Gastric paraganglioma: a case report and review of literature.

Paragangliomas (PGLs) are rare neuroendocrine tumors which overproduce catecholamines (CAs). They are extra-adrenal, catecholamine-secreting tumors occurring outside the adrenal glands. Gastric PGLs originating from extra-adrenal paraganglia are exceptionally rare, and their presentation in geriatric patients further adds to the complexity of diagnosis and management. A 72-year-old male patient presented with enduring left upper abdominal pain and anemia persisting for over a year, and hypertension for six months. Physical examination revealed epigastric discomfort and pallor. Computed tomography scans revealed enlarged lymph nodes in the lesser curvature of the stomach and thickening of the gastric antrum wall with concavity. The patient underwent three cycles of neoadjuvant therapy before radical gastrectomy for gastric cancer. These imaging findings were confirmed during surgery and intraoperative blood pressure was in fluctuation. After the successful resection of the tumor, postoperative pathology confirmed paraganglioma. During postoperative examination, it was observed that the patient's CAs and their metabolites had returned to within the normal range. Combined with the existing ten literatures, we retrospective report the clinical and pathological characteristics and treatment strategies of the rare gastric paraganglioma.

A novel strategy of combining abdominal surgery and endoscopy for the quick hemostasis of acute duodenal ulcer bleeding: a case report.

BACKGROUND: Uncontrolled ulcer bleeding of duodenal ulcer (DU) after endoscopic therapy often needs surgery. At present, cutting the bottom of the ulcer with ligation and performing its excision-lesion are the common ways to achieve immediate efficacy in stopping bleeding. For the problem of its great trauma, we seek an easy and useful technical method to reach the same therapeutic effect to stop acute bleeding. METHODS: We determined the distribution of the lesion and its innervated blood vessels under the guidance of the endoscopy and then performed suture and hemostasis on the external surface of the stomach and duodenum. RESULTS: An immediate efficacy in stopping bleeding was shown and the hemoglobin (Hb) level returned to normal after operation with no recurrence of bleeding. CONCLUSION: We created a successful and novel strategy for laparotomy-endoscopic assisted suture for DU emergency hemostasis without duodenectomy.

A novel defined cuproptosis-related gene signature for predicting the prognosis of colon adenocarcinoma.

The prognosis of colon adenocarcinoma (COAD) needs to be improved. Cuproptosis is a recently discovered cell death caused by intracellular overload of copper ions. There have been no reports about the cuproptosis-related prognostic model in COAD. First, we screened 30 differentially expressed genes (DEGs) from patients with COAD using The Cancer Genome Atlas (TCGA) database. Gene Expression Omnibus (GEO) database was used as a validation set to establish a risk model of five cuproptosis-related genes (CKDN2A, SDHB, CCS, ULK1, and CMC1) by least absolute shrinkage and selection operator (LASSO) Cox regression analysis. In both TCGA and GEO cohorts, we could see that overall survival of COAD patients of the low-risk group was longer. Combined with the clinical characteristics, the risk score was found to be an independent prognostic factor. Furthermore, single-sample Gene Set Enrichment Analysis (ssGSEA) showed that the levels of Th1 and Treg immune cells changed both in TCGA and GEO databases. Finally, clinical samples were used to verify the mRNA and protein levels of five risk-model genes. In conclusion, this model could predict the prognosis of COAD patients, and the mechanism may be related to the changes in immune cells in the tumor microenvironment (TME).

Anlotinib Benefits the αPDL1 Immunotherapy by Activating ROS/JNK/AP-1 Pathway to Upregulate PDL1 Expression in Colorectal Cancer.

