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Cell & Bioscience Nov 2023Ovarian cancer (OC) typically develops an immunosuppressive microenvironment by funtional changes of host immune cells. Dysregulated m6A level is associated with cancer...
BACKGROUND
Ovarian cancer (OC) typically develops an immunosuppressive microenvironment by funtional changes of host immune cells. Dysregulated m6A level is associated with cancer progression via the intrinsic oncogenic pathways. However, the role of m6A in regulating host immune cell function during anti-tumor immunity needs comprehensive analysis. This study aimed to investigate the role of METTL3, a catalytic subunit of the methyltransferase complex, in regulating host immune cell response against OC.
METHODS
In this study, myeloid-specific Mettl3 gene knockout (Mettl3-cKO) mice were bred using the Cre-LoxP system. Intraperitoneally injection of ID8 cells was used as a syngeneic OC model. Furthermore, the compositions of immune cell populations were analyzed by flow cytometry and single-cell sequencing. Moreover, chemokines and cytokines secretion were assessed using ELISA. Lastly, the role of METTL3 in regulating IL-1β secretion and inflammasome activation in bone marrow-derived macrophages cocultured with ID8 cells was specified by ELISA and immunoblotting.
RESULTS
It was revealed that OC cell growth was enhanced in Mettl3-cKO mice. Furthermore, a shift of decreased M1 to increased M2 macrophage polarization was observed during OC progression. Moreover, Mettl3 depletion in myeloid lineage cells increased secretion of CCL2 and CXCL2 in peritoneal lavage fluild. Interestingly, Mettl3 deficiency enhanced IL-1β secretion induced by viable ID8 cells independent of inflammasome activation and cell death. Therefore, OC cells in tumor-bearing mice trigger a slight inflammatory response with a low-to-moderate secretion of pro-inflammatory cytokines and chemokines.
CONCLUSION
This study provides new insights into METTL3-mediated m6A methylation, which regulates host immune response against OC.
PubMed: 37932814
DOI: 10.1186/s13578-023-01149-6 -
International Journal of Hyperthermia :... May 2018Radiological imaging often underestimates the extent of low volume peritoneal disease. The benefit of laparoscopy in assessing peritoneal metastases from colorectal and... (Review)
Review
INTRODUCTION
Radiological imaging often underestimates the extent of low volume peritoneal disease. The benefit of laparoscopy in assessing peritoneal metastases from colorectal and gastric cancer is accepted, but is inconclusive for appendiceal malignancy. We report our experience of diagnostic (DL) and therapeutic laparoscopy (TL) in patients with appendiceal tumours to determine indications and role in assessment and management.
METHODS
A retrospective review of a National Peritoneal Malignancy Centre's prospectively maintained database was performed. All patients with appendiceal neoplasms who underwent DL or TL between September 2011 and January 2016 were included. The indications and outcomes of the laparoscopy, complications and interval to laparotomy were evaluated.
RESULTS
Six hundred and eighty-five patients underwent surgery for appendiceal neoplasms during the study period, of which 73 (10.6%) underwent laparoscopy (50 DL, 23 TL). The main indications for DL were to clarify imaging and stage patients with high-risk histology. Indications for TL were an abnormal appendix without gross pseudomyxoma peritonei (PMP) or with low volume PMP, and concerns for fertility in the presence of PMP. DL resulted in 16 patients (32%) avoiding laparotomy because of extensive disease or no tumour found. Overall, 28 patients were assessed to have resectable disease and at laparotomy, 25/28 had complete cytoreduction with three patients unresectable. In the TL group, appendicectomy and peritoneal lavage was achieved in all four women with fertility concerns, allowing them to conceive thereafter. There were no complications.
CONCLUSIONS
Patients with high-risk appendiceal neoplasm may benefit from DL, and potentially avoid unnecessary laparotomy. TL is useful in patients with low volume PMP and may aid fertility in selected patients.
Topics: Adult; Aged; Appendiceal Neoplasms; Female; Humans; Laparoscopy; Male; Middle Aged; Prospective Studies; Retrospective Studies
PubMed: 28605985
DOI: 10.1080/02656736.2017.1338363 -
Saudi Journal of Medicine & Medical... 2017In the last 30 years, the management of liver injury has evolved significantly. The advancement of imaging studies has played an important role in the conservative... (Review)
Review
In the last 30 years, the management of liver injury has evolved significantly. The advancement of imaging studies has played an important role in the conservative approach for management. A shift from operative to nonoperative management for most hemodynamically stable patients with hepatic injury has been prompted by speed and sensitivity of diagnostic imaging and by advances in critical care monitoring. In this review article, the up-to-date recommendation on the management approach of liver trauma will be discussed.
