Function, drug resistance and prognostic effect of AKR1C2 in human cancer.

Aldo-keto reductases (ARKs), a group of reductases that rely on nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) to catalyze carbonyl, are widely found in various organisms, which play an important role in the physiological and pathological processes of human. Aldo-keto reductase family 1 member C2 (AKR1C2) as a member of the human ARKs family, can regulate steroid hormones and is abnormally expressed in many cancers. According to whether the tumor can be affected by hormones, we divide malignancies into hormone-dependent and hormone-independent types. Studies have shown that AKR1C2 is involved in regulating tumor invasion, migration, and other malignant phenotypes, eliminating reactive oxygen species (ROS), promoting chemotherapy resistance of tumor cells, and has prognostic value in some cancers. Here, we focus on the role and clinical significance of AKR1C2 in different types of tumors.

CCNO mutation as a cause of primary ciliary dyskinesia: A case report.

BACKGROUND: Primary ciliary dyskinesia (PCD) is an uncommon and genetically diverse condition. According to reports, most patients had more than 50 visits before being diagnosed with PCD, and the age at diagnosis was mostly in preschool, with an average age of about (10.9 ± 14.4) years old. CCNO is a pathogenic gene that regulates the cell cycle, and its mutation is linked to the uncommon human genetic disorder PCD. Although the prevalence of the CCNO mutation is regarded to be exceptionally low, new reports of this mutation have increased in comparison to prior ones. PCD patients with CCNO are rare, and the incidence rate is no more than 2% in whole PCD patients. CASE SUMMARY: Here, we report a case of a young Chinese woman diagnosed with PCD, who was found to carry the CCNO gene by whole exon gene sequencing. In this case, a young non-smoking Chinese female exhibiting recurrent cough and sputum at birth. Chest computed tomography (CT) showed bronchiectasis with infection, and sinus CT showed chronic sinusitis. However, the patient had no visceral transposition and no history of infertility. Under electron microscope, it was found that cilia were short and reduced in number, and no power arm of cilia was observed. Whole exon sequencing analysis of the genome of the patient showed that the patient carried CCNO pathogenic gene, exon c.303C>A nonsense mutation and c.248_252dup frameshift mutation. Her clinical symptoms and CT images were improved after two months of treatment with aerosol inhalation and oral azithromycin. CONCLUSION: The results showed that CCNO is an important cause of PCD. More mutant genes that may contribute to genetically diverse disorders like PCD have been discovered as sequencing technology has advanced. Furthermore, the increase of genetic information makes it easier to diagnose uncommon diseases in clinical practice.

Mechanism and Management of Fentanyl-Induced Cough.

Fentanyl-induced cough (FIC) often occurs after intravenous bolus administration of fentanyl analogs during induction of general anesthesia and analgesia procedure. The cough is generally benign, but sometimes it causes undesirable side effects, including elevated intra-abdominal, intracranial or intraocular pressure. Therefore, understanding the related mechanisms and influencing factors are of great significance to prevent and treat the cough. This paper reviews the molecular mechanism, influencing factors and preventive administration of FIC, focusing on the efficacy and side effects of various drugs in inhibiting FIC to provide some medical reference for anesthesiologists.

Corrigendum: Mechanism and Management of Fentanyl-Induced Cough.

[This corrects the article DOI: 10.3389/fphar.2020.584177.].

Inhibition of Delta-like Ligand 4 enhances the radiosensitivity and inhibits migration in cervical cancer via the reversion of epithelial-mesenchymal transition.

