Biomedical subjects

Ting-Chang Chang

Publications and source records attributed to Ting-Chang Chang.

At least 19 recordsLinked to original sources

PubMed2007

Positron emission tomography imaging for gynecologic malignancy.

PURPOSE OF REVIEW: The utility of positron emission tomography (PET) in gynecologic malignancy has increased rapidly in recent years. This review examines publications in this area. RECENT FINDINGS: PET scans are mostly performed using 18-fluorodeoxyglucose (FDG-PET). It is valuable in primary staging of untreated advanced cervical cancer, for posttreatment unexplained tumor marker elevation and restaging of potentially curable recurrent cervical cancer. Its value in early-stage cervical cancer is limited. In ovarian cancer, sequential imaging predicts response to neoadjuvant chemotherapy and survival. It also provides benefits when increases in serum CA 125 or computed tomography/magnetic resonance imaging defined recurrence is noted but biopsy deemed infeasible. A few studies have shown that FDG-PET may facilitate optimal management of endometrial cancer, especially for posttherapy surveillance and after salvage therapy. FDG-PET is potentially useful in selected gestational trophoblastic neoplasia by monitoring response and localizing viable tumors after chemotherapy. Scanty studies have been reported in vulvar and vaginal cancer. The methodology and prospects of using integrated PET/computed tomography in the management of gynecological cancer are discussed. Other PET compounds are briefly introduced. SUMMARY: The role of PET or PET/computed tomography has evolved from a diagnostic tool into a potential indicator of response to treatment and prognosis. Evaluating this tool by clinical impact is an attractive end point.

Endometrial Neoplasms↗

PubMed2006

Novel codon-optimized GM-CSF gene as an adjuvant to enhance the immunity of a DNA vaccine against HIV-1 Gag.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent immunomodulatory cytokine. Here we generated a novel codon-optimized murine GM-CSF gene as an adjuvant. The codon-optimized GM-CSF gene significantly increased protein expression levels in all cells tested. Although injection of the wild-type GM-CSF plasmids adjuvanted HIV-1 Gag DNA vaccine induced detectable immune responses, co-administration of plasmids encoding the codon-optimized GM-CSF sequence with the DNA vaccine resulted in a strong antibody and CTL responses and a protective immune response against infection with recombinant vaccinia virus expressing HIV-1 Gag. This novel codon-optimized GM-CSF gene offers a practical molecular strategy for potentiating immune responses to vaccines as well as other immunotherapeutic strategies.

AIDS Vaccines↗

PubMed2006

Comparative benefits and limitations of 18F-FDG PET and CT-MRI in documented or suspected recurrent cervical cancer.

PURPOSE: The purpose of this study was to assess the comparative benefits and limitations of (18)F-fluorodeoxyglucose (FDG) PET and CT-MRI in documented or suspected recurrence of cervical cancer after primary treatment. METHODS: Three patient groups were enrolled. Group A patients had biopsy-documented recurrent or persistent cervical cancer. Group B patients had suspicion of recurrent tumour on CT-MRI without biopsy proof and were potentially curable. Group C patients were in complete remission after previous definitive treatment for histologically confirmed cervical carcinoma but had elevated serum squamous cell carcinoma antigen (tumour marker) levels despite negative CT-MRI. Clinical management decisions were recorded with CT-MRI alone and with additional FDG PET. Discordances and concordances between CT-MRI and FDG PET results were identified and related to final diagnosis as based on histopathology or follow-up. RESULTS: A total of 150 patients (ten regions per patient) were eligible for analysis, with 58 in group A, 52 in group B and 40 in group C. For the 149 discordant regions, 126 (84.6%) had final diagnoses. Of these final diagnoses, there was additional benefit from FDG PET over CT-MRI in 73.8% (93/126), with FDG PET correcting false negatives (FNs) on CT-MRI in 74.2% (69/93) and correcting false positives (FPs) on CT-MRI in 25.8% (24/93). Among lesions confirmed by FDG PET, 75.4% (52/69) were extra-pelvic. There was additional benefit of CT-MRI compared with FDG PET in 26.2% (33/126): in nine (27.3%) CT-MRI results were shown to be true positive (TP) whereas FDG PET yielded FN results, while in 24 (72.7%) CT-MRI corrected FP results on FDG PET. Among the nine FNs on FDG PET that were identified by CT-MRI, four were extra-pelvic. Among the FPs on FDG PET that were excluded by CT-MRI, 79.2% (19/24) were extra-pelvic. CONCLUSION: For recurrent cervical cancer, the benefits of FDG PET exceed those of CT-MRI owing to the ability of FDG PET to identify extra-pelvic metastases and its higher sensitivity and specificity.

