Fluid shear stress regulates the survival of circulating tumor cells via nuclear expansion.

Distant metastasis mainly occurs through hematogenous dissemination, where suspended circulating tumor cells (CTCs) experience a considerable level of fluid shear stress. We recently reported that shear flow induced substantial apoptosis of CTCs, although a small subpopulation could still persist. However, how suspended tumor cells survive in shear flow remains poorly understood. This study finds that fluid shear stress eliminates the majority of suspended CTCs and increases nuclear size, whereas it has no effect on the viability of adherent tumor cells and decreases their nuclear size. Shear flow promotes histone acetylation in suspended tumor cells, the inhibition of which using one drug suppresses shear-induced nuclear expansion, suggesting that shear stress might increase nuclear size through histone acetylation. Suppressing histone acetylation-mediated nuclear expansion enhances shear-induced apoptosis of CTCs. These findings suggest that suspended tumor cells respond to shear stress through histone acetylation-mediated nuclear expansion, which protects CTCs from shear-induced destruction. Our study elucidates a unique mechanism underlying the mechanotransduction of suspended CTCs to shear flow, which might hold therapeutic promise for CTC eradication.

Regulation of Hot Electrons Transport Achieved through Controlled Electron-Phonon Coupling in Metallic Heterostructures.

The electron-phonon (e-ph) interactions are pivotal in shaping the electrical and thermal properties, and in particular, determining the carrier dynamics and transport behaviors in optoelectronic devices. By employing pump-probe spectroscopy and ultrafast microscopy, the consequential role of e-ph coupling strength in the spatiotemporal evolution of hot electrons is elucidated. Thermal transport across the metallic interface is controlled to regulate effective e-ph coupling factor Geff in Au and Au/Cr heterostructure, and their impact on nonequilibrium transport of hot electrons is examined. Via the modulation of buried Cr thickness, a strong correlation between Geff and the diffusive behavior of hot electrons is found. By enhancing Geff through the regulation of thermal transport across interface, there is a significant reduction in e-ph thermalization time, the maximum diffusion length of hot electrons, and lattice heated area which are extracted from the spatiotemporal evolution profiles. Therefore, the increased Geff significantly weakens the diffusion of hot electrons and promotes heat relaxation of electron subsystems in both time and space. These insights propose a robust framework for spatiotemporal investigations of G impact on hot electron diffusion, underscoring its significance in the rational design of advanced optoelectronic devices with high efficiency.

Prediction of esophageal cancer risk based on genetic variants and environmental risk factors in Chinese population.

BACKGROUND: Results regarding whether it is essential to incorporate genetic variants into risk prediction models for esophageal cancer (EC) are inconsistent due to the different genetic backgrounds of the populations studied. We aimed to identify single-nucleotide polymorphisms (SNPs) associated with EC among the Chinese population and to evaluate the performance of genetic and non-genetic factors in a risk model for developing EC. METHODS: A meta-analysis was performed to systematically identify potential SNPs, which were further verified by a case-control study. Three risk models were developed: a genetic model with weighted genetic risk score (wGRS) based on promising SNPs, a non-genetic model with environmental risk factors, and a combined model including both genetic and non-genetic factors. The discrimination ability of the models was compared using the area under the receiver operating characteristic curve (AUC) and the net reclassification index (NRI). The Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to assess the goodness-of-fit of the models. RESULTS: Five promising SNPs were ultimately utilized to calculate the wGRS. Individuals in the highest quartile of the wGRS had a 4.93-fold (95% confidence interval [CI]: 2.59 to 9.38) increased risk of EC compared with those in the lowest quartile. The genetic or non-genetic model identified EC patients with AUCs ranging from 0.618 to 0.650. The combined model had an AUC of 0.707 (95% CI: 0.669 to 0.743) and was the best-fitting model (AIC = 750.55, BIC = 759.34). The NRI improved when the wGRS was added to the risk model with non-genetic factors only (NRI = 0.082, P = 0.037). CONCLUSIONS: Among the three risk models for EC, the combined model showed optimal predictive performance and can help to identify individuals at risk of EC for tailored preventive measures.

Adhesion to the Brain Endothelium Selects Breast Cancer Cells with Brain Metastasis Potential.

