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1

Cervical Cancer  

MedlinePLUS

... Overview What is cervical cancer? Cervical cancer is cancer of the cervix. The cervix is part of your uterus (womb). ... your doctor does to check for signs of cancer of the cervix. The cells from your cervix are checked for ...

2

Cervical cancer  

MedlinePLUS

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

3

Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer  

ClinicalTrials.gov

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

2015-02-27

4

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

ClinicalTrials.gov

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

2015-03-11

5

Cervical Cancer  

MedlinePLUS

... Dictionary Search for Clinical Trials NCI Publications Español Cervical Cancer Definition of cervical cancer : Cancer that forms in tissues of the ... the cervix and looked at under a microscope). Cervical cancer is almost always caused by human papillomavirus ( ...

6

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

ClinicalTrials.gov

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

2014-09-22

7

ADXS11-001 High Dose HPV+ Cervical Cancer  

ClinicalTrials.gov

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

2015-02-25

8

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

PubMed Central

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 act as carriers for pharmaceutical agents or radiation sources and may even allow for the growth of cancer cells. Based on studies, which have demonstrated decreased lung, breast, and bone cancer cell functions on nanostructured compared to nanosmooth polymers, the objective of the present in vitro study was to modify titanium to possess nanotubular surface features and determine cervical cancer cell adhesion after 4 hours. Here, titanium was anodized to possess nanotubular surface features. Results demonstrated the ability to decrease cervical cancer cell adhesion by about a half on nanotubular compared to currently used nanosmooth titanium (without the use of chemotherapeutics or radiation), opening up numerous possibilities for the use of nanotubular titanium in local drug delivery or radiation treatment of cervical cancer. PMID:23493522

Crear, Jara; Kummer, Kim M; Webster, Thomas J

2013-01-01

9

Positron Emission Tomography Using Fluoromisonidazole F 18 and Fludeoxyglucose F 18 to Find Oxygen in Tumor Cells of Patients Undergoing Treatment for Newly Diagnosed Stage IB, Stage II, Stage III, or Stage IV Cervical Cancer  

ClinicalTrials.gov

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

2014-06-10

10

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

ClinicalTrials.gov

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

2014-10-09

11

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

ClinicalTrials.gov

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

2014-12-23

12

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

ClinicalTrials.gov

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

2014-06-18

13

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

ClinicalTrials.gov

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

2014-12-29

14

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

ClinicalTrials.gov

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

2015-03-23

15

Frequent ras gene mutations in squamous cell cervical cancer  

Microsoft Academic Search

Eighty samples of cervical invasive squamous cell carcinoma were examined for ras gene mutations using polymerase chain reaction (PCR) followed by restriction enzyme digestion. We found 28 (35%) cervical cancers contained ras mutations at H-ras codon 12, 49 (61%) at K-ras codon 12, and 5 (6%) at K-ras codon 13. There were no significant differences in incidence of the ras

Y. F. Wong; Tony K. H. Chung; T. H. Cheung; S. K. Lam; Y. G. Xu; Allan M. Z. Chang

1995-01-01

16

Cervical Cancer  

MedlinePLUS

... in the United States get cervical cancer. The human papillomavirus (HPV) is the main cause of cervical cancer. HPV is a common virus that is passed from one person to another during sex. At least half of sexually active people will ...

17

Cervical Squamous Cell Carcinoma  

MedlinePLUS

... increased vaginal discharge, pelvic pain, or pain during sexual intercourse. (continued on next page) Cervical Cancer Cervical Squamous Cell Carcinoma Copyright © 2011. College of American Pathologists. For use and reproduction by patients and CAP members only. Normal cervical ...

18

Zoledronic acid induces apoptosis and autophagy in cervical cancer cells.  

PubMed

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. PMID:25142231

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

2014-12-01

19

Enrichment and characterization of cancer stem?like cells from a cervical cancer cell line.  

PubMed

Cancer stem cells (CSCs) are proposed to be responsible for tumor recurrence, metastasis and the high mortality rate of cancer patients. Isolation and identification of CSCs is crucial for basic and preclinical studies. However, as there are currently no universal markers for the isolation and identification of CSCs in any type of cancer, the method for isolating CSCs from primary cancer tissues or cell lines is costly and ineffective. In order to establish a reliable model of cervical cancer stem cells for basic and preclinical studies, the present study was designed to enrich cervical cancer CSCs using a nonadhesive culture system and to characterize their partial stemness phenotypes. Human cervical cancer cells (HeLa) were cultured using a nonadhesive culture system to generate tumor spheres. Their stemness characteristics were investigated through colony formation, tumor sphere formation, self-renewal, toluidine blue staining, chemoresistance, invasion assays, reverse transcription-polymerase chain reaction, immunofluorescence staining of putative stem cell markers, including octamer-binding transcription factor 4, SRY-box 2 and aldehyde dehydrogenase 1 family, member A1, and adipogenic differentiation induction. Typical tumor spheres were formed within 5-7 days under this nonadhesive culture system. Compared with the adherent parental HeLa cells, the colony formation capacity, self-renewal potential, light cell population, cell invasion, chemoresistance and expression of putative stem cell markers of the tumor sphere cells increased significantly, and a subpopulation of tumor sphere cells were induced into adipogenic differentiation. Using the nonadhesive culture system, a reliable model of cervical cancer stem cells was established, which is inexpensive, effective and simple compared with the ultra-low attachment serum free culture method. The stemness characteristics of the tumor sphere HeLa cells mirrored the CSC phenotypes. This CSC model may be useful for basic and preclinical studies of cervical cancer and other types of cancer. PMID:24676900

Wang, Li; Guo, Huijie; Lin, Caiyu; Yang, Liuqi; Wang, Xiujie

2014-06-01

20

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

ClinicalTrials.gov

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

2014-12-29

21

Ovarian squamous cell carcinoma which metastasized 8 years after cervical conization for early microinvasive cervical cancer: a case report.  

PubMed

Squamous cell cervical carcinoma that metastasized to the ovary is common in patients with bulky tumors or locally advanced disease; however, ovarian squamous cell carcinoma that metastasized after cervical conization surgery for early microinvasive uterine cervical carcinoma is very rare. We present a case of ovarian squamous cell carcinoma that metastasized 8 years after cervical conization surgery for early microinvasive cervical carcinoma. She had no sign of recurrence in the uterine cervix. We detected human papillomavirus type 16 DNA in both cervical tissue and ovarian tissue, suggesting that ovarian squamous cell carcinoma is derived from microinvasive cervical cancer. Although there are very few cases of early microinvasive squamous cell carcinoma that metastasized to the ovary with delayed recurrence, we should pay attention strictly not only to the cervical condition but also to the ovarian condition on regular post-operative follow-up. PMID:21467082

Hidaka, Takao; Nakashima, Akitoshi; Hasegawa, Toru; Nomoto, Kazuhiro; Ishizawa, Shin; Tsuneyama, Koichi; Takano, Yasuo; Saito, Shigeru

2011-06-01

22

Glycoprotein and Glycan in Patients With Stage I, Stage II, Stage III, or Stage IV Cervical Cancer Undergoing Surgery to Remove Pelvic and Abdominal Lymph Nodes  

ClinicalTrials.gov

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

2014-12-23

23

Carbon nanowall scaffold to control culturing of cervical cancer cells  

NASA Astrophysics Data System (ADS)

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

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

2014-12-01

24

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

PubMed Central

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

2013-01-01

25

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

PubMed

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. PMID:25117446

Wang, Hongtao; Gao, Peng; Zheng, Jie

2014-09-01

26

REV3L, a Promising Target in Regulating the Chemosensitivity of Cervical Cancer Cells  

PubMed Central

REV3L, the catalytic subunit of DNA Polymerase ? (Pol?), plays a significant role in the DNA damage tolerance mechanism of translesion synthesis (TLS). The role of REV3L in chemosensitivity of cervical cancer needs exploration. In the present study, we evaluated the expression of the Pol? protein in paraffin-embedded tissues using immunohistochemistry and found that the expression of Pol? in cervical cancer tissues was higher than that in normal tissues. We then established some cervical cancer cell lines with REV3L suppression or overexpression. Depletion of REV3L suppresses cell proliferation and colony formation of cervical cancer cells through G1 arrest, and REV3L promotes cell proliferation and colony formation of cervical cancer cells by promoting G1 phase to S phase transition. The suppression of REV3L expression enhanced the sensitivity of cervical cancer cells to cisplatin, and the overexpression of REV3L conferred resistance to cisplatin as evidenced by the alteration of apoptosis rates, and significantly expression level changes of anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia sequence 1 (Mcl-1) and B-cell lymphoma-extra large (Bcl-xl) and proapoptotic Bcl-2-associated x protein (Bax). Our data suggest that REV3L plays an important role in regulating cervical cancer cellular response to cisplatin, and thus targeting REV3L may be a promising way to alter chemosensitivity in cervical cancer patients. PMID:25781640

Liu, Fei; Ren, Chunxia; Wang, Ziliang; Li, Yingyi; Tu, Xiaoyu; Yang, Gong; Cheng, Xi

2015-01-01

27

Down-Regulating Overexpressed Human Lon in Cervical Cancer Suppresses Cell Proliferation and Bioenergetics  

PubMed Central

The human mitochondrial ATP-dependent Lon protease functions in regulating the metabolism and quality control of proteins and mitochondrial DNA (mtDNA). However, the role of Lon in cancer is not well understood. Therefore, this study was undertaken to investigate the importance of Lon in cervical cancer cells from patients and in established cell lines. Microarray analysis from 30 cancer and 10 normal cervical tissues were analyzed by immunohistochemistry for Lon protein levels. The expression of Lon was also examined by immunoblotting 16 fresh cervical cancer tissues and their respective non-tumor cervical tissues. In all cases, Lon expression was significantly elevated in cervical carcinomas as compared to normal tissues. Augmented Lon expression in tissue microarrays did not vary between age, tumor-node-metastasis grades, or lymph node metastasis. Knocking down Lon in HeLa cervical cancer cells by lentivrial transduction resulted in a substantial decrease in both mRNA and protein levels. Such down-regulation of Lon expression significantly blocked HeLa cell proliferation. In addition, knocking down Lon resulted in decreased cellular bioenergetics as determined by measuring aerobic respiration and glycolysis using the Seahorse XF24 extracellular flux analyzer. Together, these data demonstrate that Lon plays a potential role in the oncogenesis of cervical cancer, and may be a useful biomarker and target in the treatment of cervical cancer. Lon; immunohistochemistry; cervical cancer; cell proliferation; cellular bioenergetics. PMID:24260536

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

2013-01-01

28

Cisplatin and Radiation Therapy Followed by Paclitaxel and Carboplatin in Treating Patients With Stage I, Stage II, Stage III, or Stage IV Cervical Cancer  

ClinicalTrials.gov

Cervical Adenocarcinoma; Cervical Adenosquamous 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

2014-12-23

29

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

PubMed

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. PMID:25651840

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

2015-04-01

30

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

PubMed

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. PMID:22820185

Samarzija, Ivana; Beard, Peter

2012-08-17

31

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

SciTech Connect

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.

Samarzija, Ivana [Ecole Polytechnique Federale Lausanne (EPFL), Department of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), 1015 Lausanne (Switzerland)] [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)] [Ecole Polytechnique Federale Lausanne (EPFL), Department of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), 1015 Lausanne (Switzerland)

2012-08-17

32

A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer  

PubMed Central

Infection by carcinogenic human papillomaviruses (HPV) results in precancers [cervical intraepithelial neoplasia (CIN)] and cancers near the ectoendocervical squamocolumnar (SC) junction of the cervix. However, the specific cells targeted by HPV have not been identified and the cellular origin of cervical cancer remains elusive. In this study, we uncovered a discrete population of SC junctional cells with unique morphology and gene-expression profile. We also demonstrated that the selected junctional biomarkers were expressed by a high percentage of high-grade CIN and cervical cancers associated with carcinogenic HPVs but rarely in ectocervical/transformation zone CINs or those associated with noncarcinogenic HPVs. That the original SC junction immunophenotype was not regenerated at new SC junctions following excision, not induced by expression of viral oncoproteins in foreskin keratinocytes, and not seen in HPV-related precursors of the vagina, vulva, and penis further support the notion that junctional cells are the source of cervical cancer. Taken together, our findings suggest that carcinogenic HPV-related CINs and cervical cancers are linked to a small, discrete cell population that localizes to the SC junction of the cervix, expresses a unique gene expression signature, and is not regenerated after excision. The findings in this study uncover a potential target for cervical cancer prevention, provide insight into the risk assessment of cervical lesions, and establish a model for elucidating the pathway to cervical cancer following carcinogenic HPV infection. PMID:22689991

Herfs, Michael; Yamamoto, Yusuke; Laury, Anna; Wang, Xia; Nucci, Marisa R.; McLaughlin-Drubin, Margaret E.; Münger, Karl; Feldman, Sarah; McKeon, Frank D.; Xian, Wa; Crum, Christopher P.

2012-01-01

33

Cervical Cancer  

MedlinePLUS

... takes several years for normal cells in the cervix to turn into cancer cells. Your health care provider can find abnormal cells by doing a Pap test to examine cells from the cervix. You may also have an HPV test. If ...

34

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

ClinicalTrials.gov

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage II Vaginal Cancer; Stage IIA 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 Squamous Cell Carcinoma

2015-03-18

35

Oncogene ATAD2 promotes cell proliferation, invasion and migration in cervical cancer.  

PubMed

The ATPase family AAA domain-containing protein 2 (ATAD2) is associated with many cellular processes, such as cell proliferation, invasion and migration. However, the molecular biological function of the ATAD2 gene in cervical cancer is unclear. The purpose of this study was to explore ATAD2 expression in cervical cancer, evaluate the relationship between the development of cervical cancer, metastasis and clinicopathological characteristics, and discuss the implications for its use in clinical treatment. Protein and mRNA expression of ATAD2 was examined in tissues and cell lines. Tumor tissues from 135 cases of cervical cancer were collected for evaluation of ATAD2 expression by immunohistochemistry and western blotting. Prognostic significance was evaluated by the Cox hazards model and Kaplan-Meier survival method. HeLa and SiHa cells were transfected with two siRNAs targeting ATAD2. ATAD2 knockdown was used to analyze cell proliferation, invasion and migration. Cell viability was evaluated with the Cell Counting ?it-8 (CCK-8) assay, cell invasion by a Transwell assay and cell migration by a wound healing/scratch migration assay. ATAD2 was shown to be highly expressed in cervical cancer tissues, both at the transcriptional and protein levels, and was correlated with poor patient survival (P<0.05). Knockdown of ATAD2 in the HeLa and SiHa cells was found to reduce the capacity for invasion and migration (P<0.05), and inhibited the growth and clonogenic potential of the HeLa and SiHa cell lines. Our results suggest that cervical cancer tissues may have highly expressed ATAD2, which is associated with tumor stage and lymph node status (P<0.05). Oncogene ATAD2 may play an important role in cervical cancer proliferation, invasion and migration. It could serve as a prognostic marker and a therapeutic target for cervical cancer. PMID:25813398

Zheng, Le; Li, Tianren; Zhang, Yi; Guo, Yi; Yao, Jihang; Dou, Lei; Guo, Kejun

2015-05-01

36

Expression of TSG101 protein and LSF transcription factor in HPV-positive cervical cancer cells  

PubMed Central

Our previous study demonstrated a decreased expression of tumor susceptibility gene 101 (TSG101) in cervical cancer cells. To identify the mechanism responsible for TSG101 downregulation during cervical cancer development, we analyzed the TSG101 promoter using cis-element cluster finder software. One of the transcription factors whose binding site was detected in the TSG101 promoter was late SV40 factor (LSF). The aim of this study was to analyze the TSG101 protein and LSF expression levels during cervical cancer development. Immunohistochemical analysis confirmed a previously observed decreased expression of TSG101, whereas quantitative polymerase chain reaction (qPCR) and immunohistochemistry analysis revealed high expression of LSF in cervical, precancer and cancer cells compared with human papillomavirus (HPV)-negative non-cancer samples. High expression of LSF in cervical cancer HPV-positive cells suggests that this protein may be important in the regulation of TSG101 expression, as well as in cervical carcinogenesis. The role of LSF as a mediator in cervical cancer development must be confirmed in future studies. PMID:24765146

BRONIARCZYK, JUSTYNA K.; WAROWICKA, ALICJA; KWA?NIEWSKA, ANNA; WOHU?-CHOLEWA, MARIA; KWA?NIEWSKI, WOJCIECH; GO?DZICKA-JÓZEFIAK, ANNA

2014-01-01

37

MicroRNA-145 contributes to enhancing radiosensitivity of cervical cancer cells.  

PubMed

In our study, transcriptome microarrays are used to identify differentially expressed miRNAs and mRNAs in cervical cancer specimens. We find that microRNA-145 (miR-145) expression is significantly decreased in cervical cancer tissues and cell lines, and is associated with advanced cancer stages, large tumor size and moderate/poor differentiation. We show that miR-145 targets the DNA damage repair-associated gene Helicase-like transcription factor (HLTF), which is involved in radio-resistance. Moreover, miR-145 over-expression in cervical cancer cells enhances radiosensitivity in vitro and in vivo. These results indicate that targeting miR-145 may be a novel radiosensitizing strategy for cervical cancer. PMID:25666710

Ye, Chen; Sun, Ning-Xia; Ma, Yan; Zhao, Qian; Zhang, Qing; Xu, Chen; Wang, Shao-Bing; Sun, Shu-Han; Wang, Fang; Li, Wen

2015-03-12

38

WWOX induces apoptosis and inhibits proliferation in cervical cancer and cell lines.  

PubMed

Cervical cancer is the second most common gynecological malignancy, but the molecular events involved in its development remain unclear. The tumor?suppressor gene, WW domain-containing oxidoreductase (WWOX), has been found to be lost in various types of cancers. Few studies have been reported detailing the function of WWOX in human cervical cancer; therefore we aimed to investigate the role played by WWOX in human cervical cancer. Immunohistochemistry was used to study preinvasive and invasive primary cervical cancer. Full length cDNA was transfected into HeLa cells to overexpress WWOX, and short hairpin RNA (shRNA) was transfected into SiHa cells to deplete its expression, respectively. The cellular levels of WWOX RNA and protein were detected by real-time PCR and western immunoblotting. Proliferation rates were assessed by methyl thiazolyl tetrazolium (MTT), plate colony formation and soft agar colony assays. Cellular apoptosis was measured by flow cytometry and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The activity of caspase-3 and its protein levels were determined by caspase-3 activity assay and western blot analysis. Xenografts were established by injecting cells into nude mice. The results showed that WWOX expression was decreased in human cervical cancer and cervical cancer cell lines. Reconstitution of WWOX in HeLa cells inhibited their proliferation and induced apoptosis, while knockdown of WWOX in SiHa cells promoted proliferation and inhibited apoptosis. Xenografts in groups of mice verified the effect in vivo. These data suggest that underexpression of WWOX is associated with cervical cancer development. Modulation of WWOX expression may be an effective and novel method for the treatment of cervical cancer. PMID:23525362

Qu, Junjie; Lu, Wen; Li, Bilan; Lu, Cong; Wan, Xiaoping

2013-05-01

39

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

PubMed

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

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

2015-03-01

40

HPV16 early gene E5 specifically reduces miRNA-196a in cervical cancer cells  

PubMed Central

High-risk human papillomavirus (HPV) type 16, which is responsible for greater than 50% of cervical cancer cases, is the most prevalent and lethal HPV type. However, the molecular mechanisms of cervical carcinogenesis remain elusive, particularly the early steps of HPV infection that may transform normal cervical epithelium into a pre-neoplastic state. Here, we report that a group of microRNAs (microRNAs) were aberrantly decreased in HPV16-positive normal cervical tissues, and these groups of microRNAs are further reduced in cervical carcinoma. Among these miRNAs, miR196a expression is the most reduced in HPV16-infected tissues. Interestingly, miR196a expression is low in HPV16-positive cervical cancer cell lines but high in HPV16-negative cervical cancer cell lines. Furthermore, we found that only HPV16 early gene E5 specifically down-regulated miRNA196a in the cervical cancer cell lines. In addition, HoxB8, a known miR196a target gene, is up-regulated in the HPV16 cervical carcinoma cell line but not in HPV18 cervical cancer cell lines. Various doses of miR196a affected cervical cancer cell proliferation and apoptosis. Altogether, these results suggested that HPV16 E5 specifically down-regulates miR196a upon infection of the human cervix and initiates the transformation of normal cervix cells to cervical carcinoma. PMID:25563170

Liu, Chanzhen; Lin, Jianfei; Li, Lianqin; Zhang, Yonggang; Chen, Weiling; Cao, Zeyi; Zuo, Huancong; Chen, Chunling; Kee, Kehkooi

2015-01-01

41

Antiapoptotic effects of estrogen in normal and cancer human cervical epithelial cells.  

PubMed

The present study investigated the antiapoptotic effects of estrogen in normal and cancer human cervical cells and the mechanisms involved. Baseline apoptosis in human cervical epithelial cells is mediated predominantly by P2X7-receptor-induced, Ca(2+)-dependent activation of the mitochondrial (caspase-9) pathway. Treatment with 10 nM 17beta-estradiol blocked apoptosis induced by the P2X7-receptor ligands ATP and 2',3'-0-(4-benzoylbenzoyl)-ATP in normal human cervical epithelial cells (hECEs) and attenuated the effect in hECEs immortalized with human papillomavirus-16 (ECE16-1) and the cancer cervical cells HT3 and CaSki. Diethylstilbestrol and to a lesser degree estrone could mimic the effects of 17beta-estradiol, whereas actinomycin-D and cycloheximide attenuated the response. The antiapoptotic effect of estrogen did not depend on cell cycle phase, and in both normal and cancer cervical cells, it involved attenuation of activation of caspase-9 and the terminal caspase-3. However, involvement of cascades upstream to the caspase-9 differed in normal vs. cancer cervical cells. In the normal hECEs estrogen blocked P2X7-receptor-induced calcium influx. In contrast, in the cancer CaSki cells, estrogen up-regulated expression of Bcl-2 and attenuated Ca(2+)-induced mitochondrial swelling (i.e. formation of mitochondrial permeability transition pores). Estrogen had no effect on P2X7-receptor-induced apoptosis in the anaplastic SiHa and Hela cells. These results point to a novel antiapoptotic effect of estrogen in the cervix that is independent of its mitogenic function. The results also suggest that cancer cervical cells evolved antiapoptotic mechanisms that enable the cells to evade apoptosis and could therefore promote tumor progression. PMID:15319352

Wang, Qifang; Li, Xin; Wang, Liqin; Feng, Ying-Hong; Zeng, Robin; Gorodeski, George

2004-12-01

42

Preferential Recruitment of Th17 Cells to Cervical Cancer via CCR6-CCL20 Pathway  

PubMed Central

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

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

2015-01-01

43

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

PubMed

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. PMID:25326774

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

2015-02-01

44

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

PubMed

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

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

2013-02-01

45

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

PubMed Central

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

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

2015-01-01

46

Cervical Cancer Prevention  

MedlinePLUS

... cancer are being studied in clinical trials. Avoiding risk factors and increasing protective factors may help prevent cancer. ... might lower your risk of cancer. The following risk factors increase the risk of cervical cancer: HPV Infection ...

47

Cervical Cancer Other Characteristics  

Cancer.gov

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

48

Cervical Cancer Screening Programs  

Cancer.gov

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

49

Cervical Cancer Screening Programs  

Cancer.gov

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

50

Cervical Cancer Other Characteristics  

Cancer.gov

Skip to Main Content Search International Cancer Screening Network Sponsored by the National Cancer Institute Home | About ICSN | Collaborative Projects | Meetings | Cancer Sites | Publications | Contact Us Cervical Cancer (Archived Tables): Home Other

51

Cervical Cancer Participation Rates  

Cancer.gov

Skip to Main Content Search International Cancer Screening Network Sponsored by the National Cancer Institute Home | About ICSN | Collaborative Projects | Meetings | Cancer Sites | Publications | Contact Us Cervical Cancer (Archived Tables): Home Participation

52

Visualization and characterization of cancer stem-like cells in cervical cancer.  

PubMed

Cancer stem cells (CSCs), defined by their differentiation capacity, self-renewal capacity, and maintenance of proliferation, have been identified in many tumors, including cervical cancer. Current studies identify CSCs by several specific biomarkers; however, it is difficult to monitor cervical CSCs in real-time in vitro and in vivo. Recent research reported the visualization of CSCs in breast cancer and gliomas using green fluorescent protein, ZsGreen, fused to a degron motif ornithine decarboxylase (ODC), which is destroyed by proteasomes. Accordingly, CSCs have low 26S proteasome activity, whereas non-CSCs have high 26S proteasome activity. Therefore, it is possible to observe CSCs by their accumulation of the fluorescent ZsGreen protein. In this study, we investigated optical imaging parameters to evaluate CSCs using two human cervical cancer cell lines: CaSki and HeLa. We defined populations as cell types having high- and low ZsGreen-cODC (high- and low-Zs, respectively) expression levels. The results of a sphere-forming assay revealed that the self-renewal ability of the high-Zs population was significantly higher than that of the low-Zs population. A tumorigenicity assay confirmed that the high-Zs population exhibited higher tumorigenic potential than the low-Zs population. The radioresistance of the high-Zs population of both HeLa and CaSki cells and the chemoresistance of the high-Zs population of CaSki cells were confirmed by a clonogenic survival assay and the tetrazolium dye assay, respectively. These results indicate that high-Zs populations of both the HeLa and CaSki cell lines possess CSC-like properties and therapeutic resistance. In conclusion, we successfully visualized CSC-like cells using a fluorescent protein system. PMID:25269542

Hayashi, Kazuhiko; Tamari, Keisuke; Ishii, Hideshi; Konno, Masamitsu; Nishida, Naohiro; Kawamoto, Koichi; Koseki, Jun; Fukusumi, Takahito; Kano, Yoshihiro; Nishikawa, Shimpei; Miyo, Masaaki; Noguchi, Kozo; Ogawa, Hisataka; Hamabe, Atsushi; Seo, Yuji; Doki, Yuichiro; Mori, Masaki; Ogawa, Kazuhiko

2014-12-01

53

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

SciTech Connect

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

Zhang, Jie [Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000 (China)] [Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000 (China); Zheng, Fangxia [Department of Radiotherapy, Liaocheng People’s Hospital, Liaocheng 252000 (China)] [Department of Radiotherapy, Liaocheng People’s Hospital, Liaocheng 252000 (China); Yu, Gang [Department for Disease Control, Tumor Hospital of Liaocheng, Liaocheng 252000 (China)] [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)] [Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000 (China); Lu, Qingyang [Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000 (China)] [Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000 (China)

2013-11-01

54

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

ClinicalTrials.gov

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

2014-12-23

55

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

PubMed Central

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

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

2013-01-01

56

Cervical Cancer  

MedlinePLUS

... cancer has spread to nearby organs or the lymph nodes , the tumors can affect how those organs work. ... invading organisms, such as bacteria that cause disease. Lymph Nodes: Small glands that filter the flow of lymph ( ...

57

Phosphorylated c-Src is a novel predictor for recurrence in cervical squamous cell cancer patients  

PubMed Central

Aims: The molecular mechanisms of the tumorigenesis and recurrence of cervical cancer are poorly understood. The objective of this study was to analyze the expression of phosphorylated c-Src (phospho-c-Src) and its clinical significance in human cervical cancer. Methods: The expression of phospho-c-Src was determined by immunohistochemistry in a total of 127 cervical specimens including 20 normal cervix tissues, 20 cases of carcinoma in situ of cervix (CIS), and 87 cases of cervical squamous cell carcinoma (CSCC). Results: The expression of phospho-Src in normal cervix, CIS, and CSCC increased gradually in ascending order (p=0.026). In addition, the expression of phospho-Src was correlated with overall (p=0.037) and recurrence (p=0.001) survival of cervical cancer. In multivariate Cox regression analysis, phospho-Src expression was an independent prognosis factor for recurrence-free survival (p=0.004). Conclusion: Our present study suggests that Src signaling may play essential role in cervical cancer progression. Phospho-Src expression may be considered as a prognostic marker to predict recurrence in CSCC. PMID:23696930

Hou, Teng; Xiao, Juan; Zhang, Huiting; Gu, Haifeng; Feng, Yanling; Li, Jundong

2013-01-01

58

Molecular biology of cervical cancer.  

PubMed

Cervical cancer is a virus-induced disease that is caused by the integration of high-risk infecting human papillomaviruses (HPV) in the host genome. For this reason, the carcinogenesis process of cervical cancer is associated to the expression of the viral oncogenic proteins E6 and E7. These proteins are capable of inactivating p53 and pRb, which induces a continuous cell proliferation with the increasing risk of accumulation of DNA damage that eventually leads to cancer. Moreover, cervical cancer can be prevented by prophylactic HPV vaccines; their molecular characteristics and mechanism of action are reviewed. Ultimately, new molecular targets for cervical cancer like proteasome, the EGFR family and IGF family are exposed. PMID:17594948

González Martín, A

2007-06-01

59

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

NASA Astrophysics Data System (ADS)

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.

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

2015-03-01

60

Use of artemisinin and its derivatives to treat HPV-infected/transformed cells and cervical cancer: a review.  

PubMed

Cervical cancer and HPV-related diseases remain a burden in the developing world. While much progress has been gained in the detection of HPV and preneoplastic cervical lesions, the rate-limiting step in the prevention of cervical cancer is management of these women. A natural compound, artemisinin, and its derivatives appear to hold promise as a simple means of treatment. Laboratory studies have shown that this compound, and its derivatives, have activity against HPV-infected and -transformed cells and cervical cancer cells. In situations of compassionate use, studies have also demonstrated efficacy in clinical situations. Well-designed clinical trials relating to its use should be undertaken. PMID:24754594

Goodrich, Sarah K; Schlegel, C Richard; Wang, Guixang; Belinson, Jerome L

2014-03-01

61

Statins inhibit the proliferation and induce cell death of human papilloma virus positive and negative cervical cancer cells.  

PubMed

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 staining. Reactive oxygen species (ROS) production was evaluated by the oxidation of 2,7-dichlorofluorescein diacetate and nitrite concentration (an indirect measure of nitric oxide (NO) production), by the Griess reaction. Inhibition of cell proliferation by atorvastatin, fluvastatin and simvastatin was dose-dependent. ViBo cells were the most responsive. Statins did not affect the cell cycle, instead they induced cell death. The antiproliferative effect in ViBo cells was completely inhibited with mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) treatments. In contrast, cell proliferation of CaSki and HeLa cells was partially (33%) rescued with these intermediates. The three statins increased ROS and nitrite production, mainly in the ViBo cell line. These results suggest that statins exert anti-tumoral effects on cervical cancer through inhibition of cell proliferation and induction of cell death and oxidative stress. Statins could be an aid in the treatment of cervical cancer, especially in HPV(-) tumors. PMID:23675166

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

2009-12-01

62

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

PubMed Central

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 staining. Reactive oxygen species (ROS) production was evaluated by the oxidation of 2,7-dichlorofluorescein diacetate and nitrite concentration (an indirect measure of nitric oxide (NO) production), by the Griess reaction. Inhibition of cell proliferation by atorvastatin, fluvastatin and simvastatin was dose-dependent. ViBo cells were the most responsive. Statins did not affect the cell cycle, instead they induced cell death. The antiproliferative effect in ViBo cells was completely inhibited with mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) treatments. In contrast, cell proliferation of CaSki and HeLa cells was partially (33%) rescued with these intermediates. The three statins increased ROS and nitrite production, mainly in the ViBo cell line. These results suggest that statins exert anti-tumoral effects on cervical cancer through inhibition of cell proliferation and induction of cell death and oxidative stress. Statins could be an aid in the treatment of cervical cancer, especially in HPV? tumors. PMID:23675166

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

2009-01-01

63

Cigarette smoke condensate-induced oxidative DNA damage and its removal in human cervical cancer cells.  

PubMed

Exposure to cigarette smoke is well documented to increase oxidative stress and could account for higher risk of cervical cancer in smokers. Cervical pre-cancerous lesions that are initiated by human papillomavirus (HPV) infection generally regress in the absence of known risk factors such as smoking. 8-oxodeoxyguanosine (8-oxodG) is a highly mutagenic oxidative DNA lesion that is formed by the oxidation of deoxyguanosine. In the present study, we examined: a) the effect of cigarette smoke condensate (CSC) on 8-oxodG formation in and its removal from HPV-transfected (ECT1/E6 E7), HPV-positive (CaSki) and HPV-negative (C33A) human cervical cancer cells, and b) the cell cycle progression and apoptosis in CSC-treated ECT1/E6 E7 cells. CSC induced 8-oxodG in a dose- (p=0.03) and time (p=0.002)-dependent fashion in ECT1/E6 E7 cells as determined by flow cytometry. A 2.4-fold higher level of 8-oxodG was observed in HPV-positive compared with HPV-negative cells. However, 8-oxodG lesions were almost completely removed 72 h post-exposure in all cell lines as determined by ImageStream analysis. This observation correlates with the 2- and 5-fold increase in the p53 levels in ECT1/E6 E7 and CaSki cells with no significant change in C33A cells. We conclude that: a) cigarette smoke constituents induce oxidative stress with higher burden in HPV-positive cervical cancer cells and b) the significant increase observed in p53 levels in wild-type cervical cells (ECT1/E6 E7 and CaSki) may be attributed to the p53-dependent DNA repair pathway while a p53-independent pathway in C33A cells cannot be ruled out. PMID:21720711

Moktar, Afsoon; Singh, Rajesh; Vadhanam, Manicka V; Ravoori, Srivani; Lillard, James W; Gairola, C Gary; Gupta, Ramesh C

2011-10-01

64

Curcumin and Emodin Down-Regulate TGF-? Signaling Pathway in Human Cervical Cancer Cells  

PubMed Central

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

Thacker, Pooja Chandrakant; Karunagaran, Devarajan

2015-01-01

65

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

PubMed

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

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

2013-07-01

66

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

PubMed Central

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

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

2015-01-01

67

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

PubMed Central

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

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

2014-01-01

68

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

ClinicalTrials.gov

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

2014-10-31

69

Rel\\/Nuclear factor-kappa B apoptosis pathways in human cervical cancer cells  

Microsoft Academic Search

Cervical cancer is considered a common yet preventable cause of death in women. It has been estimated that about 420 women out of the 1400 women diagnosed with cervical cancer will die during 5 years from diagnosis. This review addresses the pathogenesis of cervical cancer in humans with a special emphasis on the human papilloma virus as a predominant cause

Marlene F Shehata

2005-01-01

70

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

PubMed Central

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

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

2014-01-01

71

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

PubMed Central

In cervical cancer, HPV infection and disruption of mechanisms involving cell growth, differentiation, and apoptosis are strictly linked with tumor progression and invasion. Tumor microenvironment is ATP and adenosine rich, suggesting a role for purinergic signaling in cancer cell growth and death. Here we investigate the effect of extracellular ATP on human cervical cancer cells. We find that extracellular ATP itself has a small cytotoxic effect, whereas adenosine formed from ATP degradation by ectonucleotidases is the main factor responsible for apoptosis induction. The level of P2×7 receptor seemed to define the main cytotoxic mechanism triggered by ATP, since ATP itself eliminated a small subpopulation of cells that express high P2×7 levels, probably through its activation. Corroborating these data, blockage or knockdown of P2×7 only slightly reduced ATP cytotoxicity. On the other hand, cell viability was almost totally recovered with dipyridamole, an adenosine transporter inhibitor. Moreover, ATP-induced apoptosis and signaling—p53 increase, AMPK activation, and PARP cleavage—as well as autophagy induction were also inhibited by dipyridamole. In addition, inhibition of adenosine conversion into AMP also blocked cell death, indicating that metabolization of intracellular adenosine originating from extracellular ATP is responsible for the main effects of the latter in human cervical cancer cells. PMID:25103241

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

2014-01-01

72

Defective antioxidant systems in cervical cancer.  

