Search

Sepsis is a complex clinical syndrome involving both infection and a deleterious host immune response. Antimicrobial agents are key elements of sepsis treatment, yet despite great strides in antimicrobial development in the last decades, sepsis continues to be associated with unacceptably high mortality (∼30%). This is the result, on one hand, of the rise of antimicrobial resistant organisms and, on the other hand, of the dearth of effective host-directed immune therapies. A major obstacle to the development of good host-directed therapies is the lack of understanding of the host immune response. The problem is exacerbated by poor nonspecific clinical definitions of disease. Poor definitions have had a profound impact on sepsis research, from epidemiologic studies to the failed clinical trials of host-directed therapies. Therefore, better definitions must be developed to enable advancement in the field. [ABSTRACT FROM AUTHOR]

Summary: Gene expression or metabolomics data generated from clinical settings are often associated with multiple metadata (i.e. diagnosis, genotype, gender, etc.). It is of great interest to analyze and to visualize the data in these contexts. Here, we introduce INVEX—a novel web-based tool that integrates the server-side capabilities for data analysis with the browse-based technology for data visualization. INVEX has two key features: (i) flexible differential expression analysis for a wide variety of experimental designs; and (ii) interactive visualization within the context of metadata and biological annotations. INVEX has built-in support for gene/metabolite annotation and a fully functional heatmap builder.Availability and implementation: Freely available at http://www.invex.ca.Contact: bob@hancocklab.ubc.ca [ABSTRACT FROM AUTHOR]

Background Transarterial oily chemoembolization (TOCE) is frequently employed as a non-operative treatment for hepatocellular carcinoma (HCC). Serious complications of TOCE are well known but ruptured HCC as a fatal complication of TOCE has not been reported previously. Methods A retrospective study was performed on all patients who received TOCE for treatment of HCC from January 1989 to October 1996; the complication of ruptured HCC within 2 weeks from the procedure was recorded. Results During the study period, 391 patients received a total of 1443 sessions of TOCE (mean 3·7 sessions per patient) for the treatment of HCC, with an overall median survival of 10·4 months. Six patients developed ruptured tumour within 2 weeks after TOCE, resulting in an overall incidence of 1·5 per cent per patient or 0·4 per cent per procedure. All except one patient died 1–25 days after tumour rupture. Factors common to these six patients included: (1) male sex; (2) large tumour size (range 8–17 cm in diameter); (3) tumour located in the right lobe of the liver; (4) tumour ruptured after the first session of TOCE; and (5) TOCE performed as primary treatment without previous hepatic resection. Conclusion Ruptured HCC is a serious complication of TOCE although the incidence is low. It occurred predominantly in men after the first session of TOCE for a large irresectable tumour of the right lobe. [ABSTRACT FROM AUTHOR]

Homozygous arginine at codon 72 (HA72) of p53 was found in 22% of normal cervices and 30.0% of cervical cancers and no significant difference was detected between normal and cervical cancer with or without HPV 16/18. There was no correlation between HA72 and risk of cervical cancer in Chinese. [ABSTRACT FROM AUTHOR]

Background. A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods. Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results. 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions. The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus type 1 (HIV-1)-infected women have lower viral loads than men but similar rates of disease progression. We hypothesized that sex-based differences in CCR5 expression mediate viral load differences.Methods: CCR5 was analyzed by flow cytometry in disaggregated lymph node cells from untreated HIV-1-infected women (n = 28) and men (n = 27). The frequencies of HIV-1 RNA-producing cells in the lymph node were determined by in situ hybridization. Linear and generalized linear regression models were used.Results: The percentage of CCR5(+)CD3(+)CD4(+) cells was lower in women (mean, 12%) than men (mean, 16%; P = .034). Neither the percentage of CCR5(+)CD3(+)CD4(+) cells nor the CCR5 density predicted viral load or HIV-1 RNA-producing lymph node cells (P ≥ .24), after adjusting for CD4(+) T-cell count, race, and age. Women had marginally fewer HIV-1 RNA-producing cells (mean, 0.21 cells/mm(2)) than men (mean, 0.44 cells/mm(2); P = .046). After adjusting for the frequency of HIV-1 RNA-producing cells and potential confounders, the viral load in women were 0.46 log10 copies/mL lower than that in men (P = .018).Conclusions: Reduced lymph node CCR5 expression in women did not account for the viral load difference between sexes. CCR5 expression did not predict viral load or frequencies of HIV-1 RNA-producing cells, indicating that physiologic levels of CCR5 do not limit HIV-1 replication in lymph node. Less plasma virus was associated with each HIV-1 RNA-producing cell in women as compared to men, suggesting that women may either produce fewer virions per productively infected cell or more effectively clear extracellular virus. [ABSTRACT FROM AUTHOR]

Background. Human immunodeficiency virus type 1 (HIV-1)–infected women have lower viral loads than men but similar rates of disease progression. We hypothesized that sex-based differences in CCR5 expression mediate viral load differences.Methods. CCR5 was analyzed by flow cytometry in disaggregated lymph node cells from untreated HIV-1–infected women (n = 28) and men (n = 27). The frequencies of HIV-1 RNA–producing cells in the lymph node were determined by in situ hybridization. Linear and generalized linear regression models were used.Results. The percentage of CCR5+CD3+CD4+ cells was lower in women (mean, 12%) than men (mean, 16%; P = .034). Neither the percentage of CCR5+CD3+CD4+ cells nor the CCR5 density predicted viral load or HIV-1 RNA–producing lymph node cells (P ≥ .24), after adjusting for CD4+ T-cell count, race, and age. Women had marginally fewer HIV-1 RNA–producing cells (mean, 0.21 cells/mm2) than men (mean, 0.44 cells/mm2; P = .046). After adjusting for the frequency of HIV-1 RNA–producing cells and potential confounders, the viral load in women were 0.46 log10 copies/mL lower than that in men (P = .018).Conclusions. Reduced lymph node CCR5 expression in women did not account for the viral load difference between sexes. CCR5 expression did not predict viral load or frequencies of HIV-1 RNA–producing cells, indicating that physiologic levels of CCR5 do not limit HIV-1 replication in lymph node. Less plasma virus was associated with each HIV-1 RNA–producing cell in women as compared to men, suggesting that women may either produce fewer virions per productively infected cell or more effectively clear extracellular virus. [ABSTRACT FROM PUBLISHER]

