|
1
|
Jeong JH, Park HE, Kim EK, Heo CY, Park C. Assessing aesthetic outcomes of different incision types for nipple-sparing mastectomy followed by radiation therapy in prepectoral direct-to-implant breast reconstruction: a retrospective study. World J Surg Oncol 2025; 23:91. [PMID: 40089730 PMCID: PMC11909819 DOI: 10.1186/s12957-025-03730-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Accepted: 02/26/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND This study analyzes the aesthetic outcomes associated with inframammary fold (IMF) incisions compared to radial incisions, with or without a periareolar component (referred to as periareolar/radial, PR), considering nipple-sparing mastectomy (NSM) followed by prepectoral direct-to-implant (DTI) reconstruction and subsequent post-mastectomy radiotherapy (PMRT). We assessed changes in breast and nipple symmetry, nipple-to-IMF distance, and nipple Y-axis coefficients to understand how different incisions influence post-radiation aesthetic outcomes. METHODS Forty patients who underwent NSM and prepectoral DTI reconstruction followed by PMRT between September 2019 and December 2022 in a single institution were included. Patients were divided into PR incision (n = 9) and IMF incision (n = 31) groups, with the latter further separated into IMF 1 group (surgeries from 2019 to 2021, n = 13) and IMF 2 group (surgeries in 2022, n = 18). Pre- and postoperative (6-18 months after surgery) analyses of body measurements and medical photographs were conducted using the Seoul Breast Esthetic Scoring Tool (S-BEST) software, developed by same institution, to calculate breast symmetry scores, nipple-to-IMF distance, and nipple Y-axis coefficients. Statistical analyses assessed differences between groups. RESULTS All groups showed decreased breast symmetry scores postoperatively (PR group: -1.111, IMF 1 group: -0.539, IMF 2 group: -0.389) and increased nipple-to-IMF distance (PR group: 0-0.2 cm, IMF 1 group: 0.2-0.5 cm, IMF 2 group: 0.3-0.4 cm). The changes in nipple y-axis coefficients were minimal across all groups. And the PR group received a lower average radiation dose (47.64 ± 5.2 Gy) than IMF 1 group (54.45 ± 5.28 Gy) and IMF 2 group (54.07 ± 4.79 Gy). Statistical analysis indicated no significant differences across the groups (p > 0.05, Kruskal-Wallis test). CONCLUSIONS While IMF and PR incisions yielded similar aesthetic outcomes post-radiation, IMF incisions showed trends toward better symmetry, especially at higher radiation doses. These findings support the IMF incision as a favorable choice in NSM with DTI reconstruction followed by PMRT, though patient anatomy and preferences remain critical for surgical planning.
Collapse
Affiliation(s)
- Jae Hoon Jeong
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Ha Eun Park
- Graduate School of Medicine, Konkuk University, Chungju-si, Republic of Korea
| | - Eun-Kyu Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Chan Yeong Heo
- Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Chongsoo Park
- Department of Plastic and Reconstructive Surgery, Inje University Busan Paik Hospital, Inje University College of Medicine, 75 Bokji-ro, Busanjin-gu, Busan, 47392, Republic of Korea.
| |
Collapse
|
|
2
|
Fijardo M, Kwan JYY, Bissey PA, Citrin DE, Yip KW, Liu FF. The clinical manifestations and molecular pathogenesis of radiation fibrosis. EBioMedicine 2024; 103:105089. [PMID: 38579363 PMCID: PMC11002813 DOI: 10.1016/j.ebiom.2024.105089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 02/25/2024] [Accepted: 03/12/2024] [Indexed: 04/07/2024] Open
Abstract
Advances in radiation techniques have enabled the precise delivery of higher doses of radiotherapy to tumours, while sparing surrounding healthy tissues. Consequently, the incidence of radiation toxicities has declined, and will likely continue to improve as radiotherapy further evolves. Nonetheless, ionizing radiation elicits tissue-specific toxicities that gradually develop into radiation-induced fibrosis, a common long-term side-effect of radiotherapy. Radiation fibrosis is characterized by an aberrant wound repair process, which promotes the deposition of extensive scar tissue, clinically manifesting as a loss of elasticity, tissue thickening, and organ-specific functional consequences. In addition to improving the existing technologies and guidelines directing the administration of radiotherapy, understanding the pathogenesis underlying radiation fibrosis is essential for the success of cancer treatments. This review integrates the principles for radiotherapy dosimetry to minimize off-target effects, the tissue-specific clinical manifestations, the key cellular and molecular drivers of radiation fibrosis, and emerging therapeutic opportunities for both prevention and treatment.
Collapse
Affiliation(s)
- Mackenzie Fijardo
- Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada
| | - Jennifer Yin Yee Kwan
- Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | | | - Deborah E Citrin
- Radiation Oncology Branch, National Cancer Institute, Bethesda, MD, United States of America
| | - Kenneth W Yip
- Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada
| | - Fei-Fei Liu
- Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
| |
Collapse
|
|
3
|
Pilśniak A, Szlauer-Stefańska A, Tukiendorf A, Rutkowski T, Składowski K, Kamińska-Winciorek G. Dermoscopy of Chronic Radiation-Induced Dermatitis in Patients with Head and Neck Cancers Treated with Radiotherapy. Life (Basel) 2024; 14:399. [PMID: 38541724 PMCID: PMC10971316 DOI: 10.3390/life14030399] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/05/2024] [Accepted: 03/12/2024] [Indexed: 03/23/2025] Open
Abstract
Radiotherapy (RT) is an integral part of many cancer treatment protocols. Chronic radiation-induced dermatitis (CRD) is a cutaneous toxicity that occurs in one-third of all patients treated with this method. CRD is usually observed several months after completion of treatment. Typical symptoms of CRD are telangiectasia, skin discoloration, atrophy, thickening, and cutaneous fibrosis. There are currently no data in the literature on the evaluation of the dermoscopic features of CRD. The aim of this prospective study was the identification of clinical and dermoscopic features in a group of 32 patients with head and neck cancer (HNC) in whom CRD developed after RT. CRD was assessed at 3, 6, and 12 months after RT in 16, 10, and 10 patients, respectively. CRD was assessed at one time point and two time points in 28 and 4 patients, respectively. The control included skin areas of the same patient not exposed to RT. The dataset consisted of 36 clinical and 216 dermoscopic photos. Clinical evaluation was performed according to the RTOG/EORTC radiation-induced dermatitis scale. The highest score was grade 2 observed in 21 patients. Clinical observations revealed the presence of slight and patchy atrophy, pigmentation change, moderate telangiectasias, and some and total hair loss. Dotted vessels, clustered vessel distribution, white patchy scale, perifollicular white color, white structureless areas, brown dots and globules, and white lines were the most frequently noted features in dermoscopy. Three independent risk factors for chronic toxicity, such as age, gender, and surgery before RT, were identified. The dermoscopic features that had been shown in our study reflect the biological reaction of the skin towards radiation and may be used for the parametrization of CRD regarding its intensity and any other clinical consequences in the future.
