Yasuka Azuma, M. Mizuno-Kamiya, E. Takayama, Harumi Kawaki, T. Inagaki, E. Chihara, Y. Muramatsu, N. Kondoh
Aim: The aim of this study is to compare the immunomodulatory effects exerted by primary versus metastasized oral squamous cell carcinoma (OSCC) cells. Methods: Mouse OSCC cell line Sq-1979, 233 cells established from implanted Sq-1979 cells, and L cells established from the metastasized lymph node tissues of Sq-1979-implanted mice were subcutaneously inoculated into the later abdominal area of syngeneic C3H mice. The producing capabilities of interferon (IFN)-γ, a Th1 cytokine, and interleukin (IL)-10, a Th2 cytokine, by anti-CD3 antibody-stimulated spleen cells were investigated in tumor bearing-mice. Results: The quantity of IFN-γ produced by stimulated spleen cells was significantly suppressed in the mice implanted with Sq-1979, 233, and L cells. Conversely, the production of IL-10 was significantly elevated in Sq-1979 and 233 cell-implanted mice while markedly suppressed in L cell-implanted mice. Conclusion: Our results suggest that the metastasized L cells have acquired differential immunomodulatory functions compared to the original Sq-1979 and primary 233 cells.
{"title":"The producing capabilities of Interferon-γ and Interleukin-10 of spleen cells in primary and metastasized oral squamous cell carcinoma cells-implanted mice","authors":"Yasuka Azuma, M. Mizuno-Kamiya, E. Takayama, Harumi Kawaki, T. Inagaki, E. Chihara, Y. Muramatsu, N. Kondoh","doi":"10.4103/ctm.ctm_30_17","DOIUrl":"https://doi.org/10.4103/ctm.ctm_30_17","url":null,"abstract":"Aim: The aim of this study is to compare the immunomodulatory effects exerted by primary versus metastasized oral squamous cell carcinoma (OSCC) cells. Methods: Mouse OSCC cell line Sq-1979, 233 cells established from implanted Sq-1979 cells, and L cells established from the metastasized lymph node tissues of Sq-1979-implanted mice were subcutaneously inoculated into the later abdominal area of syngeneic C3H mice. The producing capabilities of interferon (IFN)-γ, a Th1 cytokine, and interleukin (IL)-10, a Th2 cytokine, by anti-CD3 antibody-stimulated spleen cells were investigated in tumor bearing-mice. Results: The quantity of IFN-γ produced by stimulated spleen cells was significantly suppressed in the mice implanted with Sq-1979, 233, and L cells. Conversely, the production of IL-10 was significantly elevated in Sq-1979 and 233 cell-implanted mice while markedly suppressed in L cell-implanted mice. Conclusion: Our results suggest that the metastasized L cells have acquired differential immunomodulatory functions compared to the original Sq-1979 and primary 233 cells.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"25 1","pages":"194 - 199"},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73464924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qingshi Zhu, Qingyao Shang, Zhi-hao Hu, Yuan Liu, Bo Li, Bo Wang, An-hui Wang
Oral cancer, which occurs in the mouth, lips, and tongue, is a multifactorial disease whose etiology involves environment, genetic, and epigenetic factors. Tobacco use and alcohol consumption are regarded as the primary risk factors for oral squamous cell carcinoma (OSCC), and betel use, other chemicals, radiation, environmental, and genetics are reported as relevant risk factors for oral carcinogenesis. The human papillomavirus infection is an independent risk factor. Traditional epidemiology studies have revealed that environmental carcinogens are risk factors for OSCC. Molecular epidemiology studies have revealed that the susceptibility to OSCC is influenced by both environmental and genetic risk factors. However, the details and mechanisms of risk factors involved in OSCC are unclear. Advanced methods and techniques used in human genome studies provide great opportunities for researchers to explore and identify (a) the details of such risk factors and (b) genetic susceptibility involved in OSCC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era into the era of genome-wide association study. In the era of precision medicine, molecular epidemiology studies should focus on biomarkers for cancer genomics and their potential utility in clinical practice. Here, we briefly reviewed several molecular epidemiology studies of OSCC, focusing on biomarkers as valuable utility in risk assessment, clinical screening, diagnosis, and prognosis prediction of OSCC in the era of precision medicine.
