Hsieh Cy

High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma

The objective of this paper is to investigate the mesothelin expression level to the clinicopathological features, chemoresponse, and to the outcome of patients with epithelial ovarian carcinoma (EOC). Mesothelin mRNA was detected by real-time quantitative reverse-transcription PCR in 139 EOC patients. Clinical characteristics, histopathological items, responses to chemotherapy, progression-free survival (PFS), and overall survival (OS) were recorded. Tumours with advanced stages had higher mesothelin than those with early stages. The chemoresistant patients showed significantly higher mesothelin than did chemosensitive patients (2.81 vs 0.43, P<0.001), irrespective of optimal or suboptimal surgery in those with advanced stages. Highly expressed levels of mesothelin were an independent but poor prognostic factor in the PFS (2.03 (1.23–3.37) P=0.006) and OS (3.72 (1.64–8.45), P=0.002) of the 139 EOC patients in multivariate analysis. In addition, patients in advanced stages with highly expressed mesothelin also had significantly worse OS, regardless of whether they had undergone optimal (13.85 (1.76–125.60), P=0.013) or suboptimal (4.47 (1.83–10.88), P=0.001) debulking surgery in multivariate analysis. Out results provide new evidence that mesothelin expression is associated with chemoresistance and with shorter disease-free survival and worse OS of patients with EOC.

Effectiveness of national cervical cancer screening programme in Taiwan: 12-year experiences

Background:We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995.Results:The invasive cancer incidence decreased by 47.8% during 1995–2006. The carcinoma in situ incidence increased 1.7-fold during 1995–2000, and decreased by 19.6% during 2000–2006.Conclusion:The Taiwan national programme has significantly decreased invasive cervical cancer.

Mechanically tunable surface plasmon resonance based on gold nanoparticles and elastic membrane polydimethylsiloxane composite

Surface plasmon in nanoscaled materials has recently attracted a great deal of attention due to its possibility in a wide range of application. From a practical standpoint, it is desirable for the devices having a tunability of surface plasmon frequency. To achieve this goal, in this study, a composite consisting of two-dimensional gold nanoparticles array embedded in elastic polydimethylsiloxane (PDMS) membrane has been synthesized. Because the elastic PDMS membrane has a high malleability, with an external stress, it is very easy to regulate the interparticle distance in the gold nanoparticle array. The change in the distance between each nanoparticle will alter the surface plasmon interaction, and hence surface plasmon frequency can be manipulated. It is found that when the interparticle distance increases, the enhanced surface plasma mutual coupling will cause the blueshift of surface plasmon resonance frequency. The observed result satisfies the forecast based on electromagnetic theory.

Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism

A novel method for generating an antigen-specific cancer vaccine and immunotherapy has emerged using a DNA vaccine. However, antigen-presenting cells (APCs) have a limited life span, which hinders their long-term ability to prime antigen-specific T cells. Connective tissue growth factor (CTGF) has a role in cell survival. This study explored the intradermal administration of DNA encoding CTGF with a model tumor antigen, human papilloma virus type 16 E7. Mice vaccinated with CTGF/E7 DNA exhibited a dramatic increase in E7-specific CD4+ and CD8+ T-cell precursors. They also showed an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with the wild-type E7 DNA. The delivery of DNA encoding CTGF and E7 or CTGF alone could prolong the survival of transduced dendritic cells (DCs) in vivo. In addition, CTGF/E7-transduced DCs could enhance a higher number of E7-specific CD8+ T cells than E7-transduced DCs. By prolonging the survival of APCs, DNA vaccine encoding CTGF linked to a tumor antigen represents an innovative approach to enhance DNA vaccine potency and holds promise for cancer prophylaxis and immunotherapy.

Graphene-lead zirconate titanate optothermal field effect transistors

We have developed a pyroelectric field effect transistor (FET) based on a graphene-lead zirconate titanate (PZT) system. Under the incidence of a laser beam, the drain current can be increased or decreased depending on the direction of the polarization of the PZT substrate. The drain current sensitivity of the optothermal FET can reach up to 360 nA/mW at a drain field of 6.7 kV/m more than 5 orders of magnitude higher than that of the photogating transistors based on carbon nanotube on SiO2/Si substrate. Graphene is an excellent component for pyroelectric FET due to its high optical transparency and conductance.

