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Keywords = avascular tumor

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29 pages, 1508 KiB  
Review
Blocking Tumoral Angiogenesis VEGF/VEGFR Pathway: Bevacizumab—20 Years of Therapeutic Success and Controversy
by Elena Chitoran, Vlad Rotaru, Daniela-Cristina Stefan, Giuseppe Gullo and Laurentiu Simion
Cancers 2025, 17(7), 1126; https://doi.org/10.3390/cancers17071126 - 27 Mar 2025
Cited by 3 | Viewed by 1577
Abstract
The “angiogenesis switch”—defined as the active process by which solid tumors develop their own circulation—plays an important role in both tumoral growth and propagation. As the malignant tumor grows and reaches a critical size, the metabolic needs as a function of an ever-increasing [...] Read more.
The “angiogenesis switch”—defined as the active process by which solid tumors develop their own circulation—plays an important role in both tumoral growth and propagation. As the malignant tumor grows and reaches a critical size, the metabolic needs as a function of an ever-increasing distance to the nearest emergent blood vessel, can no longer be covered by the microenvironment of the peritumoral tissue. Although a relatively discrete process, the “angiogenic switch” acts as a limiting stage of tumoral development present from the avascular hyperplasia phase to the vascularized neoplastic phase, providing support for tumor expansion and metastasis. Over time, research has focused on blocking the angiogenetic pathways (such as VEGF/VEGFR signaling axis) leading to the development of targeted therapeutic agents such as Bevacizumab. Objectives: We conducted a review of the molecular principles of tumoral angiogenesis and we tried to follow the history of Bevacizumab from its first approval for human usage 20 years ago to current days, focusing on the impact this agent had in solid tumor therapy. A comprehensive review of clinical trials pertaining to Bevacizumab (from the era of the preclinic trials leading to approval for human usage, to the more recent randomized trial focusing on combination targeted therapy) further details the role of this drug. We aimed to establish if this ancient drug continues to have a place in modern oncology. Conclusions: Bevacizumab, one of the first drugs targeting tumoral microenvironment, remains one of the most important oncologic agents blocking the VEGF/VEGFR angiogenic pathway. otherwise, history of 20 years marked by numerous controversies (ranging from methodological errors of clinical trials to withdrawal of approval for human usage in breast cancer patients, from discussions about severe side effects to resistance to therapy and limited efficacity), Bevacizumab continues to provide an optimal therapeutic option for many solid tumors that previously had little to no means of treatment, improving otherwise bleak outcomes. Even in the era of personalized precision oncology, Bevacizumab continues to be a key element in many therapeutic regimens both as monotherapy and in combination with newer targeted agents. Full article
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14 pages, 3828 KiB  
Article
Restoring Hip Symmetry and Its Impact on Outcomes: A Case Series on Megaprosthesis Use in Non-Oncological Patients with Complications After Total Hip Arthroplasty
by Serban Dragosloveanu, Bogdan-Sorin Capitanu, Mihnea Nicolae Moise, Diana Elena Vulpe, Radu Josanu, Mihai Emanuel Gherghe, Emi Marinela Preda, Romica Cergan and Cristian Scheau
Symmetry 2025, 17(3), 322; https://doi.org/10.3390/sym17030322 - 21 Feb 2025
Cited by 1 | Viewed by 729
Abstract
Total hip arthroplasty (THA) is commonly performed for conditions like osteoarthritis, avascular necrosis, hip fractures, and hip dysplasia. Complications following THA can result in major proximal femoral defects (MPFD), which are challenging to manage. Megaprostheses provide a solution, offering stability and early weight-bearing, [...] Read more.