Collapse
Affiliation(s)
- Aleksandra Pilśniak
- Department of Internal Medicine, Autoimmune and Metabolic Diseases, Faculty of Medical Sciences, Medical University of Silesia, 40-055 Katowice, Poland;
| | - Anastazja Szlauer-Stefańska
- Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology (MSCNRIO), 44-102 Gliwice, Poland;
| | | | - Tomasz Rutkowski
- Inpatient Department of Radiation and Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology (MSCNRIO), Gliwice Branch, 44-102 Gliwice, Poland; (T.R.); (K.S.)
| | - Krzysztof Składowski
- Inpatient Department of Radiation and Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology (MSCNRIO), Gliwice Branch, 44-102 Gliwice, Poland; (T.R.); (K.S.)
| | - Grażyna Kamińska-Winciorek
- Department of Bone Marrow Transplantation and Onco-Hematology, Skin Cancer and Melanoma Team, Maria Sklodowska-Curie National Research Institute of Oncology (MSCNRIO), 44-102 Gliwice, Poland
| |
Collapse
|
|
4
|
Wang H, Wang B, Wei J, Zheng Z, Su J, Bian C, Xin Y, Jiang X. Sulforaphane regulates Nrf2-mediated antioxidant activity and downregulates TGF-β1/Smad pathways to prevent radiation-induced muscle fibrosis. Life Sci 2022; 311:121197. [PMID: 36400201 DOI: 10.1016/j.lfs.2022.121197] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/01/2022] [Accepted: 11/11/2022] [Indexed: 11/17/2022]
Abstract
AIMS This study aimed to examine the efficacy of sulforaphane (SFN) in preventing radiation-induced muscle fibrosis (RIMF) and the potential role in nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant stress. MAIN METHODS The RIMF model was established by a single irradiation of the left thigh of C57BL/6 J mice, and the mice were then randomly divided into control, SFN, irradiation (IR), and IR + SFN (IR/SFN) groups. The serum and skeletal muscle were collected eight weeks after irradiation, and changes in oxidative stress and muscle fibrosis were detected. KEY FINDINGS The IR group showed a more obvious skeletal muscle fiber atrophy, significantly higher number of collagen fibers, and higher inflammatory cell infiltration compared to control group. Compared to the IR group, the IR/SFN group had orderly arranged muscle fibers, decreased collagen fibers, and infiltration of inflammatory cells. In addition, compared with the control group, the expression of oxidative stress-related indexes was significantly increased, accompanied by activation of the transforming growth factor (TGF-β)/Smad pathway and its downstream fibrogenic molecules in the skeletal muscle of the IR group. After SFN intervention, the above indices were significantly restored. Furthermore, SFN induced the upregulation of Nrf2, activation of AKT, and inhibition of GSK-3β and Fyn accumulation. SIGNIFICANCE These results revealed that Nrf2 plays a central role in protecting against RIMF. Furthermore, SFN prevents RIMF by activating Nrf2 via the AKT/GSK-3β/Fyn pathway.
Collapse
Affiliation(s)
- Huanhuan Wang
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China.
| | - Bin Wang
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China.
| | - Jinlong Wei
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China.
| | - Zhuangzhuang Zheng
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China.
| | - Jing Su
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China.
| | - Chenbin Bian
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China.
| | - Ying Xin
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
| | - Xin Jiang
- Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China.
| |
Collapse
|
|
5
|
Mukherjee AG, Wanjari UR, Nagarajan D, K K V, V A, P JP, T TP, Chakraborty R, Renu K, Dey A, Vellingiri B, Gopalakrishnan AV. Letrozole: Pharmacology, toxicity and potential therapeutic effects. Life Sci 2022; 310:121074. [DOI: 10.1016/j.lfs.2022.121074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 10/02/2022] [Accepted: 10/10/2022] [Indexed: 11/07/2022]
|
|
6
|
Wang L, Zhu T, Feng D, Li R, Zhang C. Polyphenols from Chinese Herbal Medicine: Molecular Mechanisms and Therapeutic Targets in Pulmonary Fibrosis. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2022; 50:1063-1094. [PMID: 35475972 DOI: 10.1142/s0192415x22500434] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Pulmonary fibrosis (PF) is a highly confounding and fatal pathological process with finite treatment options. Multiple factors such as oxidative and immune/inflammation involve key pathological processes in chronic lung disease, and their intimate interactions mediate chronic lung damage, denudation of the alveolar epithelium, hyperproliferation of type II alveolar epithelial cells (AECIIs), proliferation and differentiation of fibroblasts, and the permeability of microvessels. We reviewed the classic mechanism of PF and highlighted a few emerging mechanisms for studying complex networks in lung disease pathology. Polyphenols, as a multi-target drug, has excellent potential in the treatment of pulmonary fibrosis. We then reviewed recent advances in discovering phenolic compounds from fruits, tea, and medical herbs with the bioactivities of simultaneously regulating multiple factors (e.g., oxidative stress, inflammation, autophagy, apoptosis, pyroptosis) for minimizing pulmonary fibrosis injury. These compounds include resveratrol, curcumin, salvianolic acid B, epigallocatechin-3-gallate, gallic acid, corilagin. Each phenolic compound can exert its anti-PF effect through various mechanisms, and the signaling pathways involved in different phenolic compounds are not the same. This review summarized the available evidence on phenolic compounds' effectiveness in pulmonary diseases and explored the molecular mechanisms and therapeutic targets of phenolic compounds from Chinese herbal medicine with the properties of inhibition of ongoing fibrogenesis and resolution of existing fibrosis.
