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Sample records for cell cervical cancer

  1. Knockdown of Legumain Suppresses Cervical Cancer Cell Migration and Invasion.

    PubMed

    Meng, Fei; Liu, Wei

    2016-01-01

    Cervical cancer is the second leading type of cancer in women living in less developed countries. The pathological and molecular mechanisms of cervical cancer are not comprehensively known. Though legumain has been found to be highly expressed in various types of solid tumors, its expression and biological function in cervical cancer remain unknown. In this study, we aimed to investigate legumain expression and functions in cervical cancer. We found that legumain was highly expressed in cervical cancer cells. When knocked down, legumain expression in HeLa and SiHa cells significantly reduced its migration and invasion abilities compared with control cells. Furthermore, legumain silencing suppressed the activation of matrix metalloproteases (MMP2 and MMP3) in cervical cancer cells. This study indicates that legumain might play an important role in cervical cancer cell migration and invasion. Legumain might be a potential therapeutic target for cervical cancer therapy.

  2. Cervical Cancer

    MedlinePlus

    ... dysplasia of the cervix, vagina, or vulva • A family history of cervical cancer •Smoking •Certain sexually transmitted infections , such as chlamydia • ... to treat your cancer, you still need cervical cancer screening. Cells are taken from the upper vagina ... smallest units of a structure in the body; the building blocks for all ...

  3. Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer

    ClinicalTrials.gov

    2016-03-25

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  4. Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2014-09-22

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer

  5. FDG and FMISO PET Hypoxia Evaluation in Cervical Cancer

    ClinicalTrials.gov

    2015-06-03

    Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  6. ADXS11-001 High Dose HPV+ Cervical Cancer

    ClinicalTrials.gov

    2016-06-17

    Effects of Immunotherapy; Metastatic/Recurrent Cervical Cancer; Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Cervical Small Cell Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  7. Nanomechanical clues from morphologically normal cervical squamous cells could improve cervical cancer screening

    NASA Astrophysics Data System (ADS)

    Geng, Li; Feng, Jiantao; Sun, Quanmei; Liu, Jing; Hua, Wenda; Li, Jing; Ao, Zhuo; You, Ke; Guo, Yanli; Liao, Fulong; Zhang, Youyi; Guo, Hongyan; Han, Jinsong; Xiong, Guangwu; Zhang, Lufang; Han, Dong

    2015-09-01

    Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis.Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03662c

  8. MRI and PET Imaging in Predicting Treatment Response in Patients With Stage IB-IVA Cervical Cancer

    ClinicalTrials.gov

    2016-06-24

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Cervical Undifferentiated Carcinoma; Recurrent Cervical Carcinoma; Stage IB2 Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  9. Embryonic stem cell-specific signature in cervical cancer.

    PubMed

    Organista-Nava, Jorge; Gómez-Gómez, Yazmín; Gariglio, Patricio

    2014-03-01

    The wide range of invasive and noninvasive lesion phenotypes associated with high-risk human papillomavirus (HR-HPV) infection in cervical cancer (CC) indicates that not only the virus but also specific cervical epithelial cells in the transformation zone (TZ), such as stem cells (SCs), play an important part in the development of cervical neoplasia. In this review, we focused in an expression signature that is specific to embryonic SCs and to poorly differentiated cervical malignant tumors and we hypothesize that this expression signature may play an important role to promote cell growth, survival, colony formation, lack of adhesion, as well as cell invasion and migration in CC.

  10. Radiation Therapy Plus Cisplatin and Gemcitabine in Treating Patients With Cervical Cancer

    ClinicalTrials.gov

    2014-12-23

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  11. Cervical Cancer

    MedlinePlus

    ... the place where a baby grows during pregnancy. Cervical cancer is caused by a virus called HPV. The ... for a long time, or have HIV infection. Cervical cancer may not cause any symptoms at first. Later, ...

  12. Zoledronic acid induces apoptosis and autophagy in cervical cancer cells.

    PubMed

    Wang, I-Te; Chou, Shou-Chu; Lin, Ying-Chin

    2014-12-01

    Cervical cancer is one of the most common gynecological cancers in association with high mortality and morbidity. The present study was aimed to investigate the in vitro effects of zoledronic acid (ZA) on viability and induction of apoptosis and autophagy as well as inflammatory effects in three human cervical cancer cell lines (HeLa, SiHa, and CaSki). Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Induction of apoptosis was determined by quantitation of expression level of B cell lymphoma 2 (Bcl-2) and Bax messenger RNA (mRNA) and identification of the proteolytic cleavage of poly (ADP)-ribose polymerase (PARP) and caspase-3. Autophagic effects were examined by quantitation of mRNA expression of autophagy protein 5 (ATG5) and beclin1 and identifying accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II. Inflammatory effect was determined by measuring expression and production of IL-6 and cyclooxygenase-2 (Cox-2). The results showed ZA significantly inhibited cell viability of cervical cancer cells. ZA-induced cell death displayed features characteristic to both apoptosis and autophagy and was associated with different changes in the levels of Bcl-2 and Bax in the various cervical cancer lines. Expression of metastatic cytokines, IL-6 and Cox-2, was upregulated in the presence of ZA at low concentration. Our data revealed that ZA inhibits cervical cancer cells through the synergistic effect of apoptosis induction and autophagy activation.

  13. Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer

    ClinicalTrials.gov

    2014-06-18

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  14. Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

    ClinicalTrials.gov

    2014-12-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  15. Cisplatin and Radiation Therapy Followed by Paclitaxel and Carboplatin in Treating Patients With Stage IB-IVA Cervical Cancer

    ClinicalTrials.gov

    2016-03-16

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  16. Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells

    PubMed Central

    2012-01-01

    Background Abnormal expression of Rho-GTPases has been reported in several human cancers. However, the expression of these proteins in cervical cancer has been poorly investigated. In this study we analyzed the expression of the GTPases Rac1, RhoA, Cdc42, and the Rho-GEFs, Tiam1 and beta-Pix, in cervical pre-malignant lesions and cervical cancer cell lines. Methods Protein expression was analyzed by immunochemistry on 102 cervical paraffin-embedded biopsies: 20 without Squamous Intraepithelial Lesions (SIL), 51 Low- grade SIL, and 31 High-grade SIL; and in cervical cancer cell lines C33A and SiHa, and non-tumorigenic HaCat cells. Nuclear localization of Rac1 in HaCat, C33A and SiHa cells was assessed by cellular fractionation and Western blotting, in the presence or not of a chemical Rac1 inhibitor (NSC23766). Results Immunoreacivity for Rac1, RhoA, Tiam1 and beta-Pix was stronger in L-SIL and H-SIL, compared to samples without SIL, and it was significantly associated with the histological diagnosis. Nuclear expression of Rac1 was observed in 52.9% L-SIL and 48.4% H-SIL, but not in samples without SIL. Rac1 was found in the nucleus of C33A and SiHa cells but not in HaCat cells. Chemical inhibition of Rac1 resulted in reduced cell proliferation in HaCat, C33A and SiHa cells. Conclusion Rac1 is expressed in the nucleus of epithelial cells in SILs and cervical cancer cell lines, and chemical inhibition of Rac1 reduces cellular proliferation. Further studies are needed to better understand the role of Rho-GTPases in cervical cancer progression. PMID:22443139

  17. Chemoradiation Therapy and Ipilimumab in Treating Patients With Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2016-10-25

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  18. Atezolizumab and Bevacizumab in Treating Patients With Recurrent, Persistent, or Metastatic Cervical Cancer

    ClinicalTrials.gov

    2016-10-10

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  19. Nivolumab in Treating Patients With Persistent, Recurrent, or Metastatic Cervical Cancer

    ClinicalTrials.gov

    2016-11-01

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  20. Cell membrane softening in human breast and cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Händel, Chris; Schmidt, B. U. Sebastian; Schiller, Jürgen; Dietrich, Undine; Möhn, Till; Kießling, Tobias R.; Pawlizak, Steve; Fritsch, Anatol W.; Horn, Lars-Christian; Briest, Susanne; Höckel, Michael; Zink, Mareike; Käs, Josef A.

    2015-08-01

    Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.

  1. Tetraspanin 1 promotes invasiveness of cervical cancer cells.

    PubMed

    Hölters, Sebastian; Anacker, Jelena; Jansen, Lars; Beer-Grondke, Katrin; Dürst, Matthias; Rubio, Ignacio

    2013-08-01

    Tetraspanins are a heterogeneous group of 4-transmembrane proteins that segregate into so-called tetraspanin-enriched microdomains (TEMs) along with other cell surface proteins such as integrins. TEMs of various types are reportedly involved in the regulation of cell growth, migration and invasion of several tumour cell types, both as suppressors or supporting structures. Tetraspanin 1 (Tspan1, NET-1), a member of the transmembrane 4 superfamily (TM4SF) of tetraspanins, is overexpressed in high-grade cervical intraepithelial neoplasia (CIN) and terminal carcinomas but its precise function in the context of carcinoma of the cervix uteri is not known. Here, we present a comprehensive investigation of the role of tetraspanin 1 in the cervical cancer cell lines SiHa and HeLa. We document that tetraspanin 1 increases the invasive potential of cervical cancer cells, whereas proliferation, growth in soft agar and adhesion are largely unaffected. In line with the latter findings, our data exclude the participation of testraspanin in integrin-mediated activation of focal adhesion kinase (FAK), paxillin and phosphoinositide-3-kinase (PI3K) and in EGFR-dependent signalling to the Ras/Erk pathway. In conclusion, our data argue against a role for tetraspanin 1 as a genuine mediator of cell surface receptor signalling but rather document a role for tetraspanin 1 in the control of cervical cancer cell motility and invasion.

  2. Tetraspanin 1 promotes invasiveness of cervical cancer cells.

    PubMed

    Hölters, Sebastian; Anacker, Jelena; Jansen, Lars; Beer-Grondke, Katrin; Dürst, Matthias; Rubio, Ignacio

    2013-08-01

    Tetraspanins are a heterogeneous group of 4-transmembrane proteins that segregate into so-called tetraspanin-enriched microdomains (TEMs) along with other cell surface proteins such as integrins. TEMs of various types are reportedly involved in the regulation of cell growth, migration and invasion of several tumour cell types, both as suppressors or supporting structures. Tetraspanin 1 (Tspan1, NET-1), a member of the transmembrane 4 superfamily (TM4SF) of tetraspanins, is overexpressed in high-grade cervical intraepithelial neoplasia (CIN) and terminal carcinomas but its precise function in the context of carcinoma of the cervix uteri is not known. Here, we present a comprehensive investigation of the role of tetraspanin 1 in the cervical cancer cell lines SiHa and HeLa. We document that tetraspanin 1 increases the invasive potential of cervical cancer cells, whereas proliferation, growth in soft agar and adhesion are largely unaffected. In line with the latter findings, our data exclude the participation of testraspanin in integrin-mediated activation of focal adhesion kinase (FAK), paxillin and phosphoinositide-3-kinase (PI3K) and in EGFR-dependent signalling to the Ras/Erk pathway. In conclusion, our data argue against a role for tetraspanin 1 as a genuine mediator of cell surface receptor signalling but rather document a role for tetraspanin 1 in the control of cervical cancer cell motility and invasion. PMID:23754316

  3. Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study

    PubMed Central

    Andrae, Bengt; Sundström, Karin; Ström, Peter; Ploner, Alexander; Elfström, K Miriam; Arnheim-Dahlström, Lisen; Dillner, Joakim; Sparén, Pär

    2016-01-01

    Objectives To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. Design Nationwide population based cohort study. Setting Cancer and population registries in Sweden. Participants 3 054 328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2 899 968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. Main outcome measures Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. Results The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment

  4. Radiation Therapy and Cisplatin With or Without Epoetin Alfa in Treating Patients With Cervical Cancer and Anemia

    ClinicalTrials.gov

    2014-12-29

    Anemia; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Drug Toxicity; Radiation Toxicity; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  5. Glycoprotein and Glycan in Tissue and Blood Samples of Patients With Stage IB-IVA Cervical Cancer Undergoing Surgery to Remove Pelvic and Abdominal Lymph Nodes

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  6. Proteomic patterns of cervical cancer cell lines, a network perspective

    PubMed Central

    2011-01-01

    Background Cervical cancer is a major mortality factor in the female population. This neoplastic is an excellent model for studying the mechanisms involved in cancer maintenance, because the Human Papilloma Virus (HPV) is the etiology factor in most cases. With the purpose of characterizing the effects of malignant transformation in cellular activity, proteomic studies constitute a reliable way to monitor the biological alterations induced by this disease. In this contextual scheme, a systemic description that enables the identification of the common events between cell lines of different origins, is required to distinguish the essence of carcinogenesis. Results With this study, we sought to achieve a systemic perspective of the common proteomic profile of six cervical cancer cell lines, both positive and negative for HPV, and which differ from the profile corresponding to the non-tumourgenic cell line, HaCaT. Our objectives were to identify common cellular events participating in cancer maintenance, as well as the establishment of a pipeline to work with proteomic-derived results. We analyzed by means of 2D SDS-PAGE and MALDI-TOF mass spectrometry the protein extracts of six cervical cancer cell lines, from which we identified a consensus of 66 proteins. We call this group of proteins, the "central core of cervical cancer". Starting from this core set of proteins, we acquired a PPI network that pointed, through topological analysis, to some proteins that may well be playing a central role in the neoplastic process, such as 14-3-3ζ. In silico overrepresentation analysis of transcription factors pointed to the overexpression of c-Myc, Max and E2F1 as key transcription factors involved in orchestrating the neoplastic phenotype. Conclusions Our findings show that there is a "central core of cervical cancer" protein expression pattern, and suggest that 14-3-3ζ is key to determine if the cell proliferates or dies. In addition, our bioinformatics analysis suggests that

  7. Carbon nanowall scaffold to control culturing of cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Watanabe, Hitoshi; Kondo, Hiroki; Okamoto, Yukihiro; Hiramatsu, Mineo; Sekine, Makoto; Baba, Yoshinobu; Hori, Masaru

    2014-12-01

    The effect of carbon nanowalls (CNWs) on the culturing rate and morphological control of cervical cancer cells (HeLa cells) was investigated. CNWs with different densities were grown using plasma-enhanced chemical vapor deposition and subjected to post-growth plasma treatment for modification of the surface terminations. Although the surface wettability of the CNWs was not significantly dependent on the CNW densities, the cell culturing rates were significantly dependent. Morphological changes of the cells were not significantly dependent on the density of CNWs. These results indicate that plasma-induced surface morphology and chemical terminations enable nanobio applications using carbon nanomaterials.

  8. Clinical implication of voltage-dependent anion channel 1 in uterine cervical cancer and its action on cervical cancer cells

    PubMed Central

    Wu, Chih-Hsien; Lin, Yu-Wen; Wu, Tzu-Fan; Ko, Jiunn-Liang; Wang, Po-Hui

    2016-01-01

    Two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry were performed to investigate the influence of human nonmetastatic clone 23 type 1 (nm23-H1), a metastasis-associated gene on proteomic alterations in cancer cells of the uterine cervix. It was validated by RT-PCR and Western blot analysis. The expression of voltage-dependent anion channel 1 (VDAC1) was increased in nm23-H1 gene silenced SiHa or CaSki cervical cancer cells. The clinical implication was shown that cervical cancer tissues with positive VDAC1 immunoreactivity exhibited deep stromal invasion (>10 mm in depth) and large tumor size (> 4 cm in diameter). Cervical cancer patients with positive VDAC1 immunoreactivity displayed higher recurrence and poorer overall survival than those with negative VDAC1. Silencing of VDAC1 reduced cell proliferation and migratory ability. Mitochondrial membrane potential was decreased and reactive oxygen species generation was increased in the VDAC1 gene-silenced cervical cancer cells. Cell cycle progression and autophagy were not changed in VDAC1 silencing cells. The cytotoxicity of cisplatin was significantly enhanced by knockdown of cellular VDAC1 and the compounds that interfere with hexokinase binding to VDAC. Therapeutic strategies may be offered using VDAC1 as a target to reduce cell growth and migration, enhance the synergistic therapeutic efficacy of cisplatin and reduce cisplatin dose-limiting toxicity. PMID:26716410

  9. High expression of prolactin receptor is associated with cell survival in cervical cancer cells

    PubMed Central

    2013-01-01

    Background The altered expression of prolactin (PRL) and its receptor (PRLR) has been implicated in breast and other types of cancer. There are few studies that have focused on the analysis of PRL/PRLR in cervical cancer where the development of neoplastic lesions is influenced by the variation of the hormonal status. The aim of this study was to evaluate the expression of PRL/PRLR and the effect of PRL treatment on cell proliferation and apoptosis in cervical cancer cell lines. Results High expression of multiple PRLR forms and PRLvariants of 60–80 kDa were observed in cervical cancer cell lines compared with non-tumorigenic keratinocytes evaluated by Western blot, immunofluorecence and real time PCR. Treatment with PRL (200 ng/ml) increased cell proliferation in HeLa cells determined by the MTT assay at day 3 and after 1 day a protective effect against etoposide induced apoptosis in HeLa, SiHa and C-33A cervical cancer cell lines analyzed by the TUNEL assay. Conclusions Our data suggests that PRL/PRLR signaling could act as an important survival factor for cervical cancer. The use of an effective PRL antagonist may provide a better therapeutic intervention in cervical cancer. PMID:24148306

  10. Cervical Cancer Screening

    MedlinePlus

    ... cervical cancer in women aged 30–65 years. Human Immunodeficiency Virus (HIV): A virus that attacks certain cells of the body’s immune system and causes acquired immunodeficiency syndrome (AIDS). Human Papillomavirus ( ...

  11. Immunotherapy for Cervical Cancer

    Cancer.gov

    In an early phase NCI clinical trial, two patients with metastatic cervical cancer had a complete disappearance of their tumors after receiving treatment with a form of immunotherapy called adoptive cell transfer.

  12. Inhibiting CD146 by its Monoclonal Antibody AA98 Improves Radiosensitivity of Cervical Cancer Cells.

    PubMed

    Cheng, Huawen

    2016-01-01

    BACKGROUND Cervical cancer is one of the major causes of cancer death of females worldwide. Radiotherapy is considered effective for cervical cancer treatment, but the low radiosensitivity found in some cases severely affects therapeutic outcomes. This study aimed to reveal the role of CD146, an important adhesion molecule facilitating tumor angiogenesis, in regulating radiosensitivity of cervical cancer cells. MATERIAL AND METHODS CD146 protein expression was compared in normal cells, cervical cancer cells with lower radiosensitivity, and cervical cancer cells with higher sensitivity from cervical squamous cell carcinoma patients. Anti-CD146 monoclonal antibody AA98 was used to inhibit CD146 in human cervical cancer SiHa cells with relatively low radiosensitivity, and then the cell survival and apoptosis changes after radiation were detected by colony formation assay and flow cytometry. RESULTS CD146 protein was significantly up-regulated in cervical cancer cells (P<0.001), especially in cancer cells with lower radiosensitivity. The SiHa cells treated with AA98 showed more obvious inhibition in cell survival (P<0.05) and promotion in cell apoptosis (P<0.01) after radiation, compared to the untreated cells. More dramatic changes in apoptotic factors Caspase 3 and Bcl-XL were also detected in AA98-treated cells. CONCLUSIONS These results indicate that inhibiting CD146 improves the effect of radiation in suppressing SiHa cells. This study shows the potential of CD146 as a target for increasing radiosensitivity of cervical cancer cells, which might allow improvement in treatment outcome in cervical cancer. Further studies are necessary for understanding the detailed mechanism of CD146 in regulating radiosensitivity. PMID:27647179

  13. Inhibiting CD146 by its Monoclonal Antibody AA98 Improves Radiosensitivity of Cervical Cancer Cells

    PubMed Central

    Cheng, Huawen

    2016-01-01

    Background Cervical cancer is one of the major causes of cancer death of females worldwide. Radiotherapy is considered effective for cervical cancer treatment, but the low radiosensitivity found in some cases severely affects therapeutic outcomes. This study aimed to reveal the role of CD146, an important adhesion molecule facilitating tumor angiogenesis, in regulating radiosensitivity of cervical cancer cells. Material/Methods CD146 protein expression was compared in normal cells, cervical cancer cells with lower radiosensitivity, and cervical cancer cells with higher sensitivity from cervical squamous cell carcinoma patients. Anti-CD146 monoclonal antibody AA98 was used to inhibit CD146 in human cervical cancer SiHa cells with relatively low radiosensitivity, and then the cell survival and apoptosis changes after radiation were detected by colony formation assay and flow cytometry. Results CD146 protein was significantly up-regulated in cervical cancer cells (P<0.001), especially in cancer cells with lower radiosensitivity. The SiHa cells treated with AA98 showed more obvious inhibition in cell survival (P<0.05) and promotion in cell apoptosis (P<0.01) after radiation, compared to the untreated cells. More dramatic changes in apoptotic factors Caspase 3 and Bcl-XL were also detected in AA98-treated cells. Conclusions These results indicate that inhibiting CD146 improves the effect of radiation in suppressing SiHa cells. This study shows the potential of CD146 as a target for increasing radiosensitivity of cervical cancer cells, which might allow improvement in treatment outcome in cervical cancer. Further studies are necessary for understanding the detailed mechanism of CD146 in regulating radiosensitivity. PMID:27647179

  14. Cisplatin and Radiation Therapy With or Without Triapine in Treating Patients With Previously Untreated Stage IB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

    ClinicalTrials.gov

    2016-03-25

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB2 Cervical Cancer; Stage II Vaginal Cancer; Stage IIA1 Cervical Cancer; Stage IIA2 Cervical Cancer; Stage IIB Cervical Cancer; Stage III Vaginal Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Vaginal Adenocarcinoma; Vaginal Adenosquamous Carcinoma; Vaginal Squamous Cell Carcinoma

  15. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    SciTech Connect

    Wang, Hongtao; Gao, Peng; Zheng, Jie

    2014-09-05

    Highlights: • As{sub 2}O{sub 3} inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As{sub 2}O{sub 3} is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As{sub 2}O{sub 3}) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As{sub 2}O{sub 3} induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As{sub 2}O{sub 3} on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As{sub 2}O{sub 3} than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As{sub 2}O{sub 3} than HPV 16-positive CaSki and SiHa cells. After As{sub 2}O{sub 3} treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As{sub 2}O{sub 3} is a potential anticancer drug for cervical cancer.

  16. Down-regulating overexpressed human Lon in cervical cancer suppresses cell proliferation and bioenergetics.

    PubMed

    Nie, Xiaobo; Li, Min; Lu, Bin; Zhang, Yuxin; Lan, Linhua; Chen, Lin; Lu, Jianxin

    2013-01-01

    The human mitochondrial ATP-dependent Lon protease functions in regulating the metabolism and quality control of proteins and mitochondrial DNA (mtDNA). However, the role of Lon in cancer is not well understood. Therefore, this study was undertaken to investigate the importance of Lon in cervical cancer cells from patients and in established cell lines. Microarray analysis from 30 cancer and 10 normal cervical tissues were analyzed by immunohistochemistry for Lon protein levels. The expression of Lon was also examined by immunoblotting 16 fresh cervical cancer tissues and their respective non-tumor cervical tissues. In all cases, Lon expression was significantly elevated in cervical carcinomas as compared to normal tissues. Augmented Lon expression in tissue microarrays did not vary between age, tumor-node-metastasis grades, or lymph node metastasis. Knocking down Lon in HeLa cervical cancer cells by lentivrial transduction resulted in a substantial decrease in both mRNA and protein levels. Such down-regulation of Lon expression significantly blocked HeLa cell proliferation. In addition, knocking down Lon resulted in decreased cellular bioenergetics as determined by measuring aerobic respiration and glycolysis using the Seahorse XF24 extracellular flux analyzer. Together, these data demonstrate that Lon plays a potential role in the oncogenesis of cervical cancer, and may be a useful biomarker and target in the treatment of cervical cancer. Lon; immunohistochemistry; cervical cancer; cell proliferation; cellular bioenergetics.

  17. General Information about Cervical Cancer

    MedlinePlus

    ... Research Cervical Cancer Treatment (PDQ®)–Patient Version General Information About Cervical Cancer Go to Health Professional Version ... the NCI website . Cervical Cancer During Pregnancy General Information About Cervical Cancer During Pregnancy Treatment of cervical ...

  18. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

    PubMed Central

    ZHAO, BING; HU, MENGCAI

    2013-01-01

    Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer. PMID:24843386

  19. Lysophosphatidic Acid Inhibits Apoptosis Induced by Cisplatin in Cervical Cancer Cells

    PubMed Central

    Sui, Yanxia; Yang, Ya; Wang, Ji; Li, Yi; Ma, Hongbing; Cai, Hui; Liu, Xiaoping; Zhang, Yong; Wang, Shufeng; Li, Zongfang; Zhang, Xiaozhi; Wang, Jiansheng; Liu, Rui; Yan, Yanli; Xue, Chaofan; Shi, Xiaowei; Tan, Li; Ren, Juan

    2015-01-01

    Cervical cancer is the second most common cause of cancer death in women worldwide. Lysophosphatidic acid (LPA) level has been found significantly increased in the serum of patients with ovarian, cervical, and colon cancers. LPA level in cervical cancer patients is significantly higher than in healthy controls. LPA receptors were found highly expressed in cervical cancer cells, suggesting LPA may play a role in the development of cervical cancer. The aim of this study is to investigate the effect of LPA on the apoptosis induced by cisplatin (DDP) in cervical cancer cell line and the underlying changes in signaling pathways. Our study found that cisplatin induced apoptosis of Hela cell through inhibiting expression of Bcl-2, upregulating the expression of Bax, Fas-L, and the enzyme activity of caspase-3 (p < 0.05); LPA significantly provided protection against the apoptosis induced by cisplatin by inhibiting the above alterations in apoptotic factor caused by cisplatin (p < 0.05). Moreover, PI3K/AKT pathway was found to be important for the LPA antiapoptosis effect, and administration of PI3K/AKT partially reversed the LPA-mediated protection against cisplatin-induced apoptosis (p < 0.05). These findings have shed new lights on the LPA bioactivity in cervical cancer cells and pointed to a possible sensitization scheme through combined administration of PI3K inhibitor and cisplatin for better treatment of cervical cancer patients, especially those with elevated LPA levels. PMID:26366416

  20. Cervical cancer.

    PubMed

    Shepherd, John H

    2012-06-01

    Standard treatment for invasive cervical cancer involves either radical surgery or radiotherapy. Childbearing is therefore impossible after either of these treatments. A fertility-sparing option, however, by radical trachelectomy has been shown to be effective, provided that strict criteria for selection are followed. Fertility rates are high, whereas recurrence is low, indicating that a more conservative approach to dealing with early small cervical tumours is feasible. Careful preoperative assessment by magnetic resonance imaging scans allows accurate measurement of the tumour with precise definition to plan surgery. This will ensure an adequate clear margin by wide excision of the tumour excising the cervix by radical vaginal trachelectomy with surrounding para-cervical and upper vaginal tissues. An isthmic cerclage is inserted to provide competence at the level of the internal orifice. A primary vagino-isthmic anastomosis is conducted to restore continuity of the lower genital tract. Subsequent pregnancies require careful monitoring in view of the high risk of spontaneous premature rupture of the membranes. Delivery by classical caesarean section is necessary at the onset of labour or electively before term. Over 1100 such procedures have been carried out vaginally or abdominally, resulting in 240 live births. Radical vaginal trachelectomy with a laparoscopic pelvic-node dissection offers the least morbid and invasive route for surgery, provided that adequate surgical skills have been obtained. PMID:22353492

  1. Hedgehog pathway regulators influence cervical cancer cell proliferation, survival and migration

    SciTech Connect

    Samarzija, Ivana; Beard, Peter

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer Unknown cellular mutations complement papillomavirus-induced carcinogenesis. Black-Right-Pointing-Pointer Hedgehog pathway components are expressed by cervical cancer cells. Black-Right-Pointing-Pointer Hedgehog pathway activators and inhibitors regulate cervical cancer cell biology. Black-Right-Pointing-Pointer Cell immortalization by papillomavirus and activation of Hedgehog are independent. -- Abstract: Human papillomavirus (HPV) infection is considered to be a primary hit that causes cervical cancer. However, infection with this agent, although needed, is not sufficient for a cancer to develop. Additional cellular changes are required to complement the action of HPV, but the precise nature of these changes is not clear. Here, we studied the function of the Hedgehog (Hh) signaling pathway in cervical cancer. The Hh pathway can have a role in a number of cancers, including those of liver, lung and digestive tract. We found that components of the Hh pathway are expressed in several cervical cancer cell lines, indicating that there could exists an autocrine Hh signaling loop in these cells. Inhibition of Hh signaling reduces proliferation and survival of the cervical cancer cells and induces their apoptosis as seen by the up-regulation of the pro-apoptotic protein cleaved caspase 3. Our results indicate that Hh signaling is not induced directly by HPV-encoded proteins but rather that Hh-activating mutations are selected in cells initially immortalized by HPV. Sonic Hedgehog (Shh) ligand induces proliferation and promotes migration of the cervical cancer cells studied. Together, these results indicate pro-survival and protective roles of an activated Hh signaling pathway in cervical cancer-derived cells, and suggest that inhibition of this pathway may be a therapeutic option in fighting cervical cancer.

  2. Cervical Cancer Screening

    MedlinePlus

    ... Cancer found early may be easier to treat. Cervical cancer screening is usually part of a woman's health ... may do more tests, such as a biopsy. Cervical cancer screening has risks. The results can sometimes be ...

  3. Biomarkers in Cervical Cancer

    PubMed Central

    Yim, Eun-Kyoung; Park, Jong-Sup

    2006-01-01

    Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus (HPV) is the single most important etiological agent in cervical cancer, contributing to neoplastic progression through the action of viral oncoproteins, mainly E6 and E7. Cervical screening programs using Pap smear testing have dramatically improved cervical cancer incidence and reduced deaths, but cervical cancer still remains a global health burden. The biomarker discovery for accurate detection and diagnosis of cervical carcinoma and its malignant precursors (collectively referred to as high-grade cervical disease) represents one of the current challenges in clinical medicine and cytopathology. PMID:19690652

  4. Location and Density of Immune Cells in Precursor Lesions and Cervical Cancer.

    PubMed

    Bedoya, Astrid M; Jaramillo, Roberto; Baena, Armando; Castaño, Jorge; Olaya, Natalia; Zea, Arnold H; Herrero, Rolando; Sanchez, Gloria I

    2013-04-01

    Only a small proportion of women infected with Human Papillomavirus (HPV) develop cervical cancer. Host immune response seems to play a role eliminating the viral infection and preventing progression to cancer. Characterization of tumor infiltrating lymphocytes (TILs) in cervical pre-neoplastic lesions and cervical cancer may be helpful to understand the mechanisms that mediate this protection. The aim of this study was to determine if there are differences in the localization and density (cells/mm(2)) of CD8+ T-cells, CD4+ T-cells and Tregs (CD25 + Foxp3+) in cervical pre-neoplastic lesions and cervical cancer. Immunohistochemical analysis of sections of 96 (26 CIN1, 21 CIN2, 25 CIN3, and 24 SCC) samples revealed that regardless of CIN grades, CD8+ T-cells are more abundant than CD4+, CD25+ and Foxp3+ cells in both the stroma and epithelium. There was a higher density of CD8+ cells in the stroma of cervical cancer compared to CIN3 (OR = 4.20, 95% CI 1.2-15), CIN2 (OR = 7.86, 95% CI 1.7-36.4) and CIN1 (OR = 4.25, 95% CI 1.1-17). Studies evaluating whether these cells are recruited before or after cancer progression will be helpful to understand the role of these cells in the natural history of HPV-induced lesions.

  5. RANKL/RANK interaction promotes the growth of cervical cancer cells by strengthening the dialogue between cervical cancer cells and regulation of IL-8 secretion.

    PubMed

    Shang, Wen-Qing; Li, Hui; Liu, Li-Bing; Chang, Kai-Kai; Yu, Jia-Jun; Xie, Feng; Li, Ming-Qing; Yu, Jin-Jin

    2015-12-01

    Receptor activator for nuclear factor κB ligand (RANKL) is a member of the tumor necrosis factor (TNF) family. The interaction between RANKL and its receptor RANK plays an important role in the development and function of diverse tissues. However, the expression and role of RANKL in cervical cancer are still unknown. In the present study, we found that RANKL and RANK were highly co-expressed in cervical cancer. HeLa and SiHa cells secreted soluble RANKL (sRANKL), expressed member RANKL (mRANKL) and RANK. Recombinant human RANKL protein had no effect on the viability of HeLa and SiHa cells. Yet, blocking RANKL with an anti-human RANKL neutralizing antibody (α-RANKL) or recombinant human osteoprotegrin (OPG) protein resulted in the downregulation of Ki-67 and B-cell lymphoma 2 (Bcl-2) expression and an increase in Fas and Fas ligand (FasL) expression, as well as a high level of viability and a low level of apoptosis in the HeLa and SiHa cells. In addition, α-RANKL led to a decrease in IL-8 secretion. Recombinant human IL-8 protein reversed the effect of α-RANKL on the expression of proliferation- and apoptosis‑related molecules, and proliferation and apoptosis in the HeLa and SiHa cells. The present study suggests that a high level of mRANKL/RANK expression in cervical cancer lesions plays an important role in the rapid growth of cervical cancer cells possibly through strengthening the dialogue between cervical cancer cells and regulation of IL-8 secretion, which may be a possible target for cervical cancer therapy.

  6. Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy.

    PubMed

    Zhao, Xueqin; Zhong, Yunxin; Ye, Ting; Wang, Dajing; Mao, Bingwei

    2015-12-01

    The mechanical properties of cells are considered promising biomarkers for the early diagnosis of cancer. Recently, atomic force microscopy (AFM)-based nanoindentation technology has been utilized for the examination of cell cortex mechanics in order to distinguish malignant cells from normal cells. However, few attempts to evaluate the biomechanical properties of cells have focused on the quantification of the non-homogeneous longitudinal elasticity of cellular structures. In the present study, we applied a variation of the method of Carl and Schillers to investigate the differences between longitudinal elasticity of human cervical squamous carcinoma cells (CaSki) and normal cervical epithelial cells (CRL2614) using AFM. The results reveal a three-layer heterogeneous structure in the probing volume of both cell types studied. CaSki cells exhibited a lower whole-cell stiffness and a softer nuclei zone compared to the normal counterpart cells. Moreover, a better differentiated cytoskeleton was found in the inner cytoplasm/nuclei zone of the normal CRL2614 cells, whereas a deeper cytoskeletal distribution was observed in the probing volume of the cancerous counterparts. The sensitive cortical panel of CaSki cells, with a modulus of 0.35~0.47 kPa, was located at 237~225 nm; in normal cells, the elasticity was 1.20~1.32 kPa at 113~128 nm. The present improved method may be validated using the conventional Hertz-Sneddon method, which is widely reported in the literature. In conclusion, our results enable the quantification of the heterogeneous longitudinal elasticity of cancer cells, in particular the correlation with the corresponding depth. Preliminary results indicate that our method may potentially be applied to improve the detection of cancerous cells and provide insights into the pathophysiology of the disease. PMID:26666911

  7. Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy

    NASA Astrophysics Data System (ADS)

    Zhao, Xueqin; Zhong, Yunxin; Ye, Ting; Wang, Dajing; Mao, Bingwei

    2015-12-01

    The mechanical properties of cells are considered promising biomarkers for the early diagnosis of cancer. Recently, atomic force microscopy (AFM)-based nanoindentation technology has been utilized for the examination of cell cortex mechanics in order to distinguish malignant cells from normal cells. However, few attempts to evaluate the biomechanical properties of cells have focused on the quantification of the non-homogeneous longitudinal elasticity of cellular structures. In the present study, we applied a variation of the method of Carl and Schillers to investigate the differences between longitudinal elasticity of human cervical squamous carcinoma cells (CaSki) and normal cervical epithelial cells (CRL2614) using AFM. The results reveal a three-layer heterogeneous structure in the probing volume of both cell types studied. CaSki cells exhibited a lower whole-cell stiffness and a softer nuclei zone compared to the normal counterpart cells. Moreover, a better differentiated cytoskeleton was found in the inner cytoplasm/nuclei zone of the normal CRL2614 cells, whereas a deeper cytoskeletal distribution was observed in the probing volume of the cancerous counterparts. The sensitive cortical panel of CaSki cells, with a modulus of 0.35~0.47 kPa, was located at 237~225 nm; in normal cells, the elasticity was 1.20~1.32 kPa at 113~128 nm. The present improved method may be validated using the conventional Hertz-Sneddon method, which is widely reported in the literature. In conclusion, our results enable the quantification of the heterogeneous longitudinal elasticity of cancer cells, in particular the correlation with the corresponding depth. Preliminary results indicate that our method may potentially be applied to improve the detection of cancerous cells and provide insights into the pathophysiology of the disease.

  8. Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vulvar Cancer

    ClinicalTrials.gov

    2016-10-28

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Vulvar Cancer; Stage IB2 Cervical Cancer; Stage II Vulvar Cancer; Stage IIA1 Cervical Cancer; Stage IIA2 Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Cervical Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVA Cervical Cancer; Stage IVA Vulvar Cancer; Vulvar Adenocarcinoma; Vulvar Squamous Cell Carcinoma

  9. Klotho inhibits the capacity of cell migration and invasion in cervical cancer.

    PubMed

    Chang, Boogi; Kim, Jinsun; Jeong, Dongjun; Jeong, Yujun; Jeon, Seob; Jung, Sam-Il; Yang, Young; Kim, Keun Il; Lim, Jong-Seok; Kim, Changjin; Lee, Myeong-Sok

    2012-09-01

    Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cervical cancers. However, the mechanisms of Wnt activation in cervical cancer remain largely unknown. In the present study, we demonstrate that Klotho, a Wnt antagonist, is downregulated in invasive human cervical tumors and in a cell line we analyzed. Our data demonstrated that in vivo Klotho expression was not observed in invasive cervical carcinoma. In vitro restoration of Klotho expression in SiHa cells resulted in a decreased cell motility and invasiveness through upregulation of E-cadherin, downregulation of N-cadherin and reduced expression of MMP7 and -9. Ectopic expression of Klotho also reduced the expression of the epithelial-to-mesenchymal transition (EMT) transcription factors Slug and Twist. Furthermore, Klotho causes a significant inhibition of the Wnt/β-catenin pathway in cervical cancer cells, as supported by the expression of Wnt/β-catenin transcriptional target genes such as c-Myc and cyclin D1. Consequently, our findings demonstrate for the first time that Klotho regulates tumor invasion through the EMT process and provide novel mechanistic insights into the role of Klotho in cervical cancer progression and contribute to treatment for metastatic cervical cancer patients.

  10. Syzygium cumini inhibits growth and induces apoptosis in cervical cancer cell lines: a primary study.

    PubMed

    Barh, D; Viswanathan, G

    2008-01-01

    Cervical cancer is common among women in the Indian subcontinent and the incidences and death rates are gradually increasing over the years. Several dietary phytochemicals have been reported to have growth inhibitory and apoptotic effect on HeLa and other cervical cell lines. In this study, using Hoechst 33342 staining, MTT, Annexin V-FLUOS/PI and TUNEL assays we demonstrated that Syzygium cumini extract inhibits the growth and induces apoptosis in HeLa and SiHa cervical cancer cell lines in a dose- and time-dependent manner. The phytochemical, its mode of action and safety issues are yet to be determined. PMID:22275971

  11. Knockdown of Pentraxin 3 suppresses tumorigenicity and metastasis of human cervical cancer cells

    PubMed Central

    Ying, Tsung-Ho; Lee, Chien-Hsing; Chiou, Hui-Ling; Yang, Shun-Fa; Lin, Chu-Liang; Hung, Chia-Hung; Tsai, Jen-Pi; Hsieh, Yi-Hsien

    2016-01-01

    Pentraxin 3 (PTX3) as an inflammatory molecule has been shown to be involved in immune response, inflammation, and cancer. However, the effects of PTX3 on the biological features of cervical cancer cells in vitro and in vivo have not been delineated. Immunohistochemical staining showed that increased PTX3 expression was significantly associated with tumor grade (P < 0.011) and differentiation (P < 0.019). Knocking down PTX3 with lentivirus-mediated small hairpin RNA (shRNA) in cervical cancer cell lines resulted in inhibited cell viability, diminished colony-forming ability, and induced cell cycle arrest at the G2/M phase of the cell cycle, along with downregulated expression of cyclin B1, cdc2, and cdc25c, and upregulated expression of p-cdc2, p-cdc25c, p21, and p27. Furthermore, knockdown of PTX3 significantly decreased the potential of migration and invasion of cervical cancer cells by inhibiting matrix metalloproteidase-2 (MMP-2), MMP-9, and urokinase plasminogen activator (uPA). Moreover, in vivo functional studies showed PTX3-knockdown in mice suppressed tumorigenicity and lung metastatic potential. Conversely, overexpression of PTX3 enhanced proliferation and invasion both in vitro and in vivo. Our results demonstrated that PTX3 contributes to tumorigenesis and metastasis of human cervical cancer cells. Further studies are warranted to demonstrate PTX3 as a novel therapeutic biomarker for human cervical cancer. PMID:27377307

  12. Knockdown of Pentraxin 3 suppresses tumorigenicity and metastasis of human cervical cancer cells.

    PubMed

    Ying, Tsung-Ho; Lee, Chien-Hsing; Chiou, Hui-Ling; Yang, Shun-Fa; Lin, Chu-Liang; Hung, Chia-Hung; Tsai, Jen-Pi; Hsieh, Yi-Hsien

    2016-01-01

    Pentraxin 3 (PTX3) as an inflammatory molecule has been shown to be involved in immune response, inflammation, and cancer. However, the effects of PTX3 on the biological features of cervical cancer cells in vitro and in vivo have not been delineated. Immunohistochemical staining showed that increased PTX3 expression was significantly associated with tumor grade (P < 0.011) and differentiation (P < 0.019). Knocking down PTX3 with lentivirus-mediated small hairpin RNA (shRNA) in cervical cancer cell lines resulted in inhibited cell viability, diminished colony-forming ability, and induced cell cycle arrest at the G2/M phase of the cell cycle, along with downregulated expression of cyclin B1, cdc2, and cdc25c, and upregulated expression of p-cdc2, p-cdc25c, p21, and p27. Furthermore, knockdown of PTX3 significantly decreased the potential of migration and invasion of cervical cancer cells by inhibiting matrix metalloproteidase-2 (MMP-2), MMP-9, and urokinase plasminogen activator (uPA). Moreover, in vivo functional studies showed PTX3-knockdown in mice suppressed tumorigenicity and lung metastatic potential. Conversely, overexpression of PTX3 enhanced proliferation and invasion both in vitro and in vivo. Our results demonstrated that PTX3 contributes to tumorigenesis and metastasis of human cervical cancer cells. Further studies are warranted to demonstrate PTX3 as a novel therapeutic biomarker for human cervical cancer.

  13. Preferential recruitment of Th17 cells to cervical cancer via CCR6-CCL20 pathway.

    PubMed

    Yu, Qing; Lou, Xiang-ming; He, Yan

    2015-01-01

    Our previous studies suggest that Th17 cells accumulate within tumor tissues and correlate with recurrence of cervical cancer patients. However, the source of the increased tumor-infiltrating Th17 cells remains poorly understood. We investigated the prevalence, phenotype and trafficking property of Th17 cells in patients with cervical cancer. Our results showed that Th17 cells highly aggregated within tumor tissues in an activated phenotype with markedly increased expression of CCR6. Correspondingly, level of CCL20 in the tumor tissues was significantly higher than that in non-tumor and normal control tissues, and strongly positively associated with Th17 cells. Further, in vitro migration assay showed CCL20 had effective chemotaxis to circulating Th17 cells. In conclusion, Th17 cells are recruited into tumor tissues preferentially through CCR6-CCL20 pathway, which can serve as a novel therapeutic target for cervical cancer. PMID:25768730

  14. Spheres from cervical cancer cells display stemness and cancer drug resistance

    PubMed Central

    Liu, Huan; Wang, Haijuan; Li, Chunxiao; Zhang, Tingting; Meng, Xiting; Zhang, Ying; Qian, Haili

    2016-01-01

    Cervical cancer is one of the most common gynecological malignant tumors and is the cause of a serious health problem worldwide. An increasing amount of evidence has shown that cancer stem cells (CSCs) are present in tumors, and that these CSCs may be responsible for tumor metastasis and relapse. The present study aimed to identify and characterize a CSC population from the CaSki cell line. First, a stem cell culture medium was used to selectively expand the cancer stem-like cell spheres, and the putative stemness markers, Oct4 and Sox2, were identified. These markers were all highly expressed in the CaSki sphere-forming cells. Next, target region amplified polymorphism-polymerase chain reaction was performed and the CaSki sphere-forming cells were found to exhibit higher telomerase activity than the CaSki control cells cultured in non-stem cell medium. Using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, it was found that the CaSki sphere-forming cells were more resistant to chemotherapeutic drugs than the control CaSki cells. Using the tumor invasive assay, it was shown that the CaSki sphere-forming cells were more invasive than the control CaSki cells. These characteristics all suggested that the tumor sphere-forming cells mirrored the acknowledged CSC phenotypes. Overall, the use of a suspended sphere culture of CaSki cells may be an easy and feasible approach for enriching cancer stem-like cells in cervical cancer research. PMID:27602161

  15. Trichostatin A Enhances the Apoptotic Potential of Palladium Nanoparticles in Human Cervical Cancer Cells

    PubMed Central

    Zhang, Xi-Feng; Yan, Qi; Shen, Wei; Gurunathan, Sangiliyandi

    2016-01-01

    Cervical cancer ranks seventh overall among all types of cancer in women. Although several treatments, including radiation, surgery and chemotherapy, are available to eradicate or reduce the size of cancer, many cancers eventually relapse. Thus, it is essential to identify possible alternative therapeutic approaches for cancer. We sought to identify alternative and effective therapeutic approaches, by first synthesizing palladium nanoparticles (PdNPs), using a novel biomolecule called saponin. The synthesized PdNPs were characterized by several analytical techniques. They were significantly spherical in shape, with an average size of 5 nm. Recently, PdNPs gained much interest in various therapies of cancer cells. Similarly, histone deacetylase inhibitors are known to play a vital role in anti-proliferative activity, gene expression, cell cycle arrest, differentiation and apoptosis in various cancer cells. Therefore, we selected trichostatin A (TSA) and PdNPs and studied their combined effect on apoptosis in cervical cancer cells. Cells treated with either TSA or PdNPs showed a dose-dependent effect on cell viability. The combinatorial effect, tested with 50 nM TSA and 50 nMPdNPs, had a more dramatic inhibitory effect on cell viability, than either TSA or PdNPs alone. The combination of TSA and PdNPs had a more pronounced effect on cytotoxicity, oxidative stress, mitochondrial membrane potential (MMP), caspase-3/9 activity and expression of pro- and anti-apoptotic genes. Our data show a strong synergistic interaction between TSA and PdNPs in cervical cancer cells. The combinatorial treatment increased the therapeutic potential and demonstrated relevant targeted therapy for cervical cancer. Furthermore, we provide the first evidence for the combinatory effect and cytotoxicity mechanism of TSA and PdNPs in cervical cancer cells. PMID:27548148

  16. Trichostatin A Enhances the Apoptotic Potential of Palladium Nanoparticles in Human Cervical Cancer Cells.

    PubMed

    Zhang, Xi-Feng; Yan, Qi; Shen, Wei; Gurunathan, Sangiliyandi

    2016-01-01

    Cervical cancer ranks seventh overall among all types of cancer in women. Although several treatments, including radiation, surgery and chemotherapy, are available to eradicate or reduce the size of cancer, many cancers eventually relapse. Thus, it is essential to identify possible alternative therapeutic approaches for cancer. We sought to identify alternative and effective therapeutic approaches, by first synthesizing palladium nanoparticles (PdNPs), using a novel biomolecule called saponin. The synthesized PdNPs were characterized by several analytical techniques. They were significantly spherical in shape, with an average size of 5 nm. Recently, PdNPs gained much interest in various therapies of cancer cells. Similarly, histone deacetylase inhibitors are known to play a vital role in anti-proliferative activity, gene expression, cell cycle arrest, differentiation and apoptosis in various cancer cells. Therefore, we selected trichostatin A (TSA) and PdNPs and studied their combined effect on apoptosis in cervical cancer cells. Cells treated with either TSA or PdNPs showed a dose-dependent effect on cell viability. The combinatorial effect, tested with 50 nM TSA and 50 nMPdNPs, had a more dramatic inhibitory effect on cell viability, than either TSA or PdNPs alone. The combination of TSA and PdNPs had a more pronounced effect on cytotoxicity, oxidative stress, mitochondrial membrane potential (MMP), caspase-3/9 activity and expression of pro- and anti-apoptotic genes. Our data show a strong synergistic interaction between TSA and PdNPs in cervical cancer cells. The combinatorial treatment increased the therapeutic potential and demonstrated relevant targeted therapy for cervical cancer. Furthermore, we provide the first evidence for the combinatory effect and cytotoxicity mechanism of TSA and PdNPs in cervical cancer cells. PMID:27548148

  17. Drugs Approved for Cervical Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Cervical Cancer This page lists cancer ... in cervical cancer that are not listed here. Drugs Approved to Prevent Cervical Cancer Cervarix (Recombinant HPV ...

  18. Cervical cancer - screening and prevention

    MedlinePlus

    Cancer cervix - screening; HPV - cervical cancer screening; Dysplasia - cervical cancer screening ... Almost all cervical cancers are caused by HPV (human papilloma virus). HPV is a common virus that spreads through sexual contact. Certain types ...

  19. Studying the Physical Function and Quality of Life Before and After Surgery in Patients With Stage I Cervical Cancer

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Lymphedema; Sexual Dysfunction and Infertility; Stage IA1 Cervical Cancer; Stage IA2 Cervical Cancer; Stage IB1 Cervical Cancer

  20. miR-196a targets netrin 4 and regulates cell proliferation and migration of cervical cancer cells

    SciTech Connect

    Zhang, Jie; Zheng, Fangxia; Yu, Gang; Yin, Yanhua; Lu, Qingyang

    2013-11-01

    Highlights: •miR-196a was overexpressed in cervical cancer tissue compared to normal tissue. •miR-196a expression elevated proliferation and migration of cervical cancer cells. •miR-196a inhibited NTN4 expression by binding 3′-UTR region of NTN4 mRNA. •NTN4 inversely correlated with miR-196a expression in cervical tissue and cell line. •NTN4 expression was low in cervical cancer tissue compared to normal tissue. -- Abstract: Recent research has uncovered tumor-suppressive and oncogenic potential of miR-196a in various tumors. However, the expression and mechanism of its function in cervical cancer remains unclear. In this study, we assess relative expression of miR-196a in cervical premalignant lesions, cervical cancer tissues, and four cancer cell lines using quantitative real-time PCR. CaSki and HeLa cells were treated with miR-196a inhibitors, mimics, or pCDNA/miR-196a to investigate the role of miR-196a in cancer cell proliferation and migration. We demonstrated that miR-196a was overexpressed in cervical intraepithelial neoplasia 2–3 and cervical cancer tissue. Moreover, its expression contributes to the proliferation and migration of cervical cancer cells, whereas inhibiting its expression led to a reduction in proliferation and migration. Five candidate targets of miR-196a chosen by computational prediction and Cervical Cancer Gene Database search were measured for their mRNA in both miR-196a-overexpressing and -depleted cancer cells. Only netrin 4 (NTN4) expression displayed an inverse association with miR-196a. Fluorescent reporter assays revealed that miR-196a inhibited NTN4 expression by targeting one binding site in the 3′-untranslated region (3′-UTR) of NTN4 mRNA. Furthermore, qPCR and Western blot assays verified NTN4 expression was downregulated in cervical cancer tissues compared to normal controls, and in vivo mRNA level of NTN4 inversely correlated with miR-196a expression. In summary, our findings provide new insights about the

  1. Preventing cervical cancer globally.

    PubMed

    Schmeler, Kathleen M

    2012-11-01

    Cervical cancer is one of the leading causes of cancer and cancer-related deaths among women worldwide. More than 85% of cases and deaths occur in the developing world where the availability of effective screening is limited. In this issue of the journal, Pierce and colleagues (beginning on page 1273) describe a novel technique using a high-resolution microendoscope (HRME) to diagnose cervical dysplasia. This perspective reviews the limitations of existing cervical cancer screening methods currently in use in low-resource settings and the potential for HRME imaging to contribute to cervical cancer prevention in the developing world.

  2. Cervical Cancer

    MedlinePlus

    ... Centers for Disease Control and Prevention’s (CDC) Inside Knowledge: Get the Facts About Gynecologic Cancer campaign. The ... the facts about gynecologic cancer, providing important “inside knowledge” about their bodies and health. Get the Facts ...

  3. Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer

    ClinicalTrials.gov

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Chemotherapeutic Agent Toxicity; Cognitive Side Effects of Cancer Therapy; Psychological Impact of Cancer; Radiation Toxicity; Sexual Dysfunction and Infertility; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  4. Proteasome inhibition mediates p53 reactivation and anti-cancer activity of 6-gingerol in cervical cancer cells.

    PubMed

    Rastogi, Namrata; Duggal, Shivali; Singh, Shailendra Kumar; Porwal, Konica; Srivastava, Vikas Kumar; Maurya, Rakesh; Bhatt, M L B; Mishra, Durga Prasad

    2015-12-22

    Human papilloma virus (HPV) expressing E6 and E7 oncoproteins, is known to inactivate the tumor suppressor p53 through proteasomal degradation in cervical cancers. Therefore, use of small molecules for inhibition of proteasome function and induction of p53 reactivation is a promising strategy for induction of apoptosis in cervical cancer cells. The polyphenolic alkanone, 6-Gingerol (6G), present in the pungent extracts of ginger (Zingiber officinale Roscoe) has shown potent anti-tumorigenic and pro-apoptotic activities against a variety of cancers. In this study we explored the molecular mechanism of action of 6G in human cervical cancer cells in vitro and in vivo. 6G potently inhibited proliferation of the HPV positive cervical cancer cells. 6G was found to: (i) inhibit the chymotrypsin activity of proteasomes, (ii) induce reactivation of p53, (iii) increase levels of p21, (iv) induce DNA damage and G2/M cell cycle arrest, (v) alter expression levels of p53-associated apoptotic markers like, cleaved caspase-3 and PARP, and (vi) potentiate the cytotoxicity of cisplatin. 6G treatment induced significant reduction of tumor volume, tumor weight, proteasome inhibition and p53 accumulation in HeLa xenograft tumor cells in vivo. The 6G treatment was devoid of toxic effects as it did not affect body weights, hematological and osteogenic parameters. Taken together, our data underscores the therapeutic and chemosensitizing effects of 6G in the management and treatment of cervical cancer.

  5. Proteasome inhibition mediates p53 reactivation and anti-cancer activity of 6-Gingerol in cervical cancer cells

    PubMed Central

    Rastogi, Namrata; Duggal, Shivali; Singh, Shailendra Kumar; Porwal, Konica; Srivastava, Vikas Kumar; Maurya, Rakesh; Bhatt, Madan L.B.; Mishra, Durga Prasad

    2015-01-01

    Human papilloma virus (HPV) expressing E6 and E7 oncoproteins, is known to inactivate the tumor suppressor p53 through proteasomal degradation in cervical cancers. Therefore, use of small molecules for inhibition of proteasome function and induction of p53 reactivation is a promising strategy for induction of apoptosis in cervical cancer cells. The polyphenolic alkanone, 6-Gingerol (6G), present in the pungent extracts of ginger (Zingiber officinale Roscoe) has shown potent anti-tumorigenic and pro-apoptotic activities against a variety of cancers. In this study we explored the molecular mechanism of action of 6G in human cervical cancer cells in vitro and in vivo. 6G potently inhibited proliferation of the HPV positive cervical cancer cells. 6G was found to: (i) inhibit the chymotrypsin activity of proteasomes, (ii) induce reactivation of p53, (iii) increase levels of p21, (iv) induce DNA damage and G2/M cell cycle arrest, (v) alter expression levels of p53-associated apoptotic markers like, cleaved caspase-3 and PARP, and (vi) potentiate the cytotoxicity of cisplatin. 6G treatment induced significant reduction of tumor volume, tumor weight, proteasome inhibition and p53 accumulation in HeLa xenograft tumor cells in vivo. The 6G treatment was devoid of toxic effects as it did not affect body weights, hematological and osteogenic parameters. Taken together, our data underscores the therapeutic and chemosensitizing effects of 6G in the management and treatment of cervical cancer. PMID:26621832

  6. Proteasome inhibition mediates p53 reactivation and anti-cancer activity of 6-gingerol in cervical cancer cells.

    PubMed

    Rastogi, Namrata; Duggal, Shivali; Singh, Shailendra Kumar; Porwal, Konica; Srivastava, Vikas Kumar; Maurya, Rakesh; Bhatt, M L B; Mishra, Durga Prasad

    2015-12-22

    Human papilloma virus (HPV) expressing E6 and E7 oncoproteins, is known to inactivate the tumor suppressor p53 through proteasomal degradation in cervical cancers. Therefore, use of small molecules for inhibition of proteasome function and induction of p53 reactivation is a promising strategy for induction of apoptosis in cervical cancer cells. The polyphenolic alkanone, 6-Gingerol (6G), present in the pungent extracts of ginger (Zingiber officinale Roscoe) has shown potent anti-tumorigenic and pro-apoptotic activities against a variety of cancers. In this study we explored the molecular mechanism of action of 6G in human cervical cancer cells in vitro and in vivo. 6G potently inhibited proliferation of the HPV positive cervical cancer cells. 6G was found to: (i) inhibit the chymotrypsin activity of proteasomes, (ii) induce reactivation of p53, (iii) increase levels of p21, (iv) induce DNA damage and G2/M cell cycle arrest, (v) alter expression levels of p53-associated apoptotic markers like, cleaved caspase-3 and PARP, and (vi) potentiate the cytotoxicity of cisplatin. 6G treatment induced significant reduction of tumor volume, tumor weight, proteasome inhibition and p53 accumulation in HeLa xenograft tumor cells in vivo. The 6G treatment was devoid of toxic effects as it did not affect body weights, hematological and osteogenic parameters. Taken together, our data underscores the therapeutic and chemosensitizing effects of 6G in the management and treatment of cervical cancer. PMID:26621832

  7. RBBP6: a potential biomarker of apoptosis induction in human cervical cancer cell lines

    PubMed Central

    Moela, Pontsho; Motadi, Lesetja Raymond

    2016-01-01

    Overexpression of RBBP6 in cancers of the colon, lung, and esophagus makes it a potential target in anticancer therapy. This is especially important because RBBP6 associates with the tumor suppressor gene p53, the inactivation of which has been linked to over 50% of all cancer types. However, the expression of RBBP6 in cancer and its interaction with p53 are yet to be understood in order to determine whether or not RBBP6 is cancer promoting and therefore a potential biomarker. In this study, we manipulated RBBP6 expression levels followed by treatment with either camptothecin or γ-aminobutyric acid in cervical cancer cells to induce apoptosis or cell cycle arrest. We began by staining human cervical cancer tissue sections with anti-RBBP6 monoclonal antibody to evaluate the extent of expression of RBBP6 in patients’ specimens. We followed on with silencing the overexpression of RBBP6 and treatment with anticancer agents to evaluate how the specimens respond to combinational therapy. Apoptosis induction was evaluated through confocal microscope, and flow cytometry using annexin V staining, and also by checking the mitochondrial and caspase-3/7 activity. Cell cycle arrest was evaluated using flow cytometry through staining with propidium iodide. RBBP6 was highly expressed in cervical cancer tissue sections that were in stage II or III of development. Silencing RBBP6 followed by treatment with γ-aminobutyric acid and camptothecin seems to sensitize cells to apoptosis induction rather than cell cycle arrest. Overexpression of RBBP6 seems to promote S-phase in cell cycle and cell proliferation. These results predict a proliferative role of RBBP6 in cancer progression rather than as a cancer-causing gene. Furthermore, sensitization of cells to camptothecin-induced apoptosis by RBBP6 targeting suggests a promising tool for halting cervical cancer progression. PMID:27536134

  8. Angiogenesis in cervical cancer is mediated by HeLa metabolites through endothelial cell tissue kallikrein.

    PubMed

    Naidoo, Strinivasen; Raidoo, Deshandra Munsamy

    2009-08-01

    High vascularity correlates with poor clinical outcome in cancer of the uterine cervix. We investigated whether human cervical cancer cell (HeLa) metabolites influenced endothelial cell proliferation through the serine protease, tissue kallikrein. The angiogenic potential of tissue kallikrein is proposed due to its proteolytic, mitogenic and invasive properties. Under pre-defined conditions, we examined the regulation of tissue kallikrein simultaneously in both endothelial and HeLa cells using immunochemistry, ELISA, cell proliferation assays and in situ RT-PCR. In an endothelial-cervical carcinoma conditioned-medium model, HeLa metabolites caused a dramatic decrease in endothelial cellular tissue kallikrein and a concomitant proliferation of endothelial cells. ELISA on the conditioned media showed a dose-dependent increase of tissue kallikrein, while in situ RT-PCR demonstrated no change in tissue kallikrein mRNA in both endothelial and HeLa cells when challenged with each other's metabolites. This demonstration of the ability of cervical cancer to simultaneously manipulate both tissue kallikrein processing within endothelial cells and angiogenesis is novel. Should this occur in vivo, the tissue kallikrein released from the endothelial cells into the microenvironment may simultaneously degrade the matrix and elicit a mitogenic effect by promoting angiogenesis. Pre-treatment with TK inhibitors and/or anti-angiogenic therapies may prove to benefit future cervical cancer patients. PMID:19578768

  9. Emerging of fractal geometry on surface of human cervical epithelial cells during progression towards cancer

    PubMed Central

    Dokukin, M. E.; Guz, N. V.; Woodworth, C.D.; Sokolov, I.

    2015-01-01

    Despite considerable advances in understanding the molecular nature of cancer, many biophysical aspects of malignant development are still unclear. Here we study physical alterations of the surface of human cervical epithelial cells during stepwise in vitro development of cancer (from normal to immortal (premalignant), to malignant). We use atomic force microscopy to demonstrate that development of cancer is associated with emergence of simple fractal geometry on the cell surface. Contrary to the previously expected correlation between cancer and fractals, we find that fractal geometry occurs only at a limited period of development when immortal cells become cancerous; further cancer progression demonstrates deviation from fractal. Because of the connection between fractal behaviour and chaos (or far from equilibrium behaviour), these results suggest that chaotic behaviour coincides with the cancer transformation of the immortalization stage of cancer development, whereas further cancer progression recovers determinism of processes responsible for cell surface formation. PMID:25844044

  10. Emergence of fractal geometry on the surface of human cervical epithelial cells during progression towards cancer

    NASA Astrophysics Data System (ADS)

    Dokukin, M. E.; Guz, N. V.; Woodworth, C. D.; Sokolov, I.

    2015-03-01

    Despite considerable advances in understanding the molecular nature of cancer, many biophysical aspects of malignant development are still unclear. Here we study physical alterations of the surface of human cervical epithelial cells during stepwise in vitro development of cancer (from normal to immortal (premalignant), to malignant). We use atomic force microscopy to demonstrate that development of cancer is associated with emergence of simple fractal geometry on the cell surface. Contrary to the previously expected correlation between cancer and fractals, we find that fractal geometry occurs only at a limited period of development when immortal cells become cancerous; further cancer progression demonstrates deviation from fractal. Because of the connection between fractal behaviour and chaos (or far from equilibrium behaviour), these results suggest that chaotic behaviour coincides with the cancer transformation of the immortalization stage of cancer development, whereas further cancer progression recovers determinism of processes responsible for cell surface formation.

  11. Beclin1 overexpression inhibitis proliferation, invasion and migration of CaSki cervical cancer cells.

    PubMed

    Sun, Yang; Liu, Jia-hua; Sui, Yu-xia; Jin, Long; Yang, Yin; Lin, Sai-mei; Shi, Hong

    2011-01-01

    The influence of the autophagy-related gene Beclin1 on proliferation, invasion and metastasis of the cervical cancer CaSki cells and its possible mechanism in vitro were here targeted. After the overexpression vector pcDNA3.1-Beclin1 and RNA interference vector pSUPER-Beclin1 were transfected into CaSki cells in vitro, stable expression cell lines demonstration Beclin1 expression was upregulated, and VEGF and MMP-9 expression were decreased, leading to cell arrest in the G0/G1 phase of the cell cycle. MTT assays further revealed proliferation of cells was significantly inhibited in Beclin1-overexpressing transfectant cells, with invasion and metastasis also being inhibited in Transwell chamber assays. The present results suggest that Beclin1 inhibits invasion and metastasis of cervical cancer CaSki cells in vitro. Mechanisms probably involve Beclin1 inhibition of cell proliferation, and decreased expression of VEGF and MMP-9 proteins.

  12. PDGF beta targeting in cervical cancer cells suggest a fine-tuning of compensatory signalling pathways to sustain tumourigenic stimulation

    PubMed Central

    Tudoran, Oana Mihaela; Soritau, Olga; Balacescu, Loredana; Pop, Laura; Meurice, Guillaume; Visan, Simona; Lindberg, Staffan; Eniu, Alexandru; Langel, Ulo; Balacescu, Ovidiu; Berindan-Neagoe, Ioana

    2015-01-01

    The platelet-derived growth factor (PDGF) signalling pathway has been reported to play an important role in human cancers by modulating autocrine and paracrine processes such as tumour growth, metastasis and angiogenesis. Several clinical trials document the benefits of targeting this pathway; however, in cervical cancer the role of PDGF signalling in still unclear. In this study, we used siRNA against PDGF beta (PDGFBB) to investigate the cellular and molecular mechanisms of PDGFBB signalling in Ca Ski and HeLa cervical cancer cells. Our results show that PDGFBB inhibition in Ca Ski cells led to rapid alterations of the transcriptional pattern of 579 genes, genes that are known to have antagonistic roles in regulating tumour progression. Concomitantly, with the lack of significant effects on cervical cancer cells proliferation, apoptosis, migration or invasion, these findings suggests that cervical cancer cells shift between compensatory signalling pathways to maintain their behaviour. The observed autocrine effects were limited to cervical cancer cells ability to adhere to an endothelial cell (EC) monolayer. However, by inhibiting PDGFBB on cervical cells, we achieved reduced proliferation of ECs in co-culture settings and cellular aggregation in conditioned media. Because of lack of PDGF receptor expression on ECs, we believe that these effects are a result of indirect PDGFBB paracrine signalling mechanisms. Our results shed some light into the understanding of PDGFBB signalling mechanism in cervical cancer cells, which could be further exploited for the development of synergistic anti-tumour and anti-angiogenic therapeutic strategies. PMID:25311137

  13. Elevated Expression of Programmed Death-1 and Programmed Death Ligand-1 Negatively Regulates Immune Response against Cervical Cancer Cells

    PubMed Central

    Chen, Zhifang; Pang, Nannan; Du, Rong; Zhu, Yuejie; Fan, Lingling; Cai, Donghui

    2016-01-01

    The present study is to measure the expression of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), as well as its clinical significance in cervical cancer patients. Our results showed that different T cell subsets in patients with cervical cancer had high expression of PD-1, and DCs had high expression of PD-L1. High expression of PD-1 on Treg cells in cervical cancer patients facilitated the production of TGF-β and IL-10 but inhibited the production of IFN-γ. Cervical cancer elevated the expression of PD-1 and PD-L1 in mRNA level. PD-1 expression in peripheral blood of cervical cancer patients was related with tumor differentiation, lymph node metastasis, and invasiveness. PD-1/PD-L1 pathway inhibited lymphocyte proliferation but enhanced the secretion of IL-10 and TGF-β in vitro. In summary, our findings demonstrate that elevated levels of PD-1/PD-L1, TGF-β, and IL-10 in peripheral blood of cervical cancer patients may negatively regulate immune response against cervical cancer cells and contribute to the progression of cervical cancer. Therefore, PD-1/PD-L1 pathway may become an immunotherapy target in the future. PMID:27721577

  14. miR-92a is upregulated in cervical cancer and promotes cell proliferation and invasion by targeting FBXW7

    SciTech Connect

    Zhou, Chuanyi; Shen, Liangfang; Mao, Lei; Wang, Bing; Li, Yang; Yu, Huizhi

    2015-02-27

    MicroRNAs (miRNAs) are involved in the cervical carcinogenesis and progression. In this study, we investigated the role of miR-92a in progression and invasion of cervical cancer. MiR-92a was significantly upregulated in cervical cancer tissues and cell lines. Overexpression of miR-92a led to remarkably enhanced proliferation by promoting cell cycle transition from G1 to S phase and significantly enhanced invasion of cervical cancer cells, while its knockdown significantly reversed these cellular events. Bioinformatics analysis suggested F-box and WD repeat domain-containing 7 (FBXW7) as a novel target of miR-92a, and miR-92a suppressed the expression level of FBXW7 mRNA by direct binding to its 3′-untranslated region (3′UTR). Expression of miR-92a was negatively correlated with FBXW7 in cervical cancer tissues. Furthermore, Silencing of FBXW7 counteracted the effects of miR-92a suppression, while its overexpression reversed oncogenic effects of miR-92a. Together, these findings indicate that miR-92a acts as an onco-miRNA and may contribute to the progression and invasion of cervical cancer, suggesting miR-92a as a potential novel diagnostic and therapeutic target of cervical cancer. - Highlights: • miR-92a is elevated in cervical cancer tissues and cell lines. • miR-92a promotes cervical cancer cell proliferation, cell cycle transition from G1 to S phase and invasion. • FBXW7 is a direct target of miR-92a. • FBXW7 counteracts the oncogenic effects of miR-92a on cervical cancer cells.

