Correlation between Chlamydia Pneumoniae IgG Positive in Lung Cancer Patients and Cytokines Related to Radiation-induced Pulmonary Lesion

Background and objective There exsits intimate relationship between infection with chlamydia pneumoniae (Cpn) and lung cancer incidence. But few studies have been reported about radiation-induced pulmonary lesion in lung cancer patients infected with Cpn. The aim of this study is to explore the correlation between cytokines related to radiation-induced pulmonary lesion and Cpn IgG positive in lung cancer patients. Methods A total of 69 patients with lung cancer received chest radiotherapy. Blood samples were collected and frozen before radiotherapy (pre-RT), middle radiotherapy (mid-RT) and after radiotherapy (post-RT). Cpn IgG and levels of IL-1β, SP-A, TGF-β, and TNF-α were measured by enzymelinked immunosorbent assay (ELISA). Results In the total of 69 patients, 21 patients were Cpn IgG positive, 48 patients negative. The positive rate was 30.43%. In mid-RT concentration of IL-1β in Cpn IgG positive and negative group were (35.82±10.09) ng/L and (30.01±6.46) ng/L, with statistically significant difference (P < 0.05). Pre-RT and post-RT concentrations of IL-1β in Cpn IgG positive and negative group had no statistically significant difference. Mid-RT concentrations of SP-A in Cpn IgG positive group and negative group were (641.78±106.81) ng/L and (100.86±61.4) ng/L respectively, with statistically significant difference (P < 0.05). Post-RT concentration of SP-A in Cpn IgG positive and negative group were (657.47±115.19) ng/L and (93.23±47.15) ng/L respectively, with statistically significant difference (P < 0.05). Concentrations of TNF-α in Cpn IgG positive and negative group had no statistically significant difference. Concentrations of TGF-β in Cpn IgG positive group were (710.67±358.16) pg/mL in pre-RT, (1,002.06±542.16) pg/mL in mid-RT, (2,125.16±1,522.29) pg/mL in post-RT; those in negative group were (867.77±412.48) pg/mL, (914.05±425.70) pg/mL, (1,073.36±896.01) pg/mL. Concentration of TGF-β in post-RT between Cpn IgG positive and negative group had statistically significant difference (P < 0.05). Conclusion Cpn IgG positive in lung cancer patients influenced levels of IL-1β, SP-A, TGF-β during chest radiotherapy. This might aggravate radiation-induced pulmonary lesion

Activation of the P62-Keap1-NRF2 Pathway Protects against Ferroptosis in Radiation-Induced Lung Injury

Radiation-induced lung injury (RILI) is one of the most common, serious, and dose-limiting toxicities of thoracic radiotherapy. A primary cause for this is the radiation-induced cell death. Ferroptosis is a recently recognized form of regulated cell death, characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). The ROS generated by irradiation might be the original trigger of ferroptosis in RILI. In addition, activation of the P62-Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (NRF2) pathway has been shown to blunt ferroptosis and thus acts as a protective factor. Therefore, this study aimed to explore the protective effect of the P62-Keap1-NRF2 pathway against radiation-induced ferroptosis in alveolar epithelial cells. First, we found that radiation induced ferroptosis in vitro using a RILI cell model, which could be significantly reduced by ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor. Additionally, overexpression of P62 interacted with Keap1 to facilitate the translocation of NRF2 into the nucleus and promote the expression of its target proteins, including quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO1), and ferritin heavy chain 1 (FTH1). In summary, our results demonstrated that the activation of the P62-Keap1-NRF2 pathway prevents radiation-induced ferroptosis in RILI cells, providing a theoretical basis of finding a potential therapeutic approach for RILI

Genome-wide analyses of lung cancer after single high-dose radiation at five time points (2, 6, 12, 24, and 48 h)