Antigens, Neoplasm↗

PubMed2006

Molecular characterization of adenocarcinoma and squamous carcinoma of the uterine cervix using microarray analysis of gene expression.

In an attempt to understand the molecular mechanisms for the different clinical features between adenocarcinoma/adenosquamous carcinoma (AC/ASC) and squamous carcinoma (SC) of the uterine cervix, we analyzed gene expression profiles of different histological subtypes of cervical cancer. Cancer specimens and the surrounding normal tissue counterparts were separately collected from cervical cancer patients undergoing type III radical hysterectomy. Paired total RNA (cancer and normal tissues) was isolated and analyzed with cDNA microarrays containing duplicate spots of 7 334 sequence-verified human cDNA clones. Selected differentially expressed genes specific for AC or SC were further verified using real-time quantitative polymerase chain reaction (RTQ-PCR) and immunohistochemistry. Genes, including CEACAM5, TACSTD1, S100P and MSLN were upregulated in AC. Contrarily, genes involved in epidermal differentiation complex such as S100A9 and ANXA8 were upregulated in SC. Cross-validation of the results using an independent but comparable group of patients with known long-term outcomes (n = 63, median follow-up 70.3 months; range, 4-208 months) showed that the correlation between the selected 6 differentially expressed genes and histology was highly significant. CEACAM5 (p < 0.0001) and TACSTD1 (p = 0.009) were significant prognostic factors by multivariate Cox proportional hazards regression analysis. The combination of cDNA microarray, RTQ-PCR and immunohistochemical results of this study showed that it is possible to define different gene profiles for AC and SC. Moreover, TACSTD1 expression may be a novel poor prognostic factor.

Adenocarcinoma↗

PubMed2006

Maintenance of CD8 effector T cells by CD4 helper T cells eradicates growing tumors and promotes long-term tumor immunity.

Human papillomavirus, particularly type 16 (HPV-16), is present in more than 99% of cervical cancers, and oncogenic HPV infection is one of the most important etiologies. It is now clear that CD4(+) T cells play an important role in controlling HPV-associated lesions because immunocompromised patients have a higher frequency of HPV-associated lesions. In the current study, we characterized the significance of CD4(+) T cells in the generation of E7-specific CD8(+) T cell immune responses in mice vaccinated with SINrep5-E7/HSP70 and boosted with vac-E7/HSP70. In addition, we characterized the contribution of CD4(+) T cells to the long-term antitumor effects. We found that vaccination with CD4 depletion significantly reduced the number of E7-specific CD8(+) T cells in mice. Furthermore, CD4(+) T cells are important for the long-term anti-tumor effects generated by vaccination with SINrep5-E7/HSP70 and booster with vac-E7/HSP70. Thus, CD4 T cells clearly have an important role in successful tumor immunity and maintenance of long-term tumor antigen-specific memory responses in vaccinated mice with established tumors.

Animals↗

PubMed2006

A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene enhances CTL response and anti-tumor activity.

