We thus propose that K19 staining be further investigated as a diagnostically useful test to be applied to biopsy specimens from patients clinically suspected to have

PBC when classical histologic features are absent. “
“The response rate to sorafenib in hepatocellular carcinoma (HCC) is relatively low (0.7%-3%), however, PLX3397 cell line rapid and drastic tumor regression is occasionally observed. The molecular backgrounds and clinico-pathological features of these responders remain largely unclear. We analyzed the clinical and molecular backgrounds of 13 responders to sorafenib with significant tumor shrinkage in a retrospective study. A comparative genomic hybridization analysis using one frozen HCC sample from a responder demonstrated that the 11q13 region, a rare amplicon in HCC including the loci for FGF3 and Navitoclax price FGF4, was highly amplified. A real-time polymerase chain reaction–based copy number assay revealed that FGF3/FGF4 amplification was observed in three of the 10 HCC samples from responders in which DNA was evaluable, whereas amplification was not observed

in 38 patients with stable or progressive disease (P = 0.006). Fluorescence in situ hybridization analysis confirmed FGF3 amplification. In addition, the clinico-pathological features showed that multiple lung metastases (5/13, P = 0.006) and a poorly differentiated histological type (5/13, P = 0.13) were frequently observed in responders. A growth inhibitory assay showed that only one FGF3/FGF4-amplified and three FGFR2-amplified cancer cell lines exhibited hypersensitivity to sorafenib in vitro. Finally, an in vivo study revealed that treatment with a low dose of sorafenib was partially effective for stably and exogenously expressed FGF4 tumors, while being less effective in tumors expressing EGFP or FGF3. Conclusion:

FGF3/FGF4 amplification was observed in around 2% of HCCs. Although the sample size was relatively small, FGF3/FGF4 amplification, a poorly differentiated histological type, and multiple lung metastases were frequently observed in responders to sorafenib. Inositol monophosphatase 1 Our findings may provide a novel insight into the molecular background of HCC and sorafenib responders, warranting further prospective biomarker studies. (HEPATOLOGY 2013) Hepatocellular carcinoma (HCC) is the sixth most common cancer-related cause of death in the world annually, and the development of new primary tumors, recurrences, and metastasis are the most common causes of mortality among patients with HCC.1, 2 Sorafenib (Nexavar; Bayer Healthcare Pharmaceuticals Inc.) is a small molecule kinase inhibitor that is classified as an anti-angiogenic inhibitor.

4 Because IL-12p40 is a subunit shared by IL-12 and IL-23, deletion of this subunit disrupts both the IL-12/Th1 pathway and IL-23/Th17 pathway. The first aim of this study was to examine the role of IL-23 in liver and colon diseases of the dnTGFβRII mouse model by

deleting p19 of the IL-23 heterodimer, which is unique to this cytokine in the IL-12 family. Although IL-12 is required for the development of IFN-γ-producing Th1 cells, IL-23 induces the differentiation of naïve CD4 T cells into a highly pathogenic helper T-cell population, termed Th17, that produces IL-17A, IL-17F, IL-6, and TNF, but not IFN-γ or IL-4.5 Several previous studies have suggested a potential link between IL-17 and PBC.14-16 http://www.selleckchem.com/products/SB-203580.html Therefore, the second strategy we used in the current study was to delete the gene encoding IL-17A in efforts to examine whether this cytokine contributes to autoimmune pathogenesis in dnTGFβRII mice. Results from these studies demonstrate that disrupting the IL-23/Th17 pathway by deleting IL-23p19 abolished colitis, but had no detectable effect on the severity of cholangitis in dnTGFβRII mice, indicating that the IL-23/Th17 axis is involved in the pathogenesis of autoimmune colitis, but not in the cholangitis of this

mouse model. However, deletion of the IL-17 gene from dnTGFβRII did not affect either colitis or cholangitis, indicating that IL-17 is not a key factor in the pathogenic IL-23/Th17 axis in the spontaneous development Epacadostat of colon disease of the dnTGFβRII mouse strain. Of note, deletion of IL-23 resulted in increased levels of AMA and anti-SP100, but decreased levels of anti-GP210. The mechanism for these differential effects of IL-23 should be addressed in future studies. The autoimmune cholangitis that developed in the IL-23p19−/− mice was associated with an intact IL-12/Th1 pathway, as indicated by the high levels of IFN-γ in this PTK6 mouse strain. In contrast, cholangitis did not develop in IL-12p40−/− mice that lack the IL-12/Th1 pathway.4 Taken together, these results confirm that

