scholarly journals A novel radio-sensitization method for lung cancer therapy: enhanced radiosensitization induced by antigens/antibodies reaction after targeting tumor hypoxia using Bifidobacterium

2020 ◽  
Author(s):  
Juan Yang ◽  
Zhouxue Wu ◽  
Yao Chen ◽  
Chuanfei Hu ◽  
Dong Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Monoclonal Antibodies ◽  
Treatment Group ◽  
Tumor Growth ◽  
Combined Treatment ◽  
Proliferation Index ◽  
Bifidobacterium Infantis ◽  
Glut 1 ◽  
Pet Ct ◽  
Tnf Α

Abstract Background：The hypoxic microenvironment of solid tumors reduces the susceptibility of cancer cells to radiotherapy. Current treatments are focused on the development of anti-cancer agents that selectively target tumor cells with no toxicity to healthy tissue. Bacteria colonize and destroy tumors and have emerged as biological vectors that can survive in the tumor microenvironment. Methods：In this study, a Lewis lung carcinoma transplant mouse model was established and treated with a combination of bifidobacterium infantis (Bi), its specific monoclonal antibodies (Ab) and radiotherapy (RT). 18F-FDG PET/CT and 18F-FMISO PET/CT imaging were performed to monitor tumor growth and hypoxia in the tumor tissue. Phosphorylated histone (γ-H2AX), the proliferation index (Ki-67), platelet endothelial cell adhesion molecules (CD31), tumor necrosis factor-α (TNF-α), hypoxia inducible factor-1α (HIF-1α) and glucose transporter 1 (Glut-1) levels were assessed through immunohistochemistry. Results：The results showed that the combined treatment group (Ab+ Bi+ RT) displayed delayed tumor growth and prolonged the survival of mice. The combined treatment group also had lower levels of HIF-1α, Glut-1, and CD31 expression, and a lower uptake of FDG and FMISO. The tumors treated with the combination therapy also had lower levels of hypoxia, and increased γ-H2AX and TNF-α expression. Conclusion：Taken together, these data suggest that the combination of bifidobacterium infantis and its specific monoclonal antibodies can markedly improve the efficacy of radiotherapy for the treatment of lung cancer.

scholarly journals Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma

2020 ◽  
Author(s):  
Min-Young Kim ◽  
Jung-Young Shin ◽  
Jeong-Oh Kim ◽  
Kyoung-Hwa Son ◽  
Yeon Sil Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Mouse Model ◽  
Tumor Growth ◽  
Blood Vessels ◽  
Tumor Necrosis ◽  
Tumor Volume ◽  
Lung Squamous Cell Carcinoma ◽  
Ki 67 ◽  
Glut 1

Abstract Background: Hypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small-cell lung cancer (NSCLC) patients. Vascular disrupting agents (VDAs) mainly affect blood vessels located in the central area of the tumor and lead to a rapid decrease in blood, resulting in massive apoptotic tumor cell death. Thus, we evaluate the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examine tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study.Methods: A xenograft mouse model of lung squamous cell carcinoma was established, and the tumor was exposed to IR 5 days per week. CKD-516 was administered with ​​two treatment schedules (day 1 or days 1 and 5) 1 h after IR. After the treatment, tumor tissues were stained with hematoxylin and eosin and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated by immunohistochemical staining.Results: Short-term treatment with IR alone and CKD-516+IR (d1) significantly reduced tumor volume (p = 0.006 and p = 0.048, respectively). Treatment with CKD-516+IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516+IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (p = 0.02) and decreased HIF-1α, Glut-1, VEGF, and Ki-67 expression. Long-term administration of CKD-516+IR reduced tumor volume and delayed tumor growth. This combination also greatly reduced the number of blood vessels (p = 0.0006) and significantly enhanced tumor necrosis (p = 0.004). CKD-516+IR significantly increased HIF-1α expression (p = 0.0047), but significantly reduced VEGF expression (p = 0.0046).Conclusions: Taken together, our data show that when used in combination, CKD-516 and IR can significantly enhance anti-tumor efficacy compared to monotherapy in lung cancer xenograft mice.

scholarly journals Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma

2020 ◽  
Author(s):  
Min-Young Kim ◽  
Jung-Young Shin ◽  
Jeong-Oh Kim ◽  
Kyoung-Hwa Son ◽  
Yeon Sil Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Mouse Model ◽  
Tumor Growth ◽  
Blood Vessels ◽  
Tumor Necrosis ◽  
Tumor Volume ◽  
Lung Squamous Cell Carcinoma ◽  
Ki 67 ◽  
Glut 1

