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Functions of selenium are diverse as antioxidant, anti-inflammation, increased immunity, reduced cancer incidence, blocking tumor invasion and metastasis, and further clinical application as treatment with radiation and chemotherapy. These functions of selenium are mostly related to oxidation and reduction mechanisms of selenium metabolites. Hydrogen selenide from selenite, and methylselenol (MSeH) from Se-methylselenocyteine (MSeC) and methylseleninicacid (MSeA) are the most reactive metabolites produced reactive oxygen species (ROS); furthermore, these metabolites may involve in oxidizing sulfhydryl groups, including glutathione. Selenite also reacted with glutathione and produces hydrogen selenide via selenodiglutathione (SeDG), which induces cytotoxicity as cell apoptosis, ROS production, DNA damage, and adenosine-methionine methylation in the cellular nucleus. However, a more pronounced effect was shown in the subsequent treatment of sodium selenite with chemotherapy and radiation therapy. High doses of sodium selenite were effective to increase radiation therapy and chemotherapy, and further to reduce radiation side effects and drug resistance. In our study, advanced cancer patients can tolerate until 5000 μg of sodium selenite in combination with radiation and chemotherapy since the half-life of sodium selenite may be relatively short, and, further, selenium may accumulates more in cancer cells than that of normal cells, which may be toxic to the cancer cells. Further clinical studies of high amount sodium selenite are required to treat advanced cancer patients.

Background: Positive resection margins after conization or loop electrosurgical excision procedure (conization/LEEP) are associated with increased risks of recurrence or residual cervical intraepithelial neoplasia (CIN). Herein, we investigated the long-term outcomes of photodynamic therapy (PDT) for incomplete excision of CIN3. Methods: We retrospectively reviewed the medical charts of 73 patients treated with PDT between 2000 and 2011. Patients who underwent conization/LEEP before PDT within 6 months were included. The primary outcomes were the complete response (CR) rate after 1 year and human papillomavirus (HPV) eradication rate at 6 months after PDT. Results: A total of 34 patients with positive resection margins were finally enrolled. The median patient age was 33 years. Carcinoma in situ was diagnosed in 25 patients and CIN3 in 7 patients. The CR rate was 97.1% after 1 year. Except for one case of a persistent disease, there was no recurrence or newly developed disease during the median follow-up of 84 months (range, 12–224 months). The HPV eradication rate of PDT following conization/LEEP after 6 months was 96.9% (31/32). Photosensitivity was identified in five patients and cervical stenosis in one patient. Conclusions: In conclusion, PDT could be an effective therapeutic option for patients with a positive resection margin after conization/LEEP for CIN3. It could reduce the residual or recurrence rate of CIN lesions with tolerable adverse events.

ObjectivesThe aim of this study was to evaluate the clinicopathologic features of placental site trophoblastic tumors (PSTTs) in Korea.Methods/MaterialsTwenty patients given a diagnosis of PSTT in Korea (1990–2013) were evaluated retrospectively, including 14 patients identified through a literature review and 6 patients identified through a medical chart review of a single institution. The analysis included patient age, antecedent pregnancies, time since antecedent pregnancy, presenting symptoms, serum β-human chorionic gonadotropin level, International Federation of Gynecology and Obstetrics stage, treatment, outcome, and follow-up.ResultsThe mean age of the 20 patients was 32 years (range, 25–53 years). The antecedent pregnancies included 8 term pregnancies, 8 abortions, and 2 molar pregnancies. The time since the antecedent pregnancy was less than 1 year in 16 patients (80%). Nineteen patients (95%) presented with abnormal vaginal spotting or amenorrhea. Serum β-human chorionic gonadotropin levels ranged from normal to 13,480 mIU/mL, although most patients (80%) had a level less than 1000 mIU/mL. Seventeen patients (85%) presented with stage I disease. Ten patients (50%) underwent hysterectomy, and 14 patients (70%) were treated with chemotherapy with or without hysterectomy. In 11 evaluated patients, the median mitotic count index was 3.4 (0.4–10) per 10 high-power fields. The median follow-up time was 17 months (range, 1–68 months). There was no recurrence or death from disease.ConclusionsKorean patients with PSTT often have early-stage disease, which has a favorable prognosis even with fertility-preserving therapy. However, international studies are necessary to determine the optimal treatment and prognostic factors.

Background and Objective We aimed to evaluate responses to photodynamic therapy (PDT) and its long-term efficacy in preserving normal anatomy and function in women with premalignant lesions of the lower genital tract. Study Design/Materials and Methods Fifteen patients received PDT for vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VAIN), or vulvar Paget's disease between January 2003 and December 2013. Patients underwent colposcopy and/or vulvoscopy for assessment of lesions. Surface photoillumination with a 630-nm red laser light was applied to the lesions 48 hours after intravenous injection of 2 mg/kg photosensitizer (PSZ; Photogem®). The light dose to the lesions was 150 J/cm2. Results The median age of the 15 patients (VIN II: 3, VIN III: 4, VAIN II: 2, VAIN III: 3, Paget's disease: 3) was 42.3 years. The complete response (CR) rate was 80% (12/15) at the 3-month follow-up and 71.4% (10/14) at the 1-year follow-up. There were two cases of persistent disease at the 3-month follow-up. One patient with persistent disease underwent partial vulvectomy three times for repetitive recurrence, and the other received secondary PDT with topical 5-aminolevulinic acid (5-ALA) and subsequently showed no evidence of disease (NED). Another patient achieved 90% remission through a combination of additional alternative treatments after showing partial response (PR). In two cases of CR, recurrence was observed at the 1-year follow-up. Regarding adverse events, photosensitivity reactions such as facial edema and urticaria occurred in 13.3% (2/15) and perineal pain occurred in one patient. Conclusions PDT may be an effective alternative treatment for premalignant lesions of the female lower genital tract to preserve normal anatomy and sexual function without therapeutic impairment. Lasers Surg. Med. 47:566–570, 2015. © 2015 Wiley Periodicals, Inc.

Summary Background Vaginal radical trachelectomy (VRT) is the standard fertility preserving procedure for early stage cervical cancer patients. There have been reports in the literature, however, that VRT to be too radical procedure for early stage cervical cancer, as its post-operative obstetric morbidity was high. In this study, PDT with Loop electrosurgical excision procedure (LEEP) or conization was investigated as a less radical fertility preserving treatment alternative to VRT for early stage cervical cancer patients. Methods We analyzed data of 21 patients with early stage cervical cancer (stages IA-IIA) who underwent PDT with LEEP/conization from 2003 to 2012. LEEP or conization was performed before PDT in every case. For patients in stage IB1 or above, only those who were confirmed to be free of malignancy in frozen section by pelvic lymph node dissection received PDT. Surface photoillumination with red laser light at a wavelength of 630 nm was applied to the cervix and the endocervical canal 48 h after intravenous injection of 2 mg/kg of photosensitizer. Results Median age of the 21 patients was 31 years old (range: 22–43), 19 patients (90.5%) of whom were nulliparous. Majority of the lesions were at stage IA1 (47.6%) or IB1 (42.9%). Histologically, 80.9% were squamous cell carcinoma. 5 patients (23.8%) had a lesion of 2 cm or larger in diameter. There was one recurrence (4.7%) and no death during 52.6 months (6–114 months). Of the 13 women who attempted to get pregnant, 10 (76.9%) women conceived a total of 11 pregnancies. The first and second trimester miscarriages were 2 and 1 respectively, and 7 (70%) of the pregnancies reached the third trimester, of which 5 delivered at term. No tumor-related deaths or PDT-related severe adverse effects were noted. Conclusion PDT combined with LEEP/conization could be an effective fertility sparing conservative treatment for young patients with early stage cervical cancer.

