Search results for: tumor tissue

Authors: Emma K. Sales, Nilda G. Butardo

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The project was undertaken to determine the effects of modified tissue culture protocols e.g. age of culture and hormone levels (2,4-D) in generating somaclonal variation. Moreover, the utility of molecular markers (SSR and MSAP) in sorting off types/somaclones were investigated. Results show that somaclonal variation is in effect due to prolonged subculture and high 2,4-D concentration. The resultant variation was observed to be due to high level of methylation events specifically cytosine methylation either at the internal or external cytosine and was identified by methylation sensitive amplification polymorphism (MSAP). Simple sequence repeats (SSR) on the other hand, was able to associate a marker to a trait of interest. These therefore, show that molecular markers can be an important tool in sorting out variation/mutants at an early stage.

Keywords: methylation, MSAP, somaclones, SSR, subculture, 2, 4-D

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Authors: Ilma Robo, Saimir Heta, Vera Ostreni, Elsaida Agrushi, Eduart Kapaj

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Introduction: Cyclic hormonal fluctuations are known from literature to have a clinically visible effects on gingival tissue reactions, to the diagnosed processes of gingival inflammation. Materials and methods: At a total of 47 female patients, ad-hock presented at the University Clinic, were recorded data on effect of hormonal oscillations at periodontal treatment protocol. Oral examination was performed on soft tissue of gingiva and the oral mucous membrane, always respecting the air-drying procedure and then checking with free eye differences in oral mucosal relief. After the patients were informed about the study protocol, the purpose of the study and the ongoing procedure, verbal consensus was required. Results: The study was conducted in a total of 47 patients, out of which 13 patients were under the gingivitis classification, and 24 patients under the periodontal classification. Patients included in the study are divided by age, cycle week respectively 1,2,3 and 4.The younger age of female patients is more prone to the appearance of gingivitis, which is further aggravated by the effects of sexual hormones and the effect of the controlled or non-regulated fluctuations of the latter. Conclusions: The healing process is more fuel-intensive in the absence of high hormone levels, as they are these pro-inflammatory hormones, both in or near the ho Younger women are more open to volunteering in studies that record individual and study data that may last in time.

Keywords: gingiva, hormonal oscillations, female patients, mucosa, periodontal non-surgical treatment

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Authors: Yaya Gao, Jifeng Liu, Yafeng Liu

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Objectives: This study aimed to improve clinicians' understanding and diagnosis of the Mammary analogue secretory carcinoma of the salivary gland（MASC）. Methods: The clinical features of a MASC patient who was admitted to WestChina Hospital of Sichuan University in July 2020 were reviewed and analyzed. A 49-year-old woman with left upper neck pain for three months was admitted to the hospital. She underwent adenoma resection of the left submandibular gland 14 years ago and mucoepidermoid carcinoma resection surgery five years ago. Three months before admission, the patient developed pain in the left mandibular angle after "fatigue" and gradually developed radiation pain in the left ear, which could be relieved after rest. A mass of 1cm could be touched at the mandibular, with tenderness, poor mobility, and hard texture. No swelling, heat, pain, rupture, or pus was found on the surrounding skin. Color doppler ultrasonography of the salivary gland indicated a weak echo mass of 23*14*17mm in the left parotid gland. Results: Surgical excision was completed. Immunohistochemistry of the tumor samples after operation showed that P63（a few，+）, CK7（+）, S100（+）, DOG1（-）, Ki67（MIB-1）（+，5%），pan-TRK（+）, PAS(+) . ETV-6 gene translocation was detected in FISH in postoperative pathology, which indicated MASC. After this diagnosis, the patient sent the postoperative specimen of the second submandibular tumor to our hospital for consultation. The morphology of the two was similar. FISH detected ETV-6 gene translocation, so the second pathological diagnosis was revised to MASC. Conclusion: MASC of the salivary gland is a rare salivary gland tumor whose diagnosis depends on the result of the ETV6-NTRK3 fusion gene.

Keywords: mammary analogue secretory carcinoma, ETV6-NTRK3, salivary gland, misdiagnosed

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Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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Authors: Noha Mohammed Ismael Awad Eladal, Aala Shoukry Emara

