Application of organoids in precision immunotherapy of lung cancer (Review).

In immunotherapy, the immune system is modulated in order to treat cancer. Traditional two dimensional in vitro models and in vivo animal models are insufficient to simulate the complex tumor microenvironment (TME) in the original tumor. As tumor immunotherapy involves the immune system, additional tumor mimic models, such as patient-derived organoids, are required for the evaluation of the efficacy of immunotherapy. Furthermore, non-tumor components and host tumor cells in the TME may interact to promote cancer incidence, progression, drug resistance and metastasis. It is possible to produce organoid models for lung cancer by retaining endogenous stromal components (e.g., multiple immune cell types), supplying cancer-associated fibroblasts and exogenous immune cells, constructing tumor vasculature and adding other biological or chemical components that emulate the TME. Therefore, the lung cancer organoid culture platform may facilitate preclinical testing of immunotherapy drugs for lung cancer by mimicking immunotherapy responses. The present review summarizes current lung cancer organoid culture methods for TME modeling and discusses the use of lung cancer-derived organoids for the detection of lung cancer immunotherapy and individualized cancer immunotherapy.

Developing a Core Outcome Set for Assessing Clinical Safety Outcomes of Prostate Cancer in Clinical Trials of Traditional Chinese Medicine: Protocol for a Mixed Methods Study.

BACKGROUND: Among the common malignant tumors in men worldwide, the incidence of prostate cancer ranks second to lung cancer. This disease will bring an economic burden to patients and their families and can reduce the quality of life of patients. Researchers have conducted numerous clinical trials on the efficacy and safety of different interventions in the treatment of prostate cancer with traditional Chinese medicine (TCM) combined with standard treatment regimens. However, the currently published clinical trials exhibit inconsistent and irregular reporting of outcome measures. OBJECTIVE: The objective of this paper is to emphasize the need for a core outcome set (COS) to facilitate future prostate cancer research, aiming to improve the quality of trials and generate high-quality evidence. METHODS: This mixed methods project has three phases, as follows: (1) a scoping review of the literature to identify outcomes that have been reported in clinical trials and systematic reviews of interventions involving TCM for the treatment of prostate cancer as well as a qualitative component using interviews to obtain the views of patients with prostate cancer, their families, and their caregivers who have a history of TCM treatment; (2) a Delphi survey among stakeholders to prioritize the core outcomes-Participants will include traditional Chinese and Western medicine clinicians in prostate cancer-related directions, nurses, and methodology experts who will participate in 2 rounds of the Delphi method expert consultation to score each outcome in the list of outcome indicators; and (3) a face-to-face consensus meeting to discuss and agree on the final COS for the application of TCM in the treatment of prostate cancer. RESULTS: The protocol has been registered in PROSPERO (CRD42022356184) before the start of the review process, and we will initiate the review on August 1, 2023; results should be expected by September 1, 2023. The Delphi survey among stakeholders is expected to start in October 2023. CONCLUSIONS: The development of a core outcome set for assessing clinical safety outcomes of prostate cancer in clinical trials of TCM will provide a significant first step to assist Chinese doctors, researchers, and policy makers. TRIAL REGISTRATION: PROSPERO CRD42022356184; https://tinyurl.com/ysakz74r. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46794.

Inflammatory bowel disease and prostate cancer risk: a two-sample Mendelian randomization analysis.

Background: Previous epidemiological observational studies have reported an association between inflammatory bowel disease (IBD) and prostate cancer (PCa), but the causality is inconclusive. The purpose of this study was to evaluate the causality of IBD on PCa using the mendelian randomization (MR) analysis. Methods: We performed a two-sample MR analysis with public genome-wide association studies (GWAS) data. Eligible instrumental variables (IVs) were selected according to the three assumptions of MR analysis. The inverse-variance weighted (IVW) method was the main method. Complementary methods included the MR-Egger regression, the Weighted Median, the Simple Mode, the Weighted Mode and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Results: Genetically determined IBD did not have a causal effect on PCa (IVW P > 0.05). Additionally, there was no causal effect of Crohn's disease (CD) and ulcerative colitis (UC) on PCa in the MR analysis (IVW P > 0.05). Results of complementary methods were consistent with those of the IVW method. Conclusions: This study does not support a causal association of IBD on PCa, which is in contrast to most observational studies.

RGN as a prognostic biomarker with immune infiltration and ceRNA in lung squamous cell carcinoma.

