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Sample records for cell cervical cancer

  1. Cervical cancer stem cells.

    PubMed

    Yao, Tingting; Lu, Rongbiao; Zhang, Yizhen; Zhang, Ya; Zhao, Chenyang; Lin, Rongchun; Lin, Zhongqiu

    2015-12-01

    The concept of cancer stem cells (CSC) has been established over the past decade or so, and their role in carcinogenic processes has been confirmed. In this review, we focus on cervical CSCs, including (1) their purported origin, (2) markers used for cervical CSC identification, (3) alterations to signalling pathways in cervical cancer and (4) the cancer stem cell niche. Although cervical CSCs have not yet been definitively identified and characterized, future studies pursuing them as therapeutic targets may provide novel insights for treatment of cervical cancer. PMID:26597379

  2. Cervical Cancer

    MedlinePLUS

    ... Careers Visitor Information Search Search Home Cancer Types Cervical Cancer—Patient Version Health Professional version Overview The cervix ... the vagina (birth canal). The main types of cervical cancer are squamous cell carcinoma and adenocarcinoma. Squamous cell ...

  3. Cervical Cancer

    Cancer.gov

    Cervical cancer is a disease in which cancer develops in the tissues of the cervix. The Cancer Genome Atlas is studying the two main types of cervical cancer. Squamous cell carcinoma develops in the thin, flat, squamous cells that line the vagina. Adenocarcinoma arises in the glandular cells in the vagina that secrete mucus. Risk factors for cervical cancer include smoking and human papillomavirus (HPV) infection. In the future, the HPV vaccine will lower the infection rate.

  4. Cervical Cancer

    MedlinePLUS

    ... www.womenshealth.gov/widget/hrsa-widget-en.html Cervical cancer Cervical cancer is cancer that starts in the cervix, the lower, narrow part of the uterus (womb). Most cervical cancers are caused by the human papillomavirus (HPV). Cervical ...

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

    ClinicalTrials.gov

    2015-11-09

    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

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

    ClinicalTrials.gov

    2014-09-22

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

  7. Cervical Cancer

    MedlinePLUS

    Cervical Cancer There are five main types of cancer that affect a woman’s reproductive organs: cervical, ovarian, uterine, ... rare fallopian tube cancer.) This fact sheet about cervical cancer is part of the Centers for Disease Control ...

  8. FDG and FMISO PET Hypoxia Evaluation in Cervical Cancer

    ClinicalTrials.gov

    2015-06-03

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  10. Cervical cancer

    MedlinePLUS

    Cervical cancer is cancer that starts in the cervix. The cervix is the lower part of the uterus ( ... Worldwide, cervical cancer is the third most common type of cancer in women. It is much less common in the ...

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

    ClinicalTrials.gov

    2015-11-03

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

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

    ClinicalTrials.gov

    2014-12-23

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

  13. Cervical Cancer

    MedlinePLUS

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

  14. Cervical Cancer Prevention

    MedlinePLUS

    ... Treatment Cervical Cancer Prevention Cervical Cancer Screening Research Cervical Cancer Prevention (PDQ®) What is prevention? Cancer prevention is ... to keep cancer from starting. General Information About Cervical Cancer Cervical cancer is a disease in which malignant ( ...

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

    ClinicalTrials.gov

    2014-06-18

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

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

    ClinicalTrials.gov

    2014-12-29

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

  17. Cervical Cancer Screening

    MedlinePLUS

    ... Treatment Cervical Cancer Prevention Cervical Cancer Screening Research Cervical Cancer Screening (PDQ®) What is screening? Screening is looking ... These are called diagnostic tests . General Information About Cervical Cancer Key Points Cervical cancer is a disease in ...

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

    ClinicalTrials.gov

    2015-11-09

    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

  19. Studying Biomarkers in Diagnosing Cervical Lesions in Patients With Abnormal Cervical Cells | Division of Cancer Prevention

    Cancer.gov

    This clinical trial is studying biomarkers in diagnosing cervical lesions in patients with abnormal cervical cells. Studying biomarkers in abnormal cervical cells may improve the ability to find cervical lesions and plan effective treatment.

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

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

    ClinicalTrials.gov

    2014-12-29

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

  2. Get Tested for Cervical Cancer

    MedlinePLUS

    ... Print This Topic En español Get Tested for Cervical Cancer Browse Sections The Basics Overview Cervical Cancer Pap ... Cervical Cancer 1 of 7 sections The Basics: Cervical Cancer What is cervical cancer? Cervical cancer is cancer ...

  3. Cervical Cancer

    MedlinePLUS

    ... cancer. STIs include HPV, herpes, gonorrhea and chlamydia. HPV is the virus that can cause genital warts. It seems to be very closely connected with these changes. Risk factors for cervical cancer Starting to have sex early (before age 18) Having had many sexual partners Being infected with ...

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

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

    PubMed Central

    2013-01-01

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

  6. 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

    2015-12-01

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

  7. Immunotherapy for Cervical Cancer

    Cancer.gov

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

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

    SciTech Connect

    Wang, Hongtao; Gao, Peng; Zheng, Jie

    2014-09-05

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

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

    PubMed Central

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

    2015-01-01

    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

  10. Cervical Cancer Stage IVA

    MedlinePLUS

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

  11. Cervical Cancer Stage IVB

    MedlinePLUS

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

  12. Cervical Cancer Stage IIIA

    MedlinePLUS

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

  13. Cervical Cancer Stage IIIB

    MedlinePLUS

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

  14. Risks of Cervical Cancer Screening

    MedlinePLUS

    ... Treatment Cervical Cancer Prevention Cervical Cancer Screening Research Cervical Cancer Screening (PDQ®) What is screening? Screening is looking ... These are called diagnostic tests . General Information About Cervical Cancer Key Points Cervical cancer is a disease in ...

  15. Treatment Option Overview (Cervical Cancer)

    MedlinePLUS

    ... Cervical cancer is a disease in which malignant (cancer) cells form in the tissues of the cervix. The ... diagnosed, tests are done to find out if cancer cells have spread within the cervix or to other ...

  16. General Information about Cervical Cancer

    MedlinePLUS

    ... Cervical cancer is a disease in which malignant (cancer) cells form in the tissues of the cervix. The ... diagnosed, tests are done to find out if cancer cells have spread within the cervix or to other ...

  17. 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

    2014-12-23

    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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Samarzija, Ivana; Beard, Peter

    2012-08-17

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

  20. Screening for Cervical Cancer

    MedlinePLUS

    Clinical Guideline Annals of Internal Medicine Screening for Cervical Cancer: U.S. Preventive Services Task Force Recommendation Statement Virginia ... of a high-grade precancerous cervical lesion or cervical cancer, women with in utero exposure to diethylstilbestrol, or ...

  1. Cervical Cancer Stage IB

    MedlinePLUS

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

  2. Cervical Cancer Stage IA

    MedlinePLUS

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

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

    PubMed

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

    2015-10-23

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

  4. ICSN - Cervical Cancer

    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 Cervical

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

    2012-01-01

    Background Secreted protein acidic and rich in cysteine (SPARC), a calcium-binding matricellular glycoprotein, is implicated in the progressions of some cancers. However, no information has been available to date regarding the function of SPARC in cervical cancer cell growth and metastasis. Methods In this study, we isolated and established high invasive subclones and low invasive subclones from human cervical cancer cell lines HeLa and SiHa by the limited dilution method. Real-time q-RT-PCR, Western Blot and ICC were performed to investigate SPARC mRNA and protein expressions in high invasive subclones and low invasive subclones. Then lentivirus vector with SPARC shRNA was constructed and infected the highly invasive subclones. Real-time q-RT-PCR, Western Blot and ICC were also performed to investigate the changes of SPARC expression after viral infection. In functional assays, effects of SPARC knockdown on the biological behaviors of cervical cancer cells were investigated. The mechanisms of SPARC in cervical cancer proliferation, apoptosis and invasion were also researched. Results SPARC was over-expressed in the highly invasive subclones compared with the low invasive subclones. Knockdown of SPARC significantly suppressed cervical cancer cell proliferation, and induced cell cycle arrest at the G1/G0 phase through the p53/p21 pathway, also caused cell apoptosis accompanied by the decreased ratio of Bcl-2/Bax, and inhibited cell invasion and metastasis accompanied by down-regulated MMP2 and MMP9 expressions and up-regulated E-cadherin expression. Conclusion SPARC is related to the invasive phenotype of cervical cancer cells. Knockdown of SPARC significantly suppresses cervical cancer cell proliferation, induces cell apoptosis and inhibits cell invasion and metastasis. SPARC as a promoter improves cervical cancer cell growth and metastasis. PMID:23050783

  7. Laparoscopic surgery inhibits the proliferation and metastasis of cervical cancer cells

    PubMed Central

    Huang, Shouguo; Qin, Jie; Chen, Jin; Cheng, Hong; Meng, Qiu; Zhang, Jing; Wang, Haiyan; Li, Huaying

    2015-01-01

    Aims: The present study is to investigate the effect of laparoscopic surgery on the proliferation and metastasis of cervical cancer cells. Methods: A total of 40 patients with phase I squamous cell carcinoma of the cervix were enrolled in the study, and divided evenly into laparoscopic surgery group and laparotomy group. In addition, another 20 patients with benign uterine lesions received laparoscopic panhysterectomy using celoscopes and were enrolled as control group. Cell apoptotic rates were determined using flow cytometry. The expression of N-myc, Fas, metastasis-associated gene 1, and nm23-H1 genes in tissues were measured using quantitative real-time polymerase chain reaction. Results: Cervical cancer cell apoptosis was promoted by laparoscopic surgery, but not affected by laparotomy. The expression of apoptosis suppressor gene N-myc in cervical cancer cells was reduced by laparoscopic surgery, but not affected by laparotomy. In addition, the expression of apoptosis promoting gene Fas in cervical cancer cells was enhanced by laparoscopic surgery, but not affected by laparotomy. Similarly, the expression of metastasis promoting gene MTA1 in cervical cancer cells was lowered by laparoscopic surgery, but not affected by laparotomy. Moreover, the expression of metastasis suppressor gene nm23-H1 in cervical cancer cells was increased by laparoscopic surgery, but not affected by laparotomy. Of note, laparoscopic panhysterectomy had no effect on the apoptosis or the expression of N-myc, Fas, MTA1 and nm23-H1 genes in normal cervical cells. Conclusions: Laparoscopic surgery is a safe treatment method for cervical cancer. It inhibits the proliferation and metastasis of cancer cells, but has no such effects on normal cells. PMID:26629182

  8. Cervical Cancer Screening

    MedlinePLUS

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

  9. Prevent Cervical Cancer

    MedlinePLUS

    ... professional printing [PDF-1.5MB] Cancer Home “Prevent Cervical Cancer” Infographic Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Prevent Cervical Cancer with the Right Test at the Right Time ...

