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Find video protocols related to scientific articles indexed in Pubmed.
Promotive role of recombinant HE4 protein in proliferation and carboplatin resistance in ovarian cancer cells.
Oncol. Rep.
PUBLISHED: 06-16-2014
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Available evidence on the proliferation-promoting effect of HE4 remains controversial, and few studies have been carried out on the molecular mechanism of chemoresistance mediated by HE4. The aim of the present study was to investigate the influence of exogenous recombinant HE4 protein on proliferation and resistance to carboplatin in ovarian cancer cells. The human ovarian cancer cell line (SKOV-3) was exposed to recombinant HE4 protein (0-1 µg/ml) for different durations based on the schemes. Cell viability was evaluated by Cell Counting Kit-8 and colony formation assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Markers of apoptosis (Bax and Bcl-2) were assessed by western blotting. Furthermore, Affymetrix microarray analysis was performed to investigate transcriptome profiling. The differential expression of four genes was verified by quantitative real-time PCR. The HE4 protein enhanced cell viability, promoted accumulation of cells in the G2/M phase and attenuated carboplatin-induced apoptosis. HE4 markedly decreased the Bax/Bcl-2 ratio. Candidate genes (387) (236 upregulated and 151 downregulated) were obtained by microarray analysis. Among those upregulated, several Gene Ontology (GO) terms related to cell cycle regulation and proliferation were significantly overrepresented and those within the downregulated dataset included genes involved in several aspects of the DNA damage response such as positive regulation of apoptosis. No information concerning the EGFR-MAPK pathways in a recent report on HE4 was acquired. The mRNA expression of the candidate genes determined by quantitative real-time PCR was significantly correlated with the microarray data. The present study indicates that the HE4 protein plays a promotive role in the proliferation and resistance to carboplatin in ovarian cancer cells, implicating the value of HE4 to predict tumor growth potential and resistance to platinum-based chemotherapy in epithelial ovarian cancer (EOC).
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The role of lateral habenula-dorsal raphe nucleus circuits in higher brain functions and psychiatric illness.
Behav. Brain Res.
PUBLISHED: 05-22-2014
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Serotonergic neurons in the dorsal raphe nucleus (DRN) play an important role in regulation of many physiological functions. The lateral nucleus of the habenular complex (LHb) is closely connected to the DRN both morphologically and functionally. The LHb is a key regulator of the activity of DRN serotonergic neurons, and it also receives reciprocal input from the DRN. The LHb is also a major way-station that receives limbic system input via the stria medullaris and provides output to the DRN and thereby indirectly connects a number of other brain regions to the DRN. The complex interactions of the LHb and DRN contribute to the regulation of numerous important behavioral and physiological mechanisms, including those regulating cognition, reward, pain sensitivity and patterns of sleep and waking. Disruption of these functions is characteristic of major psychiatric illnesses, so there has been a great deal of interest in how disturbed LHb-DRN interactions may contribute to the symptoms of these illnesses. This review summarizes recent research related to the roles of the LHb-DRN system in regulation of higher brain functions and the possible role of disturbed LHb-DRN function in the pathogenesis of psychiatric disorders, especially depression.
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Nonlinear reduction in risk for colorectal cancer by oral contraceptive use: a meta-analysis of epidemiological studies.
Cancer Causes Control
PUBLISHED: 05-19-2014
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Although the relationship between oral contraceptive (OC) use and colorectal cancer (CRC) risk has been studied extensively, the results of epidemiological studies are controversial. Therefore, we carried out a meta-analysis of epidemiological studies to summarize the available evidence and to quantify the potential dose-response relation.
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c-Jun transcriptionally regulates alpha 1, 2-fucosyltransferase 1 (FUT1) in ovarian cancer.
Biochimie
PUBLISHED: 05-03-2014
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Alpha 1, 2-fucosyltransferase (FUT 1/2) is a rate-limiting enzyme that catalyzes the synthesis of Lewis y, a cell membrane-associated carbohydrate antigen. In human ovarian cancer, the upregulated expression of FUT1 and Lewis y is associated with advanced pathological stages and involved in cell proliferation, migration and invasion. However, the mechanism underlying the upregulation of FUT1 is largely unknown. Here, we identify an AP-1 binding site in FUT1 promoter in ovarian cancer cells. c-Jun promotes FUT1 expression, thereby enhancing Lewis y biosynthesis in various ovarian cancer cell lines. Moreover, EMSA, luciferase activity and ChIP assays demonstrate c-Jun directly interacts with FUT1 promoter. Furthermore, FUT1 mediates c-Jun-induced cell proliferation in ovarian cancer cells. In human ovarian cancer samples, c-Jun overexpression is linked to malignant degree and positively correlated to FUT1 and Lewis y expression. Taken together, c-Jun could transcriptionally modulate FUT1 expression in ovarian cancer, implicating the potential application of c-Jun inhibitors for human ovarian cancer therapy.
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Caregiver-Mediated Intervention Can Improve Physical Functional Recovery of Patients With Chronic Stroke: A Randomized Controlled Trial.
Neurorehabil Neural Repair
PUBLISHED: 05-03-2014
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and PURPOSE: Patients with chronic stroke may benefit from continuing rehabilitation training after hospital discharge. This study examined whether caregiver-mediated, home-based intervention (CHI) could improve physical functioning and social participation in these patients.
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Overexpression of Lewis y antigen promotes human epididymis protein 4-mediated invasion and metastasis of ovarian cancer cells.
Biochimie
PUBLISHED: 04-15-2014
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To study Human epididymis protein 4 (HE4) surface fucosylation and to determine the effects and significance of Lewis y antigen on HE4-mediated invasion and metastasis of ovarian cancer cells, we investigated four types of ovarian cancer cells and found that six fucosylated antigens (Lewis y, Lewis x, Lewis a, Lewis b, sLewis a, and sLewis x) were identified on HE4 in ovarian cancer cells. Moreover, modification of the type II sugar chain (Lewis y, Lewis x, and sLewis x) was significantly higher than the type I sugar chain (Lewis a, Lewis b, sLewis a) of the lactose series. To confirm the effects of Lewis y antigen on HE4-mediated invasion and metastasis of ovarian cancer cells, the CaoV-3 cells with high Lewis y antigen on the HE4 surface and ES-2 cells, with high Lewis x antigen but low Lewis y antigen, were investigated. We found that the expression levels of HE4 and Lewis y increased in both cell lines while the level of Lewis x didn't have any change after transfection. Furthermore, the high expression of Lewis y antigen significantly enhanced the HE4-mediated invasion and metastasis of ovarian cancer cells. The invasion and metastasis capacities were significantly decreased after Lewis y antibody blocking. This study demonstrates that overexpression of the Lewis y antigen on HE4 promotes ovarian cancer cell invasion and metastasis, which is likely to be used as a target for the clinical treatment of ovarian cancer.
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Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells.
Mol. Cancer
PUBLISHED: 04-01-2014
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The objective of the present study was to identify human epididymis protein 4 (HE4) interacting proteins and explore the mechanisms underlying their effect on ovarian cancer cell invasion and metastasis.