Background: An increasing number of clinicians are experimenting with high-dose radiation. This study focuses on the genomic effects of high-dose single-shot radiotherapy and aims to provide a dynamic map for non-small cell lung cancer (NSCLC).Methods: We used whole-transcriptome sequencing to understand the evolution at molecular levels in A549 and H1299 exposed to 10 Gy X-rays at different times (2, 6, 12, 24, and 48 h) in comparison with the no radiation group. Ingenuity pathway analysis, ceRNA analysis, enrichment analysis, and cell cycle experiments are performed for molecular analyses and function analyses.Results: Whole-transcriptome sequencing of NSCLC showed a significant dynamic change after radiotherapy within 48 h. MiR-219-1-3p and miR-221-3p, miR-503-5p, hsa-miR-455-5p, hsa-miR-29-3p, and hsa-miR-339-5p were in the core of the ceRNA related to time change. GO and KEGG analyses of the top 30 mRNA included DNA repair, autophagy, apoptosis, and ferroptosis pathways. Regulation of the cell cycle-related transcription factor E2F1 might have a key role in the early stage of radiotherapy (2.6 h) and in the later stage of autophagy (24 and 48 h). Functions involving different genes/proteins over multiple periods implied a dose of 10 Gy was related to the kidney and liver pathway. Radiation-induced cell cycle arrest at the G2/M phase was evident at 24 h. We also observed the increased expression of CCNB1 at 24 h in PCR and WB experiments.Conclusion: Our transcriptomic and experimental analyses showed a dynamic change after radiation therapy in 48 h and highlighted the key molecules and pathways in NSCLC after high-dose single-shot radiotherapy

Luteolin sensitizes the antitumor effect of cisplatin in drug-resistant ovarian cancer via induction of apoptosis and inhibition of cell migration and invasion

Abstract Luteolin, a polyphenolic flavone, has been demonstrated to exert anti-tumor activity in various cancer types. Cisplatin drug resistance is a major obstacle in the management of ovarian cancer. In the present study, we investigated the chemo-sensitizing effect of luteolin in both cisplatin-resistant ovarian cancer cell line and a mice xenotransplant model. In vitro, CCK-8 assay showed that luteolin inhibited cell proliferation in a dose-dependent manner, and luteolin enhanced anti-proliferation effect of cisplatin on cisplatin-resistant ovarian cancer CAOV3/DDP cells. Flow cytometry revealed that luteolin enhanced cell apoptosis in combination with cisplatin. Western blotting and qRT-PCR assay revealed that luteolin increased cisplatin-induced downregulation of Bcl-2 expression. In addition, wound-healing assay and Matrigel invasion assay showed that luteolin and cisplatin synergistically inhibited migration and invasion of CAOV3/DDP cells. Moreover, in vivo, luteolin enhanced cisplatin-induced reduction of tumor growth as well as induction of apoptosis. We suggest that luteolin in combination with cisplatin could potentially be used as a new regimen for the treatment of ovarian cancer

Effects of CpG oligodeoxynucleotide 1826 on acute radiation-induced lung injury in mice

BACKGROUND: The radiation-induced lung injury is a common complication from radiotherapy in lung cancer. CpG ODN is TLR9 activator with potential immune modulatory effects and sensitization of radiotherapy in lung cancer. This study aimed to examine the effect of CpG ODN on acute radiation-induced lung injury in mice. METHODS AND RESULTS: The mouse model of radiation-induced lung injury was established by a single dose of 20 Gy X-rays exposure to the left lung. The results showed that the pneumonia score was lower in RT+CpG group than in RT group on 15th and 30th days. Compared with RT group, CpG ODN reduced the serum concentrations of MDA (P < 0.05) and increased the serum concentrations of SOD, GSH (P < 0.05). The serum concentration of TNF-α in RT+CpG group was lower on 15th and 30th days post-irradiation (P < 0.05). CONCLUSION: The study demonstrated that CpG ODN has preventive effects of acute radiation-induced lung injury in mice. Lung inflammatory reaction and oxidative stress are promoted in the initiation of radiation-induced pneumonia. CpG ODN may reduce the injury of reactive oxygen species and adjust the serum TNF-α concentration in the mice after irradiation, which reduces the generation of the inflammatory cytokines

Clinical practice of precision medicine in lymphoma

Background Lymphoma is the most common malignancy in blood system. There are still unmet treatment needs in Hodgkin's and non‐Hodgkin's lymphoma. Materials & Methods We searched reviews and clinical trials on genetic medicine of lymphoma in Pubmed, the prevelance of lymphoma in Pubmed as well as SEER. Results Genetic analysis helps the practice in lymphoma. For some molecules have become diagnostic markers in some subtypes of lymphoma. Some genetic disorder could forecast the prognosis. Besides, new target drug could be chosen as individual treatment according to the genetic changes in lymphoma cells. Conclusion Precision medicine has shown promising future in the field of lymphoma