  15. Xanthohumol Induces Growth Inhibition and Apoptosis in Ca Ski Human Cervical Cancer Cells

    PubMed Central

    2015-01-01

    We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants, previously reported to be an effective anticancer agent in various cancer cell lines. The present study showed that xanthohumol was effective to inhibit proliferation of Ca Ski cells based on IC50 values using sulforhodamine B (SRB) assay. Furthermore, cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In addition, 48-hour long treatment with xanthohumol triggered externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase-9. On the other hand, Western blot analysis showed that the expression levels of cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose-dependent manner. Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol is a potent chemotherapeutic candidate for cervical cancer. PMID:25949267

  16. Fludeoxyglucose F 18 PET Scan, CT Scan, and Ferumoxtran-10 MRI Scan Before Chemotherapy and Radiation Therapy in Finding Lymph Node Metastasis in Patients With Locally Advanced Cervical Cancer or High-Risk Endometrial Cancer

    ClinicalTrials.gov

    2016-09-19

    Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage IVA Cervical Cancer

  17. GRIM-19 Restores Cervical Cancer Cell Senescence by Repressing hTERT Transcription.

    PubMed

    Zhou, Ying; Xu, Fei; Tao, Feng; Feng, Dingqing; Ling, Bin; Qian, Lili; Yang, Xia; Wang, Qingyuan; Wang, Huiyan; Zhao, Weidong; Cheng, Yong; Shan, Ge; Kalvakolanu, Dhan V; Xiao, Weihua

    2016-08-01

    High telomerase activity promotes tumor growth by stabilizing damaged chromosomes and their mitotic replication. Overactivation of telomerase activity has been reported in cervical cancer, a malignancy caused by high-risk human papillomaviruses (HR-HPVs). The HR-HPV E6 can activate hTERT promoter by interacting with E6AP or other binding proteins and by stabilizing the interaction between hTERT and E6AP. GRIM-19 is a novel tumor suppressor that affects multiple targets in a cell to regulate growth. We have previously reported the interaction of GRIM-19 with 18E6 and E6AP to disrupt the E6/E6AP complex and increase the autoubiquitination of E6AP. In this study, we characterized the interaction of GRIM-19 with 16E6 (an oncoprotein produced by HPV16) and identified the binding sites that mediate this interaction. We also found that GRIM-19 expression in cervical cancer cells could inhibit telomerase activity by inhibiting the transactivation of the hTERT promoter by E6, thereby promoting cervical cancer cell senescence. Moreover, we identified a negative correlation between GRIM-19 and hTERT expression in cervical cancer tissues. Suppression of GRIM-19 and induction of hTERT levels were associated with lymph node metastasis, advanced clinical stage, and poor prognosis. This study identified another important novel antitumor molecular link associated with GRIM-19 in the tumorigenesis. PMID:27142689

  18. The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer.

    PubMed

    Kawano, Mahiru; Mabuchi, Seiji; Matsumoto, Yuri; Sasano, Tomoyuki; Takahashi, Ryoko; Kuroda, Hiromasa; Kozasa, Katsumi; Hashimoto, Kae; Isobe, Aki; Sawada, Kenjiro; Hamasaki, Toshimitsu; Morii, Eiichi; Kimura, Tadashi

    2015-12-15

    Granulocyte-colony stimulating factor (G-CSF) producing malignant tumor has been reported to occur in various organs, and has been associated with poor clinical outcome. The aim of this study is to investigate the significance of tumor G-CSF expression in the chemosensitivity of uterine cervical cancer. The clinical data of recurrent or advanced cervical cancer patients who were treated with platinum-based chemotherapy were analyzed. Clinical samples, cervical cancer cell lines, and a mouse model of cervical cancer were employed to examine the mechanisms responsible for the development of chemoresistance in G-CSF-producing cervical cancer, focusing on myeloid-derived suppressor cells (MDSC). As a result, the tumor G-CSF expression was significantly associated with increased MDSC frequencies and compromised survival. In vitro and in vivo experiments demonstrated that the increased MDSC induced by tumor-derived G-CSF is involved in the development of chemoresistance. The depletion of MDSC via splenectomy or the administration of anti-Gr-1 antibody sensitized G-CSF-producing cervical cancer to cisplatin. In conclusion, tumor G-CSF expression is an indicator of an extremely poor prognosis in cervical cancer patients that are treated with chemotherapy. Combining MDSC-targeting treatments with current standard chemotherapies might have therapeutic efficacy as a treatment for G-CSF-producing cervical cancer.

  19. The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer

    PubMed Central

    Kawano, Mahiru; Mabuchi, Seiji; Matsumoto, Yuri; Sasano, Tomoyuki; Takahashi, Ryoko; Kuroda, Hiromasa; Kozasa, Katsumi; Hashimoto, Kae; Isobe, Aki; Sawada, Kenjiro; Hamasaki, Toshimitsu; Morii, Eiichi; Kimura, Tadashi

    2015-01-01

    Granulocyte-colony stimulating factor (G-CSF) producing malignant tumor has been reported to occur in various organs, and has been associated with poor clinical outcome. The aim of this study is to investigate the significance of tumor G-CSF expression in the chemosensitivity of uterine cervical cancer. The clinical data of recurrent or advanced cervical cancer patients who were treated with platinum-based chemotherapy were analyzed. Clinical samples, cervical cancer cell lines, and a mouse model of cervical cancer were employed to examine the mechanisms responsible for the development of chemoresistance in G-CSF-producing cervical cancer, focusing on myeloid-derived suppressor cells (MDSC). As a result, the tumor G-CSF expression was significantly associated with increased MDSC frequencies and compromised survival. In vitro and in vivo experiments demonstrated that the increased MDSC induced by tumor-derived G-CSF is involved in the development of chemoresistance. The depletion of MDSC via splenectomy or the administration of anti-Gr-1 antibody sensitized G-CSF-producing cervical cancer to cisplatin. In conclusion, tumor G-CSF expression is an indicator of an extremely poor prognosis in cervical cancer patients that are treated with chemotherapy. Combining MDSC-targeting treatments with current standard chemotherapies might have therapeutic efficacy as a treatment for G-CSF-producing cervical cancer. PMID:26666576

  20. Curcumin induces ER stress-mediated apoptosis through selective generation of reactive oxygen species in cervical cancer cells.

    PubMed

    Kim, Boyun; Kim, Hee Seung; Jung, Eun-Ji; Lee, Jung Yun; K Tsang, Benjamin; Lim, Jeong Mook; Song, Yong Sang

    2016-05-01

    Prolonged accumulation of misfolded or unfolded proteins caused by cellular stress, including oxidative stress, induces endoplasmic reticulum stress, which then activates an unfolded protein response (UPR). ER stress is usually maintained at higher levels in cancer cells as compared to normal cells due to altered metabolism in cancer. Here, we investigated whether curcumin is ER stress-mediated apoptosis in cervical cancer cells, and ROS increased by curcumin are involved in the process as an upstream contributor. Curcumin inhibited proliferation of cervical cancer cells (C33A, CaSki, HeLa, and ME180) and induced apoptotic cell death. Curcumin activated ER-resident UPR sensors, such as PERK, IRE-1α, and ATF6, and their downstream-signaling proteins in cervical cancer cells, but not in normal epithelial cells and peripheral blood mononuclear cells (PBMCs). CHOP, a key factor involved in ER stress-mediated apoptosis, was also activated by curcumin. CHOP decreased the ratio of anti-apoptotic protein Bcl-2 to pro-apoptotic protein Bax expression, and subsequently increased the apoptotic population of cervical cancer cells. Furthermore, curcumin elevated levels of intracellular reactive oxygen species (ROS) in cervical cancer cells, but not in normal epithelial cells. Scavenging ROS resulted in inhibition of ER stress and partially restored cell viability in curcumin-treated cancer cells. Collectively, these observations show that curcumin promotes ER stress-mediated apoptosis in cervical cancer cells through increase of cell type-specific ROS generation. Therefore, modulation of these differential responses to curcumin between normal and cervical cancer cells could be an effective therapeutic strategy without adverse effects on normal cells.

  1. FOXL2 suppresses proliferation, invasion and promotes apoptosis of cervical cancer cells

    PubMed Central

    Liu, Xing-Long; Meng, Yu-Han; Wang, Jian-Li; Yang, Biao-Bing; Zhang, Fan; Tang, Sheng-Jian

    2014-01-01

    FOXL2 is a transcription factor that is essential for ovarian function and maintenance, the germline mutations of which give rise to the blepharophimosis ptosis epicanthus inversus syndrome (BPES), often associated with premature ovarian failure. Recently, its mutations have been found in ovarian granulosa cell tumors (OGCTs). In this study, we measured the expression of FOXL2 in cervical cancer by immunohistochemistry and its mRNA level in cervical cancer cell lines Hela and Siha by RT-PCR. Then we overexpressed FOXL2 in Hela cells and silenced it in Siha cells by plasmid transfection and verified using western blotting. When FOXL2 was overexpressed or silenced, cells proliferation and apoptosis were determined by Brdu assay and Annexin V/PI detection kit, respectively. In addition, we investigated the effects of FOXL2 on the adhesion and invasion of Hela and Siha cells. Finally, we analyzed the influences of FOXL2 on Ki67, PCNA and FasL by flow cytometry. The results showed that FOXL2 was highly expressed in cervical squamous cancer. Overexpressing FOXL2 suppressed Hela proliferation and facilitated its apoptosis. Silencing FOXL2 enhanced Siha proliferation and inhibited its apoptosis. Meanwhile, silencing FOXL2 promoted Siha invasion, but it had no effect on cells adhesion. In addition, overexpressing FOXL2 decreased the expression of Ki67 in Hela and Siha cells. Therefore, our results suggested that FOXL2 restrained cells proliferation and enhanced cells apoptosis mainly through decreasing Ki67 expression. PMID:24817949

  2. Cervical cancer cell-derived interleukin-6 impairs CCR7-dependent migration of MMP-9-expressing dendritic cells.

    PubMed

    Pahne-Zeppenfeld, Jennifer; Schröer, Nadine; Walch-Rückheim, Barbara; Oldak, Monika; Gorter, Arko; Hegde, Subramanya; Smola, Sigrun

    2014-05-01

    Cervical carcinogenesis is a consequence of persistent infection with high-risk human papillomaviruses (HPVs). Recent studies indicate that HPV-transformed cells actively instruct their microenvironment to promote carcinogenesis. Here, we demonstrate that cervical cancer cells activate monocytes to produce their own CCL2 for further monocyte recruitment and reprogram their function during differentiation and maturation to dendritic cells (DCs). Our data show that cervical cancer cells suppress the induction of the chemokine receptor CCR7 in phenotypically mature DCs and impair their migration toward a lymph node homing chemokine, required to initiate adaptive immune responses. We confirmed the presence of CD83(+)CCR7(low) DCs in cancer biopsies. The second factor essential for DC migration, matrix-metalloproteinase MMP-9, which also has vasculogenic and protumorigenic properties, is not suppressed but upregulated in immature as well as mature DCs. We identified interleukin-6 (IL-6) as a crucial cervical cancer cell-derived mediator and nuclear factor kappaB (NF-jB) as the central signaling pathway targeted in DCs. Anti-IL-6 antibodies reverted not only NF-jB inhibition and restored CCR7-dependent migration but also blocked MMP-9 induction. This is the first report demonstrating the dissociation of CCR7 and MMP-9 expression in phenotypically mature CD83(+) DCs by cancer cells. Our results show that cervical cancer cells actively shape the local microenvironment. They induce the accumulation of myeloid cells and skew their function from immune activation to local production of protumorigenic MMP-9. Neutralizing anti-IL-6 antibodies can counteract this functional dysbalance and should therefore be considered for adjuvant cervical cancer therapy.

  3. MicroRNA-101 regulates the viability and invasion of cervical cancer cells

    PubMed Central

    Lin, Chen; Huang, Fei; Shen, Guqun; Yiming, Adilijiang

    2015-01-01

    Background: Cervical cancer has the second highest morbidity and mortality rates of any malignancy in women worldwide, and it is one of the leading causes of death in Uygur women in Xinjiang China. MicroRNAs are involved in cancer development and progression. Previously, we found that miR-101 is significantly down-regulated in cervical cancer tissues from Uyghur women. The underlying pathophysiology and relevance to tumorigenesis of miR-101 is still largely unknown. The purpose of this study was to elucidate the molecular mechanisms of miR-101 regulation of cervical cancer cell viability and invasion. Materials and methods: The expression of miR-101 in cervical cancer cell line (SiHa) was detected by real-time PCR. A miR-101 mimic was overexpressed in SiHa cells, and MTT assays were performed to determine the impact on cell proliferation. Cell would heal assays and flow cytometry were used to detect migratory ability and cellular apoptosis, respectively. Immunohistochemistry was performed to assess protein expression of the miR-101 target gene COX-2. Results: MiR-101 was endogenously expressed in SiHa cells, and alterations in its expression had profound effects on cellular migration and invasion efficiency. Overexpression of miR-101 decreased proliferation in the MTT assay (the mimics at 490 nm absorbance is lower 60% than normal, and decreased cellular motility in the cell would healing assay (transfected: 37 ± 2 m, pre-transfected 184 ± 2 m). Apoptosis rate was significantly higher with overexpression of miR-101 relative to control (transfected: 76.6%, pre-transfected: 3.5%) (P < 0.05). The expression of Cox-2 was decreased in transfected cells. Conclusions: MiR-101 likely acts as a tumor suppressor in cervical cancer. Overexpression of miR-101 decreased expression of its target gene Cox-2 and inhibited proliferation and invasion, and promoted apoptosis to suppress tumorigenicity. MiR-101 is a promising new target for the development of therapeutic strategies

  4. Sonoporation of Cervical Carcinoma Cells Affected with E6-Oncoprotein for the Treatment of Uterine Cancer

    NASA Astrophysics Data System (ADS)

    Curiel, Laura; Lee, Kyle; Pichardo, Samuel; Zehbe, Ingeborg

    2010-03-01

    Cervical cancer has been identified as the third leading cause of average years of life lost per person dying of cancer. Since essentially all cervical cancers contain copies of human papillomavirus (HPV) DNA, we propose a treatment that targets HPV-infected cells using strategies that re-introduce normal functions into the infected cells while sparing healthy cells. We propose the use of focused ultrasound in combination with microbubbles as means to deliver antibodies against the E6 protein present only in HPV positive cells. We conducted in vitro studies with cell cultures of SiHa cervical carcinoma cells seeded into Opticell™ chambers. An in-house ultrasound excitation apparatus was used to control and explore the optimal acoustic parameters in order to maximize delivery. We first validated the possibility of delivering the EX-EGFP-M02 vector (Genecopoeia) into the cells; 1.2 μL of activated microbubbles (Definity®) and 50 μg of the vector were mixed in media and then injected into the Opticell™ chamber. We used 32 μs pulses at a central frequency of 930 KHz with a repetition frequency of 1.5 kHz and total exposure duration of 30 s; six pressure values were tested (0 to 1 MPa). Fluorescence imaging was used to determine the levels of intracellular proteins and assess delivery. The delivery of an anti-α-Tubulin antibody was next tested and confirmed that the delivery into HPV16 positive cells was successful.

  5. Radiation Therapy and Cisplatin With or Without Triapine in Treating Patients With Newly Diagnosed Stage IB2, II, or IIIB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

    ClinicalTrials.gov

    2016-11-03

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB2 Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Vaginal Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Vaginal Cancer

  6. High level of MT-MMP expression is associated with invasiveness of cervical cancer cells.

    PubMed

    Gilles, C; Polette, M; Piette, J; Munaut, C; Thompson, E W; Birembaut, P; Foidart, J M

    1996-01-17

    MMP-2 (gelatinase A) has been associated with the invasive potential of many cancer cells both in vitro and in vivo. It is now becoming clear that the activation of this enzyme might be a key step in tumor invasion. This activation process has been shown to be a membrane-associated pathway inducible by various agents such as collagen type I, concanavalin A or TGF-beta, but its physiological regulation is still largely unresolved. MT-MMP was recently discovered and described as a potential gelatinase-A activator. In the present study, we investigated the expression of MT-MMP (membrane-type metalloproteinase) in cervical cancer cells both in vitro and in vivo. Comparing several in vitro-transformed cervical cell lines, previously shown to display different invasive potentials, our results showed that the ability of cells to overexpress MT-MMP mRNA following ConA induction correlated with their ability to activate gelatinase A and with a highly invasive behavior. Moreover, using immunohistochemistry and in situ hybridization, we found a higher level of MT-MMP expression in invasive cervical carcinoma and lymph node metastases compared to its expression in non-invasive CIN III lesions. Our in vivo observations also clearly demonstrated a cooperation between stromal and tumor cells for the production of MT-MMP. Taken together, our results clearly correlated high level MT-MMP expression with invasiveness, and thus suggested that MT-MMP might play a crucial role in cervical tumor invasion.

  7. Silymarin inhibits cervical cancer cell through an increase of phosphatase and tensin homolog.

    PubMed

    Yu, Hann-Chin; Chen, Li-Jen; Cheng, Kai-Chun; Li, Ying-Xiao; Yeh, Ching-Hua; Cheng, Juei-Tang

    2012-05-01

    Silymarin is an active constituent contained in the seeds of the milk thistle plant and is widely used as a hepatic protection agent due to its antioxidant-like activity. In the present study we evaluated the potential action of silymarin against cervical cancer and investigated its mechanism of action. Treatment of cervical cancer cells (C-33A) with silymarin resulted in a significant decrease in cell viability. Silymarin induced apoptosis through the modulation of Bcl-2 family proteins and activation of caspase 3. Silymarin also inhibited the phosphorylation of Akt with an increase in expression of phosphatase and tensin homolog (PTEN). We also observed that silymarin suppressed C-33A cell invasion and wound-healing migration in a concentration-dependent manner. Western-blot analysis showed that silymarin significantly inhibited the expression of matrix metalloproteinase-9 (MMP-9) in C-33A cells. Furthermore, we applied siRNA to lower the PTEN gene, which diminished the anticancer actions of silymarin. Taken together, these results show that silymarin has the potential to suppress the survival, migration and invasion of C-33A cancer cells; thus, it could be developed as a promising agent for the treatment of cervical cancer in the future.

  8. Cudrania tricuspidata Stem Extract Induces Apoptosis via the Extrinsic Pathway in SiHa Cervical Cancer Cells.

    PubMed

    Kwon, Sae-Bom; Kim, Min-Je; Yang, Jin Mo; Lee, Hee-Pom; Hong, Jin Tae; Jeong, Heon-Sang; Kim, Eun Suk; Yoon, Do-Young

    2016-01-01

    The focus of this study is the anti-cancer effects of Cudrania tricuspidata stem (CTS) extract on cervical cancer cells. The effect of CTS on cell viability was investigated in HPV-positive cervical cancer cells and HaCaT human normal keratinocytes. CTS showed significant dose-dependent cytotoxic effects in cervical cancer cells. However, there was no cytotoxic effect of CTS on HaCaT keratinocytes at concentrations of 0.125-0.5 mg/mL. Based on this cytotoxic effect, we demonstrated that CTS induced apoptosis by down-regulating the E6 and E7 viral oncogenes. Apoptosis was detected by DAPI staining, annexin V-FITC/PI staining, cell cycle analysis, western blotting, RT-PCR, and JC-1 staining in SiHa cervical cancer cells. The mRNA expression levels of extrinsic pathway molecules such as Fas, death receptor 5 (DR5), and TNF-related apoptosis-inducing ligand (TRAIL) were increased by CTS. Furthermore, CTS treatment activated caspase-3/caspase-8 and cleavage of poly (ADP-ribose) polymerase (PARP). However, the mitochondrial membrane potential and expression levels of intrinsic pathway molecules such as Bcl-2, Bcl-xL, Bax, and cytochrome C were not modulated by CTS. Taken together, these results indicate that CTS induced apoptosis by activating the extrinsic pathway, but not the intrinsic pathway, in SiHa cervical cancer cells. These results suggest that CTS can be used as a modulating agent in cervical cancer.

  9. Prevent Cervical Cancer

    MedlinePlus

    ... Fighting Cervical Cancer Worldwide Stay Informed Printable Versions Standard quality PDF [PDF-877KB] High-quality PDF for professional ... uterus, vagina, and vulva. Stay Informed Printable Versions Standard quality PDF [PDF-877KB] High-quality PDF for professional ...

  10. Antibacterial and Antimetastatic Potential of Diospyros lycioides Extract on Cervical Cancer Cells and Associated Pathogens.

    PubMed

    Bagla, V P; Lubisi, V Z; Ndiitwani, T; Mokgotho, M P; Mampuru, L; Mbazima, V

    2016-01-01

    Cervical cancer is among the most prevalent forms of cancer in women worldwide. Diospyros lycioides was extracted using hexane, ethyl acetate, acetone, and methanol and finger print profiles were determined. The leaf material was tested for the presence of flavonoids, tannins, saponins, terpenoids, and cardiac glycosides using standard chemical methods and the presence of flavonoids and phenolics using thin layer chromatography. The total phenolic content was determined using Folin-Ciocalteu procedure. The four extracts were tested for antibacterial activity using bioautography against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli. The acetone extract with the highest number of antibacterial and antioxidant compounds was assessed for its cytotoxicity on BUD-8 cells using the real-time xCELLigence system and its potential effects on metastatic cervical cancer (HeLa) cell migration and invasion were assessed using wound healing migration and invasion assays. The leaf extract tested positive for flavonoids, tannins, and terpenoids while the four different extracts tested in the antimicrobial assay contained constituents active against one or more of the organisms tested, except E. coli. The cytotoxicity of the acetone extract in real-time was concentration-dependent with potent ability to suppress the migration and invasion of HeLa cells. The finding demonstrates the acetone extract to contain constituents with antibacterial and antimetastatic effects on cervical cancer cells. PMID:27239210

  11. Antibacterial and Antimetastatic Potential of Diospyros lycioides Extract on Cervical Cancer Cells and Associated Pathogens

    PubMed Central

    Bagla, V. P.; Lubisi, V. Z.; Ndiitwani, T.; Mokgotho, M. P.; Mampuru, L.; Mbazima, V.

    2016-01-01

    Cervical cancer is among the most prevalent forms of cancer in women worldwide. Diospyros lycioides was extracted using hexane, ethyl acetate, acetone, and methanol and finger print profiles were determined. The leaf material was tested for the presence of flavonoids, tannins, saponins, terpenoids, and cardiac glycosides using standard chemical methods and the presence of flavonoids and phenolics using thin layer chromatography. The total phenolic content was determined using Folin-Ciocalteu procedure. The four extracts were tested for antibacterial activity using bioautography against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli. The acetone extract with the highest number of antibacterial and antioxidant compounds was assessed for its cytotoxicity on BUD-8 cells using the real-time xCELLigence system and its potential effects on metastatic cervical cancer (HeLa) cell migration and invasion were assessed using wound healing migration and invasion assays. The leaf extract tested positive for flavonoids, tannins, and terpenoids while the four different extracts tested in the antimicrobial assay contained constituents active against one or more of the organisms tested, except E. coli. The cytotoxicity of the acetone extract in real-time was concentration-dependent with potent ability to suppress the migration and invasion of HeLa cells. The finding demonstrates the acetone extract to contain constituents with antibacterial and antimetastatic effects on cervical cancer cells. PMID:27239210

  12. Transcriptome signature of irreversible senescence in human papillomavirus-positive cervical cancer cells

    PubMed Central

    Wells, Susanne I.; Aronow, Bruce J.; Wise, Trisha M.; Williams, Sarah S.; Couget, Jennifer A.; Howley, Peter M.

    2003-01-01

    A frequent characteristic of human papillomavirus (HPV)-positive cervical cancers is the loss of viral E2 gene expression in HPV-infected cervical epithelial cells as a consequence of viral DNA integration into the cellular genome. The expression of E2 in HPV-positive cancer cells results in the repression of the viral E6/E7 oncogenes, activation of the p53 and pRB pathways, and a G1 cell cycle arrest, followed by induction of cellular senescence. The transcriptional consequences of E2-mediated cell cycle arrest that lead to senescence currently are unknown. Using conditional senescence induction in HeLa cells and microarray analysis, we describe here the expression profile of cells irreversibly committed to senescence. Our results provide insight into the molecular anatomy of senescence pathways and its regulation by HPV on-coproteins. These include the induction of the RAB vesicular transport machinery and a general down-regulation of chromatin regulatory molecules. The repression of tumor-specific G antigens during E2 senescence supports a reversal of the tumorigenic phenotype by E2 and the potential approach of tumor-specific G antigen-specific immunotherapy for cervical cancer. PMID:12756294

  13. Detection of cancerous cervical cells using physical adhesion of fluorescent silica particles and centripetal force.

    PubMed

    Gaikwad, Ravi M; Dokukin, Maxim E; Iyer, K Swaminathan; Woodworth, Craig D; Volkov, Dmytro O; Sokolov, Igor

    2011-04-01

    Here we describe a non-traditional method to identify cancerous human cervical epithelial cells in a culture dish based on physical adhesion between silica beads and cells. It is a simple optical fluorescence-based technique which detects the relative difference in the amount of fluorescent silica beads physically adherent to surfaces of cancerous and normal cervical cells. The method utilizes the centripetal force gradient that occurs in a rotating culture dish. Due to the variation in the balance between adhesion and centripetal forces, cancerous and normal cells demonstrate clearly distinctive distributions of the fluorescent particles adherent to the cell surface over the culture dish. The method demonstrates higher adhesion of silica particles to normal cells compared to cancerous cells. The difference in adhesion was initially observed by atomic force microscopy (AFM). The AFM data were used to design the parameters of the rotational dish experiment. The optical method that we describe is much faster and technically simpler than AFM. This work provides proof of the concept that physical interactions can be used to accurately discriminate normal and cancer cells. PMID:21305062

  14. Selective permeabilization of cervical cancer cells to an ionic DNA-binding cytotoxin by activation of P2Y receptors.

    PubMed

    Bukhari, Maurish; Deng, Han; Jones, Noelle; Towne, Zachary; Woodworth, Craig D; Samways, Damien S K

    2015-06-01

    Extracellular ATP is known to permeabilize certain cell types to polyatomic cations like YO-PRO1. Here, we report that extracellularly applied ATP stimulated rapid uptake and accumulation of an otherwise weakly membrane permeable fluorescent DNA-binding cytotoxin, Hoechst 33258, into cervical cancer cells. While ATP stimulated Hoechst 33258 uptake in 20-70% of cells from seven cervical cancer cell lines, it stimulated uptake in less than 8% of cervical epithelial cells obtained from the normal transformation zone and ectocervix tissue of 11 patients. ATP-evoked Hoechst 33258 uptake was independent of ionotropic P2X receptors, but dependent on activation of P2Y receptors. Thus, we show here that cervical cancer cells can be selectively induced to take up and accumulate an ionic cytotoxin by exposure to extracellular ATP.

  15. Selective permeabilization of cervical cancer cells to an ionic DNA-binding cytotoxin by activation of P2Y receptors

    PubMed Central

    Bukhari, Maurish; Deng, Han; Jones, Noelle; Towne, Zachary; Woodworth, Craig D.; Samways, Damien S.K.

    2015-01-01

    Extracellular ATP is known to permeabilize certain cell types to polyatomic cations like YO-PRO1. Here, we report that extracellularly applied ATP stimulated rapid uptake and accumulation of an otherwise weakly membrane permeable fluorescent DNA-binding cytotoxin, Hoechst 33258, into cervical cancer cells. While ATP stimulated Hoechst 332uptake in 20–70% of cells from seven cervical cancer cell lines, it consistently stimulated uptake in less than 8% of cervical epithelial cells obtained from the normal transformation zone and ectocervix tissue of 10 patients. ATP-evoked Hoechst 33258 uptake was independent of ionotropic P2X receptors, but dependent on activation of P2Y receptors. Thus, we show here that cervical cancer cells can be selectively induced to take up and accumulate an ionic cytotoxin by exposure to extracellular ATP. PMID:25937122

  16. Anti-proliferative and apoptotic effects of Ziziphus Jujube on cervical and breast cancer cells

    PubMed Central

    Abedini, Mohammad Reza; Erfanian, Nafiseh; Nazem, Habibollah; Jamali, Sara; Hoshyar, Reyhane

    2016-01-01

    Objective: Ziziphus Jujube (Jujube) plant has exhibited numerous medicinal and pharmacological properties including antioxidant and anti-inflammatory effects. This study was carried out to investigate its anti-cancer and pro-apoptotic abilities in human cervical and breast cancer cells in vitro. Materials and Methods: The cervical OV2008 and breast MCF-7 cancer cells were incubated with different concentrations of Jujube aqueous extraction (0-3 mg/ml) for various times (0-72 h). Cell viability was assessed by Trypan Blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of two apoptosis-related genes in treated cells evaluated by quantitative Real Time -PCR analysis. Results: Jujube significantly inhibited cancer cell viability in a dose- and time- dependent manner. Herb-induced apoptosis was associated with enhanced expression of Bax and decreased Bcl2 gene leading eventually to a time-dependent six fold increase in the Bax/Bcl-2 ratio. Conclusion: These results indicated that Jujube may be a natural potential and promising agent to prevent or treat human cancers. PMID:27222827

  17. Apoptotic and autophagic cell death induced by glucolaxogenin in cervical cancer cells.

    PubMed

    Sánchez-Sánchez, L; Escobar, M L; Sandoval-Ramírez, J; López-Muñoz, H; Fernández-Herrera, M A; Hernández-Vázquez, J M V; Hilario-Martínez, C; Zenteno, E

    2015-12-01

    The antiproliferative and cytotoxic activity of glucolaxogenin and its ability to induce apoptosis and autophagy in cervical cancer cells are reported. We ascertained that glucolaxogenin exerts an inhibitory effect on the proliferation of HeLa, CaSki and ViBo cells in a dose-dependent manner. Analysis of DNA distribution in the cell-cycle phase of tumor cells treated with glucolaxogenin suggests that the anti-proliferative activity of this steroid is not always dependent on the cell cycle. Cytotoxic activity was evaluated by detection of the lactate dehydrogenase enzyme in supernatants from tumor cell cultures treated with the steroid. Glucolaxogenin exhibited null cytotoxic activity. With respect to the apoptotic activity, the generation of apoptotic bodies, the presence of active caspase-3 and annexin-V, as well as the DNA fragmentation observed in all tumor lines after treatment with glucolaxogenin suggests that this compound does indeed induce cell death by apoptosis. Also, a significantly increased presence of the LC3-II, LC3 and Lamp-1 proteins was evidenced with the ultrastructural existence of autophagic vacuoles in cells treated with this steroidal glycoside, indicating that glucolaxogenin also induces autophagic cell death. It is important to note that this compound showed no cytotoxic effect and did not affect the proliferative capacity of mononuclear cells obtained from normal human peripheral blood activated by phytohaemagglutinin. Thus, glucolaxogenin is a compound with anti-proliferative properties that induces programmed cell death in cancer cell lines, though it is selective with respect to normal lymphocytic cells. These findings indicate that this glycoside could have a selective action on tumor cells and, therefore, be worthy of consideration as a therapeutic candidate with anti-tumor potential.

  18. Apoptotic and autophagic cell death induced by glucolaxogenin in cervical cancer cells.

    PubMed

    Sánchez-Sánchez, L; Escobar, M L; Sandoval-Ramírez, J; López-Muñoz, H; Fernández-Herrera, M A; Hernández-Vázquez, J M V; Hilario-Martínez, C; Zenteno, E

    2015-12-01

    The antiproliferative and cytotoxic activity of glucolaxogenin and its ability to induce apoptosis and autophagy in cervical cancer cells are reported. We ascertained that glucolaxogenin exerts an inhibitory effect on the proliferation of HeLa, CaSki and ViBo cells in a dose-dependent manner. Analysis of DNA distribution in the cell-cycle phase of tumor cells treated with glucolaxogenin suggests that the anti-proliferative activity of this steroid is not always dependent on the cell cycle. Cytotoxic activity was evaluated by detection of the lactate dehydrogenase enzyme in supernatants from tumor cell cultures treated with the steroid. Glucolaxogenin exhibited null cytotoxic activity. With respect to the apoptotic activity, the generation of apoptotic bodies, the presence of active caspase-3 and annexin-V, as well as the DNA fragmentation observed in all tumor lines after treatment with glucolaxogenin suggests that this compound does indeed induce cell death by apoptosis. Also, a significantly increased presence of the LC3-II, LC3 and Lamp-1 proteins was evidenced with the ultrastructural existence of autophagic vacuoles in cells treated with this steroidal glycoside, indicating that glucolaxogenin also induces autophagic cell death. It is important to note that this compound showed no cytotoxic effect and did not affect the proliferative capacity of mononuclear cells obtained from normal human peripheral blood activated by phytohaemagglutinin. Thus, glucolaxogenin is a compound with anti-proliferative properties that induces programmed cell death in cancer cell lines, though it is selective with respect to normal lymphocytic cells. These findings indicate that this glycoside could have a selective action on tumor cells and, therefore, be worthy of consideration as a therapeutic candidate with anti-tumor potential. PMID:26437916

  19. The LKB1 tumor suppressor differentially affects anchorage independent growth of HPV positive cervical cancer cell lines

    SciTech Connect

    Mack, Hildegard I.D.; Munger, Karl

    2013-11-15

    Infection with high-risk human papillomaviruses is causally linked to cervical carcinogenesis. However, most lesions caused by high-risk HPV infections do not progress to cancer. Host cell mutations contribute to malignant progression but the molecular nature of such mutations is unknown. Based on a previous study that reported an association between liver kinase B1 (LKB1) tumor suppressor loss and poor outcome in cervical cancer, we sought to determine the molecular basis for this observation. LKB1-negative cervical and lung cancer cells were reconstituted with wild type or kinase defective LKB1 mutants and we examined the importance of LKB1 catalytic activity in known LKB1-regulated processes including inhibition of cell proliferation and elevated resistance to energy stress. Our studies revealed marked differences in the biological activities of two kinase defective LKB1 mutants in the various cell lines. Thus, our results suggest that LKB1 may be a cell-type specific tumor suppressor. - Highlights: • LKB1 is a tumor suppressor that is linked to Peutz-Jeghers syndrome. • Peutz-Jeghers syndrome patients have a high incidence of cervical cancer. • Cervical cancer is caused by HPV infections. • This study investigates LKB1 tumor suppressor activity in cervical cancer.

  20. Univariate and multivariate methods for chemical mapping of cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Duraipandian, Shiyamala; Zheng, Wei; Huang, Zhiwei

    2012-01-01

    Visualization of cells and subcellular organelles are currently carried out using available microscopy methods such as cryoelectron microscopy, and fluorescence microscopy. These methods require external labeling using fluorescent dyes and extensive sample preparations to access the subcellular structures. However, Raman micro-spectroscopy provides a non-invasive, label-free method for imaging the cells with chemical specificity at sub-micrometer spatial resolutions. The scope of this paper is to image the biochemical/molecular distributions in cells associated with cancerous changes. Raman map data sets were acquired from the human cervical carcinoma cell lines (HeLa) after fixation under 785 nm excitation wavelength. The individual spectrum was recorded by raster-scanning the laser beam over the sample with 1μm step size and 10s exposure time. Images revealing nucleic acids, lipids and proteins (phenylalanine, amide I) were reconstructed using univariate methods. In near future, the small pixel to pixel variations will also be imaged using different multivariate methods (PCA, clustering (HCA, K-means, FCM)) to determine the main cellular constitutions. The hyper-spectral image of cell was reconstructed utilizing the spectral contrast at different pixels of the cell (due to the variation in the biochemical distribution) without using fluorescent dyes. Normal cervical squamous cells will also be imaged in order to differentiate normal and cancer cells of cervix using the biochemical changes in different grades of cancer. Based on the information obtained from the pseudo-color maps, constructed from the hyper-spectral cubes, the primary cellular constituents of normal and cervical cancer cells were identified.

  1. Automatic Detection of Cervical Cancer Cells by a Two-Level Cascade Classification System.

    PubMed

    Su, Jie; Xu, Xuan; He, Yongjun; Song, Jinming

    2016-01-01

    We proposed a method for automatic detection of cervical cancer cells in images captured from thin liquid based cytology slides. We selected 20,000 cells in images derived from 120 different thin liquid based cytology slides, which include 5000 epithelial cells (normal 2500, abnormal 2500), lymphoid cells, neutrophils, and junk cells. We first proposed 28 features, including 20 morphologic features and 8 texture features, based on the characteristics of each cell type. We then used a two-level cascade integration system of two classifiers to classify the cervical cells into normal and abnormal epithelial cells. The results showed that the recognition rates for abnormal cervical epithelial cells were 92.7% and 93.2%, respectively, when C4.5 classifier or LR (LR: logical regression) classifier was used individually; while the recognition rate was significantly higher (95.642%) when our two-level cascade integrated classifier system was used. The false negative rate and false positive rate (both 1.44%) of the proposed automatic two-level cascade classification system are also much lower than those of traditional Pap smear review. PMID:27298758

  2. Ovarian and cervical cancer.

    PubMed Central

    Williams, C.

    1992-01-01

    Death rates from cervical cancer have already fallen this century and for patients with invasive cervical cancer five year survival rates are greater than for most solid tumours. Better screening for premalignant changes may further reduce the incidence of invasive cancer; indeed, it has been claimed that the reduction in mortality could be as high as 90%, though estimates of screening efficacy have varied greatly. For those with advanced invasive carcinoma neoadjuvant chemotherapy may reduce the risk of relapse and improve survival. Images FIG 2 p1504-a PMID:1611377

  3. Down-regulation of miR-320 associated with cancer progression and cell apoptosis via targeting Mcl-1 in cervical cancer.

    PubMed

    Zhang, Ting; Zou, Ping; Wang, Tiejun; Xiang, Jingying; Cheng, Jing; Chen, Daozhen; Zhou, Jianwei

    2016-07-01

    Our previous studies have demonstrated overexpression of Mcl-1 in cervical cancer tumorigenesis. However, the molecular mechanism of its overexpression remains not elucidated. MiR-320 has been reported to be down-regulated in various types of cancer, and bioinformatics prediction indicated that it may regulate the expression of Mcl-1. The aim of this study is to investigate the role of miR-320 and its target gene Mcl-1 in cervical cancer progression and to assess their clinical significance. miR-320 and Mcl-1 expressions in human cervical cancer tissues were investigated by qRT-PCR, in situ hybridization, and immunohistochemical staining, respectively. The clinicopathological implications of these molecules were analyzed. Bioinformatic prediction and luciferase assays were employed to identify the predicted microRNA (miRNA) which regulates Mcl-1. The apoptosis, proliferation, migration, and invasion assays were performed to investigate the effect of miR-320 on the cervical cancer cells. MiR-320 expression is significantly down-regulated versus Mcl-1 expression is up-regulated in cervical cancer tissues compared with normal controls with a negative correlation between them. Luciferase assay showed that miR-320 negatively regulates Mcl-1 expression. In addition, miR-320 induces apoptosis via down-regulation of Mcl-1 and activation of caspase-3 but inhibits cell proliferation, migration, invasion, and tumorigenesis in cervical cancer cells. Our studies show that miR-320 expression is decreased in cervical cancer, and its expression is negatively correlated with Mcl-1 expression in cervical cancer. In addition, miR-320 inhibits cervical cancer progression by down-regulation of Mcl-1. These results indicate that miR-320 may be an important biomarker and target for diagnosis and treatment of cervical cancer patient.

  4. miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1

    SciTech Connect

    Liu, Shikai; Song, Lili Zhang, Liang; Zeng, Saitian; Gao, Fangyuan

    2015-04-17

    Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3′-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity. - Highlights: • miR-21 is highly expressed in HR-HPV (+) radioresistant cervical cancer patients. • miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells. • miR-21 can decrease radiation induced G2/M block and increase S phase accumulation. • miR-21 modulates radiosensitivity cervical cancer cell by directly targeting LATS1.

  5. Enhanced Antiproliferative Effect of Carboplatin in Cervical Cancer Cells Utilizing Folate-Grafted Polymeric Nanoparticles

    NASA Astrophysics Data System (ADS)

    Ji, Jing; Zuo, Ping; Wang, Yue-Ling

    2015-11-01

    Carboplatin (CRB) possesses superior anticancer effect in cervical cancer cells with lower incidence of side effects compared to that of cisplatin. However, CRB suffers from severe side effects due to undesirable tissue distributions which contribute to the low therapeutic efficacy. Here, we report a unique folic acid-conjugated chitosan-coated poly( d- l-lactideco-glycolide) (PLGA) nanoparticles (FPCC) prepared for the selective delivery of carboplatin to the cervical cancer cells. The particles were nanosized and spherical shaped with size less than <200 nm. The presence of protective chitosan layer controlled the overall release rate of CRB from chitosan-coated PLGA nanoparticles (PCC) and FPCC. FPCC displayed a higher cellular uptake capacity in HeLa cells than compared to non-targeted nanoparticles. Selective uptake of FPCC was due to an interaction of folic acid (FA) with the folate receptors alpha (FRs-α) which is overexpressed on the HeLa and promoted active targeting. These results indicated that FPCC had a specific affinity for the cancerous, HeLa cells owing to ligand-receptor (FA-FR-α) recognition. Consistently, FPCC showed superior cytotoxic effect than any other formulations. The IC50 (concentration of the drug required to kill 50 % of the cells) value of FPCC was 0.65 μg/ml while it was 1.08, 1.56, and 2.35 μg/ml for PCC, PLGA NP, and free CRB, respectively. Consistent with the cytotoxicity assay, FPCC induced higher fraction of early as well as late apoptosis cells. Especially, FPCC induced nearly 45 % of early apoptosis cells and more than 35 % in late apoptosis. Therefore, we propose that folate-conjugated nanoparticles might have potential applications in cervical cancer therapy.

  6. Induction of mitochondrial-mediated apoptosis by Morinda citrifolia (Noni) in human cervical cancer cells.

    PubMed

    Gupta, Rakesh Kumar; Banerjee, Ayan; Pathak, Suajta; Sharma, Chandresh; Singh, Neeta

    2013-01-01

    Cervical cancer is the second most common cause of cancer in women and has a high mortality rate. Cisplatin, an antitumor agent, is generally used for its treatment. However, the administration of cisplatin is associated with side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown to have anti-cancer properties. In this study, we used Noni, cisplatin, and the two in combination to study their cytotoxic and apoptosis-inducing effects in cervical cancer HeLa and SiHa cell lines. We demonstrate here, that Noni/Cisplatin by themselves and their combination were able to induce apoptosis in both these cell lines. Cisplatin showed slightly higher cell killing as compared to Noni and their combination showed additive effects. The observed apoptosis appeared to be mediated particularly through the up-regulation of p53 and pro-apoptotic Bax proteins, as well as down- regulation of the anti-apoptotic Bcl-2, Bcl-XL proteins and survivin. Augmentation in the activity of caspase-9 and -3 was also observed, suggesting the involvement of the intrinsic mitochondrial pathway of apoptosis for both Noni and Cisplatin in HeLa and SiHa cell lines.

  7. Apoptotic potential role of Agave palmeri and Tulbaghia violacea extracts in cervical cancer cells.

    PubMed

    Mthembu, Nonkululeko N; Motadi, Lesetja Raymond

    2014-09-01

    Cervical cancer, a gynaecological malignant disorder, is a common cause of death in females in Sub-Saharan Africa, striking nearly half a million of lives each year worldwide. Currently, more than 50 % of all modern drugs in clinical use are of natural products, many of which have an ability to control cancer cells (Madhuri and Pandey, Curr Sci 96:779-783, 2009; Richter, Traditional medicines and traditional healers in South Africa, 2003). In South Africa, plants used to treat cancer are rare even though majority of our population continue to put their trust in traditional medicine. In this study we aimed to screen Agave palmeri (AG) and Tulbaghia violacea (TV) for potential role in inducing cell death in cervical cancer cell lines HeLa and ME-180, and in normal human fibroblast cell line KMST-6 cell lines. To achieve this, AG and TV crude extracts were utilized to screen for apoptosis induction, inhibition of cell proliferation followed by elucidation of the role of Bax, Bcl-2, p53, Rb, RBBP and Mdm2 genes in cervical cancer. In brief, plant leaves and roots were collected, crushed and methanolic extracts obtained. Different concentrations of the stock extracts were used to treat cancer cells and measure cell death using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and flow cytometry. Western blot was applied to measure gene expression at protein level using RBBP6, p53, Mdm2, Rb, Bax, Bcl-2 and β-actin mouse monoclonal primary antibodies (IgG) and goat anti mouse coupled with horseradish peroxidase secondary antibody from Santa Cruz Biotechnology and real time-PCR was used for mRNA expression level. Plant extracts of AG and TV were time (24 h) and dose (50, 100, 150 μg/ml) dependent in their induction of cell death with an IC50 ~ 150 μg/ml. A further mixed respond by several genes was observed following treatment with the two plant extracts where RBBP6 was seen to be spliced in cancer cells while Bax was induced and Bcl-2 was

  8. Apoptotic potential role of Agave palmeri and Tulbaghia violacea extracts in cervical cancer cells.

    PubMed

    Mthembu, Nonkululeko N; Motadi, Lesetja Raymond

    2014-09-01

    Cervical cancer, a gynaecological malignant disorder, is a common cause of death in females in Sub-Saharan Africa, striking nearly half a million of lives each year worldwide. Currently, more than 50 % of all modern drugs in clinical use are of natural products, many of which have an ability to control cancer cells (Madhuri and Pandey, Curr Sci 96:779-783, 2009; Richter, Traditional medicines and traditional healers in South Africa, 2003). In South Africa, plants used to treat cancer are rare even though majority of our population continue to put their trust in traditional medicine. In this study we aimed to screen Agave palmeri (AG) and Tulbaghia violacea (TV) for potential role in inducing cell death in cervical cancer cell lines HeLa and ME-180, and in normal human fibroblast cell line KMST-6 cell lines. To achieve this, AG and TV crude extracts were utilized to screen for apoptosis induction, inhibition of cell proliferation followed by elucidation of the role of Bax, Bcl-2, p53, Rb, RBBP and Mdm2 genes in cervical cancer. In brief, plant leaves and roots were collected, crushed and methanolic extracts obtained. Different concentrations of the stock extracts were used to treat cancer cells and measure cell death using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and flow cytometry. Western blot was applied to measure gene expression at protein level using RBBP6, p53, Mdm2, Rb, Bax, Bcl-2 and β-actin mouse monoclonal primary antibodies (IgG) and goat anti mouse coupled with horseradish peroxidase secondary antibody from Santa Cruz Biotechnology and real time-PCR was used for mRNA expression level. Plant extracts of AG and TV were time (24 h) and dose (50, 100, 150 μg/ml) dependent in their induction of cell death with an IC50 ~ 150 μg/ml. A further mixed respond by several genes was observed following treatment with the two plant extracts where RBBP6 was seen to be spliced in cancer cells while Bax was induced and Bcl-2 was

  9. Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα

    PubMed Central

    Yang, Yuhan; He, Lili; Liu, Yongmei; Xia, Shan; Fang, Aiping; Xie, Yafei; Gan, Li; He, Zhiyao; Tan, Xiaoyue; Jiang, Chunling; Tong, Aiping; Song, Xiangrong

    2016-01-01

    Cervical cancer presents extremely low PEDF expression which is associated with tumor progression and poor prognosis. In this study, folate receptor α (FRα)-targeted nano-liposomes (FLP) were designed to enhance the anti-tumor effect by targeting delivery of exogenous PEDF gene to cervical cancer cells. The targeting molecule F-PEG-Chol was firstly synthesized by a novel simpler method. FLP encapsulating PEDF gene (FLP/PEDF) with a typical lipid-membrane structure were prepared by a film dispersion method. The transfection experiment found FLP could effectively transfect human cervical cancer cells (HeLa cells). FLP/PEDF significantly inhibited the growth of HeLa cells and human umbilical vein endothelial cells (HUVEC cells) and suppressed adhension, invasion and migration of HeLa cells in vitro. In the abdominal metastatic tumor model of cervical cancer, FLP/PEDF administered by intraperitoneal injection exhibited a superior anti-tumor effect probably due to the up-regulated PEDF. FLP/PEDF could not only sharply reduce the microvessel density but also dramatically inhibit proliferation and markedly induce apoptosis of tumor cells in vivo. Moreover, the preliminary safety investigation revealed that FLP/PEDF had no obvious toxicity. These results clearly showed that FLP were desired carriers for PEDF gene and FLP/PEDF might represent a potential novel strategy for gene therapy of cervical cancer. PMID:27576898

  10. Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα.

    PubMed

    Yang, Yuhan; He, Lili; Liu, Yongmei; Xia, Shan; Fang, Aiping; Xie, Yafei; Gan, Li; He, Zhiyao; Tan, Xiaoyue; Jiang, Chunling; Tong, Aiping; Song, Xiangrong

    2016-01-01

    Cervical cancer presents extremely low PEDF expression which is associated with tumor progression and poor prognosis. In this study, folate receptor α (FRα)-targeted nano-liposomes (FLP) were designed to enhance the anti-tumor effect by targeting delivery of exogenous PEDF gene to cervical cancer cells. The targeting molecule F-PEG-Chol was firstly synthesized by a novel simpler method. FLP encapsulating PEDF gene (FLP/PEDF) with a typical lipid-membrane structure were prepared by a film dispersion method. The transfection experiment found FLP could effectively transfect human cervical cancer cells (HeLa cells). FLP/PEDF significantly inhibited the growth of HeLa cells and human umbilical vein endothelial cells (HUVEC cells) and suppressed adhension, invasion and migration of HeLa cells in vitro. In the abdominal metastatic tumor model of cervical cancer, FLP/PEDF administered by intraperitoneal injection exhibited a superior anti-tumor effect probably due to the up-regulated PEDF. FLP/PEDF could not only sharply reduce the microvessel density but also dramatically inhibit proliferation and markedly induce apoptosis of tumor cells in vivo. Moreover, the preliminary safety investigation revealed that FLP/PEDF had no obvious toxicity. These results clearly showed that FLP were desired carriers for PEDF gene and FLP/PEDF might represent a potential novel strategy for gene therapy of cervical cancer. PMID:27576898

  11. Inhibitory effect of Trolox on the migration and invasion of human lung and cervical cancer cells.

    PubMed

    Sung, Ho Joong; Kim, Yoonseo; Kang, Hyereen; Sull, Jae Woong; Kim, Yoon Suk; Jang, Sung-Wuk; Ko, Jesang

    2012-02-01

    The antioxidant 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) is implicated in migration and invasion of metastatic tumors. However, the molecular mechanism underlying the effect of Trolox on metastatic cancer cells is not known. We found that a non-cytotoxic dose of Trolox decreased phorbol 12-myristate 13-acetate (PMA)-induced invasion and migration of both A549 and HeLa cancer cells. We also found that Trolox suppressed both the expression and the proteolytic activity of matrix metalloproteinase-9 (MMP-9), and that the promoter activity of PMA-induced MMP-9 was inhibited by Trolox. Our results show that Trolox inhibits the transcriptional activity of MMP-9 by suppression of NF-κB transactivation. These results indicate that Trolox inhibits NF-κB-mediated MMP-9 expression, leading to the suppression of migration and invasion in lung and cervical cancer cells. Trolox is a potential agent for clinical use in preventing the invasion and metastasis of human malignant lung and cervical cancers.

  12. Constitutively active Notch1 induces growth arrest of HPV-positive cervical cancer cells via separate signaling pathways

    SciTech Connect

    Talora, Claudio; Cialfi, Samantha; Segatto, Oreste; Morrone, Stefania; Kim Choi, John; Frati, Luigi; Paolo Dotto, Gian; Gulino, Alberto; Screpanti, Isabella . E-mail: isabella.screpanti@uniroma1.it

    2005-05-01

    Notch signaling plays a key role in cell-fate determination and differentiation in different organisms and cell types. Several reports suggest that Notch signaling may be involved in neoplastic transformation. However, in primary keratinocytes, Notch1 can function as a tumor suppressor. Similarly, in HPV-positive cervical cancer cells, constitutively active Notch1 signaling was found to cause growth suppression. Activated Notch1 in these cells represses viral E6/E7 expression through AP-1 down-modulation, resulting in increased p53 expression and a block of pRb hyperphosphorylation. Here we show that in cervical cancer cell lines in which Notch1 ability to repress AP-1 activity is impaired, Notch1-enforced expression elicits an alternative pathway leading to growth arrest. Indeed, activated Notch1 signaling suppresses activity of the helix-loop-helix transcription factor E47, via ERK1/2 activation, resulting in inhibition of cell cycle progression. Moreover, we found that RBP-J{kappa}-dependent Notch signaling is specifically repressed in cervical cancer cells and this repression could provide one such mechanism that needs to be activated for cervical carcinogenesis. Finally, we show that inhibition of endogenous Notch1 signaling, although results in a proliferative advantage, sensitizes cervical cancer cell lines to drug-induced apoptosis. Together, our results provide novel molecular insights into Notch1-dependent growth inhibitory effects, counteracting the transforming potential of HPV.

  13. How Are Cervical Cancers and Pre-Cancers Diagnosed?

    MedlinePlus

    ... How is cervical cancer staged? How is cervical cancer diagnosed? The first step in finding cervical cancer ... systems. Tests for women with symptoms of cervical cancer or abnormal Pap results Medical history and physical ...

  14. EF5 in Finding Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Cervical, Endometrial, or Ovarian Epithelial Cancer

    ClinicalTrials.gov

    2013-01-15

    Primary Peritoneal Cavity Cancer; Stage I Endometrial Carcinoma; Stage I Ovarian Epithelial Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage II Ovarian Epithelial Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  15. Cudrania tricuspidata Stem Extract Induces Apoptosis via the Extrinsic Pathway in SiHa Cervical Cancer Cells

    PubMed Central

    Kwon, Sae-Bom; Kim, Min-Je; Yang, Jin Mo; Lee, Hee-Pom; Hong, Jin Tae; Jeong, Heon-Sang; Kim, Eun Suk; Yoon, Do-Young

    2016-01-01

    The focus of this study is the anti-cancer effects of Cudrania tricuspidata stem (CTS) extract on cervical cancer cells. The effect of CTS on cell viability was investigated in HPV-positive cervical cancer cells and HaCaT human normal keratinocytes. CTS showed significant dose-dependent cytotoxic effects in cervical cancer cells. However, there was no cytotoxic effect of CTS on HaCaT keratinocytes at concentrations of 0.125–0.5 mg/mL. Based on this cytotoxic effect, we demonstrated that CTS induced apoptosis by down-regulating the E6 and E7 viral oncogenes. Apoptosis was detected by DAPI staining, annexin V-FITC/PI staining, cell cycle analysis, western blotting, RT-PCR, and JC-1 staining in SiHa cervical cancer cells. The mRNA expression levels of extrinsic pathway molecules such as Fas, death receptor 5 (DR5), and TNF-related apoptosis-inducing ligand (TRAIL) were increased by CTS. Furthermore, CTS treatment activated caspase-3/caspase-8 and cleavage of poly (ADP-ribose) polymerase (PARP). However, the mitochondrial membrane potential and expression levels of intrinsic pathway molecules such as Bcl-2, Bcl-xL, Bax, and cytochrome C were not modulated by CTS. Taken together, these results indicate that CTS induced apoptosis by activating the extrinsic pathway, but not the intrinsic pathway, in SiHa cervical cancer cells. These results suggest that CTS can be used as a modulating agent in cervical cancer. PMID:26960190

  16. Cross-talk between Human Papillomavirus Oncoproteins and Hedgehog Signaling Synergistically Promotes Stemness in Cervical Cancer Cells

    PubMed Central

    Vishnoi, Kanchan; Mahata, Sutapa; Tyagi, Abhishek; Pandey, Arvind; Verma, Gaurav; Jadli, Mohit; Singh, Tejveer; Singh, Sukh Mahendra; Bharti, Alok C.

    2016-01-01

    Viral oncoproteins E6/E7 play key oncogenic role in human papillomavirus (HPV)-mediated cervical carcinogenesis in conjunction with aberrant activation of cellular signaling events. GLI-signaling has been implicated in metastasis and tumor recurrence of cervical cancer. However, the interaction of GLI-signaling with HPV oncogenes is unknown. We examined this relationship in established HPV-positive and HPV-negative cervical cancer cell lines using specific GLI inhibitor, cyclopamine and HPVE6/E7 siRNAs. Cervical cancer cell lines showed variable expression of GLI-signaling components. HPV16-positive SiHa cells, overexpressed GLI1, Smo and Patch. Inhibition by cyclopamine resulted in dose-dependent reduction of Smo and GLI1 and loss of cell viability with a higher magnitude in HPV-positive cells. Cyclopamine selectively downregulated HPVE6 expression and resulted in p53 accumulation, whereas HPVE7 and pRb level remained unaffected. siRNA-mediated silencing of HPV16E6 demonstrated reduced GLI1 transcripts in SiHa cells. Cervical cancer stem-like cells isolated by side population analysis, displayed retention of E6 and GLI1 expression. Fraction of SP cells was reduced in cyclopamine-treated cultures. When combined with E6-silencing cyclopamine resulted in loss of SP cell’s sphere-forming ability. Co-inhibition of GLI1 and E6 in cervical cancer cells showed additive anti-cancer effects. Overall, our data show existence of a cooperative interaction between GLI signaling and HPVE6. PMID:27678330

  17. Difference in cellular mechanics of cancer and normal cervical cells as seen with the AFM

    NASA Astrophysics Data System (ADS)

    Sokolov, Igor; Iyer, Swaminathan; Subba-Rao, Venkatesh; Woodworth, Craig

    2006-03-01

    Oncogenically transformed cells differ from their normal counter parts in many aspects, including organization and the amount of cytoskeleton. Consequently it is natural to expect to see the difference in cellular mechanics. Here we will present the study of such differences by using atomic force microscopy (AFM) in-vitro. So far the present research is the first study of mechanics of cervical cells, and the third comparative study of differences between mechanics of cancer and normal cells down with the help of AFM. Using a micron size silica ball as the AFM probe, we presumably do not overstress the cell surface as it can be in the case of the sharp AFM tip, and consequently, we may use the classical Hertz model. In contrast to the reported previously studies (bladder and fibroblast cells), we found that oncogenically transformed cervical cells are more rigid than the normal cells. The reason for such difference will be discussed. To demonstrate the complexity of the problem, we study cell mechanics in detail. The Young's modulus of rigidity clearly shows two separate regions of rigidity depending on the depth of the probe penetration. There may be two alternative explanations of the difference in rigidity of this top layer: it is either the cell membrane layer or detected long-range (presumably steric) forces due to the molecular ``brush'' of glycocalyx molecules. Experiments and modal calculations will be presented to choose between these two possibilities.

  18. Identification of NDRG1-regulated genes associated with invasive potential in cervical and ovarian cancer cells

    SciTech Connect

    Zhao, Gang; Chen, Jiawei; Deng, Yanqiu; Gao, Feng; Zhu, Jiwei; Feng, Zhenzhong; Lv, Xiuhong; Zhao, Zheng

    2011-04-29

    Highlights: {yields} NDRG1 was knockdown in cervical and ovarian cancer cell lines by shRNA technology. {yields} NDRG1 knockdown resulted in increased cell invasion activities. {yields} Ninety-six common deregulated genes in both cell lines were identified by cDNA microarray. {yields} Eleven common NDRG1-regulated genes might enhance cell invasive activity. {yields} Regulation of invasion by NDRG1 is an indirect and complicated process. -- Abstract: N-myc downstream regulated gene 1 (NDRG1) is an important gene regulating tumor invasion. In this study, shRNA technology was used to suppress NDRG1 expression in CaSki (a cervical cancer cell line) and HO-8910PM (an ovarian cancer cell line). In vitro assays showed that NDRG1 knockdown enhanced tumor cell adhesion, migration and invasion activities without affecting cell proliferation. cDNA microarray analysis revealed 96 deregulated genes with more than 2-fold changes in both cell lines after NDRG1 knockdown. Ten common upregulated genes (LPXN, DDR2, COL6A1, IL6, IL8, FYN, PTP4A3, PAPPA, ETV5 and CYGB) and one common downregulated gene (CLCA2) were considered to enhance tumor cell invasive activity. BisoGenet network analysis indicated that NDRG1 regulated these invasion effector genes/proteins in an indirect manner. Moreover, NDRG1 knockdown also reduced pro-invasion genes expression such as MMP7, TMPRSS4 and CTSK. These results suggest that regulation of invasion and metastasis by NDRG1 is a highly complicated process.

  19. A model for co-expression pattern analysis of genes implicated in angiogenesis and tumour cell invasion in cervical cancer.

    PubMed

    Van Trappen, P O; Ryan, A; Carroll, M; Lecoeur, C; Goff, L; Gyselman, V G; Young, B D; Lowe, D G; Pepper, M S; Shepherd, J H; Jacobs, I J

    2002-08-27

    To date, numerous genes have been identified which are involved in both tumour neovascularisation (angiogenesis) and tumour cell invasion, and most of them are also expressed to some extent under normal physiological conditions. However, little is known about how these genes co-express in these settings. This study was undertaken to quantitate mRNA levels in normal and malignant cervical tissues of nine selected genes (VEGF(121), VEGF(165), VEGF(189), VEGF-C, eIF-4E, b-FGF, TSP-2, MMP-2 and MMP-9) implicated in the above processes using real-time quantitative RT-PCR. In addition, the Spearman's rank correlation was used to determine their co-expression patterns. The transcript levels for the different VEGF-A splice variants (VEGF(121), VEGF(165), VEGF(189)) were at least 10-fold higher in the cancer cases, with the highest levels in the primary tumours demonstrating lympho-vascular space involvement. The lymphangiogenic factor VEGF-C and MMP-9 were upregulated 130- and 80-fold respectively in cervical cancers. The highest levels of VEGF-C mRNA were found in the lymph-node positive group. The transcript levels for b-FGF were similar in normal cervical tissue and early-stage cervical cancer, however, higher levels were found in the cervical cancers with advanced stage disease. Comparing gene transcript levels between recurrent and non-recurrent cervical cancer patients revealed significant differences (P=0.038) in transcript levels for the angiogenesis inhibitor TSP-2, with the highest levels in non-recurrent cases. Co-expression pattern analysis in normal cervical tissue revealed highly significant co-expressions (P<0.0001) between TSP-2 and most other genes analysed (VEGF(121), VEGF(165), VEGF-C, b-FGF and MMP-2). In cervical cancer, TSP-2 appears only to be highly co-expressed with MMP-2 (P<0.0001). In contrast to normal cervical tissue, we found a highly significant co-expression (P<0.0001) between MMP-9 and VEGF(189) in cervical cancer. The combined application

  20. (-)-Epigallocatechin-3-gallate induces apoptosis and inhibits invasion and migration of human cervical cancer cells.

    PubMed

    Sharma, Chhavi; Nusri, Qurrat El-Ain; Begum, Salema; Javed, Elham; Rizvi, Tahir A; Hussain, Arif

    2012-01-01

    Invasion and metastasis are the major causes of cancer-related death. Pharmacological or therapeutic interventions such as chemoprevention of the progression stages of neoplastic development could result in substantial reduction in the incidence of cancer mortality. (-)-Epigallocatechin-3-gallate (EGCG), a promising chemopreventive agent, has attracted extensive interest for cancer therapy utilizing its antioxidant, anti- proliferative and inhibitory effects on angiogenesis and tumor cell invasion. In this study, we assessed the influence of EGCG on the proliferative potential of HeLa cells by cell viability assay and authenticated the results by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Further we analyzed the anti-invasive properties of EGCG by wound migration assay and gene expression of MMP-9 and TIMP-1 in HeLa cells. Our results indicated that EGCG induced growth inhibition of HeLa cells in a dose- and time- dependent manner. It was observed that cell death mediated by EGCG was through apoptosis. Interestingly, EGCG effectively inhibited invasion and migration of HeLa cells and modulated the expression of related genes (MMP-9 and TIMP-1) . These results indicate that EGCG may effectively suppress promotion and progression stages of cervical cancer development.

  1. Nelfinavir is effective against human cervical cancer cells in vivo: a potential treatment modality in resource-limited settings

    PubMed Central

    Davis, Mitzie-Ann; Delaney, Joe R; Patel, Chandni B; Storgard, Ryan; Stupack, Dwayne G

    2016-01-01

    Objective The standard treatment for cervical cancer in developed countries includes surgery and chemoradiation, with standard of care lagging in developing countries. Even in the former case, treatment frequently yields recalcitrant tumors and women succumb to disease. Here we examine the impact of nelfinavir, an off-patent viral protease inhibitor, which has shown promise as an antineoplastic agent. Methods We evaluated the morphological and proliferative effects of the autophagy-stressing drug nelfinavir in normal and cisplatin-resistant cervical cancer cells. Immunofluorescent validation of autophagy markers was performed and the impact of nelfinavir in an in vivo model of tumor growth was determined. Results Nelfinavir exhibits cytotoxicity against both cisplatin-sensitive and -resistant ME-180 human cervical cancer cells in vitro and in vivo. Immunoblotting and immunofluorescence showed an expression of the autophagy marker LC3-II in response to nelfinavir treatment. Conclusion Nelfinavir, now available as an inexpensive generic orally dosed agent (Nelvir), is cytotoxic against cervical cancer cells. It acts by burdening the autophagy pathway to impair tumor cell survival and a modest induction of apoptosis. While further studies are needed to elucidate the optimal method of application of nelfinavir, it may represent an appealing global option for the treatment of cervical cancer. PMID:27330277

  2. IKKβ/NF-κB mediated the low doses of bisphenol A induced migration of cervical cancer cells.

    PubMed

    Ma, Xue-Feng; Zhang, Jie; Shuai, Han-Lin; Guan, Bao-Zhang; Luo, Xin; Yan, Rui-Ling

    2015-05-01

    Cervical cancer is considered as the second most common female malignant disease. There is an urgent need to illustrate risk factors which can trigger the motility of cervical cancer cells. Our present study revealed that nanomolar concentration of bisphenol A (BPA) significantly promoted the in vitro migration and invasion of cervical cancer HeLa, SiHa, and C-33A cells. Further, BPA treatment increased the expression of metalloproteinase-9 (MMP-9) and fibronectin (FN) in both HeLa and SiHa cells, while did not obviously change the expression of MMP-2, vimentin (Vim) or N-Cadherin (N-Cad). BAY 11-7082, the inhibitor of NF-κB, significantly abolished BPA induced up regulation of FN and MMP-9 in cervical cancer cells. While the inhibitors of PKA (H89), ERK1/2 (PD 98059), EGFR (AG1478), or PI3K/Akt (LY294002) had no effect on the expression of either FN or MMP-9. BPA treatment rapidly increased the phosphorylation of both IκBα and p65, stimulated nuclear translocation, and up regulated the promoter activities of NF-κB. The BPA induced up regulation of MMP-9 and FN and activation of NF-κB were mediated by phosphorylation of IKKβ via PKC signals. Collectively, our study found for the first time that BPA stimulated the cervical cancer migration via IKK-β/NF-κB signals.

  3. Tissue Inhibitor of Metalloproteinase-4 Triggers Apoptosis in Cervical Cancer Cells.

    PubMed

    Lizarraga, Floria; Ceballos-Cancino, Gisela; Espinosa, Magali; Vazquez-Santillan, Karla; Maldonado, Vilma; Melendez-Zajgla, Jorge

    2015-01-01

    Tissue inhibitor of metalloproteinase-4 (TIMP-4) is a member of extracellular matrix (ECM) metalloproteinases inhibitors that has pleiotropic functions. However, TIMP-4 roles in carcinogenesis are not well understood. Cell viability and flow cytometer assays were employed to evaluate cell death differences between H-Vector and H-TIMP-4 cell lines. Immunobloting and semi-quantitative RT-PCR were used to evaluate the expression of apoptosis regulators. We showed that TIMP-4 has apoptosis-sensitizing effects towards several death stimuli. Consistent with these findings, regulators of apoptosis from Inhibitors of Apoptosis Proteins (IAP), FLICE-like inhibitor proteins (FLIP) and Bcl-2 family members were modulated by TIMP-4. In addition, TIMP-4 knockdown resulted in cell survival increase after serum deprivation, as assessed by clonogenic cell analyses. This report shows that TIMP-4 regulates carcinogenesis through apoptosis activation in cervical cancer cells. Understanding TIMP-4 effects in tumorigenesis may provide clues for future therapies.

  4. On physical changes on surface of human cervical epithelial cells during cancer transformations

    NASA Astrophysics Data System (ADS)

    Sokolov, Igor; Dokukin, Maxim; Guz, Nataliia; Woodworth, Craig

    2013-03-01

    Physical changes of the cell surface of cells during transformation from normal to cancerous state are rather poorly studied. Here we describe our recent studies of such changes done on human cervical epithelial cells during their transformation from normal through infected with human papillomavirus type-16 (HPV-16), immortalized (precancerous), to cancerous cells. The changes were studied with the help of atomic force microscopy (AFM) and through the measurement of physical adhesion of fluorescent silica beads to the cell surface. Based on the adhesion experiments, we clearly see the difference in nonspecific adhesion which occurs at the stage of immortalization of cells, precancerous cells. The analysis done with the help of AFM shows that the difference observed comes presumably from the alteration of the cellular ``brush,'' a layer that surrounds cells and which consists of mostly microvilli, microridges, and glycocalyx. Further AFM analysis reveals the emergence of fractal scaling behavior on the surface of cells when normal cells turn into cancerous. The possible causes and potential significance of these observations will be discussed.

