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Minimally invasive image-guided therapy of primary and metastatic pancreatic cancer

World Journal of Gastroenterology 2021年第27期27卷 4322-4341页

作者： andras bibok Dae Won Kim Mokenge Malafa Bela Kis Department of Diagnostic Imaging and Interventional Radiology H.Lee Moffitt Cancer CenterTampaFL 33612United States Department of Transplantation&Surgery Radiology UnitSemmelweis UniversityBudapest 1085Hungary Department of Gastrointestinal Oncology H.Lee Moffitt Cancer CenterTampaFL 33612United States

Pancreatic cancer is a challenging malignancy with limited treatment options and poor life *** only curative option is surgical resection,but only 15%-20%of patients are resectable at presentation because more than 50%of patients has distant metastasis at diagnosis and the rest of them has locally advanced pancreatic cancer(LAPC).The standard of care first line treatment for LAPC patients is chemotherapy with or without radiation *** developments in minimally invasive ablative techniques may add to the treatment armamentarium of *** are increasing number of studies evaluating these novel ablative techniques,including radiofrequency ablation,microwave ablation,cryoablation and irreversible *** studies which included pancreatic tumor ablation,demonstrated improved overall survival in LAPC ***,the exact protocols are yet to set up to which stage of the treatment algorithm ablative techniques can be added and in what kind of treatment *** with metastatic pancreatic cancer has dismal prognosis with 5-year survival is only 3%.The most common metastatic site is the liver as 90%of pancreatic cancer patients develop liver *** is the primary treatment option for patients with metastatic pancreatic ***,when the tumor is not responding to chemotherapy or severe drug toxicity develops,locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease progression and improve survival in selected *** the last decade new therapeutic options arose with the advancement of minimally invasive technologies to treat pancreatic cancer *** new therapies have been a topic of increasing interest due to the severe prognostic implications of locally advanced and metastatic pancreatic cancer and the low comorbid risk of these *** review summarizes new ablative options for patients with LAPC and percutaneous liver-directed th

关键词： Pancreatic neoplasms Interventional radiology Ablation techniques Electroporation Radiofrequency ablation Therapeutic embolization

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Preclinical Verification of Modulated Electro-Hyperthermia —Part I. In Vitro Research

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International Journal of Clinical Medicine 2024年第7期15卷 257-298页

作者： andras Szasz Department of Biotechnics Hungarian University of Agriculture and Life Sciences Gdll Hungary

Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency modulation. The high-frequency part was chosen to select the malignant lesion using the specialties of the tumor: the higher conductivity and dielectric constant of the tumor than its host. The electric field selects the tumor, and the low-frequency amplitude modulation polarizes and excites the transmembrane proteins of the malignant cells. The dominant absorption of the energy by the microscopic clusters of the membrane rafts acts like nanoparticle heating. Exciting the membrane produces various apoptotic signals. The processes were modeled using silico and phantom experiments, which proved the concept. The preclinical verification was made in vitro and in vivo, and in the end, clinical proofs validated the method. Our objective is to follow all the development steps from the laboratory to the clinics in a trilogy of articles. This present is the first part, which deals with in silico, phantom, and in vitro research.

关键词： Modulated Electro-Hyperthermia mEHT In Silico Calculations Phantom Measurement In Vitro Experiments Thermal Effects Nonthermal Processes Apoptosis

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On the Thermal Distribution in Oncological Hyperthermia Treatments

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Open Journal of Biophysics 2024年第2期14卷 239-263页

作者： andras Szasz Department of Biotechnics Hungarian University of Agriculture and Life Sciences G&#246d&#246ll&#337 Hungary

The temperature is one of the principal controlling parameters of oncological hyperthermia. However, local heating forms a complicated thermal distribution in space and has developed over time, too. The decisional factors are the heterogeneity of the targeted volume, the electrolyte perfusions controlled by thermal homeostasis, and the spreading of the heat energy with time. A further complication is that the energy absorption sharply changes by depth, so the spatiotemporal development of the temperature distribution requires specialized methods to control. Most of the temperature imaging facilities (thermography, radiometry, electric impedance tomography, etc.) are less precise than the medical practice needs. In contrast, precise point sensing (like thermocouples, thermistors, and fluoroptical methods) is invasive and measures only a discrete point in the robustly changing thermal map. The two most precise thermal imaging methods, computer tomography, and magnetic resonance are expensive and have numerous technical complications. Our objective is to show the complexity of the temperature distribution inside the human body, and offer a relatively simple and cheap method to visualize its spatiotemporal development. A novel emerging technology, the application of ultrasound microbubble contrast agents is a promising method for solving complicated tasks of thermal distribution deep inside the living body. Noteworthy, the temperature distribution does not determine the full hyperthermia process, nonthermal effects make considerable impact, too. Additionally to the difficulties to measure the thermal heterogeneity during hyperthermia in oncology, numerous nonthermal processes, molecular and structural changes are triggered by the incoming electromagnetic energy, which presently has no spatiotemporal visualization technique. Microbubble imaging has a suitable spatiotemporal thermal resolution, and also it is sensitive to nonthermal effects. Its application for characteri