Image_8_Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient.tif

BackgroundWhole-cell tumor vaccines tend to suffer from low immunogenicity. Our previous study showed that irradiated lung cancer cell vaccines in mouse models enhance antitumor efficacy by eliciting an intensive T cells response and improving immunogenicity. Based on these findings, we developed an improved whole-cell tumor vaccine, Autologous Tumor Holo antigEn immuNe Activation (ATHENA).MethodsIn this study, we report the successful treatment of a 6-year-old male diagnosed with meningeal rhabdomyosarcoma with pulmonary and liver metastases using ATHENA. After 6 cycles of therapy, PET/CT showed the therapeutic efficacy of ATHENA. We profiled the immune response by single-cell RNA sequencing (scRNA-seq). Flow cytometry analysis was implemented to validate the status transitions of CD8+ T cells.ResultsIn CD8+ T cells, the exhausted status was weakened after treatment. The exhausted CD4+ T cells shifted towards the central memory phenotype after the treatment. Breg cells were converted to Plasma or Follicular B cells. Survival analysis for pan-cancer and transcription factor analysis indicated that such T cell and B cell transitions represent the recovery of antitumoral adaptive immune response. We validated that the proportion of CD279+CD8+ T cells were reduced and the expression of CD44 molecule was upregulated by flow cytometry assay.ConclusionSuch studies not only show that ATHENA therapy may be a promising alternative treatment for tumor patients but provide a novel idea to analyses the mechanisms of rare cases or personalized cancer treatment.</p

Image_4_Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient.tif

BackgroundWhole-cell tumor vaccines tend to suffer from low immunogenicity. Our previous study showed that irradiated lung cancer cell vaccines in mouse models enhance antitumor efficacy by eliciting an intensive T cells response and improving immunogenicity. Based on these findings, we developed an improved whole-cell tumor vaccine, Autologous Tumor Holo antigEn immuNe Activation (ATHENA).MethodsIn this study, we report the successful treatment of a 6-year-old male diagnosed with meningeal rhabdomyosarcoma with pulmonary and liver metastases using ATHENA. After 6 cycles of therapy, PET/CT showed the therapeutic efficacy of ATHENA. We profiled the immune response by single-cell RNA sequencing (scRNA-seq). Flow cytometry analysis was implemented to validate the status transitions of CD8+ T cells.ResultsIn CD8+ T cells, the exhausted status was weakened after treatment. The exhausted CD4+ T cells shifted towards the central memory phenotype after the treatment. Breg cells were converted to Plasma or Follicular B cells. Survival analysis for pan-cancer and transcription factor analysis indicated that such T cell and B cell transitions represent the recovery of antitumoral adaptive immune response. We validated that the proportion of CD279+CD8+ T cells were reduced and the expression of CD44 molecule was upregulated by flow cytometry assay.ConclusionSuch studies not only show that ATHENA therapy may be a promising alternative treatment for tumor patients but provide a novel idea to analyses the mechanisms of rare cases or personalized cancer treatment.</p

Image_2_Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient.tif

BackgroundWhole-cell tumor vaccines tend to suffer from low immunogenicity. Our previous study showed that irradiated lung cancer cell vaccines in mouse models enhance antitumor efficacy by eliciting an intensive T cells response and improving immunogenicity. Based on these findings, we developed an improved whole-cell tumor vaccine, Autologous Tumor Holo antigEn immuNe Activation (ATHENA).MethodsIn this study, we report the successful treatment of a 6-year-old male diagnosed with meningeal rhabdomyosarcoma with pulmonary and liver metastases using ATHENA. After 6 cycles of therapy, PET/CT showed the therapeutic efficacy of ATHENA. We profiled the immune response by single-cell RNA sequencing (scRNA-seq). Flow cytometry analysis was implemented to validate the status transitions of CD8+ T cells.ResultsIn CD8+ T cells, the exhausted status was weakened after treatment. The exhausted CD4+ T cells shifted towards the central memory phenotype after the treatment. Breg cells were converted to Plasma or Follicular B cells. Survival analysis for pan-cancer and transcription factor analysis indicated that such T cell and B cell transitions represent the recovery of antitumoral adaptive immune response. We validated that the proportion of CD279+CD8+ T cells were reduced and the expression of CD44 molecule was upregulated by flow cytometry assay.ConclusionSuch studies not only show that ATHENA therapy may be a promising alternative treatment for tumor patients but provide a novel idea to analyses the mechanisms of rare cases or personalized cancer treatment.</p