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Thoracic Irradiation Recruit M2 Macrophage into the Lung, Leading to Pneumonitis and Pulmonary Fibrosis

  • Park, Hae-Ran;Jo, Sung-Kee;Jung, Uhee
    • Journal of Radiation Protection and Research
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    • v.42 no.4
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    • pp.177-188
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    • 2017
  • Background: Radiation-induced pneumonitis and pulmonary fibrosis are common dose-limiting complications in patients receiving radiotherapy for lung, breast, and lymphoid cancers. In this study, we investigated the characteristics of effective immune cells related to pneumonitis and fibrosis after irradiation. Materials and Methods: After anesthesia, the whole thorax of C57BL/6 mice was irradiated at 14 Gy. The lung tissue and bronchoalveolar lavage fluid were collected at defined time points post-irradiation for the determination of histological and immunohistochemical analysis and inflammatory cell population infiltrated into the lung. Results and Discussion: Whole thoracic irradiation increased the deposition of extracellular matrix (ECM), lung weight, and pleural effusions, which started to die from 4 months later. At 4 months after irradiation, the numbers of macrophages and lymphocytes as well as neutrophils were increased dramatically in the lung. Interestingly, the macrophages that were recruited into the lung after irradiation had an enlarged foamy morphology. In addition, the expressions of chemokines (CCL-2, CCL-3, CXCL-10) for the attraction of macrophages and T cells were higher in the lung of irradiated mice. The high expressions of these chemokines were sustained up to 6 months following irradiation. In thoracic irradiated mice, infiltrated macrophages into the lung had the high levels of Mac-3 antigens on their surface and upregulated the hallmarks of alternatively activated macrophages such as arginase-1 and CD206. Furthermore, the levels of IL-4 and IL-13 were higher in a BAL fluid of irradiated mice. Conclusion: All results show that thoracic irradiation induces to infiltrate various inflammation-related immune cells, especially alternatively activated macrophages, through enhancing the expression of chemokines, suggesting that alternatively activated macrophages are most likely important for leading to pulmonary fibrosis.

Acute Pulmonary Embolism by Silicone Injection: Radiologic Findings (실리콘액 주사에 의한 급성 폐색전증: 영상의학적 소견)

  • Lee, Jae-Kyo
    • Journal of Yeungnam Medical Science
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    • v.21 no.2
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    • pp.215-223
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    • 2004
  • Silicone is widely used for medical purposes in breast augmentation and other cosmetic procedures. Illegal injections of silicone in human beings might have adverse effects and one of the serious problems is a silicone embolism. We experienced five cases of unusual respiratory difficulties after an injection of liquid silicone in the breast, vagina, uterus, and hip. They were all young adult females, who were previously healthy. One of them died after the injection. The three remaining patients were admitted because of dyspnea, coughing, chest discomfort and bilateral pulmonary infiltration after the silicone injection. A transbronchial lung biopsy and autopsy disclosed many oil like materials filling the alveolar septal capillaries. Three patients underwent a computed tomogram (CT), which revealed multifocal airspace consolidations at the peripheral and nondependent portions of both lungs, which is a different finding from other thromboembolisms. Lung scans of the disclosed abnormalities were compatible with silicone induced pulmonary embolism.

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PAMAM Dendrimers Augment Inhibitory Effects of Curcumin on Cancer Cell Proliferation: Possible Inhibition of Telomerase

  • Mollazade, Mahdie;Nejati-Koshki, Kazem;Akbarzadeh, Abolfazl;Zarghami, Nosratollah;Nasiri, Marzieh;Jahanban-Esfahlan, Rana;Alibakhshi, Abbas
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6925-6928
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    • 2013
  • Background: Despite numerous useful anticancer properties of curcumin, its utility is limited due to its hydrophobic structure. In this study, we investigated the comparative antiproliferative effect of PAMAM encapsulating curcumin with naked curcumin on the T47D breast cancer cell line. Materials and Methods: Cytotoxic effects of PAMAM dendrimers encapsulating curcumin and curcumin alone were investigated by MTT assay. After treating cells with different concentrations of both curcumin alone and curcumin encapsulated for 24h, telomerase activity was determined by TRAP assay. Results: While PAMAM dendrimers encapsulating curcumin had no cytotoxicity on cancer cells, they decreased the $IC_{50}$ for proliferation and also increased the inhibitory effect on telomerase activity. Conclusions: Considering the non-toxicity in addition to effectiveness for enhancing curcumin anticancer properties, dendrimers could be considered good therapeutic vehicles for this hydrophobic agent.