  5. [Primary cervical cancer screening].

    PubMed

    Vargas-Hernández, Víctor Manuel; Vargas-Aguilar, Víctor Manuel; Tovar-Rodríguez, José María

    2015-01-01

    Cervico-uterine cancer screening with cytology decrease incidence by more than 50%. The cause of this cancer is the human papilloma virus high risk, and requires a sensitive test to provide sufficient sensitivity and specificity for early detection and greater interval period when the results are negative. The test of the human papilloma virus high risk, is effective and safe because of its excellent sensitivity, negative predictive value and optimal reproducibility, especially when combined with liquid-based cytology or biomarkers with viral load, with higher sensitivity and specificity, by reducing false positives for the detection of cervical intraepithelial neoplasia grade 2 or greater injury, with excellent clinical benefits to cervical cancer screening and related infection of human papilloma virus diseases, is currently the best test for early detection infection of human papillomavirus and the risk of carcinogenesis.

  6. Families of microRNAs Expressed in Clusters Regulate Cell Signaling in Cervical Cancer

    PubMed Central

    Servín-González, Luis Steven; Granados-López, Angelica Judith; López, Jesús Adrián

    2015-01-01

    Tumor cells have developed advantages to acquire hallmarks of cancer like apoptosis resistance, increased proliferation, migration, and invasion through cell signaling pathway misregulation. The sequential activation of genes in a pathway is regulated by miRNAs. Loss or gain of miRNA expression could activate or repress a particular cell axis. It is well known that aberrant miRNA expression is well recognized as an important step in the development of cancer. Individual miRNA expression is reported without considering that miRNAs are grouped in clusters and may have similar functions, such as the case of clusters with anti-oncomiRs (23b~27b~24-1, miR-29a~29b-1, miR-29b-2~29c, miR-99a~125b-2, miR-99b~125a, miR-100~125b-1, miR-199a-2~214, and miR-302s) or oncomiRs activity (miR-1-1~133a-2, miR-1-2~133a-1, miR-133b~206, miR-17~92, miR-106a~363, miR183~96~182, miR-181a-1~181b-1, and miR-181a-2~181b-2), which regulated mitogen-activated protein kinases (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), NOTCH, proteasome-culling rings, and apoptosis cell signaling. In this work we point out the pathways regulated by families of miRNAs grouped in 20 clusters involved in cervical cancer. Reviewing how miRNA families expressed in cluster-regulated cell path signaling will increase the knowledge of cervical cancer progression, providing important information for therapeutic, diagnostic, and prognostic methodology design. PMID:26057746

  7. In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by CRISPR/Cas9

    SciTech Connect

    Zhen, Shuai; Hua, Ling; Takahashi, Y.; Narita, S.; Liu, Yun-Hui; Li, Yan

    2014-08-08

    Highlights: • Established CRISPR/Cas9 targeting promoter of HPV 16 and targeting E6, E7 transcript. • CRISPR/Cas9 resulted in accumulation of p53 and p21, reduced the proliferation of cervical cancer cells. • Finding inhibited tumorigenesis and growth of mice incubated by cells with CRISPR/Cas9. • CRISPR/Cas9 will be a new treatment strategy, in cervical and other HPV-associated cancer therapy. - Abstract: Deregulated expression of high-risk human papillomavirus oncogenes (E6 and E7) is a pivotal event for pathogenesis and progression in cervical cancer. Both viral oncogenes are therefore regarded as ideal therapeutic targets. In the hope of developing a gene-specific therapy for HPV-related cancer, we established CRISPR/Cas9 targeting promoter of HPV 16 E6/E7 and targeting E6, E7 transcript, transduced the CRISPR/Cas9 into cervical HPV-16-positive cell line SiHa. The results showed that CRISPR/Cas9 targeting promoter, as well as targeting E6 and E7 resulted in accumulation of p53 and p21 protein, and consequently remarkably reduced the abilities of proliferation of cervical cancer cells in vitro. Then we inoculated subcutaneously cells into nude mice to establish the transplanted tumor animal models, and found dramatically inhibited tumorigenesis and growth of mice incubated by cells with CRISPR/Cas9 targeting (promoter+E6+E7)-transcript. Our results may provide evidence for application of CRISPR/Cas9 targeting HR-HPV key oncogenes, as a new treatment strategy, in cervical and other HPV-associated cancer therapy.

  8. Aloe vera inhibits proliferation of human breast and cervical cancer cells and acts synergistically with cisplatin.

    PubMed

    Hussain, Arif; Sharma, Chhavi; Khan, Saniyah; Shah, Kruti; Haque, Shafiul

    2015-01-01

    Many of the anti-cancer agents currently used have an origin in natural sources including plants. Aloe vera is one such plant being studied extensively for its diverse health benefits, including cancer prevention. In this study, the cytotoxic potential of Aloe vera crude extract (ACE) alone or in combination with cisplatin in human breast (MCF-7) and cervical (HeLa) cancer cells was studied by cell viability assay, nuclear morphological examination and cell cycle analysis. Effects were correlated with modulation of expression of genes involved in cell cycle regulation, apoptosis and drug metabolism by RT-PCR. Exposure of cells to ACE resulted in considerable loss of cell viability in a dose- and time-dependent fashion, which was found to be mediated by through the apoptotic pathway as evidenced by changes in the nuclear morphology and the distribution of cells in the different phases of the cell cycle. Interestingly, ACE did not have any significant cytotoxicity towards normal cells, thus placing it in the category of safe chemopreventive agent. Further, the effects were correlated with the downregulation of cyclin D1, CYP 1A1, CYP 1A2 and increased expression of bax and p21 in MCF-7 and HeLa cells. In addition, low dose combination of ACE and cisplatin showed a combination index less than 1, indicating synergistic growth inhibition compared to the agents applied individually. In conclusion, these results signify that Aloe vera may be an effective anti-neoplastic agent to inhibit cancer cell growth and increase the therapeutic efficacy of conventional drugs like cispolatin. Thus promoting the development of plant-derived therapeutic agents appears warranted for novel cancer treatment strategies.

  9. Radiation effects on DNA content of cervical cancer cells: A rapid evaluation of radiation sensitivity by laser scanning cytometry

    PubMed Central

    FUJIYOSHI, NAOKI; USHIJIMA, KIMIO; KAWANO, KOUICHIRO; FUJIYOSHI, KEIZO; YAMAGUCHI, TOMOHIKO; ARAKI, YUKO; KAKUMA, TATSUYUKI; WATANABE, SUMIKO; KAKU, TSUNEHISA; NISHIDA, TAKASHI; KAMURA, TOSHIHARU

    2015-01-01

    Since uterine cervical cancer is regarded as a radiosensive tumor, ionizing radiation is the most frequently used treatment modality against the disease. Although the crucial end-point is radiation-induced cell death, the tumors are not equally sensitive to radiation. Determining the criteria that may be used to predict tumor radiosensitivity is of importance; however, little success has been achieved thus far. In radioresistant cases the therapeutic strategy should be changed, thereby avoiding ineffective or unnecessary treatment. Furthermore, identification of the underlying molecular processes leading to radioresistance may lead to novel radiosensitising strategies. Cervical smears were obtained from seven patients with locally advanced cervical cancer following each radiotherapy, and the radiation-induced damage of cancer tissue was examined by routine cytology. Since the formation of DNA double-strand breaks is considered critical for the cytocidal effect of radiation therapy, the molecular changes of the neoplastic cells were also assessed by laser scanning cytometry (LSC). Radiation-induced morphological changes of cancer cells were evident at a dose of 7.2 Gy, whereas increased DNA content (or DNA index) was observed prior to the onset of morphological changes. Molecular change was detected earlier than the morphological change of the irradiated cancer cells, indicating the feasibility of LSC in predicting the radiosensitivity of cervical cancer tissue. PMID:25469269

  10. Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade

    PubMed Central

    2013-01-01

    Background Although advanced-stage cervical cancer can benefit from current treatments, approximately 30% patients may fail after definitive treatment eventually. Therefore, exploring alternative molecular therapeutic approaches is imperatively needed for this disease. We have recently shown that activation of AMP-activated protein kinase (AMPK), a metabolic sensor, hampers cervical cancer cell growth through blocking the Wnt/β-catenin signaling activity. Here, we report that activated AMPK (p-AMPK) also inhibits cervical cancer cell growth by counteracting FOXM1 function. Methods Effect of the activation of AMPK on FOXM1 expression was examined by hypoxia and glucose deprivation, as well as pharmacological AMPK activators such as A23187, AICAR and metformin. RT Q-PCR and Western blot analysis were employed to investigate the activities of AMPK, FOXM1 and AKT/FOXO3a signaling. Results Consistent with our previous findings, the activation of AMPK by either AMPK activators such as AICAR, A23187, metformin, glucose deprivation or hypoxia significantly inhibited the cervical cancer cell growth. Importantly, we found that activated AMPK activity was concomitantly associated with the reduction of both the mRNA and protein levels of FOXM1. Mechanistically, we showed that activated AMPK was able to reduce AKT mediated phosphorylation of p-FOXO3a (Ser253). Interestingly, activated AMPK could not cause any significant changes in FOXM1 in cervical cancer cells in which endogenous FOXO3a levels were knocked down using siRNAs, suggesting that FOXO3a is involved in the suppression of FOXM1. Conclusion Taken together, our results suggest the activated AMPK impedes cervical cancer cell growth through reducing the expression of FOXM1. PMID:23819460

  11. Phospholipid-chitosan hybrid nanoliposomes promoting cell entry for drug delivery against cervical cancer.

    PubMed

    Saesoo, Somsak; Bunthot, Suphawadee; Sajomsang, Warayuth; Gonil, Pattarapond; Phunpee, Sarunya; Songkhum, Patsaya; Laohhasurayotin, Kritapas; Wutikhun, Tuksadon; Yata, Teerapong; Ruktanonchai, Uracha Rungsardthong; Saengkrit, Nattika

    2016-10-15

    This study emphasizes the development of a novel surface modified liposome as an anticancer drug nanocarrier. Quaternized N,O-oleoyl chitosan (QCS) was synthesized and incorporated into liposome vesicles, generating QCS-liposomes (Lip-QCS). The Lip-QCS liposomes were spherical in shape (average size diameter 171.5±0.8nm), with a narrow size distribution (PDI 0.1±0.0) and zeta potential of 11.7±0.7mV. In vitro mucoadhesive tests indicated that Lip-QCS possesses a mucoadhesive property. Moreover, the presence of QCS was able to induce the cationic charge on the surface of liposome. Cellular internalization of Lip-QCS was monitored over time, with the results revealing that the cell entry level of Lip-QCS was elevated at 24h. Following this, Lip-QCS were then employed to load cisplatin, a common platinum-containing anti-cancer drug, with a loading efficiency of 27.45±0.78% being obtained. The therapeutic potency of the loaded Lip-QCS was investigated using a 3D spheroid cervical cancer model (SiHa) which highlighted their cytotoxicity and apoptosis effect, and suitability as a controllable system for sustained drug release. This approach has the potential to assist in development of an effective drug delivery system against cervical cancer. PMID:27442151

  12. Anticarcinogenic effects of glycoalkaloids from potatoes against human cervical, liver, lymphoma, and stomach cancer cells.

    PubMed

    Friedman, Mendel; Lee, Kap-Rang; Kim, Hyun-Jeong; Lee, In-Seon; Kozukue, Nobuyuke

    2005-07-27

    Methods were devised for the isolation of large amounts of pure alpha-chaconine and alpha-solanine from Dejima potatoes and for the extraction and analysis of total glycoalkaloids from five fresh potato varieties (Dejima, Jowon, Sumi, Toya, and Vora Valley). These compounds were then evaluated in experiments using a tetrazolium microculture (MTT) assay to assess the anticarcinogenic effects of (a) the isolated pure glycoalkaloids separately, (b) artificial mixtures of the two glycoalkaloids, and (c) the total glycoalkaloids isolated from each of the five potato varieties. All samples tested reduced the numbers of the following human cell lines: cervical (HeLa), liver (HepG2), lymphoma (U937), stomach (AGS and KATO III) cancer cells and normal liver (Chang) cells. The results show that (a) the effects of the glycoalkaloids were concentration dependent in the range of 0.1-10 mug/mL (0.117-11.7 nmol/mL); (b) alpha-chaconine was more active than was alpha-solanine; (c) some mixtures exhibited synergistic effects, whereas other produced additive ones; (d) the different cancer cells varied in their susceptibilities to destruction; and (e) the destruction of normal liver cells was generally lower than that of cancer liver cells. The decreases in cell populations were also observed visually by reversed-phase microscopy. The results complement related observations on the anticarcinogenic potential of food ingredients.

  13. Effects of TGF-β1 on the Proliferation and Apoptosis of Human Cervical Cancer Hela Cells In Vitro.

    PubMed

    Tao, Ming-Zhu; Gao, Xia; Zhou, Tie-Jun; Guo, Qing-Xi; Zhang, Qiang; Yang, Cheng-Wan

    2015-12-01

    To investigate the effects of TGF-β1 on the proliferation and apoptosis of cervical cancer Hela cells in vitro. Human cervical cancer Hela cells were cultured in vitro and divided into the experimental and control groups. In the experimental groups, Hela cells were stimulated with different concentrations of TGF-β1 (0.01, 0.1, 1, and 10 ng/mL), while Hela cells cultured in serum-free medium without TGF-β1 were used as controls. The CCK8 method was adopted to detect the effect of TGF-β1 on Hela cell proliferation, and flow cytometry was used to determine cell apoptosis 72 h after TGF-β1 treatment. Compared with the control group, the CCK-8 tests showed that different concentrations of TGF-β1 had no obvious effect on Hela cell proliferation 24 h after treatment (P > 0.05). However, upon 48 or 72 h of treatment, TGF-β1 significantly inhibited the proliferation of Hela cells in a time- and dose-dependent manner (P < 0.05). The flow cytometry results indicated that TGF-β1 influenced the apoptosis of human cervical cancer Hela cells in a dose-dependent manner after 72 h of treatment (P < 0.05). TGF-β1 significantly inhibited the growth and induced the apoptosis of human cervical Hela cells in vitro.

  14. [Preventing cervical cancer].

    PubMed

    Simon, P; Noël, J-C

    2015-09-01

    The incidence of cervical cancer has hopefully been dropping down in our industrialized countries since the introduction of both primary and secondary prevention. Nevertheless, it is still lethal in one out of two affected women though the introduction of cytological screening has dramatically reduced the mortality. Progressive diffusion of anti-HPV vaccination, the broadening of the viral types concerned, its association with existing screening measures and finally the introduction of viral detection as a screening tool must optimize the results already obtained.

  15. CD4+ T cell-mediated antigen-specific immunotherapy in a mouse model of cervical cancer.

    PubMed

    Daniel, Dylan; Chiu, Christopher; Giraudo, Enrico; Inoue, Masahiro; Mizzen, Lee A; Chu, N Randall; Hanahan, Douglas

    2005-03-01

    A major agenda for tumor immunology is the generation of specific immune responses leading to the destruction of incipient and frank neoplasia. In this report, we show that a novel HPV16 E7 fusion protein can produce objective therapeutic responses against incipient cervical cancer in genetically engineered mice that express in the cervix the HPV16 early region genes implicated as causative agents in human cervical cancer. Although nonresponsive toward the HPV16 E7 oncoprotein in the CD8+ T-cell compartment by virtue of MHC haplotype, the mice were capable of mounting an induced CD4+ T-cell response against E7, and in addition developed spontaneous anti-E7 antibodies. HPV16/CD4-/- mice showed increased tumor burden indicative of CD4-mediated immune surveillance. Seeking to enhance the CD4 response, we immunized mice bearing incipient cervical cancer with a recombinant protein fusing E7 with a mycobacterial heat shock protein. The incidences of cervical carcinoma and of high-grade dysplasia (CIN 3) were consequently reduced by comparison to control mice. Thus, an HPV16 E7 immunogen holds promise for noninvasive treatment and prevention of human cervical cancer.

  16. Curcumin causes DNA damage and affects associated protein expression in HeLa human cervical cancer cells.

    PubMed

    Shang, Hung-Sheng; Chang, Chuan-Hsun; Chou, Yu-Ru; Yeh, Ming-Yang; Au, Man-Kuan; Lu, Hsu-Feng; Chu, Yung-Lin; Chou, Hsiao-Min; Chou, Hsiu-Chen; Shih, Yung-Luen; Chung, Jing-Gung

    2016-10-01

    Cervical cancer is one of the most common cancers in women worldwide and it is a prominent cause of cancer mortality. Curcumin is one of the major compounds from Turmeric and has been shown to induce cytotoxic cell death in human cervical cancer cells. However, there is no study to show curcumin induced DNA damage action via the effect on the DNA damage and repair protein in cervical cancer cells in detail. In this study, we investigated whether or not curcumin induced cell death via DNA damage, chromatin condensation in human cervical cancer HeLa cells by using comet assay and DAPI staining, respectively, we found that curcumin induced cell death through the induction of DNA damage, and chromatin condensation. Western blotting and confocal laser microscopy examination were used to examine the effects of curcumin on protein expression associated with DNA damage, repair and translocation of proteins. We found that curcumin at 13 µM increased the protein levels associated with DNA damage and repair, such as O6-methylguanine-DNA methyltransferase, early-onset breast cancer 1 (BRCA1), mediator of DNA damage checkpoint 1, p-p53 and p-H2A.XSer140 in HeLa cells. Results from confocal laser systems microscopy indicated that curcumin increased the translocation of p-p53 and p-H2A.XSer140 from cytosol to nuclei in HeLa cells. In conclusion, curcumin induced cell death in HeLa cells via induction of DNA damage, and chromatin condensation in vitro. PMID:27499229

  17. Curcumin causes DNA damage and affects associated protein expression in HeLa human cervical cancer cells.

    PubMed

    Shang, Hung-Sheng; Chang, Chuan-Hsun; Chou, Yu-Ru; Yeh, Ming-Yang; Au, Man-Kuan; Lu, Hsu-Feng; Chu, Yung-Lin; Chou, Hsiao-Min; Chou, Hsiu-Chen; Shih, Yung-Luen; Chung, Jing-Gung

    2016-10-01

    Cervical cancer is one of the most common cancers in women worldwide and it is a prominent cause of cancer mortality. Curcumin is one of the major compounds from Turmeric and has been shown to induce cytotoxic cell death in human cervical cancer cells. However, there is no study to show curcumin induced DNA damage action via the effect on the DNA damage and repair protein in cervical cancer cells in detail. In this study, we investigated whether or not curcumin induced cell death via DNA damage, chromatin condensation in human cervical cancer HeLa cells by using comet assay and DAPI staining, respectively, we found that curcumin induced cell death through the induction of DNA damage, and chromatin condensation. Western blotting and confocal laser microscopy examination were used to examine the effects of curcumin on protein expression associated with DNA damage, repair and translocation of proteins. We found that curcumin at 13 µM increased the protein levels associated with DNA damage and repair, such as O6-methylguanine-DNA methyltransferase, early-onset breast cancer 1 (BRCA1), mediator of DNA damage checkpoint 1, p-p53 and p-H2A.XSer140 in HeLa cells. Results from confocal laser systems microscopy indicated that curcumin increased the translocation of p-p53 and p-H2A.XSer140 from cytosol to nuclei in HeLa cells. In conclusion, curcumin induced cell death in HeLa cells via induction of DNA damage, and chromatin condensation in vitro.

  18. Deficiency of Erbin induces resistance of cervical cancer cells to anoikis in a STAT3-dependent manner

    PubMed Central

    Hu, Y; Chen, H; Duan, C; Liu, D; Qian, L; Yang, Z; Guo, L; Song, L; Yu, M; Hu, M; Shi, M; Guo, N

    2013-01-01

    Epithelial cell polarization and integration are essential to their function and loss of epithelial polarity and tissue architecture correlates with the development of aggressive tumors. Erbin is a basolateral membrane-associated protein. The roles of Erbin in establishing cell polarization and regulating cell adhesion have been suggested. Erbin is also a negative regulator in Ras-Raf-ERK (extracellular signal-regulated kinase) signaling pathway. However, the potential functions of Erbin in human cancer are basically unknown. In the present study, we show, for the first time, that loss of Erbin endows cervical cancer cells with resistance to anoikis both in vitro and in vivo and promotes the growth and metastasis of human cervical cancer xenografts in nude mice. We found that knockdown of Erbin induced the phosphorylation, nuclear translocation and transcriptional activities of signal transducer and activator of transcription factor 3 (STAT3) in cervical cancer cells. Overexpression of STAT3C or induction of endogenous STAT3 activation by interleukin (IL)-6 evidently inhibited anoikis of cervical cancer cells, whereas WP1066, a potent inhibitor of Janus-activated kinase 2 (Jak2)/STAT3, effectively blocked the effect of Erbin knockdown on cell survival under anchorage-independent conditions, indicating that loss of Erbin confers resistance of cervical cancer cells to anoikis in a STAT3-dependent manner. Interestingly, IL-6 induced STAT3 activation and Erbin expression simultaneously. Overexpression of STAT3C also significantly upregulated the level of Erbin, whereas the Jak2 inhibitor AG490 remarkably blocked not only STAT3 phosphorylation but also IL-6-induced Erbin expression. Knockdown of Erbin augmented the effects of IL-6 on STAT3 activation and anoikis resistance. In addition, by immunohistochemical analysis of Erbin expression, we demonstrate that the expression of Erbin is significantly decreased or even lost in cervical cancer tissues. These data reveal

  19. miR-224-3p inhibits autophagy in cervical cancer cells by targeting FIP200.

    PubMed

    Fang, Wang; Shu, Shan; Yongmei, Li; Endong, Zhu; Lirong, Yin; Bei, Sun

    2016-01-01

    Cervical cancer (CC) is a malignant solid tumor, which is one of the main causes of morbidity and mortality in women. Persistent High-risk human papillomavirus (hrHPV) infection is closely related to cervical cancer and autophagy has been suggested to inhibit viral infections. miRNAs have been reported to regulate autophagy in many solid tumors with many studies implicating miR-224-3p in the regulation of autophagy. In this study, we performed a miRNA microarray analysis on CC tissues and found that a large number of miRNAs with differential expressions in hrHPV-infected tissues. We identified miR-224-3p as a candidate miRNA selectively up regulated in HPV-infected tissues and cell lines. Further analysis revealed that miR-224-3p regulates autophagy in cervical cancer tissues and cell lines. While the overexpression of miR-224-3p inhibits autophagy in HPV-infected cells, knocking down endogenous miR-224-3p increases autophagy activity in the same cells. In addition, we found that miR-224-3p directly inhibits the expression of autophagy related gene, FAK family-interacting protein of 200 kDa (FIP200). In summary, we found that miR-224-3p regulates autophagy in hrHPV-induced cervical cancer cells through targeting FIP200 expression. PMID:27615604

  20. Prognostic Cell Biological Markers in Cervical Cancer Patients Primarily Treated With (Chemo)radiation: A Systematic Review

    SciTech Connect

    Noordhuis, Maartje G.; Eijsink, Jasper J.H.; Roossink, Frank; Graeff, Pauline de; Pras, Elisabeth; Schuuring, Ed; Wisman, G. Bea A.; Bock, Geertruida H. de; Zee, Ate G.J. van der

    2011-02-01

    The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in {>=}50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biological markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1{alpha}). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.

  1. miR-224-3p inhibits autophagy in cervical cancer cells by targeting FIP200

    PubMed Central

    Fang, Wang; Shu, Shan; Yongmei, Li; Endong, Zhu; Lirong, Yin; Bei, Sun

    2016-01-01

    Cervical cancer (CC) is a malignant solid tumor, which is one of the main causes of morbidity and mortality in women. Persistent High-risk human papillomavirus (hrHPV) infection is closely related to cervical cancer and autophagy has been suggested to inhibit viral infections. miRNAs have been reported to regulate autophagy in many solid tumors with many studies implicating miR-224-3p in the regulation of autophagy. In this study, we performed a miRNA microarray analysis on CC tissues and found that a large number of miRNAs with differential expressions in hrHPV-infected tissues. We identified miR-224-3p as a candidate miRNA selectively up regulated in HPV-infected tissues and cell lines. Further analysis revealed that miR-224-3p regulates autophagy in cervical cancer tissues and cell lines. While the overexpression of miR-224-3p inhibits autophagy in HPV-infected cells, knocking down endogenous miR-224-3p increases autophagy activity in the same cells. In addition, we found that miR-224-3p directly inhibits the expression of autophagy related gene, FAK family-interacting protein of 200 kDa (FIP200). In summary, we found that miR-224-3p regulates autophagy in hrHPV-induced cervical cancer cells through targeting FIP200 expression. PMID:27615604

  2. Taxol produced from endophytic fungi induces apoptosis in human breast, cervical and ovarian cancer cells.

    PubMed

    Wang, Xin; Wang, Chao; Sun, Yu-Ting; Sun, Chuan-Zhen; Zhang, Yue; Wang, Xiao-Hua; Zhao, Kai

    2015-01-01

    Currently, taxol is mainly extracted from the bark of yews; however, this method can not meet its increasing demand on the market because yews grow very slowly and are a rare and endangered species belonging to first- level conservation plants. Recently, increasing efforts have been made to develop alternative means of taxol production; microbe fermentation would be a very promising method to increase the production scale of taxol. To determine the activities of the taxol extracted from endophytic fungus N. sylviforme HDFS4-26 in inhibiting the growth and causing the apoptosis of cancer cells, on comparison with the taxol extracted from the bark of yew, we used cellular morphology, cell counting kit (CCK-8) assay, staining (HO33258/PI and Giemsa), DNA agarose gel electrophoresis and flow cytometry (FCM) analyses to determine the apoptosis status of breast cancer MCF-7 cells, cervical cancer HeLa cells and ovarian cancer HO8910 cells. Our results showed that the fungal taxol inhibited the growth of MCF-7, HeLa and HO8910 cells in a dose-and time-dependent manner. IC50 values of fungal taxol for HeLa, MCF-7 and HO8910 cells were 0.1-1.0 μg/ml, 0.001-0.01 μg/ml and 0.01- 0.1 μg/ml, respectively. The fungal taxol induced these tumor cells to undergo apoptosis with typical apoptotic characteristics, including morphological changes for chromatin condensation, chromatin crescent formation, nucleus fragmentation, apoptotic body formation and G2/M cell cycle arrest. The fungal taxol at the 0.01-1.0 μg/ ml had significant effects of inducing apoptosis between 24-48 h, which was the same as that of taxol extracted from yews. This study offers important information and a new resource for the production of an important anticancer drug by endofungus fermentation. PMID:25640339

  3. Taxol produced from endophytic fungi induces apoptosis in human breast, cervical and ovarian cancer cells.

    PubMed

    Wang, Xin; Wang, Chao; Sun, Yu-Ting; Sun, Chuan-Zhen; Zhang, Yue; Wang, Xiao-Hua; Zhao, Kai

    2015-01-01

    Currently, taxol is mainly extracted from the bark of yews; however, this method can not meet its increasing demand on the market because yews grow very slowly and are a rare and endangered species belonging to first- level conservation plants. Recently, increasing efforts have been made to develop alternative means of taxol production; microbe fermentation would be a very promising method to increase the production scale of taxol. To determine the activities of the taxol extracted from endophytic fungus N. sylviforme HDFS4-26 in inhibiting the growth and causing the apoptosis of cancer cells, on comparison with the taxol extracted from the bark of yew, we used cellular morphology, cell counting kit (CCK-8) assay, staining (HO33258/PI and Giemsa), DNA agarose gel electrophoresis and flow cytometry (FCM) analyses to determine the apoptosis status of breast cancer MCF-7 cells, cervical cancer HeLa cells and ovarian cancer HO8910 cells. Our results showed that the fungal taxol inhibited the growth of MCF-7, HeLa and HO8910 cells in a dose-and time-dependent manner. IC50 values of fungal taxol for HeLa, MCF-7 and HO8910 cells were 0.1-1.0 μg/ml, 0.001-0.01 μg/ml and 0.01- 0.1 μg/ml, respectively. The fungal taxol induced these tumor cells to undergo apoptosis with typical apoptotic characteristics, including morphological changes for chromatin condensation, chromatin crescent formation, nucleus fragmentation, apoptotic body formation and G2/M cell cycle arrest. The fungal taxol at the 0.01-1.0 μg/ ml had significant effects of inducing apoptosis between 24-48 h, which was the same as that of taxol extracted from yews. This study offers important information and a new resource for the production of an important anticancer drug by endofungus fermentation.

  4. Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D.

    PubMed

    Song, Hyunkeun; Park, Hyunjin; Park, Gabin; Kim, Yeong Seok; Lee, Hyun-Kyung; Jin, Dong-Hoon; Kang, Hyung-Sik; Cho, Dae-Ho; Hur, Daeyoung

    2014-07-01

    Corticotropin-releasing factor (CRF), a coordinator of the body's responses to stress, is found in various cancer tissues and cell lines. However, the exact abilities of CRF to manipulate natural killer (NK) cells during immune response have not been studied. NKG2D is an activating receptor that is expressed on most NK and CD8+ T cells. MHC class I-related chain A (MICA) and UL16-binding protein (ULBP) 1, 2 and 3 are well-known ligands for NKG2D. In the present study, we reported our findings regarding the role of CRF in cervical cancer cell survival. Human cervical cancer cell line, HeLa cells, had significantly higher intracellular expression of UL16-binding protein 2 (ULBP2) following CRF treatment but had only slightly increased surface expression of ULBP2. Notably, MMPi (pan-metalloproteases inhibitor) blocked the release of ULBP2 molecules from the surface of HeLa cells. Furthermore, incubating NK cells with culture supernatants from CRF-treated HeLa cells, which contained soluble NKG2D ligand, reduced NK cell activity by decreasing surface expression of NKG2D. Collectively, downregulation of NKG2D by CRF-induced soluble NKG2D ligand provides a potential mechanism by which cervical cancer cells escape NKG2D-mediated attack under stress conditions.

  5. Anticancer property of Bryophyllum pinnata (Lam.) Oken. leaf on human cervical cancer cells

    PubMed Central

    2012-01-01

    Background Bryophyllum pinnata (B. pinnata) is a common medicinal plant used in traditional medicine of India and of other countries for curing various infections, bowel diseases, healing wounds and other ailments. However, its anticancer properties are poorly defined. In view of broad spectrum therapeutic potential of B. pinnata we designed a study to examine anti-cancer and anti-Human Papillomavirus (HPV) activities in its leaf extracts and tried to isolate its active principle. Methods A chloroform extract derived from a bulk of botanically well-characterized pulverized B. pinnata leaves was separated using column chromatography with step- gradient of petroleum ether and ethyl acetate. Fractions were characterized for phyto-chemical compounds by TLC, HPTLC and NMR and Biological activity of the fractions were examined by MTT-based cell viability assay, Electrophoretic Mobility Shift Assay, Northern blotting and assay of apoptosis related proteins by immunoblotting in human cervical cancer cells. Results Results showed presence of growth inhibitory activity in the crude leaf extracts with IC50 at 552 μg/ml which resolved to fraction F4 (Petroleum Ether: Ethyl Acetate:: 50:50) and showed IC50 at 91 μg/ml. Investigations of anti-viral activity of the extract and its fraction revealed a specific anti-HPV activity on cervical cancer cells as evidenced by downregulation of constitutively active AP1 specific DNA binding activity and suppression of oncogenic c-Fos and c-Jun expression which was accompanied by inhibition of HPV18 transcription. In addition to inhibiting growth, fraction F4 strongly induced apoptosis as evidenced by an increased expression of the pro-apoptotic protein Bax, suppression of the anti-apoptotic molecules Bcl-2, and activation of caspase-3 and cleavage of PARP-1. Phytochemical analysis of fraction F4 by HPTLC and NMR indicated presence of activity that resembled Bryophyllin A. Conclusions Our study therefore demonstrates presence of

  6. Notch Signaling Activation in Cervical Cancer Cells Induces Cell Growth Arrest with the Involvement of the Nuclear Receptor NR4A2

    PubMed Central

    Sun, Lichun; Liu, Mingqiu; Sun, Guang-Chun; Yang, Xu; Qian, Qingqing; Feng, Shuyu; Mackey, L. Vienna; Coy, David H.

    2016-01-01

    Cervical cancer is a second leading cancer death in women world-wide, with most cases in less developed countries. Notch signaling is highly conserved with its involvement in many cancers. In the present study, we established stable cervical cell lines with Notch activation and inactivation and found that Notch activation played a suppressive role in cervical cancer cells. Meanwhile, the transient overexpression of the active intracellular domain of all four Notch receptors (ICN1, 2, 3, and 4) also induced the suppression of cervical cancer Hela cell growth. ICN1 also induced cell cycle arrest at phase G1. Notch1 signaling activation affected the expression of serial genes, especially the genes associated with cAMP signaling, with an increase of genes like THBS1, VCL, p63, c-Myc and SCG2, a decrease of genes like NR4A2, PCK2 and BCL-2. Particularly, The nuclear receptor NR4A2 was observed to induce cell proliferation via MTT assay and reduce cell apoptosis via FACS assay. Furthermore, NR4A2's activation could reverse ICN1-induced suppression of cell growth while erasing ICN1-induced increase of tumor suppressor p63. These findings support that Notch signaling mediates cervical cancer cell growth suppression with the involvement of nuclear receptor NR4A2. Notably, Notch/NR4A2/p63 signaling cascade possibly is a new signling pathway undisclosed. PMID:27471554

  7. Notch Signaling Activation in Cervical Cancer Cells Induces Cell Growth Arrest with the Involvement of the Nuclear Receptor NR4A2.

    PubMed

    Sun, Lichun; Liu, Mingqiu; Sun, Guang-Chun; Yang, Xu; Qian, Qingqing; Feng, Shuyu; Mackey, L Vienna; Coy, David H

    2016-01-01

    Cervical cancer is a second leading cancer death in women world-wide, with most cases in less developed countries. Notch signaling is highly conserved with its involvement in many cancers. In the present study, we established stable cervical cell lines with Notch activation and inactivation and found that Notch activation played a suppressive role in cervical cancer cells. Meanwhile, the transient overexpression of the active intracellular domain of all four Notch receptors (ICN1, 2, 3, and 4) also induced the suppression of cervical cancer Hela cell growth. ICN1 also induced cell cycle arrest at phase G1. Notch1 signaling activation affected the expression of serial genes, especially the genes associated with cAMP signaling, with an increase of genes like THBS1, VCL, p63, c-Myc and SCG2, a decrease of genes like NR4A2, PCK2 and BCL-2. Particularly, The nuclear receptor NR4A2 was observed to induce cell proliferation via MTT assay and reduce cell apoptosis via FACS assay. Furthermore, NR4A2's activation could reverse ICN1-induced suppression of cell growth while erasing ICN1-induced increase of tumor suppressor p63. These findings support that Notch signaling mediates cervical cancer cell growth suppression with the involvement of nuclear receptor NR4A2. Notably, Notch/NR4A2/p63 signaling cascade possibly is a new signling pathway undisclosed. PMID:27471554

  8. Epidemiology of uterine cervical cancer.

    PubMed

    Brinton, L A; Fraumeni, J F

    1986-01-01

    The epidemiology of cervical cancer presents a number of unique challenges, mainly with respect to disentangling correlated factors and to elucidating biological mechanisms. The available evidence suggests a complex multifactorial etiology, although the relative contributions of risk factors and their interactions remain obscure. Infectious agents are strongly suspected, but as yet not conclusively identified. It is also unclear whether there are subgroups of women or periods of life that are most susceptible to the action of infectious agents, and the contribution of the "male factor" needs to be defined. Several epidemiologic leads can be pursued through biochemical and molecular techniques. Most promising is the recent evidence linking certain HPV types to cervical abnormalities, including cancer, and newly developed probes can be incorporated into epidemiologic studies to evaluate an array of risk factors. Endocrine and metabolic assays may be helpful in clarifying the role of exogenous and possibly endogenous hormones. The effects of cigarette smoking may be further evaluated by studying constituents of tobacco smoke and their metabolites in cervical mucus. Finally, the relationship of diet to cervical cancer should be assessed by examining the levels of micronutrients, trace minerals, and other nutritional indices in body tissues and fluids, as well as through interview data. An understanding of cervical cancer etiology will require a better identification of risk factors for precursor lesions as well as factors that enhance their progression to invasive cancer. Through studies that focus on disease stage and time-related events, it should be possible to clarify the multi-stage processes involved in cervical carcinogenesis, and those factors that may inhibit as well as promote transition rates. The protective effects of screening programs deserve further attention, and research into dietary factors may lead in time to nutritional intervention. Investigation

  9. DNA cell-cycle analysis of cervical cancer by flow cytometry using simultaneous cytokeratin labelling for identification of tumour cells.

    PubMed

    Kimmig, R; Kapsner, T; Spelsberg, H; Untch, M; Hepp, H

    1995-01-01

    DNA ploidy and cell-cycle distribution were determined by flow cytometry in fresh tumour tissue of 53 cervical carcinomas. Epithelial cells were labelled by a fluorescein-isothiocyanate-conjugated cytokeratin antibody (CK6, CK18) to study the influence of contaminating stromal and inflammatory cells on results of cell-cycle analysis of tumour cells. Without identification of cytokeratin-positive cells 30/53 (57%) tumours were found to be DNA-aneuploid compared to 43/53 (81%) after gating for cytokeratin. Only 7 of 15 DNA-multiploid tumours could be detected without cytokeratin staining. In addition, cytokeratin-negative cells, which are found in all tumours, can be used as an internal standard for the calculation of ploidy and for quality control (coefficient of variation, linearity) of each individual sample. Cell-cycle analysis revealed significantly higher S-phase and G2M-phase fractions in cytokeratin-gated compared to ungated samples (13.1% versus 10.0% and 8.0% versus 5.4%; P < 0.001). This difference was more pronounced in DNA-diploid than DNA-aneuploid tumours. In conclusion, about 30% of DNA-aneuploid tumours could only be detected after cytokeratin labelling of epithelial cells. Owing to the identification of cytokeratin-positive cells the influence of non-tumoural cell elements on cell-cycle analysis was reduced markedly. Therefore, in cervical cancer, cytokeratin labelling can optimize both the determination of DNA ploidy and cell-cycle analysis.

  10. Baicalein induces apoptosis of human cervical cancer HeLa cells in vitro.

    PubMed

    Peng, Yong; Guo, Congshan; Yang, Yanhong; Li, Fenglin; Zhang, Yanxia; Jiang, Bin; Li, Qingwang

    2015-03-01

    A number of studies have shown that baicalein shows high antitumor activity in vitro and in vivo. In this study, the inhibitory effect of baicalein on human cervical cancer HeLa cells was studied in vitro. HeLa cells were treated with high (100 µg/ml) and low (50 µg/ml) doses of baicalein, and cell growth inhibition rates were examined by the MTT assay. The morphological changes of apoptotic cells were observed under the light and electron microscope, while the rate of cell apoptosis was examined by flow cytometry. The expression of apoptosis-related proteins was analyzed by western blot, and caspase-3 activation was examined by a caspase-3 activity assay and spectrophotometry. The results demonstrated that baicalein inhibits the proliferation of HeLa cells and induces apoptosis in a caspase-3-dependent pathway, through downregulation of the B-cell lymphoma 2 (Bcl-2) protein and upregulation of the Bcl-2-associated X protein (Bax), Fas, Fas ligand (FasL) and caspase-8. Thus, we conclude that baicalein induces apoptosis of HeLa cells via the mitochondrial and the death receptor pathways. Cell apoptosis in HeLa cells was most likely promoted by the activation of the proteolytic enzyme caspase-3 in both pathways.

  11. NF-κB-modulated miR-130a targets TNF-α in cervical cancer cells

    PubMed Central

    2014-01-01

    Background Nuclear factor-κB (NF-κB) induces a variety of biological processes through transcriptional gene control whose products are components in various signaling pathways. MicroRNAs are a small endogenous non-coding RNAs that regulate gene expression and are involved in tumorigenesis. Using human cervical cancer cell lines, this study aimed to investigate whether NF-κB could regulate miR-130a expression and the functions and targets of miR-130a. Methods We used the HeLa and C33A cervical cancer cell lines that were transfected with NF-κB or miR-130a overexpression plasmids to evaluate their effects on cell growth. We utilized bioinformatics, a fluorescent reporter assay, qRT-PCR and Western blotting to identify downstream target genes. Results In HeLa and C33A cells, NF-κB and miR-130a overexpression promoted cell growth, but genetic knockdowns suppressed growth. TNF-α was identified as a target of miR-130a by binding in a 3’-untranslated region (3’UTR) EGFP reporter assay and by Western blot analysis. Furthermore, low TNF-α concentrations stimulated NF-κB activity and then induced miR-130a expression, and TNF-α overexpression rescued the effects of miR-130a on cervical cancer cells. Conclusions Our findings indicate that TNF-α can activate NF-κB activity, which can reduce miR-130a expression, and that miR-130a targets and downregulates TNF-α expression. Hence, we shed light on the negative feedback regulation of NF-κB/miR-130a/TNF-α/NF-κB in cervical cancer and may provide insight into the carcinogenesis of cervical cancer. PMID:24885472

  12. Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21.

    PubMed

    Zhang, Jun; Yao, Tingting; Wang, Yaxian; Yu, Jin; Liu, Yunyun; Lin, Zhongqiu

    2016-01-01

    Recent research has found that long noncoding RNAs (lncRNAs) were involved in various human cancers. However, the role of these lncRNAs in cervical cancer remains unexplored. Therefore, we aimed to investigate the biological function of maternally expressed gene 3 (MEG3), a cancer-related lncRNA, and its underlying mechanism in cervical cancer. In this study, MEG3 expression of 108 patients' cervical cancer tissues and adjacent normal tissues was detected by quantitative real-time PCR analysis (qRT-PCR), and the functional effect of MEG3 was determined in vitro assays. We observed that MEG3 was downregulated in cervical cancer tissues, compared to the adjacent normal tissues, and was negatively related with FIGO stages, tumor size, lymphatic metastasis, HR-HPV infection and the expression of homo sapiens microRNA-21 (miR-21). Furthermore, we focused on the function and molecular mechanism of MEG3, finding that overexpression of MEG3 reduced the level of miR-21-5p expression, causing inhibition of proliferation and increased apoptosis in cervical cancer cells. In summary, our findings indicate that MEG3 function as a tumor suppressor by regulating miR-21-5p, resulting in the inhibition of tumor growth in cervical cancer. As a result, this study improves our understanding of the function of MEG3 in cervical cancer and will help to provide new potential target sites for cervical cancer treatment.

  13. Expression of WNT genes in cervical cancer-derived cells: Implication of WNT7A in cell proliferation and migration

    SciTech Connect

    Ramos-Solano, Moisés; Meza-Canales, Ivan D.; Torres-Reyes, Luis A.; Alvarez-Zavala, Monserrat; and others

    2015-07-01

    According to the multifactorial model of cervical cancer (CC) causation, it is now recognized that other modifications, in addition to Human papillomavirus (HPV) infection, are necessary for the development of this neoplasia. Among these, it has been proposed that a dysregulation of the WNT pathway might favor malignant progression of HPV-immortalized keratinocytes. The aim of this study was to identify components of the WNT pathway differentially expressed in CC vs. non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A expression was found strongly downregulated in cell lines and biopsies derived from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviral gene delivery system or after adding a recombinant human protein decreases cell proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly accelerates proliferation. Decreased WNT7A expression was due to hypermethylation at particular CpG sites. To our knowledge, this is the first study reporting reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration. - Highlights: • WNT7A is expressed in normal keratinocytes or cervical cells without lesion. • WNT7A is significantly reduced in cervical cancer-derived cells. • Restoration of WNT7A expression in HeLa decreases proliferation and cell migration. • Silencing of WNT7A in HaCaT induces an increased proliferation and migration rate. • Decreased WNT7A expression in this model is due to hypermethylation.

  14. Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid

    PubMed Central

    SORIANO-HERNANDEZ, ALEJANDRO D.; MADRIGAL-PÉREZ, DANIELA; GALVAN-SALAZAR, HECTOR R.; MARTINEZ-FIERRO, MARGARITA L.; VALDEZ-VELAZQUEZ, LAURA L.; ESPINOZA-GÓMEZ, FRANCISCO; VAZQUEZ-VUELVAS, OSCAR F.; OLMEDO-BUENROSTRO, BERTHA A.; GUZMAN-ESQUIVEL, JOSE; RODRIGUEZ-SANCHEZ, IRAM P.; LARA-ESQUEDA, AGUSTIN; MONTES-GALINDO, DANIEL A.; DELGADO-ENCISO, IVAN

    2015-01-01

    Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluated in vitro. Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10–40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50–90% of cell death corresponding to 100 µM). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug. PMID:26622892

  15. Radiotherapy of Cervical Cancer.

    PubMed

    Vordermark, Dirk

    2016-01-01

    Curative-intent radical radiotherapy of cervical cancer consists of external-beam radiotherapy, brachytherapy, and concomitant chemotherapy with cisplatin. For each element, new developments aim to improve tumor control rates or treatment tolerance. Intensity-modulated radiotherapy (IMRT) has been shown to reduce gastrointestinal toxicity and can be used to selectively increase the radiotherapy dose. Individualized, image-guided brachytherapy enables better adaptation of high-dose volumes to the tumor extension. Intensification of concomitant or sequential systemic therapy is under evaluation. PMID:27614991

  16. MAML1 regulates cell viability via the NF-{kappa}B pathway in cervical cancer cell lines

    SciTech Connect

    Kuncharin, Yanin; Sangphech, Naunpun; Kueanjinda, Patipark; Bhattarakosol, Parvapan; Palaga, Tanapat

    2011-08-01

    The Notch signaling pathway plays important roles in tumorigenesis in a context-dependent manner. In human cervical cancer, alterations in Notch signaling have been reported, and both tumor-suppressing and tumor-promoting roles of Notch signaling have been proposed; however, the precise molecular mechanisms governing these roles in cervical cancer remain controversial. MAML is a transcriptional co-activator originally identified by its role in Notch signaling. Recent evidence suggests that it also plays a role in other signaling pathways, such as the p53 and {beta}-catenin pathways. MAML is required for stable formation of Notch transcriptional complexes at the promoters of Notch target genes. Chromosomal translocations affecting MAML have been shown to promote tumorigenesis. In this study, we used a truncated dominant-negative MAML1 (DN-MAML) to investigate the role of MAML in HPV-positive cervical cancer cell lines. Three human cervical cancer cell lines (HeLa, SiHa and CaSki) expressed all Notch receptors and the Notch target genes Hes1 and MAML1. Among these 3 cell lines, constitutive appearance of cleaved Notch1 was found only in CaSki cells, which suggests that Notch1 is constitutively activated in this cell line. Gamma secretase inhibitor (GSI) treatment, which suppresses Notch receptor activation, completely abrogated this form of Notch1 but had no effect on cell viability. Overexpression of DN-MAML by retroviral transduction in CaSki cells resulted in significant decreases in the mRNA levels of Hes1 and Notch1 but had no effects on the levels of MAML1, p53 or HPV E6/E7. DN-MAML expression induced increased viability of CaSki cells without any effect on cell cycle progression or cell proliferation. In addition, clonogenic assay experiments revealed that overexpression of DN-MAML resulted in increased colony formation compared to the overexpression of the control vector. When the status of the NF-{kappa}B pathway was investigated, CaSki cells overexpressing

  17. Production of interleukin-4 in CD133+ cervical cancer stem cells promotes resistance to apoptosis and initiates tumor growth

    PubMed Central

    LIU, CHUN-TAO; XIN, YING; TONG, CHUN-YAN; LI, BING; BAO, HONG-LI; ZHANG, CAI-YUN; WANG, XUE-HUI

    2016-01-01

    The cancer stem cell (CSC) theory suggests that cancer growth and invasion is dictated by the small population of CSCs within the heterogenous tumor. The aim of the present study was to elucidate the cause for chemotherapy failure and the resistance of CSCs to apoptosis. A total of ~2.3% cluster of differentiation (CD)133+ cancer stem-like side population (SP) cells were identified in cases of uterine cervical cancer. These CD133+ SP cells were found to potently initiate tumor growth and invasion, as they exhibit transcriptional upregulation of stemness genes, including octamer-binding transcription factor-4, B-cell-specific Moloney murine leukemia virus insertion site-1, epithelial cell adhesion molecule, (sex determining region Y)-box 2, Nestin and anti-apoptotic B cell lymphoma-2. In addition, the CD133+ SP cells showed resistance to multi-drug treatment and apoptosis. The present study further showed that the secretion of interleukin-4 (IL-4) in CD133+ cervical cancer SP cells promoted cell proliferation and prevented the SP cells from apoptosis. Following the neutralization of IL-4 with anti-IL-4 antibody, the CD133+ SP cells were more sensitive to drug treatment and apoptosis. Therefore, the data obtained in the present study suggested that the autocrine secretion of IL-4 promotes increased survival and resistance to cell death in CSCs. PMID:27121303

  18. Cervical cancer screening.

    PubMed Central

    Katz, A.

    1998-01-01

    OBJECTIVE: To review the role of family physicians in screening for cancer of the cervix, to review the evidence for screening, in particular, frequency and technique for screening, and to review the reasons cervical cancer has not been prevented and the role of family physicians in addressing these failures. QUALITY OF EVIDENCE: The value of screening has been established with level II evidence. Many of the unresolved issues are not supported either way by good evidence; level II and III evidence predominates. MAIN FINDINGS: In Canada, 1350 women were predicted to be diagnosed with cancer of the cervix in 1996. Most of these women had not been screened. Minority, rural, low-income, and older women face important barriers to screening. Family physicians have a role in reaching out to these women to provide effective health care, including cancer screening. When cancer screening is performed, it should conform to recommended techniques with appropriate follow up of abnormal test results. CONCLUSIONS: Family physicians have an important role in preventing cancer of the cervix. Efforts should be concentrated on encouraging a greater proportion of eligible women to be screened. Criteria are suggested for effective screening. PMID:9721422

  19. Curcumin Nanoformulation for Cervical Cancer Treatment

    PubMed Central

    Zaman, Mohd S.; Chauhan, Neeraj; Yallapu, Murali M.; Gara, Rishi K.; Maher, Diane M.; Kumari, Sonam; Sikander, Mohammed; Khan, Sheema; Zafar, Nadeem; Jaggi, Meena; Chauhan, Subhash C.

    2016-01-01

    Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity. Thus, developing a natural product based, safe treatment modality would be a highly viable option. Curcumin (CUR) is a well-known natural compound, which exhibits excellent anti-cancer potential by regulating many proliferative, oncogenic, and chemo-resistance associated genes/proteins. However, due to rapid degradation and poor bioavailability, its translational and clinical use has been limited. To improve these clinically relevant parameters, we report a poly(lactic-co-glycolic acid) based curcumin nanoparticle formulation (Nano-CUR). This study demonstrates that in comparison to free CUR, Nano-CUR effectively inhibits cell growth, induces apoptosis, and arrests the cell cycle in cervical cancer cell lines. Nano-CUR treatment modulated entities such as miRNAs, transcription factors, and proteins associated with carcinogenesis. Moreover, Nano-CUR effectively reduced the tumor burden in a pre-clinical orthotopic mouse model of cervical cancer by decreasing oncogenic miRNA-21, suppressing nuclear β-catenin, and abrogating expression of E6/E7 HPV oncoproteins including smoking compound benzo[a]pyrene (BaP) induced E6/E7 and IL-6 expression. These superior pre-clinical data suggest that Nano-CUR may be an effective therapeutic modality for cervical cancer. PMID:26837852

  20. Down-regulation of MALAT1 inhibits cervical cancer cell invasion and metastasis by inhibition of epithelial-mesenchymal transition.

    PubMed

    Sun, Ruili; Qin, Changfei; Jiang, Binyuan; Fang, Shujuan; Pan, Xi; Peng, Li; Liu, Zhaoyang; Li, Wenling; Li, Yuehui; Li, Guancheng

    2016-03-01

    The metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a member of the long non-coding RNA (lncRNA) family, has been reported to be highly enriched in many kinds of cancers and to be a metastasis marker and a prognostic factor. In this study, we found that MALAT1 expression levels were significantly increased in cervical cancer (CC) cells and tissues. The down-regulation of MALAT1 by shRNA in CC cells inhibited the invasion and metastasis in vitro and in vivo. Microarray analysis showed that the knockdown of MALAT1 up-regulated the epithelial markers E-cadherin and ZO-1, and down-regulated the mesenchymal markers β-catenin and Vimentin. This regulation was further confirmed by subsequent observation from RT-PCR, western blot, and immunofluorescence results. Meanwhile, the transcription factor snail, which functions to modulate epithelial-mesenchymal transition (EMT), was also down-regulated at both transcript and protein levels by MALAT1 down-regulation. In addition, we found that MALAT1 expression levels were positively related to HPV infection in cervical epithelial tissues by microarray analysis. Taken together, these results suggest that MALAT1 functions to promote cervical cancer invasion and metastasis via induction of EMT, and it may be a target for the prevention and therapy of cervical cancers.

  1. Linalool Induces Cell Cycle Arrest and Apoptosis in Leukemia Cells and Cervical Cancer Cells through CDKIs

    PubMed Central

    Chang, Mei-Yin; Shieh, Den-En; Chen, Chung-Chi; Yeh, Ching-Sheng; Dong, Huei-Ping

    2015-01-01

    Plantaginaceae, a popular traditional Chinese medicine, has long been used for treating various diseases from common cold to cancer. Linalool is one of the biologically active compounds that can be isolated from Plantaginaceae. Most of the commonly used cytotoxic anticancer drugs have been shown to induce apoptosis in susceptible tumor cells. However, the signaling pathway for apoptosis remains undefined. In this study, the cytotoxic effect of linalool on human cancer cell lines was investigated. Water-soluble tetrazolium salts (WST-1) based colorimetric cellular cytotoxicity assay, was used to test the cytotoxic ability of linalool against U937 and HeLa cells, and flow cytometry (FCM) and genechip analysis were used to investigate the possible mechanism of apoptosis. These results demonstrated that linalool exhibited a good cytotoxic effect on U937 and HeLa cells, with the IC50 value of 2.59 and 11.02 μM, respectively, compared with 5-FU with values of 4.86 and 12.31 μM, respectively. After treating U937 cells with linalool for 6 h, we found an increased sub-G1 peak and a dose-dependent phenomenon, whereby these cells were arrested at the G0/G1 phase. Furthermore, by using genechip analysis, we observed that linalool can promote p53, p21, p27, p16, and p18 gene expression. Therefore, this study verified that linalool can arrest the cell cycle of U937 cells at the G0/G1 phase and can arrest the cell cycle of HeLa cells at the G2/M phase. Its mechanism facilitates the expression of the cyclin-dependent kinases inhibitors (CDKIs) p53, p21, p27, p16, and p18, as well as the non-expression of cyclin-dependent kinases (CDKs) activity. PMID:26703569

  2. Linalool Induces Cell Cycle Arrest and Apoptosis in Leukemia Cells and Cervical Cancer Cells through CDKIs.

    PubMed

    Chang, Mei-Yin; Shieh, Den-En; Chen, Chung-Chi; Yeh, Ching-Sheng; Dong, Huei-Ping

    2015-01-01

    Plantaginaceae, a popular traditional Chinese medicine, has long been used for treating various diseases from common cold to cancer. Linalool is one of the biologically active compounds that can be isolated from Plantaginaceae. Most of the commonly used cytotoxic anticancer drugs have been shown to induce apoptosis in susceptible tumor cells. However, the signaling pathway for apoptosis remains undefined. In this study, the cytotoxic effect of linalool on human cancer cell lines was investigated. Water-soluble tetrazolium salts (WST-1) based colorimetric cellular cytotoxicity assay, was used to test the cytotoxic ability of linalool against U937 and HeLa cells, and flow cytometry (FCM) and genechip analysis were used to investigate the possible mechanism of apoptosis. These results demonstrated that linalool exhibited a good cytotoxic effect on U937 and HeLa cells, with the IC50 value of 2.59 and 11.02 μM, respectively, compared with 5-FU with values of 4.86 and 12.31 μM, respectively. After treating U937 cells with linalool for 6 h, we found an increased sub-G1 peak and a dose-dependent phenomenon, whereby these cells were arrested at the G0/G1 phase. Furthermore, by using genechip analysis, we observed that linalool can promote p53, p21, p27, p16, and p18 gene expression. Therefore, this study verified that linalool can arrest the cell cycle of U937 cells at the G0/G1 phase and can arrest the cell cycle of HeLa cells at the G2/M phase. Its mechanism facilitates the expression of the cyclin-dependent kinases inhibitors (CDKIs) p53, p21, p27, p16, and p18, as well as the non-expression of cyclin-dependent kinases (CDKs) activity.

  3. In Vitro Evidence of the Presence of Mesenchymal Stromal Cells in Cervical Cancer and Their Role in Protecting Cancer Cells from Cytotoxic T Cell Activity

    PubMed Central

    Montesinos, Juan J.; Mora-García, María de L.; Mayani, Héctor; Flores-Figueroa, Eugenia; García-Rocha, Rosario; Fajardo-Orduña, Guadalupe R.; Castro-Manrreza, Marta E.; Weiss-Steider, Benny

    2013-01-01

    Mesenchymal stromal cells (MSCs) have been isolated from different tumors and it has been suggested that they support tumor growth through immunosuppression processes that favor tumor cell evasion from the immune system. To date, however, the presence of MSCs in cervical cancer (CeCa) and their possible role in tumor growth remains unknown. Herein we report on the presence of MSCs in cervical tissue, both in normal conditions (NCx-MSCs) and in CeCa (CeCa-MSCs), and described several biological properties of such cells. Our study showed similar patterns of cell surface antigen expression, but distinct differentiation potentials, when we compared both cervical MSC populations to MSCs from normal bone marrow (BM-MSCs, the gold standard). Interestingly, CeCa-MSCs were negative for the presence of human papiloma virus, indicating that these cells are not infected by such a viral agent. Also, interestingly, and in contrast to NCx-MSCs, CeCa-MSCs induced significant downregulation of surface HLA class I molecules (HLA-A*0201) on CaSki cells and other CeCa cell lines. We further observed that CeCa-MSCs inhibited antigen-specific T cell recognition of CaSki cells by cytotoxic T lymphocytes (CTLs). HLA class I downregulation on CeCa cells correlated with the production of IL-10 in cell cocultures. Importantly, this cytokine strongly suppressed recognition of CeCa cells by CTLs. In summary, this study demonstrates the presence of MSCs in CeCa and suggests that tumor-derived MSCs may provide immune protection to tumor cells by inducing downregulation of HLA class I molecules. This mechanism may have important implications in tumor growth. PMID:23656504

  4. Cigarette smoking and invasive cervical cancer

    SciTech Connect

    Brinton, L.A.; Schairer, C.; Haenszel, W.; Stolley, P.; Lehman, H.F.; Levine, R.; Savitz, D.A.

    1986-06-20

    A case-control study of 480 patients with invasive cervical cancer and 797 population controls, conducted in five geographic areas in the United States, included an evaluation of the relationship of several cigarette smoking variables to cervical cancer risk. Although smoking was correlated with both age at first intercourse and number of sexual partners, a significant smoking-related risk persisted for squamous cell carcinoma after adjustment for these factors (relative risk, 1.5). Twofold excess risks were seen for those smoking 40 or more cigarettes per day and those smoking for 40 or more years. Increased risks, however, were observed only among recent and continuous smokers. In contrast to squamous cell cancer, no relationship was observed between smoking and risk of adenocarcinoma or adenosquamous carcinoma. These results suggest a causal relationship between cigarette smoking and invasive squamous cell cervical cancer, perhaps through a late-stage or promotional event, although the mechanisms of action require further elucidation.

  5. A model for co-expression pattern analysis of genes implicated in angiogenesis and tumour cell invasion in cervical cancer

    PubMed Central

    Van Trappen, P O; Ryan, A; Carroll, M; Lecoeur, C; Goff, L; Gyselman, V G; Young, B D; Lowe, D G; Pepper, M S; Shepherd, J H; Jacobs, I J

    2002-01-01

    To date, numerous genes have been identified which are involved in both tumour neovascularisation (angiogenesis) and tumour cell invasion, and most of them are also expressed to some extent under normal physiological conditions. However, little is known about how these genes co-express in these settings. This study was undertaken to quantitate mRNA levels in normal and malignant cervical tissues of nine selected genes (VEGF121, VEGF165, VEGF189, VEGF-C, eIF-4E, b-FGF, TSP-2, MMP-2 and MMP-9) implicated in the above processes using real-time quantitative RT–PCR. In addition, the Spearman's rank correlation was used to determine their co-expression patterns. The transcript levels for the different VEGF-A splice variants (VEGF121, VEGF165, VEGF189) were at least 10-fold higher in the cancer cases, with the highest levels in the primary tumours demonstrating lympho-vascular space involvement. The lymphangiogenic factor VEGF-C and MMP-9 were upregulated 130- and 80-fold respectively in cervical cancers. The highest levels of VEGF-C mRNA were found in the lymph-node positive group. The transcript levels for b-FGF were similar in normal cervical tissue and early-stage cervical cancer, however, higher levels were found in the cervical cancers with advanced stage disease. Comparing gene transcript levels between recurrent and non-recurrent cervical cancer patients revealed significant differences (P=0.038) in transcript levels for the angiogenesis inhibitor TSP-2, with the highest levels in non-recurrent cases. Co-expression pattern analysis in normal cervical tissue revealed highly significant co-expressions (P<0.0001) between TSP-2 and most other genes analysed (VEGF121, VEGF165, VEGF-C, b-FGF and MMP-2). In cervical cancer, TSP-2 appears only to be highly co-expressed with MMP-2 (P<0.0001). In contrast to normal cervical tissue, we found a highly significant co-expression (P<0.0001) between MMP-9 and VEGF189 in cervical cancer. The combined application of real

  6. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

    PubMed Central

    2012-01-01

    Background Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Methods Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. Results CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). Conclusions We characterized a self-renewing subpopulation of CICs found among four well known human

  7. Fibronectin-integrin mediated signaling in human cervical cancer cells (SiHa).

    PubMed

    Maity, Gargi; Fahreen, Shabana; Banerji, Aniruddha; Roy Choudhury, Paromita; Sen, Triparna; Dutta, Anindita; Chatterjee, Amitava

    2010-03-01

    Interaction between cell surface integrin receptors and extracellular matrix (ECM) components plays an important role in cell survival, proliferation, and migration, including tumor development and invasion of tumor cells. Matrix metalloproteinases (MMPs) are a family of metalloproteinases capable of digesting ECM components and are important molecules for cell migration. Binding of ECM to integrins initiates cascades of cell signaling events modulating expression and activity of different MMPs. The aim of this study is to investigate fibronectin-integrin-mediated signaling and modulation of MMPs. Our findings indicated that culture of human cervical cancer cell (SiHa) on fibronectin-coated surface perhaps sends signals via fibronectin-integrin-mediated signaling pathways recruiting focal adhesion kinase (FAK) extracellular signal regulated kinase (ERK), phosphatidyl inositol 3 kinase (PI-3K), integrin-linked kinase (ILK), nuclear factor-kappa B (NF-kappaB), and modulates expression and activation of mainly pro-MMP-9, and moderately pro-MMP-2 in serum-free culture medium.

  8. The HIV-protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines

    PubMed Central

    Bandiera, Elisabetta; Todeschini, Paola; Romani, Chiara; Zanotti, Laura; Erba, Eugenio; Colmegna, Benedetta; Bignotti, Eliana; Santin, Alessandro Davide; Sartori, Enrico; Odicino, Franco Edoardo; Pecorelli, Sergio; Tassi, Renata Alessandra; Ravaggi, Antonella

    2016-01-01

    Innovative therapies in cervical cancer (CC) remain a priority. Recent data indicate that human immunodeficiency virus (HIV)-protease inhibitors used in highly active antiretroviral therapy can exert direct antitumor activities also in HIV-free preclinical and clinical models. The aim of the present study was to evaluate the antineoplastic effects of various HIV-protease inhibitors (indinavir, ritonavir and saquinavir) on primary and established CC cell lines. Two CC cell lines established in our laboratory and four commercially available CC cell lines were treated with indinavir, ritonavir and saquinavir at different concentrations and for different times. Proliferation, clonogenicity and radiosensitivity were evaluated by crystal violet staining. Proteasomal activities were assessed using a cell-based assay and immunoblotting. Cell cycle was analyzed by propidium iodide staining and flow cytometric analysis. Invasion was tested with Matrigel chambers. A t-test for paired samples was used for statistical analysis. In all cell lines, saquinavir was more effective than ritonavir in reducing cell proliferation and inhibiting proteasomal activities (P≤0.05). Conversely, indinavir exerted a negligible effect. The saquinavir concentrations required to modulate the proteasome activities were higher than those observed to be effective in inhibiting cell proliferation. In HeLa cells, saquinavir was strongly effective in inhibiting cell invasion and clonogenicity (P≤0.05) at concentrations much lower than those required to perturb proteasomal activities. Saquinavir did not contribute to increase the sensitivity of HeLa cells to X-rays. In conclusion, the present results demonstrate that saquinavir is able to significantly reduce cell proliferation, cell invasion and clonogenicity in a proteasome-independent manner in in vitro models of CC, and suggest that saquinavir could be a promising CC therapeutic agent.

  9. The HIV-protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines

    PubMed Central

    Bandiera, Elisabetta; Todeschini, Paola; Romani, Chiara; Zanotti, Laura; Erba, Eugenio; Colmegna, Benedetta; Bignotti, Eliana; Santin, Alessandro Davide; Sartori, Enrico; Odicino, Franco Edoardo; Pecorelli, Sergio; Tassi, Renata Alessandra; Ravaggi, Antonella

    2016-01-01

    Innovative therapies in cervical cancer (CC) remain a priority. Recent data indicate that human immunodeficiency virus (HIV)-protease inhibitors used in highly active antiretroviral therapy can exert direct antitumor activities also in HIV-free preclinical and clinical models. The aim of the present study was to evaluate the antineoplastic effects of various HIV-protease inhibitors (indinavir, ritonavir and saquinavir) on primary and established CC cell lines. Two CC cell lines established in our laboratory and four commercially available CC cell lines were treated with indinavir, ritonavir and saquinavir at different concentrations and for different times. Proliferation, clonogenicity and radiosensitivity were evaluated by crystal violet staining. Proteasomal activities were assessed using a cell-based assay and immunoblotting. Cell cycle was analyzed by propidium iodide staining and flow cytometric analysis. Invasion was tested with Matrigel chambers. A t-test for paired samples was used for statistical analysis. In all cell lines, saquinavir was more effective than ritonavir in reducing cell proliferation and inhibiting proteasomal activities (P≤0.05). Conversely, indinavir exerted a negligible effect. The saquinavir concentrations required to modulate the proteasome activities were higher than those observed to be effective in inhibiting cell proliferation. In HeLa cells, saquinavir was strongly effective in inhibiting cell invasion and clonogenicity (P≤0.05) at concentrations much lower than those required to perturb proteasomal activities. Saquinavir did not contribute to increase the sensitivity of HeLa cells to X-rays. In conclusion, the present results demonstrate that saquinavir is able to significantly reduce cell proliferation, cell invasion and clonogenicity in a proteasome-independent manner in in vitro models of CC, and suggest that saquinavir could be a promising CC therapeutic agent. PMID:27698818

  10. Triapine, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer or Vaginal Cancer

    ClinicalTrials.gov

    2014-04-21

    Recurrent Cervical Cancer; Recurrent Vaginal Cancer; Stage IB Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Vaginal Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer; Therapy-related Toxicity

  11. Invasive Cervical Cancer and Antidepressants

    PubMed Central

    Chan, Hsiang-Lin; Hsieh, Yi-Hsuan; Lin, Chiao-Fan; Liang, Hsin-Yi; Huang, Kuo-You; Chiu, Wei-Che; Lee, Yena; McIntyre, Roger S.; Chen, Vincent Chin-Hung

    2015-01-01

    Abstract To our knowledge, no prior population-based study has been published wherein the primary aim was to evaluate whether an association between psychotropic drug prescription and cervical cancer exists. Herein we have conducted the first study that primarily aimed to determine the association between antidepressants use and risk of invasive cervical cancer in the general population. This is a population-based study utilizing Taiwan's National Health Insurance Research Database. We identified 26,262 cases with invasive cervical cancer and 129,490 controls. We adopted the conditional logistic regression model as the statistical method and adjusted for potential confounding factors. The prescription of selective serotonin reuptake inhibitors (SSRIs) (adjusted OR = 0.93, 95% CI = 0.84–1.04), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), serotonin norepinephrine reuptake inhibitors (SNRIs), mirtazapine and bupropion, adjusting for cumulative dose, was not associated with an increased, or decreased, risk for invasive cervical cancer. An association between trazodone prescription and invasive cervical cancer was observed (adjusted OR = 1.22, 95% CI = 1.03–1.43). An association between the major classes of antidepressants and invasive cervical cancer was not observed herein. Our preliminary finding regarding a possible association between trazodone and cervical cancer requires replication. PMID:26496343

  12. Augmentation of Sodium Butyrate-induced Apoptosis by Phosphatidylinositol 3-kinase Inhibition in the Human Cervical Cancer Cell-line

    PubMed Central

    Park, Jung Kyu; Cho, Chi Heum; Ramachandran, Sabarish; Shin, So Jin; Kwon, Sang Hoon; Kwon, Sun Young

    2006-01-01

    Purpose Sodium butyrate (NaBT) is principally a histone deacetylase (HDAC) inhibitor, and it has the potential to arrest HPV-positive carcinoma cells at the G1 to S phase transition of the cell cycle. The aim of study was to determine whether phosphatidylinositol 3-kinase (PI3K) inhibition can enhance the inhibitory effect of NaBT on a human cervical cancer cell line (HeLa). Materials and Methods Cervical cancer cells (HeLa) were treated with NaBT alone or in combination with the PI3K inhibitors wortmannin or LY294002. Cell viability analysis and FACS analysis were carried out. The expressions of the cell cycle related proteins were evaluated by Western-blot analysis. Results Inhibition of PI3K enhanced NaBT-mediated apoptosis and this decreased the HeLa cell viability. Either wortmannin or LY294002, combined with NaBT, enhanced the activation of caspase 3 and caspase 9, and this enhanced the subsequent cleavage of poly (ADP-ribose) polymerase (PARP). Cervical cancer cells were arrested in the subG1 and G2/M phase, as was detected by FACS analysis. NaBT treatment in combination with PI3K inhibitors showed the increased expression of the CDK inhibitors p21Cip1/Waf1 and p27Kip1, in a p53 dependent manner, and also the increased dephosphorylation of Rb whereas there was a reduction in the expression levels of cyclin A, cyclin D1 and cyclin B1. Conclusion The results demonstrate that inhibition of PI3K enhances NaBT-mediated cervical cancer cell apoptosis through the activation of the caspase pathway. Moreover, these findings will support future investigation using the PI3K inhibitors in combination with adjuvant treatment for treating carcinoma of the cervix. PMID:19771269

  13. Circulating tumour cells and lung microvascular tumour cell retention in patients with metastatic breast and cervical cancer.

