Leptin-mediated ERK Signaling Pathway Promotes the Transformation of Rat Alveolar Type II Epithelial Cells Induced by Yunnan Tin Mine Dust / 中国肺癌杂志

BACKGROUND@#Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust.@*METHODS@#Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R₂₀₀ cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R₂₀₀ cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R₂₀₀ group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method.@*RESULTS@#Both the cells in the R group and R₂₀₀ group express leptin receptor OB-R. Compared to the R₂₀₀ group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R₂₀₀ cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R₂₀₀ group (R₂₀₀L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R₂₀₀L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R₂₀₀L group exhibited faster cell aggregation compared to the U0126-induced R₂₀₀ (R₂₀₀LU) group. Additionally, the cells in the R₂₀₀L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R₂₀₀LU group and R₂₀₀ group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R₂₀₀L group. However, when the cells in the R₂₀₀L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased.@*CONCLUSIONS@#Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust.

Study on lingual mucosa carcinogenesis of C57BL/6 mice induced by 4-nitroquinoline 1-oxide / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aimed to induce carcinogenesis of lingual mucosa in C57BL/6 mice by feeding them 4-nitroquinoline 1-oxide (4NQO) solution.</p><p><b>METHODS</b>A total of 85 C57BL/6 mice were randomly divided into distilled water control group (DD group, n=5), 1,2-propylene glycol control group (PG group, n=5), and experimental group (EP group, n= 75). The mice in the experimental group were medially fed in 15 cages. By contrast, the mice in DD, EP, and PG groups were watered with distilled water, 50 mg.L-1 4NQO solution, and 1,2-propylene glycol solution. The mice in EP group were executed every two weeks from week 0, and the mice in the control groups were sacrificed at the 28th week. The mice were weighed. Mucosal lesions were measured by macroscopic observation and histopathologic detection.</p><p><b>RESULTS</b>One mouse in EP group died of unknown reason. The weight of the mice in EP group presented weight loss compared with the mice in DD and PG groups after the 24th week. Seventy-nine macroscopic lesions were observed in the lingual mucosa, oral floor, and upper palatal and buccal mucosa. A total of 70 macroscopic lesions (88.6%) were located in the lingual mucosa. Mucosal lesions changed from simple hyperplasia to squamous cell carcinomas. Well-differentiated squamous cell carcinomas were observed in all mice of EP group by pathological section at the 28th week. No lesion was found in the mice of DD and PG groups.</p><p><b>CONCLUSION</b>The animal model of lingual squamous cell carcinomas was successfully established. The periods from 12th to 16th week and 20th to 28th week were the ideal times for the research on pathogenesis of early and medial-advanced stage during carcinogenesis of squamous cell carcinomas.</p>

Expression of survivin and PCNA in lung cancer cells induced by Gejiu mineral powder / 中国肺癌杂志

<p><b>BACKGROUND</b>Gejiu in Yunnan Province is a region where the incidence of lung cancer is high among the miners of tin mine. Our previous research team successfully induced the malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) by Gejiu mineral powder in vitro. The objective of this study is to explore the role of survivin and proliferating cell nuclear antigen (PCNA) in the pathway of the malignant transformation of BEAS-2B induced by Gejiu mineral powder.</p><p><b>METHODS</b>Protein expression of survivn and PCNA in BEAS-2B cells and its malignant transformation cells was respectively evaluated by immunofluorescence cytochemistry staining technique and immunohistochemistry.</p><p><b>RESULTS</b>(1)The expression of survivin protein was negative in BEAS-2B cells and was positive in its malignant transformation cells by immunofluorescence cytochemistry staining techniques. And the protein level of PCNA was low in BEAS-2B cells and high in its malignant transformation cells. (2)The positive expression of survivin protein in BEAS-2B cells (0/20) was significantly lower than that in its malignant transformation cells (85%, 17/20) by immunohistochemistry (P < 0.001). And the labelling index (LI) of PCNA in BEAS-2B cells was significantly lower than that in its malignant transformation cells (P < 0.001). LI of PCNA in the malignant transformation cells of BEAS-2B with positive expression of survivin was significantly higher than that with negative expression of survivin (P < 0.001).</p><p><b>CONCLUSIONS</b>(1)The up-regulation expression of survivin in malignant transforma- tion cells of BEAS-2B suggests that survivin may play an important role in the pathway of malignant transformation in BEAS-2B cells induced by Gejiu mineral powder. It may give a proof for revealing the carcinogenesis of lung cancer in Gejiu miner. Survivin may be identified as a novel potential diagnostic and therapeutic target of lung cancer in Gejiu miner. (2)The up-regulation expression of PCNA in malignant transformation cells of BEAS-2B suggests that cell proliferation may play an important role in the pathway of malignant transformation. (3)Survivin may promote cell proliferation mediated by PCNA. Survivn and PCNA may play synergetic roles in the process of malignant transformation in BEAS-2B cells induced by Gejiu mineral powder.</p>

Experiment and Pondering of Applying Bilingual Teaching to the Course of Pathology / 中华医学教育探索杂志

An experiment of applying bilingual teaching to the course of pathology on the sophomores (students in Grade 2002) was carried out in our department in April 2004. This paper will research the feasibility and necessity of the methodology,ponder the problems in the course of teaching and put forward some suggestions in order to conduct bilingual teaching smoothly on the basis of practice and theory.

The expressions of TGF-beta1 and Smad 2 mRNA on diseased glomeruli and their significance in the development of glomerulosclerosis / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the expressions of transforming growth factor-beta1 (TGF-beta1) and its signaling transduction molecule Smad 2 and their significance in the development of glomerulosclerosis.</p><p><b>METHODS</b>Using in situ hybridization and immunohistochemistry to detect Smad 2 mRNA expression and TGF-beta1, collagen IV, fibronectin expression in renal biopsies from 61 cases with a spectrum of glomerulonephritis including IgA nephropathy (40 cases), membranous glomerulonephritis (10 cases) and sclerosing glomerulonephritis (11 cases), compared with 11 cases of glomerular mild lesion with image analysis system.</p><p><b>RESULTS</b>With the exception of Smad 2 mRNA expression in mild type IgA nephropathy, all other types of diseased glomeruli showed increased expression of both TGF-beta1 and Smad 2 mRNA when compared with the 11 cases of mild glomerular lesions. The expressions of glomerular TGF-beta1 and Smad 2 mRNA positively correlated with collagen IV and fibronectin deposition in the glomeruli.</p><p><b>CONCLUSIONS</b>TGF-beta1 and Smad 2 may be involved in the excessive deposition of glomerular extracellular matrix and play an important role in the development of glomerulosclerosis.</p>