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

    PubMed

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

    2015-12-01

    Receptor activator for nuclear factor ?B ligand (RANKL) is a member of the tumor necrosis factor (TNF) family. The interaction between RANKL and its receptor RANK plays an important role in the development and function of diverse tissues. However, the expression and role of RANKL in cervical cancer are still unknown. In the present study, we found that RANKL and RANK were highly co-expressed in cervical cancer. HeLa and SiHa cells secreted soluble RANKL (sRANKL), expressed member RANKL (mRANKL) and RANK. Recombinant human RANKL protein had no effect on the viability of HeLa and SiHa cells. Yet, blocking RANKL with an anti-human RANKL neutralizing antibody (?-RANKL) or recombinant human osteoprotegrin (OPG) protein resulted in the downregulation of Ki-67 and B-cell lymphoma 2 (Bcl-2) expression and an increase in Fas and Fas ligand (FasL) expression, as well as a high level of viability and a low level of apoptosis in the HeLa and SiHa cells. In addition, ?-RANKL led to a decrease in IL-8 secretion. Recombinant human IL-8 protein reversed the effect of ?-RANKL on the expression of proliferation- and apoptosis?related molecules, and proliferation and apoptosis in the HeLa and SiHa cells. The present study suggests that a high level of mRANKL/RANK expression in cervical cancer lesions plays an important role in the rapid growth of cervical cancer cells possibly through strengthening the dialogue between cervical cancer cells and regulation of IL-8 secretion, which may be a possible target for cervical cancer therapy. PMID:26398902

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    ClinicalTrials.gov

    2015-11-03

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Vulvar Cancer; Stage IB2 Cervical Cancer; Stage II Vulvar Cancer; Stage IIA1 Cervical Cancer; Stage IIA2 Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Cervical Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVA Cervical Cancer; Stage IVA Vulvar Cancer; Vulvar Adenocarcinoma; Vulvar Squamous Cell Carcinoma

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

    PubMed Central

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

    2015-01-01

    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

  15. Smoking and Cervical Cancer

    MedlinePLUS

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

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

    PubMed

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

    2013-02-01

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

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

    SciTech Connect

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

    2013-11-01

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

  18. 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

  19. 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

  20. ICSN - Cervical Cancer

    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 Incidence and Mortality Rates Organization

  1. 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

  2. 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

  3. 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

  4. Drugs Approved for Cervical Cancer

    MedlinePLUS

    ... Ask about Your Treatment Research Drugs Approved for Cervical Cancer This page lists cancer drugs approved by the ... Used in Cervical Cancer Drugs Approved to Prevent Cervical Cancer Cervarix (Recombinant HPV Bivalent Vaccine) Gardasil (Recombinant HPV ...

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

    PubMed Central

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

    2015-01-01

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

  6. Reversal of resistance towards cisplatin by curcumin in cervical cancer cells.

    PubMed

    Roy, Madhumita; Mukherjee, Sutapa

    2014-01-01

    Epigenetic regulators like histone deacetylases (1 and 2), and viral onco-proteins (E6/E7) are known to be overexpressed in cervical cancer cells. The present study was designed to investigate the effect of curcumin on HDACs (1 and 2) and HPV E6/E7 in the cervical cancer cell line SiHa and a drug resistant clone SiHaR (derived from SiHa). It was further intended to investigate whether curcumin could sensitize the cells towards cisplatin induced cell killing by modulation of multi drug resistant proteins like MRP1 and Pgp1. Curcumin inhibited HDACs, HPV expression and differentially increased acetylation and up-regulation of p53 in SiHa and SiHaR, leading to cell cycle arrest at G1-S phase. Up-regulation of pRb, p21, p27 and corresponding inhibition of cyclin D1 and CDK4 were observed. Cisplatin resistance in SiHaR due to over-expression of MRP1 and Pgp1 was overcome by curcumin. Curcumin also sensitized both the cervical cancer cells towards cisplatin induced cell killing. Inhibition of HDACs and HPVs led to cell cycle arrest at G1/S phase by alteration of cell cycle regulatory proteins. Suppression of MRP1 and Pgp1 by curcumin resulted in sensitization of cervical cancer cells, lowering the chemotherapeutic dose of the drug cisplatin. PMID:24606473

  7. Biomarker discovery for neuroendocrine cervical cancer.

    PubMed

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

    2014-07-01

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

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

    ClinicalTrials.gov

    2015-07-16

    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

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

    PubMed

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

    2015-12-22

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

  10. CD66+ cells in cervical pre-cancers are partially differentiated progenitors with neoplastic traits

    PubMed Central

    Pattabiraman, Chitra; Hong, Shiyuan; Gunasekharan, Vignesh K; Pranatharthi, Annapurna; Bajaj, Jeevisha; Srivastava, Sweta; Krishnamurthy, H.; Ammothumkandy, Aswathy; Giri, Venkat G; Laimins, Laimonis A; Krishna, Sudhir

    2014-01-01

    Cervical cancers, a malignancy associated with oncogenic papillomaviruses, remain a major disease burden in the absence of effective implementation of preventive strategies. CD66+ cells have previously been identified as a tumor propagating subset in cervical cancers. We investigated the existence, differentiation state and neoplastic potential of CD66+ cells in a pre-cancer cell line harboring HPV31b episomes. The gene expression profile of CD66High cells overlaps with differentiated keratinocytes, neoplastic mesenchymal transition, cells of the squamo-columnar junction and cervical cancer cell line derived spheroids. There is elevated expression of DNMT1, Notch1 and the viral gene product E1^E4, in CD66High cells. Thus CD66High cells, in the absence of differentiating signals, express higher levels of key regulators of keratinocytes stemness, differentiation and the viral life cycle respectively. We also find a striking association of neoplastic traits including migration, invasion and colony formation in soft agar with CD66High cells. These properties and a distinct G2M enriched cell cycle profile are conserved in cells from cervical cancers. Principally, using a precancerous cell line, we propose that CD66High cells have an intermediate differentiation state with a cellular milieu connected with both viral replication and neoplastic potential and validate some key features in pre-cancer lesions. Such pathophysiologically relevant systems for defining cellular changes in the early phases of the disease process provide both mechanistic insight and potential therapeutic strategies. Collectively, our data provides a rationale for exploring novel therapeutic targets in CD66+ sub-sets during cancer progression. PMID:25267065

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  12. Curcumin and emodin down-regulate TGF-? signaling pathway in human cervical cancer cells.

    PubMed

    Thacker, Pooja Chandrakant; Karunagaran, Devarajan

    2015-01-01

    Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-? 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

    2015-01-01

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

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

    ClinicalTrials.gov

    2015-11-09

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

  17. NF-?B-modulated miR-130a targets TNF-? in cervical cancer cells

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2003-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

    Cervical cancer has been identified as the third leading cause of average years of life lost per person dying of cancer. Since essentially all cervical cancers contain copies of human papillomavirus (HPV) DNA, we propose a treatment that targets HPV-infected cells using strategies that re-introduce normal functions into the infected cells while sparing healthy cells. We propose the use of focused ultrasound in combination with microbubbles as means to deliver antibodies against the E6 protein present only in HPV positive cells. We conducted in vitro studies with cell cultures of SiHa cervical carcinoma cells seeded into Opticell™ chambers. An in-house ultrasound excitation apparatus was used to control and explore the optimal acoustic parameters in order to maximize delivery. We first validated the possibility of delivering the EX-EGFP-M02 vector (Genecopoeia) into the cells; 1.2 ?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.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. Abnormal Cervical Cancer Screening Test Results

    MedlinePLUS

    ... AQ FREQUENTLY ASKED QUESTIONS FAQ187 GYNECOLOGIC PROBLEMS Abnormal Cervical Cancer Screening Test Results • What is cervical cancer screening? • What causes abnormal cervical cancer screening test ...

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

    ClinicalTrials.gov

    2015-06-05

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB2 Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Vaginal Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Vaginal Cancer

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2011-04-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. Studies of traditional Chinese medicine monomer on HeLa cell of cervical cancer.

    PubMed

    Yang, Jianping; Li, Jingyu; Sun, Miaomiao; Chen, Kuisheng

    2014-07-01

    This paper is to study the effect of traditional Chinese medicine monomer including quercetin, curcumin and Glaucocalyxin A on Hela cell of cervical cancer. The inhibiting effect of quercetin, curcumin and Glaucocalyxin A on HeLa cells' proliferation is detected through using MTT method. Analysis for the effect of quercetin, curcumin and Glaucocalyxin A on proliferation cycle of Hela cell is performed through adopting flow cytometry. Three kinds of traditional Chinese medicine monomer can inhibit the growth of Hela cell, and they show dependent relationship between time and dose. Quercetin, curcumin and Glaucocalyxin A could inhibit cell proliferation, probably through making Hela cell be in stagnation and inducing its apoptosis. PMID:25016267

  10. Aberrant Expression of Oncogenic and Tumor-Suppressive MicroRNAs in Cervical Cancer Is Required for Cancer Cell Growth

    PubMed Central

    Le, Shu-Yun; Lu, Robert; Rader, Janet S.; Meyers, Craig; Zheng, Zhi-Ming

    2008-01-01

    MicroRNAs (miRNAs) play important roles in cancer development. By cloning and sequencing of a HPV16+ CaSki cell small RNA library, we isolated 174 miRNAs (including the novel miR-193c) which could be grouped into 46 different miRNA species, with miR-21, miR-24, miR-27a, and miR-205 being most abundant. We chose for further study 10 miRNAs according to their cloning frequency and associated their levels in 10 cervical cancer- or cervical intraepithelial neoplasia-derived cell lines. No correlation was observed between their expression with the presence or absence of an integrated or episomal HPV genome. All cell lines examined contained no detectable miR-143 and miR-145. HPV-infected cell lines expressed a different set of miRNAs when grown in organotypic raft cultured as compared to monolayer cell culture, including expression of miR-143 and miR-145. This suggests a correlation between miRNA expression and tissue differentiation. Using miRNA array analyses for age-matched normal cervix and cervical cancer tissues, in combination with northern blot verification, we identified significantly deregulated miRNAs in cervical cancer tissues, with miR-126, miR-143, and miR-145 downregulation and miR-15b, miR-16, miR-146a, and miR-155 upregulation. Functional studies showed that both miR-143 and miR-145 are suppressive to cell growth. When introduced into cell lines, miR-146a was found to promote cell proliferation. Collectively, our data indicate that downregulation of miR-143 and miR-145 and upregulation of miR-146a play a role in cervical carcinogenesis. PMID:18596939

  11. Cervical cancer - screening and prevention

    MedlinePLUS

    Cervical cancer is cancer that starts in the cervix. The cervix is the lower part of the uterus ( ... can do to decrease your chance of having cervical cancer. Also, tests done by your health care provider ...

  12. Stages of Cervical Cancer

    MedlinePLUS

    ... PDQ summary on Unusual Cancers of Childhood Treatment . Human papillomavirus (HPV) infection is the major risk factor for ... be at risk. Infection of the cervix with human papillomavirus (HPV) is almost always the cause of cervical ...

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-02-01

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

  15. Curcumin counteracts the proliferative effect of estradiol and induces apoptosis in cervical cancer cells.

    PubMed

    Singh, Mayank; Singh, Neeta

    2011-01-01

    Cervical cancer is the most common cancer in Indian females and is associated with infection with high-risk Human papilloma viruses (HPVs) which encode viral oncoprotein E6 and E7. Estradiol has been established as a risk factor for cervical cancer and has been shown to play a synergistic role with viral oncoproteins. Curcumin (Diferuloyl methane), a chemopreventive agent, is a natural compound extracted from Curcuma longa that allows suppression and retardation of carcinogenesis in many types of cancer and is currently being tested in various human clinical trials as it has been found to be well tolerated at higher doses with a relatively well established safety profile. The objective of this study was to test the effect of curcumin on HPV-positive and negative cervical cancer cell lines HeLa, SiHa, CaSki, and C33A pretreated with estradiol. It was found that HPV-positive cells pretreated with estradiol show reduced apoptosis as compared to curcumin by itself. However, curcumin was able to counteract the proliferative response of estradiol, and induce apoptosis. There was no difference in percentage apoptosis as compared to estradiol pretreatment in HPV-negative cell line C33A. Molecular studies showed elevation of Telomerase, viral oncoproteins E6 and E7, PCNA, p16, Cyclin D1 in HPV-positive cell lines on treatment with estradiol but after treatment with curcumin the level of E7, PCNA, and Cyclin D1 was reduced but the level of E6, Telomerase, and p16 was unaltered. Furthermore, estradiol-pretreated HPV-negative cell line C33A showed reduction in level of Telomerase, PCNA, p16, and activation of both p53 and p73 tumor suppressor proteins, thus, demonstrating the importance of E6 in estradiol-mediated protective effect. PMID:20941532

  16. Ovarian and cervical cancer.

    PubMed Central

    Williams, C.

    1992-01-01

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

  17. Human Papillomavirus and Cervical Cancer

    PubMed Central

    Burd, Eileen M.