Total hip arthroplasty (THA) is commonly performed for conditions like osteoarthritis, avascular necrosis, hip fractures, and hip dysplasia. Complications following THA can result in major proximal femoral defects (MPFD), which are challenging to manage. Megaprostheses provide a solution, offering stability and early weight-bearing, though they present their own challenges. However, maintaining hip symmetry with megaprostheses is challenging in accurately restoring femoral offset, acetabular orientation, and soft tissue tension. These factors can contribute to instability, altered biomechanics, and functional impairment. Therefore, achieving hip symmetry through femoral and acetabular offset, limb length discrepancy (LLD), and center of rotation (COR) is an important consideration. Achieving proper symmetry may improve gait, quality of life, and overall outcomes. This case series includes 10 patients with non-tumoral pathology treated with megaprostheses for complications after THA between 2014 and 2024. Megaprosthesis conversion was performed for sepsis (n = 2), aseptic loosening (n = 4), and periprosthetic fracture (n = 4). Dislocation occurred in 20%, with one case showing restored hip symmetry but dislocating due to trauma and noncompliance. Another case had an LLD of 3 cm, contributing to dislocation. Periprosthetic infection was observed in 20%, managed with a two-stage approach. Although hip symmetry was not fully restored in all patients, strict follow-up and rehabilitation were essential for improving functionality and quality of life. Megaprosthesis is an effective solution for MPFD in non-oncological patients when performed correctly. Restoring hip symmetry is challenging and depends on patient care and compliance, though it is an important factor influencing outcomes. Full article
(This article belongs to the Special Issue New Trends in Biomimetics for Life-Sciences)
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12 pages, 2604 KiB  
Article
Three-Dimensional Planning for Vascularized Bone Grafts: Implementation and Surgical Application for Complex Bone Reconstruction in the Hand and Forearm
by Maximilian Zaussinger, Karl Schwaiger, Jürgen Schwarzbauer, Kathrin Bachleitner, Matthias Holzbauer, Gudrun Ehebruster and Manfred Schmidt
J. Clin. Med. 2025, 14(2), 440; https://doi.org/10.3390/jcm14020440 - 11 Jan 2025
Cited by 1 | Viewed by 1051
Abstract
Background/Objectives: Vascularized bone grafts have been successfully established for complex bone defects. The integration of three-dimensional (3D) simulation and printing technology may aid in more precise surgical planning and intraoperative bone shaping. The purpose of the present study was to describe the implementation [...] Read more.
Background/Objectives: Vascularized bone grafts have been successfully established for complex bone defects. The integration of three-dimensional (3D) simulation and printing technology may aid in more precise surgical planning and intraoperative bone shaping. The purpose of the present study was to describe the implementation and surgical application of this innovative technology for bone reconstruction. Methods: This prospective pilot study was conducted between June 2019 and June 2024. For this evaluation, patients who received vascularized bone reconstruction assisted with 3D technology were included. For reconstruction, the free medial femoral condyle (MFC) flap was used as the vascularized bone graft. Patient-specific 3D-printed templates, based on individual 3D simulations according to defect characteristics, were used for surgical planning, including flap elevation, shaping and inset. Results: A total of six patients (five male) with an average age of 39 years (range 19–62 years) and a mean follow-up time of 15 months (range 5–24 months) were analysed. The indications were as follows: avascular necrosis of the carpal bones, a metacarpal defect after tumor resection and pseudoarthrosis after a fractured ulna. Three patients received an osteochondral and three patients received a cortico-cancellous MFC flap. Conclusions: Our evaluation of clinical application revealed enhanced preoperative planning as well as intraoperative performance. Although the implementation for this technology is challenging, the new insights gained in planning and surgical guidance have led us to incorporate this technology into our standard routine. Full article
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22 pages, 9601 KiB  
Article
Spheroid Model of Mammary Tumor Cells: Epithelial–Mesenchymal Transition and Doxorubicin Response
by Laura Lacerda Coelho, Matheus Menezes Vianna, Debora Moraes da Silva, Beatriz Matheus de Souza Gonzaga, Roberto Rodrigues Ferreira, Ana Carolina Monteiro, Adriana Cesar Bonomo, Pedro Paulo de Abreu Manso, Marcelo Alex de Carvalho, Fernando Regla Vargas and Luciana Ribeiro Garzoni
Biology 2024, 13(7), 463; https://doi.org/10.3390/biology13070463 - 21 Jun 2024
Cited by 2 | Viewed by 2879
Abstract
Breast cancer is the most prevalent cancer among women worldwide. Therapeutic strategies to control tumors and metastasis are still challenging. Three-dimensional (3D) spheroid-type systems more accurately replicate the features of tumors in vivo, working as a better platform for performing therapeutic response analysis. [...] Read more.