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Background: Wound healing after dental implant surgery is critical to the procedure's success. The aim of this study was to explore the effects of rutin+vitamin C supplementation in wound healing following the placement of dental implants. Methodology: There were 20 participants in this randomized controlled clinical trial who needed dental implants to replace missing teeth. Patients were divided into two groups, and group A received dental implants. Group B received dental implants with vitamin C administration. Follow-up appointments were performed on day 3, day 7, and day 14 post-surgery, during which soft tissue healing and pain response scores were evaluated using the visual analog scale. Postoperative digital panoramas were taken immediately after surgery, 3 months and 6 months postoperatively. Changes in bone density along with the bone-implant interface at the mesial, distal and apical sides were assessed using the digora software. Results: An independent t-test was used to compare the means of variables between the two groups. At the same time, repeated measures were employed to compare the means of variables between two groups. ANOVA was used to compare bone density for the same group at different dates. Significant increased differences were observed at the mesial, distal and apical sides Surrounding the implants of both groups per time. However, the rate of increase was significantly higher in group B The mean difference at the mesial side after 6 months was 21.99 ± 5.48 in the group B and 14.21 ± 4.95 in group A, while it read 21.74 ± 3.56 in the group B and 10.78 ± 3.90 in group A at the distal side and was 18.90 ± 5.91 in the group B and 10.39 ± 3.49 group A at the apical side. Significance was recorded at P = 0.004, P = 0.0001, and 0.001 at the mesial, distal and apical sides respectively. The mean pain score and wound healing were significantly higher in group A as compared to group B, respectively. Conclusion: The rutin c + vitamin c group significantly promoted bone healing and speeded up the osseointegration process and improved soft tissue healing.

Keywords: osseointegration, soft tissue, rutin c, dental implant

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Authors: Chengcao Sun, Shujun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, Dejia Li

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Hsa-miRNA-139-5p (miR-139-5p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-139-5p on lung cancer is still ambiguous. In this study, we investigated the role of miR-139-5p on development of lung cancer. Results indicated miR-139-5p was significantly down-regulated in primary tumor tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-139-5p in NSCLC cell lines significantly suppressed cell growth through inhibition of cyclin D1 and up-regulation of p57(Kip2). In addition, miR-139-5p induced apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-139-5p inhibited cellular metastasis through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene c-Met was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression. Taken together, our results demonstrated that miR-139-5p plays a pivotal role in lung cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis by targeting oncogenic c-Met.

Keywords: hsa-miRNA-139-5p (miR-139-5p), c-Met, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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Authors: Shackira Am, Jos T. Puthur

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The phytostabilization potential of a halophyte Acanthus ilicifolius L. has been evaluated with special attention to the nutritional as well as anatomical adaptations developed by the plant. Distribution of essential elements influenced by the excess Zn²⁺ ions in the root tissue was studied by FEG-SEM EDX microanalysis. Significant variations were observed in the uptake and allocation of mineral elements like Mg, P, K, S, Na, Si and Al in the root of A. ilicifolius. The increase in S is in correlation with the increased synthesis of glutathione which might be involved in the biosynthesis of phytochelatins. This in turn might be aiding the plant to tolerate the adverse environmental conditions by stabilizing the excess Zn in the root tissue itself. Moreover it is revealed that most of the Zn were accumulated towards the central region near the vascular tissue. Treatment with ZnSO₄ in A. ilicifolius caused significant increase in the number of glandular trichomes on the adaxial leaf surface as compared to the leaves of control plants. In addition to this, A. ilicifolius when treated with ZnSO₄, exhibited a deeply stained layer of cells immediate to the endodermis, forming more or less a ring like structure around the xylem vessels. Phloem cells in these plants were crushed/reduced in numbers. There were no such deeply stained cells forming a ring around the xylem vessels in the control plants. These adaptive responses make the plant a suitable candidate for the phytostabilization of Zn. In addition the nutritional adjustment of the plant equips them for a better survival under increased concentration of Zn²⁺.

Keywords: Acanthus ilicifolius, mineral elements, phytostabilization, zinc

Procedia PDF Downloads 159

Authors: Jasminka Mujic, Karin Milde-Langosch, Volkmar Mueller, Mirza Suljagic, Tea Becirevic, Jozo Coric, Daria Ler

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MACC1 (metastasis associated in colon cancer-1) is a prognostic biomarker for tumor progression, metastasis, and survival of a variety of solid cancers. MACC1 also causes tumor growth in xenograft models and acts as a master regulator of the HGF/MET signaling pathway. In breast cancer, the expression of MACC1 determined by immunohistochemistry was significantly associated with positive lymph node status and advanced clinical stage. The aim of the present study was to further investigate the prognostic or predictive value of MACC1 expression in breast cancer using western blot analysis and immunohistochemistry. The results of our study have shown that high MACC1 expression in breast cancer is associated with shorter disease-free survival, especially in node-negative tumors. The MACC1 might be a suitable biomarker to select patients with a higher probability of recurrence which might benefit from adjuvant chemotherapy. Our results support a biologic role and potentially open the perspective for the use of MACC1 as predictive biomarker for treatment decision in breast cancer patients.