    2003-01-01

    Of the many types of human papillomavirus (HPV), more than 30 infect the genital tract. The association between certain oncogenic (high-risk) strains of HPV and cervical cancer is well established. Although HPV is essential to the transformation of cervical epithelial cells, it is not sufficient, and a variety of cofactors and molecular events influence whether cervical cancer will develop. Early detection and treatment of precancerous lesions can prevent progression to cervical cancer. Identification of precancerous lesions has been primarily by cytologic screening of cervical cells. Cellular abnormalities, however, may be missed or may not be sufficiently distinct, and a portion of patients with borderline or mildly dyskaryotic cytomorphology will have higher-grade disease identified by subsequent colposcopy and biopsy. Sensitive and specific molecular techniques that detect HPV DNA and distinguish high-risk HPV types from low-risk HPV types have been introduced as an adjunct to cytology. Earlier detection of high-risk HPV types may improve triage, treatment, and follow-up in infected patients. Currently, the clearest role for HPV DNA testing is to improve diagnostic accuracy and limit unnecessary colposcopy in patients with borderline or mildly abnormal cytologic test results. PMID:12525422

  18. RNA interference against human papillomavirus oncogenes in cervical cancer cells results in increased sensitivity to cisplatin.

    PubMed

    Putral, Lisa N; Bywater, Megan J; Gu, Wenyi; Saunders, Nicholas A; Gabrielli, Brian G; Leggatt, Graham R; McMillan, Nigel A J

    2005-11-01

    Targeted inhibition of oncogenes in tumor cells is a rational approach toward the development of cancer therapies based on RNA interference (RNAi). Tumors caused by human papillomavirus (HPV) infection are an ideal model system for RNAi-based cancer therapies because the oncogenes that cause cervical cancer, E6 and E7, are expressed only in cancerous cells. We investigated whether targeting HPV E6 and E7 oncogenes yields cancer cells more sensitive to chemotherapy by cisplatin, the chemotherapeutic agent currently used for the treatment of advanced cervical cancer. We have designed siRNAs directed against the HPV E6 oncogene that simultaneously targets both E6 and E7, which results in an 80% reduction in E7 protein and reactivation of the p53 pathway. The loss of E6 and E7 resulted in a reduction in cellular viability concurrent with the induction of cellular senescence. Interference was specific in that no effect on HPV-negative cells was observed. We demonstrate that RNAi against E6 and E7 oncogenes enhances the chemotherapeutic effect of cisplatin in HeLa cells. The IC50 for HeLa cells treated with cisplatin was 9.4 microM, but after the addition of a lentivirus-delivered shRNA against E6, the IC50 was reduced almost 4-fold to 2.4 microM. We also observed a decrease in E7 expression with a concurrent increase in p53 protein levels upon cotreatment with shRNA and cisplatin over that seen with individual treatment alone. Our results provide strong evidence that loss of E6 and E7 results in increased sensitivity to cisplatin, probably because of increased p53 levels. PMID:16120770

  19. Homozygous Deletion of the STK11/LKB1 Locus and the Generation of Novel Fusion Transcripts in Cervical Cancer Cells

    PubMed Central

    McCabe, Michael T.; Powell, Doris R.; Zhou, Wei; Vertino, Paula M.

    2009-01-01

    The STK11/LKB1 gene encodes a ubiquitously expressed serine/threonine kinase that is mutated in multiple sporadic cancers including non-small cell lung carcinomas, pancreatic cancers, and melanomas. LKB1 affects multiple cellular functions including cell growth, cell cycle progression, metabolism, cell polarity and migration. To date, only a limited number of studies have assessed the status of LKB1 in cervical cancers. Herein, we investigate DNA methylation, DNA mutation, and transcription at the LKB1 locus in cervical cancer cell lines. We identified homozygous deletions of 25–85kb in the HeLa and SiHa cell lines. Deletion breakpoint analysis in HeLa cells revealed that the deletion resulted from an Alu-recombination mediated deletion (ARMD) and generated a novel LKB1 fusion transcript driven by an uncharacterized CpG island promoter located ~11kb upstream of LKB1. Although the homozygous deletion in SiHa cells removes the entire LKB1 gene and portions of the neighboring genes SBNO2 and c19orf26, this deletion also generates a fusion transcript driven by the c19orf26 promoter and comprised of both c19orf26 and SBNO2 sequences. Further analyses of public gene expression and mutation databases suggest that LKB1 and its neighboring genes are frequently dysregulated in primary cervical cancers. Thus, homozygous deletions affecting LKB1 in cervical cancers may generate multiple fusion transcripts involving LKB1, SBNO2, and c19orf26. PMID:20193846

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

    SciTech Connect

    Zhao, Gang; Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin ; Chen, Jiawei; Deng, Yanqiu; Gao, Feng; Zhu, Jiwei; Feng, Zhenzhong; Lv, Xiuhong; Zhao, Zheng

    2011-04-29

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

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

    MedlinePLUS

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

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

    ClinicalTrials.gov

    2013-01-15

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  4. Cervical Cancer HPV Vaccine Use

    Cancer.gov

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

  5. Cervical Cancer Rates by Race and Ethnicity

    MedlinePLUS

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Cervical Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of women getting cervical cancer or dying from cervical cancer varies by race ...

  6. Cervical Cancer Screening | Cancer Trends Progress Report

    Cancer.gov

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2014-08-08

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

  9. Reversal of hypermethylation and reactivation of the RAR?2 gene by natural compounds in cervical cancer cell lines.

    PubMed

    Jha, A K; Nikbakht, M; Parashar, G; Shrivastava, A; Capalash, N; Kaur, J

    2010-01-01

    Reactivation of tumour suppressor genes that have been silenced by promoter methylation is a very attractive molecular target for cancer therapy. The treatment of a squamous cervical cancer cell line, SiHa, with 20 ?M curcumin and genistein resulted in demethylation of promoter of the RAR?2 gene and led to the reactivation of the gene. The degree of methylation as observed by MSP decreased as the time period of treatment was increased from 72 h to 6 days. In HeLa cells (an adenocarcinoma cervical cancer cell line) there was also reversal of hypermethylation of the RAR?2 gene after six days of treatment with 20 ?M curcumin. However, allyl sulphide treatment (20 ?M) did not cause the reversal of hypermethylation until 72 h of treatment in the SiHa cell line. This is the first report to show the reversal of hypermethylation of the RAR?2 gene by genistein and curcumin in cervical cancer cell lines. Furthermore, these compounds acted as doublepronged agents as they caused apoptosis in the treated cervical cancer cell lines in addition to reversal of promoter hypermethylation. PMID:21138650

  10. [Primary cervical cancer screening].

    PubMed

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

    2015-01-01

    Cervico-uterine cancer screening with cytology decrease incidence by more than 50%. The cause of this cancer is the human papilloma virus high risk, and requires a sensitive test to provide sufficient sensitivity and specificity for early detection and greater interval period when the results are negative. The test of the human papilloma virus high risk, is effective and safe because of its excellent sensitivity, negative predictive value and optimal reproducibility, especially when combined with liquid-based cytology or biomarkers with viral load, with higher sensitivity and specificity, by reducing false positives for the detection of cervical intraepithelial neoplasia grade 2 or greater injury, with excellent clinical benefits to cervical cancer screening and related infection of human papilloma virus diseases, is currently the best test for early detection infection of human papillomavirus and the risk of carcinogenesis. PMID:26162490

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-09-01

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

  13. Cervical Cancer Prevention and Screening: Financial Issues

    MedlinePLUS

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    SciTech Connect

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

    2011-02-01

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

  18. microRNA-195 inhibits the proliferation, migration and invasion of cervical cancer cells via the inhibition of CCND2 and MYB expression

    PubMed Central

    DU, XINJIE; LIN, LI; ZHANG, LIJUN; JIANG, JIE

    2015-01-01

    The functions of microRNAs (miRNA/miR) in the development of cervical cancer remain largely undefined. The present study investigated the role of miR-195 in cervical cancer development. The expression of miR-195 mimics in the cervical cancer HeLa cell line significantly decreased the cell proliferation, migration and invasion capacities in vitro. Using miRNA target prediction algorithms and reporter assays, cyclin D2 (CCND2) and v-myb avian myeloblastosis viral oncogene homolog (MYB) were identified as direct targets of miR-195. Moreover, miR-195 repressed the expression of CCND2 and MYB in the HeLa cells at the mRNA and protein levels. Finally, the expression of miR-195 was downregulated in cervical cancer tissues compared with normal tissues. Together, these data suggest that miR-195 is a tumor suppressor in cervical cancer.

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2014-08-01

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

  1. Combining CXCL10 gene therapy and radiotherapy improved therapeutic efficacy in cervical cancer HeLa cell xenograft tumor models

    PubMed Central

    ZHAO, MING; MA, QIAN; XU, JINHUI; FU, SHAOZHI; CHEN, LANLAN; WANG, BIQIONG; WU, JINGBO; YANG, LINGLIN

    2015-01-01

    Radiotherapy is an important treatment method for cervical cancer, but the efficacy requires improvement. Therefore, novel methods of treatment are required. Previous data have demonstrated that the CXC chemokine ligand 10 (CXCL10) inhibits angiogenesis, induces apoptosis and causes avoidance of the S phase of the cell cycle in cervical cancer cells. The aim of the present study was to evaluate the anti-tumor effect of radiotherapy combined with CXCL10 gene therapy. Mouse models of cervical carcinoma were created by inoculation with HeLa cells, and were treated by combining intravenously administered plasmid-encoding CXCL10, administered 5 times (days 12, 15, 18, 21 and 24 following inoculation), with direct radiation (20 Gy/5 fractions) administered on 5 consecutive days (~day 27 after inoculation). The vessel density and tumor cell proliferation were observed by immunostaining, and apoptosis was determined using a TUNEL assay. The results revealed a significant increase in the inhibition of tumor growth, reduced vessel density, decreased cell proliferation and increased apoptosis in the tumor cells of the combination therapy group. Overall, these findings resulted in the conclusion that CXCL10 gene therapy in combination with radiotherapy is a novel effective therapeutic strategy for cervical cancer.

  2. Homozygous deletion of the STK11/LKB1 locus and the generation of novel fusion transcripts in cervical cancer cells.

    PubMed

    McCabe, Michael T; Powell, Doris R; Zhou, Wei; Vertino, Paula M

    2010-03-01

    The STK11/LKB1 gene encodes a ubiquitously expressed serine/threonine kinase that is mutated in multiple sporadic cancers including non-small cell lung carcinomas, pancreatic cancers, and melanomas. LKB1 plays a role in multiple cellular functions including cell growth, cell cycle progression, metabolism, cell polarity, and migration. To date, only a limited number of studies have assessed the status of LKB1 in cervical cancers. Herein, we investigate DNA methylation, DNA mutation, and transcription at the LKB1 locus in cervical cancer cell lines. We identified homozygous deletions of 25-85kb in the HeLa and SiHa cell lines. Deletion breakpoint analysis in HeLa cells revealed that the deletion resulted from an Alu-recombination-mediated deletion (ARMD) and generated a novel LKB1 fusion transcript driven by an uncharacterized CpG island promoter located approximately 11kb upstream of LKB1. Although the homozygous deletion in SiHa cells removes the entire LKB1 gene and portions of the neighboring genes SBNO2 and c19orf26, this deletion also generates a fusion transcript driven by the c19orf26 promoter and composed of both c19orf26 and SBNO2 sequences. Further analyses of public gene expression and mutation databases suggest that LKB1 and its neighboring genes are frequently dysregulated in primary cervical cancers. Thus, homozygous deletions affecting LKB1 in cervical cancers may generate multiple fusion transcripts involving LKB1, SBNO2, and c19orf26. PMID:20193846

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-08-01

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

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

    SciTech Connect

    Kuncharin, Yanin; Sangphech, Naunpun; Kueanjinda, Patipark; Bhattarakosol, Parvapan; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Payathai Road, Pathumwan, Bangkok 10330 ; Palaga, Tanapat

