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International Journal of Hyperthermia :... 2024Cryoablation (Cryo) is a minimally invasive treatment for tumors. Cryo can activate the body's immune response, although it is typically weak. The immune response...
BACKGROUND
Cryoablation (Cryo) is a minimally invasive treatment for tumors. Cryo can activate the body's immune response, although it is typically weak. The immune response induced by Cryo in hepatocellular carcinoma (HCC) is poorly understood. PD-1 and CTLA-4 monoclonal antibodies are immune checkpoint inhibitors used in immunotherapy for tumors. The combined use of these antibodies with Cryo may enhance the immune effect.
METHODS
A Balb/c mouse model of HCC was established and treated with Cryo, immune checkpoint blockade (ICB), or Cryo + ICB (combination therapy). The growth trend of right untreated tumors and survival time of mice were determined. The expression of apoptosis-related proteins was detected by Western blot (WB) assay. The percentages of immune cells and immunosuppressive cells were analyzed by flow cytometry. The numbers of infiltrating T lymphocytes were checked by immunohistochemistry, and the levels of T-cell-associated cytokines were detected by Quantitative real-time Polymerase Chain Reaction (qRT-PCR) assays and Enzyme-Linked Immunosorbent Assays (ELISA) assays.
RESULTS
Cryo + ICB inhibited the growth of right untreated tumors, promoted tumor cell apoptosis, and prolonged the survival time of mice. Local T-cell infiltration in right tumor tissues increased after the combination therapy, while the number of immunosuppressive cells was significantly reduced. In addition, the combination therapy may induce the production of multiple Th1-type cytokines but reduce the production of Th2-type cytokines.
CONCLUSIONS
Cryo can activate CD8 and CD4 T-cell immune responses. Cryo + ICB can relieve the immunosuppressive tumor microenvironment and shift the Th1/Th2 balance toward Th1 dominance, further enhancing the Cryo-induced T-cell immune response and resulting in a stronger antitumor immune response.
Topics: Animals; Carcinoma, Hepatocellular; Mice; Liver Neoplasms; Cryosurgery; Mice, Inbred BALB C; Immune Checkpoint Inhibitors; Disease Models, Animal; Cell Line, Tumor
PubMed: 38955354
DOI: 10.1080/02656736.2024.2373319 -
Open Biology Jul 2024mosquitoes have an exclusively phytophagous feeding habit as adults, which leads to significant differences in their morphophysiology compared with haematophagous...
mosquitoes have an exclusively phytophagous feeding habit as adults, which leads to significant differences in their morphophysiology compared with haematophagous mosquitoes. However, the molecular mechanisms of digestion in this mosquito are not well understood. In this study, RNA sequencing of the posterior midgut (PMG) of the mosquito was undertaken, highlighting its significance in mosquito digestion. Subsequently, a comparison was made between the differential gene expression of the PMG and that of the anterior midgut. It was found that the most abundant proteases in the PMG were trypsin and chymotrypsin, and the level of gene expression for enzymes essential for digestion (such as serine protease, α-amylase and pancreatic triacylglycerol lipase) and innate immune response (including catalase, cecropin-A2 and superoxide dismutase) was like that of haematophagous mosquitoes. Peritrophin-1 was detected in the entire midgut, with an elevated expression level in the PMG. Based on our findings, it is hypothesized that a non-haematophagic habit might have been exhibited by the ancestor of , and this trait may have been retained. This study represents a pioneering investigation at the molecular level of midgut contents in a non-haematophagous mosquito. The findings offer valuable insights into the evolutionary aspects of feeding habits in culicids.
Topics: Animals; Culicidae; Insect Proteins; Transcriptome; Gene Expression Profiling; Digestive System; Digestion; Gastrointestinal Tract; Phylogeny; Feeding Behavior
PubMed: 38955221
DOI: 10.1098/rsob.230437 -
Hepatology (Baltimore, Md.) Jul 2024Baveno VII consensus suggests that screening endoscopy can be spared in patients with compensated cirrhosis when spleen stiffness measurement (SSM) by...
BACKGROUND AIMS
Baveno VII consensus suggests that screening endoscopy can be spared in patients with compensated cirrhosis when spleen stiffness measurement (SSM) by vibration-controlled transient elastography (VCTE) is ≤40 kPa as they have a low probability of high-risk varices (HRV). Conversely, screening endoscopy is required in all patients with porto-sinusoidal vascular disorder (PSVD). This study aimed to evaluate the performance of SSM-VCTE to rule out HRV in patients with PSVD and signs of portal hypertension.
APPROACH RESULTS
We retrospectively included patients with PSVD, ≥1 sign of portal hypertension, without history of variceal bleeding, who underwent a SSM-VCTE within 2 years before or after an upper endoscopy in 21 VALDIG centers, divided into a derivation and a validation cohort. 154 patients were included in the derivation cohort; 43% had HRV. By multivariable logistic regression analysis, SSM-VCTE >40 kPa and serum bilirubin ≥1 mg/dL were associated with HRV. SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL had a sensitivity of 96% to rule out HRV, and could spare 38% of screening endoscopies, with 4% of HRV missed, and a 95% negative predictive value (NPV). In the validation cohort, including 155 patients, SSM combined with bilirubin could spare 21% of screening endoscopies, with 4% of HRV missed and a 94% NPV.
CONCLUSION
This study gathering a total of 309 PSVD patients showed that SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL identifies patients with PSVD and portal hypertension with a probability of HRV <5%, in whom screening endoscopy can be spared.
PubMed: 38954825
DOI: 10.1097/HEP.0000000000001004 -
Growth Factors (Chur, Switzerland) May 2024Dysregulated expression of Forkhead Box N2 (FOXN2) has been detected in various cancer types. However, the underlying mechanisms by which FOXN2 contributes to the onset...
FOXN2, identified as a novel biomarker in serum, modulates the transforming growth factor-beta signaling pathway through its interaction with partitioning defective 6 homolog alpha, contributing to the pathogenesis of gastric cancer.
BACKGROUND AND OBJECTIVE
Dysregulated expression of Forkhead Box N2 (FOXN2) has been detected in various cancer types. However, the underlying mechanisms by which FOXN2 contributes to the onset and progression of gastric cancer (GC) remain largely unexplored. This study aimed to elucidate the potential role of FOXN2 within GC, its downstream molecular mechanisms, and its feasibility as a novel serum biomarker for GC.
METHODS
Tissue samples from GC patients and corresponding non-cancerous tissues were collected. Peripheral blood samples were obtained from GC patients and healthy controls. The expression of FOXN2 was determined using quantitative real-time PCR, western blotting, and immunohistochemistry. The expression of FOXN2 in GC cells was modulated by transfection with small interfering RNA (siRNA) or the pcDNA 3.1 expression vector. Cell proliferation was assessed using the Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine incorporation assays. The migratory and invasive capacities of cells were evaluated by Transwell assays, apoptosis rates were measured by flow cytometry, and the expression of proliferative, apoptotic, and epithelial-mesenchymal transition (EMT) markers were assessed by western blot analysis.
RESULTS
FOXN2 was found to be overexpressed in the serum, tissues, and cells of GC, correlating with distant metastasis and TNM staging. FOXN2 demonstrated diagnostic value in differentiating GC patients from healthy individuals, with higher levels of FOXN2 being indicative of poorer survival rates. Silencing FOXN2 in vitro inhibited the proliferation, invasion, migration, and EMT of GC cells, while promoting apoptosis. FOXN2 was shown to regulate the transforming growth factor-beta (TGFβ) receptor signaling pathway in GC cells via its interaction with Partitioning Defective 6 Homolog Alpha (PARD6A).
CONCLUSION
In summary, our data suggest that FOXN2 acts as an oncogenic factor in GC, modulating the TGFβ pathway by binding to PARD6A, thereby influencing gastric carcinogenesis. This study underscores the functional significance of FOXN2 as a potential serum biomarker and therapeutic target in GC.