BACKGROUND: Concurrent chemoradiotherapy is the common first-line treatment for patients with advanced cervical cancer. However, radioresistance remains a major clinical challenge, which results in recurrence and poor survival. Many studies have shown the potential of Delta-like Ligand 4 (DLL4) as a novel prognostic biomarker and therapeutic target in many solid tumors. Previously, we have found that high DLL4 expression in tumor cells may predict the pelvic lymph node metastasis and poor prognosis in patients with cervical cancer. In our present study, we further studied the effects of DLL4 on the biological behavior and radiosensitivity of cervical cancer cells. METHODS: The expression of DLL4 and epithelial-mesenchymal transition (EMT) phenotype markers in cervical cancer cell lines or tissues were detected using Western blotting, and the expression of DLL4 mRNA in cervical cancer cell lines or tissues was detected using Quantitative real-time PCR. The effect of DLL4 on cell proliferation, migration, and radiosensitivity was evaluated using the CCK8 assay, flow cytometry, Transwell assays for cell invasion and migration, and Immunofluorescence staining in vitro. RESULTS: The expression of DLL4 in radiotherapy-resistant SiHa cells was significantly higher than that in radiotherapy-sensitive Me-180 cells. Furthermore, downregulation of DLL4 enhanced the radiosensitivity of SiHa and Caski cells via the inhibition of cell proliferation, promotion of radiation-induced apoptosis, and inhibition of the DNA damage repair. Moreover, downregulation of DLL4 inhibited the EMT and reduced the proliferation, invasion, and migration ability in SiHa and Caski cells. Consistent with the DLL4 expression in the cell lines, the expression of DLL4 in the tissues of the radioresistant group was also higher than that of the radiosensitive group. CONCLUSIONS: Downregulation of DLL4 inhibited the progression and increased the radiosensitivity in cervical cancer cells by reversing EMT. These results indicated the promising prospect of DLL4 against the radioresistance and metastasis of cervical cancer and its potential as a predictive biomarker for radiosensitivity and prognosis in patients with cervical cancer patients receiving concurrent chemoradiotherapy (cCRT).

Ischemic postconditioning attenuates acute kidney injury following intestinal ischemia-reperfusion through Nrf2-regulated autophagy, anti-oxidation, and anti-inflammation in mice.

Intestinal ischemia-reperfusion (IIR) often occurs during and following major cardiovascular or gut surgery and causes significant organ including kidney injuries. This study was to investigate the protective effect of intestinal ischemic postconditioning (IPo) on IIR-induced acute kidney injury (AKI) and the underling cellular signaling mechanisms with focus on the Nrf2/HO-1. Adult C57BL/6J mice were subjected to IIR with or without IPo. IIR was established by clamping the superior mesenteric artery (SMA) for 45 minutes followed by 120 minutes reperfusion. Outcome measures were: (i) Intestinal and renal histopathology; (ii) Renal function; (iii) Cellular signaling changes; (iv) Oxidative stress and inflammatory responses. IPo significantly attenuated IIR-induced kidney injury. Furthermore, IPo significantly increased both nuclear Nrf2 and HO-1 expression in the kidney, upregulated autophagic flux, inhibited IIR-induced inflammation and reduced oxidative stress. The protective effect of IPo was abolished by the administration of Nrf2 inhibitor (Brusatol) or Nrf2 siRNA. Conversely, a Nrf2 activator t-BHQ has a similar protective effect to that of IPo. Our data indicate that IPo protects the kidney injury induced by IIR, which was likely mediated through the Nrf2/HO-1 cellular signaling activation.

Aggravated intestinal ischemia­reperfusion injury is associated with activated mitochondrial autophagy in a mouse model of diabetes.