BACKGROUND Women with an infertility problem living in traditional and developing countries face extensive social pressure, infertility-related stress, and distress, which possibly affect their choices of coping strategies. The present study aims to investigate the impact of infertility-related stress and social support on coping of Vietnamese women who live with an infertility diagnosis. PARTICIPANTS AND PROCEDURE A cross-sectional study was conducted with 192 women diagnosed with infertility at two hospitals in the north and central regions of Vietnam. Participants completed a questionnaire consisting of the Multidimensional Scale of Perceived Social Support, the Copenhagen Multi-centre Psychosocial Infertility coping scales and the Fertility Problem Inventory, and questions about their sociodemographic characteristics, infertility-related history, and key social relationships. Four linear regression analyses were performed on four coping strategies: active-avoidance coping (AAC), active-confronting coping (ACC), passive-avoidance coping (PAC), and meaning-based coping (MBC). RESULTS The findings show that high infertility-related stress significantly predicted the use of avoidance coping strategies (AAC and PAC) among these women, while those with a high level of perceived social support tended to use ACC and MBC. None of the four linear regression models support the moderating role of social support in the relationship between infertility-related stress and coping styles. CONCLUSIONS The study findings show that levels of infertility-related stress and perceived social support have a direct effect on the choice of coping strategies among Vietnamese women diagnosed with infertility. The study results have practical implications in the Vietnamese context, including: (i) the development and adaptation of evidence-based and culturally appropriate interventions and counselling strategies; and (ii) social policy advocacy to better support women diagnosed with infertility, their husbands, and both as couples. [ABSTRACT FROM AUTHOR]

Ovarian cancer is highly metastatic with a poor prognosis. The serine/threonine kinase, p70 S6 kinase (p70S6K), which is a downstream effector of phosphatidylinositol 3-kinase/Akt pathway, is frequently activated in ovarian cancer. Here, we show that p70S6K is a critical regulator of the actin cytoskeleton in the acquisition of the metastatic phenotype. This regulation is through two important activities: p70S6K acts as an actin filament cross-linking protein and as a Rho family GTPase-activating protein. Ectopic expression of constitutively active p70S6K in ovarian cancer cells induced a marked reorganization of the actin cytoskeleton and promoted directional cell migration. Using cosedimentation and differential sedimentation assays, p70S6K was found to directly bind to and cross-link actin filaments. Immunofluorescence studies showed p70S6K colocalized with cytochalasin D-sensitive actin at the leading edge of motile cells. The p70S6K did not affect the kinetics of spontaneous actin polymerization, but could stabilize actin filaments by the inhibition of cofilin-induced actin depolymerization. In addition, we showed that p70S6K stimulated the rapid activation of both Rac1 and Cdc42, and their downstream effector p21-activated kinase (PAK1), but not RhoA. Depletion of p70S6K expression or inhibition of its activity resulted in significant inhibition of actin cytoskeleton reorganization and reduced migration, with a concomitant reduction in Rac1, Cdc42 and PAK1 activation, confirming that the effect was p70S6K specific. Similarly, the actin cytoskeleton reorganization/migratory phenotype could be reversed by expression of dominant negative Rac1 and Cdc42, or inhibition of PAK1. These results reveal a new direction for understanding the oncogenic roles of p70S6K in tumor progression. [ABSTRACT FROM AUTHOR]

Aims: Hydatidiform mole (HM) is the most common type of gestational trophoblastic disease. A proportion of patients with HM develop gestational trophoblastic neoplasia (GTN) requiring chemotherapy. The aim was to identify differentially expressed genes that are associated with development of GTN. Methods and results: Using cDNA microarray, differential expression of prostate stem cell antigen (PSCA) was identified in HMs that developed GTN compared with those that spontaneously regressed. Significant overexpression of PSCA RNA ( P = 0.037) and protein ( P < 0.05) in aggressive HM was verified by real-time polymerase chain reaction (PCR) and immunohistochemical analysis in 10 first-trimester placentas, 36 HM that subsequently regressed and 11 HM that developed GTN. A high level of PSCA expression was also found in three choriocarcinomas and three placental site trophoblastic tumours. A positive correlation was observed between PSCA expression and proliferation and apoptotic indices as assessed by Ki67 ( P = 0.01), mcm7 ( P = 0.001) and M30 ( P = 0.016), as well as p53 ( P < 0.01), p21WAF1/CIP1 ( P < 0.01) and mdm2 ( P = 0.002) expression. Conclusions: Overexpression of PSCA is associated with development of GTN in HM. PSCA probably plays a role in the regulation of cell growth through p53-related signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Placental trophoblast can be considered to be pseudomalignant tissue and the pathogenesis of gestational trophoblastic diseases remains to be clarified. Aims: To examine the role of caspases 8 and 10, identified by differential expression, on trophoblast tumorigenesis. Methods: cDNA array hybridisation was used to compare gene expression profiles in choriocarcinoma cell lines (JAR, JEG, and BeWo) and normal first trimester human placentas, followed by confirmation with quantitative real time polymerase chain reaction and immunohistochemistry. Caspase 10 and its closely related family member caspase 8 were analysed. Results: Downregulation of caspase 10 in choriocarcinoma was detected by both Atlas™ human cDNA expression array and Atlas™ human 1 .2 array. Caspase 10 mRNA expression was significantly lower in hydatidiform mole (p = 0.035) and chorioarcinoma (p = 0.002) compared with normal placenta. The caspase 8 and 10 proteins were expressed predominantly in the cytotrophoblast and syncytiotrophoblast, respectively, with significantly lower expression in choriocarcinomas than other trophoblastic tissues (p <0.05). Immunoreactivity for both caspase 8 and 10 correlated with the apoptotic index previously assessed by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (p = 0.02 and p = 0.04, respectively) and M30 (p < 0.001 and p = 0.003, respectively) approaches. Conclusions: These results suggest that the downregulation of capases 8 and 10 might contribute to the pathogenesis of choriocarcinoma. [ABSTRACT FROM AUTHOR]