    PubMed

    Peeters, Dieter J E; Brouwer, Anja; Van den Eynden, Gert G; Rutten, Annemie; Onstenk, Wendy; Sieuwerts, Anieta M; Van Laere, Steven J; Huget, Philippe; Pauwels, Patrick; Peeters, Marc; Vermeulen, Peter B; Dirix, Luc Y

    2015-01-28

    We have shown that in up to half of the patients with metastatic breast cancer (MBC), higher numbers of circulating tumour cells (CTCs) are present in the central venous blood (CVB) compared to the peripheral venous blood (PVB), suggesting that the lungs might retain a substantial number of CTCs. Here we report the presence of tumour cell emboli (TCE) in the microvasculature of the lungs in three out of eight patients with MBC and one patient with metastatic cervical carcinoma who had markedly elevated numbers of CTCs in the blood. All these patients suffered from symptomatic dyspnoea not easily attributable to other causes. No TCE were observed in five patients with MBC and elevated CTC counts and three patients with MBC who had low CTC counts (<5/7.5 ml). To investigate whether CTCs derived from CVB or PVB exhibit different transcriptional characteristics that might explain selective CTC retention, paired CTC samples from CVB and PVB of 12 patients with advanced breast cancer were subjected to gene expression analysis of 105 genes. No significant differences in CTC gene expression were observed. Together, these data suggest that potentially clinically relevant CTC retention in the microvasculature of the lung can occur in a subset of patients with advanced metastatic breast and cervical cancer, which seems to be transcriptionally non-selectively.

  14. MiR-124 represses vasculogenic mimicry and cell motility by targeting amotL1 in cervical cancer cells.

    PubMed

    Wan, Hai-Ying; Li, Qin-Qin; Zhang, Yan; Tian, Wei; Li, Ya-Nan; Liu, Min; Li, Xin; Tang, Hua

    2014-12-01

    miRNAs have extensive functions in differentiation, metabolism, programmed cell death, and tumor metastasis by post-transcriptional regulation. Vasculogenic mimicry is an important pathway in tumor metastasis. Many factors can regulate vasculogenic mimicry, including miRNAs. In previous studies, miR-124 was found to repress proliferation and metastasis in different types of cancers, but whether it functions in cervical cancer remained unknown. Here, we demonstrate that miR-124 can repress vasculogenic mimicry, migration and invasion in HeLa and C33A cells in vitro. Furthermore, we reveal that the effect of miR-124 on vasculogenic mimicry, migration and invasion results from its interaction with AmotL1. MiR-124 regulates AmotL1 negatively by targeting its 3'untranslated region (3'UTR). We found that miR-124 can repress the EMT process. Together, these results improve our understanding of the function of miR-124 in tumor metastasis and will help to provide new potential target sites for cervical cancer treatment.

  15. Effects of irreversible electroporation on cervical cancer cell lines in vitro.

    PubMed

    Qin, Qin; Xiong, Zheng-Ai; Liu, Ying; Yao, Chen-Guo; Zhou, Wei; Hua, Yuan-Yuan; Wang, Zhi-Liang

    2016-09-01

    The effects of irreversible electroporation (IRE) on the proliferation, migration, invasion and adhesion of human cervical cancer cell lines HeLa and SiHa were investigated in the present study. HeLa and SiHa cells were divided into a treatment group and control group. The treatment group cells were exposed to electric pulses at 16 pulses, 1 Hz frequency for 100 µsec with 1,000 V/cm strength. Cellular proliferation was determined 24 h after treatment using a Cell Counting Kit‑8 (CCK‑8) assay and carboxyfluorescein diacetate‑succinimidyl ester (CFDA‑SE) labeling assay. The different phases of the cell cycle were detected using flow cytometry. Wound healing, Transwell invasion and Matrigel adhesion assays were performed to evaluate the migration, invasion and adhesion abilities of HeLa and SiHa cells. The expression levels of metastasis‑associated proteins were determined by western blot analysis. CCK‑8 and CFSE labeling assays indicated that the inhibition of cellular proliferation occurs in cells treated with IRE. Additionally, cell cycle progression was arrested at the G1/S phase. A western blot analysis indicated that the expression levels of p53 and p21 proteins were increased, whilst those of cyclin‑dependent kinase 2 (CDK2) and proliferating cell nuclear antigen (PCNA) proteins were decreased. However, wound healing, invasion and adhesion assays indicated that cellular migration, invasion and adhesion abilities were not significantly altered following exposure to IRE. IRE was not observed to promote the migration, invasion or adhesion capacity of HeLa and SiHa cells. However, IRE may inhibit the capacity of cells to proliferate and their progression through the cell cycle in vitro. Preliminary evidence suggests that the underlying mechanism involves increased expression levels of p53 and p21 and decreased expression levels of CDK2 and PCNA. PMID:27431825

  16. HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells

    SciTech Connect

    Liu, Junye; Zhang, Jing; Wang, Xiaowu; Li, Yan; Chen, Yongbin; Li, Kangchu; Zhang, Jian; Yao, Libo; Guo, Guozhen

    2010-07-15

    Hypoxia inducible factor 1 (HIF-1), the key mediator of hypoxia signaling pathways, has been shown involved in hypoxia-induced radioresistance. However, the underlying mechanisms are unclear. The present study demonstrated that both hypoxia and hypoxia mimetic cobalt chloride could increase the radioresistance of human cervical cancer Hela cells. Meanwhile, ectopic expression of HIF-1 could enhance the resistance of Hela cells to radiation, whereas knocking-down of HIF-1 could increase the sensitivity of Hela cells to radiation in the presence of hypoxia. N-Myc downstream-regulated gene 2 (NDRG2), a new HIF-1 target gene identified in our lab, was found to be upregulated by hypoxia and radiation in a HIF-1-dependent manner. Overexpression of NDRG2 resulted in decreased sensitivity of Hela cells to radiation while silencing NDRG2 led to radiosensitization. Moreover, NDRG2 was proved to protect Hela cells from radiation-induced apoptosis and abolish radiation-induced upregulation of Bax. Taken together, these data suggest that both HIF-1 and NDRG2 contribute to hypoxia-induced tumor radioresistance and that NDRG2 acts downstream of HIF-1 to promote radioresistance through suppressing radiation-induced Bax expression. It would be meaningful to further explore the clinical application potential of HIF-1 and NDRG2 blockade as radiosensitizer for tumor therapy.

  17. Proteomic investigation into betulinic acid-induced apoptosis of human cervical cancer HeLa cells.

    PubMed

    Xu, Tao; Pang, Qiuying; Zhou, Dong; Zhang, Aiqin; Luo, Shaman; Wang, Yang; Yan, Xiufeng

    2014-01-01

    Betulinic acid is a pentacyclic triterpenoid that exhibits anticancer functions in human cancer cells. This study provides evidence that betulinic acid is highly effective against the human cervical cancer cell line HeLa by inducing dose- and time-dependent apoptosis. The apoptotic process was further investigated using a proteomics approach to reveal protein expression changes in HeLa cells following betulinic acid treatment. Proteomic analysis revealed that there were six up- and thirty down-regulated proteins in betulinic acid-induced HeLa cells, and these proteins were then subjected to functional pathway analysis using multiple analysis software. UDP-glucose 6-dehydrogenase, 6-phosphogluconate dehydrogenase decarboxylating, chain A Horf6-a novel human peroxidase enzyme that involved in redox process, was found to be down-regulated during the apoptosis process of the oxidative stress response pathway. Consistent with our results at the protein level, an increase in intracellular reactive oxygen species was observed in betulinic acid-treated cells. The proteins glucose-regulated protein and cargo-selection protein TIP47, which are involved in the endoplasmic reticulum pathway, were up-regulated by betulinic acid treatment. Meanwhile, 14-3-3 family proteins, including 14-3-3β and 14-3-3ε, were down-regulated in response to betulinic acid treatment, which is consistent with the decrease in expression of the target genes 14-3-3β and 14-3-3ε. Furthermore, it was found that the antiapoptotic bcl-2 gene was down-regulated while the proapoptotic bax gene was up-regulated after betulinic acid treatment in HeLa cells. These results suggest that betulinic acid induces apoptosis of HeLa cells by triggering both the endoplasmic reticulum pathway and the ROS-mediated mitochondrial pathway.

  18. Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion.

    PubMed

    Guo, Fengjie; Li, Yalin; Liu, Yan; Wang, Jiajia; Li, Yuehui; Li, Guancheng

    2010-03-15

    Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is suggested to be a long (~7 kb) non-coding RNA. MALAT1 is overexpressed in many human carcinomas, but its function remains unknown. To investigate the role of MALAT1 in human cervical cancer progression, we designed and used short hairpin RNA to inhibit MALAT1 expression in CaSki cells and validated its effect on cell proliferation and invasion. Changes in gene expression were analyzed by reverse transcriptase- polymerase chain reaction. Our data demonstrated that MALAT1 was involved in cervical cancer cell growth, cell cycle progression, and invasion through the regulation of gene expression, such as caspase-3, -8, Bax, Bcl-2, and BclxL, suggesting that MALAT1 could have important implications in cervical cancer biology. Our findings illustrate the biological significance of MALAT1 in cervical cancer progression and provide novel evidence that MALAT1 may serve as a therapeutic target in the prevention of human cervical cancer.

  19. Cervical cancer: Biomarkers for diagnosis and treatment.

    PubMed

    Dasari, Subramanyam; Wudayagiri, Rajendra; Valluru, Lokanatha

    2015-05-20

    Cervical cancer is a major gynecological cancer which involves uncontrolled cell division and tissue invasiveness of the female uterine cervix. With the availability of new technologies researchers have increased their efforts to develop novel biomarkers for early diagnosis, and evaluation and monitoring of therapeutic treatments. This approach will help in the development of early diagnosis and in increasing treatment efficacy with decreased recurrence. The present review explains the currently available biomarkers for cervical cancer diagnosis and prognosis. Apart from the currently available biomarkers the review also explains strategies for the development of biomarkers based on cellular and molecular approaches such as DNA, protein and other metabolic markers with suitable clinical examples. The investigations of specific proteins, enzymes and metabolites will establish more useful biomarkers for accurate detection and management of gynecological cancers especially cervical cancer.

  20. Berry extracts exert different antiproliferative effects against cervical and colon cancer cells grown in vitro.

    PubMed

    McDougall, Gordon J; Ross, Heather A; Ikeji, Magnus; Stewart, Derek

    2008-05-14

    Polyphenol-rich berry extracts were screened for their antiproliferative effectiveness using human cervical cancer (HeLa) cells grown in microtiter plates. Rowan berry, raspberry, lingonberry, cloudberry, arctic bramble, and strawberry extracts were effective but blueberry, sea buckthorn, and pomegranate extracts were considerably less effective. The most effective extracts (strawberry > arctic bramble > cloudberry > lingonberry) gave EC 50 values in the range of 25-40 microg/(mL of phenols). These extracts were also effective against human colon cancer (CaCo-2) cells, which were generally more sensitive at low concentrations but conversely less sensitive at higher concentrations. The strawberry, cloudberry, arctic bramble, and the raspberry extracts share common polyphenol constituents, especially the ellagitannins, which have been shown to be effective antiproliferative agents. However, the components underlying the effectiveness of the lingonberry extracts are not known. The lingonberry extracts were fractionated into anthocyanin-rich and tannin-rich fractions by chromatography on Sephadex LH-20. The anthocyanin-rich fraction was considerably less effective than the original extract, whereas the antiproliferative activity was retained in the tannin-rich fraction. The polyphenolic composition of the lingonberry extract was assessed by liquid chromatography-mass spectrometry and was similar to previous reports. The tannin-rich fraction was almost entirely composed of procyanidins of linkage type A and B. Therefore, the antiproliferative activity of lingonberry was caused predominantly by procyanidins. PMID:18412361

  1. Complete Regression of Metastatic Cervical Cancer After Treatment With Human Papillomavirus–Targeted Tumor-Infiltrating T Cells

    PubMed Central

    Stevanović, Sanja; Draper, Lindsey M.; Langhan, Michelle M.; Campbell, Tracy E.; Kwong, Mei Li; Wunderlich, John R.; Dudley, Mark E.; Yang, James C.; Sherry, Richard M.; Kammula, Udai S.; Restifo, Nicholas P.; Rosenberg, Steven A.; Hinrichs, Christian S.

    2015-01-01

    Purpose Metastatic cervical cancer is a prototypical chemotherapy-refractory epithelial malignancy for which better treatments are needed. Adoptive T-cell therapy (ACT) is emerging as a promising cancer treatment, but its study in epithelial malignancies has been limited. This study was conducted to determine if ACT could mediate regression of metastatic cervical cancer. Patients and Methods Patients enrolled onto this protocol were diagnosed with metastatic cervical cancer and had previously received platinum-based chemotherapy or chemoradiotherapy. Patients were treated with a single infusion of tumor-infiltrating T cells selected when possible for human papillomavirus (HPV) E6 and E7 reactivity (HPV-TILs). Cell infusion was preceded by lymphocyte-depleting chemotherapy and was followed by administration of aldesleukin. Results Three of nine patients experienced objective tumor responses (two complete responses and one partial response). The two complete responses were ongoing 22 and 15 months after treatment, respectively. One partial response was 3 months in duration. The HPV reactivity of T cells in the infusion product (as measured by interferon gamma production, enzyme-linked immunospot, and CD137 upregulation assays) correlated positively with clinical response (P = .0238 for all three assays). In addition, the frequency of HPV-reactive T cells in peripheral blood 1 month after treatment was positively associated with clinical response (P = .0238). Conclusion Durable, complete regression of metastatic cervical cancer can occur after a single infusion of HPV-TILs. Exploratory studies suggest a correlation between HPV reactivity of the infusion product and clinical response. Continued investigation of this therapy is warranted. PMID:25823737

  2. Analysis of cytosine-adenine repeats in P1 promoter region of IGF-1 gene in peripheral blood cells and cervical tissue samples of females with cervical intraepithelial lesions and squamous cervical cancer

    PubMed Central

    KWASNIEWSKI, WOJCIECH; GOZDZICKA-JOZEFIAK, ANNA; KOTARSKA, MARIA; POLAK, GRZEGORZ; BARCZYNSKI, BARTLOMIEJ; BRONIARCZYK, JUSTYNA; NOWAK, WITOLD; WOLUN-CHOLEWA, MARIA; KWASNIEWSKA, ANNA; KOTARSKI, JAN

    2015-01-01

    High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervical cancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine-adenine (CA) repeat polymorphism in the P1 promoter region of the insulin-like growth factor-1 (IGF-1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF-1, and cervical cancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low-grade squamous intraepithelial lesions (L-SILs), high-grade squamous intraepithelial lesions (H-SILs) and invasive cervical cancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF-1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme-linked immunosorbent assay. The identification of the IGF-1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF-1 in the blood serum were observed between H-SILs and controls, only (p=0.047). However, the concentration of IGF-1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H-SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF concentration in blood serum and

  3. Celecoxib, a COX-2 Selective Inhibitor, Induces Cell Cycle Arrest at the G2/M Phase in HeLa Cervical Cancer Cells.

    PubMed

    Setiawati, Agustina; Setiawati, Agustina

    2016-01-01

    Celecoxib, a selective inhibitor of COX-2, showed cytotoxic effects in many cancer cell lines including cervical cancer cells. This study investigated the effect of celecoxib on cell cycle arrest in HeLa cervical cancer cells through p53 expression. In vitro anticancer activity was determined with the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method. A double staining method was applied to investigate the mechanism of cell death, cell cycling was analyzed by flow cytometryand immunocytochemistry was employed to stain p53 expression in cells. Celecoxib showed strong cytotoxic effects and induced apoptosis with an IC50 value of 40 μM. It induced cell cycle arrest at G2/M phase by increasing level of p53 expression on HeLa cells. PMID:27221835

  4. Get Tested for Cervical Cancer

    MedlinePlus

    ... help understanding your Pap test result . What about cost? Testing for cervical cancer is covered under the ... may be able to get tested at no cost to you. If you have private insurance, check ...

  5. Network Topologies Decoding Cervical Cancer

    PubMed Central

    Jalan, Sarika; Kanhaiya, Krishna; Rai, Aparna; Bandapalli, Obul Reddy; Yadav, Alok

    2015-01-01

    According to the GLOBOCAN statistics, cervical cancer is one of the leading causes of death among women worldwide. It is found to be gradually increasing in the younger population, specifically in the developing countries. We analyzed the protein-protein interaction networks of the uterine cervix cells for the normal and disease states. It was found that the disease network was less random than the normal one, providing an insight into the change in complexity of the underlying network in disease state. The study also portrayed that, the disease state has faster signal processing as the diameter of the underlying network was very close to its corresponding random control. This may be a reason for the normal cells to change into malignant state. Further, the analysis revealed VEGFA and IL-6 proteins as the distinctly high degree nodes in the disease network, which are known to manifest a major contribution in promoting cervical cancer. Our analysis, being time proficient and cost effective, provides a direction for developing novel drugs, therapeutic targets and biomarkers by identifying specific interaction patterns, that have structural importance. PMID:26308848

  6. S100A8/A9 induces apoptosis and inhibits metastasis of CasKi human cervical cancer cells.

    PubMed

    Qin, Fengjin; Song, Yao; Li, Zijian; Zhao, Ling; Zhang, Youyi; Geng, Li

    2010-09-01

    S100 proteins, a family of Ca(2+)-binding proteins, have been linked to several human diseases in recent years. Deregulated expression of S100 proteins, including S100A9 and its partner S100A8, was reported to be associated with neoplastic disorders. In our previous study using serial analysis of gene expression, we identified decreased expressions of S100A9 and S100A8 in human cervical squamous cell carcinoma. To investigate the functions of S100A8 and S100A9 in cervical cancer, we purified recombinant S100A8 and S100A9 proteins and treated CaSki human cervical cancer cells with these proteins. We found that S100A8/A9 induced apoptosis and inhibited migration of CaSki cells; S100A8/A9 also reduced the expression of matrix metalloproteinase (MMP)-2 in CaSki cells. In summary, this study suggests that S100A8 and S100A9 have inhibitory effects on the proliferation of CaSki carcinoma cells by inducing cell apoptosis and on the invasiveness of CaSki cells.

  7. FASL -844C polymorphism is associated with increased activation-induced T cell death and risk of cervical cancer.

    PubMed

    Sun, Tong; Zhou, Yifeng; Li, Hua; Han, Xiaohong; Shi, Yuankai; Wang, Li; Miao, Xiaoping; Tan, Wen; Zhao, Dan; Zhang, Xuemei; Guo, Yongli; Lin, Dongxin

    2005-10-01

    The FAS receptor-ligand system plays a key role in regulating apoptotic cell death, and corruption of this signaling pathway has been shown to participate in tumor-immune escape and carcinogenesis. We have recently demonstrated (Sun, T., X. Miao, X. Zhang, W. Tan, P. Xiong, and D. Lin. 2004. J. Natl. Cancer Inst. 96:1030-1036; Zhang, X., X. Miao, T. Sun, W. Tan, S. Qu, P. Xiong, Y. Zhou, and D. Lin. 2005. J. Med. Genet. 42:479-484) that functional polymorphisms in FAS and FAS ligand (FASL) are associated with susceptibility to lung cancer and esophageal cancer; however, the mechanisms underlying this association have not been elucidated. We show that the FAS -1377G, FAS -670A, and FASL -844T variants are expressed more highly on ex vivo-stimulated T cells than the FAS -1377A, FAS -670G, and FASL -844C variants. Moreover, activation-induced cell death (AICD) of T cells carrying the FASL -844C allele was increased. We also found a threefold increased risk of cervical cancer among subjects with the FASL -844CC genotype compared with those with the -844TT genotype in a case-control study in Chinese women. Together, these observations suggest that genetic polymorphisms in the FAS-FASL pathway confer host susceptibility to cervical cancers, which might be caused by immune escape of tumor cells because of enhanced AICD of tumor-specific T cells.

  8. Drugs Approved for Cervical Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for cervical cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  9. Suppressing effect of resveratrol on the migration and invasion of human metastatic lung and cervical cancer cells.

    PubMed

    Kim, Yoon Suk; Sull, Jae Woong; Sung, Ho Joong

    2012-09-01

    The antioxidant 3,4',5 tri-hydroxystilbene (resveratrol), a phytoalexin found in grapes, shows cancer preventive activities, including inhibition of migration and invasion of metastatic tumors. However, the molecular mechanism underlying the effect of resveratrol on tumor metastasis, especially in human metastatic lung and cervical cancers is not clear. A non-cytotoxic dosage of resveratrol causes a reduction in the generation of reactive oxygen species, and suppresses phorbol 12-myristate 13-acetate (PMA)-induced invasion and migration in both A549 and HeLa cells. Resveratrol also decreases both the expression and the enzymatic activity of matrix metalloproteinase-9 (MMP-9), and the promoter activity of PMA-stimulated MMP-9 is also inhibited. However, resveratrol does not affect either the expression or the proteolytic activity of MMP-2. Our results also show that resveratrol suppresses the transcription of MMP-9 by the inhibition of both NF-κB and AP-1 transactivation. These results indicate that resveratrol inhibits both NF-κB and AP-1 mediated MMP-9 expression, leading to suppression of migration and invasion of human metastatic lung and cervical cancer cells. Resveratrol has potential for clinical use in preventing invasion by human metastatic lung and cervical cancers.

  10. Stromal Fibroblasts Induce CCL20 through IL6/C/EBPβ to Support the Recruitment of Th17 Cells during Cervical Cancer Progression.

    PubMed

    Walch-Rückheim, Barbara; Mavrova, Russalina; Henning, Melanie; Vicinus, Benjamin; Kim, Yoo-Jin; Bohle, Rainer Maria; Juhasz-Böss, Ingolf; Solomayer, Erich-Franz; Smola, Sigrun

    2015-12-15

    Cervical cancer is a consequence of persistent infection with human papillomaviruses (HPV). Progression to malignancy is linked to an inflammatory microenvironment comprising T-helper-17 (Th17) cells, a T-cell subset with protumorigenic properties. Neoplastic cells express only low endogenous levels of the Th17 chemoattractant CCL20, and therefore, it is unclear how Th17 cells are recruited to the cervical cancer tissue. In this study, we demonstrate that CCL20 was predominantly expressed in the stroma of cervical squamous cell carcinomas in situ. This correlated with stromal infiltration of CD4(+)/IL17(+) cells and with advancing International Federation of Gynecology and Obstetrics (FIGO) stage. Furthermore, we show that cervical cancer cells instructed primary cervical fibroblasts to produce high levels of CCL20 and to attract CD4/IL17/CCR6-positive cells, generated in vitro, in a CCL20/CCR6-dependent manner. Further mechanistic investigations identified cervical cancer cell-derived IL6 as an important mediator of paracrine CCL20 induction at the promoter, mRNA, and protein level in fibroblasts. CCL20 was upregulated through the recently described CCAAT/enhancer-binding protein β (C/EBPβ) pathway as shown with a dominant-negative version of C/EBPβ and through siRNA-mediated knockdown. In summary, our study defines a novel molecular mechanism by which cervical neoplastic cells shape their local microenvironment by instructing fibroblasts to support Th17 cell infiltration in a paracrine IL6/C/EBPβ-dependent manner. Th17 cells may in turn maintain chronic inflammation within high-grade cervical lesions to further promote cancer progression. PMID:26631268

  11. Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

    PubMed Central

    2009-01-01

    Background Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection. Methods NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays. Results We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients. Conclusion Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression. PMID:19531227

  12. Nuclear co-expression of p14ARF and p16INK4A in uterine cervical cancer-derived cell lines containing HPV.

    PubMed

    Vázquez-Vega, Salvador; Sánchez-Suárez, Lilia Patricia; Contreras-Paredes, Adriana; Castellanos-Juárez, Emilio; Peñarroja-Flores, Rubicelia; Lizano-Soberón, Marcela; Andrade-Cruz, Rafael; García-Carrancá, Alejandro; Benítez-Bribiesca, Luis

    The Papanicolaou test (Pap) has been responsible for a significant reduction of cervical cancer-related morbimortality. In order to increase its sensitivity and specificity new markers have been studied and incorporated to cytological and histological methods for diagnosis for cervical cancer, such as p16INK4A that has been considered the immunocytochemical marker of choice for detection of HPV related cancers. We considered that p14ARF could be a complementary marker in order to improve the accuracy of cytological diagnosis because its genetic proximity to p16INK4A. We performed a systematic analysis of several putative cervical cancer markers in order to evaluate their performance in the detection of malignancy, in comparison with p16INK4A and p14ARF, using immunocytochemistry (ICC), immunofluorescence (IF) and Western blot analyses. Most markers were non-specific and could not discriminate HPV infected cancer cell lines from other non HPV malignant. In contrast, nuclear co-expression of p16INK4A and p14ARF was observed only in HPV-transformed cancer cell lines. Notably, in C-33A cervical cancer cells (HPV negative), p14ARF was present in the nucleoli, but p16INK4A was conspicuously absent from the nuclei of these cells. We conclude that both markers; p16INK4A and p14ARF are complementary and should be evaluated jointly in order to improve the accuracy of cytological diagnosis of cervical cancer.

  13. Transcriptomic and Functional Pathway Analysis of Human Cervical Carcinoma Cancer Cells Response to Microtubule Inhibitor

    PubMed Central

    Wang, Jin; Yan, Bin; Liu, Song-Mei; Sun, Huanhuan; Pan, Yonglong; Guan, Daogang; Zhang, Xiaoyan; Xu, Jianqing; Ma, Haiqing

    2015-01-01

    Background: There clearly is a need for effective chemotherapy for early-stage, high-risk patients with human cervical carcinoma. Vinblastine (VBL) is a key microtubule inhibitor, but unproven in its mechanisms as an important antitumor agent in cervical carcinoma. Methods: We selected the concentration of vinblastine inducing 30% cell death for analyses assessing the DNA content, gene expression and transcriptional gene regulation of VBL-treated KB-3 cells. Results: Transcriptomic and hierarchical clustering analysis demonstrated that treatment of KB-3 cells with VBL altered the expression of a diverse group of genes with G2/M arrest, which regulated by four oncogenic or tumor suppresser transcription factors (AP1, NFKB1, RELA, and TP53). Functional pathway analysis revealed the disease response to the biological effects of vinblastine in cervical carcinoma chemotherapy including protein ubiquitination pathway, RhoGDI signaling, integrin signaling, agranulocyte adhesion and biapedesis, and actin nucleation pathways. Northern blots also confirmed that KRT-7, FN14, IER3, and ID1 were deregulated in VBL-treated KB-3 cells. Conclusion: Transcriptional time series profiles and a functional pathway analysis of VBL-treated KB-3 cells will provide a new strategy for improving microtubule inhibitor chemotherapy for cervical carcinoma. PMID:26316889

  14. Cervical Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  15. Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines.

    PubMed

    Yi, Jin-Ling; Shi, Song; Shen, Yan-Li; Wang, Ling; Chen, Hai-Yan; Zhu, Jun; Ding, Yan

    2015-01-01

    Drug combination therapies are common practice in the treatment of cancer. In this study, we evaluated the anticancer effects of myricetin (MYR), methyl eugenol (MEG) and cisplatin (CP) both separately as well as in combination against cervical cancer (HeLa) cells. To demonstrate whether MYR and MEG enhance the anticancer activity of CP against cervical cancer cells, we treated HeLa cells with MYR and MEG alone or in combination with cisplatin and evaluated cell growth and apoptosis using MTT (3 (4, 5 dimethyl thiazol 2yl) 2, 5 diphenyltetrazolium bromide) assay, LDH release assay, flow cytometry and fluorescence microscopy. The results revealed that, as compared to single drug treatment, the combination of MYR or MEG with CP resulted in greater effect in inhibiting cancer cell growth and inducing apoptosis. Cell apoptosis induction, Caspase-3 activity, cell cycle arrest and mitochondrial membrane potential loss were systematically studied to reveal the mechanisms of synergy between MYR, MEG and CP. Combination of MYR or MEG with CP resulted in more potent apoptosis induction as revealed by fluorescence microscopy using Hoechst 33258 and AO-ETBR staining. The combination treatment also increased the number of cells in G0/G1 phase dramatically as compared to single drug treatment. Mitochondrial membrane potential loss (ΛΨm) as well as Caspase-3 activity was much higher in combination treatment as compared to single drug treatment. Findings of this investigation suggest that MYR and MEG combined with cisplatin is a potential clinical chemotherapeutic approach in human cervical cancer.

  16. Transactivation of bad by vorinostat-induced acetylated p53 enhances doxorubicin-induced cytotoxicity in cervical cancer cells.

    PubMed

    Lee, Sook-Jeong; Hwang, Sung-Ook; Noh, Eun Joo; Kim, Dong-Uk; Nam, Miyoung; Kim, Jong Hyeok; Nam, Joo Hyun; Hoe, Kwang-Lae

    2014-02-14

    Vorinostat (VOR) has been reported to enhance the cytotoxic effects of doxorubicin (DOX) with fewer side effects because of the lower DOX dosage in breast cancer cells. In this study, we investigated the novel mechanism underlying the synergistic cytotoxic effects of VOR and DOX co-treatment in cervical cancer cells HeLa, CaSki and SiHa cells. Co-treatment with VOR and DOX at marginal doses led to the induction of apoptosis through caspase-3 activation, poly (ADP-ribose) polymerase cleavage and DNA micronuclei. Notably, the synergistic growth inhibition induced by the co-treatment was attributed to the upregulation of the pro-apoptotic protein Bad, as the silencing of Bad expression using small interfering RNA (siRNA) abolished the phenomenon. As siRNA against p53 did not result in an increase in acetylated p53 and the consequent upregulation of Bad, the observed Bad upregulation was mediated by acetylated p53. Moreover, a chromatin immunoprecipitation analysis showed that the co-treatment of HeLa cells with VOR and DOX increased the recruitment of acetylated p53 to the bad promoter, with consequent bad transactivation. Conversely, C33A cervical cancer cells containing mutant p53 co-treated with VOR and DOX did not exhibit Bad upregulation, acetylated p53 induction or consequent synergistic growth inhibition. Together, the synergistic growth inhibition of cervical cancer cell lines induced by co-treatment with VOR and DOX can be attributed to the upregulation of Bad, which is induced by acetylated p53. These results show for the first time that the acetylation of p53, rather than histones, is a mechanism for the synergistic growth inhibition induced by VOR and DOX co-treatments.

  17. Radiosensitization of Human Cervical Cancer Cells by Inhibiting Ribonucleotide Reductase: Enhanced Radiation Response at Low-Dose Rates

    SciTech Connect

    Kunos, Charles A.; Colussi, Valdir C.; Pink, John; Radivoyevitch, Tomas; Oleinick, Nancy L.

    2011-07-15

    Purpose: To test whether pharmacologic inhibition of ribonucleotide reductase (RNR) by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC no. 663249) enhances radiation sensitivity during low-dose-rate ionizing radiation provided by a novel purpose-built iridium-192 cell irradiator. Methods and Materials: The cells were exposed to low-dose-rate radiation (11, 23, 37, 67 cGy/h) using a custom-fabricated cell irradiator or to high-dose-rate radiation (330 cGy/min) using a conventional cell irradiator. The radiation sensitivity of human cervical (CaSki, C33-a) cancer cells with or without RNR inhibition by 3-AP was evaluated using a clonogenic survival and an RNR activity assay. Alteration in the cell cycle distribution was monitored using flow cytometry. Results: Increasing radiation sensitivity of both CaSki and C33-a cells was observed with the incremental increase in radiation dose rates. 3-AP treatment led to enhanced radiation sensitivity in both cell lines, eliminating differences in cell cytotoxicity from the radiation dose rate. RNR blockade by 3-AP during low-dose-rate irradiation was associated with low RNR activity and extended G{sub 1}-phase cell cycle arrest. Conclusions: We conclude that RNR inhibition by 3-AP impedes DNA damage repair mechanisms that rely on deoxyribonucleotide production and thereby increases radiation sensitivity of human cervical cancers to low-dose-rate radiation.

  18. Cervical cancer: a preventable death.

    PubMed

    Nour, Nawal M

    2009-01-01

    Cervical cancer kills 260,000 women annually, and nearly 85% of these deaths occur in developing nations, where it is the leading cause of cancer deaths in women. Disparities of health and poverty play a large role in this high mortality rate. Whereas routine Papanicolaou and human papillomavirus (HPV) testing has dramatically reduced cervical cancer deaths in Western nations, without proper infrastructure, facilities, and medical training, the rates of cervical cancer in developing nations will remain high. Studies on HPV DNA testing and the low-technology method of "screen and treat" are promising. In addition, reducing the cost and increasing the availability of HPV vaccines in developing nations brings hope and promise to the next generation of women. PMID:20111660

  19. Preventing Cervical Cancer with HPV Vaccines

    Cancer.gov

    Cervical cancer can be prevented with HPV vaccines. NCI-supported researchers helped establish HPV as a cause of cervical cancer. They also helped create the first HPV vaccines, were involved in the vaccine trials, and contribute to ongoing studies.

  20. IL-17A Promotes the Migration and Invasiveness of Cervical Cancer Cells by Coordinately Activating MMPs Expression via the p38/NF-κB Signal Pathway

    PubMed Central

    Chen, Kunlun; Bian, Zhuoqiong; Jinfang Wu; Gao, Qing

    2014-01-01

    Objective IL-17A plays an important role in many inflammatory diseases and cancers. We aimed to examine the effect of IL-17A on the invasion of cervical cancer cells and study its related mechanisms. Methods Wound healing and matrigel transwell assays were used to examine the effect of IL-17A on cervical cancer cell migration and invasion by a panel of cervical cancer cell lines. The levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were investigated using western blotting. The activity of p38 and nuclear factor-kappa B (NF-κB) signal pathway was detected too. Results Here, we showed that IL-17A could promote the migration and invasion of cervical cancer cells. Further molecular analysis showed that IL-17A could up-regulate the expressions and activities of MMP2 and MMP9, and down-regulate the expressions of TIMP-1 and TIMP-2. Furthermore, IL-17A also activates p38 signal pathway and increased p50 and p65 nuclear expression. In addition, treatment of cervical cancer cells with the pharmacological p38/NF-κB signal pathway inhibitors, SB203580 and PDTC, potently restored the roles of invasion and upregulation of MMPs induced by IL-17A. Conclusion IL-17A could promote the migration and invasion of cervical cancer cell via up-regulating MMP2 and MMP9 expression, and down-regulating TIMP-1 and TIMP-2 expression via p38/NF-κB signal pathway. IL-17A may be a potential target to improve the prognosis for patients with cervical cancer. PMID:25250801

  1. Cervical Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  2. [Wnt signalling pathway and cervical cancer].

    PubMed

    Ramos-Solano, Moisés; Álvarez-Zavala, Monserrat; García-Castro, Beatriz; Jave-Suárez, Luis Felipe; Aguilar-Lemarroy, Adriana

    2015-01-01

    Cervical cancer (CC) is a pathology that arises in the cervical epithelium, whose major cause of risk is human papillomavirus (HPV) infection. Due to the fact that HPV infection per se is not enough to generate a carcinogenic process, it has been proposed that alterations in the Wnt signaling pathway are involved in cervical carcinogenesis. The Wnt family consists of 13 receptors and 19 ligands, and it is highly conserved phylogenetically due to its contribution in different biological processes, such as embryogenesis and tissue regeneration. Additionally, this signaling pathway modulates various cellular functions, for instance: cell proliferation, differentiation, migration and cell polarity. This paper describes the Wnt signaling pathways and alterations that have been found in members of this family in different cancer types and, especially, in CC.

  3. DNA probes for papillomavirus strains readied for cervical cancer screening

    SciTech Connect

    Merz, B.

    1988-11-18

    New Papillomavirus tests are ready to come to the aid of the standard Papanicolauo test in screening for cervical cancer. The new tests, which detect the strains of human papillomavirus (HPV) most commonly associated with human cervical cancer, are designed to be used as an adjunct to rather than as a replacement for the Papanicolaou smears. Their developers say that they can be used to indicated a risk of developing cancer in women whose Papanicolaou smears indicate mild cervical dysplasia, and, eventually, to detect papillomavirus infection in normal Papanicolaou smears. The rationale for HPV testing is derived from a growing body of evidence that HPV is a major factor in the etiology of cervical cancer. Three HPV tests were described recently in Chicago at the Third International Conference on Human Papillomavirus and Squamous Cervical Cancer. Each relies on DNA probes to detect the presence of papillomavirus in cervical cells and/or to distinguish the strain of papillomavirus present.

  4. Cervical cancer screening at crossroads.

    PubMed

    Lynge, Elsebeth; Rygaard, Carsten; Baillet, Miguel Vazquez-Prada; Dugué, Pierre-Antoine; Sander, Bente Braad; Bonde, Jesper; Rebolj, Matejka

    2014-08-01

    Cervical screening has been one of the most successful public health prevention programmes. For 50 years, cytology formed the basis for screening, and detected cervical intraepithelial lesions (CIN) were treated surgically to prevent progression to cancer. In a high-risk country as Denmark, screening decreased the incidence of cervical cancer from 34 to 11 per 100,000, age-standardized rate (World Standard Population). Screening is, however, also expensive; Denmark (population: 5.6 million) undertakes close to half a million tests per year, and has 6-8 CIN-treated women for each prevented cancer case. The discovery of human papillomavirus (HPV) as the cause of cervical cancer dramatically changed perspectives for disease control. Screening with HPV testing was launched around 1990, and preventive HPV vaccination was licensed in 2006. Long-term randomized controlled trials (RCT) demonstrated that HPV testing provides better protection against cervical cancer than cytology, but it requires extra repeated testing. HPV vaccination RCTs, furthermore, have proved that HPV vaccination protects against vaccine-type high-grade CIN in women vaccinated prior to sexual activity, but less so in women vaccinated later. The challenge now is therefore to find an algorithm for screening of a heterogeneous population including non-vaccinated women; women vaccinated prior to start of sexual activity; and women vaccinated later.

  5. Bleomycin sulphate loaded nanostructured lipid particles augment oral bioavailability, cytotoxicity and apoptosis in cervical cancer cells.

    PubMed

    Saini, Jyoti; Bansal, Vikas; Chandra, Ankush; Madan, Jitender; Jain, Upendra Kumar; Chandra, Ramesh; Jain, Sarvesh Malviya

    2014-06-01

    In present investigation, bleomycin sulphate loaded nanostructured lipid particles (BLM-NLPs) were constructed to enhance the oral bioavailability by overwhelming the first pass hepatic metabolism. The particles size and nanoencapsulation efficiency of BLM-NLPs were measured to be 17.4±5.4nm and 45.3±3.4%, respectively. Our studies indicated that the drug was molecularly dispersed in the lipid nanocoacervates, with amorphous geometry, without altering the chemical structure, as ascertained by spectral studies. The nanoformulation, BLM-NLPs was analyzed for dissolution testing, cytotoxicity, apoptosis and cellular uptake in human cervical cancer cell line, HeLa cells. BLM-NLPs released the drug with first order kinetic in simulated intestinal fluid (pH∼6.8±0.1), characterized by initial burst and followed by slow release. Further, an enhanced cytotoxicity (∼5.6 fold lower IC50), improved intracellular concentration (∼4.38 fold) and greater degree of apoptosis was induced by BLM-NLPs in HeLa cells, as compared to BLM alone. Moreover, BLM-NLPs also showed dose-dependent internalization, as evinced by cellular uptake study. The in vivo study indicated a significantly (P<0.0001) smaller elimination rate constant (KE), volume of distribution (Vd) and clearance rate (CLTotal) for BLM-NLPs, as compared to BLM solution in post-oral administrations. This clearly depicts the retention and stability of tailored nanoformulation in intestinal absorption pathway. In addition, our nanoformulation, BLM-NLPs documented significantly (P<0.0001)∼3.4 fold (66.20±2.57%) higher bioavailability than BLM solution (19.56±0.79%). In conclusion, our in vitro and in vivo results warrant the safety, efficacy and potency of tailored nanoformulation in clinical settings.

  6. Relationship between expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and invasion ability of cervical cancer cells.

    PubMed

    Kato, Yasuhito; Yamashita, Tsuyoshi; Ishikawa, Mutsuo

    2002-01-01

    Constitutive overexpression of matrix metalloproteinases (MMPs) is frequently observed in malignant tumors. MMPs are a family of zinc endopeptidases consisting of at least 20 different members. In particular, MMP-2 and MMP-9 are reported to be closely associated with invasion and metastasis in several cancers. We investigated whether expression of MMP-2 and MMP-9 is associated with invasion ability of seven cervical cancer cells by administration of o-phenanthroline as MMP inhibitor. In two cell lines, Siha and Caski, MMP-2 mRNA and protein were expressed at high levels. After treatment with o-phenanthroline, the rate of invasion in these two cell lines was significantly decreased. In contrast, in the other two cell lines, HT-3 and Caski, high levels of MMP-9 mRNA and protein were expressed but there was no decrease in the rate of invasion in these cells after treatment with o-phenanthroline. The data suggest that expression level of MMP-2 mRNA may regulate with invasion ability of cervical cancer.

  7. Suppression of human cervical cancer cell lines Hela and DoTc2 4510 by a mixture of lysine, proline, ascorbic acid, and green tea extract.

    PubMed

    Roomi, M W; Ivanov, V; Kalinovsky, T; Niedzwiecki, A; Rath, M

    2006-01-01

    Cervical cancer, the second most common cancer in women, once metastasized, leads to poor prognosis. We investigated the antitumor effect of a nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract on human cervical cancer cells Hela (CCL-2) and DoTc2 4510 by measuring cell proliferation (MTT assay), modulation of matrix metalloproteinases (MMP)-2 and MMP-9) expression (gelatinase zymography), and cancer cell invasive potential (Matrigel). NM showed significant antiproliferative effect on CCL-2 and DoTc2 4510 cancer cells. The NM inhibited CCL-2 expression of MMP-2 and MMP-9 in a dose-dependent fashion, with virtual total inhibition of MMP-2 at 1000 microg/mL and MMP-9 at 500 microg/mL NM. Untreated DoTc2 4510 cells showed MMP-9 expression, which was enhanced with phorbol 12-myristate 13-acetate treatment. NM inhibited MMP-9 expression in a dose-dependent fashion, with virtual inhibition at 500 microg/mL. Invasion of human cervical cancer cells CCL-2 and DoTc2 4510 through Matrigel decreased in a dose-dependent fashion, with 100% inhibition at 500 microg/mL NM (P < 0.0001) and 1000 microg/mL NM (P < 0.0001), respectively. Our results suggest that the mixture of lysine, proline, arginine, ascorbic acid, and green tea extract has potential in the treatment of cervical cancer by inhibiting critical steps in cancer development and spread.

  8. Diallyl disulfide enhances carbon ion beams-induced apoptotic cell death in cervical cancer cells through regulating Tap73 /ΔNp73.

    PubMed

    Di, Cuixia; Sun, Chao; Li, Hongyan; Si, Jing; Zhang, Hong; Han, Lu; Zhao, Qiuyue; Liu, Yang; Liu, Bin; Miao, Guoying; Gan, Lu; Liu, Yuanyuan

    2015-01-01

    Diallyl disulfide (DADS), extracted from crushed garlic by steam-distillation, has been reported to provide the anticancer activity in several cancer types. However, the effect of DADS on high-LET carbon beams - induced cell death remains unknown. Therefore, we used human cervical cancer cells to elucidate the molecular effects of this diallyl sulfide. Radiotherapy remains the mainstay of treatment, especially in advanced cervical cancer and there is still space to improve the radiosensitivity to reduce radiation dosage. In this study, we found that radiation effects evoked by high-LET carbon beam was marked by inhibition of cell viability, cell cycle arrest, significant rise of apoptotic cells, regulation of transcription factor, such as p73, as well as alterations of crucial mediator of the apoptosis pathway. We further demonstrated that pretreatment of 10 µM DADS in HeLa cells exposed to radiation resulted in decrease in cell viability and increased radiosensitivity. Additionally, cells pretreated with DADS obviously inhibited the radiation-induced G2/M phase arrest, but promoted radiation-induced apoptosis. Moreover, combination DADS and the radiation exacerbated the activation of apoptosis pathways through up-regulated ration of pro-apoptotic Tap73 to anti-apoptotic ΔNp73, and its downstream proteins, such as FASLG, and APAF1. Taken together, these results suggest that DADS is a potential candidate as radio sensitive agent for cervical cancer.

  9. Diallyl disulfide enhances carbon ion beams-induced apoptotic cell death in cervical cancer cells through regulating Tap73 /ΔNp73.

    PubMed

    Di, Cuixia; Sun, Chao; Li, Hongyan; Si, Jing; Zhang, Hong; Han, Lu; Zhao, Qiuyue; Liu, Yang; Liu, Bin; Miao, Guoying; Gan, Lu; Liu, Yuanyuan

    2015-01-01

    Diallyl disulfide (DADS), extracted from crushed garlic by steam-distillation, has been reported to provide the anticancer activity in several cancer types. However, the effect of DADS on high-LET carbon beams - induced cell death remains unknown. Therefore, we used human cervical cancer cells to elucidate the molecular effects of this diallyl sulfide. Radiotherapy remains the mainstay of treatment, especially in advanced cervical cancer and there is still space to improve the radiosensitivity to reduce radiation dosage. In this study, we found that radiation effects evoked by high-LET carbon beam was marked by inhibition of cell viability, cell cycle arrest, significant rise of apoptotic cells, regulation of transcription factor, such as p73, as well as alterations of crucial mediator of the apoptosis pathway. We further demonstrated that pretreatment of 10 µM DADS in HeLa cells exposed to radiation resulted in decrease in cell viability and increased radiosensitivity. Additionally, cells pretreated with DADS obviously inhibited the radiation-induced G2/M phase arrest, but promoted radiation-induced apoptosis. Moreover, combination DADS and the radiation exacerbated the activation of apoptosis pathways through up-regulated ration of pro-apoptotic Tap73 to anti-apoptotic ΔNp73, and its downstream proteins, such as FASLG, and APAF1. Taken together, these results suggest that DADS is a potential candidate as radio sensitive agent for cervical cancer. PMID:26505313

  10. What's New in Cervical Cancer Research and Treatment?

    MedlinePlus

    ... resources for cervical cancer What`s new in cervical cancer research and treatment? New ways to prevent and treat ... Your Doctor After Treatment What`s New in Cervical Cancer Research? Other Resources and References Cancer Information Cancer Basics ...

  11. Anti-TROP2 conjugated hollow gold nanospheres as a novel nanostructure for targeted photothermal destruction of cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Liu, Ting; Tian, Jiguang; Chen, Zhaolong; Liang, Ying; Liu, Jiao; Liu, Si; Li, Huihui; Zhan, Jinhua; Yang, Xingsheng

    2014-08-01

    Photothermal ablation (PTA) is a promising avenue in the area of cancer therapeutics that destroys tumor cells through conversion of near-infrared (NIR) laser light to heat. Hollow gold nanospheres (HGNs) are one of the few materials that are capable of converting light to heat and have been previously used for photothermal ablation studies. Selective delivery of functional nanoparticles to the tumor site is considered as an effective therapeutic approach. In this paper, we demonstrated the anti-cancer potential of HGNs. HGNs were conjugated with monoclonal antibody (anti-TROP2) in order to target cervical cancer cells (HeLa) that contain abundant trophoblast cell surface antigen 2 (TROP2) on the cell surface. The efficient uptake and intracellular location of these functionalized HGNs were studied through application of inductively coupled plasma atomic emission spectroscopy (ICP-AES) and transmission electron microscopy (TEM). Cytotoxicity induced by PTA was measured using CCK-8 assay. HeLa cells incubated with naked HGNs (0.3-3 nmol L-1) within 48 h did not show obvious cytotoxicity. Under laser irradiation at suitable power, anti-TROP2 conjugated HGNs achieved significant tumor cell growth inhibition in comparison to the effects of non-specific PEGylated HGNs (P < 0.05). γH2AX assay results revealed higher occurrences of DNA-DSBs with anti-TROP2 conjugated HGNs plus laser radiation as compared to treatment with laser alone. Flow cytometry analysis showed that the amount of cell apoptosis was increased after laser irradiation with anti-TROP2 conjugated HGNs (P < 0.05). Anti-TROP2 conjugated HGNs resulted in down-regulation of Bcl-2 expression and up-regulation of Bax expression. Our study results confirmed that anti-TROP2 conjugated HGNs can selectively destroy cervical cancer cells through inducing its apoptosis and DNA damages. We propose that HGNs have the potentials to mediate targeted cancer treatment.

  12. Invasive cervical cancer in pregnancy.

    PubMed

    La Russa, M; Jeyarajah, A R

    2016-05-01

    Detection of invasive cervical cancer during pregnancy is rare, with reported incidence rates ranging from 0.05% to 0.1%. However, cervical cancer is one of the most common malignancies diagnosed during pregnancy. The management of invasive cervical cancer in pregnancy is extremely challenging and requires a multidisciplinary team approach to optimise the treatment for the patient by simultaneously providing the best chance of survival for the foetus. The approach is based mainly on the following factors: gestational age at the time of the diagnosis, stage, histological subtype, desire regarding fertility and quality of life. The gold standard treatment for this condition in pregnancy is not yet established. This is due to the absence of prospective studies and clinical trials. Therefore, its management presents a dilemma that requires individualisation of care. The various factors that need to be considered for obtaining a good outcome for both mother and child are described in this study. PMID:26586539

  13. Human cervical cancer cells use Ca2+ signalling, protein tyrosine phosphorylation and MAP kinase in regulatory volume decrease.

    PubMed

    Shen, M R; Chou, C Y; Browning, J A; Wilkins, R J; Ellory, J C

    2001-12-01

    1. This study was aimed at identifying the signalling pathways involved in the activation of volume-regulatory mechanisms of human cervical cancer cells. 2. Osmotic swelling of human cervical cancer cells induced a substantial increase in intracellular Ca2+ ([Ca2+]i) by the activation of Ca2+ entry across the cell membrane, as well as Ca2+ release from intracellular stores. This Ca2+ signalling was critical for the normal regulatory volume decrease (RVD) response. 3. The activation of swelling-activated ion and taurine transport was significantly inhibited by tyrosine kinase inhibitors (genistein and tyrphostin AG 1478) and potentiated by the tyrosine phosphatase inhibitor Na3VO4. However, the Src family of tyrosine kinases was not involved in regulation of the swelling-activated Cl- channel. 4. Cell swelling triggered mitogen-activated protein (MAP) kinase cascades leading to the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/ERK2) and p38 kinase. The volume-responsive ERK1/ERK2 signalling pathway linked with the activation of K+ and Cl- channels, and taurine transport. However, the volume-regulatory mechanism was independent of the activation of p38 MAP kinase. 5. The phosphorylated ERK1/ERK2 expression following a hypotonic shock was up-regulated by protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and down-regulated by PKC inhibitor staurosporine. The response of ERK activation to hypotonicity also required Ca2+ entry and depended on tyrosine kinase and mitogen-activated/ERK-activating kinase (MEK) activity. 6. Considering the results overall, osmotic swelling promotes the activation of tyrosine kinase and ERK1/ERK2 and raises intracellular Ca2+, all of which play a crucial role in the volume-regulatory mechanism of human cervical cancer cells. PMID:11731569

  14. Oncogenic viral protein HPV E7 up-regulates the SIRT1 longevity protein in human cervical cancer cells.

    PubMed

    Allison, Simon J; Jiang, Ming; Milner, Jo

    2009-03-02

    Senescence is blocked in human cervical keratinocytes infected with high risk human papillomavirus (e.g. HPV type16). Viral oncoproteins HPV E6 and HPV E7 access the cell cycle via cellular p53 and retinoblastoma proteins respectively. Previously we have shown that HPV E7, not HPV E6, is also responsible for cervical cancer cell survival (SiHa cells; HPV type16). We now present evidence that SIRT1, an aging-related NAD-dependent deacetylase, mediates HPV E7 survival function in SiHa cervical cancer cells. Moreover, HPV E7 up-regulates SIRT1 protein when expressed in primary human keratinocytes. Conversely, SIRT1 levels decrease following RNAi-mediated silencing of HPV E7 in SiHa cells. Silencing HPV E6 has no effect on SIRT1 but, as expected, causes marked accumulation of p53 protein accompanied by p53-mediated up-regulation of p21. However, p53 acetylation (K382Ac) was barely detectable. Since p53 is a known SIRT1 substrate we propose that elevated SIRT1 levels (induced by HPV E7) attenuate p53 pro-apoptotic capacity via its de-acetylation. Our discovery that HPV E7 up-regulates SIRT1 links a clinically important oncogenic virus with the multi-functional SIRT1 protein. This link may open the way for a more in-depth understanding of the process of HPV-induced malignant transformation and also of the inter-relationships between aging and cancer.

  15. (-)-Anonaine induces apoptosis through Bax- and caspase-dependent pathways in human cervical cancer (HeLa) cells.

    PubMed

    Chen, Chung-Yi; Liu, Tsan-Zon; Tseng, Wei-Chang; Lu, Fung-Jou; Hung, Ray-Ping; Chen, Chi-Hung; Chen, Ching-Hsein

    2008-08-01

    (-)-Anonaine has been shown to have some anticancer activities, but the mechanisms of (-)-anonaine inducing cell death of human cancer cells is not fully understood. We investigated the mechanisms of apoptosis induced by (-)-anonaine in human HeLa cancer cells. Treatment with (-)-anonaine induces dose-dependent DNA damage that is correlated with increased intracellular nitric oxide, reactive oxygen species, glutathione depletion, disruptive mitochondrial transmembrane potential, activation of caspase 3, 7, 8, and 9, and poly ADP ribose polymerase cleavage. Our data indicate that (-)-anonaine up-regulated the expression of Bax and p53 proteins in HeLa cancer cells. The apoptosis and expression of Bax induced by (-)-anonaine could be inhibited when the HeLa cells were pretreated with Boc-Asp(OMe)-fmk, which is a broad caspases inhibitor. There was no obvious DNA damage in the (-)-anonaine-treated Madin-Darby canine kidney and Vero cell lines. Both Madin-Darby canine kidney and Vero cell lines are kidney epithelial cellular morphology. These results suggest that (-)-anonaine might be considered a potent compound for chemotherapy against cervical cancer or a health food supplement for cancer chemoprevention.

  16. Leea indica Ethyl Acetate Fraction Induces Growth-Inhibitory Effect in Various Cancer Cell Lines and Apoptosis in Ca Ski Human Cervical Epidermoid Carcinoma Cells

    PubMed Central

    Yau Hsiung, Wong; Abdul Kadir, Habsah

    2011-01-01

    The anticancer potential of Leea indica, a Chinese medicinal plant was investigated for the first time. The crude ethanol extract and fractions (ethyl acetate, hexane, and water) of Leea indica were evaluated their cytotoxicity on various cell lines (Ca Ski, MCF 7, MDA-MB-435, KB, HEP G2, WRL 68, and Vero) by MTT assay. Leea indica ethyl acetate fraction (LIEAF) was found showing the greatest cytotoxic effect against Ca Ski cervical cancer cells. Typical apoptotic morphological changes such as DNA fragmentation and chromatin condensation were observed in LIEAF-treated cells. Early signs of apoptosis such as externalization of phosphatidylserine and disruption of mitochondrial membrane potential indicated apoptosis induction. This was further substantiated by dose- and time-dependent accumulation of sub-G1 cells, depletion of intracellular glutathione, and activation of caspase-3. In conclusion, these results suggested that LIEAF inhibited cervical cancer cells growth by inducing apoptosis and could be developed as potential anticancer drugs. PMID:21423690

  17. Delivery of small interfering RNAs in human cervical cancer cells by polyethylenimine-functionalized carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Huang, Yuan-Pin; Lin, I.-Jou; Chen, Chih-Chen; Hsu, Yi-Chiang; Chang, Chi-Chang; Lee, Mon-Juan

    2013-06-01

    Carbon nanotubes are capable of penetrating the cell membrane and are widely considered as potential carriers for gene or drug delivery. Because the C-C and C=C bonds in carbon nanotubes are nonpolar, functionalization is required for carbon nanotubes to interact with genes or drugs as well as to improve their biocompatibility. In this study, polyethylenimine (PEI)-functionalized single-wall (PEI-NH-SWNTs) and multiwall carbon nanotubes (PEI-NH-MWNTs) were produced by direct amination method. PEI functionalization increased the positive charge on the surface of SWNTs and MWNTs, allowing carbon nanotubes to interact electrostatically with the negatively charged small interfering RNAs (siRNAs) and to serve as nonviral gene delivery reagents. PEI-NH-MWNTs and PEI-NH-SWNTs had a better solubility in water than pristine carbon nanotubes, and further removal of large aggregates by centrifugation produced a stable suspension of reduced particle size and improved homogeneity and dispersity. The amount of grafted PEI estimated by thermogravimetric analysis was 5.08% ( w/ w) and 5.28% ( w/ w) for PEI-NH-SWNTs and PEI-NH-MWNTs, respectively. For the assessment of cytotoxicity, various concentrations of PEI-NH-SWNTs and PEI-NH-MWNTs were incubated with human cervical cancer cells, HeLa-S3, for 48 h. PEI-NH-SWNTs and PEI-NH-MWNTs induced cell deaths in a dose-dependent manner but were less cytotoxic compared to pure PEI. As determined by electrophoretic mobility shift assay, siRNAs directed against glyceraldehyde-3-phosphate dehydrogenase (siGAPDH) were completely associated with PEI-NH-SWNTs or PEI-NH-MWNTs at a PEI-NH-SWNT/siGAPDH or PEI-NH-MWNT/siGAPDH mass ratio of 80:1 or 160:1, respectively. Furthermore, PEI-NH-SWNTs and PEI-NH-MWNTs successfully delivered siGAPDH into HeLa-S3 cells at PEI-NH-SWNT/siGAPDH and PEI-NH-MWNT/siGAPDH mass ratios of 1:1 to 20:1, resulting in suppression of the mRNA level of GAPDH to an extent similar to that of DharmaFECT, a common transfection

  18. 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian Past Issues / Spring 2007 ... of this page please turn Javascript on. Gynecologic Cancers Cervical, Endometrial, and Ovarian NCI estimates that endometrial, ...

  19. Cationic Antimicrobial Peptides Derived from Crocodylus siamensis Leukocyte Extract, Revealing Anticancer Activity and Apoptotic Induction on Human Cervical Cancer Cells.

    PubMed

    Theansungnoen, Tinnakorn; Maijaroen, Surachai; Jangpromma, Nisachon; Yaraksa, Nualyai; Daduang, Sakda; Temsiripong, Theeranan; Daduang, Jureerut; Klaynongsruang, Sompong

    2016-06-01

    Known antimicrobial peptides KT2 and RT2 as well as the novel RP9 derived from the leukocyte extract of the freshwater crocodile (Crocodylus siamensis) were used to evaluate the ability in killing human cervical cancer cells. RP9 in the extract was purified by a combination of anion exchange column and reversed-phase HPLC, and its sequence was analyzed by mass spectrometry. The novel peptide could inhibit Gram-negative Vibrio cholerae (clinical isolation) and Gram-positive Bacillus pumilus TISTR 905, and its MIC values were 61.2 µM. From scanning electron microscopy, the peptide was seen to affect bacterial surfaces directly. KT2 and RT2, which are designed antimicrobial peptides using the C. siamensis Leucrocin I template, as well as RP9 were chemically synthesized for investigation of anticancer activity. By Sulforhodamine B colorimetric assay, these antimicrobial peptides could inhibit both HeLa and CaSki cancer cell lines. The IC50 values of KT2 and RT2 for HeLa and CaSki cells showed 28.7-53.4 and 17.3-30.8 µM, while those of RP9 were 126.2 and 168.3 µM, respectively. Additionally, the best candidate peptides KT2 and RT2 were used to determine the apoptotic induction on cancer cells by human apoptosis array assay. As a result, KT2 and RT2 were observed to induce apoptotic cell death in HeLa cells. Therefore, these results indicate that KT2 and RT2 with antimicrobial activity have a highly potent ability to kill human cervical cancer cells. PMID:27129462

  20. Molecular imaging in cervical cancer.

    PubMed

    Khan, Sairah R; Rockall, Andrea G; Barwick, Tara D

    2016-06-01

    Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed. PMID:26859085

  1. Lymphedema After Surgery in Patients With Endometrial Cancer, Cervical Cancer, or Vulvar Cancer

    ClinicalTrials.gov

    2014-12-23

    Lymphedema; Stage IA Cervical Cancer; Stage IA Uterine Corpus Cancer; Stage IA Vulvar Cancer; Stage IB Cervical Cancer; Stage IB Uterine Corpus Cancer; Stage IB Vulvar Cancer; Stage II Uterine Corpus Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVB Vulvar Cancer

  2. Curcumin improves the paclitaxel-induced apoptosis of HPV-positive human cervical cancer cells via the NF-κB-p53-caspase-3 pathway

    PubMed Central

    DANG, YU-PING; YUAN, XIAO-YING; TIAN, RONG; LI, DONG-GUANG; LIU, WEI

    2015-01-01

    Paclitaxel, isolated from Taxus brevifolia, is considered to be an efficacious agent against a wide spectrum of human cancers, including human cervical cancer. However, dose-limiting toxicity and high cost limit its clinical application. Curcumin, a nontoxic food additive, has been reported to improve paclitaxel chemotherapy in mouse models of cervical cancer. However, the underlying mechanisms remain unclear. In this study, two human cervical cancer cell lines, CaSki [human papilloma virus (HPV)16-positive] and HeLa (HPV18-positive), were selected in which to investigate the effect of curcumin on the anticancer action of paclitaxel and further clarify the mechanisms. Flow cytometry and MTT analysis demonstrated that curcumin significantly promoted paclitaxel-induced apoptosis and cytotoxicity in the two cervical cell lines compared with that observed with paclitaxel alone (P<0.05). Reverse transcription-polymerase chain reaction indicated that the decline of HPV E6 and E7 gene expression induced by paclitaxel was also assisted by curcumin. The expression levels of p53 protein and cleaved caspase-3 were increased significantly in the curcumin plus paclitaxel-treated HeLa and CaSki cells compared with those in the cells treated with paclitaxel alone (P<0.01). Significant reductions in the levels of phosphorylation of IκBα and the p65-NF-κB subunit in CaSki cells treated with curcumin and paclitaxel were observed compared with those in cells treated with paclitaxel alone (P<0.05). This suggests that the combined effect of curcumin and paclitaxel was associated with the NF-κB-p53-caspase-3 pathway. In conclusion, curcumin has the ability to improve the paclitaxel-induced apoptosis of HPV-positive human cervical cancer cell lines via the NF-κB-p53-caspase-3 pathway. Curcumin in combination with paclitaxel may provide a superior therapeutic effect on human cervical cancer. PMID:25780454

  3. Evaluation of the Anti-proliferative Effects of Ophiocoma erinaceus Methanol Extract Against Human Cervical Cancer Cells

    PubMed Central

    Baharara, Javad; Amini, Elaheh; Namvar, Farideh

    2016-01-01

    Background: Marine organisms provide appreciable source of novel bioactive compounds with pharmacological potential. There is little information in correlation with anti-cancer activities of brittle star. In the present study, anti-neoplastic efficacy of Ophiocoma erinaceus methanol extract against human cervical cancer cells was investigated. Methods: The HeLa cells were cultured and exposed to brittle star methanol extract for 24 and 48 hr. The anti-proliferative properties were examined by MTT assay and the type of cell death induced was evaluated through morphological changes, flow cytometry, Annexin kit and caspase assay. To assess the anti-metastatic activity, wound healing assay was conducted and photographs were taken from the scratched areas. Further, to understand molecular mechanism of cell apoptosis, the expression of Bax was evaluated. Results: The morphological analysis and MTT assay exhibited that the brittle star methanol extract can exert dose dependent inhibitory effect on cells viability (IC50, 50 μg/ml). Flow cytometry and fluorescence microscopy demonstrated increment of sub-G1 peak, early and late apoptosis in HeLa treated cells. Wound healing migration assay showed that brittle star extract has anti-neoplastic efficacy by inhibiting cell migration. Caspase assay and RT-PCR analysis revealed that brittle star methanol extract induced caspase dependent apoptosis in HeLa cells through up-regulation of caspase-3 followed by up-regulation of Bax gene which is a hallmark of intrinsic pathway recruitment. Conclusion: These results represented further insights into the chemopreventive potential of brittle star as a valuable source of unknown therapeutic agents against human cervical cancer. PMID:26855733

  4. In vitro modulation of MMP-2 and MMP-9 in human cervical and ovarian cancer cell lines by cytokines, inducers and inhibitors.

    PubMed

    Roomi, M W; Monterrey, J C; Kalinovsky, T; Rath, M; Niedzwiecki, A

    2010-03-01

    Matrix metalloproteinases (MMPs) secreted by cervical and ovarian cancer, especially MMP-2 and MMP-9, play crucial roles in tumor invasion and metastasis. We examined the effect of cytokines, mitogens, inducers and inhibitors on MMP-2 and MMP-9 expression in cervical and ovarian cancer cell lines. Human cervical (HeLa and DoTc2-4510) and ovarian (SK-OV-3) cell lines were cultured in appropriate media. At near confluence, the cells were washed with PBS and incubated in serum-free medium with various concentrations of several cytokines, mitogens and inhibitors. After 24 h the media were removed and analyzed for MMP-2 and MMP-9 by gelatinase zymography and quantitated by densitometry. HeLa and SK-OV-3 cell lines expressed MMP-2 whereas DoTc2-4510 cells expressed MMP-9. Treatment of cervical cancer cell lines (HeLa and DoTc2-4510) with PMA had no effect on MMP-2 expression and a moderate stimulatory effect in ovarian cancer cell line SK-OV-3. MMP-9 was stimulated by phorbol 12-myristate 13-acetate in HeLa cells and enhanced in DoTc2-4510. Tumor necrosis factor-alpha and interleukin-1beta, had slight inhibitory effect on HeLa cell expression of MMP-2 while lipopolysaccharide stimulated MMP-2 in HeLa cells. Doxycycline, epigallocatechin gallate, a nutrient mixture, actinomycin-D, cyclohexamide, retinoic acid and dexamethasone inhibited MMP-2 in HeLa and SK-OV-3 cell lines and inhibited MMP-9 in DoTc2-4510. Our results show that cytokines, mitogens, inducers and inhibitors have an up or down regulatory effect on MMP-2 and MMP-9 expression in ovarian and cervical cancer cell lines, suggesting these agents may be effective strategies to treat these cancers.

  5. Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells.

    PubMed

    Eiró, Noemí; Sendon-Lago, Juan; Seoane, Samuel; Bermúdez, María A; Lamelas, Maria Luz; Garcia-Caballero, Tomás; Schneider, José; Perez-Fernandez, Roman; Vizoso, Francisco J

    2014-11-15

    Evidences indicate that tumor development and progression towards a malignant phenotype depend not only on cancer cells themselves, but are also deeply influenced by tumor stroma reactivity. The present study uses mesenchymal stem cells from normal human uterine cervix (hUCESCs), isolated by the minimally invasive method of routine Pap cervical smear, to study their effect on the three main cell types in a tumor: cancer cells, fibroblasts and macrophages. Administration of hUCESCs-conditioned medium (CM) to a highly invasive breast cancer MDA-MB-231 cell line and to human breast tumors with high cell proliferation rates had the effect of reducing cell proliferation, modifying the cell cycle, inducing apoptosis, and decreasing invasion. In a xenograft mouse tumor model, hUCESCs-CM reduced tumor growth and increased overall survival. In cancer-associated fibroblasts, administration of hUCESCs-CM resulted in reduced cell proliferation, greater apoptosis and decreased invasion. In addition, hUCESCs-CM inhibited and reverted macrophage differentiation. The analysis of hUCESCs-CM (fresh and lyophilized) suggests that a complex paracrine signaling network could be implicated in the anti-tumor potential of hUCESCs. In light of their anti-tumor potential, the easy cell isolation method, and the fact that lyophilization of their CM conserves original properties make hUCESCs good candidates for experimental or clinical applications in anticancer therapy. PMID:25296979

  6. Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells

    PubMed Central

    Seoane, Samuel; Bermúdez, María A.; Lamelas, Maria Luz; Garcia-Caballero, Tomás; Schneider, José; Perez-Fernandez, Roman; Vizoso, Francisco J.

