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  1. Cervical Cancer

    Science.gov (United States)

    ... 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, ...

  2. Cervical Cancer

    Centers for Disease Control (CDC) Podcasts

    2007-03-06

    Did you know that cervical cancer rates differ by race/ethnicity and region? Or that cervical cancer can usually be prevented if precancerous cervical lesions are found by a Pap test and treated? Find out how getting regular Pap tests can save a woman's life.  Created: 3/6/2007 by National Breast and Cervical Cancer Early Detection Program.   Date Released: 4/25/2007.

  3. Small cell cervical cancer: an unusual finding at cholecystectomy.

    LENUS (Irish Health Repository)

    Boyle, Emily

    2012-02-01

    BACKGROUND: Small cell carcinoma of the cervix is a rare cancer, comprising less than 3% of all cervical neoplasms. It uniformly has a poor prognosis, and has a high mortality even with early stage disease. It can metastasise rapidly and metastatic sites include lung, liver, brain, bone, pancreas and lymph nodes. CASE: Here, we report the case of a 60-year-old woman with no symptoms of cervical pathology who developed post-renal failure following a laparoscopic cholecystectomy. The cause was bilateral ureteric obstruction from metastatic small cell cervical cancer and metastases were subsequently found on her gallbladder specimen. CONCLUSION: This is an unusual presentation of small cell cervical cancer and demonstrates the aggressive nature of this disease.

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  7. Decreased cervical cancer cell adhesion on nanotubular titanium for the treatment of cervical cancer

    OpenAIRE

    Crear J; Kummer KM; Webster TJ

    2013-01-01

    Jara Crear, Kim M Kummer, Thomas J Webster School of Engineering, Brown University, Providence, RI, USA Abstract: Cervical cancer can be treated by surgical resection, chemotherapy, and/or radiation. Titanium biomaterials have been suggested as a tool to help in the local delivery of chemotherapeutic agents and/or radiation to cervical cancer sites. However, current titanium medical devices used for treating cervical cancer do not by themselves possess any anticancer properties; such devices...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  10. Prevalence of micronuclei in exfoliated uterine cervical cells from patients with risk factors for cervical cancer

    Directory of Open Access Journals (Sweden)

    Lízia Maria Franco dos Reis Campos

    Full Text Available CONTEXT AND OBJECTIVE: Pap smears are the most common and inexpensive screening method for cervical cancer. We analyzed micronucleus prevalence in exfoliated cervical mucosa cells, to investigate associations between increased numbers of micronuclei and risk factors for cervical cancer. DESIGN AND SETTING: Analytical cross-sectional study, at Instituto de Pesquisa em Oncologia (IPON. METHODS: Exfoliated cervical cells were obtained from 101 patients between September 2004 and November 2005. Patients' ages, habits (passive or active smoking, alcoholism and numbers of sexual partners, age at first sexual intercourse, contraceptive methods used, histories of sexually transmitted diseases, use of hormone replacement therapy, numbers of pregnancies and abortions, inflammatory cytology and cervical intraepithelial neoplasia (CIN were obtained. Cells were collected using Ayre spatulas, transferred to vials containing 0.9% saline solution for micronucleus tests and analyzed at 1000x magnification. The number of micronuclei in 1,000 epithelial cells per patient sample was counted. RESULTS: Comparisons between groups with active (7.9 ± 7.8 and passive (7.2 ± 10.6 smoking versus no smoking (3.7 ± 5.1; with/without alcoholism (7.8 ± 1.4 and 6.9 ± 10.1; with/without inflammatory cytology (10.7 ± 10.5 and 1.3 ± 1.7; and with CIN I, II and III and no CIN (respectively 4.3 ± 4.3, 10.6 ± 5.3, 22.7 ± 11.9 and 1.3 ± 1.4 found elevated micronucleus prevalence (P < 0.05. CONCLUSIONS: We concluded that the prevalence of micronuclei in exfoliated uterine cervical cells was greater in patients with one or more risk factors for uterine cervical cancer than in patients without risk factors.

  11. 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

    Science.gov (United States)

    2016-10-26

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

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    2017-02-08

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

  14. Immunotherapy for Cervical Cancer

    Science.gov (United States)

    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.

  15. 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

    Science.gov (United States)

    2016-03-25

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

  16. Analysis of human papillomavirus E7 protein status in C-33A cervical cancer cells.

    Science.gov (United States)

    Kaiser, Andreas; Jenewein, Brigitte; Pircher, Haymo; Rostek, Ursula; Jansen-Dürr, Pidder; Zwerschke, Werner

    2015-02-01

    High-risk human papillomaviruses (HPV) are the main etiologic factor for the development of cervical cancer. Infections by these viruses have been detected in virtually all cervical cancers. C-33A is one of the rare cervical cancer derived cell lines considered as HPV-negative. Employing monoclonal antibodies raised against a conformational epitope of the HPV-16 E7 oncoprotein, we present evidence suggesting that E7-positive cells can be sporadically and transiently detected in C-33A cell cultures. Immunoblotting with affinity-purified rabbit polyclonal anti-HPV 16 E7 antisera and q-RT-PCR analysis suggest that these cells do probably not express HPV-16 E7. Moreover, we show that the HPV E7 protein level differs considerably between individual cells in cultures of several established cervical cancer cell lines. Our data suggest that expression of the E7 protein is variable in established cervical cancer cell lines including C-33A cells.

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

    Science.gov (United States)

    Wang, Hongtao; Gao, Peng; Zheng, Jie

    2014-09-05

    Arsenic trioxide (As2O3) 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 As2O3 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 As2O3 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 As2O3 than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As2O3 than HPV 16-positive CaSki and SiHa cells. After As2O3 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 As2O3 is a potential anticancer drug for cervical cancer.

  18. Cervical Cancer Stage IVA

    Science.gov (United States)

    ... historical Searches are case-insensitive Cervical Cancer Stage IVA Add to My Pictures View /Download : Small: 756x576 ... Large: 3150x2400 View Download Title: Cervical Cancer Stage IVA Description: Stage IVA cervical cancer; drawing and inset ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongtao [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China); Gao, Peng [Department of Internal Medicine, University of Iowa, Iowa City, IA 52242 (United States); Zheng, Jie, E-mail: jiezheng54@126.com [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China)

    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.

  20. The expression andprognostic value ofprotein tyrosine kinase 6 inearly-stage cervical squamous cell cancer

    Institute of Scientific and Technical Information of China (English)

    XiaoJingWang; YingXiong; ZeBiaoMa; JianChuanXia; YanFangLi

    2016-01-01

    Background:Protein tyrosine kinase 6 (PTK6) is overexpressed in many epithelial tumors and predicts poor progno‑sis. However, PTK6 expression status and its role in cervical squamous cell cancer are unknown. This study aimed to investigate the expression level and clinical signiifcance of PTK6 in early‑stage cervical squamous cell cancer. Methods:Quantitative reverse transcription‑polymerase chain reaction (qRT‑PCR) and western blotting analysis were performed to detect PTK6 mRNA and protein expression levels in 10 freshly frozen, early‑stage cervical squamous cell cancer specimens and adjacent non‑tumorous cervical tissues. The expression of PTK6 was detected using immuno‑histochemical staining in 150 formalin‑ifxed, paraffn‑embedded, early‑stage cervical squamous cell cancer sections and 10 normal cervical tissue sections. Results:The mRNA and protein levels of PTK6 in cancer tissues were higher than those in adjacent non‑tumorous cervical tissues. Immunohistochemical analysis showed that PTK6 was not expressed in normal cervical tissues but was overexpressed in the cytoplasm of cervical squamous cell cancer cells. The level of PTK6 expression was signiif‑cantly associated with tumor grade (P=0.020). The 5‑year overall survival rate of patients with high PTK6 expression was lower than that of patients with low PTK6 expression (81.3% vs. 96.2%,P=0.008). Multivariate Cox regression analysis showed that the expression level of PTK6 in cervical squamous cell cancer was an independent prognostic factor for patient survival (hazard ratio=5.999, 95% conifdence interval 1.622–22.191,P Conclusions:PTK6 is overexpressed in cervical squamous cell cancer. Increased PTK6 expression is associated with reduced 5‑year overall survival. PTK6 expression is an independent prognostic predictor for cervical cancer.

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

    Science.gov (United States)

    Zhao, Bing; Hu, Mengcai

    2013-12-01

    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.

  2. Fra-1 is downregulated in cervical cancer tissues and promotes cervical cancer cell apoptosis by p53 signaling pathway in vitro.

    Science.gov (United States)

    Xiao, Songshu; Zhou, Yanhong; Yi, Wei; Luo, Guijuan; Jiang, Bin; Tian, Qi; Li, Yueran; Xue, Min

    2015-04-01

    Cervical cancer is a potentially preventable disease; however, it is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths in women worldwide. Cervical cancer is thought to develop through a multistep process involving virus, tumor suppressor genes, proto-oncogenes and immunological factors. It is known that human papillomavirus (HPV) infection is necessary but insufficient to cause malignancy. At present, the etiology of cervical carcinoma remains poorly understood. In this study, we found that the expression of FOS-like antigen-1 (Fra-1) gene was downregulated in cervical cancer compared with the adjacent non-cancerous tissues by RT-qPCR, immunohistochemistry (IHC) and western blotting techniques. To uncover the effect of Fra-1 on cervical cancer, we tested and confirmed that Fra-1 significantly inhibited the proliferation of HeLa cells by MMT assays in vitro. At the same time, overexpression of Fra-1 promoted apoptosis of HeLa cells. To explore the possible mechanism of Fra-1 in cervical cancer, we tested the expression levels of key molecules in p53 signaling pathway by western blotting technology. The results showed that p53 was downregulated in cervical cancer compared with the adjacent non-cancerous tissues, but MDM2 proto-oncogene, E3 ubiquitin protein ligase (MDM2) was upregulated in cervical cancer. In vitro, the p53 was upregulated and MDM2 was downregulated in HeLa cells with Fra-1 overexpression. In summary, our results suggested that Fra-1 expression is low in cervical cancer tissues and promotes apoptosis of cervical cancer cells by p53 signaling pathway.

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

    Energy Technology Data Exchange (ETDEWEB)

    Samarzija, Ivana [Ecole Polytechnique Federale Lausanne (EPFL), Department of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), 1015 Lausanne (Switzerland); Beard, Peter, E-mail: peter.beard@epfl.ch [Ecole Polytechnique Federale Lausanne (EPFL), Department of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), 1015 Lausanne (Switzerland)

    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.

  4. Cervical cancer - screening and prevention

    Science.gov (United States)

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

  5. Targeting SPARC by lentivirus-mediated RNA interference inhibits cervical cancer cell growth and metastasis

    Directory of Open Access Journals (Sweden)

    Chen Jie

    2012-10-01

    Full Text Available Abstract Background Secreted protein acidic and rich in cysteine (SPARC, a calcium-binding matricellular glycoprotein, is implicated in the progressions of some cancers. However, no information has been available to date regarding the function of SPARC in cervical cancer cell growth and metastasis. Methods In this study, we isolated and established high invasive subclones and low invasive subclones from human cervical cancer cell lines HeLa and SiHa by the limited dilution method. Real-time q-RT-PCR, Western Blot and ICC were performed to investigate SPARC mRNA and protein expressions in high invasive subclones and low invasive subclones. Then lentivirus vector with SPARC shRNA was constructed and infected the highly invasive subclones. Real-time q-RT-PCR, Western Blot and ICC were also performed to investigate the changes of SPARC expression after viral infection. In functional assays, effects of SPARC knockdown on the biological behaviors of cervical cancer cells were investigated. The mechanisms of SPARC in cervical cancer proliferation, apoptosis and invasion were also researched. Results SPARC was over-expressed in the highly invasive subclones compared with the low invasive subclones. Knockdown of SPARC significantly suppressed cervical cancer cell proliferation, and induced cell cycle arrest at the G1/G0 phase through the p53/p21 pathway, also caused cell apoptosis accompanied by the decreased ratio of Bcl-2/Bax, and inhibited cell invasion and metastasis accompanied by down-regulated MMP2 and MMP9 expressions and up-regulated E-cadherin expression. Conclusion SPARC is related to the invasive phenotype of cervical cancer cells. Knockdown of SPARC significantly suppresses cervical cancer cell proliferation, induces cell apoptosis and inhibits cell invasion and metastasis. SPARC as a promoter improves cervical cancer cell growth and metastasis.

  6. Cervical Cancer Screening

    Science.gov (United States)

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

  7. Cervical Cancer Stage IVB

    Science.gov (United States)

    ... of the body, such as the lymph nodes, lung, liver, intestine, or bone. Stage IVB cervical cancer. Topics/Categories: Anatomy -- Gynecologic Cancer Types -- Cervical Cancer Staging Type: Color, ...

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

    Science.gov (United States)

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

    2013-04-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    2017-01-31

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

  12. Cervical Cancer Screening

    Science.gov (United States)

    ... are at increased risk for HPV infections. Other risk factors for cervical cancer include: Giving birth to many children. Smoking cigarettes. Using oral contraceptives ("the Pill"). Having a weakened immune system . Cervical Cancer Screening ...

  13. [Prognostic value of cell heterogeneity in cervical cancer determined by digital image analyzer of DNA content].

    Science.gov (United States)

    Pete, I; Gaudi, I; Szerdahelyi, A; Tóth, E; Pulay, T; Szentirmay, Z

    2000-10-01

    Frequency and prognostic value of cell heterogeneity in FIGO 1a-2a cervical cancer was examined, in 66 of patients underwent Wertheim type hysterectomy between 1989 and 1995 in National Institute of Cancer, Budapest, Hungary. A newly developed DNA image analyses (DNACE) was used in paraffin embedded tissues after enzymatic hydrolyses for evaluation of the DNA content in cervical cancer. In 30.3% of examined tissues (20/66) two subgroups was found. There was significant differences in the DNA indexes (DI) between the subgroups (p = 0.0001). In the remaining 69.7% of the cases only one subgroup was present. The frequency of two subgroups was higher between aneuploid (78.4%), or hyperploid (81.5%) type cervical cancer, however there was no significant difference between the two groups. On the other hand there was significant difference in the presence of two subgroups between the well and less differentiated cervical cancer. The frequency was higher between the less differentiated groups (p = 0.02). Looking at the prognostic value of subgroups, there was no significant correlation between the heterogeneity of cervical cancer and FIGO stage, or lymph node metastasis (p = 0.6855), or vascular/lymphatic space infiltration (p = 0.2558), or invasiveness of cancer (0.0823). There was neither significant value found between the outcome of disease and the number of subgroups present (p = 0.8738). It is though that the present of cellular heterogeneity in cervical cancer is connected with the differentiation of the cancer cells, and can be a good prognostic value in the anticipation of the aggressiveness of cervical cancer. Looking at the present result, there was no significant connection between the heterogeneity of cervical cancer and the outcome of the disease, so further examination should be done.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Suresh Singh Yadav

    2014-01-01

    Full Text Available In the network of chemokine signaling pathways, recent reports have described the SDF-1α/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-1α promotes the loss of cell adhesion while paracrine SDF-1α 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-1α 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-1α 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-1α/CXCR4 signaling in tumor microenvironment which may be promising to further delineate molecular mechanism of cervical carcinogenesis.

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

    Science.gov (United States)

    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.

  17. MICROARRAY ANALYSIS OF DIFFERENT GENE EXPRESSION OF HUMAN CERVICAL CANCER SUBCLONE CELL LINES

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Cervical cancer is the main cause of death inwomen.The influence of HPV plays an i mportantrole incervial cancer.It has been provedthat humanpapillomavirus(HPV)infectionis ani mportant fac-tor in cervical carcinogenesis.Multiple HPVinfec-tion was associated less frequently with cervical car-cinoma and with precancerous lesions compared withnor mal cytology[1].The activation of oncogene,in-activition of tumor suppressor gene and instabilityof genome are also majority reason.We establisheda cell line of human...

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

    Directory of Open Access Journals (Sweden)

    Xi-Feng Zhang

    2016-08-01

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

  19. Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer

    Science.gov (United States)

    2017-03-08

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Positive Para-Aortic Lymph Node; Positive Pelvic Lymph Node; Stage IB2 Cervical Cancer; Stage II Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  20. Treatment Option Overview (Cervical Cancer)

    Science.gov (United States)

    ... Cancer Prevention Cervical Cancer Screening Research Cervical Cancer Treatment (PDQ®)–Patient Version General Information About Cervical Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery) depends on ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jie [Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000 (China); Zheng, Fangxia [Department of Radiotherapy, Liaocheng People’s Hospital, Liaocheng 252000 (China); Yu, Gang [Department for Disease Control, Tumor Hospital of Liaocheng, Liaocheng 252000 (China); Yin, Yanhua, E-mail: yinyanhuablk@163.com [Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000 (China); Lu, Qingyang [Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000 (China)

    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

  2. Correlation of microRNA-124 expression in cervical cancer tissue with cancer cell growth and invasion

    Institute of Scientific and Technical Information of China (English)

    Yi Zhu

    2016-01-01

    Objective:To study the correlation of microRNA-124 expression in cervical cancer tissue with cancer cell growth and invasion.Methods: A total of 56 cases of cervical cancer tissue samples and 60 cases of normal cervical tissue samples were selected for study, and microRNA-124 expression levels as well as protein content of proliferation, apoptosis and invasion genes in cervical tissue samples were determined.Results: The relative expression level of miR-124 in cervical cancer tissue was significantly lower than that in normal cervical tissue and the higher the FIGO staging, the lower the relative expression level of miR-124; cervical cancer tissue with different miR-124 expression was divided into group A-D according to quartile, there were differences in the protein content of cyclinD1, CDK4, CDK6, Prdx4, TNFAIP8, Piwil2, p16, p27, Caspase-3, Ezrin, CD44v6, E-cadherin andβ-catenin in cervical cancer tissue of group A, B, C and D, and the lower the relative expression level of miR-124, the higher the protein content of cyclinD1, CDK4, CDK6, Prdx4, TNFAIP8, Piwil2 as well as Ezrin and CD44v6, and the lower the protein content of p16, p27, Caspase-3 as well as E-cadherin andβ-catenin.Conclusions: microRNA-124 shows a trend of lower expression in cervical cancer tissue and is closely related to the excessive proliferation, insufficient apoptosis and invasive growth of cancer cells.

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

    OpenAIRE

    Wai Kuan Yong; Sri Nurestri Abd Malek

    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 cont...

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

    Science.gov (United States)

    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

  5. Preventing cervical cancer globally.

    Science.gov (United States)

    Schmeler, Kathleen M

    2012-11-01

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

  6. Statins Inhibit the Proliferation and Induce Cell Death of Human Papilloma Virus Positive and Negative Cervical Cancer Cells

    OpenAIRE

    Crescencio, María Elena; Rodríguez, Emma; Páez, Araceli; Masso, Felipe A.; Montaño, Luis F.; López-Marure, Rebeca

    2009-01-01

    Statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have anti-tumoral effects on multiple cancer types; however, little is known about their effect on cervical cancer. We evaluated the effect on proliferation, cell cycle, oxidative stress and cell death of three statins on CaSki, HeLa (HPV+) and ViBo (HPV−) cervical cancer cell lines. Cell proliferation was assayed by crystal violet staining, cell cycle by flow cytometry and cell death by annexin-V st...

  7. Nitric oxide releasing photoresponsive nanohybrids as excellent therapeutic agent for cervical cancer cell lines.

    Science.gov (United States)

    Sudhesh, Priya; Tamilarasan, Kaviyarasan; Arumugam, Palaniappan; Berchmans, Sheela

    2013-09-11

    Gold nanoparticles (GNPs) that can release nitric oxide (NO) on visible-light irradiation were prepared using 2-mercapto-5-nitro benzimidazole (MNBI) as stabilizer. These nanoparticles meet overall prerequisites for biomedical applications like small sizes, water solubility, and stability. It was found that even a very low dosage of MNBI-stabilized GNPs exhibit appreciable tumor cell mortality against cervical cancer cell lines, demonstrating the role of NO in killing cancer cells.

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

    Science.gov (United States)

    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.

  9. N-WASP promotes invasion and migration of cervical cancer cells through regulating p38 MAPKs signaling pathway.

    Science.gov (United States)

    Hou, Jinxuan; Yang, Hui; Huang, Xin; Leng, Xiaohua; Zhou, Fuxiang; Xie, Conghua; Zhou, Yunfeng; Xu, Yu

    2017-01-01

    Neural Wiskott-Aldrich syndrome protein (N-WASP) is an important member of the WASP family involved in the actin cytoskeleton reorganization. Recent evidence suggests that N-WASP may play important roles in tumor progression and metastasis. However, the contribution of N-WASP to cervical cancer is still unknown. The present study focused on elucidating the role of N-WASP in the malignant behavior of cervical cancer cells. We found that N-WASP overexpressed in cervical cancer tissues compared with paired paracancerous tissues and normal tissues, and similar results were observed in several cervical cancer cell lines. Furthermore, we demonstrated that overexpression of N-WASP facilitated migration and invasion of cervical cancer cells, while downregulation of N-WASP resulted in decreased cell migration and invasion. In addition, the data showed that N-WASP might promote invasion and migration of cervical cancer cells via regulating the activity of p38 MAPKs pathway. Altogether, the study suggested that N-WASP might serve as an oncogene in cervical cancer, and provided novel insights into the mechanism that how N-WASP promoted invasion and migration of cervical cancer cells.

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

    Science.gov (United States)

    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

  11. Cervical Cancer

    Science.gov (United States)

    ... vaginal, and vulvar cancers. It is recommended for preteens (both boys and girls) aged 11 to 12 ... index. • D on’t smoke. • Use condoms during sex. * • Limit your number of sexual partners. * HPV infection ...

  12. Cervical Cancer

    Science.gov (United States)

    ... Other things may increase the risk of developing cancer following a high-risk HPV infection. These other things include: Smoking Having HIV or reduced immunity Taking birth control pills for a long time ( ...

  13. Doxycycline inhibits proliferation and induces apoptosis of both human papillomavirus positive and negative cervical cancer cell lines.

    Science.gov (United States)

    Zhao, Yan; Wang, Xinyu; Li, Lei; Li, Changzhong

    2016-05-01

    The clinical management of cervical cancer remains a challenge and the development of new treatment strategies merits attention. However, the discovery and development of novel compounds can be a long and labourious process. Drug repositioning may circumvent this process and facilitate the rapid translation of hypothesis-driven science into the clinics. In this work, we show that a FDA-approved antibiotic, doxycycline, effectively targets human papillomavirus (HPV) positive and negative cervical cancer cells in vitro and in vivo. Doxycycline significantly inhibits proliferation of a panel of cervical cancer cell lines. It also induces apoptosis of cervical cancer cells in a time- and dose-dependent manner. In addition, the apoptosis induced by doxycycline is through caspase-dependent pathway. Mechanism studies demonstrate that doxycycline affects oxygen consumption rate, glycolysis, and reduces ATP levels in cervical cancer cells. In HeLa xenograft mouse model, doxycycline significantly inhibits growth of tumour. Our in vitro and in vivo data clearly demonstrate the inhibitory effects of doxycycline on the growth and survival of cervical cancer cells. Our work provides the evidence that doxycycline can be repurposed for the treatment of cervical cancer and targeting energy metabolism may represent a potential therapeutic strategy for cervical cancer.

  14. miR-214 down-regulates ARL2 and suppresses growth and invasion of cervical cancer cells.

    Science.gov (United States)

    Peng, Ruiqing; Men, Jianlong; Ma, Rui; Wang, Qian; Wang, Yang; Sun, Ying; Ren, Jing

    2017-03-11

    Increasing evidence has shown that miRNAs are implicated in carcinogenesis and can function as oncogenes or tumor suppressor genes in human cancers. In this study, we confirmed that miR-214 is frequently down-regulated in cervical cancer compared with normal cervical tissues. Ectopic expression of miR-214 suppressed proliferation, migration and invasion of HeLa and C33A cervical cancer cells. Bioinformatics analysis revealed that ADP ribosylation factor like 2 (ARL2) was a potential target of miR-214 and was remarkably up-regulated in cervical cancer. Knockdown of ARL2 markedly inhibited cervical cancer cell proliferation, migration and invasion, similarly to over-expression of miR-214, indicating that ARL2 may function as an oncogene in cervical cancer. In conclusion, our study revealed that miR-214 acts as a tumor suppressor via inhibiting proliferation, migration and invasion of cervical cancer cells through targeting ARL2, and that both miR-214 and ARL2 may serve as prognostic or therapeutic targets for cervical cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Chuanyi [Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008 (China); Shen, Liangfang, E-mail: lfshen2008@163.com [Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008 (China); Mao, Lei; Wang, Bing; Li, Yang; Yu, Huizhi [Department of Radiation Oncology, Yueyang Second People' s Hospital, Yueyang 414000 (China)

    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.

  16. Xanthohumol induces growth inhibition and apoptosis in ca ski human cervical cancer cells.

    Science.gov (United States)

    Yong, Wai Kuan; Abd Malek, Sri Nurestri

    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.

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

    Directory of Open Access Journals (Sweden)

    Wai Kuan Yong

    2015-01-01

    Full Text Available 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.

  18. 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

    Science.gov (United States)

    2016-11-14

    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

  19. Therapeutic immunization strategies against cervical cancer : induction of cell-mediated immunity in murine models

    NARCIS (Netherlands)

    Bungener, Laura Barbara

    2004-01-01

    The aim of the study described in this thesis is the development of a therapeutic immunization strategy against cervical cancer and pre-malignant precursor lesions of cervical cancer (CIN lesions). Cervical cancer is caused by high risk human papillomavirus (HPV). Two of the early proteins of high r

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

    Science.gov (United States)

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

    2014-05-01

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

  1. Cannabidiol rather than Cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells

    OpenAIRE

    2016-01-01

    Background Cervical cancer remains a global health related issue among females of Sub-Saharan Africa, with over half a million new cases reported each year. Different therapeutic regimens have been suggested in various regions of Africa, however, over a quarter of a million women die of cervical cancer, annually. This makes it the most lethal cancer amongst black women and calls for urgent therapeutic strategies. In this study we compare the anti-proliferative effects of crude extract of Cann...

  2. Notch1 induces cell cycle arrest and apoptosis in human cervical cancer cells : involvement of nuclear factor kappa B inhibition

    NARCIS (Netherlands)

    Yao, J.; Duan, L.; Fan, M.; Yuan, J.; Wu, X.

    2007-01-01

    Notch signaling can serve as a tumor suppressor or tumor promoter in the same kind of cancer, such as human papillomavirus-positive cervical cancer cells. However, the exact mechanisms remain poorly characterized. Our studies demonstrated that constitutively overexpressed active Notch1 via stable tr

  3. 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

    Science.gov (United States)

    2017-03-23

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

  4. Histone deacetylase inhibitors inducing human cervical cancer cell apoptosis by decreasing DNA-methyltransferase 3B

    Institute of Scientific and Technical Information of China (English)

    LIU Ning; ZHAO Li-jun; LI Xiao-ping; WANG Jian-liu; CHAI Guo-lin; WEI Li-hui

    2012-01-01

    Background Histone deacetylase (HDAC) inhibitors are a group of small chemical molecules that inhibit histone deacetylase.At cell level,HDAC inhibitors have multiple biological effects such as cell cycle arrest,apoptosis,cell differentiation and auotophagy.At molecular level,HDAC inhibitors cause histone and nonhistone acetylation and induce gene expression.HDAC inhibitors are widely used in cancer therapy because of its function of inducing apoptosis.However,the mechanisms of apoptosis effect are not fully understood.TSA is a classical HDAC inhibitor and widely used in epigenetic and anti-cancer research.In this study,we selected Trichostatin A (TSA) to investigate the mechanisms of HDAC inhibitors apoptotic effect on cancer cells.Methods Cervical cancer cell lines such as Hela,Caski and normal human keratinocyte line HaCaT were treated with various concentrations of TSA.Crystal violent assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were performed to determine cell number.PARP cleavage and FITC-AnexinV were performed to determine apoptosis.DNA-methyltransferase (DNMT)1,DNMT3A and DNMT3B were determined by regular PCR,qPCR and Western Blotting.Small interfering RNA (SiRNAi) was used to knock down DNMT3B.Results HDAC inhibitors only induce cervical cancer cell apoptosis.At 1 μmol/L of TSA,86% of Hela cell and 76% of Caski went apoptosis.For normal cells,HDAC inhibitors have no cytotoxic effect at therapeutic dosage,(90.0±8.4)% of normal cell survive after treated with 1 μmol/L of TSA.We compared 1 μmol/L group with untreated control with t-test.There was no significance between 1 μmol/L group and untreated control for normal cell (P >0.05).HDAC inhibitors decreased DNMT3B in cancer cell but not in normal cell.Manually knock-down of DNMT3B induced Hela and Caski cell apoptosis.More than 99% of Hela and Caski cell went apoptosis after deprived of DNMT3B.Conclusions DNMT3B was essential to cervical cancer cell survival

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    1996-01-17

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

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

    Science.gov (United States)

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

    2012-05-01

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

  8. Cervical Cancer Cell Line Secretome Highlights the Roles of Transforming Growth Factor-Beta-Induced Protein ig-h3, Peroxiredoxin-2, and NRF2 on Cervical Carcinogenesis

    Science.gov (United States)

    Zoidakis, Jerome; Makridakis, Manousos; Lygirou, Vasiliki; Mermelekas, George; Vougas, Konstantinos; Drakakis, Peter

    2017-01-01

    Cancer cells acquire unique secretome compositions that contribute to tumor development and metastasis. The aim of our study was to elucidate the biological processes involved in cervical cancer, by performing a proteomic analysis of the secretome from the following informative cervical cell lines: SiHa (HPV16+), HeLa (HPV18+), C33A (HPV−), and HCK1T (normal). Proteins were analyzed by 2D gel electrophoresis coupled to MALDI-TOF-MS. Enrichment of secreted proteins with characteristic profiles for each cell line was followed by the identification of differentially expressed proteins. Particularly, transforming growth factor-beta-induced protein ig-h3 (Beta ig-h3) and peroxiredoxin-2 (PRDX2) overexpression in the secretome of cancer cell lines was detected and confirmed by Western blot. Bioinformatics analysis identified the transcription factor NRF2 as a regulator of differentially expressed proteins in the cervical cancer secretome. NRF2 levels were measured by both Western blot and Multiple Reaction Monitoring (MRM) in the total cell extract of the four cell lines. NRF2 was upregulated in SiHa and C33A compared to HCK1T. In conclusion, the secreted proteins identified in cervical cancer cell lines indicate that aberrant NRF2-mediated oxidative stress response (OSR) is a prominent feature of cervical carcinogenesis.

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

    Science.gov (United States)

    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.

  10. REAL-TIME DETECTION OF SURVIVIN mRNA EXPRESSION IN CERVICAL CANCER CELL LINES USING MOLECULAR BEACON IMAGING

    Institute of Scientific and Technical Information of China (English)

    An Ruifang; He Dalin; Xue Yan; Wang Shu; Xie Li; Zhao Jun; Wang Xinyang; Yang Lili

    2006-01-01

    Objective To detect the expression of survivin mRNA in cervical cancer cell lines using molecular beacon imaging technology. Methods Human cervical cancer cells (HeLa and SiHa) and human fetal lung fibroblast HFL-I were cultured in vitro. After adding 100 nmol/L survivin mRNA molecular beacon, the fluorescent signals were observed under fluorescent microscope. The expressions of survivin in cervical cancer cells and HFL-I cell were examined by immunocytochemical streptravidin-biothin peroxidase (SP) assay at the same time. Results Two kinds of survivin mRNA molecular beacon, with different color fluorescence, had strong fluorescent signal in cervical cancer cell lines, and the signal in SiHa cell line was stronger, but these signals were not found in HFL-I ; Immunocytochemical staining of positive survivin was located in the cytoplasm of cervical cancer cell lines HeLa and SiHa, whereas, no expression of survivin was detected in HFL-I cell line. Conclusion The technology of molecular beacon imaging can be used to detect the expression of survivin mRNA in viable cells successfully, and may provide a new approach to the diagnosis of early stage cervical cancer and the following-up in the clinic.

  11. Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice

    Science.gov (United States)

    Xia, Chenglai; Chen, Ruihong; Chen, Jinman; Qi, Qianqian; Pan, Yanbin; Du, Lanying; Xiao, Guohong; Jiang, Shibo

    2017-01-01

    Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki. When used in combination, these two drugs acted synergistically to inhibit the growth of human cervical cancer cells in vitro and cervical cancer cell xenograft in vivo in nude mice, and suppress cervical cancer cell migration and invasion. The protein expression of phosphoinositide 3-kinase catalytic subunit PI3K(p110α), which can promote tumor growth, was remarkably downregulated, while the tumor suppressor proteins p53 and p21 were substantially upregulated following the combinational treatment in vitro and in vivo. These results suggest that clinical use of metformin and nelfinavir in combination is expected to have synergistic antitumor efficacy and significant potential for the treatment of human cervical cancer. PMID:28252027

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

    Directory of Open Access Journals (Sweden)

    Moela P

    2016-07-01

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

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

    Science.gov (United States)

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

    2015-06-04

    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.

  14. Inhibitory effect of lanthanum chloride on migration and invasion of cervical cancer cells

    Institute of Scientific and Technical Information of China (English)

    CHEN Hongwei; LIU Sisun; MIAO Lifang; YU Lingfang; WANG Yang; GUO Fei

    2013-01-01

    Tumor metastasis remains the main reason for treatment failure and death of patients with cervical cancer.The present study was designed to explore the effects of lanthanum chloride (LaCl3) on the invasion and migration of cervical cancer cells and the underlying mechanisms.The migration and invasion of tumor cells was evaluated by a modified Transwell/Boyden chamber assays.It is well known that MMPs (Matrix metalloprotcinascs) and NF-κB (Nuclear factor-κB) pathway play important roles in migration and invasion of tumor cells,and also the expression of MMPs were regulated by NF-κB signaling.The expression of MMP-1 and MMP-9 was detected by reverse transcription polymerase chain reaction (RT-PCR); Western blot and the NF-κB-DNA-binding activity assay were used to analyze the NF-κB activity.The results indicated that LaCl3 was capable of inhibiting the cell invasion and migration of human cervical cancer Hela cells by decreasing the expression of MMP-1 and MMP-9 via blocking NF-κB pathway.

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

    Directory of Open Access Journals (Sweden)

    Ravi K Anchoori

    Full Text Available 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 α-β 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.

  16. Effect of diglycine mutant FAT10 on the proliferation and apoptosis of cervical cancer cells

    Directory of Open Access Journals (Sweden)

    Cui LI

    2015-01-01

    Full Text Available Objective To investigate the effects of FAT10ΔGG, a carboxyl-terminal diglycine deficient mutant, on the proliferation and apoptosis of cervical cancer cell line HeLa. Methods Specimens of cervical carcinoma in situ and normal cervix tissue, 5 each, were collected. The expressive levels of FAT10 protein in these specimens were detected by Western blotting. Sitedirected mutagenesis was applied to construct the mutant pcDNA3.0-flag-FAT10ΔGG plasmid. The HeLa cells were then transiently transfected with wild-type FAT10, FAT10ΔGG and empty vector (used as negative control, and the wild-type HeLa cells served as blank control. The transfection efficiency of FAT10 or FAT10ΔGG was detected by Western blotting, and cell proliferation was determined by CCK-8 assay. Cisplatin was used to induce cell apoptosis after cells were transfected for 24h, and the cell apoptotic rates of all groups were determined by flow cytometry. Results Western blotting showed a significantly increased expression of FAT10 protein in cervical carcinoma tissues compared with that in normal cervical tissue. Over-expression of wild FAT10 in HeLa cells obviously promoted cell proliferation, but this promotion was significantly inhibited in cells transfected with its diglycine mutant. Compared with blank control group (22.7%±4.2% and negative control group (24.1%±3.8%, the apoptotic rate was significantly reduced in wild FAT10 group (10.9%±2.0%, P0.05. Conclusion FAT10 can promote cell proliferation and inhibit cell apoptosis through its carboxyl-terminal diglycine motif, and it may play an essential role in carcinogenesis and development of cancer. DOI: 10.11855/j.issn.0577-7402.2014.12.01

  17. Proteomic analysis of cervical cancer cells treated with suberonylanilide hydroxamic acid

    Indian Academy of Sciences (India)

    Jianxiong He; Canhua Huang; Aiping Tong; Bin Chen; Zhi Zeng; Peng Zhang; Chunting Wang; Yuquan Wei

    2008-12-01

    Suberonylanilide hydroxamic acid (SAHA) is an orally administered histone deacetylase inhibitor (HDACI) that has shown significant antitumour activity in a variety of tumour cells. To identify proteins involved in its antitumour activity, we utilized a proteomic approach to reveal protein expression changes in the human cervical cancer cell line HeLa following SAHA treatment. Protein expression profiles were analysed by 2-dimensional polyacrylamide gel electrophoresis (2-DE) and protein identification was performed on a MALDI-Q-TOF MS/MS instrument. As a result, a total of nine differentially expressed proteins were visualized by 2-DE and Coomassie brilliant blue (CBB) staining. Further, all the changed proteins were positively identified via mass spectrometry (MS)/MS analysis. Of these, PGAM1 was significantly downregulated in HeLa cells after treatment with SAHA. Moreover, PGAM1 has been proven to be downregulated in another cervical cancer cell line (CaSki) by western blot analysis. Together, using proteomic tools, we identified several differentially expressed proteins that underwent SAHA-induced apoptosis. These changed proteins may provide some clues to a better understanding of the molecular mechanisms underlying SAHA-induced apoptosis in cervical cancer.

  18. Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines

    Science.gov (United States)

    Souza, Raquel P.; Gimenes, Fabrícia; Ratti, Bianca A.; Kaplum, Vanessa; Bruschi, Marcos L.; Nakamura, Celso V.; Maria-Engler, Silvya S.

    2017-01-01

    Recently, the cytotoxic effects of apigenin (4′,5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H2O2, decreased the Δψm, and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes. PMID:28191273

  19. Inhibition of antiviral drug cidofovir on proliferation of human papillomavirus-infected cervical cancer cells

    Science.gov (United States)

    Yang, Jing; Dai, Lv-Xia; Chen, Ming; Li, Bei; Ding, Nana; Li, Gang; Liu, Yan-Qing; Li, Ming-Yuan; Wang, Bao-Ning; Shi, Xin-Li; Tan, Hua-Bing

    2016-01-01

    In order to evaluate the potential application value of cidofovir (CDV) in the prevention of human papillomavirus (HPV) infection and treatment of cervical cancer, the inhibitory effect of CDV on the proliferation of HPV 18-positive HeLa cells in cervical cancer was preliminarily investigated, using cisplatin (DDP) as a positive control. An MTT assay was used to analyze the effects of CDV and DDP on HeLa cell proliferation. In addition, clone formation assay and Giemsa staining were used to examine the extent of HeLa cell apoptosis caused by CDV and DDP. Flow cytometry was also used to detect the shape and size of apoptotic cells following propidium iodide staining, while western blot analysis identified the expression levels of of E6 and p53 proteins in HeLa cells. A cell climbing immunofluorescence technique was used to locate the subcellular position of p53 in HeLa cells. The results demonstrated that CDV and DDP inhibited the proliferation of HeLa cells in a concentration- and time-dependent manner. Flow cytometry showed that CDV and DDP treatments resulted in cell arrest in the S-phase, and triggered programmed cell death. Furthermore, western blot analysis revealed that CDV and DDP inhibited E6 protein expression and activated p53 expression in HeLa cells. Finally, the immunofluorescence results indicated that CDV and DDP inhibited the nuclear export of p53 by E6 protein, which is required for degradation of endogenous p53 by MDM2 and human papilloma virus E6. In conclusion, CDV and DDP inhibited HeLa cell proliferation in a concentration- and time-dependent manner, reduced the expression of E6 protein, and reinstated p53 protein activity. Thus, CDV regulates cell cycle arrest and apoptosis, and may be a potential cervical cancer therapeutic strategy. PMID:27882102

  20. Inhibition of antiviral drug cidofovir on proliferation of human papillomavirus-infected cervical cancer cells.

    Science.gov (United States)

    Yang, Jing; Dai, Lv-Xia; Chen, Ming; Li, Bei; Ding, Nana; Li, Gang; Liu, Yan-Qing; Li, Ming-Yuan; Wang, Bao-Ning; Shi, Xin-Li; Tan, Hua-Bing

    2016-11-01

    In order to evaluate the potential application value of cidofovir (CDV) in the prevention of human papillomavirus (HPV) infection and treatment of cervical cancer, the inhibitory effect of CDV on the proliferation of HPV 18-positive HeLa cells in cervical cancer was preliminarily investigated, using cisplatin (DDP) as a positive control. An MTT assay was used to analyze the effects of CDV and DDP on HeLa cell proliferation. In addition, clone formation assay and Giemsa staining were used to examine the extent of HeLa cell apoptosis caused by CDV and DDP. Flow cytometry was also used to detect the shape and size of apoptotic cells following propidium iodide staining, while western blot analysis identified the expression levels of of E6 and p53 proteins in HeLa cells. A cell climbing immunofluorescence technique was used to locate the subcellular position of p53 in HeLa cells. The results demonstrated that CDV and DDP inhibited the proliferation of HeLa cells in a concentration- and time-dependent manner. Flow cytometry showed that CDV and DDP treatments resulted in cell arrest in the S-phase, and triggered programmed cell death. Furthermore, western blot analysis revealed that CDV and DDP inhibited E6 protein expression and activated p53 expression in HeLa cells. Finally, the immunofluorescence results indicated that CDV and DDP inhibited the nuclear export of p53 by E6 protein, which is required for degradation of endogenous p53 by MDM2 and human papilloma virus E6. In conclusion, CDV and DDP inhibited HeLa cell proliferation in a concentration- and time-dependent manner, reduced the expression of E6 protein, and reinstated p53 protein activity. Thus, CDV regulates cell cycle arrest and apoptosis, and may be a potential cervical cancer therapeutic strategy.

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

    Energy Technology Data Exchange (ETDEWEB)

    Mack, Hildegard I.D.; Munger, Karl, E-mail: kmunger@rics.bwh.harvard.edu

    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.