Collapse
Affiliation(s)
- Lei Wang
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.,Sino-Jan Joint Lab of Natural Health Products Research, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China
| | - Ting Zhu
- Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Qingdao 266071, P. R. China
| | - Deqin Feng
- State Key Laboratory of Microbial Resources, Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Renshi Li
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.,Sino-Jan Joint Lab of Natural Health Products Research, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China
| | - Chaofeng Zhang
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.,Sino-Jan Joint Lab of Natural Health Products Research, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China
| |
Collapse
|
|
7
|
Elkiki SM, Mansour HH, Anis LM, Gabr HM, Kamal MM. Evaluation of aromatase inhibitor on radiation induced pulmonary fibrosis via TGF- β/Smad 3 and TGF- β/PDGF pathways in rats. Toxicol Mech Methods 2021; 31:538-545. [PMID: 34036875 DOI: 10.1080/15376516.2021.1934765] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Radiation-induced pulmonary fibrosis (RIPF) is a known complication in cancer patients after getting thoracic radiotherapy. Aromatase inhibitors (AIs) as anastrozole have been used instead of tamoxifen for adjuvant endocrine treatment of postmenopausal women with hormone sensitive breast cancer. This study is to evaluate the concurrent treatment of anastrozole and RIPF in rats. Twenty four female Wistar rats were distributed into 4 groups: Control (C), Radiation group (R) (total dose 30 Gy in 10 fractions, 5 fractions/week), anastrozole group (A) (0.003 mg/200 g body weight) orally for 14 consecutive days, and Radiation + anastrozole group (R + A). Radiation exposure resulted in a significant increase (p < 0.05) in pulmonary Transforming growth factor-beta 1 (TGF-β), SMAD family member 3 (Smad3), Platelet-derived growth factor (PDGF), malondialdehyde (MDA), Total nitrate/nitrite (NO), interleukin 1β (IL-1β) and interleukin 6 (IL-6) compared to the control group. While, significant decreases (p < 0.05) in superoxide dismutase (SOD) activity, reduced glutathione (GSH) and connective tissue growth factor (CTGF) were observed in lung tissue. These alterations were minimized by anastrozole intervention. Also, anastrozole markedly hindered the lung histopathological changes observed after radiation. Concomitant use of anastrozole with radiation seems to attenuate radiation-induced pulmonary toxicity via TGF-β/Smad 3 and TGF-β/PDGF pathways in rats.
Collapse
Affiliation(s)
- Shereen M Elkiki
- Health Radiation Research Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
| | - Heba H Mansour
- Health Radiation Research Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
| | - Lobna M Anis
- Health Radiation Research Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
| | - Hanan M Gabr
- Health Radiation Research Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt
| | - Mona M Kamal
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
| |
Collapse
|
|
8
|
Constanzo J, Faget J, Ursino C, Badie C, Pouget JP. Radiation-Induced Immunity and Toxicities: The Versatility of the cGAS-STING Pathway. Front Immunol 2021; 12:680503. [PMID: 34079557 PMCID: PMC8165314 DOI: 10.3389/fimmu.2021.680503] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 04/26/2021] [Indexed: 12/20/2022] Open
Abstract
In the past decade, radiation therapy (RT) entered the era of personalized medicine, following the striking improvements in radiation delivery and treatment planning optimization, and in the understanding of the cancer response, including the immunological response. The next challenge is to identify the optimal radiation regimen(s) to induce a clinically relevant anti-tumor immunity response. Organs at risks and the tumor microenvironment (e.g. endothelial cells, macrophages and fibroblasts) often limit the radiation regimen effects due to adverse toxicities. Here, we reviewed how RT can modulate the immune response involved in the tumor control and side effects associated with inflammatory processes. Moreover, we discussed the versatile roles of tumor microenvironment components during RT, how the innate immune sensing of RT-induced genotoxicity, through the cGAS-STING pathway, might link the anti-tumor immune response, radiation-induced necrosis and radiation-induced fibrosis, and how a better understanding of the switch between favorable and deleterious events might help to define innovative approaches to increase RT benefits in patients with cancer.
Collapse
Affiliation(s)
- Julie Constanzo
- IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier, France
| | - Julien Faget
- IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier, France
| | - Chiara Ursino
- IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier, France
| | - Christophe Badie
- Cancer Mechanisms and Biomarkers Group, Radiation Effects Department, Centre for Radiation, Chemical & Environmental Hazards Public Health England Chilton, Didcot, United Kingdom
| | - Jean-Pierre Pouget
- IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier, France
| |
Collapse
|
|
9
|
Benign skull and subdural lesions in patients with prior medulloblastoma therapy. Childs Nerv Syst 2021; 37:359-366. [PMID: 32876801 DOI: 10.1007/s00381-020-04874-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 08/28/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE To report on our institutional cohort of patients and review the literature of medulloblastoma patients who developed skull/subdural-based lesions following treatment. METHODS Following institutional review board (IRB) approval, we retrospectively reviewed the medical records of four children with a history of treated medulloblastoma who developed non-specific skull-based/subdural lesions incidentally found on surveillance imaging. RESULTS Biopsies of the lesions proved the pathology to be low grade and included inflammatory myofibroblastic tumor, cortical fibrous defect consistent with fibroma, fibrous tissue, and fibrous dysplasia. The finding of calvarial or subdural fibrous lesions in children following therapy for medulloblastoma was noted in four out of 201 (136 with available follow-up data) medulloblastoma patients seen or discussed in our institution over the past 10 years. CONCLUSIONS These lesions can grow over time and pose a differential diagnostic challenge with metastatic disease when identified. The skull and subdural space should be scrutinized for secondary lesions on surveillance imaging of patients with medulloblastoma who have received craniospinal irradiation as knowledge of this benign occurrence will assist with management.