The clinical utilization of radiation therapy in Korea between 2009 and 2013

  • Kang, Jin-Kyu;Kim, Mi-Sook;Jang, Won-Il;Seo, Young Seok;Kim, Hee Jin;Cho, Chul Koo;Yoo, Hyung Jun;Paik, Eun Kyung;Cha, Yu Jin;Song, Hyun Jin
    • Radiation Oncology Journal
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    • v.34 no.2
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    • pp.88-95
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    • 2016
  • Purpose: The purpose of this study was to estimate the clinical utilization of radiation therapy (RT) in Korea between 2009 and 2013. Materials and Methods: We analyzed open claims data from the Health Insurance Review and Assessment Service. The subjects were patients who had diagnostic codes C00-C97 or D00-D48 according to the 10th revision of the International Classification of Diseases, with procedure codes indicating RT treatment. Results: The total number of patients who received RT in 2009, 2010, 2011, 2012, and 2013 were 45,571, 49,593, 54,671, 59,172, and 61,485, respectively. Among them, the total numbers of male and female patients were 20,780/24,791 in 2009, 22,711/26,882 in 2010, 24,872/29,799 in 2011, 27,101/32,071 in 2012, and 27,941/33,544 in 2013. The five cancers that were most frequently treated with RT between 2009 and 2012 were breast, lung, colorectal, liver, and uterine cervical cancers. However, the fifth most common cancer treated with RT that replaced uterine cervical cancer in 2013 was prostate cancer. The three leading types of cancer among the male patients were lung, colorectal, and liver cancers, whereas in female patients, they were breast, uterine cervical, and lung cancers. The type of cancer most commonly treated by RT was cancer of the central nervous system in patients aged 20 years or less, breast cancer in patients aged 30-50 years, and lung cancer in patients aged 60 years or more. Conclusion: Data from this study provided the clinical utilization of RT in Korea between 2009 and 2013.

Cancer Notification at a Referral Hospital of Kermanshah, Western Iran (2006-2009)

  • Rahimi, Zohreh;Kasraei, Razieh;Najafi, Farid;Tanhapoor, Maryam;Abdi, Hamed;Rahimi, Ziba;Vaisi-Raygani, Asad;Aznab, Mozafar;Moradi, Mahmoudreza
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.1
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    • pp.133-137
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    • 2015
  • Background: Cancer is a major public health problem and the leading cause of mortality in both males and females in developed and developing countries. The incidence of cancer is gender dependent. Among Iranians, it is the third cause of death. Materials and Methods: The information recorded in the files of all patients (7,695 individuals) pathologically diagnosed with cancer in Imam Reza referral hospital of Kermanshah University of Medical Sciences during the four year period of 2006-2009 were reviewed and analyzed using SPSS statistical software package version 16.0. Results: Around 61.6% of reported cancer cases were males and 38.4% were females. The most prevalent reported malignant tumors occurred at the age group of 70-79 years in males and in females these tumors were presented in the ages of 60-69 years. The most prevalent cancers among studied patients were gastrointestinal (GI) cancers with a frequency of 22.9% [gastric 10.7%, colorectal 6.9%, and esophageal 6%]. The second, third and forth prevalent cancers were blood at 16.4%, lung 13.5% and bladder 12.8%, respectively. In males the cancers of GI (25.6%) were the most prevalent followed in order of frequency by bladder (18%), blood (17.6%), lung (17.4%) and prostate (6.8%). In females the most frequent recorded cancer was breast (24.1%) followed in order of frequency by GI (20.5%), blood (14.4%), lung (7.3%), uterus (6.2%) and ovary (5.1%). Breast cancer was the most prevalent cancer (27%) in the age group of 40-49 years. Conclusions: The present study provides frequency data for various types of cancers in both males and females from a referral hospital of Kermanshah that are comparable with some reports from other areas of the country.