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

    Directory of Open Access Journals (Sweden)

    Jie Su

    2016-01-01

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

  3. Risks of Cervical Cancer Screening

    Science.gov (United States)

    ... are at increased risk for HPV infections. Other risk factors for cervical cancer include: Giving birth to many children. Smoking cigarettes. Using oral contraceptives ("the Pill"). Having a weakened immune system . Cervical Cancer Screening ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shikai; Song, Lili, E-mail: commasll@163.com; Zhang, Liang; Zeng, Saitian; Gao, Fangyuan

    2015-04-17

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

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

    Science.gov (United States)

    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 HeLa cells than compared to non-targeted nanoparticles. Selective uptake of FPCC was due to an interaction of folic acid (FA) with the folate receptors alpha (FRs-α) which is overexpressed on the HeLa and promoted active targeting. These results indicated that FPCC had a specific affinity for the cancerous, HeLa cells owing to ligand-receptor (FA-FR-α) recognition. Consistently, FPCC showed superior cytotoxic effect than any other formulations. The IC50 (concentration of the drug required to kill 50 % of the cells) value of FPCC was 0.65 μg/ml while it was 1.08, 1.56, and 2.35 μg/ml for PCC, PLGA NP, and free CRB, respectively. Consistent with the cytotoxicity assay, FPCC induced higher fraction of early as well as late apoptosis cells. Especially, FPCC induced nearly 45 % of early apoptosis cells and more than 35 % in late apoptosis. Therefore, we propose that folate-conjugated nanoparticles might have potential applications in cervical cancer therapy.

  6. Use of cell-SELEX to generate DNA aptamers as molecular probes of HPV-associated cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Jessica C Graham

    Full Text Available BACKGROUND: Disease-specific biomarkers are an important tool for the timely and effective management of pathological conditions, including determination of susceptibility, diagnosis, and monitoring efficacy of preventive or therapeutic strategies. Aptamers, comprising single-stranded or double-stranded DNA or RNA, can serve as biomarkers of disease or biological states. Aptamers can bind to specific epitopes on macromolecules by virtue of their three dimensional structures and, much like antibodies, aptamers can be used to target specific epitopes on the basis of their molecular shape. The Systematic Evolution of Ligands by EXponential enrichment (SELEX is the approach used to select high affinity aptamers for specific macromolecular targets from among the >10(13 oligomers comprising typical random oligomer libraries. In the present study, we used live cell-based SELEX to identify DNA aptamers which recognize cell surface differences between HPV-transformed cervical carcinoma cancer cells and isogenic, nontumorigenic, revertant cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Whole-cell SELEX methodology was adapted for use with adherent cell lines (which we termed Adherent Cell-SELEX (AC-SELEX. Using this approach, we identified high affinity aptamers (nanomolar range K(d to epitopes specific to the cell surface of two nontumorigenic, nontumorigenic revertants derived from the human cervical cancer HeLa cell line, and demonstrated the loss of these epitopes in another human papillomavirus transformed cervical cancer cell line (SiHa. We also performed preliminary investigation of the aptamer epitopes and their binding characteristics. CONCLUSIONS/SIGNIFICANCE: Using AC-SELEX we have generated several aptamers that have high affinity and specificity to the nontumorigenic, revertant of HPV-transformed cervical cancer cells. These aptamers can be used to identify new biomarkers that are related to carcinogenesis. Panels of aptamers, such as these may

  7. DNA methylation-independent reversion of gemcitabine resistance by hydralazine in cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Myrna Candelaria

    Full Text Available BACKGROUND: Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervical cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The cervical cancer cell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervical cancer cells via inhibition of G9A histone methyltransferase.

  8. Prognostic factors in cervical cancer

    NARCIS (Netherlands)

    Biewenga, P.

    2015-01-01

    Surgery is the standard of care for women with early stage cervical cancer; radiotherapy is the cornerstone in patients with advanced stages of disease. Recent changes in the treatment of cervical cancer involve less radical surgery in early stage cervical cancer, concomitant chemo- and radiotherapy

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

    Science.gov (United States)

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

    2013-01-01

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

  10. Expression and clinical significance of dendritic cell and transforming growth factor-beta 1 in cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Zhao; Shan; Rong; Fengnian

    2006-01-01

    Objective:To explore the density and mature status of Dendritic cell(DC) in cervical cancer and correlation with the expression of transforming growth factor-beta 1(TGF-β1).Methods:Streptavidin-peroxidase(SP) immunohistochemistry methods were used to detect S-100 DC and the expression of TGF-β1 in 20 normal cervical tissues and 53 cervical cancer tissues without any sort of chemotherapy or radiation therapy prior to resection.Medical records were reviewed,clinicopathological variables were retrieved and used for analysis.Results:Two types of DC were observed under the microscope.The expression of DC in cervical cancer was significantly higher than that in normal tissues(23.34 cells/mm2 vs 29.91 cells/mm2,P<0.05),and significantly higher in early stage than that in advanced stage(P<0.05).The expression of TGF-β1 was significantly higher in cervical cancer than that in normal tissues (P<0.025).However,there was no correaction between TGF-β1 and lymph nodes metastasis.The index of DC in cervical cancer was negatively correlated to the expression of TGF-β1 in tumor cells (r=-0.8875,P=0.0001).Conclusion:Maturation of DC in cervical cancer is inhibited.The decreased number of DC and the higher expression of TGF-β1 are due to the failure of the immunity,these may play an important role in the development of the cervical cancer.

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

    Science.gov (United States)

    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

  12. Anthelminthic drug niclosamide sensitizes the responsiveness of cervical cancer cells to paclitaxel via oxidative stress-mediated mTOR inhibition.

    Science.gov (United States)

    Chen, Liping; Wang, Li; Shen, Haibin; Lin, Hui; Li, Dan

    2017-03-04

    Drug repurposing represents an alternative therapeutic strategy to cancer treatment. The potent anti-cancer activities of a FDA-approved anthelminthic drug niclosamide have been demonstrated in various cancers. However, whether niclosamide is active against cervical cancer is unknown. In this study, we investigated the effects of niclosamide alone and its combination with paclitaxel in cervical cancer in vitro and in vivo. We found that niclosamide significantly inhibited proliferation and induced apoptosis of a panel of cervical cancer cell lines, regardless of their cellular origin and genetic pattern. Niclosamide also inhibited tumor growth in cervical cancer xenograft mouse model. Importantly, niclosamide significantly enhanced the responsiveness of cervical cancer cell to paclitaxel. We further found that niclosamide induced mitochondrial dysfunctions via inhibiting mitochondrial respiration, complex I activity and ATP generation, which led to oxidative stress. ROS scavenge agent N-acetyl-l-cysteine (NAC) completely reversed the effects of niclosamide in increasing cellular ROS, inhibiting proliferation and inducing apoptosis, suggesting that oxidative stress induction is the mechanism of action of niclosamide in cervical cancer cells. In addition, niclosamide significantly inhibited mammalian target of rapamycin (mTOR) signaling pathway in cervical cancer cells and its inhibitory effect on mTOR is modulated by oxidative stress. Our work suggests that niclosamide is a useful addition to the treatment armamentarium for cervical cancer and induction of oxidative stress may be a potential therapeutic strategy in cervical cancer.

  13. The IL-17 and Th17 cell immune response in cervical cancer : angels or demons : it depends on the context

    NARCIS (Netherlands)

    Punt, Birgitte Simone

    2015-01-01

    This thesis provides novel insights into the role of IL-17 and Th17 cells in cervical cancer. While IL-17 was shown to be predominantly produced by innate myeloid cells such as neutrophils and correlated with poor survival, Th17 cells were generally a small cell population correlated with improved s

  14. Molecular mechanism of Skp2 in promoting cervical cancer HeLa cell proliferation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective: To explore the impact of s-phase kinase-associated protein 2 (Skp2) on cervical cancer cell proliferation and the relationship between Skp2 and expression of cell regulation factors and transcription factors. Methods: RNAi technology was used to silence Skp2 gene in HeLa cells. After interference, RT-PCR was used for detection of Skp-2 mRNA, and Western blotting and flow cytometry were used for protein expression analysis. Results: siRNA significantly inhibited HeLa cell proliferation (P<0.05) and increased HeLa apoptosis, and G1/G0 phase cells were increased significantly (P<0.01). Skp2 siRNA transfected HeLa cells effectively reduced Skp2 protein levels, while p27 and p-p53 protein levels were increased significantly. RT-PCR results showed that after interference Skp2 mRNA, c-myc mRNA and cyclin A mRNA expressions decreased significantly compared with those in control group (P<0.01), and p27mRNA expression level was significantly higher (P<0.01). Conclusion: The change of Skp2 expression affects the expression of the cell cycle protein, thus affecting proliferation and apoptosis of HeLa cells. Skp2 protein plays an important role in the progression of cervical cancer; yet the specific mechanism still needs further study.

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

    Science.gov (United States)

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

    2012-02-01

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

  16. Kaempferol increases apoptosis in human cervical cancer HeLa cells via PI3K/AKT and telomerase pathways.

    Science.gov (United States)

    Kashafi, Elham; Moradzadeh, Maliheh; Mohamadkhani, Ashraf; Erfanian, Saiedeh

    2017-02-28

    Cervical cancer is one of the most frequent cancers in women worldwide. Defects in the apoptotic pathways are responsible for both the disease pathogenesis and its therapy resistance. It is thus a good candidate for treatment by pro-apoptotic agents. Kaempferol as a flavonoid has antioxidant and anti-tumor properties. Kaempferol has been shown to induce apoptosis and cell death in cancer cells. However, due to the problems in the treatment of cervical cancer, this study is designed to investigate the molecular mechanism by which kaempferol suppresses the growth of cervical cancer HeLa cell as compared with HFF cells (normal cells). Cells treated with kaempferol (12-100μM) and 5-FU (1-10μM), as the positive control, up to 72h. Cell viability was determined by MTT assay and real time PCR was used to investigate apoptosis and telomerase genes expression. The results showed that kaempferol decreased cell viability as concentration- and time-dependently. IC50 values were 10.48μM for HeLa and 707.00μM for HFF cells, as compared with 1.40μM and 16.38μM for 5-FU after 72h treatment, respectively. Also, kaempferol induced cellular apoptosis and aging through down-regulating the PI3K/AKT and hTERT pathways. This study suggests that kaempferol may be a useful adjuvant therapeutic agent in the treatment of cervical cancer.

  17. Estrogenic Activity of Coumestrol, DDT, and TCDD in Human Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Kenneth Ndebele

    2010-05-01

    Full Text Available Endogenous estrogens have dramatic and differential effects on classical endocrine organ and proliferation. Xenoestrogens are environmental estrogens that have endocrine impact, acting as both estrogen agonists and antagonists, but whose effects are not well characterized. In this investigation we sought to delineate effects of xenoestrogens. Using human cervical cancer cells (HeLa cells as a model, the effects of representative xenoestrogens (Coumestrol-a phytoestrogen, tetrachlorodioxin (TCDD-a herbicide and DDT-a pesticide on proliferation, cell cycle, and apoptosis were examined. These xenoestrogens and estrogen inhibited the proliferation of Hela cells in a dose dependent manner from 20 to 120 nM suggesting, that 17-β-estrtadiol and xenoestrogens induced cytotoxic effects. Coumestrol produced accumulation of HeLa cells in G2/M phase, and subsequently induced apoptosis. Similar effects were observed in estrogen treated cells. These changes were associated with suppressed bcl-2 protein and augmented Cyclins A and D proteins. DDT and TCDD exposure did not induce apoptosis. These preliminary data taken together, suggest that xenoestrogens have direct, compound-specific effects on HeLa cells. This study further enhances our understanding of environmental modulation of cervical cancer.

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

    Science.gov (United States)

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

    2016-09-28

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

  19. Cervical Cancer Prevention

    Science.gov (United States)

    ... infected with HPV, those who have used oral contraceptives ("the Pill") for 5 to 9 years have a risk of cervical cancer that is 3 times greater than that of women who have never used oral contraceptives. The risk is 4 times greater after 10 ...

  20. Prevent Cervical Cancer!

    Centers for Disease Control (CDC) Podcasts

    2015-01-08

    Cervical cancer can be prevented. Listen as two friends—one a doctor—talk about screening tests and early detection. Learn what test you might need.  Created: 1/8/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 1/8/2015.

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Case Studies - Cervical Cancer

    Centers for Disease Control (CDC) Podcasts

    2010-10-15

    Dr. Alan Waxman, a professor of obstetrics and gynecology at the University of New Mexico and chair of the American College of Obstetricians and Gynecologists (ACOG) committee for the underserved, talks about several case studies for cervical cancer screening and management.  Created: 10/15/2010 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

  3. Future Directions - Cervical Cancer

    Centers for Disease Control (CDC) Podcasts

    2009-10-15

    Dr. Alan Waxman, a professor of obstetrics and gynecology at the University of New Mexico and chair of the American College of Obstetricians and Gynecologists (ACOG) committee for the underserved, talks about possible changes in cervical cancer screening and management.  Created: 10/15/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Gang, E-mail: zhaog69@sjtu.edu.cn [Department of Pathology, The First People' s Hospital, Shanghai Jiaotong University, Shanghai (China); Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin (China); Chen, Jiawei, E-mail: jiaweichen2000@gmail.com [Department of Pathology, The First People' s Hospital, Shanghai Jiaotong University, Shanghai (China); Deng, Yanqiu [Pathophysiology Department, Tianjin Medical University, Tianjin (China); Gao, Feng [Department of Pathology, The First People' s Hospital, Shanghai Jiaotong University, Shanghai (China); Zhu, Jiwei [Basic Medical College, Harbin Medical University, Harbin (China); Feng, Zhenzhong; Lv, Xiuhong [Department of Pathology, The First People' s Hospital, Shanghai Jiaotong University, Shanghai (China); Zhao, Zheng [SAS Headquarters, S6013, 600 Research Drive, Cary, NC (United States)

    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.

  5. Up-regulation of Raf kinase inhibitor protein enhances chemosensitivity of cervical cancer cell

    Institute of Scientific and Technical Information of China (English)

    Xiao Chu; Xinqiang Ji; Mingcui Wang; Wenqing Zhang; Hui Ou; Chong Li

    2014-01-01

    Objective:The purpose of the study is to investigate the ef ects of up-regulation of Raf kinase inhibitor protein (RKlP) on the chemosensitivity of cervical cancer Hela cells. Methods:Eukaryotic expression plasmid pcDNA3.1(+)-ssRKIP containing human overal length RKIPcDNA was transfected into cervical cancer Hela cellby lipofectin assay, establishing a stable cellline containing a target gene by G418. Expression of RKIP in Hela cells was measured by Western blot analysis. After treatment with cisplatin of dif erent concentrations and intervals of time, the ef ect of RKIP on the proliferation of Hela cells was evaluated by MTT method. The flow cytometry was used to investigate whether the RKIP could inhibit apoptosis in Hela cells induced by cisplatin. Results:The expression of RKIP in Hela cells transfected with pcDNA3.1-ssRKIP was increased obviously. After dif erent concentrations of cisplatin treatment cells for 24, 48 and 72 h, the growth inhibition rate in Hela cells transfected with pcDNA3.1-ssRKIP was significantly higher than in control cells (P<0.05). With 5μg/mL cisplatin treatment for 24 h, pcDNA3.1-ssRKIP-transfected Hela cells had an obviously higher percentage of apoptosis (23.2 ± 0.24)%than non-transfected cells (12.4 ± 0.31)%and empty vector-transfected cells (13.4 ± 0.47)%. Without treatment of cisplatin, the percentage of apoptosis for Hela cells transfected with pcDNA3.1-ssRKIP was (5.7 ± 0.12)%, which was stil higher than those of the non-transfected cells (2.9 ± 0.21)%and empty vector-transfected cells (3 ± 0.08)%. Conclusion:Higher expres-sion of RKIP gene can improve chemosensitivitv of cervical cancer Hela cells to cisplatin.

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Floria Lizarraga

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

  9. Segmentation and abnormality detection of cervical cancer cells using fast elm with particle swarm optimization

    Directory of Open Access Journals (Sweden)

    Sukumar P.

    2015-01-01

    Full Text Available Cervical cancer arises when the anomalous cells on the cervix mature unmanageable obviously in the renovation sector. The most probably used methods to detect abnormal cervical cells are the routine and there is no difference between the abnormal and normal nuclei. So that the abnormal nuclei found are brown in color while normal nuclei are blue in color. The spread or cells are examined and the image denoising is performed based on the Iterative Decision Based Algorithm. Image Segmentation is the method of paneling a digital image into compound sections. The major utilize of segmentation is to abridge or modify the demonstration of an image. The images are segmented by applying anisotropic diffusion on the Denoised image. Image can be enhanced using dark stretching to increase the quality of the image. It separates the cells into all nuclei region and abnormal nuclei region. The abnormal nuclei regions are further classified into touching and non-touching regions and touching regions undergoes feature selection process. The existing Support Vector Machines (SVM is classified few nuclei regions but the time to taken for execution is high. The abnormality detected from the image is calculated as 45% from the total abnormal nuclei. Thus the proposed method of Fast Particle Swarm Optimization with Extreme Learning Machines (Fast PSO-ELM to classify all nuclei regions further into touching region and separated region. The iterative method for to training the ELM and make it more efficient than the SVM method. In experimental result, the proposed method of Fast PSO-ELM may shows the accuracy as above 90% and execution time is calculated based on the abnormality (ratio of abnormal nuclei regions to all nuclei regions image. Therefore, Fast PSO-ELM helps to detect the cervical cancer cells with maximum accuracy.

  10. Cytotoxicity of Selected Medicinal and Nonmedicinal Plant Extracts to Microbial and Cervical Cancer Cells

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    Gary M. Booth

    2012-01-01

    Full Text Available This study investigated the cytotoxicity of 55 species of plants. Each plant was rated as medicinal, or nonmedicinal based on the existing literature. About 79% of the medicinal plants showed some cytotoxicity, while 75% of the nonmedicinal plants showed bioactivity. It appears that Asteraceae, Labiatae, Pinaceae, and Chenopodiaceae were particularly active against human cervical cancer cells. Based on the literature, only three of the 55 plants have been significantly investigated for cytotoxicity. It is clear that there is much toxicological work yet to be done with both medicinal and nonmedicinal plants.

  11. Aspirin Has Antitumor Effects via Expression of Calpain Gene in Cervical Cancer Cells

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    Sang Koo Lee

    2008-01-01

    Full Text Available Aspirin and other nonsteroidal anti-inflammatory drugs show efficacy in the prevention of cancers. It is known that they can inhibit cyclooxygenases, and some studies have shown that they can induce apoptosis. Our objective in this study was to investigate the mechanism by which aspirin exerts its apoptosis effects in human cervical cancer HeLa cells. The effect of aspirin on the gene expression was studied by differential mRNA display RT-PCR. Among the isolated genes, mu-type calpain gene was upregulated by aspirin treatment. To examine whether calpain mediates the antitumor effects, HeLa cells were stably transfected with the mammalian expression vector pCR3.1 containing mu-type calpain cDNA (pCRCAL/HeLa, and tumor formations were measured in nude mice. When tumor burden was measured by day 49, HeLa cells and pCR/HeLa cells (vector control produced tumors of 2126 mm3 and 1638 mm3, respectively, while pCRCAL/HeLa cells produced markedly smaller tumor of 434 mm3 in volume. The caspase-3 activity was markedly elevated in pCRCAL/HeLa cells. The increased activity levels of caspase-3 in pCRCAL/HeLa cells, in parallel with the decreased tumor formation, suggest a correlation between caspase-3 activity and calpain protein. Therefore, we conclude that aspirin-induced calpain mediates an antitumor effect via caspase-3 in cervical cancer cells.

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

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    Luis Steven Servín-González

    2015-06-01

    Full Text Available 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.

  13. APOPTOSIS AND PROLIFERATION OF TUMOR CELLS IN LOCALLY ADVANCED CERVICAL CANCER AFTER NEOADJUVANT INTRAARTERIAL CHEMOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    朱雪琼; 岳天孚; 惠京; 张颖; 王德华

    2003-01-01

    Objective: Through observing the clinical response to neoadjuvant intraarterial chemotherapy in locally advanced cervical cancer and investigating the changes of p53 protein expression, proliferation and apoptosis of tumor cells after chemotherapy, to study the relationship between biological markers and chemotherapeutic response. Methods: 20 women with locally advanced squamous cervical cancer received consecutive infusion chemotherapy of five days of cisplatin and adriamycin via the superselective uterine artery. The response to chemotherapy was evaluated by gynecologic examination and ultrasonography 3 weeks after chemotherapy. The changes of apoptotic index (AI), proliferation index (PI) and p53 expression of tumor cells were detected by immunohistochemical technique. Results: The clinical response rate of locally advanced squamous cervical cancer to uterine artery infusion chemotherapy was 70%. No change of PI was found 3 weeks after treatment, but AI significantly increased from 2.79±0.76 to 4.29±1.13 (P<0.01), and AI/PI from 5.68±1.21 to 9.00±1.95 (P<0.05). On the contrary, the expression of p53 was significantly decreased (P<0.05). Patients who responded to chemotherapy showed higher PI before chemotherapy and significantly increased AI and AI/PI after chemotherapy than non-responders (P<0.05). Conclusion: Higher PI was an indication for neoadjuvant intraarterial chemotherapy. One more cycle of chemotherapy should be given to those who have significantly increased AI or AI/PI after chemotherapy, while definite treatment such as surgery or/and radiotherapy should be immediately given to those patients without increased AI or AI/PI.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhen, Shuai, E-mail: usa_2002@163.com [Baoji Maternal and Child Health Hospital, 2 Xinjian Road East, WeiBin District, Baoji City, 721000, Shanxi Province (China); Xijing Hospital, Fourth Military Medical University, Xi’an (China); Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Kyoto University, Kyoto 606-8507 (Japan); Hua, Ling [Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Takahashi, Y.; Narita, S. [Kyoto University, Kyoto 606-8507 (Japan); Liu, Yun-Hui [Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Li, Yan [Baoji Hospital of Traditional Chinese Medicine, No 43, BaoFu Road, Baoji City, Shanxi Province (China)

    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.

  15. Methylated Host Cell Gene Promoters and Human Papillomavirus Type 16 and 18 Predicting Cervical Lesions and Cancer.

    Directory of Open Access Journals (Sweden)

    Nina Milutin Gašperov

    Full Text Available Change in the host and/or human papillomavirus (HPV DNA methylation profile is probably one of the main factors responsible for the malignant progression of cervical lesions to cancer. To investigate those changes we studied 173 cervical samples with different grades of cervical lesion, from normal to cervical cancer. The methylation status of nine cellular gene promoters, CCNA1, CDH1, C13ORF18, DAPK1, HIC1, RARβ2, hTERT1, hTERT2 and TWIST1, was investigated by Methylation Specific Polymerase Chain Reaction (MSP. The methylation of HPV18 L1-gene was also investigated by MSP, while the methylated cytosines within four regions, L1, 5'LCR, enhancer, and promoter of the HPV16 genome covering 19 CpG sites were evaluated by bisulfite sequencing. Statistically significant methylation biomarkers distinguishing between cervical precursor lesions from normal cervix were primarily C13ORF18 and secondly CCNA1, and those distinguishing cervical cancer from normal or cervical precursor lesions were CCNA1, C13ORF18, hTERT1, hTERT2 and TWIST1. In addition, the methylation analysis of individual CpG sites of the HPV16 genome in different sample groups, notably the 7455 and 7694 sites, proved to be more important than the overall methylation frequency. The majority of HPV18 positive samples contained both methylated and unmethylated L1 gene, and samples with L1-gene methylated forms alone had better prognosis when correlated with the host cell gene promoters' methylation profiles. In conclusion, both cellular and viral methylation biomarkers should be used for monitoring cervical lesion progression to prevent invasive cervical cancer.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2015-09-29

    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.

  18. Prognostic cell biological markers in cervical cancer patients primarily treated with (chemo)radiation : a systematic review

    NARCIS (Netherlands)

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

    2011-01-01

    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 b

  19. HPV positive neuroendocrine cervical cancer cells are dependent on Myc but not E6/E7 viral oncogenes

    Science.gov (United States)

    Yuan, Hang; Krawczyk, Ewa; Blancato, Jan; Albanese, Christopher; Zhou, Dan; Wang, Naidong; Paul, Siddartha; Alkhilaiwi, Faris; Palechor-Ceron, Nancy; Dakic, Aleksandra; Fang, Shuang; Choudhary, Sujata; Hou, Tung-Wei; Zheng, Yun-Ling; Haddad, Bassem R.; Usuda, Yukari; Hartmann, Dan; Symer, David; Gillison, Maura; Agarwal, Seema; Wangsa, Danny; Ried, Thomas; Liu, Xuefeng; Schlegel, Richard

    2017-01-01

    Using conditional cell reprogramming, we generated a stable cell culture of an extremely rare and aggressive neuroendocrine cervical cancer. The cultured cells contained HPV-16, formed colonies in soft agar and rapidly produced tumors in immunodeficient mice. The HPV-16 genome was integrated adjacent to the Myc gene, both of which were amplified 40-fold. Analysis of RNA transcripts detected fusion of the HPV/Myc genes, arising from apparent microhomologous recombination. Spectral karyotyping (SKY) and fluorescent-in-situ hybridization (FISH) demonstrated coordinate localization and translocation of the amplified Myc and HPV genes on chromosomes 8 and 21. Similar to the primary tumor, tumor cell cultures expressed very high levels of the Myc protein and, in contrast to all other HPV-positive cervical cancer cell lines, they harbored a gain-of-function mutation in p53 (R273C). Unexpectedly, viral oncogene knockdown had no effect on the growth of the cells, but it did inhibit the proliferation of a conventional HPV-16 positive cervical cancer cell line. Knockdown of Myc, but not the mutant p53, significantly inhibited tumor cell proliferation. On the basis of these data, we propose that the primary driver of transformation in this aggressive cervical cancer is not HPV oncogene expression but rather the overexpression of Myc. PMID:28378747

  20. Effects of Curcumin on Invasion and Metastasis in the Human Cervical Cancer Cells Caski

    Institute of Scientific and Technical Information of China (English)

    Fang XU; Xiao-ling MU; Jing ZHAO

    2009-01-01

    Objective: To explore the effects of curcumin on invasion and metastasis in the human cervical cancer cells Caski.Methods: Caski cells were treated with 10, 25, 50μmol/L curcumin for 24, 48, 72 h. Proliferation of Caski cells was measured with MTT assay. When treated with 50μmol/L curcumin for 72 h, the expressions of MMP-2, MT1-MMP and NF-κB of cells were detected by Western-blot, and invasion and metastasis of Caski cells were evaluated with transwell chamber.Results: After being treated with 10μmol/L, 25μmol/L, 50μmol/L curcumin for 24, 48 and 72 h, the proliferation of Caski cells was inhibited in a dose-and time-dependent manner. The expression of MMP-2, MT1-MMP and NF-κB were decreased when being treated with 50μmol/L curcumin for 72 h. After treatment with 50μmol/L curcumin, in invasion assay, the number of cells in curcumin treated group to migrate to filter coated with Matrigel was reduced compared with control group(P<0.05). Meanwhile, in migration assay, the number of cells in curcumin treated group to migrate to filter was also decreased compared with control group (P<0.05).Conclusion: Curcumin could affect the invasion and metastasis of the human cervical cancer cells Caski. Inhibiting the expression of MMP-2, MT1-MMP and NF-κB was probably one of its molecular mechanisms.

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

    Science.gov (United States)

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

    2005-07-27

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

  2. Green synthesis of gold nanoparticles for staining human cervical cancer cells and DNA binding assay.

    Science.gov (United States)

    De, Swati; Kundu, Rikta; Ghorai, Atanu; Mandal, Ranju Prasad; Ghosh, Utpal

    2014-11-01

    Gold nanoparticles have been functionalized by non-ionic surfactants (polysorbates) used in pharmaceutical formulations. This results in the formation of more well-dispersed gold nanoparticles (GNPs) than the GNPs formed in neat water. The synthesized GNPs show good temporal stability. The synthesis conditions are mild and environmentally benign. The GNPs can bind to ct-DNA and displace bound dye molecules. The DNA-binding assay is significant as it preliminarily indicated that DNA-GNP conjugates can be formed. Such conjugates are extremely promising for applications in nanobiotechnology. The GNPs can also stain the human cervical cancer (HeLa) cells over a wide concentration range while remaining non-cytotoxic, thus providing a non invasive cell staining method. This result is very promising as we observe staining of HeLa cells at very low GNP concentrations (1 μM) while the cell viability is retained even at 10-fold higher GNP concentrations.

  3. AKT inhibitors promote cell death in cervical cancer through disruption of mTOR signaling and glucose uptake.

    Directory of Open Access Journals (Sweden)

    Ramachandran Rashmi

    Full Text Available BACKGROUND: PI3K/AKT pathway alterations are associated with incomplete response to chemoradiation in human cervical cancer. This study was performed to test for mutations in the PI3K pathway and to evaluate the effects of AKT inhibitors on glucose uptake and cell viability. EXPERIMENTAL DESIGN: Mutational analysis of DNA from 140 pretreatment tumor biopsies and 8 human cervical cancer cell lines was performed. C33A cells (PIK3CAR88Q and PTENR233* were treated with increasing concentrations of two allosteric AKT inhibitors (SC-66 and MK-2206 with or without the glucose analogue 2-deoxyglucose (2-DG. Cell viability and activation status of the AKT/mTOR pathway were determined in response to the treatment. Glucose uptake was evaluated by incubation with 18F-fluorodeoxyglucose (FDG. Cell migration was assessed by scratch assay. RESULTS: Activating PIK3CA (E545K, E542K and inactivating PTEN (R233* mutations were identified in human cervical cancer. SC-66 effectively inhibited AKT, mTOR and mTOR substrates in C33A cells. SC-66 inhibited glucose uptake via reduced delivery of Glut1 and Glut4 to the cell membrane. SC-66 (1 µg/ml-56% and MK-2206 (30 µM-49% treatment decreased cell viability through a non-apoptotic mechanism. Decreases in cell viability were enhanced when AKT inhibitors were combined with 2-DG. The scratch assay showed a substantial reduction in cell migration upon SC-66 treatment. CONCLUSIONS: The mutational spectrum of the PI3K/AKT pathway in cervical cancer is complex. AKT inhibitors effectively block mTORC1/2, decrease glucose uptake, glycolysis, and decrease cell viability in vitro. These results suggest that AKT inhibitors may improve response to chemoradiation in cervical cancer.

  4. [Preventing cervical cancer].

    Science.gov (United States)

    Simon, P; Noël, J-C

    2015-09-01

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

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

    Science.gov (United States)

    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 μM 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.

  6. Drugs Approved for Cervical Cancer

    Science.gov (United States)

    ... Human Papillomavirus (HPV) Nonavalent Vaccine Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine Drugs Approved to Treat Cervical Cancer Avastin (Bevacizumab) Bevacizumab Blenoxane (Bleomycin) Bleomycin Hycamtin (Topotecan ...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  9. REAL-TIME DETECTION OF SURVIVIN mRNA EXPRESSION IN CERVICAL CANCER CELL LINES USING MOLECULAR BEACON IMAGING

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The initiated growth of human cancer cells of-ten mostly come fromthe abnor mal expression ofgenes.Survivinis anapotosis inhibitor of IAPfami-ly,cloned by Ambrosini in1997usingthe cDNAofeffector cell protease receptor-1(EPR-1),and is thekey gene for the development and advancement oftumor.Inthe present study,the feasibility of detec-ting the expression of survivin mRNA was exam-inedincervical cancer cell lines using molecular bea-coni maging technology.MATERIALS AND METHODS1Cervical cancer cell lines and ce...

  10. CDC Vital Signs: Cervical Cancer is Preventable

    Science.gov (United States)

    ... HPV vaccine can reduce risk of cervical cancer. HPV causes most cervical cancers. Only 1 in 3 girls and 1 in ... Signs – Cervical Cancer [PSA - 0:60 seconds] Cervical Cancer Preteen and Teen Vaccines Human Papillomavirus (HPV)-Associated Cancers What Should I Know About ...

  11. Preoperative serum squamous cell carcinoma antigen levels in clinical decision making for patients with early-stage cervical cancer

    NARCIS (Netherlands)

    Reesink-Peters, N; van der Velden, J; ten Hoor, KA; Boezen, HM; de Vries, EGE; Schilthuis, MS; Mourits, MJE; Nijman, HW; Aalders, JG; Hollema, H; Pras, E; Duk, JM; van der Zee, AGJ

    2005-01-01

    PURPOSE: To prevent morbidity associated with double modality treatment, early-stage cervical cancer patients should only be offered surgery when there is a low likelihood for adjuvant radiotherapy. We analyzed whether serum squamous cell carcinoma antigen (SCC-ag) analysis allows better preoperativ

  12. Changes of the cell cycle regulators and cell cycle arrest in cervical cancer cells after cisplatin therapy

    Institute of Scientific and Technical Information of China (English)

    Ke-xiu Zhu; Ya-li Cao; Bin Li; Jia Wang; Xiao-bing Han

    2009-01-01

    Objective To investigate the changes of the cell cycle regulators ATM, Chk2 and p53 and cell cycle arrest in HeLa cells after cisplatin therapy. Methods The proliferation-inhibiting rates of HeLa cells induced by eisplatin of different concentrations were measured by MTT assays. The mRNA and protein expressions of ATM, Chk2 and p53 of HeLa cells with and withont cisplatin were detected by RT-PCR and Western blot, respectively. The cell cycle analysis was conducted by flow cytometric analysis. Results Cisplatin inhibited the proliferation of HeLa cells in a dose- and time-dependent manner. The mRNA and protein expressions of ATM, Chk2 and p53 were increased in HeLa cells treated with cisplatin. The cell cycle was arrested in G2/M phase in HeLa cells treated with cisplatin. Conclusion Activation of ATM, Chk2 and p53 might be critical in determining whether cells survive or undergo apoptesis. Targeting ATM, Chk2 and p53 pathway might he a promising strategy for reversing chemoresistance to clsplatin in cervical cancer.

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ramos-Solano, Moisés, E-mail: mrsolano84@gmail.com [División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco (Mexico); Programa de Doctorado en Ciencias Biomédica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Jalisco (Mexico); Meza-Canales, Ivan D., E-mail: imezacanales@ice.mpg.de [Department of Molecular Ecology, Max Planck Institute for Chemical Ecology, 07745 Jena (Germany); Torres-Reyes, Luis A., E-mail: torres_reyes_88@hotmail.com [División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco (Mexico); Programa de Doctorado en Ciencias Biomédica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Jalisco (Mexico); Alvarez-Zavala, Monserrat, E-mail: monse_belan@hotmail.com [División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO)-Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco (Mexico); Programa de Doctorado en Ciencias Biomédica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Jalisco (Mexico); and others

    2015-07-01

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

  15. Physical status of multiple human papillomavirus genotypes in flow-sorted cervical cancer cells

    NARCIS (Netherlands)

    Vermeulen, Christine F. W.; Jordanova, Ekaterina S.; Szuhai, Karoly; Kolkman-Uljee, Sandra; Vrede, M. Albert; Peters, Alexander A. W.; Schtturing, Ed; Fleuren, Gert Jan

    2007-01-01

    Multiple human papilloma virus (HPV) infections have been detected in cervical cancer. To investigate the significance of multiple HPV infections, we studied their prevalence in cancer samples from a low-risk (Dutch) and a high-risk (Surinamese) population and the correlation of HPV infection with t

  16. DIFFERENCES OF TUMOR MASSES AND HEMOGLOBIN LEVELS IN CERVICAL CANCER SQUAMOUS CELL TYPE PATIENTS TREATED WITH COMBINATION OF PACLITAXEL AND CARBOPLATIN CHEMOTHERAPY

    OpenAIRE

    2014-01-01

    Background: Paclitaxel and carboplatin are standard operating procedure for chemotherapy treatment of cervical cancer squamous cell carcinoma at Sanglah General Hospital, Bali-Indonesia. Chemotherapy improves outcome of cancer treatment. However, chemotherapy brings also a variety of adverse effects and complications. This study aims to evaluate the therapeutic and adverse effects of chemotherapy in patients with squamous cell cervical cancer. Methods: This is a case study of six patients wit...

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

    Energy Technology Data Exchange (ETDEWEB)

    Kuncharin, Yanin [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Sangphech, Naunpun [Biotechnology Program, Faculty of Science, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Kueanjinda, Patipark [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Bhattarakosol, Parvapan [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand); Palaga, Tanapat, E-mail: tanapat.p@chula.ac.th [Department of Microbiology, Faculty of Science, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Mei-Yin Chang

    2015-11-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Van-Tinh Nguyen

    2013-12-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    López Jacqueline

    2012-01-01

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

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

    Science.gov (United States)

    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. An animal model of buccal mucosa cancer and cervical lymph node metastasis induced by U14 squamous cell carcinoma cells.

    Science.gov (United States)

    Zhao, Xin; Pang, Liang; Qian, Yu; Wang, Qiang; Li, Yong; Wu, Mingyi; Ouyang, Zilan; Gao, Zhi; Qiu, Lihua

    2013-04-01

    The buccal mucosa is the site with the highest risk of contracting a malignancy in habitual betel quid chewers who expose the buccal mucosa to high doses of carcinogens. Of all oral cancers, those of the buccal mucosa are associated with the poorest prognoses. Therefore, it would be helpful to have an animal model to evaluate new treatment modalities for buccal mucosa cancer. In the present study, we evaluated whether the imprinting control region (ICR) mouse animal model could be employed as a cancer model for buccal mucosa cancer. Sixty male ICR mice were randomly divided into two groups, a normal group (n=10) and a cancer-induced group (n=50). Each mouse in the cancer group was inoculated with 0.05 ml U14 cancer cell suspension (1×10(7)/ml) on the buccal mucosa. Histological staining and gene expression assays revealed that neck lymph node metastasis animal models were established. After 20 days, the cheek tumor formation rate of the ICR mice reached 100%. Furthermore, the neck lymph node metastasis rate was 53%. We identified that U14 cells produce strong metastasis in ICR mice. Metastasis of the tumor to the lymph node began with carcinoma metastasis encroaching on the marginal sinus. Then it infiltrated to the cortex and medulla and the infiltration continued until the normal lymph node structure was completely damaged. This animal model may be employed in medical research on buccal mucosa cancer and cervical lymph node metastasis. In conclusion, our findings indicate that U14 cell-induced mouse buccal mucosa cancer may be a potential cancer model for human buccal mucosa squamous cell carcinoma.

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

    Science.gov (United States)

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

    2010-03-01

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

  5. Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications

    Directory of Open Access Journals (Sweden)

    Jimenez-Perez Miriam I

    2012-02-01

    Full Text Available Abstract Background Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down-modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity. Results We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT. Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells. Conclusions Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells.

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

    Science.gov (United States)

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

    2014-01-01

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

  7. Effects of Smac gene over-expression on the radiotherapeutic sensitivities of cervical cancer cell line HeLa

    Institute of Scientific and Technical Information of China (English)

    ZHENG Li-duan; XIONG Zhou-fang; ZHU Jian-wen; WANG Ze-hua

    2005-01-01

    Background The second mitochondria-derived activator of caspases (Smac) is a novel proapoptotic gene, which plays an important role in the apoptosis-inducing effects of irradiation on tumor cells. The purpose of this study was to investigate the effects of extrinsic Smac gene transfer and its over-expression in radiotherapeutic sensitivities of cervical cancer cells. Methods After the Smac gene was transferred into the cervical cancer cell line HeLa, subcloned cells were obtained by persistent G418 selection. Cellular Smac gene expression was detected by RT-PCR and Western blot, while in vitro cell viabilities were detected by trypan blue staining assay. After treatment with X-ray irradiation, cellular radiotherapeutic sensitivities were investigated by tetrazolium bromide colorimetry. Cellular apoptosis and its rate were determined by electronic microscopy, annexin V-FITC and propidium iodide staining flow cytometry. The expression and activities of cellular caspase-3 were assayed by Western blot and colorimetry. Results Smac mRNA and protein levels in HeLa/Smac cells and the selected subclone cell line of cervical cancer were significantly higher than those of HeLa (P0.05). However, after irradiation with 8 Gy X-ray, growth activities of HeLa/Smac were reduced by 22.42% (P<0.01). When compared with those of HeLa, partial HeLa/Smac cells presented characteristic morphological changes of apoptosis under electronic microscope, with higher apoptosis rates (16.4% vs. 6.2%, P<0.01); the caspase-3 expression levels in HeLa/Smac cells were improved significantly (P<0.01), while its activities were increased by 3.42 times (P<0.01).Conclusions Stable transfer of the extrinsic Smac gene and its over-expression in cervical cancer cell line could significantly enhance the expression and activities of cellular caspase-3 and ameliorate apoptosis-inducing effects of irradiation on cancer cells, which was a novel strategy to improve radiotherapeutic effects on cervical cancer.

  8. Lethality of PAK3 and SGK2 shRNAs to human papillomavirus positive cervical cancer cells is independent of PAK3 and SGK2 knockdown.

    Directory of Open Access Journals (Sweden)

    Nannan Zhou

    Full Text Available The p21-activated kinase 3 (PAK3 and the serum and glucocorticoid-induced kinase 2 (SGK2 have been previously proposed as essential kinases for human papillomavirus positive (HPV+ cervical cancer cell survival. This was established using a shRNA knockdown approach. To validate PAK3 and SGK2 as potential targets for HPV+ cervical cancer therapy, the relationship between shRNA-induced phenotypes in HPV+ cervical cancer cells and PAK3 or SGK2 knockdown was carefully examined. We observed that the phenotypes of HPV+ cervical cancer cells induced by various PAK3 and SGK2 shRNAs could not be rescued by complement expression of respective cDNA constructs. A knockdown-deficient PAK3 shRNA with a single mismatch was sufficient to inhibit HeLa cell growth to a similar extent as wild-type PAK3 shRNA. The HPV+ cervical cancer cells were also susceptible to several non-human target shRNAs. The discrepancy between PAK3 and SGK2 shRNA-induced apoptosis and gene expression knockdown, as well as cell death stimulation, suggested that these shRNAs killed HeLa cells through different pathways that may not be target-specific. These data demonstrated that HPV+ cervical cancer cell death was not associated with RNAi-induced PAK3 and SGK2 knockdown but likely through off-target effects.

  9. Lethality of PAK3 and SGK2 shRNAs to human papillomavirus positive cervical cancer cells is independent of PAK3 and SGK2 knockdown.

    Science.gov (United States)

    Zhou, Nannan; Ding, Bo; Agler, Michele; Cockett, Mark; McPhee, Fiona

    2015-01-01

    The p21-activated kinase 3 (PAK3) and the serum and glucocorticoid-induced kinase 2 (SGK2) have been previously proposed as essential kinases for human papillomavirus positive (HPV+) cervical cancer cell survival. This was established using a shRNA knockdown approach. To validate PAK3 and SGK2 as potential targets for HPV+ cervical cancer therapy, the relationship between shRNA-induced phenotypes in HPV+ cervical cancer cells and PAK3 or SGK2 knockdown was carefully examined. We observed that the phenotypes of HPV+ cervical cancer cells induced by various PAK3 and SGK2 shRNAs could not be rescued by complement expression of respective cDNA constructs. A knockdown-deficient PAK3 shRNA with a single mismatch was sufficient to inhibit HeLa cell growth to a similar extent as wild-type PAK3 shRNA. The HPV+ cervical cancer cells were also susceptible to several non-human target shRNAs. The discrepancy between PAK3 and SGK2 shRNA-induced apoptosis and gene expression knockdown, as well as cell death stimulation, suggested that these shRNAs killed HeLa cells through different pathways that may not be target-specific. These data demonstrated that HPV+ cervical cancer cell death was not associated with RNAi-induced PAK3 and SGK2 knockdown but likely through off-target effects.