Objective.The aim of this study was to assess the cost-effectiveness of serial squamous cell carcinoma antigen (SCC) monitoring in the clinical setting.Methods. All patients with squamous cell carcinoma of the cervix and SCC measurement from 1994 to 1999 were reviewed. The cost of the investigations, including blood tests, X rays, and computer tomography; and clinic visits were adjusted to 2001 dollars for all cases over the 6-year study period. The effectiveness measure was the number of cases detected by SCC monitoring before the onset of clinical symptoms or abnormal physical examination findings. Altered clinical management due to early detection was considered successful.Results. Two thousand eight hundred fifty-one SCC antigen assays were performed from 384 patients. An elevated pretreatment SCC level was associated with poorer cumulative survival over time (P < 0.05). Fifty-five patients had recurrences, with 10 local and 45 distant recurrences. SCC levels were elevated in 47 patients (85%). The median lead time was 7.8 months. The cost of finding 1 recurrence was US$4750. SCC monitoring does not alter clinical management and has no advantage over clinical examination in detecting local recurrence. Most of the recurrent diseases were detected too late for curative treatment. Only 1 patient, in whom the diagnosis could have been made by clinical examination without SCC monitoring, may have potentially benefited from exenteration.Conclusion. Posttreatment SCC monitoring is not cost-effective in the absence of curative treatment for distant spread of disease. [Copyright &y& Elsevier]

The authors report a case of persistent endometrial stromal tumour during two consecutive pregnancies. The diagnosis of endometrial stromal sarcoma (ESS) is difficult by fragmented tissue. There were a total of 19 reported cases of pregnancy after conservative management of endometrial stromal sarcoma. Monitoring of disease during pregnancy is challenging, although most patients remain in a stable condition with a follow-up duration of 2-60 months. Although the present patient had a favorable disease outcome despite having co-existing ESS sustained throughout two term pregnancies, the current evidence on the safety of this approach is still scarce and thorough counseling is mandatory if any young patients wish to retain their fertility potential. [ABSTRACT FROM AUTHOR]

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002).Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group.Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate.Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia.Clinical Trials Registration: NCT00543543; NCT00943722. [ABSTRACT FROM AUTHOR]

Purpose of investigation: The objective of this study was to review all malignant ovarian germ cell tumors (MOGCT) managed at the present center, focusing on the role of lymphadenectomy, and vincristine, actinomycin-D, cyclophosphamide (VAC) chemotherapy on treatment, and survival outcome. Materials and Methods: The authors performed a retrospective chart review of 77 patients managed for MOGCT between January 1986 and December 2012. Results: Median age at diagnosis was 26 years. The histologic subtypes included 47 (61.0%) immature teratoma, 16 (20.8%) yolk sac tumor, 9 (11.7%) dysgerminoma, and five (6.5%) mixed germ cell tumor. Of 65 patients with clinically early-stage tumors, 17 (26.1%) had lymphadenectomy performed, of which all had no lymph node metastasis on histology. The overall survival was 100% for both lymphadenectomy and no lymphadenectomy groups. Postoperative adjuvant chemotherapy was administered to 51 (66.2%) patients, 38 (74.5%) of whom received VAC chemotherapy. Complete response and overall cure rate of VAC regimen was 100% and 89.5%, respectively when used as first-line postoperative adjuvant treatment. Median follow-up period was 138 months and overall survival was 97.4%. Conclusions: Lymphadenectomy did not provide survival benefits in patients with clinically earlystage MOGCT. The VAC chemotherapy regimen can be considered as an option for primary postoperative treatment, especially in patients with early-stage disease. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to characterise the oncogenic roles of C35, a novel protein binding partner of ΔNp73, in ovarian cancer and to investigate the functional significance of C35-ΔNp73 interaction in the regulation of chemo-resistance.Methods: C35 expression was evaluated by quantitative real-time PCR in human ovarian cancer tissues and cell lines. The aggressiveness of ovarian cancer cells overexpressing C35 was examined by cell proliferation, migration, soft agar and nude mouse xenograft. The significance of C35-ΔNp73 interaction in chemo-resistance was evaluated by apoptosis assays and cell viability after cisplatin treatment.Results: The expression of C35 was significantly enhanced in human ovarian cancer tissues. Overexpression of C35 augmented proliferation, migration and tumourigenicity in ovarian cancer cell lines. C35 knockdown inhibited cell motility and cell growth. The co-expression of C35 and ΔNp73 by transient or stable transfection in ovarian cancer cells induced greater resistance to cisplatin treatment than did transfection with C35 or ΔNp73 alone. The cisplatin resistance was demonstrated to be caused by increased AKT and NFκB activity induced by C35-ΔNp73.Conclusion: Our results suggest that ΔNp73 might cooperate with C35 to promote tumour progression and contribute to cisplatin resistance in ovarian cancer cells. Future studies of the functional roles of ΔNp73 and C35 will provide insight that will aid in the establishment of new strategies and more effective therapies. [ABSTRACT FROM AUTHOR]

