Cancer associates with risk and severe events of COVID-19: A systematic review and meta-analysis.

Evidence is mounting to indicate that cancer patients may have more likelihood of having coronavirus disease 2019 (COVID-19) but lack consistency. A robust estimate is urgently needed to convey appropriate information to the society and the public, in the time of ongoing COVID-19 pandemic. We performed a systematic review and meta-analysis through a comprehensive literature search in major databases in English and Chinese, and two investigators conducted publication selection and data extraction independently. A meta-analysis was used to obtain estimates of pooled prevalence of cancer in patients with COVID-19 and determine the association of cancer with severe events, after assessment of potential heterogeneity, publication bias, and correction for the estimates when necessary. Total 38 studies comprising 7094 patients with COVID-9 were included; the pooled prevalence of cancer was estimated at 2.3% (95% confidence limit [CL] [0.018, 0.029]; P < .001) overall and 3.2% (95% CL [0.023, 0.041]; P < .001) in Hubei province; the corresponding estimates were 1.4% and 1.9% after correction for publication bias; cancer was significantly associated with the events of severe cases (odds ratio [OR] = 2.20, 95% CL [1.53, 3.17]; P < .001) and death (OR = 2.97, 95% CL [1.48, 5.96]; P = .002) in patients with COVID-19, there was no significant heterogeneity and a minimal publication bias. We conclude that cancer comorbidity is associated with the risk and severe events of COVID-19; special measures should be taken for individuals with cancer.

Inhibition of Triple-Negative Breast Cancer Tumor Growth by Electroacupuncture with Encircled Needling and Its Mechanisms in a Mice Xenograft Model.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer without effective targeted drugs. While breast cancer patients often use acupuncture for the relief of cancer-induced pain or the side effects of chemo- or radiation therapy, little information is known regarding the direct effects of electroacupuncture on TNBC tumor and its potential mechanisms. Here, we created a mice model of TNBC and electroacupuncture with encircled needling around the tumors was given to the animals daily for 3 weeks at 15-20 Hz (3 min, each time). For sham electroacupuncture control, the skin was punctured to a depth of 5 mm and then the needle was quickly withdrawn without electrical stimulation or manual needle manipulation. We found that electroacupuncture significantly inhibited TNBC tumor growth and the inhibitory rate increased gradually overtime. Mechanistic analysis showed that electroacupuncture inhibited tumor angiogenesis by reducing the expression of vascular endothelial growth factor A (VEGF-A), its receptor VEGF-R and neuropilin 1 (NRP-1). Electroacupuncture also led to a significant decrease of matrix metalloproteinase-2 (MMP-2) expression and an increase of tissue inhibitor of MMP (TIMP-2) expression. Additionally, the expression of semaphorin 3A (Sema3A) and nerve growth factor receptor (NGFR) p75 in TNBC tissue was significantly upregulated in response to electroacupuncture. Furthermore, tumor necrosis factor (TNF)-alpha level in the serum was dramatically reduced after electroacupuncture. These results showed that electroacupuncture could directly inhibit TNBC tumor growth through the inhibition of proteins related to tumor angiogenesis and extracellular matrix, the suppression of TNBC-induced inflammation and the upregulation of nerve growth factor receptors.

Enhancement of radiosensitivity of lung adenocarcinoma using a decoction from the Fuzhengzengxiao formula.

OBJECTIVE: To study the effects of a decoction of Fuzhengzengxiao formula on lung adenocarcinoma regarding the inflammatory protein S100A9 known to enhance cancer cell sensitivity. METHODS: A nude mouse model of human lung adenocarcinoma was established. The mice were randomly divided into four groups using the random number table method: Group I, control; Group II, treatment with a decoction of the Fuzhengzengxiao formula alone; Group III, treatment with radiotherapy alone; and Group IV, treatment with radiotherapy plus a decoction of Fuzhengzengxiao formula. When the tumor body was 1 cm3 in diameter, the tumor bearing mice in Groups III and IV were irradiated at a single dose of 10 Gy and the tumor inhibition rate was evaluated. The expression of S100A9 was determined using Western blotting and q-PCR (Real-time Quantitative PCR Detecting System). The sensitivity of cells containing RNAi S100A9 to radiotherapy was evaluated using the Click multiple target model,and the cell cycle was analyzed using flow cytometry. RESULTS: Relative to the control group, the expression of S100A9 in the tumors in each treatment group was decreased, especially in Group IV. The sensitizing enhancement ratio (SER) Dq was > 1 after RNAi S100A9; it decreased the surviving fraction after a 2 Gy dose exposure,and also the D0 and Dq of the tumor cells; in addition, the radiosensitivity of G2/M cells was significantly increased. CONCLUSION: The decoction of the Fuzhengzengxiao formula downregulated the expression of S100A9 in lung adenocarcinoma cells.

Electroacupuncture promotes apoptosis and inhibits axonogenesis by activating p75 neurotrophin receptor for triple-negative breast xenograft in mice.