  10. Amplified genes may be overexpressed, unchanged, or downregulated in cervical cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Oscar Vazquez-Mena

    Full Text Available 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

  11. Amplified genes may be overexpressed, unchanged, or downregulated in cervical cancer cell lines.

    Science.gov (United States)

    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.

  12. Expression of TLR4/iNOS pathway molecules in high-risk HPV-positive cervical cancer tissue and cell lines and its significance

    Institute of Scientific and Technical Information of China (English)

    Ding Wang; Zhi-Ying Li; Jiao Lu

    2016-01-01

    Objective:To study the expression of TLR4/iNOS pathway molecules in high-risk HPV-positive cervical cancer tissue and cell lines and its significance.Methods: 35 cases of patients with high-risk HPV-positive cervical cancer and 35 cases of healthy subjects receiving cervical biopsy were enrolled for study, and mRNA contents of TLRs and NOS in cervical tissue were analyzed. CaSki cell lines (HPV16-positive), Hela cell lines (HPV18-positive) and C33a cell lines (HPV-negative) were cultured, siRNA was transfected and contents of TLR4, NF-kB, iNOS and NO were detected.Results:mRNA contents of TLR4 and iNOS in high-risk HPV-positive cervical cancer tissue were significantly higher than those in normal cervical biopsy tissue, and comparison of mRNA contents of TLR3, TLR7, TLR8, TLR9, eNOS and nNOS with normal cervical biopsy tissue showed no significant differences; mRNA contents of TLR4, NF-kB and iNOS as well as NO levels in CaSki cell lines and Hela cell lines were higher than those in C33a cell lines; after transfection of TLR4 siRNA, mRNA contents of NF-kB and iNOS as well as NO levels in CaSki cell lines and Hela cell lines were lower than those transfected with negative control siRNA.Conclusions: Expression of TLR4/iNOS pathway molecules in high-risk HPV-positive cervical cancer tissue and cell lines increases, and TLR4 can increase iNOS expression and NO generation through NF-kB, thus participating in pathological process of cervical cancer caused by high-risk HPV.

  13. Cervical cancer screening at crossroads

    DEFF Research Database (Denmark)

    Lynge, Elsebeth; Rygaard, Carsten; Baillet, Miguel Vazquez-Prada;

    2014-01-01

    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...

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

    Science.gov (United States)

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

    2010-09-01

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

  15. Network Topologies Decoding Cervical Cancer.

    Directory of Open Access Journals (Sweden)

    Sarika Jalan

    Full Text Available 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.

  16. The Expression of Cyclooxygenase-2 in Cervical Cancers and Hela Cells Was Regulated by Estrogen/Progestogen

    Institute of Scientific and Technical Information of China (English)

    LI Yunguang; PU Demin; LI Yanli

    2007-01-01

    To investigate the relationship between the expression of cyclooxygenase-2 (COX-2) and menstrual cycle, the regulatory effects of 17-β-estradiol (E2) and medroxyprogesterone acetate (MPA) on the expression of COX-2 in cervical cancer Hela cells were examined. Cervical cancer specimens were obtained from 47 pre-menopausal patients. The phase of menstrual cycle was determined by case history and HE staining of uterine endometrium. COX-2 was immunohistochemically stained by SABC staining and the staining intensity was determined with computerized image analysis system.Hela cells were incubated with alcohol, E2, E2+MPA, MPA for 12, 24 and 48 h respectively. The expression of COX-2 in Hela cells was detected by Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Our results showed that the expression of COX-2 was significantly higher during proliferative phase than secretory phase (P<0.05), but there was no difference in the positive rate between proliferative phase and secretory phase (P>0.05). Incubation with E2 could significantly enhance the expression of COX-2 continually. On the contrary, E2+MPA and MPA alone could decrease the expression of COX-2 as compared with the control and E2 group (P<0.05 and P<0.01 respectively). It is concluded that the expression of COX-2 in cervical cancer of pre-menopausal patients and Hela cells was regulated by estrogen/progestogen.

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

    Science.gov (United States)

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

    2012-09-01

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

  18. Sensitization of Cervical Cancer Cells to Cisplatin by Genistein: The Role of NFB and Akt/mTOR Signaling Pathways

    Directory of Open Access Journals (Sweden)

    K. Sahin

    2012-01-01

    Full Text Available Cervical cancer is among the top causes of death from cancer in women. Cisplatin-based chemotherapy has been shown to improve survival; however, cisplatin treatment is associated with toxicity to healthy cells. Genistein has been used as an adjunct to chemotherapy to enhance the activity of chemotherapeutic agents without causing increased toxicity. The present study was designed to investigate the effect of genistein (25 μM on antitumor activity of cisplatin (250 nM on HeLa cervical cancer cells. We have examined the alterations in expression of NF-B, p-mTOR, p-p70S6K1, p-4E-BP1, and p-Akt protein levels in response to treatment. The combination of 25 μM genistein with 250 nM cisplatin resulted in significantly greater growth inhibition (. Genistein enhanced the antitumor activity of cisplatin and reduced the expression of NF-B, p-mTOR, p-p70S6K1, p-4E-BP1, and p-Akt. The results in the present study suggest that genistein could enhance the activity of cisplatin via inhibition of NF-κB and Akt/mTOR pathways. Genistein is a promising nontoxic nutritional agent that may enhance treatment outcome in cervical cancer patients when given concomitantly with cisplatin. Clinical trials of genistein and cisplatin combination are warranted to test this hypothesis.

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

    Science.gov (United States)

    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.

  20. In vitro anti-cancer activity of ethanolic extract of Momordica charantia on cervical and breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    C R Shobha

    2015-01-01

    Full Text Available Objectives: To estimate the total phenol content (TPC of the ethanolic extract of Momordica charantia (EEMC whole fruit and to study the cytotoxic activity of this extract against cell lines representing carcinomas of cervix and breast. Materials and Methods: Cervical and breast carcinoma cell lines (HeLa and MCF-7 were procured from National Center for Cell Sciences, Pune, and cultured in Dulbecco's modified eagle medium (DMEM supplemented with 10% fetal bovine serum (FBS and 1 mM L-glutamine. EEMC was prepared by graded ethanol fractionation method and the TPC determined using Folin–Ciocalteu assay. For cytotoxicity studies, 5000 cells/well in 100 μl DMEM-10% FBS medium were seeded in a 96 well plate; and treated with increasing concentration of EEMC. Efficacy of EEMC was determined by measuring the cell number using sulforhodamine B assay. Percentage inhibition was calculated using dimethyl sulfoxide vehicle control. The IC (50 value was calculated from the plot of inhibition (% in dose- and time-dependent manner using GraphPad PRISM software. Results: The total phenolic content of EEMC decreased with increasing ethanol concentration from 50% to 100%. Cytotoxicity studies identified 50% ethanolic extract as the most active fraction. A time- and dose-dependent increase in the efficacy of 50% ethanolic extract for inhibiting cervical and breast carcinoma cell growth was noticed. The IC (50 dose was 12.31 μg/ml and 0.769 μg/ml for 50% EEMC at 48 h incubation for HeLa and MCF-7 cell lines, respectively. Conclusion: The presence of high total phenolic acid content in 50% ethanolic extract indicates that the anti-cancer activity of Momordica charantia could be due to the secondary metabolites. Based on the IC (50 value we conclude that the 50% EEMC is more potent against breast cancer cell lines. Further studies are required to know the exact cause for the increase in cell inhibition at 48 h incubation than in 72 h.

  1. HeLa human cervical cancer cell migration is inhibited by treatment with dibutyryl-cAMP.

    Science.gov (United States)

    Lee, Jae-Wook; Lee, Jiyoung; Moon, Eun-Yi

    2014-07-01

    Cyclic AMP (cAMP) activates both protein kinase A (PKA) and guanine-nucleotide exchange factor exchange protein directly activated by CAMP (EPAC)-mediated Ras-related Protein1 (RAP1) GTPase that regulates various cellular functions including cell migration. Herein, we investigated whether cAMP-mediated PKA and EPAC1/RAP1 pathways differentially control HeLa cervical cancer cell migration. Although HeLa cell migration was reduced by dibutyryl-cAMP, we observed an increase in cAMP/PKA, cAMP/EPAC1/RAP1-GTPase, and RAC1-GTPase. HeLa cell migration and RAC1-GTPase were increased by treatment with 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cAMP analogue to activate EPAC-specific signaling pathways. When HeLa cells were treated with H-89, a PKA inhibitor, cell migration was enhanced but RAC1-GTPase was inhibited. In addition, cell migration induced by dibutyryl-cAMP was reversed but the activity of Rac1-GTPase was inhibited by H-89 treatment. Taken together, these data demonstrate that cAMP/PKA and cAMP/EPAC1/RAP1-GTPase might inversely control cervical cancer cell migration, although both signaling pathways may up-regulate RAC1-GTPase. It also suggests that cAMP-mediated cancer cell migration was independent of RAC1-GTPase activation.

  2. MICROARRAY ANALYSIS OF DIFFERENT GENE EXPRESSION OF HUMAN CERVICAL CANCER SUBCLONE CELL LINES

    Institute of Scientific and Technical Information of China (English)

    Chen Wei; Li Xu; Wang Xiang

    2006-01-01

    Objective To examine the differentially expressed invasion-related genes in two anchorage-independent uterine cervical carcinoma cell lines derived from the same patient using a cDNA array. Methods Two human uterine cervical carcinoma subclonal cell lines CS03 and CS07 derived from a single donor line CS1213 were established by limited dilution procedure. The two cDNA samples retro-transcribed from total RNA derived from CS03 and CS07 cells were screened by a cDNA microarray carrying 234 human cell-cycle related genes and 1011 human signal transduction and membrane receptor -associated genes, scanned with a ScanArray 3000 laser scanner. Results The cDNA microarray analysis showed that 12 genes in CS03 were up-regulated compared to CS07, and 24 genes in CS07 were up-regulated. The function of a number of differentially expressed genes was consistently associated with cell-cycle, cell proliferation, migration, apoptosis, signal transduction and tumor metastasis, including p34cdc2, TSC22, plasminogen activator inhibitor I (PAI-1)and desmosome associated protein(Pinin). Conclusion Multiple genes are differentially expressed in uterine cervical carcinoma cell lines even came from the same patient. It is suggested that these genes are involved in the different phenotypic characteristics and development of cervical carcinoma.

  3. Intermediate-Conductance-Ca2-Activated K Channel Intermediate-Conductance Calcium-Activated Potassium Channel (IKCa1) is Upregulated and Promotes Cell Proliferation in Cervical Cancer

    Science.gov (United States)

    Liu, Ling; Zhan, Ping; Nie, Dan; Fan, Lingye; Lin, Hairui; Gao, Lanyang; Mao, Xiguang

    2017-01-01

    Background Accumulating data point to intermediate-conductance calcium-activated potassium channel (IKCa1) as a key player in controlling cell cycle progression and proliferation of human cancer cells. However, the role that IKCa1 plays in the growth of human cervical cancer cells is largely unexplored. Material/Methods In this study, Western blot analysis, immunohistochemical staining, and RT-PCR were first used for IKCa1protein and gene expression assays in cervical cancer tissues and HeLa cells. Then, IKCa1 channel blocker and siRNA were employed to inhibit the functionality of IKCa1 and downregulate gene expression in HeLa cells, respectively. After these treatments, we examined the level of cell proliferation by MTT method and measured IKCa1 currents by conventional whole-cell patch clamp technique. Cell apoptosis was assessed using the Annexin V-FITC/Propidium Iodide (PI) double-staining apoptosis detection kit. Results We demonstrated that IKCa1 mRNA and protein are preferentially expressed in cervical cancer tissues and HeLa cells. We also showed that the IKCa1 channel blocker, clotrimazole, and IKCa1 channel siRNA can be used to suppress cervical cancer cell proliferation and decrease IKCa1 channel current. IKCa1 downregulation by specific siRNAs induced a significant increase in the proportion of apoptotic cells in HeLa cells. Conclusions IKCa1 is overexpressed in cervical cancer tissues, and IKCa1 upregulation in cervical cancer cell linea enhances cell proliferation, partly by reducing the proportion of apoptotic cells. PMID:28280257

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

    Directory of Open Access Journals (Sweden)

    Bravo-Cuellar Alejandro

    2009-06-01

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

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

    Science.gov (United States)

    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.

  6. A MicroRNA Expression Signature for Cervical Cancer Prognosis

    Science.gov (United States)

    Hu, Xiaoxia; Schwarz, Julie K.; Lewis, James S.; Huettner, Phyllis C.; Rader, Janet S.; Deasy, Joseph O.; Grigsby, Perry W.; Wang, Xiaowei

    2010-01-01

    Invasive cervical cancer is a leading cause of cancer death in women worldwide, resulting in about 300,000 deaths each year. The clinical outcomes of cervical cancer vary significantly and are difficult to predict. Thus, a method to reliably predict disease outcome would be important for individualized therapy by identifying patients with high-risk of treatment failures prior to therapy. In this study, we have identified a microRNA-based signature for the prediction of cervical cancer survival. MicroRNAs (miRNAs) are a newly identified family of small non-coding RNAs that are extensively involved in human cancers. Using our recently established PCR-based miRNA assays, we have analyzed 102 cervical cancers and identified two miRNAs (miR-200a and miR-9) that are likely to predict patient survival. A logistic regression model was developed based on these two miRNAs and the prognostic value of the model was subsequently validated with 42 independent cervical cancers. Furthermore, functional studies were performed to characterize the effect of miRNAs in cervical cancer cells. Our results suggest that both miR-200a and miR-9 could play important regulatory roles in cervical cancer control. In particular, miR-200a is likely to affect the metastatic potential of cervical cancer cells by simultaneously suppressing the expression of multiple genes that are important to cell motility. PMID:20124485

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

    Science.gov (United States)

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

    2014-02-14

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

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

    Science.gov (United States)

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

    2015-12-01

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

  9. IL-17A promotes the migration and invasiveness of cervical cancer cells by coordinately activating MMPs expression via the p38/NF-κB signal pathway.

    Directory of Open Access Journals (Sweden)

    Minjuan Feng

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

  10. Preventing Cervical Cancer with HPV Vaccines

    Science.gov (United States)

    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.

  11. Cervical Cancer Risk Prediction Models

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    Kato, Yasuhito; Yamashita, Tsuyoshi; Ishikawa, Mutsuo

    2002-01-01

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

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

    Science.gov (United States)

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

    2006-01-01

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

  15. Human papillomavirus and cervical cancer.

    Science.gov (United States)

    Crosbie, Emma J; Einstein, Mark H; Franceschi, Silvia; Kitchener, Henry C

    2013-09-07

    Cervical cancer is caused by human papillomavirus infection. Most human papillomavirus infection is harmless and clears spontaneously but persistent infection with high-risk human papillomavirus (especially type 16) can cause cancer of the cervix, vulva, vagina, anus, penis, and oropharynx. The virus exclusively infects epithelium and produces new viral particles only in fully mature epithelial cells. Human papillomavirus disrupts normal cell-cycle control, promoting uncontrolled cell division and the accumulation of genetic damage. Two effective prophylactic vaccines composed of human papillomavirus type 16 and 18, and human papillomavirus type 16, 18, 6, and 11 virus-like particles have been introduced in many developed countries as a primary prevention strategy. Human papillomavirus testing is clinically valuable for secondary prevention in triaging low-grade cytology and as a test of cure after treatment. More sensitive than cytology, primary screening by human papillomavirus testing could enable screening intervals to be extended. If these prevention strategies can be implemented in developing countries, many thousands of lives could be saved.

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

    Science.gov (United States)

    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

  17. IκB kinase Mediating the Downregulation of p53 and p21 by Lipopolysaccharide in Human Papillomavirus 16+ Cervical Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hui Tan; Yu Zhang; Yan Tian; Wei Tan; Ying-Hua Li

    2016-01-01

    Background:Cervical cancer is the second most common cancer of woman in the world,and human papillomavirus (HPV) infection plays an important role in the development of most of the cases.IκB kinase β (IKKβ) is a kinase-mediating nuclear factor kappa B (NF-κB) activation by phosphorylating the inhibitor ofNF-κB (IκB) and is related by some diseases caused by virus infection.However,there is little known about the correlation between IKKβ and HPV infection in cervical cancer.This study aimed to investigate the expression of IKKβ protein in cervical cancer tissues and effects of inflammation on HPV positive or negative cervical cancer cells through detecting the expression of IKKβ,IKBα,p53,and p21 proteins after treated with lipopolysaccharide (LPS) to mimic bacterial infection.We also examined the effects of LPS on cervical cancer cells after blocking IKKβ with pharmacological inhibitor.Methods:Thirty-six matched specimens of cervical cancer and adjacent normal tissues were collected and analyzed in the study.The expression of IKKβ in the tissue specimens was determined by immunohistochemical staining.In addition,Western blot was used to detect the expression level changes ofIKKβ,IκBα,p53,and p21 after LPS stimulated in the HPV16+ (SiHa) and HPV16-(C33A) cervical cancer cell lines.Furthermore,the effects of IKKβ inhibitor SC-514 on LPS-induced expression change of these proteins were investigated.Results:The expression of IKKβ was higher in cervical cancer than adjacent normal tissues,and there was no significant difference between tumor differentiation,size,and invasive depth with IKKβ expression.The LPS,which increased the expression level of IKKβ protein but decreased in the IκBα,p53 and p21 proteins,was illustrated in HPV16+ (SiHa) but not in HPV16-(C33A) cells.Moreover,IKKβ inhibitor SC-514 totally reversed the upregulation of IKKβ and downregulation of p53 and p21 by LPS in SiHa cells.Conclusions:IKKβ may mediate the downregulation of p

  18. Angels and demons: Th17 cells represent a beneficial response, while neutrophil IL-17 is associated with poor prognosis in squamous cervical cancer

    NARCIS (Netherlands)

    S. Punt (Simone); G.J. Fleuren (G.); E. Kritikou (Eva); E.W. Lubberts (Erik); J.B. Trimbos; E.S. Jordanova (Ekaterina S.); A. Gorter (Arko)

    2015-01-01

    textabstractThe role of interleukin (IL)-17 in cancer remains controversial. In view of the growing interest in the targeting of IL-17, knowing its cellular sources and clinical implications is crucial. In the present study, we unraveled the phenotype of IL-17 expressing cells in cervical cancer usi

  19. Human papillomavirus oncoproteins differentially modulate epithelial-mesenchymal transition in 5-FU-resistant cervical cancer cells.

    Science.gov (United States)

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

    2016-10-01

    Etiological role of viral proteins E6 and E7 of high-risk HPV in cervical carcinogenesis is well established. However, their contribution in chemoresistance and epithelial-mesenchymal transition (EMT) that leads to advanced metastatic lesions and chemoresistance is poorly defined. In the present study, contribution of viral oncoproteins in acquisition of EMT character during onset of chemoresistance was assessed. A chemoresistant cell line (SiHaCR) was developed from an established HPV16-positive cervical cancer cell line, SiHa, by escalating selection pressure of 5-fluorouracil (5-FU). Expression of Survivin, ABCG2, Snail, Slug, Twist, and Vimentin was examined in SiHa and SiHaCR cells by reverse transcriptase-PCR (RT-PCR) and immunoblotting assays. Mesenchymal phenotype in SiHaCR cells was confirmed by assessment of migration and invasion potentials. SiHaCR cells displayed elevated level of functional and molecular markers associated with chemoresistance (Survivin, ABCG2) and EMT (Snail, Slug, Twist, Vimentin) and reduced E-cadherin. SiHaCR also showed increased levels of HPV16 E6 and E7 transcripts. Specific silencing of HPV16 E6, but not E7 using corresponding siRNA, demonstrated a differential involvement of HPV oncogenes in manifestation of EMT. HPV16 E6 silencing resulted in reduction of Slug and Twist expression. However, the expression of Snail and Vimentin was only marginally affected. In contrast, there was an increase in the expression of E-cadherin. A reduced migration and invasion capabilities were observed only in E6-silenced SiHaCR cells, which further confirmed functional contribution of HPV16 E6 in manifestation of EMT. Taken together, our study demonstrated an active involvement of HPV16 E6 in regulation of EMT, which promotes chemoresistance in cervical cancer.

  20. Human papillomavirus 16/18 E5 promotes cervical cancer cell proliferation, migration and invasion in vitro and accelerates tumor growth in vivo.

    Science.gov (United States)

    Liao, Shujie; Deng, Dongrui; Zhang, Weina; Hu, Xiaoji; Wang, Wei; Wang, Hui; Lu, Yunping; Wang, Shixuan; Meng, Li; Ma, Ding

    2013-01-01

    High-risk human papillomaviruses (HR-HPVs) are consistently associated with human cervical cancer Additionally, the early oncoproteins of HPVs E5, E6 and E7 are known to contribute to tumor progression. The role of E5 is still nebulous. In this study, we aimed to explore the mechanism of E5 action during the human cervical carcinogenesis process. We created four cell models overexpressing HPV16 or HPV18 E5 (HPV16/18 E5) and investigated their ability to proliferate, along with their metastatic characteristics such as migration and invasion. The expression of HPV16/18 E5 protein in various cell lines was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, we compared the levels of phosphorylated paxillin as well as E-cadherin in cell models and controls by western blot analysis. Finally, we assessed the tumor growth rate of human cervical cancer cells overexpressing HPV16/18 E5 in vivo. We discovered that the expression of HPV16/18 E5 consistently increased the malignant potential of various human cervical cancer cells compared with the primary counterparts. We demonstrated the involvement of HPV16/18 E5 in proliferation, migration, invasion and regulation of the actin cytoskeleton in human cervical cancer cells. In particular we discovered that HPV16/18 E5 overexpression in human cervical cancer cells correlated with higher levels of paxillin proteins phosphorylated on tyrosine residues and with the downregulation of E-cadherin. Importantly, injection of HPV16/18 E5-overexpressing human cervical cancer cells into mice increased both HPV-and non-HPV-derived tumor growth. Collectively, our data indicate that HPV16/18 E5 influences progression of the human cervical cancer malignant phenotype. This study provides new insights into HPV16/18 E5 as a possible agent that may have an impact on the therapeutic strategies targeting human cervical cancer.

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

    Science.gov (United States)

    2014-12-23

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

  2. Characterization of adult α- and β-globin elevated by hydrogen peroxide in cervical cancer cells that play a cytoprotective role against oxidative insults.

    Directory of Open Access Journals (Sweden)

    Xiaolei Li

    Full Text Available OBJECTIVES: Hemoglobin (Hgb is the main oxygen and carbon dioxide carrier in cells of erythroid lineage and is responsible for oxygen delivery to the respiring tissues of the body. However, Hgb is also expressed in nonerythroid cells. In the present study, the expression of Hgb in human uterine cervix carcinoma cells and its role in cervical cancer were investigated. METHODOLOGY: The expression level of Hgb in cervical cancer tissues was assessed by quantitative reverse transcriptase-PCR (qRT-PCR. We applied multiple methods, such as RT-PCR, immunoblotting, and immunohistochemical analysis, to confirm Hgb expression in cervical cancer cells. The effects of ectopic expression of Hgb and Hgb mutants on oxidative stress and cell viability were investigated by cellular reactive oxygen species (ROS analysis and lactate dehydrogenase (LDH array, respectively. Both Annexin V staining assay by flow cytometry and caspase-3 activity assay were used, respectively, to evaluate cell apoptosis. RESULTS: qRT-PCR analysis showed that Hgb-α- (HBA1 and Hgb-β-globin (HBB gene expression was significantly higher in cervical carcinoma than in normal cervical tissues, whereas the expression of hematopoietic transcription factors and erythrocyte specific marker genes was not increased. Immunostaining experiments confirmed the expression of Hgb in cancer cells of the uterine cervix. Hgb mRNA and protein were also detected in the human cervical carcinoma cell lines SiHa and CaSki, and Hgb expression was up-regulated by hydrogen peroxide-induced oxidative stress. Importantly, ectopic expression of wild type HBA1/HBB or HBA1, rather than mutants HBA1(H88R/HBB(H93R unable to bind hemo, suppressed oxidative stress and improved cell viability. CONCLUSIONS: The present findings show for the first time that Hgb is expressed in cervical carcinoma cells and may act as an antioxidant, attenuating oxidative stress-induced damage in cervical cancer cells. These data provide a

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

    Science.gov (United States)

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

    2010-03-01

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

  4. Apoptosis induction in Jurkat cells and sCD95 levels in women's sera are related with the risk of developing cervical cancer

    Directory of Open Access Journals (Sweden)

    Bravo-Cuellar Alejandro

    2008-04-01

    Full Text Available Abstract Background Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95 in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls. Methods Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma. The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L were measured by ELISA kits. Results We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer. Conclusion Our results demonstrate that there is a strong correlation between low levels of sCD95 in serum of normal women and higher apoptosis induction in Jurkat cells. We suggest that an analysis of

  5. Methods for Cervical Cancer Screening

    Directory of Open Access Journals (Sweden)

    Tatiana Vargas-Revilla

    2014-12-01

    This article is divided in three sections: the first one focuses on the general impact of cervical cancer has hadin CostaRica, these condsection gathers information about different methodologies used around the world to detect this cancer and the third one makes reference to the current development of the screening devise in Mexico that works as a monitoring system and can used by women without external assistance.

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

    Science.gov (United States)

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

    2014-11-15

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2013-01-01

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

  9. Treatment protocols for cervical cancer

    Directory of Open Access Journals (Sweden)

    Vujkov Tamara

    2002-01-01

    Full Text Available Introduction Cervical cancer is the second most common cancer in women worldwide and the second cause of cancer death among women. About 95% (90% in developed countries of invasive carcinomas are of sqamous types, and 5% (10% in developed countries are adenocarcinomas. FIGO classification of cervical carcinomas, based on clinical staging and prognostic factor dictate therapeutic procedures and help in designing treatment protocols. Therapeutic modalities Surgical therapy includes conization, radical hysterectomy with pelvic lymphadenectomy and palliative operation urinary diversion and colostomy. Radiotherapy, brachytherapy and teletherapy are most recently combined with chemotherapy as concurrent chemoradiation. Discussion and conclusion No change in therapeutic modalities will ever decrease mortality rate of cervical carcinoma as much as education, prevention and early screening. The 5-year survival for locally advanced disease has not improved during the last 40 years as a result of failure to deliver therapy to the paraaortic region. Paraaortic lymph nodes should be evaluated before therapy planning by different imaging procedures, or more exactly by surgical staging: laparoscopy or laparotomy. Radical operations of cervical carcinoma should be performed by experienced surgeons, educated for this type of operation, with sufficient number of cases.

  10. Women's perspectives on illness in being screened for cervical cancer

    DEFF Research Database (Denmark)

    Hounsgaard, Lise; Augustussen, Mikaela; Møller, Helle;

    2013-01-01

    Background In Greenland, the incidence of cervical cancer caused by human papillomavirus (HPV) is 25 per 100,000 women; 2.5 times the Danish rate. In Greenland, the disease is most frequent among women aged 30–40. Systematic screening can identify women with cervical cell changes, which if untrea......Background In Greenland, the incidence of cervical cancer caused by human papillomavirus (HPV) is 25 per 100,000 women; 2.5 times the Danish rate. In Greenland, the disease is most frequent among women aged 30–40. Systematic screening can identify women with cervical cell changes, which...... of analysis: naive reading, structural analysis and critical interpretation. Results These revealed that women were unprepared for screening results showing cervical cell changes, since they had no symptoms. When diagnosed, participants believed that they had early-stage cancer, leading to feelings...

  11. In Vitro and In Vivo Synergistic Therapeutic Effect of Cisplatin with Human Papillomavirus16 E6/E7 CRISPR/Cas9 on Cervical Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Shuai Zhen

    2016-12-01

    Full Text Available PURPOSE: Human papillomavirus (HPV type 16 is one of the major etiologic factors of cervical cancer. Our study aims to investigate the potentiality of the antiviral clustered regularly interspaced short palindromic repeat (CRISPR/CRISPR-associated Cas9 system (CRISPR/Cas9 targeting the E6 and E7 oncogenes of HPV16 as a potential chemosensitizer of cisplatin (cis-diaminedichloroplatinum II; CDDP for cervical cancer. METHODS: Specifically, the therapeutic efficacy of combination of CDDP and HPV16 E6 + E7-CRISPR/Cas9 was assessed in cervical cancer cells and cervical cancer xenograft models. RESULTS: In vitro experiments showed that long-term exposure of SiHa cells to the HPV16 E6 + E7-CRISPR/Cas9 induced apoptosis, and its pro-apoptosis effect became more obvious when combined with CDDP. In vivo study found the efficacy of the combination of HPV16 E6 + E7-CRISPR/Cas9 and CDDP were superior to either of the treatments in term of apoptosis induction and metastasis inhibition. CONCLUSION: Collectively, our results suggested that HPV16 E6 + E7-CRISPR/Cas9 could be an effective sensitizer of CDDP chemotherapy in cervical cancer.

  12. Aberrant Expression of Notch1 in Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    Li Sun; Qimin Zhan; Wenhua Zhang; Yongmei Song; Tong Tong

    2007-01-01

    OBJECTIVE To investigate the putative role of the Notch1 receptor in cervical cancer carcinogenesis and progression.METHODS The expression of the Notch1 protein was analyzed by a Western-blotting approach in 40 cervical cancer and 30 normal cervical tissues.Some tissues were examined using RT-PCR To determine Mrna levels.Celluar localization of the Notch1 protein in the paraffin-embedded cervical tissues was also analyzed by immunohistochemistry.RESULTS The Notch1 protein was detected in all 30 normal cervical tissues.In contrast.only 6 samples of 40 cervical cancer tissues showed Notch1 expression.The level of the Notch1 protein expression was significantly lower in cervical cancer tissues than that in normal tissue samples.In agreement with these observations.levels of Notch1 Mrna were found to be substantially down-regulated in cervical cancer tissues.In the immunohistochemistry staining assay,the Notch1 protein was shown to localize predominantly in the cytoplasm and nucleoli of the normal cervical squamous epithelium of the cervix,but no staining was observed in the cervical cancer cells.Notch1 expression was observed to correlate with the clinical disease stage.but there were no correlations with age,tumor size,grade or lymph node metastasis (P>0.05).The levels of Notchl protein expression were significantly higher in early stages(I~lla,66.7%) compared to those in the advanced stages (Iib~IV,12.6%)(P=0.001).CONCLUSION Notch1 may play a role as a tumor suppressor in cervical tumorigenesis.Determination of Notch1 expression may be helpful for preoperative diagnosis and accuracy of staging.But its clinical use for cervical cancer requires further investigation.

  13. Cervical cancer: screening, diagnosis and staging.

    Science.gov (United States)

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

    2016-01-01

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

  14. Interleukin 10 promotes immune response by increasing the survival of activated CD8(+) T cells in human papillomavirus 16-infected cervical cancer.

    Science.gov (United States)

    Li, Li; Ma, Yan; Liu, Shuang; Zhang, Jin; Xu, Xin-Yan

    2016-10-11

    Human papillomavirus (HPV)-specific CD8(+) T cells are present in HPV-infected cervical cancer patients and have demonstrated potent antitumor properties. However, these cells cannot control tumor progression in most patients. To investigate the underlying mechanisms involved in suppressing or promoting CD8(+) T cell functions, we focused on interleukin 10 (IL-10), a pleiotropic cytokine with controversial roles in antitumor immunity. We found that compared to healthy controls, circulating CD8(+) T cells in HPV 16-infected cervical cancer patients expressed significantly higher levels of IL-10. Interestingly, these CD8(+) T cells from cervical cancer patients, but not those from healthy controls, responded to HPV 16 E6/E7 peptide stimulation by increasing IL-10 expression, demonstrating an antigen-specific IL-10 release. Addition of exogenous IL-10 improved the survival, but did not increase the proliferation, of peptide-stimulated CD8(+) T cells. CD8(+) T cells cultured in the presence of IL-10 also resulted in significantly higher interferon gamma (IFN-gamma) and granzyme B concentration, primarily due to improved cell survival. In resected cervical tumors, the frequency of tumor-infiltrating IL-10(+) CD8(+) T cells was positively correlated with the frequency of tumor-infiltrating IFN-gamma(+) and granzyme B(+) CD8(+) T cells. Tumor-associated macrophages were more potent than peripheral blood monocyte-derived macrophages at inducing IL-10 expression in CD8(+) T cells, possibly explaining the elevated IL-10(+) CD8(+) T cell frequency in cervical cancer patients. Together, these results are consistent with an immunostimulatory role of IL-10, which promoted CD8(+) T cell response by increasing the survival of activated CD8(+) T cells.

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

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

    2011-02-01

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

  18. Women's perspectives on illness in being screened for cervical cancer

    DEFF Research Database (Denmark)

    Hounsgaard, Lise; Augustussen, Mikaela; Møller, Helle;

    2013-01-01

    Background In Greenland, the incidence of cervical cancer caused by human papillomavirus (HPV) is 25 per 100,000 women; 2.5 times the Danish rate. In Greenland, the disease is most frequent among women aged 30–40. Systematic screening can identify women with cervical cell changes, which...... if untreated may cause cervical cancer. In 2007, less than 40% of eligible women in Greenland participated in screening. Objective To examine Greenlandic women's perception of disease, their understanding of the connection between HPV and cervical cancer, and the knowledge that they deem necessary to decide...... whether to participate in cervical cancer screening. Study design The methods used to perform this research were 2 focus-group interviews with 5 Danish-speaking women and 2 individual interviews with Greenlandic-speaking women. The analysis involved a phenomenological-hermeneutic approach with 3 levels...

  19. Women's perspectives on illness when being screened for cervical cancer

    DEFF Research Database (Denmark)

    Hounsgaard, Lise; Augustussen, Mikaela; Møller, Helle;

    2013-01-01

    BACKGROUND: In Greenland, the incidence of cervical cancer caused by human papillomavirus (HPV) is 25 per 100,000 women; 2.5 times the Danish rate. In Greenland, the disease is most frequent among women aged 30-40. Systematic screening can identify women with cervical cell changes, which...... if untreated may cause cervical cancer. In 2007, less than 40% of eligible women in Greenland participated in screening. OBJECTIVE: To examine Greenlandic women's perception of disease, their understanding of the connection between HPV and cervical cancer, and the knowledge that they deem necessary to decide...... whether to participate in cervical cancer screening. STUDY DESIGN: The methods used to perform this research were 2 focus-group interviews with 5 Danish-speaking women and 2 individual interviews with Greenlandic-speaking women. The analysis involved a phenomenological-hermeneutic approach with 3 levels...

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

    Directory of Open Access Journals (Sweden)

    Moon-Hong Kim

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

  1. miR-181b promotes cell proliferation and reduces apoptosis by repressing the expression of adenylyl cyclase 9 (AC9) in cervical cancer cells.

    Science.gov (United States)

    Yang, Lei; Wang, Yan-Li; Liu, Shang; Zhang, Pei-Pei; Chen, Zheng; Liu, Min; Tang, Hua

    2014-01-03

    MicroRNAs are a class of small, endogenous, non-coding RNAs that function as post-transcriptional regulators. In this study, we found that miR-181b promoted cell proliferation and inhibited cell apoptosis in cervical cancer cells. And we validated a new miR-181b target gene, adenylyl cyclase 9 (AC9). miR-181b restricted cAMP production by post-transcriptionally downregulating AC9 expression. Phenotypic experiments indicated that miR-181b and AC9 exerted opposite effects on cell proliferation and apoptosis.

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

    Science.gov (United States)

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

    2012-08-24

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

  3. Twist and YB-1 gene expression in cervical cancer and cervical intraepithelial neoplasia tissue as well as its correlation with epithelial-mesenchymal transition

    Institute of Scientific and Technical Information of China (English)

    Qin Liu; Hong Li; Yu Zhang

    2016-01-01

    Objective:To study the Twist and YB-1 gene expression in cervical cancer and cervical intraepithelial neoplasia tissue as well as its correlation with epithelial-mesenchymal transition. Methods:Normal cervical tissue, cervical intraepithelial neoplasia tissue and cervical cancer tissue were collected for study. ELISA kits were used to detect Twist, YB-1, E-cadherin,β-catenin, N-cadherin and Vimentin contents in cervical tissue, and immunohistochemistry was used to detect Twist and YB-1 expression levels in cervical tissue.Results:Twist and YB-1 contents, cell positive rate and immunohistochemical scores as well as N-cadherin and Vimentin contents in cervical cancer tissue and cervical intraepithelial neoplasia tissue were significantly higher than those in normal cervical tissue while E-cadherin andβ-catenin contents were lower than those in normal cervical tissue; Twist and YB-1 contents, cell positive rate and immunohistochemical scores as well as N-cadherin and Vimentin contents in cervical cancer tissue were significantly higher than those in cervical intraepithelial neoplasia tissue while E-cadherin andβ-catenin contents were lower than those in cervical intraepithelial neoplasia tissue; the higher the Twist and YB-1 expression levels in cervical cancer tissue, the lower the E-cadherin andβ-catenin contents, and the higher the N-cadherin and Vimentin contents.Conclusions: Twist and YB-1 gene overexpression can promote epithelial-mesenchymal transition to be involved in the occurrence of cervical cancer and cervical intraepithelial neoplasia.

  4. Nanotechnology in the management of cervical cancer.

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  6. 1-(2-Hydroxy-5-methylphenyl-3-phenyl-1,3-propanedione Induces G1 Cell Cycle Arrest and Autophagy in HeLa Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jie-Heng Tsai

    2016-08-01

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

  7. 鳞癌抗原在宫颈癌前病变及早期宫颈癌治疗中的价值%Value of squamous cell carcinoma antigen in cervical precancerous lesions and early cervical cancer therapy

    Institute of Scientific and Technical Information of China (English)

    王斌; 张月桃; 李琼珍

    2016-01-01

    目的:探讨鳞癌抗原在宫颈癌前病变及早期宫颈癌治疗中的价值。方法采用酶联接免疫吸附剂测定(ELISA)法初检,化学发光法复检测定宫颈上皮内瘤变(CINⅡ或 CINⅢ)、宫颈癌Ⅰ期与Ⅱa 期患者共134例不同临床分期宫颈鳞癌患者 SCC - Ag 水平和阳性率。术后将其分为两组(随访组和对照组),对照组只做常规宫颈病变筛查。随访两年观察比较两组患者术后两年内诊断出宫颈癌前病变的复发率。结果宫颈癌Ⅰ期和宫颈癌Ⅱa 期 SCC - Ag 水平、阳性率均明显高于宫颈上皮内瘤变(CINⅡ或 CINⅢ)组,差异具有统计学意义( P <0.05)。SCC - Ag 对术后检出宫颈肿瘤的复发率对比传统筛查方法,差异有显著性( P <0.05)。结论较高的血清 SCC 值可能意味着肿瘤恶性程度越高,血清 SCC - Ag 水平对于宫颈上皮内瘤变与宫颈癌早期的诊断、疗效判断、随访评估和复发后抢救性治疗措施均有重要的临床指导意义。%Objective To discuss the value of squamous cell carcinoma antigen in cervical precancerous lesions and early cervical cancer therapy. Methods Using ELISA for early detection,chemiluminescence review measurement of cervical intraepithelial neoplasia(CINⅡ or CINⅢ),patients with cervical cancer stage Ⅰ Ⅱa total 134 patients in different clinical stages of cervical squamous cell carcinoma SCC - Ag level and positive rate. They were divided into two groups after surgery,the control group only routine screening of cervical lesions,for a two - year fol-low - up. To observe and compare the recurrence rate of cervical lesions and early stage cervical cancer in two group of patients,more SCC - Ag value in the diagnosis of cervical cancer recurrence after surgery. Evaluating the value of SCC - Ag in the diagnosis of cervical cancer after surgical treatment of recurrence. Results The detection of postoperative recurrence rate of

  8. Effects of Geldanamycin on Expression of Bcl-2 in Human Cervical Cancer HeLa Cells

    Institute of Scientific and Technical Information of China (English)

    Xue Du; Ruoran Mi; Quanxin Qu; Ye Qu; Tianfu Yue

    2008-01-01

    OBJECTIVE Geldanamycin, a natural product of Streptomyces geldanus, binds the heat shock protein 90 (Hsp90), a cell chaperone protein that interacts with Bcl-2. In this study, we investigated whether geldanamycin (GA) inhibits proliferation of HeLa cells through induction of apoptosis by decreasing the level of Bcl-2expression.METHODS HeLa cells, a human cervical cell line, were cultured in vitro and treated with different concentrations of GA (0, 0.02, 0.2,2, 10 μmol/L) for 24 h. Or were treated for different lengths of time at a GA concentration of 10 μmol/L. Proliferation of the cells was analyzed by an MTT assay, and cell apoptosis was determined by staining the cells with annexin V. In addition, cellular mRNA levels for Bcl-2 and Hsp90 were determined by the semi-quantitative polymerase chain reaction (PCR), and the levels of Bcl-2 and Hsp90 protein expression were determined by Western blots.RESULTS Treatment of cells with GA was found to inhibit HeLa cell proliferation in a concentration and time-dependent manner. The inhibition was a result of increased cellular apoptotic levels. Further analyses showed that while the mRNA and protein expression levels of Hsp90 were-not affected, GA treatment significantly reduced the level of Bcl-2 mRNA and protein expression in a concentration-dependent manner that correlated with the observed inhibition of cell proliferation.CONCLUSION GA can inhibit proliferation and increase apoptosis of HeLa cells by decreasing the transcription and expression of an anti-apoptotic gene bcl-2, probably through interaction and functional inhibition of Hsp90.