Numerous studies have reported that diabetes is associated with an increased susceptibility to cardiac ischemia­ reperfusion injury; however, the mechanism underlying the role of diabetes during intestinal ischemia­reperfusion (IIR) has yet to be elucidated. The present study evaluated the intestinal pathological alterations and possible underlying mechanisms in a mouse model of type 1 diabetes mellitus with IIR. The effects of diabetes were investigated by assessing the histopathology, oxidative stress, inflammatory cytokine levels in intestine tissues and blood plasma, and protein expression levels of phosphatase and tensin homolog­induced putative kinase (PINK1), Parkin and the ratio of light chain 3B (LC3B) II/I. The results demonstrated that diabetes increased the Chiu's intestinal injury score, concentration of interleukin (IL)­1ß, IL­6 and tumor necrosis factor (TNF)­α, and levels of oxidative stress. Furthermore, the alterations were more pronounced in the diabetes with IIR group. The expression levels of PINK1 and Parkin, as well as the ratio of LC3BII/I, were significantly upregulated in the IIR group compared with the Sham group. Diabetes activated PINK1 and Parkin, and increased the expression of LC3BII. Furthermore, transmission electron microscopy revealed that mitochondrial destruction and the number of autophagosomes was increased in the diabetic groups compared with the non­diabetic groups. Collectively, the results of the present study suggest that diabetes increased intestinal vulnerability to IIR by enhancing inflammation and oxidative stress. Furthermore, IIR was associated with overactivation of mitochondrial autophagy; therefore, the increased vulnerability to IIR­induced intestine damage due to diabetes may be associated with PINK1/Parkin­regulated mitochondrial autophagy.

Ischemic Postconditioning Alleviates Intestinal Ischemia-Reperfusion Injury by Enhancing Autophagy and Suppressing Oxidative Stress through the Akt/GSK-3ß/Nrf2 Pathway in Mice.

AIMS: Ischemic postconditioning (IPO) has a strong protective effect against intestinal ischemia-reperfusion (IIR) injury that is partly related to autophagy. However, the precise mechanisms involved are unknown. METHODS: C57BL/6J mice were subjected to unilateral IIR with or without IPO. After 45 min ischemia and 120 min reperfusion, intestinal tissues and blood were collected for examination. HE staining and Chiu's score were used to evaluate pathologic injury. We test markers of intestinal barrier function and oxidative stress. Finally, we used WB to detect the expression of key proteins of autophagy and the Akt/GSK-3ß/Nrf2 pathway. RESULTS: IPO significantly attenuated IIR injury. Expression levels of LC3 II/I, Beclin-1, and p62 were altered during IIR, indicating that IPO enhanced autophagy. IPO also activated Akt, inhibited GSK-3ß/Nrf2 pathway. CONCLUSION: Our study indicates that IPO can ameliorate IIR injury by evoking autophagy, activating Akt, inactivating GSK-3ß, and activating Nrf2. These findings may provide novel insights for the alleviation of IIR injury.ß/Nrf2 pathway.

Which Bone Marrow Sparing Strategy and Radiotherapy Technology Is Most Beneficial in Bone Marrow-Sparing Intensity Modulated Radiation Therapy for Patients With Cervical Cancer?

BACKGROUND: To evaluate the dosimetric parameters of different bone marrow sparing strategies and radiotherapy technologies and determine the optimal strategy to reduce hematologic toxicity associated with concurrent chemoradiation (cCRT) for cervical cancer. METHODS: A total of 15 patients with Federation International of Gynecology and Obsterics (FIGO) Stage IIB cervical cancer treated with cCRT were re-planned for bone marrow (BM)-sparing plans. First, we determined the optimal BM sparing strategy for intensity modulated radiotherapy (IMRT), including a BMS-IMRT plan that used total BM sparing (IMRT-BM) as the dose-volume constraint, and another plan used os coxae (OC) and lumbosacral spine (LS) sparing (IMRT-LS+OC) to compare the plan without BM-sparing (IMRT-N). Then, we determined the optimal technology for the BMS-IMRT, including fixed-field IMRT (FF-IMRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (HT). The conformity and homogeneity of PTV, exposure volume of OARs, and efficiency of radiation delivery were analyzed. RESULTS: Compared with the IMRT-N group, the average volume of BM that received ≥10, ≥20, ≥30, and ≥40 Gy decreased significantly in both two BM-sparing groups, especially in the IMRT-LS+OC group, meanwhile, two BMS-IMRT plans exhibited the similar effect on PTV coverage and other organs at risk (OARs) sparing. Among three common IMRT techniques in clinic, HT was significantly less effective than VMAT and FF-IMRT in the aspect of BM-Sparing. Additionally, VMAT exhibited more efficient radiation delivery. CONCLUSION: We recommend the use of VMAT with OC and LS as separate dose-volume constraints in cervical cancer patients aiming at reducing hematologic toxicity associated with cCRT, especially in developing countries.

