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Connective tissue growth factor (CTGF; also known as CCN2) is an inflammatory mediator that is abundantly expressed in osteoarthritis (OA). Interleukin-1β (IL-1β) plays a pivotal role in OA pathogenesis. Berberine exhibits an anti-inflammatory effect, but the mechanisms by which it modulates CCN2-induced IL-1β expression in OA synovial fibroblasts (OASFs) remain unknown. We showed that CCN2-induced IL-1β expression is mediated by the activation of αvβ3/αvβ5 integrin-dependent reactive oxygen species (ROS) generation, and subsequent activation of apoptosis signal-regulating kinase 1 (ASK1), p38/JNK, and nuclear factor-κB (NF-κB) signaling pathways. This IL-1β expression in OASFs is attenuated by N-acetylcysteine (NAC), inhibitors of ASK1, p38, or JNK, or treatment with berberine. Furthermore, berberine also reverses cartilage damage in an experimental model of collagenase-induced OA (CIOA). We observed that CCN2 increased IL-1β expression via αvβ3/αvβ5 integrins, ROS, and ASK1, p38/JNK, and NF-κB signaling pathways. Berberine was found to inhibit these signaling components in OASFs in vitro and prevent cartilage degradation in vivo. We suggest a novel therapeutic strategy of using berberine for managing OA., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We prepared hybrid organogels, where single walled carbon nanotubes (SWNTs) were incorporated into organogel fibers. The SWNTs were covalently functionalized with organic branches that had a similar structure to the organogelator. The effect of relative interactions between the carbon nanotubes (CNTs), organogelator, and solvent molecules on the hybrid organogel structure was investigated. Compounds 1 and 2 were synthesized from 3,4,5-tris(decyloxy)benzoic acid and 1,8-diaminooctane, as an organogelator and a functional group for SWNTs, respectively. Organogelator 1 showed excellent ability to gelate alkanes and alcohols. The pristine SWNTs were oxidized by acids to create carboxylic acid groups and functionalized covalently with compound 2 using thionyl chloride. Hybrid organogels of compound 1 with functionalized SWNTs (f-SWNTs) were prepared in decane and N,N-dimethylformamide (DMF). Transmission electron microscopy (TEM) images showed that the f-SWNTs in the hybrid organogel formed in decane were mainly located inside or on the surface of the organogel fibers, while the f-SWNTs in the hybrid organogel formed in DMF were distributed evenly over the sample. When an organogelator had a different chemical structure to that of an organic functional group on the SWNT surface, SWNTs existed as large aggregates, or long bundles, which were not incorporated inside of the organogel fibers., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: To evaluate the toxicity and efficacy of a newly developed topoisomerase I inhibitor, CKD-602 in second-line therapy of ovarian cancer., Methods: We enrolled 24 patients with recurrent ovarian cancer, of median age 54 years (range, 39-64). Eleven patients had measurable lesions on CT scan, and the other 13 had increased serum CA-125 levels. Eighteen patients had platinum-sensitive disease (minimum treatment free interval > or =6 months) and 6 had platinum-resistant disease (minimum treatment free interval <6 months). CKD-602 (0.5 mg/m(2)/day) was administered intravenously for 5 days every 3 weeks. The median number of courses per patient was 6 (range, 1 to 12). Response was evaluated by the evaluation of the size of the mass by CT scan and CA-125 response., Results: The overall response rate was 45.0% (9/20), with 4 patients exhibiting partial responses and 5 patients exhibiting 75% CA-125 responses in 20 evaluable patients. Of the 9 responsive patients, 8 were platinum-sensitive (8/15, 53.3%) and 1 was platinum-resistant (1/5, 20.0%). An additional 5 patients showed stable disease, whereas 6 patients exhibited progressive lesions. Of 24 patients, the most common toxicity was hematological, with grades 3 or 4 neutropenia developing in all 24 patients (100%) and in 94 cycles (71.7%). Grade 3 thrombocytopenia developed in 4 patients (16.7%) and 6 cycles (4.6%). None of the patients experienced grades 3 and 4 gastrointestinal toxicities, including nausea, vomiting, and anorexia., Conclusions: The newly developed topoisomerase I inhibitor, CKD-602, showed activity against both platinum-sensitive and -resistant ovarian cancer, with acceptable toxicity.

Objectives: The objectives of this study are to analyze the clinical feature and overall survival rate of patients with brain metastases from epithelial ovarian cancer (EOC) and to compare the treatment outcomes of gamma-knife radiosurgery (GKS) and whole-brain radiation therapy (WBRT)., Methods: A retrospective chart review of patients diagnosed with brain metastases from EOC in a single institution between 1983 and 2005 was performed. Of 1413 patients with EOC, 18 (1.3%) developed brain metastases. Fifteen patients who were treated with GKS or WBRT were enrolled for this study. Seven patients were treated with GKS, and the remaining patients were treated with WBRT as a primary treatment modality., Results: The median age at the time of diagnosis of the primary cancer and brain metastases was 55 and 56 years, respectively. The median interval between the diagnosis of the primary cancer and brain metastases was 28 months. It was significantly associated with the overall survival rate after the diagnosis of ovarian cancer (p=0.017). There were 5 patients (33.3%) with extracranial metastases. Five patients (33.3%) had a solitary brain lesion. The median survival time after the diagnosis of brain metastases was 14 months (range, 1-59 months). Patients who were treated with GKS after brain metastasis had a longer survival time (median, 29 months) than those treated with WBRT (median, 6 months) (p=0.0061)., Conclusion: For the control of brain metastases, GKS seems to be an effective modality. GKS improves the overall survival of the patients with brain metastases from EOC.

Objectives: To assess the value and clinical impact of integrated PET/CT using (18)F-FDG in the diagnosis and management of women with suspected cervical cancer recurrence., Methods: Fifty-two patients with cervical cancer with suspected recurrence because of clinical, cytological, biochemical and radiological findings were retrospectively evaluated. A final diagnosis of recurrence was confirmed by histologic tissue biopsy or by further clinical or radiological evidence. The clinical impact of information provided by PET/CT on patient management was assessed on the basis of clinical follow-up data concerning further diagnostic or therapeutic approach., Results: Twenty-eight of 32 positive PET/CT scans (87.5%) were proven to have recurrent disease. Seventeen of 20 negative PET/CT scans (85.0%) had no evidence of disease. The sensitivity, specificity, and accuracy of PET/CT for detecting recurrence were 90.3%, 81.0%, and 86.5% respectively. PET/CT changed the management of 12 patients (23.1%) by changing treatment plan (5 patients), by initiating unplanned treatment strategy (4 patients), or by obviating the need for planned diagnostic procedures (3 patients). Median duration after performing PET/CT and last follow-up was 12 (range: 6-27) months, and the 2-year disease-free survival rate of patients with negative PET/CT scan for recurrence was significantly better than that of patients with positive PET/CT (85.0% vs. 10.9%, P=0002)., Conclusions: In patients with a suspected recurrence of cervical cancer, integrated PET/CT using (18)F-FDG provides good anatomic and functional localization of suspicious lesions, and the better diagnostic interpretation has an impact not only on clinical management and treatment planning of patients, but also on disease-free survival.

Objectives: To retrospectively evaluate the accuracy of magnetic resonance (MR) imaging for the prediction of depth of myometrial invasion in the preoperative assessment of women with endometrial carcinoma., Methods: We retrospectively reviewed the medical records and MR imaging reports of 120 women with pathologically-proven endometrial carcinoma who underwent preoperative pelvic MR imaging between June 1997 and February 2006. Tumor signal intensity, the appearance of the junctional zone (JZ), the presence of large polypoid tumors and leiomyomas were analyzed. Univariate logistic-regression analysis was performed to identify associations between incorrect MR staging and the study variables., Results: Data from 120 patients were registered for the current study and analyzed. The sensitivity, specificity and accuracy of the MR imaging in assessment of myometrial invasion among patients with endometrial carcinoma were: 50.6%, 89.2% and 62.5% respectively. MR differentiation of deep myometrial invasion from superficial disease had an 83.3% accuracy (100 of 120 cases). Isointense JZ to myometrium (P<0.001), and the presence of polypoid tumors (P=0.037) on MR imaging were significantly associated with an underestimation of myometrial invasion by endometrial carcinoma., Conclusions: Isointense JZ to myometrium and polypoid tumors are difficult to accurately evaluate for myometrial invasion of endometrial carcinoma by MR imaging.

Objectives: Our objective was to determine the frequency of a coexisting ovarian malignancy and to evaluate the feasibility of ovarian preservation in patients with early stage endometrial carcinoma., Methods: Endometrial cancer patients who received primary surgical treatment between 1992 and 2004 were identified using the institution's tumor registry. Information regarding patient age, preoperative and intraoperative evaluations, pathologic reports, and follow-up results was abstracted from medical records., Results: Coexisting ovarian malignancy was detected in 19 (7.31%) of 260 patients who underwent surgical treatment (12 metastatic and 7 synchronous primaries). The independent risk factors of a coexisting ovarian malignancy, as determined using a logistic regression model, were intraoperative extrauterine disease, non-endometrioid histology, lymph node metastasis, and patient age, and the presence of intraoperative extrauterine disease was found to most significantly predict ovarian involvement (OR=542.1; 95% CI, 57.18 to 5139.23). Seventeen of the 19 cases showed abnormal intraoperative gross findings around adnexa or other sites. Among the 206 patients without any evidence of intraoperative extrauterine disease, the coexisting ovarian malignancy rate was 0.97% (2/206), and zero for those under age of 45. In 35 patients, grossly normal ovaries were selectively saved, and no recurrence or cancer-related death occurred (median duration of follow-up: 76 months, range 3-121)., Conclusions: The risk of coexisting malignancy in patients without predictable risk factors is minimal. Therefore, it is possible to preserve ovaries in young women with early stage endometrial carcinoma with a thorough preoperative evaluation and extensive intraoperative exploration.

Objective: To evaluate the potential benefit of postoperative radiotherapy (PORT) in women with isolated full-thickness cervical stromal invasion (FTSI) as an unfavorable pathological finding after radical hysterectomy and pelvic lymph node dissection (PLND) in FIGO stages IB-IIA cervical carcinoma., Methods: A total of 1868 patients with stages IB-IIA cervical carcinoma underwent radical hysterectomy and PLND between January 1982 and December 2002. Seventy-four of these patients had isolated FTSI without any other unfavorable pathological finding, such as lymph node metastasis, microscopic parametrial involvement, involved resection margin, lympho-vascular space invasion, or large clinical tumor diameter (>4 cm). Forty-one of these patients had no adjuvant treatment (S group) and 33 received PORT (PORT group). Patients with isolated FTSI who received chemotherapy were excluded. Treatment outcomes in the PORT and S groups were compared., Results: Ten-year disease-free survival (DFS) and pelvic-failure-free survival (PFFS) of S group vs. PORT group were 73.2% vs. 92.4% (P=0.038) and 79.8% vs. 97.0% (P=0.044), respectively. According to a Cox proportional hazards model developed by forward, stepwise regression incorporating all prognostic variables, only PORT was marginally significant for DFS (RR 0.234; 95% CI 0.051-1.067; P=0.061) and significant for PFFS (RR 0.055; 95% CI 0.005-0.620; P=0.019). A grade 4 late complication developed in two patients (6%) in PORT group., Conclusion: PORT administered to patients with isolated FTSI after radical hysterectomy and PLND improves pelvic control in FIGO stages IB-IIA cervical carcinoma with acceptable morbidity.

Objectives: To evaluate the toxicity and the efficacy of paclitaxel/carboplatin chemoradiotherapy as a definitive treatment for squamous cell cancer of the uterine cervix., Methods: From March 2000 to January 2004, 33 patients with squamous cell cancer of the uterine cervix were treated with concurrent chemoradiotherapy including 2 cycles of paclitaxel (135 mg/m(2)) and carboplatin (area under the time-concentration curve 4.5 mg min/ml) at 4-week interval. Seven patients received adjuvant chemotherapy with the same chemotherapeutic regimen. All patients received external beam radiotherapy with 41.4-51.4 Gy (median 50.4 Gy) to the whole pelvis. Twenty-eight patients received boost irradiation to the cervix by brachytherapy with 25.6-43.3 Gy (median 34.6 Gy) and 5 patients by external beam radiotherapy with 10.8-14.4 Gy (median 14.4 Gy)., Results: A median follow-up period was 27 months (range: 6-53 months). Acute hematological toxicity of grade 3 or 4 developed in 20 patients (61%), and acute gastrointestinal toxicity of grade 3 developed in 1 patient (3%). Vesicovaginal fistula occurred in 2 patients (6%). All patients achieved objective response (CR 70%, PR 30%) in 2 months after termination of treatment. One patient had a local progression in cervix, and 4 patients developed distant metastases. The 3-year estimated disease-free survival rates for stages I-IIA, IIB, III and IV were 67%, 91%, 88% and 50%, respectively. The 3-year estimated survival rates for stages I-IIA, IIB, III and IV were 89%, 91%, 88% and 50%, respectively., Conclusion: Concurrent chemoradiotherapy with paclitaxel and carboplatin is effective to achieve an excellent pelvic control.

Objectives: The aim of the study was to assess whether the genetic polymorphisms were associated with the tumor response in patients treated with platinum-based neoadjuvant chemotherapy (NAC) for bulky cervical cancer., Methods: We retrospectively reviewed the clinical data and recruited paraffin-embedded, formalin-fixed tissues of 36 patients with bulky cervical carcinoma. All patients underwent two or three cycles of platinum-based NAC followed by radical hysterectomy. We determined the genotypes of each single nucleotide polymorphism (SNP) of ERCC1, ERCC2, GGH, GSTP1, MTHFR, SLC19A1 and XRCC1 using single base primer extension assay., Results: The response to platinum-based NAC was higher in patients with SNP of XRCC1 R399Q (P=0.015), and there was a significant increased chance of treatment response in women with the G/G genotype (OR 38.0; 95% CI 1.66-870.45; P=0.023). The probability of response was also higher in patients with SNP of SLC19A1 6318C/T (P=0.032). There were dose-dependent influence of the number of alleles on the response to platinum-based chemotherapy (chi2 test for linear-by-linear association; P=0.009 for XRCC1 R399Q and P=0.017 for SLC19A1 6318C/T, respectively). Moreover, the multifactor dimensionality reduction (MDR) analysis documented that the combinations of XRCC1 R399Q and GGH-401C/T genetic polymorphisms were significantly associated with response to chemotherapy (P<0.0001)., Conclusions: Genetic polymorphism of XRCC1 R399Q is associated with response to platinum-based NAC in bulky cervical cancer, and MDR analysis documented association between gene-gene interaction of XRCC1 R399Q and treatment response.

Objectives: To evaluate the efficacy of self-collected vaginal samples for high-risk HPV detection by the HPV oligonucleotide microarray method (HPVDNAChip)., Methods: One hundred and eighteen patients with abnormal Pap smears were included. Self-collected vaginal and clinician-collected cervical samples for HPV testing were obtained. The result of the HPV DNA test was compared with the histopathological diagnosis or colposcopic finding., Results: Of the 118 patients, 42 (35.6%) had >or= cervical intraepithelial neoplasia (CIN) III lesions. Using the HPVDNAChip, high-risk types of HPV were detected in 38 of these 42 patients (90.5%) with the self-collected vaginal samples and in 37 of 42 (88.1%) with the clinician-collected cervical samples. The agreement of HPVDNAchip results between self- and clinician-collected samples was very good (kappa = 0.81) with a 93.2% concordance rate. Multiple HPV infections were found in 17 of 88 (19.3%) HPV-positive clinician-collected cervical samples. The rate of multiple HPV infection tended to decrease as the degree of pathologic classification increased., Conclusion: Using the HPVDNAchip to assay for HPV infection, results from self-collected vaginal samples were compatible with those from clinician-collected cervical samples.

Objective: To evaluate the efficacy and safety of concurrent chemoradiotherapy with paclitaxel and carboplatin after hysterectomy for early stage uterine cervical carcinoma with high risk factors., Methods: Between March 2000 and July 2002, 37 patients with stages IB-IIB uterine cervical carcinoma were treated with radical hysterectomy and bilateral pelvic lymph node dissection followed by concurrent chemoradiotherapy (POCCRT) with two courses of paclitaxel (135 mg/m(2)) and carboplatin (area under the time-concentration curve 4.5 mg min/ml) at 4-week interval. All the patients received external beam radiotherapy up to 50.4 Gy to the whole pelvis. Among these, 7 patients with close or involved resection margin received boost irradiation to the vaginal cuff (4 patients with low dose rate brachytherapy and 3 patients with external beam). Median dose of boost irradiation was 14.4 Gy (range: 14.4-34.6)., Results: Toxicity to POCCRT was mainly hematological and gastrointestinal, mostly grades 1 and 2. At a median follow-up of 27 months (range; 10-46), all the patients achieved local control, and 4 patients experienced distant relapses. The failure sites were as follows: bone (2 patients), paraaortic lymph node (1 patient), and supraclavicular lymph node (1 patient)., Conclusions: Concurrent chemoradiotherapy with paclitaxel and carboplatin after hysterectomy is well tolerated and produces excellent local control rate despite of short follow-up period. This regimen could be considered for a phase III trial.

Objectives: The common G to A single nucleotide polymorphism (G870A) in the splice donor region of exon 4 enhances alternate splicing, and produces a longer half-life cyclin D1 (CCND1). This study was aimed at investigating the possible association between the G870A polymorphism in CCND1 and the risk of endometrial cancer., Methods: We assessed the association between the CCND1 G870A polymorphism and the risk of endometrial cancer in a hospital-based case-control study among 231 Korean women (77 cases; 154 matched controls). Controls were matched to cases with respect to age, menopausal status, and hormone therapy status., Result: The allele frequencies of the case subjects (A, 0.45; G, 0.55) were significantly different from those of control subjects (A, 0.58; G, 0.42) (P = 0.008). All case and control subjects were in Hardy-Weinberg equilibrium. The AA genotype was associated with a significantly elevated odds ratio (OR) of 3.18 [95% confidence interval (CI) 1.38-7.37, P = 0.007], and the AG genotype was associated with an OR of 1.38 (95% CI 0.65-2.89). When we combined the GG and AG genotypes as a reference genotype, we found that the OR for the AA genotype was 2.53 (95% CI 1.34-4.80, P = 0.004), supporting a recessive model for the A allele. Conditional logistic regression adjusted for various risk factors of endometrial cancer revealed positive associations between the AA genotype and an increased risk of endometrial cancer (OR 3.16, 95% CI 1.18-8.43, P = 0.022). However, no significant difference in endometrial cancer stage or grade was observed between the CCND1 genotypes., Conclusion: Our data suggest that the CCND1 polymorphism is associated with an increased risk of endometrial cancer. To validate this association, a large-scale population-based study is needed.

Background: Tubulo-villous adenomas are common in the colon and rectum, but extremely rare in the vagina. As far as we know, only two cases of tubulo-villous adenoma have ever been reported. We report the third case of enteric-type tubulo-villous adenoma of the vagina., Case: A 61-year-old woman presented a symptom of intermittent vaginal spotting and a tumor located outside the vaginal introitus near the urethra. The tumor was excised and pathologically confirmed as a tubulo-villous adenoma., Conclusion: Because some tubulo-villous adenomas in the colon and rectum can progress to the cancer, this case requires long-term follow-up to detect recurrence and malignant transformation.

Objective: This study was conducted to explore the association between the CpG island hypermethylation of tumor-associated genes and the polymorphisms of methyl group metabolizing enzymes in uterine cervical cancer., Methods: We analyzed CpG island hypermethylation in 15 genes (APC, CDH1, COX2, DAPK, FHIT, GSTP1, HLTF1, hMLH1, MGMT, p14, p16, RASSF1A, RUNX3, THBS1, and TIMP3) and its association with the methylene-tetrahydrofolate reductase (MTHFR) C677T and A1298C and the methionine synthase (MS) A2756G polymorphisms in 82 Korean women with uterine cervical cancer., Results: All uterine cervical cancer samples had at least one gene methylated. The average number of methylated genes was lower in patients with the heterozygous genotype of MTHFR and MS than in those with the common homozygous genotype, although this difference was not significant. The MTHFR 677 CT genotype was significantly associated with the decreased promoter hypermethylation of O(6)-methylguanine DNA methyltransferase (MGMT) (OR = 0.22, 95% confidence interval (CI) 0.07-0.70, P = 0.011). However, the MTHFR C677T and A1298C and the MS A2756G polymorphisms were not associated with an increased risk of uterine cervical cancer., Conclusion: These findings suggest that there is a possible interaction between epigenetic and genetic factors in uterine cervical cancer.

Objective: Recently, there has been considerable interest in the association of specific cancers with single nucleotide polymorphisms (SNPs). In this regard, genetic polymorphism at codon 72 (CCC/proline to CGC/arginine [Pro(72)Arg]) of the p53 gene is one of the most frequently studied subjects. An association between endometrial cancer and the polymorphism at codon 31 (AGC/serine to AGA/arginine [Ser(31)Arg]) of the p21 gene, which is known to be a downstream mediator of p53, has also been reported., Methods: The authors designed a hospital-based case-control study of 95 endometrial cancer patients and 285 non-cancer controls. For the determination of p53 and p21 polymorphism, allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism assay was applied, respectively., Results: We found statistically significant differences in the frequency of the p53 and p21 genotypes between these two groups (P < 0.001), respectively. The p53 genotypes containing the Pro allele were significantly associated with endometrial cancer with an odds ratio (OR) of 3.56 (95% confidence interval [CI] 2.10-6.04). Also, homozygous carriers of the p21 Ser allele showed a substantially increased risk of developing endometrial cancer (OR 2.68, 95% CI 1.59-4.51) as compared to homozygous and heterozygous carriers of the Arg allele. In addition, the combination of the pro allele containing genotypes of p53 and the Ser homozygous genotype of p21 posed a remarkably increased risk (OR 9.55, 95% CI 4.30-21.24) of endometrial cancer development. These significant differences were maintained throughout the groups after they were stratified by menopausal status., Conclusions: These data suggest that there is a significant association between the genetic polymorphisms of p53, p21, and specific combinations of the at-risk genotypes of these genes and the risk of developing endometrial cancer in Korean women.

Objectives: This study examines whether expression of COX-2 is associated with clinicopathological features and other molecular markers of ovarian cancer., Methods: Sixty-four paraffin-embedded tissue specimens were obtained from patients with ovarian cancer who received cytoreductive surgery and combination chemotherapy. Tissue specimens were subjected to immunohistochemical analysis using antibodies to COX-2, p53, and VEGF., Results: Increased COX-2 expression significantly correlated with histologic type (mucinous 5.6% vs. non-mucinous 65.2%, P<0.001). COX-2 expression was also significantly associated with stage, tumor grade, residual disease status, and presence of ascites. COX-2 expression correlated positively with expression of p53 (P=0.006) and VEGF (P=0.025). Although survival was lower in patients with high COX-2 expression than in those without high COX-2 expression (P<0.001), only tumor grade and stage were independent prognostic indicators. In patients with non-mucinous cancer, COX-2 expression correlated with stage (P<0.001) and presence of ascites (P=0.033)., Conclusions: Our results suggest that expression of COX-2 in ovarian cancers is specific to histologic type of tumor and is associated with poor clinicopathologic prognostic factors. Expression of COX-2 also correlates well with expression of p53 and VEGF.

Objectives: This study examines the relationship between expression of COX-1, COX-2, and vascular endothelial growth factor (VEGF), and their association with clinicopathological features in primary tumor and metastatic lymph node specimens from cervical cancer patients. The relationship between COX-2 expression and human papillomavirus (HPV) positivity was also examined., Methods: The following samples were analyzed: 97 paraffin-embedded specimens from patients with cervical cancer (Ib-IIb), including 49 primary cervical cancer specimens without lymph node metastasis and 24 primary specimens with lymph node metastasis and their metastatic lymph nodes. Immunohistochemical analysis was performed with antibodies to COX-1, COX-2, and VEGF. HPV viratype was identified by PCR and HPVDNAChip., Results: VEGF expression was strongly correlated with expression of COX-1 (P = 0.03) and not COX-2 (P = 0.12) in primary tumor and metastatic lymph nodes. COX-2 expression correlated with lymph node metastasis (P = 0.001), but not with any other clinicopathological features. The parametrial invasion showed borderline significance with COX-2 expression (P = 0.058). COX-1 or VEGF expression did not correlate with any clinicopathological features. In addition, COX-2 expression was not associated with HPV positivity.COX-1 expression is associated with VEGF expression in primary tumor tissue and at sites of metastasis to lymph nodes., Conclusion: COX-2 expression is associated with lymph node metastasis and possibly parametrial invasion, but expression of COX-1 and VEGF is not associated with clinicopathological features. COX-2 expression is not associated with HPV positivity.

Endodermal sinus tumor (EST) is a rare neoplasm which usually arises in the testis or ovary. But extragonadal EST is well recognized and may arise in a wide array of sites such as the mediastinum, vagina, and brain. We report a case of primary EST of the omentum and to our knowledge it is the first case of omental EST in the literature. A 45-year-old woman with a history of abdominal distension was treated with total abdominal hysterectomy with bilateral salpingo-oophorectomy and infracolic omentectomy, followed by four cycles of BEP (bleomycin, etoposide, cisplatin) combination chemotherapy. Microscopically, the tumor exhibited typical patterns of EST and stained for alpha-fetoprotein and cytokeratin. She has remained free of disease for 10 months of follow-up. According to previous studies, debulking surgery and BEP chemotherapy were used as primary therapy with good results. The subject of extragonadal EST is reviewed, and the possible histogenesis of this tumor at such a rare site is discussed., (Copyright 1999 Academic Press.)