Background:The purpose of this study was to characterise the oncogenic roles of C35, a novel protein binding partner of ΔNp73, in ovarian cancer and to investigate the functional significance of C35-ΔNp73 interaction in the regulation of chemo-resistance.Methods:C35 expression was evaluated by quantitative real-time PCR in human ovarian cancer tissues and cell lines. The aggressiveness of ovarian cancer cells overexpressing C35 was examined by cell proliferation, migration, soft agar and nude mouse xenograft. The significance of C35-ΔNp73 interaction in chemo-resistance was evaluated by apoptosis assays and cell viability after cisplatin treatment.Results:The expression of C35 was significantly enhanced in human ovarian cancer tissues. Overexpression of C35 augmented proliferation, migration and tumourigenicity in ovarian cancer cell lines. C35 knockdown inhibited cell motility and cell growth. The co-expression of C35 and ΔNp73 by transient or stable transfection in ovarian cancer cells induced greater resistance to cisplatin treatment than did transfection with C35 or ΔNp73 alone. The cisplatin resistance was demonstrated to be caused by increased AKT and NFκB activity induced by C35-ΔNp73.Conclusion:Our results suggest that ΔNp73 might cooperate with C35 to promote tumour progression and contribute to cisplatin resistance in ovarian cancer cells. Future studies of the functional roles of ΔNp73 and C35 will provide insight that will aid in the establishment of new strategies and more effective therapies. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the most lethal of all gynecological malignancies, and the identification of novel prognostic and therapeutic targets for ovarian cancer is crucial. It is believed that only a small subset of cancer cells are endowed with stem cell properties, which are responsible for tumor growth, metastatic progression and recurrence. NANOG is one of the key transcription factors essential for maintaining self-renewal and pluripotency in stem cells. This study investigated the role of NANOG in ovarian carcinogenesis and showed overexpression of NANOG mRNA and protein in the nucleus of ovarian cancers compared with benign ovarian lesions. Increased nuclear NANOG expression was significantly associated with high-grade cancers, serous histological subtypes, reduced chemosensitivity, and poor overall and disease-free survival. Further analysis showed NANOG is an independent prognostic factor for overall and disease-free survival. Moreover, NANOG was highly expressed in ovarian cancer cell lines with metastasis-associated property and in clinical samples of metastatic foci. Stable knockdown of NANOG impeded ovarian cancer cell proliferation, migration and invasion, which was accompanied by an increase in mRNA expression of E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1. Conversely, ectopic NANOG overexpression enhanced ovarian cancer cell migration and invasion along with decreased E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1 mRNA expression. Importantly, we found Nanog-mediated cell migration and invasion involved its regulation of E-cadherin and FOXJ1. This is the first report revealing the association between NANOG expression and clinical outcome of patients with ovarian cancers, suggesting NANOG to be a potential prognostic marker and therapeutic molecular target in ovarian cancer. [ABSTRACT FROM AUTHOR]

Artificial neural networks (ANNs) have been widely applied in electricity price forecasts due to their nonlinear modeling capabilities. However, it is well known that in general, traditional training methods for ANNs such as back-propagation (BP) approach are normally slow and it could be trapped into local optima. In this paper, a fast electricity market price forecast method is proposed based on a recently emerged learning method for single hidden layer feed-forward neural networks, the extreme learning machine (ELM), to overcome these drawbacks. The new approach also has improved price intervals forecast accuracy by incorporating bootstrapping method for uncertainty estimations. Case studies based on chaos time series and Australian National Electricity Market price series show that the proposed method can effectively capture the nonlinearity from the highly volatile price data series with much less computation time compared with other methods. The results show the great potential of this proposed approach for online accurate price forecasting for the spot market prices analysis. [ABSTRACT FROM PUBLISHER]

Background: This study aimed to evaluate traditional Chinese medicine (TCM) in improving quality of life (QOL), reducing chemotoxicity and modulating immune function in patients undergoing chemotherapy.Patients and methods: Patients with ovarian cancer were randomized to receive either TCM or placebo in addition to standard chemotherapy. The primary outcome was global health status (GHS) score, assessed by European Organization for Research and Treatment of Cancer questionnaire, while the secondary outcomes were other QOL items, chemotoxicity according to World Health Organization criteria and alterations in immune function as measured by immune cells count and the numbers of cytokines-secreting cells.Results: There was no significant difference in the GHS between the two groups. With adjustment for stage, chemotherapy type, disease status, age and baseline value, emotional function, cognitive function and nausea and vomiting were found to be worse or less improved in the TCM group compared with placebo group after six cycles of chemotherapy. The TCM group had less neutropenia after three cycles (0% grade 4 neutropenia versus 28.6%). There were no other significant differences in terms of chemotoxicity. Lymphocyte counts and cytokine activities decreased less in the TCM group.Conclusions: TCM did not improve QOL but did have some effects in terms of maintaining immune function. [ABSTRACT FROM AUTHOR]

Gonadotropin-releasing hormone (GnRH) is a potent prometastatic factor in ovarian cancer, but the intracellular signaling events are not well understood. The classical Gαq-phospholipase C signal transduction pathway known to operate in the pituitary is not involved in GnRH actions at non-pituitary targets. Here we showed that GnRH treatment of ovarian cancer cells led to a rapid and remarkable tyrosine phosphorylation of p120 catenin (p120ctn), which was mediated by P-cadherin. The use of P-cadherin small interfering RNA or neutralizing antibodies to inhibit P-cadherin expression and function resulted in diminished p120ctn activation, confirming that the effect was P-cadherin specific. On exploring how P-cadherin, which lacks intrinsic kinase activity, might regulate the activation of p120ctn, we found that P-cadherin could induce the ligand-independent activation of insulin-like growth factor-1 receptor (IGF-1R). Inhibition of IGF-1R expression or its activity significantly inhibited GnRH-induced p120ctn activation, and the subsequent cell migration and invasion. In addition, we showed that IGF-1R regulation by P-cadherin was associated with complex formation between IGF-1R and P-cadherin, and this regulation was also observed to be in vivo correlated with metastasis. Furthermore, using a mouse model of ovarian cancer metastasis, GnRH receptor knockdown was shown to diminish peritoneal dissemination of tumors and ascites formation. These findings suggest for the first time that GnRH can initiate an outside-in p120ctn signal transduction through the cross-talk between P-cadherin and IGF-1R, thus providing a novel molecular mechanism by which GnRH may control the high level of aggressiveness and invasion and metastasis potential that are characteristic of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Oral corticosteroids (OCS) in the home management of asthma exacerbations have been recommended in the NIH/NHLBI guidelines since 1991. As a routine component of written action plans, OCS treatment at home is associated with reduced emergency department (ED) visits and hospitalizations as well as decreased mortality. Methods: A literature search of English language journals from 1991 to 2009 was performed using several databases, including PubMed, EMBASE, and SCOPUS. We assessed studies that evaluated adherence to national guidelines for home management of asthma exacerbations. Results: Our review of the literature found that several studies reveal that a small percentage (<3-26%) of patients are receiving OCS at home to manage asthma exacerbations prior to an ED visit. Additional studies were found showing very low use of written action plans, strongly suggesting lack of OCS for home management of asthma exacerbations. Conclusions: Despite evidence of reduced ED visits and hospitalizations and the recommendations of national and international guidelines, the home use of OCS in managing asthma exacerbations remains unacceptably low. New strategies are needed to ensure home use of OCS as part of written action plans to prevent ED visits and hospitalizations for asthma exacerbations. [ABSTRACT FROM AUTHOR]