Keywords: breast cancer, biomarker, HGF/MET, MACC1

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Authors: Ling-Ling E., Hong-Chen Liu, Dong-Sheng Wang, Fang Su, Xia Wu, Zhan-Ping Shi, Yan Lv, Jia-Zhu Wang

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Objective: The objective of the present study is to evaluate the capacity of a tissue-engineered bone complex of recombinant human bone morphogenetic protein 2 (rhBMP-2) mediated dental pulp stem cells (DPSCs) and nano-hydroxyapatite/collagen/poly(L-lactide)(nHAC/PLA) to reconstruct critical-size alveolar bone defects in New Zealand rabbit. Methods: Autologous DPSCs were isolated from rabbit dental pulp tissue and expanded ex vivo to enrich DPSCs numbers, and then their attachment and differentiation capability were evaluated when cultured on the culture plate or nHAC/PLA. The alveolar bone defects were treated with nHAC/PLA, nHAC/PLA+rhBMP-2, nHAC/PLA+DPSCs, nHAC/PLA+DPSCs+rhBMP-2, and autogenous bone (AB) obtained from iliac bone or were left untreated as a control. X-ray and a polychrome sequential fluorescent labeling were performed post-operatively and the animals were sacrificed 12 weeks after operation for histological observation and histomorphometric analysis. Results: Our results showed that DPSCs expressed STRO-1 and vementin, and favoured osteogenesis and adipogenesis in conditioned media. DPSCs attached and spread well, and retained their osteogenic phenotypes on nHAC/PLA. The rhBMP-2 could significantly increase protein content, alkaline phosphatase (ALP) activity/protein, osteocalcin (OCN) content, and mineral formation of DPSCs cultured on nHAC/PLA. The X-ray graph, the fluorescent, histological observation and histomorphometric analysis showed that the nHAC/PLA+DPSCs+rhBMP-2 tissue-engineered bone complex had an earlier mineralization and more bone formation inside the scaffold than nHAC/PLA, nHAC/PLA+rhBMP-2 and nHAC/PLA+DPSCs, or even autologous bone. Implanted DPSCs contribution to new bone were detected through transfected eGFP genes. Conclutions: Our findings indicated that stem cells existed in adult rabbit dental pulp tissue. The rhBMP-2 promoted osteogenic capability of DPSCs as a potential cell source for periodontal bone regeneration. The nHAC/PLA could serve as a good scaffold for autologous DPSCs seeding, proliferation and differentiation. The tissue-engineered bone complex with nHAC/PLA, rhBMP-2, and autologous DPSCs might be a better alternative to autologous bone for the clinical reconstruction of periodontal bone defects.

Keywords: nano-hydroxyapatite/collagen/poly (L-lactide), dental pulp stem cell, recombinant human bone morphogenetic protein, bone tissue engineering, alveolar bone

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Authors: Amin Davoudi

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Aim: New approaches have been introduced to improve soft tissue indices of the dental implants. This systematic review aimed to investigate the effect of computer-aided design and computer-assisted manufacture (CAD/CAM) zirconia (Zr) implant abutments on periodontal aspects. Materials and Methods: Five electronic databases were searched thoroughly based on prior defined MeSH and non-MeSH keywords. Clinical studies were collected via hand searches in English language journals up to September 2020. Interproximal papilla stability, papilla recession, pink and white esthetic score (PES, WES), bone and gingival margin levels, color, and contour of soft tissue were reviewed. Results: The initial literature search yielded 412 articles. After the evaluation of abstracts and full texts, six studies were eligible to be screened. The study design of the included studies was a prospective cohort (n=3) and randomized clinical trial (n=3). The outcome was found to be significantly better for Zr than titanium abutments, however, the studies did not show significant differences between stock and CAD/CAM abutments. Conclusion: Papilla fill, WES, PES, and the distance from the contact point to dental crest bone of adjacent tooth and inter-tooth–implant distance were not significantly different between Zr CAD/CAM and Zr stock abutments. However, soft tissue stability and recession index were better in Zr CAD/CAM abutments.

Keywords: zirconia, CADCAM, periodental, implant

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Authors: Parveen Kundu, Zile Singh, Kunika Kundu, Swaran Kaur