    2011-08-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-28

    We have shown that in up to half of the patients with metastatic breast cancer (MBC), higher numbers of circulating tumour cells (CTCs) are present in the central venous blood (CVB) compared to the peripheral venous blood (PVB), suggesting that the lungs might retain a substantial number of CTCs. Here we report the presence of tumour cell emboli (TCE) in the microvasculature of the lungs in three out of eight patients with MBC and one patient with metastatic cervical carcinoma who had markedly elevated numbers of CTCs in the blood. All these patients suffered from symptomatic dyspnoea not easily attributable to other causes. No TCE were observed in five patients with MBC and elevated CTC counts and three patients with MBC who had low CTC counts (<5/7.5?ml). To investigate whether CTCs derived from CVB or PVB exhibit different transcriptional characteristics that might explain selective CTC retention, paired CTC samples from CVB and PVB of 12 patients with advanced breast cancer were subjected to gene expression analysis of 105 genes. No significant differences in CTC gene expression were observed. Together, these data suggest that potentially clinically relevant CTC retention in the microvasculature of the lung can occur in a subset of patients with advanced metastatic breast and cervical cancer, which seems to be transcriptionally non-selectively. PMID:25449778

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

    SciTech Connect

    Liu, Junye; Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an ; Zhang, Jing; Wang, Xiaowu; Li, Yan; Chen, Yongbin; Li, Kangchu; Zhang, Jian; Yao, Libo; Guo, Guozhen

    2010-07-15

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

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

    ClinicalTrials.gov

    2014-04-21

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

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

    PubMed

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

    2014-12-01

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

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

    PubMed

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

    2008-05-14

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

  13. Invasive Cervical Cancer and Antidepressants

    PubMed Central

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

    2015-01-01

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

  14. Artemisinin Represses Telomerase Subunits and Induces Apoptosis in HPV-39 Infected Human Cervical Cancer Cells.

    PubMed

    Mondal, Anushree; Chatterji, Urmi

    2015-09-01

    Artemisinin, a plant-derived antimalarial drug with relatively low toxicity on normal cells in humans, has selective anticancer activities in various types of cancers, both in vitro and in vivo. In the present study, we have investigated the anticancer effects of artemisinin in human cervical cancer cells, with special emphasis on its role in inducing apoptosis and repressing cell proliferation by inhibiting the telomerase subunits, ER? which is essential for maintenance of the cervix, and downstream components like VEGF, which is known to activate angiogenesis. Effects of artemisinin on apoptosis of ME-180 cells were measured by flow cytometry, DAPI, and annexin V staining. Expression of genes and proteins related to cell proliferation and apoptosis was quantified both at the transcriptional and translational levels by semi-quantitative RT-PCR and western blot analysis, respectively. Our findings demonstrated that artemisinin significantly downregulated the expression of ER? and its downstream component, VEGF. Antiproliferative activity was also supported by decreased telomerase activity and reduced expression of hTR and hTERT subunits. Additionally, artemisinin reduced the expression of the HPV-39 viral E6 and E7 components. Artemisinin-induced apoptosis was confirmed by FACS, nuclear chromatin condensation, annexin V staining. Increased expression of p53 with concomitant decrease in expression of the p53 inhibitor Mdm2 further supported that artemisinin-induced apoptosis was p53-dependent. The results clearly indicate that artemisinin induces antiproliferative and proapoptotic effects in HPV-39-infected ME-180 cells, and warrants further trial as an effective anticancer drug. PMID:25755006

  15. Radiosensitivity in HeLa cervical cancer cells overexpressing glutathione S-transferase ? 1

    PubMed Central

    YANG, LIANG; LIU, REN; MA, HONG-BIN; YING, MING-ZHEN; WANG, YA-JIE

    2015-01-01

    The aims of the present study were to investigate the effect of overexpressed exogenous glutathione S-transferase ? 1 (GSTP1) gene on the radiosensitivity of the HeLa human cervical cancer cell line and conduct a preliminarily investigation into the underlying mechanisms of the effect. The full-length sequence of human GSTP1 was obtained by performing a polymerase chain reaction (PCR) using primers based on the GenBank sequence of GSTP1. Subsequently, the gene was cloned into a recombinant eukaryotic expression plasmid, and the resulting construct was confirmed by restriction analysis and DNA sequencing. A HeLa cell line that was stably expressing high levels of GSTP1 was obtained through stable transfection of the constructed plasmids using lipofectamine and screening for G418 resistance, as demonstrated by reverse transcription-PCR. Using the transfected HeLa cells, a colony formation assay was conducted to detect the influence of GSTP1 overexpression on the cell radiosensitivity. Furthermore, flow cytometry was used to investigate the effect of GSTP1 overexpression on cell cycle progression, with the protein expression levels of the cell cycle regulating factor cyclin B1 detected using western blot analysis. Colony formation and G2/M phase arrest in the GSTP1-expressing cells were significantly increased compared with the control group (P<0.01). In addition, the expression of cyclin B1 was significantly reduced in the GSTP1-expressing cells. These results demonstrated that increased expression of GSTP1 inhibits radiosensitivity in HeLa cells. The mechanism underlying this effect may be associated with the ability of the GSTP1 protein to reduce cyclin B1 expression, resulting in significant G2/M phase arrest.

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

    PubMed

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

    2015-12-15

    Cervical cancer is a consequence of persistent infection with human papillomaviruses (HPV). Progression to malignancy is linked to an inflammatory microenvironment comprising T-helper-17 (Th17) cells, a T-cell subset with protumorigenic properties. Neoplastic cells express only low endogenous levels of the Th17 chemoattractant CCL20, and therefore, it is unclear how Th17 cells are recruited to the cervical cancer tissue. In this study, we demonstrate that CCL20 was predominantly expressed in the stroma of cervical squamous cell carcinomas in situ. This correlated with stromal infiltration of CD4(+)/IL17(+) cells and with advancing International Federation of Gynecology and Obstetrics (FIGO) stage. Furthermore, we show that cervical cancer cells instructed primary cervical fibroblasts to produce high levels of CCL20 and to attract CD4/IL17/CCR6-positive cells, generated in vitro, in a CCL20/CCR6-dependent manner. Further mechanistic investigations identified cervical cancer cell-derived IL6 as an important mediator of paracrine CCL20 induction at the promoter, mRNA, and protein level in fibroblasts. CCL20 was upregulated through the recently described CCAAT/enhancer-binding protein ? (C/EBP?) pathway as shown with a dominant-negative version of C/EBP? and through siRNA-mediated knockdown. In summary, our study defines a novel molecular mechanism by which cervical neoplastic cells shape their local microenvironment by instructing fibroblasts to support Th17 cell infiltration in a paracrine IL6/C/EBP?-dependent manner. Th17 cells may in turn maintain chronic inflammation within high-grade cervical lesions to further promote cancer progression. Cancer Res; 75(24); 5248-59. ©2015 AACR. PMID:26631268

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  18. 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.

  19. Network Topologies Decoding Cervical Cancer

    PubMed Central

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

    2015-01-01

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

  20. Mesenchymal stromal cells derived from cervical cancer tumors induce TGF-?1 expression and IL-10 expression and secretion in the cervical cancer cells, resulting in protection from cytotoxic T cell activity.

    PubMed

    García-Rocha, R; Moreno-Lafont, M; Mora-García, M L; Weiss-Steider, B; Montesinos, J J; Piña-Sánchez, P; Monroy-García, A

    2015-12-01

    Cervical cancer (CeCa) tumors are characterized by increased expression of TGF-?1 and IL-10, which are correlated with downregulated expression of major histocompatibility complex class I antigens (HLA-I) on cancer cells and a reduced immune response mediated by cytotoxic T lymphocytes (CTLs). Mesenchymal stromal cells (MSCs) are important components in the tumor microenvironment that have been suggested to contribute to cancer progression through the induction of TGF-?1 and IL-10. In this study, we provided evidence that MSCs derived from cervical tumors (CeCa-MSCs) cocultured with CeCa cells induced significant expression of TGF-?1 and secretion of IL-10 by CeCa cells compared to MSCs derived from the normal cervix (NCx-MSCs) and normal bone marrow (BM-MSCs; gold standard). This increase in expression was associated with a significant downregulation of HLA-I molecules and protection of the cells against specific CTL lysis. Interestingly, the addition of the neutralizing antibody anti-TGF-? to the CeCa/CeCa-MSCs coculture strongly inhibited the expression and production of IL-10 by CeCa cells. Anti-TGF-? as well as anti-IL-10 also abolished HLA-I downregulation, and reversed the inhibition of CTL cytotoxicity. These results provide evidence that TGF-?1 and IL-10 could play an important role in the downregulation of HLA-I molecules on CeCa cells induced by tumor MSCs. Our findings suggest a novel mechanism through which MSCs may protect tumor cells from immune recognition by specific CTLs. PMID:26343835

  1. New Cervical Cancer Screening Guidelines

    MedlinePLUS Videos and Cool Tools

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

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

    Chen, Xin; Liu, Lifen; Zhu, Weipei

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2011-07-15

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-12-01

    Diallyl disulfide (DADS), extracted from crushed garlic by steam-distillation, has been reported to provide the anticancer activity in several cancer types. However, the effect of DADS on high-LET carbon beams - induced cell death remains unknown. Therefore, we used human cervical cancer cells to elucidate the molecular effects of this dallyl sulfide. Radiotherapy remains the mainstay of treatment, especially in advanced cervical cancer and there is still space to improve the radiosensitivity to reduce radiation dosage. In this study, we found that radiation effects evoked by high-LET carbon beam was marked by inhibition of cell viability, cell cycle arrest, significant rise of apoptotic cells, regulation of transcription factor, such as p73, as well as alterations of crucial mediator of the apoptosis pathway. We further demonstrated that pretreatment of 10 µM DADS in HeLa cells exposed to radiation resulted in decrease in cell viability and increased radiosensitivity. Additionally, cells pretreated with DADS obviously inhibited the radiation-induced G2/M phase arrest, but promoted radiation-induced apoptosis.  Moreover, combination DADS and the radiation exacerbated the activation of apoptosis pathways through up-regulated ration of pro-apoptotic Tap73 to anti-apoptotic ?Np73, and its downstream proteins, such as FASLG, and APAF1. Taken together, these results suggest that DADS is a potential candidate as radio sensitive agent for cervical cancer. PMID:26505313

  9. Preventing Cervical Cancer with HPV Vaccines

    Cancer.gov

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

  10. CDC Vital Signs: Cervical Cancer is Preventable

    MedlinePLUS

    ... Digital Press Kit Read the MMWR Science Clips Cervical Cancer is Preventable Language: English Español (Spanish) Recommend on ... 000 More than 4,000 women die of cervical cancer each year. 93% As many as 93% of ...

  11. NIH Research Leads to Cervical Cancer Vaccine

    MedlinePLUS

    ... Issues Sexually Transmitted Diseases NIH Research Leads to Cervical Cancer Vaccine Past Issues / Fall 2008 Table of Contents ... in women, the cause of the majority of cervical cancers. Photo courtesy of Judy Folkenberg, NLM Writer By ...

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

    PubMed

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

    2014-08-29

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

    Photothermal ablation (PTA) is a promising avenue in the area of cancer therapeutics that destroys tumor cells through conversion of near-infrared (NIR) laser light to heat. Hollow gold nanospheres (HGNs) are one of the few materials that are capable of converting light to heat and have been previously used for photothermal ablation studies. Selective delivery of functional nanoparticles to the tumor site is considered as an effective therapeutic approach. In this paper, we demonstrated the anti-cancer potential of HGNs. HGNs were conjugated with monoclonal antibody (anti-TROP2) in order to target cervical cancer cells (HeLa) that contain abundant trophoblast cell surface antigen 2 (TROP2) on the cell surface. The efficient uptake and intracellular location of these functionalized HGNs were studied through application of inductively coupled plasma atomic emission spectroscopy (ICP-AES) and transmission electron microscopy (TEM). Cytotoxicity induced by PTA was measured using CCK-8 assay. HeLa cells incubated with naked HGNs (0.3-3 nmol L-1) within 48 h did not show obvious cytotoxicity. Under laser irradiation at suitable power, anti-TROP2 conjugated HGNs achieved significant tumor cell growth inhibition in comparison to the effects of non-specific PEGylated HGNs (P < 0.05). ?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.