PubMed

Cervical cancer remains a great problem for woman health, as it is the second deadly cancer of females worldwide. The infection of human papilloma virus (HPV) is the major risk factor for this cancer, although several other factors are also associated. Oxidative stress or antioxidant deficiency has been frequently identified to be associated with cervical cancer. Defects in the antioxidant enzyme systems are reported to play important role behind this antioxidant deficiency, which is responsible for the production of reactive oxygen species and ultimately, DNA damage in cervical cells. In response, cells become more vulnerable to HPV infection for cervical cancer development. Recently, antioxidant therapies or dietary supplementation of antioxidants have gained considerable interests in the cervical cancer treatment. In this study, we have reviewed the association of defective antioxidant systems and cervical cancer development. The recent advances in both of the basic and clinical research focusing on possible antioxidant therapy have also been discussed. PMID:23616011

Jiang, Bin; Xiao, Songshu; Khan, Md Asaduzzaman; Xue, Min

2013-08-01

73

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

NASA Astrophysics Data System (ADS)

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 ?L of activated microbubbles (Definity®) and 50 ?g of the vector were mixed in media and then injected into the Opticell™ chamber. We used 32 ?s 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-?-Tubulin antibody was next tested and confirmed that the delivery into HPV16 positive cells was successful.

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

2010-03-01

74

Dihydroartemisinin induces apoptosis of cervical cancer cells via upregulation of RKIP and downregulation of bcl-2.  

PubMed

Treatment of recurrent and metastatic cervical cancer remains a challenge, especially in developing countries, which lack efficient screening programs. In recent years, artemisinin and its derivatives, such as dihydroartemisinin (DHA), which were traditionally used as anti-malarial agent, have been shown to inhibit tumor growth with low toxicity to normal cells. In this study, we investigated mechanisms underlying the anti-tumor effect of DHA in cervical cancer. We evaluated the role of DHA on the expression of bcl-2 and Raf kinase inhibitor protein (RKIP), which is a suppressor of metastasis. The MTT assay was used to compare the proliferation of untreated and DHA-treated Hela and Caski cervical cancer cells. Flow cytometry was used to determine the percentage of cells at each stage of the cell cycle in untreated and DHA-treated cells. We used RT-PCR and western blots to determine the expression of bcl-2 and RKIP mRNA and proteins. We evaluated the effect of DHA treatment in nude mice bearing Hela or Caski tumors. DHA-treated cells showed a time- and dose-dependent inhibition of proliferation and a significant increase in apoptosis. The expression of RKIP was significantly upregulated and the expression of bcl-2 was significantly downregulated in DHA-treated cells compared with control cells. DHA treatment caused (1) a significant inhibition of tumor growth and (2) a significant increase in the apoptotic index in nude mice bearing Hela or Caski tumors. Our data suggest that DHA inhibits cervical cancer growth via upregulation of RKIP and downregulation of bcl-2. PMID:24335512

Hu, Chun-Jie; Zhou, Lei; Cai, Yan

2014-03-01

75

Smoking and Cervical Cancer  

MedlinePLUS

Smoking and Cervical Cancer If you smoke, you have an increased chance of developing precancerous lesions of ... returning for follow-up appointments, and to Stop Smoking! Copyright © 2003, 2008 American Society for Colposcopy and ...

76

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

PubMed

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

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

2011-04-01

77

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

PubMed

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. PMID:25623537

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

2015-02-27

78

Univariate and multivariate methods for chemical mapping of cervical cancer cells  

NASA Astrophysics Data System (ADS)

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

Duraipandian, Shiyamala; Zheng, Wei; Huang, Zhiwei

2012-01-01

79

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

PubMed Central

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

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

2015-01-01

80

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

PubMed

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

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

2015-02-01

81

Risks of Cervical Cancer Screening  

MedlinePLUS

... Trials NCI Publications Español Cervical Cancer Screening (PDQ®) Risks of Cervical Cancer Screening Key Points for This ... your need for screening tests. Screening tests have risks. Decisions about screening tests can be difficult. Not ...

82

The expression of cyclooxygenase-2 in cervical cancers and Hela cells was regulated by estrogen\\/progestogen  

Microsoft Academic Search

Summary  To investigate the relationship between the expression of cyclooxygenase-2 (COX-2) and menstrual cycle, the regulatory effects\\u000a of 17-?-estradiol (E2) and medroxyprogesterone acetate (MPA) on the expression of COX-2 in cervical cancer Hela cells were examined. Cervical cancer\\u000a specimens were obtained from 47 pre-menopausal patients. The phase of menstrual cycle was determined by case history and HE\\u000a staining of uterine endometrium.

Yunguang Li; Demin Pu; Yanli Li

2007-01-01

83

Peroxiredoxin 3 is a novel marker for cell proliferation in cervical cancer.  

PubMed

Although peroxiredoxin 3 (Prx3) has been reported to be involved in cervical cancer (CC) carcinogenesis, the significance of Prx3 in CC progression remains unclear. The present study was conducted to investigate the expression features of Prx3 to better understand the mechanism of tumor growth and invasion. Sixty-eight patients with invasive squamous cervical cancer were included in the present study. The status of human papillomavirus (HPV) infection was detected by hybridization and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed on paraffin-embedded sections using monoclonal antibodies against Prx3 and Ki67. All samples were positive for high-risk HPV, among which fifty-six samples were positive for HPV16, seven for HPV18 and five for HPV33. The expression of HPV16 E6/E7 was significantly higher in cancer areas compared to the adjacent normal epithelial tissuses. The positive cells for Prx3 and Ki67 were significantly higher in cancer cells compared to normal epitheliums and the staining pattern of Prx3 was consistent with that of Ki67 (Pearson's correlation coefficient was 0.801, P= 0.000). The upregulation of Prx3 might be a protective response to oxidative stress in the cancer microenvironment. The expression consistency of Prx3 and Ki67 suggests Prx3 to be a potential marker for cell proliferation of CC. PMID:24648924

Hu, Jing-Xia; Gao, Qun; Li, Lianqin

2013-03-01

84

Drugs Approved for Cervical Cancer  

MedlinePLUS

Other Drug Resources A to Z List of Cancer Drugs Drugs Approved for Different Types of Cancer Drugs Approved ... NCI Dictionary of Cancer Terms NCI Drug Dictionary Drugs Approved for Cervical Cancer This page lists cancer ...

85

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

PubMed

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. PMID:23534730

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

2013-01-01

86

Paris saponin VII suppressed the growth of human cervical cancer Hela cells  

PubMed Central

Background Saponins of several herbs are known to induce apoptosis in many cancer cells. The present study aimed to investigate the growth inhibitory effect of Paris saponin VII (PS VII), a kind of steroidal saponins from Chonglou (Rhizoma Paridis Chonglou), on the human cervical cancer cell line Hela and the relative molecular mechanisms. Methods Hela cells were exposed to different concentrations of PS VII (1 to 100 ?M). Inhibition of cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-ethynyl-2?-deoxyuridine (EdU) assays. The amount of apoptotic cells was evaluated by flow cytometric analysis. And the protein level of cleaved caspase-3, cleaved caspase-9, Bax, and Bcl-2 was evaluated by Western blot. Results The half maximal inhibitory concentration (IC50) value of PS VII for the growth inhibition of Hela cells was 2.62?±?0.11 ?M. PS VII increased the expression of caspase-3, caspase-9, and Bax while decreased that of Bcl-2, suggesting that PS VII may induce apoptosis through intrinsic apoptotic ways. Conclusions These data indicate that PS VII has the potential for the treatment of cervical cancer. PMID:25128382

2014-01-01

87

[Treatment of cervical cancer].  

PubMed

The treatment of uterine cervical cancer evolved the last past twenty years. The management of early stages cervical cancer is based on surgery +/- after an initial brachytherapy in order to increase loco-regional control. A conservative treatment preserving uterine and ovarian functions is sometimes possible for young patients < 40 years old wishing to conceive. This strategy allows pregnancies with low recurrence rate. Finally, the use of the sentinel lymph node staging should be validated within the next few years. The treatment of locally advanced stages is based on concomitant chemoradiation therapy, which allows obtaining an important complete tumour response rate (90%). Thereafter, the irradiation modalities will depend on the para-aortic lymph nodes status diagnosed by PET-computed tomography +/- staging laparoscopic para-aortic lymphadenectomy. The use of completion surgery may be indicated in case of cervical residual disease and has to be balanced with its specific morbidity. All the decisions are made during a multidisciplinary tumour board. PMID:25090765

Touboul, Cyril; Skalli, Dounia; Guillo, Eric; Martin, Michel; Mallaurie, Emmanuelle; Mansouri, Dhouha; Abd Al Samad, Issam; Chabi, Naima; Hospitel, Sylvie; Koskas, Martin; Haddad, Bassam

2014-06-01

88

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

SciTech Connect

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

Talora, Claudio [Department of Experimental Medicine and Pathology, Laboratory of Molecular Pathology, University 'La Sapienza', Viale Regina Elena, 324, 00161 Rome (Italy); Cialfi, Samantha [Department of Experimental Medicine and Pathology, Laboratory of Molecular Pathology, University 'La Sapienza', Viale Regina Elena, 324, 00161 Rome (Italy); Segatto, Oreste [Regina Elena Cancer Institute, Via Delle Messi d'Oro, 156, Rome 00158 (Italy); Morrone, Stefania [Department of Experimental Medicine and Pathology, Laboratory of Molecular Pathology, University 'La Sapienza', Viale Regina Elena, 324, 00161 Rome (Italy); Kim Choi, John [Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104 (United States); Frati, Luigi [Department of Experimental Medicine and Pathology, Laboratory of Molecular Pathology, University 'La Sapienza', Viale Regina Elena, 324, 00161 Rome (Italy); Institute of Biochemistry University of Lausanne Chemin de Bovaresses 155 CH-1066 Epalinges (Switzerland); Paolo Dotto, Gian [Institute of Biochemistry University of Lausanne Chemin de Bovaresses 155 CH-1066 Epalinges (Switzerland); Gulino, Alberto [Department of Experimental Medicine and Pathology, Laboratory of Molecular Pathology, University 'La Sapienza', Viale Regina Elena, 324, 00161 Rome (Italy); Neuromed Institute, Pozzilli (Italy); Screpanti, Isabella [Department of Experimental Medicine and Pathology, Laboratory of Molecular Pathology, University 'La Sapienza', Viale Regina Elena, 324, 00161 Rome (Italy) and Istituto Pasteur-Fondazione Cenci Bolognetti, University 'La Sapienza', 00161 Roma (Italy)]. E-mail: isabella.screpanti@uniroma1.it

2005-05-01

89

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

PubMed

Notch signaling plays a key role in cell-fate determination and differentiation in different organisms and cell types. Several reports suggest that Notch signaling may be involved in neoplastic transformation. However, in primary keratinocytes, Notch1 can function as a tumor suppressor. Similarly, in HPV-positive cervical cancer cells, constitutively active Notch1 signaling was found to cause growth suppression. Activated Notch1 in these cells represses viral E6/E7 expression through AP-1 down-modulation, resulting in increased p53 expression and a block of pRb hyperphosphorylation. Here we show that in cervical cancer cell lines in which Notch1 ability to repress AP-1 activity is impaired, Notch1-enforced expression elicits an alternative pathway leading to growth arrest. Indeed, activated Notch1 signaling suppresses activity of the helix-loop-helix transcription factor E47, via ERK1/2 activation, resulting in inhibition of cell cycle progression. Moreover, we found that RBP-Jkappa-dependent Notch signaling is specifically repressed in cervical cancer cells and this repression could provide one such mechanism that needs to be activated for cervical carcinogenesis. Finally, we show that inhibition of endogenous Notch1 signaling, although results in a proliferative advantage, sensitizes cervical cancer cell lines to drug-induced apoptosis. Together, our results provide novel molecular insights into Notch1-dependent growth inhibitory effects, counteracting the transforming potential of HPV. PMID:15817159

Talora, Claudio; Cialfi, Samantha; Segatto, Oreste; Morrone, Stefania; Kim Choi, John; Frati, Luigi; Paolo Dotto, Gian; Gulino, Alberto; Screpanti, Isabella

2005-05-01

90

How Are Cervical Cancers and Pre-Cancers Diagnosed?  

MedlinePLUS

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

91

Cervical Cancer HPV Vaccine Use  

Cancer.gov

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92

Disparities and Cervical Cancer  

Microsoft Academic Search

\\u000a Cervical cancer became a preventable disease with the introduction of the Papanicolaou smear (Pap smear) in the 1940s. Trend\\u000a data show that incidence rates have decreased steadily over the past several decades in both white and African American women\\u000a living in the United States (American Cancer Society 2007). Mortality rates have declined steadily over the past several decades\\u000a as well

Marcela del Carmen; Teresa Diaz-Montez

93

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

NASA Astrophysics Data System (ADS)

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

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

2006-03-01

94

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

SciTech Connect

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.

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

2011-04-29

95

In vitro and in vivo anti-cancer activity of formononetin on human cervical cancer cell line HeLa.  

PubMed

Worldwide, cervical cancer (CC) is the third most common malignancy in women, and it remains a leading cause of cancer-related death of women. Genomic studies indicate that phosphoinositide 3-kinase (PI3K)/AKT signaling is one of the most frequently deregulated pathways in several human cancers, including CC. This signaling pathway has an important role in cancer cell proliferation, survival, motility, and metabolism, and therefore could be an attractive therapeutic target. In a previous study, we used a sensitive and high-speed homogeneous assay for the detection of kinase activity and for screening of PI3K/AKT signaling inhibitors in a high-throughput screening (HTS) format and then obtain formononetin, as an O-methylated isoflavone existed in a number of plants and herbs like Astragalus membranaceus. We showed that formononetin inhibited the phosphorylation of AKT and induced the apoptosis of CC cell line HeLa in a dose-dependent manner. Furthermore, formononetin suppressed xenograft tumor growth in nude mice. Our results indicated that formononetin may be used as an anti-cancer drug for cervical cancer in the future. PMID:24272199

Jin, Yue-mei; Xu, Tian-min; Zhao, Yan-hui; Wang, Yi-chao; Cui, Man-hua

2014-03-01

96

CD3? Expression and T Cell Proliferation are Inhibited by TGF-?1 and IL10 in Cervical Cancer Patients  

Microsoft Academic Search

Introduction  Cervical cancer development from a squamous intraepithelial lesion is thought to be favored by an impaired T cell immunity.\\u000a We evaluated parameters of T cell alterations such as proliferation, cytokine, and CD3? expression in peripheral blood and\\u000a tumor-infiltrating T lymphocytes from women with squamous intraepithelial lesions (SIL) or cervical cancer (CC).\\u000a \\u000a \\u000a \\u000a Results and Discussion  T cell proliferation and cytokine messenger RNA

Cinthya E. Díaz-Benítez; Karla R. Navarro-Fuentes; Jacqueline A. Flores-Sosa; Janet Juárez-Díaz; Felipe J. Uribe-Salas; Edgar Román-Basaure; Ludwig E. González-Mena; Patricia Alonso de Ruíz; Guillermina López-Estrada; Alfredo Lagunas-Martínez; Victor H. Bermúdez-Morales; Juan M. Alcocer-González; Jesús Martínez-Barnetche; Rogelio Hernández-Pando; Yvonne Rosenstein; José Moreno; Vicente Madrid-Marina

2009-01-01

97

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

NASA Astrophysics Data System (ADS)

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

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

2013-03-01

98

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

PubMed Central

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. PMID:22500074

Booth, Gary M.; Malmstrom, Robert D.; Kipp, Erica; Paul, Alexandra

2012-01-01

99

Increased expression of oncogene-induced senescence markers during cervical squamous cell cancer development  

PubMed Central

Purpose: To investigate the expression of p15INK4b, p16INK4a and p21Waf1/Cip1 in specimens from cases of normal cervical epithelium (NCE), cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC), and to evaluate whether there is evidence implicating oncogene-induced senescence (OIS) in cervical squamous cell cancer development. Methods: The immunohistochemical expression of p15INK4b, p16INK4a and p21Waf1/Cip1 were investigated in formalin-fixed paraffin-embedded specimens from 19 NCE, 51 CIN and 21 SCC cases, respectively. Comparisons among different groups for each marker were performed with Chi-square test. Results: The expression of p15INK4b, p16INK4a and p21Waf1/Cip1 were significantly higher in both CIN and SCC compared to NCE. Furthermore, the expression of p15INK4b and p21Waf1/Cip1 was significantly higher in CIN ? compared to CIN ?, and these expressions were statistically higher in CIN ? compared to CIN ?, respectively. The p16INK4a expression was significantly higher in CIN ? compared to CIN ?. Conclusions: The results suggested that the senescence programs mediated by p15INK4b, p16INK4a and p21Waf1/Cip1 were activated during the stage of CIN and SCC, and demonstrated that senescence may play important role in preventing from NCE to SCC. PMID:25674264

Zhang, Yongsheng; Guo, Liangsheng; Xing, Pengfei; Chen, Yuanyuan; Li, Feng; Zhu, Weipei; Lu, Xueguan

2014-01-01

100

LGR5 promotes the proliferation and tumor formation of cervical cancer cells through the Wnt/?-catenin signaling pathway  

PubMed Central

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a seven transmembrane receptor known as a potential stem cell marker for intestinal crypts and hair follicles, has recently been found to be overexpressed in some types of human cancers. However, the role of LGR5 in cervical cancer remains unclear. In this study, the expression of LGR5 gradually increases from normal cervix to cervical cancer in situ and to cervical cancers as revealed by immunohistochemistry and western blot analyses. Through knocking down or overexpressing LGR5 in SiHa and HeLa cells, the expression level of LGR5 was found to be positively related to cell proliferation in vitro and to tumor formation in vivo. Further investigation indicated that LGR5 protein could significantly promote the acceleration of cell cycle. Moreover, the TOP-Flash reporter assay and western blot for ?-catenin, cyclinD1, and c-myc proteins, target genes of the Wnt/?-catenin pathway, indicated that LGR5 significantly activated Wnt/?-catenin signaling. Additionally, the blockage of Wnt/?-catenin pathway resulted in a significant inhibition of cell proliferation induced by LGR5. Taken together, these results demonstrate that LGR5 can promote proliferation and tumor formation in cervical cancer cells by activating the Wnt/?-catenin pathway. PMID:25193857

Chen, Qing; Cao, Hao-Zhe; Zheng, Peng-Sheng

2014-01-01

101

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

PubMed Central

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

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

2015-01-01

102

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

PubMed

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. PMID:25769949

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

2015-04-17

103

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

PubMed

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. PMID:16029012

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

2005-07-27

104

AKT Inhibitors Promote Cell Death in Cervical Cancer through Disruption of mTOR Signaling and Glucose Uptake  

PubMed Central

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. PMID:24705275

Rashmi, Ramachandran; DeSelm, Carl; Helms, Cynthia; Bowcock, Anne; Rogers, Buck E.; Rader, Janet; Grigsby, Perry W.; Schwarz, Julie K.

2014-01-01

105

Down-regulation of Frizzled-7 expression inhibits migration, invasion, and epithelial-mesenchymal transition of cervical cancer cell lines.  

PubMed

Frizzled-7 (FZD7) has been demonstrated as a critical receptor of the Wnt signaling and involves in tumorigenesis and metastasis in many cancer types. However, limited information was found in cervical cancer. The aim of this study was to investigate the functional role of FZD7 in migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells. HeLa and SiHa cervical carcinoma cell lines with FZD7 expression were chosen in this study. A short hairpin RNA (shRNA) construct targeting FZD7 mRNA was transfected into HeLa and SiHa cells, and the stably transfected cell lines were obtained through G418 screening. Functional experiments were further performed to assess whether FZD7 down-regulation affects the migration, invasion, and EMT of HeLa and SiHa cells. Our results revealed that down-regulation of FZD7 expression significantly inhibited cell invasion and migration, as well as decreased the expression and activities of MMP2 and MMP9 in both cell types. Additionally, FZD7 silencing resulted in down-regulation of mesenchymal markers including Vimentin and Snail while increased the levels of epithelial marker E-cadherin. We further found that decreased FZD7 expression inhibited the phosphorylation levels of JNK and c-jun in both HeLa and SiHa cells, as determined by Western blot analysis and immunofluorescence. Overall, our results indicate that shRNA-mediated knockdown of FZD7 inhibits invasion, metastasis, and EMT of cervical cancer cells. FZD7 may provide a promising therapeutic target in cervical cancer. PMID:25740178

Deng, Boya; Zhang, Siyang; Miao, Yuan; Zhang, Yi; Wen, Fang; Guo, Kejun

2015-04-01

106

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

PubMed

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

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

2015-01-01

107

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

SciTech Connect

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

Noordhuis, Maartje G.; Eijsink, Jasper J.H.; Roossink, Frank; Graeff, Pauline de [Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Pras, Elisabeth [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Schuuring, Ed [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Wisman, G. Bea A. [Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Bock, Geertruida H. de [Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Zee, Ate G.J. van der, E-mail: a.g.j.van.der.zee@og.umcg.n [Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

2011-02-01

108

Blocking eIF5A modification in cervical cancer cells alters the expression of cancer-related genes and suppresses cell proliferation.  

PubMed

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

Mémin, Elisabeth; Hoque, Mainul; Jain, Mohit R; Heller, Debra S; Li, Hong; Cracchiolo, Bernadette; Hanauske-Abel, Hartmut M; Pe'ery, Tsafi; Mathews, Michael B

2014-01-15

109

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

PubMed

Deregulated expression of high-risk human papillomavirus oncogenes (E6 and E7) is a pivotal event for pathogenesis and progression in cervical cancer. Both viral oncogenes are therefore regarded as ideal therapeutic targets. In the hope of developing a gene-specific therapy for HPV-related cancer, we established CRISPR/Cas9 targeting promoter of HPV 16 E6/E7 and targeting E6, E7 transcript, transduced the CRISPR/Cas9 into cervical HPV-16-positive cell line SiHa. The results showed that CRISPR/Cas9 targeting promoter, as well as targeting E6 and E7 resulted in accumulation of p53 and p21 protein, and consequently remarkably reduced the abilities of proliferation of cervical cancer cells in vitro. Then we inoculated subcutaneously cells into nude mice to establish the transplanted tumor animal models, and found dramatically inhibited tumorigenesis and growth of mice incubated by cells with CRISPR/Cas9 targeting (promoter+E6+E7)-transcript. Our results may provide evidence for application of CRISPR/Cas9 targeting HR-HPV key oncogenes, as a new treatment strategy, in cervical and other HPV-associated cancer therapy. PMID:25044113

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

2014-08-01

110

Infrared Microspectroscopy of Individual Human Cervical Cancer (HeLa) Cells  

PubMed Central

We report infrared (IR) spectra observed for individual, cultured human cervical cancer (HeLa) cells. Spectra were collected microscopically, in reflection/absorption modes, from cells deposited and dried on microscope slides or from cells grown directly on slides. Within the spectra of the dried cells, significant spectral heterogeneity exists that was previously attributed to different stages of the cell cycle [Boydston-White. S., et al., Biospectroscopy 1999, 5, 219–227; Holman, H. Y., et al., Biopolymers Biospectrosc 2000, 57, 329–335; Tobin, M. J., et al., in First BASIE Workshop, Karlsruhe, Germany, 2003]. The results reported here confirm earlier findings and present the possibility of determining the abundance of cells within each stage of the cycle from the IR spectra. In an accompanying paper, we show that the spectra of cells in suspension exhibit spectral intensity distributions that are different from that of the dried cells. This result has far-reaching implications for the use of infrared microspectroscopy to screen dried cell preparations for the presence of abnormal cells. PMID:15137117

Romeo, Melissa; Matthäus, Christian; Miljkovic, Milos; Diem, Max

2009-01-01

111

Infrared microspectroscopy of individual human cervical cancer (HeLa) cells.  

PubMed

We report infrared (IR) spectra observed for individual, cultured human cervical cancer (HeLa) cells. Spectra were collected microscopically, in reflection/absorption modes, from cells deposited and dried on microscope slides or from cells grown directly on slides. Within the spectra of the dried cells, significant spectral heterogeneity exists that was previously attributed to different stages of the cell cycle [Boydston-White. S., et al., Biospectroscopy 1999, 5, 219-227; Holman, H. Y., et al., Biopolymers Biospectrosc 2000, 57, 329-335; Tobin, M. J., et al., in First BASIE Workshop, Karlsruhe, Germany, 2003]. The results reported here confirm earlier findings and present the possibility of determining the abundance of cells within each stage of the cycle from the IR spectra. In an accompanying paper, we show that the spectra of cells in suspension exhibit spectral intensity distributions that are different from that of the dried cells. This result has far-reaching implications for the use of infrared microspectroscopy to screen dried cell preparations for the presence of abnormal cells. PMID:15137117

Romeo, Melissa; Matthäus, Christian; Miljkovic, Milos; Diem, Max

112

Differential expression of Oct4 in HPV-positive and HPV-negative cervical cancer cells is not regulated by DNA methyltransferase 3A  

Microsoft Academic Search

The colony-forming ability of cervical cancer is affected by many factors. Oct4, an important transcription factor, is highly\\u000a expressed in several tumors and promotes the colony-forming ability of cancer cells. Thus, it is considered a potential target\\u000a for the treatment of cancer. However, we know little about the expression level of Oct4 and its epigenetic regulatory mechanism\\u000a in cervical cancer

Dongbo Liu; Peng Zhou; Li Zhang; Gengze Wu; Yingru Zheng; Fengtian He

113

[Juglone inhibits proliferation and induces apoptosis of human cervical squamous cancer SiHa cells].  

PubMed

Objective To explore the effect of juglone on proliferation and apoptosis of human cervical squamous cancer SiHa cells. Methods Cultured SiHa cells in the exponential growth phase were grouped into blank control group and 10, 20, 50, 80 and 100 ?mol/L juglone treatment groups. Methyl thiazolyl tetrazolium (MTT) assay was adopted to observe the inhibitory effect of juglone on the proliferation of SiHa cells, and then 50% inhibitory concentration (IC50) was calculated through formula. Annexin V-FITC/PI double staining and flow cytometry were used to detect the effect of 20 ?mol/L juglone on SiHa cell apoptosis. Western blot was applied to determine the expressions of Bcl-2 and Bax. Results MTT assay showed that, compared with the control group, treatment groups all showed significant inhibitory effects on SiHa cell growth, and IC50 was 20.4 ?mol/L. Flow cytometry demonstrated that early apoptosis rate of SiHa cells in the control group was (2.46±0.37)%, and after treatment with 20 ?mol/L Juglone for 12 hours, the apoptosis rate was raised to (18.47±2.26)%; Western blot analysis showed that the expression of Bcl-2 decreased while the expression of Bax increased significantly in SiHa cells treated with 20 ?mol/L juglone. Conclusion Juglone could significantly inhibit the proliferation and induce the apoptosis of SiHa cells. PMID:25652859

Zhang, Wei; Li, Yan; Luo, Jun; Lu, Xiaojing; Chen, Moran; Zhu, Wenhe; Jiang, Yanxia

2015-02-01

114

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

SciTech Connect

The Notch signaling pathway plays important roles in tumorigenesis in a context-dependent manner. In human cervical cancer, alterations in Notch signaling have been reported, and both tumor-suppressing and tumor-promoting roles of Notch signaling have been proposed; however, the precise molecular mechanisms governing these roles in cervical cancer remain controversial. MAML is a transcriptional co-activator originally identified by its role in Notch signaling. Recent evidence suggests that it also plays a role in other signaling pathways, such as the p53 and {beta}-catenin pathways. MAML is required for stable formation of Notch transcriptional complexes at the promoters of Notch target genes. Chromosomal translocations affecting MAML have been shown to promote tumorigenesis. In this study, we used a truncated dominant-negative MAML1 (DN-MAML) to investigate the role of MAML in HPV-positive cervical cancer cell lines. Three human cervical cancer cell lines (HeLa, SiHa and CaSki) expressed all Notch receptors and the Notch target genes Hes1 and MAML1. Among these 3 cell lines, constitutive appearance of cleaved Notch1 was found only in CaSki cells, which suggests that Notch1 is constitutively activated in this cell line. Gamma secretase inhibitor (GSI) treatment, which suppresses Notch receptor activation, completely abrogated this form of Notch1 but had no effect on cell viability. Overexpression of DN-MAML by retroviral transduction in CaSki cells resulted in significant decreases in the mRNA levels of Hes1 and Notch1 but had no effects on the levels of MAML1, p53 or HPV E6/E7. DN-MAML expression induced increased viability of CaSki cells without any effect on cell cycle progression or cell proliferation. In addition, clonogenic assay experiments revealed that overexpression of DN-MAML resulted in increased colony formation compared to the overexpression of the control vector. When the status of the NF-{kappa}B pathway was investigated, CaSki cells overexpressing DN-MAML exhibited loss of phospho-I{kappa}B{alpha}, decreased total I{kappa}B{alpha} and nuclear localization of NF-{kappa}B p65, which suggests that the NF-{kappa}B pathway is hyperactivated. Furthermore, increased level of cleaved Notch1 was detected when DN-MAML was expressed. When DN-MAML-overexpressing cells were treated with GSI, significantly decreased cell viability was observed, indicating that inhibition of Notch signaling using GSI treatment and DN-MAML expression negatively affects cell viability. Taken together, targeting Notch signaling using DN-MAML and GSI treatment may present a novel method to control cell viability in cervical cancer cells.

Kuncharin, Yanin [Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand)] [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)] [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)] [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) [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)] [Department of Microbiology, Faculty of Science, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 (Thailand)

2011-08-01

115

Cervical Cancer Rates by Race and Ethnicity  

MedlinePLUS

... Fighting Cervical Cancer Worldwide Stay Informed Rates by Race and Ethnicity for Other Kinds of Cancer All ... Skin Uterine Cancer Home Cervical Cancer Rates by Race and Ethnicity Language: English Español (Spanish) Recommend on ...

116

Cigarette smoking and invasive cervical cancer  

SciTech Connect

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

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

1986-06-20

117

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

PubMed

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

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

2013-12-01

118

Multifactorial Etiology of Cervical Cancer: A Hypothesis  

PubMed Central

Cancer of the cervix is the second most common life-threatening cancer among women worldwide, with incidence rates ranging from 4.8 per 100,000 women per year in the Middle East to 44.3 per 100,000 in East Africa. Epidemiologic and clinical data demonstrate that human papillomaviruses (HPV), especially HPV-16 and HPV-18, play at least a major if not a necessary role in the etiology of cervical cancer. However, many investigators acknowledge that HPV is not sufficient to induce cervical cancer and that a multifactorial etiology is likely. HPV can be found in a growing proportion of patients with cervical cancer, approaching 100%, but is not yet found in every patient with disease. Other factors, such as herpes simplex virus type 2 infections, cigarette smoking, vaginal douching, nutrition, and use of oral contraceptives, have been proposed as contributing factors. In the first half of the 20th century, Peyton Rous and colleagues demonstrated the joint action of tars and Shope papillomavirus to consistently induce squamous cell carcinomas in rabbits. Using the Rous model as a prototype, one might hypothesize that some cases of cervical cancer arise from an interaction between oncogenic viruses and cervical tar exposures. Cervical tar exposures include cigarette smoking, use of tar-based vaginal douches, and long years of inhaling smoke from wood- and coal-burning stoves in poorly ventilated kitchens. PMID:16614679

Haverkos, Harry W.