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NGF accelerates cutaneous wound healing by promoting the migration of dermal fibroblasts via the PI3K/Akt-Rac1-JNK and ERK pathways.
Biomed Res Int
PUBLISHED: 03-06-2014
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As a well-known neurotrophic factor, nerve growth factor (NGF) has also been extensively recognized for its acceleration of healing in cutaneous wounds in both animal models and randomized clinical trials. However, the underlying mechanisms accounting for the therapeutic effect of NGF on skin wounds are not fully understood. NGF treatment significantly accelerated the rate of wound healing by promoting wound reepithelialization, the formation of granulation tissue, and collagen production. To explore the possible mechanisms of this process, the expression levels of CD68, VEGF, PCNA, and TGF-?1 in wounds were detected by immunohistochemical staining. The levels of these proteins were all significantly raised in NGF-treated wounds compared to untreated controls. NGF also significantly promoted the migration, but not the proliferation, of dermal fibroblasts. NGF induced a remarkable increase in the activity of PI3K/Akt, JNK, ERK, and Rac1, and blockade with their specific inhibitors significantly impaired the NGF-induced migration. In conclusion, NGF significantly accelerated the healing of skin excisional wounds in rats and the fibroblast migration induced by NGF may contribute to this healing process. The activation of PI3K/Akt, Rac1, JNK, and ERK were all involved in the regulation of NGF-induced fibroblast migration.
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Beclin 1 expression in ovarian tissues and its effects on ovarian cancer prognosis.
Int J Mol Sci
PUBLISHED: 03-01-2014
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Beclin 1 is an autophagy-associated protein involved in apoptosis and drug resistance, as well as various malignancies. We investigated the expression of Beclin 1 protein in ovarian epithelial tissues and correlated it with the prognosis of ovarian cancer. Beclin 1 protein expression was determined using immunohistochemistry in 148 patients with ovarian epithelial cancer, 26 with ovarian borderline tumor, 25 with benign ovarian tumor, and 30 with normal ovarian tissue. The relationships between Beclin 1 protein expression and ovarian cancer pathological characteristics were analyzed. The risk factors for ovarian cancer prognosis were analyzed using Cox's regression model. A survival curve was plotted from the follow-up data of 93 patients with ovarian cancer to analyze the effects of Beclin 1 expression on the prognosis of ovarian cancer. The positive rates of Beclin 1 were significantly higher in ovarian epithelial cancer (148) and borderline tumor (26) than in benign ovarian tumor (25) or normal ovarian tissue (30) (all p<0.001). The surgical stage and Beclin 1 expression were both independent risk factors for ovarian cancer prognosis (both p<0.05). Patients with high Beclin 1 levels showed better survival than those with low Beclin 1 levels (p=0.009). Beclin 1 protein is upregulated in ovarian epithelial cancer and is a prognostic factor of ovarian cancer.
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Expression of CD147 and Lewis y antigen in ovarian cancer and their relationship to drug resistance.
Med. Oncol.
PUBLISHED: 01-26-2014
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The purpose of this study was to investigate the relationship between the expression of CD147 and Lewis y antigen in epithelial ovarian carcinoma tissues and resistance to chemotherapeutic drugs, and its underlying clinical significance, and to analyze the correlation between the expression of CD147 and Lewis y antigen. Ninety-two ovarian cancer patients were divided into a chemotherapeutic-drug-resistant group (34 patients) and a drug-sensitive group (58 patients). Immunohistochemical assays were used to measure CD147, and Lewis y antigen to investigate their correlation with chemotherapy resistance. Multivariate logistic regression was used to analyze the relationships between risk factors and resistance to chemotherapy in ovarian cancer. Cox's model was used to analyze the relationships between risk factors and prognosis. The proportion of tissues expressing CD147 and Lewis y antigen in the drug-resistant group were 94.12 and 91.67%, respectively, which were significantly higher than those in the sensitive group (77.59 and 60.34%, respectively). The multivariate analysis indicated that the expression of CD147 and Lewis y antigen and the pathological stage of the ovarian cancer were all independent risk factors for drug resistance. Expression of CD147 and Lewis y antigen was high in the resistant group, and they correlated positively with each other. The expression of CD147 and Lewis y antigen was significantly higher in the drug-resistant group and their expression correlated positively in the ovarian epithelium. The expression of CD147 and Lewis y antigen and the pathological stage of ovarian cancer were all independent risk factors for drug resistance and prognosis in ovarian cancer.
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[Mutation analysis of EXT genes in two pedigrees with hereditary multiple exostoses].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 12-12-2013
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To detect the underlying genetic defect in two Chinese families with hereditary multiple exostoses and provide genetic counseling.
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Breastfeeding and ovarian cancer risk: a meta-analysis of epidemiologic studies.
Am. J. Clin. Nutr.
PUBLISHED: 08-21-2013
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Epidemiologic studies have yielded inconsistent findings between breastfeeding and epithelial ovarian cancer (EOC) risk.
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Conventional ultrasonography and real time ultrasound elastography in the differential diagnosis of degenerating cystic thyroid nodules mimicking malignancy and papillary thyroid carcinomas.
Asian Pac. J. Cancer Prev.
PUBLISHED: 04-30-2013
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To evaluate the diagnostic utility of conventional ultrasonography and real time ultrasound elastography in differentiating degenerating cystic thyroid nodules mimicking malignancy from papillary thyroid carcinoma.
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Mitochondrial haplotypes may modulate the phenotypic manifestation of the LHON-associated m.14484T>C (MT-ND6) mutation in Chinese families.
Mitochondrion
PUBLISHED: 04-19-2013
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Mitochondrial m.14484T>C (MT-ND6) mutation has been associated with Lebers hereditary optic neuropathy. Previous investigations revealed that the m.14484T>C mutation is a primary factor underlying the development of optic neuropathy but is not sufficient to produce a clinical phenotype. However, mitochondrial haplogroups have been proposed to modulate the phenotypic manifestation of the m.14484T>C mutation. Here, we performed the clinical, genetic evaluation and complete mitochondrial genome sequence analysis of 41 Han Chinese pedigrees carrying the m.14484T>C mutation. These families exhibited a wide range of penetrances and expressivities of optic neuropathy. The average ratio between affected male/female matrilineal relatives from 41 families was 2:1. The penetrance of optic neuropathy in these Chinese pedigrees ranged from 5.6% to 100%, with the average of 23.8%. Furthermore, the age-of-onset for optic neuropathy varied from 4 to 44 years, with the average of 19.3 years. Sequence analysis of their mitochondrial genomes identified distinct sets of polymorphisms belonging to ten Eastern Asian haplogroups, indicating that the m.14484T>C mutation occurred through recurrent origins and founder events. We showed that mitochondrial haplogroups M9, M10 and N9 increased the penetrance of optic neuropathy in these Chinese families. In particular, these mitochondrial haplogroup specific variants: m.3394T>C (MT-ND1), m.14502T>C (MT-ND4) and m.14693A>G (MT-TE) enhanced the penetrance of visual loss in these Chinese families. These data provided the direct evidence that mitochondrial modifiers modulate the variable penetrance and expressivity of optic neuropathy among Chinese pedigrees carrying the m.14484T>C mutation.
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Chemoresistance Is Associated with MUC1 and Lewis y Antigen Expression in Ovarian Epithelial Cancers.
Int J Mol Sci
PUBLISHED: 04-17-2013
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Objective: The aim of this study was to analyze the correlation and clinical significance between the expression of Mucin-1 (MUC1) and the Lewis y antigen with chemoresistance in ovarian epithelial cancers. Methods: Ovarian cancer patients (n = 92) treated at our hospital from May 2005 to July 2009 were divided, according to their treatment and follow-up outcomes, into a resistant group (n = 37) or sensitive group (n = 55). The expression of MUC1 and Lewis y antigen in ovarian cancer tissues was detected using immunohistochemistry and correlated with chemoresistance. Results: The positive rates of MUC1 and Lewis y antigen in the resistant group were both 91.89%, significantly higher than their positive rates in the sensitive group (65.45% and 69.09%, respectively, and both p < 0.05). MUC1 or Lewis y expression and the pathological stage of the tissue were independent risk factors for chemoresistance (all p < 0.05). Conclusion: The increased expression of MUC1 and the Lewis y antigen is a significant risk factor for chemoresistance in patients with ovarian epithelial cancer.
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A clinicopathological and immunohistochemical study of minimal deviation adenocarcinoma of the uterine cervix.
Med. Hypotheses
PUBLISHED: 02-27-2013
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To investigate the clinical, pathological and immunohistochemical features of minimal deviation adenocarcinoma (MDA) of the uterine cervix by conducting a retrospective study of 25 cases consecutively treated in three institutes over a 10 years period.
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The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo.
PLoS ONE
PUBLISHED: 02-20-2013
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Hypertrophic scars (HTS) and keloids are challenging problems. Their pathogenesis results from an overproduction of fibroblasts and excessive deposition of collagen. Studies suggest a possible anti-scarring effect of basic fibroblast growth factor (bFGF) during wound healing, but the precise mechanisms of bFGF are still unclear. In view of this, we investigated the therapeutic effects of bFGF on HTS animal model as well as human scar fibroblasts (HSF) model. We show that bFGF promoted wound healing and reduced the area of flattened non-pathological scars in rat skin wounds and HTS in the rabbit ear. We provide evidence of a new therapeutic strategy: bFGF administration for the treatment of HTS. The scar elevation index (SEI) and epidermal thickness index (ETI) was also significantly reduced. Histological reveal that bFGF exhibited significant amelioration of the collagen tissue. bFGF regulated extracellular matrix (ECM) synthesis and degradation via interference in the collagen distribution, the ?-smooth muscle actin (?-SMA) and transforming growth factor-1 (TGF-?1) expression. In addition, bFGF reduced scarring and promoted wound healing by inhibiting TGF?1/SMAD-dependent pathway. The levels of fibronectin (FN), tissue inhibitor of metalloproteinase-1 (TIMP-1) collagen I, and collagen III were evidently decreased, and matrix metalloproteinase-1 (MMP-1) and apoptosis cells were markedly increased. These results suggest that bFGF possesses favorable therapeutic effects on hypertrophic scars in vitro and in vivo, which may be an effective cure for human hypertrophic scars.
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High expression of Lewis y antigen and CD44 is correlated with resistance to chemotherapy in epithelial ovarian cancers.
PLoS ONE
PUBLISHED: 01-21-2013
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To measure Lewis y antigen and CD44 antigen expression in epithelial ovarian carcinoma and to correlate the levels of these antigens with clinical response to chemotherapy.
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Regulation of autophagy and ubiquitinated protein accumulation by bFGF promotes functional recovery and neural protection in a rat model of spinal cord injury.
Mol. Neurobiol.
PUBLISHED: 01-18-2013
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The role of autophagy in the recovery of spinal cord injury remains controversial; in particular, the mechanism of autophagy regulated degradation of ubiquitinated proteins has not been discussed to date. In this study, we investigated the protective role of basic fibroblast growth factor (bFGF) both in vivo and in vitro and demonstrated that excessive autophagy and ubiquitinated protein accumulation is involved in the rat model of trauma. bFGF administration improved recovery and increased the survival of neurons in spinal cord lesions in the rat model. The protective effect of bFGF is related to the inhibition of autophagic protein LC3II levels; bFGF treatment also enhances clearance of ubiquitinated proteins by p62, which also increases the survival of neuronal PC-12 cells. The activation of the downstream signals of the PI3K/Akt/mTOR pathway by bFGF treatment was detected both in vivo and in vitro. Combination therapy including the autophagy activator rapamycin partially abolished the protective effect of bFGF. The present study illustrates that the role of bFGF in SCI recovery is related to the inhibition of excessive autophagy and enhancement of ubiquitinated protein clearance via the activation of PI3K/Akt/mTOR signaling. Overall, our study suggests a new trend for bFGF drug development for central nervous system injuries and sheds light on protein signaling involved in bFGF action.
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Expression of Lewis y antigen and integrin ?v, ?3 in ovarian cancer and their relationship with chemotherapeutic drug resistance.
J. Exp. Clin. Cancer Res.
PUBLISHED: 01-16-2013
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This study investigates the expression of Lewis y antigen, integrin ?v, ?3 in epithelial ovarian cancer tissues. We further evaluate the relationship between their expression and chemotherapy resistance of ovarian cancer and its possible clinical significance.
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Parity and risk of colorectal cancer: a dose-response meta-analysis of prospective studies.
PLoS ONE
PUBLISHED: 01-01-2013
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Association between parity and colorectal cancer (CRC) risk has been investigated by several epidemiological studies but results are controversial, yet a comprehensive and quantitative assessment of this association has not been reported so far.
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Co-expression of Lewis y antigen with human epididymis protein 4 in ovarian epithelial carcinoma.
PLoS ONE
PUBLISHED: 01-01-2013
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The main aims of this study were to explore the molecular structural relationship between Human epididymis protein 4 (HE4) and Lewis y antigen by determining their expression patterns and clinical significance in ovarian epithelial carcinoma.
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Expression and correlation of Lewis y antigen and TGF-?1 in ovarian epithelial carcinoma.
Oncol. Rep.
PUBLISHED: 09-22-2011
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Lewis y is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Elevation of Lewis y is frequently observed in epithelial-derived cancers. This study aimed to detect the expression and clinical significance of the Lewis y antigen and TGF-?1 (transforming growth factor ?1) in ovarian epithelial tumors, and to evaluate the correlation between them. Immunohistochemical staining was used to detect the expression of Lewis y antigen and TGF-?1 in 60 cases of ovarian epithelial malignant tumors, 20 cases of borderline ovary tumors, 20 cases of benign ovary tumors and 10 cases of normal ovarian tissues. An immunofluorescence double labeling method was also used to detect the correlation between Lewis y antigen and TGF-?1. The positive rates of Lewis y antigen in ovarian epithelial cancer tissues was 88.33%, significantly higher compared to those of borderline ovarian tumors (60.00%) (P<0.05), benign ovarian tumors (35.00%) (P<0.01) and normal ovarian tissues (0%) (P<0.01). Its expression was not associated with clinical parameters; the positive rates of TGF-?1 in ovarian epithelial cancers were 78.33%, significantly higher compared to those of benign ovarian tumors (65.00%) (P<0.05) and normal ovarian tissues (40.00%) (P<0.05); the positive rates of the TGF-?1 and Lewis y were not associated with metastasis of lymph nodes and histological types, differentiation degree and clinical stage (P>0.05). Expression of Lewis y antigen and TGF-?1 was significantly positively associated with epithelial carcinoma. Close correlation between Lewis y, TGF-?1 and ovarian cancer was observed. Altered expression of Lewis y antigen may cause changes in TGF-?1 expression. Lewis y can increase the growth of ovarian cancer cells and the invasion ability by promoting TGF-?1 abnormal expression and by promoting angiogenesis and a change in its signal transduction pathway. This study provides theoretical evidence for the development of ovarian cancer biological treatments.
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Lewis Y regulates signaling molecules of the transforming growth factor ? pathway in ovarian carcinoma-derived RMG-I cells.
Int. J. Oncol.
PUBLISHED: 09-21-2011
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LeY (Lewis Y) is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Elevation of LeY is frequently observed in epithelial-derived cancers and is correlated to pathological staging and prognosis. To study the role of LeY on cancer cells, a stably LeY-overexpressing cell line, RMG-I-H, was developed previously by transfection of the ?1,2-fucosyltransferase gene, a key enzyme that catalyzes the synthesis of LeY, into ovarian carcinoma-derived RMG-I cells. Our studies have shown that LeY is involved in the changes in biological behavior of RMG-I-H cells. However, the mechanism is still largely unknown. In this study, we determined the structural relationship and co-localization between LeY and T?RI/T?RII, respectively, and the potential cellular signaling mechanism was also investigated. We found that both T?RI and T?RII contain the LeY structure, and the level of LeY in T?RI and T?RII in RMG-I-H cells was significantly increased. Overexpression of LeY up-regulates the phosphorylation of ERK, Akt and down-regulates the phosphorylation of Smad2/3. In addition, the phosphorylation intensity was attenuated significantly by LeY monoantibody. These findings suggest that LeY is involved in the changes in biological behavior through TGF?? receptors via Smad, ERK/MAPK and PI3K/Akt signaling pathways. We suggest that LeY may be an important composition of growth factor receptors and could be an attractive candidate for cancer diagnosis and treatment.
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The Stimulation of IGF-1R Expression by Lewis(y) Antigen Provides a Powerful Development Mechanism of Epithelial Ovarian Carcinoma.
Int J Mol Sci
PUBLISHED: 08-09-2011
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This study aimed to measure and correlate the expression of insulin-like growth factor receptor-1 (IGF-1R) and the Lewis(y) antigen in ovarian cancer cell lines and tissue samples.
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Increase in Docetaxel-Resistance of Ovarian Carcinoma-Derived RMG-1 Cells with Enhanced Expression of Lewis Y Antigen.
Int J Mol Sci
PUBLISHED: 07-11-2011
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Epithelial carcinomas of the ovary exhibit the highest mortality rate among gynecologic malignancies. Studies found that the metabolism of glycolipids or carbohydrates is associated with acquirement of anticancer drug-resistance by cancer cells. This study was to characterize possible involvement of Lewis Y (Le(Y)) antigen in the drug-resistance of cancer cells. We transfected the ?1,2-fucosyltransferase gene into human ovarian carcinoma-derived RMG-1 cells and established RMG-1-hFUT cells with enhanced expression of Le(Y). We determined the effects of docetaxel on the survival of cells by MTT assaying and observed the apoptosis of cells in the presence of docetaxel by flow cytometric analysis and by transmission electron microscopy. Plasma membranes and intracellular granules in RMG-1-hFUT cells were stained with anti-Le(Y) antibody, the intensity of the staining was higher than that in control cells. The RMG-1-hFUT cells exhibited higher resistance to docetaxel than the control cells with regard to the docetaxel concentration and time course. After treatment with 10 ?g/mL docetaxel for 72 h, the control cells, but not RMG-1-hFUT, contained abundant positively stained cell debris due to disintegration of the cytoskeleton. On transmission electron microscopy, although the control cells treated with docetaxel as above showed the following morphology, i.e., absence of villi, cells shrunken in size, pyknosis, agglutinated chromatin and cell buds containing nuclei in the process of apoptosis, the RMG-1-hFUT cells showed only agglutinated chromatin and vacuoles in the cytoplasm. In summary, cells with enhanced expression of Le(Y) were shown to acquire docetaxel-resistance, indicating the possible involvement of glycoconjugates in the drug-resistance.
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Study on the Expression and Clinical Significances of Lewis y Antigen and Integrin ?v, ?3 in Epithelial Ovarian Tumors.
Int J Mol Sci
PUBLISHED: 04-27-2011
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To detect the expression and clinical significances of Lewis y antigen and integrin ?v, ?3 in epithelial ovarian tumors, and to explore the expression correlation between Lewis y antigen and integrin ?v, ?3.
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Overexpression of Lewis(y) antigen protects ovarian cancer RMG-1 cells from carboplatin-induced apoptosis by the upregulation of Topo-I and Topo-II ?.
Anat Rec (Hoboken)
PUBLISHED: 03-15-2011
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Lewis (y) antigen, a difucosylated oligosaccharide, has been shown to be associated with malignant properties of ovarian carcinomas. In this study, we have investigated the potential role of Lewis (y) antigen, which was stably transfected into ovarian cancer RMG-1 cells, on carboplatin-induced apoptosis. Overexpression of Lewis (y) antigen effectively protected vitronectin-adherent RMG-1 cells from carboplatin-induced apoptosis as assessed by Hoechst 33258 staining and flow cytometry. Treatment with anti-Lewis (y) antigen, anti-integrin ?v, or anti-integrin ?3 antibody partially abolished the protective effect on apoptosis and markedly inhibited the expression of Topo-II ? in cells overexpressing Lewis (y) antigen (all P < 0.01). Moreover, elevated expression of Topo-I and Topo-II ? was found in Lewis (y) antigen-overexpressing cells (P < 0.01). However, no obvious changes in Topo-II ? were observed throughout the study (P > 0.05). Taken together, these data suggest that the overexpression of Lewis (y) antigen confers cell adhesion-mediated drug resistance to apoptosis in ovarian cancer cells by the upregulation of Topo-I and Topo-II ?. Therefore, the inhibition of Lewis (y) antigen may be a novel strategy of cancer chemotherapy.
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Enhancive effects of Lewis y antigen on CD44-mediated adhesion and spreading of human ovarian cancer cell line RMG-I.