Geographic specificity of nucleotide sequence variations in the coding and noncoding regions of HPV 16 genome has been reported. Little has been known, however, regarding whether these naturally occurring sequence variations of HPV 16 may result in marked differences in biological properties, such as oncogenic potential. This study was performed to identify sequence variants in the HPV 16 E7 gene derived from Korean women with cervical cancerous and noncancerous lesions, and to assess the association between the sequence variant and the cervical cancer. We examined E7 variants of HPV 16 in a total of 157 patients with no cervical disease (NCD, n = 87) or cervical neoplasia (cervical intraepithelial neoplasia 3, n = 21; cervical carcinoma, n = 49), using the nested polymerase chain reaction (PCR) and the PCR-directed sequencing methods with outer consensus and inner type-specific primers. Forty-two (NCD, n = 9; CIN 3, n = 6; cervical carcinoma, n = 27) of 157 cervical samples contained HPV 16 E7 DNA, but only 8 had prototype sequences. Four variants of the HPV 16 E7 gene were identified. The variant with a single nucleotide change at position 647 (A --> G, Asn --> Ser) was found in about 60% of DNA samples with HPV 16. The second most common variant, found in 16.7% of cases, had three silent mutations at positions 732 (T --> C), 789 (T --> C), and 795 (T --> G). Two other variants were detected, one in a patient with cervical cancer and the other in a patient with no cervical disease. One had a single nucleotide change at position 666 (G --> A) and the other had one silent mutation at position 796 (T --> C). The most common variant in Korea has a change of nucleotide affecting the predicted amino acid related with high antigenicity and binding to retinoblastoma protein. There was a statistically significant trend for this variant to be more frequently detected in cancerous lesions of the uterine cervix than in noncancerous lesions. These data suggest that naturally occurring sequence variants of HPV 16 E7 gene may have different oncogenic properties.

Background: The investigation of cervical cancer screening acceptance in relation to health beliefs and attitudes presents a challenge in a multiethnic population such as Singapore's, where the uptake is currently suboptimal in high-risk groups. This study attempts to identify cognitive barriers to screening activity in order to suggest possible directions for cervical cancer prevention efforts., Methods: A cross-sectional survey consisting of a household interview of 640 randomly selected women ages 21-65 years was performed. The screening history and future intention to have a Pap smear were elicited, and attitudes toward cancer and the Pap smear as expressed in 14 statements were measured on a five-point scale., Results: Of the respondents, 73.1% were aware of the Pap smear, and about half (49.7%) had obtained the information from a doctor or nurse. Overall, the belief in personal susceptibility to cancer was low (58.9%) and a substantial proportion (48.7%) of women were of the attitude that cancer could not be prevented. The effect on a future intention to have a smear varied between women who had had and women who had not had a smear. Among the former, perceived barriers such as discomfort and embarrassment had a significant influence, while a belief in personal susceptibility was an important determinant for the latter group., Conclusions: The means of increasing the acceptance of the Pap smear, both for the first time and subsequently, are culture-specific and must address the appropriate health beliefs and attitudes. In Singapore, such efforts should include not only influencing awareness and perceptions through public education but also reducing barriers by creating an appropriate environment for the delivery of this important health service.

Aflatoxin B1 (AFB1) is a potent hepatotoxic and hepatocarcinogenic mycotoxin. The mechanism of cellular damages caused by AFB1 has not been fully elucidated. Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenesis of many carcinogens. In this study, we investigated the induction of lipid peroxidation by AFB1 in the liver of Fischer 344 rats. Malonaldehyde (MDA) and conjugated dienes, both products of lipid peroxidation, were determined in liver homogenate and subcellular fractions. An increase of MDA and conjugated dienes in liver homogenate was detected 1 day after AFB1 administration. It reached the peak level 3 days after dosing and remained at an elevated level up to 14 days. The induction of MDA by AFB1 was also found to be dose-dependent. Measurements of lipid peroxidation in the subcellular fractions revealed that microsomes had the highest concentration of MDA, followed by those of the nuclear fraction and mitochondria. MDA concentration was not detectable in the cytosolic fraction. Further, it was found that pretreatment with selenium and vitamin E, both antioxidants, and deferoxamine, a specific iron chelator, significantly inhibited lipid peroxidation as well as liver cell damage. These results provide in vivo evidence that AFB1 can cause lipid peroxidation in rat liver. Oxidative damages caused by AFB1 may be one of the underlining mechanisms for AFB1-induced cell injury and DNA damage, which eventually lead to tumorigenesis.