  9. Mechanisms of arsenic trioxide induced apoptosis of human cervical cancer HeLa cells and protection by Bcl-2

    Institute of Scientific and Technical Information of China (English)

    邓友平; 林晨; 郑杰; 梁萧; 陈洁平; 付明; 肖培根; 吴旻

    1999-01-01

    It was recently reported that arsenic trioxide (As2O3) can induce complete remission in patients with acute promyelocytic leukemia (APL). In this present article, the biological effect of As2O3 on human cervical cancer HeLa cells and HeLa cells overexpressing Bcl-2 is studied. By MTT and colony forming ability assays, morphology alteration, flow cytometric analysis, DNA gel electrephoresis and in situ cell death detection (TUNEL), it was found that As2O3 inhibited the growth of HeLa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR, Northern blot, Western blot analysis revealed that As2O3 induced HeLa cell apoptosis possibly via decreasing the expression of c-myc and viral genes. HeLa cells overexpressing Bcl-2 partly resist As2O3 induced apoptosis, which might be relative to preventing the cells from As2O3 caused G2/M block, downregulation of c-myc gene expression and inhibition of viral gene expression was also noted, However, it was found that As2O3 at a high concentratio

  10. Induction of apoptosis by casticin in cervical cancer cells: reactive oxygen species-dependent sustained activation of Jun N-terminal kinase

    Institute of Scientific and Technical Information of China (English)

    Fanxiang Zeng; Li Tian; Fei Liu; Jianguo Cao; Meifang Quan; Xifeng Sheng

    2012-01-01

    Casticin,a polymethoxyflavone from Fructus viticis used as an anti-inflammatory agent in Chinese traditional medicine,has been reported to have anti-cancer activity.The purpose of this study was to examine the apoptotic activity of casticin on human cervical cancer cells and its molecular mechanism.We revealed a novel mechanism by which casticin-induced apoptosis occurs and showed for the first time that the apoptosis induced by casticin is mediated through generation of reactive oxygen species (ROS) and sustained activation of c-Jun N-terminal kinase (JNK) in HeLa cells.Casticin markedly increased the levels of intracellular ROS and induced the expression of phosphorylated JNK and cJun protein.Pre-treatment with N-acetylcvsteine and SP600125 effectively attenuated induction of apoptosis by casticin in HeLa cells.Moreover,casticin induced ROS production and apoptotic cell death in other cervical cancer cell lines,such as CasKi and SiHa.Importantly,casticin did not cause generation of ROS or induction of apoptosis in normal human peripheral blood mononuclear cells and embryonic kidney epithelium 293 cells.These results suggest that ROS generation and sustained JNK activation by casticin play a role in casticin-induced apoptosis and raise the possibility that treatment with casticin might be promising as a new therapy against human cervical cancer.

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

    Directory of Open Access Journals (Sweden)

    S. Rupachandra

    2014-01-01

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

  12. 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian

    Science.gov (United States)

    ... Therapy: There was a major advance in the treatment of cervical cancer when five NCI-sponsored clinical trials showed that ... to adding chemotherapy to radiation therapy in the treatment of invasive cervical cancer. (Cervical) HPV vaccine: Another major advance in the ...

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

    Science.gov (United States)

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

    2011-10-01

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

  14. CERVICAL ACID PHOSPHATASE: EVALUATION AS AN ADJUVANT TO PAPANICOLAOU SMEAR SCREENING IN CERVICAL CANCER DETECTION

    Directory of Open Access Journals (Sweden)

    Niranjan

    2015-02-01

    Full Text Available INTRODUCTION: Carcinoma of cervix accounts for 15% of all cancers diagnosed worldwide and is the second most common cancer in women. In the year 2000 there were over 4,71,000 new cases diagnosed and 2,88,000 deaths from cervical cancer. (1 Approximately 79% of these deaths occurred in developing countries. (2 Cervical cancer is preventable, but most women in poorer countries do not have access to effective screening programs. In India it is estimated that approximately 100,000 women develop cervical cancer each year. (3 Cancer cervix occupies either the top r ank or second among cancers in women in developing countries, whereas, in the developed countries cancer cervix does not find a place even in top five leading cancers in women. This is due to routine screening by cervical smear. Cervical smear cytology scr eening by Papanicolaou (Pap stained smears is the most efficacious and cost - effective method of cancer screening, decreasing the incidence and mortality from cervical cancer. (4 However, cervical smear screening has significant rates of false - positive and false - negative results, ranging from 10.3% for false positive cases to 5.6% for false negative cases. (5,6 To improve the detection and screening of cancerous and precancerous lesions of the cervix a number of sophisticated tests are available which are e xpensive and can be done only in a tertiary laboratory. To over - come this problems a cost effective cytochemical stain was introduced to measure the acid phosphatase activity in the cervical epithelium. (7 Since the description of the new Cervical Acid Phosphatase Test (CAP Test for visualization of cervical acid phosphatase activity (CAP inside abnormal cervical cells on smears, it has become possible to explore this enzyme as a biomarker for cervical dys plasia, and as a possible surrogate for PAP smear in detection of cervical intraepithelial neoplasia (CIN. AIMS AND OBJECTIVES: To assess the utility of Cervical Acid

  15. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma

    Science.gov (United States)

    Kuroda, Hiromasa; Kimura, Tadashi

    2017-01-01

    Objective To compare the survival outcomes of patients with cervical squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) among patients with locally advanced cervical cancer that were treated with definitive radiotherapy. Methods The baseline characteristics and outcome data of patients with locally advanced cervical cancer who were treated with definitive radiotherapy between November 1993 and February 2014 were collected and retrospectively reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of AC/ASC histology. Results The patients with AC/ASC of the cervix exhibited significantly shorter overall survival (OS) (p=0.004) and progression-free survival (PFS) (p=0.002) than the patients with SCC of the cervix. Multivariate analysis showed that AC/ASC histology was an independent negative prognostic factor for PFS. Among the patients who displayed AC/ASC histology, larger tumor size, older age, and incomplete response to radiotherapy were found to be independent prognostic factors. PFS was inversely associated with the number of poor prognostic factors the patients exhibited (the estimated 1-year PFS rates; 100.0%, 77.8%, 42.8%, 0.0% for 0, 1, 2, 3 factors, respectively). Conclusion Locally advanced cervical cancer patients with AC/ASC histology experience significantly worse survival outcomes than those with SCC. Further clinical studies are warranted to develop a concurrent chemoradiotherapy (CCRT) protocol that is specifically tailored to locally advanced cervical AC/ASC. PMID:28028992

  16. Immunosuppression and risk of cervical cancer

    DEFF Research Database (Denmark)

    Dugué, Pierre-Antoine; Rebolj, Matejka; Garred, Peter

    2013-01-01

    increase the risk of cervical cancer, while poor diet only moderately increased the risk. It is difficult to determine whether sexually transmitted infections other than human papillomavirus infection are independent risk factors. Identifying those groups of women likely to fail in clearing persistent...... human papillomavirus infections would help individualize screening guidelines and target immune-associated factors in the cervical cancer etiology....

  17. Cervical cancer control, priorities and new directions.

    NARCIS (Netherlands)

    Monsonego, J; Bosch, F.X.; Coursaget, P.; Cox, JT; Franco, E; Frazer, I; Sankaranarayanan, R; Schiller, J; Singer, A; Wright, TCJr; Kinney, W; Meijer, C.J.L.M.; Linder, J

    2004-01-01

    99% of cervical cancer is initiated by HPV infection. The estimated lifetime risk of cervical cancer is nevertheless relatively low (less than 1 in 20 for most community based studies). Although sensitivity and specificity of the available diagnostic techniques are suboptimal, screening for persiste

  18. Synergistic combination of fluoro chalcone and doxorubicin on HeLa cervical cancer cells by inducing apoptosis

    Science.gov (United States)

    Arianingrum, Retno; Arty, Indyah Sulistyo; Atun, Sri

    2017-03-01

    Doxorubicin (Dox), a primary chemotherapeutic agent used for cancer treatment is known to have various side effect included multidrug resistance (MDR) phenomenon. Combination chemotherapy is one of some approaches to reduce Dox side effect. Chalcones have been reported to reduce the proliferation of many cancer cells. The research were conducted to investigate the cytotoxic activity and apoptosis induction of a chalcone derivate which is containing fluoro substituent [1 - (4" - fluorophenyl) -3 - (4' - hydroxy - 3' - methoxyphenyl) - 2 - propene - 1 -on] (FHM) and its combination with Dox on HeLa cells line. The observation of the cytotoxic activity was conducted using MTT [3 - (4, 5 - dimethyl thiazol - 2 - y1) - 2.5 - diphenyltetrazolium bromide] assay. Apoptosis induction was determined by flow cytometric. The changes of cell morphology were observed using phase contrast microscopy. The combination index (CI) was used to determine the effect of the combination. The study showed that FHM inhibited the HeLa cell growth with IC50 of 34 μM, while the IC50 of Dox was 1 μM. The combination had a higher inhibitory effect on cell growth compare to the single treatment of FHM and Dox. All of the combination doses under IC50 of FHM and Dox gave synergistic (CI: - 0.7) up to strong synergistic effect (CI: 0.l - 0.3). The synergistic effects of the combination were due to their ability to induce apoptosis in the HeLa cells. According to the result, FHM was potential to be developed as a co-chemotherapeutic agent with Dox for cervical cancer.

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

    Science.gov (United States)

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

    2013-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Harminder; Avasthi, D. K.; Pujari, Geetanjali; Sarma, Asitikantha [Inter University Accelerator Centre, Aruna Asaf Ali Marg, Post box-10502, New Delhi-110067 (India)

    2013-07-18

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ya-Min Cheng

    2016-09-01

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

  3. Disruption of human papillomavirus 16 E6 gene by clustered regularly interspaced short palindromic repeat/Cas system in human cervical cancer cells

    Directory of Open Access Journals (Sweden)

    Yu L

    2014-12-01

    Full Text Available Lan Yu, Xiaoli Wang, Da Zhu, Wencheng Ding, Liming Wang, Changlin Zhang, Xiaohui Jiang, Hui Shen, Shujie Liao, Ding Ma, Zheng Hu, Hui Wang Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China Abstract: High-risk human papillomavirus (HPV, especially HPV16, is considered a main causative agent of cervical cancer. Upon HPV infection, the viral oncoprotein E6 disrupts the host tumor-suppressor protein p53, thus promoting malignant transformation of normal cervical cells. Here, we used the newly developed programmable ribonucleic acid-guided clustered regularly interspaced short palindromic repeat (CRISPR/Cas system to disrupt the HPV16 E6 gene. We showed that HPV16 E6 deoxyribonucleic acid was cleaved at specific sites, leading to apoptosis and growth inhibition of HPV16-positive SiHa and CaSki cells, but not HPV-negative C33A or human embryonic kidney 293 cells. We also observed downregulation of the E6 protein and restoration of the p53 protein. These data proved that the HPV16 E6 ribonucleic acid-guided CRISPR/Cas system might be an effective therapeutic agent in treating HPV infection-related cervical malignancy. Keywords: CRISPR/Cas system, E6, p53, SiHa, CaSki, cervical cancer

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

    Science.gov (United States)

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

    2016-03-05

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

  5. Morusin inhibits human cervical cancer stem cell growth and migration through attenuation of NF-κB activity and apoptosis induction.

    Science.gov (United States)

    Wang, Li; Guo, Huijie; Yang, Liuqi; Dong, Lihua; Lin, Caiyu; Zhang, Jie; Lin, Ping; Wang, Xiujie

    2013-07-01

    Cancer stem cells (CSCs) are believed to be responsible for tumor metastasis, recurrence, and high mortality of cancer patients due to their high tumorigenicity resistance to chemo-radiotherapy. Morusin possesses anti-cancer activity through attenuation of NF-κB activity, which is up-regulated in cancer stem cells. The purpose of this study is to confirm the growth and migration inhibition effect of morusin on human cervical CSCs, and to clarify its partial mechanism of activity. Human cervical CSCs were enriched using non-adhesive culture system. Their stemness characteristics were identified with tumor sphere formation, self-renewal, toluidine blue staining, migration assays, RT-PCR analysis, and immunofluorescence staining of putative stem cell markers, Oct4, SOX2, and ALDH1; the epithelial-to-mesenchymal (EMT) transition markers and relevant transcription factors were evaluated with Western blotting. The growth and migration inhibition effects of morusin on human cervical CSCs were tested by cell proliferation, tumor sphere formation, and transwell assay; apoptotic death of human cervical CSCs in response to morusin was measured with DAPI staining, apoptotic DNA fragmentation; NF-κBp65, Bcl-2, Bax, and caspase-3 protein expressions were detected through Western blotting. Under this non-adhesive culture system, typical tumor spheres appeared within 5-7 days, the tumor sphere formation, self-renewal, and cell migration, expressions of putative stem cell markers, EMT markers, and relevant transcription factors of the tumor sphere cells were increased significantly. After morusin treatment, the proliferation, tumor sphere formation, and migration of human cervical CSCs were decreased significantly, DAPI-stained apoptotic cells increased, apoptotic DNA fragmentations formed evidently; the expression levels of NF-κBp65 and Bcl-2 decreased significantly, Bax, and caspase-3 increased significantly in a dose-dependent manner. Using the non-adhesive culture system

  6. Human Papillomavirus 16 E6,E7 siRNAs Inhibit Proliferation and Induce Apoptosis of SiHa Cervical Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    NIE Chun-lian; GAO Guo-lan; HAN Jie; LI Hua; CHEN He-ping; HE Ming

    2008-01-01

    Objective:To evaluate the effects of HPVl6 E6/E7 siRNAs on cervical cancer SiHa cells. Methods:The expressions of the E6,E7,p53 and Rb genes were assayed by RT-PCR and Western-bloting respectively.The proliferation and apoptosis of the cells were evaluated by MTT and flow cytometry. Results:HPV 16 E6 and E7 oncogenes were selectivly downregulated by HPV 16 E6 and E7 siRNAs,which sustained at least 96 h by single dose siRNA.Furthermore,reduction of E6 and E7 oncogenes expression upregulated the expressions of P53 and RB protein and induced apoptosis in SiHa cells. Conclusion:Introduction of HPV16 E6/E7 siRNA might be a potentially potent and specific approach to inhibit proliferation and induce apoptosis of SiHa cervical cancer cells.

  7. Preferential cytotoxicity of ZnO nanoparticle towards cervical cancer cells induced by ROS-mediated apoptosis and cell cycle arrest for cancer therapy

    Science.gov (United States)

    Sirelkhatim, Amna; Mahmud, Shahrom; Seeni, Azman; Kaus, Noor Haida Mohd

    2016-08-01

    The present study aimed to synthesize multifunctional ZnO-NP samples, namely ZnO-20, ZnO-40, and ZnO-80 nm, using different approaches, to be used as efficient anticancer agents. Systematic characterizations revealed their particle sizes and demonstrated nanostructures of nanorods (ZnO-80 nm) and nanogranules (ZnO-20 and ZnO-40 nm). They exhibited significant ( p cancer cells. HeLa cell viabilities at 1 mM dose reduced to 37, 32, 15 %, by ZnO-80, ZnO-40, and ZnO-20 nm, respectively, at 48 h. However, the same dose exerted different effects of 79.6, 76, and 75 % on L929 normal cells at 48 h. Measurement of reactive oxygen species (ROS) showed a considerable ROS yields on HeLa cells by all samples with a pronounced percentage (50 %) displayed by ZnO-20 nm. Moreover, ROS-mediated apoptosis induction and blocked cell cycle progression in the S, G2/M, and G0/G1 phases significantly ( p induction was further confirmed by DNA fragmentation and Hoechst-PI costained images viewed under fluorescence microscope. Additionally, morphological changes of HeLa cells visualized under light microscope showed assortment of cell death involved shrinkage, vacuolization and apoptotic bodies' formation. Most importantly, results exposed the impact of size and morphology of ZnO samples on their toxicity to Hela cells mediated mainly by ROS production. ZnO-20 nm in disk form with its nanogranule shape and smallest particle size was the most toxic sample, followed by ZnO-40 nm and then ZnO-80 nm. An additional proposed mechanism contributed in the cell death herein was ZnO decomposition producing zinc ions (Zn2+) into the acidic cancer microenvironment due to the smaller sizes of ZnO-NPs. This mechanism has been adopted in the literatures as a size-dependent phenomenon. The emerged findings were suggested to provide new platforms in the development of therapeutics as selective agents to the fatal cervical cancer, and to benefit from the synergistic influence of size and nanostructure when

  8. Economic burden of cervical cancer in Malaysia

    Directory of Open Access Journals (Sweden)

    Sharifa E.W. Puteh

    2008-12-01

    Full Text Available Cervical cancers form the second highest number of female cancers in Malaysia, imposing a substantial amount of cost burden on its management. However, an estimation of cost burden of abnormal smears, cervical pre-invasive and invasive diseases needs to be done to show how much spending has been allocated to the problem. An expert panel committee came up with the clinical pathway and management algorithm of  cervical pre invasive and invasive diseases from July-December 2006 Malaysia. An activity based costing for each clinical pathway was done. Results were converted to USD. The cost of managing pre-invasive cervical cancers stage is USD 420,150 (Range: USD 197,158-879,679. Management of invasive cancer (new cases costs USD 51,533,233.44 (Range: USD 32,405,399.69 - USD 129,014,768.40. The cost of managing existing cases is USD 17,005,966.87 (Range: USD 10,693,781.90 - USD  28,901,587.12. The total cost of managing cervical cancers by health care providers in a public setting is around USD 75,888,329.45 (Range: USD 48,083,804.60 - USD 48,083,804.60. The outcome of this study has shown that preventive modalities such as screening have only contributed to 10.3 % of the total management cost of cervical cancer. The major cost contribution (67% came from treatment of invasive cancer especially at more advanced stages of cancer, followed by treatment of existing cases (22% and lastly on pre-invasive disease (0.6%. This study revealed that proportion of preventive modality in this country was still low, and the major cost came from actual treatment cost of cervical cancer. Therefore, heightened public cervical cancer screening in the country is needed. (Med J Indones 2008; 17: 272-80Keywords: cervical cancers, pre invasive disease, HPV vaccination

  9. Cytotoxic Effects of Native and Recombinant Frutalin, a Plant Galactose-Binding Lectin, on HeLa Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Carla Oliveira

    2011-01-01

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

  10. 紫花牡荆素体外抑制人宫颈癌HeLa细胞增殖的研究%Proliferation inhibition of human cervical cancer HeLa cells by Casticin in vitro

    Institute of Scientific and Technical Information of China (English)

    Jing Xie; Jun Bai; Xifeng Sheng; Jianguo Cao; Wanyu Xie

    2011-01-01

    Objective: The aim of the study was to investigate the effect of Casticin on proliferation inhibition of human cervical cancer HeLa cells in vitro and to unravel the associated mechanisms. Methods: Human cervical HeLa cells were cultured in vitro. The inhibitory effect of Casticin on the viability of human cervical cancer HeLa cells was evaluated by the MTT assay.The colony formation ability was detected by plate colony formation assay. Distribution of cell cycle was analyzed by flow cytometry. The protein expression levels were analyzed by Western blot. Results: Casticin significantly inhibited the growth of human cervical cancer HeLa cells in a dose- and time-dependent manner, and the IC50 was 2.82 μg/mL. The colony-forming rate was reduced drastically compared with control group (P < 0.05). The cells were markedly arrested at G2/M phase after the treatment of Casticin for 48 h. Western blot showed that the expression of p21 protein was up-regulated and protein level of Cyclin B1 was depressed by Casticin in a concentration dependent manner. Conclusion: Casticin could inhibit the cell growth and lead to cell arrest in human cervical cancer HeLa cells, and the down-regulation of Cyclin B1 protein expression and activation of p21 protein might contribute to Casticin induced cell arrest in human cervical cancer HeLa cells.

  11. Cervical cancer screening in the Faroe Islands

    DEFF Research Database (Denmark)

    Hammer, Turið; Lynge, Elsebeth; Djurhuus, Gisela W;

    2014-01-01

    Background. The Faroe Islands have had nationally organised cervical cancer screening since 1995. Women aged 25-60 years are invited every third year. Participation is free of charge. Although several European overviews on cervical screening are available, none have included the Faroe Islands. Our...... aim was to provide the first description of cervical cancer screening, and to determine the screening history of women diagnosed with cervical cancer in the Faroe Islands. Material and methods. Screening data from 1996 to 2012 were obtained from the Diagnostic Centre at the National Hospital...... 1999. At present, 7.0% of samples have abnormal cytology. Of all ASCUS samples, 76-95% were tested for HPV. A total of 58% of women diagnosed with cervical cancer did not participate in screening prior to their diagnosis, and 32% had normal cytology in the previous four years. Conclusion. Despite...

  12. Folate receptor and Ki-67 nucleoprotein expressions in cervical cancer tissue and their correlation

    Institute of Scientific and Technical Information of China (English)

    Ran Yan; Feng Li

    2016-01-01

    Objective:To detect the expression of both FR-α protein and ki-67 in cervical cancer tissues, and discuss the relationship between them and clinical significance.Methods:Using immunohistochemical method test normal cervical tissue and cervical cancer tissue before FR-α protein expression and the expression of Ki-67.Results:FR- protein expression in normal cervical tissues was positive for 7.0% while in cervical cancer tissue the positive rate was 82.1%. The difference was statistically significant. Ki-67 protein expression in normal cervical tissues was 0% while in cervical cancer tissue the positive rate was 80.2%. The difference was statistically significant. The two protein expression in cervical cancer stageⅠ,Ⅱ and stageⅢ were different, but the difference was not statistically significant. In cervical cancer tissues, both the two protein were positively correlated. There are correlations between them. Difference was statistically significant.Conclusion:FR-α elevated protein expression is involved in the pathogenesis of cervical cancer. FR-α protein expression in cervical cancer and precancerous tissue has correlation with Ki-67, FR-α protein maybe participate in the occurrence and development of the cell proliferation in cervical cancer.

  13. Effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 pathway.

    Science.gov (United States)

    Zhang, Song-An; Niyazi, Hu-Er-Xi-Dan; Hong, Wen; Tuluwengjiang, Gu-Li-Xian; Zhang, Lei; Zhang, Yang; Su, Wei-Peng; Bao, Yong-Xing

    2017-03-01

    This study aimed to investigate the effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 signaling pathway. A total of 43 adult female Wistar rats were selected and injected with HeLa cells in the caudal vein to construct a rat model of cervical cancer. All model rats were randomly divided into the radiotherapy group ( n = 31) and the control group ( n = 12). The immunophenotype of Treg cells was detected by the flow cytometry. The protein expressions of EBI3, PD-1, and PD-L1 in cervical cancer tissues were tested by the streptavidin-peroxidase method. HeLa cells in the logarithmic growth phase were divided into four groups: the blank, the negative control group, the EBI3 mimics group, and the EBI3 inhibitors group. Western blotting was used to detect PD-1 and PD-L1 protein expressions. MTT assay was performed to measure the proliferation of Treg cells. Flow cytometry was used to detect cell cycle and apoptosis, and CD4(+)/CD8(+) T cell ratio in each group. Compared with before and 1 week after radiotherapy, the percentages of CD4(+)T cells and CD8(+)T cells were significantly decreased in the radiotherapy group at 1 month after radiotherapy. Furthermore, down-regulation of EBI3 and up-regulation of PD-1 and PD-L1 were observed in cervical cancer tissues at 1 month after radiotherapy. In comparison to the blank and negative control groups, increased expression of EBI3 and decreased expressions of PD-1 and PD-L1 were found in the EBI3 mimics group. However, the EBI3 inhibitors group had a lower expression of EBI3 and higher expressions of PD-1 and PD-L1 than those in the blank and negative control groups. The EBI3 mimics group showed an increase in the optical density value (0.43 ± 0.05), while a decrease in the optical density value (0.31 ± 0.02) was found in the EBI3 inhibitors group. Moreover, compared with the blank and negative control groups, the apoptosis rates

  14. Cervical Cancer Screening with HPV Test

    Centers for Disease Control (CDC) Podcasts

    2009-10-15

    Dr. Stewart Massad, a professor in the Division of Gynecologic Oncology at Washington University in Saint Louis and a board member of the American Society for Colposcopy and Cervical Cancer Prevention (ASCCP), talks about cotesting with human papillomavirus (HPV) as part of a cervical cancer screening program.  Created: 10/15/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

  15. Recurrent integration of human papillomaviruses 16, 45, and 67 near translocation breakpoints in new cervical cancer cell lines

    NARCIS (Netherlands)

    Koopman, L A; Szuhai, K; van Eendenburg, J D; Bezrookove, V; Kenter, G G; Schuuring, E; Tanke, H; Fleuren, G J

    1999-01-01

    Progressive chromosomal changes and integration of human papillomavirus (HPV) sequences mark the development of invasive cervical cancer. Chromosomal localization of HPV integration is essential to the study of genomic regions involved in HPV-induced pathogenesis. Yet, the available information abou

  16. Socioeconomic position and survival after cervical cancer

    DEFF Research Database (Denmark)

    Ibfelt, E H; Kjær, S K; Høgdall, C;

    2013-01-01

    In an attempt to decrease social disparities in cancer survival, it is important to consider the mechanisms by which socioeconomic position influences cancer prognosis. We aimed to investigate whether any associations between socioeconomic factors and survival after cervical cancer could...... be explained by socioeconomic differences in cancer stage, comorbidity, lifestyle factors or treatment....

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  19. Cervical Cancer is Preventable! PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2014-11-05

    This 60 second Public Service Announcement is based on the November 2014 CDC Vital Signs report. Every visit to a doctor or nurse is an opportunity to prevent cervical cancer. Women can get a Pap test and HPV test to help prevent cervical cancer and adolescent boys and girls can get the HPV vaccination series to help prevent cervical and other cancers.  Created: 11/5/2014 by National Center for Injury Prevention and Control (NCIPC).   Date Released: 11/5/2014.

  20. Vital Signs-Cervical Cancer is Preventable!

    Centers for Disease Control (CDC) Podcasts

    2014-11-05

    This podcast is based on the November 2014 CDC Vital Signs report. Every visit to a doctor or nurse is an opportunity to prevent cervical cancer. Women can get a Pap test and HPV test to help prevent cervical cancer and adolescent boys and girls can get the HPV vaccination series to help prevent cervical and other cancers.  Created: 11/5/2014 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 11/5/2014.

  1. Somatic LKB1 mutations promote cervical cancer progression.

    Directory of Open Access Journals (Sweden)

    Shana N Wingo

    Full Text Available 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.

  2. Apoptotic induction activity of Dactyloctenium aegyptium (L. P.B. and Eleusine indica (L. Gaerth. extracts on human lung and cervical cancer cell lines

    Directory of Open Access Journals (Sweden)

    Pintusorn Hansakul

    2009-08-01

    Full Text Available Dactyloctenium aegyptium (L. P.B. (Yaa paak khwaai and Eleusine indica (L. Gaerth. (Yaa teen-ka have long been used in traditional Thai medicine because of their diuretic, anti-inflamatory, and antipyretic effects. The present study examined the antiproliferative and cytotoxic effects of the hexane and butanolic extracts of these two grass species. All the grass extracts exhibited selective growth inhibition effect on human lung cancer (A549 and cervical cancer (HeLa cells relative to normal human lung MRC-5 fibroblasts with IC50 values in a range of 202 to 845 mg/ml. Apparently, HeLa cellswere more sensitive to the extracts than A549 cells. Moreover, all the extracts induced lethality in both cancer cell lines atconcentrations close to 1,000 mg/ml, indicating their selective cytotoxicity effects. ELISA assay showed that only the hexaneextract of D. aegyptium (L. P.B. and E. indica (L. Gaerth. significantly increased the apoptotic level in extract-treatedA549 cells. However, DNA ladder assay detected classic DNA ladder patterns, a characteristic feature of apoptosis, in both cancer cell lines treated with all the extracts in a dose- and time-dependent manner. Taken together, these results indicatethat the cytotoxic activity of the grass extracts against lung and cervical cancer cells is mediated through the induction ofapoptosis.

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

    Directory of Open Access Journals (Sweden)

    Amit S Choudhari

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

  4. Disruption of HPV16-E7 by CRISPR/Cas System Induces Apoptosis and Growth Inhibition in HPV16 Positive Human Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Zheng Hu

    2014-01-01

    Full Text Available High-risk human papillomavirus (HR-HPV has been recognized as a major causative agent for cervical cancer. Upon HPV infection, early genes E6 and E7 play important roles in maintaining malignant phenotype of cervical cancer cells. By using clustered regularly interspaced short palindromic repeats- (CRISPR- associated protein system (CRISPR/Cas system, a widely used genome editing tool in many organisms, to target HPV16-E7 DNA in HPV positive cell lines, we showed for the first time that the HPV16-E7 single-guide RNA (sgRNA guided CRISPR/Cas system could disrupt HPV16-E7 DNA at specific sites, inducing apoptosis and growth inhibition in HPV positive SiHa and Caski cells, but not in HPV negative C33A and HEK293 cells. Moreover, disruption of E7 DNA directly leads to downregulation of E7 protein and upregulation of tumor suppressor protein pRb. Therefore, our results suggest that HPV16-E7 gRNA guided CRISPR/Cas system might be used as a therapeutic strategy for the treatment of cervical cancer.

  5. Comparison of cervical cell morphology using two different cytology techniques for early detection of pre-cancerous lesions.

    Science.gov (United States)

    Moosa, Najla Yussuf; Khattak, Nuzhat; Alam, Muhammad Irfan; Sher, Alam; Shah, Walayat; Mobashar, Shumaila; Alam, Muhammad Imran; Javid, Asima

    2014-01-01

    Cervical cancer is an issue of foremost importance globally, specifically affecting the developing nations. Significant advances have taken place with regard to diagnosis of cervical cancer, especially with screening. Appropriate screening measures can thus reduce the incidence of cervical cancer. The most desirable screening technique should be less invasive, easy to perform, cost-effective and cover a wide range of diagnostic icons. Manual liquid based cytology (MLBC) can be considered as one of the suitable technique for screening with the above-mentioned benefits. The aim of the current study was to compare two cervical screening techniques on the basis of different morphological parameters and staining parameters by using modified acetic acid Pap staining to see the possibility of reducing time economy involved in conventional Pap staining (CPS). The study was conducted on a total 88 cases and all were analyzed with both MLBC and CPS. Forty eight cases that were regarded as satisfactory on the basis of Bethesda system by both methods were further recruited for investigation. Their morphological parameters and staining quality were compared and scored according to a scoring system defined in the study. Quality indices was calculated for both staining procedures and smear techniques.

  6. Targeted treatments for cervical cancer: a review

    Directory of Open Access Journals (Sweden)

    Peralta-Zaragoza O

    2012-11-01

    Full Text Available Oscar Peralta-Zaragoza,1 Víctor Hugo Bermúdez-Morales,1 Carlos Pérez-Plasencia,2,3 Jonathan Salazar-León,1 Claudia Gómez-Cerón,1 Vicente Madrid-Marina11Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Cuernavaca, Morelos, México; 2Oncogenomics Laboratory, National Cancer Institute of Mexico, Tlalpan, México; 3Biomedicine Unit, FES-Iztacala UNAM, México City, MéxicoAbstract: Cervical cancer is the second most common cause of cancer death in women worldwide and the development of new diagnosis, prognostic, and treatment strategies merits special attention. Although surgery and chemoradiotherapy can cure 80%–95% of women with early stage cancer, the recurrent and metastatic disease remains a major cause of cancer death. Many efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent decades, research on treatment strategies has proposed several options, including the role of HPV E6 and E7 oncogenes, which are retained and expressed in most cervical cancers and whose respective oncoproteins are critical to the induction and maintenance of the malignant phenotype. Other efforts have been focused on antitumor immunotherapy strategies. It is known that during the development of cervical cancer, a cascade of abnormal events is induced, including disruption of cellular cycle control, perturbation of antitumor immune response, alteration of gene expression, and deregulation of microRNA expression. Thus, in this review article we discuss potential targets for the treatment of cervical cancer associated with HPV infection, with special attention to immunotherapy approaches, clinical trials, siRNA molecules, and their implications as gene therapy strategies against cervical cancer development.Keywords: Cervical cancer, clinical trials, gene therapy, HPV E6 and E7 oncogenes, siRNAs

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Luo-Qiao; Zhang, Yue; Yan, Huan; Liu, Kai-Jiang, E-mail: liukaijiang@126.com; Zhang, Shu, E-mail: drzhangshu@126.com

    2015-04-10

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

  8. Epidemiology of cervical cancer in Colombia

    Directory of Open Access Journals (Sweden)

    Muñoz, Nubia

    2012-12-01

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

  9. Epidemiology of cervical cancer in Colombia.

    Science.gov (United States)

    Muñoz, Nubia; Bravo, Luis Eduardo

    2012-10-01

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

  10. Epidemiology of cervical cancer in Colombia

    Directory of Open Access Journals (Sweden)

    Nubia Muñoz

    2012-12-01

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

  11. Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

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    Emanuelly Bernardes-Oliveira

    2016-01-01

    Full Text Available Bothrops jararaca (BJ and Bothrops erythromelas (BE are viper snakes found in South-Southeast and Northeast regions of Brazil, respectively. Snake venoms are bioactive neurotoxic substances synthesized and stored by venom glands, with different physiological and pharmacological effects, recently suggesting a possible preference for targets in cancer cells; however, mechanisms of snakes have been little studied. Here, we investigated the mechanism responsible for snake crude venoms toxicity in cultured cervical cancer cells SiHa and HeLa. We show that BJ and BE snake crude venoms exert cytotoxic effects to these cells. The percentage of apoptotic cells and cell cycle analysis and cell proliferation were assessed by flow cytometry and MTT assay. Detection of mitochondrial membrane potential (Rhodamine-123, nuclei morphological change, and DNA fragmentation were examined by staining with DAPI. The results showed that both the BJ and BE venoms were capable of inhibiting tumor cell proliferation, promoting cytotoxicity and death by apoptosis of target SiHa and HeLa cells when treated with BJ and BE venoms. Furthermore, data revealed that both BJ venoms in SiHa cell promoted nuclear condensation, fragmentation, and formation of apoptotic bodies by DAPI assay, mitochondrial damage by Rhodamine-123, and cell cycle block in the G1-G0 phase. BJ and BE venoms present anticancer potential, suggesting that both Bothrops venoms could be used as prototypes for the development of new therapies.

  12. Cervical cancer: screening and therapeutic perspectives.

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

    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.

  14. Inotodiol inhabits proliferation and induces apoptosis through modulating expression of cyclinE, p27, bcl-2, and bax in human cervical cancer HeLa cells.

    Science.gov (United States)

    Zhao, Li-Wei; Zhong, Xiu-Hong; Yang, Shu-Yan; Zhang, Yi-Zhong; Yang, Ning-Jiang

    2014-01-01

    Inonotus obliquus is a medicinal mushroom that has been used as an effective agent to treat various diseases such as diabetes, tuberculosis and cancer. Inotodiol, an included triterpenoid shows significant anti-tumor effect. However, the mechanisms have not been well documented. In this study, we aimed to explore the effect of inotodiol on proliferation and apoptosis in human cervical cancer HeLa cells and investigated the underlying molecular mechanisms. HeLa cells were treated with different concentrations of inotodiol. The MTT assay was used to evaluate cell proliferating ability, flow cytometry (FCM) was employed for cell cycle analysis and cell apoptosis, while expression of cyclinE, p27, bcl-2 and bax was detected by immunocytochemistry. Proliferation of HeLa cells was inhibited by inotodiolin a dose-dependent manner at 24h (r=0.9999, pHeLa cells was detected after treatment and the apoptosis rate with the concentration and longer incubation time (r=1.0, pHeLa cells and induced apoptosis in vitro. The mechanisms may be related to promoting apoptosis through increasing the expression of bax and cutting bcl-2 and affecting the cell cycle by down-regulation the expression of cyclin E and up-regulation of p27. The results further indicate the potential value of inotodiol for treatment of human cervical cancer.

  15. Costs Associated with Cervical Cancer Screening

    Centers for Disease Control (CDC) Podcasts

    2009-10-15

    Dr. Tom Cox, a practicing gynecologist and president of the American Society of Colposcopy and Cervical Pathology, provides a brief introduction to cervical cancer screening guidelines and human papillomavirus (HPV) DNA testing.  Created: 10/15/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

  16. Trends of cervical cancer in Greenland

    DEFF Research Database (Denmark)

    Sander, Bente B; Rebolj, Matejka; Lynge, Elsebeth

    2014-01-01

    BACKGROUND: Due to its extraordinarily fast economic and social transition, virtually closed borders before 1940 and, moreover, that 85% of the population has the distinctive genetics of the Inuit, Greenland is a very interesting country to study cervical cancer from a historical perspective. Nev...... with the introduction of screening. The data strongly suggested that the increased burden of cervical cancer in Greenlandic women was real and followed earlier changes in sexual behaviour; these changes were likely a consequence of the tremendous societal changes....

  17. Cervical cancer: A comprehensive approach towards extermination.

    Science.gov (United States)

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

    2016-01-01

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

  18. RESPONSE OF MONONUCLEAR CELLS TO CANCER-ASSOCIATED ANTIGENS, HUMORAL FACTORS OF IMMUNITY, AND PATHOHISTOLOGICAL FINDINGS IN WOMEN WITH GENITAL MALIGNANCIES CERVICAL EPITHELIAL DYSPLASIA

    Directory of Open Access Journals (Sweden)

    A. I. Autenshlus

    2007-01-01

    Full Text Available Abstract. In vitro response of blood mononuclear cells to cancer-associated antigens was studied in women with genital pathology, and these results were compared with serum levels of pro- and anti-inflammatory factors of immunity, like as with histological features of genital cancer and cervical epithelial dysplasia. In vitro cellular response was regarded as positive, if relative amounts of CD8-positive lymphocytes increased by > 15% following incubation of blood mononuclears with cancer-associated antigens. Positive reaction and elevated serum levels of anti-TNFα and anti-IFNγ antibodies were associated with lesser malignancy of tumor, as proven by histological findings in the women with genital cancer. A positive cellular reaction was associated with increased serum levels of IFNγ and anti-TNFα in women with grade II–III cervical epithelial dysplasia. It is concluded about potential applicability of testing mononuclears with fetal proteins, to determine a grade of malignancy for the female genital tumors, as well as a degree of regenerative disturbances of cervical epithelium.

  19. Two cytological methods for screening for cervical cancer

    DEFF Research Database (Denmark)

    Kirschner, B.; Simonsen, K.; Junge, J.

    2008-01-01

    INTRODUCTION: Denmark has had an organized screening programme for cervical cancer since the 1960s. In spite of this, almost 150 Danish women die from the disease each year. There are currently two different methods for preparation of cervical samples: conventional Papanicolaou smear and liquid......-based cytology. MATERIALS AND METHODS: In 2002, the Department of Pathology, Hvidovre Hospital changed over from the conventional Papanicolaou smear screening method to SurePath liquid-based cytology. This article is based on a retrospective comparison on data from the population screening programme for cervical...... cancer in the Municipality of Copenhagen. RESULTS: The number of tests with the diagnosis of "normal cells" decreased 1% after the conversion to liquid-based cytology, whilst the number of tests with "atypical cells" and "cells suspicious for malignancy" increased by 64.3% and 41.2% respectively...

  20. Breaking the DNA damage response to improve cervical cancer treatment.

    Science.gov (United States)

    Wieringa, Hylke W; van der Zee, Ate G J; de Vries, Elisabeth G E; van Vugt, Marcel A T M

    2016-01-01

    Every year, cervical cancer affects ∼500,000 women worldwide, and ∼275,000 patients die of this disease. The addition of platin-based chemotherapy to primary radiotherapy has increased 5-year survival of advanced-stage cervical cancer patients, which is, however, still only 66%. One of the factors thought to contribute to treatment failure is the ability of tumor cells to repair chemoradiotherapy-induced DNA damage. Therefore, sensitization of tumor cells for chemoradiotherapy via inhibition of the DNA damage response (DDR) as a novel strategy to improve therapy effect, is currently studied pre-clinically as well as in the clinic. Almost invariably, cervical carcinogenesis involves infection with the human papillomavirus (HPV), which inactivates part of the DNA damage response. This HPV-mediated partial inactivation of the DDR presents therapeutic targeting of the residual DDR as an interesting approach to achieve chemoradio-sensitization for cervical cancer. How the DDR can be most efficiently targeted, however, remains unclear. The fact that cisplatin and radiotherapy activate multiple signaling axes within the DDR further complicates a rational choice of therapeutic targets within the DDR. In this review, we provide an overview of the current preclinical and clinical knowledge about targeting the DDR in cervical cancer.

  1. Angiogenesis and antiangiogenic agents in cervical cancer

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    Tomao F

    2014-12-01

    Full Text Available Federica Tomao,1 Anselmo Papa,2 Luigi Rossi,2 Eleonora Zaccarelli,2 Davide Caruso,2 Federica Zoratto,2 Pierluigi Benedetti Panici,1 Silverio Tomao2 1Department of Gynecology and Obstetrics, Sapienza University of Rome, Policlinico Umberto I, Rome, 2Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Oncology Unit, ICOT, Latina, Italy Abstract: 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. Keywords: cervical cancer, angiogenesis, human papillomavirus, bevacizumab, target therapies

  2. Induction of Mitochondria-Mediated Apoptosis in Ca Ski Human Cervical Cancer Cells Triggered by Mollic Acid Arabinoside Isolated from Leea indica

    Directory of Open Access Journals (Sweden)

    Yau Hsiung Wong

    2012-01-01

    Full Text Available Leea indica is a medicinal plant traditionally used to treat cancer. Through bioassay-guided approach, we isolated mollic acid arabinoside (MAA, for the first time from Leea indica. Here, we present the apoptosis-inducing effect of MAA on Ca Ski cervical cancer cells. Based on DAPI staining, MAA-treated cells manifested nuclear shrinkage, condensation, and fragmentation. We further confirmed the fragmentation of DNA using TUNEL assay. During early apoptosis, MAA caused the perturbation of plasma membrane through externalization of PS, followed by the formation of apoptotic blebs. Prior to these events, MAA triggered rapid dissipation of the mitochondrial membrane potential. In the upstream, MAA increased the expression of Bax, decreased the expression of Bcl-2, and augmented the Bax/Bcl-2 ratio. These findings suggested that MAA induced mitochondrial-mediated apoptosis in Ca Ski cells and thus provide the scientific explanation for the traditional application of this herbal medicine in cancer treatment.

  3. January is Cervical Cancer Awareness Month

    Science.gov (United States)

    The Center for Global Health supports global activities to advance global cancer research, build expertise, and leverage resources across nations to address the challenges of cancer and reduce cancer deaths worldwide. Towards these aims, NCI has partnered with Pink Ribbon Red Ribbon, a global organization founded on public-private partnerships dedicated to saving women’s lives by advancing prevention, screening, and treatment for breast and cervical cancer in sub-Saharan Africa and Latin America.

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

    Science.gov (United States)

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

    2011-12-01

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

  5. U.S. Deaths from Cervical Cancer May Be Underestimated

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_163192.html U.S. Deaths From Cervical Cancer May Be Underestimated Rates ... women were factored out, Rositch's team found that U.S. cervical cancer deaths are 77 percent higher among ...