Tumor cells metastasize from a primary lesion to distant organs mainly through hematogenous dissemination, in which tumor cell re-adhesion to the endothelium is essential before extravasating into the target site. We thus hypothesize that tumor cells with the ability to adhere to the endothelium of a specific organ exhibit enhanced metastatic tropism to this target organ. This study tested this hypothesis and developed an in vitro model to mimic the adhesion between tumor cells and brain endothelium under fluid shear stress, which selected a subpopulation of tumor cells with enhanced adhesion strength. The selected cells up-regulated the genes related to brain metastasis and exhibited an enhanced ability to transmigrate through the blood-brain barrier. In the soft microenvironments that mimicked brain tissue, these cells had elevated adhesion and survival ability. Further, tumor cells selected by brain endothelium adhesion expressed higher levels of MUC1, VCAM1, and VLA-4, which were relevant to breast cancer brain metastasis. In summary, this study provides the first piece of evidence to support that the adhesion of circulating tumor cells to the brain endothelium selects the cells with enhanced brain metastasis potential.

Five New Cantharidin Derivatives from the Insect Mylabris cichorii L. and Their Potential against Kidney Fibrosis In Vitro.

Five new monoterpenoids including three 1-hydroxymethyl-2-methyl cantharimide-type derivatives (1, 2, and 5) and two 1,2-dimethyl cantharimide-type derivatives (3 and 4), together with three known compounds (6-8) were isolated from the insect Mylabris cichorii Linnaeus. The structures of these new compounds, including their absolute configurations, were characterized by detailed analysis of NMR, chemical derivatization, and quantum chemical ECD calculations. All of the compounds were tested for their biological activity against kidney fibrosis. The results revealed that compounds 2, 4, and 7 could inhibit kidney fibrosis in vitro at 40 µM by inhibiting the expression of fibronectin and collagen I in TGF-ß1-induced NRK-52e cells.

The toxicity of perfluorodecanoic acid is mainly manifested as a deflected immune function.

BACKGROUND: Perfluorodecanoic acid (PFDA) is a type of perfluoroalkyl acid (PFAA). PFDA has toxicity similar to dioxin; its effect on the body is not through a single target or a single pathway. However, the mechanism at the global level is still unclear. METHODS AND RESULTS: We treated mice with PFDA and characterized the global changes in gene expression in the liver using microarray analyses. The enriched KEGG pathways and GO analyses revealed that PFDA greatly affected the immune response, which was different from the response of gastric cells previously studied. As a proof of principle, the expressions of IL-1ß and IL-18 were both decreased after PFDA treatment, and qRT-PCR and ELISAs verified the reduction of IL-1ß and IL-18 in liver tissues. Mechanistic investigations indicated that PFDA inhibited caspase-1 activation, and decreased the mRNA levels of NLRP1, NLRP3, and NLRC4; thus, suggesting that inflammasome assemblies were suppressed. Further microarray data revealed that cIAP2 and its binding proteins, which are critical for regulating inflammasome assembly, were also repressed by PFDA. In addition, flow cytometry results revealed a significant inhibition of Th1 cell differentiation in the livers of PFDA-treated mice. CONCLUSIONS: The results of this study suggested that one of the main toxic effects of PFDA on livers was the inhibition of immune response.

Unusual sesquilignans with anti-inflammatory activities from the resin of Ferula sinkiangensis.

Sinkianlignans A - D (1-4), four new sesquilignans with an unusual architectures was characterized with a rarely α-γ', ß-γ', and γ-γ' linkage pattern, and sinkianlignans E - F (5 and 6), two lignans, were isolated from the Ferula sinkiangensis. Hypothetic biosynthetic pathway of compound 3 contain a newly formed six-membered C-ring by Diels-Alder cycloaddition. The structures of isolates were established by spectroscopic techniques and computational methods. Biological evaluation of all the isolated compounds revealed that compounds 2a and 2b could inhibit IL-6 and TNF-α production in lipopolysaccharide (LPS) induced RAW264.7 cells in a dose-dependent manner.

Structural Optimization and Improving Antitumor Potential of Moreollic Acid from Gamboge.