    2014-01-01

    Evidences indicate that tumor development and progression towards a malignant phenotype depend not only on cancer cells themselves, but are also deeply influenced by tumor stroma reactivity. The present study uses mesenchymal stem cells from normal human uterine cervix (hUCESCs), isolated by the minimally invasive method of routine Pap cervical smear, to study their effect on the three main cell types in a tumor: cancer cells, fibroblasts and macrophages. Administration of hUCESCs-conditioned medium (CM) to a highly invasive breast cancer MDA-MB-231 cell line and to human breast tumors with high cell proliferation rates had the effect of reducing cell proliferation, modifying the cell cycle, inducing apoptosis, and decreasing invasion. In a xenograft mouse tumor model, hUCESCs-CM reduced tumor growth and increased overall survival. In cancer-associated fibroblasts, administration of hUCESCs-CM resulted in reduced cell proliferation, greater apoptosis and decreased invasion. In addition, hUCESCs-CM inhibited and reverted macrophage differentiation. The analysis of hUCESCs-CM (fresh and lyophilized) suggests that a complex paracrine signaling network could be implicated in the anti-tumor potential of hUCESCs. In light of their anti-tumor potential, the easy cell isolation method, and the fact that lyophilization of their CM conserves original properties make hUCESCs good candidates for experimental or clinical applications in anticancer therapy. PMID:25296979

  7. Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells.

    PubMed

    Eiró, Noemí; Sendon-Lago, Juan; Seoane, Samuel; Bermúdez, María A; Lamelas, Maria Luz; Garcia-Caballero, Tomás; Schneider, José; Perez-Fernandez, Roman; Vizoso, Francisco J

    2014-11-15

    Evidences indicate that tumor development and progression towards a malignant phenotype depend not only on cancer cells themselves, but are also deeply influenced by tumor stroma reactivity. The present study uses mesenchymal stem cells from normal human uterine cervix (hUCESCs), isolated by the minimally invasive method of routine Pap cervical smear, to study their effect on the three main cell types in a tumor: cancer cells, fibroblasts and macrophages. Administration of hUCESCs-conditioned medium (CM) to a highly invasive breast cancer MDA-MB-231 cell line and to human breast tumors with high cell proliferation rates had the effect of reducing cell proliferation, modifying the cell cycle, inducing apoptosis, and decreasing invasion. In a xenograft mouse tumor model, hUCESCs-CM reduced tumor growth and increased overall survival. In cancer-associated fibroblasts, administration of hUCESCs-CM resulted in reduced cell proliferation, greater apoptosis and decreased invasion. In addition, hUCESCs-CM inhibited and reverted macrophage differentiation. The analysis of hUCESCs-CM (fresh and lyophilized) suggests that a complex paracrine signaling network could be implicated in the anti-tumor potential of hUCESCs. In light of their anti-tumor potential, the easy cell isolation method, and the fact that lyophilization of their CM conserves original properties make hUCESCs good candidates for experimental or clinical applications in anticancer therapy.

  8. Inhibition of proliferation of cervical and leukemic cancer cells by penicillin G.

    PubMed

    Banerjee, Aditya; Dahiya, Meetu; Anand, M T; Kumar, Sudhir

    2013-01-01

    Cancer, despite all the efforts, still causes one in five deaths worldwide. Surgery, chemotherapy and radiotherapy provide inadequate protection and instead affect normal cells along with cancer cells. The search for cancer cures from natural products (plants and animals) has been practice for over a decade and the use of purified chemical to treat cancer still continues. Several studies have been undertaken during last three decades to find the anti-cancerous property of various plant extract and toxins secreted by animals and micro-organism. These lead to the discovery of several promising molecule having anticancer activity, some of which are in clinical trial and may emerged to be a potential future drug in cancer therapy. In this study we have used penicillin to evaluate its anti-cancer activity. It shown significant effects at cellular and molecular levels against growth of HeLa and K562 cell lines. PMID:23679330

  9. RNA interference targeting extracellular matrix metalloproteinase inducer (CD147) inhibits growth and increases chemosensitivity in human cervical cancer cells.

    PubMed

    Zhang, F; Zeng, Y L; Zhang, X G; Chen, W J; Yang, R; Li, S J

    2013-01-01

    Overexpression of extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN CD147) has been implicated in the growth and survival of malignant cells. However, its presence and role in cervical cancer cells has not been well-studied. In the present study, small interfering RNA (siRNA) was designed and synthesized to breakdown the expression of CD147. The present data demonstrated that 24 and 48 hours after transfecting CD147 siRNA, both the CD147 mRNA and protein expression were significantly inhibited as determined by quantitative real-time polymerase chain reaction (RT-PCR) and immunocytochemistry. Meanwhile, simultaneous silencing of CD147 resulted in distinctly increasing MMP-9, VEGF, and MDR-1. Further studies demonstrated decreased CD147 expression, resulted in G1/S phase transition with flow cytometry analysis, as well as the resistance of the cells to 5-FU. These findings provide further evidence that CD147 may become a promising therapeutic target for human cervical cancer and a potential chemotherapy-sensitizing agent.

  10. Cervical cancer: screening, diagnosis and staging.

    PubMed

    Tsikouras, Panagiotis; Zervoudis, Stefanos; Manav, Bachar; Tomara, Eirini; Iatrakis, George; Romanidis, Constantinos; Bothou, Anastasia; Galazios, George

    2016-01-01

    Purpose: Despite the widespread screening programs, cervical cancer remains the third most common cancer in developing countries. Based on the implementation of cervical screening programs with the referred adoption of improved screening methods in cervical cytology with the knowledge of the important role of the human papilloma virus (HPV) it's incidence is decreased in the developed world. Even if cervical HPV infection is incredibly common, cervical cancer is relatively rare. Depending on the rarity of invasive disease and the improvement of detection of pre-cancerous lesions due to the participation in screening programs, the goal of screening is to detect the cervical lesions early in order to be treated before cancer is developed. In populations with many preventive screening programs, a decrease in cervical cancer mortality of 50-75% is mentioned over the past 50 years. The preventive examination of vagina and cervix smear, Pap test, and the HPV DNA test are remarkable diagnostic tools according to the American Cancer Association guidelines, in the investigation of asymptomatic women and in the follow up of women after the treatment of pre-invasive cervical cancer. The treatment of cervical cancer is based on the FIGO 2009 cervical cancer staging.

  11. Cervical cancer: screening, diagnosis and staging.

    PubMed

    Tsikouras, Panagiotis; Zervoudis, Stefanos; Manav, Bachar; Tomara, Eirini; Iatrakis, George; Romanidis, Constantinos; Bothou, Anastasia; Galazios, George

    2016-01-01

    Purpose: Despite the widespread screening programs, cervical cancer remains the third most common cancer in developing countries. Based on the implementation of cervical screening programs with the referred adoption of improved screening methods in cervical cytology with the knowledge of the important role of the human papilloma virus (HPV) it's incidence is decreased in the developed world. Even if cervical HPV infection is incredibly common, cervical cancer is relatively rare. Depending on the rarity of invasive disease and the improvement of detection of pre-cancerous lesions due to the participation in screening programs, the goal of screening is to detect the cervical lesions early in order to be treated before cancer is developed. In populations with many preventive screening programs, a decrease in cervical cancer mortality of 50-75% is mentioned over the past 50 years. The preventive examination of vagina and cervix smear, Pap test, and the HPV DNA test are remarkable diagnostic tools according to the American Cancer Association guidelines, in the investigation of asymptomatic women and in the follow up of women after the treatment of pre-invasive cervical cancer. The treatment of cervical cancer is based on the FIGO 2009 cervical cancer staging. PMID:27273940

  12. Cisplatin suppresses the growth and proliferation of breast and cervical cancer cell lines by inhibiting integrin β5-mediated glycolysis.

    PubMed

    Wang, Shaojia; Xie, Jie; Li, Jiajia; Liu, Fei; Wu, Xiaohua; Wang, Ziliang

    2016-01-01

    Cancer cells harbor lower energy consumption after rounds of anticancer drugs, but the underlying mechanism remains unclear. In this study, we investigated metabolic alterations in cancer cells exposed to cisplatin. The present study exhibited cisplatin, known as a chemotherapeutic agent interacting with DNA, also acted as an anti-metabolic agent. We found that glycolysis levels of breast and cervical cancer cells were reduced after cisplatin treatment, resulting in cells growth and proliferation inhibition. We demonstrated that cisplatin suppressed glycolysis-related proteins expression, including glucose transporter 1 (GLUT1), glucose transporter 4 (GLUT4) and lactate dehydrogenase B (LDHB), through down-regulating integrin β5 (ITGB5)/focal adhesion kinase (FAK) signaling pathway. ITGB5 overexpression rescued cisplatin-induced inhibition of cancer cell glycolysis, growth and proliferation. Conclusively, we reveal a novel insight into cisplatin-induced anticancer mechanism, suggesting alternative strategies to the current therapeutic approaches of targeting ITGB5, as well as of a combination of cisplatin with glucose up-regulation chemotherapeutic agents to enhance anticancer effect. PMID:27294003

  13. Cisplatin suppresses the growth and proliferation of breast and cervical cancer cell lines by inhibiting integrin β5-mediated glycolysis

    PubMed Central

    Wang, Shaojia; Xie, Jie; Li, Jiajia; Liu, Fei; Wu, Xiaohua; Wang, Ziliang

    2016-01-01

    Cancer cells harbor lower energy consumption after rounds of anticancer drugs, but the underlying mechanism remains unclear. In this study, we investigated metabolic alterations in cancer cells exposed to cisplatin. The present study exhibited cisplatin, known as a chemotherapeutic agent interacting with DNA, also acted as an anti-metabolic agent. We found that glycolysis levels of breast and cervical cancer cells were reduced after cisplatin treatment, resulting in cells growth and proliferation inhibition. We demonstrated that cisplatin suppressed glycolysis-related proteins expression, including glucose transporter 1 (GLUT1), glucose transporter 4 (GLUT4) and lactate dehydrogenase B (LDHB), through down-regulating integrin β5 (ITGB5)/focal adhesion kinase (FAK) signaling pathway. ITGB5 overexpression rescued cisplatin-induced inhibition of cancer cell glycolysis, growth and proliferation. Conclusively, we reveal a novel insight into cisplatin-induced anticancer mechanism, suggesting alternative strategies to the current therapeutic approaches of targeting ITGB5, as well as of a combination of cisplatin with glucose up-regulation chemotherapeutic agents to enhance anticancer effect. PMID:27294003

  14. Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines

    PubMed Central

    Yi, Jin-Ling; Shi, Song; Shen, Yan-Li; Wang, Ling; Chen, Hai-Yan; Zhu, Jun; Ding, Yan

    2015-01-01

    Drug combination therapies are common practice in the treatment of cancer. In this study, we evaluated the anticancer effects of myricetin (MYR), methyl eugenol (MEG) and cisplatin (CP) both separately as well as in combination against cervical cancer (HeLa) cells. To demonstrate whether MYR and MEG enhance the anticancer activity of CP against cervical cancer cells, we treated HeLa cells with MYR and MEG alone or in combination with cisplatin and evaluated cell growth and apoptosis using MTT (3 (4, 5 dimethyl thiazol 2yl) 2, 5 diphenyltetrazolium bromide) assay, LDH release assay, flow cytometry and fluorescence microscopy. The results revealed that, as compared to single drug treatment, the combination of MYR or MEG with CP resulted in greater effect in inhibiting cancer cell growth and inducing apoptosis. Cell apoptosis induction, Caspase-3 activity, cell cycle arrest and mitochondrial membrane potential loss were systematically studied to reveal the mechanisms of synergy between MYR, MEG and CP. Combination of MYR or MEG with CP resulted in more potent apoptosis induction as revealed by fluorescence microscopy using Hoechst 33258 and AO-ETBR staining. The combination treatment also increased the number of cells in G0/G1 phase dramatically as compared to single drug treatment. Mitochondrial membrane potential loss (ΛΨm) as well as Caspase-3 activity was much higher in combination treatment as compared to single drug treatment. Findings of this investigation suggest that MYR and MEG combined with cisplatin is a potential clinical chemotherapeutic approach in human cervical cancer. PMID:25972998

  15. Characterization and anticancer potential of ferulic acid-loaded chitosan nanoparticles against ME-180 human cervical cancer cell lines

    NASA Astrophysics Data System (ADS)

    Panwar, Richa; Sharma, Asvene K.; Kaloti, Mandeep; Dutt, Dharm; Pruthi, Vikas

    2016-08-01

    Ferulic acid (FA) is a widely distributed hydroxycinnamic acid found in various cereals and fruits exhibiting potent antioxidant and anticancer activities. However, due to low solubility and permeability, its availability to biological systems is limited. Non-toxic chitosan-tripolyphosphate pentasodium (CS-TPP) nanoparticles (NPs) are used to load sparingly soluble molecules and drugs, increasing their bioavailability. In the present work, we have encapsulated FA into the CS-TPP NPs to increase its potential as a therapeutic agent. Different concentrations of FA were tested to obtain optimum sized FA-loaded CS-TPP nanoparticles (FA/CS-TPP NPs) by ionic gelation method. Nanoparticles were characterized by scanning electron microscopy, Fourier transformation infrared spectroscopy (FTIR), thermogravimetric analyses and evaluated for their anticancer activity against ME-180 human cervical cancer cell lines. The FTIR spectra confirmed the encapsulation of FA and thermal analysis depicted its degradation profile. A concentration-dependent relationship between FA encapsulation efficiency and FA/CS-TPP NPs diameter was observed. Smooth and spherical FA-loaded cytocompatible nanoparticles with an average diameter of 125 nm were obtained at 40 µM FA conc. The cytotoxicity of 40 µM FA/CS-TPP NPs against ME-180 cervical cancer cell lines was found to be higher as compared to 40 µM native FA. Apoptotic morphological changes as cytoplasmic remnants and damaged wrinkled cells in ME-180 cells were visualized using scanning electron microscopic and fluorescent microscopic techniques. Data concluded that chitosan enveloped FA nanoparticles could be exploited as an excellent therapeutic drug against cancer cells proliferation.

  16. Src family kinase inhibitor PP2 efficiently inhibits cervical cancer cell proliferation through down-regulating phospho-Src-Y416 and phospho-EGFR-Y1173.

    PubMed

    Kong, Lu; Deng, Zhihong; Shen, Haiying; Zhang, Yuxiang

    2011-02-01

    Tyrosine (Y) kinases inhibitors have been approved for targeted treatment of cancer. However, their clinical use is limited to some cancers and the mechanism of their action remains unclear. Previous study has indicated that PP2, a selective inhibitor of the Src family of non-receptor tyrosine kinases (nRTK), efficiently repressed cervical cancer growth in vitro and in vivo. In this regard, our aims are to explore the mechanism of PP2 on cervical cancer cell growth inhibition by investigating the suppressive divergence among PP1, PP2, and a negative control compound PP3. MTT results showed that three compounds had different inhibitory effects on proliferation of two cervical cancer cells, HeLa and SiHa, and PP2 was most efficient in a time- and dose-dependent manner. Moreover, we found 10 μM PP2 down-regulated pSrc-Y416 (P < 0.05), pEGFR-Y845 (P < 0.05), and -Y1173 (P < 0.05) expression levels, while 10 μM PP1 down-regulated pSrc-Y416 (P < 0.05) and pEGFR-Y845 (P < 0.05), but not pEGFR-Y1173; 10 μM PP3 down-regulated only pEGFR-Y1173 (P < 0.05). PP2 could modulate cell cycle arrest by up-regulating p21(Cip1) and p27(Kip1) in both HeLa and SiHa cells and down-regulating expression of cyclin A, and cyclin dependent kinase-2, -4 (Cdk-2, -4) in HeLa and of cyclin B and Cdk-2 in SiHa. Our results indicate that Src pathway and EGFR pathway play different roles in the proliferation of cervical cancer cells and PP2 efficiently reduces cervical cancer cell proliferation by reduction of both Src and EGFR activity.

  17. Insulin-like growth factor II mediates epidermal growth factor-induced mitogenesis in cervical cancer cells.

    PubMed Central

    Steller, M A; Delgado, C H; Zou, Z

    1995-01-01

    There is increasing evidence that activation of the insulin-like growth factor I (IGF-I) receptor plays a major role in the control of cellular proliferation of many cell types. We studied the mitogenic effects of IGF-I, IGF-II, and epidermal growth factor (EGF) on growth-arrested HT-3 cells, a human cervical cancer cell line. All three growth factors promoted dose-dependent increases in cell proliferation. In untransformed cells, EGF usually requires stimulation by a "progression" factor such as IGF-I, IGF-II, or insulin (in supraphysiologic concentrations) in order to exert a mitogenic effect. Accordingly, we investigated whether an autocrine pathway involving IGF-I or IGF-II participated in the EGF-induced mitogenesis of HT-3 cells. With the RNase protection assay, IGF-I mRNA was not detected. However, IGF-II mRNA increased in a time-dependent manner following EGF stimulation. The EGF-induced mitogenesis was abrogated in a dose-dependent manner by IGF-binding protein 5 (IGFBP-5), which binds to IGF-II and neutralizes it. An antisense oligonucleotide to IGF-II also inhibited the proliferative response to EGF. In addition, prolonged, but not short-term, stimulation with EGF resulted in autophosphorylation of the IGF-I receptor, and coincubations with both EGF and IGFBP-5 attenuated this effect. These data demonstrate that autocrine secretion of IGF-II in HT-3 cervical cancer cells can participate in EGF-induced mitogenesis and suggest that autocrine signals involving the IGF-I receptor occur "downstream" of competence growth factor receptors such as the EGF receptor. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8618825

  18. Requirement of T-lymphokine-activated killer cell-originated protein kinase for TRAIL resistance of human HeLa cervical cancer cells

    SciTech Connect

    Kwon, Hyeok-Ran; Lee, Ki Won; Dong, Zigang; Lee, Kyung Bok; Oh, Sang-Muk

    2010-01-01

    T-lymphokine-activated killer cell-originated protein kinase (TOPK) appears to be highly expressed in various cancer cells and to play an important role in maintaining proliferation of cancer cells. However, the underlying mechanism by which TOPK regulates growth of cancer cells remains elusive. Here we report that upregulated endogenous TOPK augments resistance of cancer cells to apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Stable knocking down of TOPK markedly increased TRAIL-mediated apoptosis of human HeLa cervical cancer cells, as compared with control cells. Caspase 8 or caspase 3 activities in response to TRAIL were greatly incremented in TOPK-depleted cells. Ablation of TOPK negatively regulated TRAIL-mediated NF-{kappa}B activity. Furthermore, expression of NF-{kappa}B-dependent genes, FLICE-inhibitory protein (FLIP), inhibitor of apoptosis protein 1 (c-IAP1), or X-linked inhibitor of apoptosis protein (XIAP) was reduced in TOPK-depleted cells. Collectively, these findings demonstrated that TOPK contributed to TRAIL resistance of cancer cells via NF-{kappa}B activity, suggesting that TOPK might be a potential molecular target for successful cancer therapy using TRAIL.

  19. Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells.

    PubMed

    Tsai, Jen-Pi; Lee, Chien-Hsing; Ying, Tsung-Ho; Lin, Chu-Liang; Lin, Chia-Liang; Hsueh, Jung-Tsung; Hsieh, Yi-Hsien

    2015-10-01

    The use of dietary bioactive compounds in chemoprevention can potentially reverse, suppress, or even prevent cancer progression. However, the effects of licochalcone A (LicA) on apoptosis and autophagy in cervical cancer cells have not yet been clearly elucidated. In this study, LicA treatment was found to significantly induce the apoptotic and autophagic capacities of cervical cancer cells in vitro and in vivo. MTT assay results showed dose- and time-dependent cytotoxicity in four cervical cancer cell lines treated with LicA. We found that LicA induced mitochondria-dependent apoptosis in SiHa cells, with decreasing Bcl-2 expression. LicA also induced autophagy effects were examined by identifying accumulation of Atg5, Atg7, Atg12 and microtubule-associated protein 1 light chain 3 (LC3)-II. Treatment with autophagy-specific inhibitors (3-methyladenine and bafilomycin A1) enhanced LicA-induced apoptosis. In addition, we suggested the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of mTOR pathway by LicA. Furthermore, the inhibition of PI3K/Akt by LY294002/si-Akt or of mTOR by rapamycin augmented LicA-induced apoptosis and autophagy. Finally, the in vivo mice bearing a SiHa xenograft, LicA dosed at 10 or 20 mg/kg significantly inhibited tumor growth. Our findings demonstrate the chemotherapeutic potential of LicA for treatment of human cervical cancer.

  20. Suppressor of Cytokine Signaling (SOCS) Genes Are Silenced by DNA Hypermethylation and Histone Deacetylation and Regulate Response to Radiotherapy in Cervical Cancer Cells

    PubMed Central

    Kim, Moon-Hong; Kim, Moon-Sun; Kim, Wonwoo; Kang, Mi Ae; Cacalano, Nicholas A.; Kang, Soon-Beom; Shin, Young-Joo; Jeong, Jae-Hoon

    2015-01-01

    Suppressor of cytokine signaling (SOCS) family is an important negative regulator of cytokine signaling and deregulation of SOCS has been involved in many types of cancer. All cervical cancer cell lines tested showed lower expression of SOCS1, SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry result for SOCS proteins in human cervical tissue also confirmed that normal tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to the regulation of SOCS in other types of cancer, DNA methylation contributed to SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3 expression, however, SOCS5 expression was neither affected by DNA methylation nor histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred radioresistance to HeLa cells, which implied SOCS signaling regulates the response to radiation in cervical cancer. In this study, we have shown that SOCS expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3 expression could contribute to the radiosensitive phenotype in cervical cancer. PMID:25849377

  1. Suppressor of cytokine signaling (SOCS) genes are silenced by DNA hypermethylation and histone deacetylation and regulate response to radiotherapy in cervical cancer cells.

    PubMed

    Kim, Moon-Hong; Kim, Moon-Sun; Kim, Wonwoo; Kang, Mi Ae; Cacalano, Nicholas A; Kang, Soon-Beom; Shin, Young-Joo; Jeong, Jae-Hoon

    2015-01-01

    Suppressor of cytokine signaling (SOCS) family is an important negative regulator of cytokine signaling and deregulation of SOCS has been involved in many types of cancer. All cervical cancer cell lines tested showed lower expression of SOCS1, SOCS3, and SOCS5 than normal tissue or cell lines. The immunohistochemistry result for SOCS proteins in human cervical tissue also confirmed that normal tissue expressed higher level of SOCS proteins than neighboring tumor. Similar to the regulation of SOCS in other types of cancer, DNA methylation contributed to SOCS1 downregulation in CaSki, ME-180, and HeLa cells. However, the expression of SOCS3 or SOCS5 was not recovered by the inhibition of DNA methylation. Histone deacetylation may be another regulatory mechanism involved in SOCS1 and SOCS3 expression, however, SOCS5 expression was neither affected by DNA methylation nor histone deacetylation. Ectopic expression of SOCS1 or SOCS3 conferred radioresistance to HeLa cells, which implied SOCS signaling regulates the response to radiation in cervical cancer. In this study, we have shown that SOCS expression repressed by, in part, epigenetically and altered SOCS1 and SOCS3 expression could contribute to the radiosensitive phenotype in cervical cancer.

  2. Triggering of death receptor apoptotic signaling by human papillomavirus 16 E2 protein in cervical cancer cell lines is mediated by interaction with c-FLIP.

    PubMed

    Wang, Wei; Fang, Yong; Sima, Ni; Li, Yan; Li, Wei; Li, Li; Han, Linfei; Liao, Shujie; Han, Zhiqiang; Gao, Qinglei; Li, Kezhen; Deng, Dongrui; Meng, Li; Zhou, Jianfeng; Wang, Shixuan; Ma, Ding

    2011-01-01

    Human papillomavirus (HPV) E2 gene disruption is one of the key features of HPV-induced cervical malignant transformation. Though it is thought to prevent progression of carcinogenesis, the pro-apoptotic function of E2 protein remains poorly understood. This study shows that expression of HPV16 E2 induces apoptosis both in HPV-positive and -negative cervical cancer cell lines and leads to hyperactivation of caspase-8 and caspase-3. Activation of these signaling factors is responsible for the observed sensitivity to apoptosis upon treatment with anti-Fas antibody or TNF-α. In addition, immunoprecipitation experiments clearly show an interaction between HPV16 E2 and c-FLIP, a key regulator of apoptotic cell death mediated by death receptor signaling. Moreover, c-FLIP and a caspase-8 inhibitor protect cells from HPV16 E2-mediated apoptosis. Overexpression of c-FLIP rescues cervical cancer cells from apoptosis induced by HPV16 E2 protein expression. The data suggest that HPV16 E2 abrogates the apoptosis-inhibitory function of c-FLIP and renders the cell hypersensitive to the Fas/FasL apoptotic signal even below threshold concentration. This suggests a novel mechanism for deregulation of cervical epithelial cell growth upon HPV-induced transformation, which is of great significance in developing therapeutic strategies for intervention of cervical carcinogenesis.

  3. Overexpression of myeloid zinc finger 1 suppresses matrix metalloproteinase-2 expression and reduces invasiveness of SiHa human cervical cancer cells.

    PubMed

    Tsai, Su-Ju; Hwang, Jin-Ming; Hsieh, Shu-Ching; Ying, Tsung-Ho; Hsieh, Yi-Hsien

    2012-08-24

    Myeloid zinc finger 1 (MZF1) gene belongs to the Kruppel family of zinc finger transcription factors. MZF1 has been suggested to play an important role in the tumorigenesis, invasion, and apoptosis of various tumor cells. However, the role of MZF1 in human cervical cancer remains unclear. To investigate the molecular mechanisms of MZF1 and its functional role in human cervical cancer cell migration and invasion, we experimented on stable SiHa cells overexpressing MZF1. We found that MZF1 overexpression inhibits the migratory and invasive abilities of SiHa cervical cancer cells. In addition, the overexpression of MZF1 significantly reduces MMP-2 protein and mRNA levels. Luciferase and ChIP assays suggested that MZF1 directly binds to MMP-2 gene regulatory sequences in vivo and suppresses MMP-2 promoter activity in vitro. This study shows that MZF-1 represses MMP-2 transcription and suggests that this repression may be linked to inhibition of human cervical cancer cell migration and metastasis.

  4. Nanotechnology in the management of cervical cancer.

    PubMed

    Chen, Jiezhong; Gu, Wenyi; Yang, Lei; Chen, Chen; Shao, Renfu; Xu, Kewei; Xu, Zhi Ping

    2015-03-01

    Cervical cancer is a major disease with high mortality. All cervical cancers are caused by infection with human papillomaviruses (HPV). Although preventive vaccines for cervical cancer are successful, treatment of cervical cancer is far less satisfactory because of multidrug resistance and side effects. In this review, we summarize the recent application of nanotechnology to the diagnosis and treatment of cervical cancer as well as the development of HPV vaccines. Early detection of cervical cancer enables tumours to be efficiently removed by surgical procedures, leading to increased survival rate. The current method of detecting cervical cancer by Pap smear can only achieve 50% sensitivity, whereas nanotechnology has been used to detect HPVs with greatly improved sensitivity. In cervical cancer treatment, nanotechnology has been used for the delivery of anticancer drugs to increase treatment efficacy and decrease side effects. Nanodelivery of HPV preventive and therapeutic vaccines has also been investigated to increase vaccine efficacy. Overall, these developments suggest that nanoparticle-based vaccine may become the most effective way to prevent and treat cervical cancer, assisted or combined with some other nanotechnology-based therapy.

  5. Nanotechnology in the management of cervical cancer.

    PubMed

    Chen, Jiezhong; Gu, Wenyi; Yang, Lei; Chen, Chen; Shao, Renfu; Xu, Kewei; Xu, Zhi Ping

    2015-03-01

    Cervical cancer is a major disease with high mortality. All cervical cancers are caused by infection with human papillomaviruses (HPV). Although preventive vaccines for cervical cancer are successful, treatment of cervical cancer is far less satisfactory because of multidrug resistance and side effects. In this review, we summarize the recent application of nanotechnology to the diagnosis and treatment of cervical cancer as well as the development of HPV vaccines. Early detection of cervical cancer enables tumours to be efficiently removed by surgical procedures, leading to increased survival rate. The current method of detecting cervical cancer by Pap smear can only achieve 50% sensitivity, whereas nanotechnology has been used to detect HPVs with greatly improved sensitivity. In cervical cancer treatment, nanotechnology has been used for the delivery of anticancer drugs to increase treatment efficacy and decrease side effects. Nanodelivery of HPV preventive and therapeutic vaccines has also been investigated to increase vaccine efficacy. Overall, these developments suggest that nanoparticle-based vaccine may become the most effective way to prevent and treat cervical cancer, assisted or combined with some other nanotechnology-based therapy. PMID:25752817

  6. Heterogeneity of microRNAs expression in cervical cancer cells: over-expression of miR-196a

    PubMed Central

    Villegas-Ruiz, Vanessa; Juárez-Méndez, Sergio; Pérez-González, Oscar A; Arreola, Hugo; Paniagua-García, Lucero; Parra-Melquiadez, Miriam; Peralta-Rodríguez, Raúl; López-Romero, Ricardo; Monroy-García, Alberto; Mantilla-Morales, Alejandra; Gómez-Gutiérrez, Guillermo; Román-Bassaure, Edgar; Salcedo, Mauricio

    2014-01-01

    In recent years, the study of microRNAs associated with neoplastic processes has increased. Patterns of microRNA expression in different cell lines and different kinds of tumors have been identified; however, little is known about the alterations in regulatory pathways and genes involved in aberrant set of microRNAs. The identification of these altered microRNAs in several cervical cancer cells and potentially deregulated pathways involved constitute the principal goals of the present study. In the present work, the expression profiles of cellular microRNAs in Cervical Cancer tissues and cell lines were explored using microRNA microarray, Affymetrix. The most over-expressed was miR-196a, which was evaluated by real time PCR, and HOXC8 protein as potential target by immunohistochemistry assay. One hundred and twenty three human microRNAs differentially expressed in the cell tumor, 64 (52%) over-expressed and 59 (48%) under-expressed were observed. Among the microRNAs over-expressed, we focused on miR-196a; at present this microRNA is poorly studied in CC. The expression of this microRNA was evaluated by qRT-PCR, and HOXC8 by immunohistochemistry assay. There is not a specific microRNA expression profile in the CC cells, neither a microRNA related to HPV presence. Furthermore, the miR-196a was over-expressed, while an absence of HOXC8 expression was observed. We suggest that miR-196a could be played as oncomiR in CC. PMID:24817935

  7. Stages of Cervical Cancer

    MedlinePlus

    ... checked under a microscope for signs of cancer. Laparoscopy : A surgical procedure to look at the organs ... a laparoscope , the operation is called a total laparoscopic hysterectomy. Enlarge Hysterectomy. The uterus is surgically removed ...

  8. 1-(2-Hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione Induces G1 Cell Cycle Arrest and Autophagy in HeLa Cervical Cancer Cells

    PubMed Central

    Tsai, Jie-Heng; Hsu, Li-Sung; Huang, Hsiu-Chen; Lin, Chih-Li; Pan, Min-Hsiung; Hong, Hui-Mei; Chen, Wei-Jen

    2016-01-01

    The natural agent, 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB), has been reported to have growth inhibitory effects on several human cancer cells. However, the role of HMDB in cervical cancer remains unclear. Herein, we found that HMDB dose- and time-dependently inhibited growth of HeLa cervical cancer cells, accompanied with G1 cell cycle arrest. HMDB decreased protein expression of cyclins D1/D3/E and cyclin-dependent kinases (CDKs) 2/4/6 and reciprocally increased mRNA and protein levels of CDK inhibitors (p15, p16, p21, and p27), thereby leading to the accumulation of hypophosphorylated retinoblastoma (Rb) protein. HMDB also triggered the accumulation of acidic vesicles and formation of microtubule-associated protein-light chain 3 (LC3), followed by increased expression of LC3 and Beclin-1 and decreased expression of p62, suggesting that HMDB triggered autophagy in HeLa cells. Meanwhile, suppression of the expression of survivin and Bcl-2 implied that HMDB-induced autophagy is tightly linked to apoptosis. Exploring the action mechanism, HMDB induced autophagy via the modulation of AMP-activated protein kinase (AMPK) and mTOR signaling pathway rather than the class III phosphatidylinositol 3-kinase pathway. These results suggest that HMDB inhibits HeLa cell growth by eliciting a G1 arrest through modulation of G1 cell cycle regulators and by concomitantly inducing autophagy through the mediation of AMPK-mTOR and Akt-mTOR pathways, and may be a promising antitumor agent against cervical cancer. PMID:27527160

  9. 1-(2-Hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione Induces G1 Cell Cycle Arrest and Autophagy in HeLa Cervical Cancer Cells.

    PubMed

    Tsai, Jie-Heng; Hsu, Li-Sung; Huang, Hsiu-Chen; Lin, Chih-Li; Pan, Min-Hsiung; Hong, Hui-Mei; Chen, Wei-Jen

    2016-01-01

    The natural agent, 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB), has been reported to have growth inhibitory effects on several human cancer cells. However, the role of HMDB in cervical cancer remains unclear. Herein, we found that HMDB dose- and time-dependently inhibited growth of HeLa cervical cancer cells, accompanied with G1 cell cycle arrest. HMDB decreased protein expression of cyclins D1/D3/E and cyclin-dependent kinases (CDKs) 2/4/6 and reciprocally increased mRNA and protein levels of CDK inhibitors (p15, p16, p21, and p27), thereby leading to the accumulation of hypophosphorylated retinoblastoma (Rb) protein. HMDB also triggered the accumulation of acidic vesicles and formation of microtubule-associated protein-light chain 3 (LC3), followed by increased expression of LC3 and Beclin-1 and decreased expression of p62, suggesting that HMDB triggered autophagy in HeLa cells. Meanwhile, suppression of the expression of survivin and Bcl-2 implied that HMDB-induced autophagy is tightly linked to apoptosis. Exploring the action mechanism, HMDB induced autophagy via the modulation of AMP-activated protein kinase (AMPK) and mTOR signaling pathway rather than the class III phosphatidylinositol 3-kinase pathway. These results suggest that HMDB inhibits HeLa cell growth by eliciting a G1 arrest through modulation of G1 cell cycle regulators and by concomitantly inducing autophagy through the mediation of AMPK-mTOR and Akt-mTOR pathways, and may be a promising antitumor agent against cervical cancer. PMID:27527160

  10. Eugenol enhances the chemotherapeutic potential of gemcitabine and induces anticarcinogenic and anti-inflammatory activity in human cervical cancer cells.

    PubMed

    Hussain, Arif; Brahmbhatt, Kruti; Priyani, Anita; Ahmed, Musthaq; Rizvi, Tahir A; Sharma, Chhavi

    2011-10-01

    Administration of natural or synthetic agents to inhibit, delay, block, or reverse the initiation and promotional events associated with carcinogenesis opens a new avenue for cancer prevention and treatment to reduce cancer morbidity and mortality. Eugenol, a potential chemopreventive agent, is a component of clove and several other spices such as basil, cinnamon, and bay leaves. A number of reports have shown that eugenol possesses antiseptic, analgesic, antibacterial, and anticancer properties. The present study was undertaken to evaluate the chemopreventive potential of eugenol alone and in combination with a chemotherapeutic agent such as gemcitabine. Eugenol showed dose-dependent selective cytotoxicity toward HeLa cells in comparison to normal cells, pointing to its safe cytotoxicity profile. A combination of eugenol and gemcitabine induced growth inhibition and apoptosis at lower concentrations, compared with the individual drugs. The analysis of the data using a combination index showed combination index values of <1 indicating strong synergistic interaction. The combination thus may enhance the efficacy of gemcitabine at lower doses and minimize the toxicity on normal cells. In addition, the expression analysis of genes involved in apoptosis and inflammation revealed significant downregulation of Bcl-2, COX-2, and IL-1β on treatment with eugenol. Thus, the results suggest that eugenol exerts its anticancer activities via apoptosis induction and anti-inflammatory properties and also provide the first evidence demonstrating synergism between eugenol and gemcitabine, which may enhance the therapeutic index of prevention and/or treatment of cervical cancer.

  11. Conservative Surgery for Early Cervical Cancer.

    PubMed

    Rema, P; Ahmed, Iqbal

    2016-09-01

    There is a rising incidence of early cervical cancer in young patients as a result of screening and early detection. Treatment of cervical cancer by surgery or radiotherapy results in permanent infertility which affects the quality of life of cancer survivors. Now with improved survival rates among early cervical cancer patients, conservative surgery aiming at fertility preservation in those desiring future pregnancy is an accepted treatment. Conservative surgery is possible in early cervical cancer including micro invasive cancer and stage IB cancers less than 2 cm. Stage IA1 cervical cancer is treated effectively by cervical conisation. In stage IA2 cancers and stage IB1 cancers less than 2 cm the fertility preservation surgery is radical trachelectomy. Radical trachelectomy removes the cervix with medial parametrium and upper 2 cm vaginal cuff retaining the uterus and adnexa to allow future pregnancy. Radical trachelectomy is a safe procedure in selected patients with cancer cervix with acceptable oncologic risks and promising obstetric outcome. It should be avoided in tumours larger than 2 cm and aggressive histologic types. This article focuses on the current options of conservative surgery in early cervical cancer. PMID:27651696

  12. TP53 polymorphism, HPV infection, and risk of cervical cancer.

    PubMed

    Klug, S J; Wilmotte, R; Santos, C; Almonte, M; Herrero, R; Guerrero, I; Caceres, E; Peixoto-Guimaraes, D; Lenoir, G; Hainaut, P; Walboomers, J M; Muñoz, N

    2001-09-01

    The role of a polymorphism at position 72 of the tumor suppressor gene TP53 in the development of cervical cancer is not well established. The arginine variant of the p53 protein could be more susceptible to degradation by human papillomavirus (HPV) E6 protein than the protein containing proline. Recent studies show controversial results. We investigated a possible association between TP53 polymorphism and cervical cancer in a Peruvian population with high prevalence of HPV infection. HPV status and TP53 polymorphism were determined for 119 cases of invasive cervical cancer and 127 control women from Peru. HPV infection was detected by PCR of cervical cells or tumor biopsies. For determination of TP53 polymorphism, exon 4 of the TP53 gene was amplified by PCR, and DNA was subsequently subjected to restriction enzyme digest. Associations between TP53 polymorphism, HPV infection, and cervical cancer were assessed using logistic regression. Women homozygotes for arginine had a 2.2-fold increased risk (95% confidence interval: 0.6-7.6) for cervical cancer. The odds ratio for women heterozygotes for Arg/Pro was 3.5 (95% confidence interval: 0.9-14). Similarly increased risks were found when restricting analysis to HPV-positive women only. The distribution of TP53 genotypes in this Peruvian population was comparable with that found in Caucasians. Our results cannot rule out an association between the TP53 polymorphism at codon 72, HPV infection, and the etiology of cervical cancer. PMID:11535556

  13. Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells

    PubMed Central

    2011-01-01

    Background- Specific types of high risk Human papillomaviruses (HR-HPVs) particularly, HPV types 16 and 18 cause cervical cancer and while the two recently developed vaccines against these HPV types are prophylactic in nature, therapeutic options for treatment and management of already existing HPV infection are not available as yet. Because transcription factor, Activator Protein-1 (AP-1) plays a central role in HPV-mediated cervical carcinogenesis, we explored the possibility of its therapeutic targeting by berberine, a natural alkaloid derived from a medicinal plant species, Berberis which has been shown to possess anti-inflammatory and anti-cancer properties with no known toxicity; however, the effect of berberine against HPV has not been elucidated. Results- We studied the effect of berberine on HPV16-positive cervical cancer cell line, SiHa and HPV18-positive cervical cancer cell line, HeLa using electrophoretic mobility gel shift assays, western and northern blotting which showed that berberine could selectively inhibit constitutively activated AP-1 in a dose- and time-dependent manner and downregulates HPV oncogenes expression. Inhibition of AP-1 was also accompanied by changes in the composition of their DNA-binding complex. Berberine specifically downregulated expression of oncogenic c-Fos which was also absent in the AP-1 binding complex. Treatment with berberine resulted in repression of E6 and E7 levels and concomitant increase in p53 and Rb expression in both cell types. Berberine also suppressed expression of telomerase protein, hTERT, which translated into growth inhibition of cervical cancer cells. Interestingly, a higher concentration of berberine was found to reduce the cell viability through mitochondria-mediated pathway and induce apoptosis by activating caspase-3. Conclusion- These results indicate that berberine can effectively target both the host and viral factors responsible for development of cervical cancer through inhibition of AP-1 and

  14. Berberine reverses epithelial-to-mesenchymal transition and inhibits metastasis and tumor-induced angiogenesis in human cervical cancer cells.

    PubMed

    Chu, Shu-Chen; Yu, Cheng-Chia; Hsu, Li-Sung; Chen, Kuo-Shuen; Su, Mei-Yu; Chen, Pei-Ni

    2014-12-01

    Metastasis is the most common cause of cancer-related death in patients, and epithelial-to-mesenchymal transition (EMT) is essential for cancer metastasis, which is a multistep complicated process that includes local invasion, intravasation, extravasation, and proliferation at distant sites. When cancer cells metastasize, angiogenesis is also required for metastatic dissemination, given that an increase in vascular density will allow easier access of tumor cells to circulation, and represents a rational target for therapeutic intervention. Berberine has several anti-inflammation and anticancer biologic effects. In this study, we provided molecular evidence that is associated with the antimetastatic effect of berberine by showing a nearly complete inhibition on invasion (P < 0.001) of highly metastatic SiHa cells via reduced transcriptional activities of matrix metalloproteinase-2 and urokinase-type plasminogen activator. Berberine reversed transforming growth factor-β1-induced EMT and caused upregulation of epithelial markers such as E-cadherin and inhibited mesenchymal markers such as N-cadherin and snail-1. Selective snail-1 inhibition by snail-1-specific small interfering RNA also showed increased E-cadherin expression in SiHa cells. Berberine also reduced tumor-induced angiogenesis in vitro and in vivo. Importantly, an in vivo BALB/c nude mice xenograft model and tail vein injection model showed that berberine treatment reduced tumor growth and lung metastasis by oral gavage, respectively. Taken together, these findings suggested that berberine could reduce metastasis and angiogenesis of cervical cancer cells, thereby constituting an adjuvant treatment of metastasis control.

  15. Induction of apoptotic effects of antiproliferative protein from the seeds of Borreria hispida on lung cancer (A549) and cervical cancer (HeLa) cell lines.

    PubMed

    Rupachandra, S; Sarada, D V L

    2014-01-01

    A 35 KDa protein referred to as F3 was purified from the seeds of Borreria hispida by precipitation with 80% ammonium sulphate and gel filtration on Sephadex G-100 column. RP-HPLC analysis of protein fraction (F3) on an analytical C-18 column produced a single peak, detected at 220 nm. F3 showed an apparent molecular weight of 35 KDa by SDS PAGE and MALDI-TOF-MS analyses. Peptide mass fingerprinting analysis of F3 showed the closest homology with the sequence of 1-aminocyclopropane-1-carboxylate deaminase of Pyrococcus horikoshii. The protein (F3) exhibited significant cytotoxic activity against lung (A549) and cervical (HeLa) cancer cells in a dose-dependent manner at concentrations ranging from 10 µg to 1000 µg/mL, as revealed by the MTT assay. Cell cycle analysis revealed the increased growth of sub-G0 population in both cell lines exposed to a concentration of 1000 µg/mL of protein fraction F3 as examined from flow cytometry. This is the first report of a protein from the seeds of Borreria hispida with antiproliferative and apoptotic activity in lung (A549) and cervical (HeLa) cancer cells. PMID:24605320

  16. The apoptotic effect of hesperetin on human cervical cancer cells is mediated through cell cycle arrest, death receptor, and mitochondrial pathways.

    PubMed

    Alshatwi, Ali A; Ramesh, E; Periasamy, V S; Subash-Babu, P

    2013-12-01

    Hesperetin, a flavonoid from citrus fruits, has several bioactivities such as anti-inflammatory, antihypertensive, antiatherogenic effects. However, studies elucidating the role and the mechanism(s) of action of hesperetin in cervical cancer are sparse. In this study, we investigated the mechanism of the antiproliferative and apoptotic actions exerted by hesperetin on human cervical cancer SiHa cells. The viability of SiHa cells was evaluated using the MTT assay, apoptosis by acridine orange/ethidium bromide, propidium iodide, TUNEL assay, and Annexin V-Cy3, cell cycle distribution and mitochondrial transmembrane potential using flow cytometry, and apoptotic marker genes using quantitative real-time PCR. The treatment of SiHa cells with hesperetin (IC50, 650 μm) showed a marked concentration- and time-dependent inhibition of proliferation and induced the G2/M phase in a dose-dependent manner after 24 h. There was an attenuation of mitochondrial membrane potential with increased expression of caspase-3, caspase-8, caspase-9, p53, Bax, and Fas death receptor and its adaptor protein Fas-associated death domain-containing protein (FADD), indicating the participation of both death receptor- and mitochondria-related mechanisms. Furthermore, hesperetin-induced apoptosis was confirmed by TUNEL and Annexin V-Cy3. This study shows that hesperetin exhibits a potential anticancer activity against human cervical cancer cell lines in vitro through the reduction in cell viability and the induction of apoptosis. Altogether, these data sustain our contention that hesperetin has anticancer properties and merits further investigation as a potential therapeutic agent.

  17. MicroRNA-373 functions as an oncogene and targets YOD1 gene in cervical cancer.

    PubMed

    Wang, Luo-Qiao; Zhang, Yue; Yan, Huan; Liu, Kai-Jiang; Zhang, Shu

    2015-04-10

    miR-373 was reported to be elevated in several tumors; however, the role of miR-373 in cervical cancer has not been investigated. In this study we aimed to investigate the role of miR-373 in tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-373 was investigated using real-time reverse transcription-polymerase chain reaction assay in 45 cervical specimens and cervical cancer cell lines. The role of miR-373 in tumorigenicity of cervical cancer cells was assessed by cell proliferation, colony formation in vitro as well as tumor growth assays in vivo with the overexpression of miR-373 or gene silencing. The functional target gene of miR-373 in cervical cancer cells was identified using integrated bioinformatics analysis, gene expression arrays, and luciferase assay. We founded that the expression of miR-373 is upregulated in human cervical cancer tissues and cervical carcinoma cell lines when compared to the corresponding noncancerous tissues. Ectopic overexpression of miR-373 in human cervical cancer cells promoted cell growth in vitro and tumorigenicity in vivo, whereas silencing the expression of miR-373 decreased the rate of cell growth. YOD1 was identified as a direct and functional target of miR-373 in cervical cancer cells. Expression levels of miR-373 were inversely correlated with YOD1 levels in human cervical cancer tissues. RNAi-mediated knockdown of YOD1 phenocopied the proliferation-promoting effect of miR-373. Moreover, overexpression of YOD1 abrogated miR-373-induced proliferation of cervical cancer cells. These results demonstrate that miR-373 increases proliferation by directly targeting YOD1, a new potential therapeutic target in cervical cancer.

  18. Oral contraceptives, human papillomavirus and cervical cancer.

    PubMed

    La Vecchia, Carlo; Boccia, Stefania

    2014-03-01

    Oncogenic human papillomavirus is the key determinant of cervical cancer, but other risk factors interact with it to define individual risk. Among these, there is oral contraceptive (OC) use. A quantitative review of the link between OCs and cervical cancer was performed. Long-term (>5 year) current or recent OC use has been related to an about two-fold excess risk of cervical cancer. Such an excess risk, however, levels off after stopping use, and approaches unity 10 or more years after stopping. The public health implications of OC use for cervical cancer are limited. In any case, such implications are greater in middle-income and low-income countries, as well as in central and eastern Europe and Latin America, where cervical cancer screening and control remain inadequate.

  19. Radiosensitizing effect of gold nanoparticles in carbon ion irradiation of human cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Kaur, Harminder; Avasthi, D. K.; Pujari, Geetanjali; Sarma, Asitikantha

    2013-07-01

    Noble metal nanoparticles have received considerable attention in biotechnology for their role in bio sensing due to surface plasmon resonance, medical diagnostics due to better imaging contrast and therapy. The radiosensitization effect of gold nanoparticles (AuNP) has been gaining popularity in radiation therapy of cancer cells. The better depth dose profile of energetic ion beam proves its superiority over gamma radiation for fighting against cancer. In the present work, the glucose capped gold nanoparticles (Glu-AuNP) were synthesised and internalized in the HeLa cells. Transmission electron microscopic analysis of ultrathin sections of Glu-AuNP treated HeLa cells confirmed the internalization of Glu-AuNPs. Control HeLa cells and Glu-AuNp treated HeLa cells were irradiated at different doses of 62 MeV 12C ion beam (LET - 290keV/μm) at BIO beam line of using 15UD Pelletron accelerator at Inter University Accelerator Centre, New Delhi, India. The survival fraction was assessed by colony forming assay which revealed that the dose of carbon ion for 90% cell killing in Glu-AuNP treated HeLa cells and control HeLa cells are 2.3 and 3.2 Gy respectively. This observation shows ˜ 28% reduction of 12C6+ ion dose for Glu-AuNP treated HeLa cells as compared to control HeLa cells.

  20. Radiosensitizing effect of gold nanoparticles in carbon ion irradiation of human cervical cancer cells

    SciTech Connect

    Kaur, Harminder; Avasthi, D. K.; Pujari, Geetanjali; Sarma, Asitikantha

    2013-07-18

    Noble metal nanoparticles have received considerable attention in biotechnology for their role in bio sensing due to surface plasmon resonance, medical diagnostics due to better imaging contrast and therapy. The radiosensitization effect of gold nanoparticles (AuNP) has been gaining popularity in radiation therapy of cancer cells. The better depth dose profile of energetic ion beam proves its superiority over gamma radiation for fighting against cancer. In the present work, the glucose capped gold nanoparticles (Glu-AuNP) were synthesised and internalized in the HeLa cells. Transmission electron microscopic analysis of ultrathin sections of Glu-AuNP treated HeLa cells confirmed the internalization of Glu-AuNPs. Control HeLa cells and Glu-AuNp treated HeLa cells were irradiated at different doses of 62 MeV 12C ion beam (LET - 290keV/{mu}m) at BIO beam line of using 15UD Pelletron accelerator at Inter University Accelerator Centre, New Delhi, India. The survival fraction was assessed by colony forming assay which revealed that the dose of carbon ion for 90% cell killing in Glu-AuNP treated HeLa cells and control HeLa cells are 2.3 and 3.2 Gy respectively. This observation shows {approx} 28% reduction of {sup 12}C{sup 6+} ion dose for Glu-AuNP treated HeLa cells as compared to control HeLa cells.

  1. Sulforaphane, a Dietary Isothiocyanate, Induces G2/M Arrest in Cervical Cancer Cells through CyclinB1 Downregulation and GADD45β/CDC2 Association

    PubMed Central

    Cheng, Ya-Min; Tsai, Ching-Chou; Hsu, Yi-Chiang

    2016-01-01

    Globally, cervical cancer is the most common malignancy affecting women. The main treatment methods for this type of cancer include conization or hysterectomy procedures. Sulforaphane (SFN) is a natural, compound-based drug derived from dietary isothiocyanates which has previously been shown to possess potent anti-tumor and chemopreventive effects against several types of cancer. The present study investigated the effects of SFN on anti-proliferation and G2/M phase cell cycle arrest in cervical cancer cell lines (Cx, CxWJ, and HeLa). We found that cytotoxicity is associated with an accumulation of cells in the G2/M phases of the cell-cycle. Treatment with SFN led to cell cycle arrest as well as the down-regulation of Cyclin B1 expression, but not of CDC2 expression. In addition, the effects of GADD45β gene activation in cell cycle arrest increase proportionally with the dose of SFN; however, mitotic delay and the inhibition of proliferation both depend on the dosage of SFN used to treat cancer cells. These results indicate that SFN may delay the development of cancer by arresting cell growth in the G2/M phase via down-regulation of Cyclin B1 gene expression, dissociation of the cyclin B1/CDC2 complex, and up-regulation of GADD45β proteins. PMID:27626412

  2. Sulforaphane, a Dietary Isothiocyanate, Induces G₂/M Arrest in Cervical Cancer Cells through CyclinB1 Downregulation and GADD45β/CDC2 Association.

    PubMed

    Cheng, Ya-Min; Tsai, Ching-Chou; Hsu, Yi-Chiang

    2016-01-01

    Globally, cervical cancer is the most common malignancy affecting women. The main treatment methods for this type of cancer include conization or hysterectomy procedures. Sulforaphane (SFN) is a natural, compound-based drug derived from dietary isothiocyanates which has previously been shown to possess potent anti-tumor and chemopreventive effects against several types of cancer. The present study investigated the effects of SFN on anti-proliferation and G₂/M phase cell cycle arrest in cervical cancer cell lines (Cx, CxWJ, and HeLa). We found that cytotoxicity is associated with an accumulation of cells in the G₂/M phases of the cell-cycle. Treatment with SFN led to cell cycle arrest as well as the down-regulation of Cyclin B1 expression, but not of CDC2 expression. In addition, the effects of GADD45β gene activation in cell cycle arrest increase proportionally with the dose of SFN; however, mitotic delay and the inhibition of proliferation both depend on the dosage of SFN used to treat cancer cells. These results indicate that SFN may delay the development of cancer by arresting cell growth in the G₂/M phase via down-regulation of Cyclin B1 gene expression, dissociation of the cyclin B1/CDC2 complex, and up-regulation of GADD45β proteins. PMID:27626412

  3. Alantolactone induces apoptosis of human cervical cancer cells via reactive oxygen species generation, glutathione depletion and inhibition of the Bcl-2/Bax signaling pathway

    PubMed Central

    JIANG, YAN; XU, HANJIE; WANG, JIAFEI

    2016-01-01

    Alantolactone is the active ingredient in frankincense, and is extracted from the dry root of elecampane. It has a wide variety of uses, including as an insect repellent, antibacterial, antidiuretic, analgesic and anticancer agent. In addition, alantolactone induces apoptosis of human cervical cancer cells, however, its mechanism of action remains to be elucidated. Therefore, the present study investigated whether alantolactone was able to induce apoptosis of human cervical cancer cells, and its potential mechanisms of action were analyzed. Treatment of HeLa cells with alantolactone (0, 10, 20, 30, 40, 50 and 60 µM) for 12 h significantly inhibited growth in a dose-dependent manner. Cells treated with 30 µM of alantolactone for 0, 3, 6 and 12 h demonstrated marked induction of apoptosis in a time-dependent manner. Treatment of HeLa cells with 30 µM of alantolactone for 0, 3, 6 and 12 h significantly induced the generation of reactive oxygen species (ROS) and inhibited glutathione (GSH) production in HeLa cells in a dose-dependent manner. Alantolactone additionally markedly inhibited the Bcl-2/Bax signaling pathway in HeLa cells. Therefore, administration of alantolactone induced apoptosis of human cervical cancer cells via ROS generation, GSH depletion and inhibition of the Bcl-2/Bax signaling pathway. PMID:27313767

  4. Anticancer activity of synthetic bis(indolyl)methane-ortho-biaryls against human cervical cancer (HeLa) cells.

    PubMed

    Jamsheena, Vellekkatt; Shilpa, Ganesan; Saranya, Jayaram; Harry, Nissy Ann; Lankalapalli, Ravi Shankar; Priya, Sulochana

    2016-03-01

    Bis(indolyl)methane appended biaryls were designed, synthesized and evaluated in human cervical cancer cell lines (HeLa) for their anticancer activities and compared against normal rat cardiac myoblasts (H9C2) cells. Compounds 1-12 were synthesized, with variations in one of the phenyl unit, in a single step by condensation of biaryl-2-carbaldehydes with indole in the presence of para-toluenesulfonic acid. Compound 1 exhibited a GI50 value of 11.00 ± 0.707 μM and the derivatives, compounds 4 and 11 showed a GI50 value of 8.33 ± 0.416 μM and 9.13 ± 0.177 μM respectively in HeLa cells and was found to be non-toxic to H9C2 cells up to 20 μM. Furthermore, compounds 1, 4 and 11 induced caspase dependent cellular apoptosis in a concentration-dependent manner, reduced mitochondrial membrane potential, inhibited the cell migration and downregulated the production of MMP-2 and MMP-9 in HeLa cells.

  5. 8-p-Hdroxybenzoyl Tovarol Induces Paraptosis Like Cell Death and Protective Autophagy in Human Cervical Cancer HeLa Cells.

    PubMed

    Zhang, Cui; Jiang, Yingnan; Zhang, Jin; Huang, Jian; Wang, Jinhui

    2015-01-01

    8-p-Hdroxybenzoyl tovarol (TAW) is a germacrane-type sesquiterpenoid that can be isolated from the roots of Ferula dissecta (Ledeb.) Ledeb. In this study, the growth inhibitory effects induced by TAW were screened on some types of tumor cells, and the mechanism was investigated on TAW-induced growth inhibition, including paraptosis and autophagy in human cervical cancer HeLa cells. TAW-induced paraptosis involved extensive cytoplasmic vacuolization in the absence of caspase activation. Additionally, TAW evoked cell paraptotic death mediated by endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Autophagy induced by TAW was found to antagonize paraptosis in HeLa cells. This effect was enhanced by rapamycin and suppressed by the autophagy inhibitor, 3-methyladenine (3MA). Loss of beclin 1 (an autophagic regulator) function led to promote ER stress. Taken together, these results suggest that TAW induces paraptosis like cell death and protective autophagy in HeLa cells, which would provide a new clue for exploiting TAW as a promising agent for the treatment of cervical cancer.

  6. Breast, Cervical Cancer More Deadly in Developing Nations: Report

    MedlinePlus

    ... More Health News on: Breast Cancer Cervical Cancer Health Disparities Recent Health News Related MedlinePlus Health Topics Breast Cancer Cervical Cancer Health Disparities About MedlinePlus Site Map FAQs Contact Us Get ...

  7. Toxicity of Raw and Purified Single-Walled Carbon Nanotubes in Rat's Lung Epithelial and Cervical Cancer Cells.

    PubMed

    Goornavar, Virupaxi; Biradar, Santoshkumar; Ezeagwu, Christian; Ezeagwu, Dexter; Hall, Joseph C; Ramesh, Govindarajan T

    2015-03-01

    The increased applications of carbon nanotubes in the field of drug delivery, bioimaging and biosensors demand nanotubes to be of highest purity, free from metallic impurities and amorphous carbon. All of these sectors require a profound investigation about the toxic effects on human and the environment. Many attempts have been made to purify and surface modify the carbon nanotubes, however a detailed study on the raw and purified material has yet to be conducted. Here we present the toxicity studies of raw and the purified single-walled carbon nanotubes in rat's lung epithelial cell and cervical cancer cells (HeLa). These cells were treated with increasing concentration of 0.5 µg/mL to 50 µg/mL and the various biocompatibility assays were performed. The results showed an increased cell death with purified single-walled carbon nanotubes followed by the depletion of antioxidant levels and activation of the caspase cascade at a rapid rate compared to raw single-walled carbon nanotubes. This suggests that purified single walled carbon nanotubes are more toxic to the cells and exhibit ultra-fine particulate matter like toxicity.

  8. Cytotoxic effects of native and recombinant frutalin, a plant galactose-binding lectin, on HeLa cervical cancer cells.

    PubMed

    Oliveira, Carla; Nicolau, Ana; Teixeira, José A; Domingues, Lucília

    2011-01-01

    Frutalin is the α-D-galactose-binding lectin isolated from breadfruit seeds. Frutalin was obtained from two different sources: native frutalin was purified from its natural origin, and recombinant frutalin was produced and purified from Pichia pastoris. This work aimed to study and compare the effect of native and recombinant frutalin on HeLa cervical cancer cells proliferation and apoptosis. Furthermore, the interaction between frutalin and the HeLa cells was investigated by confocal microscopy. Despite having different carbohydrate-binding affinities, native and recombinant frutalin showed an identical magnitude of cytotoxicity on HeLa cells growth (IC₅₀~100 μg/mL) and equally induced cell apoptosis. The interaction studies showed that both lectins were rapidly internalised and targeted to HeLa cell's nucleus. Altogether, these results indicate that frutalin action is not dependent on its sugar-binding properties. This study provides important information about the bioactivity of frutalin and contributes to the understanding of the plant lectins cytotoxic activity.

  9. Pseudolaric acid B exerts antitumor activity via suppression of the Akt signaling pathway in HeLa cervical cancer cells.

    PubMed

    Li, Mingqun; Hong, Li

    2015-08-01

    Pseudolaric acid B (PAB) is a diterpene acid isolated from the bark of the root and trunk of Pseudolarix kaempferi Gordon (Pinaceae), which has demonstrated cytotoxic effects against various types of cancer. However, the mechanisms underlying the anticancer effects of PAB have remained to be elucidated. In the present study, the effects of PAB on the viability and apoptosis of HeLa cells were investigated by MTT assay, flow cytometric analysis of Annexin V-fluorescein isothiocyanate/propidium iodide staining, Rhodamine 123 staining and western blot analysis. The results demonstrated that PAB had antiproliferative and apoptosis-inducing effects on HeLa cells. PAB markedly inhibited HeLa cell viability in a time- and concentration-dependent manner. Flow cytometric analysis indicated that PAB induced apoptosis in HeLa cells in a dose-dependent manner. Treatment with PAB suppressed the expression of anti-apoptotic factor B cell lymphoma-2, and promoted the expression of pro-apoptotic factor Bcl-2-associated X protein. In addition, PAB induced an increase in Caspase-3 activity and loss of mitochondrial membrane potential, suggesting that this apoptosis may be mediated by mitochondrial pathways. Furthermore, the results of western blot analysis indicated that PAB was able to reduce Akt phosphorylation, thereby inhibiting the Akt pathway. These results suggested that PAB inhibited cell proliferation and induced apoptosis in HeLa cells, and that the anti-tumor effects of PAB were associated with inhibition of the Akt pathway. In conclusion, the results of the present study suggested that PAB may represent a novel therapeutic strategy for the treatment of human cervical cancer. However, additional studies are required to investigate the underlying apoptotic mechanisms.

  10. Long noncoding RNA-EBIC promotes tumor cell invasion by binding to EZH2 and repressing E-cadherin in cervical cancer.

    PubMed

    Sun, Ning-xia; Ye, Chen; Zhao, Qian; Zhang, Qing; Xu, Chen; Wang, Shao-bing; Jin, Zhi-jun; Sun, Shu-han; Wang, Fang; Li, Wen

    2014-01-01

    In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to play key roles in tumorgenesis. However, the contributions of lncRNAs to cervical cancer (CC) remain largely unknown. In this study, differentially expressed lncRNAs and mRNAs in cervical cancer and paired peritumoral tissues were detected by transcriptome microarray analysis. We found 708 probe sets of lncRNAs increased and 836 probe sets decreased in CC tissues, while 1288 mRNA differential probe sets increased and 901 mRNA probe sets decreased. The results were validated by quantitative real-time polymerase chain reaction (qPCR). Then, we found a specific differentially expressed lncRNA can physically bind to enhancer of zeste homolog2 (EZH2) by using RNA immunoprecipitation. We termed it as EZH2-binding lncRNA in cervical cancer [lncRNA-EBIC]. Wound healing assays and Matrigel invasion assays were used to determine the function of this lncRNA by silencing it. We observed that the migration and invasion of cervical cancer cells in vitro were inhibited upon suppression of lncRNA-EBIC by siRNA. We also found that the association between lncRNA-EBIC and EZH2 was required for the repression of E-cadherin, which was a key molecular in the metastasis of cervical cancer. Conclusion: These results demonstrated that lncRNA-EBIC was an oncogenic lncRNA, which could promote tumor cell invasion in CC by binding to EZH2 and inhibiting E-cadherin expression.

  11. Long Noncoding RNA-EBIC Promotes Tumor Cell Invasion by Binding to EZH2 and Repressing E-Cadherin in Cervical Cancer

    PubMed Central

    Zhao, Qian; Zhang, Qing; Xu, Chen; Wang, Shao-bing; Jin, Zhi-jun; Sun, Shu-han; Wang, Fang; Li, Wen

    2014-01-01

    In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to play key roles in tumorgenesis. However, the contributions of lncRNAs to cervical cancer (CC) remain largely unknown. In this study, differentially expressed lncRNAs and mRNAs in cervical cancer and paired peritumoral tissues were detected by transcriptome microarray analysis. We found 708 probe sets of lncRNAs increased and 836 probe sets decreased in CC tissues, while 1288 mRNA differential probe sets increased and 901 mRNA probe sets decreased. The results were validated by quantitative real-time polymerase chain reaction (qPCR). Then, we found a specific differentially expressed lncRNA can physically bind to enhancer of zeste homolog2 (EZH2) by using RNA immunoprecipitation. We termed it as EZH2-binding lncRNA in cervical cancer [lncRNA-EBIC]. Wound healing assays and Matrigel invasion assays were used to determine the function of this lncRNA by silencing it. We observed that the migration and invasion of cervical cancer cells in vitro were inhibited upon suppression of lncRNA-EBIC by siRNA. We also found that the association between lncRNA-EBIC and EZH2 was required for the repression of E-cadherin, which was a key molecular in the metastasis of cervical cancer. Conclusion These results demonstrated that lncRNA-EBIC was an oncogenic lncRNA, which could promote tumor cell invasion in CC by binding to EZH2 and inhibiting E-cadherin expression. PMID:25007342

  12. Osmotic shrinkage of human cervical cancer cells induces an extracellular Cl- -dependent nonselective cation channel, which requires p38 MAPK.

    PubMed

    Shen, Meng-Ru; Chou, Cheng-Yang; Hsu, Keng-Fu; Ellory, J Clive

    2002-11-29

    This study is to integrate a functional role of nonselective cation (NSC) channels into a model of volume regulation on osmotic shrinkage for human cervical cancer cells. Application of a hypertonic solution (400 mosm kg(-1)) induced cell shrinkage, which was accompanied by a 7-fold increase of inward currents at -80 mV from -4.1 +/- 0.4 pA pF(-1) to -29 +/- 1.1 pA pF(-1) (n = 36, p < 0.001). There is a good correlation of channel activity and cell volume changes. Replacement of bath Na(+) by K(+), Cs(+), Li(+), or Rb(+) did not affect the stimulated inward current significantly, but replacement by Ca(2+), Ba(2+), or the impermeable cation N-methyl-d-glucamine abolished the inward current; this demonstrates that the shrinkage-induced currents discriminate poorly between monovalent cations but are not carried by divalent cations. Replacement of extracellular Cl(-) by gluconate abolished the shrinkage-induced currents in a concentration-dependent manner without changing the reversal potential. Gadolinium (Gd(3+)) inhibited the stimulated current, whereas bumetanide and amiloride had no inhibitory effect. Cell shrinkage triggered mitogen-activated protein (MAP) kinase cascades leading to the activation of MAP/extracellular signal-regulated kinase 1/2 (ERK1/2) kinase (MEK1/2), and p38 kinase. Interference with p38 MAPK by either the specific inhibitor (SB202190), or a dominant-negative mutant profoundly suppressed the activation of the shrinkage-induced NSC channels. In contrast, the regulatory mechanism of shrinkage-induced NSC channels was independent of the volume-responsive MEK1/2 signaling pathway. More importantly, the cell volume response to hypertonicity was inhibited significantly in p38 dominant-negative mutant or by SB202190. Therefore, p38 MAPK is critically involved in the activation of a shrinkage-induced NSC channel, which plays an important role in the volume regulation of human cervical cancer cells. PMID:12226098

  13. [Cervical cancer: particularities in HIV patients].

    PubMed

    Grellier, Noémie; Quéro, Laurent

    2014-11-01

    Cervical cancer is the second most common cancer in women worldwide. It represents one of the most challenging public health problems in developing countries. HIV-infected women have a higher risk of cervical cancer which is an AIDS defining cancer. Cervical cancer treatment in HIV-infected and non-infected women is the same. HIV naive women must be prescribed combination antiretroviral therapy at the moment of HIV cancer diagnosis. A close collaboration between oncologist and infectiologist is mandatory to optimize HIV treatment. Among HIV-infected women, PAP-smear screening for early detection and treatment of precancerous cervical lesions is recommended. HPV vaccination is also recommended with the same efficacy and safety profile as the general population.

  14. EM23, a natural sesquiterpene lactone, targets thioredoxin reductase to activate JNK and cell death pathways in human cervical cancer cells.