Collapse
|
|
10
|
Gong GC, Song SR, Su J. Pulmonary fibrosis alters gut microbiota and associated metabolites in mice: An integrated 16S and metabolomics analysis. Life Sci 2020; 264:118616. [PMID: 33098825 DOI: 10.1016/j.lfs.2020.118616] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 10/09/2020] [Accepted: 10/13/2020] [Indexed: 12/17/2022]
Abstract
AIMS The "gut-lung axis" reflects intimate connection and bidirectional effect between gut and lung, involving numerous lung diseases. Pulmonary fibrosis is a progressive interstitial lung disease with high fatality rate, so far, its association with gut remains unexplored. We investigated the correlation between pulmonary fibrosis and gut microbiota. MATERIALS AND METHODS We collected feces from two pulmonary fibrotic models respectively, and performed a combinatory study using 16S rDNA sequencing and non-targeted metabonomics. Correlation matrix was used to indicate the correlation between microbiome, metabolites and fibrotic indicators, and the possibility of gut microbiota in identifying pulmonary fibrosis was assessed by ROC analysis. KEY FINDINGS 412 genera of microflora and 26 kinds of metabolites were synchronously altered with same trend in two models but differed observably with control. Among these, 7 microorganisms and 9 metabolites were the typical representatives, which were correlated significantly and highly correlated with fibrotic indicators shown by correlation matrix. ROC analysis indicated that it was dependable to identify pulmonary fibrosis by using gut microorganisms and metabolites in both models (AUC > 0.85, p < 0.01). SIGNIFICANCE In summary, our findings first revealed a previously unknown correlation between gut and pulmonary fibrosis in mouse models, which creates novel insights of the interaction between pulmonary fibrosis and gut microbiota.
Collapse
Affiliation(s)
- Gen-Cheng Gong
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510030, PR China
| | - Sheng-Ren Song
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510030, PR China; Department of Respiratory Medicine Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, PR China
| | - Jin Su
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510030, PR China.
| |
Collapse
|
|
11
|
Wallace D, Taylor DR, Pan H, Hwang S, Lucas JT, Klimo P, Upadhyaya SA, Boop FA. Treatment-related calvarial lesions in pediatric brain tumor survivors. Pediatr Blood Cancer 2020; 67:e28189. [PMID: 32286018 PMCID: PMC8674206 DOI: 10.1002/pbc.28189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Revised: 12/12/2019] [Accepted: 12/23/2019] [Indexed: 11/08/2022]
Abstract
BACKGROUND Despite improved survival, many pediatric brain tumor survivors receiving radiation therapy (RT) experience late effects. PROCEDURE To study calvarial lesions in this population, we retrospectively reviewed records of patients undergoing neurosurgical evaluation for calvarial bone lesions detected in posttreatment follow-up imaging at St. Jude Children's Research Hospital. Primary tumor diagnosis, treatment, imaging, surgical intervention, and histopathology from patients with radiographic evidence of lesions followed for ≥2 years post-RT were studied. RESULTS For 17 patients with 18 index lesions, median time to lesion manifestation was 2.34 years. Medulloblastoma patients developed lesions at a shorter interval from RT than ependymoma patients (P = .05). Twelve of 14 lesions requiring surgery were benign fibro-osseous or sclerotic. Two malignant lesions distinct from the primary tumor had genetic predisposition to malignancy. CONCLUSION Most calvarial lesions arising post-RT are benign and fibro-osseous. Serial imaging is recommended, and high index of suspicion for malignant lesions is warranted for patients genetically predisposed to cancer.
Collapse
Affiliation(s)
- David Wallace
- University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee
| | - Douglas R. Taylor
- Department of Neurosurgery, LeBonheur Children’s Hospital, Memphis, Tennessee
| | - Haitao Pan
- Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, Tennessee
| | - Scott Hwang
- Department of Diagnostic Imaging, St. Jude Children’s Research Hospital, Memphis, Tennessee
| | - John T. Lucas
- Department of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee
| | - Paul Klimo
- Department of Neurosurgery, LeBonheur Children’s Hospital, Memphis, Tennessee,Department of Surgery, St. Jude Children’s Research Hospital, Memphis, Tennessee
| | - Santhosh A. Upadhyaya
- Department of Oncology, Division of Neuro-Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee
| | - Frederick A. Boop
- Department of Neurosurgery, LeBonheur Children’s Hospital, Memphis, Tennessee,Department of Surgery, St. Jude Children’s Research Hospital, Memphis, Tennessee
| |
Collapse
|
|
12
|
Zhu HF, Yan PW, Wang LJ, Liu YT, Wen J, Zhang Q, Fan YX, Luo YH. Protective properties of Huperzine A through activation Nrf2/ARE-mediated transcriptional response in X-rays radiation-induced NIH3T3 cells. J Cell Biochem 2018; 119:8359-8367. [PMID: 29932247 DOI: 10.1002/jcb.26919] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 04/04/2018] [Indexed: 01/10/2023]
Abstract
Huperzine A (HupA), derived from Huperzia Serrata, has exhibited a variety of biological actions, in particular neuroprotective effect. However, the protective activities of HupA on murine embryonic fibroblast NIH3T3 cells after X-rays radiation have not been fully elucidated. Herein, HupA treatment dramatically promoted cell viability, abated a G0/G1 peak accumulation, and ameliorated increase of cell apoptosis in NIH3T3 cells after X-rays radiation. Simultaneously, HupA notably enhanced activities of anti-oxidant enzymes, inhibited activity of lipid peroxide, and efficiently eliminated production of reactive oxygen species in NIH3T3 cells after X-rays radiation. Dose-dependent increase of antioxidant genes by HupA were associated with up-regulated Nrf2 and down-regulated Keap-1 expression, which was confirmed by increasing nuclear accumulation, and inhibiting of degradation of Nrf2. Notably, augmented luciferase activity of ARE may explained Nrf2/ARE-mediated signaling pathways behind HupA protective properties. Moreover, expression of Nrf2 HupA-mediated was significant attenuated by AKT inhibitor (LY294002), p38 MAPK inhibitor (SB202190) and ERK inhibitor (PD98059). Besides, HupA-mediated cell viability, and ROS production were dramatically bated by LY294002, SB202190, and PD98059. Taken together, HupA effectively ameliorated X-rays radiation-induced damage Nrf2-ARE-mediated transcriptional response via activation AKT, p38, and ERK signaling in NIH3T3 cells.