Moreollic acid, a caged-tetraprenylated xanthone from Gamboge, has been indicated as a potent antitumor molecule. In the present study, a series of moreollic acid derivatives with novel structures were designed and synthesized, and their antitumor activities were determined in multifarious cell lines. The preliminary screening results showed that all synthesized compounds selectively inhibited human colon cancer cell proliferation. TH12-10, with an IC50 of 0.83, 1.10, and 0.79 µM against HCT116, DLD1, and SW620, respectively, was selected for further antitumor mechanism studies. Results revealed that TH12-10 effectively inhibited cell proliferation by blocking cell-cycle progression from G1 to S. Besides, the apparent structure-activity relationships of target compounds were discussed. To summarize, a series of moreollic acid derivatives were discovered to possess satisfactory antitumor potentials. Among them, TH12-10 displays the highest antitumor activities against human colon cancer cells, in which the IC50 values in DLD1 and SW620 are lower than that of 5-fluorouracil.

The Relationship between MALAT1 Polymorphism rs3200401 C > T and the Risk of Overall Cancer: A Meta-Analysis.

Background and Objectives: At present, the association between the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) polymorphism rs3200401 C > T and cancer risk remain controversial. The aim of this meta-analysis was to assess the association between rs3200401 C > T and cancer susceptibility. Materials and Methods: The databases of PubMed, EMBASE and Web of Science were searched for literature published in English until 1 September 2021. The odd ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association in five genetic models. Heterogeneity was assessed using the Q-test and I2 test. Begg's funnel plot and Egger's linear regression test were conducted to assess publication bias. Meta-regression analysis was used to explore potential sources of heterogeneity. Trial sequential analysis (TSA) was performed to validate the reliability of the results. Results: A total of 10 case-control studies involving 6630 cases and 7457 controls were included in this study. The pooled ORs showed no significant association between MALAT1 rs3200401 C > T and cancer risk in five genetic models. Similarly, the association was not found in the subgroups of control source, ethnicity and study quality. In the cancer type subgroup, the results demonstrated that the T allele increased the risk of colorectal cancer (CRC) compared with the C allele. (C vs. T: OR, 1.16; 95% CI, 1.01-1.33). Conclusion: In the current meta-analysis, we found no significant association between MALAT1 polymorphism rs3200401 C > T and overall cancer risk. However, the rs3200401 C > T may be linked to a higher risk of CRC, which needs more studies to be further confirmed.

MiR-448-5p/VEGFA Axis Protects Cardiomyocytes from Hypoxia Through Regulating the FAS/FAS-L Signaling Pathway.

Bioinformatics analysis showed that miR-448-5p expression in the myocardial tissue of rats with myocardial infarction significantly increased, suggesting that it may participate in myocardial cell apoptosis in myocardial infarction. This study aimed to explore the protective effects of miR-448-5p on hypoxic myocardial cells.H9C2 cells were cultured and subjected to anoxia for 2, 4, and 8 hours to establish a hypoxia model. MiR-448-5p mimic and inhibitor were transfected into the cells; then, a dual-luciferase experiment was conducted to verify the targeting relationship between miR-448-5p and VEGFA. Cell viability and apoptosis was detected by cell counting kit-8 and flow cytometry, respectively. The expressions of apoptosis-related proteins, miR-448-5p, FAS, and FAS-L were measured using western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Hypoxia-reduced H9C2 cell viability and promoted apoptosis. MiR-448-5p expression was increased after H9C2 cell hypoxia. MiR-448-5p mimic significantly inhibited the viability and promoted the apoptosis of hypoxia-induced model cells. Hypoxia promoted the expression of apoptosis-related protein B-cell lymphoma-2 (Bcl-2) and inhibited the expressions of Bcl-2-associated x protein (Bax), cleaved caspase-3, and caspase-3, whereas the effect of inhibitor on hypoxia-reduced H9C2 cell and apoptotic protein expression were opposite to miR-448-5p mimic. MiR-448-5p targeted VEGFA and regulated its expression. Silenced VEGFA expression significantly inhibited inhibitor effect on increasing cell viability and promoted apoptosis. In addition, miR-448-5p mimic inhibited the effect of hypoxia on promoting the expressions of FAS and FAS-L of H9C2 cells. Inhibitors had the opposite effect on cell hypoxia model.The miR-448-5p/VEGFA axis could protect cardiomyocytes from hypoxia through inhibiting the FAS/FAS-L signaling pathway.