IL-12/Th1 immunity is necessary and sufficient for the development of cholangitis in dnTGFβRII mice. We have recently reported that adoptive transfer of CD8 T cells from dnTGFβRII into B6/Rag1−/− mice led to liver histopathology similar to that in donor mice. In contrast, adoptive transfer of CD4 T cells predominantly induced IBD in recipient mice.13 These data demonstrated that in dnTGFβRII mice, CD8 T cells are the major pathogenic effector of cholangitis, whereas CD4 T cells are involved in IBD. This is in agreement with our current finding that whereas comparable levels of CD8 T cells are present in liver tissues of IL-23p19−/− and dnTGFβRII mice, both develop cholangitis, and that protection against colitis in IL-23p19−/− mice was associated with reduced numbers of total and activated CD4 T cells, but not CD8 T cells, in the colon.

[3] In this study, using the GIF-XP290N, we evaluated whether qualitative diagnosis (discrimination between benign and malignant) of gastric lesions is possible using nonmagnified NBI Carfilzomib ic50 endoscopy, and evaluated whether it is possible to improve endoscopic diagnostic ability and avoid unnecessary biopsies. This study was conducted at the Tokyo Medical University Hospital Endoscopy Center between August 2012 and December 2013. The subjects were 255 consecutive patients who underwent screening of the gastrointestinal tract using new ultrathin transnasal endoscopy. Their average age

was 65.2 ± 11.4 years. The male-female ratio was 2.4:1. All cases were examined using conventional white-light imaging (WLI) and nonmagnified NBI. Subject characteristics are shown in Table 1. All examination was performed by five endoscopic specialists (T.K., K.Y., S.N., H.S., M.F.).

These endoscopists were accredited by the Japan Gastroenterologiacal Endoscopy Society. When a depressed lesion was detected in the stomach, it was examined using WLI, then NBI close examination (at about 3 mm). Using WLI, we examined the lesion size and color characteristics, characteristics of the lesion surface, surrounding mucosa, this website and gastric rugae. Lesions were classified as malignant, suspected malignant, or benign. On the other hand, for close visualization Rho using NBI, we observed the mucosal structure of the lesion. Concerning mucosal structural changes, we looked for a clear demarcation line between the lesion and the surrounding mucosa, and loss, irregularity, or nonuniformity of the lesion mucosal microsurface pattern (Figs 1-3) in accordance with the magnifying endoscopy with NBI categories of Yao et al.[4] and Kaise et al.[5]; if both findings are present, the diagnosis is malignant. If either or both findings were absent, the diagnosis was benign. Biopsies were taken from all lesions for histological examination. Patients 20 years old or younger, and those

with a history of gastrointestinal surgery, including the esophagus and stomach, were excluded from this study. The study protocol conformed to the 1975 Helsinki Declaration concerning human experiments, as revised in 1983. Informed consent was obtained from all subjects. Endoscopic examinations were conducted without sedation. We used the Olympus GIF-XP290N new transnasal endoscope (outer diameter at the distal end 5.0 mm, Olympus Medical System), and an electric endoscopic system (Evis Lucera Elite, Olympus Medical System). Premedication and anesthesia to the nasal cavity were performed as previously described.[1] Anticonvulsants such as scopolamine butyl-bromide were not administered as premedication. After fixing the biopsy specimens in formalin, they were embedded in paraffin, and 4-μm slices were made.

pylori infection in childhood causes iron deficiency (ID) or iron deficiency anemia (IDA). However, most recent studies have reported no relationship between H. pylori infection and IDA [24–27]. A number of studies suggest that age maybe an important factor in the relationship between H. pylori infection and iron deficiency with a stronger association in older age groups [28–30]. In an interesting study, Muhsen et al. [28] showed mTOR inhibitor that age may be a modifier of the relationship between H. pylori infection and anemia. When stratified

by age group, H. pylori was associated with a twofold increased prevalence of anemia in school aged children compared with infants under 18 months, independent of socioeconomic variables. However, the diagnosis of H. pylori is not straightforward in young children under 18 months of age. In this study, NU7441 concentration the difference in prevalence between the school age children