The HPV oncoproteins E6 and E7 are consistently expressed in HPV-associated cancer cells and are responsible for their malignant transformation. Therefore, HPV E6 and E7 are ideal target antigens for developing vaccines and immunotherapeutic strategies against HPV-associated neoplasms. Recently, it has been demonstrated that codon optimization of the HPV-16 E7 gene resulted in highly efficient translation of E7 and increased the immunogenicity of E7-specific DNA vaccines. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a codon-optimized HPV-16 E6 DNA vaccine (pNGVL4a-E6/opt) and characterized the E6-specific CD8+ T cell immune responses as well as the protective and therapeutic anti-tumor effects in vaccinated C57BL/6 mice. Our data indicated that transfection of human embryonic kidney cells (293 cells) with pNGVL4a-E6/opt resulted in highly efficient translation of E6. In addition, vaccination with pNGVL4a-E6/opt significantly enhanced E6-specific CD8+ T cell immune responses in C57BL/6 mice. Mice vaccinated with pNGVL4a-E6/opt are able to generate potent protective and therapeutic antitumor effects against challenge with E6-expressing tumor cell line, TC-1. Thus, DNA vaccines encoding a codon-optimized HPV-16 E6 may be a promising strategy for improving the potency of prophylactic and therapeutic HPV vaccines with potential clinical implications.

Analysis of Variance↗

PubMed2006

Low value of [18F]-fluoro-2-deoxy-D-glucose positron emission tomography in primary staging of early-stage cervical cancer before radical hysterectomy.

PURPOSE: The role of positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG) in early-stage cervical cancer is unclear. We aimed to investigate the clinical benefit of FDG-PET in primary staging before radical hysterectomy and pelvic lymphadenectomy (RH-PLND). PATIENTS AND METHODS: Patients with untreated stage IA2 to IIA adenocarcinoma (AD) or adenosquamous carcinoma (ASC) or nonbulky (< or = 4 cm) squamous cell carcinoma cervical cancer with magnetic resonance imaging (MRI) -defined negative nodal metastasis were enrolled onto a prospective study with a two-stage design. All patients had a preoperative dual-phase FDG-PET, technetium-99m-sulfur colloid lymphoscintigraphy, and intraoperative sentinel lymph node (LN) detection at RH-PLND. The gold standard of LN metastasis is histologic. A sample size of 120 patients was calculated to fit study aims (diagnostic efficacy of PET and sentinel LN sampling). An interim analysis was performed when 60 patients were accrued, which led to the current report. RESULTS: There were 36 SCCs, 20 ADs, and four ASCs. Of the 60 patients, 10 (16.7%) had pelvic LN metastases, and one (1.7%) had para-aortic LN (PALN) metastasis histologically. FDG-PET detected the single PALN metastasis (one of one patient) but detected only one (10%) of the 10 pelvic LN metastases. The PET false-negative pelvic LN micrometastases measured a median of 4.0 x 3.0 mm (range, 0.5 x 0.5 to 7 x 6 mm). The second stage of this trial will be continued without PET. CONCLUSION: This study shows that dual-phase FDG-PET has little value in primary, nonbulky, stage IA2 to IIA and MRI-defined, LN-negative cervical cancer.

Adult↗

PubMed2006

Sonographic prediction of significant intertwin birth weight discordance.

OBJECT: To evaluate the usefulness of sonographic prediction of significant birth weight discordance in twin pregnancies. STUDY DESIGN: Included in the study were live twin pairs with a gestational age of 24 weeks at birth who had received a sonographic examination within 28 days of delivery. Correlation tests and ROC curves were used to evaluate the predictability of significant intertwin growth discordance. RESULTS: A total of 575 twin pregnancies were included in the study. The estimated discordance by sonographic examination proved to be an effective predictor of discordant twin growth. The birth weight discordance estimated by sonography tended to underestimate the degree of discordant twins. CONCLUSION: If a sonographic examination is done within 28 days of delivery, it is a reliable predictor of twin birth weight discordance at the following levels: 15%, 20%, 25% or 30%. In order to obtain a higher sensitivity, the cut-off value of estimated birth weight discordance needs to be decreased by 5%.

Birth Weight↗

PubMed2006

Pure XY gonadal dysgenesis and agenesis in monozygotic twins.