Objective To evaluate the response and efficacy of photodynamic therapy (PDT) with or without loop electrosurgical excision procedure (LEEP)/conization (Cone) to preserve fertility in young patients with cervical intraepithelial neoplasia (CIN) II and III. Methods We reviewed the medical records of patients with CIN who had been treated by PDT. Among a total of 73 patients who received PDT for CIN II/III between September 2000 and August 2011, 59 patients aged 40 or younger and who wished to preserve fertility were included. Patients were divided into four groups: group (I) only PDT without LEEP (n = 13), group (II) PDT combined with LEEP/Cone (n = 15), group (III) PDT due to positive LEEP/Cone margin (n = 25), group (IV) PDT for recurrent CIN after LEEP/Cone (n = 6). Surface photoillumination with red laser light at a wavelength of 630 nm was applied to the uterine cervix and endocervical canal of patients 48 hours after an intravenous injection of 2 mg/kg of photosensitizer. Results The median age of the 59 patients (CIN 2: 4, CIN 3: 22, carcinoma in situ: 31, adenocarcinoma in situ: 2) was 30.4 years. Twenty-two patients were unmarried and 38 were nulliparous. The complete remission (CR) rate was 98.1% (52/53) at 1 year follow-up except six patients followed up loss. The remaining one had recurred at 1 year after PDT, and one residual case at 3 months follow-up was regarded as CR showing NED after secondary PDT. Human papilloma virus (HPV) typing was performed. Before treatment HPV infection rate was 96.3% (52/54). HPV DNA could be no longer detected in 89.8% (44/49) and 87.0% (40/46) at 3 and 12 months after PDT. Among 29 patients who tried to be pregnant, 18 patients achieved 25 pregnancies (6 abortions, 1 ectopic, 1 preterm, 15 term, and 2 ongoing pregnancies.) There has been no fetal loss due to incompetent internal os of cervix. For adverse events, photosensitivity occurred in 13.6% (8/59) and cervical stenosis occurred in one patient. Conclusions PDT combined with or without LEEP/Cone may be a potential alternative for effective conservative treatment of CIN in young patients who wish to preserve fertility. Lasers Surg. Med. 45:564–572, 2013. © 2013 Wiley Periodicals, Inc.

Background We evaluated the efficacy and feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) using paclitaxel as consolidation therapy in patients with epithelial ovarian cancer. Methods Between November 1999 and January 2004, 18 patients with a negative second-look and 1 patient with positive peritoneal cytology only with stage Ic–IIIc epithelial ovarian cancer received consolidation intra-operative HIPEC using paclitaxel. The HIPEC was performed with open-abdomen technique, using 6 L of lactated Ringer's solution containing paclitaxel 175 mg/m2, for 90 min in hyperthermic phase (43–44°C). The survival rates were compared with 24 patients treated with conventional therapy (control group). Results The 8-year progression-free survival rates were 63.16% in the HIPEC-paclitaxel group and 29.17% in the control group (P = 0.027). The 8-year overall survival rates were 84.21% in the HIPEC-paclitaxel group and 25.00% in the control group (P = 0.0004). The time interval between initial treatment and HIPEC was statistically significant with respect to progression-free and overall survival in the HIPEC-paclitaxel group. Conclusion HIPEC with paclitaxel during 2nd-look laparotomy is feasible and relatively safe and showed a good effect on survival. In patients with epithelial ovarian cancer who have a complete pathologic response, HIPEC with paclitaxel should be considered as a consolidation treatment option. J. Surg. Oncol. 2010;101:149–155. © 2009 Wiley-Liss, Inc.

Objective Clusterin expression has been associated with various malignancies. Endometrial carcinoma is divided into endometrioid and papillary serous type carcinoma according to the histological characteristics and regarding to the unopposed estrogenic stimulation. In this study, we investigated the expression profiles of clusterin according to the histological types and the effect of estrogen stimulation on its expression in endometrial carcinoma. Method Clusterin expression in endometrial carcinoma tissues was examined by RT-PCR, Western blot analysis, and immunohistochemistry. 63 endometrioid and 10 papillary serous types of fresh cases and 81 endometrioid and 7 papillary serous types of paraffin-embedded cases were studied. Regulation of clusterin expression by β-estradiol in HEC-1B and HEC-1A cells was investigated using RT-PCR and Western blot analysis. Cell proliferative function of clusterin was examined in 293T cells. Results We found higher expression of clusterin in endometrioid compared to papillary serous carcinoma using both immunohistochemistry ( p =0.033) and Western blot analysis ( p =0.024). The mRNA and protein expressions of clusterin in endometrioid carcinoma were higher than in benign endometrium ( p =0.002). Forced expression of clusterin promoted 293T cell survival in a concentration-dependent manner, and estradiol treatment increased clusterin expression in HEC-1B but not in HEC-1A cells. Conclusions These data suggest that clusterin expression is related to endometrioid carcinoma of endometrium, in which estrogen is involved in the regulatory network of clusterin.

Uterine leiomyomas (fibroids), the most common benign tumor in women of childbearing age, can cause symptoms including dysmenorrhea, menorrhagia, urinary symptoms, pain and infertility. Hysterectomy is a common approach to treating uterine fibroids, and less invasive surgical approaches such as myomectomy and uterine artery embolization also have been shown to alleviate symptoms. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is the only totally non-invasive surgical approved method for treating uterine fibroids. In clinical trials, MRgFUS resulted in significant relief of uterine fibroid symptoms. The safe and effective use of MRgFUS is affected by fibroid type and location, position relative to adjacent anatomical structures and the presence of co-existent pelvic disease. Additionally, successful outcomes with MRgFUS have been correlated with the volume of fibroids ablated during the procedure. Thus, selection of patients in whom sufficient fibroid volumes can be treated safely using the MRgFUS system is critical for successful outcomes. The MR images in this pictorial essay provide examples of uterine fibroids for which MRgFUS should be considered and is designed to facilitate the selection of patients for whom MRgFUS is most likely to provide sustained symptom relief.

Purpose The biallelic expression of insulin-like growth factor-II (IGF2) and H19 has been reported to be associated with the progression of several tumors. Here, the promoter usage and expression levels of IGF2 and H19 are reported to be altered in cervical and endometrial cancers showing loss of imprinting (LOI). Materials and methods The imprinting status of IGF2 and H19 was examined in 32 cervical carcinomas, their matched normal tissues, 13 endometrial cancer and 33 normal endometrial tissues. Results The LOI of IGF2 was observed in 7 of 18 (39%) and 1 of 13 (8.3%) informative cervical carcinomas and informative endometrial cancers, respectively. The LOI of the H19 gene was detected in 5 of 14 (36%) and in all 11 (100%) informative cervical carcinoma cases and informative endometrial cancer cases, respectively. The use of promoter P1 was observed in the LOI tumors of IGF2, but not in the tumors showing maintenance of IGF2 imprinting (MOI), or in cervical and endometrial cancers. Unlike MOI tumors, some LOI tumors revealed a lack of IGF2 transcription from the promoter P3. The LOI tumors of IGF2 showed increased expression of the IGF2 level, but a down-regulation of the H19, relative to normal tissues, whereas the MOI tumors revealed no significant alterations. Conclusion These results suggest that the promoter P1 could be involved in the biallelic expression of IGF2, and that the altered expression of the IGF2 and H19 levels might be associated with the progression of cervical and endometrial cancers that exhibit biallelic IGF2 expression.