Development and Application of Genomic Resources in an Endangered Palaeoendemic Tree, Parrotia subaequalis (Hamamelidaceae) From Eastern China.

Parrotia subaequalis is an endangered palaeoendemic tree from disjunct montane sites in eastern China. Due to the lack of effective genomic resources, the genetic diversity and population structure of this endangered species are not clearly understood. In this study, we conducted paired-end shotgun sequencing (2 × 125 bp) of genomic DNA for two individuals of P. subaequalis on the Illumina HiSeq platform. Based on the resulting sequences, we have successfully assembled the complete chloroplast genome of P. subaequalis, as well as identified the polymorphic chloroplast microsatellites (cpSSRs), nuclear microsatellites (nSSRs) and mutational hotspots of chloroplast. Ten polymorphic cpSSR loci and 12 polymorphic nSSR loci were used to genotype 96 individuals of P. subaequalis from six populations to estimate genetic diversity and population structure. Our results revealed that P. subaequalis exhibited abundant genetic diversity (e.g., cpSSRs: Hcp = 0.862; nSSRs: HT = 0.559) and high genetic differentiation (e.g., cpSSRs: RST = 0.652; nSSRs: RST = 0.331), and characterized by a low pollen-to-seed migration ratio (r ≈ 1.78). These genetic patterns are attributable to its long evolutionary histories and low levels of contemporary inter-population gene flow by pollen and seed. In addition, lack of isolation-by-distance pattern and strong population genetic structuring in both marker systems, suggests that long-term isolation and/or habitat fragmentation as well as genetic drift may have also contributed to the geographic differentiation of P. subaequalis. Therefore, long-term habitat protection is the most important methods to prevent further loss of genetic variation and a decrease in effective population size. Furthermore, both cpSSRs and nSSRs revealed that P. subaequalis populations consisted of three genetic clusters, which should be considered as separated conservation units.

Differential expression profile of long non-coding RNA in cardiomyocytes autophagy induced by angiotensin II.

Autophagy is a ubiquitous intracellular process for cellular homeostasis maintenance by recycling damaged protein and organelles. Dysregulation of cardiomyocytes autophagic activity is implicated in various heart diseases. Recent studies had demonstrated that long non-coding RNAs (lncRNAs) played crucial roles on modulation of autophagic activity. In this study, we first established an angiotensin II-induced autophagy model on neonatal rat cardiomyocytes. Western blot assay confirmed that the expression of Beclin 1 and the conversion of soluble LC3-I to lipid bound LC3-II were significantly increased at 12 h after angiotensin II stimulation, but the cardiomyocytes surface area and hypertrophic markers expression had no significant change. Then microarray analysis and real-time PCR were applied to detect differentially expressed lncRNAs during cardiomyocytes autophagy. A total of 1,249 lncRNAs were determined as differentially expressed, including 700 upregulated lncRNAs and 549 downregulated lncRNAs. LncRNAs subgroup analysis showed there were 43 transcribed ultra-conserved noncoding RNAs (T-UCRs) differentially expressed in cardiomyocytes autophagy, of which 26 T-UCRs were upregulated and 17 T-UCRs were downregulated. Bioinformatics analysis further showed that 94 differentially expressed lncRNAs contained potential binding sites of miR-22, a pro-hypertrophic and pro-autophagic microRNA. Therefore, these differentially expressed lncRNAs might play critical roles in cardiomyocytes autophagy. This finding would provide an experimental basis for future investigation on ischemic heart disease.

Overexpression of eukaryotic initiation factor 5A2 (EIF5A2) is associated with cancer progression and poor prognosis in patients with early-stage cervical cancer.