miR-3607, a biomarker of hepatocellular carcinoma invasion and aggressiveness: Its relationship with epithelial-mesenchymal transition process.

microRNA-3607 (miR-3607) has been identified as an important biomarker, and its aberrant expression exerts a significant role in tumorigenesis. However, the biological function of miR-3607 in hepatocellular carcinoma (HCC) needs to be deciphered comprehensively. Clinical samples of HCC patients, as well as normal cases, were derived from The Cancer Genome Atlas database. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting analyses were utilized to detect the expression levels of indicated genes. Cell counting kit-8 (CCK-8), colony formation, and transwell assays were performed to assess the effect of miR-3607 in HCC cell viability, migration, and invasion. Bioinformatics analysis and luciferase reporter gene assay was applied to screen the target genes of miR-3607 and verified the association between miR-3607 and its potential target gene. Our study showed that miR-3607 expression was decreased in HCC tissues and cell lines, and its downregulation was linked with poor outcomes of HCC patients. miR-3607 was noted to inhibit HCC cell growth, colony formation, migration, and invasion. Besides, minichromosome maintenance (MCM5) was a possible target gene of miR-3607 in HCC. Overexpression of MCM5 was observed in HCC and induced unfavorable prognosis. MCM5 expression had a negative correlation with miR-3607. MCM5 can abolish the suppressive impacts of miR-3607 on HCC cell malignant behaviors and the epithelial-mesenchymal transition (EMT) process. To sum up, our results unveiled that miR-3607 could inhibit HCC cell growth, migration, and invasion by regulating MCM5 and mediating EMT process, suggesting a new probable biomarker for further treatment of HCC.

Fluid Shear Stress Induces EMT of Circulating Tumor Cells via JNK Signaling in Favor of Their Survival during Hematogenous Dissemination.

Tumor cells metastasize to distal organs mainly through hematogenous dissemination, where they experience considerable levels of fluid shear stress. Epithelial-mesenchymal transition (EMT) plays a critical role in tumor metastasis. However, how fluid shear stress influences the EMT phenotype of circulating tumor cells (CTCs) in suspension has not been fully understood. The role of shear-induced EMT in cell survival under blood shear flow remains unclear. This study shows that the majority of breast CTCs underwent apoptosis under shear flow and the surviving cells exhibited mesenchymal phenotype, suggesting that fluid shear stress induces EMT. Mechanistically, fluid shear stress-activated Jun N-terminal kinase (JNK) signaling, inhibition/activation of which suppressed/promoted the EMT phenotype. In particular, shear flow facilitated the JNK-dependent transition of epithelial CTCs into the mesenchymal status and maintained the pre-existing mesenchymal cells. Importantly, the induction of EMT suppressed the pro-apoptosis gene p53 upregulated modulator of apoptosis (PUMA) and enhanced the survival of suspended CTCs in fluid shear stress, which was rescued by overexpressing PUMA or silencing JNK signaling, suggesting that shear-induced EMT promotes CTC survival through PUMA downregulation and JNK activation. Further, the expressions of EMT markers and JUN were correlated with poor patient survival. In summary, our findings have demonstrated that fluid shear stress induces EMT in suspended CTCs via JNK signaling that promotes their survival in shear flow. This study thus unveils a new role of blood shear stress in CTC survival and facilitates the development of novel therapeutics against tumor metastasis.

Mechanics and Actomyosin-Dependent Survival/Chemoresistance of Suspended Tumor Cells in Shear Flow.