Objectives To investigate and analyze the BRCA mutations in Korean ovarian cancer patients with or without family history and to find founder mutations in this group. Methods/Materials One hundred two patients who underwent a staging operation for pathologically proven epithelial cancer between January 2013 and December 2014 were enrolled. Thirty-two patients declined to analyze BRCA1/2 gene alterations after genetic counseling and pedigree analysis. Lymphocyte specimens from peripheral blood were assessed for BRCA1/2 by direct sequencing. Results BRCA genetic test results of 70 patients were available. Eighteen BRCA1/2 mutations and 17 unclassified variations (UVs) were found. Five of the BRCA1/2 mutations and 4 of the UVs were not reported in the Breast Cancer Information Core database. One BRCA2 UV (8665_8667delGGA) was strongly suspicious to be a deleterious mutation. BRCA1/2 mutations were identified in 11 (61.1%) of 18 patients with a family history and in 7 (13.5%) of 52 patients without a family history. Candidates for founder mutations in Korean ovarian cancer patients were assessed among 39 BRCA1/2 mutations from the present study and from literature reviews. The analysis showed that 1041_1043delAGCinsT (n = 4; 10.2%) and 3746insA (n = 4; 10.2%) were possible BRCA1 founder mutations. Only one of the BRCA2 mutations (5804_5807delTTAA) was repeated twice (n = 2; 5.1%). Conclusions The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified.

Objectives. To gain a better understanding of the genes involved in the pathogenesis of gestational trophoblastic diseases, we evaluated the genome-wide expression levels of genes in complete hydatidiform mole (H-mole) as compared to normal placenta using cDNA microarray technique. Methods. The expression profiles of complete H-mole tissues were compared with those of normal placenta using cDNA microarray technique. The data obtained from 10,305 human genes were normalized by the print-tip-based LOWESS method. Significance analysis of microarray (SAM) was used to identify genes with statistically significant changes in expression. The expression levels of genes which showed significant differences between normal early placenta and complete H-mole tissues were further confirmed by RT-PCR. Results. A cDNA microarray analysis consisting of 10,305 human genes revealed significant changes in the expression of 213 genes, with 91 genes being upregulated and 122 being downregulated. SAM revealed significant changes in gene expression, including those associated with signal transduction, cell structure, transcription, and apoptosis. Further RT-PCR analysis of altered gene expression in mole tissues supported the microarray analysis results. We confirmed the upregulation of TLE4, CAPZA1, PRSS25, RNF130, and USP1 in complete H-mole tissues. Moreover, our study provides the first evidence that ELK3, LAMA3, LNK, STAT2, and TNFRSF25 are downregulated in complete H-mole compared to normal early placenta tissues. Conclusions. These findings provide a large body of information regarding gene expression profiles associated with complete H-mole tumorigenesis and allow the identification of potential targets for tumor prevention or therapy.

In this paper, the virtual material characterization of three dimensional (3D) orthogonal woven composite materials is investigated by large-scale finite element analyses to predict the elastic properties. To numerically model the complex geometry of 3D orthogonal woven composites, a unit structure including the stuffer yarns, filler yarns, weaver yarns, and the resin region is generated based on direct numerical simulation (DNS) and the unit structures with the same pattern are assembled into an orthogonal woven composite structure composed of several millions of degrees of freedom. The influence of the geometrical irregularities, such as the inconsistent tow spacing and the waviness of the filler yarn, on the mechanical properties are also discussed by separately generating the yarns and the resin. From the numerical examples, it is shown that the pattern of tow distribution affects the shear modulus, and the direct modeling of the wavy yarns can produce more accurate stiffness knockdown. It is also emphasized that large-scale numerical analyses can be one of the methodologies sufficient for the material characterization of the orthogonal woven composites and can be more applicable in the realistic structure subject to complex loading compared to the unit cell approach.

Placental site trophoblastic tumour (PSTT) is a very rare and unique form of gestational trophoblastic disease (GTD). This tumour represents a neoplastic transformation of intermediate trophoblastic cells that normally play a critical role in implantation. PSTT can occur after a normal pregnancy, abortion, term delivery, ectopic pregnancy or molar pregnancy. It displays a wide clinical spectrum, and when metastatic, can be difficult to control even with surgery and chemotherapy. Unlike other forms of GTD, PSTT is characterized by low beta-hCG levels because it is a neoplastic proliferation of intermediate trophoblastic cells. Expression, however, of human placental lactogen (hPL) is increased on histologic section as well as in the serum. The most common presenting symptoms of PSTT are vaginal bleeding and amenorrhoea. Diagnosis is confirmed by dilatation and curettage (D and E) and hysterectomy but meticulous evaluation of metastasis is mandatory. Most cases are confined to the uterus but pelvic involvement, lung and other organ metastasis has been reported. Unlike other forms of GTD, the WHO prognostic score is of little help. For the PSTT patient, surgery is the primary treatment of choice. For patients desiring future childbearing, D and C and adjuvant chemotherapy is an option. Because these tumours tend to be less sensitive than other types of GTD to chemotherapy, the most successful regimen to date has been with EMA/CO or EMA/EP. Good prognosis is anticipated in cases localized to the uterus, and when the interval between antecedent pregnancy and treatment is less than 2 years. In cases with distant metastasis or delayed treatment, the outcome is dismal. Advances in chemotherapeutic regimens have improved clinical reponse in metastatic disease.

BACKGROUND Human papillomavirus (HPV) infection is considered to play an important role in the development of cervical carcinoma, and it is known that certain HPV types, such as HPV-16 and HPV-18, are highly associated with cervical carcinoma. However, the pathologic behavior of other HPV types remains unclear. Recently, a new HPV detection technique, the HPV DNA chip, was introduced. The HPV DNA chip harbors 22 HPV probes and has the advantage of being able to detect 22 HPV types simultaneously. To evaluate the quality of the HPV DNA chip method and to identify HPV types related to cervical carcinoma and precancerous lesions, the authors performed HPV typing in cervical specimens from 1983 patients and compared their cytologic and histologic diagnoses. METHODS The HPV DNA chip was used for HPV typing. Among 1983 patients who were tested for HPV types, cervical smear cytology was performed in 1650 patients, and 677 of those patients underwent cervical biopsy. RESULTS Among the 1650 smears that were examined cytologically, 92.7% (114 of 123 smears) of low-grade squamous intraepithelial lesions (LSILs), 98.1% (106 of 108 smears) of high-grade squamous intraepithelial lesions (HSILs), and 96.3% (51 of 53 smears) of carcinomas were HPV positive, compared with only 35.1% of smears with normal cytology that were HPV positive. HPV-16 was the most prevalent type (chi-square test; P < 0.01) in LSILs (28.5%), in HSILs (51.9%), and in carcinomas (62.5%) followed by HPV-58 and a group of low-risk types (HPV-6, HPV-11, HPV-34, HPV-40, HPV-42, HPV-43,and HPV-44) in LSILs. HPV-58 (15.7%), HPV-18 (6.7%), and HPV-52 (4.6%) were the next most prevalent types after HPV-16 in HSILs. HPV-18 (11.4%) and HPV-58 (11.4%) were the second most common types in carcinomas. HPV-58 had the highest positive predictive value (54.9%) for the detection of histologically confirmed HSIL or carcinoma, whereas HPV 16 had the highest negative predictive value (80.6%). The sensitivity (96.0%) of the HPV test using the DNA chip method for detecting HSIL or carcinoma was superior compared with the sensitivity of cytologic diagnosis (83.6%). CONCLUSIONS The HPV DNA chip provides a very sensitive method for detecting 22 HPV genotypes with reasonable sensitivity (96.0%) and reasonable negative predictive value (96.9%), and it overcomes the low sensitivity of cytologic screening for the detection of HSIL or carcinoma. HPV-58, HPV-52, and HPV-56, as well as HPV-16 and HPV-18, were associated highly with HSIL and carcinoma in the current large series. In addition, multiple HPV infection was associated less frequently with cervical carcinoma and with precancerous lesions compared with normal cytology. Cancer 2003;97:1672–80. © 2003 American Cancer Society. DOI 10.1002/cncr.11235