Breast cancer is the most prevalent cancer among women worldwide. Therapeutic strategies to control tumors and metastasis are still challenging. Three-dimensional (3D) spheroid-type systems more accurately replicate the features of tumors in vivo, working as a better platform for performing therapeutic response analysis. This work aimed to characterize the epithelial–mesenchymal transition and doxorubicin (dox) response in a mammary tumor spheroid (MTS) model. We evaluated the doxorubicin treatment effect on MCF-7 spheroid diameter, cell viability, death, migration and proteins involved in the epithelial–mesenchymal transition (EMT) process. Spheroids were also produced from tumors formed from 4T1 and 67NR cell lines. MTSs mimicked avascular tumor characteristics, exhibited adherens junction proteins and independently produced their own extracellular matrix. Our spheroid model supports the 3D culturing of cells isolated from mice mammary tumors. Through the migration assay, we verified a reduction in E-cadherin expression and an increase in vimentin expression as the cells became more distant from spheroids. Dox promoted cytotoxicity in MTSs and inhibited cell migration and the EMT process. These results suggest, for the first time, that this model reproduces aspects of the EMT process and describes the potential of dox in inhibiting the metastatic process, which can be further explored. Full article
(This article belongs to the Section Cancer Biology)
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18 pages, 1639 KiB  
Article
Factors Associated with False Positive Breast Cancer Results in the Real-Time Sonoelastography Evaluation of Solid Breast Lesions
by Ivana Eremici, Andreea Borlea, Catalin Dumitru and Dana Stoian
Medicina 2024, 60(7), 1023; https://doi.org/10.3390/medicina60071023 - 21 Jun 2024
Cited by 1 | Viewed by 2538
Abstract
Background and Objectives: Breast cancer is one of the most widespread cancers among the female population around the world and is curable if diagnosed in an early stage. Consequently, breast cancer screening imaging techniques have greatly evolved and adjusted over the last [...] Read more.
Background and Objectives: Breast cancer is one of the most widespread cancers among the female population around the world and is curable if diagnosed in an early stage. Consequently, breast cancer screening imaging techniques have greatly evolved and adjusted over the last decades. Alongside mammography, sonoelastography became an important tool for breast cancer detection. However, sonoelastography still has its limitations, namely, there is still a high occurrence of false positive results in the BIRADS 4 category. The aim of our study is to identify potential false positive predictors and to ascertain the factors influencing the quality of strain ultrasound elastography for the evaluation of suspicious solid breast lesions categorized as BIRADS 4B, 4C, and 5. Materials and Methods: We conducted a retrospective study in a single private medical center in Timisoara between January 2017 and January 2022 analyzing 1625 solid breast lesions by the sonoelastography strain using a standardized BIRADS-US lexicon. Results: Our study showed that most sonoelastography factors linked to incorrect and overdiagnosis were due to a nodule dimension (OR = 1.02 per unit increase), posterior acoustic shadowing (OR = 12.26), reactive adenopathy (OR = 6.35), and an increased TES score (TES3 OR = 6.60; TES4 OR = 23.02; TES5 OR = 108.24). Regarding patient characteristics, age (OR = 1.09 per unit increase), BMI, (OR = 1.09 per unit increase), and breastfeeding history (OR = 3.00) were observed to increase the likelihood of false positive results. On the other hand, the nodules less likely to be part of the false positive group exhibited the following characteristics: a regular shape (OR = 0.27), homogenous consistency (OR = 0.42), and avascularity (OR = 0.22). Conclusions: Older age, high BMI, patients with a breastfeeding history, and those who exhibit the following specific nodule characteristics were most often linked to false positive results: large tumors with posterior acoustic shadowing and high elasticity scores, accompanied by reactive adenopathy. On the other hand, homogenous, avascular nodules with regular shapes were less likely to be misdiagnosed. Full article
(This article belongs to the Section Oncology)
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18 pages, 6090 KiB  
Review
Vascularization Reconstruction Strategies in Craniofacial Bone Regeneration
by Jiping Chen, Yu Da, Jing Yang, Guirong Zhu and Haiyan Qin
Coatings 2024, 14(3), 357; https://doi.org/10.3390/coatings14030357 - 18 Mar 2024
Cited by 1 | Viewed by 2129
Abstract
Craniofacial bone defects are usually secondary to accident trauma, resection of tumor, sever inflammation, and congenital disease. The defects of craniofacial bones impact esthetic appearance and functionality such as mastication, pronunciation, and facial features. During the craniofacial bone regeneration process, different osteogenic cells [...] Read more.