OBJECTIVE: To report a case of monozygotic twin sisters who had discordant gonadal dysgenesis although each had a normal 46,XY karyotype. DESIGN: Case report. SETTING: University tertiary hospital. PATIENT(S): Seventeen-year-old twin sisters, one with gonadal agenesis and the other with pure gonadal dysgenesis followed by dysgerminoma. INTERVENTION(S): Blood samples were obtained for karyotyping and short tandem repeat polymorphism analysis (10 markers). Both patients underwent gonadectomy. MAIN OUTCOME MEASURE(S): Both sisters are well at time of report after gonadectomy for the sister with dysgerminoma and diagnostic laparoscope for the other. RESULT(S): Dysgerminoma and atrophic ovarian stromal and tubal structures. CONCLUSION(S): Monozygotic twins can have discordant gonadal dysgenesis even though they are identical genetically.

Adolescent↗

PubMed2006

The effects of anti-P-selectin antibody on leucocyte activity related to cigarette smoke in rats.

Nicotine-induced expression of P-selectin is implicated in endothelial cell damage related to smoking. Thirty male Sprague-Dawley rats were divided into three groups: two experimental and one control. Both experimental groups were exposed to cigarette smoke for four weeks, but one group was also given anti-P-selectin antibody (100 microg IgG per 100 g body weight) intravenously. Rolling and adhesion leucocytes within the microcirculation of the cremaster muscle were measured. The urine cotinine concentrations of rats exposed to smoke were 612 ng/ml higher than those of non-smokers. Both rolling and adherent leucocytes were highest and steady in the group given anti-P-selectin antibody at about 50 and 10, respectively. There was a significant drop in both rolling and adherent leucocytes (31 to 4 and 5 to 2) after the anti-P-selectin antibody had been given. However, this effect was short-lived as both increased above those at 35 minutes by 120 minutes (p<0.001). The increase in leucocyte rolling and adherence caused by smoking can be lowered by giving anti-P-selectin antibody. The effective period in rats was two hours, with the maximal effect one hour after injection.

Animals↗

PubMed2006

Comparison between the Hybrid Capture II Test and an SPF1/GP6+ PCR-based assay for detection of human papillomavirus DNA in cervical swab samples.

We compared the efficacy of human papillomavirus (HPV) DNA detection between a PCR-based genechip (Easychip HPV Blot [hereafter referred to as HPV Blot]; King Car, Taiwan) method and Hybrid Capture II (HCII; Digene, Gaithersburg, MD) in women with previous normal (n = 146) or abnormal (> or =atypical squamous cells of undetermined significance [ASCUS] [n = 208]) cytology. A total of 354 cervical swab samples were collected for HPV DNA assay by both HCII and SPF1/GP6+ PCR followed by HPV Blot tests. Colposcopy-directed biopsy was performed if clinically indicated. Of the 354 samples, HPV-positive rates by these two methods (HCII and HPV Blot) were 12.6% and 18.2% in 143 normal samples, 36.2% and 45.7% in 105 ASCUS samples, 57.4% and 57.4% in 94 low-grade squamous intraepithelial lesion samples, and 83.3% and 75.0% in 12 high-grade squamous intraepithelial lesion samples, respectively. The concordance of HPV Blot and HCII was 80.8% (286/354), and the agreement between the methods (kappa value, 0.68) was substantial. Discrepancies were further investigated by at least one of the following three methods: direct sequencing, type-specific PCR, and HPV Blot genotyping of cervical biopsy tissue. In the 15 HCII-positive samples, HPV Blot detected only non-HCII HPV genotypes; results of further verification methods were consistent with the latter test in the 15 samples. Of the 20 samples with HCII-negative and HPV Blot-positive results, 18 were found to contain the 13 HCII high-risk genotypes by verification methods. In only 16.7% (3/18) of the HCII-positive but HPV Blot-negative samples, further studies detected the 13 HCII genotypes. We conclude that HPV Blot seemed comparable to HCII for detection of HPV DNA in cervical swab samples.

Base Sequence↗

PubMed2005

Pegylated liposomal doxorubicin (Lipo-Dox) for platinum-resistant or refractory epithelial ovarian carcinoma: a Taiwanese gynecologic oncology group study with long-term follow-up.

OBJECTIVES: To evaluate the efficacy and safety of a distearoylphosphatidylcholine pegylated liposomal doxorubicin, Lipo-Dox, in platinum-resistant or refractory epithelial ovarian cancer. METHODS: A multicenter phase II trial enrolled women with platinum-resistant or refractory epithelial ovarian carcinoma and naïve to anthracycline. Eligible patients had either measurable tumor(s) or elevated serum CA 125 titer. Lipodox was initiated with a dose of 45 mg/m2 at a 4-week interval with subsequent escalation or reduction. A total of six cycles were scheduled. RESULTS: 29 patients, 20 with platinum-resistant and 9 with platinum refractory tumors, were enrolled. Lipo-Dox was given for an average of 4.6 cycles per patient with a total of 134 cycles. Among the 26 evaluable patients, one achieved CR, 5 PR and 9 SD. The overall response rate was 23.1% (95% CI, 6.8%-39.3%) with a median response duration of 11.6 weeks. 5 of the 6 responses were in patients with resistant disease. The median progression-free duration in the SD patients was 25.7 weeks. With a median follow-up of 13.8 months, the median progression-free and median overall survivals in the 26 patients were 5.4 months and 13.8 months, respectively. Hand-foot skin reaction occurred in 4.5% and skin pigmentation in 11.2% of all treatment cycles, all were Grade 1/2. Nausea and vomiting occurred in 14.2%, while anemia, leukopenia and thrombocytopenia occurred in 20.9%, 32.8% and 9% of cycle, respectively, and were mostly Grade 1 or 2. CONCLUSION: Lipo-Dox, the third liposome encapsulated doxorubicin, at 45 mg/m2 every 4 weeks, is effective against recurrent, platinum-resistant epithelial ovarian cancers.

Adult↗

PubMed2005

Risk stratification of patients with advanced squamous cell carcinoma of cervix treated by radiotherapy alone.

PURPOSE: To identify prognostic factors for local and distant relapse and perform risk stratification for patients with advanced cervical cancer treated with radiotherapy (RT) alone. METHODS AND MATERIALS: A total of 1031 patients with Stage IB-IVA squamous cell carcinoma of the cervix treated with full-course RT but without any chemotherapy were included for analysis. Of these, 311 patients with nonbulky Stage IB-IIA disease were designated the reference group and the other 720 patients were the study group. The associations of stage, squamous cell carcinoma antigen (SCC-ag) level, hemoglobin level, age, cell differentiation, and pelvic lymph node status with treatment failure were evaluated. The independent prognostic factors were identified by multivariate analysis. The study group was further stratified into subgroups using combinations of these risk factors. RESULTS: In the study group, independent risk factors for local relapse were advanced stage and age <45 years. The 5-year local relapse-free survival rate was 86% for patients > or =45 years with bulky Stage IB-IIA or IIB disease, and was even greater, up to 90% if the SCC-ag level was <2. In contrast, it was 65% for patients with Stage IIIB who were <45 years old. The independent risk factors for distant failure were advanced stage, SCC-ag level >2, and positive pelvic lymph nodes. The 5-year distant relapse-free survival rate was 83% for patients with bulky Stage IB-IIA and IIB disease, SCC-ag level <2, and negative lymph nodes and 43% for patients with Stage III, SCC-ag level >2, and positive lymph nodes. CONCLUSION: The risk of treatment failure in advanced-stage cervical cancer patients treated by RT alone can be more precisely predicted by risk stratification. A certain subgroup of patients had better control than the others. The benefit of treating these relatively low-risk patients with additional treatment such as concurrent chemotherapy should be further evaluated in prospective studies or meta-analyses.

Adult↗

PubMed2005

Prognostic factors and impact of adjuvant chemotherapy for uterine leiomyosarcoma.

OBJECTIVE: The aim of this study was to investigate prognostic factors and impact of adjuvant therapy for uterine leiomyosarcoma (LMS). METHODS: All cases with uterine LMS were retrieved from medical registry (1984 through 2003) of Chang Gung Memorial Hospital. After excluding cases with initial surgery at outside the hospital, missing chart, and wrong pathologic diagnosis, 51 patients (41 for stage I, 7 for stage III, and 3 for stage IV) met the study criteria. Approximate stratified analysis and Cox proportional hazards model were used to adjust confounding factors. RESULTS: The median follow-up for survivors was 47 months. Five-year overall survival and recurrence-free survival (RFS) rates were 67.4% and 59.2% for the whole series. Multivariate Cox regression analyses selected age (>50 versus < or =50 years: relative risk [RR], 11.07 [95% CI 1.53-80.34]), tumor size (>11 versus < or =11 cm: RR, 11.63 [95% CI 2.14-63.12]), stage (III and IV versus I: RR, 21.24 [95% CI 2.20-204.98]), and adjuvant chemotherapy (yes versus no: RR, 0.08 [95% CI 0.01-0.81]) as significant predictors of death. Besides, surgical stage (P = 0.021), tumor size (P = 0.005), and adjuvant chemotherapy (P = 0.011) were significantly correlated with RFS. After approximate stratification, the use of adjuvant chemotherapy also significantly decreased RR of death. CONCLUSIONS: This is the first report to demonstrate benefit of adjuvant chemotherapy for LMS despite the limitation of sample size and its retrospective nature. Prospective multicenter trials are necessary to clarify the role of chemotherapy, selecting criteria, and optimal chemotherapy regimen for uterine LMS.

Adult↗

PubMed2005

18F-FDG PET in the management of endometrial cancer.

PURPOSE: Few studies have investigated the clinical impact of whole-body positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) in endometrial cancer. We aimed to assess the value of integrating FDG-PET into the management of endometrial cancer in comparison with conventional imaging alone. METHODS: All patients with histologically confirmed primary advanced (stage III/IV) or suspicious/documented recurrent endometrial cancer, with poor prognostic features (serum CA-125 >35 U/ml or unfavourable cell types), or surveillance after salvage therapy were eligible. Before FDG-PET scanning, each patient had received magnetic resonance imaging and/or computed tomography (MRI-CT). The receiver operating characteristic curve method with calculation of the area under the curve (AUC) was used to compare the diagnostic efficacy. Clinical impacts were determined on a scan basis. RESULTS: Forty-nine eligible patients were accrued and 60 studies were performed (27 primary staging, 33 post-therapy surveillance or restaging on relapse). The clinical impact was positive in 29 (48.3%) of the 60 scans. Mean standardised uptake values (SUVs) of true-positive lesions were 13.2 (range 5.7-37.4) for central pelvic lesions and 11.1 (range 1.5-37.4) for metastases. The sensitivity of FDG-PET alone (P<0.0001) or FDG-PET plus MRI-CT (P<0.0001) was significantly higher than that of MRI-CT alone in overall lesion detection. FDG-PET plus MRI-CT was significantly superior to MRI-CT alone in overall lesion detection (AUC 0.949 vs 0.872; P=0.004), detection of pelvic nodal/soft tissue metastases (P=0.048) and detection of extrapelvic metastases (P=0.010), while FDG-PET alone was only marginally superior by AUC (P=0.063). CONCLUSION: Whole-body FDG-PET coupled with MRI-CT facilitated optimal management of endometrial cancer in well-selected cases.

Adult↗

PubMed2005

Does diabetes mellitus influence the efficacy of FDG-PET in the diagnosis of cervical cancer?

