OBJECTIVE: To investigate the changes of incidence and prognosis of epithelial ovarian cancer in thirty years in Taiwan. METHODS: The databases of women with epithelial ovarian cancer during the period from 1979 to 2008 were retrieved from the National Cancer Registration System of Taiwan. The incidence and prognosis of these patients were analyzed. RESULTS: Totally 9,491 patients were included in the study. The age-adjusted incidences of epithelial ovarian cancer were 1.01, 1.37, 2.37, 3.24, 4.18, and 6.33 per 100,000 person-years, respectively, in every 5-year period from 1979 to 2008. The age-specific incidence rates increased especially in serous, endometrioid and clear cell carcinoma, and the age of diagnosis decreased from sixty to fifty years old in the three decades. Patients with mucinous, endometrioid, or clear cell carcinoma had better long-term survival than patients with serous carcinoma (log rank test, p<0.001). Patients with undifferentiated carcinoma or carcinosarcoma had poorer survival than those with serous carcinoma (log rank test, p<0.001). The mortality risk of age at diagnosis of 30-39 was significantly higher than that of age of 70 years or more (test for trend, p<0.001). The mortality risk decreased from the period of 1996-1999 (hazard ratio [HR], 0.90; p=0.054) to the period after 2000 (HR, 0.74; p<0.001) as compared with that from the period of 1991-1995. CONCLUSION: An increasing incidence and decreasing age of diagnosis in epithelial ovarian cancer patients were noted. Histological type, age of diagnosis, and treatment period were important prognostic factors for epithelial ovarian carcinoma.
Carcinoma ; Carcinosarcoma ; Female ; Humans ; Incidence ; Mucins ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Prognosis ; Taiwan

PURPOSE: We report herein major determinants and long- term outcomes of balloon dilatation (BD) for 27 pediatric patients with isolated native valvular pulmonary stenosis (VPS). MATERIALS AND METHODS: From May 1997 to May 2003, 27 pediatric patients with VPS (pressure gradients> or =40mmHg) were enrolled in this retrospective study. Single-balloon maneuver was applied in 26 patients, and double- balloon maneuver in 1. After BD, the pressure gradients were documented simultaneously by pullback maneuver by cardiac catheterization and echocardiography within 24 hours, at 1- month, 3-month, 1-year, and 4-to-10-year follow-ups. RESULTS: Before BD, the echocardiographic gradients ranged from 40 to 101mmHg (61+/-19, 55), and from 40 to 144mmHg (69+/-32, 60) by pressure recordings. After BD, the gradients ranged from 12 to 70mmHg (29+/-13, 27) by pressure recording (p<0.001), and from 11 to 64mmHg (27+/-12, 26) by echocardiography within 24 hrs (p<0.001). The ratios of the systolic pressure of the right ventricle to those of the left ventricle were 55 to 157% (89+/-28, 79%) before BD, and 30 to 79% (47+/-13, 42%) after BD p<0.001). Follow-up (7.7+/-5.7, 4.5 years) echocardiographic gradients ranged from 11 to 61mmHg (25+/-11, 24). Two patients did not have immediate success owing to infundibular spasm. Improved right ventricular compliance could be accounted for the ultimate success in these 2 patients. The ultimate successful rate was 100%. CONCLUSION: BD can achieve excellent long-term outcomes in the pediatric patients with isolated native VPS.
Adolescent ; Balloon Dilatation/adverse effects/*methods ; Child ; Child, Preschool ; Echocardiography ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Pulmonary Valve Stenosis/pathology/physiopathology/*therapy ; Retrospective Studies ; Time Factors ; Treatment Outcome

OBJECTIVETo investigate polymorphism of HLA-DRB1 in Chinese Lahu population in Yunnan.

METHODSPolymerase chain reaction-sequence specific primers (PCR-SSP) were used to determine HLA-DRB1 genotypes of 110 unrelated healthy Lahu minority people of Yunnan Province.

RESULTSSixteen alleles of DRB1 were detected in this study. The results of test showed that the genotype distributions observed were corresponded with the Hardy-Weinberg equilibrium.

CONCLUSIONThis study has obtained a more comprehensive and accurate data set of the normal allele frequencies of HLA-DRB1 in Chinese Lahu population in Yunnan Province, which may be of significance in the studies on population genetics and disease association.

Asian Continental Ancestry Group ; DNA Primers ; Ethnic Groups ; Female ; Gene Frequency ; Genotype ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Humans ; Male ; Polymerase Chain Reaction ; methods

OBJECTIVE: Adjuvant chemotherapy was introduced in patients with early-stage ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including taxane has not been established. METHODS: Patients with early-stage OC from the National Health Insurance Research database of Taiwan who received platinum plus cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3–6 cycles were recruited, and the disease-free survival (DFS) and overall survival (OS) were determined. RESULTS: A total of 1,510 early-stage OC patients, including 841 who received CP regimen and 699 who received PT regimen, were included. The 2 groups had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%; p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who received the CP regimen had a lower 5-year DFS than the patients ≤50 years of age who received the CP (p<0.001) or PT regimens (p=0.001). Additionally, patients >50 years of age who received the CP regimen had a worse 5-year OS compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age in the PT group; p=0.002 for patients ≤50 years of age in the CP group; and p=0.061 for patients ≤50 years of age in the PT group). Patients with the CP or PT regimen for 3–5 cycles had a similar 5-year DFS and OS compared to 6 cycles (p>0.050). CONCLUSION: Chemotherapeutic regimens with taxane could be recommended for early-stage OC patients >50 years of age.
Chemotherapy, Adjuvant ; Cyclophosphamide ; Disease-Free Survival ; Drug Therapy ; Humans ; National Health Programs ; Ovarian Neoplasms ; Paclitaxel ; Platinum ; Taiwan