Craniofacial bone defects are usually secondary to accident trauma, resection of tumor, sever inflammation, and congenital disease. The defects of craniofacial bones impact esthetic appearance and functionality such as mastication, pronunciation, and facial features. During the craniofacial bone regeneration process, different osteogenic cells are introduced, including primary osteoblasts or pluripotent stem cells. However, the defect area is initially avascular, resulting in the death of the introduced cells and failed regeneration. Thus, it is vital to establish vascularization strategies to build a timely and abundant blood vessel supply network. This review paper therefore focuses on the reconstruction of both osteogenesis and vasculogenesis. The current challenges, various strategies, and latest efforts applied to enhance vascularization in craniofacial bone regeneration are discussed. These involve the application of angiogenic growth factors and cell-based vascularization strategies. In addition, surface morphology, porous characters, and the angiogenic release property of scaffolds also have a fundamental effect on vasculogenesis via cell behavior and are further discussed. Full article
(This article belongs to the Special Issue Advanced Alloy Degradation and Implants)
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15 pages, 1173 KiB  
Article
Antiangiogenic Therapy Efficacy Can Be Tumor-Size Dependent, as Mathematical Modeling Suggests
by Maxim Kuznetsov and Andrey Kolobov
Mathematics 2024, 12(2), 353; https://doi.org/10.3390/math12020353 - 22 Jan 2024
Cited by 1 | Viewed by 1505
Abstract
Antiangiogenic therapy (AAT) is an indirect oncological modality that is aimed at the disruption of cancer cell nutrient supply. Invasive tumors have been shown to possess inherent resistance to this treatment, while compactly growing benign tumors react to it by shrinking. It is [...] Read more.
Antiangiogenic therapy (AAT) is an indirect oncological modality that is aimed at the disruption of cancer cell nutrient supply. Invasive tumors have been shown to possess inherent resistance to this treatment, while compactly growing benign tumors react to it by shrinking. It is generally accepted that AAT by itself is not curative. This study presents a mathematical model of non-invasive tumor growth with a physiologically justified account of microvasculature alteration and the biomechanical aspects of importance during tumor growth and AAT. In the untreated setting, the model reproduces tumor growth with saturation, where the maximum tumor volume depends on the level of angiogenesis. The outcomes of the AAT simulations depend on the tumor size at the moment of treatment initiation. If it is close to the stable size of an avascular tumor grown in the absence of angiogenesis, then the tumor is rapidly stabilized by AAT. The treatment of large tumors is accompanied by the displacement of normal tissue due to tumor shrinkage. During this, microvasculature undergoes distortion, the degree of which depends on the displacement distance. As it affects tumor nutrient supply, the stable size of a tumor that undergoes AAT negatively correlates with its size at the beginning of treatment. For sufficiently large initial tumors, the long-term survival of tumor cells is compromised by competition with normal cells for the severely limited inflow of nutrients, which makes AAT effectively curative. Full article
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45 pages, 1218 KiB  
Article
Efficient Radial-Shell Model for 3D Tumor Spheroid Dynamics with Radiotherapy
by Florian Franke, Soňa Michlíková, Sebastian Aland, Leoni A. Kunz-Schughart, Anja Voss-Böhme and Steffen Lange
Cancers 2023, 15(23), 5645; https://doi.org/10.3390/cancers15235645 - 29 Nov 2023
Cited by 5 | Viewed by 2071
Abstract
Understanding the complex dynamics of tumor growth to develop more efficient therapeutic strategies is one of the most challenging problems in biomedicine. Three-dimensional (3D) tumor spheroids, reflecting avascular microregions within a tumor, are an advanced in vitro model system to assess the curative [...] Read more.