J. Exp. Clin. Cancer Res.
PUBLISHED: 01-15-2011
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This study aimed to investigate the molecular structural relationship between cell adhesive molecule CD44 and Lewis y antigen, and determine the effects of Lewis y antigen on CD44-mediated adhesion and spreading of ovarian cancer cell line RMG-I and the Lewis y antigen-overexpressed cell line RMG-I-H.
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Expression and correlation of Lewis y antigen and integrins ?5 and ?1 in ovarian serous and mucinous carcinoma.
Int. J. Gynecol. Cancer
PUBLISHED: 12-02-2010
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This study investigates the expression and the clinical significance of Lewis y and integrins ?5 and ?1 in serous and mucinous ovarian tumors and then evaluates the association between them.
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Lewis (y) antigen overexpression increases the expression of MMP-2 and MMP-9 and invasion of human ovarian cancer cells.
Int J Mol Sci
PUBLISHED: 10-25-2010
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Lewis (y) antigen is a difucosylated oligosaccharide present on the plasma membrane, and its overexpression is frequently found in human cancers and has been shown to be associated with poor prognosis. Our previous studies have shown that Lewis (y) antigen plays a positive role in the process of invasion and metastasis of ovarian cancer cells. However, the mechanisms by which Lewis (y) antigen enhances the invasion and tumor metastasis are still unknown. In this study, we established a stable cell line constitutively expressing Lewis (y) antigen (RMG-1-hFUT) by transfecting the cDNA encoding part of the human ?1,2-fucosyltransferase (?1,2-FUT) gene into the ovarian cancer cell line RMG-1, and investigated whether Lewis (y) antigen regulates the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, and tissue inhibitors of metalloproteinases (TIMP-1) and TIMP-2. We found that RMG-1-hFUT cells exhibited higher invasive capacities than their control cells. In addition, expression of TIMP-1 and TIMP-2 was down-regulated and expression of MMP-2 and MMP-9 was up-regulated. Anti-Lewis (y) antigen antibody treatment significantly reversed the expression of TIMP-1, TIMP-2, MMP-2 and MMP-9. Taken together, we provide the first evidence that down-regulation of TIMP-1 and TIMP-2 and up-regulation of MMP-2 and MMP-9 represents one of the mechanisms by which Lewis (y) antigen promotes cell invasion.
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[Cloning of the promoter region of the trehalose-6-phosphate synthase gene TPS1 of the self-flocculating yeast and exploration of the promoter activity on ethanol stress].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 10-20-2010
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Improving stress tolerance of the microbial producers is of great importance for the process economy and efficiency of bioenergy production. Key genes influencing ethanol tolerance of brewing yeast can be revealed by studies on the molecular mechanisms which can lead to the further metabolic engineering manipulations for the improvement of ethanol tolerance and ethanol productivity. Trahalose shows protective effect on the cell viability of yeast against multiple environmental stress factors, however, further research is needed for the exploration of the underlying molecular mechanisms. In this study, the promoter region of the trehalose-6-phosphate synthase gene TPS1 was cloned from the self-flocculating yeast Saccharomyces cerevisiae flo, and a reporter plasmid based on the expression vector pYES2.0 on which the green fluorescence protein EGFP was directed by the TPS1 promoter was constructed and transformed to industrial yeast strain Saccharomyces cerevisiae ATCC4126. Analysis of the EGFP expression of the yeast transformants in presence of 7% and 10% ethanol revealed that the P(TPS1) activity was strongly induced by 7% ethanol, showing specific response to ethanol stress. The results of this study indicate that trehalose biosynthesis in self-flocculating yeast is a protective response against ethanol stress.
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Lewis Y promotes growth and adhesion of ovarian carcinoma-derived RMG-I cells by upregulating growth factors.
Int J Mol Sci
PUBLISHED: 08-09-2010
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Lewis y (LeY) antigen is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Overexpression of LeY is frequently observed in epithelial-derived cancers and has been correlated to the pathological staging and prognosis. However, the effects of LeY on ovarian cancer are not yet clear. Previously, we transfected the ovarian cancer cell line RMG-I with the ?1,2-fucosyltransferase gene to obtain stable transfectants, RMG-I-H, that highly express LeY. In the present study, we examined the proliferation, tumorigenesis, adhesion and invasion of the cell lines with treatment of LeY monoclonal antibody (mAb). Additionally, we examined the expression of TGF-?1, VEGF and b-FGF in xenograft tumors. The results showed that the proliferation and adhesion in vitro were significantly inhibited by treatment of RMG-I-H cells with LeY mAb. When subcutaneously inoculated in nude mice, RMG-I-H cells produced large tumors, while mock-transfected cells RMG-I-C and the parental cells RMG-I produced small tumors. Moreover, the tumor formation by RMG-I-H cells was inhibited by preincubating the cells with LeY mAb. Notably, the expression of TGF-?1, VEGF and b-FGF all increased in RMG-I-H cells. In conclusion, LeY plays an important role in promoting cell proliferation, tumorigenecity and adhesion, and these effects may be related to increased levels of growth factors. The LeY antibody shows potential application in the treatment of LeY-positive tumors.
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Enhancement of the adhesive and spreading potentials of ovarian carcinoma RMG-1 cells due to increased expression of integrin alpha5beta1 with the Lewis Y-structure on transfection of the alpha1,2-fucosyltransferase gene.
Biochimie
PUBLISHED: 02-12-2010
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Le(Y) antigen is known to be associated with malignant properties including metastasis and a poor prognosis of ovarian carcinomas. To clarify the mechanisms underling these properties, we established ovarian carcinoma-derived cells exhibiting enhanced expression of Le(Y) by transfection with alpha1,2-fucosyltransferase and compared their cellular properties with those of the original cells. So the human alpha1,2-fucosyltransferase gene was transfected into ovarian carcinoma-derived RMG-1 cells, which are known to contain Le(X), a precursor of Le(Y), and RMG-1-hFUT cells exhibiting enhanced expression of Le(Y) were established by selection with anti-Le(Y) antibodies, and their adhesive and spreading potentials on fibronectin-coated plates were compared with those of RMG-1 cells. Results showed that the relative expression of Le(Y) in RMG-1-hFUT cells was about 20-fold that in RMG-1 cells, and that of integrin alpha5beta1 and an integrin-mediated signal transduction molecule, focal adhesion kinase, was also increased in RMG-1-hFUT cells. Interestingly, anti-Le(Y) antibodies were revealed to immunoprecipitate integrin alpha5beta1, indicating that its oligosaccharides are composed of Le(Y), the amounts of which was substantially elevated in RMG-1-hFUT cells. The adhesion and spreading potentials on fibronectin-coated plates of RMG-1-hFUT cells were significantly enhanced in comparison to those of RMG-1 cells, and were greatly suppressed by anti-Le(Y) antibodies, indicating that Le(Y) is involved in the integrin-fibronectin interaction. These results suggested that transfection of the alpha1,2-fucosyltransferase gene into ovarian carcinoma-derived cells brought about elevated expression of integrin alpha5beta1 with Le(Y), resulting in enhancement of the adhesion and spreading potentials of cells through the integrin-fibronection interaction, which was inhibited by anti-Le(Y) antibodies. Thus, Le(Y) in integrin alpha5beta1 was thought to be involved in the enhanced cell adhesion properties of malignant ovarian carcinomas.