The purpose of this study was to evaluate the association of telomerase activity in complete hydatidiform moles with subsequent development of persistent gestational trophoblastic tumor.By means of the standard telomerase repeat assay, we examined telomerase activity in 4 normal placentas, 31 complete hydatidiform moles (16 cases of uneventful regression, according to serum levels of beta-human chorionic gonadotropin, after evacuation and 15 cases in which persistent gestational trophoblastic disease developed after evacuation), 7 invasive moles, and 5 choriocarcinoma tissue samples.Telomerase activity was detected in 13 of 15 (86.7%) complete hydatidiform moles in patients who eventually underwent chemotherapy for the treatment of persistent gestational trophoblastic tumors. All 9 patients with metastatic disease (International Federation of Gynecology and Obstetrics stage III) had telomerase activity in the initial molar tissue sample. In contrast, telomerase activity was evident in only 3 of 16 (12.5%) complete hydatidiform moles from patients with spontaneous remission after evacuation (P.05). Telomerase activity was detected in all 7 invasive moles and all 5 choriocarcinoma tissue samples but was not detected in normal placentas.The presence of telomerase activity in complete hydatidiform moles is associated with the development of persistent gestational trophoblastic tumors, such as invasive moles and choriocarcinoma.

Human papillomavirus (HPV) DNAs are often found to be integrated into the human genome in high-grade cervical intraepithelial neoplasia (CIN) as well as in invasive cervical cancers. Investigation of the relationship between the genomic status of specific HPV genes and their antibody responses to the virus-like particles (VLPs) of HPV-16 L1/L2 proteins and the in vitro translated HPV-16 E6 and E7 proteins may help to illustrate the mechanism of HPV-related cervical carcinogenesis and host immune response. Cervical cancer tissues obtained from 39 patients were studied to evaluate the physical status of HPV genes by Southern blotting, DNA-PCR, and RT-PCR of E2. The antibody response against the HPV-16 L1/L2 VLPs of serum specimens were tested by ELISA and the antibody response against the HPV-16 E6 and E7 proteins were tested by radioimmunoprecipitation assay (RIPA), respectively. Integrated forms of HPV-16 DNA were found in 23 of the 38 patients (60.5%). The HPV-16 positive cervical cancer patients showed a significantly higher prevalence rate (39.5%; 15/38) of antibodies to HPV-16 L1/L2 VLPs than that of the control group (8.7%; 2/28) (P0.05). Antibodies to HPV-16 L1/L2 VLPs were more commonly detectable in cervical cancer patients having the episomal form of HPV-16 DNA (pure episomal and mixed forms) (60%; 9/15) than in those who had only the integrated forms of HPV-16 DNA (26.1%; 6/23) (P0.05). Antibodies to E6 and E7 proteins were positive in 36.8% (14/38) and 50% (19/38) of the patients with HPV-16 positive cervical cancer, respectively. These were significantly higher than the positive rates for the control group (8.3% and 2.8%) (P0.05). The differences between sero-reactivities to E6 and E7 proteins in the patients with episomal forms of HPV-16 DNA and those with integrated forms of HPV-16 DNA were not statistically significant (P0.05). Integrated forms of HPV-16 DNA were prevalent in most patients with cervical cancer in Korea. Antibodies to HPV-16 L1/L2 VLPs, in vitro translated HPV-16 E6 and E7 proteins, appeared in a significantly larger proportion of the HPV-associated cervical cancer patients than in the controls. Antibodies to HPV-16 L1/L2 VLPs were more often detected in cervical cancer patients having the episomal form of HPV-16 DNA than in those having only integrated forms of HPV-16 DNA. Antibody responses to HPV-16 E6 and E7 proteins were not influenced by the different viral states.

Objective. The purpose of this study was to determine the independent risk factors for resistance to EMA/CO chemotherapy in gestational trophoblastic tumor (GTT), to develop a more accurate scoring system for the evaluation of high-risk GTT patients. Methods. We performed a retrospective study and reviewed 165 GTT patients who received the EMA/CO regimen. Among these patients, 27 showed resistance to EMA/CO. Results. According to the univariate analysis of risk factors, tumor age, initial human chorionic gonadotropin level, metastatic site, number of metastatic organs, unplanned operation, gravidity, and inadequate previous chemotherapy all showed statistical significance. However, the results of the stepwise–Cox proportional hazards regression of prognostic factors using multivariate analysis showed statistical significance for tumor age, number of metastatic organs, metastatic site, and previously inadequate chemotherapy. The results of the stepwise logistic regression of prognostic factors showed tumor age and number of metastatic organs as significant. According to the performance of the fitted logistic regression model, the accuracy of predicted death and survival was 80.5%. Conclusions. We determined that the following factors indicate a poor prognosis: (1) tumor age greater than 12 months, (2) number of metastatic organs greater 2, (3) incomplete previous treatment, including unplanned operation and inadequate chemotherapy. In patients with two and three of these factors, the death rates were 17.7 and 56.6%, respectively.

It is known that E2 protein of oncogenic human papillomavirus (HPV) inhibits the expression of E6 and E7 genes from their major promoters in vitro and suppresses the proliferation of cervical cancer cells. This suggests that the loss of functional E2 gene may provide selective advantages in the development of cervical cancer. Investigation of the relationship between the disruption of HPV-16/18 E2 genes by DNA integration and clinical outcome of cervical cancer may not only help to understand the mechanism of HPV-related cervical carcinogenesis, but may also provide novel management of cervical cancer. It was noted that integrated HPV-16/18 DNA was predominant in most patients with cervical cancers, marking 51 of a total of 68 cases (75%); episomal HPV DNAs were found in 5 cases (7.4%), and finally mixed forms of HPV DNAs with episome and integration were found in 12 cases (17.6%). Whole portions of E2 DNA of HPV-16 could be amplified by PCR in 19 (36.5%) of 52 cases of cervical intraepithelial neoplasia. It was shown that there was not statistically significant association with the different stages, but integrated HPV DNAs were detectable only in the patients with far-advanced stage of cervical cancers, which also means no episomal forms were detected. Episomal forms of HPV DNA were detectable in 14 (25.9%) of 54 squamous cell carcinomas (4 pure episomal forms and 10 mixed forms), whereas only 1 (8.3%) of 12 adenocarcinomas and adenosquamous cell carcinomas contained episomal viral DNA. When HPV DNA forms were compared with initial tumor size, lymphovascular space involvement, and frequency of nodal metastasis, statistically significant relationships were not found. The association of DNA integration with invasive cervical cancers was seen regardless of HPV type; however, there were differences between the integration profiles of HPV-16 and HPV-18 DNA. Of the 51 HPV-16-containing cancers, 36 (70.6%) revealed purely integrated HPV DNA, and another 10 cases (19.6%) displayed both integrated and episomal HPV DNAs. However, 5 (9.8%) cases showed only episomal copies of the HPV-16 genome. In contrast, all 17 HPV-18-containing cancers (5 cases positive for HPV-18 and 12 cases positive for both HPV-16 and -18) revealed only the integrated form of HPV-18 DNA. The expression of E6 and E7 transcripts of HPV-16/18 is uniformly correlated with the physical status of HPV DNAs. HPV E2 mRNAs were constantly expressed in the presence of the intact virus in cases with episome and mixed forms of HPV DNA. In general, amplified signals from HPV E2 RT-PCR are more intensive than those from DNA-PCR in the same patients. It is suggested that RT-PCR is a valuable method to evaluate dynamic expression of the specific gene and seems to be more sensitive than the DNA-PCR method in detecting intact E2 gene because of the gene copy numbers.