Understanding the complex dynamics of tumor growth to develop more efficient therapeutic strategies is one of the most challenging problems in biomedicine. Three-dimensional (3D) tumor spheroids, reflecting avascular microregions within a tumor, are an advanced in vitro model system to assess the curative effect of combinatorial radio(chemo)therapy. Tumor spheroids exhibit particular crucial pathophysiological characteristics such as a radial oxygen gradient that critically affect the sensitivity of the malignant cell population to treatment. However, spheroid experiments remain laborious, and determining long-term radio(chemo)therapy outcomes is challenging. Mathematical models of spheroid dynamics have the potential to enhance the informative value of experimental data, and can support study design; however, they typically face one of two limitations: while non-spatial models are computationally cheap, they lack the spatial resolution to predict oxygen-dependent radioresponse, whereas models that describe spatial cell dynamics are computationally expensive and often heavily parameterized, impeding the required calibration to experimental data. Here, we present an effectively one-dimensional mathematical model based on the cell dynamics within and across radial spheres which fully incorporates the 3D dynamics of tumor spheroids by exploiting their approximate rotational symmetry. We demonstrate that this radial-shell (RS) model reproduces experimental spheroid growth curves of several cell lines with and without radiotherapy, showing equal or better performance than published models such as 3D agent-based models. Notably, the RS model is sufficiently efficient to enable multi-parametric optimization within previously reported and/or physiologically reasonable ranges based on experimental data. Analysis of the model reveals that the characteristic change of dynamics observed in experiments at small spheroid volume originates from the spatial scale of cell interactions. Based on the calibrated parameters, we predict the spheroid volumes at which this behavior should be observable. Finally, we demonstrate how the generic parameterization of the model allows direct parameter transfer to 3D agent-based models. Full article
(This article belongs to the Section Cancer Therapy)
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15 pages, 3312 KiB  
Article
Analytical Models of Intra- and Extratumoral Cell Interactions at Avascular Stage of Growth in the Presence of Targeted Chemotherapy
by Evgeniia Lavrenteva, Constantinos Theodoropoulos and Michael Binns
Bioengineering 2023, 10(3), 385; https://doi.org/10.3390/bioengineering10030385 - 21 Mar 2023
Viewed by 1965
Abstract
In this study, we propose a set of nonlinear differential equations to model the dynamic growth of avascular stage tumors, considering nutrient supply from underlying tissue, innate immune response, contact inhibition of cell migration, and interactions with a chemotherapeutic agent. The model has [...] Read more.
In this study, we propose a set of nonlinear differential equations to model the dynamic growth of avascular stage tumors, considering nutrient supply from underlying tissue, innate immune response, contact inhibition of cell migration, and interactions with a chemotherapeutic agent. The model has been validated against available experimental data from the literature for tumor growth. We assume that the size of the modeled tumor is already detectable, and it represents all clinically observed existent cell populations; initial conditions are selected accordingly. Numerical results indicate that the tumor size and regression significantly depend on the strength of the host immune system. The effect of chemotherapy is investigated, not only within the malignancy, but also in terms of the responding immune cells and healthy tissue in the vicinity of a tumor. Full article
(This article belongs to the Special Issue Role of Computational Methods for Living Systems at Different Scales)
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Graphical abstract

9 pages, 2833 KiB  
Systematic Review
Does Diabetes Mellitus Increase the Risk of Avascular Osteonecrosis? A Systematic Review and Meta-Analysis
by Wojciech Konarski, Tomasz Poboży, Andrzej Kotela, Andrzej Śliwczyński, Ireneusz Kotela, Martyna Hordowicz and Jan Krakowiak
Int. J. Environ. Res. Public Health 2022, 19(22), 15219; https://doi.org/10.3390/ijerph192215219 - 18 Nov 2022
Cited by 16 | Viewed by 3287
Abstract
Avascular osteonecrosis (AVN) is caused by the disrupted blood supply to the bone. Most AVN cases occur in the femoral head, but other sites might be affected as well, including the jaw or distal bones of the extremities. Previous studies suggested that diabetes [...] Read more.
