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A novel phosphorus-free PASP–ED2A antiscalant exhibits good scale inhibition performance against calcium scale at a low concentration or a high temperature, better than that of PASP.

Selective functionalization via cleavage of the C–N bond of amines has proven to be challenging partly because of its relatively high bond dissociation energy, even though amines are abundant and readily available. To meet this challenge, many new transformations based on the pre-activation of the C–N bond before the cleavage have been developed. Among them, the conversion of amines into quaternary ammonium salts has certain advantages, such as easy preparation from primary, secondary, or tertiary amines, as well as stable storage and usage. Although transition metal catalysis has been frequently applied for developing new transformations via oxidative addition of the C–N bond of quaternary ammonium salts, recent studies have shown a new dimension by using green electro- or photochemical tools. In this short review, recent advances in electro-, photo-, or photoelectrochemical driven synthetic applications of quaternary ammonium salts have been summarized and discussed.1 Introduction2 Electrochemical Driven Transformations3 Photochemical Driven Transformations4 Photoelectrochemical Driven Transformations5 Conclusion and Outlook

Driven by the continuous demand for optically active fluoro-containing molecules from the chemical society, the field of fluorochemistry has emerged as a hot topic recently. While protocols focusing on catalytic asymmetric fluorination, (di)fluoroalkylation, and trifluoromethylation have been well developed, elegant strategies for the synthesis of enantioenriched monofluoro- and gem-difluoroalkenes remain highly sought after. As two vital subunits of organofluorides, both monofluoro- and gem-difluoroalkenes are pervasive within many biologically active molecules. They serve as the mimics of alkenyl, enol, and peptide bonds and the carbonyl group, respectively, which may enhance the bioactivities of the parent molecules. In addition, they are active handles for the construction of other fluorinated molecules. In this review, insightful discussions on the latest achievements of the catalytic asymmetric strategies associated with the facile synthesis of both monofluoro- and gem-difluoroalkenes are provided. The related mechanism considerations, applications in streamlining syntheses, limitations, and the opportunities of the state-of-the-art methodologies will be highlighted. We hope that this will trigger novel ideas, helping in pushing current frontiers further.

Background Several studies have previously indicated that nuclear factor erythroid 2‐related factor 2 (Nrf2) expression may promote tumor progression when the Keap1/Nrf2 pathway is activated, but few reports have demonstrated the role of cytoplasmic Nrf2 on tumorigenesis. Methods Immunohistochemistry was conducted to evaluate Nrf2 expression in 167 tumors from surgically‐resected patients with non‐small cell lung cancer (NSCLC). Univariate and multivariate analyses were performed to examine the association of Nrf2 expression with patients' prognosis. This study was conducted to examine the association of Nrf2 expression with tumor response to cisplatin‐based chemotherapy. Results Among these tumors, 56 and 32 of 167 tumors expressed Nrf2 in the cytoplasm (34% for C+/N‐) and in the cytoplasm/nucleus (19% for C+/N+), but not in the nucleus of tumor cells. Nrf2 was negatively expressed in the remainder of the tumor samples (C‐/N‐, 79 of 167, 47%). Univariate analysis indicated that patients with Nrf2 positive tumors (C+/N‐ plus C+/N+) had worse overall survival (OS), but not relapse‐free survival (RFS) than with Nrf2 negative tumors (C‐/N‐). However, patients with C+/N‐ tumors possessed worse OS and RFS than those with Nrf2 negative tumors (C‐/N‐). Multivariate analysis further confirmed the prognostic significance of patients with Nrf2 positive and C+/N‐ tumors on OS and RFS, but not on RFS for patients with Nrf2 positive tumors. Patients with Nrf2 positive and C+/N‐ tumors were determined to more frequently have an unfavorable response to cisplatin‐based chemotherapy than those with Nrf2 negative tumors. Conclusions Cytoplasmic Nrf2 expression might potentially be used to predict poor prognosis and unfavorable response to cisplatin‐based chemotherapy in patients with NSCLC. Key points The expression of cytoplasmic Nrf2 showed a significant relationship with patients' response to cisplatin‐based chemotherapy and influenced NSCLC prognosis. A proteasomal inhibitor such as carfilzomib might be used to improve the outcomes and therapeutic response to cisplatin‐based chemotherapy in patients with tumors showing cytoplasmic Nrf2 expression.

