Primary Pulmonary Meningioma With Associated Multiple Micronodules: A Case Report With Comprehensive Diagnostic Overview.

BACKGROUND: Primary pulmonary meningioma (PPM) is an exceedingly rare neoplasm originating in the meninges within the lung. Despite sharing similarities with its central nervous system (CNS) counterparts, PPM presents unique diagnostic challenges and therapeutic considerations owing to its infrequent occurrence. CASE: This case report describes a 73-year-old male who underwent chest computed tomography (CT), which revealed a mass in the posterior basal segment of the right lower lobe, suggestive of a low-grade malignant tumor approximately 30-40 mm in size. Single-port video-assisted thoracoscopic surgery (VATS) was performed to resect the mass via localized lesion excision (lung wedge resection). Intraoperative frozen section pathology indicated a low-grade malignant epithelial tumor, leading to a decision for maximal lung function preservation, considering the patient's advanced age. The surgical team opted for a localized excision to ensure negative margins. Histopathological analysis confirmed the diagnosis of epithelioid PPM, a rare subtype even among PPM cases (World Health Organization [WHO] Grade I). The patient was discharged 9 days after surgery without complications and resumed normal daily activities 1 month postoperatively. The rarity of PPM precludes a standardized treatment protocol, with surgical resection as the primary approach. However, the efficacy of adjunctive therapies remains uncertain due to limited evidence. CONCLUSION: This case report contributes to a better understanding of PPM and emphasizes the importance of a comprehensive diagnostic evaluation and individualized treatment planning for this rare entity.

The interaction between DNA methylation and tumor immune microenvironment: from the laboratory to clinical applications.

DNA methylation is a pivotal epigenetic modification that affects gene expression. Tumor immune microenvironment (TIME) comprises diverse immune cells and stromal components, creating a complex landscape that can either promote or inhibit tumor progression. In the TIME, DNA methylation has been shown to play a critical role in influencing immune cell function and tumor immune evasion. DNA methylation regulates immune cell differentiation, immune responses, and TIME composition Targeting DNA methylation in TIME offers various potential avenues for enhancing immune cytotoxicity and reducing immunosuppression. Recent studies have demonstrated that modification of DNA methylation patterns can promote immune cell infiltration and function. However, challenges persist in understanding the precise mechanisms underlying DNA methylation in the TIME, developing selective epigenetic therapies, and effectively integrating these therapies with other antitumor strategies. In conclusion, DNA methylation of both tumor cells and immune cells interacts with the TIME, and thus affects clinical efficacy. The regulation of DNA methylation within the TIME holds significant promise for the advancement of tumor immunotherapy. Addressing these challenges is crucial for harnessing the full potential of epigenetic interventions to enhance antitumor immune responses and improve patient outcomes.

CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma.

As a high metastatic tumor, patients having hepatocellular carcinoma (HCC) show poor prognosis. The carcinogenic roles of circMMP11 are generally described in the development of other cancers. However, there is a lack of studies on its involvement in HCC. Therefore, we investigated the potential role and molecular mechanisms of CircMMP11 in the development of HCC in vitro, providing preliminary evidence for the clinical treatment of HCC. First, we examined the expression of CircMMP11 in HCC tissues and cell lines in both clinical and in vitro experiments. We then used a loss-of-function assay to determine CircMMP11's regulatory role on the malignant characteristics of HCC cells. The results showed that high expression of CircMMP11 in HCC was associated with patient overall survival. Serum CircMMP11 had good diagnostic efficacy in distinguishing HCC patients from the control group. In vitro, inhibiting CircMMP11 suppressed the malignant characteristics of human HCC cell lines by directly sequestering miR-361-3p, which further affected the downstream gene HMGB1 expression. In addition, we knocked down CircMMP11 and found that its deletion inhibited the malignant characteristics of HCC cells through the miR-361-3p/HMGB1 axis.

Identification of neoantigens and immunological subtypes in clear cell renal cell carcinoma for mRNA vaccine development and patient selection.