Background:Loss of growth inhibitory response to transforming growth factor-β (TGF-β) is a common feature of epithelial cancers. Recent studies have reported that genetic lesions and overexpression of oncoproteins in TGF-β/Smads signalling cascade contribute to the TGF-β resistance. Here, we showed that the overexpressed FOXG1 was involved in attenuating the anti-proliferative control of TGF-β/Smads signalling in ovarian cancer.Methods:FOXG1 and p21WAF1/CIP1 expressions were evaluated by real-time quantitative reverse-transcription polymerase chain reaction (RT–PCR), western blot and immunohistochemical analyses. The effect of FOXG1 on p21WAF1/CIP1 transcriptional activity was examined by luciferase reporter assays. Cell lines stably expressing or short hairpin RNA interference-mediated knockdown FOXG1 were established for studying the gain-or-loss functional effects of FOXG1. XTT cell proliferation assay was used to measure cell growth of ovarian cancer cells.Results:Quantitative RT–PCR and western blot analyses showed that FOXG1 was upregulated and inversely associated with the expression levels of p21WAF1/CIP1 in ovarian cancer. The overexpression of FOXG1 was significantly correlated with high-grade ovarian cancer (P=0.025). Immunohistochemical analysis on ovarian cancer tissue array was further evidenced that FOXG1 was highly expressed and significantly correlated with high-grade ovarian cancer (P=0.048). Functionally, enforced expression of FOXG1 selectively blocked the TGF-β-induced p21WAF1/CIP1 expressions and increased cell proliferation in ovarian cancer cells. Conversely, FOXG1 knockdown resulted in a 20–26% decrease in cell proliferation together with 16–33% increase in p21WAF1/CIP1 expression. Notably, FOXG1 was able to inhibit the p21WAF1/CIP1 promoter activity in a p53-independent manner by transient reporter assays.ConclusionOur results suggest that FOXG1 acts as an oncoprotein inhibiting TGF-β-mediated anti-proliferative responses in ovarian cancer cells through suppressing p21WAF1/CIP1 transcription. [ABSTRACT FROM AUTHOR]

Objective To explore Chinese women’s perceptions of human papillomavirus (HPV) vaccination and their intention to be vaccinated. Design A cross-sectional community-based survey study. Setting Thirteen community women’s health centres of The Family Planning Association of Hong Kong. Sample A total of 1450 ethnic Chinese women aged 18 or above who attended the health centres. Methods Participants completed a written consent and an anonymous questionnaire onsite. Main outcome measures Knowledge and beliefs about HPV and HPV vaccination against cervical cancer and participants’ own intention to be vaccinated. Results About 38% of the participants ( n = 527) had heard of HPV and 50% ( n = 697) had heard of vaccination against cervical cancer. HPV infection was perceived to be stigmatising and detrimental to intimate, family and social relationships. Despite misconceptions and a grossly inadequate knowledge about HPV and HPV vaccination, 88% of the participants ( n = 1219) indicated that they would likely be vaccinated. Majority of the participants believed that sexually experienced women should be vaccinated, while 27% opposed vaccinating sexually naive women. Younger age women who perceived a disruptive impact of HPV infection on intimate relationship and their partners’ approval were significantly associated with a positive intention to be HPV vaccinated. Conclusions The easy acceptability of HPV vaccination among the mostly sexually experienced Chinese participants and their knowledge deficit on the subject may implicate potential misuse of the vaccines and a false sense of security against cervical cancer. There is a dire need for culturally sensitive and tailored education for the public, women of different ages and their partners about HPV and HPV vaccination. Emphasis must be placed on the prophylactic nature of the current vaccines, the uncertain effects when given to sexually experienced women, the importance of adolescent vaccination and the need for continued cervical screening whether vaccinated or not. [ABSTRACT FROM AUTHOR]

Aims: To assess the expression profile of the activated form of signal transducer and activator of transcription (Stat)3 in gestational trophoblastic disease (GTD) and correlate the findings with clinicopathological parameters. Methods and results: By immunohistochemistry, both cytoplasmic and nuclear expression of p-Stat3-Ser727 was demonstrated in 88 trophoblastic tissues, including placentas and GTD. Nuclear immunoreactivity of p-Stat3-Ser727 was significantly higher in hydatidiform mole (HM) ( P < 0.001) and choriocarcinoma ( P = 0.009) when compared with normal placentas. Placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT) also demonstrated higher nuclear p-Stat3-Ser727 expression than their normal trophoblast counterparts. Higher p-Stat3-Ser727 expression was confirmed in choriocarcinoma cell lines, JEG-3 and JAR, than in a normal trophoblast cell line, with both nuclear and cytoplasmic fractions demonstrated by immunoblotting. Spontaneously regressed HM showed significantly increased nuclear and cytoplasmic p-Stat3-Ser727 immunoreactivity over those that developed gestational trophoblastic neoplasia (GTN) ( P = 0.013, P = 0.039). There was a significant positive and inverse correlation between nuclear p-Stat3-Ser727 immunoreactivity and apoptotic indices [terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling and M30 CytoDeath antibody] ( P = 0.001, P < 0.001, Spearman’s ρ test) and Bcl-2 expression ( P = 0.034), respectively. Conclusions: p-Stat3-Ser727 plays a role in the pathogenesis of GTD, probably through the regulation of apoptosis. p-Stat3-Ser727 immunoreactivity is a potential marker in predicting GTN in HM. [ABSTRACT FROM AUTHOR]

The article examines the incidence of lymphocyst formation following bilateral pelvic lymphdenectomy, the change in size with time, risk factors and correlation with symptoms using three-dimensional ultrasound. According to the authors, there was no association between lymphocyst formation and diagnosis, type of operation performed, operative blood loss, adjuvant radiotherapy and number of lymph nodes removed.