A polyaspartic acid derivative (PASP-Im) as a novel scale inhibitor was synthesized by a simple green synthesis route with polysuccinimide and iminodiacetic acid as the starting materials. The as-synthesized PASP-Im was characterized via nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectrometry (FT-IR), and its scale inhibition performance was evaluated by a static scale inhibition method. Moreover, scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and density functional theory computational studies were conducted to explore the scale inhibition mechanism of PASP-Im. The findings indicate that the as-synthesized PASP-Im exhibits better antiscale performance against the CaCO3 deposits than the unmodified PASP because of the introduction of iminodiacetic acid group. It also can change the crystallization path of calcium carbonate from stable calcite to vaterite that is dispersible in water, thereby resulting in great changes in the morphology of the CaCO3 scale. Furthermore, the O and N atoms in the negatively charged functional groups (such as –NH2 and –COOH) of PASP-Im can interact with calcium ions to block the active growth point of CaCO3 crystals, which also accounts for the excellent antiscale performance of PASP-Im. With new insights into the synergy between the functional groups of the antiscale molecule and scale-forming ions, this approach would be helpful towards the development of novel high-performance anti-scaling macromolecules.

Purposes This study aimed to understand the influence of health beliefs, demographic factors, and health characteristics on the intention to undergo Pap smear testing among women in rural areas of Indonesia. Methods A descriptive cross-sectional study was conducted and 687 married women participated in the study. A convenience sampling was applied to recruit the participants from community health centres in a rural region in Indonesia. Self-reported data using the Health Beliefs Model Scale for Cervical Cancer and Pap Smear Test was collected to assess the health beliefs. Independent t-tests, simple logistic regressions, and a hierarchical logistic regression with 3 steps were run. Statistical significance for analysis was set at p, Plain language summary Cervical cancer is a leading cancer among women and a significant cause of mortality for females around the world, including Indonesia. Globally, the screening rate for cervical cancer among women in rural areas remains low. In Indonesia, the incidence and the mortality from cervical cancer remain high compared to other female cancers. The Indonesian government has offered a free Pap smear screening to women since 2014, but the screening rate is still low, around 28%. A total of 687 married women were included in the study. Approximately 80% of Indonesian women living in rural areas have never undergone a Pap smear test, and 60% of women reported a high intention of receiving a Pap smear test. Education, income, previous experience of Pap smear testing, a friend with a history of cervical cancer, perceived severity, perceived benefits, perceived barriers, and health motivations were significantly associated with the intention of Pap smear testing. Low screening rates of cervical cancer and high intentions toward the cervical cancer screening exist among rural Indonesian women. Health beliefs significantly affect the women’s intention of Pap smear testing.

Angiomyofibroblastoma (AMF) is a distinctive, rare, benign mesenchymal tumor that often occurs in the lower genital region of women. The most commonly reported location of an AMF is in the vulvovaginal area. We describe a rare case of an AMF located in the broad ligament in a 47-yr-old woman. The patient experienced menorrhagia, dysmenorrhea, and subsequent menstrual spotting. She sought help at the National Cheng Kung University Hospital. Ultrasonography showed an echo-complex mass in the left adnexal area. The patient underwent laparoscopic surgery to remove the soft tissue mass located in the left broad ligament. The final pathology of the mass was reported as an AMF. We reviewed all of the AMF cases reported in the English-language literature found in Pubmed. This case is the first of AMF located in the broad ligament.

PD‐1/PD‐L1 immunotherapy is viewed as having clinical benefits in advanced cancers but is effective in only a few patients, suggesting that an efficient combination approach is needed to improve efficacy. Immunohistochemistry analysis indicated that PD‐L1 expression was correlated with the E6 expression in tumors from 122 lung cancer patients. The poorest survival occurred in PD‐L1‐positive/E6‐positive tumor. PD‐L1 expression was increased by the expression of E6, but not the E7, oncoprotein in lung and cervical cancer cells. PD‐L1 expression was responsible for E6‐mediated colony formation and soft agar growth. Therefore, PD‐L1 secreted from tumor cells may directly promote tumor progression, particularly in E6‐positive tumors. Immune deficiency nude mice were used to test the possibility that combining anti‐PD‐L1 mAb with Lm‐LLO‐E6 vaccine could have a higher antitumor activity compared with anti‐PD‐L1 mAb or Lm‐LLO‐E6 vaccine alone. A greater antitumor activity was obtained with anti‐PD‐L1 mAb + Lm‐LLO‐E6 vaccine than with anti‐PD‐L1 mAb or Lm‐LLO‐E6 alone in subcutaneous and metastatic tumors induced by TL‐1 and SiHa cells. The longest survival time for nude mice was observed in the anti‐PD‐L1 mAb + Lm‐LLO‐E6 vaccine group. In conclusion, an anti‐PD‐L1 mAb + Lm‐LLO‐E6 vaccine may be an efficient treatment for suppression of tumor growth and metastasis induced by HPV‐infected cells.