  6. TRAILs towards improved cervical cancer treatment

    NARCIS (Netherlands)

    Maduro, John

    2009-01-01

    Cervical cancer is a life threatening disease occurring world-wide, but affecting especially women in developing countries. Standard treatment for cevical cancer varies per FIGO stage and patient related factors. In general patients with non bulky (<4 cm) FIGO stage IB and IIA are treated with a rad

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

    Directory of Open Access Journals (Sweden)

    Yukihiko Hiroshima

    Full Text Available 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 patient's 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.

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

    Directory of Open Access Journals (Sweden)

    Erin M Siegel

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  10. Expression and Effects of High-Mobility Group Box 1 in Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoao Pang

    2014-05-01

    Full Text Available We investigated the significance of high- mobility group box1 (HMGB1 and T-cell-mediated immunity and prognostic value in cervical cancer. HMGB1, forkhead/winged helix transcription factor p3 (Foxp3, IL-2, and IL-10 protein expression was analyzed in 100 cervical tissue samples including cervical cancer, cervical intraepithelial neoplasia (CIN, and healthy control samples using immunohistochemistry. Serum squamous cell carcinoma antigen (SCC-Ag was immunoradiometrically measured in 32 serum samples from 37 cases of squamous cervical cancer. HMGB1 and SCC-Ag were then correlated to clinicopathological characteristics. HMGB1 expression tends to increase as cervical cancer progresses and it was found to be significantly correlated to FIGO stage and lymph node metastasis. These findings suggest that HMGB1 may be a useful prognostic indicator of cervical carcinoma. In addition, there were significant positive relationships between HMGB1 and FOXP3 or IL-10 expression (both p < 0.05. In contrast, HMGB1 and IL-2 expression was negatively correlated (p < 0.05. HMGB1 expression may activate Tregs or facilitate Th2 polarization to promote immune evasion of cervical cancer. Elevated HMGB1 protein in cervical carcinoma samples was associated with a high recurrence of HPV infection in univariate analysis (p < 0.05. HMGB1 expression and levels of SCC-Ag were directly correlated in SCC (p < 0.05. Thus, HMGB1 may be a useful biomarker for patient prognosis and cervical cancer prediction and treatment.

  11. HPV genotypes in invasive cervical cancer in Danish women

    DEFF Research Database (Denmark)

    Kirschner, Benny; Junge, Jette; Holl, Katsiaryna;

    2013-01-01

    Human papillomavirus (HPV) genotype distribution in invasive cervical cancers may differ by geographic region. The primary objective of this study was to estimate HPV-genotype distribution in Danish women with a diagnosis of invasive cervical cancer.......Human papillomavirus (HPV) genotype distribution in invasive cervical cancers may differ by geographic region. The primary objective of this study was to estimate HPV-genotype distribution in Danish women with a diagnosis of invasive cervical cancer....

  12. The Epidemiology of Human Papillomavirus Infection and Cervical Cancer

    Directory of Open Access Journals (Sweden)

    F. Xavier Bosch

    2007-01-01

    Full Text Available Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI. The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs. The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC, the adenocarcinomas and the vast majority (i.e. > 95% of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL/Cervical Intraepithelial Neoplasia 3 (CIN3/Carcinoma in situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC for five or more years, smoking, high parity (five or more full term pregnancies and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT and Herpes Simplex Virus type 2 (HSV-2. Women exposed to the Human Immunodeficiency Virus (HIV are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer.

  13. Decreased expression of the plasminogen activator inhibitor type 1 is involved in degradation of extracellular matrix surrounding cervical cancer stem cells.

    Science.gov (United States)

    Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Takahashi, Juri; Kojima, Satoko; Yamashita, Aki; Tomio, Kensuke; Nagamatsu, Takeshi; Wada-Hiraike, Osamu; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-02-01

    The plasminogen activator (PA) system consists of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator and its receptor (uPA and uPAR). PAI-1 inhibits the activation of uPA (which converts plasminogen to plasmin), and is involved in cancer invasion and metastasis, by remodeling the extracellular matrix (ECM) through regulating plasmin. Cancer stem cells (CSCs) are a small subset of cells within tumors, and are thought to be involved in tumor recurrence and metastasis. Considering these facts, we investigated the relationship between PAI-1 and cervical CSCs. We used ALDH1 as a marker of cervical CSCs. First, we demonstrated that culturing ALDH1-high cells and ALDH-low cells on collagen IV-coted plates increased their expression of active PAI-1 (ELISA), and these increases were suggested to be at mRNA expression levels (RT-qPCR). Secondly, we demonstrated PAI-1 was indeed involved in the ECM maintenance. With gelatin zymography assays, we found that ALDH1-high cells and ALDH-low cells expressed pro-matrix metalloproteinase-2 (pro-MMP-2) irrespective of their coatings. With gelatinase/collagenase assay kit, we confirmed that collagenase activity was increased when ALDH1-low cells were exposed to TM5275, a small molecule inhibitor of PAI-1. Putting the data together, we hypothesized that cancer cells adhered to basal membrane secrete abundant PAI-1, on the other hand, cancer cells (especially CSCs rather than non-CSCs) distant from basal membrane secrete less PAI-1, which makes the ECM surrounding CSCs more susceptible to degradation. Our study could be an explanation of conflicting reports, where some researchers found negative impacts of PAI-1 expression on clinical outcomes and others not, by considering the concept of CSCs.

  14. Prevalence of cervical intraepithelial neoplasia grades II/III and cervical cancer in patients with cytological diagnosis of atypical squamous cells when high-grade intraepithelial lesions (ASC-H cannot be ruled out

    Directory of Open Access Journals (Sweden)

    Andréa Cytryn

    Full Text Available CONTEXT AND OBJECTIVE: The latest update of the Bethesda System divided the category of atypical squamous cells of undetermined significance (ASCUS into ASC-US (undetermined significance and ASC-H (high-grade intraepithelial lesion cannot be ruled out. The aims here were to measure the prevalence of pre-invasive lesions (cervical intraepithelial neoplasia, CIN II/III and cervical cancer among patients referred to Instituto Fernandes Figueira (IFF with ASC-H cytology, and compare them with ASC-US cases. DESIGN AND SETTING: Cross-sectional study with retrospective data collection, at the IFF Cervical Pathology outpatient clinic. METHODS: ASCUS cases referred to IFF from November 1997 to September 2007 were reviewed according to the 2001 Bethesda System to reach cytological consensus. The resulting ASC-H and ASC-US cases, along with new cases, were analyzed relative to the outcome of interest. The histological diagnosis (or cytocolposcopic follow-up in cases without such diagnosis was taken as the gold standard. RESULTS: The prevalence of CIN II/III in cases with ASC-H cytology was 19.29% (95% confidence interval, CI, 9.05-29.55% and the risk of these lesions was greater among patients with ASC-H than with ASC-US cytology (prevalence ratio, PR, 10.42; 95% CI, 2.39-45.47; P = 0.0000764. Pre-invasive lesions were more frequently found in patients under 50 years of age with ASC-H cytology (PR, 2.67; 95% CI, 0.38-18.83; P = 0.2786998. There were no uterine cervical cancer cases. CONCLUSION: The prevalence of CIN II/III in patients with ASC-H cytology was significantly higher than with ASC-US, and division into ASC diagnostic subcategories had good capacity for discriminating the presence of pre-invasive lesions.

  15. Development of a next generation Semliki Forest virus-based DNA vaccine against cervical cancer

    NARCIS (Netherlands)

    Van De Wall, Stephanie; Ljungberg, Karl; Peng IP, Peng; Boerma, Annemarie; Nijman, Hans W.; Liljeström, Peter; Daemen, Toos

    2014-01-01

    Cervical cancer is the second most prevalent cancer among women worldwide. The disease develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7 with transforming capacities in cervical epithelial cells. Our group pioneered

  16. A Study on Cell Signaling Pathway in Cervical Cancer%宫颈癌细胞信号通路的研究进展

    Institute of Scientific and Technical Information of China (English)

    成艳

    2012-01-01

    Human papillomavirus( HPV )is the major pathogenic factor of cervical cancer,and abnormal E cell signaling pathway often affects cell proliferation and differentiation of normal regulation, leading to cancer. Therefore, signaling pathway can be an important target for cancer treatment, through the intervention of which to adjust the target gene expression to normal, in order to achieve inhibition of tumor growth and treat-4 ment of the primary tumor. Here is to make a review on the research of the correlation between HPV, cervical cancer and recognized signaling pathway.%人类乳头瘤病毒(HPV)是宫颈癌的主要致病因子,细胞信号通路的异常往往影响细胞增殖和分化的正常调控,导致癌的发生.因此可以把信号途径作为宫颈癌治疗的重要靶点,通过对细胞信号途径的干预调整靶基因表达,使其恢复正常,以达到抑制肿瘤生长、治疗肿瘤的目的.现就HPV、宫颈癌与信号通路三者的相关性研究进行综述.

  17. Effect of β-phenylethyl isothiocyanate from cruciferous vegetables on growth inhibition and apoptosis of cervical cancer cells through the induction of death receptors 4 and 5.

    Science.gov (United States)

    Huong, Le Diem; Shim, Jung-Hyung; Choi, Kyeong-Hee; Shin, Ji-Ae; Choi, Eun-Sun; Kim, Hyung-Seop; Lee, Sook-Jeong; Kim, Sun-Ju; Cho, Nam-Pyo; Cho, Sung-Dae

    2011-08-10

    Cruciferous vegetables have been shown to have the possibility to protect against multistep carcinogenesis. β-Phenylethyl isothiocyanate (PEITC) is one component of these vegetables demonstrated to help fight many types of cancer. The present study examined the apoptotic effects of PEITC and its molecular mechanism in human cervical cancer cell lines (HEp-2 and KB). PEITC induced apoptosis to inhibit cell proliferation. According to the protein chip assay, PEITC increased the expression of the death receptors (DR4 and DR5) and cleaved caspase-3 compared to the DMSO treatment group. PEITC also induced caspase-8 and truncated BID. PEITC down-regulated the phosphorylation of extracellular-related kinase (ERK)1/2, whereas neither phospho-c-Jun NH(2)-terminal kinases (JNK) nor phospho-p38 MAPK was changed. The role of ERK in PEITC-induced apoptosis was also investigated using MEK inhibitor (PD98059). PD98059 increased the expression of DR4 and DR5, activated caspase-3, and cleaved PARP. In addition, PEITC decreased the phosphorylation of MEK. Therefore, the apoptotic mechanism of PEITC in cervical cancer cells involves the induction of DR4 and DR5 through the inactivation of ERK and MEK.

  18. Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells.

    Science.gov (United States)

    Zhang, Hongling; Liu, Gan; Zeng, Xiaowei; Wu, Yanping; Yang, Chengming; Mei, Lin; Wang, Zhongyuan; Huang, Laiqiang

    2015-01-01

    Genistein is one of the most studied isoflavonoids with potential antitumor efficacy, but its poor water solubility limits its clinical application. Nanoparticles (NPs), especially biodegradable NPs, entrapping hydrophobic drugs have promising applications to improve the water solubility of hydrophobic drugs. In this work, TPGS-b-PCL copolymer was synthesized from ε-caprolactone initiated by d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) through ring-opening polymerization and characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The genistein-loaded NPs were prepared by a modified nanoprecipitation method and characterized in the aspects of particle size, surface charge, morphology, drug loading and encapsulation efficiency, in vitro drug release, and physical state of the entrapped drug. The TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than PCL NPs. MTT and colony formation experiments indicated that genistein-loaded TPGS-b-PCL NPs achieved the highest level of cytotoxicity and tumor cell growth inhibition compared with pristine genistein and genistein-loaded PCL NPs. Furthermore, compared with pristine genistein and genistein-loaded PCL NPs, the genistein-loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer.

  19. Effects of atmospheric-pressure non-thermal bio-compatible plasma and plasma activated nitric oxide water on cervical cancer cells

    Science.gov (United States)

    Li, Ying; Ho Kang, Min; Sup Uhm, Han; Joon Lee, Geon; Ha Choi, Eun; Han, Ihn

    2017-01-01

    Atmospheric-pressure non-thermal bio-compatible plasma is a partially ionized gas with electrically charged particles. Previous studies demonstrated that dielectric barrier discharge (DBD) plasma could induce apoptosis of various cancer cells, in particular demonstrating the selective cytotoxicity of cancer cells over normal cells. Therefore, DBD plasma can be considered as a potential cancer treatment method for clinical applications. We previously developed a microwave jet plasma system, producing nitric oxide called nitric oxide-plasma activated water (NO-PAW). In this study, we explored the effects of NO-PAW on a cervical cancer cell line, in comparison with DBD plasma. The cytotoxicity results showed that the treatment of HeLa cell with DBD for 4 minutes and 7 μM concentration of NO-PAW could reach almost IC60. For the apoptosis assay, 4 minutes treatment of DBD could induce 7% apoptotic effect, whereas 7 μM NO-PAW could induce 18% apoptotic effect. In addition, we assumed that both DBD plasma and NO-PAW could induce HeLa cell apoptosis by facilitating an accumulation of intracellular reactive oxygen and nitrogen species (RONS). Although further detail on the molecular signal pathway is still needed, DBD and NO-PAW could become promising applications for effective and safe clinical trials for cancer therapy. PMID:28361987

  20. Effects of atmospheric-pressure non-thermal bio-compatible plasma and plasma activated nitric oxide water on cervical cancer cells.

    Science.gov (United States)

    Li, Ying; Ho Kang, Min; Sup Uhm, Han; Joon Lee, Geon; Ha Choi, Eun; Han, Ihn

    2017-03-31

    Atmospheric-pressure non-thermal bio-compatible plasma is a partially ionized gas with electrically charged particles. Previous studies demonstrated that dielectric barrier discharge (DBD) plasma could induce apoptosis of various cancer cells, in particular demonstrating the selective cytotoxicity of cancer cells over normal cells. Therefore, DBD plasma can be considered as a potential cancer treatment method for clinical applications. We previously developed a microwave jet plasma system, producing nitric oxide called nitric oxide-plasma activated water (NO-PAW). In this study, we explored the effects of NO-PAW on a cervical cancer cell line, in comparison with DBD plasma. The cytotoxicity results showed that the treatment of HeLa cell with DBD for 4 minutes and 7 μM concentration of NO-PAW could reach almost IC60. For the apoptosis assay, 4 minutes treatment of DBD could induce 7% apoptotic effect, whereas 7 μM NO-PAW could induce 18% apoptotic effect. In addition, we assumed that both DBD plasma and NO-PAW could induce HeLa cell apoptosis by facilitating an accumulation of intracellular reactive oxygen and nitrogen species (RONS). Although further detail on the molecular signal pathway is still needed, DBD and NO-PAW could become promising applications for effective and safe clinical trials for cancer therapy.

  1. Cervical cancer in north-eastern Libya: 2000-2008.

    Science.gov (United States)

    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.

  2. Detecting cervical cancer by quantitative promoter hypermethylation assay on cervical scrapings : A feasibility study

    NARCIS (Netherlands)

    Reesink-Peters, N; Wisman, G.B.A.; Jeronimo, C; Tokumaru, CY; Cohen, Y; Dong, SM; Klip, HG; Buikema, HJ; Suurmeijer, AJH; Hollema, H; Boezen, HM; Sidransky, D; van der Zee, AGJ

    2004-01-01

    Current morphology-based cervical cancer screening is associated with significant false-positive and false-negative results. Tumor suppressor gene hypermethylation is frequently present in cervical cancer. It is unknown whether a cervical scraping reflects the methylation status of the underlying ep

  3. The mechanism of kaempferol induced apoptosis and inhibited proliferation in human cervical cancer SiHa cell: From macro to nano.

    Science.gov (United States)

    Tu, Lv-Ying; Bai, Hai-Hua; Cai, Ji-Ye; Deng, Sui-Ping

    2016-11-01

    Kaempferol has been identified as a potential cancer therapeutic agent by an increasing amount of evidences. However, the changes in the topography of cell membrane induced by kaempferol at subcellular- or nanometer-level were still unclear. In this work, the topographical changes of cytomembrane in human cervical cancer cell (SiHa) induced by kaempferol, as well as the role of kaempferol in apoptosis induction and its possible mechanisms, were investigated. At the macro level, MTT assays showed that kaempferol inhibited the proliferation of SiHa cells in a time- and dose-dependent manner. Flow cytometry analysis demonstrated that kaempferol could induce SiHa cell apoptosis, mitochondrial membrane potential disruption, and intracellular free calcium elevation. At the micro level, fluorescence imaging by laser scanning confocal microscopy (LSCM) indicated that kaempferol could also destroy the networks of microtubules. Using high resolution atomic force microscopy (AFM), we determined the precise changes of cellular membrane induced by kaempferol at subcellular or nanometer level. The spindle-shaped SiHa cells shrank after kaempferol treatment, with significantly increased cell surface roughness. These data showed structural characterizations of cellular topography in kaempferol-induced SiHa cell apoptosis and might provide novel integrated information from macro to nano level to assess the impact of kaempferol on cancer cells, which might be important for the understanding of the anti-cancer mechanisms of drugs. SCANNING 38:644-653, 2016. © 2016 Wiley Periodicals, Inc.

  4. Natural History of HPV and Cervical Cancer

    Centers for Disease Control (CDC) Podcasts

    2009-10-12

    Dr. Phil Castle, an intramural research scientist at the National Institutes of Health, talks about the natural history of human papillomavirus (HPV) infections, and cervical cancer and other anogenital cancers.  Created: 10/12/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

  5. Radiation dose and subsequent risk for stomach cancer in long-term survivors of cervical cancer

    DEFF Research Database (Denmark)

    Kleinerman, Ruth A; Smith, Susan A; Holowaty, Eric;

    2013-01-01

    To assess the dose-response relationship for stomach cancer after radiation therapy for cervical cancer.......To assess the dose-response relationship for stomach cancer after radiation therapy for cervical cancer....

  6. Review of the Cervical Cancer Burden and Population-Based Cervical Cancer Screening in China.

    Science.gov (United States)

    Di, Jiangli; Rutherford, Shannon; Chu, Cordia

    2015-01-01

    Cervical cancer continues to be a serious public health problem in the developing world, including China. Because of its large population with geographical and socioeconomic inequities, China has a high burden of cervical cancer and important disparities among different regions. In this review, we first present an overview of the cervical cancer incidence and mortality over time, and focus on diversity and disparity in access to care for various subpopulations across geographical regions and socioeconomic strata in China. Then, we describe population-based cervical cancer screening in China, and in particular implementation of the National Cervical Cancer Screening Program in Rural Areas (NACCSPRA) and the challenges that this program faces. These include low screening coverage, shortage of qualified health care personnel and limited funds. To improve prevention of cervical cancer and obtain better cancer outcomes, the Chinese government needs to urgently consider the following key factors: reducing disparities in health care access, collecting accurate and broadly representative data in cancer registries, expanding target population size and increasing allocation of government funding for training of personnel, improving health education for women, enhancing quality control of screening services and improving a system to increase follow up for women with positive results.

  7. NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Chunhao Niu

    2016-10-01

    Full Text Available Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6 in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC. NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO stage (p = 0.006, squamous cell carcinoma antigen (p = 0.006, vital status (p < 0.001, tumor recurrence (p = 0.001, chemotherapy (p = 0.039, and lymph node metastasis (p < 0.001. Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer.

  8. EXPRESSION OF INTRON 9 IN CD44 GENE IN CERVICAL CANCER AND CIN AND ITS CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To detect the retention of intron 9 in CD44 mRNA in cervical cancer tissue, CIN, cervicitis and their exfoliated cells, and to study their clinical significance in diagnosis and treatment of early-stage, non-invasive cervical cancer. Methods: RT-PCR methods were used to detect the retention of intron 9 in CD44 mRNA in 30 cases of cervical cancer tissue, 11 cases of CIN tissue, 30 cases of cervicitis tissue and their exfoliated cells. Results: The retention rate of intron 9 in CD44 gene transcripts were 76.7% in cervical cancer tissue, 89.8% in corresponding exfoliated cells, 70.8% in CIN tissue, and 60.0% in CIN exfoliated cells, but undetected in neither cervicitis tissue nor exfoliated cells. The relative quantity of intron 9 in CD44 gene transcripts was 1.10 ( 0.12 in cervical cancer tissue, 1.21 ( 0.11 in CIN tissue, 1.11 ( 0.19 in cervical cancer exfoliated cells, 1.17 ( 0.12 in CIN exfoliated cells respectively, but undetected in neither cervicitis tissue nor exfoliated cells. The retention rate and relative content of intron 9 in CD44 gene transcripts in cervical cancer and CIN tissue and their exfoliated cells were statistically higher than that in cervicitis and their exfoliated cells (P0.05). Conclusion: Detecting the retention of intron 9 in CD44 mRNA in cervical exfoliated cells was more sensitivity than traditional cytology exam for diagnosing cervical cancer, and the techniques was worth clinical application.

  9. Changes of the cell cycle regulators and cell cycle arrest in cervical cancer cells after cisplatin therapy

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To investigate the changes of the cell cycle regulators ATM,Chk2 and p53 and cell cycle arrest in HeLa cells after cisplatin therapy. Methods The proliferation-inhibiting rates of HeLa cells induced by cisplatin of different concentrations were measured by MTT assays. The mRNA and protein expressions of ATM,Chk2 and p53 of HeLa cells with and without cisplatin were detected by RT-PCR and Western blot,respectively. The cell cycle analysis was conducted by flow cytometric analysis. Results Cisplatin...

  10. Characterization of P1 promoter activity of the -galactoside 2,6-sialyltransferase I gene (siat 1) in cervical and hepatic cancer cell lines

    Indian Academy of Sciences (India)

    Lorena Milflores-Flores; Lourdes Millán-Pérez; Gerardo Santos-López; Julio Reyes-Leyva; Verónica Vallejo-Ruiz

    2012-06-01

    The level of -galactoside 2,6-sialyltransferase I (ST6Gal I) mRNA, encoded by the gene siat1, is increased in malignant tissues. Expression is regulated by different promoters – P1, P2 and P3 – generating three mRNA isoforms H, X and YZ. In cervical cancer tissue the mRNA isoform H, which results from P1 promoter activity, is increased. To study the regulation of P1 promoter, different constructs from P1 promoter were evaluated by luciferase assays in cervical and hepatic cell lines. Deletion of a fragment of 1048 bp (−89 to +24 bp) increased 5- and 3-fold the promoter activity in C33A and HepG2 cell lines, respectively. The minimal region with promoter activity was a 37 bp fragment in C33A cells. The activity of this region does not require the presence of an initiator sequence. In HepG2 cells the minimal promoter activity was detected in the 66 bp fragment. Sp1 (−32) mutation increased the promoter activity only in HepG2 cells. HNF1 mutation decreased promoter activity in HepG2 cell line but not in C33A cells. We identified a large region that plays a negative regulation role. The regulation of promoter activity is cell type specific. Our study provides new insights into the complex transcriptional regulation of siat1 gene.

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

    Directory of Open Access Journals (Sweden)

    Rakhi Srivastava

    2011-01-01

    Full Text Available 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 μg 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.

  12. SPECIFIC IMMUNOTHERAPY AND CELLULAR IMMUNITY IN PATIENTS WITH CERVICAL CANCER

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    D. K. Kenbaeva

    2013-01-01

    Full Text Available Cellular mechanisms are quite important immunological components of tumor surveillance, being, however, most vulnerable to influence of different adverse factors, including surgery-associated stress and ionizing radiation. Our study was aimed for assessing specific effects of immunotherapy upon indices of cellular immunity in patients with cervical cancer. Eighty-eight patients with cervical cancer (clinical stage I-IIA, Т1аN0M0-T2aN0M0, who underwent appropriate surgery (for IA stage, or a combined treatment, including surgery gamma-ray teletherapy (IB, IIA stages are under study. The patients were distributed in two groups, depending on the therapy applied. Group 1 included patients subjected to surgical treatment plus and radiation therapy, Group 2 included those patients who were treated according to this protocol, with addition of a specific immunotherapy. Contents of T cells and various CD subpopulations of T-lymphocytes were identified by immunofluorescence techniques. Among patients with cervical cancer at clinical stages IA, IB, IIA, a reliable decrease in cellular immunity indices was registered, both after surgery, and during combined treatment. Introduction of specific immunotherapy to the conventional treatment schedule was associated with increase of cellular immune indices, and, in first line, the antineoplastic mechanisms (e.g., NK’s and NKT cell contents. One should point to a relatively low efficiency of this immunotherapy in combined treatment of patients with cervical cancer at IIA stage.

  13. Cyclooxygenase-2 expression in cervical cancer

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    Mandić Aljoša

    2014-01-01

    Full Text Available Background/Aim. Cyclooxygenase (COX or prostaglandin H2 synthase is the first enzyme that catalyzes the first two steps in the biosynthesis of prostaglandins from arachidonic acid. The aim of the study was to determine the expression level of COX-2 in patients with cervical cancer and compare it with that in the control group with no cervical pathology. Methods. The study included 76 patients divided into two groups: the control group - 30 patients without histopathological changes and the group A - 46 patients with cervical cancer, FIGO stage IB-IIA. Histopathological and immunohistochemical analyses were performed in these two groups of patients. Results. In the control group, the expression of COX-2 was not confirmed compared to the group A of 26 (56.52% patients. The expression of COX-2 showed a statistically significant difference in the presence of lymphocytic stromal infiltration (p = 0.0053. The expression of COX-2 was more pronounced in the stromal tissue without lymphocytic infiltration (80% vs 20%. Conclusion. A higher expression of COX-2 in cervical carcinoma without stromal lymphocytic infiltration suggests a possible paradoxical effect of COX-2 in immunosuppression. Frequent COX- 2 expression in the subgroup with poor prognostic histological parameters in the group A indicates the importance of COX-2 expression in the carcinogenesis of cervical cancer.

  14. Preoperative Arterial Interventional Chemotherapy on Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Hui; LING HU-Hua; TANG Liang-dan; ZHANG Xing-hua

    2008-01-01

    Objective:To discuss the therapeutic effect of preoperative interventional chemotherapy on cervical cancer.Methods:Preoperative interventional chemotherapy by femoral intubation was performed in 25 patients with bulky cervical cancer.The patients received bleomycin 45 mg and cisplatin or oxaliplatin 80 mg/m2.Results:25 cases(including 8 cases with stage Ⅰ and 17 cases with stage Ⅱ)received one or two courses of preoperative interventional chemotherapy.The size of the focal lesions was decreased greatly and radical hysterectomy and lymphadenectomy were performed successfully in all the patients.All of the specimens were sent for pathological examination.Lymphocyte infiltration was found more obvious in the cancer tissues as compared with their counterpart before treatment.As a result,relevant vaginal bleeding was stopped completely shortly after the treatment.Conclusion:Arterial interventional chemotherapy was proved to reduce the local size of cervical cancer and thus control the hemorrhage efficiently.The patients with cervical cancer can receive radical hysterectomy therapy after the interventional chemotherapy.

  15. Therapeutic Vaccination for HPV Induced Cervical Cancers

    Directory of Open Access Journals (Sweden)

    Joeli A. Brinkman

    2007-01-01

    Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

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

    Science.gov (United States)

    Pariente, Roberto; Pariente, José A; Rodríguez, Ana B; Espino, Javier

    2016-01-01

    Melatonin has antitumor activity via several mechanisms including its antiproliferative and pro-apoptotic effects as well as its potent antioxidant actions, although recent evidence has indicated that melatonin may perform pro-oxidant actions in tumor cells. Therefore, melatonin may be useful in the treatment of tumors in association with chemotherapy drugs. This study was intended to evaluate the in vitro effect of melatonin on the cytotoxic and pro-apoptotic actions of various chemotherapeutic agents in cervical cancer HeLa cells. Herein, we found that both melatonin and three of the chemotherapeutic drugs tested, namely cisplatin (CIS), 5-fluorouracil (5-FU), and doxorubicin, induced a decrease in HeLa cell viability. Furthermore, melatonin significantly increased the cytotoxic effect of such chemotherapeutic agents. Consistently, costimulation of HeLa cells with any chemotherapeutic agent in the presence of melatonin further increased caspase-3 activation, particularly in CIS- and 5-FU-challenged cells. Likewise, concomitant treatments with melatonin and CIS significantly enhanced the ratio of cells entering mitochondrial apoptosis due to reactive oxygen species (ROS) overproduction, substantially augmented the population of apoptotic cells, and markedly enlarged DNA fragmentation compared to the treatments with CIS alone. Nonetheless, melatonin only displayed moderate chemosensitizing effects in 5-FU-stimulated HeLa cells, as suggested by slight increments in the percentage of cells stimulated for ROS production and in the proportion of early apoptotic cells compared to the treatments with 5-FU alone. In summary, our findings provided evidence that in vitro melatonin strongly enhances CIS-induced cytotoxicity and apoptosis in HeLa cells and, hence, the indoleamine could be potentially applied to cervical cancer treatment as a powerful synergistic agent.

  17. COMPARE THE LEVEL OF SQUAMOUS CELL CARCINOMA ANTIGEN IN SERUM AND LOCAL IMMUNITY OF THE REPRODUCTIVE TRACT IN WOMEN WITH INVASIVE FORM OF CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    I. L. Baturina

    2014-01-01

    Full Text Available Abstract. Cervical cancer continues to take a leading position in the structure of cancer pathology in women. This situation calls for the search for new diagnostic criteria for prognosis of the disease. The study found that tumor marker SCCA is immunologically dependent and its detection should be carried out in conjunction with immunological parameters of cervical mucus. This is important not only for diagnosis but also for monitoring of anticancer therapy conducted to determine prognosis of the disease and preclinical detection recurrence of cervical cancer.

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

    Science.gov (United States)

    Pruski, D.; Przybylski, M.; Kędzia, W.; Kędzia, H.; Jagielska-Pruska, J.; Spaczyński, M.

    2011-12-01

    The optoelectronic method is one of the most promising concepts of biophysical program of the diagnostics of CIN and cervical cancer. Objectives of the work are evaluation of sensitivity and specificity of the optoelectronic method in the detection of CIN and cervical cancer. The paper shows correlation between the pNOR number and sensitivity/specificity of the optoelectronic method. The study included 293 patients with abnormal cervical cytology result and the following examinations: examination with the use of the optoelectronic method — Truscreen, colposcopic examination, and histopathologic biopsy. Specificity of the optoelectronic method for LGSIL was estimated at 65.70%, for HGSIL and squamous cell carcinoma of cervix amounted to 90.38%. Specificity of the optoelectronic method used to confirm lack of cervical pathology was estimated at 78.89%. The field under the ROC curve for the optoelectronic method was estimated at 0.88 (95% CI, 0.84-0.92) which shows high diagnostic value of the test in the detection of HGSIL and squamous cell carcinoma. The optoelectronic method is characterised by high usefulness in the detection of CIN, present in the squamous epithelium and squamous cell carcinoma of cervix.

  19. Squamous cell carcinoma antigen isoforms in serum from cervical cancer patients

    NARCIS (Netherlands)

    Roijer, E; de Bruijn, HWA; Dahlen, U; ten Hoor, K; Lundin, M; Nilsson, K; Soderstrom, K; Nilsson, O

    2006-01-01

    Squamous cell carcinoma antigen (SCCA) is a serological marker of squamous cell carcinomas (SCC). To study whether any of the SCCA isoforms would provide additional and more specific/sensitive clinical information than total SCCA, immunoassays specific for the different forms of SCCA (free SCCA2, to

  20. [Cervical cancer screening in Switzerland - current practice and future challenges].

    Science.gov (United States)

    Untiet, Sarah; Schmidt, Nicole; Low, Nicola; Petignat, Patrick

    2013-04-01

    At the beginning of the 20th Century, cervical cancer was the leading cause of death from cancer in women. A marked decline in cervical cancer has been observed since the 1960s, in parallel with the introduction of the Papanicolau (Pap) test as a cytological screening method. Today, Pap smear screening is still the most widely used tool for cervical cancer prevention. Testing for human papillomavirus (HPV) in cervical specimens or a combination of Pap and HPV testing are also now available. In this article we compare current guidelines for cervical cancer screening in Switzerland with those in other European countries. In view of the opportunities offered by HPV testing and, since 2008, HPV vaccination, current guidelines for cervical cancer screening should be updated. Both the choice of screening tests and general organization of cervical cancer screening should be reviewed.

  1. Cervical cancer in India--strategy for control.

    OpenAIRE

    Prabhakar A

    1992-01-01

    The available information on the incidence of cancers by site in India have indicated that of incidence of cancer of uterine cervix among women is by far the highest compared to other sites in women. The epidemiology of cervical cancer has been studied extensively in India and in other countries. The majority of factors related to cervical cancer are associated with sexual behaviour. The available evidence for control of cervical cancer is through secondary prevention, namely--early detection...

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

    Science.gov (United States)

    Ujhelyi, Zoltán; Kalantari, Azin; Vecsernyés, Miklós; Róka, Eszter; Fenyvesi, Ferenc; Póka, Róbert; Kozma, Bence; Bácskay, Ildikó

    2015-07-21

    The aim of this study was to develop topical self-microemulsifying drug delivery systems (SMEDDS) containing antitumor agents (bleomycin, cisplatin and ifosfamide) and to investigate their inhibitory potential in SMEDDS on human cervical cancer HeLa cells. The physicochemical properties of cytostatic drug loaded SMEDDS were characterized. The cytotoxicity of main components of SMEDDS was also investigated. Their IC50 values were determined. HeLa cells were treated by different concentrations of cisplatin, bleomycin and ifosfamide alone and in various SMEDDS. The inhibitory effect on cell growth was analyzed by MTT cell viability assay. Inflammation is a driving force that accelerates cancer development. The inhibitory effect of these antitumor agents has also been tested on HeLa cells in the presence of inflammatory mediators (IL-1-β, TNF-α) as an in vitro model of inflamed human cervix. Significant differences in the cytotoxicity of cytostatic drugs alone and in SMEDDS have been found in a concentration-dependent manner. The self-micro emulsifying system may potentiate the effectiveness of bleomycin, cisplatin and ifosfamide topically. The effect of SMEDDS containing antitumor agents was decreased significantly in the presence of inflammatory mediators. According to our experiments, the optimal SMEDDS formulation is 1:1:2:6:2 ratios of Isopropyl myristate, Capryol 90, Kolliphor RH 40, Cremophor RH40, Transcutol HP and Labrasol. It can be concluded that SMEDDS may increase the inhibitory effect of bleomycin, ifosfamide and cisplatin on human cervical cancer HeLa cells. Inflammation on HeLa cells hinders the effectiveness of SMEDDS containing antitumor agents. Our results might ensure useful data for development of optimal antitumor formulations.

  3. Overexpression of p53 Gene in Esophageal and Cervical Cancer and the Relationship with Radiotherapy Effects

    Institute of Scientific and Technical Information of China (English)

    张晓智; 王晓丽; 李旭

    2003-01-01

    Objective:To investigate the relationship between p53 protein overexpression in esophageal and cervical squamous cell cancer and their clinical radiosensitivity. Methods: The immuno-histochemical assays were done for 52 cases with esophageal and cervical squamous cell cancer. The relationship between the assay results and short-term radiotherapy was investigated. Results: p53 overer-pression was 52.38% and 35. 48% respectively, in esophageal cancer and cervical cancer;p53 over-expression in high differentiated squamous cell cancer was knver than these in moderate and poor differentiated cases(P0. 05). In the cases of cervical cancer, p53 overexpression had the less short-term effect(P0. 05).Conclusion:This study suggests that p53 gene has the certain relationship with tumor radiosensitivity.

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

    Directory of Open Access Journals (Sweden)

    Bing Chen

    2015-01-01

    Full Text Available 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.

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

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    Özlem Cesur

    2015-06-01

    Full Text Available 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.

  6. Microarray analysis of DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252Cf neutron and X-rays

    Directory of Open Access Journals (Sweden)

    Yang Zhen-Zhou

    2010-02-01

    Full Text Available Abstract Background The aim of the study was to obtain stable radioresistant sub-lines from the human cervical cancer cell line HeLa by prolonged exposure to 252Cf neutron and X-rays. Radioresistance mechanisms were investigated in the resulting cells using microarray analysis of DNA damage repair genes. Methods HeLa cells were treated with fractionated 252Cf neutron and X-rays, with a cumulative dose of 75 Gy each, over 8 months, yielding the sub-lines HeLaNR and HeLaXR. Radioresistant characteristics were detected by clone formation assay, ultrastructural observations, cell doubling time, cell cycle distribution, and apoptosis assay. Gene expression patterns of the radioresistant sub-lines were studied through microarray analysis and verified by Western blotting and real-time PCR. Results The radioresistant sub-lines HeLaNR and HeLaXR were more radioresisitant to 252Cf neutron and X-rays than parental HeLa cells by detecting their radioresistant characteristics, respectively. Compared to HeLa cells, the expression of 24 genes was significantly altered by at least 2-fold in HeLaNR cells. Of these, 19 genes were up-regulated and 5 down-regulated. In HeLaXR cells, 41 genes were significantly altered by at least 2-fold; 38 genes were up-regulated and 3 down-regulated. Conclusions Chronic exposure of cells to ionizing radiation induces adaptive responses that enhance tolerance of ionizing radiation and allow investigations of cellular radioresistance mechanisms. The insights gained into the molecular mechanisms activated by these "radioresistance" genes will lead to new therapeutic targets for cervical cancer.

  7. Cervical Cancer: paradigms at home and abroad

    Science.gov (United States)

    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

  8. NIH Research Leads to Cervical Cancer Vaccine

    Science.gov (United States)

    ... Current Issue Past Issues Sexually Transmitted Diseases NIH Research Leads to Cervical Cancer Vaccine Past Issues / Fall 2008 Table of Contents For ... mystery. Most important, however, is to have a vaccine which potentially can ... focusing their research on helping to produce second-generation HPV vaccines ...

  9. Recurrent cervical cancer : detection and prognosis

    NARCIS (Netherlands)

    Duyn, A; Van Eijkeren, M; Kenter, G; Zwinderman, K; Ansink, A

    2002-01-01

    Background. Only a small proportion of cervical cancer recurrences is detected during routine follow-up. We investigated which percentage of recurrences is detected during follow-up, which diagnostic tools are helpful to detect recurrent disease and which factors are of prognostic significance once

  10. Cervical Cancer: Reality and Paradigm Shift

    Directory of Open Access Journals (Sweden)

    Alfredo Quiñones Ceballos

    2014-09-01

    Full Text Available Invasive cervical carcinoma usually reaches its highest frequency between 35-50 years of age. The Cuban prevention program screens the female population aged 25 to 60 years using the Pap smear and reexamines them every three years. Despite this effort, advanced cancer is diagnosed in young women as well as in those 40 to 60 years of age.

  11. Experimental Studies on Cyclooxygenase-2 Inhibitor Induced Cervical Cancer Hela Cell Apoptosis and Its Molecular Mechanism

    Institute of Scientific and Technical Information of China (English)

    Ling YIN; Li-bei WEI; Qiu-hong QU; Xiao-peng GUO

    2007-01-01

    Objective To investigate the Hela cells growth inhibition and apoptosis possible molecular mechanisms.Methods Hela cells were treated with various concentrations(100 μmol/L,200 μmol/L,300μmol/L,400 μmol/L) ofNS-398 (selective for COX-2 inhibition). Cell growth was measured by MTT (Thiazolyl blue).Apoptosis was detected by double staining flow cytomezry (FCM).Levels of PGE2 were measured by radioimmunoassay.The expressions of COX-2 protein were also examined by Western blot analysis.Results After treated with different concentrations ofNS-398,the growth of Hela cells was suppressed significantly in a dose-and time-dependent manner (P<0. 01).The NS-398 can induce apoptosis with the apoptosis rates at 8.53%-43.46% by FCM in a dose-dependent manner.The release of PGE2 was reduced in Hela cells with the values of 69.26 ±2.13, 47.46 ±2.18,28.15 ± 1.64 and 17.01 ± 1.12,respectively,there was significant difference compared with control group (83.78 ± 1.11)(P<0. 01).The NS-398 could inhibit the activity and expression of COX-2 in a dosedependent manner and down-regulated the expression of COX-2 protein greatly.Conclusion NS-398 could inhibit the proliferation and increase apoptosis in human Hela cells.These effects may be depended on the inhibition of the expression of COX-2 and PGE2 by NS-398.

  12. Meta-analysis of type-specific human papillomavirus prevalence in Iranian women with normal cytology, precancerous cervical lesions and invasive cervical cancer: Implications for screening and vaccination.

    Science.gov (United States)

    Jalilvand, Somayeh; Shoja, Zabihollah; Nourijelyani, Keramat; Tohidi, Hamid Reza; Hamkar, Rasool

    2015-02-01

    To predict the impact of current vaccines on cervical cancer and for the improvement of screening programs, regional data on distribution of human papillomavirus (HPV) types in women with or without cervical cancer is crucial. The present meta-analysis intend to comprehensively evaluate the HPV burden in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology, as these data will help decision making in regards with screening programs and HPV vaccination in Iran. To determine the HPV prevalence and type distribution in Iranian women with or without cervical cancer, 20 published studies were included in this meta-analysis. In total, 713, 124, 104, 60, and 2577 women invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal were reviewed, respectively. Overall HPV prevalence in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology were 77.4%, 71.8%, 65.3%, 61.7%, and 8.4%, respectively. The six most common types were HPV 16, 18, 6/11, 31, and 33; among them HPV 16 was the most frequent type in all five different groups. According to this study, it was estimated that HPV vaccines could have a great impact on prevention of cervical cancer in Iran. In conclusion, this meta-analysis highlights the necessity of introducing vaccination program in Iran.

  13. Requirement for estrogen receptor alpha in a mouse model for human papillomavirus-associated cervical cancer.

    Science.gov (United States)

    Chung, Sang-Hyuk; Wiedmeyer, Kerri; Shai, Anny; Korach, Kenneth S; Lambert, Paul F

    2008-12-01

    The majority of human cervical cancers are associated with the high-risk human papillomaviruses (HPV), which encode the potent E6 and E7 oncogenes. On prolonged treatment with physiologic levels of exogenous estrogen, K14E7 transgenic mice expressing HPV-16 E7 oncoprotein in their squamous epithelia succumb to uterine cervical cancer. Furthermore, prolonged withdrawal of exogenous estrogen results in complete or partial regression of tumors in this mouse model. In the current study, we investigated whether estrogen receptor alpha (ERalpha) is required for the development of cervical cancer in K14E7 transgenic mice. We show that exogenous estrogen fails to promote either dysplasia or cervical cancer in K14E7/ERalpha-/- mice despite the continued presence of the presumed cervical cancer precursor cell type, reserve cells, and evidence for E7 expression therein. We also observed that cervical cancers in our mouse models are strictly associated with atypical squamous metaplasia (ASM), which is believed to be the precursor for cervical cancer in women. Consistently, E7 and exogenous estrogen failed to promote ASM in the absence of ERalpha. We conclude that ERalpha plays a crucial role at an early stage of cervical carcinogenesis in this mouse model.

