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Sample records for cell cervical cancer

  1. Cervical cancer

    MedlinePLUS

    Cancer - cervix ... Worldwide, cervical cancer is the third most common type of cancer in women. It is much less common in the United ... of the routine use of Pap smears . Cervical cancer starts in the cells on the surface of ...

  2. Cervical Cancer

    MedlinePLUS

    MENU Return to Web version Cervical Cancer Overview What is cervical cancer? Cervical cancer is cancer of the cervix. The cervix is part of your uterus (womb). What is a Pap smear? A Pap smear is a test your doctor does to check for signs of cancer of the cervix. The cells from your cervix are checked ...

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

    ClinicalTrials.gov

    2016-03-14

    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

    2016-03-02

    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. Temsirolimus in Treating Patients With Cervical Cancer That Is Recurrent, Locally Advanced, Metastatic, or Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2015-08-10

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

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

    ClinicalTrials.gov

    2015-11-03

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Cervical Undifferentiated Carcinoma; Recurrent Cervical 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

  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. [Cervical cancer].

    PubMed

    Mikami, Yoshiki

    2014-06-01

    The epidemiologic data demonstrated by SEER clearly show a decrease of cervical cancer over the decades due to widespread cervical cancer screening with a pap smear, although there is currently a shift in the age distribution resulting in an increase of cervical cancer among younger women, and a lower screening rate is a problem, particularly in Japan. Another peculiar trend is an increase of endocervical adenocarcinomas, and the underlying cause of this trend is still unknown. A screening program, employing the Bethesda system terminology and liquid-based cytology, combined with HPV DNA testing and p16(INK4a) immunohistochemistry/ cytochemistry, and a management guideline proposed by ASCCP, has been contributing to the early detection of cervical cancers. However, it should be kept in mind that an HPV-targeted strategy is effective only for squamous lesions, which is mostly HPV-driven neoplasms, and that unusual HPV-negative adenocarcinomas, including gastric, clear cell, and mesonephric types, are a pitfall of HPV DNA testing and vaccination. Therefore, potential biomarkers, which can be applied for both squamous and glandular lesions, are awaited. The gastric type of adenocarcinoma of the cervix, a recently described subtype, is a distinct entity showing an aggressive clinical behavior, and, importantly, is estimated to be more frequent than in western countries. PMID:25151779

  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. Tc17 Cells in Patients with Uterine Cervical Cancer

    PubMed Central

    Zhang, Yan; Hou, Fei; Liu, Xin; Ma, Daoxin; Zhang, Youzhong; Kong, Beihua; Cui, Baoxia

    2014-01-01

    Background The existence of Tc17 cells was recently shown in several types of infectious and autoimmune diseases, but their distribution and functions in uterine cervical cancer (UCC) have not been fully elucidated. Methods The frequency of Tc17 cells in peripheral blood samples obtained from UCC patients, cervical intraepithelial neoplasia (CIN) patients and healthy controls was determined by flow cytometry. Besides, the prevalence of Tc17 cells and their relationships to Th17 cells and Foxp3-expressing T cells as well as microvessels in tissue samples of the patients were assessed by immunohistochemistry staining. Results Compared to controls, patients with UCC or CIN had a higher proportion of Tc17 cells in both peripheral blood and cervical tissues, but the level of Tc17 cells in UCC tissues was significantly higher than that in CIN tissues. Besides, the increased level of Tc17 in UCC patients was associated with the status of pelvic lymph node metastases and increased microvessel density. Finally, significant correlations of infiltration between Tc17 cells and Th17 cells or Foxp3-expressing T cells were observed in UCC and CIN tissues. Conclusions This study indicates that Tc17 cell infiltration in cervical cancers is associated with cancer progression accompanied by increased infiltrations of Th17 cells and regulatory T cells as well as promoted tumor vasculogenesis. PMID:24523865

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

    ClinicalTrials.gov

    2016-03-14

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

  18. Cervical Cancer

    MedlinePLUS

    ... United States get cervical cancer. The human papillomavirus (HPV) is the main cause of cervical cancer. HPV is a common virus that is passed from ... least half of sexually active people will have HPV at some point in their lives, but few ...

  19. The Dynamics of HPV Infection and Cervical Cancer Cells.

    PubMed

    Asih, Tri Sri Noor; Lenhart, Suzanne; Wise, Steven; Aryati, Lina; Adi-Kusumo, F; Hardianti, Mardiah S; Forde, Jonathan

    2016-01-01

    The development of cervical cells from normal cells infected by human papillomavirus into invasive cancer cells can be modeled using population dynamics of the cells and free virus. The cell populations are separated into four compartments: susceptible cells, infected cells, precancerous cells and cancer cells. The model system of differential equations also has a free virus compartment in the system, which infect normal cells. We analyze the local stability of the equilibrium points of the model and investigate the parameters, which play an important role in the progression toward invasive cancer. By simulation, we investigate the boundary between initial conditions of solutions, which tend to stable equilibrium point, representing controlled infection, and those which tend to unbounded growth of the cancer cell population. Parameters affected by drug treatment are varied, and their effect on the risk of cancer progression is explored. PMID:26676766

  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. 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 within six months, much less than after HSIL (86%). Among women with histology assessment within six months, the incidence rate of cervical cancer after AGC was significantly higher than that after HSIL for up to 6.5 years. Conclusions AGC found at cervical screening is associated with a high and persistent risk of cervical cancer for up to 15 years, particularly for cervical adenocarcinoma and women with AGC at age 30-39. Compared with the reduction in risk of cancer seen after HSIL management, management of AGC seems to have been suboptimal in preventing cervical cancer. Research to optimise management is needed, and a more aggressive assessment strategy is warranted. PMID:26869597

  2. Cervical Cancer

    MedlinePLUS

    ... transmitted infections , such as chlamydia Problems with the immune system Having a mother who took a drug called diethylstilbestrol (DES) during pregnancy Is there a screening test for cervical cancer? ...

  3. 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

  4. 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

    2016-02-19

    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

  5. Cervical Cancer Screening

    MedlinePLUS

    ... cases of cervical cancer and the number of deaths due to cervical cancer since 1950. Cervical dysplasia ... for cervical cancer helps decrease the number of deaths from the disease. Regular screening of women between ...

  6. Cervical cancer.

    PubMed

    Koh, Wui-Jin; Greer, Benjamin E; Abu-Rustum, Nadeem R; Apte, Sachin M; Campos, Susana M; Chan, John; Cho, Kathleen R; Cohn, David; Crispens, Marta Ann; DuPont, Nefertiti; Eifel, Patricia J; Gaffney, David K; Giuntoli, Robert L; Han, Ernest; Huh, Warner K; Lurain, John R; Martin, Lainie; Morgan, Mark A; Mutch, David; Remmenga, Steven W; Reynolds, R Kevin; Small, William; Teng, Nelson; Tillmanns, Todd; Valea, Fidel A; McMillian, Nicole R; Hughes, Miranda

    2013-03-01

    These NCCN Clinical Practice Guidelines in Oncology for Cervical Cancer focus on early-stage disease, because it occurs more frequently in the United States. After careful clinical evaluation and staging, the primary treatment of early-stage cervical cancer is either surgery or radiotherapy. These guidelines include fertility-sparing and non-fertility-sparing treatment for those with early-stage disease, which is disease confined to the uterus. A new fertility-sparing algorithm was added for select patients with stage IA and IB1 disease.. PMID:23486458

  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. 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 6080 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

  9. 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.

  10. Cervical Cancer Stage IIIA

    MedlinePLUS

    ... My Pictures Browse Search Quick Search Image Details Cervical Cancer Stage IIIA View/Download: Small: 612x612 View Download Add to My Pictures Title: Cervical Cancer Stage IIIA Description: Stage IIIA cervical cancer; drawing ...

  11. Cervical Cancer Stage IIIB

    MedlinePLUS

    ... My Pictures Browse Search Quick Search Image Details Cervical Cancer Stage IIIB View/Download: Small: 684x636 View Download Add to My Pictures Title: Cervical Cancer Stage IIIB Description: Stage IIIB cervical cancer; drawing ...

  12. Cervical Cancer Stage IVB

    MedlinePLUS

    ... My Pictures Browse Search Quick Search Image Details Cervical Cancer Stage IVB View/Download: Small: 594x640 View Download Add to My Pictures Title: Cervical Cancer Stage IVB Description: Stage IVB cervical cancer; drawing ...

  13. Cervical Cancer Stage IVA

    MedlinePLUS

    ... Search Quick Search Image Details Cervical Cancer Stage IVA View/Download: Small: 756x576 View Download Add to My Pictures Title: Cervical Cancer Stage IVA Description: Stage IVA cervical cancer; drawing and inset ...

  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

    2016-01-28

    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. 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

  17. Cervical Cancer Stage IB

    MedlinePLUS

    ... My Pictures Browse Search Quick Search Image Details Cervical Cancer Stage IB View/Download: Small: 774x576 View Download Add to My Pictures Title: Cervical Cancer Stage IB Description: Stage IB1 and IB2 cervical ...

  18. Cervical Cancer Stage IA

    MedlinePLUS

    ... My Pictures Browse Search Quick Search Image Details Cervical Cancer Stage IA View/Download: Small: 720x576 View Download Add to My Pictures Title: Cervical Cancer Stage IA Description: Stage IA1 and IA2 cervical ...

  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. 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.

  1. Stanniocalcin 2 promotes cell proliferation and cisplatin resistance in cervical cancer.

    PubMed

    Wang, Yuxia; Gao, Ying; Cheng, Hairong; Yang, Guichun; Tan, Wenhua

    2015-10-23

    Cervical cancer is one of the most common carcinomas in the female reproductive system. Treatment of cervical cancer involves surgical removal and chemotherapy. Resistance to platinum-based chemotherapy drugs including cisplatin has increasingly become an important problem in the treatment of cervical cancer patients. We found in this study that stanniocalcin 2 (STC2) expression was upregulated in both cervical cancer tissues and cell lines. The levels of STC2 expression in cervical cancer cell lines were positively correlated with the rate of cell proliferation. Furthermore, in cisplatin resistant cervical cancer cells, the levels of STC2 expression were significantly elevated. Modulation of STC2 expression by siRNA or overexpression in cisplatin resistant cells resulted in altered cell survival, apoptosis, and cisplatin resistance. Finally, we found that there was significant difference in the activity of the MAPK signaling pathway between cisplatin sensitive and resistant cervical cancer cells, and that STC2 could regulate the activity of the MAPK signaling pathway. PMID:26361149

  2. Clinical significance of Gremlin 1 in cervical cancer and its effects on cancer stem cell maintenance.

    PubMed

    Sato, Masakazu; Kawana, Kei; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Takahashi, Juri; Adachi, Katsuyuki; Nagasaka, Kazunori; Matsumoto, Yoko; Wada-Hiraike, Osamu; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-01-01

    Gremlin 1 is one of the bone morphogenetic protein (BMP) antagonists and is also related to differentiation in combination with BMPs and is associated with various types of diseases. Gremlin 1 is overexpressed in various types of human cancers and has been reported to play a role in cervical cancer oncogenesis. However, there is no report concerning the relationship between Gremlin 1 and cervical cancer stem cells (CSCs). The objective of the present study was to identify the clinical significance of Gremlin 1 in cervical cancer and its effects on CSC‑like properties in vitro. Clinical samples were obtained. Gremlin 1 mRNA expression levels in the cervical cancer tissues were measured by RT‑qPCR and assessed for correlation with their clinical prognosis [overall survival (OS), progression-free survival (PFS)] and with other prognostic factors. In vitro, cervical cancer, CaSki cells, exposed to Gremlin 1 (1,000 ng/ml) for 24 h were evaluated for expression of undifferentiated‑cell markers (Nanog, Oct3/4, Sox2) by RT‑qPCR, the population of ALDH‑positive cells by flow cytometry and sphere‑forming ability on a ultra‑low attachment culture dish. Cervical cancer tissues from 104 patients were collected. A high mRNA expression level of Gremlin 1 was an independent poor prognostic factor of PFS but not of OS. A high mRNA expression level of Gremlin 1 was correlated with bulky (>4 cm) tumors. The Nanog mRNA expression level was significantly increased in the CaSki cells exposed to Gremlin 1 (P=0.0008) but not Oct3/4 and Sox2 mRNA expression levels. The population of ALDH‑positive cells in the Gremlin 1‑exposed cells was 1.41‑fold higher compared with the control (P=0.0184). Sphere‑forming ability was increased when 1,000 Gremlin 1‑exposed cells were seeded (P=0.0379). In cervical cancer, it is suggested that Gremlin 1 may have a role in clinical recurrence and maintaining CSC-like properties. PMID:26530461

  3. Smoking and Cervical Cancer

    MedlinePLUS

    Smoking and Cervical Cancer If you smoke, you have an increased chance of developing precancerous lesions of ... increase in the chance of developing cervical cancer. Smoking greatly increases your risk for dysplasia and cancer ...

  4. Roles of Long Non-Coding RNA CCAT2 in Cervical Cancer Cell Growth and Apoptosis.

    PubMed

    Wu, Le; Jin, Lixu; Zhang, Wenmiao; Zhang, Lifang

    2016-01-01

    BACKGROUND This study aimed to analyze the potential function of lncRNA CCAT2 in cervical cancer cell proliferation and apoptosis. MATERIAL AND METHODS Expression level of CCAT2 in cervical cancer cell lines (HeLa, CaSki, and SiHa) was detected by quantitative real-time PCR. CCAT2 knockdown was established by transfecting siRNA into human cervical cancer cells. Its effects on cell proliferation were studied using cell-counting kit-8 assay. The effect of CCAT2 on cervical cancer cells cycle and apoptosis was assessed by flow cytometry assay. RESULTS CCK8 assay showed that CCAT2 knockdown inhibited cell proliferation in HeLa, CaSki, and SiHa cells. The flow cytometry confirmed the results that knockdown of CCAT2 could induce cervical cancer cells cycle G1 phase arrestment and trigger the cells apoptosis. CONCLUSIONS LncRNA CCAT2 promoted the proliferation and survival of cervical cancer cells. PMID:26983975

  5. CD24 promotes the proliferation and inhibits the apoptosis of cervical cancer cells in vitro.

    PubMed

    Pei, Zhen; Zhu, Guangchao; Huo, Xiaolei; Gao, Lu; Liao, Shan; He, Junyu; Long, Yuehua; Yi, Hong; Xiao, Songshu; Yi, Wei; Chen, Pan; Li, Xiaoling; Li, Guiyuan; Zhou, Yanhong

    2016-03-01

    The protein CD24 is a cell surface protein that appears to function as an adhesion molecule; its expression has been shown to correlate with prognosis in a variety of tumors. Herein, we investigated the possible role and mechanism of CD24 in cervical cancer. Our results showed that CD24 was overexpressed in cervical cancer tissues compared with that in the adjacent non?cancerous tissues by qPCR, immunohistochemistry and western blotting technologies. To explore the possible mechanism of CD24 in cervical cancer, we elucidated the effect of CD24 on the proliferation and apoptosis of cervical cancer HeLa cells and found that a considerable increase in cell proliferation was observed in the HeLa cells with CD24 overexpession. The rate of cell apoptosis was decreased in the HeLa/CD24 cells compared with the HeLa or HeLa/vector cells. Cell apoptosis is closely related with a reduction in mitochondrial membrane potential (??m) and an increase in intracellular reactive oxygen species (ROS) and calcium ion (Ca2+) concentrations. Our results showed that overexpression of CD24 in the cervical cancer HeLa cells, led to an increase in ??m and a decrease in intracellular ROS and Ca2+ concentrations. Furthermore, we found that CD24 was correlated with dysregulation of the MAPK signaling pathway in cervical cancer tissues invitro. At the same time, we found that CD24 overexpression affected the expression of p38, JNK2 and c-Jun invitro. In summary, our results suggest that CD24 is upregulated in cervical cancer tissues and plays its functions by affecting the MAPK signaling pathway in cervical cancer. PMID:26707501

  6. Dataset on the effects of CYB5D2 on the distribution of HeLa cervical cancer cell cycle

    PubMed Central

    Xie, Yanyun; Shen, Yen Ting; Kapoor, Anil; Ojo, Diane; Wei, Fengxiang; De Melo, Jason; Lin, Xiaozeng; Wong, Nicholas; Yan, Judy; Tao, Lijian; Major, Pierre; Tang, Damu

    2016-01-01

    We have recently reported that CYB5D2 plays a role in suppression of cervical cancer tumorigenesis, CYB5D2 displays tumor suppression activities towards cervical cancer [1]. We provide the accompany data here describing the effects of CYB5D2 overexpression and addition of recombinant CYB5D2 on HeLa cell cycle distribution. Furthermore, we will present the conditions used to specifically determine CYB5D2 expression in primary cervical and cervical cancer tissues using immunohistochemistry (IHC) and the patient cohort involved in assessing the CYB5D2 protein levels in primary cervical and cervical cancer tissues.

  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. Inhibition of Aurora A promotes chemosensitivity via inducing cell cycle arrest and apoptosis in cervical cancer cells

    PubMed Central

    Sun, Jian-Ming; Yang, Li-Na; Xu, Han; Chang, Bin; Wang, Hua-Ying; Yang, Gong

    2015-01-01

    Aurora kinase A (AurA) regulates genomic instability and tumorigenesis in multiple cancer types. Although some studies have reported that Aur A may predict cervical cancer outcomes, its precise function and molecular mechanism in cervical cancer pathogenesis remain unclear. In this study, by overexpression or silencing of Aur A in cervical cancer cell lines, we found that overexpression of Aur A promoted cell proliferation through G1/S cell cycle transition and anti-apoptosis, xenograft tumor growth and chemoresistance to Taxol. We further found that inhibition of Aur A with its specific inhibitor VX-680 enhanced the antitumor effect of Taxol via inducing apoptosis. Moreover, the clinical analysis from tissue samples demonstrated that Aur A was overexpressed, and the expression of Aur A and pERK1/2 was negatively correlated in cervical cancer tissues. The above results may provide some potential insights in treatment of cervical cancer in clinic. PMID:26045992

  9. Risks of Cervical Cancer Screening

    MedlinePLUS

    ... cases of cervical cancer and the number of deaths due to cervical cancer since 1950. Cervical dysplasia ... for cervical cancer helps decrease the number of deaths from the disease. Regular screening of women between ...

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

    ClinicalTrials.gov

    2016-01-11

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; 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

  11. Cervical Cancer

    MedlinePLUS

    ... Managing Cancer Care Finding Health Care Services Advance Directives Using Trusted Resources What Is Cancer Cancer Statistics ... Managing Cancer Care Finding Health Care Services Advance Directives Using Trusted Resources Cancer Types Adolescents and Young ...

  12. Epigenetic Silencing of CXCR4 Promotes Loss of Cell Adhesion in Cervical Cancer

    PubMed Central

    Prasad, Shyam Babu; Das, Mitali; Kumari, Soni; Pandey, Lakshmi Kant; Singh, Sunita; Pradhan, Satyajit

    2014-01-01

    In the network of chemokine signaling pathways, recent reports have described the SDF-1?/CXCR4 axis and its role in cancer progression and metastasis. Interestingly, we found downregulation of CXCR4 at both transcript and protein level in cervical cancer cell lines and primary tumors. We also found CXCR4 promoter hypermethylation in cervical cancer cell lines and primary biopsy samples. DNA hypomethylating drug 5-AZA-2?-deoxycytidine and histone deacetylase inhibitor Trichostatin A treatments in cell lines reactivate both CXCR4 transcription and protein expression. Cell adhesion assay demonstrated that autocrine SDF-1? promotes the loss of cell adhesion while paracrine SDF-1? predominantly protects the normal cervical cells from loss of cell adhesion. Cervical cancer cell line C-33A having increased expression of CXCR4 after TSA treatment showed increased cell adhesion by paracrine source of SDF-1? in comparison to untreated C-33A. These findings demonstrate the first evidence that epigenetic silencing of CXCR4 makes the cells inefficient to respond to the paracrine source of SDF-1? leading to loss of cell adhesion, one of the key events in metastases and progression of the disease. Our results provide novel insight of SDF-1?/CXCR4 signaling in tumor microenvironment which may be promising to further delineate molecular mechanism of cervical carcinogenesis. PMID:25114911

  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. Amygdalin induces apoptosis in human cervical cancer cell line HeLa cells.

    PubMed

    Chen, Yu; Ma, Jinshu; Wang, Fang; Hu, Jie; Cui, Ai; Wei, Chengguo; Yang, Qing; Li, Fan

    2013-02-01

    Amygdalin, a naturally occurring substance, has been suggested to be efficacious as an anticancer substance. The effect of amygdalin on cervical cancer cells has never been studied. In this study, we found that the viability of human cervical cancer HeLa cell line was significantly inhibited by amygdalin. 4,6-Diamino-2-phenyl indole (DAPI) staining showed that amygdalin-treated HeLa cells developed typical apoptotic changes. The development of apoptosis in the amygdalin-treated HeLa cells were confirmed by double staining of amygdalin-treated HeLa cells with annexin V-FITC and propidium iodide (PI) along with increase in caspase-3 activity in these cells. Further studies indicated that antiapoptotic protein Bcl-2 was downregulated whereas proapoptotic Bax protein was upregulated in the amygdalin-treated HeLa cells implying involvement of the intrinsic pathway of apoptosis. In vivo, amygdalin administration inhibited the growth of HeLa cell xenografts through a mechanism of apoptosis. The results in the present study suggest that amygdalin may offer a new therapeutic option for patients with cervical cancer. PMID:23137229

  15. Novel functions and targets of miR-944 in human cervical cancer cells

    PubMed Central

    Xie, Hong; Lee, Linkiat; Scicluna, Patrick; Kavak, Ersen; Larsson, Catharina; Sandberg, Rickard; Lui, Weng-Onn

    2015-01-01

    Altered expression of specific microRNAs (miRNAs) has been observed in human cervical cancer. However, the biological functions of many of these miRNAs are yet to be discovered. We previously showed that miR-944 is significantly more abundant in cervical cancer tissues than their normal counterparts. In this study, we investigated the functions and targets of miR-944 in human cervical cancer cells. MiR-944 is located in the intron of the tumor protein p63 (TP63) gene, which is frequently overexpressed in cervical carcinomas. Using gain- and loss-of-function experiments in vitro, we demonstrate that miR-944 promotes cell proliferation, migration and invasion, but has no effect on apoptosis, in human cervical cancer cells. To identify the targets of miR-944, we performed photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation followed by deep sequencing. Among the candidate targets, we validated HECW2 (HECT domain ligase W2) and S100PBP (S100P binding protein) as direct targets of miR-944 using luciferase reporter assays and western blot analysis. Our findings reveal novel functions and targets of miR-944 in human cervical cancer cells, which may provide new insights of its role in cervical carcinogenesis. What's new? While miR-944 has been shown to be associated with tumor development and progression in several tumor types, its functions and targets remain undetermined. This study stands out as the first report of miR-944 functions and targets in human cancer. The authors demonstrate that miR-944 functions as an oncogene in human cervical cancer cells by promoting cell proliferation, migration, and invasion. In addition, they identified and validated HECW2 and S100PBP as direct targets of miR-944 in human cervical cancer cells. The findings provide new insights into the biological roles of miR-944 in human cervical cancer cells. PMID:25156441

  16. 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 functional role of miR-196a in cervical carcinogenesis and suggested a potential use of miR-196a for clinical diagnosis and as a therapeutic target.

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

    ClinicalTrials.gov

    2016-02-09

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Lymphedema; Sexual Dysfunction and Infertility; Stage IA1 Cervical Cancer; Stage IA2 Cervical Cancer; Stage IB1 Cervical Cancer

  18. Cytotoxic effect and induction of apoptosis in human cervical cancer cells by Antrodia camphorata.

    PubMed

    Yang, Pei-Yu; Hu, Dan-Ning; Liu, Fu-Shing

    2013-01-01

    Antrodia camphorata is a Chinese herb indigenous to Taiwan. Previous reports demonstrated that it could induce apoptosis in some cancer cells. The purpose of this study was to investigate the apoptotic effect of the crude extract of A. camphorata in cervical cancer cells. Two human cervical cancer cell lines, HeLa and C-33A, were treated with extract of A. camphorata (10-1000 μg/mL). We found that A. camphorata extract was cytotoxic to both cervical cancer cells in a dose- and time-dependent manner as examined by MTT assay. Treatment with A. camphorata extract at 400 μg/mL induced a 2.3- and 4.4-fold increase in oligonucleosome formation from the cleaved chromosomal DNA in HeLa and C-33A cells, respectively. A. camphorata extract also activated caspase-3, -8, and -9 activities and increased the cytosolic level of cytochrome c in both cell lines as the dosage increased. Furthermore, A. camphorata extract increased expressions of Bak, Bad and Bim, while decreasing expressions of Bcl-2 and Bcl-xL of the Bcl-2 family proteins in HeLa and C-33A cells. The expression of IAP proteins, XIAP and survivin, was also decreased in both cervical cancer cells after treatment with A. camphorata. Our in vitro study suggests that A. camphorata is cytotoxic to cervical cancer cells through both extrinsic and intrinsic apoptotic mechanisms. It could be used as a novel phytotherapeutic agent or auxiliary therapy in the treatment of cervical cancer. PMID:24117076

  19. Down-regulation of FR? inhibits proliferation and promotes apoptosis of cervical cancer cells in vitro.

    PubMed

    Bai, Li-Xia; Ding, Ling; Jiang, Shi-Wen; Kang, Hui-Jie; Gao, Chen-Fei; Chen, Chen; Zhou, Qin; Wang, Jin-Tao

    2014-01-01

    Folate receptor alpha (FR?) mediates folate uptake by endocytosis, and while folate is essential to DNA methylation and synthesis and may have an important role in proliferating cells. FR? is known to be expressed in rapidly proliferating cells, including many cancer cell lines, but there has been no systematic assessment of expression in cervical cancer cell lines. The aim of the present study was to evaluate the effects of FR? on proliferation and apoptosis of cervical cells and correlation mechanism. In this study, we investigated the biological function of FR? in Hela cells using RNA interference. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK8) assay, while cell cycling and apoptosis were assessed by flow cytometry, mRNA levels by real time- PCR and protein levels of FR?, c-Fos and c-Jun by Western blotting. The results revealed that FR? was highly expressed in Hela cells and its silencing with a small interfering RNA (siRNA) inhibited cell proliferation and induced cell apoptosis, arresting the cell cycle in G0/G1 stages while decreasing the proportion in S and G2/M stages, and suppressed the expression levels of c-Fos and c-Jun. In conclusion, the results of this study indicated that FR? down-regulation might be capable of suppressing cervical cancer cell proliferation and promoting apoptosis. It suggested that FR? might be a novel therapeutic target for cervical cancer. PMID:25081683

  20. Chemokine CCL17 induced by hypoxia promotes the proliferation of cervical cancer cell

    PubMed Central

    Liu, Li-Bing; Xie, Feng; Chang, Kai-Kai; Shang, Wen-Qing; Meng, Yu-Han; Yu, Jia-Jun; Li, Hui; Sun, Qian; Yuan, Min-Min; Jin, Li-Ping; Li, Da-Jin; Li, Ming-Qing

    2015-01-01

    Cervical cancer is often associated with hypoxia and many kinds of chemokines. But the relationship and role of hypoxia and Chemokine (C-C motif) ligand 17 (CCL17) in cervical cancer are still unknown. Here, we found that CCL17 was high expressed in cervical cancer. HeLa and SiHa cells could secrete CCL17 in a time-dependent manner. Hypoxia increased expression of CCL17 receptor (CCR4) on HeLa and SiHa cells. Treatment with recombination human CCL17 (rhCCL17) led to an elevation of cell proliferation in HeLa and SiHa cells in a dose-dependent manner. In contrast, blocking CCL17 with anti-human CCL17 neutralizing antibody (?-CCL17) played an oppose effect. However, rhCCL17 had no effect on apoptosis in cervical cancer cells. Further analysis showed that hypoxia promoted the proliferation of HeLa and SiHa cells, and these effects could be reversed by ?-CCL17. Stimulation with the inhibitor for c-Jun N-terminal kinase (JNK) or signal transducers and activator of transcription 5 (STAT5) signal pathway not only directly decreased the proliferation of HeLa and SiHa cells, but also abrogated the stimulatory effect of rhCCL17 on the proliferation of HeLa and SiHa cells. These results suggest that a high level of CCL17 in cervical cancer lesions is an important regulator in the proliferation of cervical cancer cells through JNK and STAT5 signaling pathways. In this process, hypoxia magnifies this effect by up-regulating CCR4 expression and strengthening the interaction of CCL17/CCR4. PMID:26693060

  1. Biomarker discovery for neuroendocrine cervical cancer.

    PubMed

    Lin, Li-Hsun; Chang, Shing-Jyh; Hu, Ren-Yu; Lin, Meng-Wei; Lin, Szu-Ting; Huang, Shun-Hong; Lyu, Ping-Chiang; Chou, Hsiu-Chuan; Lai, Zih-Yin; Chuang, Yung-Jen; Chan, Hong-Lin

    2014-07-01

    Neuroendocrine cervical cancer is an aggressive but rare form of cervical cancer. The majority of neuroendocrine cervical cancer patients present with advanced-stage diseases. However, the limited numbers of neuroendocrine tumor markers are insufficient for clinical purposes. Thus, we used a proteomic approach combining lysine labeling 2D-DIGE and MALDI-TOF MS to investigate the biomarkers for neuroendocrine cervical cancer. By analyzing the global proteome alteration between the neuroendocrine cervical cancer line (HM-1) and non-neuroendocrine cervical cancer lines (CaSki cells, ME-180 cells, and Hela cells), we identified 82 proteins exhibiting marked changes between HM-1 and CaSki cells, and between ME-180 and Hela cells. Several proteins involved in protein folding, cytoskeleton, transcription control, signal transduction, glycolysis, and redox regulation exhibited significant changes in abundance. Proteomic and immunoblot analyses indicated respective 49.88-fold and 25-fold increased levels of transgelin in HM-1 cells compared with that in other non-neuroendocrine cervical cancer cell lines, implying that transgelin is a biomarker for neuroendocrine cervical cancer. In summary, we used a comprehensive neuroendocrine/non-neuroendocrine cervical cancer model based proteomic approach for identifying neuroendocrine cervical cancer markers, which might contribute to the prognosis and diagnosis of neuroendocrine cervical cancer. PMID:24723343

  2. Expression and transcriptional profiling of the LKB1 tumor suppressor in cervical cancer cells

    PubMed Central

    Zhang, Xiaoli; Chen, Hanxiang; Wang, Xiao; Zhao, Weiming; Chen, Jason J.

    2016-01-01

    Objectives To characterize the biological activities of LKB1, examine LKB1 protein expression and identify LKB1-regulated genes that may serve as therapeutic targets in cervical cancer. Methods Proliferation of cervical cancer HeLa cells expressing LKB1 was examined. LKB1 expression in normal cervical tissues and cervical cancers was assessed by immunohistochemistry. Gene expression profiles of cervical cancer HeLa cells stably expressing LKB1 were analyzed by microarray. Differentially expressed genes were analyzed using Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) PATHWAY database. Quantitative RT-PCR was used to validate the microarray data. The expression of lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) was confirmed by western blotting. Results Expression of LKB1 inhibited HeLa cell proliferation and activated AMPK and was lost in more than 50% of cervical carcinomas. More than 200 genes were differentially expressed between HeLa cells with and without LKB1. Bioinformatics analysis with GO annotation indicated that LKB1 plays a role in receiving diverse stimuli and converting them into molecular signals. KEGG PATHWAY analysis showed that 8 pathways were significantly regulated. These include arginine and proline metabolism and inositol phosphate metabolism. The differential expression of 7 randomly selected genes was confirmed by quantitative RT-PCR. Furthermore, the steady-state level of INPP4B protein was up-regulated in LKB1-overexpressing cells. Conclusions This study establishes LKB1 as an important tumor suppressor in cervical cancer and sheds light on a novel signaling pathway regulated by LKB1. PMID:24792998

  3. Overexpression of TROP2 Predicts Poor Prognosis of Patients with Cervical Cancer and Promotes the Proliferation and Invasion of Cervical Cancer Cells by Regulating ERK Signaling Pathway

    PubMed Central

    Liu, Ting; Liu, Yueyang; Bao, Xiangxiang; Tian, Jiguang; Liu, Yang; Yang, Xingsheng

    2013-01-01

    Overwhelming evidence has demonstrated that the aberrant expression of the human trophoblast cell-surface antigen (TROP2) was associated with tumor aggressiveness and poor prognosis in a variety of human cancers, however the roles of TROP2 in cervical cancer have not been investigated. The purpose of our study was to elucidate the prognostic significance of TROP2 expression in patients with cervical cancer and determine its effect on tumor progression. Immunohistochemistry assay showed that 88.7% (94/106 cases) of cervical cancer specimens were positively stained with TROP2, and the overexpression of TROP2 was closely related with FIGO stage, histological grades, lymphatic metastasis, invasive interstitial depth and high expression of Ki-67. Patients with TROP2-positive staining exhibited a significantly decreased overall survival and progression free survival; it was also an independent predictor for prognosis according to multivariate analysis. Moreover, down-regulation of TROP2 mediated by siRNA in Siha and CaSki cells resulted in a strong inhibition of proliferation and invasion, TROP2 abrogation also elevated the apoptotic ratio and caused G1 arrest. Conversely, enforced expression of TROP2 in HeLa and C33A cells remarkably promoted cell growth, migration and invasion. In addition, the tumorigenic function of TROP2 was associated with the increased expressions of cyclin D1, cyclin E, CDK2 and CDK4 but reduced expression of p27 and E-cadherin via the activation of Erk1/2 signaling pathway. Furthermore, the inhibition of TROP2 expression in cervical cancer cell lines enhances sensitivity to cisplatin. The present study suggest that overexpression of TROP2 may play crucial roles in the development and pathogenesis of human cervical cancer, therefore, TROP2 may represent a prospective prognostic indicator and a potential therapeutic target of cervical cancer. PMID:24086649

  4. Cervical Cancer Screening

    MedlinePLUS

    ... the place where a baby grows during pregnancy. Cancer screening is looking for cancer before you have any ... found early may be easier to treat. Cervical cancer screening is usually part of a woman's health checkup. ...

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

    ClinicalTrials.gov

    2016-03-17

    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

  6. Up-regulation of microRNA-664 inhibits cell growth and increases cisplatin sensitivity in cervical cancer

    PubMed Central

    Yang, Yao; Liu, Hong; Wang, Xi; Chen, Long

    2015-01-01

    Background: Cervical cancer is one of the leading causes of cancer-related death in woman worldwide. In the present study, we investigated the role of microRNA 664 (miR-664) in regulating cancer migration and chemotherapy sensitivity in cervical cancer. Methods: Quantitative real-time PCR (qPCR) was used to assess the mRNA levels of miR-664 in both cervical cancer cell lines and cancer tissues from human patients. Lentiviral vector containing miR-664 mimics (lv-miR-664) was used to upregulate endogenous miR-664 in cervical cancer HeLa cells. The effects of miR-664 up-regulation on cervical cancer cell migration and cisplatin sensitivity were assessed by MTT and Cisplatin assays. Furthermore, the effect of miR-664 up-regulation on E-Cadherin expression was examined by western blot. E-Cadherin was then silenced by siRNA to examine its effect on miR-664 regulation on cervical cancer cell. Results: MiR-664 was downregulated in both cervical cancer cell lines and cancer tissues in patients. In HeLa cells, lentivirus mediated miR-664 up-regulation reduced cancer cell migration and increased chemosensitivity to cisplatin. Western blot showed E-Cadherin was upregulated upon miR-664 overexpression in HeLa cells. Genetic silencing of E-Cadherin by siRNA reversed the inhibitory effect of miR-664 up-regulation on cervical cancer cell migration. Conclusion: Our study demonstrated that miR-664 played an important role in regulating cervical cancer, possibly modulated by E-Cadherin. PMID:26770409

  7. 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

  8. 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

  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. The cytotoxic activity of Ziziphus Jujube on cervical cancer cells: In Vitro study.

    PubMed

    Hoshyar, R; Jamali, S; Fereidouni, M; Abedini, M R

    2015-01-01

    Recently, there are tendency to use natural products such as Ziziphus Jujube (Jujube) as therapeutic agents for cancer. Understanding the molecular mechanisms of anti-cancer effects of Jujube may improve the current therapeutic strategies against cervical cancer. Our MTT data showed a significant dose- and time-dependent inhibition of OV-2008 cell proliferation following Jujube administration. Moreover, qRT-PCR analyses significantly revealed the suppression of cyclin D1 and the enhancement of P53, P21 and P27 expression in treated cells. These results suggest that the herb exerts a cytotoxic effect on cervical cancer cells through alternation of the expression of the genes that are involved in regulation of cell cycle. PMID:26718441

  12. Cervical cancer vaccine development.

    PubMed

    Frazer, Ian H

    2010-09-01

    Cervical cancer is initiated by infection of cervical epithelium with human papillomavirus. Vaccines have been developed, incorporating papillomavirus viral capsids and alum based adjuvants. In extensive clinical trials these vaccines have been shown safe and effective in preventing infection with, and disease caused by, the papillomavirus genotypes they incorporate, in women not already infected. These vaccines have the potential to reduce the global burden of cervical cancer by up to 70%. PMID:20719210

  13. STAT3 correlates with stem cell-related transcription factors in cervical cancer.

    PubMed

    Wang, Hua; Cai, Hong-Bing; Chen, Lou-Lou; Zhao, Wen-Jun; Li, Pan; Wang, Zhi-Qiang; Li, Zhen

    2015-12-01

    Cancer stem cells (CSCs) are considered responsible for the high recurrence rate in cervical carcinoma. It has been demonstrated that the signal transducer and activator of transcription 3 (STAT3) is involved in the oncogenesis and takes part in mediating the effects of maintaining stem cell phenotype and pluripotency by regulating the expression of stem cell-related transcription factors. However, the correlation between STAT3 and stem cell-related transcription factors in cervical cancer has not been elucidated. In this study, we established overexpressing plasmid (GV316-STAT3) and siRNA-STAT3 for transfecting Siha cells. Cells negative or positive for Nanog, Oct4, or Sox2 were selected by flow cytometry. Proliferation and differentiation rate of Siha cells was determined by detecting the efficiency of tumor sphere formation. The expression of Nanog, Oct4 and Sox2 (cancer stem cell markers) and STAT3 was detected by quantitative real-time PCR and immunoblotting for Siha cells and by immunohistochemistry (IHC) for cervical tissues, respectively. The results showed that Nanog+, Oct4+, and Sox2+ Siha-STAT3 over-expressing cells displayed the typical non-adherent spheres. The sphere formation efficiency was significantly different between Siha-STAT3 overexpressing cells and siRNA-STAT3 cells (P<0.05). Meanwhile, the expression levels of Oct4, Nanog and Sox2 mRNA and protein were significantly higher in Siha-STAT3 overexprssing cells than in siRNA-STAT3 cells (P<0.05). In addition, the positive rate of STAT3, Nanog, Oct4 and Sox2 in cervical cancer tissues was higher than that in chronic cervicitis group (P<0.05). There was a significantly positive relationship between STAT3 and Nanog or Oct4 or Sox2 expression (all P<0.001). These results suggested that Oct4+, Sox2+, and Nanog+ cell population possesses stem cell properties in cervical cancer, which may contribute to cervical carcinogenesis and be regulated by STAT3. PMID:26670442

  14. Curcumin and Emodin Down-Regulate TGF-β Signaling Pathway in Human Cervical Cancer Cells

    PubMed Central

    Thacker, Pooja Chandrakant; Karunagaran, Devarajan

    2015-01-01

    Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling) and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug) upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer. PMID:25786122

  15. Cellular Levels of Oxidative Stress Affect the Response of Cervical Cancer Cells to Chemotherapeutic Agents

    PubMed Central

    Williams, Vonetta M.; Kokoza, Anatolii; Bashkirova, Svetlana; Duerksen-Hughes, Penelope

    2014-01-01

    Treatment of advanced and relapsed cervical cancer is frequently ineffective, due in large part to chemoresistance. To examine the pathways responsible, we employed the cervical carcinoma-derived SiHa and CaSki cells as cellular models of resistance and sensitivity, respectively, to treatment with chemotherapeutic agents, doxorubicin, and cisplatin. We compared the proteomic profiles of SiHa and CaSki cells and identified pathways with the potential to contribute to the differential response. We then extended these findings by comparing the expression level of genes involved in reactive oxygen species (ROS) metabolism through the use of a RT-PCR array. The analyses demonstrated that the resistant SiHa cells expressed higher levels of antioxidant enzymes. Decreasing or increasing oxidative stress led to protection or sensitization, respectively, in both cell lines, supporting the idea that cellular levels of oxidative stress affect responsiveness to treatment. Interestingly, doxorubicin and cisplatin induced different profiles of ROS, and these differences appear to contribute to the sensitivity to treatment displayed by cervical cancer cells. Overall, our findings demonstrate that cervical cancer cells display variable profiles with respect to their redox-generating and -adaptive systems, and that these different profiles have the potential to contribute to their responses to treatments with chemotherapy. PMID:25478571

  16. Total synthetic protoapigenone WYC02 inhibits cervical cancer cell proliferation and tumour growth through PIK3 signalling pathway.

    PubMed

    Chen, Yun-Ju; Kay, Nari; Yang, Jinn-Moon; Lin, Chih-Ta; Chang, Hsueh-Ling; Wu, Yang-Chang; Fu, Chi-Feng; Chang, Yu; Lo, Steven; Hou, Ming-Feng; Lee, Yi-Chen; Hsieh, Ya-Ching; Yuan, Shyng-Shiou

    2013-07-01

    Flavonoids have been intensively explored for their anticancer activity. In this study, a total synthetic flavonoid protoapigenone, known as WYC02, was analysed for its potential anticancer activity on human cervical cancer cells as well as the underlying mechanisms for these effects. The site-moiety maps are used to explore the binding site similarity, pharmacophore and docking pose similarity. The effect of WYC02 on cell viability, migration, invasion and apoptosis as well as the underlying mechanisms was analysed in vitro using human cervical cancer cells. The effect of WYC02 on in vivo tumour growth was assessed in a tumour xenograft study. WYC02 inhibited cell proliferation, MMPs activity, migration and invasion in cervical cancer cells. We speculated that WYC02 might inhibit the activities of PIK3 family proteins, including PIK3CA, PIK3CB, PIK3CD and PIK3CG. Indeed, WYC02 decreased the expression of PIK3 family proteins, especially PIK3CG, through ubiquitination and inhibited the activities of PIK3CG and PIK3 downstream molecules AKT1 and MTOR in cervical cancer cells. Furthermore, PIK3 signalling pathway was involved in the inhibitory effect of WYC02 on cervical cancer cell proliferation and tumour growth in vitro and in vivo. WYC02 inhibits cervical cancer cell proliferation and tumourigenesis via PIK3 signalling pathway and has the potential to be developed as a chemotherapeutic agent in cervical cancer. PMID:23387868

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

    PubMed

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

    2015-02-01

    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

  18. 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

  19. Glucose-regulated protein 94 modulates the therapeutic efficacy to taxane in cervical cancer cells.

    PubMed

    Tai, Cheng-Jeng; Wang, Jin-Wun; Su, Hou-Yu; Tai, Chen-Jei; Wang, Chien-Kai; Wu, Chun-Te; Lien, Yung-Chang; Chang, Yu-Jia

    2014-01-01

    Cervical cancer is an important health issue for women worldwide, and the endoplasmic reticulum stress pathway is important for determining the chemotherapeutic response to cancer. However, the role of glucose-regulated protein 94 (GRP94) in taxane therapy for cervical cancer remains unclear. In this study, we generated GRP94 knockdown (GRP94-KD) Hela cells using short hairpin RNAs and found that GRP94-KD cells were resistant to taxane treatment in an MTT assay. Scrambled control cells demonstrated higher levels of apoptosis when treated with taxanes in comparison to GRP94-KD cells, as determined by cell cycle profiling, 4',6-diamidino-2-phenylindole staining, and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. Caspase 3 and caspase 7 activity was also higher in scrambled control cells treated with taxane in comparison to GRP94-KD cells. Moreover, we found that depletion of GRP94 altered the levels of the apoptosis-related proteins Bcl2 and Bad, leading to sensitivity to taxane. Exposure to taxane also induced the expression of Bad in scrambled cells but not in GRP94-KD cells. In addition, the expression of Bcl2 was increased dramatically in GRP94-KD cells, whereas only a small increase was observed in scrambled cells. Therefore, we conclude that silencing GRP94 may increase resistance to taxane treatment in cervical cancer cells by altering the activation of the apoptosis pathway. In addition, GRP94 may represent a key biomarker for determining the therapeutic efficacy of taxane treatment in cervical cancer patients. PMID:23929391

  20. 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

  1. 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.