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Context: Tuberculous osteomyelitis is a relatively uncommon condition that can present with various clinical and radiological features, often mimicking bone tumors or tumor-like lesions. In endemic countries like India, tuberculosis should be considered as a potential differential diagnosis for lytic bone lesions. This study aimed to highlight the different presentations of tuberculosis that can mimic tumors or tumor-like lesions in bone and emphasize the successful outcome of antitubercular therapy (ATT) in treating these cases. Research Aim: The main objective of this research was to explore the varied presentations of tuberculosis that mimic bone tumors or tumor-like lesions both clinically and radiologically, focusing on different bones. The study aimed to raise awareness among clinicians about this possibility and highlight the importance of histopathological confirmation before initiating treatment for lytic bone lesions. Methodology: This study utilized a retrospective review of 22 patients with suspected lytic bone lesions, who were subsequently diagnosed with tuberculous osteomyelitis through histopathological examination. The cases were collected over a period of ten years. Eleven cases required curettage for extensive lesions with sequestrations, while all 22 patients received 12 months of antitubercular therapy. Findings: The study included 14 male and 8 female patients, ranging in age from 3 to 61 years, with an average age of 22.05. The clinical and radiological presentations varied, with examples including bone cysts in the metaphyseal area of long bones, lesions resembling chondroblastomas, giant cell tumors, and osteoid osteoma, as well as multifocal lytic lesions resembling metastasis or multiple myeloma. One patient had lesions in both the clavicle and hand. Lesions mimicking chondromas were also observed in the phalanges of the hand and foot metatarsal. All patients showed resolution of the lesions and no residual disability following ATT. Theoretical Importance: This study highlights the importance of considering tuberculosis as a potential differential diagnosis for lytic bone lesions, particularly in endemic regions. It emphasizes the need for histopathological confirmation to accurately diagnose tuberculous osteomyelitis, as this is considered the gold standard. Data Collection and Analysis Procedures: Data for this study were collected retrospectively from medical records and radiological images of the 22 patients. The cases were analyzed based on clinical presentation, radiological findings, and histopathological confirmation. The outcomes of antitubercular therapy were also assessed. The data were summarized and presented descriptively. Question Addressed: This study aimed to address the question of how tuberculosis can mimic different bone tumors and tumor-like lesions clinically and radiologically. It also aimed to assess the successful outcome of antitubercular therapy in treating these cases. Conclusion: Tuberculous osteomyelitis can present with varied clinical and radiological features, often mimicking bone tumors or tumor-like lesions. Clinicians should consider tuberculosis as a potential diagnosis for lytic bone lesions, especially in endemic areas. Histopathological confirmation is essential for accurate diagnosis. Antitubercular therapy is an effective treatment for tuberculous osteomyelitis, leading to the resolution of the lesions with no residual disability.

Keywords: tuberculosis, tumor, curettage, bone

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Authors: Haiyan Wang, Dongyun Wang, Yongyong Yan, Richard T. Jaspers, Gang Wu

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Mesenchymal stem cell and 3D printing-based bone tissue engineering present a promising technique to repair large-volume bone defects. Its success is highly dependent on cell attachment, spreading, osteogenic differentiation, and in vivo survival of stem cells on 3D-printed scaffolds. In this study, human salivary histatin-1 (Hst1) was utilized to enhance the interactions between human adipose-derived stem cells (hASCs) and 3D-printed β-tricalcium phosphate (β-TCP) bioceramic scaffolds. Fluorescent images showed that Hst1 significantly enhanced the adhesion of hASCs to both bioinert glass and 3D-printed β-TCP scaffold. In addition, Hst1 was associated with significantly higher proliferation and osteogenic differentiation of hASCs on 3D-printed β-TCP scaffolds. Moreover, coating 3D-printed β-TCP scaffolds with histatin significantly promotes the survival of hASCs in vivo. The ERK and p38 but not JNK signaling was found to be involved in the superior adhesion of hASCs to β-TCP scaffolds with the aid of Hst1. In conclusion, Hst1 could significantly promote the adhesion, spreading, osteogenic differentiation, and in vivo survival of hASCs on 3D-printed β-TCP scaffolds, bearing a promising application in stem cell/3D printing-based constructs for bone tissue engineering.

Keywords: 3d printing, adipose-derived stem cells, bone tissue engineering, histatin-1, osteogenesis

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Authors: Adrian Ionut Nicoara, Denisa Ionela Ene, Alina Maria Holban, Cristina Busuioc

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At present, the development of materials with biomedical applications is a domain of interest that will produce a full series of benefits in engineering and medicine. In this sense, it is required to use a natural material, and this paper is focused on the development of a composite material based on bacterial cellulose – hydroxyapatite and silver nanoparticles with applications in hard tissue. Bacterial cellulose own features like biocompatibility, non-toxicity character and flexibility. Moreover, the bacterial cellulose can be conjugated with different forms of active silver to possess antimicrobial activity. Hydroxyapatite is well known that can mimic at a significant level the activity of the initial bone. The material was synthesized by using an ultrasound probe and finally characterized by several methods. Thereby, the morphological properties were analyzed by using Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Because the synthesized material has medical application in restore the tissue and to fight against microbial invasion, the samples were tested from the biological point of view by evaluating the biodegradability in phosphate-buffered saline (PBS) and simulated body fluid (SBF) and moreover the antimicrobial effect was performed on Gram-positive bacterium Staphylococcus aureus, Gram-negative bacterium Escherichia coli, and fungi Candida albicans. The results reveal that the obtained material has specific characteristics for bone regeneration.