2005-01-01

119

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

ClinicalTrials.gov

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

2014-04-21

120

MicroRNA-214 Suppresses Growth and Invasiveness of Cervical Cancer Cells by Targeting UDP-N-acetyl-?-d-galactosamine:Polypeptide N-Acetylgalactosaminyltransferase 7*  

PubMed Central

MicroRNAs are a class of small noncoding RNAs that function as key regulators of gene expression at the post-transcriptional level. In this study, we demonstrate that miR-214 is frequently down-regulated in cervical cancer, and its expression reduces the proliferation, migration, and invasiveness of cervical cancer cells, whereas inhibiting its expression results in enhanced proliferation, migration, and invasion. miR-214 binds to the 3?-UTR of UDP-N-acetyl-?-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7), thereby repressing GALNT7 expression. Furthermore, we are the first to show, using quantitative real-time PCR, that GALNT7 is frequently up-regulated in cervical cancer. The knockdown of GALNT7 markedly inhibits cervical cancer cell proliferation, migration, and invasion, whereas ectopic expression of GALNT7 significantly enhances these properties, indicating that GALNT7 might function as an oncogene in cervical cancer. The restoration of GALNT7 expression can counteract the effect of miR-214 on cell proliferation, migration, and invasiveness of cervical cancer cells. Together, these results indicate that miR-214 is a new regulator of GALNT7, and both miR-214 and GALNT7 play important roles in the pathogenesis of cervical cancer. PMID:22399294

Peng, Rui-Qing; Wan, Hai-Ying; Li, Hai-Fang; Liu, Min; Li, Xin; Tang, Hua

2012-01-01

121

Induction of cell death in human papillomavirus 18-positive cervical cancer cells by E6 siRNA  

Microsoft Academic Search

Human cervical cancer is caused by high-risk types of human papillomavirus (HPV) such as HPV16 and HPV18, which possess the E6 and E7 oncogenes, whose concurrent expression is a prerequisite for cancer development and maintaining malignant phenotypes. Silencing these oncogenes is considered to be applicable in molecular therapies of human cervical cancer. However, it remains to be determined whether E6,

K Yamato; J Fen; H Kobuchi; Y Nasu; T Yamada; T Nishihara; Y Ikeda; M Kizaki; M Yoshinouchi

2006-01-01

122

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

PubMed

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

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

2013-02-01

123

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

PubMed Central

Betulinic acid is a pentacyclic triterpenoid that exhibits anticancer functions in human cancer cells. This study provides evidence that betulinic acid is highly effective against the human cervical cancer cell line HeLa by inducing dose- and time-dependent apoptosis. The apoptotic process was further investigated using a proteomics approach to reveal protein expression changes in HeLa cells following betulinic acid treatment. Proteomic analysis revealed that there were six up- and thirty down-regulated proteins in betulinic acid-induced HeLa cells, and these proteins were then subjected to functional pathway analysis using multiple analysis software. UDP-glucose 6-dehydrogenase, 6-phosphogluconate dehydrogenase decarboxylating, chain A Horf6-a novel human peroxidase enzyme that involved in redox process, was found to be down-regulated during the apoptosis process of the oxidative stress response pathway. Consistent with our results at the protein level, an increase in intracellular reactive oxygen species was observed in betulinic acid-treated cells. The proteins glucose-regulated protein and cargo-selection protein TIP47, which are involved in the endoplasmic reticulum pathway, were up-regulated by betulinic acid treatment. Meanwhile, 14-3-3 family proteins, including 14-3-3? and 14-3-3?, were down-regulated in response to betulinic acid treatment, which is consistent with the decrease in expression of the target genes 14-3-3? and 14-3-3?. Furthermore, it was found that the antiapoptotic bcl-2 gene was down-regulated while the proapoptotic bax gene was up-regulated after betulinic acid treatment in HeLa cells. These results suggest that betulinic acid induces apoptosis of HeLa cells by triggering both the endoplasmic reticulum pathway and the ROS-mediated mitochondrial pathway. PMID:25148076

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

2014-01-01

124

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

SciTech Connect

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

Liu, Junye [Department of Radiation Medicine, Fourth Military Medical University, Xi'an (China) [Department of Radiation Medicine, Fourth Military Medical University, Xi'an (China); Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an (China); Zhang, Jing [Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an (China)] [Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an (China); Wang, Xiaowu [Department of Radiation Medicine, Fourth Military Medical University, Xi'an (China)] [Department of Radiation Medicine, Fourth Military Medical University, Xi'an (China); Li, Yan [Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an (China)] [Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an (China); Chen, Yongbin; Li, Kangchu [Department of Radiation Medicine, Fourth Military Medical University, Xi'an (China)] [Department of Radiation Medicine, Fourth Military Medical University, Xi'an (China); Zhang, Jian [Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an (China)] [Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an (China); Yao, Libo, E-mail: bioyao@fmmu.edu.cn [Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an (China)] [Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an (China); Guo, Guozhen, E-mail: guozhengg@hotmail.com [Department of Radiation Medicine, Fourth Military Medical University, Xi'an (China)] [Department of Radiation Medicine, Fourth Military Medical University, Xi'an (China)

2010-07-15

125

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

PubMed

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

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

2014-12-01

126

Lethality of PAK3 and SGK2 shRNAs to Human Papillomavirus Positive Cervical Cancer Cells Is Independent of PAK3 and SGK2 Knockdown  

PubMed Central

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. PMID:25615606

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

2015-01-01

127

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

PubMed Central

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

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

128

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

PubMed Central

High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervical cancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine-adenine (CA) repeat polymorphism in the P1 promoter region of the insulin-like growth factor-1 (IGF-1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF-1, and cervical cancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low-grade squamous intraepithelial lesions (L-SILs), high-grade squamous intraepithelial lesions (H-SILs) and invasive cervical cancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF-1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme-linked immunosorbent assay. The identification of the IGF-1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF-1 in the blood serum were observed between H-SILs and controls, only (p=0.047). However, the concentration of IGF-1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H-SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF concentration in blood serum and tissues and the development of cervical cancer. PMID:25384883

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

2015-01-01

129

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

PubMed

High oncogenic risk human papillomaviruses (HPVs) are closely associated with cancer of the cervix. However, HPV infection alone may not be sufficient to cause cervical cancer, and other factors or cofactors may have a cumulative effect on the risk of progression from cervical HPV infection to cancer. The present study investigates the cytosine?adenine (CA) repeat polymorphism in the P1 promoter region of the insulin?like growth factor?1 (IGF?1) gene among cervical precancerous and cancer patients and healthy control females. The association between these polymorphisms, tissue and blood serum levels of IGF?1, and cervical cancer risk and progression is evaluated. The material for analysis consisted of blood cells and postoperative tissues from patients diagnosed with low?grade squamous intraepithelial lesions (L?SILs), high?grade squamous intraepithelial lesions (H?SILs) and invasive cervical cancer (ICC). A polymerase chain reaction amplification and the sequencing of DNA were used for the identification of (CA)n repeats in the IGF?1 P1 region and detection of HPV DNA. The blood serum concentration of IGF was determined by enzyme?linked immunosorbent assay. The identification of the IGF?1 protein in the cervical tissues was performed by immunohistochemical analysis. The range of the length of the CA repeats in the study DNA was 11 to 21. However, the most common allele length and genotype in the control and study patients from serum and tissues was 19 CA repeats and a homozygous genotype of CA19/19. Statistically significant differences in the concentration of IGF?1 in the blood serum were observed between H?SILs and controls, only (p=0.047). However, the concentration of IGF?1 in the group of females with CA19/19, CA19<19 and CA19>19 was significantly higher in the group of patients with H?SIL (P=0.041) and ICC (P=0.048) in comparison with the control group. An association was detected between CA repeat length <19 and/or >19, IGF concentration in blood serum and tissues and the development of cervical cancer. PMID:25384883

Kwasniewski, Wojciech; Gozdzicka-Jozefiak, Anna; Kotarska, Maria; Polak, Grzegorz; Barczynski, Bartlomiej; Broniarczyk, Justyna; Nowak, Witold; Wolun-Cholewa, Maria; Kwasniewska, Anna; Kotarski, Jan

2015-02-01

130

Cervical Cancer Screening  

MedlinePLUS

... cells will go away on their own. False-negative test results can occur. Screening test results may appear to ... is present. A woman who receives a false-negative test result (one that shows there is no cancer when ...

131

January Monthly Spotlight: Cervical Health and Cervical Cancer Disparities  

Cancer.gov

In January, CRCHD joins the nation in raising awareness for Cervical Health and Cervical Cancer Disparities. This month we share a special focus on NCI/CRCHD research programs that are trying to reduce cervical cancer disparities in underserved communities and the people who are spreading the word about the importance of early detection.

132

General Information about Cervical Cancer  

MedlinePLUS

... increased risk of cervical cancer. There are two vaccines to prevent HPV in girls and young women ... HPV) test : A laboratory test used to check DNA or RNA for certain types of HPV infection. ...

133

Drugs Approved for Cervical Cancer  

Cancer.gov

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

134

Three-dimensional endothelial-tumor epithelial cell interactions in human cervical cancers  

Microsoft Academic Search

Summary  The purpose of this study is to understand the multicellular interaction between tumor epithelial (TEC) and human umbilical\\u000a vein endothelial cells (HUVEC). The development of in vitro systems in which to coculture these cells as multicellular aggregates is very critical. Cell lines were established from\\u000a cervical tumor cells (n=6) and two from HUVEC (n=2) and they were cultured as three-dimensional

V. Chopra; T. V. Dinh; E. V. Hannigan

1997-01-01

135

Radiosensitization of human cervical cancer cells by inhibiting ribonucleotide reductase: Enhanced radiation response at low-dose-rates  

PubMed Central

Purpose To test whether pharmacologic inhibition of ribonucleotide reductase (RNR) by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) enhances radiation sensitivity during low-dose-rate ionizing radiation provided by a novel purpose-built iridium-192 cell irradiator. Methods and Materials Cells were exposed to low (11, 23, 37, 67 cGy/hour) dose-rate radiation using a custom-fabricated cell irradiator or to high (330 cGy/min) dose-rate radiation using a conventional cell irradiator. Radiation sensitivity of human cervical (CaSki, C33-a) cancer cells with or without RNR inhibition by 3-AP was evaluated by clonogenic survival and RNR activity assay. Alteration in cell cycle distribution was monitored by flow cytometry. Results Increasing radiation sensitivity of both CaSki and C33-a cells was observed with incremental rise in radiation dose-rates. 3-AP treatment led to enhanced radiation sensitivity in both cell lines, eliminating differences in cell cytotoxicity due to radiation dose rate. RNR blockade by 3-AP during low-dose-rate irradiation was associated with low RNR activity and an extended G1-phase cell cycle arrest. Conclusions We conclude that RNR inhibition by 3-AP impedes DNA damage repair mechanisms that rely on deoxyribonucleotide production, and thereby increases radiation sensitivity of human cervical cancers to low-dose-rate radiation. PMID:21470790

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

2011-01-01

136

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

SciTech Connect

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

Kunos, Charles A., E-mail: charles.kunos@UHhospitals.org [Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve School of Medicine, Cleveland, OH (United States); Colussi, Valdir C. [Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve School of Medicine, Cleveland, OH (United States); Pink, John [Department of General Medical Sciences, University Hospitals Case Medical Center and Case Western Reserve School of Medicine, Cleveland, OH (United States); Radivoyevitch, Tomas [Department of Epidemiology and Biostatistics, Case Comprehensive Cancer Center, University Hospitals Case Medical Center and Case Western Reserve School of Medicine, Cleveland, OH (United States); Oleinick, Nancy L. [Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve School of Medicine, Cleveland, OH (United States)

2011-07-15

137

Cervical Cancer Prevention and Screening: Financial Issues  

MedlinePLUS

... with lower incomes and those without insurance. Federal law Coverage of cervical cancer screening tests is mandated ... says. They also are not covered by state laws, including those about cervical cancer screening. Women who ...

138

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

PubMed Central

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

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

2014-01-01

139

DNA probes for papillomavirus strains readied for cervical cancer screening  

SciTech Connect

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.

Merz, B.

1988-11-18

140

Biological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cells  

PubMed Central

Cervical cancers/CCs are one of the commonest malignancies and the second leading cause of cancer-related death in women. Resveratrol inhibits CC cell growth but its molecular target(s) remains unclear. Since the signaling pathways mediated by STAT3, Notch1 and Wnt2 play beneficial roles in CC formation and progression, the effects of resveratrol on them in cervical adenocarcinoma (HeLa) and squamous cell carcinoma (SiHa) cells were analyzed. The biological significances of the above signaling for HeLa and SiHa cells were evaluated by treating the cells with STAT3, Wnt or Notch selective inhibitors. The frequencies of STAT3, Notch and Wnt activations in 68 cases of CC specimens and 38 non-cancerous cervical epithelia were examined by tissue microarray-based immunohistochemical staining. The results revealed that HeLa and SiHa cells treated by 100?M resveratrol showed extensive apoptosis, accompanied with suppression of STAT3, Notch and Wnt activations. Growth inhibition and apoptosis were found in HeLa and SiHa populations treated by AG490, a STAT3/JAK3 inhibitor but not the ones treated by Notch inhibitor L-685,458 or by Wnt inhibitor XAV-939. Immunohistochemical staining performed on the tissue microarrays showed that the frequencies of Notch1, Notch2, Hes1, Wnt2, Wnt5a and p-STAT3 detection as well as ?-catenin nuclear translocation in CC samples were significantly higher than that of noncancerous group (p<0.01), while the expression rate of PIAS3 was remarkably low in cancer samples (p<0.01). Our results thus demonstrate that STAT3, Wnt and Notch signaling are frequently co-activated in human CC cells and specimens and resveratrol can concurrently inhibit those signaling activations and meanwhile lead cervical squamous cell carcinoma and adenocarcinoma cells to growth arrest and apoptosis. STAT3 signaling is more critical for CC cells and is the major target of resveratrol because selective inhibition of STAT3 rather than Wnt or Notch activation commits SiHa and HeLa cells to apoptosis. PMID:25061499

Zhang, Peng; Li, Hong; Yang, Bin; Yang, Fan; Zhang, Lin-Lin; Kong, Qing-You; Chen, Xiao-Yan; Wu, Mo-Li; Liu, Jia

2014-01-01

141

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

PubMed

In present investigation, bleomycin sulphate loaded nanostructured lipid particles (BLM-NLPs) were constructed to enhance the oral bioavailability by overwhelming the first pass hepatic metabolism. The particles size and nanoencapsulation efficiency of BLM-NLPs were measured to be 17.4±5.4nm and 45.3±3.4%, respectively. Our studies indicated that the drug was molecularly dispersed in the lipid nanocoacervates, with amorphous geometry, without altering the chemical structure, as ascertained by spectral studies. The nanoformulation, BLM-NLPs was analyzed for dissolution testing, cytotoxicity, apoptosis and cellular uptake in human cervical cancer cell line, HeLa cells. BLM-NLPs released the drug with first order kinetic in simulated intestinal fluid (pH?6.8±0.1), characterized by initial burst and followed by slow release. Further, an enhanced cytotoxicity (?5.6 fold lower IC50), improved intracellular concentration (?4.38 fold) and greater degree of apoptosis was induced by BLM-NLPs in HeLa cells, as compared to BLM alone. Moreover, BLM-NLPs also showed dose-dependent internalization, as evinced by cellular uptake study. The in vivo study indicated a significantly (P<0.0001) smaller elimination rate constant (KE), volume of distribution (Vd) and clearance rate (CLTotal) for BLM-NLPs, as compared to BLM solution in post-oral administrations. This clearly depicts the retention and stability of tailored nanoformulation in intestinal absorption pathway. In addition, our nanoformulation, BLM-NLPs documented significantly (P<0.0001)?3.4 fold (66.20±2.57%) higher bioavailability than BLM solution (19.56±0.79%). In conclusion, our in vitro and in vivo results warrant the safety, efficacy and potency of tailored nanoformulation in clinical settings. PMID:24732397

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

2014-06-01

142

Epidemiologic Classification of Human Papillomavirus Types Associated with Cervical Cancer  

Microsoft Academic Search

background Infection with human papilloma virus (HPV) is the main cause of cervical cancer, but the risk associated with the various HPV types has not been adequately assessed. methods We pooled data from 11 case-control studies from nine countries involving 1918 wom- en with histologically confirmed squamous-cell cervical cancer and 1928 control wom- en. A common protocol and questionnaire were

Nubia Muñoz; F. Xavier Bosch; Silvia de Sanjosé; Rolando Herrero; Xavier Castellsagué; Keerti V. Shah; Peter J. F. Snijders; Chris J. L. M. Meijer

2003-01-01

143

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

NASA Astrophysics Data System (ADS)

Photothermal ablation (PTA) is a promising avenue in the area of cancer therapeutics that destroys tumor cells through conversion of near-infrared (NIR) laser light to heat. Hollow gold nanospheres (HGNs) are one of the few materials that are capable of converting light to heat and have been previously used for photothermal ablation studies. Selective delivery of functional nanoparticles to the tumor site is considered as an effective therapeutic approach. In this paper, we demonstrated the anti-cancer potential of HGNs. HGNs were conjugated with monoclonal antibody (anti-TROP2) in order to target cervical cancer cells (HeLa) that contain abundant trophoblast cell surface antigen 2 (TROP2) on the cell surface. The efficient uptake and intracellular location of these functionalized HGNs were studied through application of inductively coupled plasma atomic emission spectroscopy (ICP-AES) and transmission electron microscopy (TEM). Cytotoxicity induced by PTA was measured using CCK-8 assay. HeLa cells incubated with naked HGNs (0.3-3 nmol L-1) within 48 h did not show obvious cytotoxicity. Under laser irradiation at suitable power, anti-TROP2 conjugated HGNs achieved significant tumor cell growth inhibition in comparison to the effects of non-specific PEGylated HGNs (P < 0.05). ?H2AX assay results revealed higher occurrences of DNA-DSBs with anti-TROP2 conjugated HGNs plus laser radiation as compared to treatment with laser alone. Flow cytometry analysis showed that the amount of cell apoptosis was increased after laser irradiation with anti-TROP2 conjugated HGNs (P < 0.05). Anti-TROP2 conjugated HGNs resulted in down-regulation of Bcl-2 expression and up-regulation of Bax expression. Our study results confirmed that anti-TROP2 conjugated HGNs can selectively destroy cervical cancer cells through inducing its apoptosis and DNA damages. We propose that HGNs have the potentials to mediate targeted cancer treatment.

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

2014-08-01

144

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

PubMed

Photothermal ablation (PTA) is a promising avenue in the area of cancer therapeutics that destroys tumor cells through conversion of near-infrared (NIR) laser light to heat. Hollow gold nanospheres (HGNs) are one of the few materials that are capable of converting light to heat and have been previously used for photothermal ablation studies. Selective delivery of functional nanoparticles to the tumor site is considered as an effective therapeutic approach. In this paper, we demonstrated the anti-cancer potential of HGNs. HGNs were conjugated with monoclonal antibody (anti-TROP2) in order to target cervical cancer cells (HeLa) that contain abundant trophoblast cell surface antigen 2 (TROP2) on the cell surface. The efficient uptake and intracellular location of these functionalized HGNs were studied through application of inductively coupled plasma atomic emission spectroscopy (ICP-AES) and transmission electron microscopy (TEM). Cytotoxicity induced by PTA was measured using CCK-8 assay. HeLa cells incubated with naked HGNs (0.3-3 nmol L(-1)) within 48 h did not show obvious cytotoxicity. Under laser irradiation at suitable power, anti-TROP2 conjugated HGNs achieved significant tumor cell growth inhibition in comparison to the effects of non-specific PEGylated HGNs (P < 0.05). ?H2AX assay results revealed higher occurrences of DNA-DSBs with anti-TROP2 conjugated HGNs plus laser radiation as compared to treatment with laser alone. Flow cytometry analysis showed that the amount of cell apoptosis was increased after laser irradiation with anti-TROP2 conjugated HGNs (P < 0.05). Anti-TROP2 conjugated HGNs resulted in down-regulation of Bcl-2 expression and up-regulation of Bax expression. Our study results confirmed that anti-TROP2 conjugated HGNs can selectively destroy cervical cancer cells through inducing its apoptosis and DNA damages. We propose that HGNs have the potentials to mediate targeted cancer treatment. PMID:25102337

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

2014-08-29

145

Downregulation of the non-integrin laminin receptor reduces cellular viability by inducing apoptosis in lung and cervical cancer cells.  

PubMed

The non-integrin laminin receptor, here designated the 37-kDa/67-kDa laminin receptor (LRP/LR), is involved in many physiologically relevant processes, as well as numerous pathological conditions. The overexpression of LRP/LR on various cancerous cell lines plays critical roles in tumour metastasis and angiogenesis. This study investigated whether LRP/LR is implicated in the maintenance of cellular viability in lung and cervical cancer cell lines. Here we show a significant reduction in cellular viability in the aforementioned cell lines as a result of the siRNA-mediated downregulation of LRP. This reduction in cellular viability is due to increased apoptotic processes, reflected by the loss of nuclear integrity and the significant increase in the activity of caspase-3. These results indicate that LRP/LR is involved in the maintenance of cellular viability in tumorigenic lung and cervix uteri cells through the blockage of apoptosis. Knockdown of LRP/LR by siRNA might represent an alternative therapeutic strategy for the treatment of lung and cervical cancer. PMID:23472084

Moodley, Kiashanee; Weiss, Stefan F T

2013-01-01

146

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

MedlinePLUS

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

147

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

NASA Astrophysics Data System (ADS)

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

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

2013-06-01

148

Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 20–44 years: the UK National Case–Control Study of Cervical Cancer  

Microsoft Academic Search

We report results on risk factors for invasive squamous cell and adenocarcinomas of the cervix in women aged 20–44 years from the UK National Case–Control Study of Cervical Cancer, including 180 women with adenocarcinoma, 391 women with squamous cell carcinoma and 923 population controls. The risk of both squamous cell and adenocarcinoma was strongly related to the lifetime number of

J Green; A Berrington de Gonzalez; S Sweetland; V Beral; C Chilvers; B Crossley; J Deacon; C Hermon; P Jha; D Mant; J Peto; M Pike; M P Vessey

2003-01-01

149

Disruption of repressive p130-DREAM complexes by human papillomavirus 16 E6/E7 oncoproteins is required for cell-cycle progression in cervical cancer cells.  

PubMed

Human papillomaviruses (HPVs) with tropism for mucosal epithelia are the major aetiological factors in cervical cancer. Most cancers are associated with so-called high-risk HPV types, in particular HPV16, and constitutive expression of the HPV16 E6 and E7 oncoproteins is critical for malignant transformation in infected keratinocytes. E6 and E7 bind to and inactivate the cellular tumour suppressors p53 and Rb, respectively, thus delaying differentiation and inducing proliferation in suprabasal keratinocytes to enable HPV replication. One member of the Rb family, p130, appears to be a particularly important target for E7 in promoting S-phase entry. Recent evidence indicates that p130 regulates cell-cycle progression as part of a large protein complex termed DREAM. The composition of DREAM is cell cycle-regulated, associating with E2F4 and p130 in G0/G1 and with the B-myb transcription factor in S/G2. In this study, we addressed whether p130-DREAM is disrupted in HPV16-transformed cervical cancer cells and whether this is a critical function for E6/E7. We found that p130-DREAM was greatly diminished in HPV16-transformed cervical carcinoma cells (CaSki and SiHa) compared with control cell lines; however, when E6/E7 expression was targeted by specific small hairpin RNAs, p130-DREAM was reformed and the cell cycle was arrested. We further demonstrated that the profound G1 arrest in E7-depleted CaSki cells was dependent on p130-DREAM reformation by also targeting the expression of the DREAM component Lin-54 and p130. The results show that continued HPV16 E6/E7 expression is necessary in cervical cancer cells to prevent cell-cycle arrest by a repressive p130-DREAM complex. PMID:21813705

Nor Rashid, Nurshamimi; Yusof, Rohana; Watson, Roger J

2011-11-01

150

Expression of PBK/TOPK in cervical cancer and cervical intraepithelial neoplasia  

PubMed Central

objectives: To evaluate the expression of PBK/TOPK (PDZ-binding kinase/T-LAK cell-originated protein kinase) and its clinical significance in cervical cancer and cervical intraepithelial neoplasia. Methods: PBK/TOPK expression was detected in 28 cases of low-grade cervical intraepithelial neoplasia (CINI), 62 cases of high-grade intraepithelial neoplasia and 80 cases of cervical cancer by immunohistochemistry (IHC). Then, the correlation between PBK/TOPK expression and clinicopathological features was quantitatively analyzed by measuring the positive unit (PU). Results: PBK/TOPK expression was significantly greater in cervical cancer than that in high-grade intraepithelial neoplasia and CINI (P < 0.05). Meanwhile, PBK/TOPK expression in high-grade intraepithelial neoplasia was significantly higher compared with that in CINI (P < 0.05). In addition, PBK/TOPK expression in cervical cancer significantly correlated with histological type, differentiation, lymph node metastasis, vaginal and cervical invasion, TNM stage and tumor size (P < 0.05). Conclusion: PBK/TOPK expression is closely associated with cervical cancer and cervical intraepithelial neoplasia, which may be served as a useful target for tumor diagnosis and immunotherapy. PMID:25550851

Luo, Qiong; Lei, Bin; Liu, Shuguang; Chen, Yaowen; Sheng, Wenjie; Lin, Peixin; Li, Wenxia; Zhu, Haili; Shen, Hong

2014-01-01

151

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

ClinicalTrials.gov

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

2014-12-23

152

Cervical Cancer Incidence and Mortality Rates  

Cancer.gov

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

153

Get Tested for Cervical Cancer  

MedlinePLUS

... Testing for cervical cancer is covered under the Affordable Care Act , the health care reform law passed in 2010. Depending on your insurance plan, you may be able to get tested at no cost to you. If ... about the Affordable Care Act. If you don’t have insurance, find a ...

154

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

PubMed Central

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

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

2015-01-01

155

Effect of coating material on uptake of indocyanine green-loaded nanocapsules by HeLa cervical cancer cells  

NASA Astrophysics Data System (ADS)

Fluorescent molecular probes offer a potential for early cancer detection. Indocyanine green (ICG) is an FDAapproved near-infrared (NIR) fluorescent dye used in ophthalmic angiography and assessment of cardiac and hepatic functions. However, clinical applications of ICG remain very limited due to its rapid clearance from vascular circulation, unstable optical properties, non-specific interactions with plasma proteins, and inability for localized targeting. To overcome these limitations, we have encapsulated ICG within nanoconstructs composed of poly(allylamine) hydrochloride and disodium hydrogen phosphate salt. To understand the effects of coating materials on the cellular uptake of the nanocapsules, we have measured the uptake of ICG-loaded nanocapsules (ICG-NCs) with various coating materials by HeLa cancerous cervical epithelial cells in-vitro. Results of this study provide important information for the choice of appropriate coating materials that will result in maximal uptake of ICG-NCs in optical and phototherapy of cancerous tissue.

Jung, Bongsu; Lomeli, Eulieses; Anvari, Bahman

2010-02-01

156

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

PubMed

Although certain studies have demonstrated no association between the stromal cell?derived factor?1 (SDF1?3') G801A single nucleotide polymorphism (SNP) and cervical carcinoma, the interactions between the SDF1?3' G801A SNP and contraceptive use, menopausal status, parity and tobacco smoking remain to be fully elucidated. Using polymerase chain reaction?restriction fragment length polymorphism, the distribution of SDF1?3' G801A genotypes in patients with cervical cancer (n=462) against control groups (n=497) was investigated. Logistic regression analysis, adjusting for age, pregnancy, oral contraceptive use, tobacco smoking and menopausal status, did not identify the SDF1?3' G801A polymorphism as a genetic risk factor for cervical cancer. The adjusted odds ratio (OR) for patients with the A/G, vs. G/G genotype was 1.203, with a 95% confidence interval (CI) of 0.909?1.591 (P=0.196). The adjusted OR for the A/A, vs. G/G genotype was 1.296 (95% CI=0.930?1.807; P=0.125) and for the A/A or A/G, vs. G/G genotype was 1.262 (95% CI=0.964?1.653; P=0.090)]. The P?value of the ?2 test of the trend observed for the SDF1?3' G801A polymorphism was at the borderline of being statistically significant (ptrend=0.0484). Stratified analyses between the distribution of the SDF1?3' G801A genotypes and cervical cancer risks demonstrated that this polymorphism may be a risk factor for patients with a positive history of tobacco smoking (1.778; 95% CI=1.078?2.934; P=0.0235). These findings suggested that the SDF1?3' G801A polymorphism may be a genetic risk factor for cervical cancer in patients with a positive history of tobacco smoking. PMID:25672413

Roszak, Andrzej; Misztal, Matthew; Sowi?ska, Anna; Jagodzi?ski, Pawe? P

2015-06-01

157

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

PubMed Central

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

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

2014-01-01

158

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

PubMed

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

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

2015-06-15

159

Clinical significance of telomerase activation and telomeric restriction fragment (TRF) in cervical cancer  

Microsoft Academic Search

Telomerase activation was examined in 50 cases of cervical cancer, 27 normal cervix and five cervical cancer cell lines using the sensitive polymerase chain reaction (PCR)-based TRAP (telomeric repeat amplification protocol) assay. Telomeric restriction fragment (TRF) length of these specimens was measured by Southern hybridisation. Telomerase activation was common in cervical cancers and was detected in 46\\/50 cases (92%). Telomerase

D. K Zhang; H. Y. S Ngan; R. Y. S Cheng; A. N. Y Cheung; S. S Liu; S. W Tsao

1999-01-01

160

Immune-Based Treatment Shows Promise against Metastatic Cervical Cancer  

Cancer.gov

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

161

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

PubMed Central

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 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 of vulnerability and an increased need to care for themselves. Later on, an understanding of HPV as the basis for diagnosis and the realization that disease might not be accompanied by symptoms developed. The outcome for participants was a life experience, which they used to encourage others to participate in screening and to suggest ways that information about screening and HPV might reach a wider Greenlandic population. Conclusion Women living through the process of cervical disease, treatment and follow-up develop knowledge about HPV, cervical cell changes, cervical disease and their connection, which, if used to inform cervical screening programmes, will improve the quality of information about HPV, cervical cancer and screening participation. This includes that verbal and written information given at the point of screening and diagnosis needs to be complemented by visual imagery. PMID:23984277

Hounsgaard, Lise; Augustussen, Mikaela; Møller, Helle; Bradley, Stephen K.; Møller, Suzanne

2013-01-01

162

Screening for Cervical Cancer  

MedlinePLUS

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

163

The Inhibitory Effect of a Novel Polypeptide Fraction from Arca subcrenata on Cancer-Related Inflammation in Human Cervical Cancer HeLa Cells  

PubMed Central

Inflammation is known to be closely associated with the development of cancer. The study was launched in human cervical cancer HeLa cells to investigate the antitumor and anti-inflammatory effects of P2, a marine polypeptide fraction from an important fishery resource Arca subcrenata. The basic research showed that P2 could suppress the production of nitric oxide in LPS-induced RAW264.7 macrophage cells as well as the secretion of inflammatory cytokines IL-6 and TNF-? in human cervical cancer HeLa cells. For the molecular mechanisms, P2 was shown to downregulate the gene expression of proinflammatory cytokines IL-6 and IL-8 and to inhibit the COX-2 and iNOS-related pathways in HeLa cells. In consequence, P2 might inhibit tumor development by blocking the interaction between tumor microenvironment and proinflammatory mediators. All findings indicate that P2 possesses the potential to be developed as a novel agent for cancer therapy. PMID:24683359

Wu, Yu; Hu, Xianjing; Song, Liyan; Zhu, Jianhua; Yu, Rongmin

2014-01-01

164

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

PubMed

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

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

2015-05-01

165

Withaferin A induces p53-dependent apoptosis by repression of HPV oncogenes and upregulation of tumor suppressor proteins in human cervical cancer cells.  

PubMed

Cervical cancer is caused by human papilloma virus (HPV) expressing E6 and E7 oncoproteins, which are known to inactivate tumor suppressor proteins p53 and pRb, respectively. Repression of HPV oncoproteins would therefore result in reactivation of tumor suppressor pathways and cause apoptosis in cancer cells. Withaferin A (WA), the active component of the medicinal plant Withania Somnifera, has exhibited inhibitory effects against several different cancers. We examined the activity of WA on human cervical cancer cells in vitro and in vivo. WA potently inhibited proliferation of the cervical cancer cells, CaSki (IC(50) 0.45 ± 0.05 ?M). Mechanistically, WA was found to (i) downregulate expression of HPV E6 and E7 oncoproteins, (ii) induce accumulation of p53, (iii) increase levels of p21(cip1/waf1) and its interaction with proliferating cell nuclear antigen (PCNA), (iv) cause G(2)/M cell cycle arrest, associated with modulation of cyclin B1, p34(cdc2) and PCNA levels, (v) decrease the levels of STAT3 and its phosphorylation at Tyr(705) and Ser(727) and (vi) alter expression levels of p53-mediated apoptotic markers-Bcl2, Bax, caspase-3 and cleaved PARP. In vivo, WA resulted in reduction of nearly 70% of the tumor volume in athymic nude mice with essentially similar trend in the modulation of molecular markers as in vitro. This is the first demonstration indicating that WA significantly downregulates expression of HPV E6/E7 oncogenes and restores the p53 pathway, resulting in apoptosis of cervical cancer cells. Together, our data suggest that WA can be exploited as a potent therapeutic agent for the treatment and prevention of cervical cancer without deleterious effects. PMID:21859835

Munagala, Radha; Kausar, Hina; Munjal, Charu; Gupta, Ramesh C

2011-11-01

166

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

PubMed

T-lymphokine-activated killer cell-originated protein kinase (TOPK) appears to be highly expressed in various cancer cells and to play an important role in maintaining proliferation of cancer cells. However, the underlying mechanism by which TOPK regulates growth of cancer cells remains elusive. Here we report that upregulated endogenous TOPK augments resistance of cancer cells to apoptosis induced by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Stable knocking down of TOPK markedly increased TRAIL-mediated apoptosis of human HeLa cervical cancer cells, as compared with control cells. Caspase 8 or caspase 3 activities in response to TRAIL were greatly incremented in TOPK-depleted cells. Ablation of TOPK negatively regulated TRAIL-mediated NF-kappaB activity. Furthermore, expression of NF-kappaB-dependent genes, FLICE-inhibitory protein (FLIP), inhibitor of apoptosis protein 1 (c-IAP1), or X-linked inhibitor of apoptosis protein (XIAP) was reduced in TOPK-depleted cells. Collectively, these findings demonstrated that TOPK contributed to TRAIL resistance of cancer cells via NF-kappaB activity, suggesting that TOPK might be a potential molecular target for successful cancer therapy using TRAIL. PMID:19945431

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

2010-01-01

167

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

SciTech Connect

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

Kwon, Hyeok-Ran [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of)] [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of); Lee, Ki Won [Department of Bioscience and Biotechnology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701 (Korea, Republic of)] [Department of Bioscience and Biotechnology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701 (Korea, Republic of); Dong, Zigang [Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912 (United States)] [Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912 (United States); Lee, Kyung Bok [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of)] [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of); Oh, Sang-Muk, E-mail: sangmuk_oh@konyang.ac.kr [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of)] [Department of Biochemistry, College of Medicine, Konyang University, 685 Gasuwon-dong, Seo-gu, Daejeon 302-718 (Korea, Republic of)

2010-01-01

168

What Are the Key Statistics about Cervical Cancer?  

MedlinePLUS

... factors for cervical cancer? What are the key statistics about cervical cancer? The American Cancer Society's estimates ... Symptoms of Cancer Treatments & Side Effects Cancer Facts & Statistics News About Cancer Expert Voices Blog Programs & Services ...

169

Factors associated with radiosensitivity of cervical cancer.  

PubMed

Radiation therapy plays a critical role in women with advanced-stage cervical cancer worldwide, particularly in developing countries, and most of the time it may be the only available treatment. The efficacy of radiation largely depends on the radiosensitivity of the tumor. The high radiation dose associated with therapy for cervical cancer may have severe side-effects and low-dose radiation has little effect on cervical cancer. A safe and effective radiosensitizing agent is required to allow reduction of radiation doses used and of side-effects associated with radiation for cervical cancer. In recent years, great knowledge has been gained about the effects of apoptosis, cyclo-oxygenases, angiogenesis, hypoxia and temperature on radiation, making it possible to manipulate the radiation response of cervical cancer to achieve a better treatment outcome. In this mini review, some of these factors associated with the radiosensitivity of cervical cancer are discussed. PMID:25202040

Qin, Chenglu; Chen, Xuhui; Bai, Qian; Davis, Matthew R; Fang, Yujiang

2014-09-01

170

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

PubMed Central

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

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

2015-01-01

171

Expression of keratinocyte growth factor receptor (KGFR/FGFR2 IIIb) in human uterine cervical cancer.  

PubMed

Keratinocyte growth factor receptor (KGFR), also known as FGFR2 IIIb, is a splice variant of FGFR-2. KGFR is expressed in many types of epithelial cell and is activated with four known ligands [FGF-1, FGF-3, FGF-7 (also known as KGF) and FGF-10] that are predominantly synthesized by mesenchymal cells. KGFR is highly expressed in the late-proliferative phase of a normal endometrium and in endometrial adenocarcinoma. In the present study, we attempted to determine the expression and localization of KGFR in human cervical cancer cell lines and cervical cancer tissues. The KGFR protein was detected in CaSki and HeLa cells, but not in ME-180 cells of cervical cancer cell lines. In non-cancer cervical tissues, KGFR immunoreactivity was weakly expressed in the surface of squamous epithelial cells and vascular smooth muscle cells. Immunohistochemically, the KGFR protein was detected in squamous cell carcinoma in 36 of 42 (86%) cervical cancer patients. In cervical cancer tissues, KGFR was detected in 17 of 18 (94%) of patients with the keratinizing type and 19 of 24 (79%) of patients with the non-keratinizing type of cervical cancer. Furthermore, KGFR was prominently localized in proliferating reserve cells and squamous metaplastic reserve cells adjacent to cancer cells. In contrast, KGFR was not detected in cervical ductal cells in cancer or non-cancer cervical tissues. These findings may indicate that KGFR mediates the growth and differentiation of reserve cells and squamous cell carcinoma in the cervix. PMID:15069536

Kurban, Gulnar; Ishiwata, Toshiyuki; Kudo, Mitsuhiro; Yokoyama, Munehiro; Sugisaki, Yuichi; Naito, Zenya

2004-05-01

172

Chemotherapy for advanced or recurrent cervical cancer.  