OBJECTIVE: To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. METHODS: Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). RESULTS: There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07–0.68; p=0.010). Women in their 40s–50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03–1.49; p=0.020). CONCLUSION: In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.
Atypical Squamous Cells of the Cervix* ; Biopsy ; Cervical Intraepithelial Neoplasia* ; Cohort Studies* ; Colposcopy ; Cryotherapy ; Curettage ; Diagnosis ; Ethics Committees, Research ; Female ; Humans ; Incidence ; Mass Screening ; National Health Programs ; Proportional Hazards Models ; Risk Reduction Behavior ; Taiwan ; Uterine Cervical Neoplasms ; Vaginal Smears

[Objective]To establish stable glioma stem cells with a high expression level ofred fluorescent protein (RFP) in vitro.[Methods]The glioma stem cells SU2 were transfected with lentivirus vector containing RFP gene;cell expression of RFP was observed by fluorescent microscopy;RFP-positive glioma stem cells were sorted out by fluorescence-activated cell sort.The transfection efficiency of SU2 cell before transfection and 20-passaged RFP-SU2 cells after transfection were assayed by flow cytometry.Dynamic viewing was performed to observe the cell division and cloning of RFP-SU2 single cell;RFP -positive cells were collected and immunostained with antibodies against CD133 and nestin.[Results] PFP-SU2 cells grew as levitated sphere with high RFP expression;the transfection efficiency of SU2 cell before transfection was only 1.5％,while that of20-passaged RFP-SU2 cells after transfection reached to 75％.RFP-SU2 single cell could proliferate into brain tumor stem cell spheres,having the abilities of self-renewing and clonal proliferation.Immunofluorescence showed positiveCDt 33 and nestin expressions in RFP-SU2 cells.[Conclusion] A SU2/RFP cell line marked by RFP is established;and it can serve as a promising tool for further basic research.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

OBJECTIVETo study the phenotype and tumorigenicity of SHG-44 glioma stem cell spheres and the pathological characteristics of their xenograft tumors.

METHODSSHG-44 glioma cells were cultured under neural stem cell medium and glioma stem cell spheres were collected. Immunocytochemistry was used to dectet the expression of CD133, nestin, A2B5, vimentin, VEGFR-2 and IDH R132H. Cell spheres were induced using serum-containing medium, and the expression of CD133, nestin, vimentin, GFAP, β-III tubulin and GalC in the cell spheres were detected. The expression of CD133, nestin, VEGFR-2, GFAP, S-100 and CD34 in the intracranial xenograft tumor tissues was detected using immunohistochemistry. The pathological characteristics of orthotopic xenograft tumors generated from the SHG-44 glioma cells and SHG-44 glioma stem cell spheres were compared.

RESULTSSHG-44 glioma stem cell spheres were collected successfully after cultured under neural stem cell medium. The ratio of CD133(+) cells in the passage 10 SHG-44 glioma stem cell spheres was (71.63 ± 5.92)%, significantly higher than that in the SHG-44 glioma cells [(1.95 ± 1.45)%]. Immunocytochemistry showed that in the SHG-44 glioma cell spheres, the ratio of nestin(+) cells was (84.06 ± 7.58)%, vimentin(+) cells (29.11 ± 3.44)%, VEGFR 2(+) cells (64.44 ± 3.69)%, and A2B5(+) cells (14.08 ± 2.19)%. A subpopulation of cells with mutation of IDH R132H was detected harboring in the SHG-44 glioma cell spheres. After induction of differentiation with serum-containing medium, the ratio of CD133(+) cells was (1.89 ± 1.27)%, nestin(+) cells (6.67 ± 2.75)%, vimentin(+) cells (93.75 ± 2.95)%, GFAP (+) cells (91.33 ± 4.75)%, β-III tubulin(+) cells (82.36 ± 4.02)%, and GalC(+) cells (8.92 ± 3.19)%. Immunohistochemistry showed positive expression of GFAP, S-100, VEGFR-2, and negative of CD133 and nestin in the orthotopic xenograft tumors. A very small amount of human-specific CD34 cells formed a tubular structure. Compared with the SHG-44 glioma cell-formed xenograft tumor, the SHG-44 glioma stem cell-formed xenograft tumor exhibited a higher local invasiveness.

CONCLUSIONSSHG-44 glioma cell spheres are successfully collected after cultured under neural stem cell medium. They belong to the CD133(+)A2B5(-) GSC subpopulation, highly expressing VEGFR-2, possess the ability of both self-renewal and multi-directional differentiation, and may participate in the formation of vasculogenic mimicry.

Animals ; Brain Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cells, Cultured ; Glial Fibrillary Acidic Protein ; metabolism ; Glioma ; metabolism ; pathology ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Neoplastic Stem Cells ; metabolism ; pathology ; S100 Proteins ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism