scholarly journals Radioprotective Agents and Enhancers Factors. Preventive and Therapeutic Strategies for Oxidative Induced Radiotherapy Damages in Hematological Malignancies

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1116
Author(s):  
Andrea Gaetano Allegra ◽  
Federica Mannino ◽  
Vanessa Innao ◽  
Caterina Musolino ◽  
Alessandro Allegra

Radiation therapy plays a critical role in the management of a wide range of hematologic malignancies. It is well known that the post-irradiation damages both in the bone marrow and in other organs are the main causes of post-irradiation morbidity and mortality. Tumor control without producing extensive damage to the surrounding normal cells, through the use of radioprotectors, is of special clinical relevance in radiotherapy. An increasing amount of data is helping to clarify the role of oxidative stress in toxicity and therapy response. Radioprotective agents are substances that moderate the oxidative effects of radiation on healthy normal tissues while preserving the sensitivity to radiation damage in tumor cells. As well as the substances capable of carrying out a protective action against the oxidative damage caused by radiotherapy, other substances have been identified as possible enhancers of the radiotherapy and cytotoxic activity via an oxidative effect. The purpose of this review was to examine the data in the literature on the possible use of old and new substances to increase the efficacy of radiation treatment in hematological diseases and to reduce the harmful effects of the treatment.

Author(s):  
K. V. Hancharova ◽  
I. G. Tarutin ◽  
M. N. Piatkevich

Changes in the fractionation scheme of the radiotherapy course have an impact on the results of treatment of cancer patients. If changes in the fractionation scheme are not taken into account, this leads to under-irradiation of tumor cells and a possible occurrence of subsequent relapses. There are radiobiological models in order to take into account the errors in the radiation dose delivered to the tumor. They allow predicting the tumor control, as well as the toxicity level in normal tissues after traditional RT.The objective of the work is to assess the effectiveness of the absorbed dose in the event, if the fractionation scheme in the RT course changes, and to develop an algorithm that takes into account breaks between treatment sessions.In the study, the effectiveness of the radiation dose delivered to the tumor due to a change in the total treatment time is assessed analytically, a graphical dependence of the radiation dose efficiency on the duration of the unplanned interruption in the treatment of patients is built for the most common oncological localizations, an algorithm for radiotherapy procedures taking into account deviations from the standard radiation treatment pattern is developed.


2018 ◽  
Vol 5 (4) ◽  
pp. 104 ◽  
Author(s):  
Amer Najjar ◽  
Jason Johnson ◽  
Dawid Schellingerhout

Imaging plays a critical role in the management of the highly complex and widely diverse central nervous system (CNS) malignancies in providing an accurate diagnosis, treatment planning, response assessment, prognosis, and surveillance. Contrast-enhanced magnetic resonance imaging (MRI) is the primary modality for CNS disease management due to its high contrast resolution, reasonable spatial resolution, and relatively low cost and risk. However, defining tumor response to radiation treatment and chemotherapy by contrast-enhanced MRI is often difficult due to various factors that can influence contrast agent distribution and perfusion, such as edema, necrosis, vascular alterations, and inflammation, leading to pseudoprogression and pseudoresponse assessments. Amino acid positron emission tomography (PET) is emerging as the method of resolving such equivocal lesion interpretations. Amino acid radiotracers can more specifically differentiate true tumor boundaries from equivocal lesions based on their specific and active uptake by the highly metabolic cellular component of CNS tumors. These therapy-induced metabolic changes detected by amino acid PET facilitate early treatment response assessments. Integrating amino acid PET in the management of CNS malignancies to complement MRI will significantly improve early therapy response assessment, treatment planning, and clinical trial design.