Activated leukocyte cell adhesion molecule (ALCAM), also called CD166 is a 105-kDa transmembrane glycoprotein of the immunoglobin superfamily. In this study, we studied the association between ALCAM expression and tamoxifen resistance in ER + breast cancer and further investigated how ALCAM is regulated in the cancer cells. IHC staining data showed that the tumor tissues from non-responders (N = 20) generally had significantly stronger ALCAM staining than that from tamoxifen responders (N = 16). In vitro cell assay also confirmed ALCAM upregulation in tamoxifen resistant (TamR) MCF-7 cells than in tamoxifen sensitive (TamS) MCF-7 cells. ALCAM overexpression significantly alleviated 4-Hydroxytestosterone (4-OHT) induced cell viability inhibition and cell apoptosis in TamS MCF-7 cells, while ALCAM knockdown remarkably enhanced 4-OHT induced cell viability inhibition and cell apoptosis in TamR MCF-7 cells. Demethylation reagent treatment significantly restored miR-148a and miR-152 expression in TamR MCF-7 cells. MiR-148a and miR-152 can directly target ALCAM 3′UTR and decrease ALCAM expression. MiR-148a overexpression had similar effect as ALCAM siRNA on enhancing 4-OHT induced cell viability inhibition and cell apoptosis in TamR MCF-7 cells. MiR-152 overexpression alone caused growth inhibition and increased cell apoptosis in TamR MCF-7 cells. It also enhanced the effect of 4-OHT. Simultaneous inhibition of miR-148a and miR-152 significantly protected TamS MCF-7 cells from 4-OHT induced cell viability inhibition and cell apoptosis. Based on these findings, we infer that MiR-148a and miR-152 can sensitize TamR MCF-7 cells to tamoxifen at least via downregulating ALCAM.

Hepatitis B virus X protein (HBx) plays critical roles in hepatocellular tumorigenesis by activating different signaling pathways, including the c-Jun NH2-terminal kinase (JNK) pathway. Phosphorylation of paxillin (PXN) promotes cell migration via activation of the JNK signaling pathway, but PXN overexpression is not associated with poor outcome in patients with hepatocellular carcinoma (HCC). HBx gene manipulation and Western blotting indicated that phosphorylation of PXN at Serine 178 (p(S178)-PXN) by HBx may promote invasiveness in HCC cells via HBx-mediated JNK activation. Immunohistochemical analysis indicated a positive correlation between p(S178)-PXN and HBx expression levels in tumor specimens. The overall survival (OS) and relapse-free survival (RFS) were poorer in patients with high-p(S178)-PXN expressing or high-HBx expressing tumors than in patients with low-p(S178)-PXN expressing or low-HBx expressing tumors. In conclusion, phosphorylation of PXN at Serine 178 by HBx-mediated JNK activation may therefore play a critical role in tumor invasiveness and poor prognosis in patients with HBV-infected hepatocellular tumors. The expression levels of p(S178)-PXN may be a reliable prognostic biomarker to predict the clinical outcomes in patients with HBV-associated HCC.

Background: Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer-related deaths worldwide. Preclinical studies found that copper-lowering agents could re-sensitize platinum-resistant cancer cells by enhancing the human copper transporter 1 (hCtr1)-mediated uptake of platinum. In the clinic, re-sensitization of platinum-resistance in relapsed EOC has been discovered by the application of trientine plus platinum ({"type":"clinical-trial","attrs":{"text":"NCT01178112","term_id":"NCT01178112"}}NCT01178112). However, no pharmacokinetic data of trientine has been reported in cancer patients. Purpose: Our study aimed to explore the safety and activity of trientine combined with carboplatin and pegylated liposomal doxorubicin (PLD) in patients with EOC, tubal, and peritoneal cancer who experienced disease progression during platinum-based chemotherapy or showed relapse

Background/Purpose This study aims to examine the cost effectiveness of treating major cancers compared with other major illnesses in Taiwan. Methods We collected data on 395,330 patients with cancer, 125,277 patients with end-stage renal disease, and 50,481 patients under prolonged mechanical ventilation during 1998–2007. They were followed for 10–13 years to estimate lifetime survival functions using a semiparametric method. EuroQol five-dimension was used to measure the quality of life for 6189 cancer patients and 1401 patients with other illnesses. The mean utility values and healthcare costs reimbursed by the National Health Insurance were multiplied with the corresponding survival probabilities to estimate quality-adjusted life expectancies and lifetime costs, respectively. Data of 22,344 cancer patients under hospice care (considered as a comparison group) were used to conduct a cost-effectiveness analysis. Sensitivity analysis was conducted by assuming patients without treatment survived for 2 years with a quality of life value of 0.5. Results The costs of care for patients under prolonged mechanical ventilation and those with end-stage renal disease were US$41,780–53,708 per quality-adjusted life year (QALY) and US$18,222–18,465 per QALY, respectively, which are equivalent to 2.17–2.79 gross domestic product (GDP) per capita per QALY and 1.18–1.25 GDP per capita per QALY. The costs of care for the nine different cancers were less than 1 GDP per capita per QALY, with those of lung, esophagus, and liver cancers being the highest. Sensitivity analysis showed the same conclusion. Lifetime risks of six out of nine cancer sites show an increased trend. Conclusion Cancer care in Taiwan seemed cost effective compared with that of other illnesses, but prevention is necessary to make the National Health Insurance more sustainable.