    PubMed

    Shao, Fang-Yuan; Wang, Sheng; Li, Hong-Yu; Chen, Wen-Bo; Wang, Guo-Cai; Ma, Dong-Lei; Wong, Nai Sum; Xiao, Hao; Liu, Qiu-Ying; Zhou, Guang-Xiong; Li, Yao-Lan; Li, Man-Mei; Wang, Yi-Fei; Liu, Zhong

    2016-02-01

    Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants and found to have potential anticancer activities. However, the intracellular molecular targets of SLs and the underlying molecular mechanisms have not been well elucidated. In this study, we observed that EM23, a natural SL, exhibited anti-cancer activity in human cervical cancer cell lines by inducing apoptosis as indicated by caspase 3 activation, XIAP downregulation and mitochondrial dysfunction. Mechanistic studies indicated that EM23-induced apoptosis was mediated by reactive oxygen species (ROS) and the knockdown of thioredoxin (Trx) or thioredoxin reductase (TrxR) resulted in a reduction in apoptosis. EM23 attenuated TrxR activity by alkylation of C-terminal redox-active site Sec498 of TrxR and inhibited the expression levels of Trx/TrxR to facilitate ROS accumulation. Furthermore, inhibition of Trx/TrxR system resulted in the dissociation of ASK1 from Trx and the downstream activation of JNK. Pretreatment with ASK1/JNK inhibitors partially rescued cells from EM23-induced apoptosis. Additionally, EM23 inhibited Akt/mTOR pathway and induced autophagy, which was observed to be proapoptotic and mediated by ROS. Together, these results reveal a potential molecular mechanism for the apoptotic induction observed with SL compound EM23, and emphasize its putative role as a therapeutic agent for human cervical cancer. PMID:26758418

  15. Targeted treatments for cervical cancer: a review.

    PubMed

    Peralta-Zaragoza, Oscar; Bermúdez-Morales, Víctor Hugo; Pérez-Plasencia, Carlos; Salazar-León, Jonathan; Gómez-Cerón, Claudia; Madrid-Marina, Vicente

    2012-01-01

    Cervical cancer is the second most common cause of cancer death in women worldwide and the development of new diagnosis, prognostic, and treatment strategies merits special attention. Although surgery and chemoradiotherapy can cure 80%-95% of women with early stage cancer, the recurrent and metastatic disease remains a major cause of cancer death. Many efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent decades, research on treatment strategies has proposed several options, including the role of HPV E6 and E7 oncogenes, which are retained and expressed in most cervical cancers and whose respective oncoproteins are critical to the induction and maintenance of the malignant phenotype. Other efforts have been focused on antitumor immunotherapy strategies. It is known that during the development of cervical cancer, a cascade of abnormal events is induced, including disruption of cellular cycle control, perturbation of antitumor immune response, alteration of gene expression, and deregulation of microRNA expression. Thus, in this review article we discuss potential targets for the treatment of cervical cancer associated with HPV infection, with special attention to immunotherapy approaches, clinical trials, siRNA molecules, and their implications as gene therapy strategies against cervical cancer development. PMID:23144564

  16. Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells

    PubMed Central

    Ying, Tsung-Ho; Lin, Chu-Liang; Lin, Chia-Liang; Hsueh, Jung-Tsung; Hsieh, Yi-Hsien

    2015-01-01

    The use of dietary bioactive compounds in chemoprevention can potentially reverse, suppress, or even prevent cancer progression. However, the effects of licochalcone A (LicA) on apoptosis and autophagy in cervical cancer cells have not yet been clearly elucidated. In this study, LicA treatment was found to significantly induce the apoptotic and autophagic capacities of cervical cancer cells in vitro and in vivo. MTT assay results showed dose- and time-dependent cytotoxicity in four cervical cancer cell lines treated with LicA. We found that LicA induced mitochondria-dependent apoptosis in SiHa cells, with decreasing Bcl-2 expression. LicA also induced autophagy effects were examined by identifying accumulation of Atg5, Atg7, Atg12 and microtubule-associated protein 1 light chain 3 (LC3)-II. Treatment with autophagy-specific inhibitors (3-methyladenine and bafilomycin A1) enhanced LicA-induced apoptosis. In addition, we suggested the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of mTOR pathway by LicA. Furthermore, the inhibition of PI3K/Akt by LY294002/si-Akt or of mTOR by rapamycin augmented LicA-induced apoptosis and autophagy. Finally, the in vivo mice bearing a SiHa xenograft, LicA dosed at 10 or 20 mg/kg significantly inhibited tumor growth. Our findings demonstrate the chemotherapeutic potential of LicA for treatment of human cervical cancer. PMID:26311737

  17. Prognosis of Cervical Cancer in the Era of Concurrent Chemoradiation from National Database in Korea: A Comparison between Squamous Cell Carcinoma and Adenocarcinoma

    PubMed Central

    Lee, Jung-Yun; Kim, Young Tae; Kim, Sunghoon; Lee, Boram; Lim, Myong Cheol; Kim, Jae-Weon; Won, Young-Joo

    2015-01-01

    In 1999, the National Cancer Institute issued a clinical advisory strongly touting the advantage of cisplatin-based chemoradiation (CCRT) for cervical cancer patients requiring radiation for their treatment. This study aimed to compare survival outcomes of cervical squamous cell carcinoma and adenocarcinoma before and after the advent of CCRT. Data were obtained from the Korea National Cancer Incidence Database for patients who were diagnosed with cervical cancers between 1993 and 2012. We compared survival according to histologic subtypes in cervical cancer patients diagnosed before (1993–1997), during (1998–2002), and after (2003–2012) the introduction of CCRT. A total of 80,766 patients were identified, including 64,531 (79.9%) women with squamous cell carcinomas and 7,265 (9.0%) with adenocarcinoma. With the introduction of CCRT, survival trends gradually increased in patients of both histologic subtypes with regional tumors. However, survival was significantly higher in squamous cell carcinoma than in adenocarcinoma patients regardless of treatment modalities (surgery alone, P < 0.001; surgery followed by CCRT, P < 0.001; or primary CCRT, P = 0.003). Multivariate analysis showed that adenocarcinoma was an independent negative prognostic factor for survival regardless of the time period (before CCRT, hazard ratio (HR) = 1.49; 95% confidence interval (CI), 1.37–1.62; after introduction of CCRT, HR = 1.40; 95% CI, 1.30–1.50). Although the survival of adenocarcinoma has improved after the introduction of CCRT, adenocarcinoma is still associated with worse overall survival compared to squamous cell carcinoma in the era of CCRT. PMID:26660311

  18. Development of therapeutic Au-methylene blue nanoparticles for targeted photodynamic therapy of cervical cancer cells.

    PubMed

    Yu, Jiashing; Hsu, Che-Hao; Huang, Chih-Chia; Chang, Po-Yang

    2015-01-14

    Photodynamic therapy (PDT) involves the cellular uptake of a photosensitizer (PS) combined with oxygen molecules and light at a specific wavelength to be able to trigger cancer cell death via the apoptosis pathway, which is less harmful and has less inflammatory side effect than necrosis. However, the traditional PDT treatment has two main deficiencies: the dark toxicity of the PS and the poor selectivity of the cellular uptake of PS between the target cells and normal tissues. In this work, methylene blue (MB), a known effective PS, combined with Au nanoparticles (NPs) was prepared using an intermolecular interaction between a polystyrene-alt-maleic acid (PSMA) layer on the Au NPs and MB. The Au@polymer/MB NPs produced a high quantum yield of singlet oxygen molecules, over 50% as much as that of free MB, when they were excited by a dark red light source at 660 nm, but without significant dark toxicity. Furthermore, transferrin (Tf) was conjugated on the Au@polymer/MB NPs via an EDC/NHS reaction to enhance the selectivity to HeLa cells compared to 3T3 fibroblasts. With a hand-held single laser treatment (32 mW/cm) for 4 min, the new Au@polymer/MB-Tf NPs showed a 2-fold enhancement of PDT efficiency toward HeLa cells over the use of free MB at 4 times dosage. Cellular staining examinations showed that the HeLa cells reacted with Au@polymer/MB-Tf NPs and the 660 nm light excitation triggered PDT, which caused the cells to undergo apoptosis ("programmed" cell death). We propose that applying this therapeutic Au@polymer/MB-Tf nanoagent is facile and safe for delivery and cancer cell targeting to simultaneously minimize side effects and accomplish a significant enhancement in photodynamic therapeutic efficiency toward next-generation nanomedicine development.

  19. [Induction chemotherapy for locally advanced cervical cancer].

    PubMed

    Morkhov, K Yu; Nechushkina, V M; Kuznetsov, V V

    2015-01-01

    The main methods of treatment for cervical cancer are surgery, radiotherapy or their combination. During past two decades chemotherapy are increasingly being used not only in patients with disseminated forms of this disease but also in patients undergoing chemoradiotherapy or as induction therapy. Possibilities of adjuvant chemotherapy for cervical cancer are being studied. According to A.D.Kaprin and V.V. Starinskiy in 2013 in Russia, 32% of patients with newly diagnosed cervical cancer underwent only radiation therapy, 32%--combined or complex treatment, 27.3%--only surgery, and just 8.7%--chemoradiotherapy. PMID:26087600

  20. Colposcopy and High Resolution Anoscopy in Screening For Anal Dysplasia in Patients With Cervical, Vaginal, or Vulvar Dysplasia or Cancer

    ClinicalTrials.gov

    2012-06-08

    Cervical Intraepithelial Neoplasia Grade 1; Cervical Intraepithelial Neoplasia Grade 2; Cervical Intraepithelial Neoplasia Grade 3; Recurrent Cervical Cancer; Recurrent Vaginal Cancer; Recurrent Vulvar Cancer; Stage 0 Cervical Cancer; Stage 0 Vaginal Cancer; Stage 0 Vulvar Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IV Vulvar Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer

  1. E6/E7 oncoproteins of high risk HPV-16 upregulate MT1-MMP, MMP-2 and MMP-9 and promote the migration of cervical cancer cells

    PubMed Central

    Zhu, Dingjun; Ye, Mei; Zhang, Wei

    2015-01-01

    Background: E6 and E7 of high risk human papillomavirus 16 (HPV16) were reported to correlate with the cervical cancer (CC). And the presence of matrix metalloproteinases (MMPs) has also been indicated to be associated with CC. Methods: The present study investigated the expression of MMPs (MT1-MMP, MMP-2 and MMP-9) in CC cells with HPV16-E6/E7 oncoprotein(s) negative or positive, and then determined the regulation of HPV16-E6/E7 oncoproteins on the expression of MMPs (MT1-MMP, MMP-2 and MMP-9) and the migration of cervical cancer Caski and SiHa cells with RNAi technology. Results: It was demonstrated that the overexpression or the knockdown of HPV16-E6/E7 promoted or reduced MT1-MMP, MMP-2 and MMP-9 in CC cells. And the HPV16-E6, -E7 or -E6E7 influenced the migration of CC cells. The overexpression or the knockdown of them promoted or inhibited the migration of C33A or Caski/SiHa cells. Moreover, the chemical inhibition of MMP-2 or MMP-9 significantly reduced the migration of CC Caski or SiHa cells. Conclusions: Our results demonstrated that the E6-HPV16 or E7-HPV16 promoted the activity of MMP-2/9, and contributed to the migration of cervical cells. PMID:26191191

  2. Cervical cancer: disease prevention and informational support.

    PubMed

    Schwartz, Lindsay Ashley

    2009-01-01

    Cervical cancer and Human Papillomavirus (HPV) are significant health care concerns for women worldwide. Globally, in 2006, cervical cancer remains the second most common cancer in women. Infection with high-risk strains of HPV is found to be present in approximately 99% of cervical cancer cases. The Supportive Care Framework developed by Fitch (2008) will serve as a guide to the paper. The need for informational support and disease prevention initiatives will be explored. Knowledge and awareness of HPV and its link to cervical cancer amongst the general population are low. Once women are made aware of the relationship between HPV and cervical cancer, they want more information on disease prevention, transmission, detection, treatment information, symptoms and risk for developing cancer. Evidence-based nursing interventions that focus on meeting the informational needs of women and increasing awareness of HPV and cervical cancer will be proposed. Information on HPV-prophylactic vaccines and Papanicolaou (PAP) screening as primary and secondary disease prevention strategies will be discussed.

  3. Unmet clinical needs in cervical cancer screening.

    PubMed

    Rao, Jianyu; Escobar-Hoyos, Luisa; Shroyer, Kenneth R

    2016-01-01

    Cancer rates worldwide are expected to increase disproportionally in coming decades relative to the projected increase in population, especially in the developing world. The general unavailability of the Pap test and the cost of the HPV test in the developing world have precluded the deployment of effective cervical cancer screening programs in many developing countries. Recent improvements in testing technology arise from a need to overcome the significant limitations of the Pap test and HPV test, but results require first-world technology and validation. Developing countries, where cervical cancer remains one of the most important causes of cancer death, have the greatest need for an affordable, easy-to-use, and highly reliable cancer screening method that can return a diagnosis through efficient laboratory analysis or, more easily, at a woman's point of care. While research, testing, and vaccine improvements in recent years continue to lower the incidence of cervical cancer in some developed countries such as the U.S., HPV testing research needs to do more than test for the presence of virus. The tests must determine the presence and progression of cervical disease. Tests should be more sensitive and specific than Pap tests and Pap-related tests, and should be accurate in more than 90 percent of cases. Tests also need to be low-cost, objective, and easy to perform so screening programs can be widely implemented in developing countries where the need for a better cervical cancer screening test is highest. Such tests may be available through the recent advances in specific biomarkers of cervical cancer and multiplex detection technologies. Development of the next generation of cervical cancer tests that are more specific, sensitive, and informative than the traditional Pap or HPV test will make a significant impact on the reduction of cervical cancer worldwide.

  4. Emodin induces apoptosis of human cervical cancer hela cells via intrinsic mitochondrial and extrinsic death receptor pathway

    PubMed Central

    2013-01-01

    Background Emodin is a natural anthraquinone derivative isolated from the Rheum palmatum L. Aim: The aim of the present study was to investigate the effect of emodin on the apoptosis of the human cervical cancer line HeLa and to identify the mechanisms involved. Methods Relative cell viability was assessed by MTT assay after treatment with emodin. Cell apoptosis was detected with TUNEL, Hoechst 33342 staining and quantified with flow cytometry using annexin FITC-PI staining. Results The percentage of apoptotic cells was 0.8, 8.2, 22.1, and 43.7%, respectively. The mRNA levels of Caspase-9, -8 and −3 detected by Real-time PCR after treatment with emodin were significantly increased. Emodin increased the protein levels of Cytochome c, Apaf-1, Fas, FasL, and FADD but decreased the protein levels of Pro-caspase-9, Pro-caspase-8 and Pro-caspase-3. Conclusion We conclude that the emodin inhibited HeLa proliferation by inducing apoptosis through the intrinsic mitochondrial and extrinsic death receptor pathways. PMID:23866157

  5. The aqueous extract of Ficus religiosa induces cell cycle arrest in human cervical cancer cell lines SiHa (HPV-16 Positive) and apoptosis in HeLa (HPV-18 positive).

    PubMed

    Choudhari, Amit S; Suryavanshi, Snehal A; Kaul-Ghanekar, Ruchika

    2013-01-01

    Natural products are being extensively explored for their potential to prevent as well as treat cancer due to their ability to target multiple molecular pathways. Ficus religiosa has been shown to exert diverse biological activities including apoptosis in breast cancer cell lines. In the present study, we report the anti-neoplastic potential of aqueous extract of F. religiosa (FRaq) bark in human cervical cancer cell lines, SiHa and HeLa. FRaq altered the growth kinetics of SiHa (HPV-16 positive) and HeLa (HPV-18 positive) cells in a dose-dependent manner. It blocked the cell cycle progression at G1/S phase in SiHa that was characterized by an increase in the expression of p53, p21 and pRb proteins with a simultaneous decrease in the expression of phospho Rb (ppRb) protein. On the other hand, in HeLa, FRaq induced apoptosis through an increase in intracellular Ca(2+) leading to loss of mitochondrial membrane potential, release of cytochrome-c and increase in the expression of caspase-3. Moreover, FRaq reduced the migration as well as invasion capability of both the cervical cancer cell lines accompanied with downregulation of MMP-2 and Her-2 expression. Interestingly, FRaq reduced the expression of viral oncoproteins E6 and E7 in both the cervical cancer cell lines. All these data suggest that F. religiosa could be explored for its chemopreventive potential in cervical cancer. PMID:23922932

  6. The Aqueous Extract of Ficus religiosa Induces Cell Cycle Arrest in Human Cervical Cancer Cell Lines SiHa (HPV-16 Positive) and Apoptosis in HeLa (HPV-18 Positive)

    PubMed Central

    Choudhari, Amit S.; Suryavanshi, Snehal A.; Kaul-Ghanekar, Ruchika

    2013-01-01

    Natural products are being extensively explored for their potential to prevent as well as treat cancer due to their ability to target multiple molecular pathways. Ficus religiosa has been shown to exert diverse biological activities including apoptosis in breast cancer cell lines. In the present study, we report the anti-neoplastic potential of aqueous extract of F. religiosa (FRaq) bark in human cervical cancer cell lines, SiHa and HeLa. FRaq altered the growth kinetics of SiHa (HPV-16 positive) and HeLa (HPV-18 positive) cells in a dose-dependent manner. It blocked the cell cycle progression at G1/S phase in SiHa that was characterized by an increase in the expression of p53, p21 and pRb proteins with a simultaneous decrease in the expression of phospho Rb (ppRb) protein. On the other hand, in HeLa, FRaq induced apoptosis through an increase in intracellular Ca2+ leading to loss of mitochondrial membrane potential, release of cytochrome-c and increase in the expression of caspase-3. Moreover, FRaq reduced the migration as well as invasion capability of both the cervical cancer cell lines accompanied with downregulation of MMP-2 and Her-2 expression. Interestingly, FRaq reduced the expression of viral oncoproteins E6 and E7 in both the cervical cancer cell lines. All these data suggest that F. religiosa could be explored for its chemopreventive potential in cervical cancer. PMID:23922932

  7. MALAT1-miR-124-RBG2 axis is involved in growth and invasion of HR-HPV-positive cervical cancer cells.

    PubMed

    Liu, Shikai; Song, Lili; Zeng, Saitian; Zhang, Liang

    2016-01-01

    Metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1) is a large, infrequently spliced non-coding RNA aberrantly expressed in cervical cancer. But the molecular mechanisms of its oncogenic role are still not quite clear. The present study explored whether there is a competing endogenous RNAs (ceRNAs) mechanism involved in the oncogenic effect of MALAT1. MALAT1 expression was firstly verified in high-risk human papillomavirus (HR-HPV)-positive tumor tissues and cell lines. Its regulation over miR-124 and the downstream target of miR-124 in regulation of growth, invasion, and apoptosis of the cancer cells are also studied. Findings of this study confirmed higher MALAT1 expression in HR-HPV (+) cervical cancer. Knockdown of endogenous MALAT1 significantly reduced cell growth rate and invasion and increased cell apoptosis of Hela and siHa cells. Besides, knockdown of MALAT1 increased the expression of miRNA-124, while ectopic expression of miR-124 decreased MALAT1 expression. In addition, we also verified a direct interaction between miR-124 and 3'UTR of GRB2. MALAT1 can indirectly modulate GRB2 expression via competing miR-124. Knockdown of GRB2 reduced cell invasion and increased cell apoptosis. In conclusion, MALAT1 can promote HR-HPV (+) cancer cell growth and invasion at least partially through the MALAT1-miR-124-RBG2 axis. This finding might provide some useful evidence about the lncRNA interaction regulatory network in tumorigenesis cervical cancer.

  8. Mechanical trapping of the nucleus on micropillared surfaces inhibits the proliferation of vascular smooth muscle cells but not cervical cancer HeLa cells.

    PubMed

    Nagayama, Kazuaki; Hamaji, Yumi; Sato, Yuji; Matsumoto, Takeo

    2015-07-16

    The interaction between cells and the extracellular matrix on a topographically patterned surface can result in changes in cell shape and many cellular functions. In the present study, we demonstrated the mechanical deformation and trapping of the intracellular nucleus using polydimethylsiloxane (PDMS)-based microfabricated substrates with an array of micropillars. We investigated the differential effects of nuclear deformation on the proliferation of healthy vascular smooth muscle cells (SMCs) and cervical cancer HeLa cells. Both types of cell spread normally in the space between micropillars and completely invaded the extracellular microstructures, including parts of their cytoplasm and their nuclei. We found that the proliferation of SMCs but not HeLa cells was dramatically inhibited by cultivation on the micropillar substrates, even though remarkable deformation of nuclei was observed in both types of cells. Mechanical testing with an atomic force microscope and a detailed image analysis with confocal microscopy revealed that SMC nuclei had a thicker nuclear lamina and greater expression of lamin A/C than those of HeLa cells, which consequently increased the elastic modulus of the SMC nuclei and their nuclear mechanical resistance against extracellular microstructures. These results indicate that the inhibition of cell proliferation resulted from deformation of the mature lamin structures, which might be exposed to higher internal stress during nuclear deformation. This nuclear stress-induced inhibition of cell proliferation occurred rarely in cancer cells with deformable nuclei.

  9. Mechanical trapping of the nucleus on micropillared surfaces inhibits the proliferation of vascular smooth muscle cells but not cervical cancer HeLa cells.

    PubMed

    Nagayama, Kazuaki; Hamaji, Yumi; Sato, Yuji; Matsumoto, Takeo

    2015-07-16

    The interaction between cells and the extracellular matrix on a topographically patterned surface can result in changes in cell shape and many cellular functions. In the present study, we demonstrated the mechanical deformation and trapping of the intracellular nucleus using polydimethylsiloxane (PDMS)-based microfabricated substrates with an array of micropillars. We investigated the differential effects of nuclear deformation on the proliferation of healthy vascular smooth muscle cells (SMCs) and cervical cancer HeLa cells. Both types of cell spread normally in the space between micropillars and completely invaded the extracellular microstructures, including parts of their cytoplasm and their nuclei. We found that the proliferation of SMCs but not HeLa cells was dramatically inhibited by cultivation on the micropillar substrates, even though remarkable deformation of nuclei was observed in both types of cells. Mechanical testing with an atomic force microscope and a detailed image analysis with confocal microscopy revealed that SMC nuclei had a thicker nuclear lamina and greater expression of lamin A/C than those of HeLa cells, which consequently increased the elastic modulus of the SMC nuclei and their nuclear mechanical resistance against extracellular microstructures. These results indicate that the inhibition of cell proliferation resulted from deformation of the mature lamin structures, which might be exposed to higher internal stress during nuclear deformation. This nuclear stress-induced inhibition of cell proliferation occurred rarely in cancer cells with deformable nuclei. PMID:26054426

  10. Laparoscopic Fertility Sparing Management of Cervical Cancer

    PubMed Central

    Facchini, Chiara; Rapacchia, Giuseppina; Montanari, Giulia; Casadio, Paolo; Pilu, Gianluigi; Seracchioli, Renato

    2014-01-01

    Fertility can be preserved after conservative cervical surgery. We report on a 29-year-old woman who was obese, para 0, and diagnosed with cervical insufficiency at the first trimester of current pregnancy due to a previous trachelectomy. She underwent laparoscopic transabdominal cervical cerclage (LTCC) for cervical cancer. The surgery was successful and she was discharged two days later. The patient underwent a caesarean section at 38 weeks of gestation. Laparoscopic surgery is a minimally invasive approach associated with less pain and faster recovery, feasible even in obese women. PMID:24696772

  11. Epidemiology of cervical cancer in Colombia.

    PubMed

    Muñoz, Nubia; Bravo, Luis Eduardo

    2012-10-01

    Worldwide, cervical cancer is the third most common cancer in women, and the first or second most common in developing countries. Cervical cancer remains in Colombia the first cause of cancer mortality and the second cause of cancer incidence among women, despite the existence of screening programs during the last 3 decades. Bucaramanga, Manizales and Cali reported rates around 20 per 100,000and Pasto 27 per 100,000. The Cali cancer registry has reported a progressive decrease in the age standardized incidence and mortality rates of cervical cancer over the past 40 years. Reasons for the decline in incidence and mortality of cervical cancer are multiple and probably include: improvement in socio-economic conditions, decrease in parity rates and some effect of screening programs. Human papilloma Virus is the main cause of cervical cancer, HPV natural history studies have now revealed that HPVs are the commonest of the sexually transmitted infections in most populations. Most HPV exposures result in spontaneous clearance without clinical manifestations and only a small fraction of the infected persons, known as chronic or persistent carriers, will retain the virus and progress to precancerous and cancer. HPV 16 and 18 account for 70% of cervical cancer and the 8 most common types. (HPV 16, 18, 45, 33, 31, 52, 58 and 35) account for about 90% of cervical cancer. Case-control studies also allowed the identification of the following cofactors that acting together with HPV increase the risk of progression from HPV persistent infection to cervical cancer: tobacco, high parity, long term use of oral contraceptives and past infections with herpes simplex type 2 and Chlamydia trachomatis. The demonstration that infection with certain types of human papillomavirus (HPV) is not only the main cause but also a necessary cause of cervical cancer has led to great advances in the prevention of this disease on two fronts: (i) Primary prevention by the use of prophylactic HPV

  12. MicroRNA-373 functions as an oncogene and targets YOD1 gene in cervical cancer

    SciTech Connect

    Wang, Luo-Qiao; Zhang, Yue; Yan, Huan; Liu, Kai-Jiang Zhang, Shu

    2015-04-10

    miR-373 was reported to be elevated in several tumors; however, the role of miR-373 in cervical cancer has not been investigated. In this study we aimed to investigate the role of miR-373 in tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-373 was investigated using real-time reverse transcription-polymerase chain reaction assay in 45 cervical specimens and cervical cancer cell lines. The role of miR-373 in tumorigenicity of cervical cancer cells was assessed by cell proliferation, colony formation in vitro as well as tumor growth assays in vivo with the overexpression of miR-373 or gene silencing. The functional target gene of miR-373 in cervical cancer cells was identified using integrated bioinformatics analysis, gene expression arrays, and luciferase assay. We founded that the expression of miR-373 is upregulated in human cervical cancer tissues and cervical carcinoma cell lines when compared to the corresponding noncancerous tissues. Ectopic overexpression of miR-373 in human cervical cancer cells promoted cell growth in vitro and tumorigenicity in vivo, whereas silencing the expression of miR-373 decreased the rate of cell growth. YOD1 was identified as a direct and functional target of miR-373 in cervical cancer cells. Expression levels of miR-373 were inversely correlated with YOD1 levels in human cervical cancer tissues. RNAi-mediated knockdown of YOD1 phenocopied the proliferation-promoting effect of miR-373. Moreover, overexpression of YOD1 abrogated miR-373-induced proliferation of cervical cancer cells. These results demonstrate that miR-373 increases proliferation by directly targeting YOD1, a new potential therapeutic target in cervical cancer. - Highlights: • The expression of miR-373 is upregulated in human cervical cancer tissues. • miR-373 effects as oncogenic miRNA in cervical cancer in vitro and in vivo. • miR-373 increases proliferation of cervical cancer cells by directly targeting YOD1.

  13. Epidemiology and Early Detection of Cervical Cancer.

    PubMed

    Hillemanns, Peter; Soergel, Phillip; Hertel, Hermann; Jentschke, Matthias

    2016-01-01

    The new German S3 guideline 'Prevention of Cervical Cancer' published in 2016 is based on the latest available evidence about cervical cancer screening and treatment of cervical precancer. Large randomized controlled trials indicate that human papillomavirus (HPV)-based screening may provide better protection against cervical cancer than cytology alone through improved detection of premalignant disease in the first screening round prior to progression. Therefore, women aged 30 years and older should preferably be screened with HPV testing every 3-5 years (cytology alone every 2 years is an acceptable alternative). Co-testing is not recommended. Screening should start at 25 years using cytology alone every 2 years. The preferred triage test after a positive HPV screening test is cytology. Women positive for HPV 16 and HPV 18 should receive immediate colposcopy. Another alternative triage method is p16/Ki-67 dual stain cytology. The mean yearly participation rate in Germany is between 45 and 50%. Offering devices for HPV self-sampling has the potential to increase participation rates in those women who are at higher risk of developing cervical cancer. Regarding primary prevention, the 9-valent vaccine may provide protection against up to 85% of cervical intraepithelial neoplasia (CIN) 3 and 90% of cervical cancer, and is available in Europe as a 2-dose schedule from May 2016. PMID:27614953

  14. [Screening for cervical and breast cancer].

    PubMed

    Wilm, J; Schüler-Toprak, S; Ortmann, O

    2016-09-01

    Screening programs for cervical cancer and breast cancer lead to a clear reduction of mortality. Starting in 2018 screening for cervical cancer will be structured as an organized program as already exists for breast cancer. In future screening for cervical cancer will be primarily performed by human papillomavirus (HPV) testing at intervals of 5 years while cytological examination (Pap smear) will also be available as an additional or alternative procedure. For breast cancer screening in Germany an annual clinical examination with palpation and mammography screening at 2‑year intervals is provided for women aged between 50 and 69 years. In Germany only approximately 50 % of invited women have used the opportunity to participate in screening in recent years. Weighing the benefits against the harms of cancer screening programs is always important in the process of evaluation of different strategies. PMID:27577734

  15. Cervical cancer: screening and therapeutic perspectives.

    PubMed

    Sankaranarayanan, Rengaswamy; Thara, Somanathan; Esmy, Pulikottil Okkuru; Basu, Partha

    2008-01-01

    Cervical cancer is a major cause of mortality and premature death among women in their most productive years in low- and medium-resourced countries in Asia, Africa and Latin America, despite the fact that it is an eminently preventable cancer. While cytology screening programmes have resulted in a substantial reduction of cervical cancer mortality in developed countries, they have been shown to have a wide range of sensitivity in most routine settings including in developing countries. Although liquid-based cytology improves sample adequacy, claims on improved sensitivity remain controversial. Human papillomavirus testing is more sensitive than cytology, but whether this gain represents protection against future cervical cancer is not clear. Recently, in a randomized trial, the use of visual inspection with 4% acetic acid was shown to reduce cervical cancer incidence and mortality. Cryotherapy and large loop excision of the transformation zone are effective and safe treatment methods for cervical intraepithelial neoplasia. The clinical stage of cancer is the single most important prognostic factor and should be carefully evaluated in choosing optimal treatment between surgery and radiotherapy, with or without chemotherapy. At the public health level, health care infrastructure, affordability and capacity for initiating and sustaining vaccination and screening programmes are critical factors in cervical cancer control. On the other hand, an informed practitioner can utilize the multiple opportunities in routine primary care interactions for prevention, screening, early detection and prompt referral for treatment. PMID:18685274

  16. Nanoquinacrine induced apoptosis in cervical cancer stem cells through the inhibition of hedgehog-GLI1 cascade: Role of GLI-1.

    PubMed

    Nayak, Anmada; Satapathy, Shakti Ranjan; Das, Dipon; Siddharth, Sumit; Tripathi, Neha; Bharatam, Prasad V; Kundu, ChanakyaNath

    2016-01-01

    To improve the pharmacokinetics and to study the anti-cervical cancer and anti-stem cells (CSCs) mechanism of Quinacrine (QC), a spherical nano particle of QC (i.e. NQC) was prepared and characterized. QC and NQC showed higher cytotoxicity in multiple cancer cells than the normal epithelial cells. NQC exhibited more toxicity in cervical cancer cells and its CSCs than QC. A dose-dependent decreased expression of Hedgehog-GLI (HH-GLI) components were noted in NQC treated HeLa cells and its CSCs. NQC increased the expressions of negatively regulated HH-GLI components (GSK3β, PTEN) and caused apoptosis in CSCs. Reduction of GLI1 at mRNA and promoter level were noted after NQC exposure. The expressions of HH-GLI components, GLI1 promoter activity and apoptosis were unaltered in NQC treated GLI1-knockdown cells. In silico, cell based and in vitro reconstitution assay revealed that NQC inhibit HH-GLI cascade by binding to the consensus sequence (5'GACCACCCA3') of GLI1 in GLI-DNA complex through destabilizing DNA-GLI1 complex. NQC reduced the tumors size and proliferation marker Ki-67 in an in vivo xenograft mice model. Thus, NQC induced apoptosis in cancers through inhibition of HH-GLI cascade by GLI1. Detail interaction of QC-DNA-GLI complex can pave path for anticancer drug design. PMID:26846872

  17. Nanoquinacrine induced apoptosis in cervical cancer stem cells through the inhibition of hedgehog-GLI1 cascade: Role of GLI-1

    PubMed Central

    Nayak, Anmada; Satapathy, Shakti Ranjan; Das, Dipon; Siddharth, Sumit; Tripathi, Neha; Bharatam, Prasad V.; Kundu, ChanakyaNath

    2016-01-01

    To improve the pharmacokinetics and to study the anti-cervical cancer and anti-stem cells (CSCs) mechanism of Quinacrine (QC), a spherical nano particle of QC (i.e. NQC) was prepared and characterized. QC and NQC showed higher cytotoxicity in multiple cancer cells than the normal epithelial cells. NQC exhibited more toxicity in cervical cancer cells and its CSCs than QC. A dose-dependent decreased expression of Hedgehog-GLI (HH-GLI) components were noted in NQC treated HeLa cells and its CSCs. NQC increased the expressions of negatively regulated HH-GLI components (GSK3β, PTEN) and caused apoptosis in CSCs. Reduction of GLI1 at mRNA and promoter level were noted after NQC exposure. The expressions of HH-GLI components, GLI1 promoter activity and apoptosis were unaltered in NQC treated GLI1-knockdown cells. In silico, cell based and in vitro reconstitution assay revealed that NQC inhibit HH-GLI cascade by binding to the consensus sequence (5′GACCACCCA3′) of GLI1 in GLI-DNA complex through destabilizing DNA-GLI1 complex. NQC reduced the tumors size and proliferation marker Ki-67 in an in vivo xenograft mice model. Thus, NQC induced apoptosis in cancers through inhibition of HH-GLI cascade by GLI1. Detail interaction of QC-DNA-GLI complex can pave path for anticancer drug design. PMID:26846872

  18. NIH Research Leads to Cervical Cancer Vaccine

    MedlinePlus

    ... Transmitted Diseases NIH Research Leads to Cervical Cancer Vaccine Past Issues / Fall 2008 Table of Contents For ... Douglas Lowy (left) and John Schiller developed the vaccine to prevent HPV infection in women, the cause ...

  19. Antiproliferative property of n-hexane and chloroform extracts of Anisomeles malabarica (L). R. Br. in HPV16-positive human cervical cancer cells

    PubMed Central

    Preethy, Christo Paul; Padmapriya, Ramamoorthy; Periasamy, Vaiyapuri Subbarayan; Riyasdeen, Anvarbatcha; Srinag, Suresh; Krishnamurthy, Hanumanthappa; Alshatwi, Ali Abdullah; Akbarsha, Mohammad Abdulkader

    2012-01-01

    Objectives: To find the efficacy of serial extracts of Anisomeles malabarica in inhibiting proliferation of and inducing apoptosis in human cervical cancer cells, SiHa and ME 180, that are HPV 16-positive. Materials and Methods: The whole plant was extracted in n-hexane, chloroform, ethyl acetate, n-butanol, methanol, and water. The cells were treated with the extracts at increasing concentrations to find the IC50, adopting MTT ([3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]) assay. Acridine orange (AO) and ethidium bromide (EB) and Hoechst 33258 staining were adopted to assess the mode of cell death, Annexin V-Cy3 staining to evaluate one of the early apoptotic features, JC-1 staining to assess the mitochondrial membrane depolarization, comet assay for DNA fragmentation, and cell cycle analysis for the distribution of cells after treatment. Results: n-Hexane and chloroform extracts were cytotoxic to the cervical cancer cells in dose- and duration-dependent manner. The cells that responded to the treatments revealed typical apoptotic features. Early features of apoptosis, phosphatidyl serine translocation and loss of mitochondrial trans-membrane potential, were observed in the treated cells, and comet assay revealed DNA damage. In the FACS analysis, the cells accumulated in the sub-G0/G1 phase of the cell cycle, except in n-hexane- and chloroform extract–treated SiHa cells at 24 h, which showed arrest in S- and G2/M phases. Conclusions: n-Hexane and chloroform extracts of A. malabarica inhibit proliferation of and induce death in HPV16-positive cervical cancer cells, mostly by apoptosis and to some extent by necrosis. PMID:22368413

  20. Selective silencing of gene target expression by siRNA expression plasmids in human cervical cancer cells.

    PubMed

    Peralta-Zaragoza, Oscar; De-la-O-Gómez, Faustino; Deas, Jessica; Fernández-Tilapa, Gloria; Fierros-Zárate, Geny Del Socorro; Gómez-Cerón, Claudia; Burguete-García, Ana; Torres-Poveda, Kirvis; Bermúdez-Morales, Victor Hugo; Rodríguez-Dorantes, Mauricio; Pérez-Plasencia, Carlos; Madrid-Marina, Vicente

    2015-01-01

    RNA interference is a natural mechanism to silence post-transcriptional gene expression in eukaryotic cells in which microRNAs act to cleave or halt the translation of target mRNAs at specific target sequences. Mature microRNAs, 19-25 nucleotides in length, mediate their effect at the mRNA level by inhibiting translation, or inducing cleavage of the mRNA target. This process is directed by the degree of complementary nucleotides between the microRNAs and the target mRNA; perfect complementary base pairing induces cleavage of mRNA, whereas several mismatches lead to translational arrest. Biological effects of microRNAs can be manipulated through the use of small interference RNAs (siRNAs) generated by chemical synthesis, or by cloning in molecular vectors. The cloning of a DNA insert in a molecular vector that will be transcribed into the corresponding siRNAs is an approach that has been developed using siRNA expression plasmids. These vectors contain DNA inserts designed with software to generate highly efficient siRNAs which will assemble into RNA-induced silencing complexes (RISC), and silence the target mRNA. In addition, the DNA inserts may be contained in cloning cassettes, and introduced in other molecular vectors. In this chapter we describe an attractive technology platform to silence cellular gene expression using specific siRNA expression plasmids, and evaluate its biological effect on target gene expression in human cervical cancer cells. PMID:25348304

  1. Therapeutic Potential of Delivering Arsenic Trioxide into HPV-Infected Cervical Cancer Cells Using Liposomal Nanotechnology

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoyan; Li, Dong; Ghali, Lucy; Xia, Ruidong; Munoz, Leonardo P.; Garelick, Hemda; Bell, Celia; Wen, Xuesong

    2016-02-01

    Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether this could reduce drug toxicity and improve the efficacy of ATO in treating human papillomavirus (HPV)-associated cancers. HeLa, C33a, and human keratinocytes were exposed to 5 μm of ATO in both free and liposomal forms for 48 h. The stability of the prepared samples was tested using inductively coupled plasma optical emission spectrometer (ICP-OES) to measure the intracellular arsenic concentrations after treatment. Fluorescent double-immunocytochemical staining was carried out to evaluate the protein expression levels of HPV-E6 oncogene and caspase-3. Cell apoptosis was analysed by flow cytometry. Results showed that liposomal ATO was more effective than free ATO in reducing protein levels of HPV-E6 and inducing cell apoptosis in HeLa cells. Moreover, lower toxicity was observed when liposomal-delivered ATO was used. This could be explained by lower intracellular concentrations of arsenic. The slowly accumulated intracellular ATO through liposomal delivery might act as a reservoir which releases ATO gradually to maintain its anti-HPV effects. To conclude, liposome-delivered ATO could protect cells from the direct toxic effects induced by higher concentrations of intracellular ATO. Different pathways may be involved in this process, depending on local architecture of the tissues and HPV status.

  2. Cervical cancer: A comprehensive approach towards extermination.

    PubMed

    Bava, Smitha V; Thulasidasan, Arun Kumar T; Sreekanth, Chanickal N; Anto, Ruby John

    2016-01-01

    Human Papilloma Virus (HPV) is one of the most common sexually transmitted pathogen, globally. Oncogenic types of HPV are the causative agents of many neoplastic diseases, including cervical cancer, which ranks as the most common cancer affecting females in developing countries. HPV infection of the cervical epithelium and the subsequent integration of viral DNA into the host genome are the major risk factors for cervical cancer. The scientific discovery of HPV as the causal agent of cervical cancer has led to the development of HPV-based diagnostic tools. Prophylactic vaccines, based on the oncogenic HPV type virus-like particles have been introduced in several developed countries as a preliminary preventive approach. Nevertheless, it remains a continuous threat to women in developing countries, where the prophylactic vaccines are unaffordable and organized screening programmes are lacking. This warrants implementation of prevention strategies that will reduce cervical cancer-related mortality. In this review, we have discussed molecular pathogenesis of HPV infection and the risk factors associated with it. The diagnosis, treatment and prevention strategies of HPV-related cervical cancer have also been discussed.

  3. The Future of Vaccines for Cervical Cancer

    PubMed Central

    Huh, Warner K.; Roden, Richard B.S.

    2015-01-01

    Cervical cancer continues to cause significant morbidity and mortality worldwide, making prophylactic cervical cancer vaccines an important focus for cervical cancer prevention. The increasing accessibility of these vaccines worldwide has the potential to greatly decrease the incidence and burden of disease in the future. However, current prophylactic vaccines offer no therapeutic benefit for persons already infected with human papillomavirus types targeted by vaccines or persons with precancerous lesions or cervical cancer. The protection offered by current vaccines is primarily against human papillomavirus types used to derive the vaccine, although partial cross-protection for related virus types has been observed. Herein, we describe findings from preclinical and clinical studies that employ vaccine strategies that have the potential to shape the future of vaccines against cervical cancer. Modalities include prophylactic strategies to target more oncogenic virus types by using the minor capsid antigen L2 and/or by increasing the number of types used to derive virus-like particle vaccines. Therapeutic strategies include the development of vaccines against human papillomavirus early proteins (targets for cellular immunity) for the resolution of precancerous lesions and cervical cancer. Future applications of existing VLP-based vaccines are also discussed. PMID:18482559

  4. Simple trachelectomy during pregnancy for cervical cancer

    PubMed Central

    Moreno-Luna, Estefania; Alonso, Patricia; Santiago, Javier De; Zapardiel, Ignacio

    2016-01-01

    Invasive cervical cancer is rare during a pregnancy, even though it is one of the most frequently diagnosed neoplasias during that time. It is noted that around 30% of women diagnosed with cervical cancer are of reproductive age. This means that up to 3% of cases of cervical cancer are found in pregnant women or those who are in the post-birth period. A cervicovaginal Pap smear is performed as part of the regular checkup for a pregnant woman during the first visit so that cervical cancer can easily be diagnosed early in these women, detecting it early in up to 70–80% of cases. We present here the case of a patient with initial diagnosis of cervical cancer made around 20th week of pregnancy. It was then treated by a simple trachelectomy and cerclage during week 24. The pregnant woman gave birth to a healthy baby at the end of her pregnancy. Definitive treatment was completed three months after giving birth with a total hysterectomy and laparoscopic bilateral salpingectomy while preserving both ovaries. After 17 months of monitoring the patient showed no signs of reoccurrence. In conclusion, during the early stage of cervical cancer conservative management may be a reasonable option to preserve the current pregnancy. PMID:27610199

  5. Simple trachelectomy during pregnancy for cervical cancer.

    PubMed

    Moreno-Luna, Estefania; Alonso, Patricia; Santiago, Javier De; Zapardiel, Ignacio

    2016-01-01

    Invasive cervical cancer is rare during a pregnancy, even though it is one of the most frequently diagnosed neoplasias during that time. It is noted that around 30% of women diagnosed with cervical cancer are of reproductive age. This means that up to 3% of cases of cervical cancer are found in pregnant women or those who are in the post-birth period. A cervicovaginal Pap smear is performed as part of the regular checkup for a pregnant woman during the first visit so that cervical cancer can easily be diagnosed early in these women, detecting it early in up to 70-80% of cases. We present here the case of a patient with initial diagnosis of cervical cancer made around 20th week of pregnancy. It was then treated by a simple trachelectomy and cerclage during week 24. The pregnant woman gave birth to a healthy baby at the end of her pregnancy. Definitive treatment was completed three months after giving birth with a total hysterectomy and laparoscopic bilateral salpingectomy while preserving both ovaries. After 17 months of monitoring the patient showed no signs of reoccurrence. In conclusion, during the early stage of cervical cancer conservative management may be a reasonable option to preserve the current pregnancy. PMID:27610199

  6. Simple trachelectomy during pregnancy for cervical cancer

    PubMed Central

    Moreno-Luna, Estefania; Alonso, Patricia; Santiago, Javier De; Zapardiel, Ignacio

    2016-01-01

    Invasive cervical cancer is rare during a pregnancy, even though it is one of the most frequently diagnosed neoplasias during that time. It is noted that around 30% of women diagnosed with cervical cancer are of reproductive age. This means that up to 3% of cases of cervical cancer are found in pregnant women or those who are in the post-birth period. A cervicovaginal Pap smear is performed as part of the regular checkup for a pregnant woman during the first visit so that cervical cancer can easily be diagnosed early in these women, detecting it early in up to 70–80% of cases. We present here the case of a patient with initial diagnosis of cervical cancer made around 20th week of pregnancy. It was then treated by a simple trachelectomy and cerclage during week 24. The pregnant woman gave birth to a healthy baby at the end of her pregnancy. Definitive treatment was completed three months after giving birth with a total hysterectomy and laparoscopic bilateral salpingectomy while preserving both ovaries. After 17 months of monitoring the patient showed no signs of reoccurrence. In conclusion, during the early stage of cervical cancer conservative management may be a reasonable option to preserve the current pregnancy.

  7. Mechanism of the reversal effect of mifepristone on drug resistance of the human cervical cancer cell line HeLa/MMC.

    PubMed

    Chen, H; Duan, J; Zuo, F

    2014-02-27

    We examined the ability of mifepristone to reverse the in vitro drug resistance of human cervical cancer cells resistant to mitomycin-C (HeLa/MMC) cells and investigated the mechanism of this effect. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the drug resistance of HeLa/MMC cells and the reversed drug resistance in vitro. Expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and glucosylceramide synthase (GCS) were measured in HeLa and HeLa/MMC cells. The resistance index of HeLa/MMC cells on MMC was reduced from 5.02 to 1.46 after 10 mg/mL mifepristone exposure. A combination of mifepristone upregulated the Bax/Bcl-2 protein expression ratio and apoptosis in HeLa/MMC cells. GCS expression was significantly higher in HeLa/MMC cells than in HeLa cells (P < 0.01), but distinctly declined in both cell lines after mifepristone application (P < 0.01). Mifepristone reversed the resistance of HeLa/MMC cells to MMC in vitro; the overexpression of the GCS gene and the increased expression of apoptosis-related protein Bcl-2 may play important roles in the formation of multidrug resistance in cervical cancer.

  8. Effect of bitter melon (Momordica charantia Linn) on level and function of natural killer cells in cervical cancer patients with radiotherapy.

    PubMed

    Pongnikorn, Surathat; Fongmoon, Duriya; Kasinrerk, Watchara; Limtrakul, Porn-Ngam

    2003-01-01

    Cervical cancer patients have a defective immune system. There is a decrease of total white blood cell count including lymphocytes and natural killer (NK) cells. NK cells, one type of lymphocytes, play a role to eliminate cancer cells by antibody dependent cell mediated cytotoxicity (ADCC) mechanism. Previous studies have shown that P-glycoprotein (170 kDa, transmembrane protein) may be a transporter for cytokine releasing in ADCC mechanism. This study proposed to explore the role of bitter melon intake in cervical cancer patients undergoing normal treatment (radiotherapy). Subjects were divided into three groups: 1) normal control (women 35-55 years, n = 35), 2) patient control (n = 30) and 3) patient treatment (n = 30) groups. Patient control and patient treatment groups were cervical cancer patients (stage II or III) treated with radiotherapy (without or with bitter melon ingestion). Blood samples of patient control and patient treatment groups were analyzed for NK cells percentage and P-glycoprotein level. Bitter melon is a Thai herb. Previous studies have shown that bitter melon can stimulate lymphocyte activity in vitro and in vivo (mouse). The authors hope that bitter melon could stimulate the increase of NK cells percentage and P-glycoprotein level on the membrane in blood samples from cervical cancer patients who ingest bitter melon. The results showed an increased percentage of NK cells in patient control and patient treatment groups. The increase in each group is significant (p < 0.05) when compared with the percentage of NK cells from second and third blood sampling time (after radiation with of without bitter melon intake for 45 and 90 days) with first blood sampling time (before treatment). The results also show a significant decrease of P-glycoprotein level (p < 0.05) in second and third blood sampling times when compared with first blood sampling time of the patient treatment group. There was no significant difference of P-glycoprotein (P-gp) level

  9. [Epigenetic alterations in cervical cancer progression].

    PubMed

    Ríos-Romero, Magdalena; Soto-Valladares, Ana Guadalupe; Piña-Sánchez, Patricia

    2015-01-01

    Despite the use of the screening test, such as Papanicolaou, and the detection of human papillomavirus (HPV), cervical cancer remains as a public health problem in México and it is the second leading cause of death for malignant neoplasias among women. High-risk HPV infection is the main risk factor for the development of premalignant lesions and cervical cancer; however, HPV infection is not the only factor; there are various genetic and epigenetic alterations required for the development of neoplasias; some of them have been described and even in some cases they have been suggested as biomarkers for prognosis. However, in contrast with other cancer types, such as breast cancer, in cervical cancer the use of biomarkers has not been established for clinical applications. Unlike genetic alterations, epigenetic alterations are potentially reversible; in this sense, their characterization is important, since they have not only a potential use as biomarkers, but they also could represent new therapeutic targets for treatment of cervical cancer. This review describes some of the more common epigenetic alterations in cervical cancer and its potential use in routine clinical practice.

  10. Targeting Pro-Apoptotic TRAIL Receptors Sensitizes HeLa Cervical Cancer Cells to Irradiation-Induced Apoptosis

    SciTech Connect

    Maduro, John H.; Vries, Elisabeth de; Meersma, Gert-Jan; Hougardy, Brigitte; Zee, Ate G.J. van der; Jong, Steven de

    2008-10-01

    Purpose: To investigate the potential of irradiation in combination with drugs targeting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor (DR)4 and DR5 and their mechanism of action in a cervical cancer cell line. Methods and Materials: Recombinant human TRAIL (rhTRAIL) and the agonistic antibodies against DR4 and DR5 were added to irradiated HeLa cells. The effect was evaluated with apoptosis and cytotoxicity assays and at the protein level. Membrane receptor expression was measured with flow cytometry. Small-interfering RNA against p53, DR4, and DR5 was used to investigate their function on the combined effect. Results: rhTRAIL and the agonistic DR4 and DR5 antibodies strongly enhanced 10-Gy-induced apoptosis. This extra effect was 22%, 23%, and 29% for rhTRAIL, DR4, and DR5, respectively. Irradiation increased p53 expression and increased the membrane expression of DR5 and DR4. p53 suppression, as well as small-interfering RNA against DR5, resulted in a significant downregulation of DR5 membrane expression but did not affect apoptosis induced by irradiation and rhTRAIL. After small-interfering RNA against DR4, rhTRAIL-induced apoptosis and the additive effect of irradiation on rhTRAIL-induced apoptosis were abrogated, implicating an important role for DR4 in apoptosis induced through irradiation in combination with rhTRAIL. Conclusion: Irradiation-induced apoptosis is strongly enhanced by targeting the pro-apoptotic TRAIL receptors DR4 or DR5. Irradiation results in a p53-dependent increase in DR5 membrane expression. The sensitizing effect of rhTRAIL on irradiation in the HeLa cell line is, however especially mediated through the DR4 receptor.

  11. Risks of Cervical Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  12. Interference with endogenous EZH2 reverses the chemotherapy drug resistance in cervical cancer cells partly by up-regulating Dicer expression.

    PubMed

    Cai, Liqiong; Wang, Zehua; Liu, Denghua

    2016-05-01

    Cervical cancer is one of the most common female malignancies in the world, and chemotherapeutic drug resistance is a major obstacle to cancer therapy. Enhancer of zeste homolog 2 (EZH2) is an enzymatic subunit of polycomb repressive complex 2 (PRC2) and catalyzes the repressive histone H3 lysine 27 trimethylation (H3K27me3). However, the role of EZH2 on the chemotherapy drug resistance in cervical cancers remains unclear. In the present study, the cervical carcinoma specimens and paired normal tissue specimens were obtained and the expression of EZH2 was detected by western blotting. The results showed that high levels of EZH2 were detected in cervical carcinoma tissues, compared with paired control tissues (**p < 0.01). Next, three pairs of shRNA specific to EZH2 were designed and used to interfere with endogenous EZH2 expression. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays following treatment with various concentrations of cisplatin in HeLa and HeLa/DDP cells. The MTT assay results showed that knockdown of EZH2 in HeLa/DDP cells caused a 2.29- or 1.83-fold decrease in the cisplatin IC50 values (for shRNA1-EZH2, 34.88 vs. 15.21 μg/mL; p < 0.01; for shRNA3-EZH2, 34.88 vs. 19.09 μg/mL; p < 0.01). The EZH2 activity was also suppressed by 3-deazaneplanocin A (DZNep), EZH2 inhibitor, and the results demonstrated that, meanwhile, DZNep potently inhibited cell viability of HeLa/DDP cells, partly by suppression the levels of EZH2 and H3K27me3, but not H3K27me2, which was detected by western blotting analysis. Moreover, cell migration assay results showed that knockdown of EZH2 decreased cell metastasis of cervical cancer cells. Furthermore, cell cycle was detected by fluorescence-activated cell sorting (FACS) assay and the results demonstrated that interference with EZH2 expression increased the percentage of cells at G0/G1 phase and the HeLa/DDP cells were blocked at G0/G1 phase. Interestingly

  13. Human Leucine Zipper Protein sLZIP Induces Migration and Invasion of Cervical Cancer Cells via Expression of Matrix Metalloproteinase-9*

    PubMed Central

    Kang, Hyereen; Jang, Sung-Wuk; Ko, Jesang

    2011-01-01

    Extracellular proteolysis mediates tissue homeostasis. In cancer, altered proteolysis leads to abnormal tumor growth, inflammation, tissue invasion, and metastasis. Matrix metalloproteinase-9 (MMP-9) represents one of the most prominent proteinases associated with inflammation and tumorigenesis. The recently identified human transcription factor sLZIP is a member of the leucine zipper transcription factor family. Although sLZIP is known to function in ligand-induced transactivation of the glucocorticoid receptor, its exact functions and target genes are not known. In this study, we investigated the role of sLZIP in MMP-9 expression and its involvement in cervical cancer development. Our results show that sLZIP increased the expression of MMP-9 at both the mRNA and protein levels and the proteolytic activity of MMP-9 in HeLa and SiHa cells. sLZIP also increased the transcriptional activity of MMP-9 by binding directly to the cAMP-responsive element of the MMP-9 promoter region. Involvement of sLZIP in MMP-9 expression was further supported by the fact that ME-180 cells expressing sLZIP siRNA were refractory to MMP-9 expression. Results from wound healing and invasion assays showed that sLZIP enhanced both the migration and invasion of cervical cancer cells. The increased migration and invasion of HeLa and SiHa cells that were induced by sLZIP were abrogated by inhibition of the proteolytic activity of MMP-9. These results indicate that sLZIP plays a critical role in MMP-9 expression and is probably involved in invasion and metastasis of cervical cancer. PMID:22009750

  14. Human leucine zipper protein sLZIP induces migration and invasion of cervical cancer cells via expression of matrix metalloproteinase-9.

    PubMed

    Kang, Hyereen; Jang, Sung-Wuk; Ko, Jesang

    2011-12-01

    Extracellular proteolysis mediates tissue homeostasis. In cancer, altered proteolysis leads to abnormal tumor growth, inflammation, tissue invasion, and metastasis. Matrix metalloproteinase-9 (MMP-9) represents one of the most prominent proteinases associated with inflammation and tumorigenesis. The recently identified human transcription factor sLZIP is a member of the leucine zipper transcription factor family. Although sLZIP is known to function in ligand-induced transactivation of the glucocorticoid receptor, its exact functions and target genes are not known. In this study, we investigated the role of sLZIP in MMP-9 expression and its involvement in cervical cancer development. Our results show that sLZIP increased the expression of MMP-9 at both the mRNA and protein levels and the proteolytic activity of MMP-9 in HeLa and SiHa cells. sLZIP also increased the transcriptional activity of MMP-9 by binding directly to the cAMP-responsive element of the MMP-9 promoter region. Involvement of sLZIP in MMP-9 expression was further supported by the fact that ME-180 cells expressing sLZIP siRNA were refractory to MMP-9 expression. Results from wound healing and invasion assays showed that sLZIP enhanced both the migration and invasion of cervical cancer cells. The increased migration and invasion of HeLa and SiHa cells that were induced by sLZIP were abrogated by inhibition of the proteolytic activity of MMP-9. These results indicate that sLZIP plays a critical role in MMP-9 expression and is probably involved in invasion and metastasis of cervical cancer.

  15. Are Fewer Cervical Cancer Screenings Needed After HPV Vaccine?

    MedlinePlus

    ... Are Fewer Cervical Cancer Screenings Needed After HPV Vaccine? Less testing could reduce risk of false positives ... cervical cancer screening depends on the type of vaccine she had, the researchers said. Women vaccinated with ...

  16. Stromal cell-derived factor-1 G801A polymorphism and the risk factors for cervical cancer.

    PubMed

    Roszak, Andrzej; Misztal, Matthew; Sowińska, Anna; Jagodziński, Paweł P

    2015-06-01

    Although certain studies have demonstrated no association between the stromal cell‑derived factor‑1 (SDF1‑3') G801A single nucleotide polymorphism (SNP) and cervical carcinoma, the interactions between the SDF1‑3' G801A SNP and contraceptive use, menopausal status, parity and tobacco smoking remain to be fully elucidated. Using polymerase chain reaction‑restriction fragment length polymorphism, the distribution of SDF1‑3' G801A genotypes in patients with cervical cancer (n=462) against control groups (n=497) was investigated. Logistic regression analysis, adjusting for age, pregnancy, oral contraceptive use, tobacco smoking and menopausal status, did not identify the SDF1‑3' G801A polymorphism as a genetic risk factor for cervical cancer. The adjusted odds ratio (OR) for patients with the A/G, vs. G/G genotype was 1.203, with a 95% confidence interval (CI) of 0.909‑1.591 (P=0.196). The adjusted OR for the A/A, vs. G/G genotype was 1.296 (95% CI=0.930‑1.807; P=0.125) and for the A/A or A/G, vs. G/G genotype was 1.262 (95% CI=0.964‑1.653; P=0.090)]. The P‑value of the χ2 test of the trend observed for the SDF1‑3' G801A polymorphism was at the borderline of being statistically significant (ptrend=0.0484). Stratified analyses between the distribution of the SDF1‑3' G801A genotypes and cervical cancer risks demonstrated that this polymorphism may be a risk factor for patients with a positive history of tobacco smoking (1.778; 95% CI=1.078‑2.934; P=0.0235). These findings suggested that the SDF1‑3' G801A polymorphism may be a genetic risk factor for cervical cancer in patients with a positive history of tobacco smoking.

  17. Quantitative DNA Methylation Analysis of Candidate Genes in Cervical Cancer

    PubMed Central

    Siegel, Erin M.; Riggs, Bridget M.; Delmas, Amber L.; Koch, Abby; Hakam, Ardeshir; Brown, Kevin D.

    2015-01-01

    Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens. Bisulfite-modified genomic DNA was amplified and quantitative pyrosequencing completed for 10 genes (APC, CCNA, CDH1, CDH13, WIF1, TIMP3, DAPK1, RARB, FHIT, and SLIT2). A Methylation Index was calculated as the mean percent methylation across all CpG sites analyzed per gene (~4-9 CpG site) per sequence. A binary cut-point was defined at >15% methylation. Sensitivity, specificity and area under ROC curve (AUC) of methylation in individual genes or a panel was examined. The median methylation index was significantly higher in cases compared to controls in 8 genes, whereas there was no difference in median methylation for 2 genes. Compared to HPV and age, the combination of DNA methylation level of DAPK1, SLIT2, WIF1 and RARB with HPV and age significantly improved the AUC from 0.79 to 0.99 (95% CI: 0.97–1.00, p-value = 0.003). Pyrosequencing analysis confirmed that several genes are common targets for aberrant methylation in cervical cancer and DNA methylation level of four genes appears to increase specificity to identify cancer compared to HPV detection alone. Alterations in DNA methylation of specific genes in cervical cancers, such as DAPK1, RARB, WIF1, and SLIT2, may also occur early in cervical carcinogenesis and should be evaluated. PMID:25826459

  18. Quantitative DNA methylation analysis of candidate genes in cervical cancer.

    PubMed

    Siegel, Erin M; Riggs, Bridget M; Delmas, Amber L; Koch, Abby; Hakam, Ardeshir; Brown, Kevin D

    2015-01-01

    Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens. Bisulfite-modified genomic DNA was amplified and quantitative pyrosequencing completed for 10 genes (APC, CCNA, CDH1, CDH13, WIF1, TIMP3, DAPK1, RARB, FHIT, and SLIT2). A Methylation Index was calculated as the mean percent methylation across all CpG sites analyzed per gene (~4-9 CpG site) per sequence. A binary cut-point was defined at >15% methylation. Sensitivity, specificity and area under ROC curve (AUC) of methylation in individual genes or a panel was examined. The median methylation index was significantly higher in cases compared to controls in 8 genes, whereas there was no difference in median methylation for 2 genes. Compared to HPV and age, the combination of DNA methylation level of DAPK1, SLIT2, WIF1 and RARB with HPV and age significantly improved the AUC from 0.79 to 0.99 (95% CI: 0.97-1.00, p-value = 0.003). Pyrosequencing analysis confirmed that several genes are common targets for aberrant methylation in cervical cancer and DNA methylation level of four genes appears to increase specificity to identify cancer compared to HPV detection alone. Alterations in DNA methylation of specific genes in cervical cancers, such as DAPK1, RARB, WIF1, and SLIT2, may also occur early in cervical carcinogenesis and should be evaluated.

  19. MicroRNA-331-3p Suppresses Cervical Cancer Cell Proliferation and E6/E7 Expression by Targeting NRP2.

    PubMed

    Fujii, Tomomi; Shimada, Keiji; Asano, Aya; Tatsumi, Yoshihiro; Yamaguchi, Naoko; Yamazaki, Masaharu; Konishi, Noboru

    2016-01-01

    Aberrant expression of microRNAs (miRNAs) is involved in the development and progression of various types of cancers. In this study, we investigated the role of miR-331-3p in cell proliferation and the expression of keratinocyte differentiation markers of uterine cervical cancer cells. Moreover, we evaluated whether neuropilin 2 (NRP2) are putative target molecules that regulate the human papillomavirus (HPV) related oncoproteins E6 and E7. Cell proliferation in the human cervical cancer cell lines SKG-II, HCS-2, and HeLa was assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Cellular apoptosis was measured using the TdT-mediated dUTP nick end labeling (TUNEL) and Annexin V assays. Quantitative RT-PCR was used to measure the messenger RNA (mRNA) expression of the NRP2, E6, E7, p63, and involucrin (IVL) genes. A functional assay for cell growth was performed using cell cycle analyses. Overexpression of miR-331-3p inhibited cell proliferation, and induced G2/M phase arrest and apoptosis in SKG-II, HCS-2 and HeLa cells. The luciferase reporter assay of the NRP2 3'-untranslated region revealed the direct regulation of NRP2 by miR-331-3p. Gene expression analyses using quantitative RT-PCR in SKG-II, HCS-2, and HeLa cells overexpressing miR-331-3p or suppressing NRP2 revealed down-regulation of E6, E7, and p63 mRNA and up-regulation of IVL mRNA. Moreover, miR-331-3p overexpression was suppressed NRP2 expression in protein level. We showed that miR-331-3p and NRP2 were key effectors of cell proliferation by regulating the cell cycle, apoptosis. NRP-2 also regulates the expression of E6/E7 and keratinocyte differentiation markers. Our findings suggest that miR-331-3p has an important role in regulating cervical cancer cell proliferation, and that miR-331-3p may contribute to keratinocyte differentiation through NRP2 suppression. miR-331-3p and NRP2 may contribute to anti-cancer effects. PMID

  20. MicroRNA-331-3p Suppresses Cervical Cancer Cell Proliferation and E6/E7 Expression by Targeting NRP2

    PubMed Central

    Fujii, Tomomi; Shimada, Keiji; Asano, Aya; Tatsumi, Yoshihiro; Yamaguchi, Naoko; Yamazaki, Masaharu; Konishi, Noboru

    2016-01-01

    Aberrant expression of microRNAs (miRNAs) is involved in the development and progression of various types of cancers. In this study, we investigated the role of miR-331-3p in cell proliferation and the expression of keratinocyte differentiation markers of uterine cervical cancer cells. Moreover, we evaluated whether neuropilin 2 (NRP2) are putative target molecules that regulate the human papillomavirus (HPV) related oncoproteins E6 and E7. Cell proliferation in the human cervical cancer cell lines SKG-II, HCS-2, and HeLa was assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Cellular apoptosis was measured using the TdT-mediated dUTP nick end labeling (TUNEL) and Annexin V assays. Quantitative RT-PCR was used to measure the messenger RNA (mRNA) expression of the NRP2, E6, E7, p63, and involucrin (IVL) genes. A functional assay for cell growth was performed using cell cycle analyses. Overexpression of miR-331-3p inhibited cell proliferation, and induced G2/M phase arrest and apoptosis in SKG-II, HCS-2 and HeLa cells. The luciferase reporter assay of the NRP2 3′-untranslated region revealed the direct regulation of NRP2 by miR-331-3p. Gene expression analyses using quantitative RT-PCR in SKG-II, HCS-2, and HeLa cells overexpressing miR-331-3p or suppressing NRP2 revealed down-regulation of E6, E7, and p63 mRNA and up-regulation of IVL mRNA. Moreover, miR-331-3p overexpression was suppressed NRP2 expression in protein level. We showed that miR-331-3p and NRP2 were key effectors of cell proliferation by regulating the cell cycle, apoptosis. NRP-2 also regulates the expression of E6/E7 and keratinocyte differentiation markers. Our findings suggest that miR-331-3p has an important role in regulating cervical cancer cell proliferation, and that miR-331-3p may contribute to keratinocyte differentiation through NRP2 suppression. miR-331-3p and NRP2 may contribute to anti-cancer effects

  1. The Epidemiology of Human Papillomavirus Infection and Cervical Cancer

    PubMed Central

    Bosch, F. Xavier; de Sanjosé, Silvia

    2007-01-01

    Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI). The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs). The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC), the adenocarcinomas and the vast majority (i.e. > 95%) of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL)/Cervical Intraepithelial Neoplasia 3 (CIN3)/Carcinoma in situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC) for five or more years, smoking, high parity (five or more full term pregnancies) and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT) and Herpes Simplex Virus type 2 (HSV-2). Women exposed to the Human Immunodeficiency Virus (HIV) are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer. PMID:17627057

  2. The Cytotoxicity Mechanism of 6-Shogaol-Treated HeLa Human Cervical Cancer Cells Revealed by Label-Free Shotgun Proteomics and Bioinformatics Analysis

    PubMed Central

    Liu, Qun; Peng, Yong-Bo; Qi, Lian-Wen; Cheng, Xiao-Lan; Xu, Xiao-Jun; Liu, Le-Le; Liu, E-Hu; Li, Ping

    2012-01-01

    Cervical cancer is one of the most common cancers among women in the world. 6-Shogaol is a natural compound isolated from the rhizome of ginger (Zingiber officinale). In this paper, we demonstrated that 6-shogaol induced apoptosis and G2/M phase arrest in human cervical cancer HeLa cells. Endoplasmic reticulum stress and mitochondrial pathway were involved in 6-shogaol-mediated apoptosis. Proteomic analysis based on label-free strategy by liquid chromatography chip quadrupole time-of-flight mass spectrometry was subsequently proposed to identify, in a non-target-biased manner, the molecular changes in cellular proteins in response to 6-shogaol treatment. A total of 287 proteins were differentially expressed in response to 24 h treatment with 15 μM 6-shogaol in HeLa cells. Significantly changed proteins were subjected to functional pathway analysis by multiple analyzing software. Ingenuity pathway analysis (IPA) suggested that 14-3-3 signaling is a predominant canonical pathway involved in networks which may be significantly associated with the process of apoptosis and G2/M cell cycle arrest induced by 6-shogaol. In conclusion, this work developed an unbiased protein analysis strategy by shotgun proteomics and bioinformatics analysis. Data observed provide a comprehensive analysis of the 6-shogaol-treated HeLa cell proteome and reveal protein alterations that are associated with its anticancer mechanism. PMID:23243437

  3. Duchesnea phenolic fraction inhibits in vitro and in vivo growth of cervical cancer through induction of apoptosis and cell cycle arrest.

    PubMed

    Peng, Bo; Hu, Qin; Liu, Xinmin; Wang, Liwei; Chang, Qi; Li, Jianrong; Tang, Jintian; Wang, Ning; Wang, Yuqi

    2009-01-01

    Duchesnea indica (Andr.) Focke has been commonly used to treat cancer in Asian countries for centuries, and recently has been shown to possess anticancer properties in vitro and in vivo. But the underlying mechanism of the anticancer action is unclear, especially in in vivo studies. In this study, we investigated the anticancer effect and associated mechanisms of Duchesnea phenolic fraction (DPF) on cervical cancer in vitro and in vivo. Our results showed that DPF significantly inhibited cervical cancer cell proliferation in dose- and time-dependent manners. DPF induced apoptosis as determined by AO/EB staining, DNA fragmentation and flow cytometry. Some apoptosis correlated proteins were altered following DPF treatment. Bax was up-regulated while Bcl-2 was down-regulated, and the expression ratio of Bax/Bcl-2 was increased. These resulted in the translocation of Bax to mitochondria, the release of cytochrome c from the mitochondria to the cytosol and caspase-3 activation. Concurrently, DPF provoked S phase arrest along with significant down-regulation of S phase-associated proteins, such as cyclin A, cyclin E, cyclin D1 and cdk2. Transplanted U14 cervical cancer mouse model was used to evaluate the antitumor effect of DPF in vivo. Compared with control, DPF treatment markedly prolonged survival of tumor-bearing mice and dose-dependently reduced the tumor weight. DPF could induce apoptosis in tumor tissues as evidenced by increased TUNEL-positive cells, activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2. In addition, DPF significantly decreased the expression of cell proliferation markers PCNA and ki67 in tumors. All together, these data sustain our contention that DPF has anticancer properties and merits further investigation as a potential therapeutic agent.