Avascular osteonecrosis (AVN) is caused by the disrupted blood supply to the bone. Most AVN cases occur in the femoral head, but other sites might be affected as well, including the jaw or distal bones of the extremities. Previous studies suggested that diabetes could increase the risk of AVN of the jaw, but the relationship between diabetes and AVN in other bone sites is unclear. This systematic review and meta-analysis aimed to summarize the evidence from studies that had reported on the occurrence of AVN in sites other than the jaw, depending on the diagnosis of diabetes. Overall, we included 6 observational studies carried out in different populations: primary or secondary AVN of the femoral head, Takayasu arteritis, general population, kidney transplant recipients, systemic lupus erythematosus, and primary brain tumors. A random-effects meta-analysis showed that the risk of AVN in sites other than the jaw was non-significantly increased in patients with diabetes (odds ratio: 1.90, 95% confidence interval: 0.93–3.91). The pooled estimate increased and was significant after the exclusion of one study (2.46, 1.14–5.32). There was a significant heterogeneity (I2 = 65%, tau2 = 0.48, p = 0.01; prediction interval, 0.21–16.84). There was no significant publication bias (p = 0.432). In conclusion, diabetes could increase the risk of AVN in sites other than the jaw, but the available evidence is limited. There is a need for large, well-designed, population-based studies. Full article
(This article belongs to the Collection Contemporary Challenges and Problems in Health)
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19 pages, 3329 KiB  
Article
The Rate of Cisplatin Dosing Affects the Resistance and Metastatic Potential of Triple Negative Breast Cancer Cells, Independent of Hypoxia
by Omkar Bhatavdekar, Inês Godet, Daniele Gilkes and Stavroula Sofou
Pharmaceutics 2022, 14(10), 2184; https://doi.org/10.3390/pharmaceutics14102184 - 13 Oct 2022
Cited by 2 | Viewed by 2990
Abstract
To best control tumor growth and/or metastasis in triple negative breast cancer (TNBC), it may be useful to understand the effect(s) of chemotherapy delivery (i.e., the rate and pattern of exposure to the drug) on cell sub-populations that have experienced different levels of [...] Read more.
To best control tumor growth and/or metastasis in triple negative breast cancer (TNBC), it may be useful to understand the effect(s) of chemotherapy delivery (i.e., the rate and pattern of exposure to the drug) on cell sub-populations that have experienced different levels of hypoxia (and/or acidosis). In this spirit, MDA-MB-231 TNBC cells, and their hypoxia-reporter counterparts, were characterized for their sensitivity to cisplatin. When in the form of multicellular spheroids, that capture the diffusion-limited transport that generates hypoxic and acidic subregions within the avascular areas of solid tumors, the effects of the rate and pattern of exposure to cisplatin on cell viability and motility/migration potential were evaluated for each cell sub-population. We demonstrated that cell sensitivity to cisplatin was not dependent on acidosis, but cell resistance increased with exposure to hypoxia. In spheroids, the increase of the rates of cell exposure to cisplatin, at a constant cumulative dose, increased sensitivity to chemotherapy and lowered the cells’ metastatic potential, even for cells that had experienced hypoxia. This effect was also shown to be caused by nanocarriers engineered to quickly release cisplatin which deeply penetrated the spheroid interstitium, resulting in the fast and uniform exposure of the TNBC tumors to the agent. This rate and dosing-controlled model may effectively limit growth and/or metastasis, independent of hypoxia. This mode of chemotherapy delivery can be enabled by engineered nanocarriers. Full article
