A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.

BACKGROUND: The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. METHODS: We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. RESULTS: The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group. CONCLUSIONS: The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).

Genetic susceptibility to cervical squamous cell carcinoma is associated with HLA-DPB1 polymorphisms in Taiwanese women.

Cervical cancer is a multifactorial disease, and increasing evidence suggests that host immunogenetic background may contribute to its pathogenesis. Genetic variations in human leukocyte antigen (HLA) genes may alter the efficiency of immune response to human papillomavirus (HPV) antigens and have been implicated in the risk of cervical cancer. We investigated whether polymorphisms in the HLA-DPB1 gene were associated with cervical cancer risk in a Taiwanese population. HLA-DPB1 alleles and +550 G/A polymorphism were genotyped in a case-control study of 473 women with cervical squamous cell carcinoma (CSCC) and 676 healthy controls. The presence and genotypes of HPV in CSCC were determined. We found that the DPB1*05:01 and +550 A alleles were associated with decreased and increased risk of CSCC, respectively [odds ratio (OR) = 0.72, Pc = 0.001; OR = 1.25, Pc = 0.03]. In subgroup analysis based on HPV type 16 positivity, significant associations were shown in the DPB1*05:01 and *13:01 alleles (OR = 0.65, Pc = 0.0007; OR = 1.83, Pc = 0.004). Furthermore, the DPB1*05:01-G and *13:01-G haplotypes conferred decreased and increased risk of both CSCC and HPV-16 positive CSCC women, respectively (OR = 0.72, Pc = 0.0009; OR = 0.63, Pc = 0.0004 for DPB1*05:01-G; OR = 1.55, Pc = 0.03; OR = 1.84, Pc = 0.004 for DPB1*13:01-G). A risk haplotype DPB1*02:01-A was also observed in the HPV-16 positive CSCC women (OR = 1.51, Pc = 0.05). These findings suggest that HLA-DPB1 gene is involved in the CSCC development.

Immune mechanism of the antitumor effects generated by bortezomib.

Bortezomib, a proteasome inhibitor, is a chemotherapeutic drug that is commonly used to treat a variety of human cancers. The antitumor effects of bortezomib-induced tumor cell immunogenicity have not been fully delineated. In this study, we examined the generation of immune-mediated antitumor effects in response to treatment by bortezomib in a murine ovarian tumor model. We observed that tumor-bearing mice that were treated with bortezomib had CD8+ T cell-mediated inhibition of tumor growth. Furthermore, the comparison of tumor cell-based vaccines that were produced from tumor cells treated or untreated with bortezomib showed vaccination with drug-treated tumor cell-based vaccines elicited potent tumor-specific CD8+ T cell immune response with improved therapeutic antitumor effect in tumor-bearing mice. Conversely, the untreated tumor cell-based vaccines led to no appreciable antitumor response. Treatment of tumor cells with bortezomib led to the upregulation of Hsp60 and Hsp90 on the cell surface and promoted their phagocytosis by dendritic cells (DCs). However, cell surface expression of Hsp60, instead of Hsp90, is the more important determinant of whether bortezomib-treated tumor cells can generate tumor-specific CD8+ T cells. CD11c+ DCs that were treated with bortezomib in vitro had enhanced phagocytic activities. In addition, CD11c+ DCs from bortezomib-treated tumor-bearing mice had increased maturation. At lower concentrations, bortezomib had no inhibitory effects on T cell proliferation. Taken together, our data indicate that bortezomib can render tumor cells immunogenic by upregulating the cell surface expression of heat shock protein 60 and heat shock protein 90, as well as improve DC function, which results in potent immune-mediated antitumor effects.

Aggressive angiomyxoma: a small palpable vulvar lesion with a huge mass in the pelvis.

Aggressive angiomyxoma (AAM) is a rare soft tissue tumor typically in the pelvis and perineum in women of reproductive age, which is easily misdiagnosed. We describe a woman with vulvar AAM, initially mismanaged as a Bartholin cyst. However, a huge pelvic mass is noted on the following imaging studies. The characteristics of AAM on computed tomography and magnetic resonance imaging have been specified in the literature, but we further point out the potential value of sonography in diagnosing AAM. Besides, excisional biopsy may cause tumor bleeding in a case of AAM.

Genetic polymorphisms in the ITPKC gene and cervical squamous cell carcinoma risk.

Cervical cancer is caused primarily by infection with oncogenic types of human papillomavirus (HPV). However, HPV infection alone is not sufficient for the progression to cervical cancer. Host immunogenetic factors may involve in the development of this disease. Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is recently shown to act as a negative regulator of T-cell activation. We aim to study if polymorphisms in the ITPKC gene are associated with the risk of cervical cancer in Taiwanese women. ITPKC rs28493229 C/G, rs890934 G/T, rs2303723 C/T, and rs10420685 A/G polymorphisms were genotyped in a hospital-based study of 465 women with cervical squamous cell carcinoma (CSCC) and 800 age-matched healthy control women. The presence and genotypes of HPV in CSCC were determined. The frequency of G/G genotype and G allele of the ITPKC rs28493229 polymorphism was significantly higher in patients with CSCC compared with controls (OR = 1.81, 95 % CI 1.20-2.73, P = 0.005, P (c) = 0.02; OR = 1.70, 95 % CI 1.14-2.54, P = 0.008, P (c) = 0.03, respectively). No significant associations were found for other 3 polymorphisms. Haplotype analysis revealed the distribution of haplotype CGTA was significantly reduced in women with CSCC (OR = 0.59, 95 % CI 0.40-0.89, P = 0.01, P (c) = 0.04). In conclusion, we found the G/G genotype and G allele of the ITPKC rs28493229 polymorphism may contribute to the risk of CSCC in Taiwanese women. This finding provides new insights into the mechanisms of immune activation in cervical cancer.

Demoralization syndrome among cancer outpatients in Taiwan.

GOALS: This paper aims to explore characteristics of demoralization syndrome as well as the relationship between demoralization syndrome and psychosocial issues as seen through examinations of cancer outpatients in Taiwan. MATERIALS AND METHODS: Outpatients with different cancer types were enrolled in this study. The Demoralization Scale Mandarin Version (DS-MV), Patient Health Questionnaire, Beck Hopelessness Scale, and McGill Quality of Life Questionnaire-Taiwan Version were used as instruments. All data were analyzed using SPSS 18.0. RESULTS: Among the 234 patients studied (97 men and 223 women), the majority had cervical cancer (29.1%), followed by breast cancer (26.5%) and head and neck cancer (24.3%). The mean score of DS-MV was 31.05 (SD 14.87). The results of ANOVA analysis showed a significant effect of occupation F(4.209) = 7.145 (p < 0.001), cancer diagnosis F(7.206) = 3.795 (p < 0.001), and treatment F(8.206) = 3.553 (p < 0.001) on DS-MV. CONCLUSIONS: Demoralization syndrome was found to be related to psychosocial issues, different cancer types, and treatments. Further studies are recommended to better understand causes and impacts of demoralization in the quality of life and care of cancer patients.

Detecting small lung tumors in mouse models by refractive-index microradiology.

Refractive-index (phase-contrast) radiology was able to detect lung tumors less than 1 mm in live mice. Significant micromorphology differences were observed in the microradiographs between normal, inflamed, and lung cancer tissues. This was made possible by the high phase contrast and by the fast image taking that reduces the motion blur. The detection of cancer and inflammation areas by phase contrast microradiology and microtomography was validated by bioluminescence and histopathological analysis. The smallest tumor detected is less than 1 mm(3) with accuracy better than 1 × 10(-3) mm(3). This level of performance is currently suitable for animal studies, while further developments are required for clinical application.

Ovarian borderline mucinous tumor with stromal microinvasion and hemangiomatous mural nodules.

A 39-year-old female presented with abdominal distension. A right adnexal mass was found on physical examination, which was shown to be cystic on ultrasound. An exploratory laparotomy revealed a right ovarian mass, which was removed and a staging procedure was performed. Histologically, the mass was a borderline ovarian tumor with stromal microinvasion and hemangiomatous mural nodules.

Comparison in purity and antitumor effect of brand and generic paclitaxel against human ovarian cancer cells by an in vitro experimental model.

CONTEXT: The purity and the therapeutic effectiveness of the generic paclitaxel have not yet been examined and compared to the original brand form. OBJECTIVE: This study aimed to compare the in vitro purity and biological effects of original brand form (Taxol) and a generic drug of paclitaxel. MATERIALS AND METHODS: Purity was determined by high-performance liquid chromatography analysis, cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay, cell proliferation by clonogenic assay, morphology by Liu's staining, and cell cycle distribution by DNA histogram. RESULTS: Taxol and generic paclitaxel shared similar high-performance liquid chromatography profiles with a major peak at the same retention time and ultraviolet spectrum. Generic paclitaxel inhibited the cell viability to an extent greater than Taxol. By assessing the IC(50), generic paclitaxel also exhibited a greater inhibitory activity on clonogenicity of human ovarian adenocarcinoma SKOV-3 cells. Although both generic paclitaxel and Taxol arrested SKOV-3 and ES-2 cells at G2/M phase with concurrent development of hypoploid and polyploid cells, Taxol treatment exhibited markedly less extent of these changes. Observation of cellular morphology revealed a greater amount of mitotic catastrophe-like and apoptotic cells in generic paclitaxel-treated cells than Taxol-treated cells. DISCUSSION AND CONCLUSION: The results suggest that generic paclitaxel may possess a greater cell death inducing capacity and clonogenicity inhibitory activity against ovarian cancer cells than the original brand Taxol of the same purity. We conclude that this experimental model for assessing the difference between generic and brand name drugs might be considered as a reference while determining their interchangeability and could be easily established in a hospital-based laboratory.

Muscle loss during primary debulking surgery and chemotherapy predicts poor survival in advanced-stage ovarian cancer.

BACKGROUND: Sarcopenia is commonly observed in patients with advanced-stage epithelial ovarian cancer (EOC). However, the effect of body composition changes-during primary debulking surgery (PDS) and adjuvant platinum-based chemotherapy-on outcomes of patients with advanced-stage EOC is unknown. This study aimed to evaluate the association between body composition changes and outcomes of patients with stage III EOC treated with PDS and adjuvant platinum-based chemotherapy. METHODS: Pre-treatment and post-treatment computed tomography (CT) images of 139 patients with stage III EOC were analysed. All CT images were contrast-enhanced scans and were acquired according to a standardized protocol. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and total adipose tissue index were measured using CT images obtained at the L3 vertebral level. Predictors of overall survival were identified using Cox regression models. RESULTS: The median follow-up was 37.9 months. The median duration between pre-treatment and post-treatment CT was 182 days (interquartile range: 161-225 days). Patients experienced an average SMI loss of 1.8%/180 days (95% confidence interval: -3.1 to -0.4; P = 0.01) and SMD loss of 1.7%/180 days (95% confidence interval: -3.3 to -0.03; P = 0.046). SMI and SMD changes were weakly correlated with body mass index changes (Spearman ρ for SMI, 0.15, P = 0.07; ρ for SMD, 0.02, P = 0.82). The modified Glasgow prognostic score was associated with SMI loss (odds ratio: 2.42, 95% confidence interval: 1.03-5.69; P = 0.04). The median time to disease recurrence was significantly shorter in patients with SMI loss ≥5% after treatment than in those with SMI loss <5% or gain (5.4 vs. 11.2 months, P = 0.01). Pre-treatment SMI (1 cm2 /m2 decrease; hazard ratio: 1.08, 95% confidence interval: 1.03-1.11; P = 0.002) and SMI change (1%/180 days decrease; hazard ratio: 1.04, 95% confidence interval: 1.01-1.08; P = 0.002) were independently associated with poorer overall survival. SMD, body mass index, and total adipose tissue index at baseline and changes were not associated with overall survival. CONCLUSIONS: Skeletal muscle index decreased significantly during treatment and was independently associated with poor overall survival in patients with stage III EOC treated with PDS and adjuvant platinum-based chemotherapy. The modified Glasgow prognostic score might be a predictor of SMI loss during treatment.

Effect of Chemotherapy, Laparoscopy, and Cytology on Stage IC Ovarian Clear Cell Carcinoma: A Long-Term, Single-Center Study.

Ovarian clear cell carcinoma (OCCC) is the second common histology of epithelial ovarian cancer in Taiwan. Stage IC is common, especially during minimally invasive surgery. Adjuvant chemotherapy in stage IC OCCC is unavoidable, and paclitaxel-based chemotherapy in Taiwan is self-paid. However, surgical spillage from minimally invasive surgery as a cause of unfavorable prognosis is still uncertain. The information of patients with stage IC OCCC, corresponding to a period of January 1995 to December 2016, was retrospectively collected following a chart and pathology review. Data regarding surgical methods, cytology status, regimens of adjuvant chemotherapy, survivorship, progression-free survival (PFS), and overall survival (OS) period were analyzed. In total, 88 patients were analyzed, and 64 and 24 patients were treated with paclitaxel- and nonpaclitaxel-based chemotherapy, respectively. Recurrence was identical between the two groups: PFS (47.5 ± 41.36 versus 54.0 ± 53.9 months, p = 0.157) and OS (53.5 ± 38.14 versus 79.0 ± 49.42 months, p = 0.070). Of the 88 patients, 12 had undergone laparoscopy for histological confirmation before complete open staging surgery; however, their PFS (49.5 ± 46.84 versus 49.0 ± 35.55 months, p = 0.719) and OS (56.5 ± 43.4 versus 51.0 ± 32.77 months, p = 0.600) were still comparable. Cytology results were only available for 51 patients, and positive washing cytology results seemed to worsen PFS (p = 0.026) but not OS (p = 0.446). In conclusion, adjuvant nonpaclitaxel chemotherapy and laparoscopic tumor spillage before the staging operation did not worsen the outcome in stage IC OCCC. Positive washing cytology has a negative effect on PFS but not on OS.

Outcomes in Advanced Stage Epithelial Ovarian, Fallopian Tubal, and Peritoneal Cancer after Primary Surgery and Adjuvant Chemotherapies: A Single-Institute Real-World Experience.

Debulking surgery followed by systemic chemotherapy-including three-weekly intravenous paclitaxel and carboplatin (GOG-158)-is the cornerstone for advanced epithelial ovarian, fallopian tubal, and peritoneal cancer (EOC) treatment. In this scenario, Federation of Gynecology and Obstetrics (FIGO) stage, cell types, completeness of surgery, lymph nodes (LN) status, adjuvant chemotherapy regimens, survival status, progression-free survival (PFS), and overall survival (OS) of 192 patients diagnosed as having stage IIIA1-IVB EOC over January 2008-December 2017 were analyzed retrospectively. Of them, 100 (52.1%) patients had been debulked optimally. Of all cases, 64.1% and 10.9% demonstrated serous and clear-cell carcinoma. Moreover, the FIGO stage, surgery completeness, and LN status affected recurrence/persistence and mortality (all p < 0.001). Clear cell carcinoma led to shorter survival than serous carcinoma (p = 0.002). Adjuvant chemotherapy regimens were divided into five main groups according to previous clinical trials. However, choice of chemotherapy failed to demonstrate significant differences in patient outcomes. Similar results were found in the sub-analysis of optimally debulked cases, except that intraperitoneal chemotherapy could reduce mortality risk when compared with GOG-158 (p = 0.042). Notably, retroperitoneal LN dissection in all cases or optimally debulked cases reduced risks of recurrence/persistence and mortality, and prolonged PFS and OS significantly (all p < 0.05). Without optimal debulking, LN dissection led to little improvement in outcomes. Various modified chemotherapy regimens did not prolong PFS and OS or reduce recurrence/persistence and mortality risks. LN dissection is strongly recommended to improve the completeness of surgery and patient outcome. Clear cell type has a poorer outcome than serous type, which requires more aggressive treatment and follow-up.

Cytosolic phospholipase A2-{alpha} is an early apoptotic activator in PEDF-induced endothelial cell apoptosis.

