Histology and histopathology Vol.37, nº5 (2022)

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  • Publication
    Open Access
    Differential expression of Tim3 protein in colorectal cancer associated with MSI and Braf mutation
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) He, Shuyan; Lin, Qingfeng; Chen, Jie; Ma, Chenglong; Liu, Zhili; Sun, Yuejun; Mao, Weidong; Shen, Dong; Wang, Jiandong
    Tim3 is a negative immune checkpoint molecule and plays a crucial part in tumor-induced immune suppression. Tim3 is a cell surface molecule expressed on T cells marking dysfunctional CD8+ cells in various kinds of cancers. Tim3 expression was mainly reported in tumor-infiltrating lymphocytes (TILs). There are few studies focusing on the expression of Tim3 in tumor cells. Immunohistochemistry was performed to determine Tim3 expression level. The relationships between Tim3 expression in colorectal cancer cells and in tumor-infiltrating lymphocytes and cilicopathological parameters were statistically analyzed. Tim3 was differentially detected in TILs and in colorectal cancer cells. Positive expression of Tim3 in colorectal cancer cells was associated with tumor location (P=0.001), depth of tumor invasion (P<0.001), lymph node metastasis (P=0.001), TNM stage (P=0.001), MSI (P=0.008), and Braf V600E mutation (P=0.001). On the other hand, positive expression of Tim3 in TILs was only related to depth of tumor invasion (P<0.001). Positive expression of Tim3 in both colorectal cancer cells and TILs was associated with depth of tumor invasion (P<0.001), lymph node metastasis (P=0.002), TNM stage (P=0.002), MSI (P=0.039), and Braf V600E mutation (P=0.009). Kaplan-Meier survival analysis showed that Tim3 expression in colorectal cancer and in TILs was significantly associated with patient overall survival (OS) rate (P=0.039, and 0.001). Tim3 may be a potential prognostic marker and a therapy target for colorectal cancer.
  • Publication
    Open Access
    Histopathological evaluation of insulin-DMSO formula designed for direct nose-to-brain delivery
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Maher, Mustafa A.; Kandeel, Wafaa A.; Hammam, Olfat A.; Attia, Yasmeen M.; Mahmoud, Soheir; Salah, Mohamed
    The combination of insulin and DMSO is a patented (Publication No US8987199B2), noninvasive, pharmaceutically strategized preparation for direct noseto-brain delivery (DN2BD) suggested for the treatment of Alzheimer’s disease (AD). Although its main ingredients have been individually researched, no histopathological investigations have been conducted to address this combination effect on the CNS and nasal tissues in animals. The present work was, therefore, designed to investigate the potential histopathological changes induced by this new pharmaceutical combination using a newly developed refractory staining method. The findings presented herein showed no signs of treatment-related lesions or behavioral changes in Sprague Dawley rats following a three-month successive treatment with two strengths of the formula.
  • Publication
    Open Access
    Prognostic role of IRS-4 in the survival of patients with pancreatic cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Ortega, Miguel A; Pekarek, Leonel; Garcia Montero, Cielo; Fraile Martinez, Oscar; Saez, Miguel A; Asúnsolo, Angel; Alvarez Mon, Miguel A; Monserrat, Jorge; Coca, Santiago; Toledo Lobo, M. Val; García Honduvilla, Natalio; Albillos, Agustin; Buján, Julia; Alvarez Mon, Melchor; Guijarro, Luis G
    Pancreatic cancer is a malignancy of rising incidence, especially in developed countries due to causes such as sedentary lifestyles, tobacco smoking and ultraprocessed high fat and high sugar diets, amongst others. It is in fact the 7th cause of cancer-related deaths worldwide, and, in the following years, it is expected to climb upwards to 2nd position, after lung cancer. This is because it may have an asymptomatic course, and when it becomes evident it is in advanced stages, accompanied by metastasis generally. For this reason, survival rates are so low and, even in the few successful cases there is a high possibility of recurrence. Identifying new molecular biomarkers is arising as a highly useful tool for pancreatic cancer clinical management, although much research and work remain to be done in this field. Thus, the present