Histology and histopathology最新文献

Meningiomas are the most common primary intracranial neoplasms. Although they mostly exhibit a benign course, some cases recur after surgery and show high morbidity and mortality rates. In addition to currently established prognostic factors, such as the extent of surgical resection and tumor grade assessed according to World Health Organization (WHO) criteria, the prognostic significance of the immunohistochemical loss of Histone 3 trimethylation in Lysine 27 (H3 K27me3) has emerged in meningiomas. This review examined original studies that analyzed the immunohistochemical expression of H3 K27me3 in meningiomas and its correlation with various features, including overall survival (OS), recurrence-free survival (RFS), and WHO grade. A literature search was conducted in PubMed for English-language publications up to July 8, 2024. Sixteen studies were included in this review. In summary, current evidence indicates that H3 K27me3 loss is more frequent in tumors exhibiting higher biological aggressiveness, as reflected by a significant association with a higher WHO grade, proliferative index, and prognostically unfavorable methylation classes. In addition, published studies consistently indicate a negative prognostic significance for progression-recurrence-free survival (PFS/RFS) in WHO grade 2 meningiomas and OS in WHO grade 3 tumors. However, the lack of a standardized definition for H3 K27me3 loss significantly hampers the incorporation of the H3 K27me3 immunohistochemical assay into routine practice to establish the prognosis of meningiomas.

Objective: The study aimed to examine the impact of melatonin on mitigating brain inflammation and cough sensitivity resulting from exposure to particulate matter 2.5 (PM2.5).

Methods: Guinea pigs were randomly assigned to the blank control group, normal saline group, PM2.5 exposure group, and PM2.5 exposure + melatonin group. The PM2.5 exposure and PM2.5 exposure + melatonin groups were given intranasal instillations of PM2.5 suspension twice daily for 28 consecutive days. Starting on day 21, the PM2.5 exposure + melatonin group was treated with an intraperitoneal injection of melatonin at 10 pm. Cough sensitivity to citric acid, microglia activation, IL-1β and TNF-α levels in the airway and dorsal vagal complex (DVC), and ultrastructural changes in neurons within the DVC were assessed.

Results: The PM2.5 exposure group exhibited a significantly higher cough count to citric acid challenge (29.1±5.7 coughs) compared with the PM2.5 exposure + melatonin group (18.8±4.1 coughs), normal saline group (8.4±2.1 coughs), and blank control group (7.7±1.8 coughs). In addition, cough latency was shorter in the PM2.5 exposure group (26.9±6.5 seconds) than in the PM2.5 exposure + melatonin group (36.6±12.4 seconds), normal saline group (43.4±14.7 seconds), and blank control group (47.0±13.0 seconds). The PM2.5 exposure + melatonin group showed significantly reduced IL-1β (105.3±14.3 pg/ml) and TNF-α levels (113.0±23.5 pg/ml) in the DVC, as well as in the bronchoalveolar lavage fluid (IL-1β: 24.92±5.14 pg/ml, TNF-α: 12.72±3.99 pg/ml) compared with the PM2.5 exposure group (in the DVC: IL-1β: 132.7±17.6 pg/ml, TNF-α: 143.8±30.4 pg/ml; in the bronchoalveolar lavage fluid: IL-1β: 34.0±5.3 pg/ml; TNF-α: 15.8±0.8 pg/ml). Microglia in the DVC were less activated in the PM2.5 exposure + melatonin group (25.1±5.4) than in the PM2.5 exposure group (54.6±9.9). Furthermore, the PM2.5 exposure group exhibited an impaired blood-brain barrier in the DVC, which tended to alleviate the PM2.5 exposure + melatonin group.

Conclusions: Exposure to PM2.5 induces airway inflammation, central facilitation, and heightened cough sensitivity in guinea pigs. Melatonin significantly inhibits microglia activation and reduces airway and DVC inflammation, which might contribute to attenuated cough hypersensitivity.

Background: Hepatocellular carcinoma (HCC) is a cancer with high morbidity and mortality. There are limited treatment options, particularly for chemotherapy-resistant HCC patients. Circular RNA hsa_circ_0088036 was associated with the development of bladder cancer and non-small cell lung cancer. However, whether it might be a potential therapeutic target for HCC remains elusive.

Methods: Hsa_circ_0088036 expression was detected in HCC tumor tissues and cell lines using real-time PCR. The influences of hsa_circ_0088036 on proliferation and invasion as well as chemotherapy sensitivity in HCC cells were investigated by gain- and loss-of-function analyses. Associations among hsa_circ_0088036, miR-140-3p, and KIF2A were validated by real-time PCR, miRNA pull-down assay, dual-luciferase reporter assay, and western blot. Furthermore, a rescue experiment using KIF2A overexpression was performed to evaluate the regulatory mechanism of hsa_circ_0088036 in HCC cells. Additionally, the effect and mechanism of hsa_circ_0088036 were confirmed in a xenograft mouse model.

Results: Hsa_circ_0088036 was highly expressed in HCC tissues and cells, with even higher expression in oxaliplatin-resistant cells. This expression was positively correlated with tumor size and TNM stage of the patients. Overexpression of hsa_circ_0088036 promoted the proliferation and invasion of HCC cells, while silencing mediated the opposite effects. Meanwhile, knockdown of hsa_circ_0088036 enhanced chemotherapy sensitivity, including oxaliplatin, doxorubicin, and sorafenib, in HCC cells. Furthermore, hsa_circ_0088036 silencing inhibited tumor growth and increased oxaliplatin sensitivity in vivo. Mechanically, hsa_circ_0088036 functioned via the miR-140-3p/KIF2A axis with the activation of PI3K/Akt and Notch signaling pathways.

Conclusions: Hsa_circ_0088036 promoted HCC tumorigenesis and chemotherapy resistance by activating the PI3K/Akt and Notch pathways through regulating miR-140-3p/KIF2A signaling. Thus, hsa_circ_0088036 may be a potential therapeutic target in chemotherapy-resistant HCC.

Antibody-Drug Conjugates (ADCs) represent a promising class of anti-cancer substances that combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs, hence they enable a new approach of targeted therapy. The use of the ADC Entfortumab Vedotin (EV), which targets the viral receptor Nectin-4, showed an impressive clinical response in metastatic urothelial carcinoma. In this review, we present what is known about the expression of Nectin-4 in various tumor entities, focusing on immunohistochemistry as a diagnostic venue to detect positive expression, as this inexpensive technique is readily available in pathology laboratories. Various studies demonstrated expression of Nectin-4 in many solid tumor entities with the highest expression rates in urothelial carcinomas and breast cancer. To date, the relevance of the subcellular compartment of immunoreactivity (membranous vs. cytoplasmic) is still unclear in respect of its predictive value for EV therapy, which ought to be clarified in further studies.

This study aims to detect the expression of phosphorylated PERK in breast cancer using immunohistochemistry and explore its significance. We examined 134 cases of formalin-fixed and paraffin-embedded breast cancer tissues. It was found that the expression of phosphorylated PERK in ductal carcinoma was higher than that in lobular carcinoma, and the difference between them was statistically significant, suggesting that phosphorylated PERK played different roles in the occurrence and development of different types of breast cancer. Compared with Ki-67-negative breast cancer tissues, phosphorylated PERK has higher expression in Ki-67-positive tissues and is positively correlated with Ki67 expression, indicating that phosphorylated PERK plays an important role in breast cancer's malignant proliferation and progression. We also found a positive correlation between phosphorylated PERK expression and the histological grading of invasive ductal carcinoma, indicating that phosphorylated PERK plays an important role in the differentiation of invasive ductal carcinoma. Our study revealed the differential expression of phosphorylated PERK in subtypes of breast cancer. It contributed to the malignant proliferation of breast cancer and tissue differentiation of invasive ductal carcinoma of the breast.

Penile cancer is an uncommon disease compared with other urological tumors and is more common in low- and middle-income countries. Risk factors include age, ethnicity, smoking, hygiene, and human papillomavirus infection. Although carcinoma of the penis can be cured in up to 80% of cases if detected early, late diagnosis drastically reduces survival rates, especially in metastatic cases. More than 95% of cases are squamous cell carcinomas, and the degree of cell differentiation is a key histopathological factor, distinguishing between poorly (P), moderately (M), and well-differentiated (W) carcinomas, with verrucous carcinoma (V) having the best prognosis due to its low metastatic capacity. This study analyses the differential expression of several biomarkers related to cell proliferation and cell cycle, inflammation, epigenetics, and autophagy (cell cycle (IRS-4, Ki-67, RB1, CDK4, cyclin D1, ERBB2, β-catenin, and MAGE-A), inflammation (COX2, NLRP3, and AIF-1), epigenetics (HAT-1) and autophagy (ULK-1 and ATG9A) in penile carcinoma according to the degree of differentiation. Immunohistochemical techniques were performed on 34 penile squamous cell carcinoma (PSCC) samples classified into subtype V (N=6), and groups P (N=9), M (N=9), and W (N=10). The findings suggest a differential expression of molecules according to the degree of cell differentiation, with a higher differential expression of molecules according to the degree of cell differentiation, suggesting that the proteins studied could have predictive value. The study highlights the complexity of PSCC and the need for future studies to explore translational applications and search for new biomarkers to improve clinical management and understanding of this disease.

Objective: This study aimed to explore the correlation of PIM-1 with the clinicopathological features and prognosis of patients.

Method: The MTERF3 mRNA and protein expression levels in tissues were detected by western blot and immunohistochemistry. The expression and survival of PIM-1 in patients with glioma were analysed using the Gene Expression Profiling Interactive Analysis database, the Gene Expression Database of Normal and Tumor Tissues 2, and the Chinese Glioma Genome Atlas database. The relationship between PIM-1 expression and immune cells and chemokines was analysed using the Tumor Immune Estimation Resource Version 2.0 tool and the Tumor and Immune System Interactions Database. A Kaplan-Meier plot was used to estimate the correlation between PIM-1 expression and the survival of patients with glioma.

Results: The expression of PIM-1 was upregulated in glioma and was positively correlated with tumour grade. The expression of PIM-1 was significantly inhibited on the second day after transfection (p<0.05), and the inhibition was most obvious on the sixth day (p<0.01). The results of the co-expression pattern of PIM-1 showed that the expression of 5,012 genes was positively correlated with PIM-1, while the expression of 3,651 genes was negatively correlated with PIM-1. Macrophages (p<0.001), myeloid dendritic cells (p<0.001), NK cells (p<0.001), CD4 T cells (p<0.001), cancer-associated fibroblasts (p<0.001), and neutrophils (p<0.001) were positively correlated with the expression of PIM-1 in low-grade glioma.

Conclusion: PIM-1 is overexpressed in glioma and is related to the prognosis of glioblastoma multiforme, and PIM-1 may be a prognostic biomarker and therapeutic target for glioma.

As a common reproductive malignancy of the female reproductive system, cervical cancer has increasingly become a public health concern. Paeonol, which is a natural phenolic monomer, has been found to possess substantial anticancer effects in some human cancers. The present study was conceived to explore the role and mechanism of paeonol in cervical cancer. Initially, the cytotoxicity of paeonol on immortalized H8 cervical epithelial cells and the proliferation of SiHa cervical cancer cells with paeonol treatment were detected using the CCK-8 assay. Cell stemness was assessed with the spheroid formation assay while western blot was applied for the measurement of proteins associated with cell stemness. The tube formation assay was used to detect the angiogenesis of human umbilical vein endothelial cells (HUVECs) and western blot was used to estimate the expression of EMT- and angiogenesis-related proteins. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of cells were appraised via a Seahorse XFe24 Flux Analyzer. Lactate production, glucose consumption, and ATP levels were evaluated with corresponding assay kits. Western blot was applied for the evaluation of GLUT1 and HK2. The mRNA and protein expression of BACH1 before and after transfection were detected using RT-qPCR and western blot. The luciferase reporter assay was used to detect the activities of GLUT1 and HK2 promoters. In this study, we found that paeonol inhibited cell proliferation, cell stemness, EMT progress, angiogenesis, and glycolysis in cervical cancer via downregulating BACH1. In summary, paeonol impeded the progression of cervical cancer by regulating glycolytic metabolism through the inhibition of BACH1.

Cervical cancer (CC) is one of the most common gynecological malignancies in the world and poses a great threat to public health. There is inadequate knowledge of the molecular mechanisms underlying CC. This study aimed to explore the prognostic value of KIAA1429 (VIRMA, vir-Like m6A methyltransferase associated) in patients with CC and analyze its molecular mechanisms. The level of KIAA1429 in tumor specimens was tested using RT-qPCR and western blotting. Cellular biological processes were assessed using CCK-8 and Transwell assays. Xenograft experiments were used to verify the function of KIAA1429 in CC in vivo. The results manifested that KIAA1429 expression was enhanced in CC. Downregulation of KIAA1429 hindered the viability, migration, and invasion of CC cells. Moreover, LARP1 (La-related protein 1) was uncovered to be positively modulated by KIAA1429. Further, the anti-tumor impacts of KIAA1429 depletion on the phenotype of CC cells were counteracted by LARP1 amplification. Additionally, KIAA1429 deficiency suppressed the stability of LARP1 through methylating LARP1. Collectively, KIAA1429 can boost the tumorigenesis of CC via modifying LARP1 through m6A methylation to promote its stability. This work highlights the promoting effects of KIAA1429 on CC development and presents new targets for its treatment.

Background: Berberine is an active compound found in different herbs used in Chinese medicine and is well-known for its potential anticancer properties. The study aimed to figure out the role of berberine in regulating the malignant behavior of laryngeal squamous cell carcinoma (LSCC) cells.

Methods: LSCC cell lines (SNU-899 and AMC-HN-8) were treated with different concentrations of berberine (0-200 μM) to determine its cytotoxicity. The migration, invasion, and apoptosis of LSCC cells were measured by wound healing assays, Transwell assays, and flow cytometry. Western blot was performed for the quantification of proteins involved in PI3K/AKT/mTOR signaling.

Results: The viability of LSCC cells was dose-dependently reduced by berberine. Berberine dampened LSCC cell migration and invasion while augmenting cell apoptosis, as evidenced by a reduced wound closure rate, a decrease in invaded cell number, and a surge in cell apoptosis in the context of berberine stimulation. Importantly, the effects of berberine on the cancer cell process were enhanced by LY294002 (an inhibitor for PI3K) treatment. Moreover, the protein levels of phosphorylated PI3K, AKT, and mTOR were markedly reduced in response to berberine treatment.

Conclusion: Berberine inhibits cell viability, migration, and invasion but augments cell apoptosis by inactivating PI3K/AKT/mTOR signaling in LSCC.