PubMed

The primary treatment options for cervical cancer are surgery and radiation for more than a century. However, over the last 40 years chemotherapy has been building up its reputation in the management of cervical cancer in various forms such as chemoradiation, neoadjuvant chemotherapy, and palliative chemotherapy for advanced or recurrent disease. Among these, in this review, chemotherapy for advanced or recurrent cervical cancer will be discussed. PMID:23915846

Kamura, Toshiharu; Ushijima, Kimio

2013-06-01

173

Cervical Cancer: Screening and Therapeutic Perspectives  

Microsoft Academic Search

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

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

2008-01-01

174

Effect of Pleurotus ferulae extracts on viability of human lung cancer and cervical cancer cell lines  

Microsoft Academic Search

When SiHa cells were incubated for varying periods of time with extracts of PFF and PFM, the cytotoxicity of the ethanol extracts\\u000a of PFF was higher than those of the other extracts. These results indicated that the extracts from fruiting bodies ofP. ferulae contain antitumor substances. When A549, SiHa and HeLa cells were incubated with different concentrations of PFF and

DuBok Choi; Wol-Suk Cha; Si-Hyung Kang; Byoung-Rai Lee

2004-01-01

175

Clinical significance of osteopontin expression in cervical cancer  

Microsoft Academic Search

Purpose  New diagnostic markers, other than squamous cell carcinoma (SCC) antigen, are needed for the detection of cervical cancer.\\u000a Osteopontin (OPN) is a candidate frequently associated with several human malignancies. The purpose of this study was to evaluate\\u000a the clinical significance of OPN expression as a diagnostic and prognostic biomarker for cervical cancer.\\u000a \\u000a \\u000a \\u000a Methods  Immunohistochemical staining of tissue from 97 cervical cancer

HanByoul Cho; Soon Won Hong; Youn Jin Oh; Min A Kim; Eun Suk Kang; Jong Min Lee; Sang Wun Kim; Sung Hoon Kim; Jae Hoon Kim; Young Tae Kim; Kook Lee

2008-01-01

176

Wogonin induces apoptosis by suppressing E6 and E7 expressions and activating intrinsic signaling pathways in HPV-16 cervical cancer cells.  

PubMed

Wogonin is a flavonoid compound extracted from Scutellaria baicalensis and is well known as a benzodiazepine receptor ligand with anxiolytic effects. Many recent studies have demonstrated that wogonin modulates angiogenesis, proliferation, invasion, and tumor progress in various cancer tissues. We further explored the mechanism of action of wogonin on cervical cancer cells that contain or lack human papillomavirus (HPV) DNA. Wogonin was cytotoxic to HPV 16 (+) cervical cancer cells, SiHa and CaSki, but not to HPV-negative cells. We demonstrated that wogonin induced apoptosis by suppressing the expressions of the E6 and E7 viral oncogenes in HPV-infected cervical cancer CaSki and SiHa cells. The modulation of p53 and protein retinoblastoma (pRb) were also triggered by the suppression of E6 and E7 expressions. However, p53 was not altered in HPV-negative cervical cancer C33A cells. Moreover, wogonin modulated the mitochondrial membrane potential and the expression of pro- and anti-apoptotic factors such as Bax and Bcl-2. Wogonin also provoked the cleavage of caspase-3, caspase-9, and poly ADP ribose polymerase. After transfection of siRNAs to target E6 and E7, additional restoration of p53 and pRb was not induced, but processing of caspases and PARP was increased compared with wogonin treatment alone. Together, our findings demonstrated that wogonin effectively promotes apoptosis by downregulating E6 and E7 expressions and promoting intrinsic apoptosis in human cervical cancer cells. PMID:23955116

Kim, Man Sub; Bak, Yesol; Park, Yun Sun; Lee, Dong Hun; Kim, Jung Hee; Kang, Jeong Woo; Song, Hyuk-Hwan; Oh, Sei-Ryang; Yoon, Do Young

2013-08-01

177

Nanotechnology in the management of cervical cancer.  

PubMed

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. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25752817

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

2015-03-01

178

Azithromycin synergistically enhances anti-proliferative activity of vincristine in cervical and gastric cancer cells.  

PubMed

In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC50) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 ?g/mL of VCR, the respective IC50 values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs. PMID:24213508

Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming; Wang, Yujiong

2012-01-01

179

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

PubMed Central

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

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

2014-01-01

180

Aberrant cell cycle regulation in cervical carcinoma.  

PubMed

Carcinoma of the uterine cervix is one of the most common malignancies among women worldwide. Human papillomaviruses (HPV) have been identified as the major etiological factor in cervical carcinogenesis. However, the time lag between HPV infection and the diagnosis of cancer indicates that multiple steps, as well as multiple factors, may be necessary for the development of cervical cancer. The development and progression of cervical carcinoma have been shown to be dependent on various genetic and epigenetic events, especially alterations in the cell cycle checkpoint machinery. In mammalian cells, control of the cell cycle is regulated by the activity of cyclin-dependent kinases (CDKs) and their essential activating coenzymes, the cyclins. Generally, CDKs, cyclins, and CDK inhibitors function within several pathways, including the p16(INK4A)-cyclin D1-CDK4/6-pRb-E2F, p21(WAF1)- p27(KIP1)-cyclinE-CDK2, and p14(ARF)-MDM2-p53 pathways. The results from several studies showed aberrant regulation of several cell cycle proteins, such as cyclin D, cyclin E, p16(INK4A), p21(WAF1), and p27(KIP1), as characteristic features of HPV- infected and HPV E6/E7 oncogene-expressing cervical carcinomas and their precursors. These data suggested further that interactions of viral proteins with host cellular proteins, particularly cell cycle proteins, are involved in the activation or repression of cell cycle progression in cervical carcinogenesis. PMID:16259056

Kim, Young Tae; Zhao, Min

2005-10-31

181

Immunohistochemical LRIG3 Expression in Cervical Intraepithelial Neoplasia and Invasive Squamous Cell Cervical Cancer: Association with Expression of Tumor Markers, Hormones, High-Risk HPV-Infection, Smoking and Patient Outcome  

PubMed Central

The novel biomarker LRIG3 is a member of the LRIG family (LRIG1-3). While LRIG1 has been associated with favorable prognosis and LRIG2 with poor prognosis in invasive cervical cancer, little is known about the role of LRIG3. The aim of this study was to investigate the expression of LRIG3 in invasive cancer and cervical intraepithelial neoplasia (CIN) for possible correlation with other tumor markers, to hormones and smoking, as a diagnostic adjunct in CIN, and prognostic value in invasive cancer. Cervical biopsies from 129 patients with invasive squamous cell carcinoma and 170 biopsies showing low grade and high grade CIN, or normal epithelium were stained for LRIG3 and 17 additional tumor markers. Among other variables the following were included: smoking habits, hormonal contraceptive use, serum progesterone, serum estradiol, high-risk HPV-infection, menopausal status and ten-year survival. In CIN, high expression of the tumor suppressors retinoblastoma protein, p53, and p16, and Ecadherin (cell-cell interaction), or low expression of CK10, correlated to LRIG3 expression. In addition, progestogenic contraceptive use correlated to high expression of LRIG3. In invasive cancer there was a correlation between expression of the major tumor promoter c-myc and high LRIG3 expression. High LRIG3 expression correlated significantly to presence of high-risk HPV infection in patients with normal epithelium and CIN. There was no correlation between LRIG3 expression and 10-year survival in patients with invasive cell cervical cancer. LRIG3 expression is associated with a number of molecular events in CIN. Expression also correlates to hormonal contraceptive use. The results on expression of other tumor markers suggest that LRIG3 is influenced by or influences a pattern of tumor markers in cancer and precancerous cells. Further studies are needed to elucidate if LRIG3 expression might be clinically useful. PMID:24998916

Lindström, A.K.; Hellberg, D.

2014-01-01

182

HPV types and cofactors causing cervical cancer in Peru  

Microsoft Academic Search

We conducted a hospital-based case-control study in Peru of 198 women with histologically confirmed cervical cancer (173 squamous cell carcinomas and 25 cases of adenocarcinoma\\/adenosquamous carcinoma) and 196 control women. Information on risk factors was obtained by personal interview. Using PCR-based assays on exfoliated cervical cells and biopsy specimens, HPV DNA was detected in 95.3% of women with squamous cell

C Santos; N Muñoz; S Klug; M Almonte; I Guerrero; M Alvarez; C Velarde; O Galdos; M Castillo; J Walboomers; C Meijer; E Caceres

2001-01-01

183

Study finds genomic differences in types of cervical cancer  

Cancer.gov

A new study has revealed marked differences in the genomic terrain of the two most common types of cervical cancer, suggesting that patients might benefit from therapies geared to each type’s molecular idiosyncrasies. The study, published August 23, 2013 in the online version of the journal Cancer by researchers at Dana-Farber Cancer Institute and Brigham and Women’s Hospital (BWH), is the first to compare the spectrum of cancer-related gene mutations in the two main subtypes of cervical cancer – adenocarcinoma and squamous cell carcinoma.

184

Anti-proliferative and pro-apoptotic effects of 3,3'-diindolylmethane in human cervical cancer cells.  

PubMed

The antitumor effects of Indo-3-carbinol (I3C) have been proven in many human carcinoma cells. However, the roles of 3,3-diindolylmethane (DIM), an important polymer converted from I3C under pH 5.0-7.0, on the growth and proliferation of cervical cancer HeLa and SiHa cells still remain unrevealed. In the present study, we investigated the potential anti-proliferative and pro-apoptotic effects of DIM on HeLa and SiHa cells. Cell proliferation was detected by Cell Counting kit-8 and apoptosis was analyzed by flow cytometry. In addition, morphological changes accompanying cell apoptosis were observed using an inverted microscope after Hoechst 33258 staining. In addition, expression changes of proteins involved in the MAPK and PI3K pathways were determined by western blotting. DIM treatment inhibited the proliferation and induced apoptosis of HeLa and SiHa cells significantly in a time- and dose-dependent manner. Moreover, SiHa cells were more sensitive to DIM treatment than HeLa cells (P<0.05). In addition, the expression of ERK, p38 and p-p38, which are involved in the MAPK pathway, was downregulated by DIM treatment. Another protein involved in the MAPK pathway, JNK, was upregulated. Furthermore, DIM treatment significantly suppressed the expression of Akt, p-Akt, PI3K p110?, PI3K p110?, PI3K class III, GSK3-?, p-PDK1 and p-c-Raf which are involved in the PI3K pathway. These results demonstrate that DIM exerts antitumor effects on HeLa and SiHa cells through its anti-proliferative and pro-apoptotic roles, especially for SiHa cells. The molecular mechanism for these effects may be related to its regulatory effects on MAPK and PI3K pathway and apoptosis proteins. DIM may be a preventive and therapeutic agent against cervical cancer. PMID:22736073

Zhu, Junyong; Li, Yuan; Guan, Chao; Chen, Zuhua

2012-09-01

185

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

PubMed Central

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

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

2015-01-01

186

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

PubMed

Metastasis is the most common cause of cancer-related death in patients, and epithelial-to-mesenchymal transition (EMT) is essential for cancer metastasis, which is a multistep complicated process that includes local invasion, intravasation, extravasation, and proliferation at distant sites. When cancer cells metastasize, angiogenesis is also required for metastatic dissemination, given that an increase in vascular density will allow easier access of tumor cells to circulation, and represents a rational target for therapeutic intervention. Berberine has several anti-inflammation and anticancer biologic effects. In this study, we provided molecular evidence that is associated with the antimetastatic effect of berberine by showing a nearly complete inhibition on invasion (P < 0.001) of highly metastatic SiHa cells via reduced transcriptional activities of matrix metalloproteinase-2 and urokinase-type plasminogen activator. Berberine reversed transforming growth factor-?1-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. PMID:25217495

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

2014-12-01

187

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

PubMed Central

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

Rupachandra, S.; Sarada, D. V. L.

2014-01-01

188

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

PubMed

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. PMID:25747718

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

2015-04-10

189

Flexitouch® Home Maintenance Therapy or Standard Home Maintenance Therapy in Treating Patients With Lower-Extremity Lymphedema Caused by Treatment for Cervical Cancer, Vulvar Cancer, or Endometrial Cancer  

ClinicalTrials.gov

Lymphedema; Stage 0 Cervical Cancer; Stage 0 Uterine Corpus Cancer; Stage 0 Vulvar Cancer; Stage I Uterine Corpus Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Uterine Corpus Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vulvar Cancer; Stage IV Uterine Corpus Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Stage IVB Vulvar Cancer

2014-12-29

190

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

SciTech Connect

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.

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

191

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

NASA Astrophysics Data System (ADS)

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/?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 ˜ 28% reduction of 12C6+ ion dose for Glu-AuNP treated HeLa cells as compared to control HeLa cells.

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

2013-07-01

192

New insights into cervical cancer screening  

PubMed Central

Worldwide, cervical cancer is a leading cause of cancer related morbidity and mortality. For over 50 years, cervical cytology has been the gold standard for cervical cancer screening. Because of its profound effect on cervical cancer mortality in nations that have adopted screening programs, the Pap smear is widely accepted as the model screening test. Since its introduction, many studies have analyzed the Pap smear and found that it is not without its shortcomings including low sensitivity for detection of cervical intraepithelial neoplasia 2/3. Additionally, the discovery of infection with the human papillomavirus (HPV) as a necessary step in the development of cervical cancer has led to the development of HPV testing as an adjunct to cytology screening. More recently, researchers have compared HPV testing and cytology in the primary screening of cervical cancer. In this review, we will discuss cytologic testing limitations, the role of HPV DNA testing as an alternative screening tool, the impact of the HPV vaccine on screening, and future directions in cervical cancer screening. PMID:23094132

Boone, Jonathan D.; Erickson, Britt K.

2012-01-01

193

Detection of TERC amplification in cervical epithelial cells for the diagnosis of high-grade cervical lesions and invasive cancer: a multicenter study in China.  

PubMed

Because the activation of telomerase is a relatively early event in the progression of cervical carcinogenesis, the expression of the human telomerase RNA gene, TERC, has the potential to serve as a biomarker for both the diagnosis and prognosis of cervical neoplasias. In total, 83 research centers participated in the study, and 7786 patients were enrolled. TERC amplification was detected using a dual-color fluorescence in situ hybridization (FISH) probe set, and these results were compared with cytological and histological results, testing for high-risk human papillomavirus (HPV) DNA (n = 2316 for the HPV DNA test), as well as patient age. TERC amplification was found to be increased in more advanced cases of cervical carcinogenesis. Moreover, a Youden's index value and the area under the receiver operating characteristic (ROC) curve were also calculated for samples with TERC amplification and found to be higher than the same values calculated for both cytology and high-risk HPV analyses of the same samples. With regard to cytological ASCUS and LSIL findings, the combination of HPV + TERC testing showed the potential to provide effective triaging to detect CIN2(+). Therefore, TERC amplification represents a valuable genetic biomarker, which in combination with an evaluation of cytology or HPV testing, can achieve higher sensitivity and specificity in distinguishing high-grade cervical lesions and invasive cancers from low-grade lesions compared with conventional methods. PMID:20864639

Jiang, Jing; Wei, Li-Hui; Li, Ya-Li; Wu, Rui-Fang; Xie, Xing; Feng, You-Ji; Zhang, Guo; Zhao, Chao; Zhao, Yun; Chen, Zhong

2010-11-01

194

The Interactions between L-Tyrosine Based Nanoparticles Decorated with Folic Acid and Cervical Cancer Cells Under Physiological Flow  

PubMed Central

Many anticancer drugs have been established clinically, but their efficacy can be compromised by nonspecific toxicity and an inability to reach the desired cancerous intracellular spaces. In order to address these issues, researchers have explored the use of folic acid as a targeted moiety to increase specificity of chemotherapeutic drugs. To expand upon such research, we have conjugated folic acid to functionalized poly(ethylene glycol) and subsequently decorated the surface of L-tyrosine polyphosphate (LTP) nanoparticles. These nanoparticles possess the appropriate size (100–500 nm) for internalization as shown by scanning electron microscopy and dynamic light scattering. Under simulated physiological flow, LTP nanoparticles decorated with folic acid (targeted nanoparticles) show a 10-fold greater attachment to HeLa, a cervical cancer cell line, compared to control nanoparticles and to human dermal fibroblasts. The attachment of these targeted nanoparticles progresses at a linear rate, and the strength of this nanoparticle attachment is shown to withstand shear stresses of 3.0 dynes/cm2. These interactions of the targeted nanoparticles to HeLa are likely a result of a receptor-ligand binding, as a competition study with free folic acid inhibits the nanoparticle attachment. Finally, the targeted nanoparticles encapsulated with a silver based drug show increased efficacy in comparison to non-decorated (plain) nanoparticles and drug alone against HeLa cells. Thus, targeted nanoparticles are a promising delivery platform for developing anticancer therapies that over-express the folate receptors (FRs). PMID:22957928

Ditto, Andrew J.; Shah, Kush N.; Robishaw, Nikki K.; Panzner, Matthew J.; Youngs, Wiley J.; Yun, Yang H.

2012-01-01

195

Circulating Tumor Markers in Cervical Cancer  

Microsoft Academic Search

Serum levels of CA 19-9, CA 125 and CA 15-3 were measured in 91 patients with cervical cancer (16 with intraepithelial neoplasia and 75 with invasive cancer). In 35 patients with locally advanced cervical cancer, serum marker levels were measured at monthly intervals during neo-adjuvant chemotherapy. CA 19-9 was found to be abnormally high only in advanced stages with an

P. Benedetti Panici; G. Scambia; G. Baiocchi; C. Sonsini; S. Greggi; F. Battaglia; S. Mancuso

1989-01-01

196

Cervical Cancer: paradigms at home and abroad  

Cancer.gov

NCI funded a clinical trial that will have an impact on the treatment of late-stage cervical cancer, and also supported a screening trial in India using a network of community outreach workers offering low tech-screening by direct visualization of the cervix coated with dilute acetic acid (vinegar), a process known as VIA. Image depicts cervical cancer microvessel density which increases lethality of the cancer.

197

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

PubMed Central

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-1? (IL-1?), and tumor necrosis factor-? (TNF-?) 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-1?, TNF-?, and nitrates levels. At the same time, the mRNA level of COX-2 in HeLa cells was also significantly increased. These changes were attenuated by crocetin supplementation in the MCA mice. Crocetin supplementation in the MCA mice also showed protection against cervical cancer. These results suggest that crocetin may act as a chemopreventive and an anti-inflammatory agent. PMID:25874230

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

2015-01-01

198

Chlamydia trachomatis infection: implications for HPV status and cervical cancer.  

PubMed

Genital Chlamydia trachomatis (CT) infections have been identified as a major health problem concern. CT is associated with adverse effect on women reproduction and also associated with cervical hypertrophy and induction of squamous metaplasia, providing a possible relationship with human papillomavirus (HPV) infection. Infection by high-risk HPV types is crucial to the pathogenesis of invasive cervical cancer (ICC), but other co-variants/cofactors must be present for the development of malignancy. CT biological effect may damage the mucosal barrier, improving HPV infection, or may interfere in immune response and viral clearance supporting the persistence of HPV infection. Moreover, CT-related chronic cervical inflammation, decrease of lower genital tract antigen-presenting cells, inhibition of cell-mediated immunity, and anti-apoptotic capacity may influence the natural history of HPV infection, namely persistence progression or resolution. Although several epidemiological studies have stated a positive association involving CT and HPV-related cervical neoplastic lesions and/or cervical cancer (CC), the specific role of this bacterium in the pathogenesis of cervical neoplasia has not been completely clarified. The present review summarizes several studies on CT role in cervical cancer and suggests future research directions on HPV and CT interaction. PMID:24346121

Silva, Jani; Cerqueira, Fátima; Medeiros, Rui

2014-04-01

199

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

PubMed

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

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

2015-03-01

200

Quality of life measurement in women with cervical cancer: implications for Chinese cervical cancer survivors  

Microsoft Academic Search

BACKGROUND: Women with cervical cancer now have relatively good 5-year survival rates. Better survival rates have driven the paradigm in cancer care from a medical illness model to a wellness model, which is concerned with the quality of women's lives as well as the length of survival. Thus, the assessment of quality of life among cervical cancer survivors is increasingly

Ying Chun Zeng; Shirley SY Ching; Alice Y Loke

2010-01-01

201

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

PubMed Central

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

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

2013-01-01

202

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

PubMed Central

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

2013-01-01

203

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

PubMed Central

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

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

2013-01-01

204

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

PubMed

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

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

2013-01-01

205

Epidemiology of cervical cancer in Colombia  

PubMed Central

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 vaccines; and (ii) secondary prevention by increasing the accuracy of cervical cancer screening. PMID:24893303

Muñoz, Nubia

2012-01-01

206

Laparoscopic Fertility Sparing Management of Cervical Cancer  

PubMed Central

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

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

2014-01-01

207

Molecularly targeted therapies in cervical cancer. A systematic review.  

PubMed

Cervical cancer represents the third most common cause of female cancer mortality. Even with the best currently available treatment, a significant proportion of patients will experience recurrence and eventually die. Evidently, there is a clear need for the development of new agents with novel mechanisms of action in this disease. A number of biological agents modulating different signal transduction pathways are currently in clinical development, inhibiting angiogenesis, targeting epidermal growth factor receptor, cell cycle, histone deacetylases, cyclooxygenase-2 (COX-2), or mammalian target of rapamycin (mTOR). This is the first systematic review of the literature to synthesize all available data emerging from trials and evaluate the efficacy and safety of molecularly targeted drugs in cervical cancer. However, it should be stressed that relatively fewer molecularly targeted agents have been tested in cervical cancer in comparison with other cancer types; of note, no related phase 3 trials have been published and consequently no agent has been approved for use in clinical practice. Nevertheless, the promising results of bevacizumab in therapeutic trials for cervical cancer have shown that targeting the VEGF pathway is an attractive therapeutic strategy. As knowledge accumulates on the molecular mechanisms underlying carcinogenesis in the cervix, the anticipated development and assessment of molecularly targeted agents may offer a promising perspective for cervical cancer. PMID:22504292

Zagouri, Flora; Sergentanis, Theodoros N; Chrysikos, Dimosthenis; Filipits, Martin; Bartsch, Rupert

2012-08-01

208

2-5A antisense therapy directed against human telomerase RNA inhibits telomerase activity and induces apoptosis without telomere impairment in cervical cancer cells  

Microsoft Academic Search

Human telomerase RNA (hTR), an important component of telomerase, is a possible target of telomerase-based cancer gene therapy. The present study was undertaken to assess the efficacy of antisense hTR therapy using newly developed 2-5A (5?-phosphorylated 2?-5?–linked oligoadenylate)–linked oligonucleotides against cervical cancer cells. ME180 and SiHa cells were treated with 2-5A–linked antisense hTR designed to complement the region of hTR

Noriyuki Yatabe; Satoru Kyo; Seiji Kondo; Taro Kanaya; Zhuo Wang; Yoshiko Maida; Masahiro Takakura; Mitsuhiro Nakamura; Masaaki Tanaka; Masaki Inoue

2002-01-01

209

A novel human monoclonal antibody against cervical cancer: its immunoreactivity with normal tube and ovary and with ovarian tumor tissue  

Microsoft Academic Search

1-1-2D, a novel human monoclonal antibody (MAb) raised against cervical cancer, was examined for its immunohistochemical reactivity with ovarian cancer. Six of 10 ovarian cancer cell lines showed positive staining, while 3 of 5 cervical cancer cell lines were positive. Among tumor tissues, 15 of 18 (83%) ovarian serous cystadenocarcinomas and 10 of 12 (83%) ovarian clear cell adenocarcinomas were

T. Nakanishi; T. Okamoto; A. Nawa; T. Suzuki; K. Ino; Y. Wakahara; N. Horibe; S. Goto; Y. Tomoda

1995-01-01

210

A novel human monoclonal antibody against cervical cancer: its immunoreactivity with normal tube and ovary and with ovarian tumor tissue  

Microsoft Academic Search

1-1-2?D, a novel human monoclonal antibody (MAb) raised against cervical cancer, was examined for its immunohistochemical reactivity with ovarian cancer. Six of 10 ovarian cancer cell lines showed positive staining, while 3 of 5 cervical cancer cell lines were positive. Among tumor tissues, 15 of 18 (83%) ovarian serous cystadenocarcinomas and 10 of 12 (83%) ovarian clear cell adenocarcinomas were

T. Nakanishi; T. Okamoto; A. Nawa; T. Suzuki; K. Ino; Y. Wakahara; N. Horibe; S. Goto; Y. Tomoda

1995-01-01

211

University of Arizona researchers report on cervical cancer study  

Cancer.gov

Dr. Monk is nationally recognized for his expertise in cervical cancer and chairs the Gynecologic Oncology Cervical Cancer Committee for the National Cancer Institute funded Gynecologic Oncology Group for the study published in NEJM.

212

NIH Research Leads to Cervical Cancer Vaccine  

MedlinePLUS

Skip Navigation Bar Home Current Issue Past Issues Sexually Transmitted Diseases NIH Research Leads to Cervical Cancer Vaccine Past Issues / Fall 2008 Table of Contents For an enhanced version of this page please turn ...

213

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

PubMed Central

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

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

2015-01-01

214

Related Resources for Cervical Cancer Screening  

Cancer.gov

NCI has comprehensive research-based information on cancer prevention, screening, diagnosis, treatment, genetics and supportive care. Our information specialists can answer questions related to cancer, including cervical cancer screening and treatment. You can contact us by phone, online chat, or e-mail.

215

iTRAQ-based quantitative proteomic analysis of cervical cancer.  

PubMed

Cervical cancer is the seventh most common cancer overall and the third among females. To obtain systematic insight into the protein profile that participates in cervical tumor oncogenesis and improve the current target therapies, iTRAQ labeling and NanoLC-MS/MS analysis were utilized to detect differentially expressed proteins in cervical cancer. As a result, 3,647 proteins were identified, among which the expression levels of 294 proteins in cervical cancer samples were distinct from the paired non-tumor samples. Further validation of the differentially expressed proteins, including G6PD, ALDH3A1, STAT1 and HSPB1, was carried out via qRT-PCR, western blot analysis and tissue microarray. Functional analysis of one of the highly expressed proteins, G6PD, was performed using RNA interference. Attenuated G6PD expression reduced the capacity of HeLa cells to migrate and invade in vitro. Our investigation complemented the understanding of cervical cancer progression. Furthermore, the present study supports the notion that suppressing the expression of G6PD may be a promising strategy in developing novel cancer therapeutic drugs. PMID:25633909

Ding, Yibing; Yang, Min; She, Sha; Min, Haiyan; Xv, Xiaoming; Ran, Xiaoping; Wu, Yongzheng; Wang, Wei; Wang, Lei; Yi, Long; Yang, Yixuan; Gao, Qian

2015-04-01

216

I. Cervical dysplasia = abnormal tissue growth n Cervical cancer develops in the  

E-print Network

is HPV q Evidence of HPV is found in nearly 80% of cervical carcinomas q HPV strains found most system's ability to fight infection (including HPV infection) and increases the likelihood that precancerous cells will progress to cancer. A. HPV ­ carries oncogenes n It is proposed that HPV interferes

Dever, Jennifer A.

217

Treatment Option Overview (Cervical Cancer)  

MedlinePLUS

... attack specific cancer cells without harming normal cells. Monoclonal antibody therapy is a type of targeted therapy that uses antibodies made in the laboratory from a single type of immune system ... spreading. Monoclonal antibodies are given by infusion . They may be ...

218

Vaccines Against Human Papillomavirus and Cervical Cancer: Promises and Challenges  

Microsoft Academic Search

Cervical cancer and precancerous lesions of the genital tract are major threats to the health of women world- wide. The introduction of screening tests to detect cer- vical cancer precursor lesions has reduced cervical cancer rates in the developed world, but not in devel- oping countries. Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer and dyspla- sia.

Ali Mahdavi; Bradley J. Monk

219

Induction of apoptosis by hydrogen peroxide in HPV 16 positive human cervical cancer cells: involvement of mitochondrial pathway  

Microsoft Academic Search

Cervical cancer is the second most common malignant neoplasm in women, in terms of incidence and mortality rates worldwide,\\u000a and is associated with excessive inflammation. This involves the expression of both pro- and anti-apoptotic proteins that\\u000a have varied effect on tumor growth and metastasis. The objective of the present study was to elucidate the effect of hydrogen\\u000a peroxide (H2O2) on

Mayank Singh; Neeta Singh

2008-01-01

220

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

SciTech Connect

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

Maduro, John H. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Vries, Elisabeth de [Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Meersma, Gert-Jan [Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Hougardy, Brigitte; Zee, Ate G.J. van der [Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Jong, Steven de [Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)], E-mail: s.de.jong@int.umcg.nl

2008-10-01

221

HPV-related cervical disease and oropharyngeal cancer.  

PubMed

Human papillomavirus (HPV), especially HPV 16, is associated with the development of both cervical and oral cancer. We show the case of a woman affected by HPV-related cervical disease and oropharyngeal squamous cell carcinoma (OPSCC). A 41-year-old woman arrived at our Colposcopy Center following an abnormal Pap smear result (ASC-H) and a diagnosis of moderate cervical dysplasia obtained by a cervical biopsy. She underwent a colposcopy that showed a cervical abnormal transformation zone grade 2. A laser conization was performed in November 2010. Histology reported a moderate/severe dysplasia. The cone resection margins were free. Follow-up colposcopy and cytology were negative. The HPV testing showed an infection by HPV 16. In October 2012, the patient presented to the Head-Neck ER after episodes of hemoptysis; a lesion was found in the left tonsillar lodge. A biopsy was performed with a result of squamous cell carcinoma with low-grade differentiation. The HPV testing detected a high-risk HPV and the immunohistochemical analysis was positive for p16. She was treated by chemotherapy and brachytherapy. She was followed at the head-neck center with monthly visits with oral visual inspection that showed complete absence of mucosal abnormalities. HPV-related OPSCC and cervical precancerous/cancerous lesions have significant similarities in terms of pathogenesis. They are both caused largely by HPV 16, as in the present case. In conclusion, because of this association found in literature and in our case, we think that women with HPV cervical lesions should have regular surveillance for oropharyngeal cancer, whereas women with OPSCC should be encouraged to have diligent cervical screening. PMID:24584479

Lozza, Virginia; Pieralli, Annalisa; Corioni, Serena; Longinotti, Manuela; Bianchi, Claudia; Moncini, Daniela; Fallani, Maria Grazia

2014-08-01

222

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

PubMed Central

Although fully treatable in the early stages, once cervical cancer has metastasized, patient outcome is poor. The main objective of this study was to examine the effect of dietary supplementation with a nutrient mixture (NM) containing lysine, ascorbic acid, proline, green tea extract and other micronutrients on HeLa cell xenografts in nude female mice. Tumor growth was measured and immunohistochemical staining was evaluated for the following cancer markers: Ki67 (proliferation); matrix metalloproteinase (MMP)-2 and -9 (invasion/metastasis); vascular endothelial growth factor (VEGF) (angiogenesis); terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and B-cell lymphoma 2 (Bcl-2) (apoptosis); cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) (inflammation); and glutathione S-transferase ? (GST?) (a general cancer marker). Following housing for a week, 5/6-week-old female athymic nude mice (n=12) were inoculated subcutaneously with 3×106 HeLa cells in 0.2 ml phosphate-buffered saline and 0.1 ml Matrigel™ and randomly divided into two groups; control group mice were fed regular mouse chow and NM group mice the regular diet supplemented with 0.5% NM (w/w). After four weeks, the mice were sacrificed and their tumors were excised and processed for histology. The NM strongly inhibited the growth of HeLa xenografts in nude mice. The mean tumor weight was reduced to 59% (P=0.001) in the mice fed the NM compared with the tumor weight in the controlled diet mice. Ki67, MMP-2 and -9, VEGF, TUNEL, Bcl-2, COX-2, iNOS and GST? all showed a lower intensity and frequency of staining in the NM group compared with that in the control group. In conclusion, NM supplementation strongly inhibited tumor growth and cancer markers in female nude mice injected with HeLa xenografts. PMID:25574189

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

2015-01-01

223

Screening for cervical cancer and human papilloma virus: Indian context.  

PubMed

Cervical cancer remains the most common fatal cancer in Indian women. The primary underlying cause of cervical cancer is persistent infection with human papilloma virus (HPV); HPV 16 and 18 account for nearly 70% of all cervical cancers worldwide. Cytology-based cervical screening programs have been very effective, but require establishing an infrastructure and quality control mechanisms, which can be a challenge. Cervical screening by visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI) are acceptable alternatives for low-resource settings. Primary screening for cervical cancer with HPV testing is attractive but cost could be the limiting factor. A less expensive HPV test holds promise. PMID:22726999

Deodhar, Kedar K

2012-06-01

224

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

PubMed Central

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

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

2015-01-01

225

Analysis of Senate Bill 1245: Cervical Cancer Screening Test  

E-print Network

In California, the age-adjusted death rate for Hispanics inCalifornia, the age-adjusted incidence rate of cervical cancer among HispanicsCalifornia Cervical Cancer Screening, Incidence, and Mortality Race All races White Black Hispanic

California Health Benefits Review Program (CHBRP)

2006-01-01

226

Preventing Cervical Cancer: The Development of HPV Vaccines  

Cancer.gov

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

227

A panel of regulated proteins in serum from patients with cervical intraepithelial neoplasia and cervical cancer.  

PubMed

We developed a discovery-validation mass-spectrometry-based pipeline to identify a set of proteins that are regulated in serum of patients with cervical intraepithelial neoplasia (CIN) and squamous cell cervical cancer using iTRAQ, label-free shotgun, and targeted mass-spectrometric quantification. In the discovery stage we used a "pooling" strategy for the comparative analysis of immunodepleted serum and revealed 15 up- and 26 down-regulated proteins in patients with early- (CES) and late-stage (CLS) cervical cancer. The analysis of nondepleted serum samples from patients with CIN, CES, an CLS and healthy controls showed significant changes in abundance of alpha-1-acid glycoprotein 1, alpha-1-antitrypsin, serotransferrin, haptoglobin, alpha-2-HS-glycoprotein, and vitamin D-binding protein. We validated our findings using a fast UHPLC/MRM method in an independent set of serum samples from patients with cervical cancer or CIN and healthy controls as well as serum samples from patients with ovarian cancer (more than 400 samples in total). The panel of six proteins showed 67% sensitivity and 88% specificity for discrimination of patients with CIN from healthy controls, a stage of the disease where current protein-based biomarkers, for example, squamous cell carcinoma antigen (SCCA), fail to show any discrimination. Additionally, combining the six-protein panel with SCCA improves the discrimination of patients with CES and CLS from healthy controls. PMID:25232869

Boichenko, Alexander P; Govorukhina, Natalia; Klip, Harry G; van der Zee, A G J; Güzel, Co?kun; Luider, Theo M; Bischoff, Rainer

2014-11-01

228

Quantitative DNA Methylation Analysis of Candidate Genes in Cervical Cancer  

PubMed Central

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

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

2015-01-01

229

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

PubMed Central

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

2010-01-01

230

Development of Consensus Educational Materials on HPV & Cervical Cancer for Europe  

Cancer.gov

1 Development of Development of Consensus Educational Materials Consensus Educational Materials on HPV & Cervical Cancer for Europe on HPV & Cervical Cancer for Europe Philip Davies Philip Davies European Cervical Cancer Association European Cervical

231

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

PubMed Central

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. PMID:24837834

Pang, Xiaoao; Zhang, Yao; Wei, Heng; Zhang, Jing; Luo, Qingshuang; Huang, Chenglin; Zhang, Shulan

2014-01-01

232

A new E6/P63 pathway, together with a strong E7/E2F mitotic pathway, modulates the transcriptome in cervical cancer cells.  