Aim The aim of this study was to examine the psychosocial adjustment trajectory, focusing on psychological distress, sexual relationships and healthcare information, and factors which have an impact on adjustment on receiving a positive diagnosis of human papillomavirus infection. Background Human papillomavirus is a common sexually transmitted infection in females. To date, knowledge of the longitudinal psychosocial response to the diagnosis of human papillomavirus is limited. Design A prospective longitudinal design was conducted with a convenience sample. Methods Women aged 20-65 years old were followed at one, 6 and 12 months after a diagnosis of HPV. Participants completed measures of initial emotional distress and followed up psychosocial adjustment. A mixed-effects model was applied to analyse the longitudinal changes in psychosocial adjustment. Results Seventy human papillomavirus positive women participated in the study with nearly 20% of the women reporting emotional distress during their first visit. Mixed-effects model analyses showed that a trajectory of psychosocial adjustment in healthcare orientation, sexual relationship and psychosocial distress occur from one to 6 months after HPV diagnosis. However, a declining trend from 6 to 12 months was significant in healthcare orientation. Initial emotional distress was associated with changes in psychological adjustment. Conclusions Psychosocial adjustment to human papillomavirus was worse at 1 month compared with 6 and 12 months after diagnosis. Healthcare providers should offer health information and psychosocial support to women according to their disease progression.

Objective : To evaluate the role of surgery, radiation therapy and chemotherapy in the management of small cell carcinoma of the uterine cervix (SCCC) through a retrospective study of Taiwanese Gynecologic Oncology Group. Methods : We reviewed the medical records and histological files of 144 patients with FIGO stages IA–IIB SCCC treated in 11 main hospitals in Taiwan from 1987 to 2009. Results : There were 110 patients receiving primary surgery and 34 primary radiation therapy. Most patients in each group also received chemotherapy as part of primary treatment. A lower loco-regional failure rate was observed in patients who received primary radiation therapy than in those who had primary surgery (6% vs. 27%; P =0.009). The 5-year overall survival (OS) was 89% for 13 surgically treated patients with cervical tumor ≤2cm and no lymphovascular space involvement (LVSI) in whom recurrence was noted in 2 of 4 patients without receiving adjuvant chemotherapy and none in the 9 patients who had chemotherapy. Excluding these 13 patients, primary radiation therapy with at least 5cycles of platinum-based chemotherapy ( n =14, including 12 stages IB2–IIB) resulted in a 5-year OS of 78%, better than that of 46% by primary surgery ( n =97, including 40 stages IB2–IIB) ( P =0.046). Conclusions : None of the 9 patients with cervical tumor ≤2cm and no LVSI showed disease recurrence after primary surgery and adjuvant chemotherapy. For most patients with stages I–II, primary radiation therapy with aggressive chemotherapy was associated with better survival than surgery.

Objective: Pelvic endometriosis was found to be associated with oxidative stress in the peritoneal cavity. Endogenous melatonin was known for its antioxidative activities, and oral melatonin had been studied as a treatment option for endometriosis. However, the association between endogenous melatonin and endometriosis has not yet been determined. Materials and methods: A cross-sectional case-control study was implemented. Blood and urine samples from women with surgically confirmed ovarian endometriomas, benign adnexal tumors other than endometriomas, and healthy volunteers were collected and tested for cancer antigen 125 (CA125) as well as urinary 6-sulfatoxymelatonin (aMT6s), a surrogate for average serum melatonin level. Results: A total of 97 patients with endometriomas, 59 with benign ovarian tumors other than endometriomas, and 80 women without adnexal lesion were recruited. Elevated serum CA125 and decreased body mass index were found in patients with ovarian endometriosis (both p