Pathological Investigation of Vertebral Tumor Metastasis from Unknown Primaries - a Systematic Analysis

  • Zhang, Yan;Cai, Feng;Liu, Liang;Liu, Xiao-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.1047-1049
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    • 2015
  • Background: This systematic analysis was conducted to investigate pathological diagnosis of vertebral tumor metastasis with unknown primaries. Methods: Clinical studies conducted to pathologically investigate vertebral tumor metastasis were identified using a predefined search strategy. Pooled diagnosis (PD) of each pathological confirmation was calculated. Results: For vertebral tumor metastasis, 5 clinical studies which included 762 patients were considered eligible for inclusion. Systematic analysis suggested that, for all patients with vertebral tumor metastasis, dominant PD was pathologically confirmed with lung cancer in 21.7% (165/762), with breast cancer in 26.6% (203/762) and with prostate cancer in 19.2% (146/762). Other diagnosis that could be confirmed included lymphoma, multiple myeloma, renal cancer, for example, in this cohort of patients. Conclusions: This systemic analysis suggested that breast, lung and prostate lesions could be the most common pathological types of cancer for vertebral tumor metastasis formunknown primaries, and other common diagnoses could include lymphoma, multiple myeloma, renal cancer.

Dosimetric Effects of Intrafractional Organ Motion in Field-in-Field Technique for Whole-Breast Irradiation

  • Hong, Chae-Seon;Ju, Sang Gyu;Choi, Doo Ho;Han, Youngyih;Huh, Seung Jae;Park, Won;Ahn, Yong Chan;Kim, Jin Sung;Lim, Do Hoon
    • Progress in Medical Physics
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    • v.30 no.3
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    • pp.65-73
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    • 2019
  • Purpose: We evaluated the motion-induced dosimetric effects on the field-in-field (FIF) technique for whole-breast irradiation (WBI) using actual patient organ motion data obtained from cine electronic portal imaging device (cine EPID) images during treatment. Materials and Methods: Ten breast cancer patients who received WBI after breast-conserving surgery were selected. The static FIF (SFIF) plan involved the application of two parallel opposing tangential and boost FIFs. To obtain the amplitude of the internal organ motion during treatment, cine EPID images were acquired five times for each patient. The outside contour of the breast (OCB) and chest wall (CW) contour were tracked using in-house motion analysis software. Intrafractional organ motion was analyzed. The dynamic FIF (DFIF) reflecting intrafractional organ motion incorporated into the SFIF plan was calculated and compared with the SFIF in terms of the dose homogeneity index (DHI90/10) for the target and V20 for the ipsilateral lung. Results: The average motion amplitudes along the X and Y directions were 1.84±1.09 mm and 0.69±0.50 mm for OCB and 1.88±1.07 mm and 1.66±1.49 mm for CW, respectively. The maximum motion amplitudes along the X and Y directions were 5.53 and 2.08 mm for OCB and 5.22 and 6.79 mm for CW, respectively. Significant differences in DHI90/10 values were observed between SFIF and DFIF (0.94 vs 0.95, P<0.05) in statistical analysis. The average V20 for the lung in the DFIF was slightly higher than that of the SFIF in statistical analysis (19.21 vs 19.00, P<0.05). Conclusion: Our findings indicate that the FIF technique can form a safe and effective treatment method for WBI. Regular monitoring using cine EPID images can be effective in reducing motion-induced dosimetric errors.

PRR11 and SKA2 gene pair is overexpressed and regulated by p53 in breast cancer

  • Wang, Yitao;Zhang, Chunxue;Mai, Li;Niu, Yulong;Wang, Yingxiong;Bu, Youquan
    • BMB Reports
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    • v.52 no.2
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    • pp.157-162
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    • 2019
  • Our previous study found that two novel cancer-related genes, PRR11 and SKA2, constituted a classic gene pair that was regulated by p53 and NF-Y in lung cancer. However, their role and regulatory mechanism in breast cancer remain elusive. In this study, we found that the expression levels of PRR11 and SKA2 were upregulated and have a negative prognotic value in breast cancer. Loss-of-function experiments showed that RNAi-mediated knockdown of PRR11 and/or SKA2 inhibited proliferation, migration, and invasion of breast cancer cells. Mechanistic experiments revealed that knockdown of PRR11 and/or SKA2 caused dysregulation of several downstream genes, including CDK6, TPM3, and USP12, etc. Luciferase reporter assays demonstrated that wild type p53 significantly repressed the PRR11-SKA2 bidirectional promoter activity, but not NF-Y. Interestingly, NF-Y was only essential for and correlated with the expression of PRR11, but not SKA2. Consistently, adriamycin-induced (ADR) activation of endogenous p53 also caused significant repression of the PRR11 and SKA2 gene pair expression. Notably, breast cancer patients with lower expression levels of either PRR11 or SKA2, along with wild type p53, exhibited better disease-free survival compared to others with p53 mutations and/or higher expression levels of either PRR11 or SKA2. Collectively, our study indicates that the PRR11 and SKA2 transcription unit might be an oncogenic contributor and might serve as a novel diagnostic and therapeutic target in breast cancer.