AIMS: As one of the only two isoforms of the eukaryotic initiation factor (EIF)5A family, EIF5A2 plays an important role in tumour progression and prognosis evaluation. The aim of this study was to investigate EIF5A2 expression in International Federation of Gynecology and Obstetrics (FIGO) stage I-II cervical cancer and to evaluate its clinical significance. METHODS AND RESULTS: The mRNA and protein expression levels of EIF5A2 were analysed in 20 tissue samples of FIGO stage I-II cervical cancer and paired surrounding non-tumour cervical tissues by real-time polymerase chain reaction and western blot analysis. Immunohistochemistry was performed to examine EIF5A2 protein expression in paraffin-embedded tissues from 314 patients with cervical cancer. The mRNA and protein expression levels of EIF5A2 were significantly elevated in tumour tissues. The increased EIF5A2 expression was correlated with higher FIGO stage (P < 0.001), deep cervical stromal invasion (P = 0.026), lymphovascular space involvement (P = 0.002), pelvic lymph node metastasis (P < 0.001) and postoperative recurrence (P < 0.001) in patients with cervical cancer. Patients with tumours showing high EIF5A2 expression had a poorer survival time than those with normal EIF5A2 expression, especially the patients with negative pelvic lymph nodes and FIGO stage II. In addition, multivariate Cox analysis showed that high EIF5A2 expression was an independent prognostic factor for overall survival [hazard ratio 1.949; 95% confidence interval (CI) 1.116-3.404; P = 0.019] and disease-free survival (hazard ratio 1.980; 95% CI 1.189-3.297; P = 0.009). CONCLUSIONS: EIF5A2 overexpression may contribute to cancer progression and poor prognosis. Therefore, EIF5A2 could be a novel potential prognostic marker for FIGO stage I-II cervical cancer.

[Effects of Reduning injection on activity of hepatic microsomal CYP450 isozymes in rats].

To research the influence of Reduning injection on the activity and mRNA expression of cytochrome P450 (CYP450) system in rat liver microsomes. Rat liver microsomes were prepared after a seven-days continuous administration of Reduning injection. An HPLC-MS method was applied to determine the specific metabolites of CYP450 probe substrates in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. The Real-time quantitative polymerase chain reaction (Q-PCR) was applied to determine the mRNA expression levels of CYP450. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13 (P < 0.01), but did not affect CYPlA2; low dose and high dose of Reduning injection had an inhibition trend on the activity of CYP2D2, but did not statistically differ from control group; low dose of Reduning injection significantly induced the activity of CYP3A1 (P < 0.01), high dose of Reduning injection had an induce trend on the activity of CYP3A1, but did not statistically differ from control. At the mRNA level, low and high dose of Reduning injection had an induce trend on the expression of CYP1A2, 2C11, 2D1, 2E1, 3A1, but did not statistically differ from control. Reduning injection significantly induced the activity of CYP2B1. Reduning injection significantly induced the activity of CYP3A1 in mRNA expression and enzyme activity levels, which may result adverse drug reaction after being combined with macrolides antibiotics. Reduning injection significantly reduced the activity of CYP2B1, 2C12, 2C13, 2D2 in enzyme activity levels, when combined with other drugs, it should be fully taken into account of the possible drug-drug interaction in order to avoid adverse side effects.

Accuracy of using computer-aided rapid prototyping templates for mandible reconstruction with an iliac crest graft.

BACKGROUND: This study aimed to evaluate the accuracy of surgical outcomes in free iliac crest mandibular reconstructions that were carried out with virtual surgical plans and rapid prototyping templates. METHODS: This study evaluated eight patients who underwent mandibular osteotomy and reconstruction with free iliac crest grafts using virtual surgical planning and designed guiding templates. Operations were performed using the prefabricated guiding templates. Postoperative three-dimensional computer models were overlaid and compared with the preoperatively designed models in the same coordinate system. RESULTS: Compared to the virtual osteotomy, the mean error of distance of the actual mandibular osteotomy was 2.06 ± 0.86 mm. When compared to the virtual harvested grafts, the mean error volume of the actual harvested grafts was 1412.22 ± 439.24 mm3 (9.12% ± 2.84%). The mean error between the volume of the actual harvested grafts and the shaped grafts was 2094.35 ± 929.12 mm3 (12.40% ± 5.50%). CONCLUSIONS: The use of computer-aided rapid prototyping templates for virtual surgical planning appears to positively influence the accuracy of mandibular reconstruction.