{"title":"Biomarkers in molecular epidemiology study of oral squamous cell carcinoma in the era of precision medicine","authors":"Qingshi Zhu, Qingyao Shang, Zhi-hao Hu, Yuan Liu, Bo Li, Bo Wang, An-hui Wang","doi":"10.4103/ctm.ctm_32_17","DOIUrl":"https://doi.org/10.4103/ctm.ctm_32_17","url":null,"abstract":"Oral cancer, which occurs in the mouth, lips, and tongue, is a multifactorial disease whose etiology involves environment, genetic, and epigenetic factors. Tobacco use and alcohol consumption are regarded as the primary risk factors for oral squamous cell carcinoma (OSCC), and betel use, other chemicals, radiation, environmental, and genetics are reported as relevant risk factors for oral carcinogenesis. The human papillomavirus infection is an independent risk factor. Traditional epidemiology studies have revealed that environmental carcinogens are risk factors for OSCC. Molecular epidemiology studies have revealed that the susceptibility to OSCC is influenced by both environmental and genetic risk factors. However, the details and mechanisms of risk factors involved in OSCC are unclear. Advanced methods and techniques used in human genome studies provide great opportunities for researchers to explore and identify (a) the details of such risk factors and (b) genetic susceptibility involved in OSCC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era into the era of genome-wide association study. In the era of precision medicine, molecular epidemiology studies should focus on biomarkers for cancer genomics and their potential utility in clinical practice. Here, we briefly reviewed several molecular epidemiology studies of OSCC, focusing on biomarkers as valuable utility in risk assessment, clinical screening, diagnosis, and prognosis prediction of OSCC in the era of precision medicine.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"11 1","pages":"214 - 218"},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79716728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Differing from the adaptive immune checkpoint mediated by programmed cell death-1 (PD-1) PD-1-ligand or CTLA-4, the CD47 and signal regulatory protein α (SIRPα) axis is emerging as a novel innate immune checkpoint of the immune cells of myeloid lineage. A balance should be established between the dual signals, the “Don't eat me signal” of CD47-SIRPα and the “Eat me signal” of calreticulin/low-density lipoprotein receptor-related protein. The enhanced expression of CD47 molecule has been found in many cancer tissues, including malignant blood tumors (acute myeloid leukemia) and solid tumors. A therapeutic value could be achieved by counteracting the expression of CD47 in cancer cells. In the recent years, great progress has been made to develop anticancer therapies by targeting CD47 (e.g., anti-CD47 antibody), in various types of cancer. However, there are a few challenges, like “antigen sink” in the clinical translation of CD47-mediated anticancer therapies, the attention to which is crucial.
{"title":"“Eating” Cancer cells by blocking CD47 signaling: Cancer therapy by targeting the innate immune checkpoint","authors":"Y. Xiang, Li Liu","doi":"10.4103/ctm.ctm_26_17","DOIUrl":"https://doi.org/10.4103/ctm.ctm_26_17","url":null,"abstract":"Differing from the adaptive immune checkpoint mediated by programmed cell death-1 (PD-1) PD-1-ligand or CTLA-4, the CD47 and signal regulatory protein α (SIRPα) axis is emerging as a novel innate immune checkpoint of the immune cells of myeloid lineage. A balance should be established between the dual signals, the “Don't eat me signal” of CD47-SIRPα and the “Eat me signal” of calreticulin/low-density lipoprotein receptor-related protein. The enhanced expression of CD47 molecule has been found in many cancer tissues, including malignant blood tumors (acute myeloid leukemia) and solid tumors. A therapeutic value could be achieved by counteracting the expression of CD47 in cancer cells. In the recent years, great progress has been made to develop anticancer therapies by targeting CD47 (e.g., anti-CD47 antibody), in various types of cancer. However, there are a few challenges, like “antigen sink” in the clinical translation of CD47-mediated anticancer therapies, the attention to which is crucial.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"9 1","pages":"200 - 208"},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87446380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer cells express unique carbohydrate structures in glycoproteins and glycolipids, and their structures have been considered to be cancer-associated antigens. However, the involvement of their antigens in the malignant properties has not been well understood. The functional studies of glycosyltransferase genes revealed important regulatory roles of glycosylation in the malignant properties of cancer cells. In particular, we have characterized the molecular signaling pathways that are activated or inactivated by gangliosides in various cancer cells. Our results indicated that disialyl gangliosides GD3 and GD2 enhance malignant properties of human melanoma, osteosarcoma, and small cell lung cancer cells. However, monosialyl ganglioside GM1 attenuates these properties in melanoma and lung cancer cells. In addition to glycolipids, glycoproteins are also reported to be involved in regulating malignant properties and maintenance of cancer stem cells.