Brain metastasis as a late manifestation of ovarian carcinoma

This paper aims to evaluate the clinical characteristics of ovarian cancer patients with cerebral metastases. Ten ovarian cancer patients with brain metastases were retrospectively identified from a total of 539 ovarian cancer patients. Their characteristics before and at the time of diagnosis of cerebral metastases were analysed. The survival of them was also measured. Ten (1.9%) of the 539 ovarian cancer patients had brain metastases in the study period. Nine had stage III or IV tumours with either moderate or poor histological differentiation. The mean time from diagnosis of ovarian cancer to documentation of central nervous system metastasis was 24.3 months, which was 11.1 months if other sites of metastasis were involved before cerebral relapse. All of the patients with intra-cranial tumours suffered from associated neurological defects and relived by treatments. The median survival time after diagnosis of central nervous system involvement was 3 months. In this study, all ovarian cancer patients with cerebral metastases had clinical neurological symptoms. Physicians should pay more attention to ovarian cancer patients with neurological defects and arrange brain imaging studies for the early diagnosis of brain metastases and prompt management to improve quality of life.

Risk of gynaecological malignancies in cytologically atypical glandular cells: follow‐up study of a nationwide screening population

Please cite this paper as: Cheng W‐F, Chen Y‐L, You S‐L, Chen C‐J, Chen Y‐C, Hsieh C‐Y, Chen C‐A. Risk of gynaecological malignancies in cytologically atypical glandular cells: follow‐up study of a nationwide screening population. BJOG 2011;118:34–41.

Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects

Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8+ T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.

Comparison of detection of human papillomavirus 16 DNA in cervical carcinoma tissues by Southern blot hybridisation and nested polymerase chain reaction

An association between human papillomavirus (HPV) and cervical neoplasia has been widely reported and HPV DNA is commonly detected in cervical carcinoma tissues. However, estimates of the prevalence of HPV infection differs among various detection methods. Seventy cases of cervical carcinoma were screened for HPV 16 infection by Southern blot hybridisation (SBH) and nested polymerase chain reaction (PCR). According to SBH, the prevalences of HPV 16 DNA in stage I (n = 40) and stage II (n = 30) cervical carcinomas were 52.5 and 63.3%, respectively, and the overall prevalence was 57.1% (40 of 70). By nested PCR, the prevalences of HPV 16 infection in stage I and II cervical carcinomas were 87.5 and 93.3%, respectively, and the overall prevalence was 90.3%. The prevalence of HPV DNA detected by nested PCR was significantly greater than that detected by SBH. The combined concordance of positive and negative results between SBH and nested PCR was 61.4%. The discrepancy resulted mainly from 25 cases (35.7%) that were positive by PCR but negative by SBH. A small copy number of HPV DNA in the these 25 cases was documented by a semi-quantitative PCR method. The nested PCR was more sensitive than SBH and detected cases with low amounts of HPV DNA. The detection of HPV infection varied between these two prevailing detection methods and this should be kept in mind in assessing various epidemiological data concerning HPV infection.

Prognostic and predictive values of E-cadherin for patients of ovarian clear cell adenocarcinoma.

Objectives: The purpose of the study was to analyze negative versus positive immunoexpression of epithelial cadherin (E-cadherin) and p53 in patients with primary advanced ovarian clear cell adenocarcinoma (OCCA) and its significance in relation to clinical features, progression-free survival and overall survival (OS). Methods and Materials: Protein expression of E-cadherin and p53 was immunohistochemically evaluated in 61 OCCA patients with stages IIC to IV. The clinical factors studied included stage, age, CA-125, residual tumors, and chemotherapy regimens. Results: Positive p53 immunoexpression was 44.8% (26/58) of OCCAs; in contrast, E-cadherin immunoexpression was observed in 75.9% (44/58) of OCCAs. The expected 5-year OS rate of OCCA treated with paclitaxel-based chemotherapy was significantly better than non-paclitaxel-based chemotherapy (40% vs 0%, P = 0.001). The expected 5-year OS rate of OCCA patients with positive E-cadherin immunoexpression (>10%) was also significantly better than patients with negative E-cadherin immunoexpression (≤10%) (35% vs 0%, P = 0.02). The expected 5-year OS rate of those receiving paclitaxel-platinum chemotherapy was not significantly different from platinum-based chemotherapy for those with negative E-cadherin immunoexpression (P = 0.11). The expected 5-year OS rate of those receiving paclitaxel-based chemotherapy was better than non-paclitaxel-based chemotherapy for those with positive E-cadherin immunoexpression (43% vs 0%, P = 0.01). Paclitaxel-based chemotherapy and positive E-cadherin immunoexpression were 2 independent prognostic factors in OS of patients with OCCA (P = 0.01 and 0.04, respectively). Conclusions: E-cadherin is a useful prognostic marker for OCCA patients, and paclitaxel-based chemotherapy can improve survival among patients with positive E-cadherin immunoreactivity.