Objectives: To explore perceptions towards cervical cancer, human papillomavirus (HPV) infection and HPV vaccination and to identify factors affecting the acceptability of HPV vaccination among Chinese adolescent girls in Hong Kong. Methods: Six focus groups were conducted with Chinese adolescent girls (median age 16 years, age range 13-20, n = 64) in Hong Kong in April 2007. Thematic analysis was employed to identify major themes related to cervical cancer and HPV vaccination. A supplementary questionnaire was administered to all participants before and after group discussion to assess their knowledge, attitudes and intention to be vaccinated and to collect demographic information. Results: Participants' knowledge on cervical cancer was limited and HPV was largely unheard of. They had difficulty understanding the mechanism linking cervical cancer with HPV infection. Participants held a favourable attitude towards HPV vaccination but the perceived timing of vaccination varied. Barriers to vaccination include high monetary cost, uncertain length of vaccine effectiveness, low perceived risk of HPV infection, no immediate perceived need of vaccination, anticipated family disapproval and fear of the pain of injection. Factors conducive to vaccination include perceived family and peer support and medical reassurance on safety and efficacy of vaccine. The differences on knowledge, attitudes, intention to be vaccinated now and willingness to conform to significant others before and after the discussion were statistically significant, with an increased tendency towards favouring vaccination after the focus group. Conclusions: Participants favoured HPV vaccination despite not feeling an immediate need to be vaccinated. Interventions could focus on providing professional information on HPV vaccination and raising adolescents' perceived need to take preventive measures against HPV infection. [ABSTRACT FROM AUTHOR]

Aims: To investigate p63 expression in ovarian neoplasms. Methods and results: Immunohistochemistry using an antibody that detects all p63 isoforms was performed on 103 primary ovarian neoplasms of different histological types. Diffuse nuclear immunoreactivity of p63 was demonstrated in the 17 benign and five borderline Brenner tumours. Only one of the six malignant Brenner tumours displayed p63 expression. p63 immunoreactivity was absent in all the ovarian transitional cell carcinomas (TCC), but was demonstrated extensively in TCCs of the urinary bladder. Besides focal p63 expression in epidermal basal cells of immature and mature teratomas, all other ovarian lesions were devoid of p63 expression. p63 expression was also demonstrated in cervical transitional cell metaplasia and Walthard cell nests of fallopian tubes. Conclusions: Expression of p63 protein is apparently cell lineage specific and in ovarian neoplasms is confined to benign and borderline Brenner tumours. The loss of expression in malignant Benner tumours suggests a role for p63 in Brenner carcinogenesis. The distinct patterns of p63 expression in TCCs in the ovary and urinary bladder may help in their differential diagnosis. [ABSTRACT FROM AUTHOR]

Objective To investigate whether the use of an antibacterial vaginal pessary containing tetracycline and amphotericin B would reduce complications from large loop excision of the transformation zone (LLETZ). Design Prospective randomised controlled trial. Setting Department of Obstetrics and Gynaecology, University of Hong Kong. Population A total of 321 women who underwent LLETZ. Methods Women were randomised to either receiving an antimicrobial vaginal pessary twice a day for 14 days after LLETZ or no medication. Before LLETZ, endocervical and high vaginal swabs were taken for the detection of Chlamydia and other pathogens. All women were given a diary to record the degree of symptoms, such as vaginal discharge, bleeding and pain for 3 weeks. These were then compared between the two groups. Main outcome measures Bleeding, vaginal discharge and pain after LLETZ. Results There was no significant difference in the total bleeding, vaginal discharge and pain scores between the two groups. However, for women who had positive endocervical or high vaginal swabs, the treatment group had significantly less bleeding in the second week ( Z=−2.083, P= 0.037) and less overall vaginal discharge ( Z=−2.024, P= 0.043). Conclusions An antimicrobial vaginal pessary containing tetracycline and amphotericin B did not provide any significant benefit after LLETZ, except for a subgroup of women with positive vaginal or endocervical swabs. Given that this group of women cannot be identified before the procedure since swabs are not routinely taken, the use of routine prophylactic topical antibiotics cannot be recommended for the general population. [ABSTRACT FROM AUTHOR]

Promoter hypermethylation is a common phenomenon in neoplasm. The aims of this study were (a) to compare the methylation profiles in different types of ovarian tumors and (b) to determine the possible relationship between the methylation status and different clinicopathologic characteristics. We examined the promoter methylation status of 9 tumor suppressor genes (RARβ2, TMS1, RIZ1, P15, P16, PTEN, MINT31, APC and HIC1) in 89 ovarian cancers, 16 borderline ovarian tumors, 19 benign ovarian tumors, 16 normal ovarian tissue and 5 ovarian cancer cell lines. The methylation status was examined with respect to clinicopathologic characteristics of the ovarian cancer patients. Methylation indices for ovarian cancer, borderline ovarian tumor, benign ovarian tumor, normal ovarian tissue and ovarian cancer cell lines were 28.8, 20.1, 10.5, 11.8 and 42.2%, respectively. It was significantly higher in ovarian cancer, borderline ovarian tumor and ovarian cancer cell lines ( X 2 test, P < 0.001, P = 0.01 and P < 0.001, respectively) than benign or normal ovarian tissues. In ovarian cancer, concurrent methylation of at least two genes (CM2) was associated with early stage disease ( X 2 test, P = 0.035) and less recurrence ( X 2 test, P = 0.020). When the methylation statuses of the nine genes as well as CM2 were included in multivariate Cox Regression analysis, CM2 was the only independent predictor for survival ( P = 0.013). CM2 was an independent predictor for survival in ovarian cancer. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) content in ovarian carcinomas was assessed by quantitative PCR. Results show that mtDNA content in tumour cell was significantly higher than that in normal ovary. Change in mtDNA content was not related with patients' age or tumour stages. However, the average mtDNA copy number in pathological low-grade tumours was over two-fold higher than that in high-grade carcinomas (P=0.012). Moreover, type I carcinomas also had a significantly higher mtDNA copy number than in type II carcinomas (P=0.019). Change in mtDNA content might be an important genetic event in the progression of ovarian carcinomas.British Journal of Cancer (2006) 95, 1087–1091. doi:10.1038/sj.bjc.6603377 www.bjcancer.com Published online 3 October 2006 [ABSTRACT FROM AUTHOR]