{"title":"Glycosylation is involved in malignant properties of cancer cells","authors":"K. Hamamura, K. Furukawa","doi":"10.4103/ctm.ctm_28_17","DOIUrl":"https://doi.org/10.4103/ctm.ctm_28_17","url":null,"abstract":"Cancer cells express unique carbohydrate structures in glycoproteins and glycolipids, and their structures have been considered to be cancer-associated antigens. However, the involvement of their antigens in the malignant properties has not been well understood. The functional studies of glycosyltransferase genes revealed important regulatory roles of glycosylation in the malignant properties of cancer cells. In particular, we have characterized the molecular signaling pathways that are activated or inactivated by gangliosides in various cancer cells. Our results indicated that disialyl gangliosides GD3 and GD2 enhance malignant properties of human melanoma, osteosarcoma, and small cell lung cancer cells. However, monosialyl ganglioside GM1 attenuates these properties in melanoma and lung cancer cells. In addition to glycolipids, glycoproteins are also reported to be involved in regulating malignant properties and maintenance of cancer stem cells.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"121 1","pages":"209 - 213"},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76146930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent years, the research on the regulation of nuclear factor kappa B (NF-κB) signaling pathway in tumor cell apoptosis and proliferation is a hot topic. It has been reported that activated NF-κB pathway exerts antiapoptotic effect by inducing antiapoptotic and cell proliferation-related target gene expression, including the Bcl-2 family, survivin, COX-2, Cyclin Dl, and epidermal growth factor receptor, eventually leading to accelerated cell cycle progression and enhanced antiapoptotic and proliferation ability of tumor cells. However, the underlying specific mechanism has not been fully determined. Inhibiting the activation of NF-κB signaling pathway to promote the apoptosis is the topic of research on treating several conditions such as inflammation, immunity, and tumor. In this paper, the correlation between NF-κB signaling pathway and apoptosis of glioma cells is reviewed.
{"title":"The significance of nuclear factor-kappa B signaling pathway in glioma: A review","authors":"Xiaoshan Xu, Hongwei Yang, Xin Wang, Y. Tu","doi":"10.4103/ctm.ctm_48_16","DOIUrl":"https://doi.org/10.4103/ctm.ctm_48_16","url":null,"abstract":"In recent years, the research on the regulation of nuclear factor kappa B (NF-κB) signaling pathway in tumor cell apoptosis and proliferation is a hot topic. It has been reported that activated NF-κB pathway exerts antiapoptotic effect by inducing antiapoptotic and cell proliferation-related target gene expression, including the Bcl-2 family, survivin, COX-2, Cyclin Dl, and epidermal growth factor receptor, eventually leading to accelerated cell cycle progression and enhanced antiapoptotic and proliferation ability of tumor cells. However, the underlying specific mechanism has not been fully determined. Inhibiting the activation of NF-κB signaling pathway to promote the apoptosis is the topic of research on treating several conditions such as inflammation, immunity, and tumor. In this paper, the correlation between NF-κB signaling pathway and apoptosis of glioma cells is reviewed.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"7 1","pages":"181 - 184"},"PeriodicalIF":0.0,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88038833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
X. Liang, F. Yin, Yilin Liu, B. Czito, M. Palta, M. Bashir, Jing Cai