关键词： Microbubbles Thermal Heterogeneity Electric Heterogeneity Bloodstream Thermal and Nonthermal Synergy Temperature Distribution Temperature Measurements

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Preclinical Verification of Modulated Electro-Hyperthermia—Part III. Immunogenic Effects

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International Journal of Clinical Medicine 2024年第7期15卷 335-364页

作者： andras Szasz Department of Biotechnics Hungarian University of Agriculture and Life Sciences Gdll Hungary

The modulated electro-hyperthermia (mEHT) method is a unique approach that utilizes all the essential apoptotic pathways through an external radiofrequency (RF) signal. The high-frequency RF is amplitude-modulated and coupled capacitively to the target. The provided energy triggers the death receptors and FAS-FADD complexes in the malignant cells. Multi-pathway apoptosis produces immunogenic cell death (ICD). This ICD provides intracellular information about cancer cells by releasing damage-associated molecular patterns (DAMP), including membrane expression of calreticulin (CRT) and extracellular ATP, HMGB1, and HSP70, executing tumor-specific antigen presentation. The antigen-presenting cells (APCs) play a crucial role in reestablishing immune surveillance and hampering the tumor cells’ ability to hide, thereby evading immune attacks. The matured DCs (generally APCs) produce tumor-specific killer and helper T-cells, which have the potential to be active in distant metastases from the treated location. This unique mechanism of action underscores its potential in cancer treatment and extends the local mEHT treatment to the whole body anticancer therapy with an abscopal effect.

关键词： mEHT Cancer Thermal Nonthermal Immunogenic ICD DAMP Tumor-Specific Immune

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Exploring Biocomplexity in Cancer: A Comprehensive Review

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Open Journal of Biophysics 2024年第2期14卷 154-238页

作者： andras Szasz Gyula Peter Szigeti Department of Biotechnics Hungarian University of Agriculture and Life Sciences G&#246d&#246ll&#337 Hungary John von Neumann Faculty of Informatics O&#769buda University Budapest Hungary

Living objects have complex internal and external interactions. The complexity is regulated and controlled by homeostasis, which is the balance of multiple opposing influences. The environmental effects finally guide the self-organized structure. The living systems are open, dynamic structures performing random, stationary, stochastic, self-organizing processes. The self-organizing procedure is defined by the spatial-temporal fractal structure, which is self-similar both in space and time. The system’s complexity appears in its energetics, which tries the most efficient use of the available energies;for that, it organizes various well-connected networks. The controller of environmental relations is the Darwinian selection on a long-time scale. The energetics optimize the healthy processes tuned to the highest efficacy and minimal loss (minimalization of the entropy production). The organism is built up by morphogenetic rules and develops various networks from the genetic level to the organism. The networks have intensive crosstalk and form a balance in the Nash equilibrium, which is the homeostatic state in healthy conditions. Homeostasis may be described as a Nash equilibrium, which ensures energy distribution in a “democratic” way regarding the functions of the parts in the complete system. Cancer radically changes the network system in the organism. Cancer is a network disease. Deviation from healthy networking appears at every level, from genetic (molecular) to cells, tissues, organs, and organisms. The strong proliferation of malignant tissue is the origin of most of the life-threatening processes. The weak side of cancer development is the change of complex information networking in the system, being vulnerable to immune attacks. Cancer cells are masters of adaptation and evade immune surveillance. This hiding process can be broken by electromagnetic nonionizing radiation, for which the malignant structure has no adaptation strategy. Our objective is to review

关键词： Complexity Networks Small-World Genetic Mutations Self-Organizing Self-Symmetry Energetic Balance Entropy Nash Equilibrium Games Evolution Cancer Therapy

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Combining thermal scanning probe lithography and dry etching for grayscale nanopattern amplification

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Microsystems & Nanoengineering 2024年第1期10卷 335-344页

