Analytical Cellular Pathology (Amsterdam)最新文献

Tumor-associated macrophage (TAM) is a major component of tumor microenvironment (TME) and plays critical role in the progression of cancer metastasis. However, TAM-mediated regulation in gallbladder cancer (GBC) has not been fully characterized. Here, we found that exosomes derived from GBC cell polarized macrophage to M2 phenotype, which then facilitated the invasion and migration of GBC cells. We discovered that leptin was enriched in GBC cell-derived exosomes. Exosomal leptin levels promoted invasion and migration of GBC-SD cells. The inhibition of leptin not only attenuated M2 macrophage of polarization but also inhibited the invasive and migratory ability of GBC cell. In addition, GBC-SD cell-derived exosomal leptin induced M2 polarization of macrophage via activation of STAT3 signal pathway. Taken together, our results suggested that GBC cells secrete exosome-enclosed leptin facilitated cell invasion and migration via polarizing TAM.

Basal cell carcinoma (BCC) is the most common malignancy worldwide, with increasing incidence. BCCs present low mortality but high morbidity, and its pathogenesis remains unclear. Eph receptors have been implicated in tumorigenesis. EphA7 plays a role as a tumor suppressor in certain cancers. We checked EphA7 expression levels and methylation status in a set of BCCs, benign skin diseases, and compound nevus tissue samples using immunohistochemistry. EphA7 protein was positively expressed in normal basal cells, benign skin diseases, and compound nevus cells, but lost in areas of BCC tissues. We detected hypermethylation in BCC tissue samples with reduced expression of EphA7. There is a significant relationship between the expression level of EphA7 receptor protein and the methylation status of CpG islands in the EphA7 promoter region (P < 0.001). To our knowledge, this is the first study to report the EphA7 expression profile and hypermethylation of EphA7 in BCC. The role of the EphA7 gene and the status of hypermethylation in tumorigenesis and treatment of BCC warrant further investigation.

Diffuse large B cell lymphoma is the most common type of lymphoma in Egypt with an unfavorable prognosis. The tumor microenvironment is rich in immune response either T cells or macrophages. The current study is aimed at testing CD4, CD8, CD68, and MMP9 immunohistochemistry of DLBCL activities with the prognosis of the tumor. The results showed no positive relation between T cell and macrophage reaction to the tumor prognosis suggesting that this reaction is part of the tumor process and not a defense mechanism from the surrounding stroma.

[This corrects the article DOI: 10.1155/2021/7407086.].

Oral squamous cell carcinoma (OSCC) is a malignant tumour originating from the mucosal lining of the oral cavity. Its characteristics include hidden onset, high recurrence, and distant metastasis after operation. At present, clinical treatment usually includes surgery, chemotherapy, radiotherapy, or the joint use of these modalities. Unfortunately, multidrug resistant is one of the important obstacles that causes cancer chemotherapy failure. Anlotinib, which has recently been proven to have good antitumour effects, is a novel multitargeted tyrosine kinase inhibitor. However, there are few studies of the anlotinib-associated mechanism in OSCC and its underlying molecular mechanism. In our study, in vitro models of human oral squamous cell carcinoma HSC-3 cells were used to determine the efficacy of anlotinib. On the one hand, we showed that anlotinib treatment significantly reduced the viability and proliferation of HSC-3 cells and decreased cell migration by inhibiting the activation of the Akt phosphorylation pathway. On the other side, anlotinib inhibited PI3K/Akt/Bad phosphorylation and promoted apoptosis of HSC-3 cells by activating RAS protein expression. In brief, these results indicated that anlotinib had prominent antitumour activity in OSCC, mainly by inhibiting the PI3K/Akt phosphorylation pathway. This work provides evidences and a basic principle for using anlotinib to treat patients with OSCC for clinical research.

Objectives: To explore the role of microRNA-21-5p (miR-21-5p) in hypoxia/reoxygenation- (H/R-) induced HT22 cell damage.

Methods: The hypoxia/reoxygenation (H/R) model was established in mouse neuronal cells HT22. Cell Counting Kit-8 (CCK-8) and qRT-PCR were used to determine the effects of H/R treatment on cell viability and miR-21-5p expression. HT22 cells were transfected with miR-21-5p mimic or negative control (NC) followed by the induction of H/R; cell viability, apoptosis, and SOD, MDA, and LDH activities were detected. Besides, the apoptosis-related proteins including BAX, BCL2, cleaved caspase-3, and caspase-3 as well as proteins of EGFR/PI3K/AKT signaling pathways were measured by Western blot. To verify the target relation between cytoplasmic polyadenylation element binding protein 3 (CPEB3) and miR-21-5p, luciferase reporter gene experiment was performed. After cotransfection with miR-21-5p mimic and CPEB3 plasmids, the reversal effects of CPEB3 on miR-21-5p in H/R damage were studied.

Results: H/R treatment could significantly reduce the cell viability (P < 0.05) and miR-21-5p levels (P < 0.05) in HT22 cells. After overexpressing miR-21-5p, cell viability was increased (P < 0.05) under H/R treatment, and the apoptosis rate and the levels of apoptosis-related proteins were suppressed (all P < 0.05). Furthermore, SOD activity was increased (P < 0.05), while MDA and LDH activity was decreased (both P < 0.05). Besides, miR-21-5p could restore the activation of the EGFR/PI3K/AKT signaling pathway inhibited by H/R treatment (all P < 0.05). The luciferase reporter gene experiment verified that CPEB3 is the target of miR-21-5p (P < 0.05). When coexpressing miR-21-5p mimic and CPEB3 in the cells, the protective effects of miR-21-5p under H/R were reversed (all P < 0.05), and the activation of the EGFR/PI3K/AKT pathway was also inhibited (all P < 0.05).

Conclusion: This study showed that miR-21-5p may regulate the EGFR/PI3K/AKT signaling pathway by targeting CPEB3 to reduce H/R-induced cell damage and apoptosis.

This study is aimed at thoroughly exploring the expression status, clinical significance, and underlying molecular mechanism of miRNA-33a-5p in lung squamous cell carcinoma (LUSC). Here, we detected miRNA-33a-5p in 20 samples from patients with LUSCs and 20 matching non-LUSC specimens by in-house quantitative real-time PCR (RT-qPCR). Relationship between miRNA-33a-5p expression and clinicopathological traits was investigated from materials derived from miRNA sequencing and miRNA microarrays. A pool standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were calculated to evaluate the integrated expression value of miRNA-33a-5p in LUSC. Twelve online platforms were applied to select potential target genes of miRNA-33a-5p. The differentially expressed genes (DEGs) of LUSC and the candidate target genes of miRNA-33a-5p were overlapped to acquire a set of specific genes for further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interaction (PPI) network. miRNA-33a-5p overexpressed in LUSC was supported by 706 LUSC and 261 non-LUSC samples gathering from RT-qPCR, miRNA-seq, and public miRNA microarrays. The pooled SMD was 0.56 (95% CI: -0.01-1.05), and the area under the curve (AUC) of the SROC was 0.78 (95% CI: 0.74-0.82). A total of 240 genes were identified as potential target genes of miRNA-33a-5p for functional enrichment analyses; the results suggested that these target genes may participate in several vital biological processes that promote the proliferation and progression of LUSC. miRNA-33a-5p may play an essential role in the occurrence and development of LUSC by targeting hub genes (ETS1, EDNRB, CYR61, and LRRK2) derived from the PPI network. In summary, our results indicated that miRNA-33a-5p may contribute as a prospective therapeutic target in LUSC.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and affects about 8% of cirrhotic patients, with a recurrence rate of over 50%. There are numerous therapies available for the treatment of HCC, depending on cancer staging and condition of the patient. The complexity of the treatment is also justified by the unique pathogenesis of HCC that involves intricate processes such as chronic inflammation, fibrosis, and multiple molecular carcinogenesis events. During the last three decades, multiple in vivo and in vitro experiments have used somatostatin and its analogs (SSAs) to reduce the proliferative and metastatic potential of hepatoma cells by inducing their apoptosis and reducing angiogenesis and the inflammatory component of HCC. Most experiments have proven successful, revealing several different pathways and mechanisms corresponding to the aforementioned functions. Moreover, a correlation between specific effects and expression of somatostatin receptors (SSTRs) was observed in the studied cells. Clinical trials have tested either somatostatin or an analog, alone or in combination with other drugs, to explore the potential effects on HCC patients, in various stages of the disease. While the majority of these clinical trials exhibited minor to moderate success, some other studies were inconclusive or even reported negative outcomes. A complete evaluation of the efficacy of somatostatin and SSAs is still the matter of intense debate, and, if deemed useful, these substances may play a beneficial role in the management of HCC patients.

