Analytical Cellular Pathology最新文献

Objective: To study the expression, biological function, and mechanism of FKBP4 in non-small-cell lung cancer (NSCLC).

Methods: First of all, the expression of FKBP4 in NSCLC tissues and cell lines was detected by qRT-PCR; then, the effects of FKBP4 on proliferation, apoptosis, migration, and invasion of NSCLC were studied by CCK-8 assays, flow cytometry assays, wound-healing assays, and Transwell assays. After that, tumor xenografts were used to explore the effect of FKBP4 on NSCLC tumor growth in vivo, and the phosphorylation of Akt and mTOR was measured by western blot.

Results: FKBP4 was highly expressed in NSCLC tissues and cells, and its expression was closely related to NSCLC tumor size, lymph node metastasis, and patient prognosis. In vitro, FKBP4 can promote NSCLC cell proliferation, migration, and invasion and inhibit NSCLC cell apoptosis. In vivo, FKBP4 can promote NSCLC tumor growth. Furthermore, FKBP4 can promote Akt and mTOR phosphorylation and activate the Akt/mTOR signaling pathway and an mTOR inhibitor can neutralize the functions of FKBP4 in NSCLC cells.

Conclusion: FKBP4 serves as an oncogene to promote malignant processes in NSCLC, and it has the potential to be used as a biological marker and therapeutic target for NSCLC.

Summary. Oxidative stress is an important factor that is related to endothelial dysfunction. ATP-binding cassette transporter G1 (ABCG1), a regulator of intracellular cholesterol efflux, has been found to prevent endothelial activation in vessel walls. To explore the role of ABCG1 in oxidative stress production in endothelial cells, HUAECs were exposed to H₂O₂ and transfected with the specific ABCG1 siRNA or ABCG1 overexpression plasmid. The results showed that overexpression of ABCG1 by ABCG1 plasmid or liver X receptor (LXR) agonist T0901317 treatment inhibited ROS production and MDA content induced by H₂O₂ in HUAECs. Furthermore, ABCG1 upregulation blunted the activity of prooxidant NADPH oxidase and the expression of Nox4, one of the NADPH oxidase subunits. Moreover, the increased migration of Nrf2 from the cytoplasm to the nucleus and antioxidant HO-1 expression were detected in HUAECs with upregulation of ABCG1. Conversely, ABCG1 downregulation by ABCG1 siRNA increased NADPH oxidase activity and Nox4 expression and abrogated the increase at Nrf2 nuclear protein levels. In addition, intracellular cholesterol load interfered with the balance between NADPH oxidase activity and HO-1 expression. It was suggested that ABCG1 attenuated oxidative stress induced by H₂O₂ in endothelial cells, which might be involved in the balance between decreased NADPH oxidase activity and increased Nrf2/OH-1 antioxidant defense signaling via its regulation for intracellular cholesterol accumulation.

Breast cancer is the leading cause of females characterized by high invasive potential. It is necessary to explore the underlying mechanism of breast cancer metastases and to find specific therapeutic targets. PKM2 is considered a new biomarker of cancer with upregulated expression in tumor tissue. PKM2 participates in the cancer-specific Warburg effect to regulate fast glucose intake consumption. Besides, PKM2 also contributes to cancer progression, especially tumor metastasis. In this study, we showed that PKM2 is upregulated in breast cancer tissues and the upregulating of PKM2 in breast cancer correlates with poor prognosis. PKM2 can regulate tumor progression by promoting tumor cell viability and mobility. Furthermore, overexpression of PKM2 can promote EMT to encourage tumor metastasis. These findings indicate PKM2 is a potentially useful diagnostic biomarker and therapeutic target in breast cancer.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for the development of a new coronavirus disease (COVID-19), is a highly transmittable virus which, in just ten months, infected more than 40 million people in 214 countries worldwide. After inhalation, aerosols containing SARS-CoV-2 penetrate to the depths of the lungs and cause severe pneumonia, alveolar injury, and life-threatening acute respiratory distress syndrome (ARDS). Since there are no specific drugs or vaccines available to cure or prevent COVID-19 infection and COVID-19-related ARDS, a new therapeutic agent which will support oxygen supply and, at the same time, efficiently alleviate SARS-CoV-2-induced lung inflammation is urgently needed. Due to their potent immuno- and angiomodulatory characteristics, mesenchymal stem cells (MSCs) may increase oxygen supply in the lungs and may efficiently alleviate ongoing lung inflammation, including SARS-CoV-2-induced ARDS. In this review article, we described molecular mechanisms that are responsible for MSC-based modulation of immune cells which play a pathogenic role in the development of SARS-CoV-2-induced ARDS and we provided a brief outline of already conducted and ongoing clinical studies that increase our understanding about the therapeutic potential of MSCs and their secretome in the therapy of COVID-19-related ARDS.