Aim: The aim of this study was to evaluate deformable image registration (DIR)-based motion estimation of the liver for four-dimensional-computed tomography (4D-CT) and 4D-magnetic resonance imaging (MRI). Methods: Five liver cancer patients were included. Each patient was imaged with 4D-CT and 4D-MRI under an Institutional Review Board-approved protocol. Motion estimation of the liver was obtained by performing DIR on 4D-CT and 4D-MRI. A region of interest (ROI) encompassing the expert-determined gross tumor volume was used as surrogate to evaluate the accuracy of the motion estimation. ROI motion trajectories were estimated by averaging the displacement vector fields (DVFs) within the ROI during the breathing cycles for 4D-CT and 4D-MRI and were compared to those extracted from cine MR. Target registration error (TRE), correlation coefficient (CC) for phase agreement, difference in phase at maximum displacement (ΔPmax), and Dice's Similarity Coefficient (DSC) for overall motion agreement were determined. Results: As compared to 4D-CT, 4D-MRI resulted in smaller TRE in DVFs (anterior-posterior [AP]: 1.0 ± 0.4 mm vs. 1.5 ± 0.5 mm, superior-inferior [SI]: 1.9 ± 0.7 mm vs. 2.2 ± 0.8 mm), greater CC (AP: 0.67 ± 0.32 vs. 0.49 ± 0.26, SI: 0.84 ± 0.15 vs. 0.58 ± 0.28), smaller ΔPmax (AP: 1.4 ± 1.7 vs. 2.0 ± 1.0, SI: 0.4 ± 0.9 vs. 1.2 ± 0.8), and greater DSC (AP: 0.67 ± 0.08 vs. 0.61 ± 0.11, SI: 0.73 ± 0.12 vs. 0.67 ± 0.10). Conclusion: 4D-MRI can potentially provide more realistic respiratory DVFs of the liver than 4D-CT.
{"title":"Motion estimation of the liver based on deformable image registration: a comparison between four-dimensional-computed tomography and four-dimensional-magnetic resonance imaging","authors":"X. Liang, F. Yin, Yilin Liu, B. Czito, M. Palta, M. Bashir, Jing Cai","doi":"10.4103/ctm.ctm_24_17","DOIUrl":"https://doi.org/10.4103/ctm.ctm_24_17","url":null,"abstract":"Aim: The aim of this study was to evaluate deformable image registration (DIR)-based motion estimation of the liver for four-dimensional-computed tomography (4D-CT) and 4D-magnetic resonance imaging (MRI). Methods: Five liver cancer patients were included. Each patient was imaged with 4D-CT and 4D-MRI under an Institutional Review Board-approved protocol. Motion estimation of the liver was obtained by performing DIR on 4D-CT and 4D-MRI. A region of interest (ROI) encompassing the expert-determined gross tumor volume was used as surrogate to evaluate the accuracy of the motion estimation. ROI motion trajectories were estimated by averaging the displacement vector fields (DVFs) within the ROI during the breathing cycles for 4D-CT and 4D-MRI and were compared to those extracted from cine MR. Target registration error (TRE), correlation coefficient (CC) for phase agreement, difference in phase at maximum displacement (ΔPmax), and Dice's Similarity Coefficient (DSC) for overall motion agreement were determined. Results: As compared to 4D-CT, 4D-MRI resulted in smaller TRE in DVFs (anterior-posterior [AP]: 1.0 ± 0.4 mm vs. 1.5 ± 0.5 mm, superior-inferior [SI]: 1.9 ± 0.7 mm vs. 2.2 ± 0.8 mm), greater CC (AP: 0.67 ± 0.32 vs. 0.49 ± 0.26, SI: 0.84 ± 0.15 vs. 0.58 ± 0.28), smaller ΔPmax (AP: 1.4 ± 1.7 vs. 2.0 ± 1.0, SI: 0.4 ± 0.9 vs. 1.2 ± 0.8), and greater DSC (AP: 0.67 ± 0.08 vs. 0.61 ± 0.11, SI: 0.73 ± 0.12 vs. 0.67 ± 0.10). Conclusion: 4D-MRI can potentially provide more realistic respiratory DVFs of the liver than 4D-CT.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"8 1","pages":"153 - 158"},"PeriodicalIF":0.0,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84411894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanlan Li, Zheng Hu, Yufang Yin, Rongzhang He, Jian Hu, Weihao Luo, Jia Li, Gebo Wen, Li Xiao, Kai Li, Duan-fang Liao, Dixian Luo
The adaptive immune systems of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (Cas) selectively destroy nonnative DNA and defend almost all archaea and about half of the bacteria against infections. In the past years, the system has been genetically engineered to a powerful genome editing tool for a wide variety of organisms. Recently, many progresses have been made in the CRISPR-Cas systems. These improvements include applications in editing multiple genes, correcting mutation genes with one base difference, targeting nondividing cells, reducing off-target, and editing RNAs. The biomedical applications of the technology are to edit not only cells but also embryos in clinical settings. In this review, we briefly introduce the improvements of CRISPR-Cas9 gene editing methods and summarize the recent advances of this technology.