PubMed

Cervical carcinoma is associated with certain types of human papillomaviruses expressing the E6 and E7 oncogenes, which are involved in carcinogenesis through their interactions with the p53 and pRB pathways, respectively. A critical event on the path to malignant transformation is often manifested by the loss of expression of the viral E2 transcription factor due to the integration into the host genome of the viral DNA. Using microarrays, we have previously shown that reintroduction of a functional E2 in the HeLa cervical carcinoma cell line activates a cluster of p53 target genes while at the same time severely repressing a group of E2F target genes. In the present study, using new high-density microarrays containing more than 22,000 human cDNA sequences, we identified a novel p63 pathway among E2-activated genes and 38 new mitotic genes repressed by E2. We then sought to determine the pathways through which these genes were modulated and used an approach that relies on small interfering RNA to demonstrate that the p63 target genes were activated through silencing of the E6/E6AP pathway while the mitotic genes were mainly repressed through E7 silencing. Importantly, a subset of the mitotic genes was shown to be significantly induced in biopsies of stage IV cervical cancers, which points to a prominent E7 pathway in cervical carcinoma. PMID:17582001

Teissier, Sébastien; Ben Khalifa, Youcef; Mori, Marcella; Pautier, Patricia; Desaintes, Christian; Thierry, Françoise

2007-09-01

233

Cytotoxic and pro-apoptotic effects of novel ganoderic acid derivatives on human cervical cancer cells in vitro.  

PubMed

Ganoderic acid T, a triterpenic acid produced by Ganoderma lucidum, has demonstrated therapeutic potential for tumor disease. In the current work, ganoderic acid T was modified to produce more effective small-molecule inhibitors of cancer cell proliferation. Moreover, the anticancer effects of three new ganoderic acid T derivatives, i.e., (22S,24E)-3?,15?,22-triacetoxy-5?-lanosta-7,9(11),24-trien-26-oic acid ethyl ester (TLTO-Ee), (22S,24E)-3?,15?,22-triacetoxy-5?-lanosta-7,9(11),24-trien-26-oic acid propyl ester (TLTO-Pe), and (22S,24E)-3?,15?,22-triacetoxy-5?-lanosta-7,9(11),24-trien-26-oic acid amide (TLTO-A), and one known derivative, (22S,24E)-3?,15?,22-triacetoxy-5?-lanosta-7,9(11),24-trien-26-oic acid methyl ester (TLTO-Me), on the cervical cell line HeLa were investigated and compared. MTT assay indicated that, among the tested compounds, TLTO-A displayed the highest inhibitory effect on the growth of HeLa cells, whereas it showed less cytotoxicity to the non-tumorous cell line MCF-10A than ganoderic acid T. Flow cytometry analysis revealed that all the compounds caused cell cycle arrest at the G1 phase and induced apoptosis. Furthermore, they decreased the mitochondrial membrane potential and enhanced the activities of pro-apoptotic factors caspase-3 and caspase-9 in a dose-dependent manner. Accordingly, the apoptosis induction was presumed to occur through the endogenous pathway. The following order ranks both cytotoxic and pro-apoptotic effects of the compounds against HeLa cells: TLTO-A>ganoderic acid T?TLTO-Me?TLTO-Ee?TLTO-Pe. This study suggests that the carboxyl group of ganoderic acid T is not the main active group and is suitable for its further structural modification. The current work presents valuable information on the design of ganoderic acid T derivatives to develop potential chemotherapy agents. PMID:22366428

Liu, Ru-Ming; Li, Ying-Bo; Zhong, Jian-Jiang

2012-04-15

234

The detection of circulating tumor cells expressing E6/E7 HR-HPV oncogenes in peripheral blood in cervical cancer patients after radical hysterectomy.  

PubMed

The aim of this study was to establish the sensitive, specific and clinically acceptable method for detection of tumor cells (TCs) circulating in peripheral blood (PB) of cervical cancer patients without the clinically detectable risk of disease progression. The 7.5 ml of PB of healthy donor was spiked with 5 to 100 cells from SiHa or HeLa cell lines. The spiked tumor cells were collected without gradient centrifugation, by standard gradient centrifugation or by modified gradient centrifugation combined with immunomagnetic separation using EpCAM antibody with affinity for epithelial cell adhesion molecule. The number of collected TCs was determined by EpCAM-FITC-staining and their viability was detected by nested RT-PCR amplifying E6/E7 HR-HPV 16 or HR-HPV 18 oncogenes. For the technical validation of this approach the TCs separation and RT-PCRs were repeated several times. The recovery of viable TCs was reproducibly higher using modified gradient centrifugation combined with immunomagnetic separation in comparison with standard approach. The recovery of TCs in low number of spiked TCs (range from 5 - 20 TCs in 7.5 ml of PB) using modified gradient centrifugation was not reproducible. The recovery of TCs in higher number of spiked TCs (25 TCs and more in 7.5 ml of PB) was reproducible with average recovery about 50 %. The sensitivity of nested RT-PCR amplifying E6/E7 oncogenes was decisively influenced by the number of recovered TCs and the amount of cDNA introduced to RT-PCR, as well. Using this approach we were allowed to detect circulating TCs (CTCs) in cervical cancer patients without metastases, thus this procedure might become a tool to early estimation of disease progression. According to our knowledge, this is the first report describing the use of EpCAM antibody for CTCs detection in cervical cancer patients. PMID:19309226

Weismann, P; Weismanova, E; Masak, L; Mlada, K; Keder, D; Ferancikova, Z; Vizvaryova, M; Konecny, M; Zavodna, K; Kausitz, J; Benuska, J; Repiska, V

2009-01-01

235

Antigen-specific immunotherapy of cervical and ovarian cancer  

PubMed Central

Summary We contrast the efforts to treat ovarian cancer and cervical cancer through vaccination because of their different pathobiology. A plethora of approaches have been developed for therapeutic vaccination against cancer, many of which target defined tumor-associated antigens (TAAs). Persistent infection with oncogenic human papillomavirus (HPV) types is necessary cause of cervical cancer. Furthermore, cervical cancer patients frequently mount both humoral and T cell immune responses to the HPV E6 and E7 oncoproteins, whose expression is required for the transformed phenotype. Numerous vaccine studies target these viral TAAs, including recent trials that may enhance clearance of pre-malignant disease. By contrast little is known about the etiology of epithelial ovarian cancer. Although it is clear that p53 mutation or loss is a critical early event in the development of epithelial ovarian cancer, no precursor lesion has been described for the most common serous histotype, and even the location of its origin is debated. These issues have complicated the selection of appropriate ovarian TAAs and the design of vaccines. Here we focus on mesothelin as a promising ovarian TAA because it is overexpressed and immunogenic at high frequency in patients, is displayed on the cell surface and potentially contributes to ovarian cancer biology. PMID:18363994

Hung, Chien-fu; Wu, TC; Monie, Archana; Roden, Richard

2009-01-01

236

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

PubMed

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, p<0.01). A sub-G1 peak (apoptotic cells) of HeLa cells was detected after treatment and the apoptosis rate with the concentration and longer incubation time (r=1.0, p<0.01), while the percentage of cells in S phase and G2/M phase decreased significantly. Immunocytochemistry assay showed that the expression of cyclin E and bcl-2 in the treated cells significantly decreased, while the expression of p27 and bax obviously increased, compared with the control group (p<0.05). The results of our research indicate that inotodiol isolated from Inonotus obliquus inhibited the proliferation of HeLa 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. PMID:24815470

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

2014-01-01

237

International study identifies the origins of cervical cancer  

Cancer.gov

Virtually all cervical cancers are caused by HPV infections, with just two HPV types, 16 and 18, responsible for about 70 percent of all cases, according to the National Cancer Institute. Scientists have presumed for decades that the cervical cancers that develop from HPV infection arise in a specific location in the cervix. Now, new research from Brigham and Women's Hospital (BWH) in close collaboration with Harvard Medical School and the Agency for Science Technology and Research in Singapore finds that a specific population of cells that are found only in the region of the cervix called the "squamo-columnar junction" can become cancerous when infected with HPV while other cells in the cervix apparently do not. This research is published online the week of June 11 in the Proceedings of the National Academy of Sciences (PNAS).

238

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

PubMed Central

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 ?-caprolactone initiated by d-?-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.

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

2015-01-01

239

Human papillomavirus in false negative archival cervical smears: implications for screening for cervical cancer  

Microsoft Academic Search

AIM--To assess the value of detecting human papillomavirus (HPV) DNA in false negative archival cervical smears in population based screening programmes for cervical cancer. METHODS--Cytomorphologically classified false negative archival Pap smears (n = 27) taken from 18 women up to six years before cervical cancer was diagnosed were blindly mixed with 89 smears from hospital patients with a variety of

J M Walboomers; A M de Roda Husman; P J Snijders; H V Stel; E K Risse; T J Helmerhorst; F J Voorhorst; C J Meijer

1995-01-01

240

New molecular targets against cervical cancer  

PubMed Central

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

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

2014-01-01

241

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

PubMed Central

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. PMID:25565864

Yu, Lan; Wang, Xiaoli; Zhu, Da; Ding, Wencheng; Wang, Liming; Zhang, Changlin; Jiang, Xiaohui; Shen, Hui; Liao, Shujie; Ma, Ding; Hu, Zheng; Wang, Hui

2015-01-01

242

Latex of Euphorbia antiquorum induces apoptosis in human cervical cancer cells via c-jun n-terminal kinase activation and reactive oxygen species production.  

PubMed

Latex of Euphorbia antiquorum (EA) has inhibitory effects on several different cancer cell lines. However, the molecular mechanism of EA inhibitory effects on human cervical cancer HeLa cell growth has not been explored. EA induced apoptosis, which was characterized by morphological change, DNA fragmentation, increased sub-G1 population, and alterations in levels of apoptosis-associated proteins. Treatment with EA increased cell death and expression levels of caspase-8, -9, and -3. EA suppressed expression of Bcl-2, increased Bax, and reduced cleavage of Bid and the translocation of tBid to the mitochondria and the release of cytochrome c from mitochondria. EA caused a loss of mitochondrial membrane potential (??m) and an increase in cellular reactive oxygen species (ROS). EA-induced ROS formation was suppressed by cyclosporine A (an inhibitor of the ??m) or allopurinol (an effective scavenger of ROS). EA also increased expression of Fas, FasL, and c-Jun N-terminal kinase (JNK), p38, and mitogen-activated protein kinase (MAPK) and decreased expression of extracellular signal-regulated kinase (ERK) 1/2-p. Co-treatment with the JNK inhibitor SP600125 inhibited EA-induced apoptosis and the activation of caspase-8, -9, and -3. Results of this study provide support for the hypothesis that EA causes cell death via apoptotic pathways in human cervical adenocarcinoma HeLa cells. PMID:22044063

Hsieh, Wen-Tsong; Lin, Hui-Yi; Chen, Jou-Hsuan; Kuo, Yueh-Hsiung; Fan, Ming-Jen; Wu, Rick Sai-Chuan; Wu, King-Chuen; Wood, W Gibson; Chung, Jing-Gung

2011-11-01

243

Clinical significance of telomerase activation and telomeric restriction fragment (TRF) in cervical cancer.  

PubMed

Telomerase activation was examined in 50 cases of cervical cancer, 27 normal cervix and five cervical cancer cell lines using the sensitive polymerase chain reaction (PCR)-based TRAP (telomeric repeat amplification protocol) assay. Telomeric restriction fragment (TRF) length of these specimens was measured by Southern hybridisation. Telomerase activation was common in cervical cancers and was detected in 46/50 cases (92%). Telomerase activity was weak in normal cervix and was detected only in 2/27 cases (7.4%). Telomerase activity was detected in all stages of cervical cancer suggesting that it is an early event in cancer progression. The clinical significance of telomerase activation was analysed in 47 squamous cell carcinoma of the cervix. High telomerase activity was more frequently detected in advanced diseases (100% in stage III and stage IV cervical cancers combined) compared with early diseases (68.6% in stage I and stage II cancers combined). The difference was statistically significant (P < 0.02). Telomerase activity was not statistically correlated with other clinical parameters examined. This is the first report of telomeric length in human cervical cancer. Both shortening and elongation of TRF length in cervical cancers was observed. Advanced cervical cancers tended to have a wider range of variation of TRF length compared with early disease and normal cervix. There was no obvious relationship between TRF length and the clinical parameters examined including clinical staging, differentiation status of tumour, human papilloma virus (HPV) infection, recurrence rate, tumour size and invasion depth. The clinical significance of TRF length appears to be limited in cervical cancers. Our results indicate that telomerase activity is closely associated with tumour cells and may be useful as a marker for detection of tumour cells in cervical biopsies. PMID:10211104

Zhang, D K; Ngan, H Y; Cheng, R Y; Cheung, A N; Liu, S S; Tsao, S W

1999-01-01

244

Expression of transcription factor grainyhead-like 2 is diminished in cervical cancer  

PubMed Central

The transcription factor grainyhead-like 2 (GRHL2) is evolutionarily conserved in many different species, and is involved in morphogenesis, epithelial differentiation, and the control of the epithelial-mesenchymal transition. It has also recently been implicated in carcinogenesis, but its role in this remains controversial. Expression of GRHL2 has not previously been reported in cervical cancer, so the present study aimed to characterize GRHL2 expression in cervical cancer-derived cell lines (CCCLs) and cervical tissues with different grades of lesions. Microarray analysis found that the expression of 58 genes was down-regulated in CCCLs compared to HaCaT cells (non-tumorigenic human epithelial cell line). The expression of eight of these genes was validated by quantitative real-time PCR (qPCR), and GRHL2 was found to be the most down-regulated. Western blot assays corroborated that GRHL2 protein levels were strongly down-regulated in CCCLs. Cervical cells from women without cervical lesions were shown to express GRHL2, while immunohistochemistry found that positivity to GRHL2 decreased in cervical cancer tissues. In conclusion, a loss or strong reduction in GRHL2 expression appears to be a characteristic of cervical cancer, suggesting that GRHL2 down-regulation is a necessary step during cervical carcinogenesis. However, further studies are needed to delineate the role of GRHL2 in cervical cancer and during malignant progression. PMID:25550776

Torres-Reyes, Luis A; Alvarado-Ruiz, Liliana; Piña-Sánchez, Patricia; Martínez-Silva, María G; Ramos-Solano, Moisés; Olimón-Andalón, Vicente; Ortiz-Lazareno, Pablo C; Hernández-Flores, Georgina; Bravo-Cuellar, Alejandro; Aguilar-Lemarroy, Adriana; Jave-Suarez, Luis F

2014-01-01

245

Angiogenesis and antiangiogenic agents in cervical cancer  

PubMed Central

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-1?. Both of these mechanisms are able to increase expression of vascular endothelial growth factor (VEGF). Activation of VEGF promotes endothelial cell proliferation and migration, favoring formation of new blood vessels and increasing permeability of existing blood vessels. Since bevacizumab, a recombinant humanized monoclonal antibody binding to all isoforms of VEGF, has been demonstrated to significantly improve survival in gynecologic cancer, some recent clinical research has explored the possibility of using novel therapies directed toward inhibition of angiogenesis in CC too. Here we review the main results from studies concerning the use of antiangiogenic drugs that are being investigated for the treatment of CC. PMID:25506227

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

2014-01-01

246

MicroRNA-7 inhibits metastasis and invasion through targeting focal adhesion kinase in cervical cancer  

PubMed Central

MicroRNAs (miRNAs) are aberrantly expressed in cervical cancer. miR-7 has been demonstrated to function as both an oncogene and a tumor suppressor in some types of human cancers. In the present study, miR-7 was significantly downregulated in cervical cancer, especially metastatic tumors. Ectopic expression of miR-7 significantly inhibited metastasis and invasion in Hela and C33A cells. Upregulated miR-7 significantly suppressed focal adhesion kinase (FAK) at transcriptional and translational levels. Furthermore, the level of FAK was negatively correlated with miR-7 in cervical cancer tissues. In conclusion, miR-7 inhibited the metastasis and invasion of cervical cancer at least partially through targeting FAK. The findings of this study provide novel insight with potential therapeutic applications for the treatment of metastatic cervical cancer.

Hao, Zhenfeng; Yang, Jishi; Wang, Chenghai; Li, Yaoyao; Zhang, Yu; Dong, Xiaoyun; Zhou, Liulin; Liu, Jing; Zhang, Yanqing; Qian, Jing

2015-01-01

247

[Chromosomal instability in carcinogenesis of cervical cancer.  

PubMed

In order to spot common chromosomal imbalances in early and late lesions of cervical cancer that might be used as progression biomarkers, we made a search of literature in PubMed from 1996 to 2011. The medical subject headings employed were chromosomal alterations, loss of heterozygosis, cervical cancer, cervical tumorigenesis, chromosomal aberrations, cervical intraepithelial neoplasm and low-grade squamous intraepithelial lesion. The common chromosomal imbalances were gains in 8q24 (77.7 %), 20q13 (66.9 %), 3q26 (47.1 %), Xp22 (43.8 %), and 5p15 (60 %), principally. On the other hand, integration of the high-risk human papillomavirus genome into the host chromosome has been associated with the development of neoplasia, but the chromosomal imbalances seem to precede and promote such integration. Chromosomal imbalances in 8q24, 20q13, 3q21-26 and 5p15-Xp22, determined by fluorescent in situ hybridization assay or comparative genomic hybridization assay for early detection of the presence of high-risk human papillomavirus, are promising markers of cervical cancer progression. PMID:24290016

de Los Santos-Munive, Victoria; Alonso-Avelino, Juan Angel

2013-01-01

248

Antioxidants in cervical cancer: chemopreventive and chemotherapeutic effects of polyphenols.  

PubMed

Cervical cancer lesions are a major threat to the health of women, representing the second most common cancer worldwide. The unanimously recognized etiological factor in the causation of cervical cancer is the infection with human papilloma virus (HPV). HPV infection, although necessary, is not per se sufficient to induce cancer. Other factors have to be involved in the progression of infected cells to the full neoplastic phenotype. Oxidative stress represents an interesting and under-explored candidate as a promoting factor in HPV-initiated carcinogenesis. Oxidative stress is known to perturb the cellular redox status thus leading to alteration of gene expression responses through the activation of several redox-sensitive transcription factors. This signaling cascade affects both cell growth and cell death. The ability of naturally occurring antioxidants to modulate cellular signal transduction pathways, through the activation/repression of multiple redox-sensitive transcription factors, has been claimed for their potential therapeutic use as chemopreventive agents. Among these compounds, polyphenols have been found to be promising agents toward cervical cancer. In addition to acting as antioxidants, polyphenols display a wide variety of biological function including induction of apoptosis, growth arrest, inhibition of DNA synthesis and modulation of signal transduction pathways. They can interfere with each stage of carcinogenesis initiation, promotion and progression to prevent cancer development. The present review discusses current knowledge of the major molecular pathways, which are involved in HPV-driven cancerogenesis, and the ability of polyphenols to modulate these pathways. By acting at specific steps of viral transformation cascade, polyphenols have been demonstrated to selectively inhibit tumor cell growth and may be a promising therapeutic tool for treatment of cervical cancer. In addition, recent results obtained in clinical trials using polyphenols are also discussed. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease. PMID:22019724

Di Domenico, F; Foppoli, C; Coccia, R; Perluigi, M

2012-05-01

249

Optoelectronic method for detection of cervical intraepithelial neoplasia and cervical cancer  

NASA Astrophysics Data System (ADS)

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.

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

2011-12-01

250

Cervical cancer: Can it be prevented?  

PubMed

Cervical cancer prevention requires a multipronged approach involving primary, secondary and tertiary prevention. The key element under primary prevention is human papilloma virus (HPV) vaccination. So far, only prophylactic HPV vaccines which prevent HPV infection by one or more subtypes are commercially available. Therapeutic HPV vaccines which aid in clearing established infection are still under trial. Secondary prevention entails early detection of precancerous lesions and its success is determined by the population coverage and the efficacy of the screening technique. A number of techniques are in use, including cytology, visual inspection (using the naked eye, magnivisualizer, acetic acid and Lugol's iodine), HPV testing and a combination of these methods. Updated screening guidelines have been advocated by the American Cancer Society in light of the role of HPV on cervical carcinogenesis. Recent research has also focussed on novel biomarkers that can predict progression to cancer in screen positive women and help to differentiate those who need treatment from those who can be left for follow-up. Last but not the least, effective treatment of precancerous lesions can help to reduce the incidence of invasive cervical cancer and this constitutes tertiary prevention. A combination of these approaches can help to prevent the burden of cervical cancer and its antecedent morbidity and mortality, but all of these are not feasible in all settings due to resource and allocation constraints. Thus, all countries, especially low and middle income ones, have to determine their own cocktail of approaches that work before we can say with certainty that yes, cervical cancer can be prevented. PMID:25302177

Aggarwal, Pakhee

2014-10-10

251

Cervical cancer: Can it be prevented?  

PubMed Central

Cervical cancer prevention requires a multipronged approach involving primary, secondary and tertiary prevention. The key element under primary prevention is human papilloma virus (HPV) vaccination. So far, only prophylactic HPV vaccines which prevent HPV infection by one or more subtypes are commercially available. Therapeutic HPV vaccines which aid in clearing established infection are still under trial. Secondary prevention entails early detection of precancerous lesions and its success is determined by the population coverage and the efficacy of the screening technique. A number of techniques are in use, including cytology, visual inspection (using the naked eye, magnivisualizer, acetic acid and Lugol’s iodine), HPV testing and a combination of these methods. Updated screening guidelines have been advocated by the American Cancer Society in light of the role of HPV on cervical carcinogenesis. Recent research has also focussed on novel biomarkers that can predict progression to cancer in screen positive women and help to differentiate those who need treatment from those who can be left for follow-up. Last but not the least, effective treatment of precancerous lesions can help to reduce the incidence of invasive cervical cancer and this constitutes tertiary prevention. A combination of these approaches can help to prevent the burden of cervical cancer and its antecedent morbidity and mortality, but all of these are not feasible in all settings due to resource and allocation constraints. Thus, all countries, especially low and middle income ones, have to determine their own cocktail of approaches that work before we can say with certainty that yes, cervical cancer can be prevented. PMID:25302177

Aggarwal, Pakhee

2014-01-01

252

Phosphorylation of I?B? at Serine 32 by T-lymphokine-activated Killer Cell-originated Protein Kinase Is Essential for Chemoresistance against Doxorubicin in Cervical Cancer Cells*  

PubMed Central

T-lymphokine-activated killer cell-originated protein kinase (TOPK) is known to be up-regulated in cancer cells and appears to contribute to cancer cell proliferation and survival. However, the molecular mechanism by which TOPK regulates cancer cell survival still remains elusive. Here we show that TOPK directly interacted with and phosphorylated I?B? at Ser-32, leading to p65 nuclear translocation and NF-?B activation. We also revealed that doxorubicin promoted the interaction between nonphosphorylated or phosphorylated TOPK and I?B? and that TOPK-mediated I?B? phosphorylation was enhanced in response to doxorubicin. Also, exogenously overexpressed TOPK augmented transcriptional activity driven by either NF-?B or inhibitor of apoptosis protein 2 (cIAP2) promoters. On the other hand, NF-?B activity including I?B? phosphorylation and p65 nuclear translocation, as well as cIAP2 gene expression, was markedly diminished in TOPK knockdown HeLa cervical cancer cells. Moreover, doxorubicin-mediated apoptosis was noticeably increased in TOPK knockdown HeLa cells, compared with control cells, which resulted from caspase-dependent signaling pathways. These results demonstrate that TOPK is a molecular target of doxorubicin and mediates doxorubicin chemoresistance of HeLa cells, suggesting a novel mechanism for TOPK barrier of doxorubicin-mediated cervical cancer cell apoptosis. PMID:23250755

Park, Jung-Hwan; Yoon, Dae-Sung; Choi, Hye-Jin; Hahm, Dae-Hyun; Oh, Sang-Muk

2013-01-01

253

Phosphorylation of I?B? at serine 32 by T-lymphokine-activated killer cell-originated protein kinase is essential for chemoresistance against doxorubicin in cervical cancer cells.  

PubMed

T-lymphokine-activated killer cell-originated protein kinase (TOPK) is known to be up-regulated in cancer cells and appears to contribute to cancer cell proliferation and survival. However, the molecular mechanism by which TOPK regulates cancer cell survival still remains elusive. Here we show that TOPK directly interacted with and phosphorylated I?B? at Ser-32, leading to p65 nuclear translocation and NF-?B activation. We also revealed that doxorubicin promoted the interaction between nonphosphorylated or phosphorylated TOPK and I?B? and that TOPK-mediated I?B? phosphorylation was enhanced in response to doxorubicin. Also, exogenously overexpressed TOPK augmented transcriptional activity driven by either NF-?B or inhibitor of apoptosis protein 2 (cIAP2) promoters. On the other hand, NF-?B activity including I?B? phosphorylation and p65 nuclear translocation, as well as cIAP2 gene expression, was markedly diminished in TOPK knockdown HeLa cervical cancer cells. Moreover, doxorubicin-mediated apoptosis was noticeably increased in TOPK knockdown HeLa cells, compared with control cells, which resulted from caspase-dependent signaling pathways. These results demonstrate that TOPK is a molecular target of doxorubicin and mediates doxorubicin chemoresistance of HeLa cells, suggesting a novel mechanism for TOPK barrier of doxorubicin-mediated cervical cancer cell apoptosis. PMID:23250755

Park, Jung-Hwan; Yoon, Dae-Sung; Choi, Hye-Jin; Hahm, Dae-Hyun; Oh, Sang-Muk

2013-02-01

254

The role of trachelectomy in cervical cancer  

PubMed Central

Cervical cancer is one of the most common cancers in women worldwide. Because it often affects women of childbearing age (19–45 years), fertility-sparing surgery is an important issue. The article reviews current viable fertility-sparing options with a special focus on trachelectomy, including vaginal radical trachelectomy, abdominal radical trachelectomy and simple trachelectomy. Neoadjuvant chemotherapy is also discussed. Finally, the decision to proceed with fertility-sparing treatment should be a patient-driven process. PMID:25729419

Halaska, MJ; Robova, H; Pluta, M; Rob, L

2015-01-01

255

Effects of tetrahydrocurcumin on hypoxia-inducible factor-1? and vascular endothelial growth factor expression in cervical cancer cell-induced angiogenesis in nude mice.  

PubMed

Tetrahydrocurcumin (THC), one of the important in vivo metabolites of curcumin, inhibits tumor angiogenesis. Its effects on angiogenesis in cervical cancer- (CaSki-) implanted nude mice and its mechanisms on hypoxia-inducible factor-1? and vascular endothelial growth factor expression were investigated. Female BALB/c nude mice were divided into control (CON) and CaSki-implanted groups (CaSki group). One month after the injection with cervical cancer cells, mice were orally administered vehicle or 100, 300, and 500?mg/kg of THC daily for 30 consecutive days. The microvascular density (MVD) was evaluated using the CD31 expression. VEGF, VEGFR-2, and HIF-1? expression were also detected by immunohistochemistry. The MVD in CaSki + vehicle group was significantly increased compared to the CON + vehicle group. Interestingly, when treated with THC at all doses, the CaSki group showed a significant smaller number of the MVD. The CaSki + vehicle group also showed significantly increased VEGF, VEGFR-2, and HIF-1? expressions, but they were downregulated when mice were treated with THC at all doses. THC demonstrated an inhibitory effect against tumor angiogenesis in CaSki-implanted nude mice model. This effect is likely to be mediated by the downregulation of HIF-1-?, VEGF expression, and its receptor. THC could be developed into a promising agent for cancer therapy in the future. PMID:25789317

Yoysungnoen, Bhornprom; Bhattarakosol, Parvapan; Patumraj, Suthiluk; Changtam, Chatchawan

2015-01-01

256

Effects of Tetrahydrocurcumin on Hypoxia-Inducible Factor-1? and Vascular Endothelial Growth Factor Expression in Cervical Cancer Cell-Induced Angiogenesis in Nude Mice  

PubMed Central

Tetrahydrocurcumin (THC), one of the important in vivo metabolites of curcumin, inhibits tumor angiogenesis. Its effects on angiogenesis in cervical cancer- (CaSki-) implanted nude mice and its mechanisms on hypoxia-inducible factor-1? and vascular endothelial growth factor expression were investigated. Female BALB/c nude mice were divided into control (CON) and CaSki-implanted groups (CaSki group). One month after the injection with cervical cancer cells, mice were orally administered vehicle or 100, 300, and 500?mg/kg of THC daily for 30 consecutive days. The microvascular density (MVD) was evaluated using the CD31 expression. VEGF, VEGFR-2, and HIF-1? expression were also detected by immunohistochemistry. The MVD in CaSki + vehicle group was significantly increased compared to the CON + vehicle group. Interestingly, when treated with THC at all doses, the CaSki group showed a significant smaller number of the MVD. The CaSki + vehicle group also showed significantly increased VEGF, VEGFR-2, and HIF-1? expressions, but they were downregulated when mice were treated with THC at all doses. THC demonstrated an inhibitory effect against tumor angiogenesis in CaSki-implanted nude mice model. This effect is likely to be mediated by the downregulation of HIF-1-?, VEGF expression, and its receptor. THC could be developed into a promising agent for cancer therapy in the future. PMID:25789317

Yoysungnoen, Bhornprom; Patumraj, Suthiluk; Changtam, Chatchawan

2015-01-01

257

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

Cancer.gov

A study to comprehensively assess biomarkers of risk for progressive cervical neoplasia, and thus develop a new set of biomarkers that can distinguish those at highest risk of cervical cancer from those with benign infection

258

High expression of octamer transcription factor 1 in cervical cancer  

PubMed Central

Cervical carcinoma is the second most prevalent malignancy in females worldwide. The crucial etiologic factors involved in the development of cervical carcinoma include infection with papillomavirus, and the structural or functional mutation of oncogenes and tumor suppressor genes. The abnormal change of octamer transcription factor 1 (OCT1) is associated with tumor progression and a poor patient survival rate. However, little is known regarding the effect of OCT1 in cervical cancer. In the present study, flow cytometry, western blot analysis and quantitative polymerase chain reaction (qPCR) were peformed to identify differentially expressed OCT1 in cervical cancer tissue and adjacent non-cancerous tissues. The normalized OCT1 gene expression in cervical cancer was 5.98 times higher compared with the adjacent non-cancerous tissues. Western blot analysis and flow cytometry assessed the levels of OCT1 protein. The results of these two differential techniques showed that the protein expression level of OCT1 was greater in cervical cancer tissues, which corresponded with the qPCR results. Finally, as OCT1 is a potential target gene for microRNA (miR)-1467, -1185, -4493 and -3919, their expression levels were analyzed in cervical cancer tissues and adjacent non-cancerous tissues; they were downregulated by ~45% in the cervical cancer samples. The results of the present study showed that OCT1 is highly expressed in cervical cancer tissues and indicated that OCT-1 may be significant in cervical cancer. PMID:24932254

XIAO, SONGSHU; LIAO, SHAN; ZHOU, YANHONG; JIANG, BIN; LI, YUERAN; XUE, MIN

2014-01-01

259

Antioxidants in cervical cancer: Chemopreventive and chemotherapeutic effects of polyphenols  

Microsoft Academic Search

Cervical cancer lesions are a major threat to the health of women, representing the second most common cancer worldwide. The unanimously recognized etiological factor in the causation of cervical cancer is the infection with human papilloma virus (HPV). HPV infection, although necessary, is not per se sufficient to induce cancer. Other factors have to be involved in the progression of

F. Di Domenico; C. Foppoli; R. Coccia; M. Perluigi

260

A cis-acting element in the promoter of human ether à go-go 1 potassium channel gene mediates repression by calcitriol in human cervical cancer cells.  

PubMed

The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancer cells. Inhibitors of hEAG1 activity and expression represent potential therapeutic drugs in cancer. Previously, we have shown that hEAG1 expression is downregulated by calcitriol in a variety of cancer cells. Herein, we provided evidence on the regulatory mechanism involved in such repressive effect in cells derived from human cervical cancer. Our results indicate that repression by calcitriol occurs at the transcriptional level and involves a functional negative vitamin D response element (nVDRE) E-box type in the hEAG1 promoter. The described mechanism in this work implies that a protein complex formed by the vitamin D receptor-interacting repressor, the vitamin D receptor, the retinoid X receptor, and the Williams syndrome transcription factor interact with the nVDRE in the hEAG1 promoter in the absence of ligand. Interestingly, all of these transcription factors except the vitamin D receptor-interacting repressor are displaced from hEAG1 promoter in the presence of calcitriol. Our results provide novel mechanistic insights into calcitriol mode of action in repressing hEAG1 gene expression. PMID:25495694

Cázares-Ordoñez, V; González-Duarte, R J; Díaz, L; Ishizawa, M; Uno, S; Ortíz, V; Ordoñez-Sánchez, M L; Makishima, M; Larrea, F; Avila, E

2015-02-01

261

Abnormal pap smear and cervical cancer in pregnancy.  

PubMed

Pregnancy represents a unique opportunity to screen reproductive age women for cervical cancer and abnormal cervical cytology is relatively common in this population. In the absence of large, prospective clinical trials investigating the optimal management strategies for cervical dysplasia in pregnant women, consensus guidelines established by the American Society for Colposcopy and Cervical Pathology is available with considerations to this special patient population. Modalities for evaluation and management algorithms are reviewed and summarized from largely case series of pregnant women with cervical dysplasia and cervical cancer. PMID:22828115

Yang, Kathleen Y

2012-09-01

262

Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer  

PubMed Central

Introduction: Cervical cancer is the second leading cause of cancer morbidity and mortality for women around the world. Long non-coding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. Although downregulation of lncRNA GAS5 in several cancers has been studied, its role in cervical cancer remains unknown. The aim of this study is to investigate the expression, clinical significance and biological role in cervical cancer. Methods: Expression of GAS5 was analyzed in cervical cancer tissues by quantitative Real-time PCR (qRT-PCR). And its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress GAS5 expression in cervical cancer cells. In vitro assays were performed to further explore the biological functions of GAS5 in cervical cancer. Results: We found that GAS5 expression was markedly downregulated in cervical cancer tissues than in corresponding adjacent normal tissues. Decreased GAS5 expression was significantly correlated with FIGO stage, vascular invasion and lymph node metastasis. Moreover, cervical cancer patients with GAS5 lower expression have shown significantly poorer overall survival than those with higher GAS5 expression. And GAS5 expression was an independent prognostic marker of overall survival in a multivariate analysis. In vitro assays our data indicated that knockdown of GAS5 promoted cell proliferation, migration, and invasion. Conclusions: Our study presents that lncRNA GAS5 is a novel molecule involved in cervical cancer progression, which provide a potential prognostic biomarker and therapeutic target. PMID:25400758

Cao, Shihong; Liu, Weiliang; Li, Feng; Zhao, Weipin; Qin, Chuan

2014-01-01

263

Honeybee venom possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer cell line.  