Background Advances in cervical cancer management for childbearing women have led to less radical approaches. Use of fertility-sparing treatment to treat small cell neuroendocrine carcinoma (SCNEC) is challenging owing to the aggressive nature of the disease, even in early stage disease. Case presentation A 25-year-old nulligravida woman presented with malodorous vaginal discharge and was diagnosed to have an exophytic cervical SCNEC. A magnetic resonance image scan showed no evidence of parametrial invasion or distant metastasis. Clinical staging allocated her to stage IB1 disease. She underwent radical abdominal trachelectomy for reproductive purpose. Preoperative and postoperative chemotherapy with ifosfamide/etoposide/cisplatin combining gonadotropin-releasing hormone agonist were administered. She had a spontaneous, uneventful pregnancy and successfully delivered a term baby via cesarean section 7 years after treatment. Conclusion To our knowledge, we describe the first success in offering a fertility-preserving multimodality strategy to present favorable oncologic, reproductive, and obstetric outcomes in a fertile woman of stage I SCNEC. Individualized multimodality therapy may be utilized in specific patients with early-stage cervical cancer to preserve their fertility.

// Ya-Min Cheng 1, * , Po-Lin Lin 2, * , De-Wei Wu 2 , Lee Wang 3 , Chi-Chou Huang 4 and Huei Lee 2 1 Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan 2 Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan 3 Department of Public Health, Chung Shan Medical University, Taichung, Taiwan 4 Department of Surgery, Chung Shan Medical University, Taichung, Taiwan * These authors have contributed equally to this work Correspondence to: Huei Lee, email: hl@tmu.edu.tw Keywords: PSMD4; chemoresistance; Nrf2; colorectal cancer Received: July 11, 2017 Accepted: April 05, 2018 Published: May 29, 2018 ABSTRACT Nuclear Nrf2 (nNrf2) binding to the antioxidant response element may promote chemoresistance in colorectal cancer. However, the shuttling of Nrf2 between cytoplasm and nucleus in colon cancer cells has revealed the possibility that cytoplasmic location of Nrf2 (cNrf2) may play a specific role in chemoresistance. Transfection of a nuclear location sequence (NLS)-wild-type or NLS–mutated Nrf2 expression vector into a stable shNrf2 HCT116 clone using the MTT assay to examine whether chemoresistance induced by cNrf2 may be greater than nNrf2. Different specific inhibitors and small hairpin (sh)RNAs of targeting genes were used to verify the mechanistic action of cNrf2 in chemoresistance and further confirmed by an animal model. The association of cNrf2 with chemotherapeutic response in patients with colorectal cancer was statistically analyzed. The MTT assay indicated that cNrf2 may play a more important role than nNrf2 in conferring 5-fluorouracil (5-FU) and oxaliplatin resistance in HCT116 cells. Mechanistically, cNrf2-induced PSMD4 expression was responsible for chemoresistance in the NLS-mutated Nrf2-tranfected shNrf2HCT116 clone via the NF-κB/AKT/β-catenin/ZEB1 cascades. The tumor burden induced by the NLS-mutated Nrf2-transfected shNrf2HCT116 clone was completely suppressed by treatment with 5-FU in combination with carfilzomib. A higher prevalence of unfavorable chemotherapeutic response in colorectal cancer patients with cNrf2, PSMD4-positive, p-p65-positive, and nuclear β-catenin tumors was observed when compared to their counterparts. cNrf2 may play a more important role than nNrf2 in the chemoresistance of colorectal cancer. Activation of the NF-κB/AKT/β-catenin/ZEB1 cascade by PSMD4 may be responsible for cNrf2-mediated chemoresistance. Condensed abstract: CNrf2 may play a more important role than nNrf2 in conferring 5-FU and oxaliplatin resistance. This observation in patients seemed to support the findings of the cell and animal models and suggested that PSMD4 may be responsible cNrf2-mediated chemoresistance via the NF-κB/AKT/β-catenin /ZEB1 cascades.

Cervical cancer is the most common malignancy in women, for which conization or hysterectomy are the main therapy. Curcubitacin E (Cu E) is a natural compound-based drug which from the Guadi (climbing stem of Cucumic melo L). Previously shown to be an anti-tumor as well as a potent chemopreventive agent against several types of tumors. The present study, investigated anti-proliferation and apoptosis induced by Cu E in cervical cancer cell lines (HeLa and Ca Ski). The results indicate that the cytotoxicity is associated with accumulation in apoptosis but not necrosis. Cu E produced apoptosis as well as the up-regulation the expression of death receptor 5 (DR5). In addition, the DR5 gene activation in apoptosis, both effects increased proportionally with the dose of Cu E; however, mitosis delay was also dependant on the amount of Cu E treatment in the cancer cells. These results indicate that Cu E may delay cancer cell growth by apoptosis via upregulation of DR5 gene expression.