  14. Cervical Cancer Risk Prediction Models

    Cancer.gov

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

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

    PubMed

    Ramos-Solano, Moisés; Meza-Canales, Ivan D; Torres-Reyes, Luis A; Alvarez-Zavala, Monserrat; Alvarado-Ruíz, Liliana; Rincon-Orozco, Bladimiro; Garcia-Chagollan, Mariel; Ochoa-Hernández, Alejandra B; Ortiz-Lazareno, Pablo C; Rösl, Frank; Gariglio, Patricio; Jave-Suárez, Luis F; Aguilar-Lemarroy, Adriana

    2015-07-01

    According to the multifactorial model of cervical cancer (CC) causation, it is now recognized that other modifications, in addition to Human papillomavirus (HPV) infection, are necessary for the development of this neoplasia. Among these, it has been proposed that a dysregulation of the WNT pathway might favor malignant progression of HPV-immortalized keratinocytes. The aim of this study was to identify components of the WNT pathway differentially expressed in CC vs. non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A expression was found strongly downregulated in cell lines and biopsies derived from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviral gene delivery system or after adding a recombinant human protein decreases cell proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly accelerates proliferation. Decreased WNT7A expression was due to hypermethylation at particular CpG sites. To our knowledge, this is the first study reporting reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration. PMID:25978974

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

    PubMed Central

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

    2014-01-01

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

  17. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Downregulates the Expression of Protumor Factors Cyclooxygenase-2 and Inducible Nitric Oxide Synthase in a GM-CSF Receptor-Independent Manner in Cervical Cancer Cells

    PubMed Central

    Jiang, Nanyan; Tian, Zhiqiang; Tang, Jun; Ou, Rongying; Xu, Yunsheng

    2015-01-01

    Enhanced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) is associated with the pathogenic processes of various tumor types. COX-2 and iNOS expression in the immunomodulatory dendritic cells is mediated by the granulocyte macrophage-colony stimulating factor (GM-CSF), which is also expressed by cervical cancer cells; however, whether and how GM-CSF regulates COX-2 and iNOS expression in clinical cervical cancer cells remain unknown. In this study, we found that the COX-2 and iNOS expression was upregulated in the cervical cancer tissues and positively correlated with cancer metastasis and stage. About one-half of the cervical cancer tissues showed strong/moderate GM-CSF expression, while the normal cervical tissues showed >80% positive rate; no GM-CSFR protein was detectable on the cervical cancer cells. The GM-CSF expression was negatively correlated with the COX-2 and iNOS expression in the cervical cancer tissues and the functional negative regulatory effect of GM-CSF on COX-2/iNOS expression was demonstrated in various cervical cancer cell lines. Therefore, in cervical cancer cells, GM-CSF might contribute an antitumor response by inhibiting iNOS and COX-2 expression in a GM-CSFR independent manner. PMID:26257474

  18. Human papillomavirus typing and the reduction of cervical cancer risk.

    PubMed

    Jin, X W; Cash, J; Kennedy, A W

    1999-10-01

    Minor cervical cytologic abnormalities are common, but knowing which low-grade lesions will progress to cervical cancer--and therefore deserve biopsy and excision--is difficult. Since some human papillomavirus (HPV) types are strongly associated with cervical cancer, HPV typing may be a means of determining which patients with minor abnormalities require biopsy and treatment and which need only follow-up smears. This paper reviews the association between cervical cancer and HPV infection, the pathogenesis of HPV infection, the utility of HPV typing in training patients with a diagnosis of atypical squamous cells of undetermined significance, and the prospects for the development of an HPV vaccine. PMID:10535179

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  2. Lynch syndrome and cervical cancer.

    PubMed

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

    2015-12-01

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

  3. Characterization of Adult ?- and ?-Globin Elevated by Hydrogen Peroxide in Cervical Cancer Cells That Play A Cytoprotective Role Against Oxidative Insults

    PubMed Central

    Mei, Qian; Fu, Xiaobing; Han, Weidong

    2013-01-01

    Objectives Hemoglobin (Hgb) is the main oxygen and carbon dioxide carrier in cells of erythroid lineage and is responsible for oxygen delivery to the respiring tissues of the body. However, Hgb is also expressed in nonerythroid cells. In the present study, the expression of Hgb in human uterine cervix carcinoma cells and its role in cervical cancer were investigated. Methodology The expression level of Hgb in cervical cancer tissues was assessed by quantitative reverse transcriptase-PCR (qRT-PCR). We applied multiple methods, such as RT-PCR, immunoblotting, and immunohistochemical analysis, to confirm Hgb expression in cervical cancer cells. The effects of ectopic expression of Hgb and Hgb mutants on oxidative stress and cell viability were investigated by cellular reactive oxygen species (ROS) analysis and lactate dehydrogenase (LDH) array, respectively. Both Annexin V staining assay by flow cytometry and caspase-3 activity assay were used, respectively, to evaluate cell apoptosis. Results qRT-PCR analysis showed that Hgb-?- (HBA1) and Hgb-?-globin (HBB) gene expression was significantly higher in cervical carcinoma than in normal cervical tissues, whereas the expression of hematopoietic transcription factors and erythrocyte specific marker genes was not increased. Immunostaining experiments confirmed the expression of Hgb in cancer cells of the uterine cervix. Hgb mRNA and protein were also detected in the human cervical carcinoma cell lines SiHa and CaSki, and Hgb expression was up-regulated by hydrogen peroxide-induced oxidative stress. Importantly, ectopic expression of wild type HBA1/HBB or HBA1, rather than mutants HBA1H88R/HBBH93R unable to bind hemo, suppressed oxidative stress and improved cell viability. Conclusions The present findings show for the first time that Hgb is expressed in cervical carcinoma cells and may act as an antioxidant, attenuating oxidative stress-induced damage in cervical cancer cells. These data provide a significant impact not only in globin biology but also in understanding of cervical cancer pathogenesis associated with oxidative stress. PMID:23349856

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. CDC's Cervical Cancer Study

    MedlinePLUS

    ... Tests Effectiveness of Interventions to Increase Cancer Screening Adolescent and Young Adult Cancer Survivors HPV-Associated Cancers Physicians Who Use Social Media Skin Cancer Risk Behaviors Among U.S. Adults Annual ...

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

    NASA Astrophysics Data System (ADS)

    Jung, Bongsu; Lomeli, Eulieses; Anvari, Bahman

    2010-02-01

    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.

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

    ClinicalTrials.gov

    2014-12-23

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

  9. 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

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

    Cancer.gov

    Although human papillomavirus (HPV) infection is a significant factor in the development of most cervical and vulvar cancers, large population-based studies have implied an inherited predisposition to these cancers. Cell-mediated immune mechanisms, including human leukocyte antigen (HLA) type 1 and 2 cytokines, determine an individual's response to HPV infection. Investigators propose to analyze associations of HLA class I and II alleles with the risk of cervical and vulvar cancers.

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

    SciTech Connect

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

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

  14. 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. ...

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  17. What Are the Key Statistics about Cervical Cancer?

    MedlinePLUS

    ... are the key statistics about cervical cancer? The American Cancer Society's estimates for cervical cancer in the United States ... Health On The Net National Health Council © 2015 American Cancer Society, Inc. All rights reserved. The American Cancer Society ...

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

    PubMed

    González-Duarte, Ramiro José; Cázares-Ordoñez, Verna; Romero-Córdoba, Sandra; Díaz, Lorenza; Ortíz, Víctor; Freyre-González, Julio Augusto; Hidalgo-Miranda, Alfredo; Larrea, Fernando; Avila, Euclides

    2015-08-01

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

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

    SciTech Connect

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

    2013-07-18

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

    Noble metal nanoparticles have received considerable attention in biotechnology for their role in bio sensing due to surface plasmon resonance, medical diagnostics due to better imaging contrast and therapy. The radiosensitization effect of gold nanoparticles (AuNP) has been gaining popularity in radiation therapy of cancer cells. The better depth dose profile of energetic ion beam proves its superiority over gamma radiation for fighting against cancer. In the present work, the glucose capped gold nanoparticles (Glu-AuNP) were synthesised and internalized in the HeLa cells. Transmission electron microscopic analysis of ultrathin sections of Glu-AuNP treated HeLa cells confirmed the internalization of Glu-AuNPs. Control HeLa cells and Glu-AuNp treated HeLa cells were irradiated at different doses of 62 MeV 12C ion beam (LET - 290keV/?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.

  1. 8-p-Hdroxybenzoyl Tovarol Induces Paraptosis Like Cell Death and Protective Autophagy in Human Cervical Cancer HeLa Cells

    PubMed Central

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

    2015-01-01

    8-p-Hdroxybenzoyl tovarol (TAW) is a germacrane-type sesquiterpenoid that can be isolated from the roots of Ferula dissecta (Ledeb.) Ledeb. In this study, the growth inhibitory effects induced by TAW were screened on some types of tumor cells, and the mechanism was investigated on TAW-induced growth inhibition, including paraptosis and autophagy in human cervical cancer HeLa cells. TAW-induced paraptosis involved extensive cytoplasmic vacuolization in the absence of caspase activation. Additionally, TAW evoked cell paraptotic death mediated by endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Autophagy induced by TAW was found to antagonize paraptosis in HeLa cells. This effect was enhanced by rapamycin and suppressed by the autophagy inhibitor, 3-methyladenine (3MA). Loss of beclin 1 (an autophagic regulator) function led to promote ER stress. Taken together, these results suggest that TAW induces paraptosis like cell death and protective autophagy in HeLa cells, which would provide a new clue for exploiting TAW as a promising agent for the treatment of cervical cancer. PMID:26147427

  2. 8-p-Hdroxybenzoyl Tovarol Induces Paraptosis Like Cell Death and Protective Autophagy in Human Cervical Cancer HeLa Cells.

    PubMed

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

    2015-01-01

    8-p-Hdroxybenzoyl tovarol (TAW) is a germacrane-type sesquiterpenoid that can be isolated from the roots of Ferula dissecta (Ledeb.) Ledeb. In this study, the growth inhibitory effects induced by TAW were screened on some types of tumor cells, and the mechanism was investigated on TAW-induced growth inhibition, including paraptosis and autophagy in human cervical cancer HeLa cells. TAW-induced paraptosis involved extensive cytoplasmic vacuolization in the absence of caspase activation. Additionally, TAW evoked cell paraptotic death mediated by endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Autophagy induced by TAW was found to antagonize paraptosis in HeLa cells. This effect was enhanced by rapamycin and suppressed by the autophagy inhibitor, 3-methyladenine (3MA). Loss of beclin 1 (an autophagic regulator) function led to promote ER stress. Taken together, these results suggest that TAW induces paraptosis like cell death and protective autophagy in HeLa cells, which would provide a new clue for exploiting TAW as a promising agent for the treatment of cervical cancer. PMID:26147427

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

    ClinicalTrials.gov

    2014-12-29

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

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

    PubMed

    Li, Mingqun; Hong, Li

    2015-08-01

    Pseudolaric acid B (PAB) is a diterpene acid isolated from the bark of the root and trunk of Pseudolarix kaempferi Gordon (Pinaceae), which has demonstrated cytotoxic effects against various types of cancer. However, the mechanisms underlying the anticancer effects of PAB have remained to be elucidated. In the present study, the effects of PAB on the viability and apoptosis of HeLa cells were investigated by MTT assay, flow cytometric analysis of Annexin V-fluorescein isothiocyanate/propidium iodide staining, Rhodamine 123 staining and western blot analysis. The results demonstrated that PAB had antiproliferative and apoptosis-inducing effects on HeLa cells. PAB markedly inhibited HeLa cell viability in a time- and concentration-dependent manner. Flow cytometric analysis indicated that PAB induced apoptosis in HeLa cells in a dose-dependent manner. Treatment with PAB suppressed the expression of anti-apoptotic factor B cell lymphoma-2, and promoted the expression of pro-apoptotic factor Bcl-2-associated X protein. In addition, PAB induced an increase in Caspase-3 activity and loss of mitochondrial membrane potential, suggesting that this apoptosis may be mediated by mitochondrial pathways. Furthermore, the results of western blot analysis indicated that PAB was able to reduce Akt phosphorylation, thereby inhibiting the Akt pathway. These results suggested that PAB inhibited cell proliferation and induced apoptosis in HeLa cells, and that the anti-tumor effects of PAB were associated with inhibition of the Akt pathway. In conclusion, the results of the present study suggested that PAB may represent a novel therapeutic strategy for the treatment of human cervical cancer. However, additional studies are required to investigate the underlying apoptotic mechanisms. PMID:25891953

  5. What Should You Ask Your Doctor about Cervical Cancer?

    MedlinePLUS

    ... cancer? What should you ask your doctor about cervical cancer? It is important for you to have frank, ... are some questions to consider: What type of cervical cancer do I have? Has my cancer spread beyond ...