Keywords: bacterial cellulose, biomaterials, hydroxyapatite, scaffolds materials

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Authors: Ghasem Yazdanpanah, Mona Kakavand, Hassan Niknejad

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Objectives: An important issue in tissue engineering (TE) is hemocompatibility. The current engineered vessels are seriously at risk of thrombus formation and stenosis. Amnion (AM) is the innermost layer of fetal membranes that consists of epithelial and mesenchymal sides. It has the advantages of low immunogenicity, anti-inflammatory and anti-bacterial properties as well as good mechanical properties. We recently introduced the amnion as a natural biomaterial for tissue engineering. In this study, we have evaluated hemocompatibility of amnion as potential biomaterial for tissue engineering. Materials and Methods: Amnions were derived from placentas of elective caesarean deliveries which were in the gestational ages 36 to 38 weeks. Extracted amnions were washed by cold PBS to remove blood remnants. Blood samples were obtained from healthy adult volunteers who had not previously taken anti-coagulants. The blood samples were maintained in sterile tubes containing sodium citrate. Plasma or platelet rich plasma (PRP) were collected by blood sample centrifuging at 600 g for 10 min. Hemocompatibility of the AM samples (n=7) were evaluated by measuring of activated partial thromboplastin time (aPTT), prothrombin time (PT), hemolysis, and platelet aggregation tests. P-selectin was also assessed by ELISA. Both epithelial and mesenchymal sides of amnion were evaluated. Glass slide and expanded polytetrafluoroethylene (ePTFE) samples were defined as control. Results: In comparison with glass as control (13.3 ± 0.7 s), prothrombin time was increased significantly while each side of amnion was in contact with plasma (p<0.05). There was no significant difference in PT between epithelial and mesenchymal surfaces (17.4 ± 0.7 s vs. 15.8 ± 0.7 s, respectively). However, aPPT was not significantly changed after incubation of plasma with amnion epithelial and mesenchymal surfaces or glass (28.61 ± 1.39 s, 31.4 ± 2.66 s, glass, 30.76 ± 2.53 s, respectively, p>0.05). Amnion surfaces, ePTFE and glass samples have less hemolysis induction than water considerably (p<0.001), in which no differences were detected. Platelet aggregation measurements showed that platelets were less stimulated by the amnion epithelial and mesenchymal sides, in comparison with ePTFE and glass. In addition, reduction in amount of p-selectin, as platelet activation factor, after incubation of samples with PRP indicated that amnion has less stimulatory effects on platelets than ePTFE and glass. Conclusion: Amnion as a natural biomaterial has the potential to be used in tissue engineering. Our results suggest that amnion has appropriate hemocompatibility to be employed as a vascular substitute.

Keywords: amnion, hemocompatibility, tissue engineering, biomaterial

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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: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

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One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

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The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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

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

Keywords: laryngeal cancer, laryngectomy, postoperative radiotherapy, survival

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Authors: C. Gallottini, W. Di Mari, A. Amaddeo, K. Barbaro, A. Dolci, G. Dolci, L. Gallottini, G. Barraco, S. Eramo

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A group of 10 dogs (group A) with Periodontal Disease in the third stage, were subjected to regenerative therapy of periodontal tissues, by use of nano hydroxy apatite (NHA). These animals induced by general anesthesia, where treated by ultrasonic scaling, root planning, and at the end by a mucogingival flap in which it was applied NHA. The flap was closed and sutured with simple steps. Another group of 10 dogs (group B), control group, was treated only by scaling and root planning. No patient was subjected to antibiotic therapy. After three months, a check was made by inspection of the oral cavity, radiography and bone biopsy at the alveolar level. Group A showed a total restitutio ad integrum of the periodontal structures, and in group B still mild gingivitis in 70% of cases and 30% of the state remains unchanged. Numerous experimental studies both in animals and humans have documented that the grafts of porous hydroxyapatite are rapidly invaded by fibrovascular tissue which is subsequently converted into mature lamellar bone tissue by activating osteoblast. Since we acted on the removal of necrotic cementum and rehabilitating the root tissue by polishing without intervention in the ligament but only on anatomical functional interface of cement-blasts, we can connect the positive evolution of the clinical-only component of the cement that could represent this perspective, the only reason that Periodontal Disease become a Cement Disease, while all other clinical elements as nothing more than a clinical pathological accompanying.