Abstract Background: Hypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small cell lung cancer (NSCLC) patients. CKD-516, a novel vascular disrupting agent (VDA), mainly affects blood vessels in the central area of the tumor and blocks tubulin polymerization, thereby destroying the aberrant tumor vasculature with a rapid decrease in blood, resulting in massive apoptotic tumor cell death. Therefore, we evaluated the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examined tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study.Methods: A xenograft mouse model of lung squamous cell carcinoma was established, and the tumor was exposed to IR 5 days per week. CKD-516 was administered with two treatment schedules (day 1 or days 1 and 5) 1 h after IR. After treatment, tumor tissues were stained with hematoxylin and eosin, and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated using immunohistochemical staining.Results: Short-term treatment with IR alone and CKD-516+IR (d1) significantly reduced tumor volume (p = 0.006 and p = 0.048, respectively). Treatment with CKD-516+IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516+IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (p = 0.02) and decreased HIF-1α, Glut-1, VEGF, and Ki-67 expression. Long-term administration of CKD-516+IR reduced tumor volume and delayed tumor growth. This combination also greatly reduced the number of blood vessels (p = 0.0006) and significantly enhanced tumor necrosis (p = 0.004). CKD-516+IR significantly increased HIF-1α expression (p = 0.0047), but significantly reduced VEGF expression (p = 0.0046).Conclusions: Taken together, our data show that when used in combination, CKD-516 and IR can significantly enhance anti-tumor efficacy compared to monotherapy in lung cancer xenograft mice.

scholarly journals Melatonin enhances radiofrequency-induced NK antitumor immunity, causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ming Li ◽  
Bingjie Hao ◽  
Menghuan Zhang ◽  
Russel J. Reiter ◽  
Shumeng Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Antitumor Immunity ◽  
Combined Treatment ◽  
Pulmonary Nodules ◽  
Residual Tumor ◽  
Antitumor Effects ◽  
Multiple Pulmonary Nodules ◽  
Link Type ◽  
Early Lung Cancer

AbstractSurgery is the common treatment for early lung cancer with multiple pulmonary nodules, but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas. In this study, we found that a combined treatment of local radiofrequency ablation (RFA) and melatonin (MLT) greatly improved clinical outcomes for early lung cancer patients with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas. Mechanically, as demonstrated in an associated mouse lung tumor model, RFA not only effectively remove treated tumors but also stimulate antitumor immunity, which could inhibit tumor growth in non-ablated areas. MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA. Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment, which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT. Analysis of residual tumor further revealed the depressed activity of MAPK, NF-kappa B, Wnt, and Hedgehog pathways and upregulated P53 pathway in tumors, which was in line with the inhibited tumor growth. Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy. These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules. Trial registration: www.chictr.org.cn, identifier ChiCTR2100042695, http://www.chictr.org.cn/showproj.aspx?proj=120931.

scholarly journals Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Min-Young Kim ◽  
Jung-Young Shin ◽  
Jeong-Oh Kim ◽  
Kyoung-Hwa Son ◽  
Yeon Sil Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Mouse Model ◽  
Tumor Growth ◽  
Blood Vessels ◽  
Tumor Necrosis ◽  
Tumor Volume ◽  
Lung Squamous Cell Carcinoma ◽  
Ki 67 ◽  
Glut 1

Abstract Background Hypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small cell lung cancer (NSCLC) patients. CKD-516, a novel vascular disrupting agent (VDA), mainly affects blood vessels in the central area of the tumor and blocks tubulin polymerization, thereby destroying the aberrant tumor vasculature with a rapid decrease in blood, resulting in rapid tumor cell death. Therefore, we evaluated the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examined tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study. Methods A xenograft mouse model of lung squamous cell carcinoma was established, and the tumor was exposed to IR 5 days per week. CKD-516 was administered with two treatment schedules (day 1 or days 1 and 5) 1 h after IR. After treatment, tumor tissues were stained with hematoxylin and eosin, and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated using immunohistochemical staining. Results Short-term treatment with IR alone and CKD-516 + IR (d1) significantly reduced tumor volume (p = 0.006 and p = 0.048, respectively). Treatment with CKD-516 + IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516 + IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (p = 0.02) and decreased HIF-1α, Glut-1, VEGF, and Ki-67 expression. Long-term administration of CKD-516 + IR reduced tumor volume and delayed tumor growth. This combination also greatly reduced the number of blood vessels (p = 0.0006) and significantly enhanced tumor necrosis (p = 0.004). CKD-516 + IR significantly increased HIF-1α expression (p = 0.0047), but significantly reduced VEGF expression (p = 0.0046). Conclusions Taken together, our data show that when used in combination, CKD-516 and IR can significantly enhance anti-tumor efficacy compared to monotherapy in lung cancer xenograft mice.

scholarly journals Au-siRNA@ aptamer nanocages as a high-efficiency drug and gene delivery system for targeted lung cancer therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuming Yang ◽  
Yu Han ◽  
Qiuyang Sun ◽  
Jin Cheng ◽  
Caixia Yue ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Rate ◽  
Treatment Group ◽  
High Efficiency ◽  
Combined Treatment ◽  
Molecular Medicine ◽  
Anticancer Activities ◽  
Tumor Inhibition ◽  
Inhibition Ratio ◽  
Photothermal Treatment

Abstract Background Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine. Results In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group. Conclusions The development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.