Inhibition of p90RSK activation sensitizes triple-negative breast cancer cells to cisplatin by inhibiting proliferation, migration and EMT

  • Jin, Yujin;Huynh, Diem Thi Ngoc;Kang, Keon Wook;Myung, Chang-Seon;Heo, Kyung-Sun
    • BMB Reports
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    • v.52 no.12
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    • pp.706-711
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    • 2019
  • Cisplatin (Cis-DDP) is one of the most widely used anti-cancer drugs. It is applicable to many types of cancer, including lung, bladder, and breast cancer. However, its use is now limited because of drug resistance. p90 ribosomal S6 kinase (p90RSK) is one of the downstream effectors in the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathway and high expression of p90RSK is observed in human breast cancer tissues. Therefore, we investigated the role of p90RSK in the Cis-DDP resistance-related signaling pathway and epithelial-mesenchymal transition (EMT) in breast cancer cells. First, we discovered that MDA-MB-231 cells exhibited more Cis-DDP resistance than other breast cancer cells, including MCF-7 and BT549 cells. Cis-DDP increased p90RSK activation, whereas the inactivation of p90RSK using a small interfering RNA (siRNA) or dominant-negative kinase mutant plasmid overexpression significantly reduced Cis-DDP-induced cell proliferation and migration via the inhibition of matrix metallopeptidase (MMP)2 and MMP9 in MDA-MB-231 cells. In addition, p90RSK activation was involved in EMT via the upregulation of mRNA expression, including that of Snail, Twist, ZEB1, N-cadherin, and vimentin. We also investigated NF-κB, the upstream regulator of EMT markers, and discovered that Cis-DDP treatment led to NF-κB translocation in the nucleus as well as its promoter activity. Our results suggest that targeting p90RSK would be a good strategy to increase Cis-DDP sensitivity in triple-negative breast cancers.

Evaluation of Dose Reduction of Cardiac Exposure Using Deep-inspiration Breath Hold Technique in Left-sided Breast Radiotherapy (좌측 유방암 방사선 치료에서 깊은 들숨 호흡법을 이용한 심장 선량 감소 평가)

  • Jung, Joo-Young;Kim, Min-Joo;Jung, Jae-Hong;Lee, Seu-Ran;Suh, Tae-Suk
    • Progress in Medical Physics
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    • v.24 no.4
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    • pp.278-283
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    • 2013
  • Breast cancer is the leading cause of cancer death in women worldwide and the number of women breast cancer patient was increased continuously. Most of breast cancer patient has suffered from unnecessary radiation exposure to heart, lung. Low radiation dose to the heart could lead to the worsening of preexisting cardiovascular lesions caused by radiation induced pneumonitis. Also, several statistical reports demonstrated that left-sided breast cancer patient showed higher mortality than right-sided breast cancer patient because of heart disease. In radiation therapy, Deep Inspiration Breath Hold (DIBH) technique which the patient takes a deep inspiration and holds during treatment and could move the heart away from the chest wall and lung, has showed to lead to reduction in cardiac volume and to minimize the unnecessary radiation exposure to heart during treatment. In this study, we investigated the displacement of heart using DIBH CT data compared to free-breathing (FB) CT data and radiation exposure to heart. Treatment planning was performed on the computed tomography (CT) datasets of 10 patients who had received lumpectomy treatments. Heart, lung and both breasts were outlined. The prescribed dose was 50 Gy divided into 28 fractions. The dose distributions in all the plans were required to fulfill the International Commission on Radiation Units and Measurement specifications that include 100% coverage of the CTV with ${\geq}95%$ of the prescribed dose and that the volume inside the CTV receiving >107% of the prescribed dose should be minimized. Scar boost irradiation was not performed in this study. Displacement of heart was measured by calculating the distance between center of heart and left breast. For the evaluation of radiation dose to heart, minimum, maximum and mean dose to heart were calculated. The present study demonstrates that cardiac dose during left-sided breast radiotherapy can be reduced by applying DIBH breathing control technique.