Regucalcin (RGN) is a potent inhibitory protein of calcium signaling and expresses in various tissues. However, the role of RGN in the tumor immunological microenvironment in lung squamous cell carcinoma (LUSC) remains unclear. This study identified the expression of RGN from public databases and immunohistochemistry with clinical specimen. The association between RGN and the tumor immune microenvironment (TIME) was investigated in LUSC by ESTIMATE and CIBERSORT algorithms. Similarly, the Tumor IMmune Estimation Resource (TIMER) database was used to identify the correlation between RGN and immune cells. The ceRNA network was established based on the data obtained from public databases. Finally, prediction of drug response to chemotherapy and immunotherapy was performed to evaluate clinical significance. This study found that RGN expression was significantly downregulated in tumor tissues and closely related to clinical factors and prognosis of LUSC patients. Differentially expressed genes (DEGs) grouped by the expression of RGN were mostly involved in immunobiological processes such as humoral immune response and leukocyte mediated immunity. RGN and its related miRNA (has-miR-203a-3p) and lncRNAs (ZNF876P and PSMG3-AS1) constructed the novel prognosis-related ceRNA network. Plasma cells, T cells CD4 memory resting, Macrophages M0, Macrophages M1, Mast cells resting, Mast cells activated and Neutrophils showed significantly different levels of infiltration between high and low RGN expression groups. The TIMER database showed that RGN expression was positively correlated with certain immune infiltrating cells. High RGN expression group showed a higher TIDE score, a higher dysfunction score and a lower MSI score, presenting a possible lower efficacy after accepting the immunotherapy than low RGN expression group. RGN expression was closely associated with prognosis of LUSC patients and played an important role in tumor microenvironment. This suggests that RGN could be a promising biomarker for assessing immunotherapy efficacy and prognosis.

EpCAM as a Novel Biomarker for Survivals in Prostate Cancer Patients.

Background: Due to the insufficient understanding of the biological mechanisms, the improvement of therapeutic effects of prostate cancer (PCa) is limited. There is an urgent need to find the molecular mechanisms and underlying PCa to improve its early diagnosis, treatment, and prognosis. Methods: The mRNA expression profiles, survival and methylation data of PRAD were downloaded from The Cancer Genome Atlas (TCGA) database. The identification of differentially expressed genes (DEGs), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed by R software. Subsequently, we identified the key gene and validated its prognostic role from the Human Protein Atlas (HPA) database, UALCAN and the LinkedOmics database. We performd correlation analysis and constructed the ceRNA network based on the data obtained from miRbase and starBase. Finally, we performed methylation analysis and evaluated the immune cell infiltration by Tumor Immune Estimation Resource (TIMER). Results: A total of 567 DEGs were identified in PCa. ARHGEF38, SLPI, EpCAM, C1QTNF1, and HBB were regarded as target genes related to favorable overall survival (OS). Among them, EpCAM was considered as the most significant gene through the HPA database and receiver operating characteristic (ROC) analysis. A prognostic ceRNA network was constructed with EBLN3P, miR-204-5p, and EpCAM. EpCAM was found to be related to DNA methylation and tumor-infiltrating immune cells. Conclusion: Our findings provide novel insights into the tumorigenesis mechanism of PCa and contribute to the development of EpCAM as a potential prognostic biomarker in PCa.

Hispidulin inhibits proliferation, migration, and invasion by promoting autophagy via regulation of PPARγ activation in prostate cancer cells and xenograft models.

Prostate cancer (PCa) is one of the important factors of cancer deaths especially in the western countries. Hispidulin (4',5,7-trihydroxy-6-methoxyflavone) is a phenolic flavonoid compound proved to possess anticancer properties, but its effects on PCa are left to be released. The aims of this study were to investigate the effects and the relative mechanisms of Hispidulin on PCa development. Hispidulin administration inhibited proliferation, invasion, and migration, while accelerated apoptosis in Du145 and VCaP cells, which was accompanied by PPARγ activation and autophagy enhancement. The beneficial effects of Hispidulin could be diminished by PPARγ inhibition. Besides, Hispidulin administration suppressed PCa tumorigenicity in Xenograft models, indicating the anticancer properties in vivo. Therefore, our work revealed that the anticancer properties of Hispidulin might be conferred by its activation on PPARγ and autophagy.

Is COVID-19 a high risk factor for lung cancer?: A protocol for systematic review and meta-analysis.