scholarly journals Study on the Efficacy and Safety of Ambroxol Combined with Methylprednisolone in Patients with Acute Lung Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Weiwei Su ◽  
Qinglian Dong ◽  
Fangfang Jiao
Keyword(s):  
Acute Lung Injury ◽  
Treatment Group ◽  
Lung Injury ◽  
Oxygen Partial Pressure ◽  
Partial Pressure ◽  
Combined Treatment ◽  
Oxygenation Index ◽  
Arterial Blood Gas ◽  
Arterial Blood ◽  
Tnf Α

Background. There is no better treatment method towards paraquat-induced acute lung injury (ALI) at present. Ambroxol combined with methylprednisolone exhibits a significant improvement effect on ALI treatment, whereas their mechanism in ALI is still unclear. Methods. 64 patients with ALI caused by paraquat poisoning brought to our hospital from January 2015 to January 2018 were selected. They were separated into a combined treatment group (CTG) and a routine treatment group (RTG) on the basis of different treatment methods. The survival of patients was observed after 7 days of treatment. Arterial blood gas, oxygen partial pressure (PaO2), partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2), patient’s spontaneous respiratory rate (RR), tidal volume (VT), and positive end-expiratory pressure (PEEP) were observed before and after treatment for 7 days. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were analyzed. The differences of indexes between the dead patients and the survivors were observed, and the potential predictive value of death was analyzed. Results. After treatment, the indexes of patients were significantly improved in both groups compared with those before therapy. Further comparison showed that the improvement of PaO2, PaCO2, and PaO2/FiO2 in CTG was obviously higher than that in RTG ( p < 0.05 ). The improvement of RR, PEEP, and VT in CTG was obviously higher than that in RTG ( p < 0.05 ). The decreased degree of IL-6 and TNF-α in CTG was higher than that in RTG ( p < 0.05 ). The 7-day mortality rate of 64 patients was 39.06%, and there was no obvious difference in the 7-day survival rate in both groups ( p = 0.649 ). IL-6 and TNF-α were expected to be potential prediction indexes of paraquat-induced ALI. Conclusion. Ambroxol combined with methylprednisolone significantly improved the oxygen partial pressure and oxygenation index of patients with paraquat-induced ALI and inhibited the inflammatory response of patients.

scholarly journals P1-102: Correlation of [18F]FDG PET/CT imaging with Glut-1 and Glut-3 expression in non-small cell lung cancer

2007 ◽  
Vol 2 (8) ◽  
pp. S590
Author(s):  
Ie Ryung Yoo ◽  
W.H. Choi ◽  
T.J. Kim ◽  
K.Y. Lee ◽  
Y.P. Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Fdg Pet ◽  
Small Cell ◽  
Small Cell Lung ◽  
Glut 1 ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

scholarly journals Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft lung cancer mouse model

2019 ◽  
Author(s):  
Min-Young Kim ◽  
Jung-Young Shin ◽  
Jeong-Oh Kim ◽  
Kyoung-Hwa Son ◽  
Chan-Kwon Jung ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Tumor Growth ◽  
Blood Vessels ◽  
Tumor Size ◽  
Tumor Necrosis ◽  
Ki 67 ◽  
Glut 1 ◽  
Term Administration ◽  
Xenograft Mice

Abstract Background: To evaluate the anti-tumor efficacy of CKD-516 in combined with irradiation (IR) and examine tumor necrosis, delayed tumor growth, and expression of molecules involved in hypoxia and angiogenesis. Methods : A xenograft mouse model of lung cancer was established. The tumor was exposed to irradiation (IR) for 5 days per week. CKD-516 was administered with ​​two treatment schedules (day 1 or days 1 and 5) at one hour after IR. After the administration, tumor tissues were stained with hematoxylin and eosin and pimonidazole. HIF1 , Glut-1, VEGF, CD31 and Ki-67 expression were evaluated by Immunohistochemical staining. Results: With short-term administration, IR and CKD-516+IR (d1) significantly reduced tumor size ( p = 0.0062 and p = 0.0051, respectively). CKD-516+IR groups were remarkably reduced blood vessels ( p < 0.005). In particular, CKD-516+IR (d1) resulted in the most extensive tumor necrosis, which was significantly increased with large hypoxic area ( p = 0.02) and decreased HIF1 , Glut-1, VEGF, and Ki-67 expressions. Long-term administration of CKD-516+IR reduced tumor size and delayed tumor growth. This combination also greatly reduced the number of blood vessels ( p = 0.0006) and significantly enhanced tumor necrosis ( p = 0.004). CKD-516+IR notably increased HIF1 expression ( p = 0.0047), but significantly diminished VEGF expression ( p = 0.0046). Conclusion: Taken together, our results demonstrate that CKD-516 in combination with IR can significantly enhance the anti-tumor efficacy compared to CKD-516 or IR alone in lung cancer xenograft mice. Keywords: Irradiation, Tumor necrosis, Hypoxia, Squamous cell carcinoma of lung, Xenograft mice

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