  2. 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

    2015-11-09

    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

  3. 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

    2015-01-01

    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

  4. 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

  5. Adenosine uptake is the major effector of extracellular ATP toxicity in human cervical cancer cells

    PubMed Central

    Mello, Paola de Andrade; Filippi-Chiela, Eduardo Cremonese; Nascimento, Jssica; Beckenkamp, Aline; Santana, Danielle Bertodo; Kipper, Franciele; Casali, Emerson Andr; Nejar Bruno, Alessandra; Paccez, Juliano Domiraci; Zerbini, Luiz Fernando; Wink, Marcia Rosngela; Lenz, Guido; Buffon, Andria

    2014-01-01

    In cervical cancer, HPV infection and disruption of mechanisms involving cell growth, differentiation, and apoptosis are strictly linked with tumor progression and invasion. Tumor microenvironment is ATP and adenosine rich, suggesting a role for purinergic signaling in cancer cell growth and death. Here we investigate the effect of extracellular ATP on human cervical cancer cells. We find that extracellular ATP itself has a small cytotoxic effect, whereas adenosine formed from ATP degradation by ectonucleotidases is the main factor responsible for apoptosis induction. The level of P27 receptor seemed to define the main cytotoxic mechanism triggered by ATP, since ATP itself eliminated a small subpopulation of cells that express high P27 levels, probably through its activation. Corroborating these data, blockage or knockdown of P27 only slightly reduced ATP cytotoxicity. On the other hand, cell viability was almost totally recovered with dipyridamole, an adenosine transporter inhibitor. Moreover, ATP-induced apoptosis and signalingp53 increase, AMPK activation, and PARP cleavageas well as autophagy induction were also inhibited by dipyridamole. In addition, inhibition of adenosine conversion into AMP also blocked cell death, indicating that metabolization of intracellular adenosine originating from extracellular ATP is responsible for the main effects of the latter in human cervical cancer cells. PMID:25103241

  6. Neocarzinostatin induces an effective p53-dependent response in human papillomavirus-positive cervical cancer cells.

    PubMed

    Bauelos, Adriana; Reyes, Elba; Ocadiz, Rodolfo; Alvarez, Elizabeth; Moreno, Martha; Monroy, Alberto; Gariglio, Patricio

    2003-08-01

    Human papillomavirus (HPV) E6 viral oncoprotein plays an important role during cervical carcinogenesis. This oncoprotein binds the tumor suppressor protein p53, leading to its degradation via the ubiquitin-proteasome pathway. Therefore, it is generally assumed that in HPV-positive cancer cells p53 function is completely abolished. Nevertheless, recent findings suggest that p53 activity can be recovered in cells expressing endogenous E6 protein. To investigate whether p53-dependent functions controlling genome integrity, cell proliferation, and apoptosis can be reactivated in cervical cancer cells, we examined the capacity of HeLa, INBL, CaSki, C33A, and ViBo cell lines to respond to neocarzinostatin (NCS), a natural product which induces single- and double-strand breaks in DNA. We found that NCS treatment inhibits cellular proliferation through G2 cell cycle arrest and apoptosis induction. This effect was preceded by nuclear accumulation of p53 protein and by an increase of p21 transcripts. Although apoptosis was blocked in ViBo cells (HPV-negative), nuclear accumulation of transcriptionally active p53 and inhibition of cell proliferation are observed after NCS treatment. These results suggest that HPV-positive cervical cancer cells are capable of responding efficiently to DNA damage provoked by NCS treatment through a p53-dependent pathway in spite of the presence of E6 protein. PMID:12750435

  7. 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.

  8. Papillomavirus capsid mutation to escape dendritic cell-dependent innate immunity in cervical cancer.

    PubMed

    Yang, Rongcun; Wheeler, Cosette M; Chen, Xiaojiang; Uematsu, Satoshi; Takeda, Kiyoshi; Akira, Shizuo; Pastrana, Diana V; Viscidi, Raphael P; Roden, Richard B S

    2005-06-01

    Infection with oncogenic human papillomaviruses (HPVs), typified by HPV type 16 (HPV16), is a necessary cause of cervical cancer. Prophylactic vaccination with HPV16 L1 virus-like particles (VLPs) provides immunity. HPV16 VLPs activate dendritic cells and a potent neutralizing immunoglobulin G (IgG) response, yet many cervical cancer patients fail to generate detectable VLP-specific IgG. Therefore, we examined the role of the innate recognition of HPV16 L1 in VLP-induced immune responses and its evasion during carcinogenesis. Nonconservative mutations within HPV16 L1 have been described in isolates from cervical cancer and its precursor, high-grade cervical intraepithelial neoplasia (CIN). We determined the effect of mutations in L1 upon in vitro self-assembly into VLPs and their influence upon the induction of innate and adaptive immune responses in mice. Several nonconservative mutations in HPV16 L1 isolated from high-grade CIN or cervical carcinoma prevent self-assembly of L1 VLPs. Intact VLPs, but not assembly-defective L1, activate dendritic cells to produce proinflammatory factors, such as alpha interferon, that play a critical role in inducing adaptive immunity. Indeed, effective induction of L1-specific IgG1 and IgG2a was dependent upon intact VLP structure. Dendritic cell activation and production of virus-specific neutralizing IgG by VLPs requires MyD88-dependent signaling, although the L1 structure that initiates MyD88-mediated signaling is distinct from the neutralizing epitopes. We conclude that innate recognition of the intact L1 VLP structure via MyD88 is critical in the induction of high-titer neutralizing IgG. Tumor progression is associated with genetic instability and L1 mutants. Selection for assembly-deficient L1 mutations suggests the evasion of MyD88-dependent immune control during cervical carcinogenesis. PMID:15890912

  9. Down-regulation of microRNA-135b inhibited growth of cervical cancer cells by targeting FOXO1

    PubMed Central

    Xu, Yue; Zhao, Shuhua; Cui, Manhua; Wang, Qiang

    2015-01-01

    More and more evidence has confirmed that dysregulation of microRNAs (miRNAs) can conduce to the progression of human cancers. Previous studied have shown that dysregulation of miR-135b is in varieties of tumors. However, the roles of miR-135b in cervical cancer remain unknown. Therefore, our aim of this study was to explore the biological function and molecular mechanism of miR-135b in cervical cancer cell lines, discussing whether it could be a therapeutic biomarker of cervical cancer in the future. The MTT assay and ELISA-Brdu assay were used to assess cell proliferation. Cell cycle was detected by flow cytometry. Real-time quantitative polymerase chain reaction (PCR) and Western blot analyses were used to detect expressions of cyclin D1, p21, p27 and FOXO1. In our study, we found that miR-135b is up-regulated in cervical cancer cell lines. Down-regulation of miR-135b evidently inhibited proliferation and arrested cell cycle in cervical cancer cells. Bioinformatics analysis predicted that the FOXO1 was a potential target gene of miR-135b. Besides, miR-135b inhibition significantly increased expressions of the cyclin-dependent kinase inhibitors, p21/CIP1 and p27/KIP1, and decreased expression of cyclin D1. However, the high level of miR-135b was associated with increased expression of FOXO1 in cervical cancer cells. Further study by luciferase reporter assay demonstrated that miR-135b could directly target FOXO1. Down-regulation of FOXO1 in cervical cancer cells transfected with miR-135b inhibitor partially reversed its inhibitory effects. In conclusion, down-regulation of miR-135b inhibited cell growth in cervical cancer cells by up-regulation of FOXO1. PMID:26617737

  10. Physical Labeling of Papillomavirus-Infected, Immortal, and Cancerous Cervical Epithelial Cells Reveal Surface Changes at Immortal Stage

    PubMed Central

    Iyer, K. Swaminathan; Gaikwad, R. M.; Woodworth, C. D.; Volkov, D. O.

    2013-01-01

    A significant change of surface features of malignant cervical epithelial cells compared to normal cells has been previously reported. Here, we are studying the question at which progressive stage leading to cervical cancer the surface alteration happens. A non-traditional method to identify malignant cervical epithelial cells in vitro, which is based on physical (in contrast to specific biochemical) labelling of cells with fluorescent silica micron-size beads, is used here to examine cells at progressive stages leading to cervical cancer which include normal epithelial cells, cells infected with human papillomavirus type-16 (HPV-16), cells immortalized by HPV-16, and carcinoma cells. The study shows a statistically significant (at p <0.01) difference between both immortal and cancer cells and a group consisting of normal and infected. There is no significant difference between normal and infected cells. Immortal cells demonstrate the signal which is closer to cancer cells than to either normal or infected cells. This implies that the cell surface, surface cellular brush changes substantially when cells become immortal. Physical labeling of the cell surface represents a substantial departure from the traditional biochemical labeling methods. The results presented show the potential significance of physical properties of the cell surface for development of clinical methods for early detection of cervical cancer, even at the stage of immortalized, pre-malignant cells. PMID:22351422

  11. Cervical Cancer Screening

    MedlinePLUS

    ... douching, sexual intercourse, and using vaginal medications or hygiene products for 2 days before your test. You also should not have cervical cancer screening if you have your menstrual period. Glossary Biopsy: A minor surgical procedure to ...

  12. 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

    2016-03-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; 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

  13. Twist-related protein 1-mediated regulation of mesenchymal change contributes to the migration and invasion of cervical cancer cells

    PubMed Central

    WANG, DANQING; LI, QINGLI; LI, KEMIN; XIAO, PING; YIN, RUTIE

    2015-01-01

    Twist-related protein 1 (Twist1), is a class II basic helix-loop-helix transcription factor, which has been demonstrated to be a major regulator of epithelial-mesenchymal transition (EMT), and therefore is involved in promoting carcinoma metastasis. Previous studies have demonstrated that Twist1 expression is upregulated in cervical cancer cases with poor clinical outcomes. However, the mechanisms that mediate the role of Twist1 in cervical cancer metastasis are poorly understood. To the best of our knowledge, the present study provides the first evidence that the downregulation of Twist1 by short hairpin RNA lentivirus (LV-shRNA) resulted in the inhibition of invasion and migration of cervical cancer cells. Furthermore, the present study presents evidence that reducing Twist1 expression prevents cervical cancer cells from undergoing EMT. The expression of the epithelial cell marker, E-cadherin, was elevated; and the expression levels of mesenchymal cell markers [fibronectin, vimentin, matrix metalloproteinase-9 (MMP-9) and MMP-2] were reduced in the LV-sh-Twist1 group in cervical cells. Collectively, these findings indicate that Twist1-mediated modulation of EMT is important in the invasion and migration of cervical cells, and also indicates the potential therapeutic importance of strategies involving the inactivation of Twist1-mediated mesenchymal changes in cervical cancer. PMID:26722297

  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. PMID:25937122

  15. Stressing the ubiquitin-proteasome system without 20S proteolytic inhibition selectively kills cervical cancer cells.

    PubMed

    Anchoori, Ravi K; Khan, Saeed R; Sueblinvong, Thanasak; Felthauser, Alicia; Iizuka, Yoshie; Gavioli, Riccardo; Destro, Federica; Isaksson Vogel, Rachel; Peng, Shiwen; Roden, Richard B S; Bazzaro, Martina

    2011-01-01

    Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate, and for specific signaling pathways, notably HPV E6-targeted degradation of p53 and PDZ proteins. Natural compounds with antioxidant properties including flavonoids and triterpenoids hold promise as anticancer agents by interfering with ubiquitin-dependent protein degradation. An increasing body of evidence indicates that their ?-? unsaturated carbonyl system is the molecular determinant for inhibition of ubiquitin-mediated protein degradation up-stream of the catalytic sites of the 20S proteasome. Herein we report the identification and characterization of a new class of chalcone-based, potent and cell permeable chemical inhibitors of ubiquitin-dependent protein degradation, and a lead compound RAMB1. RAMB1 inhibits ubiquitin-dependent protein degradation without compromising the catalytic activities of the 20S proteasome, a mechanism distinct from that of Bortezomib. Treatment of cervical cancer cells with RAMB1 triggers unfolded protein responses, including aggresome formation and Hsp90 stabilization, and increases p53 steady state levels. RAMB1 treatment results in activation of lysosomal-dependent degradation pathways as a mechanism to compensate for increasing levels of poly-ubiquitin enriched toxic aggregates. Importantly, RAMB1 synergistically triggers cell death of cervical cancer cells when combined with the lysosome inhibitor Chloroquine. PMID:21909374

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

    PubMed

    Snchez-Snchez, L; Escobar, M L; Sandoval-Ramrez, J; Lpez-Muoz, H; Fernndez-Herrera, M A; Hernndez-Vzquez, J M V; Hilario-Martnez, 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

  17. 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.

  18. 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.

  19. Sorting and identification of side population cells in the human cervical cancer cell line HeLa

    PubMed Central

    2014-01-01

    Background Several reports have revealed that cancer stem cells (CSCs) exist in many types of solid tumors. Some studies have demonstrated that side population (SP) cells isolated from diverse cancer lines harbor cancer stem-like properties, but there are few reports examining the characteristic of SP cells in human cervical cancer. The aim of this study is 1) to find out a feasible way to detect the tumor stem-like cells in cervical cancer, and 2) to analyze the properties of the SP cells being sorted. Methods Isolated SP and non-SP cells from human cervical cancer cell line Hela by Hoechst 33342 dying method and flow cytometry analysis. Observing morphology of SP and non-SP cells. The expression of various biomarkers putatively related to cancer stem cells were investigated by immucytochemistry of SP and non-SP cells. We also analyzed cell cycle and cell apoptosis for sorted cells. The oncogenicity of the SP and non-SP cells were analyzed by tumor formation in nonobesediabeti- c/severe combined immune- deficient (NOD/SCID) mice. The drug-resistant and radiation-resistant index between SP, non-SP and Hela cells was estimated by MTS assay. Results The fraction of SP cells in Hela was approximately 1.07??0.32%. SP cells were smaller and rounder in shape than non-SP cells, and mostly showed colony-like growth. Immunocytochemistry showed that stem cell makers (Oct3/4, CD133, BCRP) were highly expressed in SP cells. Moreover, the number of apoptotic cells among non-SP cells (17.6??3.7%) was significantly higher compared with that among SP cells (4.4??1.2%). The HE staining of in vivo grown tumors result from SP cells showed more poor differentiation, though no significant differences were shown between SP and non-SP cells in NOD/SCID mice tumorigenicity. Furthermore, SP cells demonstrated a higher degree of drug resistance against trichostatin A (TSA) compared with that of non-SP and Hela cells. SP cells were also found to be more resistant against radiotherapy. Conclusions SP cells possess some characteristics of CSCs, namely high proliferation ability, chemoresistance and radioresistance, which may be helpful to elucidate novel targets for effective clinical treatments of cervical cancer in the future. PMID:24418020

  20. Ginsenoside?Rg5 induces apoptosis and DNA damage in human cervical cancer cells.

    PubMed

    Liang, Li-Dan; He, Tao; Du, Ting-Wei; Fan, Yong-Gang; Chen, Dian-Sen; Wang, Yan

    2015-02-01

    Panax ginseng is traditionally used as a remedy for cancer, inflammation, stress and aging, and ginsenoside?Rg5 is a major bioactive constituent of steamed ginseng. The present study aimed to evaluate whether ginsenoside?Rg5 had any marked cytotoxic, apoptotic or DNA?damaging effects in human cervical cancer cells. Five human cervical cancer cell lines (HeLa, MS751, C33A, Me180 and HT?3) were used to investigate the cytotoxicity of ginsenoside?Rg5 using a 3?(4,5?dimethylthiazol?2?yl)?2,5?diphenyltetrazolium bromide assay. Additionally, the effects of ginsenoside?Rg5 on the apoptosis of HeLa and MS751 cells were detected using DNA ladder assays and flow cytometry. DNA damage was assessed in the HeLa and MS751 cells using alkaline comet assays and by detection of ?H2AX focus formation. The HeLa and MS751 cells were significantly more sensitive to ginsenoside?Rg5 treatment compared with the C?33A, HT?3 and Me180 cells. As expected, ginsenoside?Rg5 induced significant concentration? and time?dependent increases in apoptosis. In addition, ginsenoside?Rg5 induced significant concentration?dependent increases in the level of DNA damage compared with the negative control. Consistent with the comet assay data, the percentage of ?H2AX?positive HeLa and MS751 cells also revealed that ginsenoside?Rg5 caused DNA double?strands to break in a concentration?dependent manner. In conclusion, ginsenoside?Rg5 had marked genotoxic effects in the HeLa and MS751 cells and, thus, demonstrates potential as a genotoxic or cytotoxic drug for the treatment of cervical cancer. PMID:25355274

  1. Ginsenoside-Rg5 induces apoptosis and DNA damage in human cervical cancer cells

    PubMed Central

    LIANG, LI-DAN; HE, TAO; DU, TING-WEI; FAN, YONG-GANG; CHEN, DIAN-SEN; WANG, YAN

    2015-01-01

    Panax ginseng is traditionally used as a remedy for cancer, inflammation, stress and aging, and ginsenoside-Rg5 is a major bioactive constituent of steamed ginseng. The present study aimed to evaluate whether ginsenoside-Rg5 had any marked cytotoxic, apoptotic or DNA-damaging effects in human cervical cancer cells. Five human cervical cancer cell lines (HeLa, MS751, C33A, Me180 and HT-3) were used to investigate the cytotoxicity of ginsenoside-Rg5 using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Additionally, the effects of ginsenoside-Rg5 on the apoptosis of HeLa and MS751 cells were detected using DNA ladder assays and flow cytometry. DNA damage was assessed in the HeLa and MS751 cells using alkaline comet assays and by detection of ?H2AX focus formation. The HeLa and MS751 cells were significantly more sensitive to ginsenoside-Rg5 treatment compared with the C-33A, HT-3 and Me180 cells. As expected, ginsenoside-Rg5 induced significant concentration- and time-dependent increases in apoptosis. In addition, ginsenoside-Rg5 induced significant concentration-dependent increases in the level of DNA damage compared with the negative control. Consistent with the comet assay data, the percentage of ?H2AX-positive HeLa and MS751 cells also revealed that ginsenoside-Rg5 caused DNA double-strands to break in a concentration-dependent manner. In conclusion, ginsenoside-Rg5 had marked genotoxic effects in the HeLa and MS751 cells and, thus, demonstrates potential as a genotoxic or cytotoxic drug for the treatment of cervical cancer. PMID:25355274

  2. The infiltration and functional regulation of eosinophils induced by TSLP promote the proliferation of cervical cancer cell.

    PubMed

    Xie, Feng; Liu, Li-Bing; Shang, Wen-Qing; Chang, Kai-Kai; Meng, Yu-Han; Mei, Jie; Yu, Jia-Jun; Li, Da-Jin; Li, Ming-Qing

    2015-08-10

    Cervical cancer is often associated with eosinophil (EOS) infiltration, but the source and the role of EOS are still largely unknown. Our previous work has established that thymic stromal lymphopoietin (TSLP) can stimulate the growth of cervical cancer cell in an autocrine manner. Here, we report that EOS infiltration of the lesion site increased gradually with the progression of cervical cancer. The increase in TSLP secretion in HeLa and SiHa cells induced by hypoxia led to a high level of chemokine CCL17 production by HeLa and SiHa cells, and recruited more EOS to the cancer lesion. In addition, TSLP derived from HeLa and SiHa cells promoted proliferation, up-regulated the levels of anti-inflammatory cytokines (IL-10, IL-4, IL-5 and IL-13), and decreased the expression of CD80 and CD86 of EOS. Such educated EOS significantly promoted proliferation and restricted the apoptosis of cervical cancer cells, which was associated with the up-regulation of Ki-67, PCNA and Bcl-2, and the down-regulation of Fas and FasL in HeLa and SiHa cells. These results suggest that a high level of TSLP in cancer lesions mediated by hypoxia is an important regulator of the progression of cervical cancer by recruiting and licensing tumor-associated EOS to promote the growth of the cervical cancer cell itself. This provides a scientific basis on which potential therapeutic strategies could be targeted to cervical cancer, especially for patients with massive infiltrations of EOS. PMID:25979231

  3. 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.

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

    PubMed

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

    2015-12-01

    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 <200nm. 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-?) 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-?) 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?g/ml while it was 1.08, 1.56, and 2.35?g/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. PMID:26608536

  5. 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 inhibited with the levels of p53 remaining the same. The two plant extracts do induce cell death, in a p53 independent manner. PMID:24993114

  6. Huaier aqueous extract inhibits cervical cancer cell proliferation via JNK/p38 pathway.

    PubMed

    Yan, Li; Liu, Xiaolin; Yin, Aijun; Wei, Yuyan; Yang, Qifeng; Kong, Beihua

    2015-09-01

    Although the anticancer effects of Huaier extract have been widely investigated, including anti-proliferate, anti-angiogenic and anti-metastatic activities, the mechanisms are not well understood. This study aimed to elucidate the inhibitory effect of Huaier extract on tumor growth in cervical cancer cells and its molecular mechanisms. Cell viability and motility were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony assays, migration, and invasive assays, respectively. The distribution of the cell cycle was analyzed by ?ow cytometry. Huaier inhibited cell viability of SiHa and C33A cells in a time- and dose-dependent manner; cell migration and invasiveness were also suppressed; Huaier was able to cause G2/M cell cycle arrest in C33A cells. The western blot results confirmed Huaier dose-dependently increased expression of phosphorylated c-Jun N-terminal kinase (JNK), p-38 and downregulated the expression of phosphorylated extracellular signal-regulated kinase (ERK) in a time- and dose-dependently manner. Invivo experiments showed that Huaier significantly suppressed the tumor volume of SiHa cell xenografts. These data suggest that Huaier may inhibit tumor proliferation in cervical cancer via the JNK/p38 signaling pathway. PMID:26201539

  7. Biomarkers in Cervical Cancer Screening

    PubMed Central

    Wentzensen, Nicolas; von Knebel Doeberitz, Magnus

    2007-01-01

    In industrialized countries, population wide cytological screening programs using the Pap test have led to a substantial reduction of the incidence of cervical cancer. Despite this evident success, screening programs that rely on Pap-stained cytological samples have several limitations. First, a number of equivocal or mildly abnormal test results require costly work up by either repeated retesting or direct colposcopy and biopsy, since a certain percentage of high grade lesions that require immediate treatment hide among these unclear test results. This work up of mildly abnormal or equivocal cytological tests consumes a large amount of the overall costs spent for cervical cancer screening. Improved triage of these samples might substantially reduce the costs. Cervical cancer is induced by persistent infections with oncogenic human papilloma viruses (HPV). While HPV infection is an indispensable factor, it is not sufficient to cause cancer. The majority of acute HPV infections induce low grade precursor lesions that are cleared spontaneously after several months in more than 90% of cases, and less than 10% eventually progress to high grade lesions or invasive cancer. Progression is characterized by the deregulated expression of the viral oncogenes E6 and E7 in infected basal and parabasal cells. Novel biomarkers that allow monitoring these essential molecular events in histological or cytological specimens are likely to improve the detection of lesions that have a high risk of progression in both primary screening and triage settings. In this review, we will discuss potential biomarkers for cervical cancer screening with a focus on the level of clinical evidence that supports their application as novel markers in refined cervical cancer screening programs. PMID:17627065

  8. Artemisinin derivative artesunate induces radiosensitivity in cervical cancer cells in vitro and in vivo

    PubMed Central

    2014-01-01

    Objective Cervical cancer is the third most common type of cancer in women worldwide and radiotherapy remains its predominant therapeutic treatment. Artesunate (ART), a derivative of artemisinin, has shown radiosensitization effect in previous studies. However, such effects of ART have not yet been revealed for cervical cancer cells. Methods The effect of ART on radiosensitivity of human cervical cancer cell lines HeLa and SiHa was assessed using the clonogenic assay. Cell cycle progression and apoptosis alterations were analyzed by flow cytometry. For in vivo study, HeLa or SiHa cells were inoculated into nude mice to establish tumors. Tissues from xenografts were obtained to detect the changes of microvessel density, apoptosis and cell cycle distribution. Microarray was used to analyze differentially expressed genes. Results ART increased the radiosensitivity of HeLa cells (SER =?1.43, P cells. Apoptosis and the G2-M phase transition induced by X-ray irradiation (IR) were enhanced by ART via increased Cyclin B1 expression in HeLa cells. Tumor growth of xenografts from HeLa but not SiHa cells was significantly inhibited by irradiation combined with ART (tumor volume reduction of 72.34% in IR?+?ART group vs. 41.22% in IR group in HeLa cells and 48.79% in IR?+?ART group vs. 44.03% in IR alone group in SiHa cells). Compared with the irradiated group, cell apoptosis was increased and the G2/M cell cycle arrest was enhanced in the group receiving irradiation combined with ART. Furthermore, compared with radiation alone, X-ray irradiation plus ART affected the expression of 203 genes that function in multiple pathways including RNA transport, the spliceosome, RNA degradation and p53 signaling. Conclusion ART potently abrogates the G2 checkpoint control in HeLa cells. ART can induce radiosensitivity of HeLa cells in vitro and in vivo. PMID:24666614

  9. 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.

  10. RIPK3 expression in cervical cancer cells is required for PolyIC-induced necroptosis, IL-1? release, and efficient paracrine dendritic cell activation

    PubMed Central

    Schmidt, Susanne V.; Seibert, Stefanie; Walch-Rckheim, Barbara; Vicinus, Benjamin; Kamionka, Eva-Maria; Pahne-Zeppenfeld, Jennifer; Solomayer, Erich-Franz; Kim, Yoo-Jin; Bohle, Rainer M.; Smola, Sigrun

    2015-01-01

    Previous studies have shown that cervical cancer cells only release low levels of pro-inflammatory cytokines owing to infection with human papillomaviruses. This results in low immunogenicity of the cancer cells. The viral dsRNA analog PolyIC has been suggested as a promising adjuvant for cervical cancer immunotherapy. However, little is known about the molecular requirements resulting in successful immune activation. Here, we demonstrate that stimulation of cervical cancer cells with PolyIC induced necroptotic cell death, which was strictly dependent on the expression of the receptor-interacting protein kinase RIPK3. Necroptotic cancer cells released interleukin-1? (IL-1?), which was required for powerful activation of dendritic cells (DC) to produce IL-12, a cytokine critical for anti-tumor responses. Again both, IL-1? release and DC activation, were strictly dependent on RIPK3 expression in the tumor cells. Of note, our in situ analyses revealed heterogeneous RIPK3 expression patterns in cervical squamous cell carcinomas and adenocarcinomas. In summary, our study identified a novel RIPK3-dependent mechanism that explains how PolyIC-treatment of cervical cancer cells leads to potent DC activation. Our findings suggest that the RIPK3 expression status in cervical cancer cells might critically influence the outcome of PolyIC-based immunotherapeutic approaches and should therefore be assessed prior to immunotherapy. PMID:25888634

  11. Screening for Cervical Cancer

    MedlinePLUS

    ... causes cervical cancer. To learn more about these tests and what happens during them, visit the Web sites listed at the end of this fact ... evidence about the benefits and harms of the test. The grades are explained in the box at ... Web site to read the full recommendation statement on ...

  12. 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 ...

  13. Cervical Cancer HPV Vaccine Use

    Cancer.gov

    Skip to Main Content Search International Cancer Screening Network Sponsored by the National Cancer Institute Home | About ICSN | Collaborative Projects | Meetings | Cancer Sites | Publications | Contact Us Cervical Cancer: Mortality Rates | Organization

  14. Apoptotic activities of thymoquinone, an active ingredient of black seed (Nigella sativa), in cervical cancer cell lines.

    PubMed

    Ichwan, Solachuddin J A; Al-Ani, Imad M; Bilal, Hakim G; Suriyah, Wastuti H; Taher, Muhammad; Ikeda, Masa A

    2014-10-31

    Thymoquinone (TQ) is the main constituent of black seed (Nigella sativa, spp) essential oil which shows promising in vitro and in vivo anti-neoplastic activities in different tumor cell lines. However, to date there are only a few reports regarding the apoptotic effects of TQ on cervical cancer cells. Here, we report that TQ stimulated distinct apoptotic pathways in two human cervical cell lines, Siha and C33A. TQ markedly induced apoptosis as demonstrated by cell cycle analysis in both cell lines. Moreover, quantitative PCR revealed that TQ induced apoptosis in Siha cells through p53-dependent pathway as shown by elevated level of p53-mediated apoptosis target genes, whereas apoptosis in C33A cells was mainly associated with the activation of caspase-3. These results support previous findings on TQ as a potential therapeutic agent for human cervical cancer. PMID:25241984

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

    SciTech Connect

    Zhao, Gang; Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin ; 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.

  17. 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

  18. Cervical Cancer Screening | Cancer Trends Progress Report

    Cancer.gov

    Screening methods used to find cervical changes that may lead to cervical cancer include the Pap test and human papillomavirus (HPV) testing. Such screening tests may find cancers early, when they are most treatable. Women who have never been screened or who have not been screened in the past 5 years face a greater risk of developing invasive cervical cancer.

  19. 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.

  20. [Primary cervical cancer screening].

    PubMed

    Vargas-Hernndez, Vctor Manuel; Vargas-Aguilar, Vctor Manuel; Tovar-Rodrguez, Jos Mara

    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. PMID:26162490

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

    PubMed Central

    Servn-Gonzlez, Luis Steven; Granados-Lpez, Angelica Judith; Lpez, Jess Adrin

    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

  2. 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.

  3. 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. PMID:25854386

  4. Regulation of p53 expression and apoptosis by vault RNA2-1-5p in cervical cancer cells

    PubMed Central

    Kong, Lu; Hao, Qi; Wang, Ying; Zhou, Ping; Zou, Binbin; Zhang, Yu-xiang

    2015-01-01

    nc886 or VRNA2-1 has recently been identified as a noncoding RNA instead of a vault RNA or a pre-microRNA. Several studies have reported that pre-miR-886 plays a tumor-suppressive role in a wide range of cancer cells through its activity as a cellular protein kinase RNA-activated (PKR) ligand and repressor. However, by sequencing stem-PCR products, we found that a microRNA originating from this precursor, vault RNA2-1-5p (VTRNA2-1-5p), occurs in cervical cancer cells. The expression levels of the predicted targets of VTRNA2-1-5p are negatively correlated with VTRNA2-1-5p levels by quantitative reversion transcription PCR (qRT-PCR). Previous results have shown that VTRNA2-1-5p is overexpressed in human cervical squamous cell carcinomas (CSCCs) compared with adjacent healthy tissues. Inhibition of VTRNA2-1-5p increases Bax protein expression and apoptotic cell death in cervical cancer cells. Our findings suggest that VTRNA2-1-5p has oncogenic activity related to the progression of cervical cancer. Here, we report that VTRNA2-1-5p directly targeted p53 expression and functioned as an oncomir in cervical cancer. VTRNA2-1-5p inhibition decreased cervical cancer cell invasion, proliferation, and tumorigenicity while increasing apoptosis and p53 expression. Interestingly, VTRNA2-1-5p inhibition also increased cisplatin-induced apoptosis of HeLa and SiHa cells. In human clinical cervical cancer specimens, low p53 expression and high VTRNA2-1-5p expression were positively associated. In addition, VTRNA2-1-5p was found to directly target the 5′ and 3′ untranslated regions (UTRs) of p53. We propose that VTRNA2-1-5p is a direct regulator of p53 and suggest that it plays an essential role in the apoptosis and proliferation of cervical cancer cells. PMID:26318295

  5. 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

  6. Cervical Cancer Prevention and Screening: Financial Issues

    MedlinePLUS

    ... pre-cancers are treated Next Topic Additional resources Cervical cancer prevention and screening: Financial issues Financial issues can ... to tell you up front. National Breast and Cervical Cancer Early Detection Program All states are making cervical ...

  7. Curcumin-mediated decrease in the expression of nucleolar organizer regions in cervical cancer (HeLa) cells.

    PubMed

    Lewinska, Anna; Adamczyk, Jagoda; Pajak, Justyna; Stoklosa, Sylwia; Kubis, Barbara; Pastuszek, Paulina; Slota, Ewa; Wnuk, Maciej

    2014-09-01

    Curcumin, the major yellow-orange pigment of turmeric derived from the rhizome of Curcuma longa, is a highly pleiotropic molecule with the potential to modulate inflammation, oxidative stress, cell survival, cell secretion, homeostasis and proliferation. Curcumin, at relatively high concentrations, was repeatedly reported to be a potent inducer of apoptosis in cancer cells and thus considered a promising anticancer agent. In the present paper, the effects of low concentrations of curcumin on human cervical cancer (HeLa) cells were studied. We found curcumin-mediated decrease in the cell number and viability, and increase in apoptotic events and superoxide level. In contrast to previously shown curcumin cytotoxicity toward different cervical cancer lines, we observed toxic effects when even as low as 1 ?M concentration of curcumin was used. Curcumin was not genotoxic to HeLa cells. Because argyrophilic nucleolar protein (AgNOR protein) expression is elevated in malignant cells compared to normal cells reflecting the rapidity of cancer cell proliferation, we evaluated curcumin-associated changes in size (area) and number of silver deposits. We showed curcumin-induced decrease in AgNOR protein pools, which may be mediated by global DNA hypermethylation observed after low concentration curcumin treatment. In summary, we have shown for the first time that curcumin at low micromolar range may be effective against HeLa cells, which may have implications for curcumin-based treatment of cervical cancer in humans. PMID:25308441

  8. Gene transfection efficacy assessment of human cervical cancer cells using dual-mode fluorescence microendoscopy

    PubMed Central

    Cha, Jaepyeong; Zhang, Jing; Gurbani, Saumya; Cheon, Gyeong Woo; Li, Min; Kang, Jin U.

    2012-01-01

    We report a novel approach to quantitatively assess gene transfection efficacy using dual-modality microendoscopy that can simultaneously monitor both laser scanning reflectance and fluorescence imaging. The system uses a 500-?m-diameter coherent fiber bundle and permits 3.5-?m lateral resolution. Both reflectance and fluorescence images obtained from two silicon avalanche photodetectors are displaying at 1 Hz and processed automatically to calculate gene transfection efficiency (the ratio of fluorescent cells among the total cells). To validate the system performance we examined the expression of cyan fluorescent protein using human cervical cancer cells (HeLa) in four commercially available reagents. The result was compared with that using a high-resolution bench-top microscope. PMID:23304654

  9. Radiation enhancing effects of sanazole and gemcitabine in hypoxic breast and cervical cancer cells in vitro

    PubMed Central

    Wu, Rong; Xiao, Yu-Ping; Xin, Yan; Chi, Feng; Xing, Rui; Xue, Ming; Wang, Nai-Qian

    2015-01-01

    Aim of the study Sanazole and gemcitabine have been proven clinically as hypoxic cell radiosensitisers. This study was conducted to determine the radiation enhancing effects of sanazole and gemcitabine when administered together at relevant concentrations into hypoxic human MCF-7 and HeLa cells. Material and methods A 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to evaluate the number of surviving cells. Cell cycle was determined by flow cytometry. Cell surviving fractions were determined by the standard in vitro colony formation assay. Results The cell colony formation assay indicated that the radiosensitivity of hypoxic MCF-7 and HeLa cells was enhanced by sanazole or gemcitabine. The combination of the two drugs displayed significant radiation enhancing effects at the irradiation doses of 6, 8, and 10 Gy in both cell lines, which were arrested in the S phase. Conclusions This study indicated that the co-administration of the two drugs may result in a beneficial gain in radio-therapy for hypoxic breast cancer and cervical cancer. PMID:26557765

  10. 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 ?g/ml, 0.001-0.01 ?g/ml and 0.01- 0.1 ?g/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 ?g/ 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

  11. 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.

  12. Proteasomal inhibition sensitizes cervical cancer cells to mitomycin C-induced bystander effect: the role of tumor microenvironment

    PubMed Central

    Singh, S V; Ajay, A K; Mohammad, N; Malvi, P; Chaube, B; Meena, A S; Bhat, M K

    2015-01-01

    Inaccessibility of drugs to poorly vascularized strata of tumor is one of the limiting factors in cancer therapy. With the advent of bystander effect (BE), it is possible to perpetuate the cellular damage from drug-exposed cells to the unexposed ones. However, the role of infiltrating tumor-associated macrophages (TAMs), an integral part of the tumor microenvironment, in further intensifying BE remains obscure. In the present study, we evaluated the effect of mitomycin C (MMC), a chemotherapeutic drug, to induce BE in cervical carcinoma. By using cervical cancer cells and differentiated macrophages, we demonstrate that MMC induces the expression of FasL via upregulation of PPAR? in both cell types (effector cells) in vitro, but it failed to induce bystander killing in cervical cancer cells. This effect was primarily owing to the proteasomal degradation of death receptors in the cervical cancer cells. Pre-treatment of cervical cancer cells with MG132, a proteasomal inhibitor, facilitates MMC-mediated bystander killing in co-culture and condition medium transfer experiments. In NOD/SCID mice bearing xenografted HeLa tumors administered with the combination of MMC and MG132, tumor progression was significantly reduced in comparison with those treated with either agent alone. FasL expression was increased in TAMs, and the enhanced level of Fas was observed in these tumor sections, thereby causing increased apoptosis. These findings suggest that restoration of death receptor-mediated apoptotic pathway in tumor cells with concomitant activation of TAMs could effectively restrict tumor growth. PMID:26492368

  13. Proteasomal inhibition sensitizes cervical cancer cells to mitomycin C-induced bystander effect: the role of tumor microenvironment.

    PubMed

    Singh, S V; Ajay, A K; Mohammad, N; Malvi, P; Chaube, B; Meena, A S; Bhat, M K

    2015-01-01

    Inaccessibility of drugs to poorly vascularized strata of tumor is one of the limiting factors in cancer therapy. With the advent of bystander effect (BE), it is possible to perpetuate the cellular damage from drug-exposed cells to the unexposed ones. However, the role of infiltrating tumor-associated macrophages (TAMs), an integral part of the tumor microenvironment, in further intensifying BE remains obscure. In the present study, we evaluated the effect of mitomycin C (MMC), a chemotherapeutic drug, to induce BE in cervical carcinoma. By using cervical cancer cells and differentiated macrophages, we demonstrate that MMC induces the expression of FasL via upregulation of PPAR? in both cell types (effector cells) in vitro, but it failed to induce bystander killing in cervical cancer cells. This effect was primarily owing to the proteasomal degradation of death receptors in the cervical cancer cells. Pre-treatment of cervical cancer cells with MG132, a proteasomal inhibitor, facilitates MMC-mediated bystander killing in co-culture and condition medium transfer experiments. In NOD/SCID mice bearing xenografted HeLa tumors administered with the combination of MMC and MG132, tumor progression was significantly reduced in comparison with those treated with either agent alone. FasL expression was increased in TAMs, and the enhanced level of Fas was observed in these tumor sections, thereby causing increased apoptosis. These findings suggest that restoration of death receptor-mediated apoptotic pathway in tumor cells with concomitant activation of TAMs could effectively restrict tumor growth. PMID:26492368

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

    PubMed

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

    2014-08-01

    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. PMID:25044113

  15. Blocking eIF5A Modification in Cervical Cancer Cells Alters the Expression of Cancer-Related Genes and Suppresses Cell Proliferation

    PubMed Central

    Mmin, Elisabeth; Hoque, Mainul; Jain, Mohit R.; Heller, Debra S.; Li, Hong; Cracchiolo, Bernadette; Hanauske-Abel, Hartmut M.; Peery, Tsafi; Mathews, Michael B.

    2016-01-01

    Cancer etiology is influenced by alterations in protein synthesis that are not fully understood. In this study, we took a novel approach to investigate the role of the eukaryotic translation initiation factor eIF5A in human cervical cancers, where it is widely overexpressed. eIF5A contains the distinctive amino acid hypusine, which is formed by a posttranslational modification event requiring deoxyhypusine hydroxylase (DOHH), an enzyme that can be inhibited by the drugs ciclopirox and deferiprone. We found that proliferation of cervical cancer cells can be blocked by DOHH inhibition with either of these pharmacologic agents, as well as by RNA interferencemediated silencing of eIF5A, DOHH, or another enzyme in the hypusine pathway. Proteomic and RNA analyses in HeLa cervical cancer cells identified two groups of proteins in addition to eIF5A that were coordinately affected by ciclopirox and deferiprone. Group 1 proteins (Hsp27, NM23, and DJ-1) were downregulated at the translational level, whereas group 2 proteins (TrpRS and PRDX2) were upregulated at the mRNA level. Further investigations confirmed that eIF5A and DOHH are required for Hsp27 expression in cervical cancer cells and for regulation of its key target I?B and hence NF-?B. Our results argue that mature eIF5A controls a translational network of cancer-driving genes, termed the eIF5A regulon, at the levels of mRNA abundance and translation. In coordinating cell proliferation, the eIF5A regulon can be modulated by drugs such as ciclopirox or deferiprone, which might be repositioned to control cancer cell growth. PMID:24220243

  16. Mixed lineage kinase domain-like protein is a prognostic biomarker for cervical squamous cell cancer

    PubMed Central

    Ruan, Jiaying; Mei, Ling; Zhu, Qian; Shi, Gang; Wang, He

    2015-01-01

    Background: The mixed lineage kinase domain-like protein (MLKL) has recently been identified as a key RIP3 (receptor interacting protein 3) downstream component of tumor necrosis factor (TNF)-induced necroptosis. Objective: To evaluate the expression and clinical significance of MLKL in cervical squamous cell carcinoma.Methods: The expression of MLKL in 54 cervical squamous carcinoma samples was detected by immuneohistochemical method. Chi-square, correlation analysis and kaplan-Meier method were used to analyze the data. Results: The MLKL expression in cervical squamous cell carcinoma was higher than that in normal cervical tissues (P = 0.004). The MLKL expression was negatively correlated with histological grade, lymphatic metastasis (P<0.05). Survival analysis showed the low expression of MLKL indicated poor prognosis. Conclusion: MLKL was a prognostic biomarker for cervical squamous cell carcinoma. PMID:26823841

  17. HPV-type-specific response of cervical cancer cells to cisplatin after silencing replication licensing factor MCM4.

    PubMed

    Das, Mitali; Prasad, Shyam Babu; Yadav, Suresh Singh; Modi, Arusha; Singh, Sunita; Pradhan, Satyajit; Narayan, Gopeshwar

    2015-12-01

    Minichoromosome maintenance (MCM) proteins play key role in cell cycle progression by licensing DNA replication only once per cell cycle. These proteins are found to be overexpressed in cervical cancer cells. In this study, we depleted MCM4, one of the MCM 2-7 complex components by RNA interference (RNAi) in four cervical cancer cell lines. The four cell lines were selected on the basis of their human papillomavirus (HPV) infection: HPV16-positive SiHa, HPV18-positive ME-180, HPV16- and HPV18-positive CaSki, and HPV-negative C-33A. The MCM4-deficient cells irrespective of their HPV status grow for several generations and maintain regular cell cycle. We did not find any evidence of augmented response to a short-term (48 h) cisplatin treatment in these MCM4-deficient cells. However, MCM4-/HPV16+ SiHa cells cannot withstand a prolonged treatment (up to 5 days) of even a sublethal dosage of cisplatin. They show increased chromosomal instability compared to their control counterparts. On the other hand, MCM4-deficient CaSki cells (both HPV16+ and 18+) remain resistant to a prolonged exposure to cisplatin. Our study indicates that cervical cancer cells may be using excess MCMs as a backup for replicative stress; however, its regulatory mechanism is dependent on the HPV status of the cells. PMID:26188903

  18. 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. PMID:26574780

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

    PubMed Central

    SORIANO-HERNANDEZ, ALEJANDRO D.; MADRIGAL-PREZ, DANIELA; GALVAN-SALAZAR, HECTOR R.; MARTINEZ-FIERRO, MARGARITA L.; VALDEZ-VELAZQUEZ, LAURA L.; ESPINOZA-GMEZ, 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 (1040% of cell death corresponding to 100 M) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (5090% of cell death corresponding to 100 M). 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

  20. [Preventing cervical cancer].

    PubMed

    Simon, P; Nol, 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. PMID:26591310

  1. Expression/localization patterns of sirtuins (SIRT1, SIRT2, and SIRT7) during progression of cervical cancer and effects of sirtuin inhibitors on growth of cervical cancer cells.

    PubMed

    Singh, Sapna; Kumar, P Uday; Thakur, Suresh; Kiran, Shashi; Sen, Bijoya; Sharma, Shreya; Rao, Vishnu Vardhan; Poongothai, A R; Ramakrishna, Gayatri

    2015-08-01

    Sirtuins belong to the family of class III histone deacetylases; its role in neoplasia is controversial as both tumor-suppressive and promoting functions have been reported. There are very few reports available, where expressions of sirtuin isoforms are comprehensively analyzed during neoplasia. Therefore, in the present study, the expression of SIRT1, SIRT2, and SIRT7 during different stages of cervical cancer progression was analyzed. The normal cervical epithelium showed feeble expression of sirtuin isoforms, SIRT1, SIRT2, and SIRT7. A significant increase in SIRT1 expression was noted in the cytoplasm as well as in the nucleus of proliferative layers of cervical epithelium in squamous intraepithelial lesions (SIL); however, in the squamous cell carcinomas (SCC), a heterogeneous pattern of SIRT1 expression varying from low to high was noted. A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal?cancer. Cervical cancer cell lines, HeLa and SiHa, showed higher levels of SIRT1 and SIRT2 in comparison to the immortalized cell counterpart, HaCaT. Specific inhibitors of SIRT1 (Ex527) and SIRT2 (AGK2) impaired the growth of the cervical cancer cells, SiHa, but not of the HaCaT cells. SIRT1 inhibition caused cell death, while SIRT2 inhibition resulted in cell cycle arrest. In conclusion, we report the overexpression of SIRT2 and SIRT7 proteins in cervical cancer and suggest probable application of sirtuin inhibitors as therapeutic targets. Further, a specific increase in the levels of SIRT1 in intraepithelial lesion makes it a promising candidate for identification of preneoplastic changes. PMID:25794641

  2. Tumor-Suppressor Gene NBPF1 Inhibits Invasion and PI3K/mTOR Signaling in Cervical Cancer Cells.

    PubMed

    Qin, Yun; Tang, Xicai; Liu, Mingxing

    2016-01-01

    The purpose of this study was to assess the effects of NBPF1 expression on cervical cancer cell invasion and apoptosis and to illustrate its potential mechanism. Human cervical cancer HeLa cells were transfected with the constructed siNBPF1 or pcDNA3.1-NBPF1 vectors. Effects of NBPF1 expression on cell invasion ability and cell apoptosis were analyzed using the Matrigel method and an Annexin V-FITC cell apoptosis kit, respectively. In addition, cell apoptosis-related proteins involved with the PI3K/mTOR signaling pathway were analyzed using Western blot. Remediation experiments were conducted to verify the effects of NBPF1 expression on cell invasion and apoptosis. Compared to the control, mRNA and protein expressions of NBPF1 were significantly decreased when cells were transfected with siNBPF1 (p?cells transfected with pcDNA3.1-NBPF1. Overexpression of NBPF1 significantly suppressed HeLa cell invasion but promoted cell apoptosis (p?cervical cancer via affecting cell invasion and apoptosis through regulating PI3K/mTOR signaling pathway. NBPF1 may be a potential therapeutic target for cervical cancer treatment. PMID:26802646

  3. 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; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 ; 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 DN-MAML exhibited loss of phospho-I{kappa}B{alpha}, decreased total I{kappa}B{alpha} and nuclear localization of NF-{kappa}B p65, which suggests that the NF-{kappa}B pathway is hyperactivated. Furthermore, increased level of cleaved Notch1 was detected when DN-MAML was expressed. When DN-MAML-overexpressing cells were treated with GSI, significantly decreased cell viability was observed, indicating that inhibition of Notch signaling using GSI treatment and DN-MAML expression negatively affects cell viability. Taken together, targeting Notch signaling using DN-MAML and GSI treatment may present a novel method to control cell viability in cervical cancer cells.

  4. Restoration of fragile histidine triad (FHIT) expression induces apoptosis and suppresses tumorigenicity in lung and cervical cancer cell lines.