Colorectal cancer (CRC) is one of the prevalent malignant tumors. This study is aimed at evaluating the mechanism of anlotinib (anlo) on tumor microenvironment (TME) in CRC, and its effects in combination with immune checkpoint inhibitors (ICIs) therapy. Firstly, MC38 and CT26 cells were both exposed to different gradient concentrations of anlo for 72 h, to investigate the cell viability and synergetic therapy efficacy with ICIs by CCK8. The results showed that anlo could obviously inhibit cell growth and showed no synergistic efficacy therapy in combination with αPDL1 in vitro. Then, we found the upregulation of programmed cell death ligand 1(PDL1) expression both in vitro and in vivo after anlo treatment. In vivo, anlo could enhance the percentage of natural killer (NK) cells and M1 macrophage cells and decrease the percentage of M2 macrophage cells in TME. Moreover, we explored the mechanism and we proved that anlo could activate reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling pathway to increase the expression levels of PDL1, IFN-α/ß/γ, and CXCL2 in two cell lines in vitro. We also proved that anlo had synergistic effects with ICIs in vivo. Finally, it could also increase the mRNA and protein PDL1 expression levels in human cell lines, which was consistent with mouse CRC cell lines. However, there are still a few limitations. On one hand, the ROS/JNK/AP-1 pathway needs to be proved whether it can be activated in human cell lines. On the other hand, the mechanism behind ROS promoting phosphorylation of JNK needs to be explored.

Copper metabolism patterns and tumor microenvironment characterization in colon adenocarcinoma.

Copper participates in biological processes such as oxygen metabolism and iron uptake, and is a key factor in immune regulation. Based on the transcription data, mutation data and clinical data of colon adenocarcinoma (COAD) patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Profiling Interactive Analysis (GEPIA2) database, the expression and mutation of copper metabolization-related genes in COAD patients and their correlation with tumor immune microenvironment were analyzed. Copper metabolization-related genes (CMRGs) were used to construct COAD subtypes and prognostic risk models for COAD patients. Furthermore, Kaplan-Meier (K-M) curve and receiver operating characteristic (ROC) curve were used to analyze the clinical value of COAD subtypes and genotyping models in distinguishing clinical characteristics of patients, and the immune infiltration of patients with different genotypes was analyzed. Finally, the clinical tissue samples from COAD patients were used to analyze the mRNA expression of genes in risk model between tumor and normal tissues by the method of Polymerase Chain Reaction (PCR). Of the 479 CMRGs, 68 genes were differentially expressed in normal and tumor tissues of COAD patients in TCGA and GEPIA2. Two subtypes with different clinical and immunological characteristics were identified by using 482 genes related to copper metabolism. Finally, a prognostic risk model consisting of five CMRGs was constructed, which could not only predict the prognosis of patients, but also correlated with COAD subtypes. In addition, some genes (glutathione S-transferase mu 1, cyclin D1and cytochrome P450 family 2 subfamily S member 1) in risk model was show significant difference between normal and tumor tissues. The COAD subtypes identified by CMRGs can help clinically distinguish patients with different prognosis and tumor progression, and the risk score can assist in clinical evaluation of patient prognosis, serving as a valuable biomarker for COAD immunotherapy.

IFNγ enhances ferroptosis by increasing JAK­STAT pathway activation to suppress SLCA711 expression in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare type of tumor with a poor prognosis. Ferroptosis is a relatively novel form of programmed cell death driven by iron­dependent lipid peroxidation accumulation. Recent evidence suggests that IFNγ facilitates erastin­induced ferroptosis, which contributed to anticancer therapy in various types of cancer. However, it has remained elusive whether the regulation of IFNγ on ferroptosis has a positive role in the treatment of ACC. Thus, the aim of the present study was to explore the effects of IFNγ on erastin­induced ferroptosis in the ACC cell line NCI­H295R and investigate the underlying mechanisms. Cell viability was assessed using a Cell Counting Kit­8 assay, an ethynyldioxyuridine proliferation assay and Live/Dead staining. The levels of iron, reactive oxygen species, lipid peroxidation and mitochondrial damage were also assessed. Western blot and reverse transcription­quantitative PCR analyses were used to determine the underlying molecular mechanisms involved in the erastin­induced ferroptosis of NCI­H295R cells. The results suggested that IFNγ promoted erastin­induced ferroptotic cell death. Furthermore, IFNγ enhanced erastin­induced ferroptosis, as evidenced by the accumulation of iron, as well as the increase in lipid peroxidation and promotion of mitochondrial damage. Further analysis suggested that IFNγ enhanced ferroptosis by suppressing the expression of solute carrier family 7 member 11, an important negative regulator of ferroptosis, and this was achieved via activation of the JAK/STAT pathway in NCI­H295R cells. The present study provided experimental evidence on the activity and mechanism of ferroptosis enhanced by IFNγ in ACC and may give critical insight into the immunotherapeutic management of ACC.