Tumor cells disseminate to distant organs mainly through blood circulation in which they experience considerable levels of fluid shear stress. However, the effects of hemodynamic shear stress on biophysical properties and functions of circulating tumor cells (CTCs) in suspension are not fully understood. In this study, we found that the majority of suspended breast tumor cells could be eliminated by fluid shear stress, whereas cancer stem cells held survival advantages over conventional cancer cells. Compared to untreated cells, tumor cells surviving shear stress exhibited unique biophysical properties: 1) cell adhesion was significantly retarded, 2) these cells exhibited elongated morphology and enhanced spreading and expressed genes related to epithelial-mesenchymal transition or hybrid phenotype, and 3) surviving tumor cells showed reduced F-actin assembly and stiffness. Importantly, inhibiting actomyosin activity promoted the survival of suspended tumor cells in fluid shear stress, whereas activating actomyosin suppressed cell survival, which might be explained by the up- and downregulation of the antiapoptosis genes. Soft surviving tumor cells held survival advantages in shear flow and higher resistance to chemotherapy. Inhibiting actomyosin activity in untreated cells enhanced chemoresistance, whereas activating actomyosin in surviving tumor cells suppressed this ability. These findings might be associated with the corresponding changes in the genes related to multidrug resistance. In summary, these data demonstrate that hemodynamic shear stress significantly influences biophysical properties and functions of suspended tumor cells. Our study unveils the regulatory roles of actomyosin in the survival and drug resistance of suspended tumor cells in hemodynamic shear flow, which suggest the importance of fluid shear stress and actomyosin activity in tumor metastasis. These findings may reveal a new, to our knowledge, mechanism by which CTCs are able to survive hemodynamic shear stress and chemotherapy and may offer a new potential strategy to target CTCs in shear flow and combat chemoresistance through actomyosin.

Retracted: microRNA-145 regulates tumor suppressor candidate 3 and mitogen-activated protein kinase pathway to inhibit the progression of colorectal cancer.

BACKGROUND: It has been reported that microRNA-145 (miR-145) is downregulated in various cancers, including colorectal cancer (CRC). However, the role of miR-145 in progress of CRC and its mechanism remains unclear. METHODS: The expressions of miR-145 and tumor suppressor candidate 3 (TUSC3) were determined in CRC tissues and cells by real-time quantitative polymerase chain reaction and Western blot analysis. The effects of miR-145 and TUSC3 on cell viability, migration, and invasion of CRC cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-trtrazolium bromide assay and trans-well chamber experiment, respectively. The interaction between miR-145 and TUSC3 was explored by bioinformatics analysis, luciferase reporter assay, and Western blot analysis. The abundances of mitogen-activated protein kinase (MAPK) signaling pathway-related proteins were measured by Western blot analysis. RESULTS: miR-145 expression was downregulated in CRC tissues and cell lines, and TUSC3 was upregulated in CRC tissues and correlated inversely with miR-145 abundance. Overexpression of miR-145 and knockdown of TUSC3 suppressed cell viability, migration, and invasion in LS174T and HCT116 cells. Moreover, TUSC3 was indicated as a novel target of miR-145 and its expression was negatively regulated by miR-145. Restoration of TUSC3 can partially reverse the inhibitory effects of miR-145 on phosphorylation of extracellular signal-regulated kinases 1 and 2 in CRC cells. CONCLUSION: miR-145 can inhibit the viability, migration, and invasion through addressing MAPK signaling pathway by targeting TUSC3 in CRC cells, providing a novel biomarker for treatment of CRC.

Effect of combined medicated thread moxibustion plus needle picking therapy of Zhuang nationality medicine on antioxidant levels in a rat model of sciatica.

OBJECTIVE: To investigate the effect and underlying mechanisms of combined medicated thread moxibustion therapy plus needle picking therapy of Zhuang nationality medicine on antioxidant levels in a rat model of sciatica. METHODS: One hundred Wistar rats, of specific pathogen free level, were randomly divided into five groups: normal control group, model group, medicated thread moxibustion group, needle picking group, and combination group. Each group contained 20 rats. In the model, medicated thread moxibustion, needle picking, and combination groups, sciatica models were established through chronic constriction injury of the sciatic nerve. After the model was established, the rats in the medicated thread moxibustion, needle picking, and combination groups were given the corresponding therapies for 21 days. The control and model groups received no treatment. Reactive oxygen species, superoxide dismutase, malondialdehyde, and total antioxidant capacity changes were determined. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit NADPH oxidases 4 (NOX4) mRNA expression and the morphology of cells were observed to detect apoptosis of gamma- aminobutyric acid ergic (GABAergic) neurons. RESULTS: Compared with control group, reactive oxygen species and malondialdehyde levels rose significantly in the model group (P < 0.01), while superoxide dismutase and total antioxidant capacity levels were lowered (P < 0.05). Compared with the model group, reactive oxygen species and malondialdehyde decreased in the needle picking group (P < 0.05), while superoxide dismutase levels were increased (P < 0.05); reactive oxygen species and malondialdehyde significantly decreased in the combination group (P < 0.01). In addition, the model group had higher NOX4 mRNA expression than that of the control group (P < 0.05), and the combination group had lower expression levels than that of the model group (P < 0.05). Apoptosis of GABAergic neurons was observed in the model group, and was attenuated after combined therapy. CONCLUSION: The medicated thread moxibustion therapy plus needle picking therapy of Zhuang nationality medicine can prevent oxidative damage in the rat model of sciatica via down-regulating NOX4 expression, improving antioxidant capacity, and inhibiting the oxidative damage pathway of GABAergic neurons.