study aims to analyze a series of molecules (IRS-4, Rb1, Ki-67 y COX-2) as candidates for prognosis and survival by immunohistochemistry techniques. Additionally, a 60-month longitudinal surveillance program was conducted, associated with diverse clinical parameters. Kaplan-Meier curves estimating the time of survival according to tumoral expression of those molecules denoted a low cumulative survival rate. Importantly, we observed that high levels of IRS-4 were significantly associated with a bad prognosis of the disease, increasing 160 times the mortality risk. In this way, our research showed a relevant value of these biomarkers in pancreatic cancer patients’ survival, opening a pathway for future research areas designed to inhibit these components
  • Publication
    Open Access
    Lidocaine represses the malignant behavior of lung carcinoma cells via the circ_PDZD8/miR-516b-5p/GOLT1A axis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Zi, Huafen; Chen, Li; Ruan, Qian
    Lung carcinoma is the most prevalent malignancy in adults. Lidocaine (Lido) has been confirmed to exert an anti-tumor role in many human cancers. However, the role and underlying mechanism of Lido in lung carcinoma remain poorly understood. Cell proliferation ability, migration, invasion, and apoptosis were measured by Colony formation, 5-ethynyl-2'- deoxyuridine (EdU), Cell Counting Kit-8 (CCK-8), transwell, and flow cytometry assays. Circ_PDZD8, microRNA-516b-5p (miR-516b-5p), and Golgi transport 1A (GOLT1A) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Protein levels of proliferating cell nuclear antigen (PCNA) and GOLT1A were examined by western blot assay. The binding relationship between miR-516b-5p and circ_PDZD8 or GOLT1A was predicted by circular RNA Interactome or Starbase 3.0 and then verified by a dual-luciferase reporter assay. The biological roles of circ_PDZD8 and Lido on lung carcinoma cell growth were examined by the xenograft tumor model in vivo. Lido suppressed proliferation, migration, invasion, and induced apoptosis in lung carcinoma cells. Circ_PDZD8 and GOLT1A were increased, miR-516b-5p was decreased in lung carcinoma tissues and cell lines. Their expression presented the opposite trend in Lido-triggered lung carcinoma cells. Circ_PDZD8 might overturn the repression of Lido on cell growth ability and metastasis in this tumor. Mechanically, circ_PDZD8 might regulate GOLT1A expression by sponging miR-516b-5p. Circ_PDZD8 weakened the anti-lung carcinoma effect of Lido in vivo. Circ_PDZD8 might mitigate the inhibitory effect of Lido on tumor cell malignancy by modulating the miR-516b-5p/GOLT1A axis, providing a novel insight for lung carcinoma treatment.
  • Publication
    Open Access
    MiR-30a-5p hampers proliferation of lung squamous cell carcinoma through targeting FBXO45
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Zeng, Fanye; You, Shuqing; Dai, Xueli
    Objective. Studies have elaborated the inhibition of miR-30a-5p on the proliferation of cancer cells. However, the regulatory mechanism of how miR30a-5p works in lung squamous cell carcinoma (LUSC) cells is obscure. Methods. Data of miRNAs/mRNAs in LUSC tissue (The Cancer Genome Atlas (TCGA)) were accessed. A differential upstream miRNA (miR-30a-5p) was obtained by differential analysis. Downstream target mRNAs were predicted and screened by several databases. The function pathways of target protein in cells were determined by gene set enrichment analysis (GSEA). Abnormal expression levels of FBXO45 and miR-30a-5p were evaluated in three LUSC cell lines. The expression levels of FBXO45 mRNA and miR-30a5p were analyzed by qRT-PCR. Western blot method was employed to assess protein levels of FBXO45, Cyclin E1, Cdk4 and Cyclin D1. How the two researched genes interact was testified by dual-luciferase method. Cell proliferative ability was compared by CCK-8 and colony formation methods. Moreover, cell cycle was tested by flow cytometry. Results. MiR-30a-5p was tested to be noticeably down-regulated in LUSC cell lines. Up-regulated FBXO45 in LUSC was targeted by miR-30a-5p. Overexpressing miR-30a-5p modulated proliferation and cell cycle in LUSC via inhibiting FBXO45. Conclusion. MiR-30a-5p hindered FBXO45 expression to repress the proliferation of LUSC. FBXO45/miR-30a-5p may shed light on future molecular treatment of LUSC.