Association between genetic polymorphisms of inflammatory response genes and the risk of ovarian cancer.

BACKGROUND/PURPOSE: Inflammation plays an important role in promoting ovarian tumorigenesis and cancer progression. However, the relationship between polymorphisms in inflammatory response genes and risk of ovarian cancer remains poorly understood. In this study, we investigated the association of PPARG Pro12Ala, IL6-174G/C, E-selectin S128R, NFKB1-94 ins/del, NFKBIA-826C/T, and ICAM-1 K469E polymorphisms with ovarian cancer risk in a Chinese population. METHODS: Genotyping of the polymorphisms was performed on 687 cases and 687 controls employing the PCR-RFLP technique, and the logistic regression model was used to measure the risk association. RESULTS: A significantly increased risk association was observed for the heterozygous genotypes of PPARG [odds ratio (OR) = 1.52, 95% confidence interval (CI) = 1.01-2.29] and E-selectin (OR = 1.77, 95% CI = 1.07-2.93) polymorphisms, as well as the homozygous ins/ins genotype of NFKB1 polymorphism (OR = 1.39, 95% CI = 1.00-1.92). By contrast, ICAM-1 KE genotype was associated with a decreased ovarian cancer risk (OR = 0.77, 95% CI = 0.60-0.98). In addition, the NFKB1 del/del + NFKBIA TT combination was also found to be associated with a decreased ovarian cancer risk, with OR = 0.12 (95% CI = 0.01-0.95). The associations of the NFKB1 and ICAM-1 polymorphisms replicated the findings of previous reports, assuring the reliability of the results obtained. CONCLUSION: NFKB1 and ICAM-1 polymorphisms could serve as useful ovarian cancer risk prediction biomarkers for the Chinese population, while the utility of PPARG and E-selectin polymorphisms as biomarkers requires further confirmation in independent ovarian cancer cohorts.

Germanicol induces selective growth inhibitory effects in human colon HCT-116 and HT29 cancer cells through induction of apoptosis, cell cycle arrest and inhibition of cell migration.

PURPOSE: The main aim of this research was to evaluate the anticancer and apoptotic effects of germanicol - a natural triterpene - in HCT-116 and HT29 human colon cancer cells and deciphering its mode of action by studying its effect on the cell cycle and cell migration. METHODS: Cell cytotoxicity was evaluated by MTT assay, while cell death was assessed by LDH assay. Fluorescence microscopy, using DAPI and acridine orange/ethidium bromide (AO-ETBR), was carried out to evaluate the effect of germanicol on cellular morphology and apoptosis induction. Apoptosis quantification was performed by Annexin V-FITC assay, while cell cycle analysis was performed by flow cytometry using propidium iodide (PI). RESULTS: The results revealed that germanicol showed selective, potent and dose-dependent cytotoxicity in HCT-116 and HT29 human colon cancer cells, while it showed lower cytotoxicity in normal colon cells (human colon fibroblast, CCD-18Co). LDH assay also showed that germanicol induced dose-dependent cell death in HCT-116 and HT29 cells. Fluorescence microscopy revealed that germanicol induced apoptosis via chromatin condensation and DNA damage in HCT-116 colon cancer cells. It also revealed that the percentage of cells with orange and red fluorescence increased when adding a germanicol dose, indicating apoptosis. Germanicol also inhibited cancer cell migration. CONCLUSION: The current findings reveal that germanicol exhibits selective antiproliferative activity against two human colon cancer cells. The normal cell line was less affected by the drug, as compared to the two cancer cell lines, indicating that germanicol will not target normal living cells. The antiproliferative effect was shown to be mediated through the induction of apoptosis and suppression of cell migration.

[miR-29b Reduces Cisplatin Resistance of Gastric Cancer Cell by Targeting PI3K/Akt Pathway].

OBJECTIVE: To investigate the regulatory effect of miR-29b on gastric cells' resistance to cisplatin. METHODS: The expression of miR-29b in gastric cancer cell line treated with cisplatin concentration gradient was detected using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. CCK8 was used to measure the cell viability after cisplatin treatment in condition of miR-29b knock-down and overexpression. RESULTS: The expression of miR-29b was significantly upregualted by cisplatin treatment,while its target gene AKT2 was downregulated. The up-regulation of miR-29b enhanced the sensitivity of gastric cancer cells to cisplatin,while the knock-down of miR-29b enhanced the cisplatin resistance. Rescue experiments demonstrated that the miR-29b might regulate cisplatin resistance of gastric cancer cell by targeting PI3K/Akt pathway. The expressions of the other two members of miR-29 family, miR-29a/c, were promoted by cisplatin treatment,but they had no significant effect on gastric cancer cell's resistance to cisplatin. CONCLUSION: miR-29b can enhance the sensitivity of S gastric cancer cell by directly targeting PI3K/Akt pathway.

Clinical Efficacy, Antibiotic Resistance Genes, Virulence Factors and Outcome of Hospital-Acquired Pneumonia Induced by Klebsiella pneumoniae Carbapenemase 2-Producing with Tigecycline Treatment in the ICU.