The plasmacytoma variant translocation 1 gene (PVT1) is an oncogenic lncRNA with regulative effect on chemosensitivity in cervical cancer. However, the underlying mechanisms were not fully understood. In this study, HPV16 positive CaSki and SiHa cells were used as in vitro cell model. Knockdown of HPV16 E7 significantly inhibited PVT1 and restored miR-195 expression. PVT1 directly interacts with EZH2 and the complex anchors in the promoter region of miR-195. PVT1 overexpression resulted in increased H3K27me3 levels in the miR-195 promoter region, while PVT1 knockdown decreased H3K27me3 levels in the promoter region. In addition, PVT1 could competitively bind with miR-195. MiR-195 overexpression suppressed PVT1 expression in the cancer cells. Both PVT1 and miR-195 could inhibit paclitaxel (PTX) induced epithelial-to-mesenchymal transition (EMT) and also sensitize CaSki cells to PTX. Based on these findings, we infer that PVT1 could decrease miR-195 expression via enhancing histone H3K27me3 in the miR-195 promoter region and also via direct sponging of miR-195. In addition, the PVT1/miR-195 axis can modulate responses of the cancer cells to PTX via regulating EMT.

High matrix metalloproteinase 1 (MMP1) expression is associated with enhanced breast cancer growth and metastasis and also might predict poor prognosis. In this study, we further investigated the functional role of MMP1 and how it is upregulated in multi-drug resistant (MDR) breast cancer cells. By retrieving microarray data in GEO datasets and the survival data in the Kaplan Meier plotter, we observed that MMP1 is significantly upregulated in MCF-7/ADR cells compared to the parental MCF-7 cells, while high MMP1 expression is associated with worse overall survival (OS) and recurrence free survival (RFS) in breast cancer patients after systematic therapy. Functional studies showed that MMP1 overexpression significantly reduced the drug sensitivity in MCF-7 cells, while MMP1 knockdown substantially enhanced the sensitivity in MCF-7/ADR cells. By performing western blotting and immunofluorescent staining, we confirmed that MCF-7/ADR cells had enhanced mesenchymal properties than MCF-7 cells. In MCF-7 cells, enforced Slug expression resulted in significant MMP1 upregulation, while in MCF-7/ADR cells, Slug knockdown led to reduced MMP1 expression. By performing bioinformatic analysis, we observed that the promoter of MMP1 has three putative Slug binding sites. The following dual luciferase assay and ChIP-qPCR verified these three binding sites. Therefore, we infer that Slug enhances MMP1 transcription via directly binding to the promoter region in breast cancer cells, which is a previously unrecognized mechanism in the development of MDR.

Objective Our previous work revealed that host genes ZNF582 , PTPRR , PAX1 , and SOX1 are highly methylated in cervical intraepithelial neoplasias grade 3 or worse (CIN3 + ). In this study, we used a standardized testing assay to evaluate the clinical efficacy of these biomarkers in the triage of cytological diagnoses of low-grade squamous intraepithelial lesions (LSILs), and compared the performance with human papillomavirus (HPV) testing. Methods This 2-year multicenter prospective study examined a population of 230 women from 12 medical centers who were diagnosed with LSILs on cervical cytology. Cervical scrapings were obtained prior to a colposcopy-directed biopsy for quantitative methylation analysis of ZNF582 , PTPRR , PAX1 , and SOX1 , and HPV testing. Using logistic regression and receiver operating characteristic curve analyses, the abilities of methylated genes and HPV to predict CIN3 + were assessed. Results Fifteen (6.5%) of the 230 women with a cytological diagnosis of LSIL were confirmed to have CIN3 + after a colposcopy-directed biopsy. Among the 4 methylated genes, ZNF582 was found to be the best biomarker for detecting CIN3 + . The sensitivities for methylated ZNF582 and HPV testing were 73% and 80%, and the specificities were 71% and 28%, respectively. The odds ratio for predicting CIN3 + using methylated ZNF582 was 6.8 (95% confidence interval (CI) 2.1–22.1), which was much better than HPV testing (OR=1.6, 95% CI 0.4–5.8). Conclusion This is the first study to show that ZNF582 methylation analysis of cervical swabs may be a promising choice in the positive triage of cytological diagnoses of LSILs.