Clear cell renal cell carcinoma (ccRCC) is a common urological malignancy with diverse histological types. This study aimed to detect neoantigens in ccRCC to develop mRNA vaccines and distinguish between ccRCC immunological subtypes for construction of an immune landscape to select patients suitable for vaccination. Using The Cancer Genome Atlas SpliceSeq database, The Cancer Genome Atlas, and the International Cancer Genome Consortium cohorts, we comprehensively analysed potential tumour antigens of ccRCC associated with aberrant alternative splicing, somatic mutation, nonsense-mediated mRNA decay factors, antigen-presenting cells, and overall survival. Immune subtypes (C1/C2) and nine immune gene modules of ccRCC were identified by consistency clustering and weighted correlation network analysis. The immune landscape as well as molecular and cellular characteristics of immunotypes were assessed. Rho-guanine nucleotide exchange factor 3 (ARHGEF3) was identified as a new ccRCC antigen for development of an mRNA vaccine. A higher tumour mutation burden, differential expression of immune checkpoints, and immunogenic cell death were observed in cases with the C2 immunotype. Cellular characteristics increased the complexity of the immune environment, and worse outcomes were observed in ccRCC cases with the C2 immunotype. We constructed the immune landscape for selecting patients with the C2 immunotype suitable for vaccination.

Effect of Shengmai Yin on Epithelial-Mesenchymal Transition of Nasopharyngeal Carcinoma Radioresistant Cells.

OBJECTIVE: To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R. METHODS: Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label. RESULTS: The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results. CONCLUSIONS: SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.

Lactate: A regulator of immune microenvironment and a clinical prognosis indicator in colorectal cancer.

Lactate can play an immunosuppressive role in the tumor microenvironment and promote tumor development by recruiting and inducing the activity of immunosuppressive cells and molecules. High lactate concentrations are important for tumor cell metastasis, angiogenesis, and treatment resistance. With the in-depth studies on tumor metabolism, lactate, one of the key factors involved in glycolysis, has been increasing emerged its characteristic clinical value in colorectal cancer (CRC). In this study, lactate genes were screened based on lactate metabolism pathways. Subsequently, the lactate subtypes were determined by clustering and analysis of the subtypes at all levels, including immune checkpoints, immune infiltration, and clinical characteristics, which revealed the biological significance of lactate metabolism in CRC. Subtype-based differential gene analysis resulted in a lactate score, which stratifies the prognosis of CRC. We discovered that 27 lactate genes and 61 lactate-phenotype genes are associated with immune cell infiltration and have a significant prognostic efficacy. The CRC patients were clustered into four subtypes and five clusters, based on lactate genes and lactate-phenotype genes, respectively. There are significant differences in survival time and activities of hallmark pathways, namely immune-related signatures and chemokines, among these subtypes and clusters. Particularly, cluster 2 and subtype 1 have significantly higher lactate scores than that of the others. In conclusion, lactate score is an independent prognostic factor for cancer that can be used as a clinical guide for predicting CRC progression and as an evaluation factor for the effect of immunotherapy in CRC.

Traditional Chinese Medicine: A Class of Potentially Reliable Epigenetic Drugs.

Epigenetic modification, especially DNA methylation, plays a nonnegligible role in the occurrence and development of tumors. Increasing studies are indicating that traditional Chinese medicine (TCM) plays a considerable anti-tumor role by regulating the process of DNA methylation modification. Studies on TCM regulating DNA methylation modification mostly focus on the whole genome and abnormal methylation status by active ingredients or single compounds and Chinese herb formula (CHF). The balance and overall concept of TCM theory coincides with the balance of DNA methylation modification in the tumor environment. Regardless of how TCM modulates epigenetics in tumor, it has been shown to bet a class of potentially reliable epigenetic drug.

Effect of GADD45G on the radioresistance of nasopharyngeal carcinoma cells.