Alternative splicing event associated with immunological features in bladder cancer.

Bladder cancer (BLCA) is the most prevalent urinary tumor with few treatments. Alternative splicing (AS) is closely related to tumor development and tumor immune microenvironment. However, the comprehensive analysis of AS and prognosis and immunological features in BLCA is still lacking. In this study, we downloaded RNA-Seq data and clinical information from The Cancer Genome Atlas (TCGA) database, and AS events were acquired from the TCGA Splice-seq. A total of eight prognostic AS events (C19orf57|47943|ES, ANK3|11845|AP, AK9|77203|AT, GRIK2|77096|AT, DYM|45472|ES, PTGER3|3415|AT, ACTG1|44120|RI, and TRMU|62711|AA) were identified by univariate analysis and least absolute shrinkage and selection operator (LASSO) regression analysis to construct a risk score model. The Kaplan-Meier analysis revealed that the high-risk group had a worse prognosis compared with the low-risk group. The area under the receiver operating characteristic (ROC) curves (AUCs) for this risk score model in 1, 3, and 5 years were 0.698, 0.742, and 0.772, respectively. One of the prognostic AS event-related genes, TRMU, was differentially expressed between tumor and normal tissues in BLCA. The single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm showed that both the risk score model and TRMU were significantly associated with tumor immune microenvironment and immune status (immune cells, immune-related pathway, and immune checkpoint) in BLCA patients. The TIMER database confirmed the relationship between the expression of TRMU and immune cells and checkpoint genes. Furthermore, Cytoscape software 3.8.0 was used to construct the regulatory network between AS and splicing factors (SFs). Our study demonstrated that AS events were powerful biomarkers to predict the prognosis and immune status in BLCA, which may be potential therapeutic targets in BLCA.

Identification of the Pyroptosis-Related Gene Signature and Risk Score Model for Colon Adenocarcinoma.

The prognosis of advanced colon adenocarcinoma (COAD) remains poor. However, existing methods are still difficult to assess patient prognosis. Pyroptosis, a lytic and inflammatory process of programmed cell death caused by the gasdermin protein, is involved in the development and progression of various tumors. Moreover, there are no related studies using pyroptosis-related genes to construct a model to predict the prognosis of COAD patients. Thus, in this study, bioinformatics methods were used to analyze the data of COAD patients downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to construct a risk model for the patient prognosis. TCGA database was used as the training set, and GSE39582 downloaded from GEO was used as the validation set. A total of 24 pyroptosis-related genes shown significantly different expression between normal and tumor tissues in COAD and seven genes (CASP4, CASP5, CASP9, IL6, NOD1, PJVK, and PRKACA) screened by univariate and LASSO cox regression analysis were used to construct the risk model. The receiver operating characteristic (ROC) and Kaplan-Meier (K-M curves) curves showed that the model based on pyroptosis-related genes can be used to predict the prognosis of COAD and can be validated by the external cohort well. Then, the clinicopathological factors were combined with the risk score to establish a nomogram with a C-index of 0.774. In addition, tissue validation results also showed that CASP4, CASP5, PRKACA, and NOD1 were differentially expressed between tumor and normal tissues from COAD patients. In conclusion, the risk model based on the pyroptosis-related gene can be used to assess the prognosis of COAD patients well, and the related genes may become the potential targets for treatment.