated that the 95% ethanolic extract of LA bark showed moderate antioxidant activity and the 50% ethanolic extract provided potent cytotoxic activity against HEp-2 and KB cells. These results confirm the traditional use of LA for the treatment of oral cancer and laryngeal cancer, and also support its ongoing use.

Keywords: antioxidant activity, cytotoxic activity, Laryngeal epidermoid carcinoma, Limonia acidissima L., oral epidermoid carcinoma

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Authors: Lakmali Anthony, Madeline Gillies

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Background Breast cancer (BC) is usually managed with surgical resection. Many outcomes traditionally used to define successful operative management, such as resection margin, do not adequately reflect patients’ experience. Patient-reported outcomes (PRO) such as Health-Related Quality of life (HRQoL) provide a means by which the impact of surgery for cancer can be reported in a patient-centered way. This exploratory cross-sectional study aims to; (1) describe postoperative HRQoL in patients who underwent primary resection in a regional Australian hospital; (2) describe the prevalence of anxiety, depression and clinically significant fear of cancer recurrence (FCR) in this population; and (3) identify demographic, psychosocial, disease and treatment factors associated with poorer self-reported HRQoL. Methods Patients who had resection of BC in a regional Australian hospital between 2015 and 2022 were eligible. Participants were asked to complete a survey designed to assess HRQoL, as well as validated instruments that assess several other psychosocial PROs hypothesized to be associated with HRQoL; emotional distress, fear of cancer recurrence, social support, dispositional optimism, body image and spirituality. Results Forty-six patients completed the survey. Clinically significant levels of FCR and emotional distress were present in this group. Many domains of HRQoL were significantly worse than an Australian reference population for BC. Demographic and disease factors associated with poor HRQoL included smoking and ongoing adjuvant systemic therapy. The primary operation was not associated with HRQoL for breast cancer. All psychosocial factors measured were associated with HRQoL. Conclusion HRQoL is an important outcome in surgery for both research and clinical practice. This study provides an overview of the quality of life in a regional Australian population of postoperative breast cancer patients and the factors that affect it. Understanding HRQoL and awareness of patients particularly vulnerable to poor outcomes should be used to aid the informed consent and shared decision-making process between surgeon and patient.

Keywords: breast cancer, surgery, quality of life, regional population

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Authors: Zakaria Mowafy Emam Mowafy, Hamed Abd Allah Hamed, Marwa Mahmoud Abd-Elmotalb, Andrew Anis Fakhray Mosaad

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The purpose of this paper is to determine the efficacy of polarized light therapy for chemotherapy-treated cancer patients who have oral mucositis. Methods of evaluation are the measurement of the WHO oral mucositis scale and the common toxicity criteria scale. Methods: Thirty cancer patients receiving chemotherapy (males and females) who had oral mucositis and ulceration pain, and their ages ranged from 30 to 55 years, were divided into two groups. Group (A), composed of 15 patients, received the Bioptron light therapy (BLT) in addition to the routine medical care of oral mucositis. Group (B) received only the routine medical care of oral mucositis; the duration of the BLT application was 10 minutes applied daily for 30 days. Results and conclusion: Results showed that the application of the BLT had valuable healing effects on oral mucositis in cancer patients receiving chemotherapy, as evidenced by the high decreases of the WHO oral mucositis scale and the common toxicity criteria scale.

Keywords: Bioptron light therapy, oral mucositis, WHO oral mucositis scale, common toxicity criteria scale

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Authors: Benoit Jauniaux, Azzam Ismail

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Objectives: The aims were to identify all incident adult cases of idiopathic inflammatory myopathies (IIMs) in the City of Leeds, UK, and to estimate the risk of cancer in IIMs as compared with the general population. Methods: Cases of IIMs were ascertained by review of all muscle biopsy reports from the Neuropathology Laboratory. A review of medical records was undertaken for each case to review the clinical diagnosis and collect epidemiological data such as age, ethnicity, sex, and comorbidities, including cancer. Leeds denominator population numbers were publicly obtainable. Results: Two hundred and six biopsy reports were identified, and after review, 50 incident cases were included in the study between June 2010 and January 2021. Out of the 50 cases, 27 were male, and 23 were female. The mean incidence rate of IIMs in Leeds throughout the study period was 7.42/1 000 000 person years. The proportion of IIMs cases with a confirmed malignancy was 22%. Compared to the general population, the relative risk of cancer was significantly greater in the IIMs population(31.56, P < 0.01). Conclusions: The incidence rate of IIMs in Leeds was consistent with data from previous literature, however, disagreement exists between different methods of IIMs case inclusion due to varying clinical criteria and definitions. IIMs are associated with increased risk of cancer however, the pathogenesis of this relationship still requires investigating. This study supports the practice of malignancy screening and long-term surveillance in patients with IIMs.

Keywords: idiopathic inflammatory myopathies, myositis, polymyositis, dermatomyositis, malignancy, epidemiology, incidence rate, relative risk

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Authors: Amina Ben Abla, Sylvie Changotade, Geraldine Rohman, Guilhem Boeuf, Cyrine Dridi, Ahmed Elmarjou, Florence Dufour, Didier Lutomski, Abdellatif Elm’semi

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Understanding cell adhesion and interaction with the extracellular matrix is essential for biomedical and biotechnological applications, including the development of biomaterials. In recent years, numerous biomaterials have emerged and were used in the field of tissue engineering. Nevertheless, the lack of interaction of biomaterials with cells still limits their bio-integration. Thus, the design of bioactive biomaterials to improve cell attachment and proliferation is of growing interest. In this study, bio-functionalized material was developed combining a synthetic polymer scaffold surface with selected domains of type III human fibronectin (FNIII-DOM) to promote cell adhesion and proliferation. Bioadhesive ligand includes cell-binding domains of human fibronectin, a major ECM protein that interacts with a variety of integrins cell-surface receptors, and ECM proteins through specific binding domains were engineered. FNIII-DOM was produced in bacterial system E. coli in 5L fermentor with a high yield level reaching 20mg/L. Bioactivity of the produced fragment was validated by studying cellular adhesion of human cells. The adsorption and immobilization of FNIII-DOM onto the polymer scaffold were evaluated in order to develop an innovative biomaterial.

Keywords: biomaterials, cellular adhesion, fibronectin, tissue engineering

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Authors: Milica Karadzic, Lidija Jevric, Sanja Podunavac-Kuzmanovic, Strahinja Kovacevic, Sinisa Markov, Aleksandar Okljesa, Andrea Nikolic, Marija Sakac, Katarina Penov Gasi

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This study considered the microbiological activity determination and molecular docking study for selected steroid derivatives of biomedical importance. Minimal inhibitory concentration (MIC) was determined for steroid derivatives against Staphylococcus aureus using macrodilution method. Some of the investigated steroid derivatives express bacteriostatic effect against Staphylococcus aureus. Molecular docking approaches are the most widely used techniques for predicting the binding mode of a ligand. Molecular docking study was done for steroid derivatives for androgen receptor negative prostate cancer cell line (PC-3) toward Human Cytochrome P450 CYP17A1. The molecules that had the smallest experimental IC50 values confirmed their ability to dock into active place using suitable molecular docking procedure. The binding disposition of those molecules was thoroughly investigated. Microbiological analysis and molecular docking study were conducted with aim to additionally characterize selected steroid derivatives for future investigation regarding their biological activity and to estimate the binding-affinities of investigated derivatives. This article is based upon work from COST Action (TD1305), supported by COST (European Cooperation and Science and Technology).

Keywords: binding affinity, minimal inhibitory concentration, molecular docking, pc-3 cell line, staphylococcus aureus, steroids

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Authors: Niousha Bagheri Khulenjani, Mohammad Saniee Abadeh

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Learning from very big datasets is a significant problem for most present data mining and machine learning algorithms. MicroRNA (miRNA) is one of the important big genomic and non-coding datasets presenting the genome sequences. In this paper, a hybrid method for the classification of the miRNA data is proposed. Due to the variety of cancers and high number of genes, analyzing the miRNA dataset has been a challenging problem for researchers. The number of features corresponding to the number of samples is high and the data suffer from being imbalanced. The feature selection method has been used to select features having more ability to distinguish classes and eliminating obscures features. Afterward, a Convolutional Neural Network (CNN) classifier for classification of cancer types is utilized, which employs a Genetic Algorithm to highlight optimized hyper-parameters of CNN. In order to make the process of classification by CNN faster, Graphics Processing Unit (GPU) is recommended for calculating the mathematic equation in a parallel way. The proposed method is tested on a real-world dataset with 8,129 patients, 29 different types of tumors, and 1,046 miRNA biomarkers, taken from The Cancer Genome Atlas (TCGA) database.