{"title":"Recent progress in technological improvement and biomedical applications of the clustered regularly interspaced short palindromic repeats/cas system","authors":"Yanlan Li, Zheng Hu, Yufang Yin, Rongzhang He, Jian Hu, Weihao Luo, Jia Li, Gebo Wen, Li Xiao, Kai Li, Duan-fang Liao, Dixian Luo","doi":"10.4103/ctm.ctm_22_17","DOIUrl":"https://doi.org/10.4103/ctm.ctm_22_17","url":null,"abstract":"The adaptive immune systems of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (Cas) selectively destroy nonnative DNA and defend almost all archaea and about half of the bacteria against infections. In the past years, the system has been genetically engineered to a powerful genome editing tool for a wide variety of organisms. Recently, many progresses have been made in the CRISPR-Cas systems. These improvements include applications in editing multiple genes, correcting mutation genes with one base difference, targeting nondividing cells, reducing off-target, and editing RNAs. The biomedical applications of the technology are to edit not only cells but also embryos in clinical settings. In this review, we briefly introduce the improvements of CRISPR-Cas9 gene editing methods and summarize the recent advances of this technology.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"92 1","pages":"174 - 180"},"PeriodicalIF":0.0,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84126678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaofeng Zhu, Y. Lei, D. Zheng, Sicong Li, V. Verma, Mutian Zhang, Qinghui Zhang, Xiaoli Tang, J. Lian, Sha X. Chang, Haijun Song, Sumin Zhou, C. Enke
Aim: High-dose rate (HDR) brachytherapy poses a special challenge to radiation safety and quality assurance (QA) due to its high radioactivity, and it is thus critical to verify the HDR source location and its radioactive strength. This study explores a new application for thermal imaging, to visualize/locate the HDR source and measure radioactivity using temperature information. A potential application would relate to HDR QA and safety improvement. Methods: Heating effects by an HDR source were studied using finite element analysis (FEA). Thermal cameras were used to visualize an HDR source inside a plastic catheter made of polyvinylidene difluoride (PVDF). Using different source dwell times, relationships between the HDR source strength and heating effects were studied, thus establishing potential daily QA criteria using thermal imaging. Results: For an Ir-192 source with a source radioactivity of 10 Ci, the decay-induced heating power inside the source was about 13.3 mW. After the HDR source was extended into the PVDF applicator and reached thermal equilibrium, thermal imaging visualized the temperature gradient of 10 K/cm along the PVDF catheter surface, which agreed with FEA modeling. For the Ir-192 source strengths ranging from 16.9 to 41.1 kU, thermal imaging could verify source activity with a relative error of 6.3% with a dwell time of 10 s, and a relative error of 2.5% with 100 s. Conclusion: Thermal imaging could be a feasible tool to visualize HDR source dwell positions and verify source integrity. Potentially, patient safety and treatment quality may be improved by integrating thermal measurements into HDR QA procedures.