(54%) and infants (15%) needs to be evaluated, as the two age groups may be from very different populations and have very different risks of both anemia and H. pylori infection. The role of H. pylori in the development of cITP continues to evolve. A multicenter, prospective, controlled study evaluating the effect of eradication of H. pylori infection in children with cITP has been conducted in 16 Italian centers [31]. Among the large cohort of patients, those who underwent successful eradication of H. pylori infection showed a significantly higher platelet mafosfamide response. Therefore, it may be appropriate to look for H. pylori infection and eventually eradicate it in children with cITP. There is a complex interplay between all the factors that determine growth in children. In examining the relationship between H. pylori and growth, few studies have accounted for the role of other confounders such as socioeconomic

or psychosocial factors, parental height, and nutrition play in determining the final height of children. Despite new information concerning the effect of H. pylori infection on poor growth, the need for well-designed studies remains. Several studies demonstrated a relationship between H. pylori colonization and alterations in the circulating levels of growth-related molecules. Ozen et al. [32] investigated the effect of H. pylori and economic status on growth parameters leptin, ghrelin, and insulin-like growth factor (IGF)-I concentrations in children. Evidence that H. pylori may impair growth significantly was confounded by socioeconomic factors as the effect was only seen in children living in unfavorable socioeconomic conditions. There are a number of longitudinal studies that support the hypothesis that H. pylori infection might influence growth rate in children [33–35]; however, none are adequately designed to evaluate confounders of growth including other gastrointestinal infections in childhood. There is little of note in new effective treatment for H. pylori infection in children.

“
“Molecular assays were used to determine the sex of 1,294 biopsied common dolphins (658 long-beaked common dolphins, Delphinus capensis, and 636 short-beaked common dolphins, D. delphis) in the Southern California Bight. Sex ratio differed substantially between the two species;

females comprised 241 (36.6%) of D. capensis samples and 410 (64.5%) of D. delphis samples. All biopsies were taken either from a large research ship or from a small, rigid-hull inflatable AZD0530 solubility dmso boat (RHIB) launched from the larger ship. When conducting replicate biopsy effort on the same schools from each vessel/platform (“Tandem Biopsy Sampling”), we found evidence that disproportionately more female D. capensis were biopsied from the RHIB than from the ship but the same was not true for

Angiogenesis inhibitor D. delphis. We suspect that these results are driven by bowriding-behavior differences between the two species. Biopsy duration, geographic location, school size, and Julian date were considered as potential covariates with sex ratio; geographic location was the only one to show strong evidence of correlation. This study also presents an alternative to the erroneous practice of comparing sex ratios to a theoretical assumption of parity (i.e., 50:50 sex ratio) when researchers avoid sampling animals paired with calves. “
“Development implies a change in allocation of resources from somatic growth to reproduction. In a highly variable environment, growth can vary from year to year thereby influencing the long-term life history perspective. The Galapagos sea lion (Zalophus wollebaeki) lives in a highly unpredictable marine environment in which food abundance varies not only seasonally, but also annually due to El Niño. Galapagos sea lions are restricted to a patch of cold upwelling waters surrounding the archipelago and are closely tied to land as nursing females alternate between foraging at sea and nursing ashore. Therefore, their offspring are especially vulnerable to ocean warming causing reduced food abundance. We found

a significant correlation between sea surface temperature (SST) and early growth: Both mass TCL at birth and linear growth within the first 2 mo of life correlated negatively with SST. Absolute mass gain was higher for males, but both sexes gained equally 1.9% of birth mass per day. Until the age of 3 yr male and female juveniles showed similar growth to an asymptotic mass of 40 and 35 kg, respectively. As a consequence of the highly variable environment, the plasticity in growth strategy of Galapagos sea lion juveniles appears wider than that of all other sea lions allowing them to cope with poor conditions. “
“Historically, the range of the southern right whale (SRW) included winter calving grounds around the North and South Islands (mainland) of New Zealand (NZ) and in the NZ subantarctic Auckland and Campbell Islands.