    PubMed

    Roz, Luca; Gramegna, Marcella; Ishii, Hideshi; Croce, Carlo M; Sozzi, Gabriella

    2002-03-19

    Loss of expression of the Fhit protein is often associated with the development of many human epithelial cancers, including lung and cervical carcinomas. Restoration of Fhit expression in cell lines derived from these tumors has however yielded conflicting results, prompting the need for careful evaluation of the oncosuppressive potential of FHIT. In the present study, we have investigated the effect of Fhit reintroduction in seven lung cancer and three cervical cancer cell lines. To achieve efficient gene transfer and high levels of transgene expression, we have used an adenoviral vector to transduce the FHIT gene. The induction of apoptosis was evaluated by using the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay and propidium iodide staining. Activation of caspases was detected by using Western blot analysis, and tumorigenic potential of transduced cells in the nude mouse was also assessed. Restoration of Fhit expression induced apoptosis in all Fhit-negative cell lines, with Calu-1, H460, and A549 being the most susceptible among the lung cancer cell lines and SiHa cells among cervical carcinomas. Activation of caspase-8 was always associated with Fhit-mediated apoptosis, and in vivo tumorigenicity was either abolished by FHIT gene transfer (in H460 and SK-Mes cells) or strongly suppressed (in A549 and SiHa cells). Our data demonstrate oncosuppressive properties and strong proapoptotic activity of the Fhit protein in lung and cervical cancer cell lines and strengthens the hypothesis of its possible use as a therapeutic tool. PMID:11891319

  5. Primary peripheral T-cell lymphoma of the vagina incidentally found at cervical cancer screening.

    PubMed

    Isobe, Rei; Mituishi, Toshimi; Omote, Mayuko; Mori, Yuichi; Ida, Koichi; Oguchi, Osamu; Nakai, Ikuko; Oguchi, Masahiko

    2016-01-01

    A 50-year-old woman was referred to our hospital because a mass lesion had been palpable through the vaginal wall during a cervical cancer screening examination. A contrast-enhanced computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed marked thickening of the vaginal wall, constituting a mass 96 mm in diameter. Abnormal FDG uptake was observed in the vaginal mass, but no other lesions were detected by positron emission tomography (PET/CT). A transvaginal biopsy from the tumor revealed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Although endoscopic examinations revealed no signs of infiltration in either the bladder or the rectum, the MRI findings suggested invasion into the adjacent rectal wall. She achieved complete remission after six courses of biweekly THP-COP therapy, to which field radiation (39.6 Gy) was added. PTCL of the vagina is rare and this case therefore merits description in the literature. PMID:26861099

  6. 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

  7. 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 ?M, respectively, compared with 5-FU with values of 4.86 and 12.31 ?M, 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

  8. 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

  9. Gliotoxin Isolated from Marine Fungus Aspergillus sp. Induces Apoptosis of Human Cervical Cancer and Chondrosarcoma Cells

    PubMed Central

    Nguyen, Van-Tinh; Lee, Jung Suck; Qian, Zhong-Ji; Li, Yong-Xin; Kim, Kil-Nam; Heo, Soo-Jin; Jeon, You-Jin; Park, Won Sun; Choi, Il-Whan; Je, Jae-Young; Jung, Won-Kyo

    2013-01-01

    Gliotoxin, a secondary metabolite produced by marine fungus Aspergillus sp., possesses various biological activities including anticancer activity. However, the mechanism underlying gliotoxin-induced cytotoxicity on human cervical cancer (Hela) and human chondrosarcoma (SW1353) cells remains unclear. In this study, we focused on the effect of gliotoxin induction on apoptosis, the activating expressions of caspase family enzymes in the cells. Apoptotic cell levels were measured through DAPI and Annexin V/Propidium Iodide (PI) double staining analysis. The apoptotic protein expression of Bcl-2 and caspase family was detected by Western blot in Hela and SW1353 cells. Our results showed that gliotoxin treatment inhibited cell proliferation and induced significant morphological changes. Gliotoxin induced apoptosis was further confirmed by DNA fragmentation, chromatin condensation and disrupted mitochondrial membrane potential. Gliotoxin-induced activation of caspase-3, caspase-8 and caspase-9, down-regulation of Bcl-2, up-regulation of Bax and cytochromec (cyt c) release showed evidence for the gliotoxin activity on apoptosis. These findings suggest that gliotoxin isolated from marine fungus Aspergillus sp. induced apoptosis in Hela and SW1353 cells via the mitochondrial pathway followed by downstream events leading to apoptotic mode of cell death. PMID:24368570

  10. 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

    2016-03-23

    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. PMID:26798987

  11. 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

  12. Curcumin Nanoformulation for Cervical Cancer Treatment.

    PubMed

    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

  13. Gene expression changes during HPV-mediated carcinogenesis: A comparison between an in vitro cell model and cervical cancer

    PubMed Central

    Wan, Fang; Miao, Xijiang; Quraishi, Iram; Kennedy, Valerie; Creek, Kim E.; Pirisi, Lucia

    2010-01-01

    We used oligonucleotide microarrays to investigate gene expression changes associated with multi-step human papillomavirus type 16 (HPV16)-mediated carcinogenesis in vitro. Gene expression profiles in 4 early passage HPV16-immortalized human keratinocyte (HKc) lines derived from different donors were compared with their corresponding 4 late-passage, differentiation-resistant cell lines, and to 4 pools of normal HKc, each composed of 3 individual HKc strains, on Agilent 22 k human oligonucleotide microarrays. The resulting data were analyzed using a modified T-test coded in R to obtain lists of differentially expressed genes. Gene expression changes identified in this model system were then compared with gene expression changes described in published studies of cervical intraepithelial neoplasia (CIN) and cervical cancer. Common genes in these lists were further studied by cluster analysis. Genes whose expression changed in the same direction as in CIN or cervical cancer (concordant) at late stages of HPV16-mediated transformation in vitro formed one major cluster, while those that changed in the opposite direction (discordant) formed a second major cluster. Further annotation found that many discordant expression changes involved gene products with an extracellular localization. Two novel genes were selected for further study: overexpression of SIX1 and GDF15, observed during in vitro progression in our model system, was confirmed in tissue arrays of cervical cancer. These micro-array-based studies show that our in vitro model system reflects many cellular and molecular alterations characteristic of cervical cancer, and identified SIX1 and GDF15 as 2 novel potential bio-markers of cervical cancer progression. PMID:18398830

  14. First ayurvedic approach towards green drugs: anti cervical cancer-cell properties of Clerodendrum viscosum root extract.

    PubMed

    Sun, Chong; Nirmalananda, Swami; Jenkins, Charles E; Debnath, Shawon; Balambika, Rema; Fata, Jimmie E; Raja, Krishnaswami S

    2013-12-01

    The concept of Ayurvedic expert guided drug discovery and development is defined and put to test systematically for the first time in literature. Western Science has explored only ~5% of the approximately 25,000 species of higher plants for drug leads. The ancient medical science of Ayurveda has however employed a much larger spectrum of plants for clinical treatment. Clerodendrum viscosum (CV), a commonly growing weed in the Indian subcontinent has been employed by S. Nirmalananda (Ayurvedic expert) for the treatment of cervical cancer. Here we isolate and characterize a water extract fraction (Cv-AP) from the root of CV and evaluate its anticervical cancer cell bioactivity. Our results indicate that Cv-AP possesses pro-apoptotic, anti-proliferative, and anti-migratory activity in a dose-dependent fashion against cervical cancer cell lines. In contrast, primary fibroblasts (control healthy cells), when exposed to similar concentrations of this extract, fail to undergo apoptosis and remain relatively unaffected. These findings suggest that Clerodendrum viscosum (CV) is a readily available source of components with potent anti-cancer activity and selective bioactivity against cervical cancer cells. The major component in CV-AP was identified as a glycoprotein via SDS Page and Concanavalin-A binding studies. This study serves to illustrate that systematic collaboration with Ayurveda is a practical and powerful strategy in drug discovery and development. PMID:23387970

  15. 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.

  16. 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?=?0.841.04), 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?=?1.031.43). 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

  17. 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

  18. 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. PMID:25449778

  19. Methanolic extract of Nigella sativa seed inhibits SiHa human cervical cancer cell proliferation through apoptosis.

    PubMed

    Hasan, Tarique N; Shafi, Gowhar; Syed, Naveed A; Alfawaz, Muhammad A; Alsaif, Mohammed A; Munshi, Anjana; Lei, Kai Y; Alshatwi, Ali A

    2013-02-01

    Nigella sativa (NS), also known as black cumin, has long been used in traditional medicine for treating various cancer conditions. In this study, we sought to investigate the potential anti-cancer effects of NS extract using SiHa human cervical cancer cells. NS showed an 88.3% inhibition of proliferation of SiHa human cervical cancer cells at a concentration of 125 microL/mL methanolic extract at 24 h, and an IC50 value 93.2 microL/mL. NS exposure increased the expression of caspase-3, -8 and -9 several-fold. The analysis of apoptosis by Dead End terminal transferase-mediated dUTP-digoxigenin end labeling (TUNEL) assay was used to further confirm that NS induced apoptosis. Thus, NS was concluded to induce apoptosis in SiHa cell through both p53 and caspases activation. NS could potentially be an alternative source of medicine for cervical cancer therapy. PMID:23513732

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

    SciTech Connect

    Liu, Junye; Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an ; 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.

  1. Proteomic Investigation into Betulinic Acid-Induced Apoptosis of Human Cervical Cancer HeLa Cells

    PubMed Central

    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 14-3-3? and 14-3-3?, were down-regulated in response to betulinic acid treatment, which is consistent with the decrease in expression of the target genes 14-3-3? and 14-3-3?. 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. PMID:25148076

  2. 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

  3. 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

  4. Restoration of microRNA?218 increases cellular chemosensitivity to cervical cancer by inhibiting cell?cycle progression.

    PubMed

    Dong, Ruofan; Qiu, Haifeng; Du, Guiqiang; Wang, Yuan; Yu, Jinjin; Mao, Caiping

    2014-12-01

    We previously reported frequent loss of microRNA?218 (miR?218) in human cervical cancer, which was associated with tumor progression and poor prognosis. In this study, we investigated whether restoration of the miR?218 level is a valid strategy for the treatment of cervical cancer. The expression of miR?218 in cervical cancer samples and cell lines was quantified by reverse transcription TaqMan quantitative (RT?q)PCR. Overexpression of miR?218 was achieved by both transient and stable transfection, using a miR?218 mimic and a miR?218?expressing plasmid, respectively. Alterations in cellular proliferation and cell?cycle progression were measured by the MTT assay and flow cytometry analysis. Nude mice bearing SiHa xenografts were used to investigate the functions of miR?218 and carboplatin on tumor growth and weight. The expression of cycle?related proteins was detected by western blotting and immunohistochemical staining. In vitro, miR?218 significantly inhibited cellular growth in all four cell lines tested (P=0.021 for CaSki, P=0.009 for HeLa, P=0.016 for SiHa, and P=0.029 for C33A). Overexpression of miR?218 induced G1 phase arrest and reduced expression of cyclin D1 and CDK4. In vivo, restoration of miR?218 notably inhibited tumor growth and decreased tumor weight. In primary cultured samples, tumors with high levels of miR?218 were more sensitive to carboplatin (R2=0.3319, P=0.0026); consistently, miR?218 overexpression suppressed tumor growth, induced cell?cycle arrest, and reduced the cyclin D1 level. Based on these and previous results, we conclude that restoration of the miR?218 level inhibits the growth of cervical cancer cells both in vitro and in vivo; furthermore, overexpression of miR?218 sensitizes cervical cancer cells to carboplatin. Our findings suggest a novel therapy for cervical cancer based on miR?218, especially in patients with reduced levels of miR?218. PMID:25310186

  5. Amplified Genes May Be Overexpressed, Unchanged, or Downregulated in Cervical Cancer Cell Lines

    PubMed Central

    Vazquez-Mena, Oscar; Medina-Martinez, Ingrid; Juárez-Torres, Eligia; Barrón, Valeria; Espinosa, Ana; Villegas-Sepulveda, Nicolás; Gómez-Laguna, Laura; Nieto-Martínez, Karem; Orozco, Lorena; Roman-Basaure, Edgar; Muñoz Cortez, Sergio; Borges Ibañez, Manuel; Venegas-Vega, Carlos; Guardado-Estrada, Mariano; Rangel-López, Angélica; Kofman, Susana; Berumen, Jaime

    2012-01-01

    Several copy number-altered regions (CNAs) have been identified in the genome of cervical cancer, notably, amplifications of 3q and 5p. However, the contribution of copy-number alterations to cervical carcinogenesis is unresolved because genome-wide there exists a lack of correlation between copy-number alterations and gene expression. In this study, we investigated whether CNAs in the cell lines CaLo, CaSki, HeLa, and SiHa were associated with changes in gene expression. On average, 19.2% of the cell-line genomes had CNAs. However, only 2.4% comprised minimal recurrent regions (MRRs) common to all the cell lines. Whereas 3q had limited common gains (13%), 5p was entirely duplicated recurrently. Genome-wide, only 15.6% of genes located in CNAs changed gene expression; in contrast, the rate in MRRs was up to 3 times this. Chr 5p was confirmed entirely amplified by FISH; however, maximum 33.5% of the explored genes in 5p were deregulated. In 3q, this rate was 13.4%. Even in 3q26, which had 5 MRRs and 38.7% recurrently gained SNPs, the rate was only 15.1%. Interestingly, up to 19% of deregulated genes in 5p and 73% in 3q26 were downregulated, suggesting additional factors were involved in gene repression. The deregulated genes in 3q and 5p occurred in clusters, suggesting local chromatin factors may also influence gene expression. In regions amplified discontinuously, downregulated genes increased steadily as the number of amplified SNPs increased (p<0.01, Spearman's correlation). Therefore, partial gene amplification may function in silencing gene expression. Additional genes in 1q, 3q and 5p could be involved in cervical carcinogenesis, specifically in apoptosis. These include PARP1 in 1q, TNFSF10 and ECT2 in 3q and CLPTM1L, AHRR, PDCD6, and DAP in 5p. Overall, gene expression and copy-number profiles reveal factors other than gene dosage, like epigenetic or chromatin domains, may influence gene expression within the entirely amplified genome segments. PMID:22412903

  6. Hydroxychloroquine facilitates autophagosome formation but not degradation to suppress the proliferation of cervical cancer SiHa cells

    PubMed Central

    LIU, QINGSONG; LUO, XIONG YAN; JIANG, HONG; YANG, MING-HUI; YUAN, GUO-HUA; TANG, ZHONG; WANG, HE

    2014-01-01

    Hydroxychloroquine (HCQ), the hydroxylated analog of chloroquine, is an antimalarial lysomotropic agent that inhibits autophagy due to lysosomal acidification, and subsequently blocks the fusion of autophagosomes with lysosomes which leads to the accumulation of autophagosomes that may accelerate tumor cell death. Given these hypothesis the aim of this study was to investigate the effects of HCQ in the inhibition of autophagy and the induction of apoptosis in cervical cancer SiHa cells. Cervical cancer SiHa cells were cultured with Hanks balanced salt solution (HBSS) as positive control of autophagy or treated with HCQ as part of the experimental groups. LC3 and P62/SQSTM1 were detected by quantitative polymerase chain reaction (qPCR) and western blotting, respectively in order to evaluate initially autophagosome formation and their degradation. Specific green fluorescent protein (GFP)-LC3 was subsequently detected by fluorescence microscopy in order to confirm the formation of autophagosomes. MTT and flow cytometry were adopted respectively to assess the proliferation and apoptosis of the SiHa cells. miRNA-9* was also investigated. The results demonstrated that HCQ increased the expressions of LC3 mRNA and LC3II protein and GFP-LC3 signalling but reduced the expression of p62/STSQM1 in cervical cancer SiHa cells. These results indicated HCQ has the ability to inhibit autophagy as incapable of degrading the autophagosome. However, HCQ may promote SiHa cell apoptosis as the MTT, apoptotic assay and miRNA-9* results revealed. HCQ has the ability to inhibit autophagy by blocking the degradation of autophagosomes and subsequently facilitates the apoptosis of cervical cancer SiHa cells. PMID:24944668

  7. 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 tissues and the development of cervical cancer. PMID:25384883

  8. Effects of Decabrominated Diphenyl Ether (PBDE-209) in Regulation of Growth and Apoptosis of Breast, Ovarian, and Cervical Cancer Cells

    PubMed Central

    Li, Zhi-Hua; Liu, Xiao-Yan; Wang, Na; Huang, Jin-Tao; Su, Chun-Hong; Xie, Fukang; Yu, Bin

    2012-01-01

    Background: Polybrominated diphenyl ethers (PBDEs), commonly used in building materials, electronics, plastics, polyurethane foams, and textiles, are health hazards found in the environment. Objective: In this study we investigated the effects of PBDE-209, a deca-PBDE, on the regulation of growth and apoptosis of breast, ovarian, and cervical cancer cells as well as the underlying protein alterations. Methods: We used MCF-7 and MCF-7/ADR (multidrug-resistant MCF-7) breast cancer cell lines, the HeLa cervical cancer cell line, the OVCAR-3 ovarian cancer cell line, and the normal CHO (Chinese hamster ovary) cell line to assess the effects of PBDE-209 using cell viability, immunofluorescence, and flow cytometric assays. Western blot assays were used to detect changes in protein expression. To assess the effects of PBDE-209 on apoptosis, we used the protein kinase Cα (PKCα) inhibitor Gö 6976, the extracellular signal-regulated kinase (ERK) inhibitor PD98059, and tamoxifen. Results: Our data indicate that PBDE-209 increased viability and proliferation of the tumor cell lines and in CHO cells in a dose- and time-dependent manner. PBDE-209 also altered cell cycle distribution by inducing the S phase or G2/M phase. Furthermore, PBDE-209 partially suppressed tamoxifen-induced cell apoptosis in the breast cancer cell lines (MCF-7 and MCF-7/ADR) but suppressed Gö 6976- and PD98059-induced apoptosis in all cell lines. At the molecular level, PBDE-209 enhanced PKCα and ERK1/2 phosphorylation in the cell lines. Conclusions: Our data demonstrate that PBDE-209 is able to promote proliferation of various cancer cells from the female reproductive system and normal ovarian CHO cells. Furthermore, it reduced tamoxifen, PKCα, and ERK inhibition-induced apoptosis. Finally, PBDE-209 up-regulated phosphorylation of PKCα and ERK1/2 proteins in tumor cells and in CHO cells. PMID:22472210

  9. Effects of tatariside G isolated from Fagopyrum tataricum roots on apoptosis in human cervical cancer HeLa cells.

    PubMed

    Li, Yuan; Wang, Su-Juan; Xia, Wei; Rahman, Khalid; Zhang, Yan; Peng, Hao; Zhang, Hong; Qin, Lu-Ping

    2014-01-01

    Cervical cancer is the second most common female carcinoma. Current therapies are often unsatisfactory, especially for advanced stage patients. The aim of this study was to explore the effects of tatariside G (TG) on apoptosis in human cervical cancer HeLa cells and the possible mechanism of action involved. An MTT assay was employed to evaluate cell viability. Hoechst 33258 staining and flow cytometry (FCM) assays were used to detect cell apoptosis. The protein expression of phosphorylated JNK, P38, ERK and Akt and cleaved caspase-3 and caspase-9 was evaluated by western blot analysis. Additionally, the mRNA expression of caspase-3 and caspase-9 was measured by fluorescent quantitative reverse transcription-PCR (FQ-RT-PCR). TG notably inhibited cell viability, enhanced the percentage of apoptotic cells, facilitated the phosphorylation of p38 MAPK and JNK proteins and caspase-3 and caspase-9 cracking, downregulated the phosphorylation level of Akt, and increased the loss of MMP and the mRNA expression of caspase-3 and caspase-9. TG-induced apoptosis is associated with activation of the mitochondrial death pathway. TG may be an effective candidate for chemotherapy against cervical cancer. PMID:25076146

  10. Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma.

    PubMed

    Yamamoto, Noriko; Kinoshita, Takashi; Nohata, Nijiro; Yoshino, Hirofumi; Itesako, Toshihiko; Fujimura, Lisa; Mitsuhashi, Akira; Usui, Hirokazu; Enokida, Hideki; Nakagawa, Masayuki; Shozu, Makio; Seki, Naohiko

    2013-12-01

    Our recent studies of microRNA (miRNA) expression signatures indicated that microRNA-29a (miR-29a) was significantly downregulated in several types of human cancers, suggesting that miR-29a may be a putative tumor-suppressive miRNA in human cancers. The aim of this study was to investigate the functional significance of miR-29a in cervical squamous cell carcinoma (SCC) and to identify novel miR-29a-regulated cancer pathways and target genes involved in cervical SCC oncogenesis and metastasis. Restoration of miR-29a in cervical cancer cell lines (CaSKi, HeLa, ME180 and Yumoto) revealed that this miRNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that heat-shock protein 47 (HSP47), a member of the serpin superfamily of serine proteinase inhibitors and a molecular chaperone involved in the maturation of collagen molecules, was a potential target of miR-29a regulation. Luciferase reporter assays showed that miR-29a directly regulated HSP47. Moreover, silencing of the HSP47 gene significantly inhibited cell migration and invasion in cancer cells and the expression of HSP47 was upregulated in cancer tissues and cervical intraepithelial neoplasia (CIN), as demonstrated by immunostaining. Downregulation of miR-29a was a frequent event in cervical SCC and miR-29a acted as a tumor suppressor by directly targeting HSP47. Recognition of tumor-suppressive miRNA-regulated molecular targets provides new insights into the potential mechanisms of cervical SCC oncogenesis and metastasis and suggests novel therapeutic strategies for treatment of this disease. PMID:24141696

  11. New Cervical Cancer Screening Guidelines

    MedlinePLUS Videos and Cool Tools

    ... reading health news for healthier living. Related MedlinePlus Health Topics Cervical Cancer Screening HPV About MedlinePlus Site ... Rockville Pike, Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page ...

  12. 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. Cancer Res; 75(24); 5248-59. ©2015 AACR. PMID:26631268

  13. 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

  14. 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.

  15. DNA methylation in human papillomavirus-infected cervical cells is elevated in high-grade squamous intraepithelial lesions and cancer

    PubMed Central

    Lee, Ki-Heon; So, Kyeong A; Hong, Sung Ran; Hwang, Chang-Sun; Kee, Mee-Kyung; Rhee, Jee Eun; Kang, Chun; Hur, Soo Young; Park, Jong Sup

    2016-01-01

    Objective DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. Methods A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. Results Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). Conclusion DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies. PMID:26768780

  16. Dual-modality fiber-optic imager (DFOI) for intracellular gene delivery in human cervical cancer cell

    NASA Astrophysics Data System (ADS)

    Cha, Jaepyeong; Zhang, Jing; Gurbani, Saumya; Li, Min; Kang, Jin U.

    2013-03-01

    The most common optical method to validate intracellular gene delivery in cancer is to detect tagged fluorescence signals from the cells. However, fluorescent detection is usually performed in vitro due to the limitation of standard microscopes. Herein, we propose a highly sensitive dual-modality fiber-optic imager (DFOI), which enables in vivo fluorescence imaging. Our system uses a coherent fiber bundle based imager capable of simultaneously performing both confocal reflectance and fluorescent microscopy. Non-viral vectors targeting human cervical cancer cells (HeLa) were used to evaluate the performance. Preliminary results demonstrated the DFOI is promising for in vivo evaluation of intracellular gene delivery.

  17. Human telomerase reverse transcriptase regulates vascular endothelial growth factor expression via human papillomavirus oncogene E7 in HPV-18-positive cervical cancer cells.

    PubMed

    Li, Fang; Cui, Jinquan

    2015-07-01

    Human papillomavirus (HPV) infection induces chronic and precancerous lesions and results in invasive cervical cancer. Human telomerase as well as inflammatory and angiogenic factors such as telomerase reverse transcriptase (hTERT) or vascular endothelial growth factor (VEGF) could play a role in regulating HPV-induced cervical cancer. This study investigated underlying molecular events in HPV-induced HPV-positive cervical cancer through hTERT and VEGF in vitro. Expressions of hTERT, a rate-limiting subunit of telomerase, and VEGF mRNA and proteins were, respectively, assessed by qRT-PCR, ELISA, and TRAP-ELISA in HPV-positive tissue samples and cervical cancer cell lines. To assess hTERT and VEGF secretion, hTERT overexpression and knockdown were conducted in HPV-18-positive Hela cells by hTERT cDNA and shRNA transfection, respectively. Then, the effect of HPV E6 and E7 on VEGF expressions was assessed in HPV-negative cervical cancer cells. Data have shown that VEGF expression levels are associated with hTERT expressions and telomerase activity in HPV-positive cervical cancer tissues and cells. Knockdown of hTERT expression down-regulated VEGF expressions, whereas overexpression of hTERT up-regulated VEGF expressions in HPV-18-positive Hela cells. Furthermore, HPV E7 oncoprotein was necessary for hTERT to up-regulate VEGF expressions in HPV-negative cervical cancer cells. Data from this current study indicate that HPV oncoproteins up-regulated hTERT and telomerase activity and in turn promoted VEGF expressions, which could be a key mechanism for HPV-induced cervical cancer development and progression. PMID:26067630

  18. β-hydroxyisovaleryl-shikonin induces human cervical cancer cell apoptosis via PI3K/AKT/mTOR signaling

    PubMed Central

    LU, DAN; QIAN, JING; LI, WEI; FENG, QIANQIAN; PAN, SHU; ZHANG, SIQUAN

    2015-01-01

    The present study aimed to investigate the inhibitory ability of β-hydroxyisovaleryl-shikonin (β-HIVS) on the proliferation of human cervical cancer HeLa cells and to identify the mechanism of this effect. The HeLa cells were treated with β-HIVS and the inhibition of cell growth was detected by an MTT assay. Flow cytometry was performed to analyze the apoptosis rate and cell cycle distribution of HeLa cells. Reverse transcription-polymerase chain reaction and western blot analysis were used to examine the expression of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway proteins. The results revealed that β-HIVS inhibited HeLa cell proliferation in a dose- and time-dependent manner. With the administration of increasing concentrations of β-HIVS, the apoptotic rate of HeLa cells was also increased. The cell cycle was slightly arrested at the S phase, with ~6% of cells in this phase, subsequent to treatment with 10 µM β-HIVS. In addition, β-HIVS markedly reduced the expression levels of PI3K, AKT, mTOR and 70-kDa ribosomal protein S6 kinase in HeLa cells. β-HIVS promoted cervical cancer cell apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway and suppressing downstream gene expression. The present study is expected to lead to the development of molecular targeted therapy for this signaling pathway as a novel method of cervical cancer treatment. PMID:26788147

  19. Fucoxanthin induces apoptosis in human cervical cancer cell line HeLa via PI3K/Akt pathway.

    PubMed

    Ye, Guoliu; Lu, Qin; Zhao, Weidong; Du, Danli; Jin, Lijie; Liu, Yusheng

    2014-11-01

    Cervical cancer (CC) is a malignant neoplasm arising from cells originating in the cervix uteri, among the top causes of death from cancer in women. In a gene expression profiling study of metabolic response to treatment, PI3K/Akt signaling pathway are associated with the development of CC. A common mechanism of Akt activation seen in cancer types is alterations in the upstream regulators of Akt such as phosphatidylinositol 3-kinase (PI3K), which is overexpressed in cervical cancer tissues, and leads to phosphorylation of Akt. Both PI3K and Akt inhibitors exist and may be therapeutically valuable. In the present study, we use MTT assay and western blot for the high-throughput screening to select specific inhibitors of PI3K/Akt signaling pathway, and then obtain fucoxanthin. Fucoxanthin is a water-soluble dietary fiber, taken from the unique slimy component of alginic cells. Various studies have pointed out that fucoxanthin is very effective for the treatment of cancer. Our results have shown that fucoxanthin induced a significant apoptosis of HeLa cells, compared with other candidates. After treatment with fucoxanthin for 24 h, the level of phosphorylation was inhibited in a dose-dependent manner, and the proteins of apoptotic markers were changed in HeLa cells. And fucoxanthin could suppress tumor growth in vivo. In addition, the mitochondrial signal transduction pathway maybe was involved in its mechanism and NF-?B activation was decreased after treatment with fucoxanthin. Therefore, fucoxanthin may be used as anti-cervical cancer drugs in the future. PMID:25113250

  20. Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein.

    PubMed Central

    Smotkin, D; Wettstein, F O

    1986-01-01

    Human papillomavirus type 16 DNA and RNA were characterized in the cervical cancer-derived CaSki cell line, which contains only integrated DNA, and in a cervical cancer, which contains predominantly plasmid DNA. In both, a major RNA can code for the early open reading frame E7 and a minor one can code for E6. The cervical cancer, but not the CaSki cell line, contains a minor RNA that can code for an intact E2 protein, and this may relate to the continued presence of plasmid DNA. The RNA mapping data suggest that the poly(A)+ RNA is transcribed from a minor fraction of the several hundred gene copies present, and in the cervical cancer these genomes appear to be integrated. The E7 protein has been identified in CaSki cells and the prevalence of its mRNA suggests a possible function in progression to, or long-term maintenance of, the malignant state. Images PMID:3014503

  1. Clinical significance of serum miR-196a in cervical intraepithelial neoplasia and cervical cancer.

    PubMed

    Liu, P; Xin, F; Ma, C F

    2015-01-01

    Previous studies have reported that miR-196a is upregulated in cervical cancer tissues and cell lines. However, whether serum miR-196a is increased in patients with cervical cancer or cervical intraepithelial neoplasia (CIN), and its potential clinical value remained unknown. In total, 105 cervical cancer patients, 86 CIN patients, and 50 healthy volunteers were recruited. Quantitative reverse transcription-polymerase chain reaction was performed to compare the serum levels miR-196a in all participants. The associations between serum miR-196a and CIN grade/clinicopathological parameters of cervical cancer were also examined. A survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were conducted to explore the independent risk factors for cervical cancer. Our results revealed that serum miR-196a levels were higher in patients with cervical cancer (P < 0.01) and CIN (P < 0.05) compared to those in healthy controls. Serum miR-196a was associated with CIN grade and various cervical cancer parameters including tumor size (P = 0.031), lymph node metastasis (P = 0.018), FIGO stage (P = 0.004), and grade (P = 0.011). Cervical cancer patients with higher serum miR-196a levels had a poorer overall survival rate (P = 0.004). Multivariate analysis revealed that high serum miR-196a was an independent predictor for poor survival of cervical cancer (HR = 3.510; 95%CI = 1.961-6.874; P = 0.025). In conclusion, our findings suggest that serum miR-196a overexpression is associated with CIN grade and cervical cancer progression. Therefore, serum miR-196a may be a reliable biomarker for early detection and prognosis of cervical cancer. PMID:26782446

  2. Up-regulation of long non-coding RNA CCAT2 correlates with tumor metastasis and poor prognosis in cervical squamous cell cancer patients

    PubMed Central

    Chen, Xin; Liu, Lifen; Zhu, Weipei

    2015-01-01

    Background: Dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in tumor progression. The purpose of this study was to investigate the relationship between lncRNA CCAT2 expression and cervical squamous cell cancer susceptibility and prognosis. Methods: Expression levels of lncRNA CCAT2 in 123 cervical squamous cell tumor specimens were determined by quantitative real-time PCR (qRT-PCR), to clarify the clinical significance of lncRNA CCAT2 in cervical squamous cell cancer, we further discussed the relationship between lncRNA CCAT2 expression and overall survival (OS) and progression-free survival (PFS). Results: In the present study, we found that lncRNA CCAT2 was up-regulated in cervical squamous cell cancer tissues compared to the adjacent non-tumor tissues. In addition, the high lncRNA CCAT2 expression was significantly associated with the FIGO stage, lymph node metastasis and depth of cervical invasion (P<0.05). Furthermore, patients with high expression of lncRNA CCAT2 had poor OS (HR=2.813, 95% CI: 1.504-6.172; P=0.017), and PFS rates (HR=3.072, 95% CI: 1.716-8.174; P=0.008). Multivariate Cox proportional hazard model analysis demonstrated that high lncRNA CCAT2 expression was an independent poor prognostic factor for cervical squamous cell cancer patients. Conclusions: Our study suggested that high expression of lncRNA CCAT2 is related to the prognosis of cervical squamous cell cancer; it may be a new prognostic biomarker and potential therapeutic target for cervical squamous cell cancer intervention. PMID:26722527

  3. 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.

  4. 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.

  5. Hypoxia inducible factor-1 mediates upregulation of urokinase-type plasminogen activator receptor gene transcription during hypoxia in cervical cancer cells.

    PubMed

    Nishi, Hirotaka; Sasaki, Toru; Nagamitsu, Yuzo; Terauchi, Fumitoshi; Nagai, Takeshi; Nagao, Toshitaka; Isaka, Keiichi

    2016-02-01

    Hypoxia occurs during development of cervical cancer and is considered to correlate with its invasion. Hypoxia mediates tumor cells to have more invasive property in a variety of cancers. Urokinase plasminogen activator receptor (uPAR) which mediates invasion is considered to be induced by hypoxia. We sought to determine the regulators of uPAR expression during hypoxia in cervical cancer. We showed that cervical cancer cell lines, CaSki and CA, were more invasive under hypoxic condition (1% O2) than under normoxic condition (20% O2) by invasion assays. Using western blot analysis, hypoxia enhanced the endogenous hypoxia-inducible factor (HIF)-1? and uPAR protein expression. uPAR mRNA level was also upregulated by hypoxia using real-time RT-PCR. Overexpression of HIF-1? which is induced by hypoxia activated the transcriptional activity of the uPAR promoter by luciferase assays. HIF-1 protein bound the putative HIF-1 response element on the uPAR promoter using electrophoretic mobility shift analysis, and additional luciferase assays show that this is essential for uPAR transactivation by HIF-1. HIF-1 overexpression enhanced the endogenous uPAR expression and introduction of siRNA for HIF-1? diminishes uPAR expression during hypoxia. These results indicate the upregulation of uPAR by hypoxia in cervical cancer cells is mediated through HIF-1. In cervical cancer tissues, we also demonstrated that uPAR protein expression was detected in cervical cancer but not in normal cervix or cervical intraepithelial neoplasia (CIN) by immunohistopathological staining. Our results provide evidence that regulation of uPAR expression by HIF-1 represents a mechanism for cervical cancer invasion during hypoxia. PMID:26718775

  6. 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.

  7. Cervical cancer screening at crossroads.

    PubMed

    Lynge, Elsebeth; Rygaard, Carsten; Baillet, Miguel Vazquez-Prada; Dugu, 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. PMID:25046198

  8. 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.

  9. Enhanced expression of PD L1 in cervical intraepithelial neoplasia and cervical cancers.

    PubMed

    Mezache, Louisa; Paniccia, Bernard; Nyinawabera, Angelique; Nuovo, Gerard J

    2015-12-01

    Programmed death ligand 1 (PD L1) expression can reduce the immune response in both infectious diseases and cancers. We thus examined PD L1 expression in cervical intraepithelial neoplasias (CINs) and cancers since they each reflect infection by human papillomavirus (HPV). PD L1 protein was not evident by immunohistochemistry in histologically normal cervical epithelia (0/55) even when adjacent to CIN or cancer. PD L1 expression was much increased in CINs (20/21=95%) and cervical squamous cell cancer (56/70=80%) and localized to the dysplastic/neoplastic squamous cells and mononuclear cells, respectively. There was also a significant increase (each P<0.001) in PD L1 detection in mononuclear cells when comparing cervical squamous cell cancers to endometrial (22/115=19%) and ovarian adenocarcinomas (5/40=13%). Co-expression analyses showed that the primary inflammatory cell that contained PD L1 was the CD8+ lymphocyte that strongly concentrated around the dysplastic CIN cells and nests of invasive squamous cancer cells. These data show that PD L1 is a solid biomarker of productive HPV infection of the cervix and that it is significantly upregulated in both the carcinoma and surrounding inflammatory cells in cervical cancer when compared with other gynecologic malignancies. This suggests that anti-PD L1 therapy may have a role in the treatment of cervical cancer. PMID:26403783

  10. Diallyl disulfide enhances carbon ion beams-induced apoptotic cell death in cervical cancer cells through regulating Tap73 /?Np73.

    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

    2015-12-01

    Diallyl disulfide (DADS), extracted from crushed garlic by steam-distillation, has been reported to provide the anticancer activity in severalcancertypes. 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 ofthis dallylsulfide. 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 theapoptosispathway. We further demonstratedthat pretreatment of 10 M 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 ?Np73, and its downstream proteins, such as FASLG, and APAF1. Taken together, these results suggest thatDADS is a potentialcandidate as radio sensitive agent for cervical cancer. PMID:26505313

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

    PubMed

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

    2014-08-29

    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). ?H2AX 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. PMID:25102337

  13. N-Benzylcinnamide induces apoptosis in HPV16 and HPV18 cervical cancer cells via suppression of E6 and E7 protein expression.

    PubMed

    Xiong, Yuanhuan; Chen, Lin; Luo, Puying

    2015-05-01

    Seventy percent of all cervical cancers are caused by human papillomavirus (HPV) infections. Natural products are being extensively explored for their potential ability to prevent and treat cervical cancers. N-benzylcinnamide (PT-3) is a natural product purified from Piper submultinerve. Whether or not PT-3 has an effect on cervical cancer cells is as yet unknown. Therefore, we set out to explore the mechanism of action behind PT-3 and how it affects cells that either contain or lack HPV DNA. Our results demonstrate that PT-3 slows the growth kinetics of CaSki (HPV-16 positive) and HeLa (HPV-18 positive) cells in a dose-dependent manner, but does not slows HPV-negative cells. Importantly, we also found that PT-3 induces apoptosis by suppressing expression of E6 and E7 viral oncogenes in HPV-infected cervical cancer CaSki and HeLa cells. Moreover, we found that suppression of E6 and E7 expression leads to modulations in p53 and protein retinoblastomas, which are not changed in HPV-negative cervical cancer C33A cells. These findings demonstrate that PT-3 can effectively promote apoptosis by downregulating expression of E6 and E7. PMID:25914202

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

    PubMed

    Ramos-Solano, Moiss; Meza-Canales, Ivan D; Torres-Reyes, Luis A; Alvarez-Zavala, Monserrat; Alvarado-Ruz, Liliana; Rincon-Orozco, Bladimiro; Garcia-Chagollan, Mariel; Ochoa-Hernndez, Alejandra B; Ortiz-Lazareno, Pablo C; Rsl, Frank; Gariglio, Patricio; Jave-Surez, Luis F; Aguilar-Lemarroy, Adriana

    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. PMID:25978974

  15. Effect of sun ginseng potentiation on epirubicin and paclitaxel-induced apoptosis in human cervical cancer cells

    PubMed Central

    Lin, Yingjia; Jiang, Dan; Li, Yang; Han, Xinye; Yu, Di; Park, Jeong Hill; Jin, Ying-Hua

    2014-01-01

    Background Sun ginseng (SG), a specific formulation of quality-controlled red ginseng, contains approximately equal amounts of three major ginsenosides (RK1, Rg3, and Rg5), which reportedly has antitumor-promoting activities in animal models. Methods MTT assay was used to assess whether SG can potentiate the anticancer activity of epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells; apoptosis status was analyzed by annexin V-FITC and PI and analyzed by flow cytometry; and apoptosis pathway was studied by analysis of caspase-3, -8, and -9 activation, mitochondrial accumulation of Bax and Bak, and cytochrome c release. Results SG remarkably enhances cancer cell death induced by epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells. Results of the mechanism study highlighted the cooperation between SG and epirubicin or paclitaxel in activating caspase-3 and -9 but not caspase-8. Moreover, SG significantly increased the mitochondrial accumulation of both Bax and Bak triggered by epirubicin or paclitaxel as well as the subsequent release of cytochrome c in the targeted cells. Conclusion SG significantly potentiated the anticancer activities of epirubicin and paclitaxel in a synergistic manner. These effects were associated with the increased mitochondrial accumulation of both Bax and Bak that led to an enhanced cytochrome c release, caspase-9/-3 activation, and apoptosis. Treating cancer cells by combining epirubicin and paclitaxel with SG may prove to be a novel strategy for enhancing the efficacy of the two drug types. PMID:25535473

  16. Lynch syndrome and cervical cancer.

    PubMed

    Antill, Yoland C; Dowty, James G; Win, Aung Ko; Thompson, Tina; Walsh, Michael D; Cummings, Margaret C; Gallinger, Steven; Lindor, Noralane M; Le Marchand, Loc; Hopper, John L; Newcomb, Polly A; Haile, Robert W; Church, James; Tucker, Katherine M; Buchanan, Daniel D; Young, Joanne P; Winship, Ingrid M; Jenkins, Mark A

    2015-12-01

    Carriers of germline mutations in DNA mismatch repair (MMR) genes are at increased risk of several cancers including colorectal and gynecologic cancers (Lynch syndrome). There is no substantial evidence that these mutations are associated with an increased risk of cervical cancer. A total of 369 families with at least one carrier of a mutation in a MMR gene (133 MLH1, 174 MSH2, 35 MSH6 and 27 PMS2) were ascertained via population cancer registries or via family cancer clinics in Australia, New Zealand, Canada, and USA. Personal and family histories of cancer were obtained from participant interviews. Modified segregation analysis was used to estimate the hazard ratio (incidence rates for carriers relative to those for the general population), and age-specific cumulative risks of cervical cancer for carriers. A total of 65 cases of cervical cancer were reported (including 10 verified by pathology reports). The estimated incidence was 5.6 fold (95% CI: 2.3-13.8; p = 0.001) higher for carriers than for the general population with a corresponding cumulative risk to 80 years of 4.5% (95% CI: 1.9-10.7%) compared with 0.8% for the general population. The mean age at diagnosis was 43.1 years (95% CI: 40.0-46.2), 3.9 years younger than the reported USA population mean of 47.0 years (p = 0.02). Women with MMR gene mutations were found to have an increased risk of cervical cancer. Due to limited pathology verification we cannot be certain that a proportion of these cases were not lower uterine segment endometrial cancers involving the endocervix, a recognized cancer of Lynch syndrome. PMID:26077226

  17. In vitro antiproliferative effect and induction of apoptosis by Retama monosperma L. extract in human cervical cancer cells.

    PubMed

    Merghoub, N; Benbacer, L; El Btaouri, H; Ait Benhassou, H; Terryn, C; Attaleb, M; Madoulet, C; Benjouad, A; El Mzibri, M; Morjani, H; Amzazi, S

    2011-01-01

    The antiproliferative effect of different extracts obtained from Retama monosperma L. was investigated on human SiHa and HeLa cervical cancer cell lines using a MTT colorimetric assay. The Retama monosperma L. dichloromethane fraction (Rm-DF) was the most active extract, exhibiting a significant cytotoxic activity on both cell lines in a dose-dependent manner, after 72 h of treatment. IC50 values obtained were 14.57 4.15 ?g/ml and 21.33 7.88 ?g/ml, for SiHa and HeLa cell lines respectively. The morphological features assessment of apoptosis in Rm-DF-treated cells showed a condensation of chromatin and apoptotic bodies, accompanied by a decrease in mitochondrial membrane potential (??m) and an increase in reactive oxygen species in both cell lines. The induction of apoptosis was further confirmed by Western blotting pro-caspase 3, Bcl2 and PARP; caspase 3 activity assay; and Annexin V labelling. Analysis of Rm-DF by CG/MS revealed the presence of five known quinolizidine alkaloids as well as, sparteine (10,97%), L-methyl cytisine (9.11%), 17-oxosparteine (3.49%), lupanine (0.93%) and anagyrine (39.63%). This study shows that Retama monosperma L. extract exhibits a potential anticancer activity against cervical cancer cell lines in vitro through the inhibition of proliferation and induction of apoptosis, which may involve a mitochondria-mediated signaling pathway. PMID:22000488

  18. 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 reagent for siRNAs. Our results indicate that the PEI-NH-SWNTs and PEI-NH-MWNTs produced in this study are capable of delivering siRNAs into HeLa-S3 cells to suppress gene expression and may therefore be considered as novel nonviral gene delivery reagents.

  19. Anticancer activity of Phyllanthus emblica Linn. (Indian gooseberry): inhibition of transcription factor AP-1 and HPV gene expression in cervical cancer cells.