PubMed

Bee venom (BV) therapy is a type of alternative medical treatment used to treat various diseases in oriental medicine. The mechanisms underlying the effects of BV remain poorly understood. In the present study, we evaluated the antiviral effect of BV on cervical carcinoma cell lines (CaSki, HeLa, C33A and TC-1). BV treatments resulted in a more significant suppression of cell growth in HPV 16-infected cells (CaSki) and a lesser suppression in HPV 18-infected cells (HeLa). However, less suppression was observed in HPV-negative C33A cells. In 10 µg/ml BV-treated CaSki cells, the mRNA expression and protein levels of HPV16 E6 and E7 were significantly decreased by BV, while HPV18 E6 and E7 mRNA expression levels were not significantly altered by 10 µg/ml BV-treated HeLa cells. The antitumor effects of BV were in accordance with in vitro data, in restricting tumor growth in vivo and were much more effective on the suppression of tumor growth. Furthermore, the mRNA and protein expression levels of HPV16 E6 and E7 were decreased by BV in TC-1 tumors. These findings demonstrated the antiviral effects of BV in HPV-infected cervical cancer cells and the anticancer effects of BV in HPV16 E6/E7-expressed TC-1 tumors. Collectively, BV plays a differential role in suppressing HPV16-infected cells (CaSki cells) and HPV18-infected cells (HeLa cells) by the downregulation of E6/E7 protein of HPV16/18. PMID:25633640

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

2015-04-01

264

Optical coherence tomography in diagnosing cervical cancer  

NASA Astrophysics Data System (ADS)

Cervical cancer remains one of the most significant problem in oncogynecology. It tends towards treatment approaches that provide termination of pathological processes along with preservation of the patient's life quality. There is a need in earlier and more accurate diagnosis of pathological states, objective assessment of physiological processes, and adequate monitoring of the course of treatment. In our previous publications we have reported unique capabilities of the Optical Coherence Tomography (OCT) to image in vivo the mucosa structure of the cervix and to monitor various physiological and pathological alterations. In this report, we present results of OCT application to diagnose different stages of cervical cancer and to control its treatment at early stages. We have performed OCT-colposcopy in 11 female patients with cervical cancer to derive OCT criteria of this disease, to provide exact demarcation of a pathological area, and to determine a real size of a tumor. We have found that, in general, borders of a tumor, defined visually and detected with OCT by violation of the basement membrane in exocervix, do not coincide. The mismatch depends on a stage of cancer and can be as much as several millimeters. This information is especially important for evaluation of linear dimension of tumors with 3 - 5 mm invasion and also for differential diagnosis between the T1 and T2 stages with cancer extension onto vagina.

Kuznetzova, Irina A.; Shakhova, Natalia M.; Kachalina, Tatiana S.; Gladkova, Natalia D.; Myakov, Alexey V.; Iksanov, Rashid R.; Feldchtein, Felix I.

2000-05-01

265

High and interrelated rates of PD-L1+CD14+ antigen-presenting cells and regulatory T cells mark the microenvironment of metastatic lymph nodes from patients with cervical cancer.  

PubMed

A better understanding of the microenvironment in relation to lymph node metastasis is essential for the development of effective immunotherapeutic strategies against cervical cancer. In the present study, we investigated the microenvironment of tumor-draining lymph nodes of patients with cervical cancer by comprehensive flow cytometry-based phenotyping and enumeration of immune-cell subsets in tumor-negative (LN(-), n = 20) versus tumor-positive lymph nodes (LN(+), n = 8), and by the study of cytokine release profiles (n = 4 for both LN(-) and LN(+)). We found significantly lower CD4(+) and higher CD8(+) T-cell frequencies in LN(+) samples, accompanied by increased surface levels of activation markers (HLA-DR; ICOS; PD-1; CTLA-4) and the memory marker CD45RO. Furthermore, in LN(+), we found increased rates of a potentially regulatory antigen-presenting cell (APC) subset (CD11c(hi)CD14(+)PD-L1(+)) and of myeloid-derived suppressor cell subsets; the LN(+) APC subset correlated with significantly elevated frequencies of FoxP3(+) regulatory T cells (Treg). After in vitro stimulation with different Toll-like receptor (TLR) ligands (PGN; Poly-IC; R848), we observed higher production levels of IL6, IL10, and TNF? but lower levels of IFN? in LN(+) samples. We conclude that, despite increased T-cell differentiation and activation, a switch to a profound immune-suppressive microenvironment in LN(+) of patients with cervical cancer will enable immune escape. Our data indicate that the CD14(+)PD-L1(+) APC/Treg axis is a particularly attractive and relevant therapeutic target to specifically tackle microenvironmental immune suppression and thus enhances the efficacy of immunotherapy in patients with metastasized cervical cancer. PMID:25361854

Heeren, A Marijne; Koster, Bas D; Samuels, Sanne; Ferns, Debbie M; Chondronasiou, Dafni; Kenter, Gemma G; Jordanova, Ekaterina S; de Gruijl, Tanja D

2015-01-01

266

Screening hospital patients for uterine cervical cancer.  

PubMed Central

Women patients admitted to a district general hospital with non-gynaecological conditions were offered a cervical smear test. In three years 2296 women were tested. Serious uterine pathology was detected in 13 patients (5.7 per 1000) and significant cytological abnormalities (dyskaryosis of all grades) in 46 (20.0 per 1000). Of the women screened 963 (41.9%) had never had a smear test before and 1608 (70.0%) were over 39 yr. The results show that cervical screening of non-gynaecological patients in hospital reaches many of the women at risk for cervical cancer who do not otherwise have smears taken and reveals considerable uterine pathology. PMID:6853729

Hudson, E; Hewertson, S; Jansz, C; Gordon, H

1983-01-01

267

Consanguinity decreases risk of breast cancercervical cancer unaffected  

Microsoft Academic Search

Marriages between third-degree and more distant relatives are common in many parts of the world. Offspring of consanguineous parents have increased morbidity and mortality related to recessive gene disorders. In a population with a high frequency of consanguinity, we examined the frequency of breast cancer (related in part to tumour genes) and cervical cancers (related to virus infection) among offspring

S Denic; A Bener

2001-01-01

268

Cervical Cancer Risk Prediction Models  

Cancer.gov

Absolute cancer risk is the probability that an individual with given risk factors and a given age will develop cancer over a defined period of time. Examples of these risk factors include race, age, sex, genetics, body mass index, family history of cancer, history of tobacco use, use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDS), physical activity, use of hormone replacement therapy, reproductive factors, history of cancer screening, and dietary factors.

269

Computer aided decision support system for cervical cancer classification  

NASA Astrophysics Data System (ADS)

Conventional analysis of a cervical histology image, such a pap smear or a biopsy sample, is performed by an expert pathologist manually. This involves inspecting the sample for cellular level abnormalities and determining the spread of the abnormalities. Cancer is graded based on the spread of the abnormal cells. This is a tedious, subjective and time-consuming process with considerable variations in diagnosis between the experts. This paper presents a computer aided decision support system (CADSS) tool to help the pathologists in their examination of the cervical cancer biopsies. The main aim of the proposed CADSS system is to identify abnormalities and quantify cancer grading in a systematic and repeatable manner. The paper proposes three different methods which presents and compares the results using 475 images of cervical biopsies which include normal, three stages of pre cancer, and malignant cases. This paper will explore various components of an effective CADSS; image acquisition, pre-processing, segmentation, feature extraction, classification, grading and disease identification. Cervical histological images are captured using a digital microscope. The images are captured in sufficient resolution to retain enough information for effective classification. Histology images of cervical biopsies consist of three major sections; background, stroma and squamous epithelium. Most diagnostic information are contained within the epithelium region. This paper will present two levels of segmentations; global (macro) and local (micro). At the global level the squamous epithelium is separated from the background and stroma. At the local or cellular level, the nuclei and cytoplasm are segmented for further analysis. Image features that influence the pathologists' decision during the analysis and classification of a cervical biopsy are the nuclei's shape and spread; the ratio of the areas of nuclei and cytoplasm as well as the texture and spread of the abnormalities. Similar features are extracted towards the automated classification process. This paper will present various feature extraction methods including colour, shape and texture using Gabor wavelet as well as various quantative metrics. Generated features are used to classify cells or regions into normal and abnormal categories. Following the classification process, the cancer is graded based on the spread of the abnormal cells. This paper will present the results of the grading process with five stages of the cancer spectrum.

Rahmadwati, Rahmadwati; Naghdy, Golshah; Ros, Montserrat; Todd, Catherine

2012-10-01

270

Visual inspection methods for cervical cancer prevention.  

PubMed

The need for simple, cost-effective screening approaches for cervical cancer prevention in low-resource countries has led to the evaluation of visual screening with 3-5% acetic acid. The low reproducibility and wide variation in accuracy reflect the subjective nature of the test. Pooled sensitivity, specificity, positive and negative predictive values were 80%, 92%, 10% and 99%, respectively, for detecting cervical intraepithelial neoplasia grade 2 or worse lesions. Realistic sensitivity of a quality- assured single visual inspection with acetic acid is around 50%. A single round of visual inspection with acetic acid screening has been associated with a 25-35% reduction in cervical cancer incidence and the frequency of cervical intraepithelial neoplasia grade 2 or worse lesions in randomised-controlled trials. Despite all its limitations, implementing visual inspection with acetic acid screening in low-resource countries may provide a pragmatic approach to building up human resources and infrastructure that may facilitate the highly anticipated low-cost, rapid human papilloma virus testing in the near future. PMID:22075441

Sankaranarayanan, Rengaswamy; Nessa, Ashrafun; Esmy, Pulikattil Okkuru; Dangou, Jean-Marie

2012-04-01

271

Long non-coding RNA HOTAIR is associated with human cervical cancer progression  

PubMed Central

The functions of many long non-coding RNAs (lncRNAs) in human cancers remain to be clarified. The lncRNA Hox transcript antisense intergenic RNA (HOTAIR) has been reported to reprogram chromatin organization and promote breast and colorectal cancer metastasis, the involvement of lncRNAs in cervical cancer is just beginning to be studied. In the present study, we examined the expression and the functional role of HOTAIR in cervical cancer. HOTAIR expression was determined in cervical cancer tissues (n=111) and corresponding normal tissues (n=40) by using real-time polymerase chain reaction, and its correlation with clinical parameters and prognosis were analyzed. To determine the effect of HOTAIR knockdown and overexpression in cervical cancer cell lines, we used the CCK-8 assay, wound healing migration and Matrigel invasion assay. The expression level of HOTAIR in cervical cancer tissues was higher than that in corresponding non-cancerous tissues. High HOTAIR expression correlated with lymph node metastasis, and reduced overall survival. A multivariate analysis showed that HOTAIR was a prognostic factor for predicting cervical cancer recurrence. Knockdown of HOTAIR reduced cell proliferation, migration, and invasion in cervical cancer cell lines. Moreover, HOTAIR regulated the expression of vascular endothelial growth factor, matrix metalloproteinase-9 and epithelial-to-mesenchymal transition (EMT)-related genes, which are important for cell motility and metastasis. Therefore, HOTAIR may promote tumor aggressiveness through the upregulation of VEGF and MMP-9 and EMT-related genes. These findings indicate that HOTAIR may represent a novel biomarker for predicting recurrence and prognosis and serve as a promising therapeutic target in cervical cancer. PMID:25405331

KIM, HEE JUNG; LEE, DAE WOO; YIM, GA WON; NAM, EUN JI; KIM, SUNGHOON; KIM, SANG WUN; KIM, YOUNG TAE

2015-01-01

272

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

PubMed Central

Cervical cancer is the second largest cause of death among women worldwide. Nowadays, this disease is preventable and curable at low cost and low risk when an accurate diagnosis is done in due time, since it is the neoplasm with the highest prevention potential. This work describes the development of an expert system able to provide a diagnosis to cervical neoplasia (CN) precursor injuries through the integration of fuzzy logics and image interpretation techniques. The key contribution of this research focuses on atypical cases, specifically on atypical glandular cells (AGC). The expert system consists of 3 phases: (1) risk diagnosis which consists of the interpretation of a patient's clinical background and the risks for contracting CN according to specialists; (2) cytology images detection which consists of image interpretation (IM) and the Bethesda system for cytology interpretation, and (3) determination of cancer precursor injuries which consists of in retrieving the information from the prior phases and integrating the expert system by means of a fuzzy logics (FL) model. During the validation stage of the system, 21 already diagnosed cases were tested with a positive correlation in which 100% effectiveness was obtained. The main contribution of this work relies on the reduction of false positives and false negatives by providing a more accurate diagnosis for CN. PMID:23690881

Domínguez Hernández, Karem R.; Aguilar Lasserre, Alberto A.; Posada Gómez, Rubén; Palet Guzmán, José A.; González Sánchez, Blanca E.

2013-01-01

273

Anticancer effects of brominated indole alkaloid Eudistomin H from marine ascidian Eudistoma viride against cervical cancer cells (HeLa).  

PubMed

Marine invertebrates called ascidians are prolific producers of bioactive substances. The ascidian Eudistoma viride, distributed along the Southeast coast of India, was investigated for its in vitro cytotoxic activity against human cervical carcinoma (HeLa) cells by the MTT assay. The crude methanolic extract of E. viride, with an IC50 of 53 ?g/ml, was dose-dependently cytotoxic. It was more potent at 100 ?g/ml than cyclohexamide (1 ?g/ml), reducing cell viability to 9.2%. Among nine fractions separated by chromatography, ECF-8 exhibited prominent cytoxic activity at 10 ?g/ml. The HPLC fraction EHF-21 of ECF-8 was remarkably dose- and time-dependently cytotoxic, with 39.8% viable cells at 1 ?g/ml compared to 51% in cyclohexamide-treated cells at the same concentration; the IC50 was 0.49 ?g/ml. Hoechst staining of HeLa cells treated with EHF-21 at 0.5 ?g/ml revealed apoptotic events such an cell shrinkage, membrane blebbing, chromatin condensation and formation of apoptotic bodies. Cell size and granularity study showed changes in light scatter, indicating the characteristic feature of cells dying by apoptosis. The cell-cycle analysis of HeLa cells treated with fraction EHF-21 at 1 ?g/ml showed the marked arrest of cells in G0/G1, S and G2/M phases and an increase in the sub G0/G1 population indicated an increase in the apoptotic cell population. The statistical analysis of the sub-G1 region showed a dose-dependent induction of apoptosis. DNA fragmentation was also observed in HeLa cells treated with EHF-21. The active EHF-21 fraction, a brominated indole alkaloid Eudistomin H, led to apoptotic death of HeLa cells. PMID:25550562

Rajesh, Rajaian Pushpabai; Annappan, Murugan

2015-01-01

274

MicroRNA?494 promotes cervical cancer proliferation through the regulation of PTEN.  

PubMed

The phosphoinositide 3?kinase (PI3K)/Akt signaling pathway appears to be a key regulator in cervical carcinogenesis. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein is principally involved in the homeostatic maintenance of PI3K/Akt signaling and PTEN has been identified to play an important role in the occurrence and development of cervical cancer. MicroRNA (miRNA)?494 has been proven to be involved in the carcinogenesis and development of various types of cancer by directly targeting PTEN. However the role, mechanism and clinical significance of miR?494 in cervical cancer have not been further reported. In the present study, we analyzed the expression of miR?494 in cervical cancer cell lines and clinical specimens by RT?qPCR, and explored the association of miR?494 with PTEN expression and clinicopathological data of cervical cancer patients. The results showed that miR?494 expression was significantly upregulated in human cervical cancer cell lines and tissues. miR?494 upregulation was significantly associated with PTEN downregulation, adverse clinicopathological characteristics, poor overall and progression?free survival and poor prognosis. In vitro experiments showed that inhibition of miR?494 suppressed cell proliferation and growth by directly targeting the 3'?untranslated region (3'?UTR) of PTEN mRNA. These findings identified a novel molecular mechanism involved in the regulation of PTEN expression and cervical cancer progression. Results of the present study indicated that miR?494 may have an essential role in the carcinogenesis and progression of cervical cancer and targeting miR?494 may be a promising therapeutic strategy for the treatment of cervical cancer. PMID:25738254

Yang, Yong-Kang; Xi, Wen-Yan; Xi, Ru-Xing; Li, Jing-Yuan; Li, Qin; Gao, Yan-E

2015-05-01

275

76 FR 30723 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)  

Federal Register 2010, 2011, 2012, 2013, 2014

...Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control...detection and control of breast and cervical cancer. The committee makes recommendations...Reform and its impact for breast and cervical cancer screening; updates on...

2011-05-26

276

77 FR 66469 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)  

Federal Register 2010, 2011, 2012, 2013, 2014

...Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control...aforementioned committee: Name: Breast and Cervical Cancer Early Detection and Control...detection and control of breast and cervical cancer. The committee makes...

2012-11-05

277

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

Federal Register 2010, 2011, 2012, 2013, 2014

...Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control...detection and control of breast and cervical cancer. The committee makes recommendations...Task Force guidelines for breast and cervical cancer screening; Impact of...

2010-02-18

278

[Pretreatment diagnostic evaluation of cervical cancer].  

PubMed

Magnetic resonance imaging (MRI) has evolved into an integral component of the pretherapeutic local staging of cervical cancer. Many recent studies have demonstrated the superiority of MRI for this indication. It is the method of choice for therapeutic decision making and planning, monitoring of the response to radiotherapy, excluding of tumor recurrence, and assessing of patients for tumor or therapy-related complications. The superiority of MRI is mainly due to its high soft-tissue contrast that allows depiction of the abdominal and pelvic organs with excellent image quality. This article provides an overview of the diagnostic potential and limitations of MRI in the primary staging of cervical cancer and supplementary imaging modalities - CT, PET, and PET/CT - on the basis of the current scientific literature. Also included is a discussion of state-of-the-art lymph node staging and the limitations of imaging in lymph node assessment. PMID:19373746

Lemke, U; Hamm, B

2009-05-01

279

Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C 12U] (Ampligen ®)  

Microsoft Academic Search

Human papilloma virus (HPV) found in 99.7% of cervical cancers represents an attractive immunotherapeutic target for novel adjuvant dendritic cell (DC) immunotherapy. DC primed with HPV antigens have been shown to be capable of inducing CTL responses powerful enough to eradicate established murine tumours expressing HPV16 antigen. The use of tumour lysate has been found to be an effective means

M Adams; H Navabi; B Jasani; S Man; A Fiander; A. S Evans; C Donninger; M Mason

2003-01-01

280

CASP7 variants modify susceptibility to cervical cancer in Chinese women  

PubMed Central

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

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

2015-01-01

281

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

SciTech Connect

Highlights: {yields} Integration of HPV into host genome critical for activation of E6 and E7 oncogenes. {yields} BAF53 is essential for higher-order chromatin structure. {yields} BAF53 knockdown suppresses E6 and E7 from HPV integrants, but not from episomal HPVs. {yields} BAF53 knockdown decreases H3K9Ac and H4K12Ac on P105 promoter of integrated HPV 18. {yields} BAF53 knockdown restores the p53-dependent signaling pathway in HeLa and SiHa cells. -- Abstract: Deregulation of the expression of human papillomavirus (HPV) oncogenes E6 and E7 plays a pivotal role in cervical carcinogenesis because the E6 and E7 proteins neutralize p53 and Rb tumor suppressor pathways, respectively. In approximately 90% of all cervical carcinomas, HPVs are found to be integrated into the host genome. Following integration, the core-enhancer element and P105 promoter that control expression of E6 and E7 adopt a chromatin structure that is different from that of episomal HPV, and this has been proposed to contribute to activation of E6 and E7 expression. However, the molecular basis underlying this chromatin structural change remains unknown. Previously, BAF53 has been shown to be essential for the integrity of higher-order chromatin structure and interchromosomal interactions. Here, we examined whether BAF53 is required for activated expression of E6 and E7 genes. We found that BAF53 knockdown led to suppression of expression of E6 and E7 genes from HPV integrants in cervical carcinoma cell lines HeLa and SiHa. Conversely, expression of transiently transfected HPV18-LCR-Luciferase was not suppressed by BAF53 knockdown. The level of the active histone marks H3K9Ac and H4K12Ac on the P105 promoter of integrated HPV 18 was decreased in BAF53 knockdown cells. BAF53 knockdown restored the p53-dependent signaling pathway in HeLa and SiHa cells. These results suggest that activated expression of the E6 and E7 genes of integrated HPV is dependent on BAF53-dependent higher-order chromatin structure or nuclear motor activity.

Lee, Kiwon; Lee, Ah-Young [Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yongin 449-791 (Korea, Republic of)] [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)] [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)] [Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yongin 449-791 (Korea, Republic of)

2011-08-26

282

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

Microsoft Academic Search

T-lymphokine-activated killer cell-originated protein kinase (TOPK) appears to be highly expressed in various cancer cells and to play an important role in maintaining proliferation of cancer cells. However, the underlying mechanism by which TOPK regulates growth of cancer cells remains elusive. Here we report that upregulated endogenous TOPK augments resistance of cancer cells to apoptosis induced by tumor necrosis factor-related

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

2010-01-01

283

Effect of ferric ions on reactive oxygen species formation, cervical cancer cell lines growth and E6/E7 oncogene expression.  

PubMed

As iron ions may participate in the pathogenesis of cancer and viral infections, the aim of this study was to monitor their influence on proliferation, E6 and E7 oncogene expression and reactive oxygen species (ROS) production in two human papilloma virus (HPV) positive cervical carcinoma cell lines (HeLa and SiHa) and one HPV negative vulvar cell line (A431). The anti-anaemic drug, ferric-sorbitol-citric acid complex (FSC) as a source of Fe(III) ions was used. Cells were treated with FSC at the concentrations between 0.001 and 1 mM Fe(III) for different time periods. Fe(III) ions inhibited the viability of HeLa and A431 cells while it had no influence on SiHa cells. Furthermore, Fe(III) treatment showed a time-dependent and a higher stimulatory effect on E6/E7 expression in SiHa cells than in HeLa cells. Fe(III) ion treatment with concentrations lower than 0.1mM showed a time and a concentration dependent intracellular ROS production in all tested cell lines, while the treatment with 1mM concentration decreased ROS production in all tested cell lines. In conclusion, Fe(III) ion treatment apart from having an anti-tumour effect, as we previously described, enhances survival of HPV 16-positive cells and might be associated with HPV oncogenesis. PMID:21044880

Poljak-Blazi, Marija; Jaganjac, Morana; Sabol, Ivan; Mihaljevic, Branka; Matovina, Mihaela; Grce, Magdalena

2011-02-01

284

Small intestine metastasis from cervical cancer with acute abdomen: A case report  

PubMed Central

Cervical cancer metastasis to the small intestine is a rare occurrence that is easily misdiagnosed as a small bowel obstruction. The present study reports the case of a 46-year-old cervical cancer patient with metastasis to the small intestine, which presented as an acute abdomen due to intestinal obstruction. Enteroscopy revealed no primary intestinal tumors. The patient underwent exploratory laparotomy and resection of the tumor of the small intestine. Pathology revealed the mass to be squamous cell carcinoma, limited to the outer muscular layer and serosa. This case demonstrates that small intestine seeding must be considered in the differential diagnosis of acute abdomen in patients with cervical cancer. PMID:25435956

QIU, HUI; YUAN, LIMEI; OU, YANGWEN; ZHU, YAN; XIE, CONGHUA; ZHANG, GONG

2015-01-01

285

Small intestine metastasis from cervical cancer with acute abdomen: A case report.  

PubMed

Cervical cancer metastasis to the small intestine is a rare occurrence that is easily misdiagnosed as a small bowel obstruction. The present study reports the case of a 46-year-old cervical cancer patient with metastasis to the small intestine, which presented as an acute abdomen due to intestinal obstruction. Enteroscopy revealed no primary intestinal tumors. The patient underwent exploratory laparotomy and resection of the tumor of the small intestine. Pathology revealed the mass to be squamous cell carcinoma, limited to the outer muscular layer and serosa. This case demonstrates that small intestine seeding must be considered in the differential diagnosis of acute abdomen in patients with cervical cancer. PMID:25435956

Qiu, Hui; Yuan, Limei; Ou, Yangwen; Zhu, Yan; Xie, Conghua; Zhang, Gong

2015-01-01

286

Barriers to Cervical Cancer Screening Among Lesbians  

PubMed Central

Abstract Objective To evaluate cervical cancer screening practices and barriers to screening in a sample of lesbians. Methods Cross-sectional survey data were collected from 225 self-identified lesbians who completed an online questionnaire. Results Of the respondents, 71% reported receiving a Pap screening test in the past 24 months (routine screeners), and 29% reported receiving a Pap screening test >24 months ago or never (nonroutine screeners). Routine screeners were more likely to be older (p?cervical cancer. Conclusions Many lesbians do not screen for cervical cancer at recommended rates. Nonroutine screeners perceive fewer benefits, more barriers, and more discrimination and are less knowledgeable about screening guidelines than routine screeners. PMID:20095905

Lydecker, Alison D.; Ireland, Lynda

2010-01-01

287

T-cell response to human papillomavirus type 58 L1, E6, And E7 peptides in women with cleared infection, cervical intraepithelial neoplasia, or invasive cancer.  

PubMed

Human papillomavirus type 58 (HPV-58) exists in a relatively high prevalence in certain parts of the world, including East Asia. This study examined the T-cell response to HPV-58 L1, E6, and E7 peptides among women with cleared infection, cervical intraepithelial neoplasia grade 2 (CIN2) or CIN3, or invasive cervical cancer (ICC). Peptides found to be reactive in the in vitro peptide binding assay or mouse-stimulating study were tested with a gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay to detect peptide-specific responses from the peripheral blood mononuclear cells (PBMC) collected from 91 HPV-58-infected women (32 with cleared infection, 16 CIN2, 15 CIN3, and 28 ICC). Four HLA-A11-restricted HPV-58 L1 peptides, located at amino acid positions 296 to 304, 327 to 335, 101 to 109, and 469 to 477, showed positive IFN-gamma ELISPOT results and were mainly from women with cleared infection. Two HLA-A11-restricted E6 peptides (amino acid positions 64 to 72 and 94 to 102) and three HLA-A11-restricted E7 peptides (amino acid positions 78 to 86, 74 to 82, and 88 to 96) showed a positive response. A response to E6 and E7 peptides was mainly observed from subjects with CIN2 or above. One HLA-A2-restricted E6 peptide, located at amino acid position 99 to 107, elicited a positive response in two CIN2 subjects. One HLA-A24-restricted L1 peptide, located at amino acid position 468 to 476, also elicited a positive response in two CIN2 subjects. In summary, this study has identified a few immunogenic epitopes for HPV-58 E6 and E7 proteins. It is worthwhile to further investigate whether responses to these epitopes have a role in clearing an established cervical lesion. PMID:20668141

Chan, Paul K S; Liu, Shih-Jen; Cheung, T H; Yeo, Winnie; Ngai, S M; Cheung, Jo L K; Chong, Pele; Man, Stephen

2010-09-01

288

Human Papillomavirus Induced Transformation in Cervical and Head and Neck Cancers  

PubMed Central

Human papillomavirus (HPV) is one of the most widely publicized and researched pathogenic DNA viruses. For decades, HPV research has focused on transforming viral activities in cervical cancer. During the past 15 years, however, HPV has also emerged as a major etiological agent in cancers of the head and neck, in particular squamous cell carcinoma. Even with significant strides achieved towards the screening and treatment of cervical cancer, and preventive vaccines, cervical cancer remains the leading cause of cancer-associated deaths for women in developing countries. Furthermore, routine screens are not available for those at risk of head and neck cancer. The current expectation is that HPV vaccination will prevent not only cervical, but also head and neck cancers. In order to determine if previous cervical cancer models for HPV infection and transformation are directly applicable to head and neck cancer, clinical and molecular disease aspects must be carefully compared. In this review, we briefly discuss the cervical and head and neck cancer literature to highlight clinical and genomic commonalities. Differences in prognosis, staging and treatment, as well as comparisons of mutational profiles, viral integration patterns, and alterations in gene expression will be addressed. PMID:25226287

Adams, Allie K.; Wise-Draper, Trisha M.; Wells, Susanne I.

2014-01-01

289

Cationic liposomes bearing IL-2 on their external surface induced mice leukocytes to kill human cervical cancer cells in vitro, and significantly reduced tumor burden in immunodepressed mice.  

PubMed

Tumor cells are known to modify their surroundings in order to escape immunologic detection, and IL-2, a killer cell activator, is one of the factors known to overcome this escape mechanism. In this regard, when we cocultured cells from the human cervical cancer cell line INBL with mice blood leukocytes, no inhibition of tumor cell growth was observed, but when a similar coculture was done in the presence of cationic liposomes bearing IL-2 on their external surface (CL-IL-2), all the INBL cells were killed. In order to evaluate whether this in vitro property of CL-IL-2 to overcome tumor cell detection by lymphocytes could also be reproduced in vivo, INBL cells were intraperitoneally (i.p.) inoculated into immunodepressed mice to produce solid tumors. We observed that the subsequent i.p. delivery of CL-IL-2 rendered the tumor masses significantly smaller. The presence of a large number of infiltrating lymphocytes on those tumors, and the fact that many had a cytotoxic CD8(+) phenotype suggests that these lymphocytes were responsible for the observed antitumor effect. Finally, the possible formation of a bridge between the IL-2R receptors on both, the lymphocytes and the INBL cells, mediated by the IL-2-bearing liposomes, and its possible effect on the activation of antitumor cytotoxic lymphocytes is discussed. PMID:20367025

Rangel-Corona, Rosalva; Corona-Ortega, Teresa; del Río-Ortiz, Itzel; Nieves-Ramírez, Miriam E; Morán-Bañuelos, Hirán; González-Tenorio, Olivia; Cáceres-Cortés, Julio Roberto; Weiss-Steider, Benny

2011-02-01

290

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

PubMed

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-? 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-? 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. PMID:24358111

Zhang, Jiarong; Li, Shuangdi; Yan, Qin; Chen, Xiaoyue; Yang, Yixia; Liu, Xuelian; Wan, Xiaoping

2013-01-01

291

Cervical cancer metastasis to the scalp presenting as alopecia neoplastica.  

PubMed

A 45-year-old Japanese woman was diagnosed in 1996 with squamous cell cancer of the cervix following an abnormal Papanicolaou smear and subsequent diagnostic conization. She underwent total abdominal hysterectomy with pelvic lymphadenectomy and was found to have poorly differentiated squamous cell carcinoma, International Federation of Gynecology and Obstetrics (FIGO) stage IB1. She remained asymptomatic until 2003 when she presented with obstructive uropathy with acute renal failure and hydronephrosis, suspected to be from the recurrence of cervical cancer. This was confirmed when computerized tomography (CT)-guided lymph node biopsy showed squamous cell carcinoma of the para-aortic lymph nodes histologically consistent with the cervical primary. In addition, there was evidence of lumbar spine metastasis by positron emission tomography (PET) and bone scans. She received several courses of chemotherapy with cisplatin and 5-fluorouracil (5FU), as well as radiation therapy. In July 2004, she was hospitalized for acute renal failure, nausea, vomiting, and anorexia. CT of the abdomen identified widespread metastases in the liver, pancreatic head, and lumbar spine. During this hospitalization, she complained of severe scalp tenderness and patchy hair loss first noticed 3 days prior to presentation. On examination of her scalp, two patches of alopecia were observed (Fig. 1). In the largest patch, there was a 5 x 2.5-cm, tender, erythematous plaque with atrophy. In the smaller patch, there was a 2 x 1.5-cm, erythematous, scaly plaque. A punch biopsy of the larger patch revealed atypical epithelial cells in nests with intravascular involvement and diminished numbers of focally miniaturized hair follicles (Fig. 2a). The scalp specimen was histologically identical with biopsy specimens of the cervical primary (Fig. 2b). There was also seborrheic dermatitis, with thick greasy scale, noted on the scalp, which resolved with fluocinolone solution. The patient decided against further treatment for her advanced cervical cancer but did accept hydromorphone for pain. She died 3 months after admission. PMID:17269974

Chung, John J; Namiki, Thomas; Johnson, Douglas W

2007-02-01

292

Epigenetics and cervical cancer: from pathogenesis to therapy.  

PubMed

Although human papillomavirus (HPV) infection has been found in most of the cervical cancer cases, additional genetic and epigenetic changes are required for disease progression. Previously, it was thought that only genetic mutation plays a key role in cervical cancer development. But recent advances in the biology of cervical cancer revealed that epigenetic alteration is common in cervical carcinogenesis and metastasis. Epigenetic alteration due to aberrant DNA methylation and histone modification has been extensively studied in cervical cancer. Recent research strategies keep insight into noncoding RNAs, especially miRNA and lncRNA. At the same time, interest has been grown to study the utility of these changes as biomarkers to determine disease progression as well as use them as the therapeutic targets. This study has been aimed to review the recent progress of epigenetic study for cervical cancer research including role of these epigenetic changes in disease progression, their prognostic values, and their use in targeted therapy. PMID:24554414

Fang, Jinchuan; Zhang, Hai; Jin, Sufang

2014-06-01

293

MicroRNA-218 enhances the radiosensitivity of human cervical cancer via promoting radiation induced apoptosis.  

PubMed

We previously reported frequent loss of microRNA-218 (miR-218) in cervical cancer, which was associated with tumor progression and poor prognosis. As microRNAs were found invovled in the regulation of radiosensitivity in various human cancers, we therefore aim to investigate the effects of miR-218 on radiosensitivity of cervical cancer in the present study. The clonogenic survival assay demonstrated that loss of miR-218 could predict radioresistance in the primary cervical cancer cells (R(2)=0.6516, P<0.001). In vitro, abundant miR-218 increased the radiosensitivity in cervical cancer cells (P<0.001 for HeLa, P=0.009 for SiHa, P=0.016 for C33A and P=0.01 for CaSki). Upregulation of miR-218 significantly enhanced the radiation-induced apoptosis, which was further enhanced by the combination of miR-218 overexpression and radiation In xenograft growth assay, combination of miR-218 overexpression and radiation notably induced cellular apoptosis and suppressed tumor growth. In conclusion, we demonstrated that miR-218 resensitized cervical cancer cells to radiation via promoting cellular apoptosis. Moreover, we proved that miR-218 as a potent predictor of radiosensitivity in cervical cancer, especially for those patients with loss of miR-218. PMID:24843318

Yuan, Wang; Xiaoyun, Han; Haifeng, Qiu; Jing, Li; Weixu, Hu; Ruofan, Dong; Jinjin, Yu; Zongji, Shen

2014-01-01

294

MicroRNA-218 Enhances the Radiosensitivity of Human Cervical Cancer via Promoting Radiation Induced Apoptosis  

PubMed Central

We previously reported frequent loss of microRNA-218 (miR-218) in cervical cancer, which was associated with tumor progression and poor prognosis. As microRNAs were found invovled in the regulation of radiosensitivity in various human cancers, we therefore aim to investigate the effects of miR-218 on radiosensitivity of cervical cancer in the present study. The clonogenic survival assay demonstrated that loss of miR-218 could predict radioresistance in the primary cervical cancer cells (R2=0.6516, P<0.001). In vitro, abundant miR-218 increased the radiosensitivity in cervical cancer cells (P<0.001 for HeLa, P=0.009 for SiHa, P=0.016 for C33A and P=0.01 for CaSki). Upregulation of miR-218 significantly enhanced the radiation-induced apoptosis, which was further enhanced by the combination of miR-218 overexpression and radiation In xenograft growth assay, combination of miR-218 overexpression and radiation notably induced cellular apoptosis and suppressed tumor growth. In conclusion, we demonstrated that miR-218 resensitized cervical cancer cells to radiation via promoting cellular apoptosis. Moreover, we proved that miR-218 as a potent predictor of radiosensitivity in cervical cancer, especially for those patients with loss of miR-218. PMID:24843318

Yuan, Wang; Xiaoyun, Han; Haifeng, Qiu; Jing, Li; Weixu, Hu; Ruofan, Dong; Jinjin, Yu; Zongji, Shen

2014-01-01

295

Isolated humeral metastasis in uterine cervical cancer: a rare entity.  

PubMed

Bone metastasis in cancer of uterine cervix, especially in the form of isolated bone involvement is a rare manifestation. Herein, we report the first case of isolated humeral metastasis in a known case of locally advanced cervical cancer. A fifty-six-year old female presented with International Federation of Gynecology and Obstetrics (FIGO) Stage IV A squamous cell carcinoma of uterine cervix. She was treated with a combination of radiation and chemotherapy and then total abdominal hysterectomy with bilateral salpingo-oophorectomy. Seven months later, she developed an isolated lytic lesion in the left humerus, which turned out to be a bone metastatic lesion. PMID:23393636

Malek, Mahrooz; Kanafi, Alireza Rajabzadeh; Pourghorban, Ramin; Nafisi-Moghadam, Reza

2012-01-01

296

Coincidental detection of T-cell rich B cell lymphoma in the para-aortic lymph nodes of a woman undergoing lymph node dissection for cervical cancer: a case report.  