ELISAs were performed according to the manufacturer’s instructions. The statistical analysis of the number of TUNEL-positive hepatocytes and the number of dividing hepatocyte nuclei in the respective liver sections was performed by way of semiquantitative counting using a light microscope (Zeiss, Jena, Germany) equipped with an ocular grid at a magnification of ×400. Forty high-power Barasertib fields equal to 10

mm2 for 3 to 4 individual mice per time point and group were evaluated. The mean values for each group/time point were compared by way of Mann-Whitney U test and analysis of variance using InStat 3 software. The statistical analysis of the survival experiments was performed using the Wilcoxon test. We have reported that mice with liver-specific expression of NS3/4A have a reduced sensitivity to liver damage induced by CCl4, LPS/D-galN, Venetoclax in vitro and TNFα/D-galN.11 A common characteristic shared by these three liver toxic stimuli

is that TNFα is involved in liver injury, suggesting that NS3/4A interferes with one or more steps of TNFα-mediated apoptosis/necrosis. TNFα signaling is characterized by simultaneous activation of both FADD- and caspase-8–dependent proapoptotic pathways and the NFκB pathway, which can inhibit the TNFα-induced cell death process. Thus, we decided to analyze the activation status of NFκB in naïve as well as TNFα/D-galN–treated NS3/4A-Tg mice and the respective non-Tg mice. The hepatic activation of NFκB is significantly enhanced after injection with TNFα/D-galN in mice with liver-specific expression of NS3/4A (Fig. 1). The TNFα-induced activation of NFκB demonstrated by a time-dependent decrease in the amount of cytoplasmic NFκB paralleled by a corresponding DNA ligase increase in the amount of nuclear NFκB was much more pronounced in NS3/4A-Tg mice compared with non-Tg mice (Fig. 1A). The nuclear translocation of NFκB induced by degradation of the endogenous NFκB

inhibitor IκB could already be detected 30 minutes after TNFα/D-galN administration and was still present 240 minutes after the start of the treatment (Fig. 1A and data not shown). A similar NS3/4A-mediated increase in NFκB activation was also evident when NS3/4A-Tg and the corresponding WT mice were treated with LPS/D-galN (Fig. 3C and data not shown). Because we had shown that the NS3/4A-mediated protection toward TNFα-induced liver damage was p38MAPK-dependent, we analyzed the effect of the p38MAPK inhibitor SB203580 on TNFα/D-galN-induced NFκB activation. Interestingly, pretreatment of NS3/4A-Tg mice with SB203580 before injection of TNFα/D-galN resulted in a reduction of nuclear NFκB levels to the levels in WT mice (Fig. 1B), suggesting a role of p38MAPK in the NS3/4A-mediated increase in NFκB activation and implying that these pathways may be connected. TNFα-induced apoptosis is mediated by the induction of caspase cleavage, with caspase-3 as the executioner caspase.

ELISAs were performed according to the manufacturer’s instructions. The statistical analysis of the number of TUNEL-positive hepatocytes and the number of dividing hepatocyte nuclei in the respective liver sections was performed by way of semiquantitative counting using a light microscope (Zeiss, Jena, Germany) equipped with an ocular grid at a magnification of ×400. Forty high-power JAK drugs fields equal to 10

mm2 for 3 to 4 individual mice per time point and group were evaluated. The mean values for each group/time point were compared by way of Mann-Whitney U test and analysis of variance using InStat 3 software. The statistical analysis of the survival experiments was performed using the Wilcoxon test. We have reported that mice with liver-specific expression of NS3/4A have a reduced sensitivity to liver damage induced by CCl4, LPS/D-galN, http://www.selleckchem.com/products/Fulvestrant.html and TNFα/D-galN.11 A common characteristic shared by these three liver toxic stimuli

is that TNFα is involved in liver injury, suggesting that NS3/4A interferes with one or more steps of TNFα-mediated apoptosis/necrosis. TNFα signaling is characterized by simultaneous activation of both FADD- and caspase-8–dependent proapoptotic pathways and the NFκB pathway, which can inhibit the TNFα-induced cell death process. Thus, we decided to analyze the activation status of NFκB in naïve as well as TNFα/D-galN–treated NS3/4A-Tg mice and the respective non-Tg mice. The hepatic activation of NFκB is significantly enhanced after injection with TNFα/D-galN in mice with liver-specific expression of NS3/4A (Fig. 1). The TNFα-induced activation of NFκB demonstrated by a time-dependent decrease in the amount of cytoplasmic NFκB paralleled by a corresponding isothipendyl increase in the amount of nuclear NFκB was much more pronounced in NS3/4A-Tg mice compared with non-Tg mice (Fig. 1A). The nuclear translocation of NFκB induced by degradation of the endogenous NFκB