Objective To estimate the lifetime gain in the health-related quality of life (HRQOL) from early detection of cervical cancer. Methods A consecutive, cross-sectional sample of 421 patients with cervical cancer was administered the World Health Organization Quality of Life-brief version questionnaires. A nationwide sample of 22,543 patients with invasive cervical cancer (ICC) was collected from the national cancer registry for estimation of lifetime survival function from 1998 to 2007, which was further multiplied by the ratio of HRQOL score functions for patients with ICC and patients with carcinoma in situ (CIS), and summed up over lifetime to obtain expected relative-quality-adjusted survival. The difference between lifetime survival and the expected relative-quality-adjusted survival gives the expected total dissatisfied time during the life course. Results In comparison with patients with CIS postconization, patients with ICC showed consistently lower scores in the physical and psychological domains and that of sexual life after adjustment for other risk factors. The expected years of life lost for an invasive cancer was 6.48 years using the general population as the reference cohort, while the durations of equivalent to living with a very dissatisfied HRQOL were 1.71 and 0.25 for the physical and psychological domains, respectively, and 1.47 years for sexual life. Validation of the extrapolation method based on a subcohort followed from the 6th to the 13th year shows a relative bias of 0.4%. Sensitivity analysis with 37,000 CIS cases as the reference cohort yields a similar result. Conclusions Early detection of cervical cancer not only avoids premature mortality but also prevents long-term living under lower HRQOL scores, including sexual life.

We aimed to determine whether PAX1/SOX1 methylation could be translated to clinical practice for cervical neoplasia detection when used alone and in combination with current cytology-based Pap screening. We conducted a multicenter case–control study in 11 medical centers in Taiwan from December 2009 to November 2010. Six hundred seventy-six patients were included in the analysis, including 330 in the training set and 346 in the testing set. Multiplex quantitative methylation-specific polymerase chain reaction (PCR) was performed with a TaqMan probe system using a LightCycler 480 Real-Time PCR System (Roche). The level of human papilloma virus (HPV) was analyzed using a Hybrid Capture 2 system (Digene). Receiver operating characteristic curves were generated to obtain the best cutoff values from the training data set. The sensitivities, specificities, and accuracies were validated in the testing set. The sensitivities for methylated (m) PAX1m and SOX1m and HPV testing for detecting CIN3+ lesions were 0.64, 0.71, and 0.89, and the specificities were 0.91, 0.77, and 0.68, respectively. Combined parallel testing of PAX1m/SOX1m tests with Pap smearing showed superior specificity (0.84/0.71 vs. 0.66, respectively) and similar sensitivity (0.93/0.96 vs. 0.97) to the combination of Pap smear results and HPV testing. Thus, combined parallel testing using Pap smears and PAX1 or SOX1 methylation tests may provide better performance than a combination of Pap smears with HPV testing in detection for cervical neoplasia.

Objectives To investigate, using three-dimensional power Doppler ultrasound (3D-PDU), alterations in cervical intratumoral vascularization during and after radiotherapy. Methods Between 2004 and 2009 we enrolled into the study 37 patients with FIGO Stages IB1–IIB cervical carcinoma who were undergoing radiotherapy. Serial 3D-PDU scans were performed during treatment, providing ultrasonographic measurement of tumor size, vascularization index, flow index and vascularization flow index, as well as monthly for 3 months post-treatment and tri-monthly thereafter, until vascularity was undetectable on two consecutive occasions. Physical examination, cervical cytology and serum marker evaluation were performed every 3–6 months for the first 5 years following treatment. Patients evaluated after a 2-year tumor-free interval and those with clinically assessed positive findings at follow-up underwent 3D-PDU to detect possible local disease. Results A total of 329 3D-PDU scans were performed in the 37 women. Cervical tumors and intratumoral vascularization disappeared within 3 months following radiotherapy, except in one patient with persistent disease. Nine patients had disease relapse, in four of whom the recurrence was local. In three of these four, there was recurrence of tumor and vascularization after a complete response. At follow-up, 3D-PDU detected local disease with 75.0% sensitivity and 98.5% specificity, while serum markers detected local disease among 34 patients with squamous cell carcinoma with 20.0% sensitivity and 77.3% specificity. Conclusions Compared with serum markers in cervical squamous cell carcinoma, 3D-PDU has higher sensitivity and specificity for detecting local recurrence or persistence in cervical carcinoma. Thus, 3D-PDU combined with clinical assessment may be a new and safe method for monitoring radiotherapy treatment response and detecting local recurrence. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

This study investigates the influence of fibroblast growth factor receptor type B (FGFRb) and fibroblast growth factor on cervical carcinogenesis associated with HPV16 E6/7 infection, using primary cancer cells isolated from Taiwanese patients with cervical cancer. Functional interaction between FGFRb in Cx cells and HPV16 E6/7 transfected Cx cells (CxWJ cells) following treatment with FGF-7, according to cell growth, invasive ability, and tumor growth in SCID mice. Our results indicate that the downregulation of FGFRb gene expression in CxWJ cells partially represses proliferation and the invasive ability provided by FGF-7 stimulation. In SCID mice, the FGF2 and FGFR1 gene expression ascend in CxWJ tumor nodule. These data provide evidence of a functional interaction between HPV16 E6/7 in FGFRb and FGF2, suggesting that cooperative stimulation of HPV E6/7 in inactivated FGFRb and the upregulation of FGF2 may be necessary to completely overcome the oncogenic function associated with the progression of cervical carcinogenesis.