PubMed

The diagnosis of cervical squamous cell carcinoma with concurrent T-cell rich B cell lymphoma in dissected lymph nodes has not been reported to our knowledge. In our case, the biopsy of an exophytic lesion at the uterine cervix showed squamous cell carcinoma in a 50-year-old woman presenting with postcoital bleeding. Type III hysterectomy, bilateral salpingo-oophorectemy, bilateral pelvic, para-aortic lymph node dissections were performed. Pathologic examination revealed a T-cell rich B cell lymphoma in some lymph nodes beside squamous cell carcinoma in several of others. ELISA for human immuno-deficiency virus (HIV) was negative. The cervical carcinoma was staged as FIGO clinical stage IB1 and the lymphoma as Ann Arbor IIA. Six cycles of CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolon) chemotherapy for the lymphoma and concomitant pelvic chemoradiotherapy with cisplatin for cervical cancer were given. In this rare coincidence, the best available therapy for each of the diseases should be considered individually. We also suggest that HIV screennig test be carried out, because both diseases may be related to human immuno-deficiency virus, although our patient is HIV-negative. PMID:14675356

Abali, H; Eren, O O; Erman, M; Uner, A H; Kose, F; Guler, N

2003-01-01

297

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

PubMed Central

The aim of the present study was to investigate the effect of heat shock protein 90 (Hsp90)-specific inhibitor geldanamycin (GA) on the proliferation and apoptosis induced by vascular endothelial growth factor-C (VEGF-C) in cervical cancer cells. HeLa cells (1×106/ml) in the logarithmic growth phase were incubated without serum for 24 h. The cells were pretreated with kinase insert domain receptor antibody (KDR)-Ab (20 ?g/ml), phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (3 ?mol/l), mitogen-activated protein kinase (MAPK) inhibitor PD98059 (30 ?mol/l) or Hsp90-specific inhibitor GA (10 ?mol/l) for 30 min, and then treated with VEGF-C (50 ng/?l) for a further 24 h. The cells were harvested for MTT analysis, annexin V-FITC/propidium iodide double staining for early apoptosis and SDS-PAGE and western blot analysis in order to determine Hsp90, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cyclin D1 expression. Treatment with VEGF-C alone induced Hsp90 protein expression in HeLa cells at all time-points. Hsp90 expression was increased 3.31-fold in VEGF-C treated HeLa cells, and this increase was attenuated in the treatment groups (2.17-, 1.69-, 1.82-fold in VEGF-C + KDR-Ab, VEGF-C + PD98059 and VEGF-C + LY294002, respectively). The proliferation of the VEGF-C-treated HeLa cells was increased ~2.13-fold, while that of the VEGF-C + GA-treated HeLa cells decreased 0.87-fold (P<0.05). Even low concentrations of GA (0.02 ?mol/l) were found to inhibit the Bcl-2 and cyclin D1 protein expression induced by VEGF-C. Therefore, the results indicate that the Hsp90-specific inhibitor GA has a critical role in the proliferation and apoptosis induced by VEGF-C in cervical cancer cells. PMID:25289059

DU, XUE; LI, YONGMEI; JING, XU; ZHAO, LINA

2014-01-01

298

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

PubMed

The aim of the present study was to investigate the effect of heat shock protein 90 (Hsp90)-specific inhibitor geldanamycin (GA) on the proliferation and apoptosis induced by vascular endothelial growth factor-C (VEGF-C) in cervical cancer cells. HeLa cells (1×10(6)/ml) in the logarithmic growth phase were incubated without serum for 24 h. The cells were pretreated with kinase insert domain receptor antibody (KDR)-Ab (20 ?g/ml), phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (3 ?mol/l), mitogen-activated protein kinase (MAPK) inhibitor PD98059 (30 ?mol/l) or Hsp90-specific inhibitor GA (10 ?mol/l) for 30 min, and then treated with VEGF-C (50 ng/?l) for a further 24 h. The cells were harvested for MTT analysis, annexin V-FITC/propidium iodide double staining for early apoptosis and SDS-PAGE and western blot analysis in order to determine Hsp90, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cyclin D1 expression. Treatment with VEGF-C alone induced Hsp90 protein expression in HeLa cells at all time-points. Hsp90 expression was increased 3.31-fold in VEGF-C treated HeLa cells, and this increase was attenuated in the treatment groups (2.17-, 1.69-, 1.82-fold in VEGF-C + KDR-Ab, VEGF-C + PD98059 and VEGF-C + LY294002, respectively). The proliferation of the VEGF-C-treated HeLa cells was increased ~2.13-fold, while that of the VEGF-C + GA-treated HeLa cells decreased 0.87-fold (P<0.05). Even low concentrations of GA (0.02 ?mol/l) were found to inhibit the Bcl-2 and cyclin D1 protein expression induced by VEGF-C. Therefore, the results indicate that the Hsp90-specific inhibitor GA has a critical role in the proliferation and apoptosis induced by VEGF-C in cervical cancer cells. PMID:25289059

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

2014-11-01

299

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

PubMed

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

Breitenecker, G

2009-12-01

300

Human Papillomavirus Testing in the Prevention of Cervical Cancer  

PubMed Central

Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment. PMID:21282563

Wentzensen, Nicolas; Wacholder, Sholom; Kinney, Walter; Gage, Julia C.; Castle, Philip E.

2011-01-01

301

Rapid induction of senescence in human cervical carcinoma cells  

NASA Astrophysics Data System (ADS)

Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. This process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased telomerase activity. We propose that the human papillomavirus E6 and E7 proteins actively prevent senescence from occurring in cervical carcinoma cells, and that once viral oncogene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancer cells may represent an alternative approach to treat human cancers.

Goodwin, Edward C.; Yang, Eva; Lee, Chan-Jae; Lee, Han-Woong; Dimaio, Daniel; Hwang, Eun-Seong

2000-09-01

302

Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery  

SciTech Connect

Purpose: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. Methods and Materials: In a retrospective cohort study data of all cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 to IVA treated with (chemo) radiation between 1994 and 2001 were analyzed. Patients underwent gynecologic examination under anesthesia 8 to 10 weeks after completion of treatment. Cervical biopsy samples were taken from patients judged to be operable. In case of residual cancer, salvage surgery was performed. Results: Between 1994 and 2001, 169 consecutive cervical cancer patients received primary (chemo) radiation, of whom 4 were lost to follow-up. Median age was 56 years (interquartile range [IQR], 44-71) and median follow-up was 3.5 years (IQR, 1.5-5.9). In each of 111 patients a biopsy sample was taken, of which 90 (81%) showed no residual tumor. Vital tumor cells were found in 21 of 111 patients (19%). Salvage surgery was performed in 13 of 21 (62%) patients; of these patients, 5 (38%) achieved long-term, complete remission after salvage surgery (median follow-up, 5.2 years; range, 3.9-8.8 years). All patients with residual disease who did not undergo operation (8/21) died of progressive disease. Locoregional control was more often obtained in patients who underwent operation (7 of 13) than in patients who were not selected for salvage surgery (0 of 8 patients) (p < 0.05). Conclusions: Gynecologic examination under anesthesia 8 to 10 weeks after (chemo) radiation with cervical biopsies allows identification of those cervical cancer patients who have residual local disease, of whom a small but significant proportion may be salvaged by surgery.

Nijhuis, Esther R. [Department of Gynecologic Oncology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Zee, Ate G.J. van der [Department of Gynecologic Oncology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Hout, Bertha A. in 't [Department of Gynecologic Oncology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Boomgaard, Jantine J. [Department of Gynecologic Oncology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Hullu, Joanne A. de [Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Pras, Elisabeth [Department of Radiation Oncology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Hollema, Harry [Department of Pathology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Aalders, Jan G. [Department of Gynecologic Oncology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Nijman, Hans W. [Department of Gynecologic Oncology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Willemse, Pax H.B. [Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Mourits, Marian J.E. [Department of Gynecologic Oncology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands)]. E-mail: m.j.e.mourits@og.umcg.nl

2006-11-01

303

Image-based brachytherapy for cervical cancer.  

PubMed

Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes. Advantages of image-based brachytherapy include: improved tumor coverage (especially for large volume disease), decreased dose to critical organs (especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging (MRI), computed tomography (CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. For practical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE (an international study of MRI-guided brachytherapy in locally advanced cervical cancer) trial, along with continued improvements in imaging, contouring, quality assurance, physics, and brachytherapy delivery promise to perpetuate the advancement of image-based brachytherapy to optimize outcomes for cervical cancer patients. PMID:25493230

Vargo, John A; Beriwal, Sushil

2014-12-10

304

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

PubMed Central

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

Chen, Junying; Ding, Nan; Ren, Fei

2015-01-01

305

Physico-chemical characteristics of ZnO nanoparticles-based discs and toxic effect on human cervical cancer HeLa cells  

NASA Astrophysics Data System (ADS)

In this study, we investigated physico-chemical properties of zinc oxide nanoparticles (ZnO NPs)-based discs and their toxicity on human cervical cancer HeLa cell lines. ZnO NPs (80 nm) were produced by the conventional ceramic processing method. FESEM analysis indicated dominant structure of nanorods with dimensions 100-500 nm in length, and 20-100 nm in diameter. The high content of ZnO nanorods in the discs probably played significant role in toxicity towards HeLa cells. Structural defects (oxygen vacancies and zinc/oxygen interstitials) were revealed by PL spectra peaks at 370-376 nm and 519-533 nm for the ZnO discs. The structural, optical and electrical properties of prepared sample have influenced the toxicological effects of ZnO discs towards HeLa cell lines via the generation of reactive oxygen species (ROS), internalization, membrane damage, and eventually cell death. The larger surface to volume area of the ZnO nanorods, combined with defects, stimulated enhanced toxicity via ROS generation hydrogen peroxide, hydroxyl radicals, and superoxide anion. The preliminary results confirmed the ZnO-disc toxicity on HeLa cells was significantly associated with the unique physicochemical properties of ZnO NPs and to our knowledge, this is the first cellular study for treatment of HeLa cells with ZnO discs made from 80 nm ZnO particles.

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

2014-10-01

306

Cervical cancer risk factors among HIV-infected Nigerian women  

PubMed Central

Background Cervical cancer is the third most common cancer among women worldwide, and in Nigeria it is the second most common female cancer. Cervical cancer is an AIDS-defining cancer; however, HIV only marginally increases the risk of cervical pre-cancer and cancer. In this study, we examine the risk factors for cervical pre-cancer and cancer among HIV-positive women screened for cervical cancer at two medical institutions in Abuja, Nigeria. Methods A total of 2,501 HIV-positive women participating in the cervical cancer screen-and-treat program in Abuja, Nigeria consented to this study and provided socio-demographic and clinical information. Log-binomial models were used to calculate relative risk (RR) and 95% confidence intervals (95%CI) for the risk factors of cervical pre-cancer and cancer. Results There was a 6% prevalence of cervical pre-cancer and cancer in the study population of HIV-positive women. The risk of screening positivity or invasive cancer diagnosis reduced with increasing age, with women aged 40 years and older having the lowest risk (RR=0.4; 95%CI=0.2–0.7). Women with a CD4 count of 650 per mm3 or more also had lower risk of screening positivity or invasive cancer diagnosis (RR=0.3, 95%CI=0.2–0.6). Other factors such as having had 5 or more abortions (RR=1.8, 95%CI=1.0–3.6) and the presence of other vaginal wall abnormalities (RR=1.9, 95%CI=1.3–2.8) were associated with screening positivity or invasive cancer diagnosis. Conclusion The prevalence of screening positive lesions or cervical cancer was lower than most previous reports from Africa. HIV-positive Nigerian women were at a marginally increased risk of cervical pre-cancer and cancer. These findings highlight the need for more epidemiological studies of cervical cancer and pre-cancerous lesions among HIV-positive women in Africa and an improved understanding of incidence and risk factors. PMID:23767681

2013-01-01

307

Thymoquinone-Loaded Nanostructured Lipid Carrier Exhibited Cytotoxicity towards Breast Cancer Cell Lines (MDA-MB-231 and MCF-7) and Cervical Cancer Cell Lines (HeLa and SiHa).  

PubMed

Thymoquinone (TQ) has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa). TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235?nm with a narrow polydispersity index (PDI) lower than 0.25. The zeta potential of TQ-NLC was greater than -30?mV. Polysorbate 80 helps to increase the stability of TQ-NLC. Differential scanning calorimetry showed that TQ-NLC has a melting point of 56.73°C, which is lower than that of the bulk material. The encapsulation efficiency of TQ in TQ-NLC was 97.63 ± 0.1798% as determined by HPLC analysis. TQ-NLC exhibited antiproliferative activity towards all the cell lines in a dose-dependent manner which was most cytotoxic towards MDA-MB-231 cells. Cell shrinkage was noted following treatment of MDA-MB-231 cells with TQ-NLC with an increase of apoptotic cell population (P < 0.05). TQ-NLC also induced cell cycle arrest. TQ-NLC was most cytotoxic towards MDA-MB-231 cells. It induced apoptosis and cell cycle arrest in the cells. PMID:25632388

Ng, Wei Keat; Saiful Yazan, Latifah; Yap, Li Hua; Wan Nor Hafiza, Wan Abd Ghani; How, Chee Wun; Abdullah, Rasedee

2015-01-01

308

Thymoquinone-Loaded Nanostructured Lipid Carrier Exhibited Cytotoxicity towards Breast Cancer Cell Lines (MDA-MB-231 and MCF-7) and Cervical Cancer Cell Lines (HeLa and SiHa)  

PubMed Central

Thymoquinone (TQ) has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa). TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235?nm with a narrow polydispersity index (PDI) lower than 0.25. The zeta potential of TQ-NLC was greater than ?30?mV. Polysorbate 80 helps to increase the stability of TQ-NLC. Differential scanning calorimetry showed that TQ-NLC has a melting point of 56.73°C, which is lower than that of the bulk material. The encapsulation efficiency of TQ in TQ-NLC was 97.63 ± 0.1798% as determined by HPLC analysis. TQ-NLC exhibited antiproliferative activity towards all the cell lines in a dose-dependent manner which was most cytotoxic towards MDA-MB-231 cells. Cell shrinkage was noted following treatment of MDA-MB-231 cells with TQ-NLC with an increase of apoptotic cell population (P < 0.05). TQ-NLC also induced cell cycle arrest. TQ-NLC was most cytotoxic towards MDA-MB-231 cells. It induced apoptosis and cell cycle arrest in the cells. PMID:25632388

Ng, Wei Keat; Saiful Yazan, Latifah; Yap, Li Hua; Wan Nor Hafiza, Wan Abd Ghani; How, Chee Wun; Abdullah, Rasedee

2015-01-01

309

Peroxisome Proliferator-Activated Receptor-Gamma Agonist 4-O-Methylhonokiol Induces Apoptosis by Triggering the Intrinsic Apoptosis Pathway and Inhibiting the PI3K/Akt Survival Pathway in SiHa Human Cervical Cancer Cells.  

PubMed

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

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

2015-03-28

310

[Uterine cervical cancer screening in kitakyushu city: present and future].  

PubMed

Uterine cervical cancer is the most common primary gynecologic malignant tumor in Japan. Conventional cervical screening Papanicolaou (Pap) test has been shown to be extremely effective in reducing cervical cancer incidence and mortality, but the consultation rate for cancer screening in Japan is markedly low, at 20% of prescribed subjects, in comparison with other developed countries. In 2001, 15,501 women (6.8%) received a Pap test in Kitakyushu City, and that was less than half of national average. From 2009, free coupons for uterine cervical cancer screening were distributed to Japanese woman who were 20, 25, 30, 35 or 40 years of age as part of the project for women-specific cancer screening. The rate of participation in Pap testing was 22.3% in 2012, with 31,970 women receiving cervical tests. It was almost as high as the national level. It's obvious that high risk human papillomavirus (HPV) is responsible for cervical cancer incidence and HPV mainly infects through sexual practice. The rate of early cervical neoplasms and invasive cancers is currently increasing in young women. Abnormal Pap tests were detected in 2.3% of the women in 2008. To increase the population's participation in this screening process, a cost-effective and efficient system should be established. National and local governments, medical institutions, companies, and educational institutions must have an accurate understanding of the current situation, and take an assertive approach in order to decrease the mortality rate of uterine cervical cancer. PMID:25224713

Matsuura, Yusuke; Oka, Haruko; Yamagata, Kazuhiro; Kikuchi, Joji; Inoue, Isao; Ohkubo, Nobuyuki; Toki, Naoyuki; Kawagoe, Toshinori; Hachisuga, Toru; Kashimura, Masamichi

2014-09-01

311

The causal relation between human papillomavirus and cervical cancer  

PubMed Central

The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented. PMID:11919208

Bosch, F X; Lorincz, A; Muñoz, N; Meijer, C J L M; Shah, K V

2002-01-01

312

Social Construction of Cervical Cancer Screening among Panamanian Women  

ERIC Educational Resources Information Center

Background: Understanding how "health issues" are socially constructed may be useful for creating culturally relevant programs for Hispanic/Latino populations. Purpose: We explored the constructed meanings of cervical cancer and cervical cancer screening among Panamanian women, as well as socio-cultural factors that deter or encourage screening…

Calvo, Arlene; Brown, Kelli McCormack; McDermott, Robert J.; Bryant, Carol A.; Coreil, Jeanine; Loseke, Donileen

2012-01-01

313

WHERE WE HAVE TRAVELLED IN CERVICAL CANCER PROTECTION  

Microsoft Academic Search

Cervical cancer was described in the time of Hippocrates, and it was commented that it had a grim prognosis. Over the centuries, various theories regarding aetiology and also treatments were proposed - in vain in the majority of cases. More and more aggressive treatments were advocated to treat those unfortunate women who were diagnosed with cervical cancer. It is only

Margaret Davy

314

A review of californium-252 neutron brachytherapy for cervical cancer  

Microsoft Academic Search

Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron-emitting radioactive isotope, californium-252 (Cf-252), for the treatment of cervical cancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced cervical cancer patients using different doses and

Yosh Maruyama; John R. van Nagell; Justine Yoneda; Elvis S. Donaldson; Holly H. Gallion; Deborah Powell; Richard J. Kryscio

1991-01-01

315

Sentinel node procedure in Ib cervical cancer: a preliminary series  

Microsoft Academic Search

The aim of this study was to determine the diagnostic accuracy and feasibility of sentinel lymph node (SLN) detection using a gamma probe in patients with Figo IB cervical cancer. Between January 1999 and September 2000, 14 patients with cervical cancer, planned for radical hysterectomy were eligible for the study. The day before radical hysterectomy we injected technetium99m-labelled nanocolloid in

T Lantzsch; M Wolters; J Grimm; T Mende; J Buchmann; G Sliutz; H Koelbl

2001-01-01

316

Cervical Cancer Among Hispanic Women: Assessing the Impact on Farmworkers  

Microsoft Academic Search

The purpose of this paper was to review the literature on Hispanic populations to outline: 1) demographics; 2) general health status; 3) cervical cancer incidence and mortality; 4) Pap smear screening rates; and 5) barriers to preventive care services. The methods: MEDLINE, Med66, Med75, and Med85 files, from 1966 to 1999, were searched for key words Hispanic health, cervical cancer

Faith Boucher; Marc B. Schenker

2002-01-01

317

Synaptonemal Complex Protein 3 Is a Prognostic Marker in Cervical Cancer  

PubMed Central

Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancer cells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P?=?0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n?=?68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n?=?108) as determined by multivariate analysis (P?=?0.020). Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervical cancer therapy. PMID:24905095

Chung, Joon-Yong; Takikita, Mikiko; Chung, Eun Joo; Kim, Bo Wook; Hewitt, Stephen M.; Kim, Tae Woo; Kim, Jae-Hoon

2014-01-01

318

Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer  

PubMed Central

Cervical cancer is the third most common cancer and the third leading cause of death among women. However, the standard treatment for cervical cancer includes cisplatin, which can cause side effects such as hematological damage or renal toxicity. New innovations in cervical cancer treatment focus on developing more effective and better-tolerated therapies such as Sp1-targeting drugs. Previous studies suggested that mithramycin A (Mith) inhibits the growth of various cancers by decreasing Sp1 protein. However, how Sp1 protein is decreased by Mith is not clear. Few studies have investigated the regulation of Sp1 protein by proteasome-dependent degradation as a possible control mechanism for the regulation of Sp1 in cancer cells. Here, we show that Mith decreased Sp1 protein by inducing proteasome-dependent degradation, thereby suppressing cervical cancer growth through a DR5/caspase-8/Bid signaling pathway. We found that prolonged Mith treatment was well tolerated after systemic administration to mice carrying cervical cancer cells. Reduction of body weight was minimal, indicating that Mith was a good therapeutic candidate for treatment of cancers in which Sp1 is involved in promoting and developing disease. PMID:25418289

Choi, Eun-Sun; Nam, Jeong-Seok; Jung, Ji-Youn; Cho, Nam-Pyo; Cho, Sung-Dae

2014-01-01

319

Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer.  

PubMed

Cervical cancer is the third most common cancer and the third leading cause of death among women. However, the standard treatment for cervical cancer includes cisplatin, which can cause side effects such as hematological damage or renal toxicity. New innovations in cervical cancer treatment focus on developing more effective and better-tolerated therapies such as Sp1-targeting drugs. Previous studies suggested that mithramycin A (Mith) inhibits the growth of various cancers by decreasing Sp1 protein. However, how Sp1 protein is decreased by Mith is not clear. Few studies have investigated the regulation of Sp1 protein by proteasome-dependent degradation as a possible control mechanism for the regulation of Sp1 in cancer cells. Here, we show that Mith decreased Sp1 protein by inducing proteasome-dependent degradation, thereby suppressing cervical cancer growth through a DR5/caspase-8/Bid signaling pathway. We found that prolonged Mith treatment was well tolerated after systemic administration to mice carrying cervical cancer cells. Reduction of body weight was minimal, indicating that Mith was a good therapeutic candidate for treatment of cancers in which Sp1 is involved in promoting and developing disease. PMID:25418289

Choi, Eun-Sun; Nam, Jeong-Seok; Jung, Ji-Youn; Cho, Nam-Pyo; Cho, Sung-Dae

2014-01-01

320

Natural killer and dendritic cells collaborate in the immune response induced by the vaccine against uterine cervical cancer.  

PubMed

Virus-like particles (VLPs) of human papillomavirus (HPV) are used as a vaccine against HPV-induced cancer, and recently we have shown that these VLPs are able to activate natural killer (NK) cells. Since NK cells collaborate with dendritic cells (DCs) to induce an immune response against viral infections and tumors, we studied the impact of this crosstalk in the context of HPV vaccination. NK cells in the presence of HPV-VLPs enhanced DC-maturation as shown by an upregulation of CD86 and HLA-DR and an increased production of IL-12p70, but not of the immunosuppressive cytokine IL-10. This activation was bidirectional. Indeed, in the presence of HPV-VLPs, DCs further activated NK cells by inducing the upregulation of cell surface activation markers (CD69 and HLA-DR). The function of NK cells was also improved as shown by an increase in IFN-? secretion and cytotoxic activity against an HPV(+) cell line. This crosstalk between NK cells and DCs needed CD40 interaction and IL-12p70 secretion, whereas NKG2D was not implicated. Our results provide insight into how VLPs interact with innate immune cells and how NK cells and DCs play a role in the immune response induced by this vaccine agent. PMID:25229656

Langers, Inge; Renoux, Virginie; Reschner, Anca; Touzé, Antoine; Coursaget, Pierre; Boniver, Jacques; Koch, Joachim; Delvenne, Philippe; Jacobs, Nathalie

2014-12-01

321

Proteomic analysis of lanthanum citrate-induced apoptosis in human cervical carcinoma SiHa cells  

Microsoft Academic Search

Lanthanides possess diverse biological effect and have been shown to promote cell proliferation and induce apoptosis. Our\\u000a previous studies showing that lanthanide citrate complex has significant antitumor activity in human cervical cancer HeLa\\u000a cells. This study aims at determining if [LaCit2]3? have the activity against another type of human cervical cancer cell line SiHa and the changes in protein expression

Liming ShenZiyao LanXiaohong Sun; Ziyao Lan; Xiaohong Sun; Lei Shi; Qiong Liu; Jiazuan Ni

2010-01-01

322

Downregulation of glutathione peroxidase 3 is associated with lymph node metastasis and prognosis in cervical cancer.  

PubMed

Glutathione peroxidase 3 (GPX3) is a member of the glutathione peroxidase family of selenoproteins and is one of the key defensive enzymes against oxidative damages to host cells. Downregulation of GPX3 due to its promoter hypermethylation has been documented in several different types of cancer, indicating that GPX3 functions as a possible tumor suppressor. In the present study, we showed that GPX3 is also significantly downregulated in cervical cancer tissues compared to normal cervical tissues by qRT-PCR analyses and immunohistostainings. GPX3 expression was significantly related to lymph node metastasis and prognosis in cervical cancer patients. Treatment of cervical cancer cells with 5-aza-2'-deoxycytidine restored the expression of GPX3 and methylation-specific PCR (MSP) confirmed the CpG methylation of the GPX3 gene. Our results indicate that promoter methylation is one of the major causes of GPX3 downregulation in cervical cancer and GPX3 could serve as a predictive biomarker for lymph node metastasis and prognosis of cervical cancer. PMID:24788695

Zhang, Xianglan; Zheng, Zhenlong; Yingji, Shen; Kim, Hyeyeon; Jin, Renshun; Renshu, Li; Lee, Doo Young; Roh, Mi Ryung; Yang, Sanghwa

2014-06-01

323

Identification of differentially-expressed genes by DNA methylation in cervical cancer  

PubMed Central

To identify novel cervical cancer-related genes that are regulated by DNA methylation, integrated analyses of genome-wide DNA methylation and RNA expression profiles were performed using the normal and tumor regions of tissues from four patients; two with cervical cancer and two with pre-invasive cancer. The present study identified 19 novel cervical cancer-related genes showing differential RNA expression by DNA methylation. A number of the identified genes were novel cervical cancer-related genes and their differential expression was confirmed in a publicly available database. Among the candidate genes, the epigenetic regulation and expression of three genes, CAMK2N1, ALDH1A3 and PPP1R3C, was validated in HeLa cells treated with a demethylating reagent using methylation-specific polymerase chain reaction (PCR) and quantitative PCR, respectively. From these results, the expression of the CAMK2N1, ALDH1A3 and PPP1R3C genes are were shown to be suppressed in cervical cancers by DNA methylation. These genes may be involved in the progression or initiation of cervical cancer. PMID:25789025

LEE, HEUN-SIK; YUN, JUN HO; JUNG, JUNGHEE; YANG, YOUNG; KIM, BONG-JO; LEE, SUNG-JONG; YOON, JOO HEE; MOON, YONG; KIM, JEONG-MIN; KWON, YONG-IL

2015-01-01

324

Unique microRNA expression profiles in cervical cancer.  

PubMed

Cervical cancer is the second leading cause of death among female patients with cancer in the world. Our aim was to analyze cervical cancer cases, in the Southwestern Transdanubian Region of Hungary, with regard to human papillomavirus (HPV) genotype and histological and clinical grading. After HPV testing and genotyping, the expressions of eight different pre-microRNAs (miR-21, miR-27a, miR-34a, miR-146a, miR-155, miR-196a, miR-203, miR-221) in formalin-fixed paraffin-embedded (FFPE) primary human cervical cancer samples were evaluated with the help of the LightCycler 480 PCR System (Roche). Statistically significant overexpression of miR-21 (p=0.004), miR-27a (p=0.018), miR-34a (p<0.001), miR-155 (p=0.021), miR-196a (p=0.032), miR-203 (p=0.037) and miR-221 (p=0.017) were observed in squamous cell carcinoma, regardless of HPV status and clinical grading. Significant overexpression of miR-21 (p=0.004), miR-27a (p=0.02), miR-34a (p<0.001), miR-196a (p=0.027) and miR-221 (p=0.031) was characteristic of HPV-positive squamous cell carcinomas in contrast to adenocarcinomas of the same HPV status. PMID:23749909

Gocze, Katalin; Gombos, Katalin; Juhasz, Krisztina; Kovacs, Krisztina; Kajtar, Bela; Benczik, Marta; Gocze, Peter; Patczai, Balazs; Arany, Istvan; Ember, Istvan

2013-06-01

325

The association of herpes simplex virus with cervical cancer a mathematical model, and exploration of an approach to retrieve viral genetic information from transformed cells  

Microsoft Academic Search

A review of the available evidence relating herpes simplex type 2 (HSV-2) to cervical cancer in humans showed reasonable circumstantial evidence to suspect the participation of HSV-2 in the pathogenesis of the tumors. The best evidence was provided by seroepidemiological data, however, variations were observed among the data obtained from different populations. A mathematical model based on causal considerations and

Jose Campione-Piccardo

1981-01-01

326

Concurrent chemoradiotherapy in cervical cancer (a new paradigm in cervical cancer treatment).  

PubMed

During the last century, the mainstay for the treatment of uterine cervix cancer has been via two main primary treatment modalities, these being radical surgery (radical hysterectomy and regional lymph nodes dissection) and radiotherapy. Generally, radical surgery is restricted to stages I and IIa of FIGO (the International Federation of Gynecology and Obstetrics) Classification, while radiotherapy may be applied to all stages of cervical cancer. In 1999 the National Cancer Institute Clinical Announcement established concurrent chemoradiotherapy as a new primary treatment modality, which is the focus of this review. PMID:12497658

Ryu, Hee-Sug

2002-12-01

327

Immunotherapy for Cervical Cancer: Research Status and Clinical Potential  

PubMed Central

The high-risk types of human papillomavirus (HPV) have been found to be associated with most cervical cancers and play an essential role in the pathogenesis of the disease. Despite recent advances in preventive HPV vaccine development, such preventive vaccines are unlikely to reduce the prevalence of HPV infections within the next few years, due to their cost and limited availability in developing countries. Furthermore, preventive HPV vaccines may not be capable of treating established HPV infections and HPV-associated lesions, which account for high morbidity and mortality worldwide. Thus, it is important to develop therapeutic HPV vaccines for the control of existing HPV infection and associated malignancies. Therapeutic vaccines are quite different from preventive vaccines in that they require the generation of cell-mediated immunity, particularly T cell-mediated immunity, instead of the generation of neutralizing antibodies. The HPV-encoded early proteins, E6 and E7 oncoproteins, form ideal targets for therapeutic HPV vaccines since they are consistently expressed in HPV-associated cervical cancer and its precursor lesions and thus play crucial roles in the generation and maintenance of HPV-associated disease. Our review will cover the various therapeutic HPV vaccines for cervical cancer, including live vector-based, peptide or protein-based, nucleic acid-based, and cell-based vaccines targeting the HPV E6 and/or E7 antigens. Furthermore, we will review the studies using therapeutic HPV vaccines in combination with other therapeutic modalities and review the latest clinical trials on therapeutic HPV vaccines. PMID:20199126

Su, Jun-Han; Wu, Anjui; Scotney, Elizabeth; Ma, Barbara; Monie, Archana; Hung, Chien-Fu; Wu, T.-C.

2010-01-01

328

Is 58% sensitivity for detection of cervical intraepithelial neoplasia 3 and invasive cervical cancer optimal for cervical screening?  

PubMed Central

Recent Food and Drug Administration (FDA) approval of a Roche cobas human papillomavirus (HPV) test application as a first line primary cervical screening tool in women 25 and older introduces a new era of complex cervical screening choices. Perhaps the most surprising findings in Roche's supporting ATHENA trial data were the unexpectedly low verification bias-adjusted CIN3+ sensitivities documented by the FDA for both the proposed cobas HPV testing algorithm (58.26%) and Pap testing algorithm (42.63%). These unexpectedly low sensitivity estimates suggest intuitively that there is still considerable room for improvement in cervical screening, and available data from large systems point to routine cytology and HPV co-testing as offering the greatest protection against development of cervical cancer. Observational studies of large populations screened over time remain essential to document actual protection from development of cervical cancer with any new cervical screening options, as natural history studies and available data from large systems indicate that most CIN2/3 cases detected in short term clinical trials would not progress to invasive cervical cancer. Interpretation of ATHENA trial data and its application to routine clinical practice is further limited by published studies which document that a significant proportion of CIN2/3 biopsy diagnoses in the ATHENA trial could not be confirmed as accurate when evaluated with p16 immunohistochemistry and that cytology laboratory performance in the trial was notably suboptimal. PMID:24987445

Austin, R. Marshall; Zhao, Chengquan

2014-01-01

329

Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16INK4A re-expression related to UHRF1 and DNMT1 down-regulation  

PubMed Central

Several reports have described the potential effects of natural compounds as anti-cancer agents in vitro as well as in vivo. The aim of this study was to evaluate the anti-cancer effect of Limoniastrum guyonianum aqueous gall extract (G extract) and luteolin in the human cervical cancer HeLa cell line, and, if so, to clarify the underlying mechanism. Our results show that G extract and luteolin inhibited cell proliferation and induced G2/M cell cycle arrest in a concentration and time-dependent manner. Both natural products induced programmed cell death as confirmed by the presence of hypodiploid G0/G1 cells. These effects are associated with an up-regulation of the expression of the tumor suppressor gene p16INK4A and a down-regulation of the expression of the anti-apoptotic actor UHRF1 and its main partner DNMT1. Moreover, G extract- and luteolin-induced UHRF1 and DNMT1 down-regulation is accompanied with a global DNA hypomethylation in HeLa cell line. Altogether our results show that G extract mediates its growth inhibitory effects on human cervical cancer HeLa cell line likely via the activation of a p16INK4A -dependent cell cycle checkpoint signalling pathway orchestrated by UHRF1 and DNMT1 down-regulation. PMID:23688286

2013-01-01

330

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

ClinicalTrials.gov

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

2014-12-23

331

Evaluation of one- and two-photon activated photodynamic therapy with pyropheophorbide-a methyl ester in human cervical, lung and ovarian cancer cells.  