Silencing of integrin-linked kinase suppresses in vivo tumorigenesis of human ovarian carcinoma cells.

Integrin-linked kinase (ILK) plays a role in the regulation of multiple cellular functions (e.g., promoting cell migration and proliferation, but inhibiting cell adhesion). This study investigated the inhibitory effects of ILK gene knockdown on the regulation of in vivo tumorigenesis of human ovarian carcinoma cells in nude mouse xenografts. HO-8910 cells were transfected with an ILK antisense oligonucleotide (ILK-ASO) to silence the ILK gene. Expression of ILK mRNA and protein was evaluated by RT-PCR and western blotting, respectively. The cell cycle was assessed by flow cytometric analysis. Cells with or without ILK-ASO transfection were subcutaneously injected into nude mice. The mouse body weight, tumor formation, tumor size and tumor weight were determined up to 30 days after inoculation. Tumor cells transfected with ILK-ASO had significantly decreased ILK mRNA and protein expression (P<0.01) when compared to the control cells. ILK gene silencing significantly increased the number of cells in the G0/G1 phase (67.61 vs. 43.29%, χ2=1197.15, P<0.01). After tumor cell inoculation, tumor cells transfected with ILK-ASO showed significantly delayed tumor formation when compared to control (9.10±0.74 vs. 5.30±0.67 days, respectively; P<0.01). In addition, tumor growth was suppressed in the 30 days following inoculation (P<0.01 compared with the controls). The average tumor weight in the ILK-ASO group was statistically lower than that of the control group (1.29±0.11 vs. 1.57±0.13 g, respectively; P<0.01). This study demonstrated that ILK-ASO transfection efficiently downregulated ILK expression in human ovarian carcinoma HO-8910 cells and that ILK gene silencing suppressed tumor growth in nude mice xenografts.

A meta-analytic review of ERCC1/MDR1 polymorphism and chemosensitivity to platinum in patients with advanced non-small cell lung cancer.

BACKGROUND: Platinum-based regimens are used as standard first-line chemotherapy in non-small cell lung cancer (NSCLC) patients. To study if pharmacogenetic approach may allow a tailored selection of platinum chemotherapy for advanced NSCLC, we performed a meta-analysis to compare chemosensitivity to platinum with different ERCC1 C118T/ MDR1 C3435T single-nucleotide polymorphism (SNP). METHODS: Relevant studies were identified by searching the PubMed, Embase, Cochrane, OVID, Springer, EBSCO and CNKI databases. Inclusion criteria were patients with advanced NSCLC who received platinum-based chemotherapy, an evaluated polymorphism of ERCC/MDR1 and overall response rate. We excluded duplicate publications, letters and review articles. The RevMan 4.2 and STATA 11 package were used to do comprehensive quantitative assessment. RESULTS: A total of 11 studies were included in this meta-analysis. For studies evaluating ERCC1 C118T, test for heterogeneity was done (χ(2) = 13.41, P = 0.1), and the odds ratio (OR) for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 1.50 (95% CI 1.09 - 2.06, P = 0.01). In four studies evaluating MDR1 polymorphism, test for heterogeneity was also done (χ(2) = 3.22, P = 0.36), and the OR for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 2.30 (95% CI 1.44 - 3.68, P = 0.0005). CONCLUSIONS: The results indicated that platinum-based chemotherapy sensitivity was significantly associated with polymorphism of ERCC1 C118T and MDR1 C3435T SNP. In further perspective studies, the ERCC1/MDR1 SNPs might serve as simple and less invasive biomarkers for personalized chemotherapy with platinum-based anticancer drugs.