A cell line designated CUMO-2 has been established from an undifferentiated ovarian carcinoma. The s.c. injection of cells into nude mice gave rise to fast-growing tumors, while the i.p. route induced a peritoneal carcinomatosis with ascites. Histopathologically, the transplanted s.c. tumors closely resembled the original tumor, but tumors developed in the peritoneal cavity were highly anaplastic. The epithelial nature of the cells was confirmed by ultrastructural analysis. Sequential cytogenetic analyses on early and late passages revealed highly aneuploid tumor cells with consistent structural aberrations of chromosomes 1, 3, 8 and 11. CUMO-2 cells were found to produce CA 125 in vitro and in vivo. Cytosol estrogen receptor (ER) was found but progesterone receptor (PR) was not measured. HLA typing indicated the presence of DR8 and DQw4. A gonadotropin-releasing hormone (Gn-RH) analog inhibited cell growth and Gn-RH receptor mRNA was detected by reverse transcription/polymerase chain reaction in this cell line. Administration of transforming growth factor beta 1 inhibited both cell growth and c-myc mRNA expression. This cell line demonstrated a conformational band shift in exon 7 of the p53 gene. It was a frameshift mutation.

Objective We evaluated the effectiveness of photodynamic therapy (PDT) as a conservative fertility-sparing treatment in young women with early-stage endometrial cancer. Methods We reviewed the medical records of patients with endometrial cancer who had been treated with PDT. Of the patients with endometrioid adenocarcinoma, we included those younger than 35 years and in whom the lesion was confined to the endometrium. Surface photoillumination with red laser light at a wavelength of 630 nm was applied to the uterine endometrial cavity and endocervical canal of patients 48 hours after an intravenous injection of 2 mg/kg of photosensitizer. Complete response was pathologically defined as the complete disappearance of adenocarcinoma or hyperplastic tissue. Results Sixteen patients were included in the study. Their mean age was 30.7 years, and the mean body mass index was 24.6 kg/m2. The mean follow-up period was 78 months. Photodynamic therapy was used in 11 patients as primary treatment and in 5 patients as secondary treatment for recurrence after primary hormonal therapy. Complete remission was observed in 12 (75%) of the 16 patients. Of these 12 patients, 4 experienced recurrence (33%). Two of the 4 patients who experienced recurrence showed complete remission after the next course of PDT, and 1 of the 4 nonresponders also showed complete remission after the second course of PDT. The final response rate was therefore 68%. Of the 7 women who attempted to get pregnant, 4 had 7 successful pregnancies (57%, 4/7), resulting in 6 live births. No tumor-related deaths or PDT-related severe adverse effects were noted. Conclusions Photodynamic therapy can be an effective conservative treatment method for fertility sparing in young patients with early-stage endometrial adenocarcinoma.

The presence of oncogenic HPV DNAs (HPV-16/18) in cervical carcinomas and their normal and metastatic pelvic lymph nodes and the expression patterns of proliferating cell nuclear antigen (PCNA) in cervical carcinomas were retrospectively studied to elucidate the possible roles of them in malignant transformation and progression of the disease. HPV-16/18 DNAs were detected by polymerase chain reaction using HPV E6 type-specific primers in 79 patients with cervical cancer: 31 patients who had pelvic lymph node metastasis (group I) and 48 patients without pelvic lymph node metastasis (group II) who were proven by pathologic examination of surgical specimens. HPV-16 or -18 DNAs were detectable in cervical carcinoma tissues in 60 patients from 79 cervical cancer patients (75.9%; HPV-16 was 67.1% and HPV-18 was 8.9%). HPV DNAs were amplified from metastatic pelvic lymph nodes in 13 patients of group I (42%) and from nonmetastatic lymph nodes in 7 group I patients (22.5%). Recurrence was identified in 9 group I patients (29.0%) in 3 years of follow-up. HPV DNAs were amplified from nonmetastatic lymph nodes in 11 group II patients (22.9%). Two group II patients, who had HPV-16 DNA by PCR in nonmetastatic nodes, were recurrent. PCNA was overexpressed in 66.7% of HPV-16- or -18-positive cervical cancers and 16.7% of HPV-16- or -18-negative cervical cancers. However, the expression levels of PCNA in cervical cancers were not influenced by the presence of oncogenic HPV DNA or pathologic metastasis in the pelvic lymph nodes. In conclusion, HPV DNA could be amplified from some metastatic and nonmetastatic pelvic lymph nodes and the detectability of oncogenic HPV DNA in pelvic lymph nodes may represent the poor outcome in the treatment of disease. The expression of PCNA protein which was associated with presence of oncogenic HPV DNAs in cervical cancers, suggesting activation of S phase of cell cycle, may contribute to the malignant progression by HPV-16 or -18.

Ninty-two patients with locally advanced stages IB, IIA, and IIB cervical cancers, who had completed 4 years of follow-up after treatment with preoperative adjuvant chemotherapy prior to radical surgery, were compared with 138 patients in same disease status who were treated with radical surgery without preoperative adjuvant chemotherapy. In the patients treated with preoperative adjuvant chemotherapy (VBP scheme), the chemotherapeutic response was more favorable in squamous cell carcinomas (87%) than that in adenocarcinomas (38%). The detection rate of pelvic lymph node metastasis from the surgical specimens of radical operation was higher in the patients of radical surgery without preoperative chemotherapy (34%; 47/138) than that in the preoperative adjuvant chemotherapeutic patients (17%; 16/92, P = 0.005). Recurrence occurred in 50 of 138 patients (35.5%) who were treated by radical surgery without preoperative chemotherapy and in 17 of 92 patients (18.5%) who were treated with preoperative adjuvant chemotherapy followed by radical surgery. The difference of recurrence rate between two groups was statistically significant ( P = 0.004). The tumor-free survival of preoperative adjuvant chemotherapeutic patients was significantly longer than those in the patients without preoperative chemotherapy ( P = 0.0067). Tumor response to chemotherapy was a valuable prognostic factor in management of patients and preoperative adjuvant chemotherapy was beneficial in reducing pelvic lymph node metastases, reducing recurrences, and prolonging the survival of the patients with locally advanced cervical cancers, especially in stage IIA.

By employing neoadjuvent chemotherapy (NCT) before radical hysterectomy (RS) and pelvic radiotherapy (RT) in bulky locally advanced cervical cancer (IB, IIA, IIB), the study was focused to update the results of the author's therapeutic experience with multimodal treatment by observing tumor free survivals along with related prognostic factors in different treatment modalities with NCT. The chemotherapy regimen for induction is composed of Vinblastin, Bleomycin and cis-Platin regimen (VBP). The effect of neoadjuvent chemotherapy was evaluated by the WHO definition of clinical response (CR, PR, ST, PG). As a result of NCT study in the stage IA, IIA, and IIB cervical cancer patients recurrence occurred in 50 out of 138 patients (35.5%) treated with radical hysterectomy only (RS) compared with 17 out of 92 patients (18.5%) treated with NCT followed by radical surgery. In conjunction with the NCT study in the cervical cancer, another two groups of patients who were treated by neoadjuvent chemotherapy followed by radical hysterectomy (NCST) and adjuvent radiation (NCSRT) were evaluated in the high-risk patients of cervical cancer with stage IB, IIA, and IIB. Primary responses in the NCST group (n = 61) were CR (68.9%), PR (22.9%), ST (4.9%) and PG (3.3%) respectively, while the chemoresponse of the NCSRT group (n = 101) were CR (65.3%), PR (18.9%), ST (4.9%) and PG (10.9%), respectively. The survival rates of the NCSRT group (n = 101) were 100% in all 1-5 years in CR group, while the rate of the NCST group was 100% at 1 year and 98.5% at 5 years in the CR group of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

