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Technology in Cancer Research &... Jan 2019Intraoperative radiotherapy differs from the more commonly used external beam radiation with respect to fractionation, radiation energy, dose rate, and target volume,...
Intraoperative radiotherapy differs from the more commonly used external beam radiation with respect to fractionation, radiation energy, dose rate, and target volume, which may influence the irradiated cells in a complex manner. However, experimental studies of intraoperative radiotherapy are limited. Intrabeam is a frequently used intraoperative radiotherapy device; we evaluated its effects on the proliferation, apoptosis, migration, and invasion of MCF-7 human breast cancer cells. We performed colony formation assays for cells irradiated with single radiation doses of 0 to 16 Gy. Other cells were irradiated with single radiation doses of 0 to 6 Gy and then continued to be cultured. We measured cell-cycle distributions and apoptosis rates 24 hours later, using flow cytometry, and performed wound-healing assays, Transwell tests, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling staining 4 weeks later. Colony formation assays showed no positive colonies from cells irradiated with doses of ≥6 Gy. In flow cytometry, the experimental groups had higher late-apoptosis/necrosis rates ( P < .01) and higher percentages of cells arrested in G phase ( P < .01). Experimental groups also had much lower scratch-repair rates in the wound healing assay ( P < .001) and higher apoptosis rates in the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling assay ( P < .05). In Transwell tests, the 4 Gy and 6 Gy groups had fewer invading cells than the control group ( P < .05). Single-dose irradiation of 6 Gy with the Intrabeam device can effectively inhibit proliferation, migration, and invasiveness and promote apoptosis in MCF-7 cells with long-lasting effects.
Topics: Apoptosis; Breast Neoplasms; Cell Movement; Cell Proliferation; Female; Gamma Rays; Humans; MCF-7 Cells; Neoplasm Invasiveness; Wound Healing
PubMed: 30929609
DOI: 10.1177/1533033819840706 -
Journal of Magnetic Resonance (San... Jul 2018Radiation therapy (RT) plays a central role in the treatment of primary brain tumors. However, despite recent advances in RT treatment, local recurrences following...
Radiation therapy (RT) plays a central role in the treatment of primary brain tumors. However, despite recent advances in RT treatment, local recurrences following therapy remain common. Radiation necrosis (RN) is a severe, late complication of radiation therapy in the brain. RN is a serious clinical problem often associated with devastating neurologic complications. Therapeutic strategies, including neuroprotectants, have been described, but have not been widely translated in routine clinical use. We have developed a mouse model that recapitulates all of the major pathologic features of late-onset RN for the purposes of characterizing the basic pathogenesis of RN, identifying non-invasive (imaging) biomarkers of RN that might allow for the radiologic discernment of tumor and RN, systematic testing of tumor and RN therapeutics, and exploring the complex interplay between RN pathogenesis and tumor recurrence. Herein, we describe the fundamental clinical challenges associated with RN and the progress made towards addressing these challenges by combining our novel mouse model of late-onset RN and magnetic resonance imaging (MRI). MRI techniques discussed include conventional T1- and T2-weighted imaging, diffusion-weighted imaging, magnetization transfer, and measures of tissue oxygenation. Studies of RN mitigation and neuroprotection are described, including the use of anti-VEGF antibodies, and inhibitors of GSK-3β, HIF-1α, and CXCR4. We conclude with some future perspectives on the irradiated brain and the study and treatment of recurrent tumor growing in an irradiated tumor microenvironment.
Topics: Animals; Antibodies, Blocking; Biomarkers; Brain; Brain Neoplasms; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Mice; Necrosis; Neoplasm Recurrence, Local; Nerve Tissue Proteins; Neuroprotective Agents; Radiation Injuries, Experimental; Radiation-Protective Agents; Radiotherapy; Tumor Microenvironment
PubMed: 29705034
DOI: 10.1016/j.jmr.2018.03.011 -
The Journal of International Advanced... Sep 2022This study aimed to compare the cytotoxic, cytostatic, and ototoxic effects of lipoplatin compared to cisplatin application in the subcutaneous xenograft nude mouse...