Keywords: cancer classification, feature selection, deep learning, genetic algorithm

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Authors: Lakmali Anthony, Madeline Gillies

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Purpose: Long-term survivorship in colorectal cancer (CRC) is increasing as mortality decreases, leading to increased focus on patient-reported outcomes such as quality of life (QoL). CRC patients often have decreased QoL even after treatment is complete. This systematic review of the literature aims to identify psychosocial factors associated with decreased QoL in post-treatment CRC patients. Methodology: This systematic review was performed in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The search was conducted in MEDLINE, EMBASE, and PsychINFO using MeSH headings. The two authors screened studies for relevance and extracted data. Results: Seventeen studies were identified, including 6,272 total participants (mean = 392, 58% male) with a mean age of 60.6 years. The European Organisation for Research and Treatment of Cancer QLQ-C30 was the most common measure of QoL (n=14, 82.3%). Most studies (n=15, 88.2%) found that emotional distress correlated with poor global QoL. This was most commonly measured with the Hospital Anxiety & Depression Scale (n=11, 64.7%). Other psychosocial factors associated with QoL were lack of social support, body image, and financial difficulties. Clinicopathologic determinants included presence of stoma and metastasis. Conclusion: This systematic review provides a summary of the psychosocial determinants of poor QoL in post-treatment CRC patients, as well as the most commonly reported measures of these. An understanding of these potentially modifiable determinants of poor outcome is pivotal to the provision of quality, patient-centred care in surgical oncology.

Keywords: colorectal cancer, cancer surgery, quality of life, oncology, social determinants

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Authors: Mrinal Kanti Bhowmik, Shawli Bardhan Jr., Debotosh Bhattacharjee

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Human skin containing temperature value more than absolute zero, discharges infrared radiation related to the frequency of the body temperature. The difference in infrared radiation from the skin surface reflects the abnormality present in human body. Considering the difference, detection and forecasting the temperature variation of the skin surface is the main objective of using Medical Infrared Thermography(MIT) as a diagnostic tool for pain detection. Medical Infrared Thermography(MIT) is a non-invasive imaging technique that records and monitors the temperature flow in the body by receiving the infrared radiated from the skin and represent it through thermogram. The intensity of the thermogram measures the inflammation from the skin surface related to pain in human body. Analysis of thermograms provides automated anomaly detection associated with suspicious pain regions by following several image processing steps. The paper represents a rigorous study based survey related to the processing and analysis of thermograms based on the previous works published in the area of infrared thermal imaging for detecting inflammatory pain diseases like arthritis, spondylosis, shoulder impingement, etc. The study also explores the performance analysis of thermogram processing accompanied by thermogram acquisition protocols, thermography camera specification and the types of pain detected by thermography in summarized tabular format. The tabular format provides a clear structural vision of the past works. The major contribution of the paper introduces a new thermogram acquisition standard associated with inflammatory pain detection in human body to enhance the performance rate. The FLIR T650sc infrared camera with high sensitivity and resolution is adopted to increase the accuracy of thermogram acquisition and analysis. The survey of previous research work highlights that intensity distribution based comparison of comparable and symmetric region of interest and their statistical analysis assigns adequate result in case of identifying and detecting physiological disorder related to inflammatory diseases.

Keywords: acquisition protocol, inflammatory pain detection, medical infrared thermography (MIT), statistical analysis

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Authors: Kyriaki Hatziagapiou, Konstantinos Bethanis, Olti Nikola, Elias Christoforides, Eleni Koniari, Eleni Kakouri, George Lambrou, Christina Kanaka-Gantenbein