Keywords: nanoidroxiaphatite, parodontal disease, cement disease, regenerative therapy

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Authors: Raziyeh Mohammadi

Abstract:

At present, nanoparticles are used for various biomedical applications where they facilitate laboratory diagnostics and therapeutics. The performance of nanoparticles for biomedical applications is often assessed by their narrow size distribution, suitable magnetic saturation, and low toxicity effects. Superparamagnetic iron oxide nanoparticles have received great attention due to their applications as contrast agents for magnetic resonance imaging (MRI. (Processes in the tissue where the blood brain barrier is intact in this way shielded from the contact to this conventional contrast agent and will only reveal changes in the tissue if it involves an alteration in the vasculature. This technique is very useful for detecting tumors and can even be used for detecting metabolic functional alterations in the brain, such as epileptic activity.SPIONs have found application in Magnetic Resonance Imaging (MRI) and magnetic hyperthermia. Unlike bulk iron, SPIONs do not have remnant magnetization in the absence of the external magnetic field; therefore, a precise remote control over their action is possible.

Keywords: nanoparticles, MRI, biomedical, iron oxide, spions

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Authors: Oday A. Al-Juhaishi, Sa`ad M. Ismail, Hung-Hsun Yen, Christina M. Murray, Helen M. S. Davies

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The functional anatomy of the fascia in the greyhound is still poorly understood, and incompletely described. The basic knowledge of fascia stems mainly from anatomical, histological and ultrastructural analyses. In this study, twelve specimens of hindlimbs from six fresh greyhound cadavers (3 male, 3 female) were used to examine the topographical relationships of the superficial fascia with the skin and underlying tissue. The first incision was made along the dorsal midline from the level of the thoracolumbar junction caudally to the level of the mid sacrum. The second incision was begun at the level of the first incision and extended along the midline of the lateral aspect of the hindlimb distally, to just proximal to the tarsus, and, the skin margins carefully separated to observe connective tissue links between the skin and superficial fascia, attachment points of the fascia and the relationships of the fascia with blood vessels that supply the skin. A digital camera was used to record the anatomical features as they were revealed. The dissections identified fibrous septa connecting the skin with the superficial fascia and deep fascia in specific areas. The presence of the adipose tissue was found to be very rare within the superficial fascia in these specimens. On the extensor aspects of some joints, a fusion between the superficial fascia and deep fascia was observed. This fusion created a subcutaneous bursa in the following areas: a prepatellar bursa of the stifle, a tarsal bursa caudal to the calcaneus bone, and an ischiatic bursa caudal to the ischiatic tuberosity. The evaluation of blood vessels showed that the perforating vessels passed through fibrous septa in a perpendicular direction to supply the skin, with the largest branch noted in the gluteal area. The attachment points between the superficial fascia and skin were mainly found in the region of the flexor aspect of the joints, such as caudal to the stifle joint. The numerous fibrous septa between the superficial fascia and skin that have been identified in some areas, may create support for the blood vessels that penetrate fascia and into the skin, while allowing for movement between the tissue planes. The subcutaneous bursae between the skin and the superficial fascia where it is fused with the deep fascia may be useful to decrease friction between moving areas. The adhesion points may be related to the integrity and loading of the skin. The attachment points fix the skin and appear to divide the hindlimb into anatomical compartments.

Keywords: attachment points, fibrous septa, greyhound, subcutaneous bursa, superficial fascia

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Authors: Ji Un Shin, Wei Mao, Hyuk Sang Yoo

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Electrospinning is a versatile tool for fabricating nano-structured polymeric materials. Gelatin hydrogels are considered to be a good material for cell cultivation because of high water swellability as well as good biocompatibility. Three-dimensional (3-D) cell cultivation is a desirable method of cell cultivation for preparing tissues and organs because cell-to-cell interactions or cell-to-matrix interactions can be much enhanced through this approach. For this reason, hydrogels were widely employed as tissue scaffolds because they can support cultivating cells and tissue in multi-dimensions. Major disadvantages of hydrogel-based cell cultivation include low mechanical properties, lack of topography, which should be enhanced for successful tissue engineering. Herein we surface-immobilized gelatin on the surface of nanofibrous matrix for 3-D cell cultivation in topographical cues added environments. Electrospun nanofibers were electrospun with injection of poly(caprolactone) through a single nozzle syringe. Electrospun meshes were then chopped up with a high speed grinder to fine powders. This was hydrolyzed in optimized concentration of sodium hydroxide solution from 1 to 6 hours and harvested by centrifugation. The freeze-dried powders were examined by scanning electron microscopy (SEM) for revealing the morphology and fibrilar shaped with a length of ca. 20um was observed. This was subsequently immersed in gelatin solution for surface-coating of gelatin, where the process repeated up to 10 times for obtaining desirable coating of gelatin on the surface. Gelatin-coated nanofibrils showed high waterswellability in comparison to the unmodified nanofibrils, and this enabled good dispersion properties of the modified nanofibrils in aqueous phase. The degree of water-swellability was increased as the coating numbers of gelatin increased, however, it did not any meaning result after 10 times of gelatin coating process. Thus, by adjusting the gelatin coating times, we could successfully control the degree of hydrophilicity and water-swellability of nanofibrils.