Objectives: To observe the effect of Inonotus obliquus polysaccharide (IOP) on the proliferation, invasion, migration, and apoptosis of osteosarcoma cells and to elucidate its underlying molecular mechanism.

Methods: IOP was extracted from Inonotus obliquus, human osteosarcoma MG-63 cells and U2OS cells were cultured in vitro, and the effects of IOP on the proliferation, migration, invasion, and apoptosis of MG-63 cells and U2OS cells were determined by CCK-8 assays, cell scratch assays, transwell assays, and flow cytometry, respectively. Western blot was used to detect the expression of related proteins in the Akt/mTOR and NF-κB signaling pathways.

Results: Compared with the control group, MG-63 cells and U2OS cells treated with IOP of 80 μg/ml, 160 μg/ml, and 320 μ g/ml in the experimental group had significantly lower proliferation activity, decreased migration and invasion ability, and increased apoptosis rate (P < 0.05). Furthermore, IOP could significantly inhibit the activation of the Akt/mTOR and NF-κB signaling pathway (P < 0.05).

Conclusion: IOP can regulate the proliferation, migration, invasion, and apoptosis of osteosarcoma cells by inhibiting the activation of the Akt/mTOR signaling pathway. It has antitumor activity on osteosarcoma and has the potential of clinical application in osteosarcoma treatment.

Papillary adenoma of the lung is a rather rare tumor. We will present a case of papillary adenoma in the lung with malignant transformation in a 65-year-old male patient. A high dense soft tissue mass was detected in the lateral segment of the right middle lobe by CT examination. Cytologically, the tumor contained the benign cells similar to normal alveolar epithelium and the malignant cells which were significantly enlarged and irregular, crowded, or overlapping. Immunohistochemical staining showed that the epithelial cells were diffusely positive for TTF-1, napsin-A, and CK7, but were negative for p63, p40, CK5/6, CgA, Syn, CD56, and TG. The Ki67 index was about 5%. All of these evidences indicated that it was a case of papillary adenoma with malignant transformation. Thus, it should be noted that more active treatment measures should be taken to treat pulmonary papillary adenoma.

Bladder cancer (BC) is one of the tumors which occur most frequently in urological system, but less is known about the expression of tight junction proteins and its clinical significance in BC. In this study, expression of claudin-4, zonula occludens-1 (ZO-1) and zonula occludens-1 nucleic acid-binding protein (ZONAB), in BC tissues, adjacent nontumor tissue (ANTT), and BC cell lines was examined by Western blotting, semiquantitative RT-PCR, and immunohistochemistry, and then, the clinical significance of these proteins was investigated. The mRNA and protein expression of ZONAB were significantly upregulated, while those of ZO-1 was significantly downregulated in some BC cell lines and tissues in comparison with nontumor urothelial cell lines and ANTT. High expression rate of ZO-1 and ZONAB had negative correlation in BC tissues and was also correlated with muscle-invasive lesions in BC tissues. In conclusion, the expression of tight junction proteins is significantly altered in BC and ZO-1, and ZONAB interaction might be involved in BC development.