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Lewis(y) antigen stimulates the growth of ovarian cancer cells via regulation of the epidermal growth factor receptor pathway.
Oncol. Rep.
PUBLISHED: 02-04-2010
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Lewis(y) antigen is an oligosaccharide containing two fucoses, and is expressed variously in 75% of ovarian tumors, where its high expression level predicts poor prognosis. The effect and the possible mechanism of Lewis(y) on the proliferation of human ovarian cancer cells are still largely unkown. We report here that transfecting alpha1,2-FT gene into RMG-I cells increased the expression of Lewis(y) and promoted cell proliferation. In alpha1,2-FT-transfected cells, the Lewis(y) content of EGFR was increased dramatically. Tyrosine phosphorylation of EGFR was elevated. Concomitantly, tyrosine phosphorylation of Akt, ERK1/2 was also upregulated. Moreover, the expression of HER2/neu mRNA and protein, the tyrosine phosphorylation of HER2/ neu were also elveated, while the expression of p27 was significantly reduced. However, the expression of EGFR and the relative content of Lewis(y) on HER2/neu were unchanged. The above-mentioned alterations were correlated with the Lewis(y) content of EGFR and alpha1,2-FT expression in cells. In addition, the phosphorylation intensity and difference in phosphorylation intensity between cells with different expression of alpha1,2-FT were attenuated significantly by the inhibitor of EGFR tyrosine kinase and by the mono-antibody to Lewis(y). Meanwhile, the reduction in p27 and the difference in its expression among the two cell lines were also blocked by the Lewis(y) antibody. The PI3K signaling pathway was more important than the MAPK pathway in the regulation of p27 expression. These findings provide strong evidence that increased expression of Lewis(y) promotes cell proliferation through regulating the phosphorylation and expression of some molecules involved in the EGFR/PI3K-signaling pathway.
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[Effect of Lewis y antigen on regulating gene expression of partial drug resistance associated proteins in human ovarian cancer cell line RMG-I-H].
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
PUBLISHED: 09-24-2009
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To investigate the influence of Lewis y antigen on the gene expression of partial drug resistance associated proteins in human ovarian cancer cell line RMG-I-H.
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Effects of Lewis Y antigen on the gene expression of multiple drug resistance-associated proteins in human ovarian cancer RMG-I-H cells.
Med. Oncol.
PUBLISHED: 09-09-2009
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The effects of Lewis Y antigen on the gene expression of multiple drug resistance-associated proteins in human ovarian cancer RMG-I-H cells were unclear by now. In this study, we detected the gene expression of multiple drug resistance-associated proteins (MRP) in RMG-I-H cells and RMG-I-H cells treated with anti-Lewis Y monoclonal antibody to investigate the association between Lewis Y antigen and the gene expression of drug resistance-associated proteins. Compared with RMG-I cells, the expression of MRP1, MRP2, protein kinase C-alpha (PKC-alpha), and topoisomerase I (Topo I) mRNAs in RMG-I-H cells were significantly upregulated, while the MDR-1 mRNA was downregulated. Immunochemistry analyses indicated that the in vitro and in vivo expression levels of MDR-1 protein (P-gp) in RMG-I-H cells were significantly higher than those in RMG-I cells. After RMG-I-H cells were treated with anti-Lewis Y monoclonal antibody, the expression levels of MDR-1, MRP1, MRP2, PKC-alpha, and Topo I mRNAs gradually decreased with the prolongation of treatment duration. In contrast, no obvious changes were noted in the expression levels of these mRNAs in the non-treatment group. At 6 h after treatment, the relative levels of MDR-1, MRP1, MRP2, PKC-alpha, and Topo I mRNAs in the antibody treatment group were significantly lower than those in the non-treatment group. In conclusion, Lewis Y antigen is closely associated with regulating the gene expression of multiple drug resistance-associated proteins.
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Lewis y antigen promotes the proliferation of ovarian carcinoma-derived RMG-I cells through the PI3K/Akt signaling pathway.
J. Exp. Clin. Cancer Res.
PUBLISHED: 08-30-2009
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Lewis y antigen is difucosylated oligosaccharide and is carried by glycoconjugates at cell surface. Elevated expression of Lewis y has been found in 75% of ovarian tumor, and the high expression level is correlated to the tumors pathological staging and prognosis. This study was to investigate the effect and the possible mechanism of Lewis y on the proliferation of human ovarian cancer cells.
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Pharmacokinetics of CTLA4Ig fusion protein in healthy volunteers and patients with rheumatoid arthritis.
Acta Pharmacol. Sin.
PUBLISHED: 03-06-2009
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To evaluate single-dose and multiple-dose pharmacokinetics of cytotoxic T-lymphocyte-associated antigen 4 fusion protein (CTLA4Ig) in healthy volunteers and patients with rheumatoid arthritis (RA).
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The role of herbal PPAR modulators in the treatment of cardiometabolic syndrome.
Pharmacol. Res.
PUBLISHED: 02-19-2009
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For thousands of years, natural medicines have played an important role in treating and preventing human diseases worldwide. Natural products offer large structural diversity, and modern techniques for separation, structure elucidation, screening and combinatorial synthesis have led to revitalization of plant products as sources of new drugs. The number of people with cardiometabolic syndrome is increasing worldwide. This is expected to increase the prevalence of potentially harmful distortions of lipid distribution and thus intensify the need for appropriate intervention. With increasing evidence of the pathophysiological importance of the dyslipidaemia associated with type 2 diabetes mellitus, hypertension and insulin resistance, a more aggressive approach to lipid management is required. Nuclear receptors are an attractive and promising target for drug development. Functioning as transcription factors and thereby controlling cellular processes at the level of gene expression, modulation of nuclear receptor activity produces selective alterations in downstream gene expression. These characteristics, combined with their involvement in significant diseases, make nuclear receptors a key target for the development of disease-specific therapy. This review examines natural product libraries as a rich source of ligands for nuclear receptors and their potential as promising therapeutic agents for clinical practice. Continual evolution in drug discovery from plants remains an important source of new pharmaceuticals. Furthermore, by uncovering the regulatory mechanisms and transcriptional targets of the PPARs and other related receptors, it will be possible to provide a comprehensive insight into the pathogenesis of metabolic disease and, at the same time, offer valuable information for rational drug design, ultimately leading to a reduction in the chronic microvascular complications of cardiometabolic syndrome.