Collapse
Affiliation(s)
- Huan-Feng Zhu
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Peng-Wei Yan
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Li-Jun Wang
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Ya-Tian Liu
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Jing Wen
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Qian Zhang
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Yan-Xin Fan
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P.R. China
| | - Yan-Hong Luo
- Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P.R. China
| |
Collapse
|
|
13
|
Landeen KC, Spanos WC, Gromer L. Topical superoxide dismutase in posttreatment fibrosis in patients with head and neck cancer. Head Neck 2018; 40:1400-1405. [PMID: 29756397 DOI: 10.1002/hed.25119] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 11/04/2017] [Accepted: 01/23/2018] [Indexed: 11/07/2022] Open
Abstract
BACKGROUND Topical superoxide dismutase (SOD) has been shown to decrease postradiation fibrosis in some cancers but has not demonstrated an effect in patients with head and neck cancer. The purpose of this study was to determine if topical SOD is an effective treatment for postradiation neck fibrosis. METHODS This was a randomized prospective blinded clinical study of topical SOD versus placebo for the treatment of neck fibrosis. Measures of fibrosis grade and quality of life were obtained at baseline and after 3 months of treatment. RESULTS Improvement in fibrosis score was comparable between the 2 study arms at 3 months. CONCLUSION Both study groups showed improvement but the differences between groups was not statistically significant. Topical SOD likely has limited benefit for posttreatment neck fibrosis but this study confirms other published evidence of benefit from active physical therapy of posttreatment fibrosis in patients with head and neck cancer.
Collapse
Affiliation(s)
- Kelly C Landeen
- Vanderbilt University Medical Center Department of Otolaryngology - Head and Neck Surgery (PGY-1), Nashville, Tennessee
| | - William C Spanos
- Department of Otolaryngology - Head and Neck Surgery, Sanford University of South Dakota Medical Center, Sanford Research, Sioux Falls, South Dakota
| | - Laurie Gromer
- Department of Otolaryngology - Head and Neck Surgery, Sanford University of South Dakota Medical Center, Sanford Research, Sioux Falls, South Dakota
| |
Collapse
|
|
14
|
Abstract
The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-dependent pathway is one of the most integral pathways linked to cell metabolism, proliferation, differentiation, and survival. This pathway is dysregulated in a variety of diseases, including neoplasia, immune-mediated diseases, and fibroproliferative diseases such as pulmonary fibrosis. The mTOR kinase is frequently referred to as the master regulator of this pathway. Alterations in mTOR signaling are closely associated with dysregulation of autophagy, inflammation, and cell growth and survival, leading to the development of lung fibrosis. Inhibitors of mTOR have been widely studied in cancer therapy, as they may sensitize cancer cells to radiation therapy. Studies also suggest that mTOR inhibitors are promising modulators of fibroproliferative diseases such as idiopathic pulmonary fibrosis (IPF) and radiation-induced pulmonary fibrosis (RIPF). Therefore, mTOR represents an attractive and unique therapeutic target in pulmonary fibrosis. In this review, we discuss the pathological role of mTOR kinase in pulmonary fibrosis and examine how mTOR inhibitors may mitigate fibrotic progression.
Collapse
|
|
15
|
Abstract
Treatment sequelae such as trismus, shoulder dysfunction syndrome resulting from spinal accessory nerve palsy, and radiotherapy-induced neck fibrosis are often overlooked when in the management of head and neck cancer patients. This chapter examines these underappreciated issues and their corresponding physical therapy intervention based on current evidence. Head and neck cancer survivors must contend with these disabilities for years after treatment has been concluded. A few quit their jobs which puts a tremendous burden on them and their families with a diminished quality of life. The physical rehabilitative needs of head and neck cancer patients and useful interventions to help meet them are addressed.
Collapse
|
|
16
|
Citrin DE, Prasanna PGS, Walker AJ, Freeman ML, Eke I, Barcellos-Hoff MH, Arankalayil MJ, Cohen EP, Wilkins RC, Ahmed MM, Anscher MS, Movsas B, Buchsbaum JC, Mendonca MS, Wynn TA, Coleman CN. Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of an NCI Workshop, September 19, 2016. Radiat Res 2017; 188:1-20. [PMID: 28489488 PMCID: PMC5558616 DOI: 10.1667/rr14784.1] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
A workshop entitled "Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate" (held in Rockville, MD, September 19, 2016) was organized by the Radiation Research Program and Radiation Oncology Branch of the Center for Cancer Research (CCR) of the National Cancer Institute (NCI), to identify critical research areas and directions that will advance the understanding of radiation-induced fibrosis (RIF) and accelerate the development of strategies to mitigate or treat it. Experts in radiation biology, radiation oncology and related fields met to identify and prioritize the key areas for future research and clinical translation. The consensus was that several known and newly identified targets can prevent or mitigate RIF in pre-clinical models. Further, basic and translational research and focused clinical trials are needed to identify optimal agents and strategies for therapeutic use. It was felt that optimally designed preclinical models are needed to better study biomarkers that predict for development of RIF, as well as to understand when effective therapies need to be initiated in relationship to manifestation of injury. Integrating appropriate endpoints and defining efficacy in clinical trials testing treatment of RIF were felt to be critical to demonstrating efficacy. The objective of this meeting report is to (a) highlight the significance of RIF in a global context, (b) summarize recent advances in our understanding of mechanisms of RIF,
Collapse
Affiliation(s)
- Deborah E. Citrin
- Radiation Oncology Branch, Center for Cancer Research, Bethesda, Maryland
| | - Pataje G. S. Prasanna
- Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland
| | - Amanda J. Walker
- Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
| | - Michael L. Freeman
- Department of Radiation Oncology, Vanderbilt School of Medicine, Nashville, Tennessee
| | - Iris Eke
- Radiation Oncology Branch, Center for Cancer Research, Bethesda, Maryland
| | - Mary Helen Barcellos-Hoff
- Department of Radiation Oncology, University of California, San Francisco, San Francisco, California
| | | | - Eric P. Cohen
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
| | - Ruth C. Wilkins
- Radiobiology Division, Consumer and Clinical Radiation Protection Bureau, Health Canada, Ottawa, Ontario
| | - Mansoor M. Ahmed
- Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland
| | - Mitchell S. Anscher
- Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia
| | - Benjamin Movsas
- Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan
| | - Jeffrey C. Buchsbaum
- Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland
| | - Marc S. Mendonca
- Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia
| | - Thomas A. Wynn
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - C. Norman Coleman
- Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland
| |
Collapse
|
|
17
|
Wen WX, Lee SY, Siang R, Koh RY. Repurposing Pentoxifylline for the Treatment of Fibrosis: An Overview. Adv Ther 2017; 34:1245-1269. [PMID: 28484954 DOI: 10.1007/s12325-017-0547-2] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Indexed: 12/20/2022]
Abstract
Fibrosis is a potentially debilitating disease with high morbidity rates. It is estimated that half of all deaths that occur in the USA are attributed to fibrotic disorders. Fibrotic disorders are characterized primarily by disruption in the extracellular matrix deposition and breakdown equilibrium, leading to the accumulation of excessive amounts of extracellular matrix. Given the potentially high prevalence of fibrosis and the paucity of agents currently available for the treatment of this disease, there is an urgent need for the identification of drugs that can be utilized to treat the disease. Pentoxifylline is a methylxanthine derivative that is currently approved for the treatment of vascular diseases, in particular, claudication. Pentoxifylline has three main properties: improving the rheological properties of blood, anti-inflammatory, and antioxidative. Recently, the effectiveness of pentoxifylline in the treatment of fibrosis via attenuating and reversing fibrotic lesions has been demonstrated in several clinical trials and animal studies. As a result of the limited availability of antifibrotic agents in the long-term treatment of fibrosis that can attenuate and even reverse fibrotic lesions effectively, it would be of particular importance to consider the potential clinical utility of pentoxifylline in the treatment of fibrosis. Thus, this paper discusses the evolving roles of pentoxifylline in the treatment of different types of fibrosis.