    PubMed

    Mahata, Sutapa; Pandey, Arvind; Shukla, Shirish; Tyagi, Abhishek; Husain, Syed Akhtar; Das, Bhudev Chandra; Bharti, Alok Chandra

    2013-01-01

    Plant products of Phyllanthus emblica Linn. are traditionally consumed for its immense nutritive and medicinal values. However, the molecular mechanism(s) by which it exerts it effects is less understood. In this study, we investigated mechanism of action of P. emblica fruit extract (PE) by studying its effect on activator protein-1 (AP-1) activity and human papillomavirus (HPV) transcription that are essential for tumorigenicity of cervical cancer cells. PE resulted in a dose-and time-dependent inhibition of DNA binding activity of constitutively active AP-1 in both HPV16-positive (SiHa) and HPV18-positive (HeLa) cervical cancer cells. PE-induced AP-1 inhibition was found mediated through downregulation of constituent AP-1 proteins, c-Jun, JunB, JunD, and c-Fos; however, the kinetics of their inhibition varied in both the cell types. Inhibition of AP-1 by PE was accompanied by suppression of viral transcription that resulted in growth inhibition of cervical cancer cells. Growth inhibitory activity of PE was primarily manifested through induction of apoptotic cell death. These results suggest that P. emblica exhibits its anticancer activities through inhibition of AP-1 and targets transcription of viral oncogenes responsible for development and progression of cervical cancer thus indicating its possible utility for treatment of HPV-induced cervical cancers. PMID:23682787

  20. Downregulation of CCR5 inhibits the proliferation and invasion of cervical cancer cells and is regulated by microRNA-107

    PubMed Central

    CHE, LI-FAN; SHAO, SU-FANG; WANG, LI-XIN

    2016-01-01

    Cervical cancer is among the most prevalent forms of cancer worldwide. C-C chemokine receptor type 5 (CCR5) is hypothesized to be a key functional protein involved in tumorigenesis. However, the role of CCR5 in cervical cancer remains unclear. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to evaluate the mRNA and protein expression levels of CCR5 in human cervical carcinoma tissues. Furthermore, a small interfering RNA was employed to knockdown CCR5 in HeLa and C33A cells. MTT, colony formation and Transwell assays were performed to determine the effects of this knockdown on cell viability, proliferation and invasion. In addition, micro RNA (miR)-107 was identified as a potential candidate regulator of CCR5 using miR prediction algorithms, and the effects of miR-107 and its antisense miR on CCR5 mRNA expression were determined. The results of the present study indicated that CCR5 is overexpressed in human cervical cancer tissues compared with adjacent normal tissues, and its downregulation inhibits cervical cancer cell growth and proliferation. Furthermore, the downregulation of CCR5 appears to suppress cervical cancer cell invasion. Finally, the tumor suppressor miR-107 was able to directly target CCR5 and inhibit its expression. These results suggest that the upregulation of CCR5, which is inhibited by miR-107, may play a carcinogenic role in cervical cancer and could provide a novel therapeutic target in the future. PMID:26893637

  1. Relevance of activated leukocyte cell adhesion molecule (ALCAM) in tumor tissue and sera of cervical cancer patients

    PubMed Central

    2012-01-01

    Background An altered expression of the activated leukocyte cell adhesion molecule (ALCAM) is associated with cancer progression in various cancer types. In some cancers ALCAM has a prognostic value or is predictive for the benefit of therapeutic interventions. To date there are no data on the role of ALCAM in cervical cancer available. Methods In this study, ALCAM expression was analysed by immunohistochemistry (IHC) in tissue samples of 233 patients with cervical cancer, among them 178 with complete follow-up information. In addition, soluble (s-)ALCAM was measured in sera of a subset of the included patients (n = 55) by enzyme-linked immunosorbent assay (ELISA). Results ALCAM overexpression was detected (immunoreactive score (IRS) 2-12) in 58.4% of the cervical cancer samples. The normal ectocervical or endocervical epithelium showed no ALCAM reactivity. In untreated patients, ALCAM overexpression in tumor tissue tended to be associated with shorter cancer-specific survival (CSS) and disease-free survival (DFS). Patients, whose tumor samples showed ALCAM overexpression receiving a cytotoxic therapy like radiotherapy or chemoradiation, however, had a favourable prognosis compared to those patients, whose cancers showed no or minimal ALCAM staining. This effect was particularly apparent in patients receiving chemoradiation where the CSS was significantly longer in patients with ALCAM-positive tumors (p = 0.038; cumulative incidence rates at 96 months 8%, 95% CI 0%-23%, and 26%, CI 3%-43% in ALCAM-positive and ALCAM-negative cases, respectively). Median preoperative s-ALCAM concentration in sera from tumor patients was 27.6 ng/ml (range 17.5-55.1 ng/ml, mean 28.9 ng/ml), serum levels did not correlate with intratumoral ALCAM expression. Conclusions The data of our retrospective study suggest that the prognostic value of ALCAM expression in cervical carcinoma might be therapy-dependent, and that ALCAM might function as a predictive marker for the response to chemoradiation. This should be confirmed in further, prospective studies. PMID:22475274

  2. 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, ...

  3. Whole-transcriptome analysis of flow-sorted cervical cancer samples reveals that B cell expressed TCL1A is correlated with improved survival

    PubMed Central

    Punt, Simone; Corver, Willem E.; van der Zeeuw, Sander A.J.; Kielbasa, Szymon M.; Osse, Elisabeth M.; Buermans, Henk P.J.; de Kroon, Cornelis D.

    2015-01-01

    Cervical cancer is typically well infiltrated by immune cells. Because of the intricate relationship between cancer cells and immune cells, we aimed to identify both cancer cell and immune cell expressed biomarkers. Using a novel approach, we isolated RNA from flow-sorted viable EpCAM+ tumor epithelial cells and CD45+ tumor-infiltrating immune cells obtained from squamous cell cervical cancer samples (n = 24). Total RNA was sequenced and differential gene expression analysis of the CD45+ immune cell fractions identified TCL1A as a novel marker for predicting improved survival (p = 0.007). This finding was validated using qRT-PCR (p = 0.005) and partially validated using immunohistochemistry (p = 0.083). Importantly, TCL1A was found to be expressed in a subpopulation of B cells (CD3−/CD19+/CD10+/CD34−) using multicolor immunofluorescence. A high TCL1A/CD20 (B cell) ratio, determined in total tumor samples from a separate patient cohort using qRT-PCR (n = 52), was also correlated with improved survival (p = 0.027). This is the first study demonstrating the prognostic value of separating tumor epithelial cells from tumor-infiltrating immune cells and determining their RNA expression profile for identifying putative cancer biomarkers. Our results suggest that intratumoral TCL1A+ B cells are important for controlling cervical cancer development. PMID:26299617

  4. Cervical cancer: screening and prevention.

    PubMed

    Behtash, Nadereh; Mehrdad, Nili

    2006-01-01

    Cancer of the cervix is the second most common life-threatening cancer among women worldwide and both incidence and mortality rates are likely to be underestimated in developing countries. HPV high risk strains play at least the major if not an absolutely necessary role in the etiology. The concept of cervical intraepithelial neoplasia (CIN) was introduced in 1968 as an equivalent to the term dysplasia, which means abnormal maturation. Cervical cancer progresses slowly from preinvasive CIN to invasive cancer and therefore screening for dysplasia is an important public health effort worldwide, given the accessibility of the primary organ site, the acceptability of current screening methods, and the long preinvasive period in which to detect disease and successfully intervene. It is widely accepted that detection and treatment of HPV-related dysplastic epithelial change in the form of CIN-2 and CIN-3 can prevent the development of invasive cervical cancer in individual patients. The mainstay of screening programs has been the Pap smear, introduced originally by George Papanicolaou in 1941. However, considerable numbers of false-negative Pap smears may occur with the traditional Pap technique, mostly due to sampling error. More recently, the use of liquid-based technologies such as ThinPrep and AutoCyte Prep have gained popularity, in part because of evidence suggesting reduction in the incidence of inadequate smears. It is also hoped that the ability to identify patients with oncogenic HPV types will lead to improved detection in women more likely to have squamous intraepithelial lesions. Hybrid Capture 2 is the latest refinement of HPV tests and has been described as having enhanced sensitivity. HPV DNA testing can be used as an adjunct to cytology in routine cervical disease screening programs. Establishment of the link between HPV and cervical cancer has further provided the impetus for research into prophylactic vaccination against the most common HPV types associated with the disease, HPV 16 and 18. Initial studies have provided evidence that L1 virus-like particle vaccines against HPV types (as monovalent, bivalent, or quadrivalent vaccines) prevent at least 90% of incident and persistent infections and their associated precursors of cervical cancer. This vaccine has sustained long-term vaccine efficacy against incident and persistent infections and in the long term should provide an answer to the cervical cancer problem. For the vast majority of women who have already been infected, however, continued screening and resection need to be emphasized. PMID:17250453

  5. T0070907, a PPAR ? Inhibitor, Induced G2/M Arrest Enhances the Effect of Radiation in Human Cervical Cancer Cells Through Mitotic Catastrophe

    PubMed Central

    An, Zhengzhe; Muthusami, Sridhar; Yu, Jae-Ran

    2014-01-01

    Overexpression of peroxisome proliferator activator receptor ? (PPAR?) has been implicated in many types of cancer including cervical cancer. Radiation therapy remains the main nonsurgical modality for the treatment of cervical cancer. The present study reports the impact of pharmacological inhibition of PPAR? in enhancing the radiosensitization of cervical cancer cells in vitro. Three cervical cancer cell lines (HeLa, SiHa, and Me180) were treated with a PPAR? inhibitor, T0070907, and/or radiation. The changes in protein, cell cycle, DNA content, apoptosis, and cell survival were analyzed. The PPAR? is differentially expressed in cervical cancer cells with maximum expression in ME180 cells. T0070907 has significantly decreased the tubulin levels in a time-dependent manner in ME180 cells. The decrease in the tubulin levels after T0070907 in ME180 and SiHa cells was associated with significant increase in the cells at the G2/M phase. The changes in the tubulin and G2/M phase were not evident in HeLa cells. T0070907 reduced the protein levels of PPAR?; however, PPAR? silencing had no effect on the ?-tubulin level in ME180 cells suggesting the PPAR?-dependent and -independent actions of T0070907. To ascertain the impact of synergistic effect of T0070907 and radiation, HeLa and ME180 cells were pretreated with T0070907 and subjected to radiation (4 Gy). Annexin V-fluorescein isothiocyanate analysis revealed increased apoptosis in cells treated with radiation and T0070907 when compared to control and individual treatment. In addition, T0070907 pretreatment enhanced radiation-induced tetraploidization reinforcing the additive effect of T0070907. Confocal analysis of tubulin confirmed the onset of mitotic catastrophe in cells treated with T0070907 and radiation. These results strongly suggest the radiosensitizing effects of T0070907 through G2/M arrest and mitotic catastrophe. PMID:24642720

  6. Tim-3 Expression in Cervical Cancer Promotes Tumor Metastasis

    PubMed Central

    Cao, Yang; Zhou, Xiaoxi; Huang, Xiaoyuan; Li, Qinlu; Gao, Lili; Jiang, Lijun; Huang, Mei; Zhou, Jianfeng

    2013-01-01

    Background T cell immunoglobulin mucin-3 (Tim-3) has been identified as a negative regulator of anti-tumor immunity. Recent studies highlight the important role of Tim-3 in the CD8+ T cell exhaustion that takes place in both human and animal cancer models. However, the nature of Tim-3 expression in the tumor cell and the mechanism by which it inhibits anti-tumor immunity are unclear. This present study aims to determine Tim-3 is expressed in cervical cancer cells and to evaluate the role of Tim-3 in cervical cancer progression. Methodology A total of 85 cervical tissue specimens including 43 human cervical cancer, 22 cervical intraepithelial neoplasia (CIN) and 20 chronic cervicitis were involved. Tim-3 expression in tumor cells was detected and was found to correlate with clinicopathological parameters. Meanwhile, expression of Tim-3 was assessed by RT-PCR, Western Blot and confocal microscopy in cervical cancer cell lines, HeLa and SiHa. The migration and invasion potential of Hela cells was evaluated after inhibiting Tim-3 expression by ADV-antisense Tim-3. Conclusions We found that Tim-3 was expressed at a higher level in the clinical cervical cancer cells compared to the CIN and chronic cervicitis controls. We supported this finding by confirming the presence of Tim-3 mRNA and protein in the cervical cell lines. Tim-3 expression in tumor cells correlated with clinicopathological parameters. Patients with high expression of Tim-3 had a significant metastatic potential, advanced cancer grades and shorter overall survival than those with lower expression. Multivariate analysis showed that Tim-3 expression was an independent factor for predicting the prognosis of cervical cancer. Significantly, down-regulating the expression of Tim-3 protein inhibited migration and invasion of Hela cells. Our study suggests that the expression of Tim-3 in tumor cells may be an independent prognostic factor for patients with cervical cancer. Moreover, Tim-3 expression may promote metastatic potential in cervical cancers. PMID:23335978

  7. Factors affecting platinum sensitivity in cervical cancer

    PubMed Central

    KATO, RINA; HASEGAWA, KIYOSHI; TORII, YUTAKA; UDAGAWA, YASUHIRO; FUKASAWA, ICHIO

    2015-01-01

    The present study aimed to investigate the association between nedaplatin (NDP) sensitivity and the expression of biological factors in cervical cancer. A total of 45 cervical cancer specimens, including 18 pretreatment biopsies and 27 surgical specimens, were used in histoculture drug response assays to determine the chemosensitivity of cervical cancer specimens to NDP. Each specimen was assessed for immunohistochemical expression of Ki-67, p53, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3, cyclooxygenase-2 (COX-2), and excision repair cross-complementation group 1 (ERCC1). The results revealed that low or negative expression of p53, Bcl-2 and COX-2, and high or positive expression of cleaved caspase-3 were significantly correlated with high sensitivity to NDP. However, there were no significant differences in Ki-67, Bax or ERCC1 expression between the low and high sensitivity groups. These findings indicate that sensitivity to platinum may be easily predicted by immunostaining for the detection of these specific factors in pretreatment biopsies or surgical specimens. The expression profiles of these targets may therefore provide additional information for planning individualized chemotherapy in the treatment of cervical cancer.

  8. Roles of Foxp3 in the occurrence and development of cervical cancer

    PubMed Central

    Luo, Qingshuang; Zhang, Shulan; Wei, Heng; Pang, Xiaoao; Zhang, Huijie

    2015-01-01

    Objective: This study aimed to evaluate the relationship between forkhead box P3 (Foxp3) expression and clinicopathological characteristics of cervical cancer and to explore the influence of Foxp3 on the biological behaviors of cervical cancer cells. Methods: In this study, immunohistochemistry, lentivirus mediated transfection, Transwell assay; CCK-8 assay, real-time PCR and flow cytometry were employed to confirm the roles of Foxp3 in the occurrence and development of cervical cancer. Results: Foxp3 and p16INK4a were highly expressed in the cervical cancer and their expressions were related to the FIGO stage, tumor size, lymph node metastasis and serum SCC. Foxp3 had a high expression in the cervical cancer cells, tumor interstitium and metastatic lymph nodes. Foxp3 expression was positively related to p16INK4a expression in the cervical cancer. Foxp3 expression in the cervical cancer was negatively related to the prognosis: high Foxp3 expression predicted a poor prognosis. Silencing of Foxp3 was able to inhibit the proliferation and invasiveness of cervical cancer cells, promote their apoptosis, and induce the change in cell cycle. Silencing of Foxp3 also reduced the mRNA and protein expressions of p16INK4a in cervical cancer cells. Conclusion: Foxp3 is highly expressed in the cervical cancer, and able to facilitate the proliferation and invasiveness of cervical cancer, change cell cycle and inhibit their apoptosis, resulting in the occurrence, development and metastasis of cervical cancer. PMID:26464616

  9. 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

  10. S100A14, a mediator of epithelial-mesenchymal transition, regulates proliferation, migration and invasion of human cervical cancer cells

    PubMed Central

    Wang, Xiangyu; Yang, Jing; Qian, Jingfeng; Liu, Zhihua; Chen, Hongyan; Cui, Zhumei

    2015-01-01

    S100A14 is an EF-hand calcium-binding protein that has been reported to exert its biological effects on different types of cells. However, the potential clinical significance and biological functions of S100A14 in cervical cancer has not yet been clarified. In this study, we firstly examined the correlation between S100A14 expression and clinical-pathological parameters in cervical cancers. Next, we observed the effect of S100A14 on cell cycle progression, cell proliferation, migration and invasion by employing lentiviral-mediated overexpression and knockdown of S100A14 in cervical cancer cells. Furthermore, we investigated the underlying mechanism of S100A14 affecting cell migration and invasion. Immunohistochemistry analysis demonstrated that S100A14 expression was associated with the International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.025) and lymph node (LN) metastasis (P = 0.001). Functional assays showed that S100A14 overexpression increased the proportion of G2/M phase, promoted cell proliferation, migration, and invasion, whereas S100A14 knockdown exhibited adverse effect on above properties. Mechanistic investigation demonstrated that S100A14 can act as a mediator of epithelial-mesenchymal transition (EMT). And overexpression of S100A14 increased expression of N-cadherin and Vimentin while decreased expression of E-cadherin. The opposite results were observed in S100A14-silenced cells. Taken together, our data indicate that S100A14 has a crucial role in cervical cancer progression. This study significantly increases our understanding of S100A14 functional roles in cervical cancer, which may lead to the development of a novel therapeutic target for cervical cancer. PMID:26101712

  11. PinX1, a novel target gene of p53, is suppressed by HPV16 E6 in cervical cancer cells.

    PubMed

    Wu, Gengze; Liu, Dongbo; Jiang, Ke; Zhang, Li; Zeng, Yijun; Zhou, Peng; Zhong, Dan; Gao, Min; He, Fengtian; Zheng, Yingru

    2014-02-01

    The aberrant activation of telomerase is critical for the initiation and development of human cervical cancer, which is dependent on the activation of human telomerase reverse transcriptase (hTERT). Recently, Pin2/TRF1-interacting protein X1 (PinX1) has been identified as a suppressor of hTERT. It has been found that the telomerase is activated while the level of PinX1 is decreased in cervical cancer. However, the regulatory mechanism of PinX1 in cervical cancer cells remains unclear. In the present study, we demonstrated that the level of PinX1 is regulated by p53, and p53 functions as a transcriptional factor to directly activate the expression of PinX1 in cervical cancer cells. Moreover, we found that HPV16 E6 suppresses the expression of PinX1 via inhibiting p53 transcriptional activity, resulting in the enhancement of telomerase activity. This study not only for the first time shows that PinX1 is a novel target gene of p53 but also suggests that suppression of p53/PinX1 pathway may be a novel mechanism by which HPV16 E6 enhances the telomerase activity in cervical cancer cells. PMID:24412852

  12. 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

  13. 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; Bermdez, Mara A.; Lamelas, Maria Luz; Garcia-Caballero, Toms; Schneider, Jos; 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

  14. Identification of human papillomavirus-16 E6 variation in cervical cancer and their impact on T and B cell epitopes.

    PubMed

    Kumar, Anoop; Hussain, Showket; Yadav, Inderjit Singh; Gissmann, Lutz; Natarajan, K; Das, Bhudev C; Bharadwaj, Mausumi

    2015-06-15

    The infection with high-risk human papillomavirus (HR-HPV) is the most important risk factor for development of cervical cancer. The intra-type variations of HPV have different biological and pathological consequences with respect to disease progression. In the present study, six major Indian variants were experimentally identified in E6 gene of HPV-16 and showed their impact on immunogenicity by in silico methods. Four different phylogenetic lineages were observed in sequences including European (E) prototype, European variant, Asian and American Asian variant classes and complete absence of African phylogenetic lineages. On the prediction of B- and T-cell epitopes, 18 and 23 potent epitopes for MHC-II alleles, 10 potent MHC-I and 15 B-cell epitopes in each reference and variant sequence were identified. Interestingly, the presence of variation H78Y and L83V result in creation of four new epitopes for the HLA-DQA1*0101/DQB1*0501. Out of 15 B-cell predicted epitopes, three most potent epitopes were identified in both reference and variant sequence. Notably the amino acid stretch from amino acid 16-60 and 76-94 are very important for the immunological properties of E6 protein because these regions contain majority of the predicted epitopes. In future, this could control the cervical cancer by targeting these amino acid stretches for the development of HPV-16 vaccine. PMID:25800725

  15. Idaein chloride induced p53 dependent apoptosis in cervical cancer cells through inhibition of viral oncoproteins.

    PubMed

    Natarajan, Thillainathan; Anandhi, Manickam; Aiswarya, Dilipkumar; Ramkumar, Rajendiran; Kumar, Subramanian; Perumal, Pachiappan

    2016-02-01

    Host dependent expression of early HPV oncoproteins, E6 and E7 play central role in the formation of cervical carcinoma. Presently, we have shown that the cyanidin analog, idaein chloride treatment induced dose dependent apoptosis (IC50=2.579?g/ml) in HPV positive - HeLa cells. Flow cytometric analysis showed arrest of cell cycle at G1 phase with an increased sub G1 cell population on 12th h of exposure. The recorded reduced expression levels of cell cycle proteins - cyclin D, cdk 4 and cdk 6 confirmed the occurrence of cell cycle arrest at G1 phase. In addition, the idaein chloride significantly inhibited the expression of E6 and E7 proteins, resulting in p53 re-expression and hence triggering of p53 dependent apoptosis. This has been further supported by the recorded variations in the expression patterns of p21/WAF, pRb and E2F regulatory proteins. In case of mitochondrial apoptotic markers, the expression of Bax was restored and Bcl-2 level got decreased at 12th h. Cleaved caspases 3 & 9 and PARP were also observed after 3h of treatment. Interestingly, the epigenetic regulatory enzymes (DNMTs) were inhibited by idaein chloride. Thus, idaein chloride could be a potent source for developing a drug against cervical carcinoma. PMID:26586108

  16. 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

    2015-10-01

    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.

  17. MiR-17-5p targets TP53INP1 and regulates cell proliferation and apoptosis of cervical cancer cells.

    PubMed

    Wei, Qian; Li, Yi-Xuan; Liu, Min; Li, Xin; Tang, Hua

    2012-08-01

    MicroRNAs are a class of small endogenous noncoding RNAs that function as post-transcriptional regulators. Tumor protein p53-induced nuclear protein 1 (TP53INP1) is a p53 target gene and is a major player in the stress response. Here, we identified TP53INP1 as a target of miR-17-5p. miR-17-5p suppressed cell growth and promoted apoptosis of cervical cancer cells, whereas the effects of TP53INP1 were opposite, and ectopic expression of TP53INP1 counteracted the suppression of cell growth caused by miR-17-5p. The same correlations between miR-17-5p and TP53INP1 were observed in cervical cancer tissues. Together, these results indicated that miR-17-5p functions as a tumor suppressor in cervical cancer cells by targeting TP53INP1. PMID:22730212

  18. 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

  19. Screening for Cervical Cancer

    MedlinePLUS

    ... Evidence-Based Practice Recommendations About the USPSTF Task Force 101 Resources Our Members Our Partners Reports to ... Professionals Recommendations from The Community Preventive Services Task Force on Promoting Cancer Screening Cancer Control P.L. ...

  20. Inhibitory effect and mechanisms of microRNA-146b-5p on the proliferation and metastatic potential of Caski human cervical cancer cells.

    PubMed

    Shen, Cuiping; Yang, Hui; Liu, Hong; Wang, Xiuqin; Zhang, Youzhong; Xu, Rui

    2015-05-01

    Cervical cancer is a common cause of cancer?associate mortality in females, and metastasis is strongly associated with failure of cervical cancer treatment. Previous studies have indicated that microRNA (miR)?146b?5p is involved in the inhibition of proliferation and metastasis of numerous human cancer types. The aim of the present study was to explore the inhibitory effect of miR?156b?5p on the proliferation and metastatic potential of Caski human cervical cancer cells, as well as to determine the mechanisms by which it proceeds. The results demonstrated that miR?146b?5p was able to inhibit the proliferative, invasive and adhesive potential and block the cell cycle progression of Caski human cervical cancer cells, as determined using MTS and transwell assays as well as flow cytometry. Furthermore, quantitative polymerase chain reaction and western blot analysis revealed that transfection with miR?146b?5p decreased the mRNA and protein expression levels of C?X?C chemokine receptor type 4, matrix metalloproteinase?2 and ?9, c?Myc, cyclin D1 and human papilloma virus 16. In addition, the secretion levels of transforming growth factor??, monocyte chemoattractant protein?1 and tumor necrosis factor??, the telomerase activity, the phosphorylation of c?Jun N?terminal protein kinase and protein kinase B and the transcriptional activities of nuclear factor??B, signal transducer and activator of transcription?3 and ?5 were reduced. However, increased levels of p27 and p53 were detected in the miR?146b?5p?overexpressing Caski cells. These results indicate that miR?146b?5p may be a potential therapeutic strategy for the treatment of cervical cancer through regulation of cell chemotaxis and the cell cycle. PMID:25572123

  1. Locking Src/Abl Tyrosine Kinase Activities Regulate Cell Differentiation and Invasion of Human Cervical Cancer Cells Expressing E6/E7 Oncoproteins of High-Risk HPV.

    PubMed

    Yasmeen, Amber; Alachkar, Amal; Dekhil, Hafedh; Gambacorti-Passerini, Carlo; Al Moustafa, Ala-Eddin

    2010-01-01

    In this study, we compared the effects of SKI-606 with Iressa, Src/Abl and EGF-R kinase inhibitors, respectively, on selected parameters in HeLa and SiHa cervical cancer cell lines, which express E6/E7 oncoproteins of high-risk HPV types 18 and 16, respectively. Our results show that SKI-606 and Iressa inhibit cell proliferation and provoke G(0)-G(1) cell cycle arrest and reduction of S and G(2)-M phase using 2 and 5??M concentrations of these inhibitors. In contrast, SKI-606 induces differentiation to an epithelial phenotype "mesenchymal-epithelial transition"; thus SKI-606 causes a dramatic decrease in cell motility and invasion abilities of HeLa and SiHa cancer cells, in comparison to untreated cells and Iressa-treated cells in which these parameters are only slightly affected. These changes are accompanied by a regulation of the expression patterns of E-cadherin and catenins. The molecular pathway analysis of Src/Abl inhibitor revealed that SKI-606 blocks the phosphorylation of ?-catenin and consequently converts its role from a transcriptional regulator to a cell-cell adhesion molecule. Our findings indicate that SKI-606 inhibits signaling pathways involved in regulating tumor cell migration and invasion genes via ?-catenin alteration, suggesting that Src inhibitor, in comparison to EGF-R, is a promising therapeutic agent for human cervical cancer. PMID:20862378

  2. 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.

  3. Cervical Cancer, Version 2.2015.

    PubMed

    Koh, Wui-Jin; Greer, Benjamin E; Abu-Rustum, Nadeem R; Apte, Sachin M; Campos, Susana M; Cho, Kathleen R; Chu, Christina; Cohn, David; Crispens, Marta Ann; Dorigo, Oliver; Eifel, Patricia J; Fisher, Christine M; Frederick, Peter; Gaffney, David K; Han, Ernest; Huh, Warner K; Lurain, John R; Mutch, David; Fader, Amanda Nickles; Remmenga, Steven W; Reynolds, R Kevin; Teng, Nelson; Tillmanns, Todd; Valea, Fidel A; Yashar, Catheryn M; McMillian, Nicole R; Scavone, Jillian L

    2015-04-01

    The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel's discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA's approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches. PMID:25870376

  4. Cordycepin increases radiosensitivity in cervical cancer cells by overriding or prolonging radiation-induced G2/M arrest.

    PubMed

    Seong, Da Bin; Hong, Semie; Muthusami, Sridhar; Kim, Won-Dong; Yu, Jae-Ran; Park, Woo-Yoon

    2016-01-15

    Cordycepin (3-deoxyadenosine) has many pharmacological activities. We studied the radiosensitising effect of cordycepin and the underlying mechanisms relating to cell cycle changes in two human uterine cervical cancer cell lines, ME180 and HeLa cells. Cordycepin produced concentration- and time-dependent reductions in cell viability with more pronounced effects in ME180 cells. Cells pre-treated with cordycepin showed lower cell survival than those exposed to irradiation only. Radiation-induced expression of the histone, ?-H2AX, and apoptosis were also increased following cordycepin pre-treatment. In ME180 cells, pre-treatment with cordycepin reduced radiation-induced G2/M arrest and this G2/M checkpoint override was sustained for longer than in HeLa cells, where G2/M arrest was observed earlier and more briefly, the number of HeLa cells in the G2/M phase was subsequently increased. Cordycepin produced different effects on the expression of p53 and cell cycle checkpoint proteins in these two cell lines. It can be assumed that the mechanism underlying cordycepin-mediated radiosensitisation involves multiple effects that are primarily based on the induction of p53-mediated apoptosis and modulation of the expression of cell cycle checkpoint molecules. PMID:26688569

  5. New vaccine prevents cervical cancer.

    PubMed

    2006-01-01

    The Food and Drug Administration has approved Gardasil, the first vaccine developed to prevent cervical cancer and precancerous genital lesions and genital warts due to certain types of human papillomavirus (HPV). The vaccine is approved for use in females ages 9 years to 26 years. Gardasil was evaluated and approved in six months under the FDA's priority review process--a process for products with potential to provide significant health benefits. PMID:17326311

  6. Cellular uptake of 9-hydroxypheophorbide-? and its photoactivation to induce ER stress-related apoptosis in human cervical cancer cells.

    PubMed

    Ahn, Jin Chul; Biswas, Raktim; Moon, Jeong Hwan; Chung, Phil Sang

    2014-01-01

    The 9-hydroxypheophorbide-? (9-HPbD) is a chlorophyll derivative and was found to be very effective for photodynamic therapy of tumor cells. The current study investigates uptake, retention, and intracellular localization of 9-HPbD by HeLa, human cervical cancer cells via fluorescence spectrophotometry and confocal laser scanning microscopy, and its photodynamic effect against human cervical carcinoma cell. HeLa cells exposed to 9-HPbD exhibited a linear uptake of photosensitizer during the first 12 h, and after removal of 9-HPbD, cell fluorescence was observed to decrease gradually over the next 12 h. Cells treated with 9-HPbD and stained with a panel of organelle-specific fluorescence probes (MitoTracker, LysoTracker, and ER-Tracker) revealed an intracellular fluorescence distribution restricted to cytoplasmic compartments with no detectable fluorescence in the nucleus. The 9-HPbD showed cytotoxicity effect against HeLa cells in 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Endoplasmic reticulum (ER) disruption and cellular calcium dynamics also showed a photoactivation followed by cell death. The apoptotic effect of 9-HPbD was confirmed by caspase 3 activity study and immunofluorescence study of caspase 12. Morphological observation through the transmission electron microscopy and scanning electron microscopy also confirmed that 9-HPbD can induce apoptosis in HeLa cells. Therefore, it can be concluded that maximum uptake and clearance time of 9-HPbD was 12 h with endoplasmic reticulum as the major organelle site in cellular uptake, and 9-HPbD can induce apoptosis in HeLa cells through ER stress-related pathways via activation of caspase 12. PMID:23649612

  7. Synergistic anticancer activity of dietary tea polyphenols and bleomycin hydrochloride in human cervical cancer cell: Caspase-dependent and independent apoptotic pathways.

    PubMed

    Alshatwi, Ali A; Periasamy, Vaiyapuri Subbarayan; Athinarayanan, Jegan; Elango, Ramesh

    2016-03-01

    Bleomycin is a chemotherapeutic agent that is frequently used in the treatment of various cancers. Bleomycin causes serious adverse effects via antioxidant defense abnormalities against reactive oxygen species (ROS). However, the current cervical cancer monodrug therapy strategy has failed to produce the expected outcomes; hence, combinational therapies are gaining great interest. Tea polyphenols are also effective antioxidative and chemo-preventive agents. However, the combined effect of tea polyphenol (TPP) and bleomycin (BLM) against cervical cancer remains unknown. In this study, we focused on the potential of TPP on BLM anticancer activity against cervical cancer cells. Cervical cancer cells (SiHa) were treated with various concentrations of TPP, BLM and TPP combined with BLM (TPP-BLM), and their effects on cell growth, intracellular reactive oxygen species, poly-caspase activity, early apoptosis and the expression of caspase-3, caspase-8 and caspase-9, Bcl-2 and p53 were assessed. The MTT assay revealed that the SiHa cells were less sensitive to growth inhibition by TPP treatment compared with both BLM and the combination therapy. Nuclear staining indicated that exposure to TPP-BLM increased the percentage of apoptotic nuclei compared with a mono-agent treatment. Caspase activation assay demonstrated that proportion of early and late apoptotic/secondary necrotic cells was higher in the cells treated with the combination therapy than in those treated with either TPP or BLM alone. The TPP-BLM treatment synergistically induced apoptosis through caspase-3, caspase-8 and caspase-9 activation, Bcl-2 upregulation and p53 overexpression. This study suggests that TPP-BLM may be used as an efficient antioxidant-based combination therapy for cervical cancer. PMID:26800624

  8. Cervical cancer: A comprehensive approach towards extermination.

    PubMed

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

    2016-05-01

    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. Key messages HPV-related cervical cancer: risk factors, diagnosis and prevention strategies. HPV pathogenesis, diagnosis, and prevention strategies of cervical cancer. Risk factors, diagnosis and prevention strategies of HPV-related cervical cancer. PMID:26911282

  9. Human papillomavirus vaccine and cervical cancer prevention.

    PubMed

    Oaknin, Ana; Barretina, Ma Pilar

    2008-12-01

    Cervical cancer is one of the most common types of cancer in women worldwide, with the highest rates observed in underdeveloped countries. In the last decades, its incidence has decreased after the implementation of screening programs, mainly in developed countries. Infection with high-risk oncogenic HPV is associated with precancerous lesions and cervical cancer. Advances in the understanding of the role of HPV in the etiology of high-grade cervical lesions (CIN 2/3) and cervical cancer have led to the development, evaluation and recommendation of two prophylactic HPV vaccines. This review article provides a summary of the studies related with their development and efficacy. PMID:19068451

  10. 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

  11. Inhibitory effect of snake venom toxin on NF-?B activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression.

    PubMed

    Lee, Hye Lim; Park, Mi Hee; Hong, Ji Eun; Kim, Dae Hwan; Kim, Ji Young; Seo, Hyen Ok; Han, Sang-Bae; Yoon, Joo Hee; Lee, Won Hyoung; Song, Ho Sueb; Lee, Ji In; Lee, Ung Soo; Song, Min Jong; Hong, Jin Tae

    2016-02-01

    We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-?B) activity in several cancer cells. NF-?B is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-?B, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12?g/ml) inhibited the growth of cervical cancer cells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-?B activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-?B inhibitor (Phenylarsine oxide, 0.1?M) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancer cells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-?B inactivation. Using TNF-related apoptosis-inducing ligand resistance cancer cells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancer cells through down-regulation of NF-?B, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1mg/kg) inhibited tumor growth accompanied with inactivation of NF-?B. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervical cancer, or as an adjuvant agent for chemoresistant cancer cells. PMID:25417048

  12. Ultrabright Fluorescent Mesoporous Silica Nanoparticles for Prescreening of Cervical Cancer

    PubMed Central

    Palantavida, Shajesh; Guz, Nataliia V.; Woodworth, C.D.; Sokolov, I.

    2013-01-01

    We report on the first functional use of recently introduced ultrabright fluorescent mesoporous silica nanoparticles, which are functionalized with folic acid, to distinguish cancerous and precancerous cervical epithelial cells from normal cells. The high brightness of the particles is advantageous for fast and reliable identification of both precancerous and cancerous cells. Normal and cancer cells were isolated from three healthy women and three cancer patients. Three precancerous cell lines were derived by immortalization of primary cultures of normal cells with human papillomavirus type-16 (HPV-16) DNA. We observed substantially different particle internalization by normal and cancerous/precancerous cells after a short incubation time of 15 minutes. Compared to HPV-DNA and cell pathology tests, which are currently used for prescreening of cervical cancer, we demonstrated that the specificity of our method was similar (94-95%), whereas its sensitivity was significantly better (95-97%) than the sensitivity of those currently used tests (16%-82%). PMID:23665420

  13. Molecular profiling of cervical cancer progression

    PubMed Central

    Hagemann, T; Bozanovic, T; Hooper, S; Ljubic, A; Slettenaar, V I F; Wilson, J L; Singh, N; Gayther, S A; Shepherd, J H; Van Trappen, P O A

    2007-01-01

    Most cancer patients die of metastatic or recurrent disease, hence the importance to identify target genes upregulated in these lesions. Although a variety of gene signatures associated with metastasis or poor prognosis have been identified in various cancer types, it remains a critical problem to identify key genes as candidate therapeutic targets in metastatic or recurrent cancer. The aim of our study was to identify genes consistently upregulated in both lymph node micrometastases and recurrent tumours compared to matched primary tumours in human cervical cancer. Taqman Low-Density Arrays were used to analyse matched tumour samples, obtained after laser-capture microdissection of tumour cell islands for the expression of 96 genes known to be involved in tumour progression. Immunohistochemistry was performed for a panel of up- and downregulated genes. In lymph node micrometastases, most genes were downregulated or showed expressions equal to the levels found in primary tumours. In more than 50% of lymph node micrometastases studied, eight genes (AKT, BCL2, CSFR1, EGFR1, FGF1, MMP3, MMP9 and TGF-?) were upregulated at least two-fold. Some of these genes (AKT and MMP3) are key regulators of epithelialmesenchymal transition in cancer. In recurrent tumours, almost all genes were upregulated when compared to the expression profiles of the matched primary tumours, possibly reflecting their aggressive biological behaviour. The two genes showing a consistent downregulated expression in almost all lymph node metastases and recurrent tumours were BAX and APC. As treatment strategies are very limited for metastatic and recurrent cervical cancer, the upregulated genes identified in this study are potential targets for new molecular treatment strategies in metastatic or recurrent cervical cancer. PMID:17242701

  14. Effects and Mechanism of Baicalin on Apoptosis of Cervical Cancer HeLa Cells In-vitro

    PubMed Central

    Peng, Yong; Fu, Zhan-zhao; Guo, Cong-Shan; Zhang, Yan-Xia; Di, Ya; Jiang, Bin; Li, Qing-Wang

    2015-01-01

    The objective of this study was to observe the apoptosis-inducing effect and mechanism of baicalin on human cervical cancer HeLa cells. The inhibitory effect of baicalin on the growth of HeLa cells was measured by MTT assay, and cell proliferation and migration was analyzed by cell scratch assay. Morphological changes of apoptotic cells were viewed by the light microscope and electron microscope, and cell growth arrest was confirmed by flow cytometry. Moreover, Western blot was used for investigating the expression of apoptosis related proteins; spectrophotometry was used to examine Caspase-3 activation. Our results showed that baicalin could inhibit the proliferation of HeLa Cells via induction of apoptosis in a time and dose-dependent manner (P<0.01). Apoptotic signaling induced by baicalin was characterized by up-regulating Bax, Fas, FasL and Caspase-8 protein expression, and down-regulating of Bcl-2 protein expression. These results indicated that baicalin-induced apoptosis involved activation Caspase-3 in HeLa cells through the intracellular mitochondrial pathway and the surface death receptor pathway. PMID:25561931

  15. Autophagy promotes paclitaxel resistance of cervical cancer cells: involvement of Warburg effect activated hypoxia-induced factor 1-?-mediated signaling

    PubMed Central

    Peng, X; Gong, F; Chen, Y; Jiang, Y; Liu, J; Yu, M; Zhang, S; Wang, M; Xiao, G; Liao, H

    2014-01-01

    Paclitaxel is one of the most effective chemotherapy drugs for advanced cervical cancer. However, acquired resistance of paclitaxel represents a major barrier to successful anticancer treatment. In this study, paclitaxel-resistant HeLa sublines (HeLa-R cell lines) were established by continuous exposure and increased autophagy level was observed in HeLa-R cells. 3-Methyladenine or ATG7 siRNA, autophagy inhibitors, could restore sensitivity of HeLa-R cells to paclitaxel compared with parental HeLa cells. To determine the underlying molecular mechanism, differentially expressed proteins between HeLa and HeLa-R cells were identified by two-dimensional gel electrophoresis coupled with electrospray ionization quadrupole time-of-flight MS/MS. We found glycolysis-associated proteins were upregulated in HeLa-R cell lines. Inhibition of glycolysis by 2-deoxy-D-glucose or koningic acid could decrease autophagy and enhance sensitivity of HeLa-R cells to paclitaxel. Moreover, glycolysis could activate HIF1-?. Downregulation of HIF1-? by specific siRNA could decrease autophagy and resensitize HeLa-R cells to paclitaxel. Taken together, a possible Warburg effect activated HIF1-?-mediated signaling-induced autophagic pathway is proposed, which may provide new insight into paclitaxel chemoresistance. PMID:25118927

  16. Cervical cancer screening. Organised screening to avoid unnecessary conisation.

    PubMed

    2010-08-01

    The incidence of cervical cancer and related deaths has fallen gradually since 1970 in several European countries. The following article examines the role of screening in this reduced mortality, and the potential harms of cervical screening, based on a review of the literature using the standard Prescrire methodology. Cervical cancer is mainly due to persistent infection with certain types of human papillomavirus. Progression to invasive cervical cancer is slow and infrequent. Cervical screening is based on taking a sample of superficial cervical cells for the detection of atypical cells associated with malignant transformation. Women with suspect findings initially undergo colposcopy, followed by more invasive procedures such as biopsy, conisation and surgery, if necessary. Detection of high-grade lesions is similarly efficient whether the sampled cervical epithelial cells are examined immediately on slides or first suspended in a preservative solution (liquid-based cytology). The sensitivity of cervical smear testing for detecting high-grade intraepithelial lesions depends on the sample quality and the experience and training of the person who collects the sample and the person who reads the slides. False-positive and false-negative results are frequent. There are no randomised trials comparing outcomes between women who have regular cervical screening and women who are never screened. Several case-control studies have shown a strong statistical correlation between screening and a reduced risk of cervical cancer. In particular, a British study showed that the risk of being diagnosed with invasive cancer between the ages of 40 and 65 years was 4 times lower among women who had been screened in the previous 5 years than in women who had not been screened. Historical studies, which can only provide a low level of evidence, suggest that the decline in cervical cancer mortality observed in several parts of the world is proportional to participation in screening. In England, the decline in cervical cancer accelerated when screening was better organised and participation increased markedly. Conisation consists of partial surgical excision of the cervix, sometimes for diagnostic purposes after a suspect smear result. It can cause bleeding and has been linked to a risk of preterm delivery in subsequent pregnancies. Most comparative studies have focused on organised screening programmes. In one case-control study, organised screening was more effective than opportunistic screening in reducing the incidence of cervical cancer. The results of case-control studies and epidemiological studies suggest that screening is unnecessary before the age of 21, or in the 3 years after first intercourse. Some data suggest that screening should continue until age 70, at least for some women. Pregnancy is associated with an increased frequency of atypical cells. Immunodepression, due to HIV infection for example, increases the risk of cervical cancer, but the optimal screening frequency for these women is not known. All current guidelines recommend colposcopy for women with high-grade lesions, with a view to performing a biopsy or conisation. In summary, screening has not been shown to reduce the risk of cervical cancer in randomised controlled trials, but retrospective comparisons strongly suggest that regular well-organised smear testing prevents a number of deaths due to cervical cancer. It should be remembered that many cellular atypia found on cervical smears never progress to cancer. The frequency of overdiagnosis has not been studied. Smear-based screening appears to have very few serious adverse effects. In practice, despite the lack of solid evidence, it seems unreasonable not to recommend screening for cervical cancer. Organised screening is preferable to opportunistic screening performed without quality controls and without research to optimise screening strategy. PMID:20939454

  17. Cervical Cancer Rates by Race and Ethnicity

    MedlinePLUS

    ... from cervical cancer varies by race and ethnicity. Incidence Rates by Race/Ethnicity “Incidence rate” means how many women out of a ... which numbers have been reported. The cervical cancer incidence rate is grouped by race and ethnicity. The ...

  18. Induction of Apoptotic Effects of Antiproliferative Protein from the Seeds of Borreria hispida on Lung Cancer (A549) and Cervical Cancer (HeLa) Cell Lines

    PubMed Central

    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?g to 1000?g/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?g/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

  19. 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.

  20. 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.

  1. Calcitriol increases Dicer expression and modifies the microRNAs signature in SiHa cervical cancer cells.

    PubMed

    Gonzlez-Duarte, Ramiro Jos; Czares-Ordoez, Verna; Romero-Crdoba, Sandra; Daz, Lorenza; Ortz, Vctor; Freyre-Gonzlez, Julio Augusto; Hidalgo-Miranda, Alfredo; Larrea, Fernando; Avila, Euclides

    2015-08-01

    MicroRNAs play important roles in cancer biology. Calcitriol, the hormonal form of vitamin D3, regulates microRNAs expression in tumor cells. In the present study we asked if calcitriol would modify some of the components of the microRNA processing machinery, namely, Drosha and Dicer, in calcitriol-responsive cervical cancer cells. We found that calcitriol treatment did not affect Drosha mRNA; however, it significantly increased Dicer mRNA and protein expression in VDR-positive SiHa and HeLa cells. In VDR-negative C33-A cells, calcitriol had no effect on Dicer mRNA. We also found a vitamin D response element in Dicer promoter that interacts in vitro to vitamin D and retinoid X receptors. To explore the biological plausibility of these results, we asked if calcitriol alters the microRNA expression profile in SiHa cells. Our results revealed that calcitriol regulates the expression of a subset of microRNAs with potential regulatory functions in cancer pathways, such as miR-22, miR-296-3p, and miR-498, which exert tumor-suppressive effects. In summary, the data indicate that in SiHa cells, calcitriol stimulates the expression of Dicer possibly through the vitamin D response element located in its promoter. This may explain the calcitriol-dependent modulation of microRNAs whose target mRNAs are related to anticancer pathways, further adding to the various anticancer mechanisms of calcitriol. PMID:26111345

  2. Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and Invasion of Human Cervical Cancer Cells

    PubMed Central

    Wang, Sen; An, Weifang; Yao, Yunhong; Chen, Renhuai; Zheng, Xiaoxuan; Yang, Wanyong; Zhao, Yi; Hu, Xinrong; Jiang, Enping; Bie, Yanhong; Chen, Zhangquan; Ouyang, Ping; Zhang, He; Xiong, Hui

    2015-01-01

    Objectives: The most recently discovered cytokine interleukin 37 (IL-37) received growing attention. Its function on tumor is largely unknown. Here, we investigated the biological function of IL-37 on cervical cancer (CC). Materials and methods: HPV+ Hela cells and HPV- C33A cells were used. RT-qPCR was performed to detect the transcription of IL-37, STAT3, TNF-?and IL-1?. Western blotting was used for protein detection. CCK-8 assay and transwell assay were employed for cell proliferation and invasion detection, respectively. Results: Successful gene transfection of IL-37 suppressed the proliferation and invasion of CC. Interestingly, IL-37 showed higher anticancer ability in HPV+ Hela cells than that in HPV- C33A cells. Then, the molecular mechanism of IL-37 anticancer was explored. Firstly, we found that IL-37 inhibited STAT3 expression at both mRNA and protein levels. IL-37 also down regulated the phosphorylation of STAT3. Secondly, blockage of STAT3 using siRNAs reduced significantly the ability of IL-37 to suppress cell proliferation and invasion. Thirdly, STAT3 knockdown reduced markedly the inhibition of IL-37 on the transcription of tumor-derived TNF-? and IL-1?, indicating the contribution of STAT3 for the cancer associated antiinflammation of IL-37. Finally, STAT3 up regulation restored the ability of cell proliferation, cell invasion and the expression of inflammatory cytokines, TNF-? and IL-1?. Conclusions: IL-37 suppressed cell proliferation and invasion of CC and STAT3 is involved in this process. Thus, IL-37 emerges as a new anticancer cytokine for CC. This study demonstrated a new biological function of IL-37 and offered a potential molecule for CC treatment. PMID:26316892

  3. 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 11.000.707?M and the derivatives, compounds 4 and 11 showed a GI50 value of 8.330.416?M and 9.130.177?M respectively in HeLa cells and was found to be non-toxic to H9C2 cells up to 20?M. 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. PMID:26807764

  4. 8-p-Hdroxybenzoyl Tovarol Induces Paraptosis Like Cell Death and Protective Autophagy in Human Cervical Cancer HeLa Cells

    PubMed Central

    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. PMID:26147427

  5. A new 2-pyrone derivative, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one, synergistically enhances radiation sensitivity in human cervical cancer cells.