Keywords: nano, fiber, cell, tissue

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Authors: Amr A. Fouad, Waleed H. Albuali, Iyad Jresat

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The protective effect of thymoquinone (TQ) was investigated in rats exposed to testicular injury induced by sodium arsenite (10mg/kg/day, orally, for two days). TQ treatment (10mg/kg/day, intraperitoneal injection) was applied for five days, starting three day before arsenic administration. TQ significantly attenuated the arsenic-induced decreases of serum testosterone, and testicular reduced glutathione level, and significantly decreased the elevations of testicular malondialdehyde and nitric oxide levels resulted from arsenic administration. Also, TQ ameliorated the arsenic-induced testicular tissue injury observed by histopathological examination. In addition, TQ decreased the arsenic-induced expression of inducible nitric oxide synthase and caspase-3 in testicular tissue. It was concluded that TQ may represent a potential candidate to protect against arsenic-induced testicular injury.

Keywords: thymoquinone, arsenic, testes, rats

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Authors: Abder-Rahman Ali, Antoine Vacavant, Manuel Grand-Brochier, Adélaïde Albouy-Kissi, Jean-Yves Boire

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In this paper, we present a new segmentation approach for liver lesions in regions of interest within MRI (Magnetic Resonance Imaging). This approach, based on a two-cluster Fuzzy C-Means methodology, considers the parameter variable compactness to handle uncertainty. Fine boundaries are detected by a local recursive merging of ambiguous pixels with a sequential forward floating selection with Zernike moments. The method has been tested on both synthetic and real images. When applied on synthetic images, the proposed approach provides good performance, segmentations obtained are accurate, their shape is consistent with the ground truth, and the extracted information is reliable. The results obtained on MR images confirm such observations. Our approach allows, even for difficult cases of MR images, to extract a segmentation with good performance in terms of accuracy and shape, which implies that the geometry of the tumor is preserved for further clinical activities (such as automatic extraction of pharmaco-kinetics properties, lesion characterization, etc).

Keywords: defuzzification, floating search, fuzzy clustering, Zernike moments

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Authors: Luciano Tarantino, Emanuele Balzano, Paolo Tarantino, Riccardo Aurelio Nasto, Aurelio Nasto

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Liver transplantation (OLT) is contraindicate in Portal Vein tumor Thrombosis (PVTT) from Hepatocellular Carcinoma at hepatic hilum(pH-HCC) Surgery,Thermal ablation and chemotherapy show poorer outcomes Electrochemotherapy (ECT) has been successfully used in patients with pH-HCC with PVTT. We report the results of ECT as downstaging aimed to definitive cure by OLT. F.P. 53 years HBV related Cirrhosis Child-Pugh B7 class; EGDS F2 aesophageal Varices. Diabetes. April 2016 : Enhanced Computed Tomography (CT) detected HCC(n.3 nodules in VII-VIII-VI;diameter range=25 cm) and PVTT of right portal vein. The patient was considered ineligible for OLT. May 2016: first ablation session with percutaneous Radiofrequency-ablation(RFA) of 3 HCC-nodules . August 2016: second ablation session with ECT of PVTT. CT october 2016: disappearance of PVTT and patent right portal vein. No intraparenchymal recurrence. CT march 2017: No recurrence in portal vein and in the left lobe. local recurrence in the VII-VIII segments. May 2017 : transarterial chemoembolization (TACE) of right lobe recurrences. CT October 2017: patent right portal vein. No recurrence. The patient was reconsidered for OLT. He underwent OLT in April 2018. At 36-months follow-up , no intrahepatic recurrence of HCC occurred. March 2021: enhanced CT and PET/CT detected a single small nodule (1.5 cm) uptaking tracer in the left upper pulmonary lobe, no hepatic recurrence . CT-guided FNB showed metastasis from HCC . June 2021: left lung upper lobectomy . At the current time the patient is alive and recurrence-free at 64 months follow-up. ECT Could be aneffective technique as pre-OLT dowstaging in HCC with PVTT.

Keywords: liver tumor ablation, interventional ultrasound, electrochemotherapy, liver transplantation

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Authors: Monisha Edirisooriya, Wilma Jack, Dominique Twelves, Jennifer Royds, Fiona Scott, Nicola Mason, Arran Turnbull, J. Michael Dixon