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Odor coding by modules of coherent mitral/tufted cells in the vertebrate olfactory bulb.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-30-2009
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Odor representation in the olfactory bulb (OB) undergoes a transformation from a combinatorial glomerular map to a distributed mitral/tufted (M/T) cell code. To understand this transformation, we analyzed the odor representation in large populations of individual M/T cells in the Xenopus OB. The spontaneous [Ca(2+)] activities of M/T cells appeared to be irregular, but there were groups of spatially distributed neurons showing synchronized [Ca(2+)] activities. These neurons were always connected to the same glomerulus. Odorants elicited complex spatiotemporal response patterns in M/T cells where nearby neurons generally showed little correlation. But the responses of neurons connected to the same glomerulus were virtually identical, irrespective of whether the responses were excitatory or inhibitory, and independent of the distance between them. Synchronous neurons received correlated EPSCs and were coupled by electrical conductances that could account for the correlated responses. Thus, at the output stage of the OB, odors are represented by modules of distributed and synchronous M/T cells associated with the same glomeruli. This allows for parallel input to higher brain centers.
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Elevated Levels of Lewis Y and Integrin ?5?1 Correlate with Chemotherapeutic Drug Resistance in Epithelial Ovarian Carcinoma.
Int J Mol Sci
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Objective: To measure Lewis y and integrin ?(5)?(1) expression in epithelial ovarian carcinoma and to correlate the levels of these molecules with ovarian carcinoma chemotherapy and prognosis. Methods: The study population included 34 ovarian carcinoma patients with chemotherapeutic drug-resistance, six partially drug-sensitive cases, and 52 drug-sensitive cases (92 total). Immunochemistry was used to determine expression of Lewis y antigen and integrin ?(5)?(1) in ovarian carcinoma tissues, and correlation of these molecules with chemotherapy resistance was further investigated, Multi-factor logistic regression analysis was applied to investigate: age, surgical stage, grade, subtype of patient cases, metastasis of lymph nodes, residual tumor size, expression levels of Lewis y antigen and integrin ?(5)?(1) correlation with ovarian carcinoma chemotherapy resistance. Results: The expression rates of Lewis y antigen and integrins ?(5) and ?(1) were significantly greater in the drug-resistant group (91.17%, 85.29%, 88.24%) than the partially sensitive (50.00%, 33.33%, 50.00%) or sensitive groups (61.54%, 57.69%, 55.77%). Binary logistic regression analysis revealed that surgical stage, residual tumor size, and expression of integrin ?(5) and Lewis y in ovarian carcinoma tissues were independent risk factors for chemotherapeutic drug resistance. Conclusions: Overexpression of Lewis y and integrin ?(5) are strong risk factors for chemotherapeutic drug resistance in ovarian carcinoma patients.
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Autophagy-independent enhancing effects of Beclin 1 on cytotoxicity of ovarian cancer cells mediated by proteasome inhibitors.
BMC Cancer
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The ubiquitin-proteasome system and macroautophagy (hereafter referred to autophagy) are two complementary pathways for protein degradation. Emerging evidence suggests that proteasome inhibition might be a promising approach for tumor therapy. Accumulating data suggest that autophagy is activated as a compensatory mechanism upon proteasome activity is impaired.
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Flavonoid Myricetin Modulates GABA(A) Receptor Activity through Activation of Ca(2+) Channels and CaMK-II Pathway.
Evid Based Complement Alternat Med
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The flavonoid myricetin is found in several sedative herbs, for example, the St. Johns Wort, but its influence on sedation and its possible mechanism of action are unknown. Using patch-clamp technique on a brain slice preparation, the present study found that myricetin promoted GABAergic activity in the neurons of hypothalamic paraventricular nucleus (PVN) by increasing the decay time and frequency of the inhibitory currents mediated by GABA(A) receptor. This effect of myricetin was not blocked by the GABA(A) receptor benzodiazepine- (BZ-) binding site antagonist flumazenil, but by KN-62, a specific inhibitor of the Ca(2+)/calmodulin-stimulated protein kinase II (CaMK-II). Patch clamp and live Ca(2+) imaging studies found that myricetin could increase Ca(2+) current and intracellular Ca(2+) concentration, respectively, via T- and L-type Ca(2+) channels in rat PVN neurons and hypothalamic primary culture neurons. Immunofluorescence staining showed increased phosphorylation of CaMK-II after myricetin incubation in primary culture of rat hypothalamic neurons, and the myricetin-induced CaMK-II phosphorylation was further confirmed by Western blotting in PC-12 cells. The present results suggest that myricetin enhances GABA(A) receptor activity via calcium channel/CaMK-II dependent mechanism, which is distinctively different from that of most existing BZ-binding site agonists of GABA(A) receptor.
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Age at menarche and risk of ovarian cancer: a meta-analysis of epidemiological studies.
Int. J. Cancer
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Epidemiological studies have reported inconsistent associations between menarcheal age and ovarian cancer risk. To our knowledge, a meta-analysis for the association between menarcheal age and ovarian cancer has not been reported. Relevant published studies of menarcheal age and ovarian cancer were identified using MEDLINE, EMBASE and Web of Science through the end of April 2012. Two authors (T-T.G. and Q-J.W.) independently assessed eligibility and extracted data. We pooled the relative risks (RRs) from individual studies using a random-effects model and performed heterogeneity and publication bias analyses. A total of 27 observational studies consisting of 22 case-control and five cohort studies were included in our analysis. In a pooled analysis of all studies, a statistically significant inverse association was observed between menarcheal age (for the oldest compared to the youngest category) and ovarian cancer risk (RR = 0.85; 95% confidence interval [CI] = 0.75-0.97). The pooled RRs of ovarian cancer for the oldest versus the youngest categories of menarcheal age in prospective and case-control studies were 0.89 (95% CI = 0.76-1.03) and 0.84 (95% CI = 0.70-0.99), respectively. Inverse associations between menarcheal age and ovarian cancer risk were observed in most subgroups; however, the significant association was restricted to invasive and borderline serous ovarian cancer. In conclusion, findings from this meta-analysis support that menarcheal age was inversely associated with the risk of ovarian cancer. More large studies are warranted to stratify these results by different cancer grading and histotype of ovarian cancer.
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Exogenous basic fibroblast growth factor inhibits ER stress-induced apoptosis and improves recovery from spinal cord injury.
CNS Neurosci Ther
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To investigate the mechanism of endoplasmic reticulum (ER) stress-induced apoptosis as well as the protective action of basic fibroblast growth factor (bFGF) both in vivo and in vitro.
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Efficacy analysis of combining three comparative-omics profilings to screen candidate biological macromolecules.
Mol. Biol. Rep.
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To evaluate the efficacy of integrated comparative omics in screening candidate biological macromolecules, three methods, namely, 2-DE + MALDI-TOF-MS, tumor-associated cDNA microarray and whole-transcriptome cDNA microarray were examined by three biotechnological companies to compare a stable transfected cell line with its control one. The results showed that the percentages of the up-regulate in three methods are largely consistent. 21.59 % of tumor-associated microarray results are the same with that of whole-transcriptome microarray. SOD2 is the unique intersection of three methods. Consulting the results of pI and Mw derived from microarray cannot increase the detection rate of target molecules during protein spot selection for mass spectrometry. Two protein spots with different regulating directions were identified to be the same protein. Conclusively, proteomic and genomic methods reveal the macromolecular changes from different aspects. Their detection ranges are complementary. The combination of different genomic methods can improve the validity and stability and reduce the noise changes. However, it is no sense to compare proteomics with genomics.