  14. Cervical Cancer Screening in Underserved Populations

    Centers for Disease Control (CDC) Podcasts

    2009-10-15

    Dr. Lisa Flowers, a specialist in human papillovarius (HPV)-related diseases and Director of Colposcopy at Emory University School of Medicine, talks about cervical cancer screening in underinsured or uninsured women.  Created: 10/15/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

  15. Securinine from Phyllanthus glaucus Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells

    Science.gov (United States)

    Krauze-Baranowska, Mirosława; Ochocka, J. Renata

    2016-01-01

    Background The Securinega-type alkaloids occur in plants belonging to Euphorbiaceae family. One of the most widely distributed alkaloid of this group is securinine, which was identified next to allosecurinine in Phyllanthus glaucus (leafflower). Recently, some Securinega-type alkaloids have paid attention to its antiproliferative potency towards different cancer cells. However, the cytotoxic properties of allosecurinine have not yet been evaluated. Methods The cytotoxicity of the extract, alkaloid fraction obtained from P. glaucus, isolated securinine and allosecurinine against HeLa cells was evaluated by real-time xCELLigence system and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and 7-amino-actinomycin (7-AAD) staining and confirmed with fluorescent Hoechst 33342 dye. The assessment of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, the level of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), caspase-3/7 activity and cell cycle analysis were measured by flow cytometry. The enzymatic activity of caspase-9 was assessed by a luminometric assay. The expression of apoptosis associated genes was analyzed by real-time PCR. Results The experimental data revealed that securinine and the alkaloid fraction were significantly potent on HeLa cells growth inhibition with IC50 values of 7.02 ± 0.52 μg/ml (32.3 μM) and 25.46 ± 1.79 μg/ml, respectively. The activity of allosecurinine and Phyllanthus extract were much lower. Furthermore, our study showed that the most active securinine induced apoptosis in a dose-dependent manner in the tested cells, increased the percentage of ROS positive cells and depolarized cells as well as stimulated the activity of ERK1/2, caspase-9 and -3/7. Securinine also induced cell cycle arrest in S phase. Real-time PCR analysis showed high expression of TNFRSF genes in the cells stimulated with securinine. Conclusions Securinine

  16. Expression of Pin1 and Ki67 in Cervical Cancer and Their Significance

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to investigate the expression levels of Pin1 mRNA and protein in cervical cancer and its association with Ki67 and their clinical significance, amplification of Pin1 gene was examined by RT-PCR, and the expression of both Pin1 and Ki67 protein was detected by immunohistochemistry in cervical cancer tissues. It was shown that the expression levels of Pin1 were higher in cervical cancer than in normal cervical tissues (P<0.05). The expression of Pin1 protein was increased progressively along with the disease process from normal cervix to CIN and to cervical cancer (P<0. 05). No significant difference in the Pin1 expression was found between disease stages (FIGO),pathological grades or pelvic lymph node metastasis status (P>0.05). The expression of Pin1 was significantly higher in adenocarcinoma than insquamous carcinoma of the uterine cervix (P<0.05).In cervical cancer, the overexpression of Pin1 was positively correlated with that of Ki67 (P<0.05). These results suggested that the overexpression of Pin1 was closely related with cancer cell proliferation or progression of cervical cancer and contributed to oncogenesis. Pin1 may serve as a potential marker for cervical cancer diagnosis.

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

    OpenAIRE

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

    2013-01-01

    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....

  18. Plasma proteome analysis of cervical intraepithelial neoplasia and cervical squamous cell carcinoma

    Indian Academy of Sciences (India)

    Mee Lee Looi; Saiful Anuar Karsani; Mariati Abdul Rahman; Ahmad Zailani Hatta Mohd Dali; Siti Aishah Md Ali; Wan Zurinah Wan Ngah; Yasmin Anum Mohd Yusof

    2009-12-01

    Although cervical cancer is preventable with early detection, it remains the second most common malignancy among women. An understanding of how proteins change in their expression during a particular diseased state such as cervical cancer will contribute to an understanding of how the disease develops and progresses. Potentially, it may also lead to the ability to predict the occurrence of the disease. With this in mind, we aimed to identify differentially expressed proteins in the plasma of cervical cancer patients. Plasma from control, cervical intraepithelial neoplasia (CIN) grade 3 and squamous cell carcinoma (SCC) stage IV subjects was resolved by two-dimensional gel electrophoresis and the resulting proteome profiles compared. Differentially expressed protein spots were then identified by mass spectrometry. Eighteen proteins were found to be differentially expressed in the plasma of CIN 3 and SCC stage IV samples when compared with that of controls. Competitive ELISA further validated the expression of cytokeratin 19 and tetranectin. Functional analyses of these differentially expressed proteins will provide further insight into their potential role(s) in cervical cancer-specific monitoring and therapeutics.

  19. Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells

    Directory of Open Access Journals (Sweden)

    Zhang H

    2015-03-01

    , the genistein-loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer. Keywords: nanomedicine, genistein, TPGS-b-PCL, drug delivery, anticancer effect, cytotoxicity

  20. Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED)

    Science.gov (United States)

    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

  1. Cervical cancer prevention: new tools and old barriers.

    Science.gov (United States)

    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 =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.

  2. DeltaNp63alpha repression of the Notch1 gene supports the proliferative capacity of normal human keratinocytes and cervical cancer cells.

    Science.gov (United States)

    Yugawa, Takashi; Narisawa-Saito, Mako; Yoshimatsu, Yuki; Haga, Kei; Ohno, Shin-ichi; Egawa, Nagayasu; Fujita, Masatoshi; Kiyono, Tohru

    2010-05-15

    The p53 family member p63 is a master regulator of epithelial development. One of its isoforms, DeltaNp63alpha, is predominantly expressed in the basal cells of stratified epithelia and plays a fundamental role in control of regenerative potential and epithelial integrity. In contrast to p53, p63 is rarely mutated in human cancers, but it is frequently overexpressed in squamous cell carcinomas (SCC). However, its functional relevance to tumorigenesis remains largely unclear. We previously identified the Notch1 gene as a novel transcriptional target of p53. Here, we show that DeltaNp63alpha functions as a transcriptional repressor of the Notch1 gene through the p53-responsive element. Knockdown of p63 caused upregulation of Notch1 expression and marked reduction in proliferation and clonogenicity of both normal human keratinocytes and cervical cancer cell lines overexpressing DeltaNp63alpha. Concomitant silencing of Notch1 significantly rescued this phenotype, indicating the growth defect induced by p63 deficiency to be, at least in part, attributable to Notch1 function. Conversely, overexpression of DeltaNp63alpha decreased basal levels of Notch1, increased proliferative potential of normal human keratinocytes, and inhibited both p53-dependent and p53-independent induction of Notch1 and differentiation markers upon genotoxic stress and serum exposure, respectively. These results suggest that DeltaNp63alpha maintains the self-renewing capacity of normal human keratinocytes and cervical cancer cells partly through transcriptional repression of the Notch1 gene and imply a novel pathogenetical significance of frequently observed overexpression of DeltaNp63alpha together with p53 inactivation in SCCs.

  3. [Papillomavirus and cervical cancer in Chile].

    Science.gov (United States)

    O'Ryan, Miguel; Valenzuela, María Teresa

    2008-11-01

    Molecular, clinical and epidemiological studies have established beyond doubt that human papiloma viruses (HPV) cause cervical cancer. The virus is also associated with genital warts and other less common cancers in oropharynx, vulva, vagina and penis. Worldwide, VPH genotypes 16 and 18 are the most common high risk genotypes, detected in near 70% of women with cervical cancer. The discovery of a cause-effect relationship between several carcinogenic microorganisms and cancer open avenues for new diagnostic, treatment and prevention strategies. In this issue of Revista Médica de Chile, two papers on HPV are presented. Guzman and colleagues demonstrate that HPV can be detected in 66% to 77% of healthy male adolescents bypolymerase chain reaction and that positivity depends on the site of the penis that is sampled. These results support the role of male to female transmission of high risk HPVs in Chile and should lead to even more active educational campaigns. The second paper provides recommendations for HPV vaccine use in Chile, generated by the Immunization Advisory Committee of the Chilean Infectious Disease Society. To issue these recommendations, the Committee analyzes the epidemiological information available on HPV infection and cervical cancer in Chile, vaccine safety and effectiveness data, and describes cost-effectiveness studies. Taking into account that universal vaccination is controversial, the Committee favors vaccine use in Chile and it's incorporation into a national program. However, there is an indication that the country requires the implementation of an integrated surveillance approach including cross matching of data obtained from HPV genotype surveillance, monitoring of vaccination coverage, and surveillance of cervical cancer. The final decision of universal vaccine use in Chile should be based on a through analysis of information.ev Mid Chile

  4. Effect of matrine combined with cisplatin on endocrine function and malignant biological behavior of cervical cancer SiHa cell line

    Institute of Scientific and Technical Information of China (English)

    Lan-Jiao Guo; Fang Lan; Meng-Li Wang

    2016-01-01

    Objective:To investigate the effect of matrine combined with cisplatin on endocrine function and malignant biological behavior of cervical cancer SiHa cell line.Methods:Cervical cancer SiHa cell lines were cultured and divided into control group,cisplatin (CDDP) group, oxymatrine (OMT) group and combined group. Then cell viability and migration capability as well as malignant biological molecules and miRNAs contents were detected.Results: (1) Malignant biological behavior: cell viability and migration rate of CDDP group, OMT group and combined group were lower than those of control group; cell viability and migration rate of combined group were lower than those of CDDP group and OMT group; (2) Endocrine function: HIF-1α, GDF-15, P450arom, HDAC2, ANXA2, miR-21 and miR-155 contents of CDDP group , OMT group and combined group were lower than those of control group, and miR-143 and miR-424 contents were higher than those of control group; HIF-1α, GDF-15, P450arom, HDAC2, ANXA2, miR-21 and miR-155 contents of combined group were lower than those of CDDP group and OMT group, and miR-143 and miR-424 contents were higher than those of CDDP group and OMT group.Conclusions:Matrine combined with cisplatin treatment can inhibit cell proliferation and migration, reduce the expression of malignant biological molecules and regulate the contents of related miRNAs.

  5. Paraneoplastic SIADH and Dermatomyositis in Cervical Cancer: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Guy Jones

    2009-11-01

    Full Text Available We present the first known case of a patient with cervical squamous cell carcinoma complicated by paraneoplastic syndromes of both dermatomyositis and inappropriate secretion of antidiuretic hormone (SIADH. The patient in this case presented with generalized body pain and vaginal bleeding. Her cervical cancer was diagnosed as stage IIB by physical exam, imaging, and cervical biopsy, her dermatomyositis was confirmed by muscle and skin biopsy, and her SIADH was diagnosed based on laboratory findings.

  6. Assessment of Cytotoxic Activity of Rosemary (Rosmarinus officinalis L.), Turmeric (Curcuma longa L.), and Ginger (Zingiber officinale R.) Essential Oils in Cervical Cancer Cells (HeLa)

    Science.gov (United States)

    Santos, P. A. S. R.; Avanço, G. B.; Nerilo, S. B.; Marcelino, R. I. A.; Janeiro, V.; Valadares, M. C.

    2016-01-01

    The objective of this study was to evaluate the cytotoxic activity of rosemary (REO, Rosmarinus officinalis L.), turmeric (CEO, Curcuma longa L.), and ginger (GEO, Zingiber officinale R.) essential oils in HeLa cells. Cytotoxicity tests were performed in vitro, using tetrazolium (MTT) and neutral red assays for evaluation of antiproliferative activity by different mechanisms, trypan blue assay to assess cell viability and evaluation of cell morphology for Giemsa to observe the cell damage, and Annexin V to evaluate cell death by apoptosis. CEO and GEO exhibited potent cytotoxic activity against HeLa cells. IC50 obtained was 36.6 μg/mL for CEO and 129.9 μg/mL for GEO. The morphology of HeLa cells showed condensation of chromatin, loss of cell membrane integrity with protrusions (blebs), and cell content leakage for cells treated with CEO and GEO, from the lowest concentrations studied, 32.81 μg/mL of CEO and 32.12 μg/mL of GEO. The Annexin V assay revealed a profile of cell death by apoptosis for both CEO and GEO. The results indicate cytotoxic activity in vitro for CEO and GEO, suggesting potential use as anticancer agents for cervical cancer cells. PMID:28042599

  7. Assessment of Cytotoxic Activity of Rosemary (Rosmarinus officinalis L., Turmeric (Curcuma longa L., and Ginger (Zingiber officinale R. Essential Oils in Cervical Cancer Cells (HeLa

    Directory of Open Access Journals (Sweden)

    P. A. S. R. Santos

    2016-01-01

    Full Text Available The objective of this study was to evaluate the cytotoxic activity of rosemary (REO, Rosmarinus officinalis L., turmeric (CEO, Curcuma longa L., and ginger (GEO, Zingiber officinale R. essential oils in HeLa cells. Cytotoxicity tests were performed in vitro, using tetrazolium (MTT and neutral red assays for evaluation of antiproliferative activity by different mechanisms, trypan blue assay to assess cell viability and evaluation of cell morphology for Giemsa to observe the cell damage, and Annexin V to evaluate cell death by apoptosis. CEO and GEO exhibited potent cytotoxic activity against HeLa cells. IC50 obtained was 36.6 μg/mL for CEO and 129.9 μg/mL for GEO. The morphology of HeLa cells showed condensation of chromatin, loss of cell membrane integrity with protrusions (blebs, and cell content leakage for cells treated with CEO and GEO, from the lowest concentrations studied, 32.81 μg/mL of CEO and 32.12 μg/mL of GEO. The Annexin V assay revealed a profile of cell death by apoptosis for both CEO and GEO. The results indicate cytotoxic activity in vitro for CEO and GEO, suggesting potential use as anticancer agents for cervical cancer cells.

  8. Breast and cervical cancer risk in India: An update

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    Smita Asthana

    2014-01-01

    Full Text Available Background: Breast and cervical cancers are two major cancers among Indian women. Analysis of trends would help in planning and organization of programs for control of these cancers. Objective: The objective of the following study is to compute risk of breast and cervical cancers using updated data from different cancer registries of India and study of its trends. Materials and Methods: Data on incidence rates of breast and cervical cancers were obtained from six major cancer registries of India for the years 1982-2008 and from the recently initiated cancer registries, North Eastern Registries of India with a total of 21 registries. Annual percent change in incidence and risk in terms of one in number of women likely to develop cancer was estimated for both the cancers in various registries. Results: The annual percentage change in incidence ranged from 0.46 to 2.56 and −1.14 to −3.4 for breast and cervical cancers respectively. Trends were significant for both cancers in the registries of Chennai, Bangalore, Mumbai and Delhi except Barshi and Bhopal. North East region showed decrease in risk for breast and cervical cancers whereas increasing trend was observed in Imphal (West and for cervical cancer in Silchar. Conclusion: North Eastern region recorded decline in the incidence of breast cancer which is contrary to the observation in other registries, which showed increase in breast cancer and decline in cervical cancer incidences.

  9. Development of an Expert System as a Diagnostic Support of Cervical Cancer in Atypical Glandular Cells, Based on Fuzzy Logics and Image Interpretation

    Directory of Open Access Journals (Sweden)

    Karem R. Domínguez Hernández

    2013-01-01

    Full Text Available 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.

  10. Detection of STAT2 in early stage of cervical premalignancy and in cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Liang Zeng; Li-Hua Gao; Li-Jun Cao; De-Yun Feng; Ya Cao; Qi-Zhi Luo; Ping Yu; Ming Li

    2012-01-01

    Objective:To measure the expression pattern ofSTAT2 in cervical cancer initiation and progression in tissue sections from patients with cervicitis, dysplasia, and cervical cancer. Methods:Antibody against humanSTAT2 was confirmed by plasmids transient transfection andWestern blot.Immunohistochemistry was used to detectSTAT2 expression in the cervical biopsies by using the confirmed antibody againstSTAT2 as the primary antibody.Results:It was found that the overall rate of positiveSTAT2 expression in the cervicitis, dysplasia and cervical cancer groups were38.5%,69.4% and76.9%, respectively.TheSTAT2 levels are significantly increased in premalignant dysplasia and cervical cancer, as compared to cervicitis(P<0.05). Noticeably,STAT2 signals were mainly found in the cytoplasm, implying thatSTAT2 was not biologically active.Conclusions:These findings reveal an association between cervical cancer progression and augmentedSTAT2 expression.In conclusion,STAT2 increase appears to be an early detectable cellular event in cervical cancer development.

  11. Computer aided decision support system for cervical cancer classification

    Science.gov (United States)

    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

  12. Morphological evaluation of rentgenendovaskular interventions for cervical cancer

    Directory of Open Access Journals (Sweden)

    A. V. Vazhenin

    2012-01-01

    Full Text Available The paper presents the results of an analysis of therapeutic pathomorphosis after rentgenoendovaskular interventions in patients with cervical cancer. Found more significant changes after chemoembolization with low (10% 3rd class pathomorphosis dominated by downward 2 nd degree. Index of effect indicates more effective therapy with chemoembolization than embolization. The morphological changes in cervi- cal tissue squamous cell cancer after rentgenoendovaskular treatment are followed by circulatory parenchyma tumor destruction. Changes of tumor cells are qualitatively consistent character and were based in nekrobiosis dystrophy with subsequent necrosis of tumor tissue, and varying degrees of popularity.

  13. The male role in cervical cancer

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    Castellsagué Xavier

    2003-01-01

    Full Text Available Experimental, clinical, and epidemiological evidence strongly suggests that genital Human Papillomaviruses (HPVs are predominantly sexually transmitted. Epidemiological studies in virginal and HPV-negative women clearly indicate that sexual intercourse is virtually a necessary step for acquiring HPV. As with any other sexually transmitted disease (STD men are implicated in the epidemiological chain of the infection. Penile HPVs are predominantly acquired through sexual contacts. Sexual contacts with women who are prostitutes play an important role in HPV transmission and in some populations sex workers may become an important reservoir of high-risk HPVs. Acting both as "carriers" and "vectors" of oncogenic HPVs male partners may markedly contribute to the risk of developing cervical cancer in their female partners. Thus, in the absence of screening programs, a woman's risk of cervical cancer may depend less on her own sexual behavior than on that of her husband or other male partners. Although more rarely than women, men may also become the "victims" of their own HPV infections as a fraction of infected men are at an increased risk of developing penile and anal cancers. Male circumcision status has been shown to reduce the risk not only of acquiring and transmitting genital HPVs but also of cervical cancer in their female partners. More research is needed to better understand the natural history and epidemiology of HPV infections in men.

  14. The use of MYBL2 as a novel candidate biomarker of cervical cancer.

    Science.gov (United States)

    Martin, Cara M; Astbury, Katharine; Kehoe, Louise; O'Crowley, Jacqueline Barry; O'Toole, Sharon; O'Leary, John J

    2015-01-01

    Cervical cancer is the third most common cancer affecting women worldwide. It is characterized by chromosomal aberrations and alteration in the expression levels of many cell cycle regulatory proteins, driven primarily by transforming human papillomavirus (HPV) infection. MYBL2 is a member of the MYB proto-oncogene family that encodes DNA binding proteins. These proteins are involved in cell proliferation and control of cellular differentiation. We have previously demonstrated the utility of MYBL2 as a putative biomarker for cervical pre-cancer and cancer. In this chapter we describe the methodological approach for testing MYBL2 protein expression in tissue biopsies from cases of cervical intraepithelial neoplasia (CIN) and cervical cancer, using immunohistochemistry techniques on the automated immunostaining platform, the Ventana BenchMark LT. The protocol outlines the various steps in the procedure from cutting tissue sections, antibody optimization, antigen retrieval, immunostaining, and histological review.

  15. 75 FR 7282 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

    Science.gov (United States)

    2010-02-18

    ... HUMAN SERVICES Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and... cervical cancer. The committee makes recommendations regarding national program goals and objectives... Force guidelines for breast and cervical cancer screening; Impact of the revised clinical...

  16. Correlates of Cervical Cancer Screening among Vietnamese American Women

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    Grace X. Ma

    2012-01-01

    Full Text Available Objective. Vietnamese American women are at the greatest risk for cervical cancer but have the lowest cervical cancer screening rates. This study was to determine whether demographic and acculturation, healthcare access, and knowledge and beliefs are associated with a prior history of cervical cancer screening among Vietnamese women. Methods. Vietnamese women (n=1450 from 30 Vietnamese community-based organizations located in Pennsylvania and New Jersey participated in the study and completed baseline assessments. Logistic regression analyses were performed. Results. Overall levels of knowledge about cervical cancer screening and human papillomavirus (HPV are low. Factors in knowledge, attitude, and beliefs domains were significantly associated with Pap test behavior. In multivariate analyses, physician recommendation for screening and having health insurance were positively associated with prior screening. Conclusion. Understanding the factors that are associated with cervical cancer screening will inform the development of culturally appropriate intervention strategies that would potentially lead to increasing cervical cancer screening rates among Vietnamese women.

  17. Frequencies and role of regulatory T cells in patients with (pre)malignant cervical neoplasia

    NARCIS (Netherlands)

    Visser, J.; Nijman, H. W.; Hoogenboom, B.-N.; Jager, P.; van Baarle, D.; Schuuring, E.; Abdulahad, W.; Miedema, F.; van der Zee, A. G.; Daemen, T.

    2007-01-01

    Oncogenic human papillomavirus (HPV)-infection is crucial for developing cervical cancer and its precursor lesions [cervical intraepithelial neoplasia (CIN)]. Regulatory T cells (T-regs) might be involved in the failure of the immune system to control the development of HPV-induced cancer. We invest

  18. Suppression of HPV E6 and E7 expression by BAF53 depletion in cervical cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kiwon; Lee, Ah-Young [Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yongin 449-791 (Korea, Republic of); Kwon, Yunhee Kim [Department of Life and Nanopharmaceutical Science and Department of Biology, Kyunghee University, Seoul 130-701 (Korea, Republic of); Kwon, Hyockman, E-mail: hmkwon@hufs.ac.kr [Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yongin 449-791 (Korea, Republic of)

    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

  19. Biological evaluation of a cytotoxic 2-substituted benzimidazole copper(II) complex: DNA damage, antiproliferation and apoptotic induction activity in human cervical cancer cells.

    Science.gov (United States)

    Qiao, Xin; Ma, Zhong-Ying; Shao, Jia; Bao, Wei-Guo; Xu, Jing-Yuan; Qiang, Zhao-Yan; Lou, Jian-Shi

    2014-02-01

    Exploring novel chemotherapeutic agents is a great challenge in cancer medicine. To that end, 2-substituted benzimidazole copper(II) complex, [Cu(BMA)Cl2]·(CH3OH) (1) [BMA = N,N'-bis(benzimidazol-2-yl-methyl)amine], was synthesized and its cytotoxicity was characterized. The interaction between complex 1 and calf thymus DNA was detected by spectroscopy methods. The binding constant (K b = 1.24 × 10(4 )M(-1)) and the apparent binding constant (K app = 6.67 × 10(6 )M(-1)) of 1 indicated its moderate DNA affinity. Complex 1 induced single strand breaks of pUC19 plasmid DNA in the presence of H2O2 through an oxidative pathway. Cytotoxicity studies proved that complex 1 could inhibit the proliferation of human cervical carcinoma cell line HeLa in both time- and dose-dependent manners. The results of nuclei staining by Hoechst 33342 and alkaline single-cell gel electrophoresis proved that complex 1 caused cellular DNA damage in HeLa cells. Furthermore, treatment of HeLa cells with 1 resulted in S-phase arrest, loss of mitochondrial potential, and up-regulation of caspase-3 and -9 in HeLa cells, suggesting that complex 1 was capable of inducing apoptosis in cancer cells through the intrinsic mitochondrial pathway.

  20. Stathmin is involved in arsenic trioxide-induced apoptosis in human cervical cancer cell lines via PI3K linked signal pathway.

    Science.gov (United States)

    Wang, Xi; Ren, Ji-Hong; Lin, Fang; Wei, Jun-Xia; Long, Min; Yan, Lin; Zhang, Hui-Zhong

    2010-09-15

    Although the mechanisms of arsenic trioxide (As2O3)-induced apoptosis have been elucidated extensively in hematologic cancers, those in solid tumors have yet to be clearly defined. In the present study, we show that As2O3 triggers apoptosis through the intrinsic pathway and significantly downregulates stathmin expression. Decreased stathmin expression is necessary for the dissipation of mitochondrial membrane potential (Δ ψm), the translocation of cytochrome C from the mitochondria to the cytosol, and subsequent cell death. Overexpression of wild type stathmin effectively delays As2O3-mediated mitochondrial events. Conversely, expression of a small interfering RNA (siRNA) targeting stathmin enhances As2O3-triggered apoptosis in cell culture and in mouse models. Furthermore, we demonstrate that As2O3-induced stathmin downregulation is mediated through the phosphatidylinositol-3-kinase (PI3K) signaling pathway, and that a PI3K inhibitor effectively attenuated stathmin downregulation and cell apoptosis upon As2O3-treatment. These data support a stathmin-dependent pathway of As2O3-mediated cell death in solid tumor cells, and indicate that stathmin is a target of the PI3K/Akt pathway in cervical cancer cells. All these results may provide a rationale for improving the efficacy of As2O3 as a therapeutic agent through combination treatment with stathmin inhibition or PI3K/Akt inhibitors.

  1. Cervical cancer prevention and treatment in Latin America.

    Science.gov (United States)

    Lopez, Melissa S; Baker, Ellen S; Maza, Mauricio; Fontes-Cintra, Georgia; Lopez, Aldo; Carvajal, Juan M; Nozar, Fernanda; Fiol, Veronica; Schmeler, Kathleen M

    2017-02-07

    Cervical cancer is a preventable disease with a known etiology (human papillomavirus), effective preventive vaccines, excellent screening methods, and a treatable pre-invasive phase. Surgery is the primary treatment for pre-invasive and early-stage disease and can safely be performed in many low-resource settings. However, cervical cancer rates remain high in many areas of Latin America. This article presents a number of evidence-based strategies being implemented to improve cervical cancer outcomes in Latin America.

  2. Drug Delivery Approaches for the Treatment of Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Farideh Ordikhani

    2016-07-01

    Full Text Available Cervical cancer is a highly prevalent cancer that affects women around the world. With the availability of new technologies, researchers have increased their efforts to develop new drug delivery systems in cervical cancer chemotherapy. In this review, we summarized some of the recent research in systematic and localized drug delivery systems and compared the advantages and disadvantages of these methods.

  3. Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPK-dependent NF-κB signaling pathway.

    Directory of Open Access Journals (Sweden)

    Ruey-Hwang Chou

    Full Text Available Fisetin (3,3',4',7-tetrahydroxyflavone, a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion.

  4. Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPK-dependent NF-κB signaling pathway.

    Science.gov (United States)

    Chou, Ruey-Hwang; Hsieh, Shu-Ching; Yu, Yung-Luen; Huang, Min-Hsien; Huang, Yi-Chang; Hsieh, Yi-Hsien

    2013-01-01

    Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion.

  5. Human Papillomavirus Induced Transformation in Cervical and Head and Neck Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Allie K. [Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229 (United States); Wise-Draper, Trisha M. [Division of Hematology/Oncology, University of Cincinnati Medical Center, University of Cincinnati, Cincinnati, OH 45229 (United States); Wells, Susanne I., E-mail: Susanne.Wells@cchmc.org [Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229 (United States)

    2014-09-15

    Human papillomavirus (HPV) is one of the most widely publicized and researched pathogenic DNA viruses. For decades, HPV research has focused on transforming viral activities in cervical cancer. During the past 15 years, however, HPV has also emerged as a major etiological agent in cancers of the head and neck, in particular squamous cell carcinoma. Even with significant strides achieved towards the screening and treatment of cervical cancer, and preventive vaccines, cervical cancer remains the leading cause of cancer-associated deaths for women in developing countries. Furthermore, routine screens are not available for those at risk of head and neck cancer. The current expectation is that HPV vaccination will prevent not only cervical, but also head and neck cancers. In order to determine if previous cervical cancer models for HPV infection and transformation are directly applicable to head and neck cancer, clinical and molecular disease aspects must be carefully compared. In this review, we briefly discuss the cervical and head and neck cancer literature to highlight clinical and genomic commonalities. Differences in prognosis, staging and treatment, as well as comparisons of mutational profiles, viral integration patterns, and alterations in gene expression will be addressed.

  6. Human Papillomavirus Induced Transformation in Cervical and Head and Neck Cancers

    Directory of Open Access Journals (Sweden)

    Allie K. Adams

    2014-09-01

    Full Text Available 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.

  7. Interferon-β induced microRNA-129-5p down-regulates HPV-18 E6 and E7 viral gene expression by targeting SP1 in cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Jiarong Zhang

    Full Text Available Infection by human papillomavirus (HPV can cause cervical intraepithelial neoplasia (CIN and cancer. Down-regulation of E6 and E7 expression may be responsible for the positive clinical outcomes observed with IFN treatment, but the molecular basis has not been well determined. As miRNAs play an important role in HPV induced cervical carcinogenesis, we hypothesize that IFN-β can regulate the expressions of specific miRNAs in cervical cancer cells, and that these miRNAs can mediate E6 and E7 expression, thus modulate their oncogenic potential. In this study, we found that miR-129-5p to be a candidate IFN-β inducible miRNA. MiR-129-5p levels gradually decrease with the development of cervical intraepithelial lesions. Manipulation of miR-129-5p expression in Hela cells modulates HPV-18 E6 and E7 viral gene expression. Exogenous miR-129-5p inhibits cell proliferation in Hela cells, promotes apoptosis and blocks cell cycle progression in Hela cells. SP1 is a direct target of miR-129-5p in Hela cells. This study is the first report of a cellular miRNA with anti-HPV activity and provides new insights into regulatory mechanisms between the HPV and the IFN system in host cells at the miRNA level.

  8. 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.

    Science.gov (United States)

    Aytac Korkmaz, Sevcan

    2016-05-05

    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.

  9. 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

    Science.gov (United States)

    Aytac Korkmaz, Sevcan

    2016-05-01

    The aim of this article is to provide early detection of cervical cancer by using both Atomic Force Microscope (AFM) and Scanning Electron Microscope (SEM) images of same patient. When the studies in the literature are examined, it is seen that the AFM and SEM images of the same patient are not used together for early diagnosis of cervical cancer. AFM and SEM images can be limited when using only one of them for the early detection of cervical cancer. Therefore, multi-modality solutions which give more accuracy results than single solutions have been realized in this paper. Optimum feature space has been obtained by Discrete Wavelet Entropy Energy (DWEE) applying to the 3 × 180 AFM and SEM images. Then, optimum features of these images are classified with Jensen Shannon, Hellinger, and Triangle Measure (JHT) Classifier for early diagnosis of cervical cancer. However, between classifiers which are Jensen Shannon, Hellinger, and triangle distance have been validated the measures via relationships. Afterwards, accuracy diagnosis of normal, benign, and malign cervical cancer cell was found by combining mean success rates of Jensen Shannon, Hellinger, and Triangle Measure which are connected with each other. Averages of accuracy diagnosis for AFM and SEM images by averaging the results obtained from these 3 classifiers are found as 98.29% and 97.10%, respectively. It has been observed that AFM images for early diagnosis of cervical cancer have higher performance than SEM images. Also in this article, surface roughness of malign AFM images in the result of the analysis made for the AFM images, according to the normal and benign AFM images is observed as larger, If the volume of particles has found as smaller. She has been a Faculty Member at Fırat University in the Electrical- Electronic Engineering Department since 2007. Her research interests include image processing, computer vision systems, pattern recognition, data fusion, wavelet theory, artificial neural

  10. Biologia molecular do câncer cervical Molecular biology of cervical cancer

    Directory of Open Access Journals (Sweden)

    Waldemar Augusto Rivoire

    2006-01-01

    Full Text Available A carcinogênese é um processo de múltiplas etapas. Alterações no equilíbrio citogenético ocorrem na transformação do epitélio normal a câncer cervical. Numerosos estudos apoiam a hipótese de que a infecção por HPV está associada com o desenvolvimento de alterações malignas e pré-malignas do trato genital inferior. Neste trabalho são apresentadas as bases para a compreensão da oncogênese cervical. O ciclo celular é controlado por proto-oncogenes e genes supressores. Quando ocorrem mutações, proto-oncogenes tornam-se oncogenes, que são carcinogênicos e causam multiplicação celular excessiva. A perda da ação de genes supressores funcionais pode levar a célula ao crescimento inadequado. O ciclo celular também pode ser alterado pela ação de vírus, entre eles o HPV (Human Papiloma Virus, de especial interesse na oncogênese cervical. Os tipos de HPV 16 e 18 são os de maior interesse, freqüentemente associados a câncer cervical e anal. O conhecimento das bases moleculares que estão envolvidas na oncogênese cervical tem sido possível devido a utilização de técnicas avançadas de biologia molecular. A associação destas técnicas aos métodos diagnósticos clássicos, poderão levar a uma melhor avaliação das neoplasias cervicais e auxiliar no desenvolvimento de novas terapias, talvez menos invasivas e mais efetivas.Carcinogenesis involves several steps. Disorders of the cytogenetic balance occur during the evolution from normal epithelium to cervical cancer. Several studies support the hypothesis that the Human Papiloma Virus (HPV infection is associated to development of premalignant and malignant lesions of cervical cancer. In this review we show the basis to understand cervical oncogenesis. The cell cycle is controlled by protooncogenes and supressive genes. This orchestrated cell cycle can be affected by virus such as HPV. Of special interest in the cervical carcinogenesis are the HPV subtypes 16 and 18

  11. Design, synthesis and cytotoxicity of novel N-benzylpiperidin-4-one oximes on human cervical cancer cells

    Indian Academy of Sciences (India)

    Someshwar D Dindulkar; Ira Bhatnagar; Rupesh L Gawade; Vedavati G Puranik; Se-Kwon Kim; Dong Hyun Anh; Paramasivam Parthiban; Yeon Tae Jeong

    2014-05-01

    A series of fifteen diversified N-benzylpiperidin-4-one oximes were synthesized and characterized by their NMR spectral data. Additionally, single-crystal XRD analysis was performed for the representative symmetrically and unsymmetrically substituted molecules. All the synthesized oximes from unsymmetrical ketones existed as E-isomer as witnessed by their NMR and XRD data. Among the synthesized target compounds that evaluated for their in vitro cytotoxicity against human cervical carcinoma (HeLa) cells, five compounds were potent with IC50 < 17 M. 1-Benzyl-2,6-bis(4-isopropylphenyl)-3-methylpiperidin-4-one oxime 3c with an IC50 of 13.88 M was found to be the best active compound as depicted by the microscopic analysis.

  12. Knowledge about Cervical Cancer and Barriers of Screening Program among Women in Wufeng County, a High-Incidence Region of Cervical Cancer in China

    OpenAIRE

    Yao Jia; Shuang Li; Ru Yang; Hang Zhou; Qunying Xiang; Ting Hu; Qinghua Zhang; Zhilan Chen; Ding Ma; Ling Feng

    2013-01-01

    PURPOSE: Cervical cancer screening is an effective method for reducing the incidence and mortality of cervical cancer, but the screening attendance rate in developing countries is far from satisfactory, especially in rural areas. Wufeng is a region of high cervical cancer incidence in China. This study aimed to investigate the issues that concern cervical cancer and screening and the factors that affect women's willingness to undergo cervical cancer screening in the Wufeng area. PARTICIPANTS ...

  13. Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes in cervical intraepithelial neoplasia and cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Yu Huang; Jia Zhang; Zhu-Mei Cui; Jing Zhao; Ye Zheng

    2013-01-01

    The chemokine CXCL12 is highly expressed in gynecologic tumors and is widely known to play a biologically relevant role in tumor growth and spread.Recent evidence suggests that CXCL16,a novel chemokine,is overexpressed in inflammation-associated tumors and mediates pro-tumorigenic effects of inflammation in prostate cancer.We therefore analyzed the expression of CXCL12 and CXCL16 and their respective receptors CXCR4 and CXCR6 in cervical intraepithelial neoplasia (CIN) and cervical cancer and further assessed their association with clinicopathologic features and outcomes.Tissue chip technology and immunohistochemistry were used to analyze the expression of CXCL12,CXCR4,CXCL16,and CXCR6 in healthy cervical tissue (21 cases),CIN (65 cases),and cervical carcinoma (60 cases).The association of protein expression with clinicopathologic features and overall survival was analyzed.These four proteins were clearly detected in membrane and cytoplasm of neoplastic epithelial cells,and their distribution and intensity of expression increased as neoplastic lesions progressed through CIN1,CIN2,and CIN3 to invasive cancer.Furthermore,the expression of CXCR4 was associated significantly with the histologic grade of cervical carcinoma,whereas the expression of CXCR6 was associated significantly with lymph node metastasis.In Kaplan-Meier analysis,patients with high CXCR6 expression had significantly shorter overall survival than did those with low CXCR6 expression.The elevated co-expression levels of CXCL12/CXCR4 and CXCL16/CXCR6 in CIN and cervical carcinoma suggest a durative process in cervical carcinoma development.Moreover,CXCR6 may be useful as a biomarker and a valuable prognostic factor for cervical cancer.

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

    DEFF Research Database (Denmark)

    Obel, J; McKenzie, J; Buenconsejo-Lum, L E

    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...... 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...

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

    Directory of Open Access Journals (Sweden)

    Munawwar Ali Khan

    2015-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  17. General Information about Cervical Cancer

    Science.gov (United States)

    ... Resources Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... Contacts Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training ...

  18. Preventive vaccines for cervical cancer Vacunas para prevenir el cáncer cervical

    Directory of Open Access Journals (Sweden)

    COSETTE M WHEELER

    1997-07-01

    Full Text Available The potential use of vaccines for the human papillomavirus (HPV in the prevention and treatment of cervical cancer is a possibility in the near future. Close to 20 genotypes of HPV, of the 75 that have been identified, infect the femine genital tract, but four subtypes (16, 18, 31 and 45 have been associated in close to 80% of cervical cancers. this article proposes that in order to design an effective prophylactic vaccine against HPV infection, an adequate immune response should be guaranteed through four goals; a activation of antigens present in the cell; b overcoming the host response and viral genetic variability in the T cell response; c generation of high levels of T and B memory cells; and d persistence of antigens.El potencial uso de vacunas de virus del papiloma humano (VPH en la prevención y tratamiento del cáncer cervical posiblemente será implementado durante los próximos años. Cerca de los 20 genotipos de VPH de los 75 que se encuentran identificados infectan el tracto genital femenino, pero son cuatro subtipos: 16, 18, 31 y 45 los que se han asociado en cerca de 80% a cáncer cervical. En este ensayo se plantea que para poder diseñar una vacuna profiláctica contra la infección de VPH, efectiva, se debe garantizar una adecuada respuesta inmune a través de cuatro metas: a activación de antígenos presentes en la célula; b superar la respuesta del huésped y la variabilidad genética viral en la respuesta de células T; c generación de altos niveles de células T y B de memoria, y d persistencia de antígenos.

  19. High Expression of Stromal Cell-Derived Factor 1 (SDF-1) and NF-κB Predicts Poor Prognosis in Cervical Cancer.

    Science.gov (United States)

    Song, Zhiwang; Zhang, Xia; Ye, Xiaojuan; Feng, Chan; Yang, Guang; Lu, Yonglin; Lin, Yun; Dong, Chunyan

    2017-01-11

    BACKGROUND SDF-1 and NF-κB are associated with the prognosis of a wide range of cancers, but their value in cervical cancer remains controversial. The aim of this study was to investigate the expression of SDF-1and NF-κB in cervical cancer and their significance in clinical prognosis. MATERIAL AND METHODS The expression of SDF-1and NF-κB in 105 formalin-fixed, paraffin-embedded cervical cancer tissues and the adjacent tissues was examined by immunohistochemistry (IHC). The results were semi-quantitatively scored and analyzed by chi-square test. The overall survival times (OS) were collected by follow-up and analyzed by Kaplan-Meier analysis. RESULTS The expression level of both SDF-1and NF-κB in cervical cancer are higher than that in the adjacent tissues (PSDF-1 expression are correlated with tumor size and FIGO histology grade (PSDF-1or NF-κB tended to have much shorter survival time than patients with negative expression. In addition, multivariate Cox regression analysis demonstrated that SDF-1 expression and lymph node metastasis are independent predictors of the OS in cervical cancer patients. CONCLUSIONS The expression of SDF-1 is significantly associated with tumor size and FIGO histology grade. The expression of NF-κB is significantly associated with tumor size, FIGO histology grade, and lymph node metastasis. The positive SDF-1or NF-κB expression is significantly correlated with poor prognosis. These may be valuable biomarkers for the prognosis and the potential therapeutic targets of cervical cancer.

  20. p16INK4 expression in precursor lesions of squamous cell cervical cancer related to the presence of HPV-DNA

    Directory of Open Access Journals (Sweden)

    A.E.G. Godoy

    2008-07-01

    Full Text Available The purpose of the present study was to identify the expression of p16INK4 in cervical cancer precursor lesions by immunohistochemistry and to correlate it with lesion grade and presence of human papillomavirus (HPV infection. Cervical specimens from 144 women seen consecutively at the gynecology outpatient clinic of our institution from December 2003 to May 2005 were analyzed by cytopathology, histopathology, polymerase chain reaction for HPV-DNA, and p16INK4 immunostaining. Histologically normal biopsies, HPV-DNA negative by polymerase chain reaction, were used as control. HPV-DNA prevalence, including the control group, was 68.1% and the prevalence of p16INK4 expression was 55.0%. The percentage of cells stained by p16INK4 ranged from 10 to 100%, both in the group consisting of cervical intraepithelial neoplasia (CIN1/HPV specimens and in the group of CIN2/CIN3 specimens with P value of 0.0001. p16INK4 expression was 48.3% in the CIN1/HPV group, as opposed to 94.3% in the CIN2/CIN3 group (P = 0.001, showing a statistically significant difference between the two groups. The quantitative method used here is simple and less subjective than the different semiquantitative methods described in the literature. In view of the different definitions of a p16INK4-positive case, it is almost impossible to compare the findings reported by different investigators. This study confirms the association between p16INK4 and CIN2 and CIN3 lesions. Moreover, it shows that some low grade lesions expressed high levels of this protein. This may indicate that such low grade lesions may be predisposed to progress to high grade lesions. This means that p16INK4 may be a strong marker for "neoplastic lesions" induced by HPV and not just an infection marker.