Collapse
Affiliation(s)
- Wei Xiong Wen
- International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia
| | - Siang Yin Lee
- Colloids and Interface Science Centre, Centre of Excellence, RRIM Sungai Buloh Research Station, Malaysian Rubber Board, 47000, Sungai Buloh, Selangor, Malaysia
| | - Rafaella Siang
- International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia
- Acute Medicine, George Eliot Hospital NHS Trust, College St, Nuneaton, UK
| | - Rhun Yian Koh
- International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
| |
Collapse
|
|
18
|
Dieleman F, Phan T, van den Hoogen F, Kaanders J, Merkx M. The efficacy of hyperbaric oxygen therapy related to the clinical stage of osteoradionecrosis of the mandible. Int J Oral Maxillofac Surg 2017; 46:428-433. [DOI: 10.1016/j.ijom.2016.12.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 11/26/2016] [Accepted: 12/09/2016] [Indexed: 10/20/2022]
|
|
19
|
Abstract
Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients’ quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF). RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and radiomics that allow scientists and clinicians to select patients who are at risk of the development of chronic radiation dermatitis. Novel treatment methods and clinical trials are strongly needed to provide more efficacious therapies.
Collapse
Affiliation(s)
- Mateusz Spałek
- Department of Radiotherapy I, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| |
Collapse
|
|
20
|
Kolahian S, Fernandez IE, Eickelberg O, Hartl D. Immune Mechanisms in Pulmonary Fibrosis. Am J Respir Cell Mol Biol 2016; 55:309-22. [DOI: 10.1165/rcmb.2016-0121tr] [Citation(s) in RCA: 176] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
|
|
21
|
Altinok A, Yildirim S, Altug T, Sut N, Ober A, Ozsahin E, Azria D, Bese N. Aromatase inhibitors decrease radiation-induced lung fibrosis: Results of an experimental study. Breast 2016; 28:174-7. [DOI: 10.1016/j.breast.2016.04.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Revised: 03/16/2016] [Accepted: 04/09/2016] [Indexed: 11/26/2022] Open
|
|
22
|
Perera AP, Mehta GU, Pratt D, Quezado MM, Gilbert MR, Heiss JD. Diagnosis of a growing radiation-induced skull lesion in a patient: an unusual scar. J Neurosurg 2015; 125:561-4. [PMID: 26684773 DOI: 10.3171/2015.7.jns15989] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
New lesions arising from within an area of previous irradiation often present a diagnostic dilemma, with new malignancy or metastasis of particular concern. The authors report a case of reactive fibroblast proliferation emerging from a previous radiation field and presenting as a growing lesion of the frontal and parietal skull. Following complete gross resection of the skull lesion and histopathological analysis, it was discovered that this lesion consisted of dense fibroblast proliferation with areas of osteonecrosis. This unusual reactive phenomenon offers a novel differential diagnosis for a new contrast-enhancing lesion in a region of previous radiation.
Collapse
Affiliation(s)
- Andrea P Perera
- Barts and the London SMD, Queen Mary University of London, United Kingdom;,Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke
| | - Gautam U Mehta
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke
| | | | | | - Mark R Gilbert
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - John D Heiss
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke
| |
Collapse
|
|
23
|
Adipose-Derived Stem Cells Alleviate Radiation-Induced Muscular Fibrosis by Suppressing the Expression of TGF-β1. Stem Cells Int 2015; 2016:5638204. [PMID: 26649050 PMCID: PMC4663335 DOI: 10.1155/2016/5638204] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 08/12/2015] [Accepted: 08/31/2015] [Indexed: 02/07/2023] Open
Abstract
We aim to investigate the effects of adipose-derived stem cells (ASCs) transplantation on irradiation-induced skeletal muscle fibrosis. Sixty-four rabbits were randomly divided into ASCs group and PBS group followed by irradiation at unilateral hip with a single dose of 80 Gy. Nonirradiated side with normal skeletal muscle served as normal control. Skeletal muscle tissues were collected from eight rabbits in each group at 1 w, 4 w, 8 w, and 26 w after irradiation. Migration of ASCs was observed in the peripheral tissues along the needle passage in the injured muscle. The proportion of the area of collagen fibers to the total area in sections of ASCs group was lower than those of PBS groups at 4 w, 8 w, and 26 w after irradiation. Significant decrease was noted in the integrated optimal density of the transforming growth factor β1 (TGF-β1) in the ASCs group compared with those of PBS group at 4 w, 8 w, and 26 w after irradiation. Moreover, the expression of TGF-β1 was lower in the ASCs group compared to those of the PBS group at each time point determined by Western blot analysis. ASCs transplantation could alleviate irradiation fibrosis by suppressing the level of TGF-β1 in the irradiated skeletal muscle.