Background: Tumor budding is a promising prognostic indicator in several cancers especially in colorectal cancer. However, only few studies have been conducted to assess and validate its prognostic value in laryngeal squamous cell carcinoma; none of which used pancytokeratin immunohistochemistry. In view of the modest results of treatment of laryngeal squamous cell carcinoma, the need of new prognostic indicators becomes of paramount importance. Aim of the Study. We aim to evaluate tumor budding in laryngeal squamous cell carcinoma, by haematoxylin and eosin, as well as by pancytokeratin immunohistochemistry. Material and Methods. A retrospective study on 118 cases of laryngeal squamous cell carcinoma from archives of Pathology Lab of Ain Shams University Specialized Hospital and Ain Shams University Hospitals from January 2014 to January 2017. The ENT and histopathology reports were reviewed to determine clinicopathologic data of the patients.

Results: Tumor budding shows high statistically significant relations (p = 0.0001 for each) with important clinicopathological parameters of laryngeal carcinoma (site, grade, tumor stage, lymph node stage, lymph node extracapsular invasion, and vascular invasion). The extent of tumor budding correlated with overall survival, local recurrence disease free, and distant metastasis disease free (p = 0.001 for each). Multivariate analysis showed tumor budding to be an independent prognostic factor affecting progression-free survival. There was a moderate agreement between H&E and IHC by pancytokeratin as regards detection of budding among study cases (kappa = 0.593).

Conclusions: Tumor budding was correlated with poor prognostic clinicopathologic indicators in laryngeal squamous cell carcinoma. It is recommended to use pancytokeratin immunohistochemistry to evaluate tumor budding in laryngeal squamous cell carcinoma especially in confusing cases.

Background: PD-L1 expression is an important predictive factor of response to therapy with immune checkpoint inhibitors (ICIs). This study was designed to retrospectively analyze the concordance of PD-L1 measurements using three different assays (Dako22C3, Dako28-8, and SP142) in NSCLC patients and to find possible predictors of high PD-L1 expression.

Materials and methods: Data of 144 patients with histologically confirmed NSCLC and available PD-L1 measurements treated at the Taoyuan General Hospital from 2018 to 2019 were retrospectively reviewed in the study. Patients' characteristics, including age, sex, clinical stage (T, N, and M) of NSCLC (AJCC, 8^th edition), and EGFR/ALK alterations, were analyzed for association with PD-L1 expression.

Results: Measurements of PD-L1 expression levels with Dako22C3 and Dako28-8 were comparable while SP142 showed lower levels of PD-L1 expression. The overall agreement between Dako22C3 and Dako28-8 was 82.2% and 91.6% for both 1% and 50% TPS cut-offs, respectively. The above findings were confirmed by Cohen's kappa. In addition, we found that PD-L1 expression was significantly associated with advanced N stage but not with T and M stages.

Conclusion: Dako22C3 and Dako28-8 showed comparable results in assessing PD-L1 levels. Future prospective studies are needed to validate these findings. N stage may be a good predictor for PD-L1 expression.

The application of ultrasound and microbubbles (USMB-) mediated microRNA (miR) is a promising approach of gene delivery for cancer treatment. We aimed to discuss the effects of USMB-miR-505 on cervical cancer (CC) development. miR-505 mediated by USMB was prepared. The effect of miR-505 on its transfection efficiency and the effect of miR-505 on HeLa cell proliferation, cell cycle, apoptosis, migration, and invasion were studied. The target gene of miR-505 was predicted, and its expression in CC was detected. The effect of the target gene on HeLa cells was further verified. USMB-miR-505 showed a higher transfection efficiency than miR-505 alone. The inhibitory effect of miR-505 mediated by USMB on HeLa cells was better than miR-505. miR-505 targeted AKT2, which was upregulated in CC. Overexpression of AKT2 reversed the inhibitory effect of USMB-miR-505 on HeLa cell malignant behaviors. Overall, we highlighted that USMB-miR-505 inhibited HeLa cell malignant behaviors by targeting AKT2.