inhibitor IκB could already be detected 30 minutes after TNFα/D-galN administration and was still present 240 minutes after the start of the treatment (Fig. 1A and data not shown). A similar NS3/4A-mediated increase in NFκB activation was also evident when NS3/4A-Tg and the corresponding WT mice were treated with LPS/D-galN (Fig. 3C and data not shown). Because we had shown that the NS3/4A-mediated protection toward TNFα-induced liver damage was p38MAPK-dependent, we analyzed the effect of the p38MAPK inhibitor SB203580 on TNFα/D-galN-induced NFκB activation. Interestingly, pretreatment of NS3/4A-Tg mice with SB203580 before injection of TNFα/D-galN resulted in a reduction of nuclear NFκB levels to the levels in WT mice (Fig. 1B), suggesting a role of p38MAPK in the NS3/4A-mediated increase in NFκB activation and implying that these pathways may be connected. TNFα-induced apoptosis is mediated by the induction of caspase cleavage, with caspase-3 as the executioner caspase.

While similar ultrastructural changes were also observed in patients with CD, they were not significantly different from the controls. Functionally, these patients showed increase in intestinal permeability along with dilated TJs. After 6 months of treatment in both the groups, there was improvement in the ultrastructural parameters of BMN 673 the TJs. Conclusion: Disruption of integrity of tight junctions (loss of pentalaminar

structure, dilatation of TJs, disarrayed microvilli) are characteristic of both celiac disease and Crohn’s disease and forms the basis of increase in intestinal permeability. These changes are not disease specific. The ultrastructural changes of the tight junctions and microvilli improve (not completely) with healing of lesions at 6 months after treatment which is reflected functionally by improvement in intestinal permeability; however the improvement in ultrastructural changes are incomplete suggesting 6 months

is not good enough for complete normalization of ultra-structural changes. Key Word(s): 1. LY294002 nmr Tight Junction; 2. Celiac Disease; 3. Crohn’s disease; 4. HPLC; Presenting Author: PRASENJIT DAS Additional Authors: POOJA GOSWAMI, ANILK VERMA, SIDDHARTHDATTA GUPTA, TAPOSHK DAS, TAPAS NAG, VINEET AHUJA, GOVINDK MAKHARIA Corresponding Author: GOVINDK MAKHARIA Affiliations: All India Institute of Medical Sciences Objective: The apical most part of intercellular junction

called tight junctions (TJ) are regulated by a host of transmembrane and cytoplasmic proteins, which in turn maintains the integrity of these junctions. Abnormalities in tight junctions have been implicated in the pathogenesis of celiac disease (CeD) and Crohn’s disease (CD). Since the mechanisms of abnormalities in intestinal permeability Exoribonuclease are different in CeD and CD; we planned to study if there was a differencein the expression and semiquantitation of a few key tight junction proteins in them at baseline and at six months after treatment. Methods: Endoscopic mucosal biopsies from treatment naïve patients with CeD (n = 24), activeCD (n = 28) and 15 control subjects were subjected to histological examination (Modified Marsh grade), immunohistochemical staining of key TJ proteins [transmembrane proteins (claudin-2, 3, 4, occludin and JAM) and cytoplasmic protein (ZO-1)]. The expression patterns of the TJ proteins were validated by western blot analysisfor the same set of proteins. The expression and semiquantitation of these proteins were assessed after 6 monthsof appropriate treatment. Functional analysis of tight junctions was assessed by estimating lactulose and mannitol ratio in urine using HPLC.

The www.selleckchem.com/products/MLN-2238.html authors thank Naoko Kawahara,

Takashi Nakamura, and Keiko Takeshita for their technical assistance. Additional Supporting Information may be found in the online version of this article. “
“Hair disorders that have been described in association with pegylated interferon–ribavirin combination treatment include canities, hypertrichosis, telogen effluvium, and the most common cutaneous side-effect by far, alopecia. Alopecia is a heterogeneous disease characterized by hair loss on the scalp or any hair-bearing surface with a wide range of clinical presentations, from a single patch of hair loss to complete loss of hair on the entire body (alopecia universalis). Although some cases of reversible alopecia universalis associated with pegylated interferon–ribavirin combination therapy have been reported in the published work, irreversible alopecia universalis