作者： Berke Erbas Ana Conde-Rubio Xia Liu Joffrey Pernollet Zhenyu Wang Arnaud Bertsch Marcos Penedo Georg Fantner Mitali Banerjee andras Kis Giovanni Boero Juergen Brugger Microsystems Laboratory École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Center of MicroNanoTechnology(CMi) EPFLLausanne 1015Switzerland Laboratory of Nanoscale Electronics and Structures École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Laboratory for Bio-and Nano-Instrumentation École Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Laboratory of Quantum Physics Topology and CorrelationsÉcole Polytechnique Fédérale de Lausanne(EPFL)Lausanne 1015Switzerland Present address:Institute of Materials Science of Barcelona ICMAB-CSIC Campus UABBellaterra 08193Spain Present address:School of Integrated Circuits and Electronics MIIT Key Laboratory for Low-Dimensional Quantum Structure and DevicesBeijing Institute of TechnologyBeijing 100081China

Grayscale structured surfaces with nanometer-scale features are used in a growing number of applications in optics and *** scanning probe lithography achieves a lateral resolution below 10 nm and a vertical resolution below 1 nm,but its maximum depth in polymers is ***,we present an innovative combination of nanowriting in thermal resist and plasma dry etching with substrate cooling,which achieves up to 10-fold amplification of polymer nanopatterns into SiO_(2) without proportionally increasing surface *** nanopatterns in SiO_(2) with 400 nm pitch and 150 nm depth are fabricated free of shape distortion after dry *** exemplify the possible applications of the proposed method,grayscale dielectric nanostructures are used for scalable manufacturing through nanoimprint lithography and for strain nanoengineering of 2D *** a method for aspect ratio amplification and smooth grayscale nanopatterning has the potential to find application in the fabrication of photonic and nanoelectronic devices.

关键词： lithography thermal pattern

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匈牙利佩奇大学与北京林业大学的环境设计类教育比较分析及启示

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中国林业教育 2024年第1期42卷 39-45页

作者：赵大鹏 Hutter Akos Greg andras 北京林业大学艺术设计学院北京100083 佩奇大学工程与信息技术学院匈牙利佩奇7624

佩奇大学是匈牙利颇具影响力的高校,在环境设计类教育领域经验丰富、成果突出。其建筑系与北京林业大学环境设计系在学科定位、办学和发展理念等层面存在诸多相似之处,有一定的可比性。以佩奇大学建筑系教育项目和北京林业大学环境设计... 详细信息

佩奇大学是匈牙利颇具影响力的高校,在环境设计类教育领域经验丰富、成果突出。其建筑系与北京林业大学环境设计系在学科定位、办学和发展理念等层面存在诸多相似之处,有一定的可比性。以佩奇大学建筑系教育项目和北京林业大学环境设计专业为研究对象,对环境设计类教育进行比较分析发现:①在教学理念方面,前者重点强调文化传承和专业实践;后者从生态、可持续的视角切入,重点关注绿色设计、生态宜居等,强调以绿色生态理念为主、多种方向并行。②在课程设置方面,前者以建筑设计为主线,注重专业化、职业化,强调与实践紧密联系;后者涉及内容丰富,覆盖的知识面宽,横向拓展性强,具有综合化、多样化的特点,但存在知识深度不够、技术层面的内容不足且落地性较差等问题。③在教学组织方面,前者实行导师组负责制和小组授课,有利于促进师生间的相互交流和了解;后者以分班制方式进行大班授课,各班级学生学习的同一类型室内或景观设计课程通常由不同的任课教师负责组织教学。这一相互独立的平行授课模式虽然带给学生多元的思维方法和设计成果,但也造成师生和生生间的交流机会少且不深入以及相互了解的渠道较窄等问题。④在教学效果方面,从课程作业质量和个人发展能力这2个评价教学效果和质量的重要参考指标看,前者培养的学生设计能力和研究能力较强,富有创新性,设计完成度高、落地性较强,无论是进入职场还是继续深造都取得了丰厚的成果;后者培养的学生设计能力较强但研究能力相对较弱,设计作品特色显著但设计的完成深度和推理的严谨性等存在不足,以从事环境设计或相关实践工作为主,并在业内获得较高声望。通过比较分析,两校在环境设计类教育教学方面各具特点,各有各的优势和不足。以此为启示,对中国环境设计类教育的发展进行了深入思考,并提出相应的建议措施。一是在坚守自身特色的前提下,优化课程设置,使学生在初步建构起专业学理框架的基础上能扎实、系统地掌握某一专业分支领域的知识。二是明确教育理念,主动调整设计的使命、角色和方法;完善教学过程,注重理论联系实际,强化校企联合,探索能够有效发挥每位教师之擅长的教学模式。三是改进教学方法,重构学生的学习过程;加强对外交流,培养学生的全球化意识。

关键词：匈牙利佩奇大学北京林业大学环境设计类教育教学理念课程设置教学过程教学效果比较研究

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