2021 ◽  
Vol 11 ◽  
Author(s):  
Christopher P. Cifarelli ◽  
Geraldine M. Jacobson

Despite the continued controversy over defining an optimal delivery mechanism, the critical role of adjuvant radiation in the management of surgically resected primary and metastatic brain tumors remains one of the universally accepted standards in neuro-oncology. Local disease control still ranks as a significant predictor of survival in both high-grade glioma and treated intracranial metastases with radiation treatment being essential in maximizing tumor control. As with the emergence and eventual acceptance of cranial stereotactic radiosurgery (SRS) following an era dominated by traditional radiotherapy, evidence to support the use of intraoperative radiotherapy (IORT) in brain tumors requiring surgical intervention continues to accumulate. While the clinical trial strategies in treating glioblastoma with IORT involve delivery of a boost of cavitary radiation prior to the planned standard external beam radiation, the use of IORT in metastatic disease offers the potential for dose escalation to the level needed for definitive adjuvant radiation, eliminating the need for additional episodes of care while providing local control equal or superior to that achieved with SRS in a single fraction. In this review, we explore the contemporary clinical data on IORT in the treatment of brain tumors along with a discussion of the unique dosimetric and radiobiological factors inherent in IORT that could account for favorable outcome data beyond those seen in other techniques.


2007 ◽  
Vol 107 (1) ◽  
pp. 84-93 ◽  
Author(s):  
John W. Hopewell ◽  
William T. Millar ◽  
K. Kian Ang

✓A review of the radiobiological factors that influence the response of the brain to radiation is provided in relation to stereotactic radiosurgery (SRS). The prospects for intervention after radiation treatment to selectively modulate the expression of late central nervous system (CNS) injury is considered, as well as an account of recent interest in the use of radiation enhancers to selectively increase the response of tumors to radiation. Brain necrosis in humans, after conventional irradiation, indicates that the risk of necrosis increases rapidly after an equivalent single dose of 12 or 13 Gy. When single-dose treatments are extended due to 60Co decay or planned extension of treatment times, account should be taken of the effects of the repair of sublethal radiation damage to DNA on the efficacy of treatment. Both repair capacity and repair kinetics will also influence tumor control, but parameters to quantify this effect have not yet been established. The volume of CNS tissue that has been irradiated affects the tissue response, but this effect is only significant for volumes less than 0.05 cm3. The gain obtained from irradiation of small volumes is reduced, however, when focal irradiation is given within a wider field of irradiation. Based on a vascular hypothesis explaining the pathogenesis of late CNS damage, approaches designed to selectively modulate the frequency of late CNS damage have been validated. Given the high intrinsic radioresistance of some tumors, as opposed to the presence of hypoxia, an interest has developed in the use of selective radiation enhancers in the treatment of tumors. The compound presently available has proved to be disappointing clinically due to toxicity at effective doses, when repeated administration is required. However, when given at high single doses it is less toxic and may be more effective. Less toxic radiation enhancers need to be developed.


Author(s):  
Vijaya Ramadas Mandala

The main contention of Shooting a Tiger is that hunting during the colonial period was not merely a recreational activity, but a practice intimately connected with imperial governance. The book positions shikar or hunting at the heart of colonial rule by demonstrating that, for the British in India, it served as a political, practical, and symbolic apparatus in the consolidation of power and rule during the nineteenth and early twentieth centuries. The book analyses early colonial hunting during the Company period, and then surveys different aspects of hunting during the high imperial decades in the later nineteenth and early twentieth centuries. The book draws upon an impressive array of archival material and uses a wide range of evidence to support its contentions. It examines hunting at a variety of social and ethnic levels—military, administrative, elite, princely India, Indian professional hunters, and in terms of Indian auxiliaries and (sometimes) resisters. It also deals with different geographical contexts—the plains, the mountains, north and south India. The exclusive privilege of hunting exercised by the ruling classes, following colonial forest legislation, continued to be extended to the Indian princes who played a critical role in sustaining the lavish hunts that became the hallmark of the late nineteenth-century British Raj. Hunting was also a way of life in colonial India, undertaken by officials and soldiers alike alongside their everyday duties, necessary for their mental sustenance and vital for the smooth operation of the colonial administration. There are also two final chapters on conservation, particularly the last chapter focusing on two British hunter-turned-conservationists, Jim Corbett and Colonel Richard Burton.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1063
Author(s):  
Antonella Castellano ◽  
Michele Bailo ◽  
Francesco Cicone ◽  
Luciano Carideo ◽  
Natale Quartuccio ◽  
...  