Topics: Humans; Stomach Neoplasms; Forkhead Transcription Factors; Signal Transduction; Biomarkers, Tumor; Male; Female; Middle Aged; Transforming Growth Factor beta; Epithelial-Mesenchymal Transition; Cell Proliferation; Cell Line, Tumor; Apoptosis; Cell Movement; Aged; Gene Expression Regulation, Neoplastic
PubMed: 38954805
DOI: 10.1080/08977194.2023.2297700 -
PloS One 2024Pancreatic adenocarcinoma is an extremely aggressive neoplasm, with many challenges to be overcome in order to achieve a truly effective treatment. It is characterized...
INTRODUCTION
Pancreatic adenocarcinoma is an extremely aggressive neoplasm, with many challenges to be overcome in order to achieve a truly effective treatment. It is characterized by a mostly immunosuppressed environment, with dysfunctional immune cells and active immunoinhibitory pathways that favor tumor evasion and progression. Thus, the study and understanding of the tumor microenvironment and the various cells subtypes and their functional capacities are essential to achieve more effective treatments, especially with the use of new immunotherapeutics.
METHODS
Seventy cases of pancreatic adenocarcinoma divided into two groups 43 with resectable disease and 27 with unresectable disease were analyzed using immunohistochemical methods regarding the expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), and human leukocyte antigen G (HLA-G) molecules as well as the populations of CD4+ and CD8+ T lymphocytes, regulatory T cells (Tregs), and M2 macrophages (MM2). Several statistical tests, including multivariate analyses, were performed to examine how those immune cells and immunoinhibitory molecules impact the evolution and prognosis of pancreatic adenocarcinoma.
RESULTS
CD8+ T lymphocytes and M2 macrophages predominated in the group operated on, and PD-L2 expression predominated in the unresectable group. PD-L2 was associated with T stage, lymph node metastasis, and clinical staging, while in survival analysis, PD-L2 and HLA-G were associated with a shorter survival. In the inoperable cases, Tregs cells, MM2, PD-L1, PD-L2, and HLA-G were positively correlated.
CONCLUSIONS
PD-L2 and HLA-G expression correlated with worse survival in the cases studied. Tumor microenvironment was characterized by a tolerant and immunosuppressed pattern, mainly in unresectable lesions, where a broad positive influence was observed between immunoinhibitory cells and immune checkpoint proteins expressed by tumor cells.
Topics: Humans; Pancreatic Neoplasms; Male; Female; Adenocarcinoma; Middle Aged; Aged; Tumor Microenvironment; B7-H1 Antigen; HLA-G Antigens; Programmed Cell Death 1 Ligand 2 Protein; Prognosis; CD8-Positive T-Lymphocytes; Adult; T-Lymphocytes, Regulatory; Aged, 80 and over; Macrophages
PubMed: 38954689
DOI: 10.1371/journal.pone.0305648 -
IEEE Journal of Biomedical and Health... Jul 2024Presents corrections to the paper, Multi-View Feature Transformation Based SVM+ for Computer-Aided Diagnosis of Liver Cancers With Ultrasound Image.
Presents corrections to the paper, Multi-View Feature Transformation Based SVM+ for Computer-Aided Diagnosis of Liver Cancers With Ultrasound Image.
Topics: Humans; Liver Neoplasms; Ultrasonography; Image Interpretation, Computer-Assisted; Support Vector Machine; Liver; Diagnosis, Computer-Assisted
PubMed: 38954561
DOI: 10.1109/JBHI.2024.3404528 -
Techniques in Coloproctology Jul 2024Bladder drainage is systematically used in rectal cancer surgery; however, the optimal type of drainage, transurethral catheterization (TUC) or suprapubic... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Bladder drainage is systematically used in rectal cancer surgery; however, the optimal type of drainage, transurethral catheterization (TUC) or suprapubic catheterization (SPC), is still controversial. The aim was to compare the rates of urinary tract infection on the fourth postoperative day (POD4) between TUC and SPC, after rectal cancer surgery regardless of the day of removal of the urinary drain.
METHODS
This randomized clinical trial in 19 expert colorectal surgery centers in France and Belgium was performed between October 2016 and October 2019 and included 240 men (with normal or subnormal voiding function) undergoing mesorectal excision with low anastomosis for rectal cancer. Patients were followed at postoperative days 4, 30, and 180.