Purpose/objectives To assess knowledge and attitudes regarding cervical cancer and human papillomavirus (HPV) among undergraduate women in Taiwan. Design A descriptive cross-sectional design. Setting Five universities in southern Taiwan. Sample 953 undergraduate women aged 17-36 years. Methods The self-administered HPV Belief questionnaire was used to collect data on knowledge and beliefs regarding cervical cancer, Pap testing, and HPV. Main research variables Knowledge, beliefs, cervical cancer, Pap testing, HPV, likelihood of cervical cancer, and HPV infection. Findings Seventy percent of participants agreed that cervical cancer could be prevented and was a severe disease, and 80% knew the purpose of Pap testing. Forty-nine percent were aware of HPV. Undergraduate women with an awareness of HPV were more likely to be older, studying a health-related major, have a higher class standing, have a personal history of gynecologic visits, and have had a Pap test. Neither family history of gynecologic cancer nor sexual experience predicted HPV awareness, although sexual experience had a significant association with the knowledge and beliefs of cervical cancer. Most of the undergraduate women believed themselves unlikely to acquire cervical cancer or HPV infection. Conclusions Undergraduate women in Taiwan have limited knowledge of cervical cancer and HPV. Awareness of the likelihood of HPV infection is low among undergraduate women, even those who are sexually active. Implications for nursing Educational campaigns focusing on cervical cancer screening and HPV infection are needed, particularly for sexually active undergraduate women.

This study was aimed to identify the expression and the correlation of insulin-like growth factor-1 (IGF-1) system and their prognostic impacts in cervical cancer. Seventy-two patients with early-stage cervical cancer were eligible. We obtained the serum levels of total IGF-1 and IGF binding protein-3 (IGFBP-3) by enzyme-linked immunosorbent assay and the expression of IGF-1 receptor (IGF-1R) in cancerous tissue by immuno-fluorescent (IF) stains. The 5-year recurrence-free and overall survival rates were significantly lower (P=0.003 and P=0.01, respectively) among patients with high-grade expression of tissue IGF-1R, compared with those with low-grade expression. After adjustment for other factors, preoperative serum total IGF-1 or IGFBP-3 levels failed to predict cancer death and recurrence. High-grade expression of IGF-1R and elevated preoperative squamous cell carcinoma antigen level were independent predictors of both death and recurrence, and combination of both factors could further help identify the subgroup of patients at higher death risk. The IF staining indicates the colocalisation of IGF-1 and IGF-1R in the cancerous tissues, whereas the IGF-1R expression is not correlated with circulating levels of IGF-1 or IGFBP-3. In early-stage cervical cancer, IGF-1 system may have a paracrine or autocrine function and the adverse impacts on prognosis by IGF-1R overexpression are implicated.

Squamous cell carcinoma antigen (SCCA) is a tumor marker for patients with squamous cell carcinoma of uterine cervix, lung, and esophagus. It was encoded by two highly homologous genes, SCCA1 and SCCA2. However, the relevance of SCCA genes to squamous cell carcinogenesis and patient outcome remains far from clear. In this study, by using laser microdissection and real-time quantitative polymerase chain reaction procedures, the messenger RNA (mRNA) expression of the SCCA1 and SCCA2 genes in normal, dysplastic, and malignant squamous epithelia from uterine cervical tissues were analyzed and correlated with outcome of cancer patients. We found that the SCCA2/A1 mRNA ratios were progressively increased from normal, dysplastic, to cancer cells, and the mean ratio was significantly higher in cancer tissues than that in normal epithelium (P= 0.02). The SCCA2/A1 mRNA ratios were not significantly associated with types of human papillomavirus infection (P > 0.05). High SCCA2/SCCA1 mRNA ratios (ratio >1) were an independent predictor of disease recurrence (relative risk: 3.58; P= 0.003). Of the 38 patients with cervical cancer, 12 patients with high SCCA2/SCCA1 mRNA ratios had a significant lower 2-year disease-free survival of only 50%, while it was 92% in those with low SCCA2/SCCA1 mRNA ratios (P < 0.001). In conclusion, our study indicated that the ratios of SCCA2 to SCCA1 RNA were increased during the process of cervical carcinogenesis, and patients with elevated SCCA2/A1 ratio carried a higher risk for recurrence in early-stage uterine cervical cancer.