PubMed: 30787766
DOI: 10.4103/1658-631X.204868 -
Annals of Surgical Oncology May 2017Positive peritoneal cytology is classified as M1 disease in gastric and pancreatic cancer. While peritoneal cytology is typically obtained by laparoscopic peritoneal... (Clinical Trial)
Clinical Trial
BACKGROUND
Positive peritoneal cytology is classified as M1 disease in gastric and pancreatic cancer. While peritoneal cytology is typically obtained by laparoscopic peritoneal lavage, this study sought to examine the feasibility and safety of performing this percutaneously, with monitored anesthesia care and in combination with other diagnostic procedures to condense and expedite the staging process.
METHODS
Patients with gastric or pancreatic cancer scheduled for laparoscopy with peritoneal lavage were prospectively enrolled to undergo intraoperative percutaneous peritoneal lavage prior to laparoscopic peritoneal lavage. Saline was infused through a percutaneously-inserted catheter and fluid was collected for peritoneal cytology. Three-quadrant washings collected during laparoscopy were also sent for peritoneal cytology. The primary outcome was to evaluate the sensitivity and specificity of percutaneous peritoneal lavage for detecting positive peritoneal cytology compared with the gold standard of laparoscopic peritoneal lavage, while the secondary outcome was to determine safety.
RESULTS
Percutaneous peritoneal lavage was successfully performed in 70 of 76 patients (92%). Ten of 48 gastric cancer patients (21%) and three of 22 pancreatic cancer patients (14%) had positive percutaneous and laparoscopic peritoneal cytology. Two additional gastric cancer patients had positive laparoscopic peritoneal cytology only. Sensitivity and specificity of percutaneous peritoneal lavage compared with laparoscopic peritoneal lavage were 87% and 100%, respectively. No complications occurred with percutaneous peritoneal lavage.
CONCLUSIONS
Percutaneous peritoneal lavage is a safe and effective minimally invasive alternative to laparoscopic peritoneal lavage for the diagnosis of metastatic gastric and pancreatic cancer. It is possible this can be utilized in an outpatient setting, such as during endoscopy, to allow for earlier diagnosis of M1 disease and decreased time to appropriate treatment.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Laparoscopy; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Peritoneal Lavage; Peritoneal Neoplasms; Prospective Studies; Sensitivity and Specificity; Stomach Neoplasms
PubMed: 28058561
DOI: 10.1245/s10434-016-5757-3 -
International Journal of Molecular... Nov 2021Peritonitis caused by LPS is a severe clinical challenge, which causes organ damage and death. However, the mechanism of LPS-induced peritonitis has not been fully...
Peritonitis caused by LPS is a severe clinical challenge, which causes organ damage and death. However, the mechanism of LPS-induced peritonitis has not been fully revealed yet. Here, we investigated the transcriptome profile of the peritoneal tissue of LPS-induced peritonitis in mice. A model of LPS-induced peritonitis in mice was established (LPS 10 mg/kg, i.p.), and the influence of TAK 242 (TLR4 inhibitor) on the level of inflammatory cytokines in mouse peritoneal lavage fluid was investigated by using an ELISA test. Next, the peritoneal tissues of the three groups of mice (Control, LPS, and LPS+TAK 242) ( = 6) were isolated and subjected to RNA-seq, followed by a series of bioinformatics analyses, including differentially expressed genes (DEGs), enrichment pathway, protein-protein interaction, and transcription factor pathway. Then, qPCR verified-hub genes that may interact with TAK 242 were obtained. Subsequently, the three-dimensional structure of hub proteins was obtained by using homology modeling and molecular dynamics optimization (300 ns). Finally, the virtual docking between TAK 242 and hub proteins was analyzed. Our results showed that TAK 242 significantly inhibited the production of inflammatory cytokines in the peritoneal lavage fluid of mice with peritonitis, including IL-6, IFN-γ, IL-1β, NO, and TNF-α. Compared with the Control group, LPS treatment induced 4201 DEGs (2442 down-regulated DEGs and 1759 up-regulated DEGs). Compared with the LPS group, 30 DEGs were affected by TAK 242 (8 down-regulated DEGs and 22 up-regulated DEGs). A total of 10 TAK 242-triggered hub genes were obtained, and the possible docking modes between TAK 242 and hub proteins were acquired. Overall, our data demonstrated that a large number of DEGs were affected in LPS-triggered peritonitis mice. Moreover, the TLR4 inhibitor TAK 242 is capable of suppressing the inflammatory response of LPS-induced peritonitis. Our work provides clues for understanding the pathogenesis of LPS-induced peritonitis in mice.