    PubMed

    Woo, Soo-Jung; Kim, Min-Jung; Kim, Rae-Kwon; Yoon, Chang-Hwan; Lim, Eun-Jung; An, Sungkwan; Suh, Yongjoon; Song, Ji-Young; Kim, In Gyu; Cho, Cheon-Gyu; Lee, Su-Jae

    2012-01-01

    Radiation resistance can be overcome by a combination treatment with chemical modifiers. Here, we showed that treatment with 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP), a new 2-pyrone derivative, in combination with ionizing radiation enhances the sensitivity of human cervical cancer cells to ionizing radiation through overproduction of reactive oxygen species (ROS). The combined treatment with BHP and ionizing radiation caused a decrease in clonogenic survival and an increase in apoptotic cell death in cervical cancer cells. The combined treatment promoted conformational activation of Bax and led to mitochondrial apoptotic cell death. The combination treatment also induced a marked increase in intracellular ROS level. Inhibition of ROS attenuated the radiosensitizing effect of BHP, concurrent with a decrease in Bax activation, a decrease in mitochondrial cell death, and an increase in clonogenic survival. These results indicate that BHP synergistically enhances sensitivity of human cervical cancer cells to ionizing radiation through elevation of intracellular ROS and that ROS-dependent Bax activation is critically involved in the increase in apoptotic cell death induced by the combined treatment with BHP and ionizing radiation. PMID:21849886

  6. 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 g/mL to 50 g/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. PMID:26413627

  7. 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. PMID:25891953

  8. 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

  9. Human papillomavirus and vaccination in cervical cancer.

    PubMed

    Wang, Kung-Liahng

    2007-12-01

    Cervical cancer is not only the most frequently reported cancer among women, but also the most common female genital tract neoplasm in Taiwan. Early detection is effective, because the development, maintenance and progression of precursor lesions (cervical intraepithelial neoplasia [CIN]) evolve slowly into invasive cancer, typically over a period of more than 10 years. It is now recognized that human papillomavirus (HPV) infection is a necessary cause for over 99% of cervical cancer cases. Advances in the understanding of the causative role of HPV in the etiology of high-grade cervical lesions (CIN 2/3) and cervical cancer have led to the development, evaluation and recommendation of HPV-based technologies for cervical cancer prevention and control. The prevention of HPV infection before the onset of CIN is now possible with recently available prophylactic HPV vaccines, e.g. the quadrivalent Gardasil (Merck & Co., NJ, USA) and bivalent Cervarix (GlaxoSmithKline, London, UK). This review article provides an up-to-date summary of recent studies and available information concerning HPV and vaccination in cervical cancer. PMID:18182340

  10. Green synthesis of bimetallic Au@Pt nanostructures and their application for proliferation inhibition and apoptosis induction in human cervical cancer cell.

    PubMed

    Alshatwi, Ali A; Athinarayanan, Jegan; Periasamy, Vaiyapuri Subbarayan

    2015-03-01

    Bimetallic Au@Pt nanostructures (Au@Pts) are potential candidates for optical, electrical, catalytic and biological applications. However, methods for the fabrication of Au@Pts using total tea polyphenols (TPPs), studies of the mechanism of action of Au@Pts on biological systems and studies on the application of Au@Pts in cancer diagnosis and therapy are sparse. In this study, we developed a simple, eco-friendly and low-cost method for the synthesis of Au@Pts to examine the cytotoxic effect of these Au@Pts on human cervical cancers in vitro. The gold and platinum ions were successfully reduced simultaneously using TPPs at room temperature. The prepared Au@Pts were characterized using UV-Vis spectrophotometery, X-ray diffractometery (XRD), energy-dispersive X-ray spectroscopy (EDS), and transmission electron microscopy (TEM). EDS and XRD confirmed the formation of the Au@Pt. Formation of Au@Pts with a size of 5-20 nm was confirmed using TEM. The cytotoxic properties of the Au@Pts were evaluated in human cervical cancer cells (SiHa). The cell viability results revealed that Au@Pts induce cell death in a dose- and time-dependent manner. The morphological features of the Au@Pt-exposed SiHa cells were observed and indicated cell death via cell shrinkage, intranucleosomal DNA fragmentation and chromatin condensation. During progression of the different phases of the cell cycle, the proportion of cells in the G2/M phase of the treated SiHa cells was significantly increased, which strongly confirmed that the Au@Pts induced apoptosis through the G2/M phase check points. Our findings demonstrate the activity of Au@Pts against cervical cancer cells and reveal strategies for the development of highly active bimetallic nanostructures for cancer therapeutics. PMID:25764083

  11. 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. PMID:25494339

  12. Breast and Cervical Cancer Screening

    PubMed Central

    Ludman, Evette J.; Ichikawa, Laura E.; Simon, Gregory E.; Rohde, Paul; Arterburn, David; Operskalski, Belinda H.; Linde, Jennifer A.; Jeffery, Robert W.

    2010-01-01

    Background Obesity and depression may each be associated with less cervical and breast cancer screening. Studies have examined obesity or depression alone, but not together, despite the established link between them. Purpose To disentangle the effects of depression and obesity on receipt of breast and cervical cancer screening. Methods A stratified sampling design was used to recruit women aged 40–65 years with information on BMI from an integrated health plan in Washington in 2003–2005. A telephone survey included the PHQ-9 for depression, weight, and height. Automated data assessed Paps for 3097 women over a 3-year period and screening mammograms over a 2-year period for 2163 women aged ≥51 years. Logistic regression models (conducted in 2008) examined the association between obesity and depression and receipt of screening tests. Results In univariate logistic regression models, women were less likely to receive a Pap if they were obese (OR = 0.53, 95% CI 0.41–0.69) or depressed (OR = 0.60, 95% CI= 0.42–0.87). Women were less likely to receive a screening mammogram if they were depressed (OR = 0.45, 95% CI= 0.30–0.67). In multivariable models, only obesity remained significantly associated with lower likelihood of Pap screening (OR =0.67, 95% CI= 0.0.49–0.93) and only depression remained significantly associated with less screening mammography (OR =0.49, 95% CI 0.31–0.76). Obesity and depression did not interact significantly in either model. Conclusions Obesity and depression appear to have specific effects on receipt of different cancer screening tests. PMID:20171532

  13. 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

  14. 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 (19931997), during (19982002), and after (20032012) 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), 1.371.62; after introduction of CCRT, HR = 1.40; 95% CI, 1.301.50). 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

  15. Overexpression of Notch1 is associated with the progression of cervical cancer

    PubMed Central

    SUN, YAN; ZHANG, RUI; ZHOU, SHUJUAN; JI, YUQIANG

    2015-01-01

    Cervical cancer is the third most common malignancy worldwide, accounting for 250,000 mortalities annually. Notch1, an important regulator of cell-fate decisions and differentiation, has been found to be overexpressed in certain types of cancer. However, the role of Notch1 in cervical carcinogenesis remains unclear. In the present study, immunohistochemical staining and western blot analysis revealed that Notch1 expression was significantly higher in cervical cancer tissues than that in normal cervical tissues. Furthermore, statistical analysis revealed that Notch1 expression was significantly associated with tumor differentiation and tumor stage. These findings indicated that Notch1 expression was associated with the progression of cervical cancer. The western blot assay also identified a positive correlation between Notch1 and Ki67 expression in cervical cancer tissues, which suggested that Notch1 expression may be associated with the proliferation of cervical cancer. In order to further evaluate the specific role of Notch1 in cervical cancer progression, its expression in SiHa and C33A cells was knocked down using small interfering RNA. It was revealed that the knockdown of Notch1 in SiHa and C33A cells resulted in significant inhibition of cell proliferation and colony formation in vitro. These results indicated that Notch1 was able to promote cell proliferation in cervical cancer. In conclusion, the results of the present study indicated that Notch1 may function as a promoter in cervical carcinogenesis. PMID:26137140

  16. The Korean guideline for cervical cancer screening.

    PubMed

    Min, Kyung Jin; Lee, Yoon Jae; Suh, Mina; Yoo, Chong Woo; Lim, Myong Cheol; Choi, Jaekyung; Ki, Moran; Kim, Yong Man; Kim, Jae Weon; Kim, Jea Hoon; Park, Eal Whan; Lee, Hoo Yeon; Lim, Sung Chul; Cho, Chi Heum; Hong, Sung Ran; Dang, Ji Yeon; Kim, Soo Young; Kim, Yeol; Lee, Won Chul; Lee, Jae Kwan

    2015-07-01

    The incidence rate of cervical cancer in Korea is still higher than in other developed countries, notwithstanding the national mass-screening program. Furthermore, a new method has been introduced in cervical cancer screening. Therefore, the committee for cervical cancer screening in Korea updated the recommendation statement established in 2002. The new version of the guideline was developed by the committee using evidence-based methods. The committee reviewed the evidence for the benefits and harms of the Papanicolaou test, liquid-based cytology, and human papillomavirus (HPV) testing, and reached conclusions after deliberation. The committee recommends screening for cervical cancer with cytology (Papanicolaou test or liquid-based cytology) every three years in women older than 20 years of age (recommendation A). The cervical cytology combined with HPV test is optionally recommended after taking into consideration individual risk or preference (recommendation C). The current evidence for primary HPV screening is insufficient to assess the benefits and harms of cervical cancer screening (recommendation I). Cervical cancer screening can be terminated at the age of 74 years if more than three consecutive negative cytology reports have been confirmed within 10 years (recommendation D). PMID:26197860

  17. Apoptosis Induction of Salvia chorassanica Root Extract on Human Cervical Cancer Cell Line

    PubMed Central

    Parsaee, Heydar; Asili, Javad; Mousavi, Seyed Hadi; Soofi, Hojjat; Emami, Seyed Ahmad; Tayarani-Najaran, Zahra

    2013-01-01

    Salvia chorassanica Bunge is one of the Iranian endemic species of Salvia. There is not any reported literature on S. chorassanica. This study was designed to examine the in-vitro anti-proliferative and proapoptotic effects of the methanol extract of S. chorassanica and its fractions on HeLa cell line. Cells were cultured in EX-CELL, an animal free medium specially designed for HeLa cell line and incubated with different concentrations of plant extracts. Cell viability was quantified by MTS assay. Apoptotic cells were determined using propidium iodide (PI) staining of DNA fragmentation by flow cytometry (sub-G1 peak). Activity of caspase -3, -8 and -9 was measured by the caspase colorimetric kit assay. S. chorassanica inhibited the growth of malignant cells and the CH2Cl2 fraction was determined as the most cytotoxic fraction in comparison with other fractions. The calculated IC50 values for methanol extract, n-hexane, CH2Cl2 and EtOAc fractions were 8.841, 5.45, 2.38, and 58.03 ?g/mL, respectively. S. chorassanica induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that the cytotoxic mechanism is characterized by apoptosis induction. The activity of caspase-3 and 8 proteins in treated HeLa cells was significantly higher than that of the control while caspase-9 activity did not change significantly. Based on the result obtained from our study, the apoptosis pathway involved in S. chorassanica-induced cell death may be through the extrinsic pathway and it can be a novel promising candidate in the treatment of cancer. PMID:24250574

  18. Heat shock protein 90 inhibitor mycoepoxydiene modulates kinase signaling in cervical cancer cells and inhibits in-vivo tumor growth.

    PubMed

    Lin, Peng; Yi, Yuting; Lu, Mingke; Wang, Miaomiao; Yang, Yang; Lu, Yue; Song, Siyang; Zheng, Zhonghui; Deng, Xianming; Zhang, Lianru

    2015-01-01

    Heat shock protein 90 (Hsp90) functions within multiple signaling pathways on the basis of its ability to serve as a chaperone for more than 100 client proteins. Thus, inhibition of Hsp90 alone can trigger numerous pathways. Mycoepoxydiene (MED) can inhibit Hsp90 function and induce apoptosis in cervical cancer cells. However, the antitumor efficacy of MED in vivo is still not clear. We examined the efficacy of MED in a mouse xenograft model to further elucidate HeLa cell fate and also assessed the mechanism of altered protein signaling in response to this compound in vitro. Our data showed that Hsp90 inhibition simultaneously triggers signaling that regulates both cell death and cell proliferation, and that HeLa cell death may be a result of the disequilibrium of these signals. MED induces cell death as a result of the destabilization of Akt and IKK, which may promote cell death through a reduction in the activation of Bad and nuclear factor-?B. However, MED also induces the MEK/ERK pathway, which is classically considered to promote cell survival. MEK/ERK activation leads to an increase in p21, a cyclin-dependent kinase inhibitor, and is independent of Raf, but is shown to be mediated by p53. MED also leads to a decrease in several additional G2/M regulatory proteins independent of the MEK/ERK pathway. These results indicate an interesting mechanism of cross-talk between the inhibition of Akt phosphorylation and the activation of the MEK pathway by MED and provide in-vivo evidence for the potential of inhibiting Hsp90 as a candidate anticancer treatment. PMID:25014191

  19. Somatic LKB1 Mutations Promote Cervical Cancer Progression

    PubMed Central

    Wingo, Shana N.; Gallardo, Teresa D.; Akbay, Esra A.; Liang, Mei-Chi; Contreras, Cristina M.; Boren, Todd; Shimamura, Takeshi; Miller, David S.; Sharpless, Norman E.; Bardeesy, Nabeel; Kwiatkowski, David J.; Schorge, John O.; Wong, Kwok-Kin; Castrillon, Diego H.

    2009-01-01

    Human Papilloma Virus (HPV) is the etiologic agent for cervical cancer. Yet, infection with HPV is not sufficient to cause cervical cancer, because most infected women develop transient epithelial dysplasias that spontaneously regress. Progression to invasive cancer has been attributed to diverse host factors such as immune or hormonal status, as no recurrent genetic alterations have been identified in cervical cancers. Thus, the pressing question as to the biological basis of cervical cancer progression has remained unresolved, hampering the development of novel therapies and prognostic tests. Here we show that at least 20% of cervical cancers harbor somatically-acquired mutations in the LKB1 tumor suppressor. Approximately one-half of tumors with mutations harbored single nucleotide substitutions or microdeletions identifiable by exon sequencing, while the other half harbored larger monoallelic or biallelic deletions detectable by multiplex ligation probe amplification (MLPA). Biallelic mutations were identified in most cervical cancer cell lines; HeLa, the first human cell line, harbors a homozygous 25 kb deletion that occurred in vivo. LKB1 inactivation in primary tumors was associated with accelerated disease progression. Median survival was only 13 months for patients with LKB1-deficient tumors, but >100 months for patients with LKB1-wild type tumors (P = 0.015, log rank test; hazard ratio = 0.25, 95% CI = 0.083 to 0.77). LKB1 is thus a major cervical tumor suppressor, demonstrating that acquired genetic alterations drive progression of HPV-induced dysplasias to invasive, lethal cancers. Furthermore, LKB1 status can be exploited clinically to predict disease recurrence. PMID:19340305

  20. Somatic LKB1 mutations promote cervical cancer progression.

    PubMed

    Wingo, Shana N; Gallardo, Teresa D; Akbay, Esra A; Liang, Mei-Chi; Contreras, Cristina M; Boren, Todd; Shimamura, Takeshi; Miller, David S; Sharpless, Norman E; Bardeesy, Nabeel; Kwiatkowski, David J; Schorge, John O; Wong, Kwok-Kin; Castrillon, Diego H

    2009-01-01

    Human Papilloma Virus (HPV) is the etiologic agent for cervical cancer. Yet, infection with HPV is not sufficient to cause cervical cancer, because most infected women develop transient epithelial dysplasias that spontaneously regress. Progression to invasive cancer has been attributed to diverse host factors such as immune or hormonal status, as no recurrent genetic alterations have been identified in cervical cancers. Thus, the pressing question as to the biological basis of cervical cancer progression has remained unresolved, hampering the development of novel therapies and prognostic tests. Here we show that at least 20% of cervical cancers harbor somatically-acquired mutations in the LKB1 tumor suppressor. Approximately one-half of tumors with mutations harbored single nucleotide substitutions or microdeletions identifiable by exon sequencing, while the other half harbored larger monoallelic or biallelic deletions detectable by multiplex ligation probe amplification (MLPA). Biallelic mutations were identified in most cervical cancer cell lines; HeLa, the first human cell line, harbors a homozygous 25 kb deletion that occurred in vivo. LKB1 inactivation in primary tumors was associated with accelerated disease progression. Median survival was only 13 months for patients with LKB1-deficient tumors, but >100 months for patients with LKB1-wild type tumors (P = 0.015, log rank test; hazard ratio = 0.25, 95% CI = 0.083 to 0.77). LKB1 is thus a major cervical tumor suppressor, demonstrating that acquired genetic alterations drive progression of HPV-induced dysplasias to invasive, lethal cancers. Furthermore, LKB1 status can be exploited clinically to predict disease recurrence. PMID:19340305

  1. Laparoscopic fertility sparing management of cervical cancer.

    PubMed

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

    2014-04-01

    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

  2. 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

  3. 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

  4. 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 (GSK3?, 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

  5. NIH Research Leads to Cervical Cancer Vaccine

    MedlinePLUS

    Skip Navigation Bar Home Current Issue Past Issues Sexually Transmitted Diseases NIH Research Leads to Cervical Cancer Vaccine Past ... Community-wide treatment of curable sexually transmitted infections (STDs) reduced STD rates, and improved pregnancy outcomes, but ...

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

    PubMed

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

    2016-12-01

    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. PMID:26887578

  7. 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.

  8. Complementary Roles of Squamous Cell Carcinoma Antigen and 18F-FDG PET/CT in Suspected Recurrence of Cervical Squamous Cell Cancer

    PubMed Central

    Hu, Ying-Ying; Fan, Wei; Zhang, Xu; Liang, Pei-Yan; Lin, Xiao-Ping; Zhang, Ya-Rui; Li, Yuan-Hua

    2015-01-01

    Purpose: To assess the clinical value of FDG PET/CT and evaluate the complementary roles of serum squamous cell carcinoma antigen (SCCAg) and FDG PET/CT in the diagnosis of suspected recurrent of cervical squamous cell cancer. Methods: Serum SCCAg levels were retrospectively reviewed in patients previously treated for cervical squamous cell carcinoma, who had suspected recurrence of cervical cancer and who had undergone FDG PET/CT scans. The clinical impact of elevated SCCAg (>1.5 ng/ml) and negative SCCAg (?1.5 ng/ml) levels were analyzed based on the results of PET/CT and final diagnosis. Results: The overall patient-based sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of PET/CT for the detection of tumor recurrence or malignancy were 100% (86/86), 80.8% (21/26), 95.5% (107/112), 94.5% (86/91) and 100% (21/21), respectively. Of the 112 patients included in this study, recurrence or malignancy was detected by PET/CT in 62 of the 64 patients with elevated SCCAg, compared to 24 of the 48 patients with negative SCCAg levels. The overall patient-based PPV, NPV, sensitivity and accuracy of SCCAg for the detection of tumor recurrence or malignancy were 96.9% (62/64), 50% (24/48), 72.1% (62/86) and 76.8% (86/112), respectively. The five false-positive PET/CT results were all associated with patients with negative SCCAg levels. The PPV of positive PET/CT-associated elevated SCCAg for the detection of tumor recurrence or malignancy was 100% (62/62). The NPV of negative SCCAg-associated negative PET/CT was 100% (19/19). Conclusions: Serum SCCAg evaluation and FDG PET/CT imaging can be complementary techniques in cases of suspected recurrent cervical squamous cancer. Positive PET/CT with elevated SCCAg can predict recurrence. Although PET/CT cannot confidently be deferred due to a negative SCCAg test, the possibility of a false-positive PET/CT in those cases may have diagnostic importance. PMID:25663947

  9. Proteomic analysis of progressive factors in uterine cervical cancer.

    PubMed

    Choi, Yoon Pyo; Kang, Suki; Hong, Sunghee; Xie, Xianhe; Cho, Nam Hoon

    2005-04-01

    Human papillomavirus (HPV) infections play a crucial role in the progress of cervical cancer. The high-risk HPV types are frequently associated with the development of malignant lesions. Some of the latest studies have demonstrated that the high-risk HPV 16 and 18 are predominantly detected in the more aggressive cancers. In the present study, we aimed to establish the proteomic profiles and characterization of the tumor related proteins by using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). For proteomic analysis, patients infected by HPV 16 or 18 were included in this study. We compared nuclear protein and cytoplasmic protein, separately by using the subcellular fraction. Differential protein spots between cervical cancer with high-risk HPV, HPV 16 or HPV 18, and HaCaT cell lines were characterized by 2-DE. Those proteins analyzed by peptide mass fingerprinting based on MALDI-TOF MS and database searching were the products of oncogenes or proto-oncogenes, and the others were involved in the regulation of cell cycle, for general genomic stability, telomerase activation, and cell immortalization. However, there was no difference in protein characterization for cervical cancer between HPV 16 and HPV 18 infection. Nonetheless, these data are valuable for the mass identification of differentially expressed proteins involved in human uterine cervical cancer. Moreover, the data has enormous value for establishing the human uterine cervical cancer proteome database that can be used in screening a molecular marker for the further study of human uterine cervical cancer, and also for studying any correlation among the cancers induced by HPV. PMID:15838902

  10. Latex of Euphorbia antiquorum-induced S-phase arrest via active ATM kinase and MAPK pathways in human cervical cancer HeLa cells.

    PubMed

    Hsieh, Wen-Tsong; Lin, Hui-Yi; Chen, Jou-Hsuan; Lin, Wen-Chung; Kuo, Yueh-Hsiung; Wood, W Gibson; Lu, Hsu-Feng; Chung, Jing-Gung

    2015-09-01

    Latex of Euphorbia antiquorum (EA) has demonstrated great chemotherapeutic potential for cancer. However, the mechanisms of anti-proliferation of EA on cancer cell remain to be further investigated. The purpose of this study was to explore the influence of EA in human cervical cancer cells. Here, the cell cycle distribution by flow cytometry was examined and the protein expression by the western blotting methods was analyzed. From the cytometric results it was shown that EA-induced S-phase arrest in a concentration manner both in human cervical cancer HeLa and CaSki cells. According the western blot results it was illustrated that EA could downregulate early cyclin E1-Cdk2; and cyclin A-Cdc2 provides a significant additional quantity of S-phase promotion, that in turn promoted the expression of p21(waf1/cip1) and p27(kip1) which were the inhibitors in the complex of cyclin A and Cdc2 that led to cell cycle arrest. Moreover, EA promoted the activation of ataxia telangiectasia mutated (ATM) and check-point kinase-2 (Chk2); however, it negatively regulated the expression of Topoisomerases I and II, Cdc25A, and Cdc25C signaling. Caffeine, an ATM/ATR inhibitor significantly reversed EA downregulation in the levels of Cdc25A. Furthermore, JNK inhibitor SP600125 and p38 MAPK inhibitor SB203580 both could reverse the EA upregulation of the protein of Chk2 level, significantly. This study, therefore, revealed that EA could downregulate topoisomerase, and activate ATM kinase, which then induce parallel Chk 1/2 and MAPK signaling pathways to promote the degradation of Cdc25A to induced S-phase arrest in human cervical cancer HeLa cells. PMID:24706497

  11. DNA methylation changes in cervical cancers.

    PubMed

    Lu, Qiang; Ma, Dehua; Zhao, Shuping

    2012-01-01

    Cervical carcinoma is one of the major causes of death in women worldwide. It is difficult to foresee a dramatic increase in cure rate even with the most optimal combination of cytotoxic drugs, surgery, and radiation; therefore, testing of molecular targeted therapies against this malignancy is highly desirable. Cervical cancer is a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes, leading to activation of oncogenes and inactivation or loss of tumor suppressor genes (TSGs). In the last decade, in addition to genetic alterations, epigenetic inactivation of TSGs by promoter hypermethylation has been recognized as an important and alternative mechanism in tumorigenesis. In cervical cancer, epigenetic alterations can affect the expression of papillomavirus as well as host genes in relation to stages representing the multistep process of carcinogenesis. Here we discuss these epigenetic alterations in cervical cancer focusing on DNA methylation. PMID:22359292

  12. Cervical cancer in India and HPV vaccination.

    PubMed

    Kaarthigeyan, K

    2012-01-01

    Cervical cancer, mainly caused by Human Papillomavirus infection, is the leading cancer in Indian women and the second most common cancer in women worldwide. Though there are several methods of prevention of cervical cancer, prevention by vaccination is emerging as the most effective option, with the availability of two vaccines. Several studies have been published examining the vaccine's efficacy, immunogenicity and safety. Questions and controversy remain regarding mandatory vaccination, need for booster doses and cost-effectiveness, particularly in the Indian context. PMID:22754202

  13. Distribution and location of Daxx in cervical epithelial cells with high risk human papillomavirus positive

    PubMed Central

    2014-01-01

    Aims To provide the basis for further exploring the effect and its mechanism of Death domain associated protein (Daxx) on the progress of cervical carcinoma induced by human papillomavirus (HPV), the distribution and location of Daxx in cervical carcinoma with high risk HPV(HR-HPV) positive was analyzed. Methods The samples of normal cervical epithelial cells, cervical intraepithelial neoplasia grade I (CINI), CINII CINIII and cervical cancers were collected. Immunohistochemistry assay was used to analyze the distributions and locations of Daxx in the cervical tissue. Indirect immunoinfluorescence test was utilized to observe the locations of Daxx in Caski cells with HPV16 positive. Results Under the light microscopy, the brown signals of Daxx distributed in the nuclei of normal cervical epithelial cells; Daxx mainly distributed in nuclear membrane and there were a small amount of Daxx in the nuclei in CINI. Daxx intensively distributed in the cytoplasm and cell membrane in CINII, CINIII and cervical cancer. Under fluorescent microscopy, the distribution and location of Daxx in Caski cells was similarly to that in cervical cells of CINII, CINIII and cervical cancer. Conclusion In the progress of the cervical cancer, Daxx gradually translocates from nucleus into nuclear membrane, cytoplasm and cell membrane. Daxx locates in the cytoplasm and cell membrane in CINII, CINIII and cervical cancer. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4671548951113870. PMID:24398161

  14. Cervical and Vaginal Cancer Screening (Pap Test and Pelvic Exam)

    MedlinePLUS

    ... service covered? Search Medicare.gov for covered items Cervical & vaginal cancer screenings How often is it covered? Medicare Part ... pay for them. Related resources National Cancer Institutecervical cancer information CDCcervical cancer information U.S. Preventive Services ...

  15. 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.

  16. Effects of a nutrient mixture on immunohistochemical localization of cancer markers in human cervical cancer HeLa cell tumor xenografts in female nude mice

    PubMed Central

    ROOMI, M.W.; KALINOVSKY, T.; CHA, J.; ROOMI, N.W.; NIEDZWIECKI, A.; RATH, M.

    2015-01-01

    Although fully treatable in the early stages, once cervical cancer has metastasized, patient outcome is poor. The main objective of this study was to examine the effect of dietary supplementation with a nutrient mixture (NM) containing lysine, ascorbic acid, proline, green tea extract and other micronutrients on HeLa cell xenografts in nude female mice. Tumor growth was measured and immunohistochemical staining was evaluated for the following cancer markers: Ki67 (proliferation); matrix metalloproteinase (MMP)-2 and -9 (invasion/metastasis); vascular endothelial growth factor (VEGF) (angiogenesis); terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and B-cell lymphoma 2 (Bcl-2) (apoptosis); cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) (inflammation); and glutathione S-transferase ? (GST?) (a general cancer marker). Following housing for a week, 5/6-week-old female athymic nude mice (n=12) were inoculated subcutaneously with 3106 HeLa cells in 0.2 ml phosphate-buffered saline and 0.1 ml Matrigel and randomly divided into two groups; control group mice were fed regular mouse chow and NM group mice the regular diet supplemented with 0.5% NM (w/w). After four weeks, the mice were sacrificed and their tumors were excised and processed for histology. The NM strongly inhibited the growth of HeLa xenografts in nude mice. The mean tumor weight was reduced to 59% (P=0.001) in the mice fed the NM compared with the tumor weight in the controlled diet mice. Ki67, MMP-2 and -9, VEGF, TUNEL, Bcl-2, COX-2, iNOS and GST? all showed a lower intensity and frequency of staining in the NM group compared with that in the control group. In conclusion, NM supplementation strongly inhibited tumor growth and cancer markers in female nude mice injected with HeLa xenografts. PMID:25574189

  17. A reusable localized surface plasmon resonance biosensor for quantitative detection of serum squamous cell carcinoma antigen in cervical cancer patients based on silver nanoparticles array

    PubMed Central

    Zhao, Qianying; Duan, Ruiqi; Yuan, Jialing; Quan, Yi; Yang, Huan; Xi, Mingrong

    2014-01-01

    Squamous cell carcinoma antigen (SCCa), as a tumor biomarker, plays an important role in adjuvant diagnosis, treatment evaluation, and prognosis prediction for cervical cancer patients. Localized surface plasmon resonance (LSPR) technique based on noble metal nanoparticles bypasses the disadvantages of traditional testing strategies, in terms of free-labeling, short assay time, good sensitivity, and selectivity. Herein, we develop a novel and reusable LSPR biosensor for the detection of SCCa. First, a triangle-shaped silver nanoparticle array was fabricated using the nanosphere lithography method. Next, we investigated and verified the feasibility of amino coupling method using 11-mercaptoundecanoic acid (MUA) to form a functionalized chip surface with monoclonal anti-SCCa antibodies on the silver nanoparticles for distinct detection of SCCa. Different concentrations of SCCa were successfully tested in both buffer and human serum by the ultrasensitive and specific LSPR system, with a linear quantitative detection range of 0.11,000 pM under optimal conditions. With appropriate regeneration solution, for example 50 mM glycine-HCl (pH 2.0), the LSPR biosensor featured effective fabrication reproducibility, which reduced both production cost and testing time. Our study represents the first application of the LSPR biosensor in cervical cancer, and demonstrates that the rapid, simple, and reusable nanochip can serve as a potential alternative for clinical serological diagnosis of SCCa in cervical cancer patients. PMID:24591830

  18. Pharmacologic inhibition of ATR and ATM offers clinically important distinctions to enhancing platinum or radiation response in ovarian, endometrial, and cervical cancer cells

    PubMed Central

    Teng, Pang-ning; Bateman, Nicholas W.; Darcy, Kathleen M.; Hamilton, Chad A.; Maxwell, George Larry; Bakkenist, Christopher J.; Conrads, Thomas P.

    2015-01-01

    Objective Significant reductions in gynecologic (GYN) cancer mortality and morbidity require treatments that prevent and reverse resistance to chemotherapy and radiation. The objective of this study was to determine if pharmacologic inhibition of key DNA damage response kinases in GYN cancers would enhance cell killing by platinum-based chemotherapy and radiation. Methods A panel of human ovarian, endometrial and cervical cancer cell lines were treated with platinum drugs or ionizing radiation (IR) along with small molecule pharmacological kinase inhibitors of Ataxia telangiectasia mutated (ATM) and ATM and Rad-3-related (ATR). Results Pharmacologic inhibition of ATR significantly enhanced platinum drug response in all GYN cancer cell lines tested, whereas inhibition of ATM did not enhance the response to platinum drugs. Co-inhibition of ATM and ATR did not enhance platinum kill beyond that observed by inhibition of ATR alone. By contrast, inhibiting either ATR or ATM enhanced the response to IR in all GYN cancer cells, with further enhancement achieved with co-inhibition. Conclusions These studies highlight actionable mechanisms operative in GYN cancer cells with potential to maximize response of platinum agents and radiation in newly diagnosed as well as recurrent gynecologic cancers. PMID:25560806

  19. How protective is cervical cancer screening against cervical cancer mortality in developing countries? The Colombian case

    PubMed Central

    2010-01-01

    Background Cervical cancer is one of the top causes of cancer morbidity and mortality in Colombia despite the existence of a national preventive program. Screening coverage with cervical cytology does not explain the lack of success of the program in reducing incidence and mortality rates by cervical cancer. To address this problem an ecological analysis, at department level, was carried out in Colombia to assess the relationship between cervical screening characteristics and cervical cancer mortality rates. Methods Mortality rates by cervical cancer were estimated at the department level for the period 2000-2005. Levels of mortality rates were compared to cervical screening coverage and other characteristics of the program. A Poisson regression was used to estimate the effect of different dimensions of program performance on mortality by cervical cancer. Results Screening coverage ranged from 28.7% to 65.6% by department but increases on this variable were not related to decreases in mortality rates. A significant reduction in mortality was found in departments where a higher proportion of women looked for medical advice when abnormal findings were reported in Pap smears. Geographic areas where a higher proportion of women lack health insurance had higher rates of mortality by cervical cancer. Conclusions These results suggest that coverage is not adequate to prevent mortality due to cervical cancer if women with abnormal results are not provided with adequate follow up and treatment. The role of different dimensions of health care such as insurance coverage, quality of care, and barriers for accessing health care needs to be evaluated and addressed in future studies. PMID:20846446

  20. 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: 0.971.00, 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

  1. 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. PMID:25826459

  2. Tumor-Targeting Salmonella typhimurium A1-R in Combination with Trastuzumab Eradicates HER-2-Positive Cervical Cancer Cells in Patient-Derived Mouse Models

    PubMed Central

    Hiroshima, Yukihiko; Zhang, Yong; Zhao, Ming; Zhang, Nan; Murakami, Takashi; Maawy, Ali; Mii, Sumiyuki; Uehara, Fuminari; Yamamoto, Mako; Miwa, Shinji; Yano, Shuya; Momiyama, Masashi; Mori, Ryutaro; Matsuyama, Ryusei; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M.

    2015-01-01

    We have previously developed mouse models of HER-2-positive cervical cancer. Tumors in nude mice had histological structures similar to the original tumor and were stained by anti-HER-2 antibody in the same pattern as the patients cancer. We have also previously developed tumor-targeting Salmonella typhimurium A1-R and have demonstrated its efficacy against patient-derived tumor mouse models, both alone and in combination. In the current study, we determined the efficacy of S. typhimurium A1-R in combination with trastuzumab on a patient-cancer nude-mouse model of HER-2 positive cervical cancer. Mice were randomized to 5 groups and treated as follows: (1) no treatment; (2) carboplatinum (30 mg/kg, ip, weekly, 5 weeks); (3) trastuzumab (20 mg/kg, ip, weekly, 5 weeks); (4) S. typhimurium A1-R (5 107 CFU/body, ip, weekly, 5 weeks); (5) S. typhimurium A1-R (5 107 CFU/body, ip, weekly, 5 weeks) + trastuzumab (20 mg/kg, ip, weekly, 5 weeks). All regimens had significant efficacy compared to the untreated mice. The relative tumor volume of S. typhimurium A1-R + trastuzumab-treated mice was smaller compared to trastuzumab alone (p = 0.007) and S. typhimurium A1-R alone (p = 0.039). No significant body weight loss was found compared to the no treatment group except for carboplatinum-treated mice (p = 0.021). Upon histological examination, viable tumor cells were not detected, and replaced by stromal cells in the tumors treated with S. typhimurium A1-R + trastuzumab. The results of the present study suggest that S. typhimurium A1-R and trastuzumab in combination are highly effective against HER-2-expressing cervical cancer. PMID:26047477

  3. The roles and clinical significance of microRNAs in cervical cancer.

    PubMed

    Wang, Fenfen; Li, Baohua; Xie, Xing

    2016-02-01

    Cervical carcinogenesis induced by persistent human papillomavirus (HPV) infection represents a stepwise progression from precursors to invasive cervical cancer. Accumulated evidence has shown aberrant expression of microRNAs (miRNAs) in cervical cancer tissues and cells. Further studies reveal that miRNAs play key roles in the initiation and progression of cervical cancer, via specific signaling pathways, including E6-p53, E7-pRb, phosphoinositide-3 kinase (PI3K)-Akt, Notch, Wnt/?-catenin, and Hedgehog pathways. Some studies demonstrate that miRNAs might serve as biomarkers or therapeutic targets, presenting a potential prospect in clinical practice. All results provide new insights into the function of miRNAs and the pathogenesis of cervical cancer induced by viral oncoproteins. New approaches for miRNA-based prevention and management for cervical cancer will be developed in the future. PMID:26356641

  4. Ets1 and Elk1 transcription factors regulate cancerous inhibitor of protein phosphatase 2A expression in cervical and endometrial carcinoma cells

    PubMed Central

    Pallai, Rajash; Bhaskar, Aishwarya; Sodi, Valerie; Rice, Lyndi M.

    2012-01-01

    Cancerous inhibitor of protein phosphatase 2A (CIP2A) has been identified as a proto-oncogene that is overexpressed in various types of human cancers. CIP2A acts by inhibiting protein phosphatase 2A-dependent destabilization of c-Myc, resulting in increased cell proliferation. Here, we have characterized the proximal promoter region of the human CIP2A gene in cervical, endometrial and liver carcinoma cells. The 5? flanking minimal proximal promoter of the CIP2A gene consists of putative binding sites for Ets1 and Elk1 in forward and reverse orientations. Here, we show that Ets1 and Elk1 binding is essential for CIP2A basal expression in several urogenital cancer cell lines. Interestingly, both Ets1 and Elk1 are required together for CIP2A expression, as siRNA knockdown of Ets1 and Elk1 together decreased CIP2A gene transcription, whereas knockdown of Ets1 or Elk1 alone had no effect. Moreover, ectopic expression of Ets1 and Elk1 together increased CIP2A expression. To gain physiological significance of the Ets1 and Elk1 regulation we observed, a panel of matched human cervical carcinoma samples was analyzed for the expression of CIP2A and Ets1 and/or Elk1. We found a direct correlation between the levels of CIP2A and the levels of Ets1 and Elk1. Our results suggest that the binding of Ets1 and Elk1 together to the proximal CIP2A promoter is absolutely required for CIP2A expression in cervical, endometrial and liver carcinoma cell lines. Thus, different factors regulate CIP2A expression in a cell-type specific manner. As previous work has shown a requirement for only Ets1 in prostate and gastric carcinomas, our results now indicate that CIP2A regulation is more complex than previously determined. PMID:23117818

  5. Decreased expression of the plasminogen activator inhibitor type1 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 type1 (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. PMID:26676222

  6. Claudin 1 Expression Characterizes Human Uterine Cervical Reserve Cells

    PubMed Central

    Zinner, Balzs; Gyngysi, Benedek; Babarczi, Edit; Kiss, Andrs

    2013-01-01

    Stem cells participate in cervical carcinogenesis but their function and exact features are still not clear. One type of stem-like cells are endocervical reserve cells (RCs), and their association with other normal/altered cervical cells is not exactly known. Epithelial cells are attached to each other by tight junctions. Their dominant components are the claudin proteins, which show changed expression in cancer; however, no data are available on their pattern. Expressions of various claudins (1, 2, 3, 4, 7), occludin, cytokeratins 5/6 and 7, and p63 were analyzed in 60 paraffin-embedded cervical samples. Immunohistochemical reactions were evaluated semiquantitatively and statistically. Claudin 1 was as high in RCs as in cervical intraepithelial neoplasia (CIN) and higher than in suprabasal squamous epithelial cells, contrary to the negative glandular and squamous basal cells. Claudin 2 was positive in all cell types except parabasal cells, whereas claudins 4 and 7 were weakly positive and claudin 3 was negative in all cell types. Occludin was positive in RCs, basal/parabasal cells, and CIN, whereas glandular cells were negative. This is a first report that describes the intermediate claudin pattern of RCs, demonstrating that it differs from that of cervical glandular and squamous basal cells, but showing an expression similar to the strong claudin 1 expression detected in cervical neoplastic cells. PMID:23900598

  7. 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

  8. New molecular targets against cervical cancer

    PubMed Central

    Duenas-Gonzalez, Alfonso; Serrano-Olvera, Alberto; Cetina, Lucely; Coronel, Jaime

    2014-01-01

    Cervical cancer is the third most commonly diagnosed cancer worldwide and the fourth leading cause of cancer death in women. Major advances but still insufficient achievements in the treatment of locally advanced and high-risk early stage patients have occurred in the last decade with the incorporation of concurrent cisplatin with radiation and, lately, gemcitabine added to cisplatin chemoradiation. Despite a number of clinical studies incorporating molecular-targeted therapy as radiosensitizers being in progress, so far, only antiangiogenic therapy with bevacizumab added to cisplatin chemoradiation has demonstrated safety and shown encouraging results in a Phase II study. In advanced disease, cisplatin doublets do not have a great impact on the natural history of the disease with median survival rates not exceeding 13 months. The first Phase III study of bevacizumab, added to cisplatin or a non-cisplatin-containing doublet, showed significant increase in both overall survival and progression-free survival. Further studies are needed before bevacizumab plus chemotherapy can be considered the standard of care for advanced disease. Characterization of the mutational landscape of cervical cancer has already been initiated, indicating that, for now, few of these targetable alterations match with available agents. Progress in both the mutational landscape knowledge and developments of novel targeted therapies may result in more effective and individualized treatments for cervical cancer. The potential efficacy of knocking down the key alterations in cervical cancer – E6 and E7 human papillomavirus oncoproteins – must not be overlooked. PMID:25525394

  9. Radiobiological Response of Cervical Cancer Cell Line in Low Dose Region: Evidence of Low Dose Hypersensitivity (HRS) and Induced Radioresistance (IRR)

    PubMed Central

    Singh, Rabiraja; George, Daicy; Vijaykumar, T.S.; John, Subhashini

    2015-01-01

    Background Purpose of the present study was to examine the response of cervical cancer cell line (HeLa cell line) to low dose radiation using clonogenic assay and mathematical modeling of the low dose response by Joiners induced repair model. Materials and Methods Survival of HeLa cells following exposure to single and fractionated low doses of ? (gamma)-ray, 6 MV, and 15 MV photon was measured by clonogenic assay. Results HeLa cell line demonstrated marked low dose response consisting of an area of HRS and IRR in the dose region of <1 Gy. The two gradients of the low dose region (?s and ?r) were distinctly different with a transition dose (Dc) of 0.28-0.40 cGy. Conclusion HeLa cell line demonstrates marked HRS and IRR with distinct transition dose. This may form the biological basis of the clinical study to investigate the chemo potentiating effect of low dose radiation in cervical cancer. PMID:26266200

  10. 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. PMID:24800833

  11. Candidates for Tumor Markers of Cervical Cancer Discovered by Proteomic Analysis

    PubMed Central

    Song, Jae Yun; Bae, Hyo Sook; Koo, Do Hyoung; Lee, Jae Kwan; Jung, Hak Hyun; Lee, Kyu Wan

    2012-01-01

    Cervical cancer is the second most common gynecological cancer among Korean women. While nationwide screening program has developed, the pathogenesis of cervical cancer is unknown. The aim of this study was to compare the protein expression profiles between cervical squamous carcinomas and normal cervical tissues in order to identify proteins that are related to the cancer. Three cervical cancer tissue samples and three normal cervical tissue samples were obtained and protein expression was compared and was identified in the samples with the use of matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). A total of 20 proteins that showed up-regulated expression in the cervical cancer tissue samples were selected and identified. Seven proteins were matched to allograft inflammatory factor 1 (AIF-1), actine-like protein 2 (ALP2), brain type fatty acid-binding protein (B-FABP), NCK adaptor protein 1 (NCK-1), islet cell autoantigen 1 (ICA69), cationic trypsinogen (PRSS1), and cyclin-dependent kinase 4 (CDK4), but the remaining 13 proteins were unidentifiable. After confirmation by RT-PCR, Western blotting and immunohistochemistry, we found that B-FABP, NCK-1, and CDK4 were related to the pathogenesis of cervical cancer. These proteins are suggested as candidates of new pathological tumor markers for cervical cancer. PMID:23255846

  12. Inhibition of Human Cervical Cancer Cell Growth by Ethanolic Extract of Boerhaavia diffusa Linn. (Punarnava) Root

    PubMed Central

    Srivastava, Rakhi; Saluja, Daman; Dwarakanath, Bilikere S.; Chopra, Madhu

    2011-01-01

    In Indian traditional medicine, Boerhaavia diffusa (punarnava) roots have been widely used for the treatment of dyspepsia, jaundice, enlargement of spleen, abdominal pain and as an anti-stress agent. Pharmacological evaluation of the crude ethanolic extract of B. diffusa roots has been shown to possess antiproliferative and immunomodulatory properties. The extract of B. diffusa was studied for anti-proliferative effects on the growth of HeLa cells and for its effect on cell cycle. Bio-assays of extracts from B. diffusa root showed that a methanol?:?chloroform fraction (BDF 5) had an antiproliferative effect on HeLa cells. After 48?h of exposure, this fraction at a concentration of 200??g?mL?1 significantly reduced cell proliferation with visible morphological changes in HeLa cells. Cell cycle analysis suggests that antiproliferative effect of BDF 5 could be due to inhibition of DNA synthesis in S-phase of cell cycle in HeLa cells, whereas no significant change in cell cycle was detected in control cells. The fraction BDF 5 caused cell death via apoptosis as evident from DNA fragmentation and caspase-9 activation. Thus the extract has potential to be evaluated in detail to assess the molecular mechanism-mediated anticancer activities of this plant. PMID:21869896

  13. Evaluation of the antitumour activity of Rinvanil and Phenylacetylrinvanil on the cervical cancer tumour cell lines HeLa, CaSKi and ViBo.

    PubMed

    Snchez-Snchez, Luis; Alvarado-Sansininea, Jess J; Escobar, Mara L; Lpez-Muoz, Hugo; Hernndez-Vzquez, Jos M V; Monsalvo-Montiel, Ivn; Demare, Patricia; Regla, Ignacio; Weiss-Steider, Benny

    2015-07-01

    Capsaicin is a potent inducer of apoptosis in tumourreceptor potential vanilloid 1 (TRPV1). The present study determined the IC50 and cytotoxic and apoptotic activities of the Capsaicin analogues Rinvanil and Phenylacetylrinvanil (PhAR) on three cervical cancer cell lines: HeLa, CaSKi and ViBo. These analogues possess an increased affinity for TRPV1 receptors. The IC50 obtained proved to be cytotoxic for all three cell lines; however, in the cells treated with Capsaicin both active caspase-3 and nuclear fragmentation were present. Capsaicin and its analogues also inhibited the normal proliferation of lymphocytes, suggesting that they are non-selective antitumour compounds. Finally, we discuss the possible loss of the relation between apoptosis and affinity to TRPV1, and the need for other strategies to synthesise Capsaicin analogues that can be useful in cancer treatments. PMID:25864613

  14. Angiogenesis and antiangiogenic agents in cervical cancer

    PubMed Central

    Tomao, Federica; Papa, Anselmo; Rossi, Luigi; Zaccarelli, Eleonora; Caruso, Davide; Zoratto, Federica; Benedetti Panici, Pierluigi; Tomao, Silverio

    2014-01-01

    Standard treatment of cervical cancer (CC) consists of surgery in the early stages and of chemoradiation in locally advanced disease. Metastatic CC has a poor prognosis and is usually treated with palliative platinum-based chemotherapy. Current chemotherapeutic regimens are associated with significant adverse effects and only limited activity, making identification of active and tolerable novel targeted agents a high priority. Angiogenesis is a complex process that plays a crucial role in the development of many types of cancer. The dominant role of angiogenesis in CC seems to be directly related to human papillomavirus-related inhibition of p53 and stabilization of hypoxia-inducible factor-1α. Both of these mechanisms are able to increase expression of vascular endothelial growth factor (VEGF). Activation of VEGF promotes endothelial cell proliferation and migration, favoring formation of new blood vessels and increasing permeability of existing blood vessels. Since bevacizumab, a recombinant humanized monoclonal antibody binding to all isoforms of VEGF, has been demonstrated to significantly improve survival in gynecologic cancer, some recent clinical research has explored the possibility of using novel therapies directed toward inhibition of angiogenesis in CC too. Here we review the main results from studies concerning the use of antiangiogenic drugs that are being investigated for the treatment of CC. PMID:25506227

  15. 20(s)-ginsenoside Rg3-loaded magnetic human serum albumin nanospheres applied to HeLa cervical cancer cells in vitro.

    PubMed

    Yang, Rui; Chen, Daozhen; Li, Mengfei; Miao, Fengqin; Liu, Peidang; Tang, Qiusha

    2014-01-01

    20(s)-ginsenoside Rg3 is extracted from traditional Chinese medicine, red ginseng. However, due to its poor aqueous solubility and low oral bioavailability, the use of 20(s)-Rg3 is limited. This study aimed to explore a method of preparing nano-sized 20(s)-ginsenoside Rg3 particle named 20(s)-ginsenoside Rg3-loaded magnetic human serum albumin nanospheres (20(s)-Rg3/HSAMNP) to change dosage form to improve its aqueous solubility and bioavailability. 20(s)-Rg3/HSAMNP were prepared by the desolvation-crosslinking method. The character of 20(s)-Rg3/HSAMNP was detected. An antiproliferative effect and cell apoptosis rates of 20(s)-Rg3/HSAMNP on human cervical cancer cells were determined by the MTT assay and flow cytometry, respectively. TEM analysis showed that 20(s)-Rg3/HSAMNP were approximately spherical and uniform in size. Thermodynamic testing showed that the corresponding magnetic fluid of a specific concentration rosed to a steady temperature of 42-65?C. Iron content was approximately 3 mg/mL. Drug encapsulation efficiency was approximately 70%. The potential of 20(s)-Rg3/HSAMNP combined with magnetic hyperthermia therapy to inhibit cell growth and induce apoptosis was much more prominent than that of the other groups. A new dosage form of 20(s)-Rg3 was prepared, which effectively induced apoptosis in HeLa cervical cancer cells in vitro when combined with hyperthermia. PMID:25226895

  16. Optoelectronic method for detection of cervical intraepithelial neoplasia and cervical cancer

    NASA Astrophysics Data System (ADS)

    Pruski, D.; Przybylski, M.; K?dzia, W.; K?dzia, H.; Jagielska-Pruska, J.; Spaczy?ski, 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.

  17. A model and nomogram to predict tumor site origin for squamous cell cancer confined to cervical lymph nodes

    PubMed Central

    Ali, Arif N; Switchenko, Jeffrey M; Kim, Sungjin; Kowalski, Jeanne; El-Deiry, Mark W; Beitler, Jonathan J

    2014-01-01

    Background The current study was conducted to develop a multifactorial statistical model to predict the specific head and neck (H&N) tumor site origin in cases of squamous cell carcinoma confined to the cervical lymph nodes (unknown primaries). Methods The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for patients with an H&N tumor site who were diagnosed between 2004 and 2011. The SEER patients were identified according to their H&N primary tumor site and clinically positive cervical lymph node levels at the time of presentation. The SEER patient data set was randomly divided into 2 data sets for the purposes of internal split-sample validation. The effects of cervical lymph node levels, age, race, and sex on H&N primary tumor site were examined using univariate and multivariate analyses. Multivariate logistic regression models and an associated set of nomograms were developed based on relevant factors to provide probabilities of tumor site origin. Results Analysis of the SEER database identified 20,011 patients with H&N disease with both site-level and lymph node-level data. Sex, race, age, and lymph node levels were associated with primary H&N tumor site (nasopharynx, hypopharynx, oropharynx, and larynx) in the multivariate models. Internal validation techniques affirmed the accuracy of these models on separate data. Conclusions The incorporation of epidemiologic and lymph node data into a predictive model has the potential to provide valuable guidance to clinicians in the treatment of patients with squamous cell carcinoma confined to the cervical lymph nodes. PMID:25060659

  18. Cervical cancer screening service utilisation in UK.

    PubMed

    Labeit, Alexander; Peinemann, Frank; Kedir, Abbi

    2013-01-01

    This study investigates empirically how past screening behaviour, individual and household characteristics affect the current uptake of cervical cancer screening in UK. For the conceptual framework, we use a modified Grossman model which is extended for non-economic factors. A dynamic version of a random effects panel probit model with initial conditions is estimated on the balanced sub-sample of the data. The analysis sample is restricted to women of age 16 and older and grouped into different age categories with respect to the NHS Cervical Screening Programme (NHSCSP). As dataset a balanced panel data of 857 women with 11,998 observations from the British Household Panel Study (BHPS) for the period from 1992 to 2008 is used for the analysis. Results suggest show that previous screening uptake, age, partner status, employment status and a previous GP visit have a significant influence on the likelihood of the uptake of cervical cancer screening. PMID:23917486

  19. Diallyl sulfide promotes cell-cycle arrest through the p53 expression and triggers induction of apoptosis via caspase- and mitochondria-dependent signaling pathways in human cervical cancer Ca Ski cells.

    PubMed

    Chiu, Tsan-Hung; Lan, Kai-Ying; Yang, Mei-Due; Lin, Jen-Jyh; Hsia, Te-Chun; Wu, Chin-Tung; Yang, Jai-Sing; Chueh, Fu-Shin; Chung, Jing-Gung

    2013-01-01

    Diallyl sulfide (DAS) is a component of garlic (Alliaceae family). Although diallyl polysulfide has been shown to exhibit anticancer activities, no report explored DAS-affected cell death in human cervical cancer cells in vitro. This study investigated DAS affected on cell-cycle regulation and apoptosis in human cervical cancer Ca Ski cells. DAS at 25-100 ?M decreased the viability of Ca Ski cells by increasing G0/G1 phase arrest followed by induction of apoptosis in concentration- and time-dependent effects. Flow cytomteric assay indicated that DAS (75 ?M) promoted the production of Ca(2+) accumulation and decreased the level of mitochondrial membrane potential in Ca Ski cells. Western blotting showed that 75 ?M of DAS-induced G0/G1 phase arrest was mediated through the increased expression of p21, p27, and p53 with a simultaneous decrease in CDK2, CDK6, and CHK2 expression. The characteristics of apoptosis, such as morphological changes and DNA condensation, altered the ratio of Bax/Bcl-2 and sub-G1 phase occurred in Ca Ski cells after exposure to DAS. Furthermore, DAS induced mitochondrial dysfunction, leading to the release of cytochrome c for causing apoptosis in Ca Ski cells. These findings suggest that DAS might be a potential chemotherapeutic agent for the treatment of cervical cancer. PMID:23530650

  20. Melatonin sensitizes human cervical cancer HeLa cells to cisplatin-induced cytotoxicity and apoptosis: effects on oxidative stress and DNA fragmentation.

    PubMed

    Pariente, Roberto; Pariente, Jos A; Rodrguez, 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 invitro 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 invitro 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. PMID:26462739

  1. 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?cervical-like constructs constitute a novel model system for a range of fundamental and applied studies related to cervical remodeling. PMID:20121593

  2. Cervical tissue engineering using silk scaffolds and human cervical cells.

    PubMed

    House, Michael; Sanchez, Cristina C; Rice, William L; Socrate, Simona; Kaplan, David L

    2010-06-01

    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

  3. An overview of prevention and early detection of cervical cancers

    PubMed Central

    Mishra, Gauravi A.; Pimple, Sharmila A.; Shastri, Surendra S.

    2011-01-01

    Cervical cancer still remains the most common cancer affecting the Indian women. India alone contributes 25.41% and 26.48% of the global burden of cervical cancer cases and mortality, respectively. Ironically, unlike most other cancers, cervical cancer can be prevented through screening by identifying and treating the precancerous lesions, any time during the course of its long natural history, thus preventing the potential progression to cervical carcinoma. Several screening methods, both traditional and newer technologies, are available to screen women for cervical precancers and cancers. No screening test is perfect and hence the choice of screening test will depend on the setting where it is to be used. Similarly, various methods are available for treatment of cervical precancers and the selection will depend on the cost, morbidity, requirement of reliable biopsy specimens, resources available, etc. The recommendations of screening for cervical cancer in the Indian scenario are discussed. PMID:22557777

  4. The enhanced inhibitory effect of different antitumor agents in self-microemulsifying drug delivery systems on human cervical cancer HeLa cells.

    PubMed

    Ujhelyi, Zoltn; Kalantari, Azin; Vecsernys, Mikls; Rka, Eszter; Fenyvesi, Ferenc; Pka, Rbert; Kozma, Bence; Bcskay, Ildik

    2015-01-01

    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-?, TNF-?) 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. PMID:26197311

  5. 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 Lugols 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

  6. Cervical cancer: Can it be prevented?

    PubMed

    Aggarwal, Pakhee

    2014-10-10

    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

  7. The Subcellular Localisation of the Human Papillomavirus (HPV) 16 E7 Protein in Cervical Cancer Cells and Its Perturbation by RNA Aptamers

    PubMed Central

    Cesur, zlem; 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

  8. Crocetin Downregulates the Proinflammatory Cytokines in Methylcholanthrene-Induced Rodent Tumor Model and Inhibits COX-2 Expression in Cervical Cancer Cells

    PubMed Central

    Chen, Bing; Hou, Zhao-Hui; Dong, Zhe; Li, Chun-Dong

    2015-01-01

    The effect of crocetin (C20H24O4) on methylcholanthrene- (MCA-) induced uterine cervical cancer in mice was studied in this paper. After the mice were treated orally with crocetin, maleic dialdehyde (MDA), polymorphonuclear cells (PMN), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were examined by ELISA or immunohistochemistry. The inducible nitric oxide synthase (iNOS) activation in HeLa cells was analyzed using fluorescence microscopy for light microscopic examination. The MCA mice showed a significant increase in plasma MDA, PMN, IL-1β, TNF-α, and nitrates levels. At the same time, the mRNA level of COX-2 in HeLa cells was also significantly increased. These changes were attenuated by crocetin supplementation in the MCA mice. Crocetin supplementation in the MCA mice also showed protection against cervical cancer. These results suggest that crocetin may act as a chemopreventive and an anti-inflammatory agent. PMID:25874230

  9. Electrical Bioimpedance Analysis: A New Method in Cervical Cancer Screening

    PubMed Central

    Das, Soumen; Chatterjee, Jyotirmoy

    2015-01-01

    Cervical cancer is the second most common female cancer worldwide and a disease of concern due to its high rate of incidence of about 500,000 women annually and is responsible for about 280,000 deaths in a year. The mortality and morbidity of cervical cancer are reduced through mass screening via Pap smear, but this technique suffers from very high false negativity of around 30% to 40% and hence the sensitivity of this technique is not more than 60%. Electrical bioimpedance study employing cytosensors over a frequency range offers instantaneous and quantitative means to monitor cellular events and is an upcoming technique in real time to classify cells as normal and abnormal ones. This technology is exploited for label-free detection of diseases by identifying and measuring nonbiological parameters of the cell which may carry the disease signature.

  10. 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…

  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. 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

  13. The relevance of molecular biomarkers in cervical cancer patients treated with radiotherapy

    PubMed Central

    Kilic, Sarah; Cracchiolo, Bernadette; Gabel, Molly; Haffty, Bruce

    2015-01-01

    Background Radiotherapy (RT) plays an integral role in the combined-modality management of cervical cancer. Various molecular mechanisms have been implicated in the adaptive cellular response to RT. Identification of these molecular processes may permit the prediction of treatment outcome and enhanced radiation-induced cancer cell killing through tailoring of the management approach, and/or the employment of selective inhibitors of these pathways. Methods PubMed was searched for studies presenting biomarkers of cervical cancer radioresistance validated in patient studies or in laboratory experimentation. Results Several biomarkers of cervical cancer radioresistance are validated by patient survival or recurrence data. These biomarkers fall into categories of biological function including hypoxia, cell proliferation, cell-cell adhesion, and evasion of apoptosis. Additional radioresistance biomarkers have been identified in exploratory experiments. Conclusions Biomarkers of radioresistance in cervical cancer may allow molecular profiling of individual tumors, leading to tailored therapies and better prognostication and prediction of outcomes. PMID:26605307

  14. 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

  15. 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

  16. [Anti-HPV vaccination: preventing cervical cancer].

    PubMed

    Simon, P; Dupond, I

    2006-09-01

    Two anti-HPV vaccine will soon be registered on the Belgian market. Providing immunity against the L1 protein of several oncogenic types of Papilloma virus, they aim at protecting against cervical cancer and several precancerous lesions. It has been known for years that oncogenic HPV infection of the uterine cervix is a prerequisite to the development of cervical cancer. This is supported by epidemiological has well as biological observations. That is why vaccines against capsid protein of these viruses had been developed. Two of these vaccines are about to be registered in Belgium. Cervarix (GSK) is directed against HPV 16 and 18 which are associated to ca 70% of the cervical cancers in the world. Gardasil (Sanofi Pasteur MSD) propose a vaccination against L1 protein of HPV 16 and 18, but also against HPV 6 and 11 which are responsible of benign lesions of the ano genital area (condylomas). The results obtained so far are very promising considering their preventive efficacy on persistant infections and cervical dysplasias. Two recent publications must be discussed: first, the protection offered by Cervarix is maintained for 4.5 years at least, second, vaccination by Gardasil of patients already infected by one of the HPV types (16, 18, 6, 11) provides a 100% efficacy in preventing diseases caused by the remaining types. It is therefore probable that HPV vaccination will not only concerns naive patients from any contact with HPV but also patients having already be in contact with these viruses. PMID:17091900

  17. Honeybee venom possesses anticancer and antiviral effects by differential inhibition of HPV E6 andE7 expression on cervical cancer cell line.

    PubMed

    Kim, Yong-Wan; Chaturvedi, Pankaj Kumar; Chun, Sung Nam; Lee, Yang Gu; Ahn, Woong Shick

    2015-04-01

    Bee venom (BV) therapy is a type of alternative medical treatment used to treat various diseases in oriental medicine. The mechanisms underlying the effects of BV remain poorly understood. In the present study, we evaluated the antiviral effect of BV on cervical carcinoma cell lines (CaSki, HeLa, C33A and TC-1). BV treatments resulted in a more significant suppression of cell growth in HPV16-infected cells (CaSki) and a lesser suppression in HPV18-infected cells (HeLa). However, less suppression was observed in HPV-negative C33A cells. In 10g/ml BV-treated CaSki cells, the mRNA expression and protein levels of HPV16 E6 and E7 were significantly decreased by BV, while HPV18 E6 and E7 mRNA expression levels were not significantly altered by 10g/ml BV-treated HeLa cells. The antitumor effects of BV were in accordance with invitro data, in restricting tumor growth invivo and were much more effective on the suppression of tumor growth. Furthermore, the mRNA and protein expression levels of HPV16 E6 and E7 were decreased by BV in TC-1 tumors. These findings demonstrated the antiviral effects of BV in HPV-infected cervical cancer cells and the anticancer effects of BV in HPV16 E6/E7-expressed TC-1 tumors. Collectively, BV plays a differential role in suppressing HPV16-infected cells (CaSki cells) and HPV18-infected cells (HeLa cells) by the downregulation of E6/E7 protein of HPV16/18. PMID:25633640

  18. Problems of cervical cancer screening programmes

    PubMed Central

    Rang, E.H.; Tod, E.D.M.

    1988-01-01

    The feasibility of using an age-sex register as a basis for a cervical cancer screening programme was investigated in a London practice serving both inner city and suburban populations. Only about 25% of 810 women aged 35-59 years who had not recently been screened responded to an invitation to attend a practice well woman clinic for a cervical smear. Nearly 30% of the invitations were returned `not known at this address' and there was no reply from the remaining 45%. A high proportion of incorrect addresses considerably reduces the effectiveness of a cancer screening programme based on an age-sex register covering an area with a mobile population and also makes it difficult to follow up women with abnormal smears adequately. Opportunistic screening remains essential and every effort should be made to encourage women to be responsible for their own cancer screening programmes. PMID:3255814

  19. A systematic study on dysregulated microRNAs in cervical cancer development.

    PubMed

    He, Yuqing; Lin, Juanjuan; Ding, Yuanlin; Liu, Guodong; Luo, Yanhong; Huang, Mingyuan; Xu, Chengkai; Kim, Taek-Kyun; Etheridge, Alton; Lin, Mi; Kong, Danli; Wang, Kai

    2016-03-15

    MicroRNAs (miRNAs) are short regulatory RNAs that modulate the transcriptome and proteome at the post-transcriptional level. To obtain a better understanding on the role of miRNAs in the progression of cervical cancer, meta-analysis and gene set enrichment analysis were used to analyze published cervical cancer miRNA studies. From 85 published reports, which include 3,922 cases and 2,099 noncancerous control tissue samples, 63 differentially expressed miRNAs (DEmiRNAs) were identified in different stages of cervical cancer development (CIN 1-3 and CC). It was found that some of the dysregulated miRNAs were associated with specific stages of cervical cancer development. To illustrate the impact of miRNAs on the pathogenesis of cervical cancer, a miRNA-mRNA interaction network on selected pathways was built by integrating viral oncoproteins, dysregulated miRNAs and their predicted/validated targets. The results indicated that the deregulated miRNAs at the different stages of cervical cancer were functionally involved in several key cancer related pathways, such as cell cycle, p53 and Wnt signaling pathways. These dysregulated miRNAs could play an important role in cervical cancer development. Some of the stage-specific miRNAs can also be used as biomarkers for cancer classification and monitoring the progression of cancer development. PMID:26032913

  20. Development of an expert system as a diagnostic support of cervical cancer in atypical glandular cells, based on fuzzy logics and image interpretation.

    PubMed

    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

  1. 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

  2. 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. Similar features are extracted towards the automated classification process. This paper will present various feature extraction methods including colour, shape and texture using Gabor wavelet as well as various quantative metrics. Generated features are used to classify cells or regions into normal and abnormal categories. Following the classification process, the cancer is graded based on the spread of the abnormal cells. This paper will present the results of the grading process with five stages of the cancer spectrum.

  3. 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 ?g/ml, was dose-dependently cytotoxic. It was more potent at 100 ?g/ml than cyclohexamide (1 ?g/ml), reducing cell viability to 9.2%. Among nine fractions separated by chromatography, ECF-8 exhibited prominent cytoxic activity at 10 ?g/ml. The HPLC fraction EHF-21 of ECF-8 was remarkably dose- and time-dependently cytotoxic, with 39.8% viable cells at 1 ?g/ml compared to 51% in cyclohexamide-treated cells at the same concentration; the IC50 was 0.49 ?g/ml. Hoechst staining of HeLa cells treated with EHF-21 at 0.5 ?g/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 ?g/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

  4. 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

  5. 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 structure or nuclear motor activity.

  6. Screening for cervical cancer in Poland.

    PubMed

    Wronkowski, Z; Zieli?ski, J; Rekosz, M

    1993-01-01

    Despite the growing number of PAP tests performed in Poland every year, (approximately 3 million per year in 1992) the mortality rates of cervical cancer are stable or increasing. With the intention of changing this unfavourable situation, a team of specialists in 1988 has developed a model for cervical cancer screening in Poland. Six experimental centres were chosen for the implementation of this model. The principles of the screening system were as follows: 1) population-based; 2) individual invitations; 3) computer assisted; 4) reproducible; 5) cytotechnicians' participation; 6) target population 30-60 years; 7) frequency of PAP tests: every 3 years. Preliminary data from the population of 25,841 which was covered by the screening campaign in Warsaw showed a 70.1% attendance rate and detectability of 3 cases per 1,000 screened women. PMID:8200380

  7. 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

  8. Treatment of invasive cervical cancer: Rijeka experience.

    PubMed

    Haller, Herman; Rupci?, Stanislav; Kratevi?, Maja; Begonia, Ruzica; Stamatovi?, Miroslav; Mamula, Ozren

    2007-04-01

    The aim of this retrospective analysis was to evaluate the survival rate in 661 patients with cervical cancer regarding two time periods 1990-1996 and 1997-2003 and the specific stage related risk factors. The respective five-year survival was 71.7% and 80.0%. Analyzing the risk factors in the univariate and multivariate regression modalities ultimately only two parameters, the two time periods and FIGO staging were found to be independent prognostic factors. The observed total improvement in the survival rate of the second time period is followed by an increase in conservative surgery in stage TIA1, a reduction in the use of adjuvant radiotherapy among operable stages Tlbl, Tlb2 and T2A, while the treatment of locally advanced cervical cancer did not differ significantly. PMID:17598517

  9. Chemoradiotherapy for cervical cancer in 2010.

    PubMed

    Klopp, Ann H; Eifel, Patricia J

    2011-02-01

    The introduction of concurrent chemotherapy and radiotherapy for the definitive treatment of cervical cancer constituted a major advance in the management of cervical cancer, resulting in a significant improvement in local control, progression-free survival, and overall survival. Since the publication of the results of seminal trials demonstrating the benefits of platinum-based chemotherapy, investigations of new cytotoxic and targeting agents have continued. The success of these studies has been limited in part because the side effects of standard platinum-based chemoradiation regimens already approach the limits of tolerability. Future progress will depend on identifying new agents without overlapping toxic effects, improving supportive care, and minimizing the toxic effects of radiation. PMID:21042887

  10. Hypoxia-Inducible Factor-1 Facilitates Cervical Cancer Progression in Human Papillomavirus Type 16 Transgenic Mice

    PubMed Central

    Lu, Zhi Hong; Wright, Jason D.; Belt, Brian; Cardiff, Robert D.; Arbeit, Jeffrey M.

    2007-01-01

    Advanced cervical cancer remains a vexing clinical challenge despite screening programs. Many of these cancers are hypoxic, and expression of the ? subunit of the major regulator of the hypoxic cellular response, the transcription factor hypoxia-inducible factor-1 (HIF-1), is correlated with poor prognosis. Here, we tested a functional role for HIF-1? in pathogenesis of cervical cancer in estrogen-treated transgenic mice. Double-transgenic (DTG) mice developed locally invasive cervical cancers 70 times larger than K14-HPV16 mice. In vivo bromodeoxyuridine incorporation was elevated in DTG cancers without a significant increase in apoptosis. HIF-1? gain of function did not up-regulate canonical HIF-1 targets in premalignant DTG cervices, in contrast to elevation of these targets in K14-HIF-1? transgenic cervices. The DTG transcriptional signature included up-regulation of mRNAs encoding cytokines and chemokines, immune signaling molecules, extracellular proteases, and cell motility factors, as well as reduced expression of cell adhesion and epithelial differentiation genes. Importantly, a set of gene markers derived from the DTG transcriptome predicted cervical cancer progression in patients. This study suggests a novel paradigm for HIF-1 function evident in multistage carcinogenesis as opposed to established malignancies, including interaction with viral oncogenes to induce multiple genomic networks in premalignancy that fosters the development of advanced cervical cancer. PMID:17600126

  11. Association between RASSF1A Promoter Hypermethylation and Oncogenic HPV Infection Status in Invasive Cervical Cancer: a Meta-analysis.

    PubMed

    Li, Jin-Yun; Huang, Tao; Zhang, Cheng; Jiang, Dan-Jie; Hong, Qing-Xiao; Ji, Hui-Hui; Ye, Meng; Duan, Shi-Wei

    2015-01-01

    Cervical carcinoma is the main cause of cancer-related mortality in women and is correlated with more than 15 risk cofactors, including infection of cervical cells with high-risk types of HPV (hrHPV). Indeed, both aberrant methylation of the RASSF1A promoter and hrHPV infection are often observed in cervical carcinomas. The purpose of our meta-analysis was to evaluate the role of RASSF1A promoter methylation and hrHPV infection in cervical cancer. Our meta-analysis involved 895 cervical cancer patients and 454 control patients from 15 studies. Our results suggested that RASSF1A promoter hypermethylation increased the risk of cervical cancer (OR=9.77, 95%CI=[3.06, 31.26], P=0.0001, I2=78%). By grouping cases according to cancer subtypes, we found that HPV infection was higher in cervical squamous cell carcinomas (SCCs) than in cervical adenocarcinomas/ adenosquamous cancers (ACs/ASCs) (OR=4.00, 95%CI=[1.41, 11.30], P=0.009, I2=55%). Interestingly, HPV infection tended to occur in cervical cancers with relatively low levels of RASSF1A promoter methylation (OR=0.59, 95%CI=[0.36, 0.99], P=0.05, I2=0%). Our study provides evidence of a possible interaction between HPV infection and RASSF1A promoter methylation in the development of cervical cancers. PMID:26320446

  12. CASP7 variants modify susceptibility to cervical cancer in Chinese women.

    PubMed

    Shi, Ting-Yan; He, Jing; Wang, Meng-Yun; Zhu, Mei-Ling; Yu, Ke-Da; Shao, Zhi-Ming; Sun, Meng-Hong; Wu, Xiaohua; Cheng, Xi; Wei, Qingyi

    2015-01-01

    Polymorphisms in Caspase-7 (CASP7) may modulate the programmed cell death and thus contribute to cervical cancer risk. In this case-control study of 1,486 cervical cancer cases and 1,301 controls, we investigated associations between four potentially functional polymorphisms in CASP7 and cervical cancer risk and evaluated their locus-locus interaction effects on the risk. The genotype-phenotype correlation was performed by a generalized linear regression model. We found that the rs4353229 polymorphism was associated with cervical cancer risk (under a recessive model: crude OR = 1.20, 95% CI = 1.02-1.40). Compared with the TT genotype, the rs10787498GT genotype was associated with an increased cervical cancer risk (adjusted OR = 1.19, 95% CI = 1.00-1.41). Combination analysis showed that subjects with four putative risk genotypes had a 1.54-fold increased cancer risk, compared with those who carried three or less putative risk genotypes. We also observed significant locus-locus joint effects on the risk, which may be mediated by the polymorphisms regulating CASP7 mRNA expression. Subsequent multifactor dimensionality reduction and classification and regression tree analyses indicated that the CASP7 genotypes might have a locus-locus interaction effect that modulated cervical cancer risk. Out data suggest that CASP7 polymorphisms may interact to modify cervical cancer risk by a possible mechanism of regulating CASP7 mRNA expression. PMID:25784056

  13. Effect of apolipoprotein B mRNA-editing catalytic polypeptide-like protein-3G in cervical cancer

    PubMed Central

    Xu, Yanhua; Leng, Junhong; Xue, Fang; Dong, Ruiqian

    2015-01-01

    Cervical cancer is one of the most common gynecologic cancers. The role of apolipoprotein B mRNA-editing catalytic polypeptide-like protein-3G (APCBEC-3G) in cervical cancer has yet to be elucidated. This study intends to explore the effect ofAPCBEC-3G on cervical cancer cell proliferation and invasion. In vitro, the cervical cancer cell line Hela was transfected by APCBEC-3G plasmid. The mRNA and protein expression levels of APCBEC-3G were detected by Real-time PCR and Western blot, respectively. Cervical cancer cell proliferation was determined by MTT. Transwell assay was applied to measure the effect of APCBEC-3G on cell invasion. APCBEC-3G mRNA and protein increased significantly after transfection (P<0.05) and cervical cancer cell proliferation and invasive ability were decreased significantly (P<0.05). APOBEC-3G serves as a suppressor of cervical cancer cell proliferation and invasion. Our research provides theoretical basis for further investigationAPOBEC-3G effect in cervical cancer occurrence and development. PMID:26722417

  14. Opting Out of Cervical Cancer Screening

    PubMed Central

    Cooper, Crystale Purvis; Saraiya, Mona

    2015-01-01

    Background Some primary care physicians choose not to provide cervical cancer screening. Purpose To investigate the characteristics and screening beliefs of family practitioners and internists who treat adult women in outpatient settings but perform no routine Pap tests. Methods A survey of U.S. primary care physicians (N = 892) was conducted and analyzed in 2012. Results Participants who performed no Pap tests during a typical month (17.2% of family practitioners and 44.3% of internists) generally reported that they referred patients to gynecologists for cervical cancer screening. The most significant predictor of Pap test non-provision was agreement that patients are best served by having Pap tests performed by gynecologists (AOR = 8.80, 95% CI = 5.58, 13.88, p < 0.001). Conclusions The perception that patients benefit from cervical cancer screening administered by gynecologists may deter screening in primary care settings, resulting in missed opportunities to offer screening to women who are never or rarely screened. PMID:24953518

  15. Fisetin Inhibits Migration and Invasion of Human Cervical Cancer Cells by Down-Regulating Urokinase Plasminogen Activator Expression through Suppressing the p38 MAPK-Dependent NF-?B 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-?B 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-?B 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

  16. 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. PMID:26921605

  17. 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

  18. Lymphedema After Surgery in Patients With Endometrial Cancer, Cervical Cancer, or Vulvar Cancer | Division of Cancer Prevention

    Cancer.gov

    This clinical trial studies lymphedema after surgery in patients with endometrial cancer, cervical cancer, or vulvar cancer. Collecting information over time about how often lymphedema occurs in patients undergoing surgery and lymphadenectomy for endometrial cancer, cervical cancer, and vulvar cancer may help doctors learn more about the disease and plan the best treatment.

  19. Cervical cancer screening among Chinese Americans

    PubMed Central

    Taylor, Victoria M.; Jackson, J. Carey; Tu, Shin-Ping; Yasui, Yutaka; Schwartz, Stephen M.; Kuniyuki, Alan; Acorda, Elizabeth; Lin, Kathy; Hislop, Gregory

    2006-01-01

    Study purpose Chinese women in North America have high rates of invasive cervical cancer and low levels of Papanicolaou (Pap) testing use. This study examined Pap testing barriers and facilitators among Chinese American women. Basic procedures A community-based, in-person survey of Chinese women was conducted in Seattle, Washington during 1999. Four hundred and thirty-two women in the 2079 years age-group were included in this analysis. The main outcome measures were a history of at least one previous Pap smear and Pap testing within the last 2 years. Main findings Nineteen percent of the respondents had never received cervical cancer screening and 36% had not been screened in the previous 2 years. Eight characteristics were independently associated with a history of at least one Pap smear: being married, thinking Pap testing is necessary for sexually inactive women, lack of concerns about embarrassment or cancer being discovered, having received a physician or family recommendation, having obtained family planning services in North America, and having a regular provider. The following characteristics were independently associated with recent screening: thinking Pap testing is necessary for sexually inactive women, lack of concern about embarrassment, having received a physician recommendation, having obtained obstetric services in North America, and having a regular provider. Principal conclusions Pap testing levels among the study respondents were well below the National Cancer Institutes Year 2000 goals. The findings suggest that cervical cancer control interventions for Chinese are more likely to be effective if they are multifaceted. 2002 International Society for Preventive Oncology. Published by Elsevier Science Ltd. All rights reserved. PMID:12102148

  20. 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.

  1. Sulforaphane Reverses the Expression of Various Tumor Suppressor Genes by Targeting DNMT3B and HDAC1 in Human Cervical Cancer Cells

    PubMed Central

    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. PMID:26161119

  2. Effect of a heat shock protein 90-specific inhibitor on the proliferation and apoptosis induced by VEGF-C in cervical cancer cells.

    PubMed

    DU, Xue; Li, Yongmei; Jing, Xu; Zhao, Lina

    2014-11-01

    The aim of the present study was to investigate the effect of heat shock protein 90 (Hsp90)-specific inhibitor geldanamycin (GA) on the proliferation and apoptosis induced by vascular endothelial growth factor-C (VEGF-C) in cervical cancer cells. HeLa cells (110(6)/ml) in the logarithmic growth phase were incubated without serum for 24 h. The cells were pretreated with kinase insert domain receptor antibody (KDR)-Ab (20 ?g/ml), phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (3 ?mol/l), mitogen-activated protein kinase (MAPK) inhibitor PD98059 (30 ?mol/l) or Hsp90-specific inhibitor GA (10 ?mol/l) for 30 min, and then treated with VEGF-C (50 ng/?l) for a further 24 h. The cells were harvested for MTT analysis, annexin V-FITC/propidium iodide double staining for early apoptosis and SDS-PAGE and western blot analysis in order to determine Hsp90, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cyclin D1 expression. Treatment with VEGF-C alone induced Hsp90 protein expression in HeLa cells at all time-points. Hsp90 expression was increased 3.31-fold in VEGF-C treated HeLa cells, and this increase was attenuated in the treatment groups (2.17-, 1.69-, 1.82-fold in VEGF-C + KDR-Ab, VEGF-C + PD98059 and VEGF-C + LY294002, respectively). The proliferation of the VEGF-C-treated HeLa cells was increased ~2.13-fold, while that of the VEGF-C + GA-treated HeLa cells decreased 0.87-fold (P<0.05). Even low concentrations of GA (0.02 ?mol/l) were found to inhibit the Bcl-2 and cyclin D1 protein expression induced by VEGF-C. Therefore, the results indicate that the Hsp90-specific inhibitor GA has a critical role in the proliferation and apoptosis induced by VEGF-C in cervical cancer cells. PMID:25289059

  3. [Cervical cancer screening: past--present--future].

    PubMed

    Breitenecker, G

    2009-12-01

    Despite the undisputed and impressive success which has been achieved since the 1960s by cervical cytology in the fight against cervical cancer and its precursor stages, during which the mortality rate in industrialized countries over the last 40 years has been reduced by two-thirds to three-quarters, a perfect and error-free screening procedure is still a long way off and will probably never be reached. There are two main reasons for this, the lack of adequate coverage and suboptimal quality and assessment of smears. Two screening procedures are in use Europe, an opportunistic and an organized system. Both systems have many advantages but also disadvantages. In organized programs the coverage is higher (up to 80%), although similar numbers are also achieved by non-organized programs over a 3-year cycle, even if they cannot be so exactly documented. The decision on which system is used depends on the health system of the country, public or non-public, and many other national circumstances. However, in both systems prerequisites for a satisfactory result is a high quality in the sampling technique, the processing and the assessment. Therefore, several guidelines have been introduced by state and medical societies for internal and external quality assurance. New technologies, such as thin-layer cytology or automation for replacement or support of conventional cytology liquid-based cytology proved not to be superior enough to justify the high costs of these systems. The recognition of the strong causal relationship between persistent infection with high-risk human papillomavirus (HPV) types and cervical cancer and its precursors has resulted in the development of comparably simple tests. Primary screening using HPV typing alone is not recommended in opportunistic screening due to the low specificity but high sensitivity because it leads to many clinically irrelevant results which place women under stress. In organized screening HPV testing is always and only possible in combination with cytology. Various models and approaches are in the testing phase and appear promising. HPV testing is on the other hand well accepted and recommended as a triage test to select women with equivocal smear results (Pap group III, ASCUS) if a biopsy is required or can be followed up and also for follow-up of patients after cone biopsy. However, vaccination of young girls against oncogenic HPV types which has now become widespread still leaves many questions open for the future because the observation period is too short. There is justified hope that this will become a valuable tool in cervical cancer control and may lead to a substantial reduction in the burden of cervical cancer in the future. However, as the current vaccines on the market do not cover all oncogenic virus types and the effects of vaccination will only be observed after many years, the necessity of a cytological screening will remain unrestricted. Therefore, cervical cytology will remain as the trusted, simple to use, economic and proven, like no other method for early cancer detection, efficient procedure even in the foreseeable future. If carried out with the highest quality demands it will play a central role in the early detection of cervical cancer. PMID:19756616

  4. Cervical cancer prevented by screening: Long-term incidence trends by morphology in Norway.

    PubMed

    Lnnberg, Stefan; Hansen, Bo Terning; Haldorsen, Tor; Campbell, Suzanne; Schee, Kristina; Nygrd, Mari

    2015-10-01

    Both major morphologic types of cervical cancer, squamous cell carcinoma (SCC) and adenocarcinoma (AC), are causally related to persistent infection with high-risk human papillomavirus (hrHPV), but screening has primarily been effective at preventing SCC. We analysed incidence trends of cervical cancer in Norway stratified by morphologies over 55 years, and projected SCC incidence in the absence of screening by assessing the changes in the incidence rate of AC. The Cancer Registry of Norway was used to identify all 19,530 malignancies in the cervix diagnosed in the period 1956-2010. The majority of these (82.9%) were classified as SCCs, 10.5% as ACs and the remaining 6.6% were of other or undefined morphology. By joint-point analyses of a period of more than five decades, the average annual percentage change in the age-standardised incidence was -1.0 (95%CI: -2.1-0.1) for cervical SCC, 1.5 (95%CI:1.1-1.9) for cervical AC and -0.9 (95%CI: -1.4 to -0.3) for cervical cancers of other or undefined morphology. The projected age-standardised incidence rate of cervical SCC in Norway, assuming no screening, was 28.6 per 100,000 woman-years in 2010, which compared with the observed SCC rate of 7.3 corresponds to an estimated 74% reduction in SCC or a 68% reduction due to screening in the total cervical cancer burden. Cytology screening has impacted cervical cancer burden more than suggested by the overall observed cervical cancer incidence reduction since its peak in the mid-1970s. The simultaneous substantial increase in cervical adenocarcinoma in Norway is presumably indicative of an increase in exposure to HPV over time. PMID:25833121

  5. 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.

  6. 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. PMID:26751970

  7. 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.

  8. 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.

  9. MiR-20a Promotes Cervical Cancer Proliferation and Metastasis In Vitro and In Vivo

    PubMed Central

    Chen, Junying; Ding, Nan; Ren, Fei

    2015-01-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that are critical regulators of various diseases. MicroRNA-20a (miR-20a) has previously significantly altered in a range of cancers. In this study, we detected the relationship between miR-20a and the development of cervical cancer by qRT-PCR, we found that the expression level of miR-20a was significantly higher in cervical cancer patients than in normal controls, the aberrant expression of miR-20a was correlated with lymph node metastasis, histological grade and tumor diameter. Then we successfully established the stable anti-miR-20a cervical cancer cell lines by lentivirus. Inhibited miR-20a prevented tumor progression by modulating cell cycle, apoptosis, and metastasis in vitro and in vivo. TIMP2 and ATG7 were proved to be direct targets of miR-20a, using luciferase assay and western blot. These results indicate that miR-20a suppresses the proliferation, migration and invasion of cervical cancer cell through targeting ATG7 and TIMP2. Our results support the involvement of miR-20a in cervical tumorigenesis, especially lymph node metastasis. We propose that miRNAs might be used as therapeutic agent for cervical cancer. PMID:25803820

  10. DNA vaccines for cervical cancer: from bench to bedside

    PubMed Central

    Hung, Chien-Fu; Monie, Archana; Alvarez, Ronald D.; Wu, T.-C.

    2011-01-01

    More than 99% of cervical cancers have been associated with human papillomaviruses (HPVs), particularly HPV type 16. The clear association between HPV infection and cervical cancer indicates that HPV serves as an ideal target for development of preventive and therapeutic vaccines. Although the recently licensed preventive HPV vaccine, Gardasil, has been shown to be safe and capable of generating significant protection against specific HPV types, it does not have therapeutic effect against established HPV infections and HPV-associated lesions. Two HPV oncogenic proteins, E6 and E7, are consistently co-expressed in HPV-expressing cervical cancers and are important in the induction and maintenance of cellular transformation. Therefore, immunotherapy targeting E6 and/or E7 proteins may provide an opportunity to prevent and treat HPV-associated cervical malignancies. It has been established that T cell-mediated immunity is one of the most crucial components to defend against HPV infections and HPV-associated lesions. Therefore, effective therapeutic HPV vaccines should generate strong E6/E7-specific T cell-mediated immune responses. DNA vaccines have emerged as an attractive approach for antigen-specific T cell-mediated immunotherapy to combat cancers. Intradermal administration of DNA vaccines via a gene gun represents an efficient way to deliver DNA vaccines into professional antigen-presenting cells in vivo. Professional antigen-presenting cells, such as dendritic cells, are the most effective cells for priming antigen-specific T cells. Using the gene gun delivery system, we tested several DNA vaccines that employ intracellular targeting strategies for enhancing MHC class I and class II presentation of encoded model antigen HPV-16 E7. Furthermore, we have developed a strategy to prolong the life of DCs to enhance DNA vaccine potency. More recently, we have developed a strategy to generate antigen-specific CD4+ T cell immune responses to further enhance DNA vaccine potency. The impressive preclinical data generated from our studies have led to several HPV DNA vaccine clinical trials. PMID:18160838

  11. DNA vaccines for cervical cancer: from bench to bedside.

    PubMed

    Hung, Chien-Fu; Monie, Archana; Alvarez, Ronald D; Wu, T-C

    2007-12-31

    More than 99% of cervical cancers have been associated with human papillomaviruses (HPVs), particularly HPV type 16. The clear association between HPV infection and cervical cancer indicates that HPV serves as an ideal target for development of preventive and therapeutic vaccines. Although the recently licensed preventive HPV vaccine, Gardasil, has been shown to be safe and capable of generating significant protection against specific HPV types, it does not have therapeutic effect against established HPV infections and HPV-associated lesions. Two HPV oncogenic proteins, E6 and E7, are consistently co-expressed in HPV-expressing cervical cancers and are important in the induction and maintenance of cellular transformation. Therefore, immunotherapy targeting E6 and/or E7 proteins may provide an opportunity to prevent and treat HPV-associated cervical malignancies. It has been established that T cell-mediated immunity is one of the most crucial components to defend against HPV infections and HPV-associated lesions. Therefore, effective therapeutic HPV vaccines should generate strong E6/E7-specific T cell-mediated immune responses. DNA vaccines have emerged as an attractive approach for antigen-specific T cell-mediated immunotherapy to combat cancers. Intradermal administration of DNA vaccines via a gene gun represents an efficient way to deliver DNA vaccines into professional antigen-presenting cells in vivo. Professional antigen-presenting cells, such as dendritic cells, are the most effective cells for priming antigen-specific T cells. Using the gene gun delivery system, we tested several DNA vaccines that employ intracellular targeting strategies for enhancing MHC class I and class II presentation of encoded model antigen HPV-16 E7. Furthermore, we have developed a strategy to prolong the life of DCs to enhance DNA vaccine potency. More recently, we have developed a strategy to generate antigen-specific CD4(+) T cell immune responses to further enhance DNA vaccine potency. The impressive pre- clinical data generated from our studies have led to several HPV DNA vaccine clinical trials. PMID:18160838

  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. 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…

  14. Peroxisome proliferator-activated receptor-gamma agonist 4-O-methylhonokiol induces apoptosis by triggering the intrinsic apoptosis pathway and inhibiting the PI3K/Akt survival pathway in SiHa human cervical cancer cells.