PubMed

Two-photon activated photodynamic therapy (2-? PDT) has the potential of treating deeper tumors and/or improving tumor targeting. Here, we evaluated the one- and two-photon activated PDT efficacy of pyropheophorbide-a methyl ester (MPPa), a second-generation photosensitizer derived from chlorophyll a. We show that MPPa, when activated by femtosecond (fs) laser pulses at 674 nm, has high one-photon (1-?) PDT efficacy against cisplatin-sensitive human cervical (HeLa) and cisplatin-resistant human lung (A549) and ovarian (NIH:OVCAR-3) cancer cells. At a low light dose of 0.06 J cm(-2), the IC50 (the MPPa concentration required to kill 50% of the cells) was determined to be 5.3 ± 0.3, 3.4 ± 0.3 and 3.6 ± 0.4 ?M for HeLa, A549 and NIH:OVCAR-3 cells, respectively. More significantly, we also show that MPPa can be effectively activated by an 800 nm, 120 fs laser through 2-? excitation; at a light dose causing no measurable photocytotoxicity in the absence of photosensitizer, the corresponding IC50 values were measured to be 4.1 ± 0.3, 9.6 ± 1.0 and 1.6 ± 0.3 ?M, respectively. These results indicate that MPPa is a potent photosensitizer for both 1- and 2-? activated PDT with potential applications for difficult-to-treat tumors by conventional therapies. PMID:24607610

Luo, Ting; Wilson, Brian C; Lu, Qing-Bin

2014-03-01

332

Aqueous Cinnamon Extract (ACE-c) from the bark of Cinnamomum cassia causes apoptosis in human cervical cancer cell line (SiHa) through loss of mitochondrial membrane potential  

PubMed Central

Background Chemoprevention, which includes the use of synthetic or natural agents (alone or in combination) to block the development of cancer in human beings, is an extremely promising strategy for cancer prevention. Cinnamon is one of the most widely used herbal medicines with diverse biological activities including anti-tumor activity. In the present study, we have reported the anti-neoplastic activity of cinnamon in cervical cancer cell line, SiHa. Methods The aqueous cinnamon extract (ACE-c) was analyzed for its cinnamaldehyde content by HPTLC analysis. The polyphenol content of ACE-c was measured by Folin-Ciocalteau method. Cytotoxicity analysis was performed by MTT assay. We studied the effect of cinnamon on growth kinetics by performing growth curve, colony formation and soft agar assays. The cells treated with ACE-c were analyzed for wound healing assay as well as for matrix metalloproteinase-2 (MMP-2) expression at mRNA and protein level by RT-PCR and zymography, respectively. Her-2 protein expression was analyzed in the control and ACE-c treated samples by immunoblotting as well as confocal microscopy. Apoptosis studies and calcium signaling assays were analyzed by FACS. Loss of mitochondrial membrane potential (??m) in cinnamon treated cells was studied by JC-1 staining and analyzed by confocal microscopy as well as FACS. Results Cinnamon alters the growth kinetics of SiHa cells in a dose-dependent manner. Cells treated with ACE-c exhibited reduced number of colonies compared to the control cells. The treated cells exhibited reduced migration potential that could be explained due to downregulation of MMP-2 expression. Interestingly, the expression of Her-2 oncoprotein was significantly reduced in the presence of ACE-c. Cinnamon extract induced apoptosis in the cervical cancer cells through increase in intracellular calcium signaling as well as loss of mitochondrial membrane potential. Conclusion Cinnamon could be used as a potent chemopreventive drug in cervical cancer. PMID:20482751

2010-01-01

333

Combination chemotherapy with cisplatin and bleomycin in advanced cervical cancer.  

PubMed

Seventeen patients with advanced and recurrent squamous cell cervical cancer were treated with a combination of cisplatin and bleomycin. One complete and nine partial responses were observed (53%). The median duration of response was 8 months and the median survival was 12.7 months (5 months for nonresponders). Response was documented, particularly in patients with nodal disease and lung metastases. No life-threatening toxic effects were reported. This combination appears to be as effective as other combinations, has low toxicity, is well-tolerated, and merits further study. PMID:6203640

Bloch, B; Nel, C P; Kriel, A; Atad, J; Goldberg, G

1984-06-01

334

Update on prevention and screening of cervical cancer  

PubMed Central

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

McGraw, Shaniqua L; Ferrante, Jeanne M

2014-01-01

335

Different cervical cancer screening approaches in a Chinese multicentre study  

PubMed Central

To evaluate alternative cervical cancer screening methods, digital colposcopy and collection of cervical exfoliated cells for liquid-based cytology (LBC) and hybrid capture 2 (HC2) testing were performed among 2562 women aged 15–59 years in three study sites in the People's Republic of China (rural Shanxi province, Shenyang city in Liaoning province and Shenzhen city in Guangdong province). Visual inspection with acetic acid (VIA) was also evaluated independently from colposcopy. A total of 74 cases of histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were identified, and 16 CIN2+ cases were imputed among unbiopsied women to correct for verification bias. Corrected sensitivity for CIN2+ was 37% for VIA, 54% for colposcopy, 87% for LBC with a threshold of atypical cells of undetermined significance (LBC?ASCUS), 90% for HC2, 84% for LBC using HC2 to triage ASCUS and 96% for positivity to LBC?ASCUS or HC2. For VIA, sensitivity was much lower among women ?40 years (12%) than those aged ?39 years (50%). Specificity varied from 77% for positivity to LBC?ASCUS or HC2, up to 94% for LBC using HC2 to triage ASCUS. In conclusion, LBC, HC2 and their combinations performed well, whereas VIA missed a majority of CIN2+, particularly in older women. Digital colposcopy performed better than VIA, but still missed nearly half of CIN2+ in this study. PMID:19127262

Li, N; Shi, J-F; Franceschi, S; Zhang, W-H; Dai, M; Liu, B; Zhang, Y-Z; Li, L-K; Wu, R-F; De Vuyst, H; Plummer, M; Qiao, Y-L; Clifford, G

2009-01-01

336

Application of the Carolina Framework for Cervical Cancer Prevention  

PubMed Central

Objective The Carolina Framework for Cervical Cancer Prevention describes 4 main causes of cervical cancer incidence: human papillomavirus (HPV) infection, lack of screening, screening errors, and not receiving follow-up care. We present 2 applications of the Carolina Framework in which we identify high-need counties in North Carolina and generate recommendations for improving prevention efforts. Methods We created a cervical cancer prevention need index (CCPNI) that ranked counties on cervical cancer mortality, HPV vaccine initiation and completion, Pap smear screening, and provision of Pap tests to rarely- or never-screened women. In addition, we conducted in-depth interviews with 19 key informants from programs and agencies involved in cervical cancer prevention in North Carolina. Results North Carolina’s 100 counties varied widely on individual CCPNI components, including annual cervical cancer mortality (median 2.7/100,000 women; range 0.0–8.0), adolescent girls’ HPV vaccine initiation (median 42%; range 15%–62%), and Pap testing in the previous 3 years among Medicaid-insured adult women (median 59%; range 40%–83%). Counties with the greatest prevention needs formed 2 distinct clusters in the northeast and south-central regions of the state. Interviews generated 9 recommendations to improve cervical cancer prevention in North Carolina, identifying applications to specific programs and policies in the state. Conclusions This study found striking geographic disparities in cervical cancer prevention need in North Carolina. Future prevention efforts in the state should prioritize high-need regions as well as recommended strategies and applications in existing programs. Other states can use the Carolina Framework to increase the impact of their cervical cancer prevention efforts. PMID:24333357

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

2014-01-01

337

Cervical Adenocarcinoma  

MedlinePLUS

... The most common subtype of cervical cancer, called squamous cell carcinoma, arises from the surface lining of the ectocervix, ... successful at decreasing the number of patients with squamous cell carcinoma of the cervix, it has not yet been ...

338

Cervical Cancer: Development of Targeted Therapies Beyond Molecular Pathogenesis  

PubMed Central

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

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

2014-01-01

339

Functional variants in TNFAIP8 associated with cervical cancer susceptibility and clinical outcomes.  

PubMed

Tumor necrosis factor-?-induced protein 8 (TNFAIP8) is an anti apoptotic and pro-oncogenic signaling molecule involved in the process of immunity, carcinogenesis and tumor progression. Single nucleotide polymorphisms (SNPs) at microRNA-binding sites may change messenger RNA target gene function, thus leading to cancer susceptibility and tumor progression. In this study of 1584 cervical cancer cases and 1394 cancer-free female controls, we investigated associations between three potentially functional SNPs in TNFAIP8 family genes and cervical cancer risk as well as platinum resistance and clinical outcomes in Eastern Chinese women. We found that the TNFAIP8-rs11064 variant GG genotype was associated with an increased risk of cervical cancer compared with AA/AG genotypes (adjusted odds ratio = 2.16, 95% confidence interval = 1.16-4.03, P = 0.015). Further in vitro and ex vivo functional experiments demonstrated that the TNFAIP8-rs11064 variant G allele weakened the binding affinity of miR-22 to the TNFAIP8 3'-untranslated region (UTR) in four cancer cell lines, resulting in increased production of the TNFAIP8 protein in the patients' cervical tissues. In the survival subset, the high TNFAIP8 protein expression was significantly associated with both resistance to cisplatin and nedaplatin, recurrence and death from cervical cancer. Taken together, in the absence of information on human papillomavirus (HPV) infection, the TNFAIP8-rs11064 SNP may function by affecting the affinity of miR-22 binding to the 3'-UTR of TNFAIP8 and regulating TNFAIP8 expression, thus contributing to cervical cancer risk. Additionally, the increased TNFAIP8 protein expression may predict platinum resistance and clinical outcomes in cervical cancer patients. Larger, prospective studies with detailed HPV infection data are warranted to validate our findings. PMID:23299407

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

2013-04-01

340

Image-Guided Radiotherapy and -Brachytherapy for Cervical Cancer  

PubMed Central

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

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

2015-01-01

341

Breast and Cervical Cancer Prevention and Treatment Act of 2000  

MedlinePLUS

... or cervical cancer through a federal screening program. Contacts for More Information NBCCEDP contacts can answer questions ... Listen to audio/podcast Follow us on Twitter Contact Us: Centers for Disease Control and Prevention Division ...

342

ICSN Biennial Meeting - Copenhagen 2008 - Abstracts - Cervical Cancer Screening  

Cancer.gov

ICSN Biennial Meeting 2008 Helsingør, Denmark Attendance Rate (2003-2005) of the Hungarian Organized, Nation-Wide Cervical Cancer Screening Program Authors: I Boncz, A Sebestyén Affiliation: Department of Health Economics, Policy & Management, University

343

Gene Dosage Analysis Yields Insights into Cervical Cancer Origins and Resistance to Therapy | Physical Sciences in Oncology  

Cancer.gov

A hallmark of cervical cancer is the pronounced genetic heterogeneity found within the cells that make up a tumor, particularly in terms of gaining multiple copies of certain genes and losing copies of others.

344

Cancer Control P.L.A.N.E.T. - Cervical Cancer Screening  

Cancer.gov

Skip to content Links to comprehensive cancer control resources for public health professionals Home | About This Site | FAQ | Sponsors Cervical Cancer Learn why these resources are important Data State Cancer Profiles (CDC, NCI) - Statistics for prioritizing

345

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

Cancer.gov

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

346

Recent advances in optical imaging for cervical cancer detection  

Microsoft Academic Search

Cervical cancer is one of the most common and lethal gynecological malignancies in both developing and developed countries,\\u000a and therefore, there is a considerable interest in early diagnosis and treatment of precancerous lesions. Although the current\\u000a standard care mainly based on cytology and colposcopy has reduced rates of cervical cancer morbidity and mortality, many lesions\\u000a are still missed or overcalled

Irene M. Orfanoudaki; Dimitra Kappou; Stavros Sifakis

347

Cervical cancer worry and screening among appalachian women.  

PubMed

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

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

2015-04-01

348

Evaluation of 40 x 22 mm coverslip area in cervical cancer screening.  

PubMed

Nine hundred and twenty-three smears covered by 40 x 22 mm size coverslips were examined inside and outside the coverslip area to determine whether this coverslip size could be responsible for missed dyskaryotic cells in conventional cervical cancer screening. There was no instance when abnormal cells seen outside the coverslip were not also present within the coverslipped area. PMID:9523128

Oommen, R; Curling, M; Adams, C; Barrett, E; Titmuss, E; Widdowson, A

1998-02-01

349

Thymosin Beta-4, Actin-Sequestering Protein Regulates Vascular Endothelial Growth Factor Expression via Hypoxia-Inducible Nitric Oxide Production in HeLa Cervical Cancer Cells  

PubMed Central

Vascular endothelial growth factor (VEGF) is an important regulator of neovascularization. Hypoxia inducible nitric oxide (NO) enhanced the expression of VEGF and thymosin beta-4 (T?4), actin sequestering protein. Here, we investigated whether NO-mediated VEGF expression could be regulated by T?4 expression in HeLa cervical cancer cells. Hypoxia inducible NO production and VEGF expression were reduced by small interference (si) RNA of T?4. Hypoxia response element (HRE)-luciferase activity and VEGF expression were increased by the treatment with N-(?-D-Glucopyranosyl)-N2-acetyl-S-nitroso-D, L-penicillaminamide (SNAP-1), to generate NO, which was inhibited by the inhibition of T?4 expression with T?4-siRNA. In hypoxic condition, HRE-luciferase activity and VEGF expression were inhibited by the treatment with NG-monomethyl-L-arginine (L-NMMA), an inhibitor to nitric oxide synthase (NOS), which is accompanied with a decrease in T?4 expression. VEGF expression inhibited by L-NMMA treatment was restored by the transfection with pCMV-T?4 plasmids for T?4 overexpression. Taken together, these results suggest that T?4 could be a regulator for the expression of VEGF via the maintenance of NOS activity. PMID:25593639

Ryu, Yun-Kyoung; Lee, Jae-Wook; Moon, Eun-Yi

2015-01-01

350

Systemic Therapy for Cervical Cancer with Potentially Regulatable Oncolytic Adenoviruses  

E-print Network

,3,4 , Koichi Takayama5 , Ari Ristima¨ki6 , Renee A. Desmond7 , Akseli Hemminki1,3 * 1 Cancer Gene Therapy GroupSystemic Therapy for Cervical Cancer with Potentially Regulatable Oncolytic Adenoviruses Anna, Molecular Cancer Biology Program and Transplantation Laboratory and Finnish Institute for Molecular Medicine

Hemminki, Akseli

351

Knowledge, attitudes and practices regarding cervical cancer and screening among Haitian health care workers.  

PubMed

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

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

2014-11-01

352

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

PubMed Central

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

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

2014-01-01

353

Berberine modulates AP1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells  

Microsoft Academic Search

Background-  Specific types of high risk Human papillomaviruses (HR-HPVs) particularly, HPV types 16 and 18 cause cervical cancer and while\\u000a the two recently developed vaccines against these HPV types are prophylactic in nature, therapeutic options for treatment\\u000a and management of already existing HPV infection are not available as yet. Because transcription factor, Activator Protein-1\\u000a (AP-1) plays a central role in HPV-mediated

Sutapa Mahata; Alok C Bharti; Shirish Shukla; Abhishek Tyagi; Syed A Husain; Bhudev C Das

2011-01-01

354

Methylation Patterns of the IFN-? Gene in Cervical Cancer Tissues  

PubMed Central

Objective: To explore the relationship between methylation of interferon gamma (IFN-?) gene and tumorigenesis in cervical cancer tissues, the biopsy specimens of cervical cancer and cervical intraepithelial neoplasia (CIN) (I-III) patients as well as normal controls were collected and analyzed. Methods: The methylation of the IFN-? gene was verified by using methylation-specific PCR and DNA sequencing analysis, and the expression levels of IFN-? mRNA were detected using quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: The methylation rates of the IFN-? gene were significantly higher in cervical cancer tissues (15/43, 34.9%) than those in CIN (3/23, 13.0% of CIN I; 6/39, 15.4% of CIN II/III) and normal cervical tissues (2/43, 4.7%) (P < 0.01). Furthermore, the mRNA expression of IFN-? in cervical tumors with methylation (0.71 ± 0.13, n = 8) was lower than that in those without methylation (1.58 ± 0.32, n = 27) (P < 0.05). Likewise, the IFN-? expression levels in CIN II/III tissues with methylation (0.87 ± 0.16, n = 5) were significantly (P < 0.01) lower compared to those without methylation (2.12 ± 0.27, n = 32). Conclusion: The hypermethylation of IFN-? gene may be related with tumorigenesis of cervical cancer. PMID:25208560

Ma, Dong; Jiang, Chunyang; Hu, Xiaoli; Li, Qingzhao; Li, Tingting; Yang, Yanyan; Li, Ou

2014-01-01

355

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

PubMed

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

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

2015-07-01

356

Contributions in the domain of cancer research: Review Human papillomaviruses and their role in cervical cancer  

E-print Network

Contributions in the domain of cancer research: Review Human papillomaviruses and their role papillomaviruses (HPVs) have been linked to a variety of human diseases, most notably can- cer of the cervix of cervical cancer. Key words. Cervical cancer; papillomavirus; gene expression; viral oncogene; early protein

Gaston, Kevin

357

An automatic segmentation method for multispectral microscopic cervical cell images  

NASA Astrophysics Data System (ADS)

We have been developing a computer-aided diagnosis (CAD) system for automatically recognizing cervical cancer cells from Papanicolaou smear. Considering that pathological changes of cervix can be indicated by the abnormity of the nucleus of intermediate cell, the key task of this system is to find the intermediate cells and segment the nucleus precisely. This paper presents a novel approach for automatic segmentation of microscopic cervical cell images using multispectral imaging techniques. In order to capture images at different wavelengths, a Liquid Crystal Tunable Filter (LCTF) device is used to provide wavelength selection from 400nm to 720nm with an increment of 10nm. Considering the spectral variances of background, nucleus and cytoplasm, background is extracted firstly from the microscopic images by calculating pixel intensity variance at 470nm, 530nm, 570nm, 580nm and 650nm. Then superficial cells are extracted apart from intermediate cells easily at 530nm 650nm because of the different pixel intensity distribution of the two kinds of cells at these two wavelengths. To segment the nucleus from intermediate cells, we adopt two procedures. Firstly, the nuclei are roughly segmented apart by using an iterative maximum deviation between-cluster algorithm. Secondly, a novel rigorous algorithm based on active contour model is adopted to achieve more exact nuclei segmentation. Using the method proposed in this paper, we did experiments on over 300 cervical smears, and the results show that this method is more robust and precise.

Zhang, Hongbo; Zeng, Libo; Ke, Hengyu; Lei, Junfeng; Xu, Xianze; Zheng, Hong; Wu, Qiongshui; Wang, DianCheng; Zhang, Yunfei

2006-03-01

358

How does hypoxia inducible factor-1? participate in enhancing the glycolysis activity in cervical cancer?  

PubMed

The objective of this study is to explore the role of hypoxia inducible factor-1 (HIF-1) in glycolysis activity and its relationship with malignant biologic behaviors of cervical cancer. Immunohistochemistry was performed to study the protein expression and distribution of HIF-1? and glucose transport protein 1 (GLUT1) in cervical tissue of 158 cases, including 28 with normal cervical epithelium, 32 with cervical intraepithelial neoplasia, and 98 with invasive cervical cancer. Cobalt(II) chloride was used to induce hypoxia in Hela and Siha cells; the biologic behaviors of cells cultured in normal or hypoxic environments were monitored by colorimetric, Transwell, flow cytometry, and enzyme-linked immunosorbent assay; immunocytochemistry, Western blot, and reverse transcription-polymerase chain reaction were used to observe gene and protein expression of HIF-1?, GLUT1, and hexokinase II in cell lines during normoxia and hypoxia. The expression of HIF-1? and GLUT1 gradually increased from normal cervical tissue to cervical intraepithelial neoplasia, then to cervical cancer. There were significant differences among these groups (P < .05). HIF-1? was strongly associated with pathologic differentiation, clinic stage, magnitude of lesions, and patient age, whereas GLUT1 was associated with lymphatic metastasis (P < .05). HIF-1? was strongly associated with expression of GLUT1 (P < .05). In hypoxia, proliferation, invasion, resistance to apoptosis, and glycolysis of both Hela and Siha were enhanced compared with cells in normoxia (P < .05). Both gene and protein expressions of GLUT1 and hexokinase II were strengthened, whereas only the protein expression of HIF-1? was stronger in hypoxia than that in normoxia (P < .05). The results of Hela in normoxia and in hypoxia were similar to those of Siha (P > .05). HIF-1? plays a key role in cervical cancer both in vivo and in vitro. The role of HIF-1? can be implemented mainly by up-regulating its downstream gene, such as GLUT1, and the main mechanism may enhance glycolytic ability. Strong up-regulation and the role of HIF-1? suggest that HIF-1? could be an important factor in the onset and progression of cervical cancer and could be an attractive therapeutic molecular target for that type of cancer. PMID:23375385

Cheng, Yanxiang; Chen, Gantao; Hong, Li; Zhou, Limei; Hu, Min; Li, Bingshu; Huang, Jinling; Xia, Liangbin; Li, Cuilan

2013-06-01

359

[Electrosurgery of cervical changes and its place in cervical cancer prophylaxis].  

PubMed

For many years electrosurgical procedures have been used to treat cervical changes. The equipment and the technique of performing these procedures have evolved considerably during the recent years. The Fisher cone and electrocoagulation of the cervix have been replaced with the LLETZ/LEEP procedure. Low cost, the simplicity of performance, high safety and high therapeutic effectiveness in treating precancerous cervical changes make the LLETZ/LEEP procedure a very good method of accomplishing the cervical cancer preventive program. The indications, contra-indications, the technique of performance along with postoperative complications after the LLETZ/LEEP procedure and the physical basics of electrosurgical procedures were thoroughly presented in the article. PMID:20088401

Rokita, Wojciech; Stanis?awska, Marta; Spaczy?ski, Marek; Nowak-Markwitz, Ewa; Kedzia, Witold

2009-11-01

360

Human leukocyte antigen (HLA)-G and cervical cancer immunoediting: a candidate molecule for therapeutic intervention and prognostic biomarker?  

PubMed

While persistent infection with oncogenic types of human Papillomavirus (HPV) is required for cervical epithelial cell transformation and cervical carcinogenesis, HPV infection alone is not sufficient to induce tumorigenesis. Only a minor fraction of HPV infections produce high-grade lesions and cervical cancer, suggesting complex host-virus interactions. Based on its pronounced immunoinhibitory properties, human leukocyte antigen (HLA)-G has been proposed as a possible prognostic biomarker and therapeutic target relevant in a wide variety of cancers and viral infections, but to date remains underexplored in cervical cancer. Given the possible influence of HLA-G on the clinical course of HPV infection, cervical lesions and cancer progression, a better understanding of HLA-G involvement in cervical carcinogenesis might contribute to two aspects of fundamental importance: 1. Characterization of a novel diagnostic/prognostic biomarker to identify cervical cancer and to monitor disease stage, critical for patient screening; 2. Identification of HLA-G-driven immune mechanisms involved in lesion development and cancer progression, leading to the development of strategies for modulating HLA-G expression for treatment purposes. Thus, this systematic review explores the potential involvement of HLA-G protein expression and polymorphisms in cervical carcinogenesis. PMID:25453366

Gimenes, Fabrícia; Teixeira, Jorge Juarez Vieira; de Abreu, André Luelsdorf Pimenta; Souza, Raquel Pantarotto; Pereira, Monalisa Wolski; da Silva, Vânia Ramos Sela; Bôer, Cinthia Gandolfi; Maria-Engler, Silvya Stuchi; Bonini, Marcelo Gialluisi; Borelli, Sueli Donizete; Consolaro, Márcia Edilaine Lopes

2014-12-01

361

[Epidemiology and risk factors of the cervical squamous cell carcinoma].  

PubMed

Neoplasm of the cervix, especially squamous cell cancer, is one of the most common malignancy of female genital organs. It etiology is complex; however, human papilloma virus (mostly HPV type 18, 16 and 45) infection seems to be the most important one. Other risk factors include: early sexual initiation, multiple pregnancies and labors, concomitant infections (Chlamydia trachomatis, Neisseria gonorrhea, HSV2 - herpes simplex virus) of the genital tract, AIDS, immunosuppressive therapy, smoking and low socioeconomic status. The incidence of cervical cancer is particularly high in developing countries, while in countries where government founding for the prevention and health education is high, the diseases is significantly less likely to occur. The incidence and mortality rate of the cervical cancer can be substantially reduced by systematic screening cytological examinations. For such reason a liquid-based cytology is currently preferred. Implementation of HPV vaccines decrease the risk of infection, but effect on rate of the cervical cancer has to be confirmed in long-time prospective clinical and epidemiological studies. PMID:23009008

Mocarska, Agnieszka; Staros?awska, Elzbieta; Zelazowska-Cie?li?ska, Iwonna; ?osicki, Marek; Stasiewicz, Dominika; Kieszko, Dariusz; Burdan, Franciszek

2012-08-01

362

Health systems challenges in cervical cancer prevention program in Malawi  

PubMed Central

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

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

2015-01-01

363

Induction of human cervical squamous cell carcinoma by sequential transfection with human papillomavirus 16 DNA and viral Harvey ras.  

PubMed

Clinical and epidemiological data are consistent with the hypothesis that human papillomaviruses (HPVs) are a factor in genital, particularly cervical cancer. Although HPV16 and 18 are found primarily in cervical malignancy, the transfection of HPV16 or 18 DNA into cervical cells results in immortalization but not tumorigenicity. The addition of activated Ha-ras, an oncogene found in some cervical cancers expressing HPV16 or 18, to HPV16-immortalized human cervical cells results in malignancy as proven by the formation of cystic squamous cell carcinomas by HPV16-Ha-ras cells in nude mice. This two-stage model utilizing relevant human cells demonstrates that HPVs play a critical role in cervical malignancy and provides a system for elucidating critical cellular changes associated with progression to malignancy. PMID:2541388

DiPaolo, J A; Woodworth, C D; Popescu, N C; Notario, V; Doniger, J

1989-04-01

364

Msi1 promotes tumor growth and cell proliferation by targeting cell cycle checkpoint proteins p21, p27 and p53 in cervical carcinomas  

PubMed Central

Musashi RNA-binding protein1 (Msi1), a member of the RNA-binding protein family, has been reported to be a diagnostic marker and potential therapeutic target in some cancers, its function in cervical cancer remains unknown. In this study, we found Msi1 was highly expressed in cervical cancer tissues, and over-expressing Msi1 in cervical cancer cells enhanced tumor formation and cell proliferation and accelerated cells into the S phase. Whereas, down-regulating Msi1 by shRNA in cervical cancer cells inhibited tumor formation and cell proliferation and slowed cell into the S phase, suggesting that Msi1 might act as cell cycle regulator. Immunohistochemistry assay showed the negative correlation between Msi1 and p21, p27 and p53, suggesting that Msi1 might regulate these cycle regulators in cervical cancer. Moreover, the expression of the p21, p27 and p53 proteins were down-regulated in Msi1 overexpressing cervical cancer cells and up-regulated in shMsi1 cervical cancer cells. Luciferase assays and RNA-protein binding assays confirmed that Msi1 could bind to the mRNA 3?UTRs of p21, p27 and p53 and suppress the translation of these proteins. Our findings provide new evidence that Msi1 might promote cell proliferation by accelerating the cell cycle by directly targeting p21, p27 and p53. PMID:25362645

Liu, Xian; Yang, Wen-Ting; Zheng, Peng-Sheng

2014-01-01

365

[Vaccination against human papilloma virus and cervical cancer].  

PubMed

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

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

2011-01-01

366

Serum one-carbon metabolites and risk of cervical cancer.  

PubMed

Most cases of cervical cancer are associated with human papilloma virus (HPV) infection of high risk types. In folate deficiency, heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) interferes with HPV16 viral capsid protein synthesis. We aimed to study the importance of 1-carbon metabolism in cervical carcinogenesis by examining serum vitamin B12 (cobalamin), homocysteine, folate levels, and the RNA and protein expression of HPV16 L1, L2, E6, E7, and to correlate them with hnRNP-E1 expression and HPV infection in normals, squamous intraepithelial lesions (SILs), and cervical cancer subjects. Serum cobalamin, folate, and homocysteine were estimated using kits, RNA by real time PCR and proteins by Western blotting. We observed that lower folate and vitamin B12 levels were associated with HPV infection. hnRNP-E1 progressively decreased from normals (100%) to SILs (75%) to cervical cancer (52.6%). The findings show that HPV16 E6 and E7 are overexpresed whereas HPV16 L1 and L2 are downregulated at mRNA and protein levels in cervical cancer as compared to normals and SILs. The results indicate that perhaps the reduced expression of hnRNP-E1 might be involved with the cervical cancer pathogenesis, with folate playing a role in the natural history of HPV infection. PMID:24848140

Pathak, Sujata; Bajpai, Deepti; Banerjee, Ayan; Bhatla, Neerja; Jain, Sunesh Kumar; Jayaram, Hiremagular N; Singh, Neeta

2014-01-01

367

Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C(12)U] (Ampligen R).  

PubMed

Human papilloma virus (HPV) found in 99.7% of cervical cancers represents an attractive immunotherapeutic target for novel adjuvant dendritic cell (DC) immunotherapy. DC primed with HPV antigens have been shown to be capable of inducing CTL responses powerful enough to eradicate established murine tumours expressing HPV16 antigen. The use of tumour lysate has been found to be an effective means of priming DC with tumour associated antigens in animal models and in clinical trials leading to significant anti-tumour responses. Autologous DC primed with sonicated HPV expressing tumour lysate have been shown to be capable of inducing HPV specific classes I and II T-cell immunity in a pilot clinical study.Synthetic double stranded polyribonucleotides are effective in vitro activation/maturation agents capable of inducing a stable mature DC phenotype producing high levels of IL12. However, the prototype polymer poly [I]:poly [G] has proved to be clinically toxic. Preliminary in vitro data have demonstrated that a novel clinically non-toxic analogue polymer poly [I]:poly [C(12)U] (Ampligen R) can effectively induce in vitro maturation of human monocyte derived DC with sustained bioactive IL12 production. Human monocyte derived DC primed with tumour lysate and matured with synthetic dsRNA may therefore offer an effective way of optimising Th1 specific anti-cancer T-cell responses in cancer patients. This strategy is currently being tested in a clinical trial in patients with cervical cancer. PMID:12531360

Adams, M; Navabi, H; Jasani, B; Man, S; Fiander, A; Evans, A S; Donninger, C; Mason, M

2003-01-30

368

Disparities in cervical and breast cancer mortality in Brazil  

PubMed Central

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

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

2014-01-01

369

Cervical cancer: a missed health priority in Tanzania.  

PubMed

Cervical cancer is a malignant neoplasm of the cervix uteri. It is the second commonest cancer in women worldwide and is among the largest causes of global cancer mortality. Human papilloma virus (HPV) which is transmitted sexually, particularly subtypes 16 and 18 are responsible for causing majority of cervical cancer cases worldwide. The disease is one of the most preventable and curable carcinomas if detected and treated at an early enough stage. The effective prevention and control of the disease depends on, among others, the effective screening program coupled with knowledge and awareness of women population on the disease's risk factors and available screening services. Pap-test screening that is widely used in Western countries and proved to be effective in reducing the incidence of cervical cancer is not so popular in Tanzania, and so is HPV vaccine. This review examines the literatures on cervical cancer situation and explores various evidence-based cost-effective strategies and approaches that could be employed to confront the rising cervical cancer burden in the country. PMID:23120931

Saleh, F H

2011-12-01

370

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

ERIC Educational Resources Information Center

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

Ehrhardt, Jeanie

2007-01-01

371

Breast and cervical cancer screening behaviours among colorectal cancer survivors in Nova Scotia  

PubMed Central

Purpose We analyzed patterns and factors associated with receipt of breast and cervical cancer screening in a cohort of colorectal cancer survivors. Methods Individuals diagnosed with colorectal cancer in Nova Scotia between January 2001 and December 2005 were eligible for inclusion. Receipt of breast and cervical cancer screening was determined using administrative data. General-population age restrictions were used in the analysis (breast: 40–69 years; cervical: 21–75 years). Kaplan–Meier and Cox proportional hazards models were used to assess time to first screen. Results Of 318 and 443 colorectal cancer survivors eligible for the breast and cervical cancer screening analysis respectively, 30.1% [95% confidence interval (ci): 21.2% to 39.0%] never received screening mammography, and 47.9% (95% ci: 37.8% to 58.0%) never received cervical cancer screening during the study period. Receipt of screening before the colorectal cancer diagnosis was strongly associated with receipt of screening after diagnosis (hazard ratio for breast cancer screening: 4.71; 95% ci: 3.42 to 6.51; hazard ratio for cervical cancer screening: 6.83; 95% ci: 4.58 to 10.16). Conclusions Many colorectal cancer survivors within general-population screening age recommendations did not receive breast and cervical cancer screening. Future research should focus on survivors who meet age recommendations for population-based cancer screening. PMID:25302037

Corkum, M.; Urquhart, R.; Kephart, G.; Hayden, J.A.; Porter, G.

2014-01-01

372

Upregulation of URI/RMP gene expression in cervical cancer by high-throughput tissue microarray analysis  

PubMed Central

URI, or RMP, is a RNA polymerase II subunit RPB5-associated protein known to play essential roles in ubiquitination and transcription. Recently, we and others have shown that URI/RMP is also important for progression of hepatocellular carcinoma, ovarian, and prostate cancers. To identify the mechanistic basis of URI/RMP during multiple cellular processes, we investigated URI/RMP expression in a tissue microarray (TMA) containing multiple normal human tissues. The results showed that URI/RMP is ubiquitously but differentially expressed in these human tissues which partially explains its multiple cellular functions. To elucidate the role of URI/RMP during oncogenesis of multiple malignancies, especially the tumors of reproductive system, we analyzed URI/RMP expression in a TMA containing multiple reproductive system tumors. We did not observe significant difference of URI/RMP expression between cancerous and adjacent tissues of the prostate, breast, ovarian, and endometrial cancers. However, increased URI/RMP expression was observed in two of the three cases of cervical SCC (squamous cell carcinoma) cells compared to their adjacent epithelial cells. Moreover, we detected significantly upregulated URI/RMP expression not only in cervical cancers but also in pre-cancerous CINs (cervical intra-epithelial neoplasias) in a TMA that covers the whole spectrum of normal cervix, CINs, and cervical cancers. No difference of URI/RMP expression was observed between CINs and cervical cancers. Given the high risk of CINs (especially CIN3) turning into cervical cancer if left untreated, the increased URI/RMP expression in CINs as well as in cervical cancers suggest a clinical relevance of URI/RMP upon cervical cancer tumorigenesis and worth further investigation. PMID:23573313

Gu, Junxia; Li, Xiaoyun; Liang, Yuting; Qiao, Longwei; Ran, Deyuan; Lu, Yaojuan; Li, Xingang; Wei, Wenxiang; Zheng, Qiping

2013-01-01

373

Large scale study of HPV genotypes in cervical cancer and different cytological cervical specimens in Thailand.  

PubMed

Identification of high-risk HPV genotypes in patients is essential for vaccination and prevention programs while the geographic distribution of cervical cancer varies widely. HPV 16 is the major cause of cervical cancer followed by HPV 18, HPV 31, HPV 52, or HPV 58 depending on geographic area. In this study, the distribution of HPV genotypes in cervical specimens from women living in Thailand was analyzed by HPV testing with electrochemical DNA chip and PCR direct sequencing. The 716 specimens were grouped according to their cytological grades; 100 normal, 100 low-grade squamous intraepithelial lesions, 100 high grade squamous intraepithelial lesions, and 416 specimens of cervical cancer. The results showed that HPV 16, HPV 18, HPV 52, and HPV 58 are the most common HPV genotypes in Thailand, respectively. With respect to age, women below the age of 26 years were almost negative for high-risk HPV DNA exclusively. Conversely, high prevalence of high-risk HPV DNA and abnormal cytology were usually found in women between 26 and 45 years while cervical cancer was detected mainly in women above the age of 45 years. To increase protection efficiency, a vaccine including HPV 52 and HPV 58 should be offered to Asian women, and primary HPV screening should start at 26-30 years of age. PMID:24127280

Chansaenroj, Jira; Junyangdikul, Pairoj; Chinchai, Teeraporn; Swangvaree, Sukumarn; Karalak, Anant; Gemma, Nobuhiro; Poovorawan, Yong

2014-04-01

374

Screening for HPV Outperforms Pap Test for Cervical Cancer Published on Cancer Network (http://www.cancernetwork.com)  

E-print Network

Screening for HPV Outperforms Pap Test for Cervical Cancer Published on Cancer Network (http://www.cancernetwork.com) Screening for HPV Outperforms Pap Test for Cervical Cancer News [1] | November 08, 2013 | Cervical Cancer [2 trials from Europe shows that HPV-based screening resulted in a greater long-term protection from

Serfling, Robert