The development of radioresistance by nasopharyngeal carcinoma (NPC) cells almost always results in tumor recurrence and metastasis, making clinical treatment of the disease difficult. In this study, the mechanism of radioresistance in NPC cells was investigated. First, a gene array and quantitative reverse-transcription-PCR assays were used to screen for genes exhibiting significantly altered expression in the DNA damage signaling pathway. Based on those results, GADD45G was further studied in the context of radioresistance. A GADD45G-knockout NPC cell line (CNE-2R-KO) was constructed using CRISPR-Cas9 technology and used for a comparison of differences in radioresistance with other radiosensitive and radioresistant NPC cells, as evaluated using colony formation assays. Cell cycle changes were observed using flow cytometry. Cell proliferation and migration were measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and wound healing assays, respectively. The sequencing results revealed the successful construction of the CNE-2R-KO cell line, the radiosensitivity of which was higher than that of its parent radioresistant cell line owing to the GADD45G knockout. This was likely related to the increase in the number of cells in the G1 phase and decrease in those in the S1 phase as well as the increased cell proliferation rate and decreased migratory ability. GADD45G is associated with radioresistance in NPC cells and likely has a role in the occurrence and metastasis of NPC.

Chemical profiling of Houttuynia cordata Thunb. by UPLC-Q-TOF-MS and analysis of its antioxidant activity in C2C12 cells.

Houttuynia cordata Thunb. ("Yu-Xing-Cao"), a traditional Chinese medicinal herb, has long been used to treat various diseases. However, detailed information regarding the chemical constituents of H. cordata aqueous extract is lacking, and the molecular basis of its beneficial effects on muscle is unknown. To investigate these points, in this study, we used ultra-performance liquid chromatography coupled with quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) in positive and negative ion modes to profile and identify the major constituents of H. cordata water extract. A total of 63 peaks were identified based on mass and fragmentation characteristics, including 29 organic acids and their glycosides, 17 flavonoids, 7 volatiles, 4 pyrimidine and purine derivatives, 2 alkaloids, 2 amino acids, 1 isovanillin, and 1 coumarin. The total flavonoid and polyphenol contents of the extract were 4.77 and 139.15 mg/mL, respectively, by ultraviolet spectrophotometry. The cytoprotective activity of H. cordata aqueous extract was evaluated using C2C12 cells treated with tumor necrosis factor (TNF)-α to induce oxidative challenge. The TNF-α induced decrease in cell viability was reversed by treatment for 48 h with the extract; moreover, superoxide dismutase activity was increased while reactive oxygen species level was decreased. These results provide molecular-level evidence for the antioxidant effect of H. cordata extract and highlight its therapeutic potential for the treatment of muscle injury or diseases caused by oxidative stress.

Effect of Shengmai Yin on the DNA methylation status of nasopharyngeal carcinoma cell and its radioresistant strains.

Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radiotherapy in various cancers and helps achieve radiotherapy's clinical efficacy. In this study, we explored the interaction mechanism among SMY, DNA methylation, and nasopharyngeal carcinoma (NPC). We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R) using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation. SMY may restore its original DNA methylation status, and thus, enhance radiosensitivity. Furthermore, we confirmed that the differential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression. This downregulation of TNC inhibited NPC cell radiation resistance, migration, and invasion. Furthermore, we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention. DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.

Curcumin Enhances Radiosensitization of Nasopharyngeal Carcinoma via Mediating Regulation of Tumor Stem-like Cells by a CircRNA Network.

Circular RNAs (circRNAs) are involved in cancer development via inhibition of miRNAs, which are associated with differentiation, proliferation, migration, and carcinogenicity. Curcumin has antioxidant and anti-cancer properties, and it has also been used as a radiosensitizer. In this study, we explored the potential relationships among curcumin, circRNAs, and nasopharyngeal carcinoma (NPC). We compared the differences in circRNA levels in NPC cell lines after radiotherapy and after treatment with curcumin, using a high-throughput microarray. Further, a circRNA-miRNA-mRNA interaction network between radiation resistance NPC cell lines and tumor stem cells was constructed by applying bioinformatics. Finally, it was demonstrated by reverse transcription-quantitative polymerase chain reaction assay and wound healing assay that curcumin could enhance radiosensitization of NPC cell lines via mediating regulation of tumor stem-like cells by the "hsa_circRNA_102115"-"hsa-miR-335-3p"-"MAPK1" interaction network.

Curcumin enhances radiosensitization of nasopharyngeal carcinoma by regulating circRNA network.

Circular RNAs (circRNAs) are involved in the regulation of gene expression in different physiological and pathological processes. These macromolecules can act as microRNA (miRNA) sponges and play an important role as gene regulators throughout the circRNA-miRNA pathway. In this study, we established a radioresistance model with the nasopharyngeal carcinoma cell line CNE-2, and then analyzed the differences in the circRNAs between radioresistant and normal nasopharyngeal carcinoma cell lines using a high-throughput microarray. Tested circRNAs included 1042 upregulated and 1558 downregulated circRNAs. Relevant signaling pathways associated with the circRNAs and their target miRNAs were analyzed using bioinformatics analysis to determine the radioresistance of the differentially expressed circRNAs. Curcumin was used to treat irradiated cell lines, and changes in the circRNA before and after curcumin treatment were analyzed to investigate the radiosensitization effects of curcumin. The results showed that curcumin could regulate the circRNA-miRNA-messenger RNA network and inhibit the epidermal growth factor receptor (EGFR), signal transducers and activators of transcription 3 (STAT3), and growth factor receptor-bound protein 2 (GRB2) to achieve radiosensitization. Thus, circRNA acted as a miRNA sponge and regulated the expression of miRNA, thereby affecting EGFR, STAT3, and GRB2 expression and radiosensitization.

[Effects of Shengmai Jianghuang San on intestinal flora in nude mice with radio resistant cells of nasopharyngeal carcinoma].

Modern pharmacological studies have shown that Shengmai San has the effects of enhancing immunity and improving blood circulation, and Curcumae Longae Rhizoma(Jianghuang) has anti-inflammatory, anti-cancer, anti-oxidation and other functions. Shengmai San combined with Jianghuang is a new research direction in the study of anti-tumor of traditional Chinese medicines. The main treatment for nasopharyngeal carcinoma is radiation therapy, but radiation therapy can cause a variety of side effects, and it also changes the composition of the intestinal flora. In this study, the 16 s rDNA sequencing platform was used to perform macro-sequence sequencing of the intestinal flora samples of nude mice bearing the veins of Shengmai Jianghuang San, and then the results of intestinal flora data were analyzed to investigate the effect of Shengmai Jianghuang San on tumors. The results showed that Shengmai Jianghuang San combined with irradiation could enhance the therapeutic effect of tumor treatment. Radiation therapy would reduce the total number and diversity of intestinal flora in nude mice, and also change the structure of the flora. Shengmai Jianghuang San could protect the diversity of colonies, and also partially restore the colony imbalance caused by irradiation. This study provides a research idea for Shengmai Jianghuang San as a sensitizing adjuvant for radiotherapy of nasopharyngeal carcinoma.

In vitro and in vivo anti-malignant melanoma activity of Alocasia cucullata via modulation of the phosphatase and tensin homolog/phosphoinositide 3-kinase/AKT pathway.