Background: All-trans retinoic acid (ATRA) is a natural vitamin A derivative that has a profound effect on the regulation of cell growth, differentiation and death. Aim: To investigate the tissue dynamic and cellular invasion effects of ATRA in choriocarcinoma (CCA}, an aggressive trophoblastic tumour, by using a three-dimensional organotypic culture model system and cell invasion assay, respectively. Methods: An organotypic culture model of two CCA cell lines, JAR and JEG, was established. The effects of 1 μM ATRA on proliferation, differentiation and apoptosis on this CCA model were assessed by morphological assessment of the mitotic and apoptotic figures as well as by Ki-67 and caspase-related M30 cytoDeath antibody immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay. The effect of ATRA on p53 and its regulated protein product, WAF1/Cip1, was also evaluated with D07 and p21WAFI antibodies, respectively. Moreover, the effect of ATRA on cellular (CCA) invasion was also investigated with Cell Invasion Kit on the JEG cell line. Results: ATRA was found to induce marked apoptosis in organotypic cultures of both cell lines, as evidenced by increased M30-positive cells (p<0.0001) and increased TUNEL-positive cells (p<0.0001) in treated cultures; to decrease proliferation, as evidenced by decreased Ki-67-positive cells (p<0.0001); and to decrease p53-DO7 immunoreactivity (p<0.0001) and increase p21WAF1 (<00001} immunoreactivity. 1.5 μM ATRA was found to effectively inhibit JEG cell invasion in the cell invasion assay. Conclusion: ATRA treatment was found to inhibit invasion and proliferation and enhance apoptosis, probably by the activation of caspases and induction of differentiation. ATRA and synthetic retinoids may be alternative agents for the treatment of CCA. [ABSTRACT FROM AUTHOR]

Aims: To assess the expression of Id proteins in trophoblastic tissues and to correlate this with clinical parameters, proliferative and apoptotic indices as well as to related oncogene expression. Methods and results: Immunohistochemistry for Id1, Id2, Id3 and Id4 was performed on 83 trophoblastic tissues including 17 normal first-trimester placentas, seven term placentas, 47 hydatidiform moles (HM), and 12 spontaneous miscarriages. The four Id proteins were predominantly expressed in the villous and implantation site intermediate trophoblast. Expression of Id1 in HM was significantly higher than that in normal placenta (P = 0.0006) and spontaneous miscarriage (P = 0.0001) but did not correlate with subsequent development of gestational trophoblastic neoplasia (GTN). Id1 expression correlated with the proliferation index as assessed by MCM7 (P = 0.003) and Ki67 (P = 0.017) and with the apoptotic activity assessed by TUNEL (P = 0.001) and M30 CytoDeath antibody (P = 0.013). Moreover, the expression of Idi correlated with the expression of p53 (P = 0.004), p21WAF1/CIP1 (P = 0.003) but not with p16 (P = 0.107). Conclusions: Id proteins may play a role in the regulation of proliferative and apoptotic activity in trophoblastic tissue and are potentially useful in differentiating molar and non-molar gestation, but are not helpful in predicting GTN. [ABSTRACT FROM AUTHOR]

Li S S, Xue W C, Khoo U S, Ngan H Y S, Chan K Y K, Tam I Y S, Chiu P M, Ip P P C, Tam K F&Cheung A N Y(2005)Histopathology46,307–313Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a tissue microarray and clinicopathological analysis: To assess, in tissue microarray (TMA), the proliferative activity of endometrial carcinoma using one of the minichromosome maintenance (MCM) proteins (MCM7), and to explore its potential value for prognosis. MCM proteins are essential for eukaryotic DNA replication and have recently been used to define the proliferative compartments in human tissues.: Immunohistochemistry for MCM7 and Ki67 was performed on TMAs constructed from 212 cases of endometrial carcinoma. MCM7 and Ki67 expression was quantified according to the extent of nuclear staining. An analysis was carried out of the association between MCM7 expression and that of Ki67 and the clinicopathological characteristics of endometrial carcinoma. MCM7 and Ki67 immunoreactivity was clearly evident in the nuclei of tumour cells. MCM7 and Ki67 labelling indices in endometrial carcinomas correlated with each other (P < 0.001). A significant correlation existed between the MCM7 labelling index and histological grade (P = 0.008) and patients' age at diagnosis (P < 0.001). Well-differentiated carcinomas and younger patients had a lower MCM7 index. Poor survival was observed in patients with endometrial carcinoma with a high MCM7 index (P = 0.03) and MCM7 was found to be an independent prognostic factor by multivariate analysis (P = 0.04). The Ki67 labelling index correlated with histological grade (P = 0.01) but had no significant prognostic impact (P = 0.50).: In this TMA study on endometrial carcinoma, MCM7 was found to be a more reliable and useful marker than Ki67 in assessing tumour proliferation and in the prognosis of patients. [ABSTRACT FROM AUTHOR]

