Role of Defects of Carbon Nanomaterials in the Detection of Ovarian Cancer Cells in Label-Free Electrochemical Immunosensors.

Developing label-free immunosensors to detect ovarian cancer (OC) by cancer antigen (CA125) is essential to improving diagnosis and protecting women from life-threatening diseases. Four types of carbon nanomaterials, such as multi-wall carbon nanotubes (MWCNTs), vapor-grown carbon fiber (VGCFs), graphite KS4, and carbon black super P (SP), have been treated with acids to prepare a carbon nanomaterial/gold (Au) nanocomposite. The AuNPs@carbon nanocomposite was electrochemically deposited on a glassy carbon electrode (GCE) to serve as a substrate to fabricate a label-free immunosensor for the detection of CA125. Among the four AuNPs@carbon composite, the AuNPs@MWCNTs-based sensor exhibited a high sensitivity of 0.001 µg/mL for the biomarker CA125 through the square wave voltammetry (SWV) technique. The high conductivity and surface area of MWCNTs supported the immobilization of AuNPs. Moreover, the carboxylic (COO-) functional groups in MWCNT improved to a higher quantity after the acid treatment, which served as an excellent support for the fabrication of electrochemical biosensors. The present method aims to explore an environmentally friendly synthesis of a layer-by-layer (LBL) assembly of AuNPs@carbon nanomaterials electrochemical immunoassay to CA125 in a clinical diagnosis at a low cost and proved feasible for point-of-care diagnosis.

4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway.

Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P=0.027) and depleting Atg-5 in ES-2 cell lines significantly induced apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreased autophagic flux in ovarian cancer cells via inhibition of the PI3K/Akt/mTOR/p70S6K signaling pathway. Similar to Atg-5 silencing, 4-AAQB-induced autophagy inhibition significantly enhanced cell death in vitro. These results are comparable to those of hydroxychloroquine (HCQ). In addition, 4-AAQB/cisplatin synergistically induced apoptosis in ovarian cancer cells. In vivo, 4-AAQB/cisplatin also significantly induced apoptosis and autophagy in an ES-2 mouse xenografts model. This is the first report demonstrating the efficacy of 4-AAQB alone or in combination with cisplatin on the suppression of ovarian cancer via Atg-5-dependent autophagy. We believe these findings will be beneficial in the development of a novel anti-ovarian cancer therapeutic strategy.

DNA methylation as a biomarker for the detection of hidden carcinoma in endometrial atypical hyperplasia.

OBJECTIVE: Women with atypical hyperplasia (AH) are often found to have endometrial carcinoma (EC) at hysterectomy. The purpose of this study was to evaluate whether the hypermethylation of specific genes found by methylomic approaches to the study of gynecologic cancers is a biomarker for EC in women with AH. METHODS: We evaluated the methylation of AJAP1, HS3ST2, SOX1, and PTGDR from 61 AH patients undergoing hysterectomy. Endometrial biopsy samples were analyzed by bisulfite conversion and quantitative methylation-specific polymerase chain reaction. A methylation index was used to predict the presence of cancer. To confirm the silencing effects of DNA methylation, immunohistochemical analysis of AJAP1, HS3ST2, and SOX1 was performed using tissue microarray. RESULTS: Fourteen (23%) patients had EC at hysterectomy. AJAP1, HS3ST2, and SOX1 were highly methylated in the EC patients' biopsy samples (p≤0.023). AJAP1, HS3ST2, and SOX1 protein expression was significantly higher in patients with AH only (p≤0.038). The predictive value of AJAP1, HS3ST2, and SOX1 methylation for EC was 0.81, 0.72, and 0.70, respectively. Combined testing of both AJAP1 and HS3ST2 methylation had a positive predictive value of 56%, methylation of any one of AJAP1, SOX1, or HS3ST2 had a 100% negative predictive value. CONCLUSIONS: Hypermethylation of AJAP1, HS3ST2, and SOX1 is predictive of EC in AH patients. Testing for methylation of these genes in endometrial biopsy samples may be a hysterectomy-sparing diagnostic tool. Validation of these new genes as biomarkers for AH screening in a larger population-based study is warranted.

Electrochemical immunosensing by carbon ink/carbon dot/ZnO-labeled-Ag@polypyrrole composite biomarker for CA-125 ovarian cancer detection.