Performance enhancement of blue light-emitting diodes without an electron-blocking layer by using special designed p-type doped InGaN barriers.

In this study, the characteristics of the nitride-based blue light-emitting diode (LED) without an electron-blocking layer (EBL) are analyzed numerically. The emission spectra, carrier concentrations in the quantum wells (QWs), energy band diagrams, electrostatic fields, and internal quantum efficiency (IQE) are investigated. The simulation results indicate that the LED without an EBL has a better hole-injection efficiency and smaller electrostatic fields in its active region over the conventional LED with an AlGaN EBL. The simulation results also show that the LED without an EBL has severe efficiency droop. However, when the special designed p-type doped InGaN QW barriers are used, the efficiency droop is markedly improved and the electroluminescence (EL) emission intensity is greatly enhanced which is due to the improvement of the hole uniformity in the active region and small electron leakage.

Identification of pathways involved in paclitaxel activity in cervical cancer.

Paclitaxel is one of the key chemotherapeutic drugs widely used to treat various types of cancer. Many cervical cancer patients exhibit selectivity in response to thereapy, however, which is considered to be correlated with drug-gene-pathways. The aim of this study was to identify pathways involved in paclitaxel activity in cervical cancer. Gene expression data was obtained from the NCBI Gene Expression Omnibus and the associations between paclitaxel and genes from DrugBank, MATADOR, TTD, CTD and SuperTarget databases. Differentially expressed genes in cervical cancer were identified using the significance analysis of microarrays (SAM) statistical technique. Pathway analysis was performed according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database using the software package SubpathwayMiner to predict target genes of paclitaxel in cervical cancer and regulated pathways. We found that paclitaxel, which exhibits anticancer activity in cervical cancer, may interact with these differentially expressed genes and their corresponding signaling pathways. Our study presents the first in-depth, large-scale analysis of pathways involved in paclitaxel activity in cervical cancer. Interestingly, these pathways have not been reported to be involved in other tumors. Thus our findings may contribute to the understanding of the mechanisms underlying paclitaxel resistance in cervical cancer.

[Influences of human beta-defensin 1 on the replication and expression of HPV18 in Hela cell].

OBJECTIVE: Investigate the influences of human beta-defensinl (hbetaD1) on the replication and expression of HPV18 in Hela cell. METHODS: Gene transfection: mediated by Fugen HD, hbetaD1/psectag plasmid was transfected to Hela cell [hbetaD1/psectag : liposome complexes (hbetaD1/psectag : lip)group], and control groups [psectag : liposome complexes(psectag : lip) group and blank group) were also established. After transfection, the expression of the target gene in Hela cell was investigated by the method of immunocytochemistry. 48 h and 72 h after the transfection, the change of the copy number of HPV18 DNA in Hela cell was investigated respectively by the quantitative fluorescent PCR method, and the change of the HPV18 E6 mRNA in Hela cell was evaluated by the semiquantitative RT-PCR. RESULTS: 48 h and 72 h after the transfection of hbetaD1/psectag plasmid to Hela cell, hbetaD1 was expressed in both of the two groups, and the latter showed a tendency of stronger expression. Compared with the control groups, the copy number of HPV18 DNA in Hela cell in the hbetaD1/psectag : lip group increased at 48 h and decreased at 72 h after the transfection, but the change was not statistically significant. 48 h after the transfection, compared with the control groups, the expression of HPV18 E6 mRNA in Hela cell in the hbetaD1/psectag : lip group changed a little; and 72 h after the transfection, the expression level of HPV18 E6 mRNA decreased significantly (P < 0.05). CONCLUSION: hbetaD1 displayed an inhibitory effect to the expression of HPV18 mRNA in Hela cell in a concentration-dependent pattern, but no significant effect on the duplication of HPV18 DNA.