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[The analysis of Lebers hereditary optic neuropathy associated with mitochondrial tRNAAla C5601T mutation in seven Han Chinese families].
Yi Chuan
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We reported here the clinical, genetic, and molecular characterization of Lebers hereditary optic neuropathy (LHON) with C5601T mutation in seven Chinese families. The ophthalmologic examinations of seven Chinese families who were clinically diagnosed LHON were conducted. Strikingly, these families exhibited very low penetrance of visual impairment, and the penetrance was 9.5%, 14.3%, 4.5%, 8.3%, 10.0%, 22.2% and 25.0%. Meanwhile, entire mitochondrial genome of seven probands was amplified by PCR using 24 pairs of oligonucleotide primers with overlapping fragments. Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated G11778A, G3460A and T14484C mutations but the presence of homoplastic LHON associated tRNAAla C5601T mutation in probands and other matrilineal relatives. These mtDNA polymorphism sites belongs to the Asian haplogroups G2, G2a1, G2a1, G2, G2b, G2a1 and G2. By analyzing mitochondrial genome, seven LHON families all carry the C5601T mutation. The C5601T mutation occurs at the highly conserved nucleotide (conventional position 59) of tRNAAla, thereby contributing to the structural formation and stabilization of functional tRNAs and leading to mitochondrial dysfunction involved in visual impairment. The incomplete penetrance of visual loss in these seven Chinese pedigrees strongly indicates that the tRNAAla C5601T mutation was itself insufficient to produce a clinical phenotype. The lack of functional mtDNA variants in these pedigrees ruled out the role of mitochondrial background in the phenotypic expression of visual loss. Therefore, nuclear backgrounds and environmental factors seem to be modifying factors for the phenotypic manifestation of the tRNAAla C5601T mutation in the seven Chinese families.
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Hippocampal place fields emerge upon single-cell manipulation of excitability during behavior.
Science
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The origin of the spatial receptive fields of hippocampal place cells has not been established. A hippocampal CA1 pyramidal cell receives thousands of synaptic inputs, mostly from other spatially tuned neurons; however, how the postsynaptic neurons cellular properties determine the response to these inputs during behavior is unknown. We discovered that, contrary to expectations from basic models of place cells and neuronal integration, a small, spatially uniform depolarization of the spatially untuned somatic membrane potential of a silent cell leads to the sudden and reversible emergence of a spatially tuned subthreshold response and place-field spiking. Such gating of inputs by postsynaptic neuronal excitability reveals a cellular mechanism for receptive field origin and may be critical for the formation of hippocampal memory representations.
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Clinical implications of REST and TUBB3 in ovarian cancer and its relationship to paclitaxel resistance.
Tumour Biol.
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The objective of this study was to examine the expression levels of RE1-silencing transcription factor (REST) and class III ?-tubulin (TUBB3) in ovarian cancer and to determine if there is a correlation between their expression and resistance to chemotherapy in ovarian cancer. The protein expression of REST and TUBB3 in ovarian cancer was detected by Western blot analysis. REST expression was inhibited by small interfering ribonucleic acid (siRNA) in human ovarian cancer cell lines. The levels of REST and TUBB3 protein expression were detected by immunohistochemistry. The relationship between REST and TUBB3 expression and chemotherapy resistance, clinicopathological parameters, and prognosis of ovarian cancer was then determined. The present study found that REST was more highly expressed in the ovarian SKOV3 carcinoma cell line compared to the paclitaxel-resistant ovarian cancer cell line, SKOV3/TAX (P = 0.01). In contrast, TUBB3 was more highly expressed in SKOV3/TAX cells compared to SKOV3 cells (P = 0.01). After REST siRNA interference, TUBB3 expression increased in SKOV3 cells. REST expression was significantly higher in the paclitaxel-sensitive group compared to the paclitaxel-resistant group (70.7 % vs. 37.0 %, P < 0.05). However, TUBB3 expression was significantly lower in the paclitaxel-sensitive group compared to the paclitaxel-resistant group (47.6 % vs. 77.8 %, P < 0.05). Notably, REST was more highly expressed in TUBB3-negative cases than TUBB3-positive cases (P < 0.05). Univariate analyses indicated that both REST and TUBB3 expression were unrelated to tumor differentiation, histological type, and clinical stage (all P > 0.05). According to the Cox regression model, negative REST and positive TUBB3 protein expression was detected as independent prognostic factors (P = 0.003 and P = 0.005, respectively). REST and TUBB3 protein may be potential biomarkers for chemoresistance and prognosis in ovarian cancer.
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Risperidone enhances the vulnerability to stroke in hypertensive rats.
CNS Neurosci Ther
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Stroke is the second most common cause of death and a major cause of disability worldwide. Risperidone is an atypical antipsychotic drug that may increase the risk of stroke. The present work examined whether risperidone enhances the vulnerability to stroke in hypertensive rats and the potential mechanisms underlying such action.
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Expression of high-risk HPV DNA and CK19 in pelvic lymph nodes in stage Ia-IIa cervical cancer and their clinical value.
Oncol. Rep.
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The aim of this study was to investigate the detection rate and methods of micrometastases in early-stage cervical cancer by detecting the expression of high-risk HPV DNA and CK19 in pelvic lymph nodes. A total of 104 lymph nodes with/without pathologically confirmed metastases, from 28 patients with early-stage cervical cancer, were included for detection of high-risk HPV DNA and CK19 expression using in situ hybridization and immunohistochemistry, respectively. The detection rate of high-risk HPV DNA and CK19 in lymph nodes in patients with pathologically-confirmed lymph node metastases was higher compared to that in lymph nodes in patients without pathologically-confirmed lymph node metastases (P<0.001). In all 80 pathologically-negative lymph nodes, the positivity rates of high-risk HPV DNA and CK19 detection were 45 and 25%, respectively. In 57 lymph nodes in patients without pathologically-confirmed lymph node metastases the positivity rates of high-risk HPV DNA and CK19 detection were 43.5 and 24.6%. The detection rate of high-risk HPV DNA and CDK19 in 15 patients without pathologically-confirmed lymph node metastases were 60 and 46.6%, respectively. The detection rates of high-risk HPV DNA and CK19 in 104 lymph nodes were 56.7 and 41.3% (KI=0.46). The results of the two detection methods showed good consistency. Both detection of high-risk HPV DNA by in situ hybridization, and CK19 by immunohistochemical method detected lymph node micrometastases in early-stage cervical cancer. As a method of detection on the molecular level, in situ hybridization was more sensitive for the detection of lymph node micrometastases in early-stage cervical cancer.
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Lewis y Regulate Cell Cycle Related Factors in Ovarian Carcinoma Cell RMG-I in Vitro via ERK and Akt Signaling Pathways.
Int J Mol Sci
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To investigate the effect of Lewis y overexpression on the expression of proliferation-related factors in ovarian cancer cells.
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