In this work, we demonstrated a novel cancer antigen 125 (CA125) biomarker detection based on electrochemical immunosensor. The biomarker on conductive composite materials of carbon ink/carbon dot/zine oxide (C-ink/CD/ZnO) was employed as an electrode platform by using ITO substrate to enhance the interaction of antibodies (Ab) with supporting catalytic performance of ZnO as a labeling signal molecule. They were a scientist attention for biosensor with chemical stability, strong biocompatibility, high conductive signal, and accuracy. Moreover, the nanocomposite of silver@polypyrrole (Ag@PPy) was used as a potential redox mediator. The labeled construction with Ag@PPy was more accuracy than that of a free-labeled. The created immunosensor was a wide linear range as 1 ag·mL-1 - 100 ng·mL-1 and a low limitation of detection as 0.1 fg·mL-1 under the optimal condition. This suggested that the immunosensor is considered to be an accurate and efficient diagnostic tool for CA125 and other biomarkers detection in actual sample analysis for clinic.

Classification of Vascular Hotspots and Micro-Vessel Flow Velocity Waveforms in Low-Grade Squamous Intraepithelial Lesions and HPV Condyloma of the Cervix.

To assess hotspot micro-vessel flow velocity waveforms in human papillomavirus (HPV) cervical infections using transvaginal power Doppler ultrasound (TV-PDU) and to explore the associations of these sonographic parameters with HPV condyloma and low-grade squamous intraepithelial lesions (LSIL) of the cervix. A total of 39 patients with cervical HPV infections with abnormal cytology and colposcopy results (26 cases of LSIL; 13 cases of HPV condyloma) were enrolled to assess the vascular classification of the cervix and micro-vessel flow velocity using TV-PDU before treatment; 40 individuals with a pathologically normal cervix were used as the control group; seven parameters were measured, including vascular grading classification (Class I, Class II, and Class III), lowest pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end-diastolic velocity (ED), time average maximum velocity (TAMV), and the vascular index (VI = PS/ED). According to vascular classification, most LSILs were class I (69.2%, 18/26), followed by class II (26.9%, 7/26) and class III (3.8%, 1/26). Most HPV condylomas were class I (92.3%, 12/13), and one was class II (7.7%, 1/13). PI, RI, VI (p < 0.0001), and the PSs (p < 0.05) were significantly lower in these cases than in the controls. The ED and TAMV were not significantly different between the patients and controls (p = 0.4985 and p = 0.1564). No sonographic parameter was significantly different between LSIL and HPV condyloma. The mean PI, RI, and VI were significantly lower in LSIL than in the controls. For HPV condyloma, a PI of 1.07 had an 84.6% sensitivity, 85.0% specificity, and an AUC of 88.8%; for LSIL, a PI of 1.08 had a 100% sensitivity, 85% specificity, and an AUC of 94.2%; for HPV infection (HPV condyloma + LSIL), a PI of 1.08 had a 94.9% sensitivity, 85% specificity, and an AUC of 92.4%. Hotspot vascular classification and micro-vessel flow velocity waveforms may provide a potential practical method for the auxiliary diagnosis of cervical HPV infection. The PI may represent a valuable index for distinguishing the micro-vessel flow velocity waveforms in LSIL and HPV condyloma. Since the case numbers were limited in the current study, further validation is needed.

Cervical Power Doppler Angiography with Micro Vessel Blood Flow Indices in the Auxiliary Diagnosis of Acute Cervicitis.

We have conducted cervical imaging of uterine and micro-vessel flow velocity waveforms in acute pelvic inflammatory disease (PID) by transvaginal power Doppler ultrasound (TVPDU) in order to explore the associations of sonographic parameters with simple and complex cervicitis. Thirty-eight patients with acute PID (26 with acute simple cervicitis and 12 with complex cervicitis) were enrolled for an assessment of vascular grading of cervix and micro-vessel flow velocity using TVPDU before treatment. Seven parameters, including vascular grading (VG), lowest pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end diastolic velocity (ED), time average maximum velocity (TAMV), and vascular index (VI = PS/ED), were measured and recorded. Forty-one healthy patients were assessed as the control group. Vascular grading (VG) was significantly higher in the study group than the control group (p < 0.0001). The PI, RI, and VI were significantly lower in the study group than control group (p < 0.0001). No significant associations were observed between seven sonographic parameters and acute simple or/and complex cervicitis. For acute simple cervicitis, a PI cutoff of 1.1 had a sensitivity of 85.4% and a specificity of 92.1% (area under ROC curve [AUC], 93.2%). A RI of 0.6 had a sensitivity of 85.4% and a specificity of 78.9% (AUC, 86.1%). A VI of 2.6 had a sensitivity of 85.4% and a specificity of 78.9% (AUC, 84.9%). Power Doppler angiography of micro-vessel flow velocity waveforms in the cervix could represent a practical method to assist the diagnosis of pelvic inflammatory disease presented as acute cervicitis detected on transvaginal ultrasound before medical or surgical treatment. Cervical PI may be a useful index to detect micro-vessel flow velocity waveforms in acute cervicitis and differentiate acute simple cervicitis from complex cervicitis.