Pigment epithelium-derived factor (PEDF) is an intrinsic antiangiogenic factor and a potential therapeutic agent. Previously, we discovered the mechanism of PEDF-induced apoptosis of human umbilical vein endothelial cells (HUVECs) as sequential induction/activation of p38 mitogen-activated protein kinase (MAPK), peroxisome proliferator-activated receptor gamma (PPAR-gamma), and p53. In the present study, we investigated the signaling role of cytosolic calcium-dependent phospholipase A(2)-alpha (cPLA(2)-alpha) to bridge p38 MAPK and PPAR-gamma activation. PEDF induced cPLA(2)-alpha activation in HUVECs and in endothelial cells in chemical burn-induced vessels on mouse cornea. The cPLA(2)-alpha activation is evident from the phosphorylation and nuclear translocation of cPLA(2)-alpha as well as arachidonic acid release and the cleavage of PED6, a synthetic PLA(2) substrate. Such activation can be abolished by p38 MAPK inhibitor. The PEDF-induced PPAR-gamma activation, p53 expression, caspase-3 activity, and apoptosis can be abolished by both cPLA(2) inhibitor and small interfering RNA targeting cPLA(2)-alpha. Our observation not only establishes the signaling role of cPLA(2)-alpha but also for the first time demonstrates the sequential activation of p38 MAPK, cPLA(2)-alpha, PPAR-gamma, and p53 as the mechanism of PEDF-induced endothelial cell apoptosis.

Involvement of p29 in DNA damage responses and Fanconi anemia pathway.

Human p29 is a chromatin-associated protein and the silencing of p29 expression increases cell population in G(1) phase and decreases phosphorylation levels of Chk1 and Chk2 in response to UV treatment. To further characterize the function of p29, U2OS and Fanconi anemia complementation group G (FA-G) cells with constitutive p29 expression have been established. Analyses of these cells identified increased phosphorylation levels of Chk1 and Chk2, which were accompanied by elevated amounts of chromatin-associated Mre11-Rad50-Nbs1 complex and ATR-IP. Monoubiquitination of the FA ID complex was restored in p29 stably expressing FA-G cells. Moreover, lower tumor incidence was observed in mp29 transgenic mice after UV irradiation. These results suggest the involvement of p29 in the DNA damage responses and Fanconi anemia pathway.

Trafficking of multipotent mesenchymal stromal cells from maternal circulation through the placenta involves vascular endothelial growth factor receptor-1 and integrins.

Maternal cells can become engrafted in various fetal organs during pregnancy. The nature of the cells and the mechanisms of maternofetal cell trafficking are not clear. We demonstrate that human lineage-negative, CD34-negative (Lin(-)CD34(-)) multipotent mesenchymal stromal cells express alpha(2), alpha(4), alpha(5), and beta(1) integrins, which mediate their adhesion to endothelium, and vascular endothelial growth factor receptor-1 (VEGFR-1), which mediates their response to vascular endothelial growth factor A (VEGF-A). A maternal-fetal VEGF-A concentration gradient exists across the placental barrier, and cord blood plasma induces transendothelial and trans-Matrigel migration of stem cells in vitro. Migration is inhibited by a VEGF-A-neutralizing antibody or antibodies against VEGFR-1 or integrin alpha(2), alpha(4), alpha(5), or beta(1). When Lin(-)CD34(-) multipotent mesenchymal stromal cells are transferred to rat maternal venous blood, they traffic through the placenta, engraft in various fetal organs, and persist in offspring for at least 12 weeks. Cell proliferation ability is retained in the xenogeneic placenta. Maternofetal trafficking is significantly reduced by blocking antibodies against integrins alpha(2), alpha(4), alpha(5), and beta(1) or VEGFR-1. These results suggest that maternal microchimerism arises by the trafficking of multipotent mesenchymal stromal cells via VEGF-A- and integrin-dependent pathways across the hemochorial placenta to fetal tissues.

Oxaliplatin regulates DNA repair responding to ionizing radiation and enhances radiosensitivity of human cervical cancer cells.