PURPOSE: Compared with computed tomography (CT) and magnetic resonance imaging (MRI), positron emission tomography (PET) may have additional value in the assessment of primary and recurrent cervical cancer. However, the degree of tumour uptake of (18)F-2-fluoro-2-deoxy-D: -glucose (FDG) uptake is sometimes influenced by diabetes mellitus (DM). Therefore, we conducted this prospective study to compare the diagnostic ability of FDG-PET in patients with cervical cancer complicated by DM and those without DM. METHODS: Patients with untreated locally advanced primary or clinically curable recurrent cervical carcinoma were enrolled. Both FDG-PET and MRI/CT scans were performed within 2 weeks. Patients were categorised into the following groups: hyperglycaemic DM (fasting blood sugar >126 mg/dl), euglycaemic DM and non-DM. The lesions were confirmed histologically or by clinical follow-up. The receiver operating characteristic curve method, with calculation of the area under the curve (AUC), was used to evaluate the discriminative power. RESULTS: From February 2001 to January 2003, 219 patients (75 with primary and 144 with recurrent cervical cancer) were eligible for analysis. Sixteen had hyperglycaemic DM, 12 had euglycaemic DM and 191 were in the non-DM group. The diagnostic power of PET in the hyperglycaemic DM, euglycaemic DM and non-DM groups did not differ significantly with regard to the identification of either metastatic lesions (AUC, 0.967/0.947/0.925, P>0.05) or primary tumours/local recurrence (AUC, 0.950/0.938/0.979, P>0.05). Considering all DM patients, PET showed a significantly higher detection power than MRI/CT scans in respect of metastatic lesions (AUC=0.956 vs 0.824, P=0.012). CONCLUSION: In comparison with its accuracy in non-DM patients, the accuracy of PET in cervical cancer patients with mild to moderate DM was not significantly reduced.

Adult↗

PubMed2005

Enhancement of DNA vaccine potency through linkage of antigen gene to ER chaperone molecules, ER-60, tapasin, and calnexin.

DNA vaccines have emerged as an attractive approach for generating antigen-specific immunotherapy. Strategies that enhance antigen presentation may potentially be used to enhance DNA vaccine potency. Previous experiments showed that chimeric DNA vaccines utilizing endoplasmic reticulum (ER) chaperone molecules, such as Calreticulin (CRT), linked to an antigen were capable of generating antigen-specific CD8+ T cell immune responses in vaccinated mice. In this study, we tested DNA vaccines encoding the ER chaperone molecules ER-60, tapasin (Tap), or calnexin (Cal), linked to human papillomavirus type 16 (HPV-16) E7 for their abilities to generate E7-specific T cell-mediated immune responses and antitumor effects in vaccinated mice. Our results demonstrated that vaccination with DNA encoding any of these chaperone molecules linked to E7 led to a significant increase in the frequency of E7-specific CD8+ T cell precursors and generated stronger antitumor effects against an E7-expressing tumor in vaccinated mice compared to vaccination with wild-type E7 DNA. Our data suggest that DNA vaccines employing these ER chaperone molecules linked to antigen may enhance antigen-specific CD8+ T cell immune responses, resulting in a significantly more potent DNA vaccine.

Animals↗

PubMed2005

Outcome and prognostic factors in ovarian germ cell malignancies.

OBJECTIVES: This study was undertaken to investigate the outcome and prognostic factors in patients with ovarian germ cell malignancies (OGCMs). METHODS: A total of 93 patients with OGCMs were retrospectively reviewed, among whom 84 patients had primary treatment at Chang Gung Memorial Hospital (CGMH) between 1984 and 2003. The other nine patients were primarily treated outside and referred for follow-up (n = 1), adjuvant chemotherapy (n = 4), or salvage therapy after recurrence (n = 4). The clinicopathological and treatment-related characteristics were analyzed for association with the occurrence of tumor persistence/recurrence or death. RESULTS: Of the study patients, 32 had dysgerminoma (DSG), 29 immature teratoma (IMT), 23 endodermal sinus tumor, 7 mixed germ cell tumors, and 1 each had choriocarcinoma and embryonal carcinoma. The median follow-up of survivors was 66 months (range, 12-236 months). The median time to recurrence or progression was 8 months. There were 11 treatment failures with 6 died of cancer. The 5-year survival rate was 97.4% for those primarily treated at CGMH. Histology (DSG/IMT versus non-DSG/IMT) (P < 0.0001) and International Federation of Gynecology and Obstetrics stage (P = 0.001) were significantly associated with treatment failure, while histology (P = 0.0004), salvage high-dose chemotherapy (HD-CT) after primary chemotherapy failed (P = 0.0405), and residual tumor after salvage surgery (P = 0.0014) were significant prognostic factors for overall survival. CONCLUSIONS: Prognosis of OGCMs is excellent if managed with standard treatment initially. Aggressive HD-CT with salvage surgery needs to be applied for recurrent/persistent disease after primary chemotherapy.

Adolescent↗