Physiology and potential application of NKT cells: a minireview.

CD1d-restricted T (NKT) cells are potent regulators of autoimmunity, tumor immunity, and transplantation-related immunity. NKT cells are a subset of innate lymphocytes that recognize endogenous or exogenous glycolipids in the context of CD1d molecules. Recent progress in the research of NKT cells has proved that NKT cells function as a bridge between innate and adaptive immunity in anticancer immunity. Furthermore, NKT cells also function as a bridge to tolerance or rejection of grafts in organ transplantation. Harnessing the function of NKT cells, and trying to put it into clinical application in the treatment of autoimmune disease, anticancer cell immunotherapy, and organ transplantation are the dreams of immunologists. This minireview will focus on the physiology of NKT cells and potential clinical application.

Improved cervical cancer screening in premenopausal women by combination of Pap smear and speculoscopy.

OBJECTIVE: This study was done to evaluate the efficacy of the Pap smear, speculoscopy, and a combination of Pap smear and speculoscopy (PapSure examination) in pre- and postmenopausal women. STUDY DESIGN: All women were screened using the Pap smear and speculoscopy and combination of both (PapSure examination) in the multicenter trial. Final diagnosis of each patient was based on a histological evaluation of the colposcopic target biopsy. Results were analyzed using a proportional comparison test, sensitivity, specificity, and predictive value with significance determined at p<0.05. RESULTS: Of 1813 women screened, 1701 were eligible for analysis. Two hundred and fourteen women (12.6%) received at least one positive screening test result. Of the 1084 colposcopic biopsy specimens obtained, 24 showed low-grade squamous intraepithelial lesion (LSIL) and 19 high-grade SIL (HSIL). HSIL were considered test-positive. Rate of colposcopy was 21.5% (125/582) in the premenopausal group and 63.9% (321/502) in the postmenopausal group (p<0.001). For premenopausal women, speculoscopy (75.0%) or PapSure (91.7%) provided higher sensitivity than Pap smear (50%) (p<0.05). In postmenopausal women, no statistical significance in sensitivity existed between PapSure (85.7%) and Pap smear (57.1%). Speculoscopy (96.8%) or PapSure (96.5%) had lower specificity than Pap smear (99.6%) (p<0.001). CONCLUSION: PapSure was an accurate alternative screening method to Pap smear or speculoscopy for cervical intraepithelial lesions because of a significantly higher sensitivity along with adequate specificity for premenopausal women; however, PapSure was not a more effective cervical screening method for postmenopausal women.

Successful rescue of an early interstitial pregnancy after failed systemic methotrexate treatment: a case report.

BACKGROUND: Interstitial (cornual) pregnancy is a rare and life-threatening disease. Although systemic treatment with methotrexate (MTX) in an unruptured interstitial pregnancy has been used to preserve the entirety of the uterus, surgery is often used as a rescue method in failed cases. Use of an ultrasound-guided local injection can be a good alternative to surgery. CASE: A 30-year-old woman, gravida 1, para 0, with an interstitial pregnancy at 10 weeks of gestation, was successfully treated with an ultrasound-guided 100-mg MTX injection after a failed response to 3-dose intramuscular 100-mg MTX treatment (300 mg in total). Regular menstruation occurred 1 month after the local MTX injection. The serum beta-human chorionic gonadotropin level was undetectable 49 days later, and the residual mass had disappeared 6 months later, CONCLUSION: Local injection of MTX may be a good means of managing an unruptured interstitial pregnancy to preserve the entirety of the uterus after failed systemic MTX treatment. Use of a local MTX injection may be a better choice than that of systemic MTX treatment.

Effect of a selective nonsteroidal anti-inflammatory drug, celecoxib, on the reproductive function of female mice.