This study is aimed at establishing a lipopolysaccharide- (LPS-) induced primary ovarian insufficiency (POI) mouse model and investigating the underlying mechanism. C57BL/6N female mice were intraperitoneally injected with low-dose LPS (0.5 mg/kg) once daily for 14 days, high-dose LPS (2.5 mg/kg) twice weekly for 2 weeks, or cyclophosphamide (CTX; 150 mg/kg) once weekly for 2 weeks. Ovarian function was assessed by measuring the length of estrous cycle, the number of primordial follicles, and the levels of serum hormones. Expression and production of interleukin 1β (IL-1β) were determined to evaluate ovarian inflammation. Histopathological examination was performed to examine ovarian fibrosis. TUNEL assay was carried out to evaluate granulosa cell apoptosis. Western blotting was performed to measure the levels of inflammation-, fibrosis-, and apoptosis-related proteins in the mouse ovaries. Like CTX, both low- and high-dose LPS significantly impaired ovarian functions in mice, as evidenced by extended lengths of estrous cycles, reduced counts of primordial follicles, and alterations in the levels of serum hormones. Also, LPS promoted granulosa cell apoptosis and ovarian fibrosis in mice. However, LPS but not CTX promoted IL-1β expression and production in mice. Moreover, LPS but not CTX enhanced TLR, p-p65, p65, and MyD88 expression in mouse ovaries, suggesting that LPS differs from CTX in triggering ovarian inflammation. In general, continuous low-dose LPS stimulation was less potent than high-dose LPS to affect the ovarian functions. In conclusion, LPS may induce ovarian inflammation, fibrosis, and granulosa cell apoptosis and can be used to establish a POI model in mice.

Background: Hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) are the common diagnostic/prognostic markers in breast cancer. Few articles have recently reported the correlation between cytology and molecular subtypes. We combined nuclear morphological characteristics with HR and HER2 status to observe the relationship and provide ideas for machine learning.

Methods: We reanalyzed fine-needle aspiration cytology samples and core-needle puncture histological specimens from 142 patients with invasive breast cancer between March 2019 and December 2019, and the findings were compared with the two groups (HR+/HER2- and HR-/HER2+) following nuclear cytomorphological features: nuclear/cytoplasmic ratio, difference of nuclear size, nuclear pleomorphism, chromatin feature, nuclear membrane and nucleoli, and Nottingham grading.

Results: Two groups were significantly associated with the difference of nuclear size, nuclear pleomorphism, and nucleoli (P < 0.001) and consistent with histological grading (P < 0.001). Moreover, nucleolar characteristics of size and number had obviously statistical significance (P < 0.001). Multiple micro-nucleoli were frequently seen in the HR+/HER2- group compared with the HR-/HER2+ group which mostly were observed centered medium-large nucleoli. We described four interesting nuclear morphologies in the experiment.

Conclusions: There were significant differences in nuclear characteristics between two groups. HR and HER2 status not only might be predicted in cytological samples, but some specific nuclear morphological features might have potential value to help us understand molecular function and predict more information.