{"title":"A feasibility study of applying thermal imaging to assist quality assurance of high-dose rate brachytherapy","authors":"Xiaofeng Zhu, Y. Lei, D. Zheng, Sicong Li, V. Verma, Mutian Zhang, Qinghui Zhang, Xiaoli Tang, J. Lian, Sha X. Chang, Haijun Song, Sumin Zhou, C. Enke","doi":"10.4103/ctm.ctm_25_17","DOIUrl":"https://doi.org/10.4103/ctm.ctm_25_17","url":null,"abstract":"Aim: High-dose rate (HDR) brachytherapy poses a special challenge to radiation safety and quality assurance (QA) due to its high radioactivity, and it is thus critical to verify the HDR source location and its radioactive strength. This study explores a new application for thermal imaging, to visualize/locate the HDR source and measure radioactivity using temperature information. A potential application would relate to HDR QA and safety improvement. Methods: Heating effects by an HDR source were studied using finite element analysis (FEA). Thermal cameras were used to visualize an HDR source inside a plastic catheter made of polyvinylidene difluoride (PVDF). Using different source dwell times, relationships between the HDR source strength and heating effects were studied, thus establishing potential daily QA criteria using thermal imaging. Results: For an Ir-192 source with a source radioactivity of 10 Ci, the decay-induced heating power inside the source was about 13.3 mW. After the HDR source was extended into the PVDF applicator and reached thermal equilibrium, thermal imaging visualized the temperature gradient of 10 K/cm along the PVDF catheter surface, which agreed with FEA modeling. For the Ir-192 source strengths ranging from 16.9 to 41.1 kU, thermal imaging could verify source activity with a relative error of 6.3% with a dwell time of 10 s, and a relative error of 2.5% with 100 s. Conclusion: Thermal imaging could be a feasible tool to visualize HDR source dwell positions and verify source integrity. Potentially, patient safety and treatment quality may be improved by integrating thermal measurements into HDR QA procedures.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"51 1","pages":"159 - 166"},"PeriodicalIF":0.0,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89216793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Moonat, Gangxiong Huang, P. Dhupkar, Keri L Schadler, N. Gordon, E. Kleinerman
Aim: To test whether combining interleukin (IL)-11Rα chimeric antigen receptor (CAR) T-cells with an anti-programmed death (PD-1) antibody (an immune checkpoint inhibitor) is an effective therapeutic approach in osteosarcoma (OS), allowing improved tumor eradication. Methods: IL-11Rα-CAR T-cells were cocultured in vitro with human LM7 OS tumor cells (with and without anti-PD-1 antibody). Coculture of LM7 cells with purified T-cells served as the control. Cytotoxicity and surface PD-1 expression were analyzed in all groups. Results: PD-1 expression increased during expansion of CAR T-cells. Exposure of immune cells to tumor cells in vitro subsequently decreased surface PD-1 expression on the CAR T-cells. Addition of an anti-PD-1 antibody (Clone J110) to further decrease surface PD-1 expression on CAR T-cells before coculture did not enhance cytotoxic effects of the CAR T-cells against LM7 cells. Conclusion: This combination of IL-11Rα-CAR T-cells and an anti-PD-1 antibody did not provide any additional cytotoxic benefit over IL-11Rα-CAR T-cell therapy alone in this setting. Further studies are needed as simple interference with surface PD-1 expression alone may not be sufficient to inhibit this immune checkpoint pathway to then enhance IL-11Rα-CAR T-cell therapeutic effects.
{"title":"Combination of Interleukin-11Rα chimeric antigen receptor T-cells and programmed death-1 blockade as an approach to targeting osteosarcoma cells In vitro","authors":"H. Moonat, Gangxiong Huang, P. Dhupkar, Keri L Schadler, N. Gordon, E. Kleinerman","doi":"10.4103/ctm.ctm_3_17","DOIUrl":"https://doi.org/10.4103/ctm.ctm_3_17","url":null,"abstract":"Aim: To test whether combining interleukin (IL)-11Rα chimeric antigen receptor (CAR) T-cells with an anti-programmed death (PD-1) antibody (an immune checkpoint inhibitor) is an effective therapeutic approach in osteosarcoma (OS), allowing improved tumor eradication. Methods: IL-11Rα-CAR T-cells were cocultured in vitro with human LM7 OS tumor cells (with and without anti-PD-1 antibody). Coculture of LM7 cells with purified T-cells served as the control. Cytotoxicity and surface PD-1 expression were analyzed in all groups. Results: PD-1 expression increased during expansion of CAR T-cells. Exposure of immune cells to tumor cells in vitro subsequently decreased surface PD-1 expression on the CAR T-cells. Addition of an anti-PD-1 antibody (Clone J110) to further decrease surface PD-1 expression on CAR T-cells before coculture did not enhance cytotoxic effects of the CAR T-cells against LM7 cells. Conclusion: This combination of IL-11Rα-CAR T-cells and an anti-PD-1 antibody did not provide any additional cytotoxic benefit over IL-11Rα-CAR T-cell therapy alone in this setting. Further studies are needed as simple interference with surface PD-1 expression alone may not be sufficient to inhibit this immune checkpoint pathway to then enhance IL-11Rα-CAR T-cell therapeutic effects.