BACKGROUND: The aim of the present study was to determine if long-term use of a cyclooxygenase-2 (COX-2) inhibitor affects fertility or ovulation in female mice. METHODS: Twenty-four female mice, 25 days of age, were given a selective COX-2 inhibitor: 3 mg/kg celecoxib (n = 8), 5 mg/kg celecoxib (n = 8),or placebo (n = 8) in a random fashion. Eight female mice, 10-11 weeks old, given 3 mg/kg celecoxib (n = 4) or placebo (n = 4) were subjected to continuous mating studies. RESULTS: Results from the 24 mice (n = 8 for each group) showed that oocyte number was not significantly different between female mice treated with either 3 mg/kg or 5 mg/kg celecoxib and placebo (21.4 +/- 2.5, 21.5 +/- 3.3, 23.3 +/- 3.8, respectively). From the continuous mating study, the litter size of female mice treated with celecoxib was not significantly different (8.2 +/- 1.3 pups/litter) compared to those treated with placebo (8.3 +/- 1.2 pups/litter). In addition, female mice treated with celecoxib had an average of 2.8 +/- 0.5 litters in a 12-week period, which was similar to female mice treated with placebo (3.0 +/- 0.8 litters/female). CONCLUSION: This study suggests that use of low-dose (

Alpha 2,6-sialyltransferase I expression in the placenta of patients with preeclampsia.

BACKGROUND: The expression of sialyl-glycoconjugates changes during development, differentiation and oncogenic transformation, tumor invasion and metastasis. Similarly, in the early stage of pregnancy, trophoblast cells have to undergo adhesion, invasion, and proliferation to develop a healthy placenta; the cytobiologic behavior is similar to tumor growth and invasion. Inadequate trophoblast invasion to the spiral artery in the 2nd trimester of pregnancy was believed to be correlated with pregnancy complications, including preeclampsia. METHODS: Alterations in alpha2,6-sialyltransferase I (ST6Gal I) mRNA in the placental tissues of women with preeclampsia (n=20) and without preeclampsia (n=20 used as a control) were examined by semiquantitative reverse transcription-polymerase chain reaction and real-time quantitative reverse transcription-polymerase chain reaction. The transcription regulators of ST6Gal I including a "constitutive" promoter (Y + Z form), "hepatic" promoter (H form), and lymphoblastic promoter (X form) were investigated. The enzyme activity of ST6Gal I was also examined. RESULTS: Both mRNA expression and enzyme activity of ST6Gal I did not show a significant difference in the placental tissues of the women of both groups. The transcription regulators of ST6Gal I, including the Y+Z form and the H form, also failed to show any difference. The X form, seldom detected in the study, was excluded from analysis. CONCLUSION: Our results suggested that ST6Gal I was not involved in the pathogenesis of the preeclampsia.

Methylomics of nitroxidative stress on precancerous cells reveals DNA methylation alteration at the transition from in situ to invasive cervical cancer.

Epigenetic dysregulation is important in cervical cancer development, but the underlying mechanism is largely unknown. Increasing evidence indicates that DNA methylation is sensitive to changes in microenvironmental factors, such as nitric oxide (NO) in the chronic inflammatory cervix. However, the epigenomic effects of NO in cancer have not been investigated. In this study, we explored the methylomic effects of nitroxidative stress in HPV-immortalized precancerous cells. Chronic NO exposure promoted the acquisition of malignant phenotypes such as cell growth, migration, invasion, and anchorage-independent growth. Epigenetic analysis confirmed hypermethylation of PTPRR. Whole-genome methylation analysis showed BOLA2B, FGF8, HSPA6, LYPD2, and SHE were hypermethylated in cells. The hypermethylation BOLA2B, FGF8, HSPA6, and SHE was confirmed in cervical scrapings from invasive cancer, but not in CIN3/CIS, CIN2 and CIN1 (p=0.019, 0.023, 0.023 and 0.027 respectively), suggesting the role in the transition from in situ to invasive process. Our results reveal that nitroxidative stress causes epigenetic changes in HPV-infected cells. Investigation of these methylation changes in persistent HPV infection may help identify new biomarkers of DNA methylation for cervical cancer screening, especially for precancerous lesions.

An epigenetic signature of adhesion molecules predicts poor prognosis of ovarian cancer patients.