Concurrent chemoradiotherapy is a standard treatment of locally advanced cervical carcinoma. The most widely used drug for chemoirradiation is cisplatin. However, its toxicity and drug resistance remain major concerns in clinical practice. This study was designed to evaluate the effect of oxaliplatin, another platinum compound, on enhancing radiosensitivity in cervical cancer cell lines. Human HeLa and SiHa cells were used. Cell survival after irradiation with or without oxaliplatin pretreatment was assessed by performing colony-formation assays. Sensitizer enhancement ratios were calculated using a linear quadratic model. Cell morphology was observed after staining with Wright dye. To evaluate the machinery to repair DNA damage, cellular protein was subjected to Western blotting to assess the expression of damage-related molecules. Nontoxic doses of oxaliplatin were 5 and 10 micromol/L for HeLa and SiHa cells, respectively. Pretreatment with oxaliplatin markedly decreased, with a greater extent than cisplatin, the survival of irradiated HeLa cells. Maximal sensitizer enhancement ratios of oxaliplatin at 37% survival were 3.4 for HeLa cells and 4.8 for SiHa cells. Oxaliplatin pretreatment enhanced the cell cycle arrest in the G2/M phase and the radiation-induced mitotic catastrophe. Oxaliplatin modulated radiation-induced DNA double-strand breaks, as indicated by delayed abrogation of gamma-H2AX, attenuation of radiation-induced phosphorylation of ataxia telangiectasia-mutated kinase and checkpoint kinase 2. In conclusion, oxaliplatin sensitized human HeLa and SiHa cells to ionizing radiation. This effect may involve modulation of ataxia telangiectasia-mutated kinase and checkpoint kinase 2 activation during DNA damage repair.

Treatment of gestational trophoblastic neoplasia according to the FIGO 2000 staging and scoring system: a 20 years' experience.

OBJECTIVE: To reassess the efficacy of the Federation of Gynecology and Obstetrics (FIGO) 2000 staging and risk factor scoring system in comparison to the original World Health Organization (WHO) prognostic scoring system (1983) in a single-institute setting. DESIGN: Retrospective review of the medical records of 89 patients with gestational trophoblastic neoplasia. SETTING: Mackay Memorial Hospital, Taipei, a regional referral center for northern Taiwan, over a 20-year period. METHODS: All selected patients were classified retrospectively by the original WHO prognostic scoring system (1983) and the FIGO 2000 system. MAIN OUTCOME MEASURE: Efficacy as the correlation of risk categorization by percentage of patients between the original WHO scoring system (1983) and the FIGO 2000 system. RESULTS: The correlation was 97%. Only two patients were classified as middle risk group in the original WHO system (1983), but as high-risk group by the FIGO 2000 system. CONCLUSION: There was good correlation between the original WHO (1983) and FIGO 2000 systems. Treatment outcomes by FIGO 2000 system were somewhat better than by the original WHO classification.

Zoledronic acid, an aminobisphosphonate, modulates differentiation and maturation of human dendritic cells.

Zoledronic acid (ZOL), an effective nitrogen-containing bisphosphonate against excessive bone loss, has been shown affecting the function of cells of both innate and acquired immunity. In this study, we tested the effect of ZOL on differentiation and maturation of human myeloid dendritic cells (DC). When ZOL (1.1 to 10 microM) was added to the culture of starting monocytes, but not to immature DC, the recovery rate of DC was markedly reduced in a concentration-dependent manner. The mature DC differentiated in the presence of ZOL had fewer and shorter cell projections. ZOL treatment affected DC differentiation and maturation in terms of lower expression of CD1a, CD11c, CD83, CD86, DC-SIGN, HLA-DR, and, in contrast, higher expression of CD80. IL-10 production by DC was inhibited by ZOL treatment whereas IL-12p70 secretion remained unchanged. Interestingly, ZOL augmented the allostimulatory activity of DC on naive CD4(++)CD45(+)RA(++) T cells in terms of their proliferation and interferon-gamma production. Addition of geranylgeraniol abrogated the effect of ZOL on DC differentiation and prenylation of Rap1A. It suggests that ZOL redirects DC differentiation toward a state of atypical maturation with allostimulatory function and this effect may go through prevention of Rap1A prenylation.

Predicting factors related to nurses' intention to leave, job satisfaction, and perception of quality of care in acute care hospitals.

High nursing turnover is a problem facing many countries, including Taiwan, and can be very challenging for nursing leaders and hospital administrators. More than one-third of the nurses participating in this study considered leaving their current jobs. Understanding what factors influenced nurses to leave their jobs should be of interest to nursing leaders and hospital administrators in today's changing health care environment. Factors related to intention to leave, including wage dissatisfaction and work shift, should be addressed by hospital administrators. The findings can help hospital administrators and nursing leaders to develop strategies that minimize nurses' intention to leave behaviors, stabilize the nursing workforce, maintain hospital-employee relationships, and prevent nurses from experiencing burnout.