  1. The expression of SHH signaling pathway in cervical cancer or cervical intraepithelial neoplasia cells and its significance%SHH信号通路在宫颈癌或宫颈上皮内瘤变细胞中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    阿艳妮; 江敏; 汤云; 刘维琴

    2016-01-01

    Objective To investigate the expression and significance of Shh,Ptch,Smo protein and its downstream transcription factors Glil,Gli2,Gli3 protein in Sonic hedgehog signaling pathway in cervical cancer or cervical intraepithelial neoplasia.Method Sonic hedgehog signaling pathway expression in 57 cases of normal cervical epithelium (NC),86 cases of cervical intraepithelial neoplasia (CIN) tissues,137 cases of cervical squamous cell carcinoma (SCC) tissues were detected by immunohistochemical method.Results The expression of Shh,Ptch,Smo protein and its downstream transcription factors Glil,Gli2 and Gli3 protein in normal cervical tissues,cervical intraepithelial neoplasia tissue and cervical cancer tissue showed a gradual upward trend,with statistically significant difference among three groups (P<0.05).The expression of Shh,Ptch and Smo protein in cervical carcinoma were positively correlated with lymph node metastasis (P<0.01).Conclusion The high activation of Sonic hedgehog signaling pathway in cervical cancer patients is closely related to the occurrence and metastasis of cervical cancer.%目的 探讨Sonic hedgehog(SHH)信号通路中Shh、Ptch、Smo蛋白及其下游转录因子Gli1、Gli2、Gli3蛋白在宫颈癌或宫颈上皮内瘤变细胞中的表达及其意义.方法 采用免疫组织化学方法分别检测57例正常宫颈上皮组织(NC),86例宫颈上皮内瘤变组织(CIN),137例子宫颈鳞状细胞癌组织(SCC)中Sonic hedgehog信号通路的表达.结果 Shh、Ptch、Smo蛋白及其下游转录因子Gli1、Gli2、Gli3蛋白在正常宫颈组织、宫颈上皮内瘤变组织及宫颈癌组织的表达呈逐渐上升趋势,三组比较差异有统计学意义(P<0.05),Shh、Ptch、Smo蛋白在宫颈癌中的表达与淋巴结转移成正相关(P<0.01).结论 Sonic hedgehog信号通路在宫颈癌患者体内高度激活与宫颈癌的发病、转移密切相关.

  2. Multiple human papilloma virus infections predominant in squamous cell cervical carcinoma in Bandung

    Directory of Open Access Journals (Sweden)

    Edhyana Sahiratmadja

    2015-12-01

    Full Text Available BACKGROUND Persistent infection of high risk genotypes of human papilloma virus (hrHPV has been established as the etiological cause for cervical cancer, and the most prevalent genotypes that infect the cervical tissue are HPV-16 and HPV-18. However, HPV genotype profile has been shown to differ according to geographical distribution across the globe. The present study aimed to determine the HPV genotype distribution in cervical cancer patients from Bandung, Indonesia. METHODS During the period of July – November 2010 viral DNA was extracted from randomly chosen cervical cancer biopsies and subjected to genotype determination using the diagnostic linear array genotyping test (Roche. The distribution of HPV genotypes was explored and the prevalence of HPV genotypes was mapped. RESULTS Of 96 cervical cancer tissue samples, 76 (79.2% were histopathologically classified as squamous cell cervical carcinoma. Due to the high cost of HPV genotyping tests, only twenty-five samples were randomly genotyped. Almost 90% of the cervical cancer patients were multiply infected with HPV-16 in combination with HPV-18, HPV-45, or HPV-52. The HPV-16 genotype had the highest prevalence, all samples being infected with HPV-16. CONCLUSION The cervical cancer cases were predominantly infected by multiple hrHPVs with HPV-16 as the major genotype among other hrHPVs, supporting the carcinogenic role of this hrHPV. Therefore, screening for hrHPVs in the general population is urgently needed as a means of early detection of cervical cancer.

  3. Cervical cancer screening policies and coverage in Europe

    DEFF Research Database (Denmark)

    Anttila, Ahti; von Karsa, Lawrence; Aasmaa, Auni;

    2009-01-01

    The aim of the study was to compare current policy, organisation and coverage of cervical cancer screening programmes in the European Union (EU) member states with European and other international recommendations. According to the questionnaire-based survey, there are large variations in cervical...... with education, training and communication among women, medical professionals and authorities are required, accordingly. The study indicates that, despite substantial efforts, the recommendations of the Council of the EU on organised population-based screening for cervical cancer are not yet fulfilled. Decision......-makers and health service providers should consider stronger measures or incentives in order to improve cervical cancer control in Europe....

  4. THE TREATMENT AND EVOLUTION OF CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    Eduard Crauciuc,

    2010-09-01

    Full Text Available The purpose of this study is to establish the evolution of cervical cancer after applying a conventional treatment. Materials and methods. The study was performed on a number of 1249 patients who were suspected of having cervical neoplasia, and who were monitored between 2006-2010 in „Elena-Doamna” Clinical Hospital of Obstetrics and Gynecology in Ia�i, the Military Hospital Gala�i, the County Hospital Gala�i and the Emergency Hospital Buzau. Results and discussions. The study proved the effectiveness of the conservative treatment for the patients who were diagnosed using cytology, colposcopy, biopsy and histopathology, with or without HPV viral infection. Conclusions. The patients with an early diagnose have a 15% higher surviving probability. The patients who responded to the conservative preoperative treatment well are more likely to survive than the patients who did not respond favourably to the conservative preoperative treatment.

  5. Reduced expression of tissue factor pathway inhibitor-2 contributes to apoptosis and angiogenesis in cervical cancer

    Directory of Open Access Journals (Sweden)

    Zhang Qiao

    2012-01-01

    Full Text Available Abstract Background Tissue factor pathway inhibitor-2 (TFPI-2 is an extracellular matrix associated broad-spectrum Kunitz-type serine proteinase inhibitor. Recently, down regulation of TFPI-2 was suggested to be involved in tumor invasion and metastasis in some cancers. Methods This study involved 12 normal cervical squamous epithelia, 48 cervical intraepithelial neoplasia (CIN, and 68 cervical cancer. The expression of TFPI-2, Ki-67 and vascular endothelial growth factor (VEGF were investigated by immunohistochemistry staining. The apoptolic index(AI was determined with an in situ end-labeling assay(TUNEL. And the marker of CD34 staining was used as an indicator of microvessel density (MVD. Results TFPI-2 expression has a decreasing trend with the progression of cervical cancer and was significantly correlated with FIGO stage, lymph node metastasis and HPV infection. In addition, there were significant positive correlations between the grading of TFPI-2 expression and AI(P = 0.004. In contrast, the expression of TFPI-2 and VEGF or MVD was negatively correlated (both p Conclusions The results suggested that the expression of TFPI-2 had a decreasing trend with tumor progression of cervical cancer. There was a close association between the expression of TFPI-2 and tumor cell apoptosis and angiogenesis in patients with cervical cancer. TFPI-2 may play an inhibitive role during the development of cervical cancer.

  6. Activation of miR-9 by human papillomavirus in cervical cancer.

    Science.gov (United States)

    Liu, Weijun; Gao, Ge; Hu, Xiaoxia; Wang, Yuhui; Schwarz, Julie K; Chen, Jason J; Grigsby, Perry W; Wang, Xiaowei

    2014-11-30

    Cervical cancer is the third most common cancer in women worldwide, leading to about 300,000 deaths each year. Most cervical cancers are caused by human papillomavirus (HPV) infection. However, persistent transcriptional activity of HPV oncogenes, which indicates active roles of HPV in cervical cancer maintenance and progression, has not been well characterized. Using our recently developed assays for comprehensive profiling of HPV E6/E7 transcripts, we have detected transcriptional activities of 10 high-risk HPV strains from 87 of the 101 cervical tumors included in the analysis. These HPV-positive patients had significantly better survival outcome compared with HPV-negative patients, indicating HPV transcriptional activity as a favorable prognostic marker for cervical cancer. Furthermore, we have determined microRNA (miRNA) expression changes that were correlated with tumor HPV status. Our profiling and functional analyses identified miR-9 as the most activated miRNA by HPV E6 in a p53-independent manner. Further target validation and functional studies showed that HPV-induced miR-9 activation led to significantly increased cell motility by downregulating multiple gene targets involved in cell migration. Thus, our work helps to understand the molecular mechanisms as well as identify potential therapeutic targets for cervical cancer and other HPV-induced cancers.

  7. Cytotoxic Activity of 3,6-Dihydroxyflavone in Human Cervical Cancer Cells and Its Therapeutic Effect on c-Jun N-Terminal Kinase Inhibition

    Directory of Open Access Journals (Sweden)

    Eunjung Lee

    2014-08-01

    Full Text Available Previously we have shown that 3,6-dihydroxyflavone (3,6-DHF is a potent agonist of the human peroxisome proliferator-activated receptor (hPPAR with cytotoxic effects on human cervical cancer cells. To date, the mechanisms by which 3,6-DHF exerts its antitumor effects on cervical cells have not been clearly defined. Here, we demonstrated that 3,6-DHF exhibits a novel antitumor activity against HeLa cells with IC50 values of 25 μM and 9.8 μM after 24 h and 48 h, respectively. We also showed that the anticancer effects of 3,6-DHF are mediated via the toll-like receptor (TLR 4/CD14, p38 mitogen-activated protein kinase (MAPK, Jun-N terminal kinase (JNK, extracellular-signaling regulated kinase (ERK, and cyclooxygenase (COX-2 pathways in lipopolysaccharide (LPS-stimulated RAW264.7 cells. We found that 3,6-DHF showed a similar IC50 (113 nM value to that of the JNK inhibitor, SP600125 (IC50 = 118 nM in a JNK1 kinase assay. Binding studies revealed that 3,6-DHF had a strong binding affinity to JNK1 (1.996 × 105 M−1 and that the 6-OH and the carbonyl oxygen of the C ring of 3,6-DHF participated in hydrogen bonding interactions with the carbonyl oxygen and the amide proton of Met111, respectively. Therefore, 3,6-DHF may be a candidate inhibitor of JNKs, with potent anticancer effects.

  8. Limitations of Colposcopy in Early Invasive Cervical Cancer Detection

    OpenAIRE

    Grubišić, Goran

    2007-01-01

    Colposcopy is a key element in the diagnostic chain required to reduce cervical cancer mortality but it has limitations in the diagnosis of malignant disease. In the Republic of Croatia the Croatian Society for Colposcopy and Cervical Pathology started constructing guidelines for early detection, therapy and follow-up of patients with early invasive cervical cancer in order to achieve the best possible results in diagnosis, therapy and follow-up. From 2001 to 2006 Croatian society ...

  9. Understanding cervical cancer in the context of developing countries

    Directory of Open Access Journals (Sweden)

    Farhad Ali

    2012-01-01

    Full Text Available Cancer is one of the leading causes of deaths worldwide. Among the women, gynecological cancers are most common. Cervical cancer is a main gynecological cancer of the women. The global burden of cervical cancer is disproportionately high among the developing countries where 85 per cent of the estimated 493, 000 new cases and 273, 000 deaths occur worldwide. There are several dimensions of the problem. Cervical cancer is a problem where people are poor, where the socio-economic status of the women is low and sometimes specific ethnicity also posses additional risk to the women to develop cervical cancer. Human papillomavirus infection is a main risk factor for the cervical cancer however there are some other factors which increase the risk. Among them some are number of sexual partners, age of first sexual intercourse, infection of sexually transmitted diseases, use of hormonal contraceptives, parity, age, smoking, food and diet. Apart from these factors, some other issues, such as policy on cancer, capacity of health system, socio-economic and cultural factors and awareness among the women are also associated with the cervical cancer related morbidity and mortality across the developing countries. There some interventions which give promising results in terms of reducing cervical cancer related morbidity and mortality. Among them visual inspection of cervix with acetic acid followed by treatment is one such effective method.

  10. Global methylation silencing of clustered proto-cadherin genes in cervical cancer: serving as diagnostic markers comparable to HPV.

    Science.gov (United States)

    Wang, Kai-Hung; Lin, Cuei-Jyuan; Liu, Chou-Jen; Liu, Dai-Wei; Huang, Rui-Lan; Ding, Dah-Ching; Weng, Ching-Feng; Chu, Tang-Yuan

    2015-01-01

    Epigenetic remodeling of cell adhesion genes is a common phenomenon in cancer invasion. This study aims to investigate global methylation of cell adhesion genes in cervical carcinogenesis and to apply them in early detection of cancer from cervical scraping. Genome-wide methylation array was performed on an investigation cohort, including 16 cervical intraepithelial neoplasia 3 (CIN3) and 20 cervical cancers (CA) versus 12 each of normal, inflammation and CIN1 as controls. Twelve members of clustered proto-cadherin (PCDH) genes were collectively methylated and silenced, which were validated in cancer cells of the cervix, endometrium, liver, head and neck, breast, and lung. In an independent cohort including 107 controls, 66 CIN1, 85 CIN2/3, and 38 CA, methylated PCDHA4 and PCDHA13 were detected in 2.8%, 24.2%, 52.9%, and 84.2% (P diagnostic markers for cervical cancer noninferior to HPV.

  11. 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

    Directory of Open Access Journals (Sweden)

    Wei Keat Ng

    2015-01-01

    Full Text Available Thymoquinone (TQ has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7 and cervical cancer cell lines (HeLa and SiHa. TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235 nm with a narrow polydispersity index (PDI lower than 0.25. The zeta potential of TQ-NLC was greater than −30 mV. Polysorbate 80 helps to increase the stability of TQ-NLC. Differential scanning calorimetry showed that TQ-NLC has a melting point of 56.73°C, which is lower than that of the bulk material. The encapsulation efficiency of TQ in TQ-NLC was 97.63 ± 0.1798% as determined by HPLC analysis. TQ-NLC exhibited antiproliferative activity towards all the cell lines in a dose-dependent manner which was most cytotoxic towards MDA-MB-231 cells. Cell shrinkage was noted following treatment of MDA-MB-231 cells with TQ-NLC with an increase of apoptotic cell population (P<0.05. TQ-NLC also induced cell cycle arrest. TQ-NLC was most cytotoxic towards MDA-MB-231 cells. It induced apoptosis and cell cycle arrest in the cells.

  12. Synergistic effect of fisetin combined with sorafenib in human cervical cancer HeLa cells through activation of death receptor-5 mediated caspase-8/caspase-3 and the mitochondria-dependent apoptotic pathway.

    Science.gov (United States)

    Lin, Ming-Te; Lin, Chia-Liang; Lin, Tzu-Yu; Cheng, Chun-Wen; Yang, Shun-Fa; Lin, Chu-Liang; Wu, Chih-Chien; Hsieh, Yi-Hsien; Tsai, Jen-Pi

    2016-05-01

    Combining antitumor agents with bioactive compounds is a potential strategy for improving the effect of chemotherapy on cancer cells. The goal of this study was to elucidate the antitumor effect of the flavonoid, fisetin, combined with the multikinase inhibitor, sorafenib, against human cervical cancer cells in vitro and in vivo. The combination of fisetin and sorafenib synergistically induced apoptosis in HeLa cells, which is accompanied by a marked increase in loss of mitochondrial membrane potential. Apoptosis induction was achieved by caspase-3 and caspase-8 activation which increased the ratio of Bax/Bcl-2 and caused the subsequent cleavage of PARP level while disrupting the mitochondrial membrane potential in HeLa cells. Decreased Bax/Bcl-2 ratio level and mitochondrial membrane potential were also observed in siDR5-treated HeLa cells. In addition, in vivo studies revealed that the combined fisetin and sorafenib treatment was clearly superior to sorafenib treatment alone using a HeLa xenograft model. Our study showed that the combination of fisetin and sorafenib exerted better synergistic effects in vitro and in vivo than either agent used alone against human cervical cancer, and this synergism was based on apoptotic potential through a mitochondrial- and DR5-dependent caspase-8/caspase-3 signaling pathway. This combined fisetin and sorafenib treatment represents a novel therapeutic strategy for further clinical developments in advanced cervical cancer.

  13. ZBRK1 acts as a metastatic suppressor by directly regulating MMP9 in cervical cancer.

    Science.gov (United States)

    Lin, Li-Fang; Chuang, Chih-Hung; Li, Chien-Feng; Liao, Ching-Chun; Cheng, Chun-Pei; Cheng, Tian-Lu; Shen, Meng-Ru; Tseng, Joseph T; Chang, Wen-Chang; Lee, Wen-Hwa; Wang, Ju-Ming

    2010-01-01

    The BRCA1-interacted transcriptional repressor ZBRK1 has been associated with antiangiogenesis, but direct evidence of a tumor suppressor role has been lacking. In this study, we provide evidence of such a role in cervical carcinoma. ZBRK1 levels in cervical tumor cells were significantly lower than in normal cervical epithelial cells. In HeLa cervical cancer cells, enforced expression inhibited malignant growth, invasion, and metastasis in a variety of in vitro and in vivo assays. Expression of the metalloproteinase MMP9, which is known to be an important driver of invasion and metastasis, was found to be inversely correlated with ZBRK1 in tumor tissues and a target for repression in tumor cells. Our findings suggest that ZBRK1 acts to inhibit metastasis of cervical carcinoma, perhaps by modulating MMP9 expression.

  14. Cervical Cancer Screening | Cancer Trends Progress Report

    Science.gov (United States)

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  15. Expression and clinical significance of sulfiredoxin expression in cervical squamous cell carcinoma tissue

    Directory of Open Access Journals (Sweden)

    Xiao-yan CHEN

    2015-10-01

    Full Text Available Objective To inquire into the expression and its clinical significance of sulfiredoxin (Srx in cervical squamous cell carcinoma tissue. Methods SABC immunohistochemical method was used to detect the expression levels of Srx in specimens of 104 cervical squamous cell carcinoma and the corresponding adjacent tissues, 15 cervical intraepithelial neoplasm (CIN Ⅲ, and 20 normal cervical squamous cell epithelium tissue. The relationship between the expression of Srx protein and clinical pathological parameters of the cancer was also analyzed. Results The positive expression rates of Srx in CIN Ⅲ and cervical squamous cell carcinoma [73.3%(11/15 and 82.7%(86/104, respectively] were significantly higher than that in normal cervical tissue [35.0%(7/20, χ2=17.778, P=0.000]. Meanwhile, Srx expression in cervical cancer specimens was significantly higher than that in normal adjacent tissues (χ2=56.224, P=0.000. The positive expression of Srx in cervical squamous cell carcinoma was significantly correlated with lymph node metastasis, the depth of cancer invasion, and the infiltration of blood vessels (P0.05. Conclusion The higher expression of Srx protein might be a valuable marker for the early diagnosis and evaluation of prognosis in patients with cervical squamous cell carcinoma. DOI: 10.11855/j.issn.0577-7402.2015.08.11

  16. European cervical cancer screening:experiences and results

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Europe has devoted great efforts to cervical cancer screening over 30 years.The mortality was generally declining although incidence rates of cervical cancer among young women have been increasing in many countries of Europe.The efficiency of screening,however,needs to be addressed by planners for an improved cost-effectiveness in the future.

  17. Paclitaxel and carboplatin concurrent with radiotherapy for primary cervical cancer

    NARCIS (Netherlands)

    De Vos, FYFL; Bos, AME; Gietema, JA; Pras, E; Van Der Zee, AGJ; De Vries, EGE; Willemse, PHB

    2004-01-01

    Background: Concurrent radiochemotherapy is currently considered the new standard treatment in locally advanced cervical cancer. Patients and Methods: Eight women with cervical cancer stage IB2-IVA were treated with standard radiation therapy in combination with standard carboplatin (AUC=2, once wee

  18. An overview of innovative techniques to improve cervical cancer screening

    NARCIS (Netherlands)

    Nijhuis, Esther R.; Reesink-Peters, Nathalie; Wisman, G. Bea A.; Nijman, Hans W.; van Zanden, Jelmer; Volders, Haukeline; Hollema, Harry; Suurmeijer, Albert J. H.; Schuuring, Ed; van der Zee, Ate G. J.

    2006-01-01

    Although current cytomorphology-based cervical cancer screening has reduced the incidence of cervical cancer, Pap-smears are associated with high false positive and false negative rates. This has spurred the search for new technologies to improve current screening. New methodologies are automation o

  19. Breaking the DNA damage response to improve cervical cancer treatment

    NARCIS (Netherlands)

    Wieringa, Hylke W.; van der Zee, Ate G. J.; Vries, de Elisabeth G. E.; van Vugt, Marcel A. T. M.

    2016-01-01

    Every year, cervical cancer affects similar to 500,000 women worldwide, and similar to 275,000 patients die of this disease. The addition of platin-based chemotherapy to primary radiotherapy has increased 5-year survival of advanced-stage cervical cancer patients, which is, however, still only 66%.

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

    Science.gov (United States)

    ... html Are Fewer Cervical Cancer Screenings Needed After HPV Vaccine? Less testing could reduce risk of false positives ... said. Women vaccinated with earlier versions of the HPV vaccine -- which protect against the two worst cancer-causing ...

  1. Screening, HPV Vaccine Can Prevent Cervical Cancer: FDA

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_163464.html Screening, HPV Vaccine Can Prevent Cervical Cancer: FDA Agency recommends ... cancer, which is caused by the human papillomavirus (HPV). An FDA-approved vaccine called Gardasil 9 protects ...

  2. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer:

    DEFF Research Database (Denmark)

    Vale, Claire; Jakobsen, Anders

    2008-01-01

    BACKGROUND: After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated, and some important clinical questions...

  3. Common filaggrin gene mutations and risk of cervical cancer

    DEFF Research Database (Denmark)

    Bager, Peter; Wohlfahrt, Jan; Sørensen, Erik

    2015-01-01

    BACKGROUND: As carriers of filaggrin gene (FLG) mutations may have a compromised cervical mucosal barrier against human papillomavirus infection, our primary objective was to study their risk of cervical cancer. METHODS: We genotyped 586 cervical cancer patients for the two most common FLG...... mutations, R501X and 2282del4, using blood from the Copenhagen Hospital Biobank, Denmark. Controls (n = 8050) were genotyped in previous population-based studies. Information on cervical cancer, mortality and emigration were obtained from national registers. Odds ratios (OR) were estimated by logistic...... and stratification by cancer stage. RESULTS: The primary results showed that FLG mutations were not associated with the risk of cervical cancer (6.3% of cases and 7.7% of controls were carriers; OR adjusted 0.81, 95% CI 0.57-1.14; OR adjusted+ weighted 0.96, 95% CI 0.58-1.57). Among cases, FLG mutations increased...

  4. Human papillomavirus type 16 E6 suppresses microRNA-23b expression in human cervical cancer cells through DNA methylation of the host gene C9orf3.

    Science.gov (United States)

    Au Yeung, Chi Lam; Tsang, Tsun Yee; Yau, Pak Lun; Kwok, Tim Tak

    2017-01-06

    Oncogenic protein E6 of human papillomavirus type 16 (HPV-16) is believed to involve in the aberrant methylation in cervical cancer as it upregulates DNA methyltransferase 1 (DNMT1) through tumor suppressor p53. In addition, DNA demethylating agent induces the expression of one of the HPV-16 E6 regulated microRNAs (miRs), miR-23b, in human cervical carcinoma SiHa cells. Thus, the importance of DNA methylation and miR-23b in HPV-16 E6 associated cervical cancer development is investigated. In the present study, however, it is found that miR-23b is not embedded in any typical CpG island. Nevertheless, a functional CpG island is predicted in the promoter region of C9orf3, the host gene of miR-23b, and is validated by methylation-specific PCR and bisulfite genomic sequencing analyses. Besides, c-MET is confirmed to be a target gene of miR-23b. Silencing of HPV-16 E6 is found to increase the expression of miR-23b, decrease the expression of c-MET and thus induce the apoptosis of SiHa cells through the c-MET downstream signaling pathway. Taken together, the tumor suppressive miR-23b is epigenetically inactivated through its host gene C9orf3 and this is probably a critical pathway during HPV-16 E6 associated cervical cancer development.

  5. Vaginal delivery of carboplatin-loaded thermosensitive hydrogel to prevent local cervical cancer recurrence in mice.

    Science.gov (United States)

    Wang, Xue; Wang, Jin; Wu, Wenbin; Li, Hongjun

    2016-11-01

    Local tumor recurrence after cervical cancer surgery remains a clinical problem. Vaginal delivery of thermosensitive hydrogel may be suited to reduce tumor relapse rate with more efficacy and safety. A pilot study was carried out to evaluate the efficacy of carboplatin-loaded poloxamer hydrogel to prevent local recurrence of cervical cancer after surgery. In vivo vaginal retention evaluation of 27% poloxamer hydrogel in mice was proven to be a suitable vaginal drug delivery formulation due to its low gelation temperature. A mimic orthotopic cervical/vaginal cancer recurrence model after surgery was established by injecting murine cervical cancer cell line U14 into the vaginal submucosa to simulate the residual tumor cells infiltrated in the surgical site, followed by drug administration 24 h later to interfere with the formation/recurrence of the tumor. By infusing fluorescein sodium-loaded hydrogel into the vagina of mice, a maximized accumulation of fluorescein sodium (Flu) in the vagina was achieved and few signals were observed in other organs. When used in the prevention of the cervical cancer formation/recurrence in mice, the carboplatin-loaded poloxamer hydrogel exhibited great efficacy and systemic safety. In conclusion, thermosensitive hydrogel presents a simple, practical approach for the local drug delivery via vagina against cervical cancer recurrence.

  6. Virally mediated cervical cancer in the iatrogenically immunocompromised: applications for psychoneuroimmunology.

    Science.gov (United States)

    Jensen, Sally E; Lehman, Brandy; Antoni, Michael H; Pereira, Deidre B

    2007-08-01

    Oncogenic or high-risk (HR) human papillomavirus (HPV) infection is implicated in the pathogenesis of a number of cancers, including cervical cancer. HPV infected individuals who are immunocompromised secondary to acquired (e.g., human immunodeficiency virus [HIV]) or iatrogenic (e.g., systemic lupus erythematosus [SLE] patients and organ and hematopoeitic stem cell transplant recipients undergoing immunosuppressive therapy) immune deficiency are particularly at risk for HPV-initiated cervical neoplasia and cancer. Psychoneuroimmunologic (PNI) research has demonstrated that psychosocial factors such as stress, pessimism, and sleep quality may play a role in the promotion of HPV-mediated cervical neoplasia in HIV-positive women. However, no research to our knowledge has examined PNI mechanisms of HPV-mediated cervical neoplasia and cancer in women who are undergoing iatrogenic immunosuppressive therapy for the treatment of autoimmune disease or the prevention of graft-rejection. This article reviews the PNI mechanisms that may underlie the promotion of HPV-mediated cervical neoplasia and applies this model to HPV-infected women who are iatrogenically immunosuppressed, an understudied population at-risk for cervical cancer. Female transplant recipients, one such group, may provide a unique paradigm in which to explore further PNI mechanisms of HPV-mediated cervical neoplasia.

  7. Changes in knowledge of cervical cancer following introduction of human papillomavirus vaccine among women at high risk for cervical cancer

    Directory of Open Access Journals (Sweden)

    L. Stewart Massad

    2015-04-01

    Conclusion: Substantial gaps in understanding of HPV and cervical cancer prevention exist despite years of health education. While more effective educational interventions may help, optimal cancer prevention may require opt-out vaccination programs that do not require nuanced understanding.

  8. Advancing cervical cancer prevention in India: implementation science priorities.

    Science.gov (United States)

    Krishnan, Suneeta; Madsen, Emily; Porterfield, Deborah; Varghese, Beena

    2013-01-01

    Cervical cancer is the leading cause of cancer mortality in India, accounting for 17% of all cancer deaths among women aged 30 to 69 years. At current incidence rates, the annual burden of new cases in India is projected to increase to 225,000 by 2025, but there are few large-scale, organized cervical cancer prevention programs in the country. We conducted a review of the cervical cancer prevention research literature and programmatic experiences in India to summarize the current state of knowledge and practices and recommend research priorities to address the gap in services. We found that research and programs in India have demonstrated the feasibility and acceptability of cervical cancer prevention efforts and that screening strategies requiring minimal additional human resources and laboratory infrastructure can reduce morbidity and mortality. However, additional evidence generated through implementation science research is needed to ensure that cervical cancer prevention efforts have the desired impact and are cost-effective. Specifically, implementation science research is needed to understand individual- and community-level barriers to screening and diagnostic and treatment services; to improve health care worker performance; to strengthen links among screening, diagnosis, and treatment; and to determine optimal program design, outcomes, and costs. With a quarter of the global burden of cervical cancer in India, there is no better time than now to translate research findings to practice. Implementation science can help ensure that investments in cervical cancer prevention and control result in the greatest impact.

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

    Directory of Open Access Journals (Sweden)

    Yingjia Lin

    2015-01-01

    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.

  10. Inotodiol对宫颈癌HeLa细胞增殖的影响%effect of Inotodiol on proliferation of cervical cancer HeLa cells

    Institute of Scientific and Technical Information of China (English)

    赵丽微; 钟秀宏; 杨淑艳; 杨宁江

    2013-01-01

    目的:研究桦褐孔菌单体(Inotodiol)对宫颈癌HeLa细胞增殖的影响.方法:采用MTT法检测Inotodiol对HeLa细胞的增殖抑制率;通过倒置显微镜、HE染色观察HeLa细胞形态学改变;通过免疫细胞化学法检测核增殖抗原Ki-67表达.结果:随着Inotodiol浓度增加及作用时间延长,抑制率明显增强,差异有统计学意义(P<0.05).Inotodiol作用于Hela细胞后,形态学观察示细胞凋亡.Inotodiol组Ki-67表达明显降低,与对照组相比差异有统计学意义(P<0.01).结论:Inoto-diol对宫颈癌HeLa细胞有明显的抑制增殖和诱导凋亡作用.%Objective: To research the effect of Inotodiol on proliferation of cervical cancer HeLa cells.Methods: MTT assay was used to detect the inhibition rate of Inotodiol on proliferation of HeLa cells.The morphological changes of HeLa cells were observed by invert microscope and HE staining.The expression of Ki - 67 was detected by immunocytochemical method.Results: The inhibition rate increased significantly with the increase of Inotodiol concentration and the time, there was statistically significant difference (P < 0.05) .Apoptosis of HeLa cells was observed after treated with Inotodiol.The expression level of Ki - 67 in Inotodiol group decreased significantly, compared with control group, there was statistically significant difference (P <0.01 ) .Conclusion: Inotodiol can inhabit proliferation and induce apoptosis of cervical cancer HeLa cells significantly.

  11. Effect of lipid raft on the growth of cervical cancer cells%脂筏对子宫颈癌细胞生长的影响

    Institute of Scientific and Technical Information of China (English)

    程艳香; 徐红; 周利梅; 黄金玲; 李秉枢; 胡敏

    2012-01-01

    目的 探讨脂筏对子宫颈癌细胞生长的影响并初步探讨其作用机制.方法 将HeLa细胞系分为不处理对照组、脂筏干扰剂组及NADPH氧化酶抑制剂组,四甲基偶氮唑蓝(MTT)法测定各组培养24h后的细胞存活率,Western blot法检测各组细胞内缺氧诱导因子1α(HIF-1α)蛋白相对含量.结果 与对照组相比脂筏干扰剂组细胞的生长速度明显减慢(0.612±0.051与0.984±0.034),NADPH氧化酶抑制剂组显示了类似的效应(0.591±0.074与0.984±0.034),差异有统计学意义(t=4.062,P< 0.05).与对照组相比脂筏干扰剂组及NADPH氧化酶抑制剂组HIF-1α的表达量也明显降低(1.79±0.14与2.56±0.22; 1.54±0.12与2.56±0.22),差异有统计学意义(t=2.423,P< 0.05).结论 脂筏可能通过NADPH氧化酶激活途径激活HIF-1α及其下游原癌基因促进子宫颈癌细胞的生长,脂筏干扰剂及NADPH氧化酶抑制剂可能成为子宫颈癌药物治疗新的研究方向.%Objective To explore the effect of lipid raft on cervical cancer cell growth and its mechanisms Methods HeLa cells in logarithmic phase were divided into three groups including control group, lipid raft interference agent group,and NADPH oxidase inhibitors group.Cells were treated with fre sh medium,3 μmol/L Apocynin and 1 mmol/L M-beta CD, respectively, for 24 h.Cell survival rate was detected using the MTT method, and the HIF-1α level was examined by Western-blot. Results Cell growths of the lipid raft interference agent group and NADPH oxidase inhibitors group were significantly slower than control group,(0.612±0.051 vs 0.984±0.034,0.591 ±0.074 vs 0.984±0.034,t=4.062,P<0.05).HIF-1α expression in the lipid raft interference agent group and NADPH oxidase inhibitors group was also significantly reduced compared with control group (1.79±0.14 vs 2.56±0.22 and 1.54±0.12 vs 2.56±0.22) and the difference was significant (t=2.423,P<0.05). Conclusion Lipid raft-NADPH oxidase pathway may

  12. Human papillomavirus DNA in plasma of patients with HPV16 DNA-positive uterine cervical cancer.

    OpenAIRE

    Shimada, Takako; Yamaguchi, Naohiro; Nishida, Noriyuki; Yamasaki, Kentaro; Miura, Kiyonori; Katamine, Shigeru; Masuzaki, Hideaki

    2010-01-01

    OBJECTIVES: The squamous cell carcinoma antigen is considered the most accurate serologic tumor marker for uterine cervical carcinoma. However, serum squamous cell carcinoma antigen levels were found to correlate significantly with clinical severity of atopic dermatitis and chronic renal failure. The present study was conducted in patients with human papillomavirus 16 DNA-positive uterine cervical cancer to determine the plasma level of human papillomavirus 16 DNA and the diagnostic values of...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  15. Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research.

    Science.gov (United States)

    Lee, Sung Jong; Yang, Andrew; Wu, T C; Hung, Chien Fu

    2016-09-01

    Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.

  16. Risk of cervical cancer after completed post-treatment follow-up of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Helmerhorst, Theo; Habbema, Dik;

    2012-01-01

    To compare the risk of cervical cancer in women with histologically confirmed cervical intraepithelial neoplasia who returned to routine screening after having completed post-treatment follow-up with consecutive normal smear test results with women with a normal primary smear test result....

  17. Correlation of DNA Ploidy with Progression of Cervical Cancer

    Directory of Open Access Journals (Sweden)

    M. Singh

    2008-01-01

    Full Text Available The majority of squamous cell carcinomas of cervix are preceded by visible changes in the cervix, most often detected by cervical smear. As cervical cancer is preceded by long precancerous stages, identification of the high-risk population through detection of DNA ploidy may be of importance in effective management of this disease. Here we attempted to correlate aneuploid DNA patterns and their influence on biological behavior of flow-cytometry analysis of DNA ploidy which was carried out in cytologically diagnosed cases of mild (79, moderate (36, and severe (12 dysplasia, as well as “atypical squamous cells of unknown significance (ASCUS” (57 along with controls (69, in order to understand its importance in malignant progression of disease. Cytologically diagnosed dysplasias, which were employed for DNA ploidy studies, 39 mild, 28 moderate, and 11 severe dysplasia cases were found to be aneuploid. Out of the 69 control subjects, 6 cases showed aneuploidy pattern and the rest 63 subjects were diploid. An aneuploidy pattern was observed in 8 out of 57 cases of cytologically evaluated ASCUS. The results of the followup studies showed that aberrant DNA content reliably predicts the occurrence of squamous cell carcinoma in cervical smear. Flow cytometric analysis of DNA ploidy may provide a strategic diagnostic tool for early detection of carcinoma cervix. Therefore, it is a concept of an HPV screening with reflex cytology in combination with DNA flow cytometry to detect progressive lesions with the greatest possible sensitivity and specificity.

  18. LOSS OF HETEROZYGOSITY ON CHROMOSOME 17p13.3 IN OVARIAN CANCER AND CERVICAL CANCER

    Institute of Scientific and Technical Information of China (English)

    Zhang Guoling; Yang Huijian; Xu Kaili; Zhou Jin; Qin Ruidi; Lu Minghua

    1998-01-01

    Objective:To identify the loss of heterozygosity (LOH) on chromosome 17p13.3 in ovarian cancer and cervical cancer. Methods: The frequency of LOH on chromosome 17p13.3 in DNA samples from 24 ovarian cancers, 9 cervical cancers, and 13 non-malignant gynecological diseases were determined respectively, using Southern blot method with probe PYNZ.22. Results:LOH on 17p13.3 was found in 12 of 24 (50.0%) ovarian cancers (including a borderline mucinous cystadenoma), 4of 9 (44.4%) cervical carcinomas, and 1 of 13 (7.7%) nonmalignant gynecological diseases, which was cervical intraepithelial neoplasm HI (CIN Ⅲ) (P<0.01).Conclusion: These results show that LOH on 17p13.3 is associated with ovarian cancer and cervical cancer,suggesting that detection of LOH on 17p13.3 may be helpful to understand the molecular pathogenesis of ovarian cancer and cervical cancer.

  19. 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

    Science.gov (United States)

    2016-10-26

    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

  20. Screening and identification of the peptides specifically binding to cervical cancer HeLa cell%宫颈癌HeLa细胞特异性结合肽的筛选及鉴定

    Institute of Scientific and Technical Information of China (English)

    何晓娟; 郭彩霞; 杨陈; 梁晓秋

    2012-01-01

    Background and purpose: Molecular targeted therapy was paid much attention for its good therapeutic effects on cervical cancer and deeply decreased the injuries of the human body. This study aimed to screen and identify the peptides specifically binding to cervical cancer by using phage display in vivo. It may be the targeting vector of the chemotherapeutics and be the basic of the targeted drugs of cervical cancer. Methods: Human cervical cancer HeLa cell was cultured in vivo and the tumor animal model was made in nude mice. After phage peptide library was injected in mouse by intravenous injection and heart perfusion was carried out after 15 minutes, cervical cancer was harvested. Cervical cancer specific peptides that used in the next screening were obtained after amplification and purification in vivo. After 3 circulations, the affinity and specificity of phage clones to cervical cancer cells were preliminary indentified by enzyme linked immunosorbent assay (ELISA) and immunohistochemistry. The positive phage clone was amplified and the sequences were analyzed to determine the collective sequence. Results: The 10 phage clones were identified by ELISA, 8 of them were specially bound to the HeLa cell line which had the same amino acid sequence that is LLRSTGF. Conclusion: The peptides specifically binding to cervical cancer HeLa cell are screened and identified. All the results lay the foundation for the development of diagnostic reagents and drugs of cervical cancer.%背景与目的:宫颈癌的分子靶向治疗具有很好的疗效,同时可以显著减少抗癌药物对人体自身的损伤,因此备受关注.本研究利用噬菌体体内展示技术筛选及鉴定宫颈癌特异性结合肽,将有可能成为化疗药物的靶向载体,为宫颈癌靶向药物治疗奠定基础.方法:体外培养宫颈癌HeLa细胞接种裸鼠,建立肿瘤动物模型.将随机肽库尾静脉注入裸鼠体内,循环15 min,心脏灌注后回收肿瘤组织噬菌体扩增

  1. Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients

    Directory of Open Access Journals (Sweden)

    Imajoh Masayuki

    2012-08-01

    Full Text Available Abstract Background Merkel cell polyomavirus (MCPyV was identified originally in Merkel cell carcinoma (MCC, a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i the major histological type of cervical cancer is the SCC; (ii the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV. In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs were also studied. Results Formalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19% and 4/16 cervical ACs (25% were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs. Conclusions This study provides the first observation that MCPyV coexists in a subset

  2. Slug inhibits the proliferation and tumor formation of human cervical cancer cells by up-regulating the p21/p27 proteins and down-regulating the activity of the Wnt/β-catenin signaling pathway via the trans-suppression Akt1/p-Akt1 expression

    Science.gov (United States)

    Cui, Nan; Yang, Wen-Ting; Zheng, Peng-Sheng

    2016-01-01

    Slug (Snai2) has been demonstrated to act as an oncogene or tumor suppressor in different human cancers, but the function of Slug in cervical cancer remains poorly understood. In this study, we demonstrated that Slug could suppress the proliferation of cervical cancer cells in vitro and tumor formation in vivo. Further experiments found that Slug could trans-suppress the expression of Akt1/p-Akt1 by binding to E-box motifs in the promoter of the Akt1 gene and then inhibit the cell proliferation and tumor formation of cervical cancer cells by up-regulating p21/p27 and/or down-regulating the activity of the Wnt/β-catenin signaling pathway. Therefore, Slug acts as a tumor suppressor during cervical carcinogenesis. PMID:27036045

  3. Update on prevention and screening of cervical cancer

    Science.gov (United States)

    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

  4. Screening for cervical cancer: when theory meets reality

    Directory of Open Access Journals (Sweden)

    Nygård Mari

    2011-06-01

    Full Text Available Abstract 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.

  5. Novel Somatic Copy Number Alteration Identified for Cervical Cancer in the Mexican American Population

    Directory of Open Access Journals (Sweden)

    Alireza Torabi

    2016-08-01

    Full Text Available Cervical cancer affects millions of Americans, but the rate for cervical cancer in the Mexican American is approximately twice that for non-Mexican Americans. The etiologies of cervical cancer are still not fully understood. A number of somatic mutations, including several copy number alterations (CNAs, have been identified in the pathogenesis of cervical carcinomas in non-Mexican Americans. Thus, the purpose of this study was to investigate CNAs in association with cervical cancer in the Mexican American population. We conducted a pilot study of genome-wide CNA analysis using 2.5 million markers in four diagnostic groups: reference (n = 125, low grade dysplasia (cervical intraepithelial neoplasia (CIN-I, n = 4, high grade dysplasia (CIN-II and -III, n = 5 and invasive carcinoma (squamous cell carcinoma (SCC, n = 5 followed by data analyses using Partek. We observed a statistically-significant difference of CNA burden between case and reference groups of different sizes (>100 kb, 10–100 kb and 1–10 kb of CNAs that included deletions and amplifications, e.g., a statistically-significant difference of >100 kb deletions was observed between the reference (6.6% and pre-cancer and cancer (91.3% groups. Recurrent aberrations of 98 CNA regions were also identified in cases only. However, none of the CNAs have an impact on cancer progression. A total of 32 CNA regions identified contained tumor suppressor genes and oncogenes. Moreover, the pathway analysis revealed endometrial cancer and estrogen signaling pathways associated with this cancer (p < 0.05 using Kyoto Encyclopedia of Genes and Genomes (KEGG. This is the first report of CNAs identified for cervical cancer in the U.S. Latino population using high density markers. We are aware of the small sample size in the study. Thus, additional studies with a larger sample are needed to confirm the current findings.