E6 and E7 proteins, the transforming proteins of oncogenic HPVs, are known to be associated with the occurrence of cervical cancer. In radioimmunoprecipitation assays in which in vitro-transcripted and translated HPV-16 E6 and E7 proteins were used, patients with HPV-16-associated invasive cervical cancer (group I) had greater seroreactivity than patients in most of the other groups, including patients with invasive cervical cancer who were infected with other types of HPVs (group II), cervical cancer patients with nondetectable HPVs (group III), patients with HPV-16-associated cervical intraepithelial neoplasia (group IV), and unaffected normal controls with noncervical lesions (group V) (P < 0.05). The sera of patients in group I, when compared with the sera of other groups, were significantly reactive with one and/or two proteins (P < 0.05). Antibodies to HPV-16 E6 and E7 proteins were detected in patients with invasive cancer more than in those with CIN. The positive rates for E6 protein were 4.2% (1/24), 43.8% (7/16), 57.1% (8/14), 100% (5/5), and 100% (1/1), and the positive rates of E7 protein were 4.2% (1/24), 12.5% (2/16), 35.7% (5/14), 60% (3/5), and 100% (1/1) from CINs through stages I, IIa, IIb, and III of HPV-16-associated cervical cancers, respectively. The positive rates for E6 and E7 proteins were significantly increased with the advancing of the clinical stages of cervical cancer (P < 0.05 for E6 and E7). To examine the change in antibody titers of HPV-16 E7 protein during diagnosis, treatment, and follow-up, we tested serial serum samples from 14 patients of group I. The antibody titers were correlated to the clinical course of disease in some cases. The positive levels of E7 antibody were decreased when the treatment was effective, but in 1 patient who had shown recurrence or progression, positive seroreactivity was maintained. Antibodies to HPV-16 E6 and E7 proteins might be effective virus-specific and disease state-specific markers of HPV-16-associated cervical cancer.

The histopathologic features of cervical dysplasia (20 cases) and cervical carcinoma (15 cases) in Korean women were correlated with the presence of human papillomaviruses (HPVs) as determined by polymerase chain reaction technology on paraffin-processed specimens. A segment of the E6 open reading frame of several HPV types (HPV 6, 11, 16, 18, 31, 33, and 35) was amplified using primers which were synthesized to contain 50% G + C, in order to give optimum annealing for the amplification of HPVs. All specimens were also tested for amplification of the cellular β-globin gene. HPV was found in 19 (54%) cases. The HPV types were HPV 6 in 1 case (3%), HPV 16 in 15 cases (43%), HPV 18 in 2 cases (6%), and HPV 33 in 3 cases (9%). HPV was identified in 16 of 25 (64%) β-globin-positive and 3 of 10 (30%) β-globin-negative tissues. HPV types 11, 31, and 35 were not detected in any of the specimens. HPV 6, 18, and 33 were detected only in preneoplastic lesions, and co-infection with these three viruses was observed in one case of severe dysplasia. HPV type 16 was found in 8 (40%) premalignant lesions and in 7 (47%) invasive carcinomas. These data indicate that HPVs are found along the entire spectrum of cervical neoplasia. HPV 16 was the predominant virus in invasive cancer of the cervix.

Microsatellite instability (MSI) has been reported in 25% to 45% of sporadic endometrial carcinoma. The clinicopathologic and molecular characteristics of MSI-high phenotype in colorectal and gastric carcinomas have been widely investigated; however, the clinicopathologic impact of MSI on endometrial carcinomas remained unclear. This study was performed to determine the clinicopathologic and molecular significance of MSI in endometrial carcinomas. We analyzed the MSI status using National Cancer Institute-recommended 5 microsatellite markers, and the immunohistochemical profiles of various regulatory proteins of cell cycle and apoptosis using tissue microarray in 100 endometrial carcinomas. The results were compared between MSI-high and MSI(-) groups as for the traditional clinicopathologic prognostic parameters and the immunoreactivities of various regulatory proteins. We especially focused on the endometrioid type adenocarcinoma to exclude the bias from nonendometrioid type adenocarcinomas with more aggressiveness and a close association with MSI(-) phenotype. The incidence of MSI-high phenotype was significantly higher in endometrioid type than in nonendometrioid serous type (20% vs. 0%, P

World Wide Web is nearly ubiquitous and the tremendous growing number of Web information strongly requires a structuring framework by which an overview visualization of Web sites has provided as a visual surrogate for the users. We have a viewpoint that the Web site is a directed graph with nodes and arcs where the nodes correspond to Web pages and the arcs correspond to hypertext links between the Web pages. In dealing with the WWW, the goal in this paper is not to derive a naive shortest path or a fast access method, but to generate an optimal structure based on the context centric weight. We modeled a Web site formally so that a linear programming model can be formulated. Even if changes such as modification of the query terms, the optimized Web site structure can be maintained in terms of sensitivity.

Objectives. To evaluate the clinical effect of intraperitoneal hyperthermic chemotherapy (IPHC) in ovarian cancer patients. Patients and methods. We retrospectively reviewed 117 stages Ic–III ovarian cancer patients, who were diagnosed at the Gynecology Department of Kangnam St. Mary's Hospital between January 1994 and January 2000. Of these, 57 patients underwent cytoreductive surgery (conventional treatment) with IPHC and 60 patients (control group) underwent conventional treatment only. IPHC consisted of administering a mixture of 350 mg/m 2 of carboplatin and 5,000,000 IU/m 2 of interferon-α, and maintaining the intraperitoneal temperature at 43–44°C during surgery. Results. The overall 5-year survival rate was 58.6%; that of the IPHC group was 63.4% vs. 52.8% in the control group, with significantly higher survival in the IPHC group ( P = 0.0078). Considering stage III ovarian cancer patients only ( n = 74), the survival rate was 53.8% in the IPHC group ( n = 35) and 33.3% in the control group ( n = 39) and was significantly higher in the IPHC group ( P = 0.0015). For stage III ovarian cancer patients whose tumor was reduced to less than 1 cm during a second procedure ( n = 53), the 5-year survival rate was 65.6% in patients who underwent IPHC ( n = 26) and 40.7% in the control patients ( n = 27) ( P = 0.0046). IPHC was an independent prognostic factor that was not affected by surgical staging, tumor size after second surgery, or patient age, according to a multivariate analysis (Hazard ratio=0.496, P = 0.0176). Conclusion. Our study suggests that IPHC is a promising new treatment modality in ovarian cancer.

