Diagnostic significance of a color Doppler ultrasound combined with serum CXCL16 and E-cad in cervical cancer.

BACKGROUND: The use of effective non-invasive diagnostic markers in the early stage of cervical cancer is lacking currently. This study sought to investigate the value of color Doppler ultrasound combined with serum CXC chemokine ligand-16 (CXCL16) and epithelial cadherin (E-cad) levels in diagnosing cervical cancer. METHODS: Two hundreds cervical cancer patients admitted in our hospital between May 2018 and April 2020 were selected as the observation group. The control group included 100 healthy participants. The ultrasound parameters, and the serum CXCL16 and E-cad levels between the two groups and patients at different pathological stages were compared. The correlations between disease progress and ultrasound and serological indexes were analyzed. The diagnostic efficiency of an ultrasound and measures of serum CXCL16 and E-cad levels were compared as well. RESULTS: The peak systolic velocity (PSV) of the observation group was significantly higher than that of the control group (P<0.05). In case of the resistance index (RI), the results were the opposite to the PSV (P<0.05). The PSV (P<0.05) and RI (P<0.05) were significantly different among different pathological stages. The serum CXCL16 (P<0.05) and E-cad (P<0.05) levels of participants in the observation group were significantly higher than those of patients in the control group. A pairwise comparison showed that the serum CXCL16 and E-cad levels increased significantly as the pathological stages of the cancer progressed. The diagnosis and disease progression of cervical cancer were positively correlated with PSV, CXCL16, and E-cad levels, and negatively correlated with the RI. Combining an ultrasound diagnosis with serum CXCL16 and E-cad levels had significantly higher diagnostic sensitivity than that of any individual indicator in patients with cervical cancer. The curve analysis showed that the cut-off values of PSV, the RI, CXCL16 and E-cad were 14.25, 0.50, 40.15 ng/mL and 85.36 pmmol/L, respectively. CONCLUSIONS: The sensitivity of color Doppler ultrasound combined with serum CXCL16 and E-cad levels in the diagnosis of cervical cancer is high. Thus, it is recommended that it be used in clinics.

HE4 overexpression decreases pancreatic cancer Capan-1 cell sensitivity to paclitaxel via cell cycle regulation.

BACKGROUND: Paclitaxel is a first-line chemotherapy drug for pancreatic, ovarian, endometrial cancers and other malignancies. However, its efficacy is often compromised by decreased cell sensitivity or the development of resistance. Human epididymis protein 4 (HE4) is highly expressed in gynecologic and pancreatic cancer tissues, and its serum levels are used for patient triage and assistant diagnosis of gynecologic cancers. Previous studies have shown that HE4 overexpression could promote cancer cell proliferation and the growth of tumor xenografts, which suggests its potential involvement in cancer chemosensitivity. METHODS: Two pancreatic cancer cell lines, Capan-1 and Suit-2, were transiently transfected with an HE4 overexpression plasmid, and transfected cells were treated with paclitaxel. S-phase cells were labeled using BrdU, and cell positivity rates were determined by counting BrdU-positive cells. Following HE4 overexpression and/or drug treatment, a western blotting analysis was performed to determine the protein alterations of PCNA and p21, two important cell cycle regulators. RESULTS: HE4 overexpression not only promoted the proliferation of the Capan-1 pancreatic cells, but also significantly decreased cell sensitivity to paclitaxel. Results from western blotting showed that paclitaxel inhibited cell proliferation by decreasing the expression of PCNA and increasing the expression of p21. Data analysis indicated interactive actions between HE4 function and paclitaxel effects, both converging to cell cycle regulation. CONCLUSION: These findings suggest that HE4 could be a potential therapeutic target for the sensitization of pancreatic cancer cells to paclitaxel treatment. HE4 expression levels may be used to predict the sensitivity of pancreatic cancer patients to paclitaxel.

Culture characters, genetic background, estrogen/progesterone receptor expression, and tumorigenic activities of frequently used sixteen endometrial cancer cell lines.