Alocasia cucullata, a Chinese herb, has been used as an anticancer treatment in southern China. Phosphatase and tensin (PTEN), is a tumor suppressor gene and the loss of PTEN expression may activate the phosphoinositide-3-kinase (PI3K)/AKT signaling pathway which play a key role in tumors formation and progression. In this study, we evaluated the anti-melanoma effect and the underlying mechanism of 50% ethanolic extract of A. cucullata (EAC) in vitro and in vivo. Using MTT, wound healing, and transwell assays, we found that EAC suppressed the proliferation, migration, and invasion of melanoma cells (B16-F10, A375 and A2058) in a dose-dependent manner. We also found that EAC suppresses B16-F10 tumor growth in a xenografted mouse model. Western blot analysis revealed that the expression level of PTEN was up-regulated, and phosphorylation of PI3K and AKT reduced in B16-F10 cells and tumor tissues after EAC treatment. No significant differences were observed in PI3K and AKT expression. Moreover, immunohistochemistry showed that the number of PTEN-positive cells in tumor tissues increased and that of p-AKT-positive cells decreased with EAC treatment, corroborating the western blot results. Our data reveal that EAC can inhibit malignant melanoma in vitro and in vivo and suggest that its anti-tumor effect is associated with modulation of the PTEN/ PI3K/AKT signaling pathway. In summary, our findings highlight a promising herbal remedy for the treatment of malignant melanoma, which warrants further study.

Association between Wnt inhibitory factor 1 and receptor tyrosine kinase-like orphan receptor 2 protein expression and the clinical pathological significance in benign and malignant pancreatic lesions.

Pancreatic cancer is one of the most malignant types of tumor. It is important to elucidate the underlying molecular mechanisms of pancreatic tumorigenesis and to identify novel biomarkers as therapeutic targets of pancreatic cancer. In the present study, the protein expression levels of Wnt inhibitory factor 1 (WIF1) and receptor tyrosine kinase-like orphan receptor 2 (ROR2) were examined in a collection of pancreatic ductal carcinoma and benign pancreatic lesion tissue samples using immunohistochemistry. The positive expression rate of WIF1 protein in pancreatic ductal carcinoma was demonstrated to be significantly decreased compared with that of the paracancerous tissue, benign lesions and wild-type pancreatic tissue (P=0.002, P<0.0001, P=0.001, respectively). The positive expression rate of ROR2 protein in pancreatic ductal carcinoma was demonstrated to be significantly increased compared with that of the paracancerous tissue, benign lesions and wild-type pancreatic tissue (P<0.0001). There was a negative association between WIF1 and ROR2 expression in the pancreatic ductal carcinoma samples (P=0.004). The survival period of patients with negative WIF1 and positive ROR2 protein expression was demonstrated to be significantly decreased compared with that of patients with positive WIF1 and negative ROR2 protein expression (P<0.0001). The expression levels of WIF1 and ROR2 protein reflected the incidence, development, clinical and biological behavior, and prognosis of pancreatic ductal carcinoma. Patients with negative WIF1 and positive ROR2 protein expression had poor prognosis. The results indicate that WIF1 and ROR2 are important biomarkers in pancreatic cancer.

XRCC1 genetic polymorphism acts a potential biomarker for lung cancer.

Lung cancer is one of the most common but serious cancers in the world. Both the X-ray repair cross-complementing group 1 (XRCC1) gene and the human multidrug resistance 1 (MDR1) gene are important candidate genes influencing the susceptibility to various diseases, including lung cancer. This study aimed to assess the correlation of genetic polymorphisms in XRCC1 and MDR1 with the susceptibility to lung cancer. In this study, a total of 320 lung cancer patients and 346 cancer-free controls in Chinese population were enrolled in this study. Data about the clinical characteristics and related risk factors of lung cancer were collected by questionnaires. The single-nucleotide polymorphisms (SNPs) of XRCC1 and MDR1 genes were genotyped by created restriction site-polymerase chain reaction method. Our data showed that the risk for lung cancer increased significantly among the variant Arg194Trp (C > T, rs1799782) and Arg399Gln (G > A, rs25487) of XRCC1, but there are no significant differences in the allelic and genotypic frequencies of c.1564A > T and c.3073A > C of MDR1 between lung cancer patients and cancer-free controls. In conclusion, these preliminary results suggest that the C > T, rs1799782 and C > T, rs25487 of XRCC1 genetic variants might be used as molecular markers for detecting lung cancer susceptibility.