BACKGROUND
This study aimed to compare the cytotoxic, cytostatic, and ototoxic effects of lipoplatin compared to cisplatin application in the subcutaneous xenograft nude mouse neuroblastoma tumor model.
METHODS
In this study, C1300 neuroblastoma cells were administered subcutaneously to 21 male nude mice. When the tumor reached 150 mm3 diameter, mice were randomized into 3 groups. Saline, cisplatin, and lipoplatin were given intraperitoneally. The auditory function tests were performed before administration and 72 hours after administration. Mice were sacrificed and the tumor and cochlea were removed after 72 hours. Histopathologic evaluation of necrosis and apoptosis was determined by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Cyclooxygenase 2, superoxide dismutase 2, and inducible nitric oxide synthase levels were determined by immunohistochemistry in tissue samples.
RESULTS
Apoptosis and necrosis rates were higher in lipoplatin group than in cisplatin group (P=.035 and P=.010, respectively) in tumor tissue. In the spiral ganglion, apoptosis and necrosis were lower in the lipoplatin group than in cisplatin group (P=.002 and P=.002, respectively). Cyclooxygenase 2 pattern in the cochlea was positive in both control and lipoplatin group and negative in cisplatin group (P=.001). Superoxide dismutase 2 and inducible nitric oxide synthase 2 protein expressions showed no difference between groups. The auditory functions were similar to baseline values and had a better threshold value in lipoplatin group than cisplatin group.
CONCLUSION
For the treatment of neuroblastoma, the use of lipoplatin seems to be beneficial in reducing side effects of cisplatin. We recommend that the mechanism of these properties of lipoplatin should be evaluated in further studies.
Topics: Animals; Antineoplastic Agents; Cisplatin; Cyclooxygenase 2; Male; Mice; Mice, Nude; Necrosis; Neuroblastoma; Nitric Oxide Synthase Type II; Ototoxicity
PubMed: 36063095
DOI: 10.5152/iao.2022.21268 -
Seminars in Radiation Oncology Jan 2010Radiation related effects in children and adults limit the delivery of effective radiation doses and result in long-term morbidity affecting function and quality of... (Review)
Review
Radiation related effects in children and adults limit the delivery of effective radiation doses and result in long-term morbidity affecting function and quality of life. Improvements in our understanding of the etiology and biology of these effects, including the influence of clinical variables, dosimetric factors, and the underlying biological processes have made treatment safer and more efficacious. However, the approach to studying and understanding these effects differs between children and adults. Using the pulmonary and skeletal organ systems as examples, comparisons are made across the age spectrum for radiation related effects, including pneumonitis, pulmonary fibrosis, osteonecrosis, and fracture. Methods for dosimetric analysis, incorporation of imaging and biology as well a length of follow-up are compared, contrasted, and discussed for both organ systems in children and adults. Better understanding of each age specific approach and how it differs may improve our ability to study late effects of radiation across the ages.
Topics: Adult; Age Distribution; Aging; Child; Dose-Response Relationship, Radiation; Fractures, Bone; Humans; Lung Diseases; Osteonecrosis; Radiation Dosage; Radiation Injuries; Radiation Tolerance; Radiotherapy
PubMed: 19959028
DOI: 10.1016/j.semradonc.2009.09.001 -
Journal of Neuro-oncology May 2024Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and... (Meta-Analysis)
Meta-Analysis Comparative Study Review
PURPOSE
Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms.
METHODS
PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes.
RESULTS
Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT).
CONCLUSION
Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.