  6. Low Proteolytic Clipping of Histone H3 in Cervical Cancer

    OpenAIRE

    Sandoval-Basilio, Jorge; Serafín-Higuera, Nicolás; Reyes-Hernandez, Octavio D.; Serafín-Higuera, Idanya; Leija-Montoya, Gabriela; Blanco-Morales, Magali; Sierra-Martínez, Monica; Ramos-Mondragon, Roberto; García, Silvia; López-Hernández, Luz Berenice; Yocupicio-Monroy, Martha; Alcaraz-Estrada, Sofia L.

    2016-01-01

    Chromatin in cervical cancer (CC) undergoes chemical and structural changes that alter the expression pattern of genes. Recently, a potential mechanism, which regulates gene expression at transcriptional levels is the proteolytic clipping of histone H3. However, until now this process in CC has not been reported. Using HeLa cells as a model of CC and human samples from patients with CC, we identify that the H3 cleavage was lower in CC compared with control tissue. Additionally, the histone H3...

  7. Involvement of mitochondria and caspase pathways in N-demethyl-clarithromycin-induced apoptosis in human cervical cancer HeLa cell

    Institute of Scientific and Technical Information of China (English)

    Ai-min QIAO; Takashi IKEJIMA; Shini-chi TASHIRO; Satoshi ONODERA; Wei-ge ZHANG; Ying-liang WU

    2006-01-01

    Aim: To study the mechanisms by which N-demethyl-clarithromycin (NDC) induces human cervical cancer HeLa cell apoptosis in vitro. Methods: The viability of N-demethyl-clarithromycin-induced HeLa cells was measured by MTT assay. Apoptotic cells with condensed nuclei were visualized by phase contrast microscopy. Nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis. Measurement of mitochondrial transmembrane potential was analyzed by a FACScan flowcytometer. Caspase-3, poly-(ADP-ribose) polymerase (PARP), caspase-activated DNase (ICAD), Bcl-2, Bax, p53, and SIRT1 protein expression and the release of cytochrome c were detected by Western blot analysis. Results: N-demethyl-clarithromycin, an anti-inflammatory substance, inhibited HeLa cell growth in a dose- and time-dependent manner.N-demethyl-clarithromycin induced HeLa cell death through the apoptotic pathways. The pan-caspase inhibitor (z-VAD-fmk), caspase-3 inhibitor (z-DEVD-fmk) and the caspase-9 inhibitor (z-LEHD-fmk) partially enhanced cell viability induced by N-demethyl-clarithromycin, but the caspase-8 inhibitor (z-IETD-fmk) had almost no effect. Caspase-3 was activated then followed by the degradation of caspase-3 substrates, the inhibitor of ICAD and PARP. Simultaneously, mitochondrial transmembrane potential was markedly reduced and the release of cytochrome c in the cytosol was increased.N-demethyl-clarithromycin upregulated the expression ratio of mitochondrial Bax/Bcl-2, and significantly increased the expression of the p53 protein. It also downregulated anti-apoptotic protein SIRT1 expression. Conclusion: N-demethyl-clarithromycin induced apoptosis in HeLa cells via the mitochondrial pathway.

  8. Preventive vaccines for cervical cancer Vacunas para prevenir el cáncer cervical

    OpenAIRE

    Wheeler, Cosette M.

    1997-01-01

    The potential use of vaccines for the human papillomavirus (HPV) in the prevention and treatment of cervical cancer is a possibility in the near future. Close to 20 genotypes of HPV, of the 75 that have been identified, infect the femine genital tract, but four subtypes (16, 18, 31 and 45) have been associated in close to 80% of cervical cancers. this article proposes that in order to design an effective prophylactic vaccine against HPV infection, an adequate immune response should be guarant...

  9. Youtube as a source of information on cervical cancer

    Directory of Open Access Journals (Sweden)

    Janak Adhikari

    2016-01-01

    Full Text Available Background: Cervical cancer is the third most common cancer worldwide. Accurate information about cervical cancer to general public can lower the burden of the disease including its mortality. Aims: We aimed to look at the quality of information available in YouTube for cervical cancer. Materials and Methods: We searched YouTube (http://www.youtube.com for videos using the keyword "Cervical cancer" on November 12, 2015. Videos were then analyzed for their source and content of information. Results: We studied 172 videos using the keyword "Cervical cancer" on November 12, 2015. We found that there were videos describing the personal stories, risk factors, and the importance of screening. However, videos discussing all the aspects of cancers were lacking. Likewise, videos from the reputed organization were also lacking. Conclusion: Although there were numerous videos available in cervical cancer, videos from reputed organizations including Center for Disease Control and Prevention, American Cancer Society, and World Health Organization were lacking. We strongly believe that quality videos from such organizations via YouTube can help lower the burden of disease.

  10. Comparison of Linear Array and Line Blot Assay for Detection of Human Papillomavirus and Diagnosis of Cervical Precancer and Cancer in the Atypical Squamous Cell of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study▿

    OpenAIRE

    Castle, Philip E.; Gravitt, Patti E.; Solomon, Diane; Wheeler, Cosette M.; Schiffman, Mark

    2007-01-01

    We evaluated Linear Array (LA), a newly commercialized PGMY09/11 L1 consensus primer PCR test that detects 37 human papillomavirus (HPV) genotypes by reverse line blot hybridization, for the detection of individual HPV genotypes and carcinogenic HPV and its clinical performance for detecting 2-year cumulative cervical precancer and cancer using archived specimens from the Atypical Squamous Cell of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion Triage Study. LA...

  11. HPV16 variant lineage, clinical stage, and survival in women with invasive cervical cancer

    Directory of Open Access Journals (Sweden)

    Zuna Rosemary E

    2011-10-01

    Full Text Available Abstract Background HPV16 variants are associated with different risks for development of CIN3 and invasive cancer, although all are carcinogenic. The relationship of HPV 16 variants to cancer survival has not been studied. Methods 155 HPV16-positive cervical cancers were categorized according to European and non-European variant patterns by DNA sequencing of the E6 open reading frame. Clinico-pathologic parameters and clinical outcome were collected by chart review and death registry data. Results Of the 155 women (mean age 44.7 years; median follow-up 26.7 months, 85.2% harbored European variants while 14.8% had non-European sequences. HPV16 variants differed by histologic cell type (p = 0.03 and stage (1 vs. 2+; p = 0.03. Overall, 107 women (68.0% were alive with no evidence of cancer, 42 (27.1% died from cervical cancer, 2 (1.3% were alive with cervical cancer, and 4 (2.6% died of other causes. Death due to cervical cancer was associated with European variant status (p Conclusions Overall, invasive cervical cancers with non-European variants showed a less aggressive behavior than those with European variants. These findings should be replicated in a population with more non-European cases.

  12. Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan.

    Science.gov (United States)

    Loya, Asif; Serrano, Beatriz; Rasheed, Farah; Tous, Sara; Hassan, Mariam; Clavero, Omar; Raza, Muhammad; De Sanjosé, Silvia; Bosch, F Xavier; Alemany, Laia

    2016-07-30

    Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0-91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7-83.3), compared to Asia (71.6%; 69.9-73.4) and worldwide (70.8%; 69.9-71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9-15.7 vs. 19.8%; 18.3-21.3 and 18.5%; 17.7-19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases.

  13. THE CONSTRUCTION AND EXPRESSION OF THE MURINE SCFV GENE IN E. COLI AGAINST HUMAN CERVICAL CANCER

    Institute of Scientific and Technical Information of China (English)

    Wang Ying; Chen Wei; Li Xu

    2006-01-01

    Objective To obtain the gene of murine Single chain Fv fragment (ScFv) against human cervical cancer and to express it in E. coli. Methods The variable region gene fragments of the heavy and light chains, which were amplified respectively using recombinant DNA techniques from CsA125 hybridoma cells, were spliced together through a flexible linker to ScFv against human cervical cancer. The ScFv genes were then cloned into expression vector pCANTAB 5E and expressed in E. coli HB2151 and TG1 respectively. The soluble ScFv were characterized by SDS PAGE and Western blot. The antigen-binding activities of the soluble and phage displayed ScFv were assayed by ELISA and cell immunohistochemical analysis. Results The expressed ScFv antibodies were soluble and phage displayed. The soluble ScFv secreted and expressed in E. coli HB2151 induced by IPTG were confirmed with SDS-PAGE, Western blot and ELISA. The specific binding capacity of the soluble and phage displayed ScFv to the surface associated antigen of human cervical cancer cell line was further confirmed with immunohistochemical studies. Conclusion The soluble and phage displayed ScFv expressed in E. coli against human cervical cancer showed high, specific affinity for the cervical cancer cell line surface associated antigen.

  14. GENERAL AWARNANCE OF HUMAN PAPILLOMA VIRUS VACCINE AGAINST CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    SAFILA NAVEED

    2014-01-01

    Full Text Available We have conducted a survey program on the awarnance of HPV vaccine of cervical cancer in common people. Methods: For this survey we perform 2 steps. First we made a questionnaires in which we ask to female of different belongs to different education field either they are married or not. Secondly we gone in the different hospitals of Karachi and observe treatment, diagnosis, vaccination availability and frequency of cervical cancer. Results:From questionnaire we observed that only 1 % female are aware about cervical cancer and its vaccine i.e. HPV, even female belongs medical field are not aware about it. Form hospital survey we observed that frequency of cervical cancer is very less but in Shaukat Khanum hospital 90 cases reported out of 1803 cancer. The given treatment is radiology, chemotherapy and surgery.

  15. Isolation and identification of side population cells in human cervical cancer and analysis of biological characteristics%人宫颈癌侧群细胞的分选及其生物学特性的研究

    Institute of Scientific and Technical Information of China (English)

    宋菁华; 王克芳; 李斌; 张军

    2012-01-01

    Objective To isolate side population (SP) cells from human cervical cancer cells and to determine the characteristics of cancer stem cells, so as to investigate the feasibility of starting research on cervical cancer stem cells from the SP cells. Methods The human cervical cancer cells were obtained from fresh human cervical cancer tissue of 40 patients who were diagnosed as cervical cancer. Flow cytometry and Hoechst 33342 dye efflux assay were used to isolate SP cells and NSP cells from the cervical cancer cells. The proliferation and differentiation of the two sub - population cells were observed. The two sub - population cells were injected into nude mice subcutaneously to observe their tumorigenesis ability. The inhibition rates of SP and NSP cells were assessed after treatment with chemotherapy drugs ( cisplatin) to evaluate the resistance. Results The proportion of SP cells excluding Hoechst 33342 dye in the human cervical cancer cells was 2. 04% ±0. 93% , and the proportion of the SP cells was decreased with the the degree of reduction of differentiation(P <0. 05). Cell growth curve indicated that proliferative capacity of the SP cells was better than the NSP cells (P<0. 05). The SP cells demonstrated stronger tumorigenesis ability in nude mice. As few as 1 x 103 SP cells could give rise to new tumors in xenotransplantation, with a tumorigenesis ability 100 times as high as that of the NSP cells. The time of tumor formation was significantly reduced. After treatment with different concentrations of chemotherapy drugs (cisplatin) for 24h, the SP cells had significantly lower inhibition rate than the NSP cells ( P < 0. 05 ). Conclusion Human cervical cancer cells contains a small subpopulation of cells excluding Hoechst 33342 dye. The more poorly the cell line differentiated, the fewer the proportion it contained. The SP cells has better proliferative capacity in vitro and stronger tumorigenicity than the NSP cells, with strongly resistant to chemotherapy

  16. [Human papillomavirus detection in cervical cancer prevention].

    Science.gov (United States)

    Picconi, María Alejandra

    2013-01-01

    Cervical cancer (CC), which is strongly associated to high-risk human papillomavirus (hr-HPV) infection, continues being a significant health problem in Latin America. The use of conventional cytology to detect precancerous cervical lesions has had no major impact on reducing CC incidence and mortality rates, which are still high in the region. New screening tools to detect precancerous lesions became available, which provide great opportunities for CC prevention, as do highly efficacious HPV vaccines able to prevent nearly all lesions associated with HPV-16 and -18 when applied before viral exposure. Currently, hr-HPV testing represents an invaluable component of clinical guidelines for screening, management and treatment of CC and their precursor lesions. Many testing strategies have been developed that can detect a broad spectrum of hr-HPV types in a single assay; however, only a small subset of them has documented clinical performance for any of the standard HPV testing indications. HPV tests that have not been validated and lack proof of reliability, reproducibility and accuracy should not be used in clinical management. Once incorporated into the lab, it is essential to submit the whole procedure of HPV testing to continuous and rigorous quality assurance to avoid sub-optimal, potentially harmful practices. Recent progress and current status of these methods are discussed in this article.

  17. In vitro Antiproliferative and Apoptosis Inducing Effect of Allium atroviolaceum Bulb Extract on Breast, Cervical, and Liver Cancer Cells

    Science.gov (United States)

    Khazaei, Somayeh; Esa, Norhaizan M.; Ramachandran, Vasudevan; Hamid, Roslida A.; Pandurangan, Ashok K.; Etemad, Ali; Ismail, Patimah

    2017-01-01

    Natural products are considered potent sources for novel drug discovery and development. The multiple therapeutic effects of natural compounds in traditional medicine motivate us to evaluate the cytotoxic activity of bulb of Allium atroviolaceum in MCF7 and MDA-MB-231, HeLa and HepG2 cell lines. The bulb methanol extract of A. atroviolaceum was found to be an active cell proliferation inhibitor at the time and dose dependent manner. Determination of DNA content by flow cytometry demonstrated S and G2/M phase arrest of MCF-7 cell, correlated to Cdk1 downregulation, S phase arrest in MDA-MB-231 which is p53 and Cdk1-dependent, sub-G0 cell cycle arrest in HeLa aligned with Cdk1 downregulation, G0/G1, S, G2/M phase arrest in HepG2 which is p53-dependent. Apoptosis as the mechanism of cell death was confirmed by morphology study, caspases activity assay, as well as apoptosis related gene expression, Bcl-2. Caspase-8, -9, and -3 activity with downregulation of Bcl-2 illustrated occurrence of both intrinsic and extrinsic pathways in MCF7, while caspase-3 and -8 activity revealed extrinsic pathway of apoptosis, although Bcl-2 downregulated. In HeLa cells, the activity of caspase-9 and -3 and downregulation of Bcl-2 shows intrinsic pathway or mitochondrial pathway, whereas HepG2 shows caspase independent apoptosis. Further, the combination of the extract with tamoxifen against MCF7 and MDA-MB-231 and combination with doxorubicin against HeLa and HeG2 demonstrated synergistic effect in most concentrations, suggests that the bulb of A. atroviolaceum may be useful for the treatment of cancer lonely or in combination with other drugs. PMID:28197098

  18. Upregulation of kazrin F by miR-186 suppresses apoptosis but promotes epithelial-mesenchymal transition to contribute to malignancy in human cervical cancer cells

    Science.gov (United States)

    Liu, Chang; Wang, Jinghua; Hu, Yang; Xie, Hong; Liu, Min; Tang, Hua

    2017-01-01

    Objective Previous studies have identified that kazrin is a constituent of desmosome and influences intercellular adhesion, growing development and morphology. We previously cloned another new isoform, kazrin F and found that it has anti-apoptotic effects on human glioma cell line. To further explore whether kazrin F is involved in tumorigenesis, we investigated its expression and role in cervical cancer (CC) cells. Methods The role of kazrin F and miR-186 in CC was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation, transwell, and apoptosis assays. Using enhanced green fluorescent protein (EGFP) reporter assays, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, we identified kazrin F post-transcriptional regulation by miR-186. Results We demonstrate that kazrin F is highly expressed in CC tissues compared with the adjacent noncancerous tissues and promotes cell proliferation, colony formation, migration and invasion in HeLa and C33A cells by suppressing apoptosis and facilitating epithelial-to-mesenchymal transition (EMT). Furthermore, miR-186 was confirmed as a regulator of kazrin F dysregulation. An EGFP reporter assay proved that miR-186 directly targets the 3’-untranslated region (3’UTR) of kazrin F and downregulates its expression, and miR-186 expression showed an inverse correlation with kazrin F levels in CC tissues. In addition, overexpression of miR-186 suppressed the malignant behaviors of CC cells. The ectopic expression of kazrin F rescued the inhibitory effects of miR-186. Conclusions Our findings indicate that the upregulation of kazrin F due to downregulated miR-186 levels contributes to malignancy, and highlight the significance of kazrin F in CC tumorigenesis. PMID:28373753

  19. Cervical cancer screening in Greenland, 1997-2011

    DEFF Research Database (Denmark)

    Holst, Signe; Wohlfahrt, Jan; Kjær, Susanne K;

    2016-01-01

    OBJECTIVE: In spite of the high incidence of cervical cancer in Greenland, no assessment has been made of the impact of organized cervical screening, introduced in 1998, in relation to occurrence of high-grade cervical lesions. The objectives of the present study were to estimate coverage...... of the screening program and to examine possible changes in cervical intraepithelial neoplasia (CIN3) incidence in Greenland during 1997-2011 according to calendar period and age. METHODS: Using nationwide registries, we calculated age-standardized incidence rates for all women born and living in Greenland...

  20. Distribution of HPV Genotypes and Involvement of Risk Factors in Cervical Lesions and Invasive Cervical Cancer: A Study in an Indian Population

    Science.gov (United States)

    Srivastava, Shikha; Shahi, U P; Dibya, Arti; Gupta, Sadhana; Roy, Jagat K

    2014-01-01

    Human papilloma virus (HPV) is considered as the main sexually transmitted etiological agent for the cause and progression of preneoplastic cervical lesions to cervical cancer. This study is discussing the prevalence of HPV and its genotypes in cervical lesions and invasive cervical cancer tissues and their association with various risk factors in women from Varanasi and its adjoining areas in India. A total of 122 cervical biopsy samples were collected from SS Hospital and Indian Railways Cancer Institute and Research Centre, Varanasi and were screened for HPV infection by PCR using primers from L1 consensus region of the viral genome. HPV positive samples were genotyped by type-specific PCR and sequencing. The association of different risk factors with HPV infection in various grades of cervical lesion was evaluated by chi-square test. A total of 10 different HPV genotypes were observed in women with cervicitis, CIN, invasive squamous cell cervical carcinoma and adenocarcinoma. Increased frequency of HPV infection with increasing lesion grade (p=0.002) was observed. HPV16 being the predominant type was found significantly associated with severity of the disease (p=0.03). Various socio- demographic factors other than HPV including high parity (p<0.0001), rural residential area (p<0.0001), elder age (p<0.0001), low socio-economic status (p<0.0001) and women in postmenopausal group (p<0.0001) were also observed to be associated with cervical cancer.These findings show HPV as a direct cause of cervical cancer suggesting urgent need of screening programs and HPV vaccination in women with low socio-economic status and those residing in rural areas. PMID:25035855

  1. Survival analysis of cervical cancer using stratified Cox regression

    Science.gov (United States)

    Purnami, S. W.; Inayati, K. D.; Sari, N. W. Wulan; Chosuvivatwong, V.; Sriplung, H.

    2016-04-01

    Cervical cancer is one of the mostly widely cancer cause of the women death in the world including Indonesia. Most cervical cancer patients come to the hospital already in an advanced stadium. As a result, the treatment of cervical cancer becomes more difficult and even can increase the death's risk. One of parameter that can be used to assess successfully of treatment is the probability of survival. This study raises the issue of cervical cancer survival patients at Dr. Soetomo Hospital using stratified Cox regression based on six factors such as age, stadium, treatment initiation, companion disease, complication, and anemia. Stratified Cox model is used because there is one independent variable that does not satisfy the proportional hazards assumption that is stadium. The results of the stratified Cox model show that the complication variable is significant factor which influent survival probability of cervical cancer patient. The obtained hazard ratio is 7.35. It means that cervical cancer patient who has complication is at risk of dying 7.35 times greater than patient who did not has complication. While the adjusted survival curves showed that stadium IV had the lowest probability of survival.

  2. Needs and priorities of women with endometrial and cervical cancer

    DEFF Research Database (Denmark)

    Jeppesen, Mette Moustgaard; Mogensen, Ole; Dehn, Pernille

    2015-01-01

    and 34.7% of endometrial cancer patients. Both the patient groups experienced significant lymphedema post-treatment [endometrial cancer (p = 0.006) and cervical cancer (p = 0.002)]. Further, urological problems were more prevalent post-treatment in endometrial cancer patients (p = 0.018), while sexual...... with endometrial and cervical cancer experience emotional problems prior to therapy and lymphedema, and urological and sexual problems following treatment. An awareness of these problems may facilitate early identification of women with unmet needs and enable individualized follow-up adjusted for such patient...

  3. Bevacizumab improves survival for patients with advanced cervical cancer

    Science.gov (United States)

    Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis

  4. Delivering cervical cancer prevention services in low-resource settings.

    Science.gov (United States)

    Bradley, J; Barone, M; Mahé, C; Lewis, R; Luciani, S

    2005-05-01

    The goals of any cervical cancer prevention program should be threefold: to achieve high coverage of the population at risk, to screen women with an accurate test as part of high-quality services, and to ensure that women with positive test results are properly managed. This article focuses on the experiences of the Alliance for Cervical Cancer Prevention (ACCP) in delivery of screening and treatment services as part of cervical cancer prevention projects in Africa, Latin America, and Asia. Research and experience show that cervical cancer can be prevented when strategies and services are well planned and well managed and when attention is paid to program monitoring and evaluation. Coordination of program components, reduction of the number of visits, improvement of service quality, and flexibility in how services are delivered are all essential features of an effective service.

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

    Science.gov (United States)

    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.

  6. Effect of Rhizoma Curcumae on proliferation and immune function of Hela cells of cervical cancer%莪术对人宫颈癌Hela细胞增殖及免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    任艳珍; 索玉平; 李晓旭; 郭敏红

    2015-01-01

    目的:探讨莪术对人宫颈癌细胞的增殖及免疫功能的影响。方法将50只裸鼠移植瘤模型简单随机分成5组,分别给予不同的处理,观察小鼠的免疫功能及癌组织的病理结果变化;用 M TT 方法检测莪术水煎液对宫颈癌 Hela 细胞的抑制作用。结果莪术抑制宫颈癌细胞的生长,最高达(71.2±3.4)%,呈时间、浓度依赖性;不同剂量莪术组与顺铂组相比较,莪术对小鼠免疫功能影响不大,白细胞降低不明显,差异有统计学意义;病理切片可见莪术治疗组的癌组织可出现不同程度的坏死。结论莪术抑制宫颈癌细胞的生长,促进癌细胞凋亡,对机体的不良反应小,较安全。%Objective Effect of Rhizoma Curcumae proliferation and immune function of cervical cancer cell . Methods The model of transplanted tumor of 50 mice were randomly divided into 5 groups ,were given different treatment ,pathological results observation of immune function of mice and cancer tissue changes ;inhibitory effect on Hela cells of cervical cancer by M T T method for detection of zedoary Decoction• Results Rhizoma Curcumae inhibit the growth of cervical cancer cells ,up to (71 .2 ± 3 .4)% ,which shows the dependent of time and concen‐tration ;Compare cisplatin group with different doses of Rhizoma Curcumae group ,little effect of Rhizoma Cur‐cumae on immune function in mice ,the decrease of white blood cell is not obvious ,the difference is statistically significant ;pathological section shows cancer tissue of Rhizoma Curcuma treatment group can appear different de‐gree of necrosis .Conclusion Conclusion Rhizoma Curcumae inhibit the growth of cervical cancer cells ,and pro‐mote apoptosis of cancer cells ,small side effects on the body ,relatively safe.

  7. Quality of life characteristics inpatients with cervical cancer

    DEFF Research Database (Denmark)

    Bjelic-Radisic, Vesna; Jensen, Pernille T; Vlasic, Karin Kuljanic

    2012-01-01

    Annually about 500,000 women worldwide are diagnosed with cervical cancer. For many patients, young age at the time of diagnosis and a good prognosis regarding the disease imply a long life with the side-effects and sequels of various treatment options. The present study investigated the extent...... to which different quality of life (QoL) domains in patients during and after treatment for cervical cancer are affected according to menopausal status, treatment status and treatment modality....

  8. Screening and cervical cancer cure: population based cohort study

    OpenAIRE

    Andrae, B.; Andersson, T. M.-L.; Lambert, P C; Kemetli, L.; Silfverdal, L.; Strander, B.; Ryd, W.; Dillner, J.; Tornberg, S.; Sparen, P.

    2012-01-01

    Objective To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death. Design Nationwide population based cohort study. Setting Sweden. Participants All 1230 women with cervical cancer diagnosed during 1999-2001 in Sweden prospectively followed up for an average of 8.5 years. Main outcome measures Cure proportions and five year relative survival ratios, stratified by screening history, mode of detection, age...

  9. Low adherence to cervical cancer screening after subtotal hysterectomy

    DEFF Research Database (Denmark)

    Andersen, Lea Laird; Møller, Lars Mikael Alling; Gimbel, Helga Margrethe

    2015-01-01

    have unnecessary tests performed after total hysterectomy. Clarification of the use of cervical/vaginal smears after hysterectomy is needed to identify women at risk of cervical dysplasia or cancer. FUNDING: Research Foundation of Region Zealand, University of Southern Denmark, Nykøbing Falster......INTRODUCTION: A reason for not recommending subtotal hysterectomy is the risk of cervical pathology. We aimed to evaluate cervical cancer screening and to describe cervical pathology after subtotal and total hysterectomy for benign indications. METHODS: Data regarding adherence to screening...... and pathology results from the national Danish registry (Patobank) were obtained on women from a randomised clinical trial and an observational study of subtotal versus total abdominal hysterectomy from the time of surgery until 2014. RESULTS: We included 501 women (259 subtotal hysterectomies and 242 total...

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

    Directory of Open Access Journals (Sweden)

    Valle Sabrina

    2009-02-01

    Full Text Available Abstract 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.

  11. Incidence of cervical dysplasia and cervical cancer in women living with HIV in Denmark

    DEFF Research Database (Denmark)

    Thorsteinsson, Kristina; Ladelund, Steen; Jensen-Fangel, Søren;

    2014-01-01

    INTRODUCTION: Women living with HIV (WLWH) are reportedly at increased risk of invasive cervical cancer (ICC). WLWH in Denmark attend the National ICC screening program less often than women in the general population. We aimed to estimate the incidence of cervical dysplasia and ICC in WLWH...... and hazard ratios (HRs) for time from inclusion to first cervical intraepithelial neoplasia (CIN)/ICC and time from first normal cervical cytology to first CIN/ICC were estimated. Sensitivity analyses were performed to include prior screening outcome, screening intensity and treatment of CIN...... with normal baseline cytology, incidences of CIN1+ and CIN2+ were higher in WLWH. However, incidences were comparable between WLWH and controls adherent to the National ICC screening program. CONCLUSIONS: Overall, WLWH develop more cervical disease than controls. However, incidences of CIN are comparable...

  12. Trends in the incidence of cervical cancer and severe precancerous lesions in Denmark, 1997-2012

    DEFF Research Database (Denmark)

    Baldur-Felskov, Birgitte; Munk, Christian; Nielsen, Thor Schütt Svane;

    2015-01-01

    PURPOSE: The incidence of cervical cancer, including squamous cell carcinoma (SCC), has been decreasing in several developed countries since the onset of organized screening programs; in some countries, however, the incidence of adenocarcinoma has increased among young women. We investigated...... the Danish incidence trends during 1997-2011 when cervical screening coverage was high. Incidences of cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) were also assessed, with the latest part of the study period coinciding with introduction of free-of-charge human......, importantly, they decreased significantly during 2009-2012 in women aged ≤20 years. CONCLUSIONS: The Danish screening program has successfully reduced the incidence of cervical cancer, especially of SCC in older women; however, the program has not significantly reduced the incidence in young women...

  13. Breast and cervical cancer screening programme implementation in 16 countries

    DEFF Research Database (Denmark)

    Dowling, Emily C; Klabunde, Carrie; Patnick, Julietta;

    2010-01-01

    There is a continuing need to monitor and evaluate the impact of organized screening programmes on cancer incidence and mortality. We report results from a programme assessment conducted within the International Cancer Screening Network (ICSN) to understand the characteristics of cervical screening...... programmes within countries that have established population-based breast cancer screening programmes....

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

    Science.gov (United States)

    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.

  15. Exploration of FoxM1 and downstream related target molecule expression in cervical cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Yi-Chong Yuan; QiongYang

    2016-01-01

    Objective:To study the expression of FoxM1 and downstream related target molecules in cervical cancer tissue.Methods:Cervical cancer tissue and normal cervical tissue were collected to detect the expression of FoxM1, proliferation-related genes (CDK6 and CDK8) and angiogenesis-related genes (VEGFA, VEGFB and VEGFC); Hela cells were cultured and transfected with FoxM1 siRNA, and then expression of CDK6, CDK8, VEGFA, VEGFB and VEGFC were detected.Results:mRNA contents of FoxM1, CDK6, CDK8, VEGFA, VEGFB and VEGFC in cervical cancer tissue were significantly higher than those in normal cervical tissue; mRNA content of FoxM1 was positively correlated with mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC; mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC of FoxM1-siRNA group were significantly lower than those of negative control-siRNA group.Conclusion:FoxM1 expression abnormally increases in cervical cancer tissue, and its downstream target genes include CDK6, CDK8, VEGFA, VEGFB and VEGFC.

  16. Objective Diagnosis of Cervical Cancer by Tissue Protein Profile Analysis

    Science.gov (United States)

    Patil, Ajeetkumar; Bhat, Sujatha; Rai, Lavanya; Kartha, V. B.; Chidangil, Santhosh

    2011-07-01

    Protein profiles of homogenized normal cervical tissue samples from hysterectomy subjects and cancerous cervical tissues from biopsy samples collected from patients with different stages of cervical cancer were recorded using High Performance Liquid Chromatography coupled with Laser Induced Fluorescence (HPLC-LIF). The Protein profiles were subjected to Principle Component Analysis to derive statistically significant parameters. Diagnosis of sample types were carried out by matching three parameters—scores of factors, squared residuals, and Mahalanobis Distance. ROC and Youden's Index curves for calibration standards were used for objective estimation of the optimum threshold for decision making and performance.

  17. Gene expression profiling in cervical cancer: identification of novel markers for disease diagnosis and therapy.

    LENUS (Irish Health Repository)

    Martin, Cara M

    2012-02-01

    Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus is the single most important etiological agent in cervical cancer. HPV contributes to neoplastic progression through the action of two viral oncoproteins E6 and E7, which interfere with critical cell cycle pathways, p53, and retinoblastoma. However, evidence suggests that HPV infection alone is insufficient to induce malignant changes and other host genetic variations are important in the development of cervical cancer. Advances in molecular biology and high throughput gene expression profiling technologies have heralded a new era in biomarker discovery and identification of molecular targets related to carcinogenesis. These advancements have improved our understanding of carcinogenesis and will facilitate screening, early detection, management, and personalised targeted therapy. In this chapter, we have described the use of high density microarrays to assess gene expression profiles in cervical cancer. Using this approach we have identified a number of novel genes which are differentially expressed in cervical cancer, including several genes involved in cell cycle regulation. These include p16ink4a, MCM 3 and 5, CDC6, Geminin, Cyclins A-D, TOPO2A, CDCA1, and BIRC5. We have validated expression of mRNA using real-time PCR and protein by immunohistochemistry.

  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

    Directory of Open Access Journals (Sweden)

    Felicia Paulraj

    2015-06-01

    Full Text Available 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.

  19. Identification of biomarkers for cervical cancer in peripheral blood lymphocytes using oligonucleotide microarrays

    Institute of Scientific and Technical Information of China (English)

    SHENG Jie; ZHANG Wei-yuan

    2010-01-01

    Background Oligonucleotide microarrays are increasingly being used to identify gene expression profiles that associated with complex genetic diseases. Peripheral lymphocytes communicate with cells and extracellular matrixes in almost all tissues and organs in human body, suggesting that the gene expression profiles in peripheral lymphocytes may reflect the presence of disease in the body. This study aimed to identify molecular biomarkers for cervical cancer in peripheral blood lymphocytes by using oligonucleotide microarrays.Methods Total RNA was extracted from peripheral blood lymphocytes of 24 early stage cervical cancer patients and 18 healthy controls. We used 22K Human Genome microarrays to profile peripheral blood lymphocytes from 4 early stage cervical cancer patients and compared their gene expression profiles with those from 3 healthy controls. Differentially expressed genes would be identified if they had adjusted P values of less than 0.05 and a groupwise average fold change greater than 1.5 or less than 0.67. Then the selected 5 genes were validated in the remaining 20 early stage cervical cancer patients and the 15 healthy controls by using real-time reverse-transcription polymerase chain reaction (RT-PCR).Results Genes identified by the gene selection program expressed differently between the blood samples of the early stage cervical cancer patients and those of the healthy controls. To validate the gene expression data, 5 genes were analyzed by real-time RT-PCR. In three of the 5 identified genes, tenasin-c (TNC), nuceolin (NCL), and enolase 2 (ENO2) showed a significant up-regulation in the blood samples of the early stage cervical cancer patients versus that of the healthy controls.Conclusions The up-regulation of TNC, NCL, and ENO2 in peripheral blood may be used to identify novel blood biomarkers for detecting cervical cancer in a clinically accessible surrogate tissue, and thus to provide a possibility to develop a noninvasive and predictive

  20. Pathways of cervical cancer screening among Chinese women

    Directory of Open Access Journals (Sweden)

    Ma GX

    2013-06-01

    Full Text Available Grace X Ma,1 Min Qi Wang,2 Xiang S Ma,3 Steven E Shive,4 Yin Tan,5 Jamil I Toubbeh51Department of Public Health, College of Health Professions, Temple University, Philadelphia, PA, 2Department of Public and Community Health, University of Maryland, College Park, MD, 3College of Health Professions and School of Medicine, Temple University, Philadelphia, PA, 4Center for Asian Health, Temple University, and Department of Health, East Stroudsburg University, East Stroudsburg, PA, 5Center for Asian Health, Department of Public Health, College of Health Professions, Temple University, Philadelphia, PA, USABackground: The purpose of this community-based study was to develop a structural equation model for factors contributing to cervical cancer screening among Chinese American women.Methods: A cross-sectional design included a sample of 573 Chinese American women aged 18 years and older. The initial step involved use of confirmatory factor analysis, that included the following variables: access to and satisfaction with health care, and enabling and predisposing cultural and health beliefs. Structural equation model analyses were conducted on factors related to cervical cancer screening.Results: Age, marital status, employment, household income, and having health insurance, but not educational level, were significantly related to cervical screening status. Predisposing and enabling factors were positively associated with cervical cancer screening. The cultural factor was significantly related to the enabling factor or the satisfaction with health care factor.Conclusion: This model highlights the significance of sociocultural factors in relation to cervical cancer screening. These factors were significant, with cultural, predisposing, enabling, and health belief factors and access to and satisfaction with health care reinforcing the need to assist Chinese American women with poor English fluency in translation and awareness of the importance of cervical

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

    Science.gov (United States)

    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.

  2. Detection of miRNA-21 content in cervical cancer tissue and preliminary analysis of its downstream target molecules

    Institute of Scientific and Technical Information of China (English)

    Rong Shen; Jian-Wu Gao; Yan-Yu Li; Peng Teng

    2015-01-01

    Objective:To study the miRNA-21 content in cervical cancer tissue and analyze its downstream target molecules.Methods:Patients with different FIGO stages of cervical cancer and healthy subjects were selected, cervical cancer tissue and normal cervical tissue were collected, and contents of miRNA-21 and apoptotic genes were detected; cervical cancer SiHa cells were cultured, miRNA-21 mimics and inhibitors were transfected, and then apoptotic gene contents were detected.Results:miRNA-21 contents in different stages of cervical cancer tissue were all higher than those in normal cervical tissue, mRNA contents of p16ink4a, ASPP1, Fas and GRIM-19 were lower than those in normal tissue, and mRNA contents of p16ink4a, ASPP1, Fas and GRIM-19 were negatively correlated with miRNA-21 contents; after miRNA-21 mimics were transfected, mRNA contents of p16ink4a, ASPP1, Fas and GRIM-19 significantly decreased, and after miRNA-21 inhibitors were transfected, mRNA contents of p16ink4a, ASPP1, Fas and GRIM-19 significantly increased.Conclusion:miRNA-21 contents in cervical cancer tissue significantly increase; downstream target genes of this miRNA may be apoptotic genes p16ink4a, ASPP1, Fas and GRIM-19.

  3. Transcription factor KLF4 regulates microRNA-544 that targets YWHAZ in cervical cancer.

    Science.gov (United States)

    Mao, Langyong; Zhang, Yan; Deng, Xiaolong; Mo, Wenjuan; Yu, Yao; Lu, Hong

    2015-01-01

    The deregulation of microRNAs has been demonstrated in various tumor processes. Here, we report that microRNA-544 (miR-544) is decreased in cervical cancer tissues compared with normal cervical tissues. To identify the mechanisms involved in miR-544 deregulation, we studied the regulation of miR-544 expression at the transcriptional level. We first identified the transcriptional start site of miR-544 by 5' rapid amplification of cDNA ends and subsequently determined the miR-544 promoter. We discovered that the transcription factor Krueppel-like factor 4 (KLF4) is involved in the transcriptional regulation of miR-544 through interaction with the miR-544 promoter. In addition, we found that miR-544 directly targets the YWHAZ oncogene and functions as a tumor suppressor in cervical cancer cells. miR-544 is involved in cell cycle regulation and suppresses cervical cancer cell proliferation, colony formation, migration and invasion in a manner associated with YWHAZ downregulation. In summary, our findings demonstrate that KLF4 upregulates miR-544 transcription by activating the miR-544 promoter and that miR-544 functions as a tumor suppressor by targeting YWHAZ. Therefore, miR-544 may be a potential novel therapeutic target and prognostic marker for cervical cancer.

  4. Surface activity, lipid profiles and their implications in cervical cancer.

    Directory of Open Access Journals (Sweden)

    Preetha A

    2005-01-01

    Full Text Available Background: The profiles of lipids in normal and cancerous tissues may differ revealing information about cancer development and progression. Lipids being surface active, changes in lipid profiles can manifest as altered surface activity profiles. Langmuir monolayers offer a convenient model for evaluating surface activity of biological membranes. Aims: The aims of this study were to quantify phospholipids and their effects on surface activity of normal and cancerous human cervical tissues as well as to evaluate the role of phosphatidylcholine (PC and sphingomyelin (SM in cervical cancer using Langmuir monolayers. Methods and Materials: Lipid quantification was done using thin layer chromatography and phosphorus assay. Surface activity was evaluated using Langmuir monolayers. Monolayers were formed on the surface of deionized water by spreading tissue organic phase corresponding to 1 mg of tissue and studying their surface pressure-area isotherms at body temperature. The PC and SM contents of cancerous human cervical tissues were higher than those of the normal human cervical tissues. Role of PC and SM were evaluated by adding varying amounts of these lipids to normal cervical pooled organic phase. Statistical analysis: Student′s t-test (p < 0.05 and one-way analysis of variance (ANOVA was used. Results: Our results reveals that the phosphatidylglycerol level in cancerous cervical tissue was nearly five folds higher than that in normal cervical tissue. Also PC and sphingomyelin SM were found to be the major phospholipid components in cancerous and normal cervical tissues respectively. The addition of either 1.5 µg DPPC or 0.5 µg SM /mg of tissue to the normal organic phase changed its surface activity profile to that of the cancerous tissues. Statistically significant surface activity parameters showed that PC and SM have remarkable roles in shifting the normal cervical lipophilic surface activity towards that of cancerous lipophilic

  5. Correlation of abnormal DNMT1 and MeCP2 expression with cell biological characteristics in cervical lesion tissue

    Institute of Scientific and Technical Information of China (English)

    Wei Lin; Sha Ma

    2016-01-01

    Objective:To study the correlation of abnormal DNMT1 and MeCP2 expression with cell biological characteristics in cervical lesion tissue.Methods:Cervical cancer tissue and para-carcinoma tissue were collected from cervical cancer patients who received surgery in our hospital from May 2012 to October 2015, and HPV types as well as the expression levels of DNMTs, MeCP2, PBK, TOPK, Snail, Slug, SALL4 and Cat L were determined.Results:Protein levels of DNMT1, DNMT2, DNMT3a, DNMT3b, DNMT3l and MeCP2 in cervical cancer tissue were significantly higher than those in para-carcinoma tissue, and the rising trend of DNMT1 expression level was the most significant; protein levels of DNMT1, DNMT2, DNMT3a, DNMT3b, DNMT3l and MeCP2 in cervical cancer tissue with high-risk HPV infection were significantly higher than those in cervical cancer tissue with normal HPV infection; in cervical cancer tissue with high expression of DNMT1 and MeCP2, PBK, TOPK, Snail, Slug, SALL4 and Cat L levels were significantly higher than those in cervical cancer tissue with low expression of DNMT1 and MeCP2.Conclusions:Abnormally high expression of DNMT1 and MeCP2 in cervical cancer tissue may up-regulate the expression of a variety of malignant biological molecules by increasing methylation level.

  6. Cervical cancer screening in primary health care setting in Sudan

    DEFF Research Database (Denmark)

    Ibrahim, Ahmed; Aro, Arja R.; Rasch, Vibeke;

    2012-01-01

    OBJECTIVE: To determine the feasibility of visual inspection with the use of acetic acid (VIA) as a screening method for cervical cancer, an alternative to the Pap smear used in primary health care setting in Sudan, and to compare sensitivity, specificity, positive and negative predictive values....../119 (73.9%) were positive for cervical intraepithelial neoplasia. VIA had higher sensitivity than Pap smear (74.2% versus 72.9%; P = 0.05) respectively. Out of 88 confirmed positive cases, 22 (25.0%) cases were invasive cervical cancer in stage 1, of which 19 versus three were detected by VIA and Pap...... of this study showed that VIA has higher sensitivity and lower specificity compared to Pap smear, but a combination of both tests has greater sensitivity and specificity than each test independently. It indicates that VIA is useful for screening of cervical cancer in the primary health care setting in Sudan...

  7. Prospects for primary prevention of cervical cancer in developing countries

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    Franceschi Silvia

    2003-01-01

    Full Text Available The HPV types that cause cervical cancer are sexually transmitted, but there is little evidence that infection can be avoided by behavioural changes, such as condom use. In contrast, prophylactic vaccines against HPV infection are likely to have high efficacy. In principle, the effectiveness of HPV vaccination as a strategy for cervical cancer control can be measured either by monitoring secular trends in cervical cancer incidence or by conducting randomized trials. The former approach is unlikely to provide convincing evidence of effectiveness, since cervical cancer rates are subject to strong secular trends that are independent of intervention measures. A few