DNA methylation is a promising biomarker for cancer. The epigenetic effects of cell adhesion molecules may affect the therapeutic outcome and the present study examined their effects on survival in ovarian cancer. We integrated methylomics and genomics datasets in The Cancer Genome Atlas (n = 391) and identified 106 highly methylated adhesion-related genes in ovarian cancer tissues. Univariate analysis revealed the methylation status of eight genes related to progression-free survival. In multivariate Cox regression analysis, four highly methylated genes (CD97, CTNNA1, DLC1, HAPLN2) and three genes (LAMA4, LPP, MFAP4) with low methylation were significantly associated with poor progression-free survival. Low methylation of VTN was an independent poor prognostic factor for overall survival after adjustment for age and stage. Patients who carried any two of CTNNA1, DLC1 or MFAP4 were significantly associated with poor progression-free survival (hazard ratio: 1.59; 95% confidence interval: 1.23, 2.05). This prognostic methylation signature was validated in a methylomics dataset generated in our lab (n = 37, hazard ratio: 16.64; 95% confidence interval: 2.68, 103.14) and in another from the Australian Ovarian Cancer Study (n = 91, hazard ratio: 2.43; 95% confidence interval: 1.11, 5.36). Epigenetics of cell adhesion molecules is related to ovarian cancer prognosis. A more comprehensive methylomics of cell adhesion molecules is needed and may advance personalized treatment with adhesion molecule-related drugs.

Cyclooxygenase-2 expression is higher in ovarian cancer tissue adjacent to endometriosis than in ovarian cancer without comorbid endometriosis.

OBJECTIVES: The purpose of this study was to examine if COX-2, CK7 and CK20 are involved in the malignant transformation of endometriosis. METHODS: We compared COX-2, CK7 and CK20 expressions between isolated endometriosis lesions and endometriosis lesions adjacent to ovarian carcinoma and between isolated ovarian carcinoma and ovarian carcinoma with implants of endometriosis. Immunoreactivity was quantified using an immunohistochemical scoring system that corresponds to an image analysis-based system. RESULTS: There was no difference in COX-2, CK7 and CK20 expressions between the isolated endometriosis lesions and the endometriosis lesions adjacent to ovarian carcinoma. Similarly, CK7 and CK20 were equally expressed between the isolated ovarian carcinoma and the ovarian carcinoma with implants of endometriosis. The COX-2 over-expression rate was greater in ovarian carcinoma that was associated with endometriosis than in isolated ovarian carcinoma (27.8% versus 5.6%, P = 0.083). In endometrioid type ovarian carcinoma, the difference in COX-2 expression was statistically significant (50% versus 0%, P = 0.023). CONCLUSIONS: COX-2 over-expression may be a result of the malignant transformation of endometriosis to endometrioid type ovarian cancer or may represent an interaction between the two cellular components. With respect to cytokeratins, neither CK7 nor CK20 appear to be involved in the malignant transformation of endometriosis.

Laparoscopic uterosacral nerve ablation and chronic pelvic pain.

Chronic pelvic pain is a complicated syndrome comprised of different types of pain, including dysmenorrhea, deep dyspareunia, and intermenstrual pain, which can make interpretation difficult. Therefore, investigation of this complex syndrome requires very careful consideration. Accumulating data from several randomized studies, we have now come to realize that LUNA can be an option in a few circumstances, especially for control of menstrual pain without endometriosis; however, its effectiveness may not extend to other indications, such as alleviating secondary dysmenorrhea associated with endometriosis (although it could, however, be reached by presacral neurectomy). Juang et al's article reports a very preliminary experience in the treatment of primary deep dyspareunia, presenting a promising perspective yet without sufficient evidence on the management of deep dyspareunia. A randomized controlled study with an adequate number of patients is warranted.

Umbilicus as the only site of metastasis in recurrent ovarian cancer.

We present 2 rare cases of umbilical metastases (Sister Mary Joseph's nodule) as the first sign of late recurrent ovarian cancer. Two patients with ovarian cancer treated with optimal debulking surgery plus chemotherapy were regularly followed up postoperatively. An isolated umbilical nodule was noted accidentally 8 years and 3 years, respectively, after the initial operation. Abdominal computed tomography (CT) for both patients showed a 1.8-cm mass and a 2.3-cm mass with negative peritoneal tumor seeding. Other tumor surveys, including CA125, showed negative findings. Both patients had exploratory laparotomy and complete excision of the umbilical tumor. The pathology showed an isolated metastatic adenocarcinoma without evidence of other metastases. Both patients were treated with 4-course postoperative adjuvant chemotherapy of carboplatin and paclitaxel. Both patients have been in complete clinical remission for 22 months and 12 months, respectively. In addition to tumor marker CA125, a careful and thorough physical examination, assisted by modern imaging evaluation, is the best method for detecting early recurrence in patients with previously treated ovarian cancer. Although an umbilical metastasis usually indicates advanced disease with disseminating peritoneal spread, it does not always imply inoperable or incurable disease. Intensive treatment can improve the outcome.