PURPOSE: The aim of this study was to investigate the anti-tumor effect of electroacupuncture (EA) on mice bearing breast tumors by regulating p75 neurotrophin receptor (p75NTR) and remodelling intratumoral innervation. METHODS: Female BALB/c mice were implanted with 4T1 breast tumor cells to establish a murine mammary cancer model. Tumor volume and weight were measured to evaluate tumor growth. Cell apoptosis was assessed by TUNEL assay. The relative expression of p75NTR, TrkA, TrkB, NGF and proNGF were detected by immunohistochemistry. Neurotransmitter and neurotrophin were detected by enzyme-linked immunosorbent assay. Intratumoral innervation was confirmed by ß3-tubulin and TH labeling immunohistochemistry. The antagonist TAT-Pep5 was employed to determine if the effects of EA on tumor growth and cell apoptosis were mediated by p75NTR. RESULTS: Peritumoral EA alleviated tumor growth especially after 14 days of intervention. Apoptosis index in the tumor tissue was obviously decreased after EA. Meanwhile, EA intervention significantly upregulated the expression of p75NTR and proNGF, along with a decline in the tumor growth and an increase in the cell apoptosis. Besides, EA reduced local sympathetic innervation and downregulated sympathetic neurotransmitter NE level in the local tumor. Furthermore, p75NTR antagonist alleviated EA-mediated cell apoptosis and intratumoral innervation. CONCLUSIONS: One mechanism of EA intervention for alleviating tumor progression is mediated by p75NTR to promote apoptosis and decrease intratumoral axonogenesis in the tumor microenvironment.

Development and Validation of an Immune-Related Long Non-coding RNA Prognostic Model in Glioma.

Background: Long non-coding RNAs (lncRNAs) play an important role in the immune processes of glioma. Immune related lncRNAs (IRlncRs) may be a critical prognosis in patients with glioma. The current study aimed to construct a glioma immune-related prognosis model by IRlncRs. Methods: Transcriptome RNA-sequencing data of glioma were obtained from The Cancer Genome Atlas (TCGA) and an immune­related risk score (IRRS) model was constructed by Lasso and multivariate Cox regression analysis. Receiver Operating Characteristic (ROC) curves were used to assess the sensitivity and specificity of the prognosis on IRRS. A predictive nomogram and a time-dependent ROC curve was performed in training and validation cohort. We explored the relationships between survival­related IRlncRs (sIRlncRs) and clinicopathologic parameters. Functional annotation of the sIRlncRs was investigated by gene set enrichment analysis (GSEA) and principal component analysis (PCA). The relationships between IRRS model and immune cell infiltration and co-expression network analysis among the sIRlncRs were performed for molecular mechanism study. Results: A total of 10 sIRlncRs were enrolled to build IRRS model. The IRRS was identified as an independent prognostic factor and correlated with the overall survival (AUC =0.880). The nomogram was constructed successfully with IRRS, age and grade as variables. Immune cell infiltration analysis indicated that B cells, neutrophil, dendritic and macrophage cells were positively correlated with IRRS. PCA and GSEA illustrated that the lncRNA signature enrolled the IRRS model was closely related to immune status. Additionally, co-expression network showed that there was a strong correlation between 10 sIRlncRs at the transcriptional level. Conclusion: We successfully constructed a remarkable clinical model of sIRlncRs with potential prognostic value for glioma patients, which provides an insight into immunological research and treatment strategies of glioma.

[Discussion on registry study of acupuncture-moxibustion for malignant pleural effusion].

Malignant pleural effusion (MPE) is one of the common complications of tumor. Acupuncture-moxibustion therapy has several advantages for treatment of MPE. Acupuncture is regarded as a complex individualized intervention, and its characteristics of TCM is difficult to be reflected by strict randomized controlled trials. The registry study provides more possibilities for the data collection of individualized diagnosis and treatment under the guidance of the overall concept and syndrome differentiation, and is more suitable for data management and collection of large samples and multi-center trials in the real-world study. It has become an opportunity to carry out real-world study of acupuncture for MPE. There are many challenges in the registry study of acupuncture for MPE. However, it is of great significance to collect real-world data of acupuncture for MPE to improve the clinical effect of MPE and provide a new clinical research method for acupuncture in tumors and related complications.

RNA interference-mediated gene silencing of cyclophilin A enhances the radiosensitivity of PAa human lung adenocarcinoma cells in vitro.

Radiotherapy is currently the major therapeutic strategy for patients with lung cancer. However, radioresistance and various side effects continue to present challenging issues for this form of treatment. A recent study demonstrated that cyclophilin A (CyPA) was overexpressed in non-small cell lung cancer and, therefore, presents a novel potential therapeutic target. In addition, gene-radiotherapy is a novel method for cancer treatment. Therefore, the objective of the present study was to investigate the potential effect of CyPA silencing on radiosensitivity in human lung adenocarcinoma in vitro. The stable CyPA-silencing lung adenocarcinoma (PAa) cell line was generated using lentivirus-mediated small hairpin RNAs. The knockdown of CyPA was determined using fluorescent microscopy and western blot analysis. Cells were irradiated using various doses of cobalt-60 (0, 2, 4, 6 and 8 Gy). The radiosensitizing effects were determined by a clonogenic survival assay. Apoptosis and cell cycle distribution were evaluated using flow cytometry. Silencing of CyPA significantly increased the apoptosis of PAa cells. In addition, the radiosensitivity of cells was markedly enhanced following CyPA silencing. Furthermore, silencing of CyPA, in combination with irradiation, induced G2/M phase cell cycle arrest. Taken together, the data suggest that the silencing of CyPA, combined with radiation therapy, may increase the therapeutic efficacy of lung cancer treatment through regulation of the cell cycle and apoptosis-associated signaling pathways.