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

    PubMed

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

    2015-03-01

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

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

    PubMed

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

    2015-01-14

    Photodynamic therapy (PDT) involves the cellular uptake of a photosensitizer (PS) combined with oxygen molecules and light at a specific wavelength to be able to trigger cancer cell death via the apoptosis pathway, which is less harmful and has less inflammatory side effect than necrosis. However, the traditional PDT treatment has two main deficiencies: the dark toxicity of the PS and the poor selectivity of the cellular uptake of PS between the target cells and normal tissues. In this work, methylene blue (MB), a known effective PS, combined with Au nanoparticles (NPs) was prepared using an intermolecular interaction between a polystyrene-alt-maleic acid (PSMA) layer on the Au NPs and MB. The Au@polymer/MB NPs produced a high quantum yield of singlet oxygen molecules, over 50% as much as that of free MB, when they were excited by a dark red light source at 660 nm, but without significant dark toxicity. Furthermore, transferrin (Tf) was conjugated on the Au@polymer/MB NPs via an EDC/NHS reaction to enhance the selectivity to HeLa cells compared to 3T3 fibroblasts. With a hand-held single laser treatment (32 mW/cm) for 4 min, the new Au@polymer/MB-Tf NPs showed a 2-fold enhancement of PDT efficiency toward HeLa cells over the use of free MB at 4 times dosage. Cellular staining examinations showed that the HeLa cells reacted with Au@polymer/MB-Tf NPs and the 660 nm light excitation triggered PDT, which caused the cells to undergo apoptosis ("programmed" cell death). We propose that applying this therapeutic Au@polymer/MB-Tf nanoagent is facile and safe for delivery and cancer cell targeting to simultaneously minimize side effects and accomplish a significant enhancement in photodynamic therapeutic efficiency toward next-generation nanomedicine development. PMID:25494339

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

    PubMed Central

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

    2015-01-01

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

  9. Proteomics-based approach to elucidate the mechanism of antitumor effect of curcumin in cervical cancer.

    PubMed

    Madden, Krystal; Flowers, Lisa; Salani, Ritu; Horowitz, Ira; Logan, Sanjay; Kowalski, Kevin; Xie, Jun; Mohammed, Sulma I

    2009-01-01

    Cervical cancer is the second leading cause of cancer death for women in the world. A potential target for preventing and treating cervical cancer is cyclooxygenase-2 (cox-2). Curcumin is an anti-inflammatory agent that is known to have anti-cox-2 activity. In this study we examined the expression of cox-2 in cervical cancer and its precursors by immunohistochemistry. The effect of curcumin in inhibiting cervical cancer cells was determined via 2-dimensional gel electrophoresis, data analysis, and ingenuity pathway analysis. No significant differences in the expression of cox-2 in squamous cell carcinoma, and carcinoma in situ were observed. However, there was a statistically significant difference in the expression of cox-2 in adenocarcinoma in comparison to normal (p value=0.01) and squamous cell carcinoma (p value=0.02) tissues. Proteins associated with cancer and cell cycle were significantly altered in cultured cells. Curcumin may have antitumor effect in cervical cancer. PMID:19058955

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

    PubMed

    Silva, Jani; Cerqueira, Fátima; Medeiros, Rui

    2014-04-01

    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

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

    PubMed

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

    2015-07-16

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

  12. Human papillomavirus and vaccination in cervical cancer.

    PubMed

    Wang, Kung-Liahng

    2007-12-01

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

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

    PubMed

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

    2013-01-01

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

  14. Somatic LKB1 Mutations Promote Cervical Cancer Progression

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    Cancer.gov

    This study seeks to develop sensitive, specific, and inexpensive approaches to cervical cancer screening as alternatives to the traditional Pap test and cervical human papillomavirus (HPV) DNA testing.

  17. The Korean guideline for cervical cancer screening.

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Chen, H; Duan, J; Zuo, F

    2014-01-01

    We examined the ability of mifepristone to reverse the in vitro drug resistance of human cervical cancer cells resistant to mitomycin-C (HeLa/MMC) cells and investigated the mechanism of this effect. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the drug resistance of HeLa/MMC cells and the reversed drug resistance in vitro. Expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and glucosylceramide synthase (GCS) were measured in HeLa and HeLa/MMC cells. The resistance index of HeLa/MMC cells on MMC was reduced from 5.02 to 1.46 after 10 mg/mL mifepristone exposure. A combination of mifepristone upregulated the Bax/Bcl-2 protein expression ratio and apoptosis in HeLa/MMC cells. GCS expression was significantly higher in HeLa/MMC cells than in HeLa cells (P < 0.01), but distinctly declined in both cell lines after mifepristone application (P < 0.01). Mifepristone reversed the resistance of HeLa/MMC cells to MMC in vitro; the overexpression of the GCS gene and the increased expression of apoptosis-related protein Bcl-2 may play important roles in the formation of multidrug resistance in cervical cancer. PMID:24634186

  1. Screening for cervical cancer in Jamaica.

    PubMed

    Fletcher, H

    1999-04-01

    Invasive cervical cancer is a leading cause of death in Jamaica despite the availability of Pap smear screening. 90% of women who die from cervical cancer have never been screened. The effectiveness of Pap smear screening depends on women's knowledge of and attitudes toward screening, the availability of this service, the adequacy of laboratory facilities to process the smears, staffing of clinics and laboratories, quality control, a system of recall of women with positive smears, and economic factors. This article reviews the impact of each of these factors in the Jamaican context. Most women have heard of the Pap smear but believe its purpose is to detect rather than prevent cervical cancer. Screening rates are low among poor, uneducated women. As a result of staff shortages in government laboratories, there is a long delay before Pap smear results are returned. The problem of cervical cancer is severe enough in Jamaica to justify the reallocation of funds from less critical areas. PMID:12349102

  2. Treatment Options by Stage (Cervical Cancer)

    MedlinePLUS

    ... PDQ summary on Unusual Cancers of Childhood Treatment . Human papillomavirus (HPV) infection is the major risk factor for ... be at risk. Infection of the cervix with human papillomavirus (HPV) is almost always the cause of cervical ...

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

    SciTech Connect

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

    2008-10-01

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

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

    PubMed Central

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

    2015-01-01

    Although fully treatable in the early stages, once cervical cancer has metastasized, patient outcome is poor. The main objective of this study was to examine the effect of dietary supplementation with a nutrient mixture (NM) containing lysine, ascorbic acid, proline, green tea extract and other micronutrients on HeLa cell xenografts in nude female mice. Tumor growth was measured and immunohistochemical staining was evaluated for the following cancer markers: Ki67 (proliferation); matrix metalloproteinase (MMP)-2 and -9 (invasion/metastasis); vascular endothelial growth factor (VEGF) (angiogenesis); terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and B-cell lymphoma 2 (Bcl-2) (apoptosis); cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) (inflammation); and glutathione S-transferase ? (GST?) (a general cancer marker). Following housing for a week, 5/6-week-old female athymic nude mice (n=12) were inoculated subcutaneously with 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

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

    PubMed

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

    2016-01-01

    Every year, cervical cancer affects ?500,000 women worldwide, and ?275,000 patients die of this disease. The addition of platin-based chemotherapy to primary radiotherapy has increased 5-year survival of advanced-stage cervical cancer patients, which is, however, still only 66%. One of the factors thought to contribute to treatment failure is the ability of tumor cells to repair chemoradiotherapy-induced DNA damage. Therefore, sensitization of tumor cells for chemoradiotherapy via inhibition of the DNA damage response (DDR) as a novel strategy to improve therapy effect, is currently studied pre-clinically as well as in the clinic. Almost invariably, cervical carcinogenesis involves infection with the human papillomavirus (HPV), which inactivates part of the DNA damage response. This HPV-mediated partial inactivation of the DDR presents therapeutic targeting of the residual DDR as an interesting approach to achieve chemoradio-sensitization for cervical cancer. How the DDR can be most efficiently targeted, however, remains unclear. The fact that cisplatin and radiotherapy activate multiple signaling axes within the DDR further complicates a rational choice of therapeutic targets within the DDR. In this review, we provide an overview of the current preclinical and clinical knowledge about targeting the DDR in cervical cancer. PMID:26643553

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

    MedlinePLUS

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-01-01

    Squamous cell carcinoma antigen (SCCa), as a tumor biomarker, plays an important role in adjuvant diagnosis, treatment evaluation, and prognosis prediction for cervical cancer patients. Localized surface plasmon resonance (LSPR) technique based on noble metal nanoparticles bypasses the disadvantages of traditional testing strategies, in terms of free-labeling, short assay time, good sensitivity, and selectivity. Herein, we develop a novel and reusable LSPR biosensor for the detection of SCCa. First, a triangle-shaped silver nanoparticle array was fabricated using the nanosphere lithography method. Next, we investigated and verified the feasibility of amino coupling method using 11-mercaptoundecanoic acid (MUA) to form a functionalized chip surface with monoclonal anti-SCCa antibodies on the silver nanoparticles for distinct detection of SCCa. Different concentrations of SCCa were successfully tested in both buffer and human serum by the ultrasensitive and specific LSPR system, with a linear quantitative detection range of 0.1-1,000 pM under optimal conditions. With appropriate regeneration solution, for example 50 mM glycine-HCl (pH 2.0), the LSPR biosensor featured effective fabrication reproducibility, which reduced both production cost and testing time. Our study represents the first application of the LSPR biosensor in cervical cancer, and demonstrates that the rapid, simple, and reusable nanochip can serve as a potential alternative for clinical serological diagnosis of SCCa in cervical cancer patients. PMID:24591830

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-02-01

    The plasminogen activator (PA) system consists of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator and its receptor (uPA and uPAR). PAI-1 inhibits the activation of uPA (which converts plasminogen to plasmin), and is involved in cancer invasion and metastasis, by remodeling the extracellular matrix (ECM) through regulating plasmin. Cancer stem cells (CSCs) are a small subset of cells within tumors, and are thought to be involved in tumor recurrence and metastasis. Considering these facts, we investigated the relationship between PAI-1 and cervical CSCs. We used ALDH1 as a marker of cervical CSCs. First, we demonstrated that culturing ALDH1-high cells and ALDH-low cells on collagen IV-coted plates increased their expression of active PAI-1 (ELISA), and these increases were suggested to be at mRNA expression levels (RT-qPCR). Secondly, we demonstrated PAI-1 was indeed involved in the ECM maintenance. With gelatin zymography assays, we found that ALDH1-high cells and ALDH-low cells expressed pro-matrix metalloproteinase-2 (pro-MMP-2) irrespective of their coatings. With gelatinase/collagenase assay kit, we confirmed that collagenase activity was increased when ALDH1-low cells were exposed to TM5275, a small molecule inhibitor of PAI-1. Putting the data together, we hypothesized that cancer cells adhered to basal membrane secrete abundant PAI-1, on the other hand, cancer cells (especially CSCs rather than non-CSCs) distant from basal membrane secrete less PAI-1, which makes the ECM surrounding CSCs more susceptible to degradation. Our study could be an explanation of conflicting reports, where some researchers found negative impacts of PAI-1 expression on clinical outcomes and others not, by considering the concept of CSCs. PMID:26676222