Collapse
|
|
24
|
Bourgier C, Levy A, Vozenin MC, Deutsch E. Pharmacological strategies to spare normal tissues from radiation damage: useless or overlooked therapeutics? Cancer Metastasis Rev 2012; 31:699-712. [DOI: 10.1007/s10555-012-9381-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
|
|
25
|
Hamama S, Delanian S, Monceau V, Vozenin MC. Therapeutic management of intestinal fibrosis induced by radiation therapy: from molecular profiling to new intervention strategies et vice et versa. FIBROGENESIS & TISSUE REPAIR 2012; 5:S13. [PMID: 23259677 PMCID: PMC3368760 DOI: 10.1186/1755-1536-5-s1-s13] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Chronic toxicities of locoregional and systemic oncological treatments commonly develop in long-term cancer survivors. Amongst these toxicities, post-radiotherapeutic complications alter patient's quality of life. Reduction of exposure of normal tissues can be achieved by optimization of radiotherapy. Furthermore, understanding of the fibrogenic mechanisms has provided targets to prevent, mitigate, and reverse late radiation-induced damages. This mini-review shows how (i) global molecular studies using gene profiling can provide tools to develop new intervention strategies and (ii) how successful clinical trials, conducted in particular with combined pentoxifylline-vitamin E, can take benefice of biological and molecular evidences to improve our understanding of fibrogenic mechanisms, enhance the robustness of proposed treatments, and lead ultimately to better treatments for patient's benefice.
Collapse
Affiliation(s)
- Saad Hamama
- INSERM U-1030 "Molecular Radiotherapy" Institut Gustave Roussy, Villejuif, France ; "Molecular Radiotherapy", Université Paris Sud Paris XI, France
| | - Sylvie Delanian
- INSERM U-1030 "Molecular Radiotherapy" Institut Gustave Roussy, Villejuif, France ; "Molecular Radiotherapy", Université Paris Sud Paris XI, France ; Unité de Radiopathologie, Service Oncologie-Radiothérapie, Hôpital Saint-Louis, APHP, Paris, France
| | - Virginie Monceau
- INSERM U-1030 "Molecular Radiotherapy" Institut Gustave Roussy, Villejuif, France
| | - Marie-Catherine Vozenin
- INSERM U-1030 "Molecular Radiotherapy" Institut Gustave Roussy, Villejuif, France ; "Molecular Radiotherapy", Université Paris Sud Paris XI, France
| |
Collapse
|
|
26
|
Complete Restoration of Refractory Mandibular Osteoradionecrosis by Prolonged Treatment with a Pentoxifylline-Tocopherol-Clodronate Combination (PENTOCLO): A Phase II Trial. Int J Radiat Oncol Biol Phys 2011; 80:832-9. [DOI: 10.1016/j.ijrobp.2010.03.029] [Citation(s) in RCA: 197] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2009] [Revised: 02/08/2010] [Accepted: 03/10/2010] [Indexed: 11/22/2022]
|
|
27
|
Soluble TNF-α Receptor I Encoded on Plasmid Vector and Its Application in Experimental Gene Therapy of Radiation-Induced Lung Fibrosis. Arch Immunol Ther Exp (Warsz) 2011; 59:315-26. [DOI: 10.1007/s00005-011-0133-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Accepted: 03/07/2011] [Indexed: 01/10/2023]
|
|
28
|
Liu Y, Yu H, Zhang C, Cheng Y, Hu L, Meng X, Zhao Y. Protective effects of berberine on radiation-induced lung injury via intercellular adhesion molecular-1 and transforming growth factor-beta-1 in patients with lung cancer. Eur J Cancer 2008; 44:2425-32. [PMID: 18789680 DOI: 10.1016/j.ejca.2008.07.040] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2008] [Revised: 07/19/2008] [Accepted: 07/24/2008] [Indexed: 01/06/2023]
Abstract
PURPOSE To investigate the protective effects of berberine on radiation-induced lung injury (RILI) in non-small cell lung cancer (NSCLC) patients treated with radiotherapy. PATIENTS AND METHODS In this randomised, double-blind study, 90 patients with NSCLC were divided into two groups. The trial group received radiation therapy plus berberine, and the control group received radiation therapy plus a placebo for 6 weeks. Soluble intercellular adhesion molecular-1 (sICAM-1) and transforming growth factor-beta-1 (TGF-beta1) were measured. RILI and pulmonary function were evaluated at 6 weeks and 6 months after treatment, respectively. RESULTS Of the 90 patients enroled, 43 in the control group and 42 in the trial group completed the study. The incidence of RILI was significantly lower in the trial group at 6 weeks and 6 months than that in the control group (45.2% versus 72.1% and 35.7% versus 65.1%, respectively, both P<0.05). sICAM-1 levels in the trial group were significantly lower at weeks 6 and 12 (373.64+/-89.33 versus 459.53+/-123.59 and 447.83+/-111.21 versus 513.91+/-150.46, both P<0.01), and plasma TGF-beta1 levels were lower at week 3 and 6 (5.43+/-1.47 versus 6.22+/-1.78 and 5.93+/-2.39 versus 7.67+/-2.74, P<0.05 and 0.01, respectively) in comparison with the control group. Significant differences were observed in FEV1 (P=0.033) and DLCO (P=0.003) between patients receiving berberine and those receiving placebo. Independent-samples T-test showed reductions from baseline FVC at week 6 (P<0.05), and FEV1 and DLCO at month 6 (P<0.05 and 0.01, respectively) in the trial group were significantly smaller than that in the control group. CONCLUSION Berberine significantly reduced the incidence of RILI, improved PF and decreased the levels of sICAM-1 and TGF-beta1. The exact mechanisms remain to be further explored.