Single-dose sertaconazole vaginal tablet treatment of vulvovaginal candidiasis.

BACKGROUND: Vulvovaginal candidiasis (WC) is a bothersome disease in women. Poor compliance with the continuous use of antifungal vaginal drugs often results in treatment failure. The aim of the present study was to evaluate the efficacy, acceptability, and safety of single-dose sertaconazole vaginal tablet (500 mg) treatment compared with conventional 3-dose econazole vaginal tablet (150 mg) treatment for VVC. METHODS: In this open, randomized, and comparative study, 40 symptomatic patients with VVC confirmed by the smear method were enrolled. Patients in group A were treated with single-dose sertaconazole vaginal tablet and those in group B were treated continuously with econazole vaginal tablet for 3 days. RESULTS: The characteristics of the patients in both groups were comparable and without statistical difference. Group A showed a significantly better clearance rate for candidiasis than group B (100% vs. 72.2% on day 7, p = 0.013; 100% vs. 77.8% on day 14, p = 0.030), based on smear method results. Group A showed a more rapid response for symptom relief than group B on day 7, but there was no difference in overall symptom relief between group A and group B on day 14. CONCLUSION: Single-dose sertaconazole proved to be a more convenient and symptom-relieving treatment for VVC. The advantages of such management are worthy of further study in women with relapse VVC.

Natural progression of menstrual pain in nulliparous women at reproductive age: an observational study.

BACKGROUND: Menstrual pain can be alleviated after childbirth. The purpose of this observational study was to evaluate the natural progression of menstrual pain among nulliparous women at their reproductive age. METHODS: A questionnaire-based study of perimenopausal women with a history of primary dysmenorrhea was performed. The study subjects were recruited between July 1, 2001 and June 30, 2005. Severity of menstrual pain was graded using a multidimensional scoring system. RESULTS: A total of 247 nulliparous women with primary dysmenorrhea were enrolled, and of these, 218 patients were eligible for analysis. Patients who had more frequent intercourse (p = 0.016), fewer associated systemic symptoms (p = 0.028), and use of oral contraceptive pills (p = 0.039) tended to have a higher chance of an improvement in dysmenorrhea after age 40. Multidimensional scoring distribution over chronologic age revealed that patients had significantly improved menstrual pain after 40 years of age. CONCLUSION: For nulliparous women with primary dysmenorrhea, the severity of menstrual pain decreased significantly after age 40. More studies are needed to explore this phenomenon from a biochemical or molecular basis.

Radioimmunotherapy and apoptotic induction on CK19-overexpressing human cervical carcinoma cells with Re-188-mAbCx-99.

BACKGROUND: The overexpression of Ck19 antigen occurs frequently in human carcinomas. The strategy and mechanism of radioimmunotherapy using Re-188-mAbCx-99 to Ck19 on human cervical carcinoma cells was investigated in this study. MATERIALS AND METHODS: Using mAbCx-99, the overexpression of Ck19 protein in lysates of cell lines and tissues from various patients' cervixes were verified by immunobinding and immunoblot analysis. The therapeutic effect of Re-188-mAbCx-99 on ME180 cells was examined in vitro by cell proliferation, apoptosis, DNA fragmentation and intemucleosomal levels. RESULTS: A relatively high expression of Ck19 was found in all human cervical carcinoma cell lines (4- to 44-fold) and in tissue lysates (26.8- to 79-fold) from patients (31 out of 34) with cervical, endometrial or ovarian carcinomas compared with that of benign or normal control samples. The growth inhibition of ME180, CC7T and Hela cells were significantly higher (p < 0.001) in the Re-188-mAbCx-99-treated (60-80%) than in the Re-188-MOPCIgG1-treated lines (8-18%) after 72-h treatment. After 48 h of treatment with Re-188-mAbCx-99, ME180 cells significantly exhibited DNA fragmentation and morphological features of apoptosis. This effect markedly elevated the expression of p21, p53 and Bcl-xS protein, while the Mcl-1 and Caspase-8 proteins were down-regulated. CONCLUSION: We suggest that an elevated Ck19 level is associated with disease stage in most patients with cervical cancer. The therapeutic effect of Re-188-mAbCx-99 was verified through apoptosis on targeting the enriched Ck19 protein of carcinoma cells.