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

    PubMed

    Wang, Fenfen; Li, Baohua; Xie, Xing

    2016-02-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  14. Claudin 1 Expression Characterizes Human Uterine Cervical Reserve Cells

    PubMed Central

    Zinner, Balázs; Gyöngyösi, Benedek; Babarczi, Edit; Kiss, András

    2013-01-01

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

  15. 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

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

    PubMed

    Sánchez-Sánchez, Luis; Alvarado-Sansininea, Jesús J; Escobar, María L; López-Muñoz, Hugo; Hernández-Vázquez, José M V; Monsalvo-Montiel, Iván; Demare, Patricia; Regla, Ignacio; Weiss-Steider, Benny

    2015-07-01

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

  17. Screening of cervical cancer in Catalonia 2006–2012

    PubMed Central

    de Sanjosé, Silvia; Ibáñez, Raquel; Rodríguez-Salés, Vanesa; Peris, Mercè; Roura, Esther; Diaz, Mireia; Torné, Aureli; Costa, Dolors; Canet, Yolanda; Falguera, Gemma; Alejo, Maria; Espinàs, Josep Alfons; Bosch, F. Xavier

    2015-01-01

    The early detection of intraepithelial lesions of the cervix, through the periodic examination of cervical cells, has been fundamental for the prevention of invasive cervical cancer and its related mortality. In this report, we summarise the cervical cancer screening activities carried out in Catalonia, Spain, within the National Health System during 2008–2011. The study population covers over two million women resident in the area. The evaluation includes 758,690 cervical cytologies performed on a total of 595,868 women. The three-year coverage of cervical cytology among women aged between 25 and 65 years was 40.8%. About 50% of first screened women with negative results had not returned to the second screening round. The introduction of high-risk human papillomavirus DNA (HPV) detection, as a primary screening cotest with cytology among women over age 40 with a poor screening history, significantly improved the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), being far superior to cytology alone. Cotesting did not improve the detection of CIN2+. The use of the HPV test for the triage of atypical squamous cell undetermined significance (ASC-US) improved the selection of women at high risk of CIN2+. Sampling (both cytology and HPV test) was largely performed by midwives (66.7%), followed by obstetricians (23.8%) and nurses (7%). Over half of the centres (54.8%) had full use of online medical records. During the study period, educational activities for professionals and for women were carried out periodically. The organisation of screening as a population activity in which women are actively called to the screening visit and the introduction of HPV testing as a primary screening tool are strongly recommended to ensure the maximum population impact in the reduction of the cervical cancer burden. PMID:25987901

  18. Ensembles of Radial Basis Function Networks for Spectroscopic Detection of Cervical Pre-Cancer

    E-print Network

    Tumer, Kagan

    only by breast cancer [American Cancer Society, 1995]. The mortality related to cervical cancer can cancer related deaths were reported in the United States alone, in 1995 [American Cancer Society, 1995,000-300,000 cells per slide), the American Society of Cytology has proposed that a cyto-technologist should

  19. 20(s)-ginsenoside Rg3-loaded magnetic human serum albumin nanospheres applied to HeLa cervical cancer cells in vitro.

    PubMed

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

    2014-01-01

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

  20. Angiogenesis and antiangiogenic agents in cervical cancer

    PubMed Central

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

    2014-01-01

    Standard treatment of cervical cancer (CC) consists of surgery in the early stages and of chemoradiation in locally advanced disease. Metastatic CC has a poor prognosis and is usually treated with palliative platinum-based chemotherapy. Current chemotherapeutic regimens are associated with significant adverse effects and only limited activity, making identification of active and tolerable novel targeted agents a high priority. Angiogenesis is a complex process that plays a crucial role in the development of many types of cancer. The dominant role of angiogenesis in CC seems to be directly related to human papillomavirus-related inhibition of p53 and stabilization of hypoxia-inducible factor-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

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

    PubMed

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

    2015-01-01

    The aim of this study was to develop topical self-microemulsifying drug delivery systems (SMEDDS) containing antitumor agents (bleomycin, cisplatin and ifosfamide) and to investigate their inhibitory potential in SMEDDS on human cervical cancer HeLa cells. The physicochemical properties of cytostatic drug loaded SMEDDS were characterized. The cytotoxicity of main components of SMEDDS was also investigated. Their IC50 values were determined. HeLa cells were treated by different concentrations of cisplatin, bleomycin and ifosfamide alone and in various SMEDDS. The inhibitory effect on cell growth was analyzed by MTT cell viability assay. Inflammation is a driving force that accelerates cancer development. The inhibitory effect of these antitumor agents has also been tested on HeLa cells in the presence of inflammatory mediators (IL-1-?, TNF-?) as an in vitro model of inflamed human cervix. Significant differences in the cytotoxicity of cytostatic drugs alone and in SMEDDS have been found in a concentration-dependent manner. The self-micro emulsifying system may potentiate the effectiveness of bleomycin, cisplatin and ifosfamide topically. The effect of SMEDDS containing antitumor agents was decreased significantly in the presence of inflammatory mediators. According to our experiments, the optimal SMEDDS formulation is 1:1:2:6:2 ratios of Isopropyl myristate, Capryol 90, Kolliphor RH 40, Cremophor RH40, Transcutol HP and Labrasol. It can be concluded that SMEDDS may increase the inhibitory effect of bleomycin, ifosfamide and cisplatin on human cervical cancer HeLa cells. Inflammation on HeLa cells hinders the effectiveness of SMEDDS containing antitumor agents. Our results might ensure useful data for development of optimal antitumor formulations. PMID:26197311

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

    PubMed Central

    2010-01-01

    Background The aim of the study was to obtain stable radioresistant sub-lines from the human cervical cancer cell line HeLa by prolonged exposure to 252Cf neutron and X-rays. Radioresistance mechanisms were investigated in the resulting cells using microarray analysis of DNA damage repair genes. Methods HeLa cells were treated with fractionated 252Cf neutron and X-rays, with a cumulative dose of 75 Gy each, over 8 months, yielding the sub-lines HeLaNR and HeLaXR. Radioresistant characteristics were detected by clone formation assay, ultrastructural observations, cell doubling time, cell cycle distribution, and apoptosis assay. Gene expression patterns of the radioresistant sub-lines were studied through microarray analysis and verified by Western blotting and real-time PCR. Results The radioresistant sub-lines HeLaNR and HeLaXR were more radioresisitant to 252Cf neutron and X-rays than parental HeLa cells by detecting their radioresistant characteristics, respectively. Compared to HeLa cells, the expression of 24 genes was significantly altered by at least 2-fold in HeLaNR cells. Of these, 19 genes were up-regulated and 5 down-regulated. In HeLaXR cells, 41 genes were significantly altered by at least 2-fold; 38 genes were up-regulated and 3 down-regulated. Conclusions Chronic exposure of cells to ionizing radiation induces adaptive responses that enhance tolerance of ionizing radiation and allow investigations of cellular radioresistance mechanisms. The insights gained into the molecular mechanisms activated by these "radioresistance" genes will lead to new therapeutic targets for cervical cancer. PMID:20184742

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

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    Cancer.gov

    Human papillomavirus (HPV) infection plays a significant role in the development of cervical cancer. However, most infections regress spontaneously and few progress to cervical cancer. Therefore, factors other than HPV infection likely are involved in cervical carcinogenesis. Methylation of CpG islands in the promoter regions of host and viral genes can lead to loss of gene function and has been observed in a number of cancers, including cervical.

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

    Cancer.gov

    This study explores the cervical cancer-related knowledge and behaviors of mothers and the potential of the mother-daughter relationship using daughter-initiated cervical cancer prevention in South Africa. The relationship has implications for effecting intergenerational prevention behavior for cervical cancer. This study will contribute formative data towards a better understanding of the potential of daughters to serve as advocates to promote cervical cancer screening with their mothers in order to develop effective and innovative methods to promote screening for cervical cancer.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

    Tetrahydrocurcumin (THC), one of the important in vivo metabolites of curcumin, inhibits tumor angiogenesis. Its effects on angiogenesis in cervical cancer- (CaSki-) implanted nude mice and its mechanisms on hypoxia-inducible factor-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

  9. Cervical cancer: Can it be prevented?

    PubMed Central

    Aggarwal, Pakhee

    2014-01-01

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

  10. Cervical Tissue Engineering Using Silk Scaffolds and Human Cervical Cells

    PubMed Central

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

    2010-01-01

    Spontaneous preterm birth is a frequent complication of pregnancy and a common cause of morbidity in childhood. Obstetricians suspect abnormalities of the cervix are implicated in a significant number of preterm births. The cervix is composed of fibrous connective tissue and undergoes significant remodeling in preparation for birth. We hypothesized that a tissue engineering strategy could be used to develop three-dimensional cervical-like tissue constructs that would be suitable for investigating cervical remodeling. Cervical cells were isolated from two premenopausal women undergoing hysterectomy for a benign gynecological condition, and the cells were seeded on porous silk scaffolds in the presence or absence of dynamic culture and with 10% or 20% serum. Morphological, biochemical, and mechanical properties were measured during the 8-week culture period. Cervical cells proliferated in three-dimensions and synthesized an extracellular matrix with biochemical constituents and morphology similar to native tissue. Compared to static culture, dynamic culture was associated with significantly increased collagen deposition (p?cervical-like constructs constitute a novel model system for a range of fundamental and applied studies related to cervical remodeling. PMID:20121593

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

    PubMed

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

    2010-06-01

    Spontaneous preterm birth is a frequent complication of pregnancy and a common cause of morbidity in childhood. Obstetricians suspect abnormalities of the cervix are implicated in a significant number of preterm births. The cervix is composed of fibrous connective tissue and undergoes significant remodeling in preparation for birth. We hypothesized that a tissue engineering strategy could be used to develop three-dimensional cervical-like tissue constructs that would be suitable for investigating cervical remodeling. Cervical cells were isolated from two premenopausal women undergoing hysterectomy for a benign gynecological condition, and the cells were seeded on porous silk scaffolds in the presence or absence of dynamic culture and with 10% or 20% serum. Morphological, biochemical, and mechanical properties were measured during the 8-week culture period. Cervical cells proliferated in three-dimensions and synthesized an extracellular matrix with biochemical constituents and morphology similar to native tissue. Compared to static culture, dynamic culture was associated with significantly increased collagen deposition (p < 0.05), sulfated glycosaminoglycan synthesis (p < 0.05), and mechanical stiffness (p < 0.05). Serum concentration did not affect measured variables. Relevant human tissue-engineered cervical-like constructs constitute a novel model system for a range of fundamental and applied studies related to cervical remodeling. PMID:20121593

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

    PubMed

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

    2015-04-01

    Bee venom (BV) therapy is a type of alternative medical treatment used to treat various diseases in oriental medicine. The mechanisms underlying the effects of BV remain poorly understood. In the present study, we evaluated the antiviral effect of BV on cervical carcinoma cell lines (CaSki, HeLa, C33A and TC-1). BV treatments resulted in a more significant suppression of cell growth in 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

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

    Cancer.gov

    Risk for cervical cancer may depend on human papillomavirus (HPV) subtype, viral load in cervical tissue, and the persistence of infection. The risk of cervical cancer due to HPV infection may be modified by an individual's genetics, specifically, a group of alleles that code for the human leukocyte antigen (HLA).