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Glioblastoma multiforme (GBM) remains a serious health challenge, as current therapeutic modalities continue to yield unsatisfactory results, with the average survival rarely exceeding 1-2 years. Natural compounds still provide some of the most promising approaches for discovering new drugs. The non-psychotropic cannabidiol (CBD) deriving from Cannabis sativa L. provides such promise. CBD is endowed with anticancer, antioxidant, and genoprotective properties as established in vitro and in in vivo experiments. CBD’s selectivity towards cancer cells and its safe profile suggest its usage in cancer therapies. However, the bioavailability of oral CBD is low due to poor aqueous solubility, erratic gastrointestinal absorption, and significant first-pass metabolism, hampering its therapeutic potential and resulting in a variable pharmacokinetic profile. In this context, CBD can take great advantage of nanomedicine-based formulation strategies. Cyclodextrins (CDs) are cyclic oligosaccharides used in the pharmaceutical industry to incorporate apolar molecules inside their hydrophobic cavity, increasing their stability, water solubility, and bioavailability or decreasing their side effects. CBD-inclusion complexes with CDs could be a good strategy to improve its properties, like solubility and stability to harness its full therapeutic potential. The current research aims to study the potential cytotoxic effect of CBD and CBD-CDs complexes CBD-RMβCD (randomly methylated β-cyclodextrin) and CBD-HPβCD (hydroxypropyl-b-CD) on the A172 glioblastoma cell line. CBD is diluted in 10% DMSO, and CBD/CDs solutions are prepared by mixing solid CBD, solid CDs, and dH2O. For the biological assays, A172 cells are incubated at a range of concentrations of CBD, CBD-RMβCD and CBD-HPβCD, RMβCD, and HPβCD (0,03125-4 mg/ml) at 24, 48, and 72 hours. Analysis of cell viability after incubation with the compounds is performed with Alamar Blue viability assay. CBD’s dilution to DMSO 10% was inadequate, as crystals are observed; thus cytotoxicity experiments are not assessed. CBD’s solubility is enhanced in the presence of both CDs. CBD/CDs exert significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72, and 96 hours versus cells not exposed); as their concentration and time of exposure increases, the reduction of resazurin to resofurin decreases, indicating a reduction in cell viability. The cytotoxic effect is more pronounced in cells exposed to CBD-HPβCD for all concentrations and time-points. RMβCD and HPβCD at the highest concentration of 4 mg/ml also exerted antitumor action per se since manifesting cell growth inhibition. The results of our study could afford the basis of research regarding the use of natural products and their inclusion complexes as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgments: The research is partly funded by ΙΚΥ (State Scholarships Foundation) – Post-doc Scholarships-Partnership Agreement 2014-2020.

Keywords: cannabidiol, cyclodextrins, glioblastoma, hydroxypropyl-b-Cyclodextrin, randomly-methylated-β-cyclodextrin

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Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

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Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

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Authors: Dimitrie Marinceu, Alan Murchison

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The Canadian Used Fuel Container (UFC) is a mid-size hemispherical headed copper coated steel container measuring 2.5 meters in length and 0.5 meters in diameter containing 48 used fuel bundles. The contained used fuel produces significant gamma radiation requiring automated assembly processes to complete the assembly. The design throughput of 2,500 UFCs per year places constraints on equipment and hot cell design for repeatability, speed of processing, robustness and recovery from upset conditions. After UFC assembly, the UFC is inserted into a Buffer Box (BB). The BB is made from adequately pre-shaped blocks (lower and upper block) and Highly Compacted Bentonite (HCB) material. The blocks are practically ‘sandwiching’ the UFC between them after assembly. This paper identifies one possible approach for the BB automatic assembly cell and processes. Automation of the BB assembly will have a significant positive impact on nuclear safety, quality, productivity, and reliability.

Keywords: used fuel packing plant, automatic assembly cell, used fuel container, buffer box, deep geological repository

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Authors: Mansha Kotwani

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The specific spatio-temporal calcium concentration patterns are required by the fibroblasts to maintain its structure and functions. Thus, calcium concentration is regulated in cell at different levels in various activities of the cell. The variations in cytosolic calcium concentration largely depend on the buffers present in cytosol and influx of calcium into cytosol from ER through IP3Rs or Raynodine receptors followed by reuptake of calcium into ER through sarcoplasmic/endoplasmic reticulum ATPs (SERCA) pump. In order to understand the mechanisms of wound repair, tissue remodeling and growth performed by fibroblasts, it is of crucial importance to understand the mechanisms of calcium concentration regulation in fibroblasts. In this paper, a model has been developed to study calcium distribution in NRK fibroblast in the presence of buffers and ER flux with SERCA pump. The model has been developed for two dimensional unsteady state case. Appropriate initial and boundary conditions have been framed along with physiology of the cell. Finite element technique has been employed to obtain the solution. The numerical results have been used to study the effect of buffers, ER flux and source amplitude on calcium distribution in fibroblast cell.

Keywords: buffers, IP3R, ER flux, SERCA pump, source amplitude

Procedia PDF Downloads 243