The accuracy of target delineation in radiation treatment (RT) planning of cerebral gliomas is crucial to achieve high tumor control, while minimizing treatment-related toxicity. Conventional magnetic resonance imaging (MRI), including contrast-enhanced T1-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, represents the current standard imaging modality for target volume delineation of gliomas. However, conventional sequences have limited capability to discriminate treatment-related changes from viable tumors, owing to the low specificity of increased blood-brain barrier permeability and peritumoral edema. Advanced physiology-based MRI techniques, such as MR spectroscopy, diffusion MRI and perfusion MRI, have been developed for the biological characterization of gliomas and may circumvent these limitations, providing additional metabolic, structural, and hemodynamic information for treatment planning and monitoring. Radionuclide imaging techniques, such as positron emission tomography (PET) with amino acid radiopharmaceuticals, are also increasingly used in the workup of primary brain tumors, and their integration in RT planning is being evaluated in specialized centers. This review focuses on the basic principles and clinical results of advanced MRI and PET imaging techniques that have promise as a complement to RT planning of gliomas.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3143
Author(s):  
Sergey E. Parfenyev ◽  
Sergey V. Shabelnikov ◽  
Danila Y. Pozdnyakov ◽  
Olga O. Gnedina ◽  
Leonid S. Adonin ◽  
...  

Breast cancer is the most frequently diagnosed malignant neoplasm and the second leading cause of cancer death among women. Epithelial-to-mesenchymal Transition (EMT) plays a critical role in the organism development, providing cell migration and tissue formation. However, its erroneous activation in malignancies can serve as the basis for the dissemination of cancer cells and metastasis. The Zeb1 transcription factor, which regulates the EMT activation, has been shown to play an essential role in malignant transformation. This factor is involved in many signaling pathways that influence a wide range of cellular functions via interacting with many proteins that affect its transcriptional functions. Importantly, the interactome of Zeb1 depends on the cellular context. Here, using the inducible expression of Zeb1 in epithelial breast cancer cells, we identified a substantial list of novel potential Zeb1 interaction partners, including proteins involved in the formation of malignant neoplasms, such as ATP-dependent RNA helicase DDX17and a component of the NURD repressor complex, CTBP2. We confirmed the presence of the selected interactors by immunoblotting with specific antibodies. Further, we demonstrated that co-expression of Zeb1 and CTBP2 in breast cancer patients correlated with the poor survival prognosis, thus signifying the functionality of the Zeb1–CTBP2 interaction.


2020 ◽  
Vol 26 (1) ◽  
pp. 6-13 ◽  
Author(s):  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
Serkan Levent ◽  
Begüm Nurpelin Sağlik ◽  
Betül Kaya Çavuşoğlu ◽  
...  

AbstractCancer is one of the most common causes of death in the world. Despite the importance of combating cancer in healthcare systems and research centers, toxicity in normal tissues and the low efficiency of anticancer drugs are major problems in chemotherapy. Nowadays the aim of many medical research projects is to discover new safer and more effective anticancer agents. 1,3,4-Thiadiazole compounds are important fragments in medicinal chemistry because of their wide range of biological activities, including anticancer activities. The aim of this study was to determine the capacity of newly synthesized 1,3,4-thiadiazole compounds as chemotherapeutic agents. The structures of the obtained compounds were elucidated using 1H-NMR, 13C-NMR and mass spectrometry. Although the thiadiazole derivatives did not prove to be significantly cytotoxic to the tumour tissue cultures, compound 4i showed activity against the C6 rat brain cancer cell line (IC50 0.097 mM) at the tested concentrations.


Author(s):  
Mingyi Zhou ◽  
Zhuo Yang ◽  
Danbo Wang ◽  
Peng Chen ◽  
Yong Zhang

Abstract Background As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. Methods We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR. Results Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Conclusion Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.


2020 ◽  
Vol 34 (04) ◽  
pp. 265-271
Author(s):  
Marc W. Herr ◽  
Aurora G. Vincent ◽  
Meghan A. Skotnicki ◽  
Yadranko Ducic ◽  
Spiros Manolidis

AbstractRadiation therapy plays a critical role in the treatment of malignancies involving the head and neck. Although the therapeutic effects of ionizing radiation are achieved, normal tissues are also susceptible to injury and significant long-term sequelae. Osteoradionecrosis of the temporal bone (ORNTB) is among the many complications that can arise after therapy. ORNTB is a debilitating and potentially lethal condition that continues to challenge patients and treating physicians. Herein, we review the pathophysiology, presentation, work-up, and management of ORNTB.


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