(This article belongs to the Special Issue Engineering and Characterisation of Novel Nanomedicine Formulations)
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17 pages, 11428 KiB  
Article
Enhancement of Medical Images through an Iterative McCann Retinex Algorithm: A Case of Detecting Brain Tumor and Retinal Vessel Segmentation
by Yassir Edrees Almalki, Nisar Ahmed Jandan, Toufique Ahmed Soomro, Ahmed Ali, Pardeep Kumar, Muhammad Irfan, Muhammad Usman Keerio, Saifur Rahman, Ali Alqahtani, Samar M. Alqhtani, Mohammed Awaji M. Hakami, Alqahtani Saeed S, Waleed A. Aldhabaan and Abdulrahman Samir Khairallah
Appl. Sci. 2022, 12(16), 8243; https://doi.org/10.3390/app12168243 - 17 Aug 2022
Cited by 11 | Viewed by 2686
Abstract
Analyzing medical images has always been a challenging task because these images are used to observe complex internal structures of the human body. This research work is based on the study of the retinal fundus and magnetic resonance images (MRI) for the analysis [...] Read more.
Analyzing medical images has always been a challenging task because these images are used to observe complex internal structures of the human body. This research work is based on the study of the retinal fundus and magnetic resonance images (MRI) for the analysis of ocular and cerebral abnormalities. Typically, clinical quality images of the eyes and brain have low-varying contrast, making it challenge to diagnose a specific disease. These issues can be overcome, and preprocessing or an image enhancement technique is required to properly enhance images to facilitate postprocessing. In this paper, we propose an iterative algorithm based on the McCann Retinex algorithm for retinal and brain MRI. The foveal avascular zone (FAZ) region of retinal images and the coronal, axial, and sagittal brain images are enhanced during the preprocessing step. The High-Resolution Fundus (HRF) and MR brain Oasis images databases are used, and image contrast and peak signal-to-noise ratio (PSNR) are used to assess the enhancement step parameters. The average PSNR enhancement on images from the Oasis brain MRI database was about 3 dB with an average contrast of 57.4. The average PSNR enhancement of the HRF database images was approximately 2.5 dB with a contrast average of 40 over the database. The proposed method was also validated in the postprocessing steps to observe its impact. A well-segmented image was obtained with an accuracy of 0.953 and 0.0949 on the DRIVE and STARE databases. Brain tumors were detected from the Oasis brain MRI database with an accuracy of 0.97. This method can play an important role in helping medical experts diagnose eye diseases and brain tumors from retinal images and Oasis brain images. Full article
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15 pages, 644 KiB  
Review
Bone Infarcts and Tumorigenesis—Is There a Connection? A Mini-Mapping Review
by Wojciech Konarski, Tomasz Poboży, Martyna Hordowicz, Andrzej Śliwczyński, Ireneusz Kotela, Jan Krakowiak and Andrzej Kotela
Int. J. Environ. Res. Public Health 2022, 19(15), 9282; https://doi.org/10.3390/ijerph19159282 - 29 Jul 2022
Cited by 5 | Viewed by 3011
Abstract
(1) Background: Avascular necrosis (AVN) may affect every part of the bone. Epiphyseal infarcts are likely to be treated early because most are symptomatic. However, meta- and diaphyseal infarcts are silent and are diagnosed incidentally. Sarcomas developing in the necrotic bone are extremely [...] Read more.