Topics: Humans; Bevacizumab; Radiation Injuries; Necrosis; Laser Therapy; Central Nervous System Neoplasms; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors
PubMed: 38619777
DOI: 10.1007/s11060-024-04650-1 -
The Journal of Investigative Dermatology Nov 1994The capacity of ultraviolet B (UVB) radiation to damage the cutaneous immune system has been extensively documented, and there is good reason to believe that UVB-induced... (Review)
Review
The capacity of ultraviolet B (UVB) radiation to damage the cutaneous immune system has been extensively documented, and there is good reason to believe that UVB-induced damage is a critical, albeit permissive, factor in the development of sunlight-induced skin cancers. A summary of the evidence shows that acute, low-dose UVB protocols, which resemble quantitatively and qualitatively the manner in which human beings typically experience sun exposure, alter the cutaneous immune system in at least two important ways: they impair the induction of contact hypersensitivity to cutaneous antigens, and induce antigen-specific tolerance. In mice there is compelling evidence that immunogenetic factors dictate whether UVB radiation will impair contact hypersensitivity induction or not. The genetic loci that contain the relevant polymorphic alleles include tumor necrosis factor-alpha and lipopolysaccharide. Because the effects of UVB radiation on contact hypersensitivity induction are mimicked by intracutaneous injections of subinflammatory doses of tumor necrosis factor-alpha or cis-urocanic acid, the favored hypothesis to explain the mechanism of action of UVB radiation in UVB-susceptible individuals is that UVB-dependent transformation of trans- to cis-urocanic acid in the epidermis triggers the intracutaneous release of excess amounts of tumor necrosis factor-alpha. By transiently immobilizing Langerhans cells and other local antigen-presenting cells within the skin, the requirement that hapten be brought to the draining lymph node to sensitive naive hapten-specific T cells is not met, and contact hypersensitivity fails to develop. Because the UVB-susceptibility and UVB-resistance traits have also been demonstrated in human beings, the hypothesis is advanced that these traits are similarly under control of immunogenetic factors, and that a constellation of immune susceptibility genes contributes to the risk of developing sunlight-induced skin cancer. The cellular and molecular basis of UVB-induced tolerance is not as well described, but current evidence suggests that different mechanisms, and presumably different polymorphic genes, dictate whether tolerance will emerge after UVB exposure in mice. Because acute, low-dose UVB also induces tolerance in human beings, the immunogenetic factors that dictate tolerance of this type may also contribute to the risk of developing sunlight-induced skin cancer.
Topics: Animals; Dermatitis, Contact; Haptens; Humans; Immune System; Immunosuppression Therapy; Neoplasms, Radiation-Induced; Radiation Injuries, Experimental; Radiation Tolerance; Skin; Ultraviolet Rays
PubMed: 7963670
DOI: 10.1111/1523-1747.ep12399400 -
Radiation Oncology (London, England) May 2020Radiation-induced temporal lobe necrosis (TLN) is one of the late post-radiotherapy complications in nasopharyngeal cancer (NPC) patients. Since NPC is common to have... (Review)
Review
Radiation-induced temporal lobe necrosis (TLN) is one of the late post-radiotherapy complications in nasopharyngeal cancer (NPC) patients. Since NPC is common to have skull base infiltration, irradiation of the temporal lobes is inevitable despite the use of the more advanced intensity-modulated radiotherapy (IMRT). Moreover, the diagnosis and treatment of TLN remain challenging. In this review, we discuss the diagnosis of TLN with conventional and advanced imaging modalities, onset and predictive parameters of TLN development, the impact of IMRT on TLN in terms of incidence and dosimetric analyzes, and the recent advancements in the treatment of TLN.
Topics: Cranial Irradiation; Humans; Nasopharyngeal Neoplasms; Necrosis; Radiation Injuries; Radiotherapy, Intensity-Modulated; Temporal Lobe
PubMed: 32414378
DOI: 10.1186/s13014-020-01560-0 -
Yonsei Medical Journal Jan 2024Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity...
PURPOSE
Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity remains unknown. We analyzed the relationship between the RT dose to the fornix and symptomatic radiation necrosis (SRN).
MATERIALS AND METHODS
A total of 67 patients treated between 2009 and 2019 were analyzed. SRN was defined according to the following three criteria: 1) radiographic findings, 2) symptoms attributable to the lesion, and 3) treatment resulting in symptom improvement. Various contours, including the fornix, were delineated. Univariate and multivariate analyses of the relationship between RT dose and SRN, as well as receiver operating characteristic curve analysis for cut-off values, were performed.
RESULTS
The most common location was the frontal lobe (n=40, 60%). Gross total resection was performed in 38 patients (57%), and 42 patients (63%) received procarbazine, lomustine, and vincristine chemotherapy. With a median follow-up of 42 months, the median overall and progression-free survival was 74 months. Sixteen patients (24%) developed SRN. In multivariate analysis, age and maximum dose to the fornix were associated with the development of SRN. The cut-off values for the maximum dose to the fornix and age were 59 Gy (equivalent dose delivered in 2 Gy fractions) and 46 years, respectively. The rate of SRN was higher in patients whose maximum dose to the fornix was >59 Gy (13% vs. 43%, =0.005).