BACKGROUND: This study aimed to determine the in vitro and in vivo properties of sixteen frequently used endometrial cancer (EC) cell lines, including the cell proliferation rate, morphology, hormone receptor expression patterns, PTEN, hMLH1 expression, p53 mutation, karyotype, and tumorigenicity in mouse xenograt model. METHODS: Twelve type I (AN3, ECC-1, EN, EN-1, EN-11, HEC-1A, HEC1B, Ishikawa, KLE, MFE-280, MFE-296, MFE-319) and four type II (ARK1, ARK2, HEC-155/180, SPEC-2) endometrial cancer cell lines were studied. Cell proliferation and morphology were determined using cell growth curves and light microscopy, respectively. Real-time PCR was performed to measure the mRNA levels of target genes. Denaturing High Performance Chromatography (DHPLC) screening and PCR/sequencing were performed to identify p53 mutations. G-banding was applied for karyotyping. Tumorigenicity was evaluated using mouse xenograft. RESULTS: The population doubling time of the cell lines ranged between 19 and 41 h. Ishikawa, ECC-1, and MFE-280 have high while AN3 and EN1 have low expression of ER-α and ER-ß. Expression of total PR and PR-B uniformly decreased in all type II cell lines and several type I cell lines (AN3, HEC-1A, HEC1B, KLE, EN-1). Regression analyses revealed significant correlations between PR-B and total PR (p < .001), between isoforms ER-α and ER-ß (p < .001), and between total PR and ER (p < .001), mRNA levels in type I cell lines. p53 mutations were detected in exons 5-8 of seven out of twelve type I and one out of four type II cell lines. PTEN expression was more uniformly suppressed in type II than type I cells, while hMLH1 did not show this pattern. All the five cell lines tested contained severe karyotype abnormalities. Mouse xenograft results indicated that HEC-1A, HEC-1B and EN-1 type I as well as ARK1 and ARK2 type II cell lines had potent tumorigenic activities. Low PR-B and ER-α expression in type I cell lines were associated with high tumorigenic activity. CONCLUSIONS: This study provides resource information on EC cell lines commonly used in laboratories, which could be used for choosing cell lines suitable for specific research purposes. The results of karyotype analysis and p53 mutation together with hormone receptor expression pattern and morphology comparison strongly suggested an independent nature of these cell lines, excluding the possibility of cross-contamination between cell lines. Additionally, this information suggests potential directions for future studies on the pathogenic mechanisms of endometrial cancer.

A tag SNP in syncytin-2 3-UTR significantly correlates with the risk of severe preeclampsia.

BACKGROUND: Preeclampsia is a disease that frequently complicates pregnancy and poses a serious threat to maternal and fetal health. The causes and pathogenic mechanisms of preeclampsia are poorly defined. Genetic predisposition could be an important etiological factor. Previous studies have demonstrated that syncytin-1 and syncytin-2, encoded by the genes ERVWE1 and ERVFRDE-1, are involved in the pathogenesis of preeclampsia. METHODS: In this study, we applied multiplex PCR and MALDI-TOF MS techniques to analyze six selected tag SNPs of ERVWE1 and ERVFRDE-1 in 120 preeclampsia patients and 181 normal controls. RESULTS: One SNP polymorphism (rs9393931) with the recessive TT genotype located in the 3-UTR of ERVFRDE-1 gene was found to be significantly associated with an increased risk of preeclampsia (OR (95% CI) = 2.05 (1.27-3.32); p = 2.8 × 10-3). No significant correlation of this polymorphism with the clinical severity of preeclampsia, e.g. the extent of hypertension, was detected between carrier and non-carrier patients. CONCLUSIONS: These results suggested that genetic predisposition in ERVFRDE-1 may be associated with an increased risk of preeclampsia. This polymorphism is possibly involved in the regulation of syncytin-2 expression in preeclamptic placenta.

IgG Antibody 3D Structures and Dynamics.

Antibodies are vital for human health because of their ability to function as nature's drugs by protecting the body from infection. In recent decades, antibodies have been used as pharmaceutics for targeted therapy in patients with cancer, autoimmune diseases, and cardiovascular diseases. Capturing the dynamic structure of antibodies and characterizing antibody fluctuation is critical for gaining a deeper understanding of their structural characteristics and for improving drug development. Current techniques for studying three-dimensional (3D) structural heterogeneity and variability of proteins have limitations in ascertaining the dynamic structural behavior of antibodies and antibody-antigen complexes. Here, we review current techniques used to study antibody structures with a focus on the recently developed individual-particle electron tomography (IPET) technique. IPET, as a particle-by-particle methodology for 3D structural characterization, has shown advantages in studying structural variety and conformational changes of antibodies, providing direct imaging data for biomolecular engineering to improve development and clinical application of synthetic antibodies.