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Objective. The YY1 mutation has been suggested as one of the indicators that explains development of cervical neoplasia by episomal-type HPV. To extend this hypothesis, we examined whether a mutation(s) in the YY1 site is functionally related to the invasiveness of cervical neoplasia and the physical status of HPV DNA. Methods. The URR sequences were obtained by PCR amplification of HPV-16 genome from CIN and invasive cancer patients and cloned into pUC18 for sequencing and into pBLCAT8+ for functional CAT assay. Results. Our previous data classified HPV-infected patients into three groups: 3 cancer cases carrying episomal HPV DNA; 12 cancer cases carrying integrated HPV DNA; 12 CIN cases carrying episomal HPV DNA. The specific variants in HPV-16 URR were found in Korean women: G→A transition at nt 7520 (100%, 27/27), A→C transition at nt 7729 (70%; 19/27), and G→A transition at nt 7841 (78%; 21/27). Selective mutations were observed at the YY1 binding sites of HPV-16 URR in the 3 patients with invasive cervical cancer who have the episomal forms of HPV-16 DNA: A→C transition at nt 7484 and G→A transition at nt 7488 (YY1-binding site 2; from 7481 to 7489). Additionally, C→T transition at nt 7785 (YY1-binding site 3; from 7781 to 7790) was found in 2 of 3 patients. No YY1 site mutations were detected in the 12 CIN patients and in the HPV-integrated invasive cancer patients. To determine whether these mutations have effects on the expression of HPV E6/E7 genes driven by URR, the transient transfection assay was employed using URR-CAT reporter plasmid. The relative activities of three URR mutants from episomal HPV-16 DNA of cervical cancers were two- to fourfold higher than that of the HPV-16 URR prototype. In contrast, the URRs from integrated HPV-16 DNA in cervical cancer and from episomal HPV-16 DNA in CIN, where no mutation of the YY1 binding site was detected, showed similar levels of promoter activity to that of the URR prototype. Conclusions. Our results support the hypothesis that the mutation at the YY1 binding site is functionally related to the development of cervical neoplasia caused by episomal HPV-16 DNA in Korean cervical cancer patients. Thus, mutation in the YY1 site of episomal HPV-16 URR may play a corresponding role of HPV integration in the progression of cervical cancer.

The p16 gene was identified as cyclin-dependent kinase inhibitor (CDKI) and this may negatively regulate the cell cycle by acting as a tumor suppressor. Using tissue microdissection, the molecular changes at p16 and Rb genes were analysed in the spectrum of disease from dysplasia to invasive cancer of the uterine cervix. Six of 27 (22%) cases informative for D9S171 and IFNA of 9p21-22 marker (p16INK4a) showed loss of one or both alleles in at least one of these loci. LOH of pRb was detected in 29% (5/17). Gene alterations at p16 and pRb loci were only detectable in some cases of HPV-16/18 DNA positive cervical cancer. Three cases demonstrated mutational changes of p16INK4a, and the alterations were determined to be G to T shift, suggesting transitional missense mutation. In summary, the inactivation of the p16/cdk-cyclin/Rb cascade may play an additional role during the malignant progression in HPV-16/18 positive cervical cancers.

Purpose. The purpose of this study was to evaluate reproductive performance of patients with gestational trophoblastic disease (GTD) after completion of treatment and follow-up periods. Patients and methods. Subjects comprised 115 patients who became pregnant after having been judged completely cured after a follow-up period of at least 1 year. There were 77 hydatidiform-mole patients who had a natural cure and 38 gestational trophoblastic tumor patients who were cured after chemotherapy. We studied these patients with respect to parameters concerning pregnancy outcome. Results. Average age at first pregnancy was 28.0 and average number of past deliveries was 1.3. After a 1-year contraception period, the average time to the next pregnancy was 0.8 year, with 59 of 115 (51.3%) women becoming pregnant within 1 year after pregnancy was permitted and 98 women (85.2%) conceiving within 3 years. Results of the pregnancies after cure of GTD did not deviate from normal ranges in separated analyses of complete mole (CM), partial mole (PM), and gestational trophoblastic tumor. Rate of repeat mole was found to be high, occurring in 5 of 115 (4.3%) cases. Rates of antepartum and postpartum complications did not deviate from normal ranges, and there was nothing peculiar about the neonatal sex and weight. Conclusion. GTD and chemotherapy rarely affect later pregnancies; however, the rate of repeat mole is relatively high.

Recently, a variety of HPV-related proteins have been synthesized and their utility as diagnostic and prognostic markers in cervical cancers needs to be assessed. The ability to generate preparative amounts of HPV-16 L1/L2 VLPs and E6, E7 proteins may have implications for the development of a serologic assay to detect anti-HPV-16 virion immune responses. The purpose of the study is to improve the way of proper management of the cervical cancer by investigating the utility of the recently developed HPV-16 L1/L2 VLPs, HPV-16 E6, E7 proteins as the clinical serologic markers through antibody reactions by comparison with those of SCCA and CEA which have been used as tumor markers for cervical cancer.The serologic responses in Korean women with cervical neoplasia by ELISA using HPV-16 L1/L2 VLPs and radioimmunoprecipitation assay (RIPA) using in vitro translated HPV-16 E6, E7 proteins were investigated. PCR using E6 type-specific primers for HPV-16/18 was used to determine the presence and type of HPV infection (normal controls, 15 cases; preinvasive lesions, 28 cases; invasive cervical cancers, 124 cases).The sera of 34% (42/124) of cervical cancers were positive for SCCA and the sera of 18% (22/124) of cervical cancers were positive for CEA. The positivity of SCCA was increased with advancing clinical stages, but the antibody levels were not correlated with clinical stage of disease. The sera of 7% (1/15) of normal controls, 39% (11/28) of preinvasive lesions, and 56% (70/124) of patients with cervical cancer were ELISA positive for HPV-16 L1/L2 VLPs (P0.05). The sera of 7% (2/28) of preinvasive lesions and 51% (63/124) of cervical cancers were positive for in vitro translated HPV-16 E6 protein (P0.05) and the sera of 11% (3/28) of preinvasive lesions and 33% (41/124) of cervical cancers were positive for in vitro translated HPV-16 E7 protein (P0.05). The antibody levels to HPV-16 E7 protein were correlated to clinical stage and tumor burden in a significant number of cervical cancers.These data suggest that a considerable number of patients with cervical neoplasia generated positive antibody response to L1/L2 VLPs and in vitro translated E6, E7 proteins of HPV-16. These HPV-16-associated proteins might be disease-specific markers which could be useful in an adjunctive diagnostic assay and a seroepidemiologic study of HPV-related cervical neoplasia. In particular, the monitoring of antibody to HPV-16 E7 protein seems to be valuable in the proper management of cervical cancers for specific tumor markers.

Sixty-seven patients with squamous cell carcinoma of the uterine cervix (FIGO Stages IB2, IIA, and IIB) were reviewed to evaluate the pretreatment level of squamous cell carcinoma antigen (SCC) and carcinoembryonic antigen (CEA) which may be used to predict a subset of patients with poor prognosis. The rate of pathologic pretreatment serum level of SCC increased significantly in cases with Stage IIB compared to that of Stages IB2 and IIA (50% versus 16.3%). The rate of pathologic pretreatment serum level of CEA did not show any difference between these two groups (29.2% versus 30.2%). The 48-month disease-free survival for patients with pathologic pretreatment serum levels for one or both tumor-associated antigens (TAAs) was 40.0% versus 91.7% for patients with normal levels (log-rank test, P < 0.005) in Stages IB2 and IIA. Patients who had a pathologic pretreatment serum level for one or both TAAs showed higher incidence of lymph node metastasis than patients with normal levels (36.7% versus 10.8%). The patients who had pathologic pretreatment serum levels for both TAAs and lymph node metastasis have the poorest prognosis. The pretreatment serum levels for one or both TAAs make it possible to predict the clinical response to neoadjuvant chemotherapy consisting of cis-platinum (DDP) and 5-fluorouracil (5-FU). Our findings suggest that pretreatment of SCC in conjunction with CEA is a valuable tumor marker to predict the prognosis of squamous cell carcinoma of the uterine cervix and to foresee a clinical response to subsequent neoadjuvant chemotherapy.