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"24 1","pages":"139 - 145"},"PeriodicalIF":0.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90317605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: Cancer-associated fibroblasts (CAFs) are the key cellular components of the tumor stroma. CAFs express fibroblast activation protein (FAP) and FAP-targeted immunotherapies have shown potent antitumor effects in preclinical mouse studies, highlighting their central role in tumorigenesis. However, safety concerns have been raised in regard to FAP-targeted immunotherapies since bone marrow failure and cachexia were observed in transgenic models and preclinical studies. Here, we describe a novel oncolytic virotherapy by locally targeting FAP within tumor tissue. Methods: T-cell engager-armed oncolytic vaccinia virus (TEA-VV) that encodes a secretory bi-specific T-cell engager consisting of two single-chain variable fragments specific for murine CD3 and fibroblast activation protein (mFAP-TEA-VV) was generated. The antitumor effects of mFAP-TEA-VV were compared to unmodified VVs using standard in vitro immunological assays and an immunocompetent B16 melanoma mouse model. Results: In vitro, the ability of mFAP-TEA-VV to replicate within tumor cells and induce oncolysis was similar to that of unmodified VVs. However, in co-culture assays, only mFAP-TEA-VV induced bystander killing of noninfected FAP-expressing cells in the presence of murine T-cells. In vivo, mFAP-TEA-VV enhanced viral titer within the tumor and had potent antitumor activity in comparison to control VVs in an immunocompetent B16 melanoma mouse model. Importantly, the improved viral spread of mFAP-TEA-VV correlated with the destruction of tumor stroma. Conclusion: Arming oncolytic VVs with an FAP-targeted T-cell engager may be a promising improvement to oncolytic virus therapy for solid tumors.
{"title":"A T-cell engager-armed oncolytic vaccinia virus to target the tumor stroma","authors":"Feng Yu, Bangxing Hong, Xiao-tong Song","doi":"10.4103/ctm.ctm_13_17","DOIUrl":"https://doi.org/10.4103/ctm.ctm_13_17","url":null,"abstract":"Aim: Cancer-associated fibroblasts (CAFs) are the key cellular components of the tumor stroma. CAFs express fibroblast activation protein (FAP) and FAP-targeted immunotherapies have shown potent antitumor effects in preclinical mouse studies, highlighting their central role in tumorigenesis. However, safety concerns have been raised in regard to FAP-targeted immunotherapies since bone marrow failure and cachexia were observed in transgenic models and preclinical studies. Here, we describe a novel oncolytic virotherapy by locally targeting FAP within tumor tissue. Methods: T-cell engager-armed oncolytic vaccinia virus (TEA-VV) that encodes a secretory bi-specific T-cell engager consisting of two single-chain variable fragments specific for murine CD3 and fibroblast activation protein (mFAP-TEA-VV) was generated. The antitumor effects of mFAP-TEA-VV were compared to unmodified VVs using standard in vitro immunological assays and an immunocompetent B16 melanoma mouse model. Results: In vitro, the ability of mFAP-TEA-VV to replicate within tumor cells and induce oncolysis was similar to that of unmodified VVs. However, in co-culture assays, only mFAP-TEA-VV induced bystander killing of noninfected FAP-expressing cells in the presence of murine T-cells. In vivo, mFAP-TEA-VV enhanced viral titer within the tumor and had potent antitumor activity in comparison to control VVs in an immunocompetent B16 melanoma mouse model. Importantly, the improved viral spread of mFAP-TEA-VV correlated with the destruction of tumor stroma. Conclusion: Arming oncolytic VVs with an FAP-targeted T-cell engager may be a promising improvement to oncolytic virus therapy for solid tumors.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"45 1","pages":"122 - 132"},"PeriodicalIF":0.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91528989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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