Identification of putative odorant binding protein genes in Asecodes hispinarum, a parasitoid of coconut leaf beetle (Brontispa longissima) by antennal RNA-Seq analysis.

Asecodes hispinarum (Hymenoptera: Eulophidae) is an endoparasitoid and an efficient biological control agent which attacks larvae of Brontispa longissima, a serious insect pest of Palmae plants in China. Odorant binding proteins (OBPs) are believed to be important for transporting semiochemicals through the aqueous sensillar lymph to the olfactory receptor cells within the insect antennal sensilla. No previous study has reported on OBPs in A. hispinarum. In this study, we conducted the large-scale identification of OBP genes from the antennae of A. hispinarum by using transcriptome sequencing. Approximately 28.4 million total raw reads and about 27.3 million total clean reads were obtained, and then 46,363 unigenes were assembled. Of these unigenes, a total of 21,263 can be annotated in the NCBI non-redundant database. Among the annotated unigenes, 16,623 of them can be assigned to GO (Gene Ontology). Furthermore, we identified 8 putative OBP genes, and a phylogenetic tree analysis was performed to characterize the 8 OBP genes. In addition, the expression of the 8 OBP genes in different A. hispinarum body tissues was analyzed by real-time quantitative polymerase chain reaction (qRT-PCR). The results indicated that the 8 OBP genes were expressed accordingly to sexes and tissues, but all highly expressed in antennae. The finding of this study will lay the foundation for unraveling molecular mechanisms of A. hispinarum chemoperception.

Odorant binding characteristics of three recombinant odorant binding proteins in Microplitis mediator (Hymenoptera: Braconidae).

Odorant binding proteins (OBPs) are believed to be important for transporting semiochemicals through the aqueous sensillar lymph to the olfactory receptor cells within the insect antennal sensilla. In this study, three new putative OBP genes, MmedOBP8-10, were identified from a Microplitis mediator (Hymenoptera: Braconidae) antennal cDNA library. Quantitative real-time PCR (qRT-PCR) analysis revealed that all three of the OBP genes were expressed mainly in the antennae of adult wasps. The three OBPs were recombinantly expressed in Escherichia coli and purified by Ni ion affinity chromatography. Fluorescence competitive binding assays were performed using N-phenyl-naphthylamine as a fluorescent probe and 45 small organic compounds as competitors. These assays demonstrated that the three M. mediator OBPs can bind a broad range of odorant molecules with different binding affinities. They can bind the following ligands: nonane, farnesol, nerolidol, nonanal, ß-ionone, acetic ether, and farnesene. In a Y-tube assay with these ligands as odor stimuli and paraffin oil as a control, all ligands, except nerolidol and acetic ether, were able to elicit behavioral responses in adult M. mediator. The wasps were significantly attracted to ß-ionone, nonanal, and farnesene and repelled by nonane and farnesol. The results of this work provide insight into the chemosensory functions of the OBPs in M. mediator.

[Effects of hyperthermia combined platinum-based drugs on ovarian cancer cell lines SKOV3].