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Introduction: Excision biopsy has been the investigation of choice for patients presenting with pathological axillary lymphadenopathy without a breast abnormality. Core biopsy of nodes can provide sufficient tissue for diagnosis and has advantages in terms of morbidity and speed of diagnosis. This study evaluates the diagnostic accuracy of core biopsy in patients presenting with axillary lymphadenopathy. Methods: Between 2009 and 2019, 165 patients referred to the Edinburgh Breast Unit had a total of 179 axillary lymph node core biopsies. Results: 152 (92%) of the 165 initial core biopsies were deemed to contain adequate nodal tissue. Core biopsy correctly established malignancy in 75 of the 78 patients with haematological malignancy (96%) and in all 28 patients with metastatic carcinoma (100%) and correctly diagnosed benign changes in 49 of 57 (86%) patients with benign conditions. There were no false positives and no false negatives. In 67 (85.9%) of the 78 patients with hematological malignancy, there was sufficient material in the first core biopsy to allow the pathologist to make an actionable diagnosis and not ask for more tissue sampling prior to treatment. There were no complications of core biopsy. On follow up, none of the patients with benign cores has been shown to have malignancy in the axilla and none with lymphoma had their initial disease incorrectly classified. Conclusions: This study shows that core biopsy is now the investigation of choice for patients presenting with axillary lymphadenopathy even in those suspected as having lymphoma.

Keywords: core biopsy, excision biopsy, axillary lymphadenopathy, non-breast malignancy

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Authors: Rizwan Alam, Ikhtiar Khan, Aqib Iqbal

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Plants are naturally exposed to a wide variety of environmental stresses. The stresses may be biotic or/and abiotic. These environmental stresses have adverse effects on photosynthesis, water relation and nutrients uptake of plants. Fertilization of plants with exogenous minerals can enhance the drought tolerance in plants. In this experiment, canola (Brassica napus) was treated with solutions of calcium nitrate in different concentrations before the imposition of drought stress for 10 days. It was observed that drought stress decreased the tissue-K, Ca and K/Ca ratio of canola seedlings. The tissue-carbon and nitrogen contents were also depressed by the drought stress. Application of calcium nitrate, however, could alleviate the adverse effects of drought stress by showing a positive effect on all the aforementioned parameters.

Keywords: Brassica napus, calcium, carbon, potassium

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Authors: Mustafa Abu Ghalia, Mohammed Seddik

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The design and development of a new class of biomaterial has gained particular interest in producing polymer scaffold for biomedical applications. Improving mechanical properties, biological and controlling pores scaffold are important factors to provide appropriate biomaterial for implement in soft tissue repair and regeneration. In this study, poly-ε-caprolactone (PCL) /polyethylene glycol (PEG) copolymer (80/20) incorporated with CNF scaffolds were made employing solvent casting and particulate leaching methods. Four mass percentages of CNF (1, 2.5, 5, and 10 wt.%) were integrated into the copolymer through a silane coupling agent. Mechanical properties were determined using Tensile Tester data acquisition to investigate the effect of porosity, pore size, and CNF contents. Tensile strength obtained for PCL/PEG- 5 wt.% CNF was 16 MPa, which drastically decreased after creating a porous structure to 7.1 MPa. The optimum parameters of the results were found to be 5 wt.% for CNF, 240 μm for pore size, and 83% for porosity. Scanning electron microscopy (SEM) micrograph reveals that consistent pore size and regular pore shape were accomplished after the addition of CNF-5 wt. % into PCL/PEG. The results of mass loss of PCL/PEG reinforced-CNF 1% have clearly enhanced to double values compared with PCL/PEG copolymer and three times with PCL/PEG scaffold-CNF 1%. In addition, all PCL/PEG reinforced and scaffold- CNF were partially disintegrated under composting conditions confirming their biodegradable behavior. This also provides a possible solution for the end life of these biomaterials.

Keywords: PCL/PEG, cellulose nanofibers, tissue engineering, biodegradation, compost polymers

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Authors: Sukhwinder K. Bhullar, M. B. G. Jun

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The developments in biomedical industry have demanded the development of biocompatible, high performance materials to meet higher engineering specifications. The general requirements of such materials are to provide a combination of high stiffness and strength with significant weight savings, resistance to corrosion, chemical resistance, low maintenance, and reduced costs. Auxetic materials which come under the category of smart materials offer huge potential through measured enhancements in mechanical properties. Unique deformation mechanism, providing cushioning on indentation, automatically adjustable with its strength and thickness in response to forces and having memory returns to its neutral state on dissipation of stresses make them good candidate in biomedical industry. As simple extension and compression of tissues is of fundamental importance in biomechanics, therefore, to study the elastic behaviour of auxetic soft tissues implant is targeted in this paper. Therefore development and characterization of auxetic soft tissue implant is studied in this paper. This represents a real life configuration where soft tissue such as meniscus in knee replacement, ligaments and tendons often are taken as transversely isotropic. Further, as composition of alternating polydisperse blocks of soft and stiff segments combined with excellent biocompatibility make polyurethanes one of the most promising synthetic biomaterials. Hence selecting auxetic polyurathylene foam functional characterization is performed and compared with conventional polyurathylene foam.

Keywords: auxetic materials, deformation mechanism, enhanced mechanical properties, soft tissues

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