has not yet been reported in relation to pegylated interferon and ribavirin combination treatment. For the first time, we report a case of irreversible alopecia Cell Cycle inhibitor universalis during pegylated interferon–ribavirin combination therapy in a man infected with hepatitis C virus in the absence of clinical or biochemical evidence of immunological disorders or thyroid dysfunction at any time before, during or after antiviral therapy. “
” The Journal of Gastroenterology and Hepatology (JGH), an official journal of the Asian Pacific Association of Gastroenterology (APAGE) and an affiliated journal of several national gastroenterology and liver associations, will soon have a new Editor-in-Chief. From January 2013 Professor Mamoru Watanabe takes on this important leadership role, after completion of Professor Geoff Farrell’s 6-year term. Dr Watanabe is a Professor and Chairman in the Department of Gastroenterology and Hepatology, Department of Endoscopy, Tokyo Medical and

Dental University. 5-Fluoracil ic50 He is also the Director in the Advanced Clinical Center for Inflammatory Bowel Disease in this major teaching and academic Hospital. I have known Dr Watanabe both personally and professionally during the past 30 years. He is a best friend of mine. We both graduated from the same School of Medicine, Keio University in Tokyo and worked in the same Department of Internal Medicine in Keio for 20 years. He was a 3-year junior to me, and I was his first supervisor for his clinical training in the Department of Gastroenterology in Keio. On the basis of this longstanding interaction, I hold him in the highest esteem, both as a physician and scientist, and know he will continue to make major leadership contributions to both clinical and basic investigations in gastroenterology. It has been more than 25 years since JGH was born from the Asia-Pacific Region.

Lcn2 was also reported to be a biomarker in cholangiocarcinoma;[35] these findings suggest that the role of Lcn2 is dependent on the liver tumor with an epithelial phenotype. Our results are in good agreement with previous observations in cancer of the ovary, where Lcn2 expression is almost completely absent in tissue samples from normal ovaries, but strongly expressed in both borderline and grade

1 tumors, and weakly to moderately expressed in grade 2 and 3 tumors.[4] Furthermore, moderate to strong expression of Lcn2 was observed in the epithelial ovarian cancer cell lines SKOV3 and OVCA433, while no expression was detected in mesenchymal-like OVHS1, PEO36, or HEY cell lines. Taken together, Lcn2 expression appears to be linked Atezolizumab supplier to the epithelial phenotype of tumors and is lost as the tumor progresses and becomes undifferentiated. Lcn2 has been implicated in the induction of cellular proliferation because its expression is associated with a variety of proliferative cells.[36, 37] Lcn2 expression is required for Bcr-Abl-induced FK506 research buy tumorigenesis in leukemia

cells.[38] Lcn2 expression promotes breast tumor growth and progression,[39-41] and also increases colon cancer migration and invasion.[42] Furthermore, down-regulation of Lcn2 by antisense RNA suppresses human esophageal many carcinoma SHEEC cell invasion in vivo by reducing matrix metalloproteinase (MMP)−9 activity.[43] In the present study, Lcn2 suppressed the proliferation, migration, and invasion of EMT phenotypic HCC cells in vitro and tumor growth and metastasis in vivo. This is consistent with results

from a previous study that reported that Lcn2 suppressed Ras-transformed 4T1 mouse mammary tumor cell invasiveness in vitro and tumor growth and lung metastases in vivo.[9] Furthermore, Lcn2 blocked human colon cancer KM12SM cell invasion and liver metastasis.[10] A recent study also proposed that Lcn2 may act as a suppressor of invasion and angiogenesis in advanced pancreatic cancer cells.[11] These apparently conflicting observations could be due to distinct functions of Lcn2 in different cell types. Our focus in this study was to determine the mechanisms by which Lcn2 inhibits growth factor-mediated EMT in association with invasion and metastasis in HCC. Loss of E-cadherin expression has been associated with activation of the EGF/EGFR cascade in several cancer types, including pancreatic cancer and cervical cancer.[25, 27] EGF-induced EMT phenotypes were inhibited in the presence of AG1478, an inhibitor of EGF receptor tyrosine kinase activity. Lim et al.[4] reported that EGF down-regulated both E-cadherin and Lcn2 expression in ovarian cancer cells.