    PubMed

    Hyun, Seungyeon; Kim, Man Sub; Song, Yong Seok; Bak, Yesol; Ham, Sun Young; Lee, Dong Hun; Hong, Jintae; Yoon, Do Young

    2015-03-01

    4-O-Methylhonokiol (MH), a bioactive compound derived from Magnolia officinalis, is known to exhibit antitumor effects in various cancer cells. However, the precise mechanism of its anticancer activity in cervical cancer cells has not yet been studied. In this study, we demonstrated that MH induces apoptosis in SiHa cervical cancer cells by enhancing peroxisome proliferator-activated receptor-gamma (PPAR?) activation, followed by inhibition of the PI3K/Akt pathway and intrinsic pathway induction. MH upregulated PPAR? and PTEN expression levels while it decreased p-Akt in the MH-induced apoptotic process, thereby supporting the fact that MH is a PPAR? activator. Additionally, MH decreased the expression of Bcl-2 and Bcl-XL, inducing the intrinsic pathway in MH-treated SiHa cells. Furthermore, MH treatment led to the activation of caspase-3/caspase-9 and proteolytic cleavage of polyADP ribose polymerase. The expression levels of Fas (CD95) and E6/E7 oncogenes were not altered by MH treatment. Taken together, MH activates PPAR?/PTEN expression and induces apoptosis via suppression of the PI3K/Akt pathway and mitochondria-dependent pathways in SiHa cells. These findings suggest that MH has potential for development as a therapeutic agent for human cervical cancer. PMID:25563418

  15. 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

    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 56.73C, 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

  16. 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 56.73C, 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

  17. PSCA rs2294008 polymorphism contributes to the decreased risk for cervical cancer in a Chinese population.

    PubMed

    Wang, Shizhi; Wu, Shenshen; Zhu, Haixia; Ding, Bo; Cai, Yunlang; Ni, Jing; Wu, Qiang; Meng, Qingtao; Zhang, Xin; Zhang, Chengcheng; Li, Xiaobo; Wang, Meilin; Chen, Rui; Jin, Hua; Zhang, Zhengdong

    2016-01-01

    Recently, three genome-wide association studies have identified the PSCA (prostate stem cell antigen) rs2294008 polymorphism (C > T) associated with susceptibility to gastric cancer, bladder cancer, and duodenal ulcers, highlighting its critical role in disease pathogenesis. Given PSCA is reported to be overexpressed in cervical cancer and the rs2294008 can influence PSCA transcription, we aimed to determine the role of rs2294008 in susceptibility to cervical cancer. The genotyping was performed in the 1126 cases and 1237 controls. Our results showed the rs2294008 TT genotype significantly associated with a reduced risk of cervical cancer (adjusted OR = 0.55, 95% CI = 0.38-0.79; recessive model). Stratified analyses revealed that the association was restricted to the subgroups of age > 49 years, parity ≤ 1, abortion and early-stage cervical cancer. Immunohistochemistry assay showed the individuals carrying the TT genotype having lower PSCA expression than those with CC/CT genotypes. In summary, the PSCA rs2294008 polymorphism may serve as a biomarker of cervical cancer, particularly of early-stage cervical cancer. PMID:27001215

  18. PSCA rs2294008 polymorphism contributes to the decreased risk for cervical cancer in a Chinese population

    PubMed Central

    Wang, Shizhi; Wu, Shenshen; Zhu, Haixia; Ding, Bo; Cai, Yunlang; Ni, Jing; Wu, Qiang; Meng, Qingtao; Zhang, Xin; Zhang, Chengcheng; Li, Xiaobo; Wang, Meilin; Chen, Rui; Jin, Hua; Zhang, Zhengdong

    2016-01-01

    Recently, three genome-wide association studies have identified the PSCA (prostate stem cell antigen) rs2294008 polymorphism (C > T) associated with susceptibility to gastric cancer, bladder cancer, and duodenal ulcers, highlighting its critical role in disease pathogenesis. Given PSCA is reported to be overexpressed in cervical cancer and the rs2294008 can influence PSCA transcription, we aimed to determine the role of rs2294008 in susceptibility to cervical cancer. The genotyping was performed in the 1126 cases and 1237 controls. Our results showed the rs2294008 TT genotype significantly associated with a reduced risk of cervical cancer (adjusted OR = 0.55, 95% CI = 0.38–0.79; recessive model). Stratified analyses revealed that the association was restricted to the subgroups of age > 49 years, parity ≤ 1, abortion and early-stage cervical cancer. Immunohistochemistry assay showed the individuals carrying the TT genotype having lower PSCA expression than those with CC/CT genotypes. In summary, the PSCA rs2294008 polymorphism may serve as a biomarker of cervical cancer, particularly of early-stage cervical cancer. PMID:27001215

  19. Targeting angiogenesis in advanced cervical cancer.

    PubMed

    Eskander, Ramez N; Tewari, Krishnansu S

    2014-11-01

    Patients with advanced stage or recurrent cervical cancer represent a population with limited chemotherapeutic options. More specifically, patients with recurrent disease have a poor salvage rate, with a 5-year survival rate of less than 10%. This year, the first prospective phase III clinical trial exploring the anti-angiogenic agent, bevacizumab, was published, meeting its primary endpoint, with a significant improvement in overall survival. As such, a review of anti-angiogenic therapy in the treatment of this disease is warranted. PMID:25364393

  20. Reducing cervical cancer among First Nations women.

    PubMed

    Clarke, H F; Joseph, R; Deschamps, M; Hislop, T G; Band, P R; Atleo, R

    1998-03-01

    First Nations women in British Columbia have a four to six times higher mortality rate from cancer of the cervix than do women in the general population. Their participation in the provincial Cervical Cytology Screening Program (CCSP) is less regular and less frequent than other women in B.C. Likewise, they have more difficulty in obtaining culturally suitable health care services from respectful and consistent professionals. These issues should be of critical concern to nurses, as nurses provide the majority of health services to First Nations people. PMID:9633320

  1. Study of the UTMD-Based Delivery System to Induce Cervical Cancer Cell Apoptosis and Inhibit Proliferation with shRNA targeting Survivin

    PubMed Central

    Chen, Zhi-Yi; Liang, Kun; Lin, Yan; Yang, Feng

    2013-01-01

    Apoptosis induction by short hairpin RNA (shRNA) expression vectors could be an efficient and promising strategy for cancer gene therapy. Ultrasound-targeted microbubble destruction (UTMD) is an appealing technique. In this study, we investigated the apoptosis induction and suppression of cell proliferation in vivo transfected by the UTMD-based shRNA delivery system. Nude mice with transplanted tumors of cervical cancer were randomly arranged into three groups: control group, plasmid injection and ultrasound (P + US), P + UTMD group. Expressions of Survivin and proliferating cell nuclear antigen (PCNA), Bcl-2, Bax, Caspase-3, Ki-67, nucleostemin (NS) were investigated by immunohistochemistry. Furthermore, microvessel density (MVD) was detected by CD34 protein expressions and apoptotic index (AI) was measured by TUNEL. As compared with those in the control and P + US groups, protein expressions of PCNA, Ki-67, Bcl-2, Survivin and NS in P + UTMD groups were down-regulated markedly, while those of Bax, Caspase-3 were up-regulated significantly (p < 0.05). MVD decreased significantly, whereas AI increased remarkably (p < 0.05). We suggested that UTMD-based shRNA delivery system could induce apoptosis and inhibit proliferation significantly, without causing any apparently adverse effect, representing a new, promising technology that would be used in the future gene therapy and research. PMID:23325045

  2. 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

  3. 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

  4. Relationship between hWAPL polymorphisms and cervical cancer susceptibility

    PubMed Central

    Li, Li; Jiao, Gen-Long; Qin, Shuang; Xiao, Qing

    2015-01-01

    Purpose: To analyze the correlation of the polymorphisms of human wing-apart like (hWAPL) gene (rs7083506 and rs11202058) with the susceptibility to cervical cancer. Besides, the relationship of haplotypes between the polymorphisms with cervical cancer susceptibility was analyzed. Methods: Taqman probe genotyping method was adopted to detect the genotype distribution of hWAPL rs7083506 and rs11202058 polymorphisms in 117 cervical cancer patients and 128 healthy controls. Linkage disequilibrium and haplotypes were analyzed by Haploview software. χ2 test was utilized to analyze the differences of genotype, allele and haplotype frequencies between the case and control groups. Results: Correlation analysis of hWAPL rs7083506 and rs11202058 polymorphisms with cervical cancer susceptibility was based on the five genetic models. TT genotype of rs7083506 increased the susceptibility of cervical cancer in TT vs. CC model and TT vs. CT+TT model (OR=2.249, 95% CI=1.018-4.970; OR=2.287, 95% CI=1.069-4.896). For rs11202058, the A allele increased the cervical cancer susceptibility (A vs. G, OR=1.502, 95% CI=1.005-2.245). No significant correlation was observed between rs11202058 genotypes and cervical cancer susceptibility. We performed the haplotype analysis between the two polymorphisms, and found that T-A haplotype significantly correlated with cervical cancer, the susceptibility of cervical cancer increased to 1.78 times. Conclusions: Rs7083506 and rs11202058 polymorphisms of hWAPL and their haplotype T-A were associated with cervical cancer. PMID:26722608

  5. 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. PMID:20310056

  6. MiR-125a suppresses tumor growth, invasion and metastasis in cervical cancer by targeting STAT3

    PubMed Central

    Lin, Zhi; Zhang, Xuelin; Kang, Lei; Han, Baiyu; Meng, Jing; Yan, Zhifeng; Yan, Xiang; Jiao, Shunchang

    2015-01-01

    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. PMID:26389681

  7. 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. PMID:26389681

  8. Advancing Cervical Cancer Prevention in India: Implementation Science Priorities

    PubMed Central

    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. PMID:24217555

  9. MicroRNA miR-16-1 regulates CCNE1 (cyclin E1) gene expression in human cervical cancer cells

    PubMed Central

    Zubillaga-Guerrero, Ma Isabel; Alarcón-Romero, Luz del Carmen; Illades-Aguiar, Berenice; Flores-Alfaro, Eugenia; Bermúdez-Morales, Víctor Hugo; Deas, Jessica; Peralta-Zaragoza, Oscar

    2015-01-01

    MicroRNAs are involved in diverse biological processes through regulation of gene expression. The microRNA profile has been shown to be altered in cervical cancer (CC). MiR-16-1 belongs to the miR-16 cluster and has been implicated in various aspects of carcinogenesis including cell proliferation and regulation of apoptosis; however, its function and molecular mechanism in CC is not clear. Cyclin E1 (CCNE1) is a positive regulator of the cell cycle that controls the transition of cells from G1 to S phase. In CC, CCNE1 expression is frequently upregulated, and is an indicator for poor outcome in squamous cell carcinomas (SCCs). Thus, in the present brief communication, we determine whether the CCNE1 gene is regulated by miR-16-1 in CC cells. To identify the downstream cellular target genes for upstream miR-16-1, we silenced endogenous miR-16-1 expression in cell lines derived from CC (C-33 A HPV-, CaSki HPV16+, SiHa HPV16+, and HeLa HPV18+ cells), using siRNAs expressed in plasmids. Using a combined bioinformatic analysis and RT-qPCR, we determined that the CCNE1 gene is targeted by miR-16-1 in CC cells. SiHa, CaSki, and HeLa cells demonstrated an inverse correlation between miR-16-1 expression and CCNE1 mRNA level. Thus, miR-16-1 post-transcriptionally down-regulates CCNE1 gene expression. These results, suggest that miR-16-1 plays a vital role in modulating cell cycle processes in CC. PMID:26629104

  10. Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression

    PubMed Central

    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. PMID:26818472

  11. Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression.

    PubMed

    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. PMID:26818472

  12. 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.

  13. 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. PMID:26173416

  14. Screening history of cervical cancers in Emilia-Romagna, Italy: defining priorities to improve cervical cancer screening.

    PubMed

    Rossi, Paolo Giorgi; Caroli, Stefania; Mancini, Silvia; de' Bianchi, Priscilla Sassoli; Finarelli, Alba C; Naldoni, Carlo; Bucchi, Lauro; Falcini, Fabio

    2015-03-01

    Most invasive cervical cancers in industrialized countries are due to the lack of Pap test coverage, very few are due to screening failures. This study aimed at quantifying the proportion of invasive cancers occurring in nonscreened or underscreened women and that in women with a previous negative screening, that is, screening failure, during the first two screening rounds (1996-2002) and in the following rounds (2003-2008) in the Emilia-Romagna region. All cases of invasive cancers registered in the regional cancer registry between 1996 and 2008 were classified according to screening history through a record linkage with the screening programme registry. The incidence significantly decreased from 11.6/100 000 to 8.7/100 000; this decrease is due to a reduction in squamous cell cancers (annual percentage change -6.2; confidence interval: -7.8, -4.6) and advanced cancers (annual percentage change -6.6; confidence interval: -8.8, -4.3), whereas adenocarcinomas and microinvasive cancers were essentially stable. The proportion of cancers among women not yet invited and among nonresponders decreased over the two periods, from 45.5 to 33.3%. In contrast, the proportion of women with a previous negative Pap test less than 5 years and 5 years or more before cancer incidence increased from 5.7 to 13.3% and from 0.3 to 5.5%, respectively. Although nonattendance of the screening programme remains the main barrier to cervical cancer control, the introduction of a more sensitive test, such as the human papillomavirus DNA test, could significantly reduce the burden of disease. PMID:24787379

  15. Identification of pathways involved in paclitaxel activity in cervical cancer.

    PubMed

    Qiao, Wen-Juan; Cheng, Hai-Yan; Li, Chun-Quan; Jin, Hong; Yang, Shan-Shan; Li, Xia; Zhang, Yun-Yan

    2011-01-01

    Paclitaxel is one of the key chemotherapeutic drugs widely used to treat various types of cancer. Many cervical cancer patients exhibit selectivity in response to thereapy, however, which is considered to be correlated with drug-gene-pathways. The aim of this study was to identify pathways involved in paclitaxel activity in cervical cancer. Gene expression data was obtained from the NCBI Gene Expression Omnibus and the associations between paclitaxel and genes from DrugBank, MATADOR, TTD, CTD and SuperTarget databases. Differentially expressed genes in cervical cancer were identified using the significance analysis of microarrays (SAM) statistical technique. Pathway analysis was performed according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database using the software package SubpathwayMiner to predict target genes of paclitaxel in cervical cancer and regulated pathways. We found that paclitaxel, which exhibits anticancer activity in cervical cancer, may interact with these differentially expressed genes and their corresponding signaling pathways. Our study presents the first in-depth, large-scale analysis of pathways involved in paclitaxel activity in cervical cancer. Interestingly, these pathways have not been reported to be involved in other tumors. Thus our findings may contribute to the understanding of the mechanisms underlying paclitaxel resistance in cervical cancer. PMID:21517239

  16. [Human papilloma virus and cervical cancer].

    PubMed

    Berumen-Campos, Jaime

    2006-01-01

    Cervical cancer (CC) is the second most common cause of death from cancer among women worldwide and about 80% of the half of million new cases detected every year, occurs in less-developed countries. Human papillomavirus is an obligate factor for the development of CC, since some HPVtype are detected in 100% of CC. HPV16 and HPV18 are the most common viral types, accounting for about 50% and 15% of CC, respectively. HPV infection is the most common sexual transmitted infection, with an estimated prevalence of about 2-44% among sexually active young women. However, only a very small fraction of these infections evolve to CC (1-2 out of 1000), indicating that some other factors should be important in the evolution of the disease. Preventive vaccines against HPVs 16 and 18 have been developed, and in phase III clinical trials they have demonstrated 100% efficacy for prevention of persistent infection and high risk cervical squamous intraepithelial neoplasias positive for these HPV types, suggesting that these vaccines, if made widely available, will dramatically reduce the burden of CC. PMID:19031679

  17. Volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer

    PubMed Central

    Xie, Feng-Feng; Pan, Shi-Shi; Ou, Rong-Ying; Zheng, Zhen-Zhen; Huang, Xiao-Xiu; Jian, Meng-Ting; Qiu, Jian-Ge; Zhang, Wen-Ji; Jiang, Qi-Wei; Yang, Yang; Li, Wen-Feng; Shi, Zhi; Yan, Xiao-Jian

    2015-01-01

    Volasertib (BI 6727), a highly selective and potent inhibitor of PLK1, has shown broad antitumor activities in the preclinical and clinical studies for the treatment of several types of cancers. However, the anticancer effect of volasertib on cervical cancer cells is still unknown. In the present study, we show that volasertib can markedly induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreased protein expressions of PLK1 substrates survivin and wee1 in human cervical cancer cells. Furthermore, volasertib also enhances the intracellular reactive oxidative species (ROS) levels, and pretreated with ROS scavenger N-acety-L-cysteine totally blocks ROS generation but partly reverses volasertib-induced apoptosis. In addition, volasertib significantly potentiates the activity of cisplatin to inhibit the growth of cervical cancer in vitro and in vivo. In brief, volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer, suggesting the combination of volasertib and cisplatin may be a promising strategy for the treatment of patients with cervical cancer. PMID:26885445

  18. Dinuclear copper(I) complexes containing cyclodiphosphazane derivatives and pyridyl ligands: synthesis, structural studies, and antiproliferative activity toward human cervical and breast cancer cells.

    PubMed

    Balakrishna, Maravanji S; Suresh, D; Rai, Ankit; Mague, Joel T; Panda, Dulal

    2010-10-01

    Several mixed-ligand copper(I) complexes of cyclodiphosphazanes, [(t)BuNP(NC(4)H(8)X)](2) (1, X = O; 2, X = NMe), were synthesized by reacting the octanuclear copper(I) complexes [Cu(8)(?(2)-I)(8){[(t)BuNP(NC(4)H(8)X)](2)}(4)] (3, X = O; 4, X = NMe) with various pyridyl ligands. Interaction of the metallomacrocyclic complex 3 or 4 with pyridine, 2,2'-bipyridine, and 1,10-phenanthroline afforded the neutral dinuclear complexes [(C(5)H(5)N)(4)Cu(2)I(2){[(t)BuNP(NC(4)H(8)X)](2)}] (5, X = O; 6, X = NMe), [(2,2'-bpy)(2)Cu(2)I(2){[(t)BuNP(NC(4)H(8)X)](2)}] (7, X = O; 8, X = NMe), and [(1,10-phen)(2)Cu(2)I(2){[(t)BuNP(NC(4)H(8)X)](2)}] (9, X = O; 10, X = NMe), respectively, in good yield. The new dinuclear complexes 3, 5, and 7-9 were tested for their cytotoxic properties against human cervical cancer (HeLa) cells. The results indicated that all of the copper complexes have in vitro antitumor activity either similar to or better than that of cisplatin, a widely used anticancer drug. Among the compounds tested, complex 9 showed the most potent inhibitory activity in HeLa cells. In addition, complex 9 was found to potently inhibit proliferation of human breast cancer cells (MCF-7), highly metastatic breast cancer cells (MDA-MB 231), and nontransformed Chinese hamster ovary (CHO) cells. Complex 9 inhibited proliferation of these cells in culture more potently than cisplatin; for example, complex 9 was found to inhibit proliferation of HeLa and MCF-7 cells 3 and 5 times more efficiently than cisplatin. Complex 9 treatment damaged the DNA integrity, blocked the cells in the G1 phase of the cell cycle, and induced apoptosis via a p53-dependent pathway. The molecular structures of complexes 9 and 10 were confirmed by single-crystal X-ray diffraction studies. PMID:20812680

  19. Screening for cervical cancer: when theory meets reality

    PubMed Central

    2011-01-01

    Cervical cancer screening reduces morbidity and mortality due to cervical cancer. However, there are many factors that determine the success of any cervical cancer prevention effort: the prevalence of human papillomavirus infection in general population, the existence of an organized screening program and the corresponding coverage, the existence and quality of the field and laboratory facilities for screening and diagnostic follow-up, and the facilities available for treating diagnosed lesions. Monitoring the patient path or "chain of action" for each patient with an abnormal screening result is of crucial importance. Cost-effectiveness models are widely used by decision-makers to determine which cervical cancer screening program would maximize health benefits within a given, usually limited, set of resources. Regardless of their level of sophistication, however, these models cannot replace empirical evaluations of the effectiveness of screening programs. Cervical cancer prevention activities need to be monitored and evaluated in each country where they are introduced to see that they meet performance standards. Policy-makers responsible for allocating resources for cervical cancer prevention have a duty to allocate resources not only for cervical cancer screening, but also for screening program surveillance. PMID:21668947

  20. Update on prevention and screening of cervical cancer

    PubMed Central

    McGraw, Shaniqua L; Ferrante, Jeanne M

    2014-01-01

    Cervical cancer is the third most common cause of cancer in women in the world. During the past few decades tremendous strides have been made toward decreasing the incidence and mortality of cervical cancer with the implementation of various prevention and screening strategies. The causative agent linked to cervical cancer development and its precursors is the human papillomavirus (HPV). Prevention and screening measures for cervical cancer are paramount because the ability to identify and treat the illness at its premature stage often disrupts the process of neoplasia. Cervical carcinogenesis can be the result of infections from multiple high-risk HPV types that act synergistically. This imposes a level of complexity to identifying and vaccinating against the actual causative agent. Additionally, most HPV infections spontaneously clear. Therefore, screening strategies should optimally weigh the benefits and risks of screening to avoid the discovery and needless treatment of transient HPV infections. This article provides an update of the preventative and screening methods for cervical cancer, mainly HPV vaccination, screening with Pap smear cytology, and HPV testing. It also provides a discussion of the newest United States 2012 guidelines for cervical cancer screening, which changed the age to begin and end screening and lengthened the screening intervals. PMID:25302174

  1. Patient, Physician, and Nurse Factors Associated With Entry Onto Clinical Trials and Finishing Treatment in Patients With Primary or Recurrent Uterine, Endometrial, or Cervical Cancer

    ClinicalTrials.gov

    2016-02-09

    Recurrent Cervical Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Uterine Corpus Sarcoma; Stage I Uterine Corpus Cancer; Stage I Uterine Sarcoma; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Uterine Corpus Cancer; Stage II Uterine Sarcoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Uterine Sarcoma; Stage IV Uterine Corpus Cancer; Stage IV Uterine Sarcoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

  2. Aberrant Hypermethylation of SALL3 with HPV Involvement Contributes to the Carcinogenesis of Cervical Cancer

    PubMed Central

    Wei, Xing; Zhang, Shaohua; Cao, Di; Zhao, Minyi; Zhang, Qian; Zhao, Juan; Yang, Ting; Pei, Meili; Wang, Li; Li, Yang; Yang, Xiaofeng

    2015-01-01

    Objective This study aimed to investigate the methylation status of the promoter region of spalt-like transcription factor 3 (SALL3) and the expression of SALL3 in cervical cancer to explore the function of this gene in cervical cancer carcinogenesis. Methods The methylation status of SALL3 was detected by methylation-specific PCR, and SALL3 gene expression was assessed by real-time quantitative PCR in the cervical cancer cell lines, SiHa, HeLa and C33A, as well as in cervical cancer tissue samples (n = 23), matched pericarcinomatous tissue samples (n = 23) and normal cervix tissue samples (n = 17). MTT was used to measure the cell viability and proliferation capacity of SiHa and HeLa cells. Results The SALL3 promoter was completely methylated in SiHa cells, unmethylated in C33A cells and partially methylated in HeLa cells. After treatment of SiHa and HeLa cells with 5 μM and 10 μM of 5-Azacytidine (5-Aza), respectively, the methylation level of the SALL3 promoter decreased and observed increase in the degree of unmethylation in a dose-dependent manner. Moreover, the relative expression of SALL3 mRNA increased as the concentration of 5-Aza increased in SiHa (p<0.05) and HeLa (p<0.05) cells. This above-mentioned increase in SALL3 mRNA in SiHa cells was more remarkable than that observed in HeLa cells. Cell proliferation capacity also decreased after administration of 5-Aza to SiHa and HeLa cells (p<0.05). Methylation of the SALL3 promoter was observed in 15 of 23 (65.21%) cervical cancer tissue samples, 15 of 23 (65.21%) matched pericarcinomatous tissue samples and 5 of 17 (29.41%) normal cervical tissue samples (p<0.05). SALL3 mRNA expression was significantly lower in cervical cancer and pericarcinomatous tissues compared with normal cervical tissues (p<0.05). In all cervix tissue samples, HPV infection was positively associated with hypermethylation of the promoter region of SALL3 (p<0.05, r = 0.408), and the expression of SALL3 mRNA in HPV-positive tissues was lower than that in HPV-negative tissues (p<0.05). Conclusion The aberrant hypermethylation of SALL3 together with HPV involvement inactivated its function as a tumor suppressor and contributed to carcinogenesis in cervical cancer. PMID:26697877

  3. B5, a thioredoxin reductase inhibitor, induces apoptosis in human cervical cancer cells by suppressing the thioredoxin system, disrupting mitochondrion-dependent pathways and triggering autophagy.

    PubMed

    Shao, Fang-Yuan; Du, Zhi-Yun; Ma, Dong-Lei; Chen, Wen-Bo; Fu, Wu-Yu; Ruan, Bi-Bo; Rui, Wen; Zhang, Jia-Xuan; Wang, Sheng; Wong, Nai Sum; Xiao, Hao; Li, Man-Mei; Liu, Xiao; Liu, Qiu-Ying; Zhou, Xiao-Dong; Yan, Hai-Zhao; Wang, Yi-Fei; Chen, Chang-Yan; Liu, Zhong; Chen, Hong-Yuan

    2015-10-13

    The synthetic curcumin analog B5 is a potent inhibitor of thioredoxin reductase (TrxR) that has potential anticancer effects. The molecular mechanism underlying B5 as an anticancer agent is not yet fully understood. In this study, we report that B5 induces apoptosis in two human cervical cancer cell lines, CaSki and SiHa, as evidenced by the downregulation of XIAP, activation of caspases and cleavage of PARP. The involvement of the mitochondrial pathway in B5-induced apoptosis was suggested by the dissipation of mitochondrial membrane potential and increased expression of pro-apoptotic Bcl-2 family proteins. In B5-treated cells, TrxR activity was markedly inhibited with concomitant accumulation of oxidized thioredoxin, increased formation of reactive oxygen species (ROS), and activation of ASK1 and its downstream regulatory target p38/JNK. B5-induced apoptosis was significantly inhibited in the presence of N-acetyl-l-cysteine. Microscopic examination of B5-treated cells revealed increased presence of cytoplasmic vacuoles. The ability of B5 to activate autophagy in cells was subsequently confirmed by cell staining with acridine orange, accumulation of LC3-II, and measurement of autophagic flux. Unlike B5-induced apoptosis, autophagy induced by B5 is not ROS-mediated but a role for the AKT and AMPK signaling pathways is implied. In SiHa cells but not CaSki cells, B5-induced apoptosis was promoted by autophagy. These data suggest that the anticarcinogenic effects of B5 is mediated by complex interplay between cellular mechanisms governing redox homeostasis, apoptosis and autophagy. PMID:26439985

  4. B5, a thioredoxin reductase inhibitor, induces apoptosis in human cervical cancer cells by suppressing the thioredoxin system, disrupting mitochondrion-dependent pathways and triggering autophagy

    PubMed Central

    Ma, Dong-Lei; Chen, Wen-Bo; Fu, Wu-Yu; Ruan, Bi-Bo; Rui, Wen; Zhang, Jia-Xuan; Wang, Sheng; Wong, Nai Sum; Xiao, Hao; Li, Man-Mei; Liu, Xiao; Liu, Qiu-Ying; Zhou, Xiao-dong; Yan, Hai-Zhao; Wang, Yi-Fei; Chen, Chang-Yan; Liu, Zhong; Chen, Hong-Yuan

    2015-01-01

    The synthetic curcumin analog B5 is a potent inhibitor of thioredoxin reductase (TrxR) that has potential anticancer effects. The molecular mechanism underlying B5 as an anticancer agent is not yet fully understood. In this study, we report that B5 induces apoptosis in two human cervical cancer cell lines, CaSki and SiHa, as evidenced by the downregulation of XIAP, activation of caspases and cleavage of PARP. The involvement of the mitochondrial pathway in B5-induced apoptosis was suggested by the dissipation of mitochondrial membrane potential and increased expression of pro-apoptotic Bcl-2 family proteins. In B5-treated cells, TrxR activity was markedly inhibited with concomitant accumulation of oxidized thioredoxin, increased formation of reactive oxygen species (ROS), and activation of ASK1 and its downstream regulatory target p38/JNK. B5-induced apoptosis was significantly inhibited in the presence of N-acetyl-l-cysteine. Microscopic examination of B5-treated cells revealed increased presence of cytoplasmic vacuoles. The ability of B5 to activate autophagy in cells was subsequently confirmed by cell staining with acridine orange, accumulation of LC3-II, and measurement of autophagic flux. Unlike B5-induced apoptosis, autophagy induced by B5 is not ROS-mediated but a role for the AKT and AMPK signaling pathways is implied. In SiHa cells but not CaSki cells, B5-induced apoptosis was promoted by autophagy. These data suggest that the anticarcinogenic effects of B5 is mediated by complex interplay between cellular mechanisms governing redox homeostasis, apoptosis and autophagy. PMID:26439985

  5. Application of the Carolina Framework for Cervical Cancer Prevention

    PubMed Central

    Moss, Jennifer L.; McCarthy, Schatzi H.; Gilkey, Melissa B.; Brewer, Noel T.

    2014-01-01

    Objective The Carolina Framework for Cervical Cancer Prevention describes 4 main causes of cervical cancer incidence: human papillomavirus (HPV) infection, lack of screening, screening errors, and not receiving follow-up care. We present 2 applications of the Carolina Framework in which we identify high-need counties in North Carolina and generate recommendations for improving prevention efforts. Methods We created a cervical cancer prevention need index (CCPNI) that ranked counties on cervical cancer mortality, HPV vaccine initiation and completion, Pap smear screening, and provision of Pap tests to rarely- or never-screened women. In addition, we conducted in-depth interviews with 19 key informants from programs and agencies involved in cervical cancer prevention in North Carolina. Results North Carolinas 100 counties varied widely on individual CCPNI components, including annual cervical cancer mortality (median 2.7/100,000 women; range 0.08.0), adolescent girls HPV vaccine initiation (median 42%; range 15%62%), and Pap testing in the previous 3 years among Medicaid-insured adult women (median 59%; range 40%83%). Counties with the greatest prevention needs formed 2 distinct clusters in the northeast and south-central regions of the state. Interviews generated 9 recommendations to improve cervical cancer prevention in North Carolina, identifying applications to specific programs and policies in the state. Conclusions This study found striking geographic disparities in cervical cancer prevention need in North Carolina. Future prevention efforts in the state should prioritize high-need regions as well as recommended strategies and applications in existing programs. Other states can use the Carolina Framework to increase the impact of their cervical cancer prevention efforts. PMID:24333357

  6. Fatalistic Beliefs and Cervical Cancer Screening Among Mexican Women.

    PubMed

    Marvn, Ma Luisa; Ehrenzweig, Yamilet; Catillo-Lpez, Rosa Lilia

    2016-01-01

    Fatalistic beliefs about cervical cancer were studied in 464 Mexican women, and how such beliefs relate to participation in cervical cancer screening was evaluated. Rural women were less likely than urban women to have had a Pap test and more likely to believe that the illness is due to bad luck or fate. These were also the beliefs most associated with nonscreening among rural women, whereas for urban women the belief most associated with nonscreening was "there is not much I can do to prevent cervical cancer." PMID:25256106

  7. Primary strategies for HPV infection and cervical cancer prevention.

    PubMed

    Harper, Diane M; Demars, Leslie R

    2014-06-01

    Counseling messages for tobacco cessation, condom use, circumcision, and selective choice in the number of sexual partners can help reduce the risk of cervical cancer. Other sexual behavioral and reproductive risk factors for cervical cancer are a younger age at first intercourse and at first full-term pregnancy as well as increasing duration of combined hormonal oral contraceptive use. Micronutrients and supplements can reduce the risk of human papillomavirus infection, persistence, progression, and regression. Some human papillomavirus infections can be prevented by vaccination. Cervical cancer is best prevented by screening. PMID:24686336

  8. [Epidemiological overview of uterine cervical cancer].

    PubMed

    Hernndez-Hernndez, Dulce M; Apresa-Garca, Teresa; Patln-Prez, Rosa Ma

    2015-01-01

    The World Health Organization (WHO) reported more than 6 million cases of cancer worldwide in women during 2008; 57.2 % of those cases occurred in less developed countries. Cervical cancer (CC) ranks third in the world in all cancers affecting women, with an estimated of 530 000 new cases. CC has multiple causes and it arises by the association of various risk factors. The main factor is related to the human papillomavirus infection (HPV), which acts as a necessary but not sufficient cause. Also, the interaction with other cofactors has an impact on the development and severity of this neoplasm. Survival is related to the timeliness of care and, therefore, to more access to health services. CC is a neoplasm considered a preventable cancer; thus, it is possible to save more than 150 000 lives by 2030 if control measures are applied with opportunity. The aim of this work is to review the CC in different geographical areas and to make an analysis of risk factors related to this neoplasm. PMID:26462510

  9. Identification of human patatin-like phospholipase domain-containing protein 1 and a mutant in human cervical cancer HeLa cells.

    PubMed

    Chang, Ping-An; Sun, Ying-Jian; Huang, Fei-Fei; Qin, Wen-Zhen; Chen, Yu-Ying; Zeng, Xin; Wu, Yi-Jun

    2013-10-01

    Recently members of mammalian patatin-like phospholipase domain containing (PNPLA) protein family have attracted attention for their critical roles in diverse aspects of lipid metabolism and signal pathway. Until now little has been known about the characteristics of PNPLA1. Here, the full length coding cDNA sequence of human PNPLA1 (hPNPLA1) was cloned for the first time, which encoded a polypeptide with 532 amino acids containing the whole patatin domain. Tissue expression profiles analysis showed that low mRNA levels of hPNPLA1 existed in various tissues, except high expression in the digestive system, bone marrow and spleen. Subcellular distribution of hPNPLA1 tagged with green fluorescence protein mainly localized to lipid droplets. Furthermore, a nonsense mutation of PNPLA1 in human cervical cancer HeLa cells was identified. The hPNPLA1 mutant encoded a protein of 412 amino acids without the C-terminal domain and did not colocalize to lipid droplets, which suggested that the C-terminal region of hPNPLA1 affected lipid droplet binding. These results identified hPNPLA1 and a mutant in HeLa cells, and provided insights into the structure and function of PNPLA1. PMID:24057234

  10. Mapping HPV Vaccination and Cervical Cancer Screening Practice in the Pacific Region-Strengthening National and Regional Cervical Cancer Prevention

    PubMed Central

    Obel, J; McKenzie, J; Buenconsejo-Lum, LE; Durand, AM; Ekeroma, A; Souares, Y; Hoy, D; Baravilala, W; Garland, SM; Kjaer, SK; Roth, A

    2015-01-01

    Objective To provide background information for strengthening cervical cancer prevention in the Pacific by mapping current human papillomavirus (HPV) vaccination and cervical cancer screening practices, as well as intent and barriers to the introduction and maintenance of national HPV vaccination programmes in the region. Materials and Methods A cross-sectional questionnaire-based survey among ministry of health officials from 21 Pacific Island countries and territories (n=21). Results Cervical cancer prevention was rated as highly important, but implementation of prevention programs were insufficient, with only two of 21 countries and territories having achieved coverage of cervical cancer screening above 40%. Ten of 21 countries and territories had included HPV vaccination in their immunization schedule, but only two countries reported coverage of HPV vaccination above 60% among the targeted population. Key barriers to the introduction and continuation of HPV vaccination were reported to be: (i) Lack of sustainable financing for HPV vaccine programs; (ii) Lack of visible government endorsement; (iii) Critical public perception of the value and safety of the HPV vaccine; and (iv) Lack of clear guidelines and policies for HPV vaccination. Conclusion Current practices to prevent cervical cancer in the Pacific Region do not match the high burden of disease from cervical cancer. A regional approach, including reducing vaccine prices by bulk purchase of vaccine, technical support for implementation of prevention programs, operational research and advocacy could strengthen political momentum for cervical cancer prevention and avoid risking the lives of many women in the Pacific. PMID:25921158

  11. DCCPS: BRP: PCRB: Key Initiatives: HPV and Cervical Cancer Research

    Cancer.gov

    Most cases of human papillomavirus (HPV) infection do not progress to cervical cancer. Epidemiologic studies suggest that the variation in progression can be attributed to inherited genetic factors. However, because the genes responsible for this process have not been determined, it is not yet possible to identify which women with HPV infection or preinvasive cervical intraepithelial neoplasia (CIN) will need treatment.

  12. Interaction among folate, riboflavin, genotype, and cancer, with reference to colorectal and cervical cancer.

    PubMed

    Powers, Hilary J

    2005-12-01

    Epidemiological studies have linked low folate intake with an increased risk of epithelial cancers, including colorectal cancer and cervical cancer. Riboflavin has received much less attention, but there is increasing interest in the well-established role that flavins play in folate metabolism and the possible synergy of a protective effect between these 2 vitamins. Folate plays a key role in DNA synthesis, repair, and methylation, and this forms the basis of mechanistic explanations for a putative role for folate in cancer prevention. The role of folate in these processes may be modulated by genotype for the common C677T thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), homozygosity for which is associated with lower enzyme activity, lower plasma and red blood cell folate, and elevated plasma homocysteine. Riboflavin, as FAD, is a cofactor for MTHFR and there is evidently some interaction among riboflavin status, folate status, and genotype in determining plasma homocysteine, a functional marker of folate status. The MTHFR C677T polymorphism appears to interact with folate and riboflavin in modulating cancer risk in a manner that varies according to cancer site. Most evidence points to a protective effect of this polymorphism for risk of colorectal cancer, but the effect on cervical cancer risk is not clear. The effect of this polymorphism on cancer risk seems to be further modulated by other factors, including alcohol and, in the case of cervical cancer, infection with the human papilloma virus. An additional factor determining the effect of diet and genotype interactions on cancer risk may be the stage of cancer development. PMID:16317155

  13. Cervical Cancer: Development of Targeted Therapies Beyond Molecular Pathogenesis

    PubMed Central

    Knoff, Jayne; Yang, Benjamin; Hung, Chien-Fu; Wu, T.-C.

    2014-01-01

    It is well known that human papillomavirus (HPV) is the causative agent of cervical cancer. The integration of HPV genes into the host genome causes the upregulation of E6 and E7 oncogenes. E6 and E7 proteins inactivate and degrade tumor suppressors p53 and retinoblastoma, respectively, leading to malignant progression. HPV E6 and E7 antigens are ideal targets for the development of therapies for cervical cancer and precursor lesions because they are constitutively expressed in infected cells and malignant tumors but not in normal cells and they are essential for cell immortalization and transformation. Immunotherapies are being developed to target E6/E7 by eliciting antigen-specific immune responses. siRNA technologies target E6/E7 by modulating the expression of the oncoproteins. Proteasome inhibitors and histone deacetylase inhibitors are being developed to indirectly target E6/E7 by interfering with their oncogenic activities. The ultimate goal for HPV-targeted therapies is the progression through clinical trials to commercialization. PMID:24533233

  14. Structurally related ganoderic acids induce apoptosis in human cervical cancer HeLa cells: Involvement of oxidative stress and antioxidant protective system.

    PubMed

    Liu, Ru-Ming; Li, Ying-Bo; Liang, Xiang-Feng; Liu, Hui-Zhou; Xiao, Jian-Hui; Zhong, Jian-Jiang

    2015-10-01

    Ganoderic acids (GAs) produced by Ganoderma lucidum possess anticancer activities with the generation of reactive oxygen species (ROS). However, the role of oxidative stress in apoptotic process induced by GAs is still undefined. In this study, the effects of four structurally related GAs, i.e. GA-T, GA-Mk, and two deacetylated derivatives of GA-T (GA-T1 and GA-T2) on the antioxidant defense system and induced apoptosis in cervical cancer cells HeLa were investigated invitro. Our results indicated that the tested GAs (5-40?M) induced apoptotic cell death through mitochondrial membrane potential decrease and activation of caspase-9 and caspase-3. Furthermore, GAs increased the generation of intracellular ROS and attenuated antioxidant defense system by decreasing glutathione (GSH) level, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities. The above effects were remarkably blocked by the exogenous antioxidants, i.e. N-acetylcysteine, catalase and diphenyleneiodonium chloride. The potency of the four GAs toward induced apoptosis, generation of ROS and suppression of antioxidant defense system was in the order of: GA-T>GA-Mk?GA-T1>GA-T2 in HeLa cells. These findings suggest that GAs induced mitochondria-dependent cell apoptosis in HeLa cells are mediated via enhancing oxidative stress and depressing antioxidant defense. Additionally, the acetylation of hydroxyl groups in GAs may contribute to their pro-oxidant activities and cytotoxicity, which is helpful to the development of novel chemotherapy agents. PMID:26282491

  15. Recurrence of cervical cancer in mice after selective estrogen receptor modulator therapy.

    PubMed

    Spurgeon, Megan E; Chung, Sang-Hyuk; Lambert, Paul F

    2014-02-01

    Estrogen and its nuclear receptor, estrogen receptor ?, are necessary cofactors in the initiation and multistage progression of carcinogenesis in the K14E6/E7 transgenic mouse model of human papillomavirus-associated cervical cancer. Recently, our laboratory reported that raloxifene, a selective estrogen receptor modulator, promoted regression of high-grade dysplasia and cancer that arose in the cervix of K14E6/E7 transgenic mice treated long-term with estrogen. Herein, we evaluated the recurrence of cervical cancer after raloxifene therapy in our preclinical model of human papillomavirus-associated cervical carcinogenesis. We observed recurrence of cervical cancer in mice re-exposed to estrogen after raloxifene treatment, despite evidence suggesting the antagonistic effects of raloxifene persisted in the reproductive tract after treatment had ceased. We also observed recurrence of neoplastic disease in mice that were not retreated with exogenous estrogen, although the severity of disease was less. Recurrent neoplastic disease and cancers retained functional estrogen receptor ? and responded to retreatment with raloxifene. Moreover, continuous treatment of mice with raloxifene prevented the emergence of recurrent disease seen in mice in which raloxifene was discontinued. These data suggest that cervical cancer cells are not completely eradicated by raloxifene and rapidly expand if raloxifene treatment is ceased. These findings indicate that a prolonged treatment period with raloxifene might be required to prevent recurrence of neoplastic disease and lower reproductive tract cancers. PMID:24418098

  16. Aspirin and Acetaminophen Use and the Risk of Cervical Cancer

    PubMed Central

    Friel, Grace; Liu, Cici S.; Kolomeyevskaya, Nonna V.; Hampras, Shalaka S.; Kruszka, Bridget; Schmitt, Kristina; Cannioto, Rikki A.; Lele, Shashikant B.; Odunsi, Kunle O.; Moysich, Kirsten B.

    2016-01-01

    Objective In this study, we investigated whether regular use of aspirin or acetaminophen was associated with risk of cervical cancer in women treated at an American cancer hospital. Methods This case-control study included 328 patients with cervical cancer and 1,312 controls matched on age and decade enrolled. Controls were women suspected of having but not ultimately diagnosed with a neoplasm. Analgesic use was defined as regular (at least once per week for ?6 months), frequent (?7 tablets/week), very long term (?11 years), or frequent, long term (?7 tablets per week for ?5 years). Results Compared to nonusers, frequent aspirin use was associated with decreased odds of cervical cancer (odds ratio, 0.53; 95%confidence interval, 0.290.97). A slightly larger association was observed with frequent, long-term use of aspirin (odds ratio, 0.46; 95% confidence interval, 0.220.95). Acetaminophen use was not associated with the risk of cervical cancer. Conclusions Our findings suggest that frequent and frequent, long-term use of aspirin is associated with decreased odds of cervical cancer. To our knowledge, this is the first US-based study examining these associations. Given the widespread use of nonsteroidal anti-inflammatory drugs and acetaminophen worldwide, further investigations of the possible role of analgesics in cervical cancer, using a larger sample size with better-defined dosing regimens, are warranted. PMID:25856123

  17. Fluorescence spectra of blood and urine for cervical cancer detection

    NASA Astrophysics Data System (ADS)

    Masilamani, Vadivel; AlSalhi, Mohamad Saleh; Vijmasi, Trinka; Govindarajan, Kanaganaj; Rathan Rai, Ram; Atif, Muhammad; Prasad, Saradh; Aldwayyan, Abdullah S.

    2012-09-01

    In the current study, the fluorescence emission spectra (FES) and Stokes shift spectra (SSS) of blood and urine samples of cervical cancer patients were obtained and compared to those of normal controls. Both spectra showed that the relative intensity of biomolecules such as porphyrin, collagen, Nicotinamide adenine dinucleotide, and flavin were quite out of proportion in cervical cancer patients. The biochemical mechanism for the elevation of these fluorophores is not yet definitive; nevertheless, these biomolecules could serve as tumor markers for diagnosis, screening, and follow-up of cervical cancers. To the best of our knowledge, this is the first report on FES and SSS of blood and urine of cervical cancer patients to give a sensitivity of 80% and specificity of 78%.

  18. Older Hispanic women, health literacy, and cervical cancer screening.

    PubMed

    Flores, Bertha E; Acton, Gayle J

    2013-11-01

    Approximately 90 million people in the United States lack basic literacy skills, which affect health behaviors. Cervical cancer is preventable and treatable, yet few older Hispanic women seek screening and continue to be a high-risk group for cervical cancer. A literature review was conducted to address the relationship between cervical cancer screening, health literacy, and older Hispanic women. Eighty studies were reviewed, and nine addressed health literacy and Hispanic women. One study addressed the association between functional health literacy and Pap smear screening among older Hispanic women. Few studies have explored the association between preventive cervical cancer screening and health literacy among older Hispanic women. Nurses must assess health literacy and be prepared to provide care, which is culturally, and linguistically appropriate to improve health outcomes. Further research is needed to be inclusive of all populations including older Hispanic women. PMID:23729023

  19. Immunotherapy and targeted therapy for cervical cancer: an update.

    PubMed

    Menderes, Gulden; Black, Jonathan; Schwab, Carlton L; Santin, Alessandro D

    2016-01-01

    The prognosis of patients with metastatic cervical cancer is poor with a median survival of 8-13 months. Despite the potency of chemotherapeutic drugs, this treatment is rarely curative and should be considered palliative only. In the last few years, a better understanding of Human papillomavirus tumor-host immune system interactions and the development of new therapeutics targeting immune check points have renewed interest in the use of immunotherapy in cervical cancer patients. Moreover, next generation sequencing has emerged as an attractive option for the identification of actionable driver mutations and other markers. In this review, we provide background information on the molecular biology of cervical cancer and summarize immunotherapy studies, targeted therapies, including those with angiogenesis inhibitors and tyrosine kinase inhibitors recently completed or currently on-going in cervical cancer patients. PMID:26568261

  20. Grantee Spotlight: Dr. Kolawole Okuyemi - Improving Cervical Cancer Screening Attitudes

    Cancer.gov

    Dr. Kolawole Okuyumi is studying cervical cancer screening attitudes and behaviors of African immigrants and refugees in Minnesota, and introducing “cancer” and “cervix” to their everyday vocabulary.

  1. Image-Guided Radiotherapy and -Brachytherapy for Cervical Cancer

    PubMed Central

    Dutta, Suresh; Nguyen, Nam Phong; Vock, Jacqueline; Kerr, Christine; Godinez, Juan; Bose, Satya; Jang, Siyoung; Chi, Alexander; Almeida, Fabio; Woods, William; Desai, Anand; David, Rick; Karlsson, Ulf Lennart; Altdorfer, Gabor

    2015-01-01

    Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer. PMID:25853092

  2. Image-guided radiotherapy and -brachytherapy for cervical cancer.

    PubMed

    Dutta, Suresh; Nguyen, Nam Phong; Vock, Jacqueline; Kerr, Christine; Godinez, Juan; Bose, Satya; Jang, Siyoung; Chi, Alexander; Almeida, Fabio; Woods, William; Desai, Anand; David, Rick; Karlsson, Ulf Lennart; Altdorfer, Gabor

    2015-01-01

    Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer. PMID:25853092

  3. Epidemiology and costs of cervical cancer screening and cervical dysplasia in Italy

    PubMed Central

    Rossi, Paolo Giorgi; Ricciardi, Alessandro; Cohet, Catherine; Palazzo, Fabio; Furnari, Giacomo; Valle, Sabrina; Largeron, Nathalie; Federici, Antonio

    2009-01-01

    Background We estimated the number of women undergoing cervical cancer screening annually in Italy, the rates of cervical abnormalities detected, and the costs of screening and management of abnormalities. Methods The annual number of screened women was estimated from National Health Interview data. Data from the Italian Group for Cervical Cancer Screening were used to estimate the number of positive, negative and unsatisfactory Pap smears. The incidence of CIN (cervical intra-epithelial neoplasia) was estimated from the Emilia Romagna Cancer Registry. Patterns of follow-up and treatment costs were estimated using a typical disease management approach based on national guidelines and data from the Italian Group for Cervical Cancer Screening. Treatment unit costs were obtained from Italian National Health Service and Hospital Information System of the Lazio Region. Results An estimated 6.4 million women aged 25–69 years undergo screening annually in Italy (1.2 million and 5.2 million through organized and opportunistic screening programs, respectively). Approximately 2.4% of tests have positive findings. There are approximately 21,000 cases of CIN1 and 7,000–17,000 cases of CIN2/3. Estimated costs to the healthcare service amount to €158.5 million for screening and €22.9 million for the management of cervical abnormalities. Conclusion Although some cervical abnormalities might have been underestimated, the total annual cost of cervical cancer prevention in Italy is approximately €181.5 million, of which 87% is attributable to screening. PMID:19243586

  4. [Current Status and Perspective of Chemoradiotherapy for Uterine Cervical Cancer].