Topics: Animals; Cytokines; Gene Expression Profiling; Gene Expression Regulation; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Peritoneal Lavage; Peritoneum; Peritonitis; Signal Transduction; Sulfonamides; Toll-Like Receptor 4; Transcriptome
PubMed: 34884814
DOI: 10.3390/ijms222313008 -
World Journal of Gastrointestinal... Mar 2023Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free... (Clinical Trial)
Clinical Trial
BACKGROUND
Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free cancer cells may still exist after resection. In addition, the surgery itself may lead to the dissemination of tumor cells. Therefore, it is necessary to remove residual tumor cells. Recently, some researchers found that extensive intraoperative peritoneal lavage (EIPL) plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients. However, few studies explored the safety and long-term outcome of EIPL after curative gastrectomy.
AIM
To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL.
METHODS
According to the inclusion and exclusion criteria, a total of 150 patients with advanced GC were enrolled in this study. The patients were randomly allocated to two groups. All patients received laparotomy. For the non-EIPL group, peritoneal lavage was washed using no more than 3 L of warm saline. In the EIPL group, patients received 10 L or more of saline (1 L at a time) before the closure of the abdomen. The surviving rate analysis was compared by the Kaplan-Meier method. The prognostic factors were carried out using the Cox appropriate hazard pattern.
RESULTS
The basic information in the EIPL group and the non-EIPL group had no significant difference. The median follow-up time was 30 mo (range: 0-45 mo). The 1- and 3-year overall survival (OS) rates were 71.0% and 26.5%, respectively. The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group ( < 0.05). For the OS of patients, the EIPL, Borrmann classification, tumor size, N stage, T stage and vascular invasion were significant indicators. Then multivariate analysis revealed that EIPL, tumor size, vascular invasion, N stage and T stage were independent prognostic factors. The prognosis of the EIPL group was better than the non-EIPL group ( < 0.001). The 3-year survival rate of the EIPL group (38.4%) was higher than the non-EIPL group (21.7%). For the recurrence-free survival (RFS) of patients, the risk factor of RFS included EIPL, N stage, vascular invasion, type of surgery, tumor location, Borrmann classification, and tumor size. EIPL and tumor size were independent risk factors. The RFS curve of the EIPL group was better than the non-EIPL group ( = 0.004), and the recurrence rate of the EIPL group (24.7%) was lower than the non-EIPL group (46.4%). The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group ( < 0.05).
CONCLUSION
EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess. In addition, the overall survival curve and RFS curve were better in the EIPL group.
PubMed: 37032799
DOI: 10.4240/wjgs.v15.i3.430 -
Saudi Pharmaceutical Journal : SPJ :... Jun 2024Post-operative peritoneal adhesions (PA) are a common and important clinical problem. In this study, we focused on the ameliorative efficacy of ginger and gingerol...
Intra-peritoneal lavage of rhizome and its active constituent gingerol impede inflammation, angiogenesis, and fibrosis following post-operative peritoneal adhesion in male rats.
Post-operative peritoneal adhesions (PA) are a common and important clinical problem. In this study, we focused on the ameliorative efficacy of ginger and gingerol compounds on surgical-induced peritoneal adhesion, and their strategies that disrupted the PA formation pathways to suppress their incidence. First, liquid chromatography-mass spectrometry (LC-MS) was established to separate and identify several chemical groups of ginger rhizome extract. In the next steps, male Wistar albino rats were randomly selected and divided into various groups, namely sham, control, ginger extract (0.6, 1.8, 5 %w/v), and gingerol (0.05, 0.1, 0.3, and 1 %w/v). Finally, we investigated the macroscopic parameters such as wound healing, body weight as well as spleen height and weight. In addition, visual peritoneal adhesion assessment was performed via Nair et al and Adhesion Scoring Scheme. Moreover, the microscopic parameters and biological assessment was performed via and immunoassays. The present findings revealed significant improvement in wound healing and reduction of the adhesion range, as Nair et al. and Adhesion Scoring Scheme scoring, in both the ginger and gingerol groups compared to the PA group (). Whereas, gingerol (0.3 % w/v) was able to increase the body weight in rats () at end stage of experiment. Also, inflammation, angiogenesis, and fibrosis were significantly decreased due to the downregulation of interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF), respectively, in the ginger and gingerol groups compared to the PA group (). In contrast, the levels of IL-10 were increased in the ginger and gingerol groups compared to the control group (). Our results proved that ginger rhizome and gingerol, as novel therapeutic compounds, could be used to prevent PA for their beneficial anti-inflammatory as well as anti-fibrosis properties in clinical trials. However, further clinical studies are required to approve the effectiveness of ginger and gingerol.
PubMed: 38737808
DOI: 10.1016/j.jsps.2024.102092 -
Revista Do Colegio Brasileiro de... 2020to assess whether laparoscopy with peritoneal lavage is superior to computed tomography for staging gastric adenocarcinoma and whether it can modify the surgical... (Comparative Study)
Comparative Study
OBJECTIVE
to assess whether laparoscopy with peritoneal lavage is superior to computed tomography for staging gastric adenocarcinoma and whether it can modify the surgical approach.
METHODS
we conducted a retrospective study of 46 patients with gastric adenocarcinoma treated by the digestive surgery team of the Passo Fundo Clinics Hospital (RS), from January 2015 to December 2018, and submitted to laparoscopy with preoperative peritoneal lavage. All patients underwent preoperative clinical staging with computed tomography.
RESULTS
of the 46 patients analyzed, the majority had tumors located in the cardia (34.8%), poorly differentiated (69.6%), and subtype signet ring cells (65.2%). In 91.3%, the computed tomography scan did not identify peritoneal carcinomatosis or distant metastasis. Among these patients with negative computed tomography for distant disease, 21.8% had positive peritoneal lavage for neoplastic cells and had their therapeutic approaches modified.
CONCLUSION
laparoscopy and peritoneal lavage altered the surgical decision in 21.8% of patients, providing a more reliable preoperative staging in gastric adenocarcinoma.
Topics: Adenocarcinoma; Aged; Digestive System Surgical Procedures; Female; Gastrectomy; Humans; Laparoscopy; Male; Middle Aged; Neoplasm Staging; Peritoneal Lavage; Preoperative Care; Retrospective Studies; Stomach Neoplasms; Tomography, X-Ray Computed
PubMed: 32022110
DOI: 10.1590/0100-6991e-20192314 -
Journal of Gastric Cancer Jan 2024Liquid biopsy, a minimally invasive procedure that causes minimal pain and complication risks to patients, has been extensively studied for cancer diagnosis and... (Review)
Review
Liquid biopsy, a minimally invasive procedure that causes minimal pain and complication risks to patients, has been extensively studied for cancer diagnosis and treatment. Moreover, it facilitates comprehensive quantification and serial assessment of the whole-body tumor burden. Several biosources obtained through liquid biopsy have been studied as important biomarkers for establishing early diagnosis, monitoring minimal residual disease, and predicting the prognosis and response to treatment in patients with cancer. Although the clinical application of liquid biopsy in gastric cancer is not as robust as that in other cancers, biomarker studies using liquid biopsy are being actively conducted in patients with gastric cancer. Herein, we aimed to review the role of various biosources that can be obtained from patients with gastric cancer through liquid biopsies, such as blood, saliva, gastric juice, urine, stool, peritoneal lavage fluid, and ascites, by dividing them into cellular and acellular components. In addition, we reviewed previous studies on the diagnostic, prognostic, and predictive biomarkers for gastric cancer using liquid biopsy and discussed the limitations of liquid biopsy and the challenges to overcome these limitations in patients with gastric cancer.
PubMed: 38225764
DOI: 10.5230/jgc.2024.24.e5 -
Frontiers in Medicine 2022Excessive inflammation and increased apoptosis of macrophages contribute to organ damage and poor prognosis of sepsis. Ginkgolic acid (GA) is a natural constituent...
BACKGROUND
Excessive inflammation and increased apoptosis of macrophages contribute to organ damage and poor prognosis of sepsis. Ginkgolic acid (GA) is a natural constituent extracted from the leaves of , that can regulate inflammation and apoptosis. The present study aims to investigate the potential effect of GA in treating sepsis and its possible mechanisms.
MATERIALS AND METHODS
Here, a classic septic mice model and a lipopolysaccharide (LPS)-induced RAW 264.7 inflammation model were established. Cytokines in serum and culture supernatant were detected by ELISA, and the mRNA levels of them were examined by PCR. Hematoxylin and eosin (H&E) staining was performed to determine histopathological changes in liver, lung and kidney. Bacterial burden in the blood, peritoneal lavage fluids (PLFs) and organs were observed on Luria-Bertani agar medium. Flow cytometry and western blotting was used to detect apoptosis and the expression level of apoptosis related molecules, respectively. Moreover, the levels of SUMOylation were detected by western blotting. The activity of NF-κB p65 was assessed by immunofluorescence staining and western blotting.
RESULTS
The result showed that GA promoted inflammatory responses, reduced bacterial clearance, aggravated organ damage, and increased mortality in septic mice. GA increased apoptosis in peritoneal macrophages (PMs) and RAW 264.7 cells. Meanwhile, GA inhibited SUMOylation and increased the nuclear translocation of NF-κB p65 as well as its phosphorylation level.
CONCLUSION
Collectively, GA promotes inflammation and macrophage apoptosis in sepsis, which may be mediated by inhibiting the SUMOylation process and increasing NF-κB p65 activity.
PubMed: 36743669
DOI: 10.3389/fmed.2022.1108882