  4. Decreased expression of the plasminogen activator inhibitor type 1 is involved in degradation of extracellular matrix surrounding cervical cancer stem cells.

    PubMed

    Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Takahashi, Juri; Kojima, Satoko; Yamashita, Aki; Tomio, Kensuke; Nagamatsu, Takeshi; Wada-Hiraike, Osamu; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-02-01

    The plasminogen activator (PA) system consists of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator and its receptor (uPA and uPAR). PAI-1 inhibits the activation of uPA (which converts plasminogen to plasmin), and is involved in cancer invasion and metastasis, by remodeling the extracellular matrix (ECM) through regulating plasmin. Cancer stem cells (CSCs) are a small subset of cells within tumors, and are thought to be involved in tumor recurrence and metastasis. Considering these facts, we investigated the relationship between PAI-1 and cervical CSCs. We used ALDH1 as a marker of cervical CSCs. First, we demonstrated that culturing ALDH1-high cells and ALDH-low cells on collagen IV-coted plates increased their expression of active PAI-1 (ELISA), and these increases were suggested to be at mRNA expression levels (RT-qPCR). Secondly, we demonstrated PAI-1 was indeed involved in the ECM maintenance. With gelatin zymography assays, we found that ALDH1-high cells and ALDH-low cells expressed pro-matrix metalloproteinase-2 (pro-MMP-2) irrespective of their coatings. With gelatinase/collagenase assay kit, we confirmed that collagenase activity was increased when ALDH1-low cells were exposed to TM5275, a small molecule inhibitor of PAI-1. Putting the data together, we hypothesized that cancer cells adhered to basal membrane secrete abundant PAI-1, on the other hand, cancer cells (especially CSCs rather than non-CSCs) distant from basal membrane secrete less PAI-1, which makes the ECM surrounding CSCs more susceptible to degradation. Our study could be an explanation of conflicting reports, where some researchers found negative impacts of PAI-1 expression on clinical outcomes and others not, by considering the concept of CSCs.

  5. Influence of continuous intervention on growth and metastasis of human cervical cancer cells and expression of RNAmiR-574-5p.

    PubMed

    Ma, D L; Li, J Y; Liu, Y E; Liu, C M; Li, J; Lin, G Z; Yan, J

    2016-01-01

    This study was carried out to acquire solid evidence that some common treatments could affect micro ribonucleic acids (miRNAs) by revealing the regulatory effect of genes, so as to provide a reference for further exploration of the prevention and treatment of cervical cancer. Nude mouse tumorigenicity assay was used to study the effect of inhibiting miR-574-5p on development and tumorigenic ability of Henrietta Lacks (HeLa) tumor. Cell wound scratch assay, flow cytometry and real-time quantitative polymerase chain reaction (RT-qPCR) were adopted to study the effects of anoxia and temperature, etc., on expression of miR-574-5p and QKI in HeLa as well as on the clone and migration ability of cells, to provide prevention and treatment of cervical cancer with new ideas and evidence. The results demonstrated that cervical cancer tissues had a significantly increased miR-574-5p expression compared with para-carcinoma tissues; conversely, Gomafu, overall QKI (pan-QKI) and QKI-5 messenger ribonucleic acid (mRNA) and protein expression all decreased. Part of the common nursing methods had a certain influence on miR-574-5p expression, HeLa reproduction and metastasis, and even cell cycle. For example, ultraviolet (UV) irradiation was effective in decreasing miR-574-5p expression of HeLa and inhibiting cell migration; severe hypoxia significantly decreased the survival rate of HeLa, leading to the increase of programmed death percentage and cell ratio in G2/M phase as well as the decrease of cell ratio in G1 phase. Incubation at different temperatures also affected miR-574-5p expression and cell proliferation. Thus, it can be known that miR-574-5p, Gomafu and QKI expression in cervical cancer tissues and para-carcinoma tissues are significantly up-regulated or down-regulated. Some treatments, such as UV irradiation, hypoxia, incubation temperatures, etc., can affect miR-574-5p expression and HeLa proliferation as well as metastases in different degrees. These findings provide

  6. Influence of continuous intervention on growth and metastasis of human cervical cancer cells and expression of RNAmiR-574-5p.

    PubMed

    Ma, D L; Li, J Y; Liu, Y E; Liu, C M; Li, J; Lin, G Z; Yan, J

    2016-01-01

    This study was carried out to acquire solid evidence that some common treatments could affect micro ribonucleic acids (miRNAs) by revealing the regulatory effect of genes, so as to provide a reference for further exploration of the prevention and treatment of cervical cancer. Nude mouse tumorigenicity assay was used to study the effect of inhibiting miR-574-5p on development and tumorigenic ability of Henrietta Lacks (HeLa) tumor. Cell wound scratch assay, flow cytometry and real-time quantitative polymerase chain reaction (RT-qPCR) were adopted to study the effects of anoxia and temperature, etc., on expression of miR-574-5p and QKI in HeLa as well as on the clone and migration ability of cells, to provide prevention and treatment of cervical cancer with new ideas and evidence. The results demonstrated that cervical cancer tissues had a significantly increased miR-574-5p expression compared with para-carcinoma tissues; conversely, Gomafu, overall QKI (pan-QKI) and QKI-5 messenger ribonucleic acid (mRNA) and protein expression all decreased. Part of the common nursing methods had a certain influence on miR-574-5p expression, HeLa reproduction and metastasis, and even cell cycle. For example, ultraviolet (UV) irradiation was effective in decreasing miR-574-5p expression of HeLa and inhibiting cell migration; severe hypoxia significantly decreased the survival rate of HeLa, leading to the increase of programmed death percentage and cell ratio in G2/M phase as well as the decrease of cell ratio in G1 phase. Incubation at different temperatures also affected miR-574-5p expression and cell proliferation. Thus, it can be known that miR-574-5p, Gomafu and QKI expression in cervical cancer tissues and para-carcinoma tissues are significantly up-regulated or down-regulated. Some treatments, such as UV irradiation, hypoxia, incubation temperatures, etc., can affect miR-574-5p expression and HeLa proliferation as well as metastases in different degrees. These findings provide

  7. Tonsillar and other upper aerodigestive tract cancers among cervical cancer patients and their husbands.

    PubMed

    Hemminki, K; Dong, C; Frisch, M

    2000-12-01

    The study aimed at probing the possible role of human papillomavirus (HPV) infection in squamous cell carcinomas of the upper aerodigestive tract, with a special reference to tonsillar cancer. We used the Swedish Family Cancer Database to analyse second cancers in the upper aerodigestive tract of women first diagnosed with in-situ or invasive cervical cancer. First cancers of their husbands were also analysed. Standardized incidence ratios (SIRs) were calculated for female and male cancers, adjusted for age at diagnosis, period, sex, socio-economic status and residential area. Among women, increases were observed at many sites, but tonsillar cancers were increased only among women aged 50 years or more at diagnosis of in-situ cervical cancer (SIR 2.58). The increases at these sites are probably ascribed to the effects HPV, smoking, alcohol or their interaction. Husbands of cervical cancer patients developed an excess (SIR over 2.00) of both tonsillar cancer (SIR 2.39 when wife with in-situ cancer and SIR 2.72 when wife with invasive cervical cancer) and cancer of the tongue. The excess of tonsillar cancer among husbands of women with HPV-associated neoplastic lesions of the cervix supports the a priori hypothesis that HPV may be involved in tonsillar carcinogenesis.

  8. Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells.

    PubMed

    Zhang, Hongling; Liu, Gan; Zeng, Xiaowei; Wu, Yanping; Yang, Chengming; Mei, Lin; Wang, Zhongyuan; Huang, Laiqiang

    2015-01-01

    Genistein is one of the most studied isoflavonoids with potential antitumor efficacy, but its poor water solubility limits its clinical application. Nanoparticles (NPs), especially biodegradable NPs, entrapping hydrophobic drugs have promising applications to improve the water solubility of hydrophobic drugs. In this work, TPGS-b-PCL copolymer was synthesized from ε-caprolactone initiated by d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) through ring-opening polymerization and characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The genistein-loaded NPs were prepared by a modified nanoprecipitation method and characterized in the aspects of particle size, surface charge, morphology, drug loading and encapsulation efficiency, in vitro drug release, and physical state of the entrapped drug. The TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than PCL NPs. MTT and colony formation experiments indicated that genistein-loaded TPGS-b-PCL NPs achieved the highest level of cytotoxicity and tumor cell growth inhibition compared with pristine genistein and genistein-loaded PCL NPs. Furthermore, compared with pristine genistein and genistein-loaded PCL NPs, the genistein-loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer.

  9. Margins for cervical and vulvar cancer.

    PubMed

    Khanna, Namita; Rauh, Lisa A; Lachiewicz, Mark P; Horowitz, Ira R

    2016-03-01

    Surgery is the primary treatment for vulvar cancer as well as early-stage carcinoma of the cervix. This article reviews the significance of margin status after surgery on overall survival, need for further surgical intervention, and role for possible adjuvant therapy. It summarizes the abundant literature on margin status in vulvar cancer and highlights the need for further investigation on the prognostic significance of margins in cervical cancer. In addition, it reviews other important operative considerations.

  10. Screening of cervical cancer in Catalonia 2006–2012

    PubMed Central

    de Sanjosé, Silvia; Ibáñez, Raquel; Rodríguez-Salés, Vanesa; Peris, Mercè; Roura, Esther; Diaz, Mireia; Torné, Aureli; Costa, Dolors; Canet, Yolanda; Falguera, Gemma; Alejo, Maria; Espinàs, Josep Alfons; Bosch, F. Xavier

    2015-01-01

    The early detection of intraepithelial lesions of the cervix, through the periodic examination of cervical cells, has been fundamental for the prevention of invasive cervical cancer and its related mortality. In this report, we summarise the cervical cancer screening activities carried out in Catalonia, Spain, within the National Health System during 2008–2011. The study population covers over two million women resident in the area. The evaluation includes 758,690 cervical cytologies performed on a total of 595,868 women. The three-year coverage of cervical cytology among women aged between 25 and 65 years was 40.8%. About 50% of first screened women with negative results had not returned to the second screening round. The introduction of high-risk human papillomavirus DNA (HPV) detection, as a primary screening cotest with cytology among women over age 40 with a poor screening history, significantly improved the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), being far superior to cytology alone. Cotesting did not improve the detection of CIN2+. The use of the HPV test for the triage of atypical squamous cell undetermined significance (ASC-US) improved the selection of women at high risk of CIN2+. Sampling (both cytology and HPV test) was largely performed by midwives (66.7%), followed by obstetricians (23.8%) and nurses (7%). Over half of the centres (54.8%) had full use of online medical records. During the study period, educational activities for professionals and for women were carried out periodically. The organisation of screening as a population activity in which women are actively called to the screening visit and the introduction of HPV testing as a primary screening tool are strongly recommended to ensure the maximum population impact in the reduction of the cervical cancer burden. PMID:25987901

  11. [The role of developmental HOX genes in cervical cancer].

    PubMed

    López-Romero, Ricardo; Marrero-Rodríguez, Daniel; Romero-Morelos, Pablo; Villegas, Vanessa; Valdivia, Alejandra; Arreola, Hugo; Huerta-Padilla, Víctor; Salcedo, Mauricio

    2015-01-01

    Cervical cancer (CC) is a multifactorial disease associated to genetic, environmental and epigenetic factors, being the infection by human papillomavirus the main etiologic agent. Additionally, the alteration in the expression of transcription factors has been considered of importance for the development of this tumor. HOX genes encode a group of transcription factors involved in cellular proliferation and differentiation processes during the development of embryonic structures in vertebrates; their aberrant expression is associated with tumorigenesis and metastasis. A range of evidence suggests a role for HOX genes in the development of cervical neoplastic cell. Studies in CC cell lines, primary tumors and premalignant lesions have suggested the involvement of HOXA1, HOXC5, C6, C8 and C10, HOXD9 and HOXD13 in the process of cervical carcinogenesis. Also, the de novo expression of genes HOXB2, B4, B13 and HOXC11-C13 appears to be involved in the process of malignant transformation of cervical epithelial cell. These data would allow to open a field in search of new molecular markers in cervical cancer and the development of new therapeutic strategies for this malignancy.

  12. Cervical cancer in north-eastern Libya: 2000-2008.

    PubMed

    Ben Khaial, F; Bodalal, Z; Elramli, A; Elkhwsky, F; Eltaguri, A; Bendardaf, R

    2014-08-01

    Libya is a country with a low population, listed under the EMRO. Using registers and patient records from a major primary oncology clinic, data was gathered from Libyan cervical cancer patients and various parameters were studied across 9 years. Out of 4,090 female cancer cases during the study period, 1.8% were cervical cancer (n = 74). The average age of presentation was 53 years, with most of the cases (60%, n = 44) being premenopausal. Approximately 65% (n = 48) of cervical cancer patients are diagnosed at later stages (i.e. stages III and IV). The majority of these cases are squamous cell carcinoma (83.8%, n = 62), while 16.2% (n = 12) were found to be adenocarcinoma. Patients with squamous cell carcinoma presented at later stages more often than those with adenocarcinoma. Human papilloma virus was strongly implicated in cervical cancer, with 94% (n = 63) of those who were tested being positive for HPV-16 (82.5%, n = 52) and HPV-18 (12.7%, n = 8). Diagnosis was most frequently made through biopsy (97.3%, n = 72) as opposed to Pap smears (2.7%, n = 2). Most Libyan patients were put through chemotherapy (75%, n = 55) and triple therapy (surgery with combined chemotherapy and radiotherapy) was the most common (38%, n = 28) modality of treatment. Comparisons were made between Libya and other nations, either in the developed world or neighbouring countries. The major problem of cervical cancer in Libya is delayed presentation and hence, all the recommendations focus on increased awareness for the populace, implementation of a national cancer control plan and a national screening programme.

  13. Effects of irradiation for cervical cancer on subsequent breast cancer

    SciTech Connect

    Harlan, L.C.M.

    1985-01-01

    Previous research suggests that cervical cancer patients have a lower risk of breast cancer than women in the general population. Possible explanations include opposing risk factors for cervical cancer and breast cancer, the effect of irradiation used to treat cervical cancer, or both. The purpose of this study was to explore the relationship between irradiation for cervical cancer and the subsequent development of breast cancer. There was no statistically significant relationship between radiation to the ovarian area and the risk of breast cancer in this study. However, the results were consistent with a 19% reduction in risk for women irradiated for cervical cancer when compared to nonirradiated women. In a dose-response analysis, there was a nonsignificant trend of decreased risk of breast cancer with increased radiation up to 1800 rad. There was no consistent pattern for higher doses. The trend, although nonsignificant, differed by age. Women <60 years of age at irradiation were generally at a lower risk of breast cancer than nonirradiated women. Women over 59 years were at an increased risk. There are some potentially important findings from this study which might influence medical care. These should be examined in the larger International Radiation Study.

  14. A molecular beacon-based method for screening cervical cancer.

    PubMed

    Han, Suxia; Li, Ling; Jia, Xi; Ou, Wei; Ma, Jinlu; Wang, Hao; Zhao, Jing; Zhu, Qing

    2012-11-01

    The aim of this study is to develop a new screening method, molecular beacon (MB) imaging, for detection of cervical cancer and to determine its potential clinical applications by examining the sensitivity and specificity of target-specific MBs. Two target-specific molecular beacons were designed and synthesized for survivin and HPV16E6 mRNA. The two designed MBs and a random control MB were used to detect cervical cancer cell lines and a normal cell line. RT-PCR and western blot targeting survivin and HPV16E6 was done for verification. Furthermore the sensitivity and the specificity of the survivin and HPV16E6 mRNA MBs were examined in smears from 125 clinical cervical patients. The survivin and HPV16E6 mRNA MBs generated a strong fluorescence signal in cervical cancer cell lines, but not in the normal cell line, while the random control MB did not generated any signal in both cell lines. The fluorescence intensity correlated well with the gene expression levels in the cells determined by reverse transcription-PCR and Western blot analysis. The clinical sensitivity and the specificity of survivin MB-FITC were 72.5 and 77% while those of HPV16E6 MB-Cy3 were 96.1% and 71.6%, respectively. A parallel test of the two target MBs showed that the sensitivity increased to 98% and the specificity was 70.2%. The survivin and HPV16E6 mRNA MBs showed good reliability and sensitivity. They have great potential for clinical use in cervical cancer screening.

  15. Expression of transcription factor grainyhead-like 2 is diminished in cervical cancer

    PubMed Central

    Torres-Reyes, Luis A; Alvarado-Ruiz, Liliana; Piña-Sánchez, Patricia; Martínez-Silva, María G; Ramos-Solano, Moisés; Olimón-Andalón, Vicente; Ortiz-Lazareno, Pablo C; Hernández-Flores, Georgina; Bravo-Cuellar, Alejandro; Aguilar-Lemarroy, Adriana; Jave-Suarez, Luis F

    2014-01-01

    The transcription factor grainyhead-like 2 (GRHL2) is evolutionarily conserved in many different species, and is involved in morphogenesis, epithelial differentiation, and the control of the epithelial-mesenchymal transition. It has also recently been implicated in carcinogenesis, but its role in this remains controversial. Expression of GRHL2 has not previously been reported in cervical cancer, so the present study aimed to characterize GRHL2 expression in cervical cancer-derived cell lines (CCCLs) and cervical tissues with different grades of lesions. Microarray analysis found that the expression of 58 genes was down-regulated in CCCLs compared to HaCaT cells (non-tumorigenic human epithelial cell line). The expression of eight of these genes was validated by quantitative real-time PCR (qPCR), and GRHL2 was found to be the most down-regulated. Western blot assays corroborated that GRHL2 protein levels were strongly down-regulated in CCCLs. Cervical cells from women without cervical lesions were shown to express GRHL2, while immunohistochemistry found that positivity to GRHL2 decreased in cervical cancer tissues. In conclusion, a loss or strong reduction in GRHL2 expression appears to be a characteristic of cervical cancer, suggesting that GRHL2 down-regulation is a necessary step during cervical carcinogenesis. However, further studies are needed to delineate the role of GRHL2 in cervical cancer and during malignant progression. PMID:25550776

  16. NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer

    PubMed Central

    Niu, Chunhao; Sun, Xiaoying; Zhang, Weijing; Li, Han; Xu, Liqun; Li, Jun; Xu, Benke; Zhang, Yanna

    2016-01-01

    Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6) in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC). NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.006), squamous cell carcinoma antigen (p = 0.006), vital status (p < 0.001), tumor recurrence (p = 0.001), chemotherapy (p = 0.039), and lymph node metastasis (p < 0.001). Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer. PMID:27775588

  17. The role of MALAT1 correlates with HPV in cervical cancer.

    PubMed

    Jiang, Yan; Li, Yuehui; Fang, Shujuan; Jiang, Binyuan; Qin, Changfei; Xie, Pingli; Zhou, Guohua; Li, Guancheng

    2014-06-01

    Cervical cancer, the second most common type of cancer in women worldwide, is responsible for >275,100 mortalities each year and is associated with high-risk human papilloma virus (HR-HPV). HPVs have two important oncogenes, E6 and E7, which have crucial roles in malignant transformation in cervical cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA originally identified in non-small cell lung cancer. Previous studies have revealed that MALAT1 is expressed in numerous tissue types, and is significant in maintaining the normal function of the body. However, it also appeared to be notably upregulated in numerous carcinoma types compared with adjacent non-cancerous tissues. In the present study, it was identified that MALAT1 expression was upregulated in cervical cancer cell lines compared with normal cervical squamous cell samples. Further study into the effect of MALAT1 on cellular phenotype revealed that MALAT1 was able to promote cell migration and proliferation. Of note, it was revealed that the expression of MALAT1 was decreased with the knockdown of HPV16 E6/E7 in CaSki cells. Furthermore, the investigations in clinical samples also revealed that MALAT1 was expressed in HPV-positive cervical squamous cells, but not in HPV-negative normal cervical squamous cells. These results indicate that HPV correlates with MALAT1 deregulation in cervical cancer.

  18. Use of rhenium-188 for in vivo imaging and treatment of human cervical cancer cells transfected with lentivirus expressing sodium iodide symporter.

    PubMed

    Zhang, Min; Shi, Shuo; Guo, Rui; Miao, Yin; Li, Biao

    2016-10-01

    Although survival rates for cervical cancer have improved, they need further improvement in patients with distant metastases. The sodium iodine symporter (NIS) gene has often been used in cancer therapy and imaging. We examined the therapeutic effects of rhenium-188 (188Re) in a cervical cancer xenograft model expressing the NIS gene under the control of the tumor-specific human telomerase reverse transcriptase (hTERT) promoter. We constructed two recombinant lentiviral vectors expressing enhanced green fluorescent protein (eGFP) or the NIS gene driven by the hTERT promoter. To determine the tumor-specific transcriptional activity of the hTERT promoter, the eGFP-expressing vector was stably transfected into tumor cells and normal cells. A cervical cancer HeLa cell line stably expressing NIS (HeLa-TERTNIS) was created and examined in a similar way. HeLa and HeLa-TERTNIS tumor xenografts were transplanted in nude mice, and in vivo 188Re distribution was measured using micro-SPECT/CT imaging. The therapeutic effects of 188Re were assessed over 21 days on the basis of tumor volume and the immunohistochemical findings of excised tumors. eGFP expression controlled by the hTERT promoter was substantially higher in the tumor cells than normal cells. Quantitative PCR and western blotting confirmed that HeLa-TERTNIS cells expressed high levels of NIS mRNA and protein, respectively. Further, 188Re uptake and accumulation were significantly higher in HeLa-TERTNIS cells and xenografts than HeLa cells and xenografts. In vitro and in vivo, 188Re significantly reduced the survival of HeLa-TERTNIS cells and inhibited the growth of HeLa-TERTNIS xenografts, respectively. Immunohistochemical staining showed that HeLa-TERTNIS xenograft tumors expressed higher levels of NIS and caspase-3 and lower levels of Ki-67 than HeLa xenograft tumors. Our findings indicated that hTERT promoter-driven expression of the NIS gene in HeLa cells led to 188Re uptake and therapeutic effects. Thus, NIS

  19. [Chromosomal instability in carcinogenesis of cervical cancer.

    PubMed

    de Los Santos-Munive, Victoria; Alonso-Avelino, Juan Angel

    2013-01-01

    In order to spot common chromosomal imbalances in early and late lesions of cervical cancer that might be used as progression biomarkers, we made a search of literature in PubMed from 1996 to 2011. The medical subject headings employed were chromosomal alterations, loss of heterozygosis, cervical cancer, cervical tumorigenesis, chromosomal aberrations, cervical intraepithelial neoplasm and low-grade squamous intraepithelial lesion. The common chromosomal imbalances were gains in 8q24 (77.7 %), 20q13 (66.9 %), 3q26 (47.1 %), Xp22 (43.8 %), and 5p15 (60 %), principally. On the other hand, integration of the high-risk human papillomavirus genome into the host chromosome has been associated with the development of neoplasia, but the chromosomal imbalances seem to precede and promote such integration. Chromosomal imbalances in 8q24, 20q13, 3q21-26 and 5p15-Xp22, determined by fluorescent in situ hybridization assay or comparative genomic hybridization assay for early detection of the presence of high-risk human papillomavirus, are promising markers of cervical cancer progression.

  20. Optoelectronic method for detection of cervical intraepithelial neoplasia and cervical cancer

    NASA Astrophysics Data System (ADS)

    Pruski, D.; Przybylski, M.; Kędzia, W.; Kędzia, H.; Jagielska-Pruska, J.; Spaczyński, M.

    2011-12-01

    The optoelectronic method is one of the most promising concepts of biophysical program of the diagnostics of CIN and cervical cancer. Objectives of the work are evaluation of sensitivity and specificity of the optoelectronic method in the detection of CIN and cervical cancer. The paper shows correlation between the pNOR number and sensitivity/specificity of the optoelectronic method. The study included 293 patients with abnormal cervical cytology result and the following examinations: examination with the use of the optoelectronic method — Truscreen, colposcopic examination, and histopathologic biopsy. Specificity of the optoelectronic method for LGSIL was estimated at 65.70%, for HGSIL and squamous cell carcinoma of cervix amounted to 90.38%. Specificity of the optoelectronic method used to confirm lack of cervical pathology was estimated at 78.89%. The field under the ROC curve for the optoelectronic method was estimated at 0.88 (95% CI, 0.84-0.92) which shows high diagnostic value of the test in the detection of HGSIL and squamous cell carcinoma. The optoelectronic method is characterised by high usefulness in the detection of CIN, present in the squamous epithelium and squamous cell carcinoma of cervix.

  1. Downregulation of a novel human gene, ROGDI, increases radiosensitivity in cervical cancer cells

    PubMed Central

    Chen, Yi-Fan; Cho, Jonathan J.; Huang, Tsai-Hua; Tseng, Chao-Neng; Huang, Eng-Yen; Cho, Chung-Lung

    2016-01-01

    ABSTRACT ROGDI is a protein that contains a leucine zipper domain and may be involved in cell proliferation. In addition, ROGDI is associated with genome stability by regulating the activity of a DNA damage marker, γ-H2AX. The role of ROGDI in tumor radiosensitization has not been investigated. Previous studies have indicated that radiosensitivity is associated with DNA repair and the cell cycle. In general, the G2/M DNA damage checkpoint is more sensitive to radiation, whereas the G1/S phase transition is more resistant to radiation. Inhibition of cyclin-dependent kinases (CDKs) can lead to a halt of cell cycle progression and a stay at different phases or checkpoints. Our data show that the downregulation of ROGDI led to a decreased expression of CDK 1, 2, cyclin A, B and resulted in a G2/M phase transition block. In addition, the downregulation of ROGDI increased cell accumulation at the G2 phase as detected using flow cytometry and decreased cell survival as revealed by clonogenic assay in HeLa and C33A cells following irradiation. These findings suggest that the downregulation of ROGDI can mediate radiosensitivity by blocking cells at G2/M, the most radiosensitive phase of the cell cycle, as well as exerting deleterious effects in the form of DNA damage, as shown by increased γ-H2AX activation. PMID:27636029

  2. Chlamydia Trachomatis Infection-Associated Risk of Cervical Cancer

    PubMed Central

    Zhu, Haiyan; Shen, Zhaojun; Luo, Hui; Zhang, Wenwen; Zhu, Xueqiong

    2016-01-01

    Abstract As whether Chlamydia trachomatis infection increases the risk of cervical cancer is controversial in the literature, we performed a meta-analysis. Based on a comprehensive search of publications in the Medline, Cochrane, and EMBASE databases, we identified and extracted data from all relevant articles examining C. trachomatis infection and the risk of cervical cancer. The quality of each included study was assessed according to the 9-star Newcastle–Ottawa scale. The strength of association between the C. trachomatis and risk of cervical cancer was estimated by odds ratio (OR) and 95% confidence intervals (CIs). This review was registered at PROSPERO with registration No. CRD42014015672. A total of 22 studies with 4291 cervical cancer cases and 7628 controls were identified. Overall, C. trachomatis was significantly linked to increased cervical cancer risk in prospective studies (OR = 2.21, 95% CI: 1.88–2.61, P < 0.001), as well as in retrospective studies (OR = 2.19, 95% CI: 1.74–2.74, P < 0.001). Additionally, with a multivariate logistic regression analysis adjusted for HPV and age, C. trachomatis infection was identified as an independent predictor of cervical cancer in 11 studies (OR = 1.76, 95% CI: 1.03–3.01, P = 0.04). Coinfection of human papilloma virus and C. trachomatis has a higher risk of cervical cancer (OR = 4.03, 95% CI: 3.15–5.16, P < 0.001). A subgroup analysis based on histological type indicated an elevated risk for both squamous cell carcinoma (OR = 2.21, 95% CI: 2.00–2.45, P < 0.001), and adenocarcinoma (OR = 1.61, 95% CI: 1.21–2.15, P = 0.001), in associated with C. trachomatis. Subgroup analysis by where C. trachomatis infection was detected showed a significantly higher risk of cervical cancer associated with C. trachomatis infection detected in serum (OR = 2.20, 95% CI: 2.01–2.42, P < 0.001), cervical tissue blocks (OR = 2.88, 95% CI: 1.21–6.83, P = 0

  3. Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selective tumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells.

    PubMed

    Kim, Hye-Sun; Yi, Bo-Rim; Hwang, Kyung-A; Kim, Seung U; Choi, Kyung-Chul

    2013-10-01

    The aim of the present study was to investigate the therapeutic efficacy of genetically engineered stem cells (GESTECs) expressing bacterial cytosine deaminase (CD) and/or human interferon-beta (IFN-β) gene against HeLa cervical cancer and the migration factors of the GESTECs toward the cancer cells. Anticancer effect of GESTECs was examined in a co-culture with HeLa cells using MTT assay to measure cell viability. A transwell migration assay was performed so as to assess the migration capability of the stem cells to cervical cancer cells. Next, several chemoattractant ligands and their receptors related to a selective migration of the stem cells toward HeLa cells were determined by real-time PCR. The cell viability of HeLa cells was decreased in response to 5-fluorocytosine (5-FC), a prodrug, indicating that 5-fluorouracil (5-FU), a toxic metabolite, was converted from 5-FC by CD gene and it caused the cell death in a co-culture system. When IFN-β was additionally expressed with CD gene by these GESTECs, the anticancer activity was significantly increased. In the migration assay, the GESTECs selectively migrated to HeLa cervical cancer cells. As results of real-time PCR, chemoattractant ligands such as MCP-1, SCF, and VEGF were expressed in HeLa cells, and several receptors such as uPAR, VEGFR2, and c-kit were produced by the GESTECs. These GESTECs transduced with CD gene and IFN-β may provide a potential of a novel gene therapy for anticervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs.

  4. Melatonin sensitizes human cervical cancer HeLa cells to cisplatin-induced cytotoxicity and apoptosis: effects on oxidative stress and DNA fragmentation.

    PubMed

    Pariente, Roberto; Pariente, José A; Rodríguez, Ana B; Espino, Javier

    2016-01-01

    Melatonin has antitumor activity via several mechanisms including its antiproliferative and pro-apoptotic effects as well as its potent antioxidant actions, although recent evidence has indicated that melatonin may perform pro-oxidant actions in tumor cells. Therefore, melatonin may be useful in the treatment of tumors in association with chemotherapy drugs. This study was intended to evaluate the in vitro effect of melatonin on the cytotoxic and pro-apoptotic actions of various chemotherapeutic agents in cervical cancer HeLa cells. Herein, we found that both melatonin and three of the chemotherapeutic drugs tested, namely cisplatin (CIS), 5-fluorouracil (5-FU), and doxorubicin, induced a decrease in HeLa cell viability. Furthermore, melatonin significantly increased the cytotoxic effect of such chemotherapeutic agents. Consistently, costimulation of HeLa cells with any chemotherapeutic agent in the presence of melatonin further increased caspase-3 activation, particularly in CIS- and 5-FU-challenged cells. Likewise, concomitant treatments with melatonin and CIS significantly enhanced the ratio of cells entering mitochondrial apoptosis due to reactive oxygen species (ROS) overproduction, substantially augmented the population of apoptotic cells, and markedly enlarged DNA fragmentation compared to the treatments with CIS alone. Nonetheless, melatonin only displayed moderate chemosensitizing effects in 5-FU-stimulated HeLa cells, as suggested by slight increments in the percentage of cells stimulated for ROS production and in the proportion of early apoptotic cells compared to the treatments with 5-FU alone. In summary, our findings provided evidence that in vitro melatonin strongly enhances CIS-induced cytotoxicity and apoptosis in HeLa cells and, hence, the indoleamine could be potentially applied to cervical cancer treatment as a powerful synergistic agent.

  5. [Cervical cancer screening in Switzerland - current practice and future challenges].

    PubMed

    Untiet, Sarah; Schmidt, Nicole; Low, Nicola; Petignat, Patrick

    2013-04-01

    At the beginning of the 20th Century, cervical cancer was the leading cause of death from cancer in women. A marked decline in cervical cancer has been observed since the 1960s, in parallel with the introduction of the Papanicolau (Pap) test as a cytological screening method. Today, Pap smear screening is still the most widely used tool for cervical cancer prevention. Testing for human papillomavirus (HPV) in cervical specimens or a combination of Pap and HPV testing are also now available. In this article we compare current guidelines for cervical cancer screening in Switzerland with those in other European countries. In view of the opportunities offered by HPV testing and, since 2008, HPV vaccination, current guidelines for cervical cancer screening should be updated. Both the choice of screening tests and general organization of cervical cancer screening should be reviewed.

  6. The enhanced inhibitory effect of different antitumor agents in self-microemulsifying drug delivery systems on human cervical cancer HeLa cells.

    PubMed

    Ujhelyi, Zoltán; Kalantari, Azin; Vecsernyés, Miklós; Róka, Eszter; Fenyvesi, Ferenc; Póka, Róbert; Kozma, Bence; Bácskay, Ildikó

    2015-07-21

    The aim of this study was to develop topical self-microemulsifying drug delivery systems (SMEDDS) containing antitumor agents (bleomycin, cisplatin and ifosfamide) and to investigate their inhibitory potential in SMEDDS on human cervical cancer HeLa cells. The physicochemical properties of cytostatic drug loaded SMEDDS were characterized. The cytotoxicity of main components of SMEDDS was also investigated. Their IC50 values were determined. HeLa cells were treated by different concentrations of cisplatin, bleomycin and ifosfamide alone and in various SMEDDS. The inhibitory effect on cell growth was analyzed by MTT cell viability assay. Inflammation is a driving force that accelerates cancer development. The inhibitory effect of these antitumor agents has also been tested on HeLa cells in the presence of inflammatory mediators (IL-1-β, TNF-α) as an in vitro model of inflamed human cervix. Significant differences in the cytotoxicity of cytostatic drugs alone and in SMEDDS have been found in a concentration-dependent manner. The self-micro emulsifying system may potentiate the effectiveness of bleomycin, cisplatin and ifosfamide topically. The effect of SMEDDS containing antitumor agents was decreased significantly in the presence of inflammatory mediators. According to our experiments, the optimal SMEDDS formulation is 1:1:2:6:2 ratios of Isopropyl myristate, Capryol 90, Kolliphor RH 40, Cremophor RH40, Transcutol HP and Labrasol. It can be concluded that SMEDDS may increase the inhibitory effect of bleomycin, ifosfamide and cisplatin on human cervical cancer HeLa cells. Inflammation on HeLa cells hinders the effectiveness of SMEDDS containing antitumor agents. Our results might ensure useful data for development of optimal antitumor formulations.

  7. Cervical cancer: Can it be prevented?

    PubMed Central

    Aggarwal, Pakhee

    2014-01-01

    Cervical cancer prevention requires a multipronged approach involving primary, secondary and tertiary prevention. The key element under primary prevention is human papilloma virus (HPV) vaccination. So far, only prophylactic HPV vaccines which prevent HPV infection by one or more subtypes are commercially available. Therapeutic HPV vaccines which aid in clearing established infection are still under trial. Secondary prevention entails early detection of precancerous lesions and its success is determined by the population coverage and the efficacy of the screening technique. A number of techniques are in use, including cytology, visual inspection (using the naked eye, magnivisualizer, acetic acid and Lugol’s iodine), HPV testing and a combination of these methods. Updated screening guidelines have been advocated by the American Cancer Society in light of the role of HPV on cervical carcinogenesis. Recent research has also focussed on novel biomarkers that can predict progression to cancer in screen positive women and help to differentiate those who need treatment from those who can be left for follow-up. Last but not the least, effective treatment of precancerous lesions can help to reduce the incidence of invasive cervical cancer and this constitutes tertiary prevention. A combination of these approaches can help to prevent the burden of cervical cancer and its antecedent morbidity and mortality, but all of these are not feasible in all settings due to resource and allocation constraints. Thus, all countries, especially low and middle income ones, have to determine their own cocktail of approaches that work before we can say with certainty that yes, cervical cancer can be prevented. PMID:25302177

  8. The Subcellular Localisation of the Human Papillomavirus (HPV) 16 E7 Protein in Cervical Cancer Cells and Its Perturbation by RNA Aptamers

    PubMed Central

    Cesur, Özlem; Nicol, Clare; Groves, Helen; Mankouri, Jamel; Blair, George Eric; Stonehouse, Nicola J.

    2015-01-01

    Human papillomavirus (HPV) is the most common viral infection of the reproductive tract, affecting both men and women. High-risk oncogenic types are responsible for almost 90% of anogenital and oropharyngeal cancers including cervical cancer. Some of the HPV “early” genes, particularly E6 and E7, are known to act as oncogenes that promote tumour growth and malignant transformation. Most notably, HPV-16 E7 interacts with the tumour suppressor protein pRb, promoting its degradation, leading to cell cycle dysregulation in infected cells. We have previously shown that an RNA aptamer (termed A2) selectively binds to HPV16 E7 and is able to induce apoptosis in HPV16-transformed cervical carcinoma cell lines (SiHa) through reduction of E7 levels. In this study, we investigated the effects of the A2 aptamer on E7 localisation in order to define its effects on E7 activity. We demonstrate for the first time that E7 localised to the plasma membrane. In addition, we show that A2 enhanced E7 localisation in the ER and that the A2-mediated reduction of E7 was not associated with proteasomal degradation. These data suggest that A2 perturbs normal E7 trafficking through promoting E7 ER retention. PMID:26131956

  9. Microarray analysis of DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252Cf neutron and X-rays

    PubMed Central

    2010-01-01

    Background The aim of the study was to obtain stable radioresistant sub-lines from the human cervical cancer cell line HeLa by prolonged exposure to 252Cf neutron and X-rays. Radioresistance mechanisms were investigated in the resulting cells using microarray analysis of DNA damage repair genes. Methods HeLa cells were treated with fractionated 252Cf neutron and X-rays, with a cumulative dose of 75 Gy each, over 8 months, yielding the sub-lines HeLaNR and HeLaXR. Radioresistant characteristics were detected by clone formation assay, ultrastructural observations, cell doubling time, cell cycle distribution, and apoptosis assay. Gene expression patterns of the radioresistant sub-lines were studied through microarray analysis and verified by Western blotting and real-time PCR. Results The radioresistant sub-lines HeLaNR and HeLaXR were more radioresisitant to 252Cf neutron and X-rays than parental HeLa cells by detecting their radioresistant characteristics, respectively. Compared to HeLa cells, the expression of 24 genes was significantly altered by at least 2-fold in HeLaNR cells. Of these, 19 genes were up-regulated and 5 down-regulated. In HeLaXR cells, 41 genes were significantly altered by at least 2-fold; 38 genes were up-regulated and 3 down-regulated. Conclusions Chronic exposure of cells to ionizing radiation induces adaptive responses that enhance tolerance of ionizing radiation and allow investigations of cellular radioresistance mechanisms. The insights gained into the molecular mechanisms activated by these "radioresistance" genes will lead to new therapeutic targets for cervical cancer. PMID:20184742

  10. Cervical Cancer: paradigms at home and abroad

    Cancer.gov

    NCI funded a clinical trial that will have an impact on the treatment of late-stage cervical cancer, and also supported a screening trial in India using a network of community outreach workers offering low tech-screening by direct visualization of the cer

  11. Cervical Cancer Screening and Perceived Information Needs

    ERIC Educational Resources Information Center

    Whynes, David K.; Clarke, Katherine; Philips, Zoe; Avis, Mark

    2005-01-01

    Purpose: To identify women's sources of information about cervical cancer screening, information which women report receiving during Pap consultations, information they would like to receive, and the relationships between perceived information needs, personal characteristics and information sources. Design/methodology/approach: Logistic regression…

  12. Flexitouch® Home Maintenance Therapy or Standard Home Maintenance Therapy in Treating Patients With Lower-Extremity Lymphedema Caused by Treatment for Cervical Cancer, Vulvar Cancer, or Endometrial Cancer

    ClinicalTrials.gov

    2014-12-29

    Lymphedema; Stage 0 Cervical Cancer; Stage 0 Uterine Corpus Cancer; Stage 0 Vulvar Cancer; Stage I Uterine Corpus Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Uterine Corpus Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vulvar Cancer; Stage IV Uterine Corpus Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Stage IVB Vulvar Cancer

  13. Strategies against human papillomavirus infection and cervical cancer.

    PubMed

    Jung, Woon-Won; Chun, Taehoon; Sul, Donggeun; Hwang, Kwang Woo; Kang, Hyung-Sik; Lee, Duck Joo; Han, In-Kwon

    2004-12-01

    Papillomaviruses infect a wide variety of animals, including humans. The human papillomavirus (HPV), in particular, is one of the most common causes of sexually transmitted disease. More than 200 types of HPV have been identified by DNA sequence data, and 85 HPV genotypes have been well characterized to date. HPV can infect the basal epithelial cells of the skin or inner tissue linings, and are, accordingly, categorized as either cutaneous or mucosal type. HPV is associated with a panoply of clinical conditions, ranging from innocuous lesions to cervical cancer. In the early 1980s, studies first reported a link between cervical cancer and genital HPV infection. Genital HPV infections are now recognized to be a major risk factor in at least 95% of cervical cancers. 30 different HPV genotypes have been identified as causative of sexually transmitted diseases, most of which induce lesions in the cervix, vagina, vulva, penis, and anus, as the result of sexual contact. There is also direct evidence demonstrating that at least four of these genotypes are prerequisite factors in cervical cancer. The main aim of this review was to evaluate the current literature regarding the pathovirology, diagnostics, vaccines, therapy, risk groups, and further therapeutic directions for HPV infections. In addition, we reviewed the current status of HPV infections in South Korean women, as evidenced by our data.

  14. The role of trachelectomy in cervical cancer

    PubMed Central

    Halaska, MJ; Robova, H; Pluta, M; Rob, L

    2015-01-01

    Cervical cancer is one of the most common cancers in women worldwide. Because it often affects women of childbearing age (19–45 years), fertility-sparing surgery is an important issue. The article reviews current viable fertility-sparing options with a special focus on trachelectomy, including vaginal radical trachelectomy, abdominal radical trachelectomy and simple trachelectomy. Neoadjuvant chemotherapy is also discussed. Finally, the decision to proceed with fertility-sparing treatment should be a patient-driven process. PMID:25729419

  15. Requirement for Estrogen Receptor Alpha in a Mouse Model for Human Papillomavirus-Associated Cervical Cancer

    PubMed Central

    Chung, Sang-Hyuk; Wiedmeyer, Kerri; Shai, Anny; Korach, Kenneth S.; Lambert, Paul F.

    2008-01-01

    The majority of human cervical cancers are associated with the high-risk human papillomaviruses (HPVs), which encode the potent E6 and E7 oncogenes. Upon prolonged treatment with physiological levels of exogenous estrogen, K14E7 transgenic mice expressing HPV-16 E7 oncoprotein in their squamous epithelia succumb to uterine cervical cancer. Furthermore, prolonged withdrawal of exogenous estrogen results in complete or partial regression of tumors in this mouse model. In the current study we investigated whether estrogen receptor alpha (ERα) is required for the development of cervical cancer in K14E7 transgenic mice. We demonstrate that exogenous estrogen fails to promote either dysplasia or cervical cancer in K14E7/ERα−/− mice despite the continued presence of the presumed cervical cancer precursor cell type, reserve cells, and evidence for E7 expression therein. We also observed that cervical cancers in our mouse models are strictly associated with atypical squamous metaplasia (ASM), which is believed to be the precursor for cervical cancer in women. Consistently, E7 and exogenous estrogen failed to promote ASM in the absence of ERα. We conclude that ERα plays a crucial role at an early stage of cervical carcinogenesis in this mouse model. PMID:19047174

  16. Cervical Tissue Engineering Using Silk Scaffolds and Human Cervical Cells

    PubMed Central

    Sanchez, Cristina C.; Rice, William L.; Socrate, Simona; Kaplan, David L.

    2010-01-01

    Spontaneous preterm birth is a frequent complication of pregnancy and a common cause of morbidity in childhood. Obstetricians suspect abnormalities of the cervix are implicated in a significant number of preterm births. The cervix is composed of fibrous connective tissue and undergoes significant remodeling in preparation for birth. We hypothesized that a tissue engineering strategy could be used to develop three-dimensional cervical-like tissue constructs that would be suitable for investigating cervical remodeling. Cervical cells were isolated from two premenopausal women undergoing hysterectomy for a benign gynecological condition, and the cells were seeded on porous silk scaffolds in the presence or absence of dynamic culture and with 10% or 20% serum. Morphological, biochemical, and mechanical properties were measured during the 8-week culture period. Cervical cells proliferated in three-dimensions and synthesized an extracellular matrix with biochemical constituents and morphology similar to native tissue. Compared to static culture, dynamic culture was associated with significantly increased collagen deposition (p < 0.05), sulfated glycosaminoglycan synthesis (p < 0.05), and mechanical stiffness (p < 0.05). Serum concentration did not affect measured variables. Relevant human tissue-engineered cervical-like constructs constitute a novel model system for a range of fundamental and applied studies related to cervical remodeling. PMID:20121593

  17. Effects of tetrahydrocurcumin on hypoxia-inducible factor-1α and vascular endothelial growth factor expression in cervical cancer cell-induced angiogenesis in nude mice.

    PubMed

    Yoysungnoen, Bhornprom; Bhattarakosol, Parvapan; Patumraj, Suthiluk; Changtam, Chatchawan

    2015-01-01

    Tetrahydrocurcumin (THC), one of the important in vivo metabolites of curcumin, inhibits tumor angiogenesis. Its effects on angiogenesis in cervical cancer- (CaSki-) implanted nude mice and its mechanisms on hypoxia-inducible factor-1α and vascular endothelial growth factor expression were investigated. Female BALB/c nude mice were divided into control (CON) and CaSki-implanted groups (CaSki group). One month after the injection with cervical cancer cells, mice were orally administered vehicle or 100, 300, and 500 mg/kg of THC daily for 30 consecutive days. The microvascular density (MVD) was evaluated using the CD31 expression. VEGF, VEGFR-2, and HIF-1α expression were also detected by immunohistochemistry. The MVD in CaSki + vehicle group was significantly increased compared to the CON + vehicle group. Interestingly, when treated with THC at all doses, the CaSki group showed a significant smaller number of the MVD. The CaSki + vehicle group also showed significantly increased VEGF, VEGFR-2, and HIF-1α expressions, but they were downregulated when mice were treated with THC at all doses. THC demonstrated an inhibitory effect against tumor angiogenesis in CaSki-implanted nude mice model. This effect is likely to be mediated by the downregulation of HIF-1-α, VEGF expression, and its receptor. THC could be developed into a promising agent for cancer therapy in the future.

  18. Effects of Tetrahydrocurcumin on Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor Expression in Cervical Cancer Cell-Induced Angiogenesis in Nude Mice

    PubMed Central

    Yoysungnoen, Bhornprom; Patumraj, Suthiluk; Changtam, Chatchawan

    2015-01-01

    Tetrahydrocurcumin (THC), one of the important in vivo metabolites of curcumin, inhibits tumor angiogenesis. Its effects on angiogenesis in cervical cancer- (CaSki-) implanted nude mice and its mechanisms on hypoxia-inducible factor-1α and vascular endothelial growth factor expression were investigated. Female BALB/c nude mice were divided into control (CON) and CaSki-implanted groups (CaSki group). One month after the injection with cervical cancer cells, mice were orally administered vehicle or 100, 300, and 500 mg/kg of THC daily for 30 consecutive days. The microvascular density (MVD) was evaluated using the CD31 expression. VEGF, VEGFR-2, and HIF-1α expression were also detected by immunohistochemistry. The MVD in CaSki + vehicle group was significantly increased compared to the CON + vehicle group. Interestingly, when treated with THC at all doses, the CaSki group showed a significant smaller number of the MVD. The CaSki + vehicle group also showed significantly increased VEGF, VEGFR-2, and HIF-1α expressions, but they were downregulated when mice were treated with THC at all doses. THC demonstrated an inhibitory effect against tumor angiogenesis in CaSki-implanted nude mice model. This effect is likely to be mediated by the downregulation of HIF-1-α, VEGF expression, and its receptor. THC could be developed into a promising agent for cancer therapy in the future. PMID:25789317

  19. Current Evidence and Potential Mechanisms of Therapeutic Action of PEDF in Cervical Cancer Treatment.

    PubMed

    Han, J; Guo, J

    2015-01-01

    Cervical cancer is the second leading gynecological malignancy threat to the health of women in the world. However, few improvements in the efficacy of treatments of cervical cancer have been reported for the recurrent and metastasis patterns. As an endogenous antitumor agent, pigment epithelium derived factor (PEDF) has attracted wide attention, and its sensitivity to estrogen suggests a special role in female tumors, including cervical cancer. This review aims to summarize recent findings, the role of PEDF in cervical cancer treatment, and enhance the current understanding of the antitumor properties of PEDF such as inhibiting angiogenesis and metastasis, inducing tumor cell apoptosis and differentiation, and modulating cellular immunity against cervical cancer. The production and delivery of PEDF, as well as derived short peptides and their respective receptors will also be discussed.

  20. Securinine from Phyllanthus glaucus Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells

    PubMed Central

    Krauze-Baranowska, Mirosława; Ochocka, J. Renata

    2016-01-01

    Background The Securinega-type alkaloids occur in plants belonging to Euphorbiaceae family. One of the most widely distributed alkaloid of this group is securinine, which was identified next to allosecurinine in Phyllanthus glaucus (leafflower). Recently, some Securinega-type alkaloids have paid attention to its antiproliferative potency towards different cancer cells. However, the cytotoxic properties of allosecurinine have not yet been evaluated. Methods The cytotoxicity of the extract, alkaloid fraction obtained from P. glaucus, isolated securinine and allosecurinine against HeLa cells was evaluated by real-time xCELLigence system and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and 7-amino-actinomycin (7-AAD) staining and confirmed with fluorescent Hoechst 33342 dye. The assessment of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, the level of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), caspase-3/7 activity and cell cycle analysis were measured by flow cytometry. The enzymatic activity of caspase-9 was assessed by a luminometric assay. The expression of apoptosis associated genes was analyzed by real-time PCR. Results The experimental data revealed that securinine and the alkaloid fraction were significantly potent on HeLa cells growth inhibition with IC50 values of 7.02 ± 0.52 μg/ml (32.3 μM) and 25.46 ± 1.79 μg/ml, respectively. The activity of allosecurinine and Phyllanthus extract were much lower. Furthermore, our study showed that the most active securinine induced apoptosis in a dose-dependent manner in the tested cells, increased the percentage of ROS positive cells and depolarized cells as well as stimulated the activity of ERK1/2, caspase-9 and -3/7. Securinine also induced cell cycle arrest in S phase. Real-time PCR analysis showed high expression of TNFRSF genes in the cells stimulated with securinine. Conclusions Securinine

  1. Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED)

    Cancer.gov

    A study to comprehensively assess biomarkers of risk for progressive cervical neoplasia, and thus develop a new set of biomarkers that can distinguish those at highest risk of cervical cancer from those with benign infection

  2. The paradigm shift in cervical cancer screening in Germany.

    PubMed

    Hillemanns, Peter

    2016-01-01

    With the adoption of the Cancer Screening and Registration Law (KFRG, 2013) based on the National Cancer Plan, the so far opportunistic cervical cancer screening in Germany is to be converted to an organized screening program. This decision in Germany is consistent with the new EU Guidelines and, in anticipation of the upcoming German S3 guideline for cervical cancer screening.

  3. MicroRNA-148b Acts as a Tumor Suppressor in Cervical Cancer by Inducing G1/S-Phase Cell Cycle Arrest and Apoptosis in a Caspase-3-Dependent Manner

    PubMed Central

    Mou, Zongmei; Xu, Xiangting; Dong, Mei; Xu, Jin

    2016-01-01

    Background The purpose of our study was to investigate the role of microRNA (miR)-148b in cervical cancer. Material/Methods The expression of miR-148b was determined in HPV-16-immortalized cervical epithelial cell line CRL-2614 cells and in cervical cancer cell line HeLa cells. The miR-148b mimics or scrambled RNA were then transfected into Hela cells. Forty-eight hours after transfection, the mRNA expression of miR-148b and DNA methyltransferase 1 (DNMT1) were confirmed. Cell proliferation ability (cell viability and colony formation ability), invasion ability, and apoptosis were assessed after transfection with miR-148b mimics or scrambled RNA, as well as the protein expression of cyclin D1 and caspase-3. Results The expression of miR-148b was significantly downregulated in HeLa cells compared with CRL2614 cells (P<0.05), but was statistically upregulated by transfection with miR-148b mimics compared with the cells transfected with scrambled RNA (P<0.05). Also, we found that the expression of DNMT1 was significantly decreased by transfection with miR-148b mimics (P<0.05). Additionally, miR-148b mimics significantly decreased the cell proliferation ability and invasion ability, and statistically induced apoptosis. Furthermore, the expression of cyclin D1 protein was significantly decreased and the expression of caspase-3 protein was significantly increased by miR-148b mimics compared with that in the cells transfected with scrambled RNA (P<0.05). Conclusions Our results suggest that overexpression of miR-148b protects against cervical cancer by inducing G1/S-phase cell cycle arrest and apoptosis through caspase-3-dependent manner, and overexpression of miR-148b might develop a therapeutic intervention for cervical cancer. PMID:27505047

  4. [Cervical cancer is a clinical challenge].

    PubMed

    Bjurberg, Maria; Beskow, Catharina; Kannisto, Päivi; Lindahl, Gabriel

    2015-01-01

    Cervical cancer is the third most common female cancer world wide. In Sweden, some 450 cases are diagnosed annually. One out of three affected Swedish women is under the age of 40. Survival for all stages is 73 % in Sweden. Human papilloma virus (HPV) can be detected in the majority of all cervical cancers. Treatment consists of surgery for early stages, and a combination of chemoradiation and brachytherapy for locally advanced disease. For metastatic disease, the treatment is palliative. Late side effects after treatment may have serious impact on the quality of life. There is a strong need for more efficient treatment of metastatic disease. Current lines of research include surgical strategies, optimised radiotherapy, neoadjuvant therapy, targeted therapy, and immunotherapy including therapeutic vaccines. PMID:26646957

  5. Optical coherence tomography in diagnosing cervical cancer

    NASA Astrophysics Data System (ADS)

    Kuznetzova, Irina A.; Shakhova, Natalia M.; Kachalina, Tatiana S.; Gladkova, Natalia D.; Myakov, Alexey V.; Iksanov, Rashid R.; Feldchtein, Felix I.

    2000-05-01

    Cervical cancer remains one of the most significant problem in oncogynecology. It tends towards treatment approaches that provide termination of pathological processes along with preservation of the patient's life quality. There is a need in earlier and more accurate diagnosis of pathological states, objective assessment of physiological processes, and adequate monitoring of the course of treatment. In our previous publications we have reported unique capabilities of the Optical Coherence Tomography (OCT) to image in vivo the mucosa structure of the cervix and to monitor various physiological and pathological alterations. In this report, we present results of OCT application to diagnose different stages of cervical cancer and to control its treatment at early stages. We have performed OCT-colposcopy in 11 female patients with cervical cancer to derive OCT criteria of this disease, to provide exact demarcation of a pathological area, and to determine a real size of a tumor. We have found that, in general, borders of a tumor, defined visually and detected with OCT by violation of the basement membrane in exocervix, do not coincide. The mismatch depends on a stage of cancer and can be as much as several millimeters. This information is especially important for evaluation of linear dimension of tumors with 3 - 5 mm invasion and also for differential diagnosis between the T1 and T2 stages with cancer extension onto vagina.

  6. [Papillomavirus and cervical cancer in Chile].

    PubMed

    O'Ryan, Miguel; Valenzuela, María Teresa

    2008-11-01

    Molecular, clinical and epidemiological studies have established beyond doubt that human papiloma viruses (HPV) cause cervical cancer. The virus is also associated with genital warts and other less common cancers in oropharynx, vulva, vagina and penis. Worldwide, VPH genotypes 16 and 18 are the most common high risk genotypes, detected in near 70% of women with cervical cancer. The discovery of a cause-effect relationship between several carcinogenic microorganisms and cancer open avenues for new diagnostic, treatment and prevention strategies. In this issue of Revista Médica de Chile, two papers on HPV are presented. Guzman and colleagues demonstrate that HPV can be detected in 66% to 77% of healthy male adolescents bypolymerase chain reaction and that positivity depends on the site of the penis that is sampled. These results support the role of male to female transmission of high risk HPVs in Chile and should lead to even more active educational campaigns. The second paper provides recommendations for HPV vaccine use in Chile, generated by the Immunization Advisory Committee of the Chilean Infectious Disease Society. To issue these recommendations, the Committee analyzes the epidemiological information available on HPV infection and cervical cancer in Chile, vaccine safety and effectiveness data, and describes cost-effectiveness studies. Taking into account that universal vaccination is controversial, the Committee favors vaccine use in Chile and it's incorporation into a national program. However, there is an indication that the country requires the implementation of an integrated surveillance approach including cross matching of data obtained from HPV genotype surveillance, monitoring of vaccination coverage, and surveillance of cervical cancer. The final decision of universal vaccine use in Chile should be based on a through analysis of information.ev Mid Chile

  7. Expression of cancer stem markers could be influenced by silencing of p16 gene in HeLa cervical carcinoma cells.

    PubMed

    Wu, H; Zhang, J; Shi, H

    2016-01-01

    Effect of the tumor suppression gene p16 on the biological characteristics of HeLa cervical carcinoma cells was explored. The expression of p16 protein was increased in HeLa tumor sphere cells, and no significant difference in tumor spheres from the first to the fourth passages. Compared with those of parental HeLa cells, the proportion of CD44+/CD24- and ABCG2+ cells increased significantly in tumor spheres. However after the cells were silenced by the p16-sh289 vector, expression of P16 protein and the cell number of CD44+/CD24- and ABCG2+ decreased. Moreover, HeLa cells with p16 gene silencing showed decreased abilities of sphere formation and matrigel invasion. More HeLa cells with p16 gene silence were needed for tumor formation in nude mice. Tumor size and weight in mouse model established with p16 gene silenced HeLa cells were less than those with HeLa parental cell model. The present results indicate that silencing of the p16 gene inhibits expression of cancer stem cell markers and tumorigenic ability of HeLa cells.

  8. The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression

    PubMed Central

    He, Chunbo; Mao, Dagan; Hua, Guohua; Lv, Xiangmin; Chen, Xingcheng; Angeletti, Peter C; Dong, Jixin; Remmenga, Steven W; Rodabaugh, Kerry J; Zhou, Jin; Lambert, Paul F; Yang, Peixin; Davis, John S; Wang, Cheng

    2015-01-01

    The Hippo signaling pathway controls organ size and tumorigenesis through a kinase cascade that inactivates Yes-associated protein (YAP). Here, we show that YAP plays a central role in controlling the progression of cervical cancer. Our results suggest that YAP expression is associated with a poor prognosis for cervical cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo signaling pathway and activate YAP to induce cervical cancer cell proliferation and migration. Activated YAP allows for up-regulation of TGF-α, AREG, and EGFR, forming a positive signaling loop to drive cervical cancer cell proliferation. HPV E6 protein, a major etiological molecule of cervical cancer, maintains high YAP protein levels in cervical cancer cells by preventing proteasome-dependent YAP degradation to drive cervical cancer cell proliferation. Results from human cervical cancer genomic databases and an accepted transgenic mouse model strongly support the clinical relevance of the discovered feed-forward signaling loop. Our study indicates that combined targeting of the Hippo and the ERBB signaling pathways represents a novel therapeutic strategy for prevention and treatment of cervical cancer. PMID:26417066

  9. Development of an Expert System as a Diagnostic Support of Cervical Cancer in Atypical Glandular Cells, Based on Fuzzy Logics and Image Interpretation

    PubMed Central

    Domínguez Hernández, Karem R.; Aguilar Lasserre, Alberto A.; Posada Gómez, Rubén; Palet Guzmán, José A.; González Sánchez, Blanca E.

    2013-01-01

    Cervical cancer is the second largest cause of death among women worldwide. Nowadays, this disease is preventable and curable at low cost and low risk when an accurate diagnosis is done in due time, since it is the neoplasm with the highest prevention potential. This work describes the development of an expert system able to provide a diagnosis to cervical neoplasia (CN) precursor injuries through the integration of fuzzy logics and image interpretation techniques. The key contribution of this research focuses on atypical cases, specifically on atypical glandular cells (AGC). The expert system consists of 3 phases: (1) risk diagnosis which consists of the interpretation of a patient's clinical background and the risks for contracting CN according to specialists; (2) cytology images detection which consists of image interpretation (IM) and the Bethesda system for cytology interpretation, and (3) determination of cancer precursor injuries which consists of in retrieving the information from the prior phases and integrating the expert system by means of a fuzzy logics (FL) model. During the validation stage of the system, 21 already diagnosed cases were tested with a positive correlation in which 100% effectiveness was obtained. The main contribution of this work relies on the reduction of false positives and false negatives by providing a more accurate diagnosis for CN. PMID:23690881

  10. Computer aided decision support system for cervical cancer classification

    NASA Astrophysics Data System (ADS)

    Rahmadwati, Rahmadwati; Naghdy, Golshah; Ros, Montserrat; Todd, Catherine

    2012-10-01

    Conventional analysis of a cervical histology image, such a pap smear or a biopsy sample, is performed by an expert pathologist manually. This involves inspecting the sample for cellular level abnormalities and determining the spread of the abnormalities. Cancer is graded based on the spread of the abnormal cells. This is a tedious, subjective and time-consuming process with considerable variations in diagnosis between the experts. This paper presents a computer aided decision support system (CADSS) tool to help the pathologists in their examination of the cervical cancer biopsies. The main aim of the proposed CADSS system is to identify abnormalities and quantify cancer grading in a systematic and repeatable manner. The paper proposes three different methods which presents and compares the results using 475 images of cervical biopsies which include normal, three stages of pre cancer, and malignant cases. This paper will explore various components of an effective CADSS; image acquisition, pre-processing, segmentation, feature extraction, classification, grading and disease identification. Cervical histological images are captured using a digital microscope. The images are captured in sufficient resolution to retain enough information for effective classification. Histology images of cervical biopsies consist of three major sections; background, stroma and squamous epithelium. Most diagnostic information are contained within the epithelium region. This paper will present two levels of segmentations; global (macro) and local (micro). At the global level the squamous epithelium is separated from the background and stroma. At the local or cellular level, the nuclei and cytoplasm are segmented for further analysis. Image features that influence the pathologists' decision during the analysis and classification of a cervical biopsy are the nuclei's shape and spread; the ratio of the areas of nuclei and cytoplasm as well as the texture and spread of the abnormalities

  11. Antiproliferative and Apoptosis Inducing Effects of Non-Polar Fractions from Lawsonia inermis L. in Cervical (HeLa) Cancer Cells.

    PubMed

    Kumar, Manish; Kaur, Paramjeet; Kumar, Subodh; Kaur, Satwinderjeet

    2015-04-01

    Two non-polar fractions viz. hexane (Hex-LI) and chloroform fraction (CHCl3-LI) of Lawsonia inermis were studied for their antiproliferative potential in various cancer cell lines viz. HeLa, MCF-7, A549 and C6 glioma cells. Both the fractions showed more than 60 % of growth inhibition in all the tested cell lines at highest tested concentration. In clonogenic assay, different concentrations of Hex-LI and CHCl3-LI decreased the number and size of colonies as compared to control in HeLa cells. The apoptotic effects as nuclear condensation, fragmentation were visualized with Hoechst-33342 staining of HeLa cells using confocal microscope. Both fractions induced apoptotic cell death in human cervical carcinoma (HeLa) cells as evident from flow cytometric analysis carried out using Annexin V-FITC and propidium iodide dyes. CHCl3-LI treated cells significantly induced apoptosis (25.43 %) in comparison to control. Results from Neutral Comet assay demonstrated that both fractions induced double stranded breaks (DSB's) in HeLa cells. Our data indicated that Hex-LI and CHCl3-LI treated cells showed significant increase of 32.2 and 18.56 % reactive oxygen species (ROS) levels in DCFH-DA assay respectively. Further, experimental studies to decipher exact pathway via which these fractions induce cell death are in progress.

  12. The use of MYBL2 as a novel candidate biomarker of cervical cancer.

    PubMed

    Martin, Cara M; Astbury, Katharine; Kehoe, Louise; O'Crowley, Jacqueline Barry; O'Toole, Sharon; O'Leary, John J

    2015-01-01

    Cervical cancer is the third most common cancer affecting women worldwide. It is characterized by chromosomal aberrations and alteration in the expression levels of many cell cycle regulatory proteins, driven primarily by transforming human papillomavirus (HPV) infection. MYBL2 is a member of the MYB proto-oncogene family that encodes DNA binding proteins. These proteins are involved in cell proliferation and control of cellular differentiation. We have previously demonstrated the utility of MYBL2 as a putative biomarker for cervical pre-cancer and cancer. In this chapter we describe the methodological approach for testing MYBL2 protein expression in tissue biopsies from cases of cervical intraepithelial neoplasia (CIN) and cervical cancer, using immunohistochemistry techniques on the automated immunostaining platform, the Ventana BenchMark LT. The protocol outlines the various steps in the procedure from cutting tissue sections, antibody optimization, antigen retrieval, immunostaining, and histological review.

  13. Anticancer effects of brominated indole alkaloid Eudistomin H from marine ascidian Eudistoma viride against cervical cancer cells (HeLa).

    PubMed

    Rajesh, Rajaian Pushpabai; Annappan, Murugan

    2015-01-01

    Marine invertebrates called ascidians are prolific producers of bioactive substances. The ascidian Eudistoma viride, distributed along the Southeast coast of India, was investigated for its in vitro cytotoxic activity against human cervical carcinoma (HeLa) cells by the MTT assay. The crude methanolic extract of E. viride, with an IC50 of 53 μg/ml, was dose-dependently cytotoxic. It was more potent at 100 μg/ml than cyclohexamide (1 μg/ml), reducing cell viability to 9.2%. Among nine fractions separated by chromatography, ECF-8 exhibited prominent cytoxic activity at 10 μg/ml. The HPLC fraction EHF-21 of ECF-8 was remarkably dose- and time-dependently cytotoxic, with 39.8% viable cells at 1 μg/ml compared to 51% in cyclohexamide-treated cells at the same concentration; the IC50 was 0.49 μg/ml. Hoechst staining of HeLa cells treated with EHF-21 at 0.5 μg/ml revealed apoptotic events such an cell shrinkage, membrane blebbing, chromatin condensation and formation of apoptotic bodies. Cell size and granularity study showed changes in light scatter, indicating the characteristic feature of cells dying by apoptosis. The cell-cycle analysis of HeLa cells treated with fraction EHF-21 at 1 μg/ml showed the marked arrest of cells in G0/G1, S and G2/M phases and an increase in the sub G0/G1 population indicated an increase in the apoptotic cell population. The statistical analysis of the sub-G1 region showed a dose-dependent induction of apoptosis. DNA fragmentation was also observed in HeLa cells treated with EHF-21. The active EHF-21 fraction, a brominated indole alkaloid Eudistomin H, led to apoptotic death of HeLa cells.

  14. Anticancer effects of brominated indole alkaloid Eudistomin H from marine ascidian Eudistoma viride against cervical cancer cells (HeLa).