    PubMed

    Toita, Takafumi; Ariga, Takuro; Kasuya, Goro; Hashimoto, Seiji; Maemoto, Hitoshi; Heianna, Joichi; Kakinohana, Yasumasa; Murayama, Sadayuki

    2015-10-01

    Fifteen years has passed since the NCI announced the clinical importance of concurrent chemoradiotherapy (CCRT) in radiotherapy for patients with locoregionally advanced uterine cervical cancer. Numerous clinical trials have been performed to further improve the outcomes of CCRT. In addition to investigations of chemotherapeutic regimens and schedules, adaptation of novel radiotherapy methods such as image-guided brachytherapy (IGBT) and intensity-modulated radiotherapy (IMRT) is encouraged in CCRT for cervical cancer. PMID:26489545

  5. Cervical cancer worry and screening among appalachian women.

    PubMed

    Kelly, Kimberly M; Schoenberg, Nancy; Wilson, Tomorrow D; Atkins, Elvonna; Dickinson, Stephanie; Paskett, Electra

    2015-04-01

    Although many have sought to understand cervical cancer screening (CCS) behavior, little research has examined worry about cervical cancer and its relationship to CCS, particularly in the underserved, predominantly rural Appalachian region. Our mixed method investigation aimed to obtain a more complete and theoretically-informed understanding of the role of cancer worry in CCS among Appalachian women, using the Self-Regulation Model (SRM). Our quantitative analysis indicated that the perception of being at higher risk of cervical cancer and having greater distress about cancer were both associated with greater worry about cancer. In our qualitative analysis, we found that, consistent with the SRM, negative affect had a largely concrete-experiential component, with many women having first-hand experience of the physical consequences of cervical cancer. Based on the results of this manuscript, we describe a number of approaches to lessen the fear associated with CCS. Intervention in this elevated risk community is merited and may focus on decreasing feelings of worry about cervical cancer and increasing communication of objective risk and need for screening. From a policy perspective, increasing the quantity and quality of care may also improve CCS rates and decrease the burden of cancer in Appalachia. PMID:25416153

  6. Sphingosine kinase 1 is a reliable prognostic factor and a novel therapeutic target for uterine cervical cancer

    PubMed Central

    Cho, Young-Jae; Choi, Jung-Joo; Lee, Yoo-Young; Kim, Tae-Joong; Choi, Chel-Hun; Song, Sang Yong; Kim, Byoung-Gie; Bae, Duk-Soo; Lee, Jeong-Won

    2015-01-01

    Sphingosine kinase 1 (SPHK1), an oncogenic kinase, has previously been found to be upregulated in various types of human malignancy and to play a crucial role in tumor development and progression. Although SPHK1 has gained increasing prominence as an important enzyme in cancer biology, its potential as a predictive biomarker and a therapeutic target in cervical cancer remains unknown. SPHK1 expression was examined in 287 formalin-fixed, paraffin-embedded cervical cancer tissues using immunohistochemistry, and its clinical implications and prognostic significance were analyzed. Cervical cancer cell lines including HeLa and SiHa were treated with the SPHK inhibitors SKI-II or FTY720, and effects on cell survival, apoptosis, angiogenesis, and invasion were examined. Moreover, the effects of FTY720 on tumor growth were evaluated using a patient-derived xenograft (PDX) model of cervical cancer. Immunohistochemical analysis revealed that expression of SPHK1 was significantly increased in cervical cancer compared with normal tissues. SPHK1 expression was significantly associated with tumor size, invasion depth, FIGO stage, lymph node metastasis, and lymphovascular invasion. Patients with high SPHK1 expression had lower overall survival and recurrence-free survival rates than those with low expression. Treatment with SPHK inhibitors significantly reduced viability and increased apoptosis in cervical cancer cells. Furthermore, FTY720 significantly decreased in vivo tumor weight in the PDX model of cervical cancer. We provide the first convincing evidence that SPHK1 is involved in tumor development and progression of cervical cancer. Our data suggest that SPHK1 might be a potential prognostic marker and therapeutic target for the treatment of cervical cancer. PMID:26311741

  7. A lectin-based diagnostic system using circulating antibodies to detect cervical intraepithelial neoplasia and cervical cancer.

    PubMed

    Jin, Yingji; Kim, Seung Cheol; Kim, Hyoung Jin; Ju, Woong; Kim, Yun Hwan; Kim, Hong-Jin

    2016-01-01

    In the present study, we developed serological strategies using immunoglobulin fractions obtained by protein A chromatography to screen for cervical cancer and cervical intraepithelial neoplasia I (CIN I). The reactivities of the immunoglobulins purified from sera of women with normal cytology, CIN I and cervical cancer were compared in enzyme-linked immunosorbent assays (ELISA) and enzyme-linked lectin assays (ELLAs). To capture the immunoglobulins, ELISAs and ELLAs were performed in protein A immobilized microplates. The reactivity of immunoglobulin in ELISA was in the increasing order normal cytology, CIN I and cervical cancer, while that in ELLAs for detecting fucosylation was in the decreasing order normal cytology, CIN I and cervical cancer. It was confirmed that women with CIN I were distinguishable from women with normal cytology or women with cervical cancer in the ELISA or the ELLA for detecting fucosylation with considerable sensitivity and specificity. Women with cervical cancer were also distinguishable from women with normal cytology with high sensitivity (ELISA: 97%, ELLA: 87%) and specificity (ELISA: 69%, ELLA: 72%). Moreover, the logistic regression model of the ELISA and the ELLA discriminated cervical cancer from normal cytology with 93% sensitivity and 93% specificity. These results indicate that the ELISAs and the ELLAs have great potential as strategies for primary screening of cervical cancer and CIN. It is expected that the ELISA and the ELLA can provide new insights to understand systemic changes of serum immunoglobulins during cervical cancer progression. PMID:26358468

  8. Understanding cervical cancer: an exploration of lay perceptions, beliefs and knowledge about cervical cancer among the Acholi in northern Uganda

    PubMed Central

    2014-01-01

    Background Cervical cancer is the most common cancer affecting women in Uganda; yet community understanding of the disease is limited. We explored community perceptions, beliefs and knowledge about the local names, causes, symptoms, course, treatment, and prognosis of cervical cancer in order to inform targeted interventions to promote early help-seeking. Methods Twenty four focus group discussions (FGD) with men and women aged 18 59years and ten key informant interviews with persons aged???60years were conducted at two sites in Gulu district between May and June 2012. A semi-structured interview guide informed by Kleinmans illness explanatory model and literature on community awareness of cervical cancer was used to collect data. Data analysis was supported with use of ATLAS.ti 6.1 in coding, organizing and tracking data segments. We used content analysis technique in data analysis and organised data into a structured format under distinct themes and categories. Results Cervical cancer was known by the local name two remo, meaning an illness that manifests with bleeding. Respondents believed that early onset of sexual activity, multiple male sexual partners and multi-parity cause cervical cancer. Respondents in half of FGDs also reported that use of condoms and family planning pills and injections cause cervical cancer. Symptoms of cervical cancer reported included vaginal bleeding, watery vaginal discharge and lower abdominal and waist pain. Respondents in most of the FGDs and key informants perceived cervical cancer as a chronic illness and that it can be treated with both modern and traditional medicines. The majority thought that cervical cancer treatment was supportive; the illness is not curable. Conclusions While some lay beliefs about the causes of cervical cancer suggest some understanding of aetiology of the disease, other perceived causes particularly those related to use of family planning and condoms are potentially hurtful to public health. Awareness campaigns to promote early help-seeking for cervical cancer symptoms need to be culturally-sensitive and context-specific; and include messages on symptoms, risk factors, course, treatment and prognoses. PMID:25028122

  9. National Cancer Institute Research on Human Papillomavirus and Cervical Cancer - March 11, 2004

    Cancer.gov

    National Cancer Institute Research on Human Papillomavirus and Cervical Cancer Statement of Edward L. Trimble M.D., M.P.H National Cancer Institute National Institutes of Health Department of Health and Human Services Before the House Committee

  10. New strategies in advanced cervical cancer: from angiogenesis blockade to immunotherapy.

    PubMed

    Tewari, Krishnansu S; Monk, Bradley J

    2014-11-01

    Cervical cancer remains unique among solid tumor malignancies. Persistent infection with oncogenic subtypes of the human papillomavirus (HPV) results in carcinogenesis, predominantly occurring at the cervical transformation zone where endocervical columnar cells undergo metaplasia to a stratified squamous epithelium. The molecular cascade involving viral oncoproteins, E6 and E7 and their degradative interactions with cellular tumor suppressor gene products, p53 and pRb, respectively, has been precisely delineated. The precursor state of cervical neoplasia may last for years allowing for ready detection through successful screening programs in developed countries using cervical cytology and/or high-risk HPV DNA testing. Prophylactic HPV L1 capsid protein vaccines using virus-like-particle technology have been developed to prevent primary infection by the most common high-risk HPVs (16 and 18). Women who lack access to health care and those who undergo sporadic screening remain at risk. Although radical surgery (including fertility-sparing surgery) is available for patients with early-stage cancers, and chemoradiation plus high-dose-rate brachytherapy can cure the majority of those with locally advanced disease, patients with metastatic and nonoperable recurrent cervical cancer constitute a high-risk population with an unmet clinical need. On August 14, 2014, the FDA approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer. This review will highlight advances in translational science, antiangiogenesis therapy and immunotherapy for advanced disease. PMID:25104084

  11. Co-expression of metalloproteinases 11 and 12 in cervical scrapes cells from cervical precursor lesions

    PubMed Central

    Valdivia, Alejandra; Peralta, Ral; Matute-Gonzlez, Manuel; Garca Cebada, Juan Manuel; Casasola, Ivonne; Jimnez-Medrano, Cristina; Aguado-Prez, Rogelio; Villegas, Vanessa; Gonzlez-Bonilla, Cesar; Manuel-Apolinar, Leticia; Ibez, Miguel; Salcedo, Mauricio

    2011-01-01

    The metalloproteinases (MMP) 11 and 12 have been shown to be expressed in cervical cancer (CC). In order to extend our previous results, these MMPs were evaluated in cervical precursor lesions. One hundred seventeen cervical scrapes: thirty-six normal, thirty-six Low grade squamous lesions (LSIL), thirty-six High grade (HSIL), nine CC; and, also ninety-nine paraffin-embedded cervical lesions: fifteen normal cervices, thirty eight LSIL, sixteen HSIL, and five CC were collected. The samples were analyzed for relative expression by real time RT-PCR or immunohistochemistry assay. We were able to identify a relative increased expression of MMP11 in 75% and 78% from LSIL and HSIL samples, respectively. While MMP12 expression was 64% and 75% in LSIL and HSIL, respectively. Positive samples for MMP11 expression were also positive for MMP12 expression and also increased according to illness progression. In the tissues, MMP11 or MMP12 expression was observed in the cytoplasm of the neoplastic cells, while in the normal epithelium was absent. The reaction was always stronger for MMP12 than MMP11. MMP11 expression was present in 77% and 66% of LSIL and HSIL, while MMP12 expression was 73% and 68%. There was a relationship between MMP11 or MMP12 expression and HPV infection. Our data are showing a relationship between diagnostic of precursor lesions and the MMP11 and 12 expressions, suggesting that their expression could be an early event in the neoplastic lesions of the cervix and could have clinical significance. PMID:22076168

  12. Knowledge, Attitudes and Practices Regarding Cervical Cancer and Screening among Haitian Health Care Workers

    PubMed Central

    Zahedi, Leilah; Sizemore, Emma; Malcolm, Stuart; Grossniklaus, Emily; Nwosu, Oguchi

    2014-01-01

    It is estimated that Haiti has the highest incidence of cervical cancer in the Western Hemisphere. There are currently no sustainable and affordable cervical cancer screening programs in Haiti. The current status of screening services and knowledge of health care professionals was assessed through a Knowledge, Attitudes, and Practices survey on cervical cancer screening and prevention. It was distributed to Project Medishare for Haiti health care workers (n = 27) in the Central Plateau. The majority (22/27) of participants stated pre-cancerous cells could be detected through screening, however, only four had ever performed a pap smear. All of the participants felt a screening program should be started in their area. Our data establishes that knowledge is fairly lacking among healthcare workers and there is an opportunity to train them in simple, cost effective screen-and-treat programs that could have a great impact on the overall health of the population. PMID:25390794

  13. BRIP1 inhibits the tumorigenic properties of cervical cancer by regulating RhoA GTPase activity

    PubMed Central

    ZOU, WEI; MA, XIANGDONG; HUA, WEI; CHEN, BILIANG; HUANG, YANHONG; WANG, DETANG; CAI, GUOQING

    2016-01-01

    Breast cancer 1, early onset (BRCA1)-interacting protein 1 (BRIP1), a DNA-dependent adenosine triphosphatase and DNA helicase, is required for BRCA-associated DNA damage repair functions, and may be associated with the tumorigenesis and aggressiveness of various cancers. The present study investigated the expression of BRIP1 in normal cervix tissues and cervical carcinoma via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry assays. BRIP1 expression was observed to be reduced in squamous cancer tissue and adenocarcinoma compared with normal cervix tissue, and there were significant correlations between the reduction in BRIP1 expression and unfavorable variables, including the International Federation of Gynecologists and Obstetricians stage and presence of lymph node metastases. In order to elucidate the role of BRIP1 in cervical cancer, a BRIP1 recombinant plasmid was constructed and overexpressed in a cervical cancer cell line (HeLa). The ectopic expression of BRIP1 markedly inhibited the tumorigenic properties of HeLa cells in vitro, as demonstrated by decreased cell growth, invasion and adhesion, and increased cell apoptosis. In addition, it was identified that the inhibitory tumorigenic properties of BRIP1 may be partly attributed to the attenuation of RhoA GTPase activity. The present study provides a novel insight into the essential role of BRIP1 in cervical cancer, and suggests that BRIP1 may be a useful therapeutic target for the treatment of this common malignancy. PMID:26870246

  14. Socioecological perspectives on cervical cancer and cervical cancer screening among Asian American women.

    PubMed

    Lee, Jongwon; Carvallo, Mauricio

    2014-10-01

    Although cervical cancer is one of the most commonly diagnosed cancers among Vietnamese American women (VAW) and Korean American women (KAW), both groups consistently report much lower rates of cervical cancer screening compared with other Asian ethnic subgroups and non-Hispanic Whites. This study aimed to explore multilevel factors that may underlie low screening rates among VAW and KAW living in a city where their ethnic communities are relatively small. The socioecological model was used as a conceptual framework. Thirty participants were conveniently recruited from ethnic beauty salons run by VA and KA cosmetologists in Albuquerque, New Mexico. The participants' average age was 44.6 years (SD = .50; range = 21-60). Most participants were married (80 %) and employed (73.3 %), and had health insurance (83.3 %). A qualitative interview was conducted in Vietnamese or Korean and transcribed verbatim. A thematic content analysis was used to identify major codes, categories, and patterns across the transcripts. The study identified several factors at the individual (e.g., pregnancy, poverty, personality), interpersonal (e.g., family responsibility, mother as influential referent), and community (e.g., lack of availability, community size) levels. The study sheds light on four major areas that must be taken into consideration in the development of culturally appropriate, community-based interventions aimed to reduce disparities in cervical cancer screening among ethnic minority women in the United States: (1) ethnic community size and geographic location; (2) cross-cultural similarities and dissimilarities; (3) targeting of not only unmarried young women, but also close referents; and (4) utilization of trusted resources within social networks. PMID:24863746

  15. MET receptor is a potential therapeutic target in high grade cervical cancer

    PubMed Central

    Miekus, Katarzyna; Pawlowska, Marta; Seku?a, Ma?gorzata; Drabik, Grazyna; Madeja, Zbigniew; Adamek, Dariusz; Majka, Marcin

    2015-01-01

    Cervical cancer is one of the leading causes of death among women suffering from tumors. Current treatment options are insufficient. Here, we investigated the MET receptor as a potential molecular target in advanced cervical cancer. Downregulation of MET receptor expression via RNA interference in different cervical carcinoma cell lines dramatically decreased tumor growth and forced tumor differentiation in vivo. MET receptor silencing also led to a dramatic decrease in cell size and a decrease in proliferation rate under normal and stress conditions. MET receptor downregulation also resulted in decreased cyclin D1 and c-myc levels but did not increase apoptosis. Subsequent experiments showed that downregulation of the MET receptor decreased the expression of a key regulator of the epithelial-to-mesenchymal transition, SLUG. and increased the expression of E-cadherin, a hallmark of the epithelial phenotype. Moreover, MET downregulation impairs expression and signaling of CXCR4 receptor, responsible for invasive phenotype. Taken together, our results strongly suggest that the MET receptor influences the oncogenic properties of cervical carcinoma cells in vitro and in vivo. These findings highlight a unique role of the MET receptor in cervical carcinoma cells and indicate the MET receptor as a potential therapeutic target for advanced cervical carcinoma. PMID:25888626

  16. Screening for characteristic microRNAs between pre-invasive and invasive stages of cervical cancer.

    PubMed

    Zhu, Xiao-Lu; Wen, Shang-Yun; Ai, Zhi-Hong; Wang, Juan; Xu, Yan-Li; Teng, Yin-Cheng

    2015-07-01

    The aim of the present study was to investigate the characteristic microRNAs (miRNAs) expressed during the pre-invasive and invasive stages of cervical cancer. A gene expression profile (GSE7803) containing 21 invasive squamous cell cervical carcinoma samples, 10 normal squamous cervical epithelium samples and seven high-grade squamous intraepithelial cervical lesion samples, was obtained from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using significance analysis of microarray software, and a Gene Ontology (GO) enrichment analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery. The miRNAs that interacted with the identified DEGs were selected, based on the TarBase v5.0 database. Regulatory networks were constructed from these selected miRNAs along with their corresponding target genes among the DEGs. The regulatory networks were visualized using Cytoscape. A total of 1,160 and 756 DEGs were identified in the pre-invasive and invasive stages of cervical cancer, respectively. The results of the GO enrichment demonstrated that the DEGs were predominantly involved in the immune response and the cell cycle, in the pre?invasive and invasive stages, respectively. Furthermore, a total of 18 and 26 characteristic miRNAs were screened in the pre?invasive and invasive stages, respectively. These miRNAs may be potential biomarkers and targets for the diagnosis and treatment of the different stages of cervical cancer. PMID:25695263

  17. Cervical cytology and the diagnosis of cervical cancer in older women

    PubMed Central

    Landy, Rebecca; Castanon, Alejandra; Dudding, Nick; Lim, Anita Wey Wey; Hollingworth, Antony; Hamilton, Willie

    2015-01-01

    Objectives Most non-screen-detected cervical cancers are advanced stage. We assess the potential for cytology to expedite diagnosis when used outside of routine call and recall screening for cervical cancer. Methods Two cohorts of women with cytology that did not appear to have been taken as part of routine screening, nested within a census of cervical cytology, in England between April 2007 and March 2010 were studied: 93,322 women aged 4069 at first cytology, and 14,668 women aged ?70. The diagnostic performance of high grade cervical squamous intraepithelial lesion (HSIL) or worse cytology was estimated. We also estimated case-fatality from stage distribution in women aged ?66 with and without cytology in the year prior to diagnosis. Results There were 259 cancers diagnosed in women aged 4069 at first cytology, and 78 in women aged ?70. The sensitivity of cytology ? HSIL for cancer was 89% and 83% respectively, and the number of women needed to test to identify one cancer was 404 (95% confidence interval [CI]: 355462) and 226 (95% CI: 177292) respectively. Women aged ?66 with cytology within a year of diagnosis had earlier stage cancers than those without, corresponding to a 1722% reduction in case fatality. Conclusions Cervical cytology is an excellent identifier of cancer among women tested outside routine screening call and recall. Its use as a triage tool, for instance in women with vague gynaecological symptoms, could facilitate earlier stage diagnosis and reduce cervical cancer mortality. PMID:26346038

  18. The Curcumin Analogue 1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one Induces Apoptosis and Downregulates E6 and E7 Oncogene Expression in HPV16 and HPV18-Infected Cervical Cancer Cells.

    PubMed

    Paulraj, Felicia; Abas, Faridah; Lajis, Nordin H; Othman, Iekhsan; Hassan, Sharifah Syed; Naidu, Rakesh

    2015-01-01

    In an effort to study curcumin analogues as an alternative to improve the therapeutic efficacy of curcumin, we screened the cytotoxic potential of four diarylpentanoids using the HeLa and CaSki cervical cancer cell lines. Determination of their EC50 values indicated relatively higher potency of 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17, 1.03 ± 0.5 μM; 2.6 ± 0.9 μM) and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13, 2.8 ± 0.4; 6.7 ± 2.4 μM) in CaSki and HeLa, respectively, with significantly greater growth inhibition at 48 and 72 h of treatment compared to the other analogues or curcumin. Based on cytotoxic and anti-proliferative activity, MS17 was selected for comprehensive apoptotic studies. At 24 h of treatment, fluorescence microscopy detected that MS17-exposed cells exhibited significant morphological changes consistent with apoptosis, corroborated by an increase in nucleosomal enrichment due to DNA fragmentation in HeLa and CaSki cells and activation of caspase-3 activity in CaSki cells. Quantitative real-time PCR also detected significant down-regulation of HPV18- and HPV16-associated E6 and E7 oncogene expression following treatment. The overall data suggests that MS17 treatment has cytotoxic, anti-proliferative and apoptosis-inducing potential in HPV-positive cervical cancer cells. Furthermore, its role in down-regulation of HPV-associated oncogenes responsible for cancer progression merits further investigation into its chemotherapeutic role for cervical cancer. PMID:26132907

  19. Health systems challenges in cervical cancer prevention program in Malawi

    PubMed Central

    Maseko, Fresier C.; Chirwa, Maureen L.; Muula, Adamson S.

    2015-01-01

    Background Cervical cancer remains the leading cause of cancer death among women in sub-Saharan Africa. In Malawi, very few women have undergone screening and the incidence of cervical cancer is on the increase as is the case in most developing countries. We aimed at exploring and documenting health system gaps responsible for the poor performance of the cervical cancer prevention program in Malawi. Design The study was carried out in 14 randomly selected districts of the 29 districts of Malawi. All cervical cancer service providers in these districts were invited to participate. Two semi-structured questionnaires were used, one for the district cervical cancer coordinators and the other for the service providers. The themes of both questionnaires were based on World Health Organization (WHO) health system frameworks. A checklist was also developed to audit medical supplies and equipment in the cervical cancer screening facilities. The two questionnaires together with the medical supplies and equipment checklist were piloted in Chikwawa district before being used as data collection tools in the study. Quantitative data were analyzed using STATA and qualitative in NVIVO. Results Forty-one service providers from 21 health facilities and 9 district coordinators participated in the study. Our findings show numerous health system challenges mainly in areas of health workforce and essential medical products and technologies. Seven out of the 21 health facilities provided both screening and treatment. Results showed challenges in the management of the cervical cancer program at district level; inadequate service providers who are poorly supervised; lack of basic equipment and stock-outs of basic medical supplies in some health facilities; and inadequate funding of the program. In most of the health facilities, services providers were not aware of the policy which govern their work and that they did not have standards and guidelines for cervical cancer screening and treatment. Conclusion Numerous health system challenges are prevailing in the cervical cancer prevention program in Malawi. These challenges need to be addressed if the health system is to improve on the coverage of cervical cancer screening and treatment. PMID:25623612

  20. [Human papilloma virus and cervical cancer. An historical review on the development of research on cancer of the cervix uteri in Venezuela].

    PubMed

    García-Tamayo, Jorge; Molina, Julia; Blasco-Olaetxea, Eduardo

    2010-06-01

    The history on the relationship of VPH infection and cervical cancer was examined. Findings were initially reported in Maracaibo(1971), later in Mexico(1973) and thereafter several studies on the ultrastructure and immunohistochemistry of VPH infection and its role on cervical cancer were described. The ultrastructural findings of viral particles of HPV and their proteins, as well as their role in the incorporation of the viral genome to the human cervical cells were also described. Glycoproteins on the surface of cervical cells were reviewed and their importance on HPV infection was related to p16, blood group antigens and early genetic changes in the cell cycle with loss of heterozigocity, all of which, stimulated by the high risk HPV infection lead to cervical cancer. PMID:20928978

  1. [Vaccination against human papilloma virus and cervical cancer].

    PubMed

    Kidon, Mona Iankovic; Shechter, Edward; Toubi, Elias

    2011-01-01

    The human papilloma virus family (HPV], mainly HPV 16, 18 but less HPV 31, 45 were proven to be the cause of cervical intraepithelial neoplasia and cancer. Following natural infection, only half of the infected women develop neutralizing antibodies and even these were of a very Low titer and found to be ineffective. Hence, an efficient vaccination followed by the development of long tasting neutralizing antibodies is needed. Two different vaccines are now Licensed in IsraeL: Cervarix and Gardasil. The first is composed of viral-like particles of HPV 16, 18 and a complex of two adjuvants (aluminum salts and MPL [TLR-4 agonist]). The second is composed of 4 HPV types, HPV 16, 18 (related to cervical cancer] and HPV 6, 11 (related to condyloma). Cervarix is characterized by inducing long lasting titers of neutralizing antibodies and a higher level of memory B cells. Surveillance of Gardasil vaccines reveals a decrease in the titer of neutralizing antibodies, namely those against HPV 18. In addition, to the high titer of antibodies against HPV 16, 18, Cervarix offers 100% protection against additional HPV types mainly 13 and 45. This cross protection is considered to be one of the important advantages over Gardasil. Both vaccines present a strong safety profile. Final clinical outcomes are the subject of many future studies. PMID:21449154

  2. Epidemiology of cervical cancer with special focus on India.

    PubMed

    Sreedevi, Aswathy; Javed, Reshma; Dinesh, Avani

    2015-01-01

    Cervical cancer is on the declining trend in India according to the population-based registries; yet it continues to be a major public health problem for women in India. Multifactorial causation, potential for prevention, and the sheer threat it poses make cervical cancer an important disease for in-depth studies, as has been attempted by this paper. This paper attempts to review the available knowledge regarding the epidemiology and pattern of cervical cancer; types of HPV (human papilloma virus) prevalent among cervical cancer patients and among women in general, high-risk groups such as commercial sex workers, and HIV (human immunodeficiency virus)-positive women; and the role of the national program on cancer in control efforts. The peak age of incidence of cervical cancer is 55-59 years, and a considerable proportion of women report in the late stages of disease. Specific types of oncogenic HPV-16, 18 have been identified in patients with cervical cancer. Other epidemiological risk factors are early age at marriage, multiple sexual partners, multiple pregnancies, poor genital hygiene, malnutrition, use of oral contraceptives, and lack of awareness. A multipronged approach is necessary which can target areas of high prevalence identified by registries with a combination of behavior change communication exercises and routine early screening with VIA. Sensitizing the people of the area, including menfolk, is necessary to increase uptake levels. Vaccination against types 16 and 18 can also be undertaken after taking into confidence all stakeholders, including the parents of adolescent girls. Preventing and treating cervical cancer and reducing the burden are possible by targeting resources to the areas with high prevalence. PMID:25931830

  3. Epidemiology of cervical cancer with special focus on India

    PubMed Central

    Sreedevi, Aswathy; Javed, Reshma; Dinesh, Avani

    2015-01-01

    Cervical cancer is on the declining trend in India according to the population-based registries; yet it continues to be a major public health problem for women in India. Multifactorial causation, potential for prevention, and the sheer threat it poses make cervical cancer an important disease for in-depth studies, as has been attempted by this paper. This paper attempts to review the available knowledge regarding the epidemiology and pattern of cervical cancer; types of HPV (human papilloma virus) prevalent among cervical cancer patients and among women in general, high-risk groups such as commercial sex workers, and HIV (human immunodeficiency virus)-positive women; and the role of the national program on cancer in control efforts. The peak age of incidence of cervical cancer is 5559 years, and a considerable proportion of women report in the late stages of disease. Specific types of oncogenic HPV-16, 18 have been identified in patients with cervical cancer. Other epidemiological risk factors are early age at marriage, multiple sexual partners, multiple pregnancies, poor genital hygiene, malnutrition, use of oral contraceptives, and lack of awareness. A multipronged approach is necessary which can target areas of high prevalence identified by registries with a combination of behavior change communication exercises and routine early screening with VIA. Sensitizing the people of the area, including menfolk, is necessary to increase uptake levels. Vaccination against types 16 and 18 can also be undertaken after taking into confidence all stakeholders, including the parents of adolescent girls. Preventing and treating cervical cancer and reducing the burden are possible by targeting resources to the areas with high prevalence. PMID:25931830

  4. Disparities in cervical and breast cancer mortality in Brazil

    PubMed Central

    Girianelli, Vania Reis; Gamarra, Carmen Justina; Azevedo e Silva, Gulnar

    2014-01-01

    OBJECTIVE To analyze cervical and breast cancer mortality in Brazil according to socioeconomic and welfare indicators. METHODS Data on breast and cervical cancer mortality covering a 30-year period (1980-2010) were analyzed. The data were obtained from the National Mortality Database, population data from the Brazilian Institute of Geography and Statistics database, and socioeconomic and welfare information from the Institute of Applied Economic Research. Moving averages were calculated, disaggregated by capital city and municipality. The annual percent change in mortality rates was estimated by segmented linear regression using the joinpoint method. Pearsons correlation coefficients were conducted between average mortality rate at the end of the three-year period and selected indicators in the state capital and each Brazilian state. RESULTS There was a decline in cervical cancer mortality rates throughout the period studied, except in municipalities outside of the capitals in the North and Northeast. There was a decrease in breast cancer mortality in the capitals from the end of the 1990s onwards. Favorable socioeconomic indicators were inversely correlated with cervical cancer mortality. A strong direct correlation was found with favorable indicators and an inverse correlation with fertility rate and breast cancer mortality in inner cities. CONCLUSIONS There is an ongoing dynamic process of increased risk of cervical and breast cancer and attenuation of mortality because of increased, albeit unequal, access to and provision of screening, diagnosis and treatment. PMID:25119941

  5. Human Papillomavirus Genome-Wide Identification of T-Cell Epitopes for Peptide Vaccine Development Against Cervical Cancer: An Integration of Computational Analysis and Experimental Assay.

    PubMed

    Li, Bo; Zheng, Xianfang; Hu, Chuancui; Cao, Yunxia

    2015-10-01

    Human papillomavirus (HPV) has long been documented as the primary factor causing cervical cancer and other complications, and development of immunotherapeutic vaccines against HPV is thought to be an important approach in preventing women from HPV infections. It is known that the first step in vaccine development is to find potent T-cell epitopes in HPV proteins that can be effectively recognized and presented by the human leukocyte antigen (HLA) system. In the current study, we proposed a synthetic pipeline that integrates computational analysis and experimental assay to discover new peptide epitopes from HPV genome with high affinity to the HLA-A*0201, one of the most frequent HLA allele in Caucasian and Asian populations. In the procedure, a structure-based three-dimensional quantitative structure-activity relationship (3D-QSAR) methodology was described and several 3D-QSAR predictors were established using a set of activity-known HLA binders. The best predictor was then employed to perform extrapolation over the HPV genome to screen potential protein fragments with high HLA binding potency. Consequently, 10 peptides were suggested as promising candidates and their affinities toward HLA-A*0201 were assayed using a standard T2 cell surface stabilization test. Four peptides--LLITSNINA from protein E1 (BL50 = 7244 nM), VLLCVCLLI from protein E5 (BL50 = 9118 nM), VLLLWITAA from protein E5 (BL50 = 3388 nM), and LLMGTLGIV from protein E7 (BL50 = 5500 nM)--were identified as high-affinity binders. Further, the structural basis and binding mode of HLA-A*0201-LLITSNINA complex was examined in detail, revealing a complicated network of nonbonded interactions across the complex interface that should render high stability and specificity for the interaction system. PMID:26418056

  6. What School Nurses Need to Know about Cervical Cancer, HPV, and the New Vaccine

    ERIC Educational Resources Information Center

    Ehrhardt, Jeanie

    2007-01-01

    At least 12,000 women are diagnosed with cervical cancer each year in the United States, accounting for at least 4,000 deaths. Worldwide, cervical cancer is the second most common type of cancer among women. The human papilloma virus (HPV) has been linked to at least 70% of all cervical cancer. HPV can be divided into 2 categories: (a) low risk,

  7. Risk Factors for Cervical Cancer in Criminal Justice Settings

    PubMed Central

    Mueller, Shane; Clark, C. Brendan; Cropsey, Karen L.

    2011-01-01

    Abstract Background Women in criminal justice settings have an increased prevalence of cervical cancer compared with the general population. However, little is known about abnormal cervical cancer screening results among women in jail and community-based criminal justice settings. Thus, the aims of this study were to compare the prevalence of self-reported abnormal Papanicolou (Pap) test results in women in jail and under community criminal justice supervision and to examine factors associated with abnormal Pap tests in these criminal justice settings. Methods We analyzed data from two cross-sectional surveys of women in jails and community corrections in two Southern cities (n=380) about their history of abnormal Pap tests and risk factors for cervical cancer. Univariate analyses (analysis of variance [ANOVA] and chi-square) and a binary logistic regression analysis were conducted to test associations between a history of abnormal Pap testing and factors known to be associated with cervical cancer. Results Nearly half of the women surveyed (n=163, 43%) reported ever having an abnormal Pap test. There was a high prevalence of risk factors for cervical cancer among women with and without an abnormal Pap test. After controlling for age and race, there were significant associations between an abnormal Pap test and inconsistent use of barrier protection (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.18-3.43), having a history of gynecologic infections (OR 1.68, 95% CI 1.05-2.67), and having a history of sexually transmitted diseases (OR 1.92, 95% CI 1.17-3.15). Conclusions Women in jail and under community justice supervision reported a high prevalence of risk factors for cervical cancer. Because of their high prevalence of abnormal Pap testing, women in criminal justice settings may be appropriate targets for improved cervical cancer screening, prevention with human papillomavirus (HPV) vaccination, risk reduction education, and treatment. PMID:22004180

  8. Cervical cancer screening in Belgium and overscreening of adolescents.

    PubMed

    Van Kerrebroeck, Helena; Makar, Amin

    2016-03-01

    There has been a marked decrease in the incidence of cervical cancer thanks to cytological screening with the Pap smear test. In Belgium, this screening is rather opportunistic. Over 39% of Belgian women between 25 and 64 years of age are never or only rarely screened by cytological tests. Moreover, there is an excess use of Pap smears because of women who rely on their yearly cervical smear and because many Pap smears are obtained from women beyond the target age range of 25 to 64 years. Sexually active adolescents are increasingly being recognized as a population distinct from adult women. They are at a high risk of acquiring the human papillomavirus (HPV), but most infections and cervical intraepithelial lesions caused by HPV are efficiently cleared by the immune system. We present a description of cervical cancer screening in Belgium using the database of the National Health Insurance Institute (RIZIV/INAMI) and the Belgian Health Care Knowledge Centre (KCE). We describe why elimination of Pap testing in the adolescent population reduces costs and harms without increasing cervical cancer rates. Expectant management, education on the risk factors for cervical cancer and HPV persistence, and HPV vaccination are very important in adolescents and young adults. PMID:25812038

  9. Activation of p53/p21/PUMA alliance and disruption of PI-3/Akt in multimodal targeting of apoptotic signaling cascades in cervical cancer cells by a pentacyclic triterpenediol from Boswellia serrata.

    PubMed

    Bhushan, Shashi; Malik, Fayaz; Kumar, Ajay; Isher, Harpreet Kaur; Kaur, Indu Pal; Taneja, Subhash Chandra; Singh, Jaswant

    2009-12-01

    Cervical carcinoma is a growing menace to women health worldwide. This study reports the apoptotic cell death in human cervical cancer HeLa and SiHa cells by a pentacyclic triterpenediol (TPD) from Boswellia serrata by a mechanism different from reported in HL-60 cells. It caused oxidative stress by early generation of nitric oxide and reactive oxygen species that robustly up regulated time-dependent expression of p53/p21/PUMA while conversely abrogating phosphatidylinositol-3-kinase (PI3K)/Akt pathways in parallel. TPD also decreased the expression of PI3K/pAkt, ERK1/2, NF-kappaB/Akt signaling cascades which coordinately contribute to cancer cell survival through these distinct pathways. The tumor suppressor p53 pathway predominantly activated by TPD further up-regulated PUMA, which concomitantly decreased the Bcl-2 level, caused mitochondrial membrane potential loss with attendant translocation of Bax and drp1 to mitochondria and release of pro-apoptotic factors such as cytochrome c and Smac/Diablo to cytosol leading to caspases-3 and -9 activation. In addition both the phospho-p53 and p21 were found to accumulate heavily in the nuclear fraction with attendant decrease in topoisomarase II and survivin levels. On the contrary, TPD did not affect the extrinsic signaling transduction pathway effectively through apical death receptors. Interestingly, N-acetyl cysteine, ascorbate and s-methylisothiourea (sMIT) rescued cells significantly from TPD induced DNA damage and caspases activation. TPD may thus find usefulness in managing and treating cervical cancer. PMID:19544329

  10. Improving compliance with cervical cancer screening guidelines

    PubMed Central

    Goodell, Cara; Castro, Eduardo; Thomas, Jen; Kuehl, Thomas J.; Wehbe-Janek, Hania; Hinskey, Meghan

    2015-01-01

    Current cervical cancer screening guidelines for the care of healthy women include HPV cotesting with all Papanicolaou (Pap) smears after the age of 30. To improve compliance with current guidelines, we instituted two processes: first, simplifying the ordering process to a single order for Pap smear plus HPV cotesting using an electronic medical record system (EMR); and second, providing education for clinic staff. Baseline and postintervention data were collected by retrospective chart review. Patients were selected during three intervals: prior to the transition to Epic EMR, after the transition to Epic, and after an educational intervention. Compliance with standard guidelines was evaluated in relation to the trial intervals, type of provider, patient age, and duration from the previous Pap smear. Provider type was analyzed by considering gynecologists versus nongynecologist providers, and physicians versus mid-level providers. Overall, the percentage of compliance with HPV test ordering did not differ (P = 0.21) between intervals. Univariate analyses performed to identify factors likely to be associated with the practice of ordering HPV cotesting only involved the type of provider. In conclusion, transition to Epic and a training session had minimal impact on compliance with ordering HPV cotesting at the time of a Pap smear except among family practice physicians, who did significantly improve their compliance rate. Gynecologists and mid-level providers were more compliant with ordering HPV cotesting throughout, but did not significantly improve after the interventions. PMID:26424938

  11. Nominated texture based cervical cancer classification.

    PubMed

    Mariarputham, Edwin Jayasingh; Stephen, Allwin

    2015-01-01

    Accurate classification of Pap smear images becomes the challenging task in medical image processing. This can be improved in two ways. One way is by selecting suitable well defined specific features and the other is by selecting the best classifier. This paper presents a nominated texture based cervical cancer (NTCC) classification system which classifies the Pap smear images into any one of the seven classes. This can be achieved by extracting well defined texture features and selecting best classifier. Seven sets of texture features (24 features) are extracted which include relative size of nucleus and cytoplasm, dynamic range and first four moments of intensities of nucleus and cytoplasm, relative displacement of nucleus within the cytoplasm, gray level cooccurrence matrix, local binary pattern histogram, tamura features, and edge orientation histogram. Few types of support vector machine (SVM) and neural network (NN) classifiers are used for the classification. The performance of the NTCC algorithm is tested and compared to other algorithms on public image database of Herlev University Hospital, Denmark, with 917 Pap smear images. The output of SVM is found to be best for the most of the classes and better results for the remaining classes. PMID:25649913

  12. Cervical Cancer Along with Unknown Cirrhosis: A Misdiagnosed Case

    PubMed Central

    Aminimoghaddam, Soheila; Mahmoudzadeh, Fatemeh; Maghsoudnia, Andisheh

    2015-01-01

    Background: Cervical cancer is the second most common malignancy in women worldwide. Vaginal bleeding and vaginal discharge are the most common symptoms. Although ascites has been reported in cases with cervical cancer, it is due to other causes such as ovarian metastasis. Case Presentation: A 78-year-old diabetic woman who presented with ascites and abdominopelvic mass was misdiagnosed with ovarian cancer and treated with neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant radiotherapy. However, pathology confirmed locally advanced cervical cancer stage IV in this patient. She was discharged from the hospital three weeks after surgery with no serious complications. Discussion: Considering all signs and symptoms to reach a verdict would reduce such malpractices and consequently lead to select the best management and treatment.

  13. Physical Activity and Cervical Cancer Testing among American Indian Women

    ERIC Educational Resources Information Center

    Muus, Kyle J.; Baker-Demaray, Twyla B.; Bogart, T. Andy; Duncan, Glen E.; Jacobsen, Clemma; Buchwald, Dedra S.; Henderson, Jeffrey A.

    2012-01-01

    Purpose: Studies have shown that women who engage in high levels of physical activity have higher rates of cancer screening, including Papanicalaou (Pap) tests. Because American Indian (AI) women are at high risk for cervical cancer morbidity and mortality, we examined Pap screening prevalence and assessed whether physical activity was associated

  14. Design The Cervical Cancer Detector Use The Artificial Neural Network

    NASA Astrophysics Data System (ADS)

    Intan Af'idah, Dwi; Didik Widianto, Eko; Setyawan, Budi

    2013-06-01

    Cancer is one of the contagious diseases that become a public health issue, both in the world and in Indonesia. In the world, 12% of all deaths caused by cancer and is the second killer after cardiovascular disease. Early detection using the IVA is a practical and inexpensive (only requiring acetic acid). However, the accuracy of the method is quite low, as it can not detect the stage of the cancer. While other methods have a better sensitivity than the IVA method, is a method of PAP smear. However, this method is relatively expensive, and requires an experienced pathologist-cytologist. According to the case above, Considered important to make the cancer cervics detector that is used to detect the abnormality and cervical cancer stage and consists of a digital microscope, as well as a computer application based on artificial neural network. The use of cervical cancer detector software and hardware are integrated each other. After the specifications met, the steps to design the cervical cancer detection are: Modifying a conventional microscope by adding a lens, image recording, and the lights, Programming the tools, designing computer applications, Programming features abnormality detection and staging of cancer.

  15. Physical Activity and Cervical Cancer Testing among American Indian Women

    ERIC Educational Resources Information Center

    Muus, Kyle J.; Baker-Demaray, Twyla B.; Bogart, T. Andy; Duncan, Glen E.; Jacobsen, Clemma; Buchwald, Dedra S.; Henderson, Jeffrey A.

    2012-01-01

    Purpose: Studies have shown that women who engage in high levels of physical activity have higher rates of cancer screening, including Papanicalaou (Pap) tests. Because American Indian (AI) women are at high risk for cervical cancer morbidity and mortality, we examined Pap screening prevalence and assessed whether physical activity was associated…

  16. CERVICAL CANCER CONTROL RESEARCH IN VIETNAMESE AMERICAN COMMUNITIES

    PubMed Central

    Taylor, Victoria M.; Nguyen, Tung T.; Jackson, J. Carey; McPhee, Stephen J.

    2009-01-01

    Census data show that the US Vietnamese population now exceeds 1,250,000. Cervical cancer among Vietnamese American women has been identified as an important health disparity. Available data indicate the cervical cancer disparity may be due to low Pap testing rates rather than variations in HPV infection rates and/or types. The cervical cancer incidence rates among Vietnamese and non-Latina white women in California during 20002002 were 14.0 and 7.3 per 100,000, respectively. Only 70% of Vietnamese women who participated in the 2003 California Health Interview Survey reported a recent Pap smear, compared to 84% of non-Latina white women. Higher levels of cervical cancer screening participation among Vietnamese women are strongly associated with current/previous marriage, having a usual source of care/doctor, and previous physician recommendation. Vietnamese language media campaigns and lay health worker intervention programs have been effective in increasing Pap smear use in Vietnamese American communities. Cervical cancer control programs for Vietnamese women should address knowledge deficits; enable women who are without a usual source of care to find a primary care doctor; and improve patient-provider communication by encouraging health care providers to recommend Pap testing, as well as by empowering women to ask for testing. PMID:18990732

  17. Optimal management of cervical cancer in HIV-positive patients: a systematic review

    PubMed Central

    Ntekim, Atara; Campbell, Oladapo; Rothenbacher, Dietrich

    2015-01-01

    The clinical management of cervical cancer in HIV-positive patients has challenges mainly due to the concerns on immune status. At present, their mode of management is similar to HIV-seronegative patients involving the use of chemotherapy and radiotherapy concurrently as indicated. HIV infection, cancer, radiotherapy, and chemotherapy lower immunity through reduction in CD4 cell counts. At present there are no treatment guidelines for HIV-positive patients. This study was done to systematically review the literature on cervical cancer management in HIV-positive patients and treatment outcomes. A systematic literature search was done in the major databases to identify studies on the management of HIV-positive patients with cervical cancer. Identified studies were assessed for eligibility and inclusion in the review following the guidelines of The Cochrane Handbook for Systematic Reviews and CRD's (Centre for Reviews and Dissemination) guidance for undertaking reviews in health care. Eight eligible studies were identified from the literature. Three of them were prospective while five were retrospective studies. Notably, the average age at diagnosis of cervical cancer in HIV-positive patients was a decade lower than in seronegative patients. There was no difference in distribution of stages of disease at presentation between HIV-positive and negative patients. Mild acute toxicity (Grades 1 and 2) was higher in HIV-positive patients than in HIV-negative patients in hematopoietic system. In the grades 3 and 4 reactions, anemia was reported in 4% versus 2% while gastrointestinal reactions were reported in 5% versus 2% respectively. In general, patients who were started early on HAART had higher rates of treatment completion. The study supports the suggestion that HAART should be commenced early at cervical cancer diagnosis in HIV-positive patients diagnosed with cervical cancer to ensure less toxicity and better treatment compliance. PMID:26136407

  18. MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells

    SciTech Connect

    Yao, Qing; Xu, Hui; Zhang, Qian-Qian; Zhou, Hui; Qu, Liang-Hu

    2009-10-23

    MicroRNAs are involved in cancer-related processes. The microRNA-21(miR-21) has been identified as the only miRNA over-expressed in a wide variety of cancers, includi