(1) Background: Avascular necrosis (AVN) may affect every part of the bone. Epiphyseal infarcts are likely to be treated early because most are symptomatic. However, meta- and diaphyseal infarcts are silent and are diagnosed incidentally. Sarcomas developing in the necrotic bone are extremely rare, but they have been reported in the literature. (2) Methods: We conducted a mapping review of recent evidence regarding these malignancies. Methods: A mapping review using a systematic search strategy was conducted to answer research questions. We limited our research to the last ten years (2012–2022). (3) Results: A total of 11 papers were identified, including 9 case reports and 3 case series. The pathomechanism of carcinogenesis in AVN was not investigated to date. Histologically, most tumors were malignant fibrous histiocytoma. The prognosis is relatively poor, especially for patients with metastases, but adjuvant chemotherapy may increase short- and long-term survival. (4) Conclusions: Since AVN-related malignancies are sporadic, no prospective studies have been conducted. The majority of evidence comes from small case series. More research is needed to identify the risk factors that would justify follow-up of patients after bone infarcts at higher risk of developing a malignancy. Full article
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26 pages, 6143 KiB  
Article
Morphometrical, Morphological, and Immunocytochemical Characterization of a Tool for Cytotoxicity Research: 3D Cultures of Breast Cell Lines Grown in Ultra-Low Attachment Plates
by Fernanda Malhão, Ana Catarina Macedo, Alice Abreu Ramos and Eduardo Rocha
Toxics 2022, 10(8), 415; https://doi.org/10.3390/toxics10080415 - 24 Jul 2022
Cited by 14 | Viewed by 3448
Abstract
Three-dimensional cell cultures may better mimic avascular tumors. Yet, they still lack characterization and standardization. Therefore, this study aimed to (a) generate multicellular aggregates (MCAs) of four breast cell lines: MCF7, MDA-MB-231, and SKBR3 (tumoral) and MCF12A (non-tumoral) using ultra-low attachment (ULA) plates, [...] Read more.
Three-dimensional cell cultures may better mimic avascular tumors. Yet, they still lack characterization and standardization. Therefore, this study aimed to (a) generate multicellular aggregates (MCAs) of four breast cell lines: MCF7, MDA-MB-231, and SKBR3 (tumoral) and MCF12A (non-tumoral) using ultra-low attachment (ULA) plates, (b) detail the methodology used for their formation and analysis, providing technical tips, and (c) characterize the MCAs using morphometry, qualitative cytology (at light and electron microscopy), and quantitative immunocytochemistry (ICC) analysis. Each cell line generated uniform MCAs with structural differences among cell lines: MCF7 and MDA-MB-231 MCAs showed an ellipsoid/discoid shape and compact structure, while MCF12A and SKBR3 MCAs were loose, more flattened, and presented bigger areas. MCF7 MCAs revealed glandular breast differentiation features. ICC showed a random distribution of the proliferating and apoptotic cells throughout the MCAs, not fitting in the traditional spheroid model. ICC for cytokeratin, vimentin, and E-cadherin showed different results according to the cell lines. Estrogen (ER) and progesterone (PR) receptors were positive only in MCF7 and human epidermal growth factor receptor 2 (HER-2) in SKBR3. The presented characterization of the MCAs in non-exposed conditions provided a good baseline to evaluate the cytotoxic effects of potential anticancer compounds. Full article
(This article belongs to the Section Toxicology)
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14 pages, 3371 KiB  
Article
Τhe Study of Square Periodic Perturbations as an Immunotherapy Process on a Tumor Growth Chaotic Model
by Dionysios Sourailidis, Christos Volos, Lazaros Moysis, Efthymia Meletlidou and Ioannis Stouboulos
Dynamics 2022, 2(2), 161-174; https://doi.org/10.3390/dynamics2020008 - 6 Jun 2022
Cited by 2 | Viewed by 2512
Abstract
In the present study, the simulation of an immunotherapy effect for a known dynamical system, that describes the process for avascular, vascular, and metastasis tumor growth based on a chemical network model, has been presented. To this end, square signals of various amplitudes [...] Read more.
In the present study, the simulation of an immunotherapy effect for a known dynamical system, that describes the process for avascular, vascular, and metastasis tumor growth based on a chemical network model, has been presented. To this end, square signals of various amplitudes have been used, to model the effect of external therapy control, in order to affect the population of immune cells. The results of the simulations show that for certain values of the amplitude of the square signal, the populations of the proliferating tumor cells in the vascular and metastasis stages have been reduced. Full article
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