Collapse
Affiliation(s)
- Yunfang Liu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University, Qilu Hospital, Jinan, Shandong Province, China.
| | | | | | | | | | | | | |
Collapse
|
|
29
|
Hoven-Gondrie ML, Thijssens KMJ, Geertzen JHB, Pras E, van Ginkel RJ, Hoekstra HJ. Isolated limb perfusion and external beam radiotherapy for soft tissue sarcomas of the extremity: long-term effects on normal tissue according to the LENT-SOMA scoring system. Ann Surg Oncol 2008; 15:1502-10. [PMID: 18330652 PMCID: PMC2277454 DOI: 10.1245/s10434-008-9850-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2007] [Revised: 02/04/2008] [Accepted: 02/04/2008] [Indexed: 12/01/2022]
Abstract
Background With the combined treatment procedure of isolated limb perfusion (ILP), delayed surgical resection and external beam radiotherapy (EBRT) for locally advanced soft tissue sarcomas (STS) of the extremities, limb salvage rates of more than 80% can be achieved. However, long-term damage to the healthy surrounding tissue cannot be prevented. We studied the late effects on the normal tissue using the LENT-SOMA scoring system. Patients and Methods A total of 32 patients—median age 47 (range 14–71) years—were treated for a locally advanced STS with ILP, surgical resection and often adjuvant 60–70 Gy EBRT. After a median follow-up of 88 (range 17–159) months, the patients were scored, using the LENT-SOMA scales, for the following late tissue damage: muscle/soft tissue, peripheral nerves, skin/subcutaneous tissue and vessels. Results According to the individual SOM parameters of the LENT-SOMA scales, 20 patients (63%) scored grade-3 toxicity on one or more separate items, reflecting severe symptoms with a negative impact on daily activities. Of these patients, 3 (9%) even scored grade-4 toxicity on some of the parameters, denoting irreversible functional damage necessitating major therapeutic intervention. Conclusions In evaluating long-term morbidity after a combined treatment procedure for STS of the extremity, using modified LENT-SOMA scores, two-thirds of patients were found to have experienced serious late toxic effects.
Collapse
Affiliation(s)
- Miriam L Hoven-Gondrie
- Department of Surgical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, Groningen, 9700 RB, The Netherlands
| | | | | | | | | | | |
Collapse
|
|
30
|
Bourgier C, Vozenin-Brotons MC, Arriagada R. Enhanced local control by radiation boost in breast cancer: back side of the coin? J Clin Oncol 2007; 25:5841-3; author reply 5844-5. [PMID: 18089888 DOI: 10.1200/jco.2007.14.6035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
|
|
31
|
Haydont V, Bourgier C, Pocard M, Lusinchi A, Aigueperse J, Mathé D, Bourhis J, Vozenin-Brotons MC. Pravastatin Inhibits the Rho/CCN2/extracellular matrix cascade in human fibrosis explants and improves radiation-induced intestinal fibrosis in rats. Clin Cancer Res 2007; 13:5331-40. [PMID: 17875761 DOI: 10.1158/1078-0432.ccr-07-0625] [Citation(s) in RCA: 102] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSES Intestinal complications after radiotherapy are caused by transmural fibrosis and impair the quality of life of cancer survivors. Radiation fibrosis was considered permanent and irreversible, but recently, its dynamic nature was shown, providing new opportunities for the development of antifibrotic therapies. Among these new targets, we identified the Rho/ROCK pathway and thought to investigate whether pravastatin treatment inhibits Rho pathway activation and elicits an antifibrotic action. EXPERIMENTAL DESIGN Rho and ROCK activities were monitored in human explants presenting radiation fibrosis remodeling after incubation with pravastatin. Subsequent modulation of CCN2, type I collagen, and fibronectin expression were assessed ex vivo and in intestinal smooth muscle cells derived from radiation enteropathy. Then, the therapeutic relevance of the antifibrotic action of pravastatin was explored in vivo in a rat model of chronic radiation fibrosis (19 Gy X-rays) treated with 30 mg/kg/d pravastatin in the drinking water. RESULTS The results obtained with human explants show that pravastatin specifically inhibits Rho activity in submucosal mesenchymal cells. Pravastatin also elicits ROCK inhibition, and subsequent CCN2 production in human explants and smooth muscle cells isolated from radiation enteropathy. Inhibition of type I collagen and fibronectin does occur, showing that pravastatin modulates the secretory phenotype of mesenchymal cells. Lastly, curative pravastatin administration improves radiation enteropathy in rats. This structural improvement is associated with decreased deposition of CCN2 and subsequent decreased extracellular matrix deposition. CONCLUSION Targeting established fibrosis with pravastatin is an efficient and safe antifibrotic strategy in radiation-induced enteropathy, and is easily transferable into the clinic.
Collapse
Affiliation(s)
- Valérie Haydont
- UPRES EA 27-10 Radiosensibilité des Tumeurs et Tissus Sains, Institut de Radioprotection et de Sûreté Nucléaire/Institut Gustave Roussy, Villejuif, France
| | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Haydont V, Vozenin-Brotons MC. Maintenance of radiation-induced intestinal fibrosis: cellular and molecular features. World J Gastroenterol 2007; 13:2675-83. [PMID: 17569135 PMCID: PMC4147115 DOI: 10.3748/wjg.v13.i19.2675] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2006] [Revised: 01/11/2007] [Accepted: 02/25/2007] [Indexed: 02/06/2023] Open
Abstract
Recent advances in cell and molecular radiobiology clearly showed that tissue response to radiation injury cannot be restricted to a simple cell-killing process, but depends upon continuous and integrated pathogenic processes, involving cell differentiation and crosstalk between the various cellular components of the tissue within the extracellular matrix. Thus, the prior concept of primary cell target in which a single-cell type (whatever it's epithelial or endothelial cells) dictates the whole tissue response to radiation injury has to be replaced by the occurrence of coordinated multicellular response that may either lead to tissue recovery or to sequel development. In this context, the present review will focus on the maintenance of the radiation-induced wound healing and fibrogenic signals triggered by and through the microenvironment toward the mesenchymal cell compartment, and will highlight how sequential and sustained modifications in cell phenotypes will in cascade modify cell-to-cell interactions and tissue composition.
Collapse
Affiliation(s)
- Valérie Haydont
- Laboratoire UPRES EA 27-10, Radiosensibilite des tumeurs et tissus sains, Institut de Radioprotection et de Sûreté Nucléaire/Institut Gustave Roussy, Villejuif, France
| | | |
Collapse
|