INTRODUCTION: COVID-19 has become a common threat to global human health and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Some asymptomatic patients with early-stage lung cancer who have COVID-19 receive surgical treatment but develop severe pneumonia and other complications or even experience postoperative death, and they may have a worse prognosis compared with healthy individuals infected with COVID-19. However, there is no evidence that COVID-19 is a risk factor for lung cancer patients. This systematic review aims to evaluate the incidence and prognosis of COVID-19 in lung cancer patients and provide evidence-based medical support for clinical treatment. METHODS: We will search 6 medical databases to identify eligible studies published from the establishment of the database to the present. The quality of the included literature will be evaluated using the bias risk assessment tool in Cochrane 5.1.0, and a meta-analysis will be performed using Stata 14.0. Heterogeneity will be statistically assessed using χ2 tests. RESULTS: The study will integrate existing research findings to investigate the prevalence and severity rate of patients with lung cancer infected with SARS-CoV-2 and analyze the prognosis and adverse clinical outcomes in patients with or without COVID-19. CONCLUSION: The results of this study provide evidence to support whether COVID-19 is a risk factor for lung cancer and provide guidance for clinical prevention and treatment based on the evidence obtained in light of the unpredictable threat posed by COVID-19. ETHICS AND DISSEMINATION: Ethics approval is not required for this systematic review as it will involve the collection and analysis of secondary data. The results of the review will be reported in international peer-reviewed journals. PRORPERO REGISTRATION NUMBER: CRD42020195967.

Prostate cancer: a risk factor for COVID-19 in males?: A protocol for systematic review and meta analysis.

INTRODUCTION: COVID-19 is now a global pandemic. Although there are very few studies describing the characteristics of SARS-CoV-2 infections in patients with prostate cancer, these patients are likely to be more susceptible to COVID-19 than healthy people because of their immunosuppressed state. However, there is no evidence that prostate cancer is a risk factor for COVID-19. METHODS: We searched the Wanfang database, the China Science Journal Citation Report (VIP database), the China National Knowledge Infrastructure (CNKI), Web of Science, EMBASE, PubMed, and the Cochrane Library for studies related to the topic. We designed a standardized data extraction sheet and used Epidata software 3.1 for data extraction. In accordance with the Cochrane 5.1.0 standard, both a quality assessment and a risk assessment were carried out for the research meeting the inclusion criteria. The data were analyzed using Revman 5.3 and Stata 13.0 software. RESULTS: The study integrated existing research findings and a meta-analysis of the data to investigate the prevalence of prostate cancer in males infected with SARS-CoV-2 and the adverse clinical outcomes in male patients with or without COVID-19. CONCLUSION: The results of this research may provide a basis for judging if prostate cancer is a risk factor for males infected with SARS-CoV-2, and the findings can effectively help to prevent COVID-19 in patients with prostate cancer. ETHICS AND DISSEMINATION: Ethics approval is not required for this systematic review as it will involve the collection and analysis of secondary data. The results of the review will be reported in international peer-reviewed journals PRORPERO REGISTRATION NUMBER:: CRD42020194071.

Anticancer effects of curcumin on nude mice bearing lung cancer A549 cell subsets SP and NSP cells.

Curcumin is a key polyphenolic curcuminoid extracted from the root of turmeric rhizome Curcuma longa Linn, which is a frequently used Chinese herb for the treatment of cancer. The aim of the present study was to investigate the mechanism of the inhibitory effects of curcumin on nude mice with lung cancer A549 cell subsets side population (SP) and non-SP (NSP) cells. BALB/c mice were subcutaneously injected with the tumor cells of A549 SP or NSP subsets consisting of 1×109 cells/l (0.2 ml in total). After 16 days of inoculation with A549, the mice were intraperitoneally injected with curcumin (100 mg/kg, 0.2 ml) once every other day, eight times in total. A series of assays were performed to detect the effects of curcumin on: i) Tumor weight and size; ii) Notch and hypoxia inducible factor 1 (HIF-1) mRNA expression by quantitative polymerase chain reaction; and iii) vascular endothelial growth factor (VEGF) and nuclear factor-κB (NF-κB) by immunohistochemistry. It was determined that curcumin decreased the tumor weight and size, downregulated the expression of Notch and HIF-1 mRNA and suppressed the VEGF and NF-κB expression. These results indicated that curcumin inhibited lung cancer growth through the regulation of angiogenesis mediated by VEGF signaling.

[Laboratory techniques for the diagnosis of prostate cancer: An update].

The prevalence of prostate cancer is increasing, which is one of the leading causes of malignancy-associated deaths of males. Because the early symptoms of prostate cancer are not obvious, 20% of the patients have metastasis at the time of initial diagnosis. The low rate of early diagnosis of prostate cancer has contributed to a higher mortality rate in China than in Europe and the United States. Highly specific and sensitive diagnostic markers exist in the blood, urine and semen of prostate cancer patients. Combined laboratory techniques can improve the rate of the early diagnosis of prostate cancer, help early treatment, and prolong the survival of the patients.