Purpose: Tigecycline is an agent for carbapenemase-producing Klebsiella pneumonia (KPC-KP), given its penetration into lung tissues. Our study focused on the molecular and clinical efficacy of tigecycline for hospital-acquired pneumonia (HAP) in the ICU. Patients and Methods: A retrospective cohort study of 52 adult KPC-KP HAP patients by searching hospital medical records from January 2018 to December 2020 was established to investigate the epidemiology of KPC-KP infections for tigecycline treatment and the associated clinical efficacy of tigecycline. The KPC-KP isolates underwent multilocus sequence typing. Molecular typing, antimicrobial resistance, and virulence profiling were also analyzed by whole-genome sequencing of KPC-KP. Results: Among 52 patients with KPC-KP, the ICU mortality rate was 14/52 (27%), and there was no significant statistical difference in mortality between the effective group and failure group (p = 0.754). However, the duration of tigecycline was statistically different between the two groups of patients (14.4 vs 10 days, p=0.046). The total bacterial clearance rate was 6/52 (11.5%). There was no significant statistical difference in both groups (p=0.416). Antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were negatively correlated with clinical efficacy (p = 0.011, OR = 1.237). Conclusions: Blakpc was the main carbapenemase in all K. pneumoniae strains. ST11-KL64 KPC-KP was the most common virulence factors in KPC-KP isolates. This study suggested that antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were independent mortality risk factors for patients with Klebsiella pneumoniae carbapenemase-2 producing K. pneumoniae infections, when during the tigecycline treatment. Molecular analysis of K. pneumoniae may provide an option when choosing the antimicrobial treatment.

Dosimetric evaluation of helical tomotherapy and volumetric-modulated arc therapy for malignant pleural mesothelioma: a planning study for dose escalation.

BACKGROUND: To compare the dosimetric differences between helical tomotherapy (HT) and volumetric-modulated arc therapy (VMAT) treatment plans for inoperable malignant pleural mesothelioma (MPM). METHODS: Ten patients with inoperable MPM were retrospectively planned with the HT and VMAT techniques, and the dose-volume histogram (DVH)-based parameters of the planning target volume (PTV) and organs at risk (OARs) were compared. RESULTS: Compared with the VMAT plans, the target homogeneity index (HI) and conformity index (CI) of the HT plans were significantly better (HI: 1.04±0.01 vs. 1.11±0.03, CI: 0.80±0.07 vs. 0.71±0.12, respectively) (P<0.001, P=0.013, respectively). Regarding the OARs, including the ipsilateral lung, contralateral lung, heart, and spinal cord, the differences among the V30 (Vx: fraction of volume receiving >5, 10, 20, and 30 Gy, respectively) of the ipsilateral lung and V5, V10, and V20 of the contralateral lung were statistically significant (P=0.031, P=0.030, P=0.021, P=0.003, respectively). However, there was no significant differences between HT plans and VMAT plans, regarding the V5, V10 and V20 of the ipsilateral lung, V3 of the contralateral lung, V5 and Dmean of the heart, and Dmax of the cord. The treatment delivery time of the VMAT was significantly shorter than that of the HT (mean delivery time: 3.27±1.65 vs. 11.11±3.75 min, respectively) (P<0.001). CONCLUSIONS: Compared to the VMAT plans, the HT plans not only demonstrated more optimal target coverage and conformity but also considerably reduced the dose-volume parameters of the OARs in both low-dose areas in contralateral lung and high-dose areas in ipsilateral lung and contralateral lung, which is correlated to radiation injury. However, the treatment delivery time of the HT plans was longer.

Differential expression of Dickkopf-1 among non-small cell lung cancer cells.

Dickkopf-1 (DKK1) is a negative regulator of the Wnt/ß-catenin signaling pathway, which is expressed in various human cancers. It was hypothesized that DKK1 was oncogenic and involved in invasive growth in non-small cell lung cancer (NSCLC) cells. The present study aimed to investigate whether DKK1 gene expression levels differ among various NSCLC cells. The DKK1 expression pattern was analyzed in various human NSCLC cell lines and tissues. The DKK1 protein and gene expression levels were quantified using immunoblotting, polymerase chain reaction analysis and immunohistochemistry. The majority of the lung cancer cell lines analyzed revealed increased expression levels of DKK1. Furthermore, DKK1 expression was highly transactivated in the majority of these cancer cell lines. Clinical samples were obtained from 98 NSCLC patients for immunohistochemical analysis. Of the 98 samples analyzed, 62 (63.3%) demonstrated positive staining for DKK1, whereas the remaining 36 (37%) exhibited negative staining. However, no immunohistopathological staining was detected in normal tissues. The relative effects of DKK1 were assessed in a high-expression cell line (LTEP-a-2) and a low-expression cell line (95D). The differential expression of genes involved in cell cycle, apoptosis, signaling pathway, invasion and metastasis were evaluated, relative to DKK1 levels. In conclusion, the results of the present study indicated that DKK1 functioned as a key regulator in the progression of NSCLC. The results confirmed the differential expression of DKK1 in NSCLC cells, which may present a potential therapeutic target for cancer prevention.