Aims: To assess the potential value of chromosome in situ hybridisation (CISH), Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology to help detect carcinoma cells and precursors. Method: Sixty ThinPrep processed cervical cytology samples were studied: 23 cases within the normal limit, 1 3 low grade squamous intraepithelial lesions (LSILs), 10 high grade squamous intraepithelial lesions (HSILs), six squamous cell carcinomas, three endocervical adenocarcinomas, two cervical adenosquamous cell carcinomas, and three endometrial adenocorcinomas. CISH was performed with DNA probes specific for the pericentromeric re9ions of chromosome 11 and 16. Hybridisation signals were visualised with the streptavidin-biotin peroxidase technique. The monoclonal MIB1 and polyclonal TRT-H231 antibodies were used to detect Ki-67 and telomerase immunoreactivity, respectively. Results: Non-specific background staining was almost absent in CISH slides. Normal squamous and glandular cells showed a diploid chromosomal pattern. A relative gain in chromosomes 11 and 16 (aneusomy) was seen in HSIL and the carcinomas (p<0.0001). In MIB1 stained smears, normal cells and koilocytes showed inconspicuous immunoreactivity, whereas strongly immunoreactive nuclei were found in cancer cells and HSIL (p<0.0001). Not only carcinoma and HSIL cells, but also some normal cells, showed cytoplasmic staining for telomerase. Conclusions: These preliminary results indicate that ThinPrep processed cervical smears are suitable for CISH and immunocytochemical studies. The neoplastic squamous and glandular cells were easily identified based on nuclear aneusomy and strong Ki-67 immuoreactivity in the context of abnormal nuclear morphology. This is the first study to apply CISH in cervical cytology using an immunoenzymatic approach. [ABSTRACT FROM AUTHOR]

To investigate the occurrence of somatic mitochondrial DNA (mtDNA) mutations in human primary endometrial carcinomas, we sequenced the D-loop region, the 12S and 16S rRNA genes of mtDNA of cancer tissues and their matched normal controls. About 56% (28 out of 50) of cases carry one or more somatic changes in mtDNA including deletion, point mutation and mitochondrial microsatellite instability (mtMSI), namely the change in length of short base-repetitive sequences of mtDNA. In particular, mtMSI was frequently detected in 89% (25 out of 28) of all the cases carrying somatic changes followed by point mutations (25%; seven out of 28) and deletion (3.5%; one out of 28). The CCCCCTCCCC sequences located in the Hypervariable Regions I and II of the D-loop and 12S rRNA gene are instability hot spot regions in endometrial carcinomas. It is suggested that errors in replication may account for the high frequency of mtMSI in human endometrial carcinomas. The relatively high prevalence of mtMSI may be a potential new tool for detection of endometrial cancer. [ABSTRACT FROM AUTHOR]

Objective. Theaim of this study was to determine the prevalence of high-risk oncogenic human papillomaviruses (HPVs) in malignant lesions from Hong Kong Chinese women with carcinomas of the upper genital tract.Methods. The presence of high-risk HPVs in 55 cases of endometrial adenocarcinomas and 60 cases of primary epithelial ovarian cancers was detected by polymerase chain reaction (PCR) using consensus primers complementary to late 1 (L1) gene of the genital HPVs. Amplified PCR products were verified and typed by Southern blot analysis using 32P-labeled DNA probes prepared from cloned HPV-16 and -18 plasmids. To confirm the presence of high-risk HPV types in the tumor tissues, PCR amplification using HPV type 16- and 18-specific primers for part of the E6 gene were also carried out.Results. While HPV-18 was not detected, HPV-16 DNA sequences were identified in 5 (9.1%) of the 55 studied endometrial carcinoma samples. Of the 5 HPV-16-positive cases, there were 4 stage I, and 1 stage II endometrial cancer. In addition, 6 (10%) of the 60 epithelial ovarian carcinomas were positive for high-risk HPVs, which included 5 cases with HPV-16 and 1 case with HPV-18. Clinical staging revealed that 5 of the 6 HPV-positive cases were stage I and the remaining case was stage III ovarian cancer. Histology of the 6 HPV-positive cases showed that there were 1 case of clear-cell adenocarcinoma, 1 case of mucinous cystadenocarcinoma, and 4 cases of mucinous tumor of borderline malignancy. No other HPV types were detected.Conclusion. High-risk HPV was detected in ∼10% of the tumor samples from women with upper genital tract carcinomas. As compared to the high positive rate of HPV infections in cervical cancer, it appears that HPV infection plays a relatively minor role in the pathogenesis of endometrial and ovarian carcinomas. [Copyright &y& Elsevier]

This study investigated the enhanced antitumor activity of Ad5-p53 in combination with mitomycin C (MMC) or cisplatin (DDP) in cervical cancer cell lines SiHa and C-33A. MMC and DDP inhibited the growth of SiHa and C-33A cells in a dose-dependent manner, and the combination of MMC or DDP with Ad5-p53 showed a stronger growth inhibition than those treated with either Ad5-p53, MMC, or DDP alone. As evidenced by the formation of the approximately 200 bp DNA ladder and the appearance of sub-G1 peak, both MMC and DDP induced apoptosis in cervical cancer cells. Western blot analysis of p53 showed that MMC/DDP did not induce the increase of p53 protein in SiHa cells nor the increase of the cellular and nuclear p53 protein in Ad5-p53 transfected Saos-2 cells. Taken together, these results suggested that the combination of Ad5-p53 and MMC/DDP may serve as an effective therapeutic regime for human cervical cancer treatment. [ABSTRACT FROM AUTHOR]

Characterizing a microlensing planet is done by modeling an observed lensing light curve. In this process, it is often confronted that solutions of different lensing parameters result in similar light curves, causing difficulties in uniquely interpreting the lens system, and thus understanding the causes of different types of degeneracy is important. In this work, we show that incomplete coverage of a planetary perturbation can result in degenerate solutions even for events where the planetary signal is detected with a high level of statistical significance. We demonstrate the degeneracy for an actually observed event OGLE-2012-BLG-0455/MOA-2012-BLG-206. The peak of this high-magnification event (Amax ∼ 400) exhibits very strong deviation from a point-lens model with Δχ2 ≳ 4000 for data sets with a total of 6963 measurements. From detailed modeling of the light curve, we find that the deviation can be explained by four distinct solutions, i.e., two very different sets of solutions, each with a twofold degeneracy. While the twofold (so-called close/wide) degeneracy is well understood, the degeneracy between the radically different solutions is not previously known. The model light curves of this degeneracy differ substantially in the parts that were not covered by observation, indicating that the degeneracy is caused by the incomplete coverage of the perturbation. It is expected that the frequency of the degeneracy introduced in this work will be greatly reduced with the improvement of the current lensing survey and follow-up experiments and the advent of new surveys. [ABSTRACT FROM AUTHOR]