CONCLUSION
The maximum dose to the fornix was a significant factor for SRN development. While fornix sparing may help maintain neurocognitive function, additional studies are needed.
Topics: Humans; Oligodendroglioma; Brain Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Vincristine; Radiation Dosage; Necrosis
PubMed: 38154474
DOI: 10.3349/ymj.2023.0112 -
Cancer Treatment and Research... 2022Cyberknife robotic radiosurgery (RRS) provides single-session high-dose radiotherapy of brain tumors with a steep dose gradient and precise real-time image-guided motion...
OBJECTIVE
Cyberknife robotic radiosurgery (RRS) provides single-session high-dose radiotherapy of brain tumors with a steep dose gradient and precise real-time image-guided motion correction. Although RRS appears to cause more radiation necrosis (RN), the radiometabolic changes after RRS have not been fully clarified. F-FET-PET/CT is used to differentiate recurrent tumor (RT) from RN after radiosurgery when MRI findings are indecisive. We explored the usefulness of dynamic parameters derived from F-FET PET in differentiating RT from RN after Cyberknife treatment in a single-center study population.
METHODS
We retrospectively identified brain tumor patients with static and dynamic F-FET-PET/CT for suspected RN after Cyberknife. Static (tumor-to-background ratio) and dynamic PET parameters (time-activity curve, time-to-peak) were quantified. Analyses were performed for all lesions taken together (TOTAL) and for brain metastases only (METS). Diagnostic accuracy of PET parameters (using mean tumor-to-background ratio >1.95 and time-to-peak of 20 min for RT as cut-offs) and their respective improvement of diagnostic probability were analyzed.
RESULTS
Fourteen patients with 28 brain tumors were included in quantitative analysis. Time-activity curves alone provided the highest sensitivities (TOTAL: 95%, METS: 100%) at the cost of specificity (TOTAL: 50%, METS: 57%). Combined mean tumor-to-background ratio and time-activity curve had the highest specificities (TOTAL: 63%, METS: 71%) and led to the highest increase in diagnosis probability of up to 16% p. - versus 5% p. when only static parameters were used.
CONCLUSIONS
This preliminary study shows that combined dynamic and static F-FET PET/CT parameters can be used in differentiating RT from RN after RRS.
Topics: Brain Neoplasms; Fluorine Radioisotopes; Humans; Necrosis; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiation Injuries; Radiosurgery; Retrospective Studies; Robotic Surgical Procedures; Tyrosine
PubMed: 35688103
DOI: 10.1016/j.ctarc.2022.100583 -
International Journal of Surgery... Dec 2015The etiology of osteonecrosis of the femoral head (ONFH) is multifactorial. Treatment of ONFH is disease stage dependent. For early stages, femoral head preservation... (Review)
Review
The etiology of osteonecrosis of the femoral head (ONFH) is multifactorial. Treatment of ONFH is disease stage dependent. For early stages, femoral head preservation procedures are preferred including core decompression, muscle pedicle grafting and de-rotational osteotomy. Core decompression with bone grafting is considered the gold standard. However, the results are inconsistence and unpredictable. An effective non-invasive method of treatment is imperative. Recently, extracorporeal shockwave therapy (ESWT) has shown beneficial effects in ONFH. ESWT improves pain and function of the hip and regression of the ONFH lesion. ESWT is more effective than core decompression with or without bone grafting, cocktail therapy that combined HBO, ESWT and oral alendronate is shown effective for patients with early osteonecrosis. The purpose of the article is to review, update and summarize the clinical treatment of ONFH using shockwave therapy.
Topics: Alendronate; Bone Density Conservation Agents; Combined Modality Therapy; Femur Head Necrosis; High-Energy Shock Waves; Humans; Hyperbaric Oxygenation; Lupus Erythematosus, Systemic
PubMed: 26188081
DOI: 10.1016/j.ijsu.2015.06.080