OBJECTIVE: To investigate the effects and mechanisms of hyperthermia combined with various platinum-based drugs cis-platinum (DDP), carboplatin (CBP), oxaliplatin (OXA) on the proliferation and apoptosis of ovarian cancer cell lines SKOV3. METHODS: SKOV3 cells were treated with different concentrations of anticancer drugs DDP (final concentration respectively 0, 1.25, 2.5, 5.0, 10.0, 20.0 microg/mL), CBP and OXA (both final concentration respectively 0, 2.5, 5.0, 10.0, 20.0, 40 microg/mL) at a temperature of 42 degrees C for hyperthermia or 37 degrees C for normal temperature. Methyl thiazolyl tetrazolium (MTT) method was used to test growth ratios of ovarian cancer cell lines SKOV3. Real-time PCR was adopted to detect the expression level of excision repair cross-complementing group 1 (ERCC1) and Survivin mRNA in SKOV3 cells. RESULTS: DDP, CBP and OXA inhibited the growth of SKOV3 in a dose-dependent manner (P < 0.05). Hyperthermia could increase the sensitivity of SKOV3 to cis-platinum, carboplatin and oxaliplatin (P < 0.05). The half inhibitory concentration (IC50) values of DDP, CBP and OXA were (7.271 +/- 0.096) microg/mL, (37.609 +/- 0.779) microg/mL and (28.328 +/- 0.698) microg/mL respectively. When combined with hyperthermia, the IC50 values of DDP, CBP, and OXA were (2.075 +/- 0.244) microg/mL, (19.591 +/- 0.453) microg/mL, (19.089 +/- 0.424) microg/mL (P < 0.05). The increased sensitivity index was 2.075 +/- 0.244 for cis-platinum, 1.92 +/- 0.044 for carboplatin, 1.484 +/- 0.039 for oxaliplatin. After the treatment of hyperthermia, the expression of ERCC1 and Survivin mRNA showed downward trend. ERCC1 decreased more significantly in the group of hyperthermia combined with carboplatin, and Survivin decreased more significantly in the group of hyperthermia combined with oxaliplatin (P < 0.05). CONCLUSION: Hyperthermia can enhance the sensitivity of ovarian cancer SKOV3 cells to platinum-based drugs, which may be related to the down regulation of ERCC1 and Survivin expression.

[Expression of CLIC1 and IGFBP7 in complete hydatidiform mole].

OBJECTIVE: To investigate the expression level of chloride intracellular channel 1 (CLIC1) and insulin-like growth factor binding protein 7 (IGFBP7) in complete hydatidiform mole (CHM) and estimate the relationship between the expression level and clinical prognosis. METHODS: Immunohistochemistry (IHC) method was used to detect the expression level of P57(KIP2) in order to differentiate CHM. CLIC1 and IGFBP7 expression level of CHM were measured by IHC method then. RESULTS: (1) According to the P57(KIP2) expression result 66 patients were diagnosed as CHM (85.71%). Fourteen of 66 patients progressed into gestational trophoblastic neoplasia (GTN), which accounted for 21.21%. (2) The results of IHC showed that CLIC1 significantly higher expressed in malignant group than spontaneous regressive group (P = 0.014). IGFBP7 significantly down-regulated in malignant group (P = 0.002). (3) Pearson correlation analysis results revealed that there were no relation between the expression of CLIC1 and IGFBP7 (P = 0.761). Logistic regression analysis indicated that down-regulation of IGFBP7 was the independent risk factors of CHM progression, P = 0.005, OR = 8.493 (95% confidence interval (CI): 1.878-38.401); Serum hCG > 5 x 10(5) mIU/mL was the independent risk factors of CHM progression too, P = 0.011, OR = 11.251 (95% CI: 1.731-73.151). (4) Receiver operator characteristic curve (ROC curve) results showed that the area under the curve (AUC) of CLIC1 was 0.707. The optimum cut off was 10.5, and correspondingly sensitivity was 42.90%, specificity 94.20%. AUC of IGFBP7 was 0.764. The optimum cut off was 7.0, and the correspondingly sensitivity and specificity were 64.30% and 78.80% respectively. Combining the two markers in series, the sensitivity of predicting the prognosis of CHM was 21.42%, while the specificity was 100%. When combining in parallel, the sensitivity and specificity were 85.71% and 71.15% respectively. CONCLUSION: Up-regulation of CLIC1 and down-regulation of IGFBP7 might pay an important role in progression of CHM, but there was no relationship between the expression levels of them. The predictive values of malignance transformation of CHM with the two biomarkers were with certain accuracy, and combining them in parallel test could improve accuracy. They are promising to be candidate prognostic markers of CHM.