    PubMed

    Rajesh, Rajaian Pushpabai; Annappan, Murugan

    2015-01-01

    Marine invertebrates called ascidians are prolific producers of bioactive substances. The ascidian Eudistoma viride, distributed along the Southeast coast of India, was investigated for its in vitro cytotoxic activity against human cervical carcinoma (HeLa) cells by the MTT assay. The crude methanolic extract of E. viride, with an IC50 of 53 μg/ml, was dose-dependently cytotoxic. It was more potent at 100 μg/ml than cyclohexamide (1 μg/ml), reducing cell viability to 9.2%. Among nine fractions separated by chromatography, ECF-8 exhibited prominent cytoxic activity at 10 μg/ml. The HPLC fraction EHF-21 of ECF-8 was remarkably dose- and time-dependently cytotoxic, with 39.8% viable cells at 1 μg/ml compared to 51% in cyclohexamide-treated cells at the same concentration; the IC50 was 0.49 μg/ml. Hoechst staining of HeLa cells treated with EHF-21 at 0.5 μg/ml revealed apoptotic events such an cell shrinkage, membrane blebbing, chromatin condensation and formation of apoptotic bodies. Cell size and granularity study showed changes in light scatter, indicating the characteristic feature of cells dying by apoptosis. The cell-cycle analysis of HeLa cells treated with fraction EHF-21 at 1 μg/ml showed the marked arrest of cells in G0/G1, S and G2/M phases and an increase in the sub G0/G1 population indicated an increase in the apoptotic cell population. The statistical analysis of the sub-G1 region showed a dose-dependent induction of apoptosis. DNA fragmentation was also observed in HeLa cells treated with EHF-21. The active EHF-21 fraction, a brominated indole alkaloid Eudistomin H, led to apoptotic death of HeLa cells. PMID:25550562

  15. Suppression of HPV E6 and E7 expression by BAF53 depletion in cervical cancer cells

    SciTech Connect

    Lee, Kiwon; Lee, Ah-Young; Kwon, Yunhee Kim; Kwon, Hyockman

    2011-08-26

    Highlights: {yields} Integration of HPV into host genome critical for activation of E6 and E7 oncogenes. {yields} BAF53 is essential for higher-order chromatin structure. {yields} BAF53 knockdown suppresses E6 and E7 from HPV integrants, but not from episomal HPVs. {yields} BAF53 knockdown decreases H3K9Ac and H4K12Ac on P105 promoter of integrated HPV 18. {yields} BAF53 knockdown restores the p53-dependent signaling pathway in HeLa and SiHa cells. -- Abstract: Deregulation of the expression of human papillomavirus (HPV) oncogenes E6 and E7 plays a pivotal role in cervical carcinogenesis because the E6 and E7 proteins neutralize p53 and Rb tumor suppressor pathways, respectively. In approximately 90% of all cervical carcinomas, HPVs are found to be integrated into the host genome. Following integration, the core-enhancer element and P105 promoter that control expression of E6 and E7 adopt a chromatin structure that is different from that of episomal HPV, and this has been proposed to contribute to activation of E6 and E7 expression. However, the molecular basis underlying this chromatin structural change remains unknown. Previously, BAF53 has been shown to be essential for the integrity of higher-order chromatin structure and interchromosomal interactions. Here, we examined whether BAF53 is required for activated expression of E6 and E7 genes. We found that BAF53 knockdown led to suppression of expression of E6 and E7 genes from HPV integrants in cervical carcinoma cell lines HeLa and SiHa. Conversely, expression of transiently transfected HPV18-LCR-Luciferase was not suppressed by BAF53 knockdown. The level of the active histone marks H3K9Ac and H4K12Ac on the P105 promoter of integrated HPV 18 was decreased in BAF53 knockdown cells. BAF53 knockdown restored the p53-dependent signaling pathway in HeLa and SiHa cells. These results suggest that activated expression of the E6 and E7 genes of integrated HPV is dependent on BAF53-dependent higher-order chromatin

  16. Epidemiology of cervical cancer in Latin America

    PubMed Central

    Capote Negrin, Luis G

    2015-01-01

    The basic aspects of the descriptive epidemiology of cervical cancer in Latin America are presented. A decrease in the incidence and mortality rates has been observed in the period from 2000 to 2012 in all countries across the region, this has not occurred at the same proportions, and in many countries, observed figures of incidence and mortality are among the highest levels in the world. In Latin America, calculating a mean measure of the numbers from the GLOBOCAN data from 2000 to 2012, we can observe a difference of up to fivefold of the incidence (Puerto Rico 9,73 Vs Bolivia 50,73) and almost seven times for mortality (Puerto Rico 3,3 Vs Nicaragua 21,67). A report of the epidemiology, risk factors, and evaluation of screening procedures regarding the possible impact of the human papillomavirus (HPV) vaccine I in the prevention of cervical cancer is presented. PMID:26557875

  17. Biological evaluation of a cytotoxic 2-substituted benzimidazole copper(II) complex: DNA damage, antiproliferation and apoptotic induction activity in human cervical cancer cells.

    PubMed

    Qiao, Xin; Ma, Zhong-Ying; Shao, Jia; Bao, Wei-Guo; Xu, Jing-Yuan; Qiang, Zhao-Yan; Lou, Jian-Shi

    2014-02-01

    Exploring novel chemotherapeutic agents is a great challenge in cancer medicine. To that end, 2-substituted benzimidazole copper(II) complex, [Cu(BMA)Cl2]·(CH3OH) (1) [BMA = N,N'-bis(benzimidazol-2-yl-methyl)amine], was synthesized and its cytotoxicity was characterized. The interaction between complex 1 and calf thymus DNA was detected by spectroscopy methods. The binding constant (K b = 1.24 × 10(4 )M(-1)) and the apparent binding constant (K app = 6.67 × 10(6 )M(-1)) of 1 indicated its moderate DNA affinity. Complex 1 induced single strand breaks of pUC19 plasmid DNA in the presence of H2O2 through an oxidative pathway. Cytotoxicity studies proved that complex 1 could inhibit the proliferation of human cervical carcinoma cell line HeLa in both time- and dose-dependent manners. The results of nuclei staining by Hoechst 33342 and alkaline single-cell gel electrophoresis proved that complex 1 caused cellular DNA damage in HeLa cells. Furthermore, treatment of HeLa cells with 1 resulted in S-phase arrest, loss of mitochondrial potential, and up-regulation of caspase-3 and -9 in HeLa cells, suggesting that complex 1 was capable of inducing apoptosis in cancer cells through the intrinsic mitochondrial pathway.

  18. Human papillomavirus, current vaccines, and cervical cancer prevention.

    PubMed

    Teitelman, Anne M; Stringer, Marilyn; Averbuch, Tali; Witkoski, Amy

    2009-01-01

    Human papillomavirus infection, the most common sexually transmitted infection in the United States, is associated with the development of cervical cancer. The new human papillomavirus vaccine advances cervical cancer prevention; however, provider-recommended screening with Papanicolaou tests and lifestyle modifications are still needed. Widespread implementation of the vaccine and delivering cervical cancer screening to underserved populations remain a challenge. Nurses are ideally suited to address these needs by providing education to patients and families. PMID:19208050

  19. The Prevalence of Human Papillomavirus in Cervical Cancer in Iran.

    PubMed

    Mortazavi, SH; Zali, MR; Raoufi, M; Nadji, M; Kowsarian, P; Nowroozi, A

    2002-01-01

    Background: The human papiloma virus (HPV), which is sexually transmitted, and most commonly causes genital warts, has been linked to cervical intraepithelial neoplasia and invasive carcinoma. Of ninety plus types of HPV, HPV-16 is the most prevalent in cervical cancer, followed by HPV-18, and HPV-33. As HPV's implication has not been assessed in the Middle East the main focus of this retrospective study was to determine the prevalence of HPV -16,18, and 33 in cases of cervical cancer from Iran. Material and Methods: This retrospective study covered 100 patients with uterine cervical carcinomas who were referred to two referral centers for cancer in Tehran-Iran. Pathological blocks were collected for these cases and initial review of the blocks showed poor specimens in 18 cases, which left 82 cases for the study. These samples were histologically examined to verify the presence and the type of carcinoma. The next step was in situ hybridzation for the detection of HPV common DNA. In Situ hybridization was preformed on all samples. Finally, Polymerase Chain Reaction (PCR) was preformed for the HPV types 16, 18, and 33. PCR amplification of exon 5 of the p53 gene was used as an internal control for the integrity of DNA. Takara PCR Human papilloma Detection method was used which includes primer for HPV 16, 18, and 33. Three primers were used alone, or in combination, in order to increase the sensitivity of the detection. Results: The majority of tumors were squamous cell carcinomas (87%). The rest were adenosquamous carcinoma and adenocarcinomas. None of the 82 different cervical carcinoma tissue samples were found to be positive by in situ hybridization. In the PCR samples, amplification of DNA was observed for 69 tumor specimens. In the remainning13 cases, the DNA in fixed tissue was degraded, as verified by the absence of an internal control band (p53). Out of the total 69 tumors (85.5%) with adequate DNA contained HPV band on PCR. The majority (73.9%) of HPV

  20. Drug Delivery Approaches for the Treatment of Cervical Cancer

    PubMed Central

    Ordikhani, Farideh; Erdem Arslan, Mustafa; Marcelo, Raymundo; Sahin, Ilyas; Grigsby, Perry; Schwarz, Julie K.; Azab, Abdel Kareem

    2016-01-01

    Cervical cancer is a highly prevalent cancer that affects women around the world. With the availability of new technologies, researchers have increased their efforts to develop new drug delivery systems in cervical cancer chemotherapy. In this review, we summarized some of the recent research in systematic and localized drug delivery systems and compared the advantages and disadvantages of these methods. PMID:27447664

  1. HPV types and cofactors causing cervical cancer in Peru.

    PubMed

    Santos, C; Muñoz, N; Klug, S; Almonte, M; Guerrero, I; Alvarez, M; Velarde, C; Galdos, O; Castillo, M; Walboomers, J; Meijer, C; Caceres, E

    2001-09-28

    We conducted a hospital-based case-control study in Peru of 198 women with histologically confirmed cervical cancer (173 squamous cell carcinomas and 25 cases of adenocarcinoma/adenosquamous carcinoma) and 196 control women. Information on risk factors was obtained by personal interview. Using PCR-based assays on exfoliated cervical cells and biopsy specimens, HPV DNA was detected in 95.3% of women with squamous cell carcinoma and in 92.0% of women with adenocarcinoma/adenosquamous carcinoma compared with 17.7% in control women. The age-adjusted odds ratio was 116.0 (95% Cl = 48.6-276.0) for squamous cell carcinoma and 51.4 (95% Cl = 11.4-232.0) for adenocarcinoma/adenosquamous carcinoma. The commonest types in women with cervical cancer were HPV 16, 18, 31, 52 and 35. The association with the various HPV types was equally strong for the two most common types (HPV 16 and 18) as for the other less common types. In addition to HPV, long-term use of oral contraceptives and smoking were associated with an increased risk. HPV is the main cause of both squamous cell carcinoma and adenocarcinoma in Peruvian women. PMID:11592767

  2. EphB2 promotes cervical cancer progression by inducing epithelial-mesenchymal transition.

    PubMed

    Gao, Qing; Liu, Wei; Cai, Jiangyi; Li, Mu; Gao, Yane; Lin, Wenjing; Li, Zongfang

    2014-02-01

    EphB2, a receptor tyrosine kinase for ephrin ligands, is overexpressed in various cancers and plays an important role in tumor progression. However, the expression and functions of EphB2 in cervical cancer remain unknown. In this study, we performed immunohistochemistry in clinical cervical specimens and found that EphB2 was overexpressed in the cervical cancer specimens, and its expression correlated with cancer progression. The percentage of EphB2-positive cells increased gradually from 28% in the normal cervix to 40% in high-grade squamous intraepithelial lesions, and ultimately to 69.8% in squamous cell carcinomas (P < .05). We overexpressed EphB2 in HeLa cells and silenced EphB2 in cervical cancer (C33A) cells, which expressed low and high levels of EphB2, respectively. Exogenous EphB2 promoted cell migration, invasion, and an epithelial-mesenchymal transition (EMT) signature, which is a complex process that occurs during organogenesis and cancer metastasis, whereas EphB2 silencing had the opposite effect (P < .05). Furthermore, HeLa cells with exogenous EphB2 exhibited a stem cell-like state that promoted tumorsphere formation in vitro and exhibited tumorigenesis potential in vivo (P < .05), whereas EphB2 silencing in C33A cells inhibited these stem cell properties (P < .05). In addition, we investigated the intracellular signaling pathways in cervical cancer and found that R-Ras expression correlated positively with EphB2 in clinical samples, and its activity was regulated by EphB2 in cervical cancer. These findings demonstrate that EphB2 plays an important role in cervical cancer progression by orchestrating an EMT program through R-Ras activation.

  3. Fisetin Inhibits Migration and Invasion of Human Cervical Cancer Cells by Down-Regulating Urokinase Plasminogen Activator Expression through Suppressing the p38 MAPK-Dependent NF-κB Signaling Pathway

    PubMed Central

    Chou, Ruey-Hwang; Hsieh, Shu-Ching; Yu, Yung-Luen; Huang, Min-Hsien; Huang, Yi-Chang; Hsieh, Yi-Hsien

    2013-01-01

    Fisetin (3,3’,4’,7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion. PMID:23940799

  4. Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPK-dependent NF-κB signaling pathway.

    PubMed

    Chou, Ruey-Hwang; Hsieh, Shu-Ching; Yu, Yung-Luen; Huang, Min-Hsien; Huang, Yi-Chang; Hsieh, Yi-Hsien

    2013-01-01

    Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion.

  5. Cervical cancer screening in low- and middle-income countries.

    PubMed

    Ditzian, Lauren R; David-West, Gizelka; Maza, Mauricio; Hartmann, Beatrix; Shirazian, Taraneh; Cremer, Miriam

    2011-01-01

    Cervical cancer is a leading cause of death among women in the developing world. Conventional cytology-based cervical cancer screening programs have been largely ineffectual at reducing the cervical cancer burden in low-resource settings. In response, alternative strategies have been tested, such as visual inspection with acetic acid (VIA) screening and human papillomavirus (HPV) DNA-based testing. This manuscript reviews literature addressing the programmatic approaches to implementing cervical cancer screening programs in low-resource settings, highlighting the challenges, barriers, and successes related to the use of cytology, VIA, and HPV-DNA based screening programs.

  6. Molecular mechanisms of cisplatin resistance in cervical cancer

    PubMed Central

    Zhu, Haiyan; Luo, Hui; Zhang, Wenwen; Shen, Zhaojun; Hu, Xiaoli; Zhu, Xueqiong

    2016-01-01

    Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. PMID:27354763

  7. MiR-375 Is Epigenetically Downregulated by HPV-16 E6 Mediated DNMT1 Upregulation and Modulates EMT of Cervical Cancer Cells by Suppressing lncRNA MALAT1

    PubMed Central

    Liu, Shikai; Song, Lili; Yao, Hairong; Zhang, Liang; Xu, Dongkui; Gao, Fangyuan; Li, Qian

    2016-01-01

    Epigenetic modulation is an important mechanism of miRNA dysregulation in cervical cancer. In this study, we firstly studied how this mechanism contributes to miR-375 downregulation in cervical cancer cells. Then, we further studied the association between miR-375 and MALAT1 (metastasis associated lung adenocarcinoma transcript 1) in epithelial mesenchymal transition (EMT) of the cancer cells. HPV-16 positive SiHa and CaSki cells were used as in vitro model. Our data showed that HPV-16 E6 positively modulated DNMT1 expression in both SiHa and CaSki cells. Knockdown of DNMT1 partly restored miR-375 levels in the cells. The following methylation-specific PCR (MSP) assay and qRT-PCR analysis showed that methylation was common in the promoter region of miR-375 in both SiHa and CaSki cells and demethylation partly restored miR-375 levels in the cells. Therefore, we infer that miR-375 is downregulated partly due to promoter hypermethylation mediated by DNMT1 in HPV-16 positive cervical cancer cells. Our bioinformatics analysis showed that MALAT1 has three putative binding sites with miR-375 and the following dual luciferase assay confirmed two of them. QRT-PCR analysis showed that miR-375 overexpression significantly reduced MALAT1 expression, while MALAT1 overexpression reversely suppressed miR-375 levels. Therefore, we infer that there is a reciprocal regulation between miR-375 and MALAT1 in the cells. In SiHa cells, miR-375 overexpression or MALAT1 siRNA partly restored E-cadherin expression, significantly reduced N-cadherin and also reduced invasion capacity of SiHa cells. Therefore, these results suggest that miR-375 and MALAT1 form a functional axis modulating EMT in cervical cancer. PMID:27658300

  8. Human papillomavirus induced transformation in cervical and head and neck cancers.

    PubMed

    Adams, Allie K; Wise-Draper, Trisha M; Wells, Susanne I

    2014-09-15

    Human papillomavirus (HPV) is one of the most widely publicized and researched pathogenic DNA viruses. For decades, HPV research has focused on transforming viral activities in cervical cancer. During the past 15 years, however, HPV has also emerged as a major etiological agent in cancers of the head and neck, in particular squamous cell carcinoma. Even with significant strides achieved towards the screening and treatment of cervical cancer, and preventive vaccines, cervical cancer remains the leading cause of cancer-associated deaths for women in developing countries. Furthermore, routine screens are not available for those at risk of head and neck cancer. The current expectation is that HPV vaccination will prevent not only cervical, but also head and neck cancers. In order to determine if previous cervical cancer models for HPV infection and transformation are directly applicable to head and neck cancer, clinical and molecular disease aspects must be carefully compared. In this review, we briefly discuss the cervical and head and neck cancer literature to highlight clinical and genomic commonalities. Differences in prognosis, staging and treatment, as well as comparisons of mutational profiles, viral integration patterns, and alterations in gene expression will be addressed.

  9. Human Papillomavirus Induced Transformation in Cervical and Head and Neck Cancers

    PubMed Central

    Adams, Allie K.; Wise-Draper, Trisha M.; Wells, Susanne I.

    2014-01-01

    Human papillomavirus (HPV) is one of the most widely publicized and researched pathogenic DNA viruses. For decades, HPV research has focused on transforming viral activities in cervical cancer. During the past 15 years, however, HPV has also emerged as a major etiological agent in cancers of the head and neck, in particular squamous cell carcinoma. Even with significant strides achieved towards the screening and treatment of cervical cancer, and preventive vaccines, cervical cancer remains the leading cause of cancer-associated deaths for women in developing countries. Furthermore, routine screens are not available for those at risk of head and neck cancer. The current expectation is that HPV vaccination will prevent not only cervical, but also head and neck cancers. In order to determine if previous cervical cancer models for HPV infection and transformation are directly applicable to head and neck cancer, clinical and molecular disease aspects must be carefully compared. In this review, we briefly discuss the cervical and head and neck cancer literature to highlight clinical and genomic commonalities. Differences in prognosis, staging and treatment, as well as comparisons of mutational profiles, viral integration patterns, and alterations in gene expression will be addressed. PMID:25226287

  10. E3 ubiquitin ligase isolated by differential display regulates cervical cancer growth in vitro and in vivo via microRNA-143

    PubMed Central

    Li, Jibin; Wang, Xinling; Zhang, Yanshang; Zhang, Yan

    2016-01-01

    Cervical cancer is one of the most common gynecological cancers worldwide. Aberrant expression of E3 ubiquitin ligase isolated by differential display (EDD) has been detected in various types of tumor and has been demonstrated to have an important role in carcinogenesis, tumor growth and drug resistance. However, the role of EDD in cervical cancer and its underlying molecular mechanisms remains unknown. The present study aimed to investigate the role of EDD in the tumorigenicity of cervical cancer. EDD expression levels were measured using reverse transcription-quantitative polymerase chain reaction and western blotting in SiHa, HeLa, CaSki, c-41 and c-33A cervical cancer cell lines and cervical cancer tissue specimens. A functional study was performed using cell proliferation, colony formation, cell apoptosis assays in vitro and tumor growth assays in vivo with EDD either overexpressed or silenced. In the present study, EDD expression levels were significantly upregulated in cervical cancer cell lines and tissue samples. EDD knockdown significantly inhibited colony formation, cell proliferation and tumor growth and accelerated cell apoptosis in the cervical cancer cell lines and tissue samples. Furthermore, microRNA (miR)-143 expression levels were low in cervical cancer tissue samples and were negatively correlated with EDD expression. miR-143 silencing eliminated the effect of EDD on cell proliferation, colony formation and cell apoptosis in the cervical cancer cells, which suggested that miR-143 is critical for EDD-mediated regulation of cervical cancer cell growth. The results of the present study indicated that EDD may promote cervical cancer growth in vivo and in vitro by targeting miR-143. In conclusion, EDD may have an oncogenic role in cervical cancer and may serve as a potential therapeutic target for the treatment of patients with cervical cancer. PMID:27446260

  11. Diagnosis of cervical cancer cell taken from scanning electron and atomic force microscope images of the same patients using discrete wavelet entropy energy and Jensen Shannon, Hellinger, Triangle Measure classifier.

    PubMed

    Aytac Korkmaz, Sevcan

    2016-05-01

    The aim of this article is to provide early detection of cervical cancer by using both Atomic Force Microscope (AFM) and Scanning Electron Microscope (SEM) images of same patient. When the studies in the literature are examined, it is seen that the AFM and SEM images of the same patient are not used together for early diagnosis of cervical cancer. AFM and SEM images can be limited when using only one of them for the early detection of cervical cancer. Therefore, multi-modality solutions which give more accuracy results than single solutions have been realized in this paper. Optimum feature space has been obtained by Discrete Wavelet Entropy Energy (DWEE) applying to the 3×180 AFM and SEM images. Then, optimum features of these images are classified with Jensen Shannon, Hellinger, and Triangle Measure (JHT) Classifier for early diagnosis of cervical cancer. However, between classifiers which are Jensen Shannon, Hellinger, and triangle distance have been validated the measures via relationships. Afterwards, accuracy diagnosis of normal, benign, and malign cervical cancer cell was found by combining mean success rates of Jensen Shannon, Hellinger, and Triangle Measure which are connected with each other. Averages of accuracy diagnosis for AFM and SEM images by averaging the results obtained from these 3 classifiers are found as 98.29% and 97.10%, respectively. It has been observed that AFM images for early diagnosis of cervical cancer have higher performance than SEM images. Also in this article, surface roughness of malign AFM images in the result of the analysis made for the AFM images, according to the normal and benign AFM images is observed as larger, If the volume of particles has found as smaller.

  12. Diagnosis of cervical cancer cell taken from scanning electron and atomic force microscope images of the same patients using discrete wavelet entropy energy and Jensen Shannon, Hellinger, Triangle Measure classifier

    NASA Astrophysics Data System (ADS)

    Aytac Korkmaz, Sevcan

    2016-05-01

    The aim of this article is to provide early detection of cervical cancer by using both Atomic Force Microscope (AFM) and Scanning Electron Microscope (SEM) images of same patient. When the studies in the literature are examined, it is seen that the AFM and SEM images of the same patient are not used together for early diagnosis of cervical cancer. AFM and SEM images can be limited when using only one of them for the early detection of cervical cancer. Therefore, multi-modality solutions which give more accuracy results than single solutions have been realized in this paper. Optimum feature space has been obtained by Discrete Wavelet Entropy Energy (DWEE) applying to the 3 × 180 AFM and SEM images. Then, optimum features of these images are classified with Jensen Shannon, Hellinger, and Triangle Measure (JHT) Classifier for early diagnosis of cervical cancer. However, between classifiers which are Jensen Shannon, Hellinger, and triangle distance have been validated the measures via relationships. Afterwards, accuracy diagnosis of normal, benign, and malign cervical cancer cell was found by combining mean success rates of Jensen Shannon, Hellinger, and Triangle Measure which are connected with each other. Averages of accuracy diagnosis for AFM and SEM images by averaging the results obtained from these 3 classifiers are found as 98.29% and 97.10%, respectively. It has been observed that AFM images for early diagnosis of cervical cancer have higher performance than SEM images. Also in this article, surface roughness of malign AFM images in the result of the analysis made for the AFM images, according to the normal and benign AFM images is observed as larger, If the volume of particles has found as smaller. She has been a Faculty Member at Fırat University in the Electrical- Electronic Engineering Department since 2007. Her research interests include image processing, computer vision systems, pattern recognition, data fusion, wavelet theory, artificial neural

  13. Significance of microvascular density (MVD) in cervical cancer recurrence.

    PubMed

    Cantu De León, D; Lopez-Graniel, C; Frias Mendivil, M; Chanona Vilchis, G; Gomez, C; De La Garza Salazar, J

    2003-01-01

    The purpose of this retrospective study of 118 patients with squamous cell cervical cancer from January 1990 to December 1993 was to evaluate angiogenesis as predictive factor of recurrence in cervical cancer stages II-III treated with standard radiotherapy. Microvessel density (MVD) was evaluated and correlated with other prognostic factors. MVD was greater than 20 in 67.8% of patients with recurrence (P = 0.002) in comparison to 39% of patients without. Disease-free survival was shorter in stage IIA and MVD >20 (P = 0.0193) as well as for stage IIB (P < 0.05 ), but not for IIIB (P = 0.1613 ). Global survival was significantly shorter when MVD was >20 (P = 0.0316). For stage IIA and MVD >20 survival was shorter (P = 0.0008) for stage IIB (P < 0.05) but not for IIIB (P = 0.14). Patients younger than 40 years and MVD >20 had poorer disease-free interval and survival (P = 0.0029). MVD in patients with squamous cell cervical cancer stage II and age younger than 40 may play a role in predicting recurrence and survival. PMID:14675324

  14. [Cervical cancer screening in Germany. Current status].

    PubMed

    Schneider, V

    2012-07-01

    Cervical cancer screening was introduced in Germany 40 years ago and the incidence of cancer of the cervix has subsequently decreased by close to 70%. The remaining incidence of 5,600 cases per year represents only 2.8% of all newly occurring cases of cancer in women and these cases occur mainly in patients who do not participate in regular screening. Thus, cervical cancer screening by cytological smears has been proven to be successful. The structure of the German cancer screening program is characterized by decentralized organization, exclusive involvement of medical specialists such as gynecologists and pathologists and strict quality assurance. The recruitment is 50% on a yearly basis and the cumulative participation over 3 years reaches 79%. Since 2008 all laboratories are required to report complete data sets to local quality control agencies.The Joint Federal Committee in charge of evaluating new technologies in Germany mandated an inquiry into the possible role of screening by human papillomavirus (HPV) testing. According to this report published by the Institute for Quality Assurance and Efficiency in Healthcare there are indications for advantages. There are, however, no data in the literature as to possible disadvantages of HPV testing. A similar study for the US Preventive Services Task Force was published in May 2011 with almost identical conclusions.

  15. Association between war and cervical cancer among Vietnamese women.

    PubMed

    Huynh, My Linh D; Raab, Stephen S; Suba, Eric J

    2004-07-10

    Decades ago, cervical cancer was the leading form of cancer among women in both North Vietnam and South Vietnam. Currently, cervical cancer rates are considerably lower in the northern region of the country. We performed a case-control study to measure factors associated with the development of cervical cancer among Vietnamese women. Questionnaire-based interviews were conducted with 202 women in southern Vietnam and 97 women in northern Vietnam. Case subjects were women hospitalized with cervical cancer. Control subjects were women hospitalized with extrauterine neoplasms. Data were analyzed using logistic regression, and odds ratios for the development of invasive cervical cancer were measured. The development of invasive cervical cancer was significantly associated with military service by husbands during the Second Indochinese War and with parity status. Odds ratio for the development of cervical cancer among southern Vietnamese women whose husbands had served in the armed forces was 2.6 (95% CI = 1.2-5.5). Odds ratio for the development of cervical cancer among northern women whose husbands had served in the armed forces was 3.9 (95% CI = 1.5-10.4) if their husbands had been stationed in South Vietnam during the war years. Northern women whose husbands had served in the military experienced no significant increase in cervical cancer risk if their husbands had been stationed in North Vietnam during the war years. Geographic and temporal variation in cervical cancer rates among Vietnamese women was associated with the movement of soldiers. These findings may be useful for cervical cancer prevention efforts in Vietnam and in other countries.

  16. Treatment Option Overview (Cervical Cancer)

    MedlinePlus

    ... checked under a microscope for signs of cancer. Laparoscopy : A surgical procedure to look at the organs ... a laparoscope , the operation is called a total laparoscopic hysterectomy. Enlarge Hysterectomy. The uterus is surgically removed ...

  17. Sulforaphane Reverses the Expression of Various Tumor Suppressor Genes by Targeting DNMT3B and HDAC1 in Human Cervical Cancer Cells.

    PubMed

    Ali Khan, Munawwar; Kedhari Sundaram, Madhumitha; Hamza, Amina; Quraishi, Uzma; Gunasekera, Dian; Ramesh, Laveena; Goala, Payal; Al Alami, Usama; Ansari, Mohammad Zeeshan; Rizvi, Tahir A; Sharma, Chhavi; Hussain, Arif

    2015-01-01

    Sulforaphane (SFN) may hinder carcinogenesis by altering epigenetic events in the cells; however, its molecular mechanisms are unclear. The present study investigates the role of SFN in modifying epigenetic events in human cervical cancer cells, HeLa. HeLa cells were treated with SFN (2.5 µM) for a period of 0, 24, 48, and 72 hours for all experiments. After treatment, expressions of DNMT3B, HDAC1, RARβ, CDH1, DAPK1, and GSTP1 were studied using RT-PCR while promoter DNA methylation of tumor suppressor genes (TSGs) was studied using MS-PCR. Inhibition assays of DNA methyl transferases (DNMTs) and histone deacetylases (HDACs) were performed at varying time points. Molecular modeling and docking studies were performed to explore the possible interaction of SFN with HDAC1 and DNMT3B. Time-dependent exposure to SFN decreases the expression of DNMT3B and HDAC1 and significantly reduces the enzymatic activity of DNMTs and HDACs. Molecular modeling data suggests that SFN may interact directly with DNMT3B and HDAC1 which may explain the inhibitory action of SFN. Interestingly, time-dependent reactivation of the studied TSGs via reversal of methylation in SFN treated cells correlates well with its impact on the epigenetic alterations accumulated during cancer development. Thus, SFN may have significant implications for epigenetic based therapy.

  18. Rapid induction of senescence in human cervical carcinoma cells

    NASA Astrophysics Data System (ADS)

    Goodwin, Edward C.; Yang, Eva; Lee, Chan-Jae; Lee, Han-Woong; Dimaio, Daniel; Hwang, Eun-Seong

    2000-09-01

    Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. This process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased telomerase activity. We propose that the human papillomavirus E6 and E7 proteins actively prevent senescence from occurring in cervical carcinoma cells, and that once viral oncogene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancer cells may represent an alternative approach to treat human cancers.

  19. Human papillomavirus testing in the prevention of cervical cancer.

    PubMed

    Schiffman, Mark; Wentzensen, Nicolas; Wacholder, Sholom; Kinney, Walter; Gage, Julia C; Castle, Philip E

    2011-03-01

    Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment.

  20. Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery

    SciTech Connect

    Nijhuis, Esther R.; Zee, Ate G.J. van der; Hout, Bertha A. in 't; Boomgaard, Jantine J.; Hullu, Joanne A. de; Pras, Elisabeth; Hollema, Harry; Aalders, Jan G.; Nijman, Hans W.; Willemse, Pax H.B.; Mourits, Marian J.E. . E-mail: m.j.e.mourits@og.umcg.nl

    2006-11-01

    Purpose: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. Methods and Materials: In a retrospective cohort study data of all cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 to IVA treated with (chemo) radiation between 1994 and 2001 were analyzed. Patients underwent gynecologic examination under anesthesia 8 to 10 weeks after completion of treatment. Cervical biopsy samples were taken from patients judged to be operable. In case of residual cancer, salvage surgery was performed. Results: Between 1994 and 2001, 169 consecutive cervical cancer patients received primary (chemo) radiation, of whom 4 were lost to follow-up. Median age was 56 years (interquartile range [IQR], 44-71) and median follow-up was 3.5 years (IQR, 1.5-5.9). In each of 111 patients a biopsy sample was taken, of which 90 (81%) showed no residual tumor. Vital tumor cells were found in 21 of 111 patients (19%). Salvage surgery was performed in 13 of 21 (62%) patients; of these patients, 5 (38%) achieved long-term, complete remission after salvage surgery (median follow-up, 5.2 years; range, 3.9-8.8 years). All patients with residual disease who did not undergo operation (8/21) died of progressive disease. Locoregional control was more often obtained in patients who underwent operation (7 of 13) than in patients who were not selected for salvage surgery (0 of 8 patients) (p < 0.05). Conclusions: Gynecologic examination under anesthesia 8 to 10 weeks after (chemo) radiation with cervical biopsies allows identification of those cervical cancer patients who have residual local disease, of whom a small but significant proportion may be salvaged by surgery.

  1. Fertility-preserving options for cervical cancer.

    PubMed

    Plante, Marie; Roy, Michel

    2006-04-01

    Childbearing is one of the most important life goals for many women, and fertility preservation is a very important factor in the overall quality of life of cancer survivors. Cervical cancer frequently affects young women; because some women tend to delay childbearing, fertility preservation must be considered when treatment options are discussed. Over the past decade, the radical trachelectomy procedure has become a well established fertility-preserving option for young women with early-stage cancer; this procedure is associated with low morbidity, good oncologic outcome, and a high proportion of pregnancies that reach the third trimester and babies that are delivered at term. This article will review available literature on the vaginal radical trachelectomy procedure and data from other surgical approaches, such as the abdominal radical trachelectomy. In addition, the potential future application of neoadjuvant chemotherapy followed by fertility-preserving surgery in patients with locally advanced cervical cancer will be examined. Finally, ultraconservative surgical approaches (eg, conization alone with or without laparoscopic lymphadenectomy) in very early-stage disease will be discussed.

  2. Image-based brachytherapy for cervical cancer.

    PubMed

    Vargo, John A; Beriwal, Sushil

    2014-12-10

    Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes. Advantages of image-based brachytherapy include: improved tumor coverage (especially for large volume disease), decreased dose to critical organs (especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging (MRI), computed tomography (CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. For practical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE (an international study of MRI-guided brachytherapy in locally advanced cervical

  3. Elevated expression of flotillin-1 is associated with lymph node metastasis and poor prognosis in early-stage cervical cancer

    PubMed Central

    Li, Zheng; Yang, Yang; Gao, Yang; Wu, Xiaoliu; Yang, Xielan; Zhu, Yingjie; Yang, Hongying; Wu, Lin; Yang, Chengang; Song, Libing

    2016-01-01

    Accumulating evidence has revealed that the expression of the lipid raft protein flotillin-1 is elevated in various human cancers, but the role flotillin-1 plays in the carcinogenesis of cervical cancer remains unclear. The expression profile of flotillin-1 was assayed using real-time PCR, western blotting, and immunohistochemical (IHC) staining in cervical cancer cell lines and cancer tissues with paired adjacent noncancerous cervical tissues. The expression of flotillin-1 protein was detected by IHC staining in a large cohort of 308 paraffin-embedded cervical cancer tissues. Ectopic expression and the short hairpin RNA interference approach were employed to determine the role of flotillin-1 in cervical cancer cell metastasis and the possible mechanism involved. Flotillin-1 expression protein and mRNA were significantly upregulated in cervical cancer cell lines and cancer tissues; elevated expression of flotillin-1 protein in early-stage cervical cancer was significantly associated with pelvic lymph node metastasis (P < 0.001), and was an independent predictive factor of poor overall survival. Moreover, flotillin-1 up- and downregulation remarkably affected cervical cancer cell motility and invasion, respectively, through epithelial-mesenchymal transition (EMT) regulated by the Wnt/β-catenin and nuclear factor-κB (NF-κB) pathways. Our results suggest that flotillin-1 facilitates cervical cancer cell metastasis through Wnt/β-catenin and NF-κB pathway-regulated EMT and that the flotillin-1 expression profile serves not only as novel predictor of pelvic lymph node metastasis, but also as neoteric risk factor for patients with early-stage cervical cancer. PMID:27073721

  4. [Global expression analysis in uterine cervical cancer: metabolic pathways and altered genes].

    PubMed

    Vázquez-Ortíz, Guelaguetza; Piña-Sanchez, Patricia; Hidalgo, Alfredo; Lazos, Minerva; Moreno, José; Alvarado, Isabel; Cruz, Fernando; Hernández, Dulce M; Pérez-Plascencia, Carlos; Salcedo, Mauricio

    2005-01-01

    High risk human papillomavirus (HPV) infection is considered to be the most important etiological factor of Cervical Uterine Cancer. In order to determine the global expression pattern and to identify possible molecular markers of cervical cancer, cDNA arrays with probe sets complementary to 8,000 human genes were used to examine the expression profiles among 5 cell lines derived from human cervical cancer, three HPV16(+) tumor samples and three normal cervical tissues HPV(-). The levels of expression of different cellular processes were identified. Hierarchical clustering was performed and the gene expression using RT-PCR was confirmed. Two genes were found to be consistently overexpressed in invasive cervical cancer biopsies; one of them, IL-6 was previously reported to be overexpressed in cervical cancer and one novel gene, MMP10, previously not known to be related to cervical cancer. Hierarchical clustering of the expression data revealed that samples with common HPV type infection grouped together, maybe this could mean that differences between HPV types could be indirectly determined by expression profiles.

  5. Therapeutic Vaccines Against Human Papillomavirus and Cervical Cancer

    PubMed Central

    Cid-Arregui, Angel

    2009-01-01

    Cervical cancer and its precursor intra-epithelial lesions are linked to infection by a subset of so-called “highrisk” human papillomavirus types, which are estimated to infect nearly four hundred million women worldwide. Two prophylactic vaccines have been commercialized recently targeting HPV16 and 18, the most prevalent viral types found in cervical cancer, which operate through induction of capsid-specific neutralizing antibodies. However, in patients with persistent infection these vaccines have not been found to protect against progression to neoplasia. Attempts are being made to develop therapeutic vaccines targeting nonstructural early viral proteins. Among these, E6 and E7 are the preferred targets, since they are essential for induction and maintenance of the malignant phenotype and are constitutively expressed by the transformed epithelial cells. Here are reviewed the most relevant potential vaccines based on HPV early antigens that have shown efficacy in preclinical models and that are being tested in clinical studies, which should determine their therapeutic capacity for eradicating HPV-induced premalignant and malignant lesions and cure cervical cancer. PMID:19915722

  6. Therapeutic vaccines against human papillomavirus and cervical cancer.

    PubMed

    Cid-Arregui, Angel

    2009-01-01

    Cervical cancer and its precursor intra-epithelial lesions are linked to infection by a subset of so-called "highrisk" human papillomavirus types, which are estimated to infect nearly four hundred million women worldwide. Two prophylactic vaccines have been commercialized recently targeting HPV16 and 18, the most prevalent viral types found in cervical cancer, which operate through induction of capsid-specific neutralizing antibodies. However, in patients with persistent infection these vaccines have not been found to protect against progression to neoplasia. Attempts are being made to develop therapeutic vaccines targeting nonstructural early viral proteins. Among these, E6 and E7 are the preferred targets, since they are essential for induction and maintenance of the malignant phenotype and are constitutively expressed by the transformed epithelial cells. Here are reviewed the most relevant potential vaccines based on HPV early antigens that have shown efficacy in preclinical models and that are being tested in clinical studies, which should determine their therapeutic capacity for eradicating HPV-induced premalignant and malignant lesions and cure cervical cancer. PMID:19915722

  7. Activation of miR-9 by human papillomavirus in cervical cancer.

    PubMed

    Liu, Weijun; Gao, Ge; Hu, Xiaoxia; Wang, Yuhui; Schwarz, Julie K; Chen, Jason J; Grigsby, Perry W; Wang, Xiaowei

    2014-11-30

    Cervical cancer is the third most common cancer in women worldwide, leading to about 300,000 deaths each year. Most cervical cancers are caused by human papillomavirus (HPV) infection. However, persistent transcriptional activity of HPV oncogenes, which indicates active roles of HPV in cervical cancer maintenance and progression, has not been well characterized. Using our recently developed assays for comprehensive profiling of HPV E6/E7 transcripts, we have detected transcriptional activities of 10 high-risk HPV strains from 87 of the 101 cervical tumors included in the analysis. These HPV-positive patients had significantly better survival outcome compared with HPV-negative patients, indicating HPV transcriptional activity as a favorable prognostic marker for cervical cancer. Furthermore, we have determined microRNA (miRNA) expression changes that were correlated with tumor HPV status. Our profiling and functional analyses identified miR-9 as the most activated miRNA by HPV E6 in a p53-independent manner. Further target validation and functional studies showed that HPV-induced miR-9 activation led to significantly increased cell motility by downregulating multiple gene targets involved in cell migration. Thus, our work helps to understand the molecular mechanisms as well as identify potential therapeutic targets for cervical cancer and other HPV-induced cancers.

  8. Viola plant cyclotide vigno 5 induces mitochondria-mediated apoptosis via cytochrome C release and caspases activation in cervical cancer cells.

    PubMed

    Esmaeili, Mohammad Ali; Abagheri-Mahabadi, Nazanin; Hashempour, Hossein; Farhadpour, Mohsen; Gruber, Christian W; Ghassempour, Alireza

    2016-03-01

    Cyclotides describe a unique cyclic peptide family that displays a broad range of biological activities including uterotonic, anti-bacteria, anti-cancer and anti-HIV. The vigno cyclotides consist of vigno 1-10 were reported recently from Viola ignobilis. In the present study, we examined the effects of vigno 5, a natural cyclopeptide from V. ignobilis, on cervical cancer cells and the underlying mechanisms. We found that vigno 5-treated Hela cells were killed off by apoptosis in a dose-dependent manner within 24h, and were characterized by the appearance of nuclear shrinkage, cleavage of poly (ADP-ribose) polymerase (PARP) and DNA fragmentation. The mitochondrial pathway of apoptosis revealed that cytochrome C is released from mitochondria to cytosol, associated with the activation of caspase-9 and -3, and the cleavage of poly (ADP-ribose) polymerase (PARP). Overall, the results indicate that vigno 5 induces apoptosis in part via the mitochondrial pathway, which is associated with a release of cytochrome C and elevated activity of caspase-9 and -3 in Hela cells.

  9. ZBRK1 acts as a metastatic suppressor by directly regulating MMP9 in cervical cancer.

    PubMed

    Lin, Li-Fang; Chuang, Chih-Hung; Li, Chien-Feng; Liao, Ching-Chun; Cheng, Chun-Pei; Cheng, Tian-Lu; Shen, Meng-Ru; Tseng, Joseph T; Chang, Wen-Chang; Lee, Wen-Hwa; Wang, Ju-Ming

    2010-01-01

    The BRCA1-interacted transcriptional repressor ZBRK1 has been associated with antiangiogenesis, but direct evidence of a tumor suppressor role has been lacking. In this study, we provide evidence of such a role in cervical carcinoma. ZBRK1 levels in cervical tumor cells were significantly lower than in normal cervical epithelial cells. In HeLa cervical cancer cells, enforced expression inhibited malignant growth, invasion, and metastasis in a variety of in vitro and in vivo assays. Expression of the metalloproteinase MMP9, which is known to be an important driver of invasion and metastasis, was found to be inversely correlated with ZBRK1 in tumor tissues and a target for repression in tumor cells. Our findings suggest that ZBRK1 acts to inhibit metastasis of cervical carcinoma, perhaps by modulating MMP9 expression.

  10. Physico-chemical characteristics of ZnO nanoparticles-based discs and toxic effect on human cervical cancer HeLa cells

    NASA Astrophysics Data System (ADS)

    Sirelkhatim, Amna; Mahmud, Shahrom; Seeni, Azman; Kaus, Noor Haida Mohd.; Sendi, Rabab

    2014-10-01

    In this study, we investigated physico-chemical properties of zinc oxide nanoparticles (ZnO NPs)-based discs and their toxicity on human cervical cancer HeLa cell lines. ZnO NPs (80 nm) were produced by the conventional ceramic processing method. FESEM analysis indicated dominant structure of nanorods with dimensions 100-500 nm in length, and 20-100 nm in diameter. The high content of ZnO nanorods in the discs probably played significant role in toxicity towards HeLa cells. Structural defects (oxygen vacancies and zinc/oxygen interstitials) were revealed by PL spectra peaks at 370-376 nm and 519-533 nm for the ZnO discs. The structural, optical and electrical properties of prepared sample have influenced the toxicological effects of ZnO discs towards HeLa cell lines via the generation of reactive oxygen species (ROS), internalization, membrane damage, and eventually cell death. The larger surface to volume area of the ZnO nanorods, combined with defects, stimulated enhanced toxicity via ROS generation hydrogen peroxide, hydroxyl radicals, and superoxide anion. The preliminary results confirmed the ZnO-disc toxicity on HeLa cells was significantly associated with the unique physicochemical properties of ZnO NPs and to our knowledge, this is the first cellular study for treatment of HeLa cells with ZnO discs made from 80 nm ZnO particles.

  11. The causal relation between human papillomavirus and cervical cancer

    PubMed Central

    Bosch, F X; Lorincz, A; Muñoz, N; Meijer, C J L M; Shah, K V

    2002-01-01

    The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented. PMID:11919208

  12. Social Construction of Cervical Cancer Screening among Panamanian Women

    ERIC Educational Resources Information Center

    Calvo, Arlene; Brown, Kelli McCormack; McDermott, Robert J.; Bryant, Carol A.; Coreil, Jeanine; Loseke, Donileen

    2012-01-01

    Background: Understanding how "health issues" are socially constructed may be useful for creating culturally relevant programs for Hispanic/Latino populations. Purpose: We explored the constructed meanings of cervical cancer and cervical cancer screening among Panamanian women, as well as socio-cultural factors that deter or encourage screening…

  13. Synergistic effect of fisetin combined with sorafenib in human cervical cancer HeLa cells through activation of death receptor-5 mediated caspase-8/caspase-3 and the mitochondria-dependent apoptotic pathway.

    PubMed

    Lin, Ming-Te; Lin, Chia-Liang; Lin, Tzu-Yu; Cheng, Chun-Wen; Yang, Shun-Fa; Lin, Chu-Liang; Wu, Chih-Chien; Hsieh, Yi-Hsien; Tsai, Jen-Pi

    2016-05-01

    Combining antitumor agents with bioactive compounds is a potential strategy for improving the effect of chemotherapy on cancer cells. The goal of this study was to elucidate the antitumor effect of the flavonoid, fisetin, combined with the multikinase inhibitor, sorafenib, against human cervical cancer cells in vitro and in vivo. The combination of fisetin and sorafenib synergistically induced apoptosis in HeLa cells, which is accompanied by a marked increase in loss of mitochondrial membrane potential. Apoptosis induction was achieved by caspase-3 and caspase-8 activation which increased the ratio of Bax/Bcl-2 and caused the subsequent cleavage of PARP level while disrupting the mitochondrial membrane potential in HeLa cells. Decreased Bax/Bcl-2 ratio level and mitochondrial membrane potential were also observed in siDR5-treated HeLa cells. In addition, in vivo studies revealed that the combined fisetin and sorafenib treatment was clearly superior to sorafenib treatment alone using a HeLa xenograft model. Our study showed that the combination of fisetin and sorafenib exerted better synergistic effects in vitro and in vivo than either agent used alone against human cervical cancer, and this synergism was based on apoptotic potential through a mitochondrial- and DR5-dependent caspase-8/caspase-3 signaling pathway. This combined fisetin and sorafenib treatment represents a novel therapeutic strategy for further clinical developments in advanced cervical cancer.

  14. Thymoquinone-Loaded Nanostructured Lipid Carrier Exhibited Cytotoxicity towards Breast Cancer Cell Lines (MDA-MB-231 and MCF-7) and Cervical Cancer Cell Lines (HeLa and SiHa)

    PubMed Central

    Ng, Wei Keat; Saiful Yazan, Latifah; Yap, Li Hua; Wan Nor Hafiza, Wan Abd Ghani; How, Chee Wun; Abdullah, Rasedee

    2015-01-01

    Thymoquinone (TQ) has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa). TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235 nm with a narrow polydispersity index (PDI) lower than 0.25. The zeta potential of TQ-NLC was greater than −30 mV. Polysorbate 80 helps to increase the stability of TQ-NLC. Differential scanning calorimetry showed that TQ-NLC has a melting point of 56.73°C, which is lower than that of the bulk material. The encapsulation efficiency of TQ in TQ-NLC was 97.63 ± 0.1798% as determined by HPLC analysis. TQ-NLC exhibited antiproliferative activity towards all the cell lines in a dose-dependent manner which was most cytotoxic towards MDA-MB-231 cells. Cell shrinkage was noted following treatment of MDA-MB-231 cells with TQ-NLC with an increase of apoptotic cell population (P < 0.05). TQ-NLC also induced cell cycle arrest. TQ-NLC was most cytotoxic towards MDA-MB-231 cells. It induced apoptosis and cell cycle arrest in the cells. PMID:25632388

  15. Phthalocyanine-mediated photodynamic therapy induces cell death and a G /G{sub 1} cell cycle arrest in cervical cancer cells

    SciTech Connect

    Haywood-Small, S.L. . E-mail: s.l.hankin@sheffield.ac.uk; Vernon, D.I.; Griffiths, J.; Schofield, J.; Brown, S.B.

    2006-01-13

    We have developed a series of novel photosensitizers which have potential for anticancer photodynamic therapy (PDT). Photosensitizers include zinc phthalocyanine tetra-sulphonic acid and a family of derivatives with amino acid substituents of varying alkyl chain length and degree of branching. Subcellular localization of these photosensitizers at the phototoxic IC{sub 5} concentration in human cervical carcinoma cells (SiHa Cells) was similar to that of the lysosomal dye Lucifer Yellow. Subsequent nuclear relocalization was observed following irradiation with 665 nm laser light. The PDT response was characterized using the Sulforhodamine B cytotoxicity assay. Flow cytometry was used for both DNA cell cycle and dual Annexin V-FITC/propidium iodide analysis. Phototoxicity of the derivatives was of the same order of magnitude as for tetrasulphonated phthalocyanine but with an overall trend of increased phototoxicity with increasing amino acid chain length. Our results demonstrate cell death, inhibition of cell growth, and G /G{sub 1} cell cycle arrest during the phthalocyanine PDT-mediated response.

  16. Human papillomavirus E5 protein induces expression of the EP4 subtype of prostaglandin E2 receptor in cyclic AMP response element-dependent pathways in cervical cancer cells.

    PubMed

    Oh, Jung-Min; Kim, Su-Hyeong; Lee, Yun-Il; Seo, Miran; Kim, So-Young; Song, Yong-Sang; Kim, Woo-Ho; Juhnn, Yong-Sung

    2009-01-01

    Human papillomavirus (HPV) is the major cause of uterine cervical cancer, but the role of the HPV E5 in carcinogenesis is not clearly understood. Prostaglandins are known to contribute to carcinogenesis of cervical cancer, and we therefore investigated the effect of HPV16 E5 on the expression of prostaglandin E2 (PGE2) receptors and underlying mechanisms. Stable expression of the E5 induced expression of the EP4 subtype of PGE2 receptors in C33A cervical cancer cells, and transfection of E5 small interfering RNA (siRNA) decreased it. EP4 protein expression was increased in human cervical cancer tissues, and EP4 mediated E5-induced increase in anchorage-independent colony formation and vascular endothelial growth factor expression. E5 induced cyclooxygenase-2 (COX-2) expression, and COX-2 increased PGE2 secretion and EP4 expression. The induction of EP4 by PGE2 and E5 was inhibited by an EP4 antagonist, inhibitors of cyclic adenosine monophosphate-dependent protein kinase or phosphatidylinositol 3-kinase, and a cyclic adenosine monophosphate response element (CRE) decoy. E5 increased the luciferase expression controlled by a variant CRE of the EP4 promoter, and it also increased the binding of cyclic adenosine monophosphate response element binding protein (CREB) to oligonucleotides containing this CRE. We conclude that the HPV16 E5 protein induces EP4 receptor protein in cervical cancer cells and that this induction involves epidermal growth factor receptor, COX-2, PGE2, EP2 and EP4, protein kinase A, CREB and CRE.

  17. MiR-125a suppresses tumor growth, invasion and metastasis in cervical cancer by targeting STAT3.

    PubMed

    Fan, Zhongyi; Cui, Hanzhi; Xu, Xiaojie; Lin, Zhi; Zhang, Xuelin; Kang, Lei; Han, Baiyu; Meng, Jing; Yan, Zhifeng; Yan, Xiang; Jiao, Shunchang

    2015-09-22

    MiR-125a has been characterized as a tumor suppressor in several cancers. However, the role of miR-125a in cervical cancer is unknown. In this study, we found the expression of miR-125a was downregulated in cervical cancer patients, and negatively correlated with the tumor size, FIGO stage, and preoperative metastasis. Kaplan-Meier analysis showed that miR-125a expression predicted favorable outcome for cervical cancer patients. Dual luciferase assays identified the STAT3 gene as a novel direct target of miR-125a. Functional studies showed that miR-125a overexpression significantly suppressed the growth, invasion and epithelial-mesenchymal transition (EMT) of cervical cancer cells both in vitro and in vivo via decreasing STAT3 expression. Moreover, miR-125a conferred to G2/M cell cycle arrest, accompanied by inhibition of several G2/M checkpoint proteins. Mechanistically, inactivation of miR-125a during cervical carcinogenesis was caused by HPV suppression of p53 expression. Clinically, STAT3, the expression of which, predicted poorer outcome, was inversely correlated with miR-125a in cervical cancer. These data highlight the importance of miR-125a in the cell proliferation and progression of cervical cancer, and indicate that miR-125a may be a useful therapeutic target for cervical cancer.

  18. Practice Bulletin No. 157 Summary: Cervical Cancer Screening and Prevention.

    PubMed

    2016-01-01

    The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.3 per 100,000 women in 2011 (1). The American Cancer Society (ACS) estimated that there would be 12,900 new cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (2). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases of the disease and 265,672 resultant deaths each year (3). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed (4, 5).New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the results. In addition, there are different risk-benefit considerations for women at different ages, as reflected in age-specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer screening (6), as did the U.S. Preventive Services Task Force (USPSTF) (7). Subsequently, in 2015, ASCCP and the Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA) (8). The purpose of this document is to provide a review of the best available evidence regarding the prevention and early detection of cervical cancer.

  19. Practice Bulletin No. 157: Cervical Cancer Screening and Prevention.

    PubMed

    2016-01-01

    The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.3 per 100,000 women in 2011 (). The American Cancer Society (ACS) estimated that there would be 12,900 new cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases of the disease and 265,672 resultant deaths each year (). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed ().New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the results. In addition, there are different risk-benefit considerations for women at different ages, as reflected in age-specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer screening (), as did the U.S. Preventive Services Task Force (USPSTF) (). Subsequently, in 2015, ASCCP and the Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA) (). The purpose of this document is to provide a review of the best available evidence regarding the prevention and early detection of cervical cancer.

  20. Practice Bulletin No. 157: Cervical Cancer Screening and Prevention.

    PubMed

    2016-01-01

    The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.3 per 100,000 women in 2011 (). The American Cancer Society (ACS) estimated that there would be 12,900 new cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases of the disease and 265,672 resultant deaths each year (). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed ().New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the results. In addition, there are different risk-benefit considerations for women at different ages, as reflected in age-specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer screening (), as did the U.S. Preventive Services Task Force (USPSTF) (). Subsequently, in 2015, ASCCP and the Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA) (). The purpose of this document is to provide a review of the best available evidence regarding the prevention and early detection of cervical cancer. PMID:26695583

  1. Practice Bulletin No. 157 Summary: Cervical Cancer Screening and Prevention.

    PubMed

    2016-01-01

    The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.3 per 100,000 women in 2011 (1). The American Cancer Society (ACS) estimated that there would be 12,900 new cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (2). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases of the disease and 265,672 resultant deaths each year (3). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed (4, 5).New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the results. In addition, there are different risk-benefit considerations for women at different ages, as reflected in age-specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer screening (6), as did the U.S. Preventive Services Task Force (USPSTF) (7). Subsequently, in 2015, ASCCP and the Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA) (8). The purpose of this document is to provide a review of the best available evidence regarding the prevention and early detection of cervical cancer. PMID:26695578

  2. Practice Bulletin No. 168: Cervical Cancer Screening and Prevention.

    PubMed

    2016-10-01

    The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.3 per 100,000 women in 2011 (1). The American Cancer Society (ACS) estimated that there would be 12,900 new cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (2). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases of the disease and 265,672 resultant deaths each year (3). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed (4, 5).New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the results. In addition, there are different risk-benefit considerations for women at different ages, as reflected in age-specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer screening (6), as did the U.S. Preventive Services Task Force (USPSTF) (7). Subsequently, in 2015, ASCCP and the Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA) (8). The purpose of this document is to provide a review of the best available evidence regarding the prevention and early detection of cervical cancer. PMID:27661651

  3. Practice Bulletin No. 168 Summary: Cervical Cancer Screening and Prevention.

    PubMed

    2016-10-01

    The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.3 per 100,000 women in 2011 (1). The American Cancer Society (ACS) estimated that there would be 12,900 new cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (2). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases of the disease and 265,672 resultant deaths each year (3). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed (4, 5).New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the results. In addition, there are different risk-benefit considerations for women at different ages, as reflected in age-specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer screening (6), as did the U.S. Preventive Services Task Force (USPSTF) (7). Subsequently, in 2015, ASCCP and the Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA) (8). The purpose of this document is to provide a review of the best available evidence regarding the prevention and early detection of cervical cancer. PMID:27661643

  4. Cervical cancer prevention: new tools and old barriers.

    PubMed

    Scarinci, Isabel C; Garcia, Francisco A R; Kobetz, Erin; Partridge, Edward E; Brandt, Heather M; Bell, Maria C; Dignan, Mark; Ma, Grace X; Daye, Jane L; Castle, Philip E

    2010-06-01

    Cervical cancer is the second most common female tumor worldwide, and its incidence is disproportionately high (>80%) in the developing world. In the United States, in which Papanicolaou (Pap) tests have reduced the annual incidence to approximately 11,000 cervical cancers, >60% of cases are reported to occur in medically underserved populations as part of a complex of diseases linked to poverty, race/ethnicity, and/or health disparities. Because carcinogenic human papillomavirus (HPV) infections cause virtually all cervical cancer, 2 new approaches for cervical cancer prevention have emerged: 1) HPV vaccination to prevent infections in younger women (aged < or =18 years) and 2) carcinogenic HPV detection in older women (aged > or =30 years). Together, HPV vaccination and testing, if used in an age-appropriate manner, have the potential to transform cervical cancer prevention, particularly among underserved populations. Nevertheless, significant barriers of access, acceptability, and adoption to any cervical cancer prevention strategy remain. Without understanding and addressing these obstacles, these promising new tools for cervical cancer prevention may be futile. In the current study, the delivery of cervical cancer prevention strategies to these US populations that experience a high cervical cancer burden (African-American women in South Carolina, Alabama, and Mississippi; Haitian immigrant women in Miami; Hispanic women in the US-Mexico Border; Sioux/Native American women in the Northern Plains; white women in the Appalachia; and Vietnamese-American women in Pennsylvania and New Jersey) is reviewed. The goal was to inform future research and outreach efforts to reduce the burden of cervical cancer in underserved populations.

  5. Cervical Cancer Prevention: New Tools and Old Barriers

    PubMed Central

    Scarinci, Isabel C.; Garcia, Francisco A. R.; Kobetz, Erin; Partridge, Edward E.; Brandt, Heather M.; Bell, Maria C.; Dignan, Mark; Ma, Grace X.; Daye, Jane L.; Castle, Philip E.

    2010-01-01

    Cervical cancer is the second most common female tumor worldwide and its incidence is disproportionately high (>80%) in the developing world. In the U.S., where Pap tests have reduced the annual incidence to approximately 11,000 cervical cancers, more than 60% of cases occur in medically-underserved populations as part of a complex of diseases linked to poverty, race/ethnicity, and/or health disparities. Because carcinogenic human papillomavirus (HPV) infections cause virtually all cervical cancer, two new approaches for cervical cancer prevention have emerged: 1) HPV vaccination to prevent infections in younger women (≤18 years old) and 2) carcinogenic HPV detection in older women (≥30 years old). Together, HPV vaccination and testing, if used in an age-appropriate manner, have the potential to transform cervical cancer prevention particularly among underserved populations. Yet significant barriers of access, acceptability, and adoption to any cervical cancer prevention strategy remain. Without understanding and addressing these obstacles, these promising new tools for cervical cancer prevention may be futile. We share our experiences in the delivery of cervical cancer prevention strategies to U.S. populations experiencing high cervical cancer burden: African-American women in South Carolina, Alabama, Mississippi; Haitian immigrant women in Miami; Hispanic women in the U.S.-Mexico Border; Sioux/Native American women in the Northern Plains; white women in the Appalachia; and Vietnamese-American women in Pennsylvania and New Jersey. Our goal is to inform future research and outreach efforts to reduce the burden of cervical cancer in underserved populations. PMID:20310056

  6. Advancing cervical cancer prevention in India: implementation science priorities.

    PubMed

    Krishnan, Suneeta; Madsen, Emily; Porterfield, Deborah; Varghese, Beena

    2013-01-01

    Cervical cancer is the leading cause of cancer mortality in India, accounting for 17% of all cancer deaths among women aged 30 to 69 years. At current incidence rates, the annual burden of new cases in India is projected to increase to 225,000 by 2025, but there are few large-scale, organized cervical cancer prevention programs in the country. We conducted a review of the cervical cancer prevention research literature and programmatic experiences in India to summarize the current state of knowledge and practices and recommend research priorities to address the gap in services. We found that research and programs in India have demonstrated the feasibility and acceptability of cervical cancer prevention efforts and that screening strategies requiring minimal additional human resources and laboratory infrastructure can reduce morbidity and mortality. However, additional evidence generated through implementation science research is needed to ensure that cervical cancer prevention efforts have the desired impact and are cost-effective. Specifically, implementation science research is needed to understand individual- and community-level barriers to screening and diagnostic and treatment services; to improve health care worker performance; to strengthen links among screening, diagnosis, and treatment; and to determine optimal program design, outcomes, and costs. With a quarter of the global burden of cervical cancer in India, there is no better time than now to translate research findings to practice. Implementation science can help ensure that investments in cervical cancer prevention and control result in the greatest impact.

  7. Inhibitors of differentiation-1 promotes nitrosopyrrolidine-induced transformation of HPV 16-immortalized cervical epithelial cell

    PubMed Central

    Xie, Lingxia; Li, Jinke; Zhang, Yi; Liu, Bao; Peng, Xue; Lin, Yong; Xu, Wenming; Hu, Lina

    2014-01-01

    Our previous study implied a correlation between inhibitors of differentiation-1 (Id-1) and cervical cancer development. However, how Id-1 contributes to cervical carcinogenesis is unknown. In the present study, we used an in vitro transformation model to investigate the role of Id-1 in the transformation of cervical cells. Human papillomavirus (HPV)-immortalized cervical epithelial cells (H8) were successfully transformed by exposure to the carcinogen N-nitrosopyrrolidine (NPYR). The expression of both Id-1 RNA and protein was significantly increased in transformed H8 cells, suggesting a possible role of Id-1 in cervical cell transformation. Ectopic expression of Id-1 in H8 cells potentiated NPYR-induced cell transformation. In contrast, silencing of Id-1 suppressed NPYR-induced H8 cell transformation. In addition, the expression of HPV E6 and E7 oncoproteins was upregulated while that of the tumor suppressors p53 and pRb was suppressed after H8 cell transformation. Our results suggest that Id-1 plays an oncogenic role in HPV-related cervical carcinogenesis, which sheds light on cervical cancer development mechanisms and implies that Id-1 is a potential target for cervical cancer prevention and therapy. PMID:24628854

  8. Human papillomavirus type 16 E7 oncoprotein upregulates the retinoic acid receptor-beta expression in cervical cancer cell lines and K14E7 transgenic mice.

    PubMed

    Gutiérrez, Jorge; García-Villa, Enrique; Ocadiz-Delgado, Rodolfo; Cortés-Malagón, Enoc M; Vázquez, Juan; Roman-Rosales, Alejandra; Alvarez-Rios, Elizabeth; Celik, Haydar; Romano, Marta C; Üren, Aykut; Lambert, Paul F; Gariglio, Patricio

    2015-10-01

    Persistent infection with high-risk human papillomaviruses is the main etiological factor in cervical cancer (CC). The human papillomavirus type 16 (HPV16) E7 oncoprotein alters several cellular processes, regulating the expression of many genes in order to avoid cell cycle control. Retinoic acid receptor beta (RARB) blocks cell growth, inducing differentiation and apoptosis. This tumor suppressor gene is gradually silenced in late passages of foreskin keratinocytes immortalized with HPV16 and in various tumors, including CC, mainly by epigenetic modifications. We investigated the effect of E7 oncoprotein on RARB gene expression. We found that HPV16 E7 increases RARB mRNA and RAR-beta protein expression both in vitro and in the cervix of young K14E7 transgenic mice. In E7-expressing cells, RARB overexpression is further increased in the presence of the tumor suppressor p53 (TP53) R273C mutant. This effect does not change when either C33-A or E7-expressing C33-A cell line is treated with Trichostatin A, suggesting that E7 enhances RARB expression independently of histone deacetylases inhibition. These findings indicate that RARB overexpression is part of the early molecular events induced by the E7 oncoprotein.

  9. Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression

    NASA Astrophysics Data System (ADS)

    Li, Wei; Yu, K. N.; Bao, Lingzhi; Shen, Jie; Cheng, Cheng; Han, Wei

    2016-01-01

    Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. However, the mechanism underlying its biological effects remains unclear. In this study, we investigated the inhibitory effect of NTP on the invasion of HeLa cells, and explored the possible mechanism. Our results showed that NTP exposure for 20 or 40 s significantly suppressed the migration and invasion of HeLa cells on the basis of matrigel invasion assay and wound healing assay, respectively. Moreover, NTP reduced the activity and protein expression of the matrix metalloproteinase (MMP)-9 enzyme. Western blot analysis indicated that NTP exposure effectively decreased phosphorylation level of both ERK1/2 and JNK, but not p38 MAPK. Furthermore, treatment with MAPK signal pathway inhibitors or NTP all exhibited significant depression of HeLa cells migration and MMP-9 expression. The result showed that NTP synergistically suppressed migration and MMP-9 expression in the presence of ERK1/2 inhibitor and JNK inhibitor, but not p38 MAPK inhibitor. Taken together, these findings suggested that NTP exposure inhibited the migration and invasion of HeLa cells via down-regulating MMP-9 expression in ERK1/2 and JNK signaling pathways dependent manner. These findings provide hints to the potential clinical research and therapy of NTP on cervical cancer metastasis.

  10. The lncRNA PVT1 Contributes to the Cervical Cancer Phenotype and Associates with Poor Patient Prognosis.

    PubMed

    Iden, Marissa; Fye, Samantha; Li, Keguo; Chowdhury, Tamjid; Ramchandran, Ramani; Rader, Janet S

    2016-01-01

    The plasmacytoma variant translocation 1 gene (PVT1) is an lncRNA that has been designated as an oncogene due to its contribution to the phenotype of multiple cancers. Although the mechanism by which PVT1 influences disease processes has been studied in multiple cancer types, its role in cervical tumorigenesis remains unknown. Thus, the present study was designed to investigate the role of PVT1 in cervical cancer in vitro and in vivo. PVT1 expression was measured by quantitative PCR (qPCR) in 121 invasive cervical carcinoma (ICC) samples, 30 normal cervix samples, and cervical cell lines. Functional assays were carried out using both siRNA and LNA-mediated knockdown to examine PVT1's effects on cervical cancer cell proliferation, migration and invasion, apoptosis, and cisplatin resistance. Our results demonstrate that PVT1 expression is significantly increased in ICC tissue versus normal cervix and that higher expression of PVT1 correlates with poorer overall survival. In cervical cancer cell lines, PVT1 knockdown resulted in significantly decreased cell proliferation, migration and invasion, while apoptosis and cisplatin cytotoxicity were significantly increased in these cells. Finally, we show that PVT1 expression is augmented in response to hypoxia and immune response stimulation and that this lncRNA associates with the multifunctional and stress-responsive protein, Nucleolin. Collectively, our results provide strong evidence for an oncogenic role of PVT1 in cervical cancer and lend insight into potential mechanisms by which PVT1 overexpression helps drive cervical carcinogenesis. PMID:27232880

  11. 75 FR 7282 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-18

    ... HUMAN SERVICES Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and... Force guidelines for breast and cervical cancer screening; Impact of the revised clinical screening recommendations for both breast and cervical cancer on the National Breast and Cervical Cancer Early...

  12. [Photodynamic therapy (PDT) for early cervical cancer].

    PubMed

    Muroya, T; Suehiro, Y; Umayahara, K; Akiya, T; Iwabuchi, H; Sakunaga, H; Sakamoto, M; Sugishita, T; Tenjin, Y

    1996-01-01

    The incidence of carcinoma in situ (CIS) and dysplasia of the uterine cervix has been increasing among young women in recent years. Most of these patients want to preserve their fertility. Also, to accommodate high-risk patients with complications, elderly patients, and those who refuse surgery, we perform PDT as a method to preserve fertility. The technique required for PDT is relatively simple, and can be performed without anesthesia, since it causes no pain or bleeding. PDT, with the use of Excimer Dye Laser (EDL), a type of low pulse laser, has a considerably higher degree of tissue penetration, even compared to PDT using Argon Dye Laser (ADL). Also, PDT using EDL can manage glandular involvement of CIN, and its special feature of selective destruction of malignant cells with almost no effect on normal tissues is noteworthy. Beginning in 1995, PDT using YAG-OPO Laser with a variable laser wavelength has been performed. PDT is performed 48 hours after intravenous injection of 1.5 mg/kg to 2 mg/kg photosensitizer Porfimer sodium (PHE) when the difference in density of PHE becomes greatest between malignant cells and normal tissue. The most advanced features of our method compared to conventional radiation which uses cut fiber are: First, by using colposcope with an optical path for the laser, it is possible to show a 10 mm circular spot at the focus of observation. With this method, cervical lesions can be observed and checked while receiving stable and precise photoradiation by using colposcope through direct observation. Second, for cervical canal treatment, by using a cervical probe to administer photoradiation in the forward direction in the cervical canal and to the side walls, 70% of the laser light is scattered to the side walls, so that all of the cervical canal can be radiated. Also, the cervical canal probe used to administer photoradiation, by inserting 2 cm to 3 cm depending on the conditions of the cervical canal and withdrawing the probe 1 mm, can

  13. Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research.

    PubMed

    Lee, Sung Jong; Yang, Andrew; Wu, T C; Hung, Chien Fu

    2016-09-01

    Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.

  14. Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research

    PubMed Central

    2016-01-01

    Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer. PMID:27329199