Epidemiological studies have shown that chronic inflammation predisposes individuals to different types of cancer and that microbial infections can trigger chronic inflammation. Porphyromonas gingivalis is a major microbial pathogen in periodontitis, which is a chronic inflammatory condition of the oral cavity and one of the most common infectious diseases. In this study, we examined the effect of P. gingivalis on oral cancer cells to define the role of chronic periodontitis on the development and/or progression of oral cancers. P. gingivalis-infected cells showed reduced proliferation rates and a concomitant G1 arrest compared with non-infected cells. One mechanism through which P. gingivalis blocked cell cycle progression in oral cancer cells was through ROS production, which induced autophagy. We conclude that the suppression of cell proliferation and cell cycle progression through autophagy may serve as an alternative to apoptosis to eliminate transformed cells. Autophagy represents a survival strategy against environmentally stressful conditions, such as the pathogenic invasion of P. gingivalis, and the prolonged survival of P. gingivalis-infected cells may contribute to the malignant progression of oral cancer cells. Citation Format: Tae Jin Cho, Vok Hee Woo, Jeom Il Choi, Seung Jo Kim, Hong In Shin, Bong Soo Park, Dae Geun Park, Hae Ryoun Park. Porphyromonas gingivalis-induced autophagy suppresses cell proliferation through G1 arrest in oral cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B13.

The developed or less developed countries where basic conditions for the screening of cervical cancer are quite different in terms of essential factors such as accuracy of cytology, cost effectiveness and development of new methods of diagnosis. Considering these factors the screening program made by annual Pap smear with adjunctive cervicography and HPV DNA test in the women aged from 20 to 69 years may have universal validity.

The quality of a plastic product is determined by the material used, the mold design, and the processing conditions. The objectives of a mold design consist of a mold cooling system, a runner system, and associated gate locations with their types and sizes, and cavity design. Meanwhile, the most important processing conditions during the fill phase are the mold temperature, the melt temperature, and the filling time. In this paper, we use genetic algorithm to optimize molding conditions, which consist of the mold temperature, the melt temperature, and the filling time, based upon the results from flow simulation.

Objectives: This study was to investigate the adjunctive diagnostic utility of HPV fusion proteins from the sera in the patients with cervical neoplasia. Immunologic researches on host factors in HPV infection could contribute to better understanding of patho-physiologic mechanisms of cervical carcinogenesis, and provide valuable informations for HPV vaccine development. Methods: Prevalence of antibodies against human papillomavirus (HPV) in sera of the patients with carcinomas (n = 81), precancers (n = 25) of uterine cervix and normal controls (n = 40) in Korean women were investigated by Western blot immunoassay using partially purified TrpE fusion recombinant proteins for HPV-6b and HPV-16. Results: In 81 patients with cervical cancer, 15 (19%) and 54 (67%) patients were positive for antibodies to at least one of the tested recombinant proteins related to HPV-6b or HPV-16, respectively. And in 25 patients with HPV-related squamous intraepithelial lesion (SIL) of cervix, 10 were positive for at least one of the tested antibodies for HPV-6b gene products (40%) and 11 were positive for HPV-16 related antibodies (44%). The prevalence rates of antibodies for HPV-6b in the sera of SIL patients were significantly higher than those from the sera of cervical cancer patients (p < 0.05). There was an inverse correlation between increasing the positivity against HPV-16 E6 protein and progression of cervical lesions, but there was no significant correlation between the positivities of the other antibodies to HPV-16 and the severity of disease. Conclusion: These results suggest that the recombinant proteins related to HPV-6b and HPV-16 could be useful in evaluation of the patients with HPV-related cervical lesions and these might play an adjunctive role in diagnosis and management of cervical neoplasia.

The purpose of this study is to evaluate the MR findings of gestational trophoblastic tumors (GTTs). Ten patients who confirmed the diagnosis (4 choriocarcinomas and 6 invasive moles) constituted the basis of our study. The MR findings from these patients were prospectively correlated with the histopathology of resected tumor specimens. MR findings of 4 patients with choriocarcinomas were well-defined, hemorrhagic masses with central necrosis. In contrast, 6 patients with invasive moles showed ill-defined, permeative masses with densely enhanced solid components and tiny cystic lesions. The trophoblastic proliferation, coagulation necrosis, and molar villi had varying signal intensities on T1- and T2-weighted images. Our results suggest that MR imaging is a promising tool for noninvasive morphologic analysis of GTTs.

This report discusses a pregnancy case following a series of two consecutive magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) procedures for the treatment of two different myomas in an individual patient. Both procedures were completed without adverse events, and the patient conceived naturally four months after treatment. At 39 weeks, she gave birth to a healthy baby girl, via a vaginal delivery. There were no complications in the pregnancy or during labor.

Objective To report a successful treatment of symptomatic adenomyosis using magnetic resonance–guided focused ultrasound surgery (MRgFUS). Design Case study. Setting General hospital. Patient(s) A 47-year-old premenopausal woman with focal symptomatic adenomyosis. Intervention(s) MRgFUS. Main Outcome Measure(s) Score on the Uterine Fibroids Symptoms Quality of Life (UFS-QOL) questionnaire and the degree of menstrual pain. Result(s) Uterine Fibroids Symptoms reduced from 53 to 28 and the degree of menstrual pain reduced from 10 to 5. Conclusion(s) For adenomyosis patients who wish to preserve their uterus, MRgFUS may be a promising alternative to hysterectomy. Additional studies of the safety and efficacy of MRgFUS in this indication should be conducted.

Objective : To establish the use of a HPV oligo-DNA chip for early diagnosis and prognosis assessment in cervical cancer. Methods : HPV PCR general primers and a oligo-DNA chip have been constructed by using HPV genomic sequences on the webs and computer programs. With a total of 344 random cervical scrapes, their efficacies were explored based on pathology. Results : All subjects (n=48) with diagnosis of low squamous intraepithelial lesion (LSIL) were positives for both HPV PCRs and oligo-DNA chip tests, whereas 44 out of 286 subjects (264 cases of NIL and 22 cases of ASCUS) were detected HPV positives. The proportion of each genotypes in HPV positive subjects were 38.0% (HPV-16), 16.3% (HPV-58), 9.8% (HPV-52) and 35.9% (others). Conclusion : This study gives favorable result to establish a novel method using HPV oligo-DNA chip with PCR general primers, based on the clinical trials in random subjects although the scale is small in size. In the future, a diverse of comparative and systematic clinical studies should be followed.

Objective : The purposes of this study are to determine the effectiveness of photodynamic therapy(PDT) and to compare the effectiveness between PDT and LEEP in the management of cervical intraepithelial neoplasia. Materials and Methods : A comparative study of 52 young women with cervical intraepithelial neoplasia at Comprehensive Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Pochon CHA University Medical College from May 2002 to August 2003,was followed up more than 6 months. All of 52 cases had Pap smear, punch biopsy, cervicogram, HPV test before and after management. 26 cases were treated with PDT. 26 cases were treated with LEEP, All PDT-treated cases received (2mg/kg) I.V. and a diode laser(Ceralas PDT, ceramoptec GmbH, Bonn Germany) providing light at 635 nm with total light dose of 150 J/cm2 at 48 hours. Clinical characteristics between two group had statistically no difference. Student T-test and -test were used to compare the effectiveness between PDT and LEEP. Results : Cure rate of cervical intraepithelial neoplasias was 92.3% in photodynamic therapy group, and 96.0% in the LEEP group. Eradication of HPV infection was 83.3% in photodynamic therapy group and 81% in the LEEP group. Postoperative complications were tolerable in photodynamic therapy group. Conclusions : The cure rates and eradication of HPV infection of photodynamic therapy were comparable with LEEP in the management of cervical intraepithelial neoplasias. The photodynamic therapy may be an alternative method for selective tissue destruction to preserve fertility in the management of cervical intraepithelial neoplasia.