RESULTS
In 208 patients (median age 66 years [IQR 58-71]) randomized to TUC (n = 99) or SPC (n = 109), the rate of urinary infection at POD4 was not significantly different whatever the type of drainage (11/99 (11.1%) vs. 8/109 (7.3%), 95% CI, - 4.2% to 11.7%; p = 0.35). There was significantly more pyuria in the TUC group (79/99 (79.0%) vs. (60/109 (60.9%), 95% CI, 5.7-30.0%; p = 0.004). No difference in bacteriuria was observed between the groups. Patients in the TUC group had a shorter duration of catheterization (median 4 [2-5] vs. 4 [3-5] days; p = 0.002). Drainage complications were more frequent in the SPC group at all followup visits.
CONCLUSIONS
TUC should be preferred over SPC in male patients undergoing surgery for mid and/or lower rectal cancers, owing to the lower rate of complications and shorter duration of catheterization.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT02922647.
Topics: Humans; Male; Rectal Neoplasms; Middle Aged; Aged; Urinary Catheterization; Drainage; Urinary Tract Infections; Postoperative Complications; Urinary Bladder; Belgium
PubMed: 38954131
DOI: 10.1007/s10151-024-02950-2 -
Cancer Immunology, Immunotherapy : CII Jul 2024Tissue-resident memory CD103+CD8+ T cells (CD103+CD8+ TRMs) are important components of anti-tumor immunity. However, the significance of CD103+CD8+ TRMs in colorectal...
BACKGROUND
Tissue-resident memory CD103+CD8+ T cells (CD103+CD8+ TRMs) are important components of anti-tumor immunity. However, the significance of CD103+CD8+ TRMs in colorectal cancer (CRC) and their advantages remain unclear.
METHODS
Clinical data and specimens were used to evaluate the significance of CD103+CD8+ TRMs in CRC. A mouse subcutaneous tumorigenesis model and colony-formation assay were conducted to evaluate the anti-tumor effects of CD103+CD8+ TRMs. Finally, the infiltration density and function of CD103+CD8+ TRMs in the tumors were evaluated using flow cytometry.
RESULTS
In this study, we showed that highly infiltrated CD103+CD8+ TRMs were associated with earlier clinical stage and negative VEGF expression in CRC patients and predicted a favorable prognosis for CRC/CRC liver metastases patients. Interestingly, we also found that CD103+CD8+ TRMs may have predictive potential for whether CRC develops liver metastasis in CRC. In addition, we found a positive correlation between the ratio of the number of α-SMA+ vessels to the sum of the number of α-SMA+ and CD31+ vessels in CRC, and the infiltration level of CD103+CD8+ TRMs. In addition, anti-angiogenic therapy promoted infiltration of CD103+CD8+ TRMs and enhanced their ability to secrete interferon (IFN)-γ, thus further improving the anti-tumor effect. Moreover, in vivo experiments showed that compared with peripheral blood CD8+ T cells, CD103+CD8+ TRMs infused back into the body could also further promote CD8+ T cells to infiltrate the tumor, and they had a stronger ability to secrete IFN-γ, which resulted in better anti-tumor effects.
CONCLUSION
We demonstrated that CD103+CD8+ TRMs have the potential for clinical applications and provide new ideas for combined anti-tumor therapeutic strategies, such as anti-tumor angiogenesis therapy and CAR-T combined immunotherapy.
Topics: Colorectal Neoplasms; Integrin alpha Chains; Animals; Humans; CD8-Positive T-Lymphocytes; Mice; Liver Neoplasms; Antigens, CD; Prognosis; Female; Male; Immunologic Memory; Biomarkers, Tumor; Memory T Cells; Lymphocytes, Tumor-Infiltrating; Middle Aged
PubMed: 38954030
DOI: 10.1007/s00262-024-03709-2 -
Cancer Immunology, Immunotherapy : CII Jul 2024Insofar as they play an important role in the pathogenesis of colorectal cancer (CRC), this study analyzes the serum profile of cytokines, chemokines, growth factors,...
Insofar as they play an important role in the pathogenesis of colorectal cancer (CRC), this study analyzes the serum profile of cytokines, chemokines, growth factors, and soluble receptors in patients with CRC and cancer-free controls as possible CRC signatures. Serum levels of 65 analytes were measured in patients with CRC and age- and sex-matched cancer-free controls using the ProcartaPlex Human Immune Monitoring 65-Plex Panel. Of the 65 tested analytes, 8 cytokines (CSF-3, IFN-γ, IL-12p70, IL-18, IL-20, MIF, TNF-α and TSLP), 8 chemokines (fractalkine, MIP-1β, BLC, Eotaxin-1, Eotaxin-2, IP-10, MIP-1a, MIP-3a), 2 growth factors (FGF-2, MMP-1), and 4 soluble receptors (APRIL, CD30, TNFRII, and TWEAK), were differentially expressed in CRC. ROC analysis confirmed the high association of TNF-α, BLC, Eotaxin-1, APRIL, and Tweak with AUC > 0.70, suggesting theranostic application. The expression of IFN-γ, IL-18, MIF, BLC, Eotaxin-1, Eotaxin-2, IP-10, and MMP1 was lower in metastatic compared to non-metastatic CRC; only AUC of MIF and MIP-1β were > 0.7. Moreover, MDC, IL-7, MIF, IL-21, and TNF-α are positively associated with tolerance to CRC chemotherapy (CT) (AUC > 0.7), whereas IL-31, Fractalkine, Eotaxin-1, and Eotaxin-2 were positively associated with resistance to CT. TNF-α, BLC, Eotaxin-1, APRIL, and Tweak may be used as first-line early detection of CRC. The variable levels of MIF and MIP-1β between metastatic and non-metastatic cases assign prognostic nature to these factors in CRC progression. Regarding tolerance to CT, MDC, IL-7, MIF, IL-21, and TNF-α are key when down-regulated or resistant to treatment is observed.
Topics: Humans; Colorectal Neoplasms; Female; Male; Cytokines; Middle Aged; Aged; Intercellular Signaling Peptides and Proteins; Chemokines; Treatment Outcome; Biomarkers, Tumor; Adult; Prognosis; Case-Control Studies
PubMed: 38954024
DOI: 10.1007/s00262-024-03746-x -
Cancer Immunology, Immunotherapy : CII Jul 2024In the intricate landscape of the tumor microenvironment, tumor-associated macrophages (TAMs) emerge as a ubiquitous cellular component that profoundly affects the... (Review)
Review
In the intricate landscape of the tumor microenvironment, tumor-associated macrophages (TAMs) emerge as a ubiquitous cellular component that profoundly affects the oncogenic process. The microenvironment of hepatocellular carcinoma (HCC) is characterized by a pronounced infiltration of TAMs, underscoring their pivotal role in modulating the trajectory of the disease. Amidst the evolving therapeutic paradigms for HCC, the strategic reprogramming of metabolic pathways presents a promising avenue for intervention, garnering escalating interest within the scientific community. Previous investigations have predominantly focused on elucidating the mechanisms of metabolic reprogramming in cancer cells without paying sufficient attention to understanding how TAM metabolic reprogramming, particularly lipid metabolism, affects the progression of HCC. In this review article, we intend to elucidate how TAMs exert their regulatory effects via diverse pathways such as E2F1-E2F2-CPT2, LKB1-AMPK, and mTORC1-SREBP, and discuss correlations of TAMs with these processes and the characteristics of relevant pathways in HCC progression by consolidating various studies on TAM lipid uptake, storage, synthesis, and catabolism. It is our hope that our summary could delineate the impact of specific mechanisms underlying TAM lipid metabolic reprogramming on HCC progression and provide useful information for future research on HCC and the development of new treatment strategies.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Lipid Metabolism; Tumor-Associated Macrophages; Tumor Microenvironment; Animals; Cellular Reprogramming; Signal Transduction; Metabolic Reprogramming
PubMed: 38954021
DOI: 10.1007/s00262-024-03748-9