  14. Cervical cancer screening: Less testing, smarter testing.

    PubMed

    Jin, Xian Wen; Sikon, Andrea; Yen-Lieberman, Belinda

    2011-11-01

    In its 2009 recommendations for cervical cancer screening, the American College of Obstetricians and Gynecologists (ACOG) calls for less-frequent but smarter screening that integrates testing for human papillomavirus (HPV) infection with the Papanicolaou (Pap) test. We review the recommendations from this and other organizations and how and why they are evolving. PMID:22049541

  15. Cervical Cancer: paradigms at home and abroad

    Cancer.gov

    NCI funded a clinical trial that will have an impact on the treatment of late-stage cervical cancer, and also supported a screening trial in India using a network of community outreach workers offering low tech-screening by direct visualization of the cer

  16. Cervical Cancer Screening and Perceived Information Needs

    ERIC Educational Resources Information Center

    Whynes, David K.; Clarke, Katherine; Philips, Zoe; Avis, Mark

    2005-01-01

    Purpose: To identify women's sources of information about cervical cancer screening, information which women report receiving during Pap consultations, information they would like to receive, and the relationships between perceived information needs, personal characteristics and information sources. Design/methodology/approach: Logistic regression…

  17. 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

  18. The paradigm shift in cervical cancer screening in Germany.

    PubMed

    Hillemanns, Peter

    2016-01-01

    With the adoption of the Cancer Screening and Registration Law (KFRG, 2013) based on the National Cancer Plan, the so far opportunistic cervical cancer screening in Germany is to be converted to an organized screening program. This decision in Germany is consistent with the new EU Guidelines and, in anticipation of the upcoming German S3 guideline for cervical cancer screening. PMID:26514679

  19. New cervical cancer screening strategy: combined Pap and HPV testing.

    PubMed

    Jin, Xian Wen; Zanotti, Kristine; Yen-Lieberman, Belinda

    2005-02-01

    Our strategy for cervical cancer screeing is being revolutionized by our new understanding of how human papillomavirus (HPV) contributes to carcinogenesis and the natural history of cervical cancer. The American Cancer Society and the American College of Obstetricians and Gynecologists now recommend combined HPV and Papanicolaou (Pap) testing for cervical cancer screening in women age 30 or older. However, although incorporation of HPV DNA testing into primary screening provides clear benefits, it also raises new questions. PMID:15757169

  20. Antiproliferative and Apoptosis Inducing Effects of Non-Polar Fractions from Lawsonia inermis L. in Cervical (HeLa) Cancer Cells.

    PubMed

    Kumar, Manish; Kaur, Paramjeet; Kumar, Subodh; Kaur, Satwinderjeet

    2015-04-01

    Two non-polar fractions viz. hexane (Hex-LI) and chloroform fraction (CHCl3-LI) of Lawsonia inermis were studied for their antiproliferative potential in various cancer cell lines viz. HeLa, MCF-7, A549 and C6 glioma cells. Both the fractions showed more than 60 % of growth inhibition in all the tested cell lines at highest tested concentration. In clonogenic assay, different concentrations of Hex-LI and CHCl3-LI decreased the number and size of colonies as compared to control in HeLa cells. The apoptotic effects as nuclear condensation, fragmentation were visualized with Hoechst-33342 staining of HeLa cells using confocal microscope. Both fractions induced apoptotic cell death in human cervical carcinoma (HeLa) cells as evident from flow cytometric analysis carried out using Annexin V-FITC and propidium iodide dyes. CHCl3-LI treated cells significantly induced apoptosis (25.43 %) in comparison to control. Results from Neutral Comet assay demonstrated that both fractions induced double stranded breaks (DSB's) in HeLa cells. Our data indicated that Hex-LI and CHCl3-LI treated cells showed significant increase of 32.2 and 18.56 % reactive oxygen species (ROS) levels in DCFH-DA assay respectively. Further, experimental studies to decipher exact pathway via which these fractions induce cell death are in progress. PMID:25931778

  1. Optical coherence tomography in diagnosing cervical cancer

    NASA Astrophysics Data System (ADS)

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

    2000-05-01

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

  2. The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression

    PubMed Central

    He, Chunbo; Mao, Dagan; Hua, Guohua; Lv, Xiangmin; Chen, Xingcheng; Angeletti, Peter C; Dong, Jixin; Remmenga, Steven W; Rodabaugh, Kerry J; Zhou, Jin; Lambert, Paul F; Yang, Peixin; Davis, John S; Wang, Cheng

    2015-01-01

    The Hippo signaling pathway controls organ size and tumorigenesis through a kinase cascade that inactivates Yes-associated protein (YAP). Here, we show that YAP plays a central role in controlling the progression of cervical cancer. Our results suggest that YAP expression is associated with a poor prognosis for cervical cancer. TGF-? and amphiregulin (AREG), via EGFR, inhibit the Hippo signaling pathway and activate YAP to induce cervical cancer cell proliferation and migration. Activated YAP allows for up-regulation of TGF-?, AREG, and EGFR, forming a positive signaling loop to drive cervical cancer cell proliferation. HPV E6 protein, a major etiological molecule of cervical cancer, maintains high YAP protein levels in cervical cancer cells by preventing proteasome-dependent YAP degradation to drive cervical cancer cell proliferation. Results from human cervical cancer genomic databases and an accepted transgenic mouse model strongly support the clinical relevance of the discovered feed-forward signaling loop. Our study indicates that combined targeting of the Hippo and the ERBB signaling pathways represents a novel therapeutic strategy for prevention and treatment of cervical cancer. PMID:26417066

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Rajesh, Rajaian Pushpabai; Annappan, Murugan

    2015-01-01

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

  5. Computer aided decision support system for cervical cancer classification

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Lee, Kiwon; Lee, Ah-Young; Kwon, Yunhee Kim; Kwon, Hyockman

    2011-08-26

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

  8. 76 FR 30723 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-26

    ...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...

  9. 77 FR 66469 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-05

    ...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...

  10. 75 FR 7282 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-18

    ...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...

  11. 75 FR 7282 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-18

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

  12. Epidemiology of cervical cancer in Latin America

    PubMed Central

    Capote Negrin, Luis G

    2015-01-01

    The basic aspects of the descriptive epidemiology of cervical cancer in Latin America are presented. A decrease in the incidence and mortality rates has been observed in the period from 2000 to 2012 in all countries across the region, this has not occurred at the same proportions, and in many countries, observed figures of incidence and mortality are among the highest levels in the world. In Latin America, calculating a mean measure of the numbers from the GLOBOCAN data from 2000 to 2012, we can observe a difference of up to fivefold of the incidence (Puerto Rico 9,73 Vs Bolivia 50,73) and almost seven times for mortality (Puerto Rico 3,3 Vs Nicaragua 21,67). A report of the epidemiology, risk factors, and evaluation of screening procedures regarding the possible impact of the human papillomavirus (HPV) vaccine I in the prevention of cervical cancer is presented. PMID:26557875

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

    Cancer.gov

    In the United States, Hispanic women have significantly higher rates of cervical cancer than non-Hispanic White women. Human papillomavirus (HPV), a sexually transmitted infection, is the central cause of invasive cervical and other anogenital cancers, including anal, penile, vaginal and vulvar cancers. Little is known, however, about the prevalence, incidence, and clearance of HPV infection in men.

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

    PubMed Central

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

    2014-01-01

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

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

    Cancer.gov

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

  16. Rapid induction of senescence in human cervical carcinoma cells

    NASA Astrophysics Data System (ADS)

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

    2000-09-01

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

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

    PubMed Central

    Ali Khan, Munawwar; Kedhari Sundaram, Madhumitha; Hamza, Amina; Quraishi, Uzma; Gunasekera, Dian; Ramesh, Laveena; Goala, Payal; Al Alami, Usama; Ansari, Mohammad Zeeshan; Rizvi, Tahir A.; Sharma, Chhavi; Hussain, Arif

    2015-01-01

    Sulforaphane (SFN) may hinder carcinogenesis by altering epigenetic events in the cells; however, its molecular mechanisms are unclear. The present study investigates the role of SFN in modifying epigenetic events in human cervical cancer cells, HeLa. HeLa cells were treated with SFN (2.5?µM) for a period of 0, 24, 48, and 72 hours for all experiments. After treatment, expressions of DNMT3B, HDAC1, RAR?, CDH1, DAPK1, and GSTP1 were studied using RT-PCR while promoter DNA methylation of tumor suppressor genes (TSGs) was studied using MS-PCR. Inhibition assays of DNA methyl transferases (DNMTs) and histone deacetylases (HDACs) were performed at varying time points. Molecular modeling and docking studies were performed to explore the possible interaction of SFN with HDAC1 and DNMT3B. Time-dependent exposure to SFN decreases the expression of DNMT3B and HDAC1 and significantly reduces the enzymatic activity of DNMTs and HDACs. Molecular modeling data suggests that SFN may interact directly with DNMT3B and HDAC1 which may explain the inhibitory action of SFN. Interestingly, time-dependent reactivation of the studied TSGs via reversal of methylation in SFN treated cells correlates well with its impact on the epigenetic alterations accumulated during cancer development. Thus, SFN may have significant implications for epigenetic based therapy. PMID:26161119

  18. RhoC is essential in TGF-?1 induced epithelial-mesenchymal transition in cervical cancer cells

    PubMed Central

    HE, XIAOQI; QIAN, YING; CAI, HUILAN; YANG, SHOUHUA; CAI, JING; WANG, ZEHUA

    2015-01-01

    Epithelial-mesenchymal transition (EMT) is a critical process in the promotion of epithelial tumor progression and metastasis. The present study aimed to investigate the role of Ras homolog gene family, member C (RhoC) guanosine triphosphatase (GTPase) in transforming growth factor (TGF)-?1 induced EMT. EMT occurred in human cervical carcinoma SiHa cells following TGF-?1 stimulation for 4 days, as demonstrated by the appearance of mesenchymal morphology, reorganization of the actin cytoskeleton, reduced E-cadherin expression and increased Vimentin expression, which was associated with increased RhoC expression and activity. However, EMT was not observed in cells that were pretreated with RhoC siRNA prior to TGF-?1 stimulation. Downregulation of RhoC 4 days following TGF-?1 stimulation was not able to reverse the existing EMT. In addition, TGF-?1 promoted the invasion of the control SiHa cells but not that of the cells in which RhoC was downregulated. In conclusion, RhoC expression is activated by TGF-?1, and sufficient RhoC expression levels are essential for TGF-?1-induced EMT.

  19. Uterine cervical cancer with brain metastasis as the initial site of presentation.

    PubMed

    Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

    2015-07-01

    Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7?months after diagnosis of brain metastasis. PMID:25656985

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

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

    PubMed Central

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

    2015-01-01

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

  2. Phthalocyanine-mediated photodynamic therapy induces cell death and a G /G{sub 1} cell cycle arrest in cervical cancer cells

    SciTech Connect

    Haywood-Small, S.L. . E-mail: s.l.hankin@sheffield.ac.uk; Vernon, D.I.; Griffiths, J.; Schofield, J.; Brown, S.B.

    2006-01-13

    We have developed a series of novel photosensitizers which have potential for anticancer photodynamic therapy (PDT). Photosensitizers include zinc phthalocyanine tetra-sulphonic acid and a family of derivatives with amino acid substituents of varying alkyl chain length and degree of branching. Subcellular localization of these photosensitizers at the phototoxic IC{sub 5} concentration in human cervical carcinoma cells (SiHa Cells) was similar to that of the lysosomal dye Lucifer Yellow. Subsequent nuclear relocalization was observed following irradiation with 665 nm laser light. The PDT response was characterized using the Sulforhodamine B cytotoxicity assay. Flow cytometry was used for both DNA cell cycle and dual Annexin V-FITC/propidium iodide analysis. Phototoxicity of the derivatives was of the same order of magnitude as for tetrasulphonated phthalocyanine but with an overall trend of increased phototoxicity with increasing amino acid chain length. Our results demonstrate cell death, inhibition of cell growth, and G /G{sub 1} cell cycle arrest during the phthalocyanine PDT-mediated response.

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

    SciTech Connect

    Nijhuis, Esther R.; Zee, Ate G.J. van der; Hout, Bertha A. in 't; Boomgaard, Jantine J.; Hullu, Joanne A. de; Pras, Elisabeth; Hollema, Harry; Aalders, Jan G.; Nijman, Hans W.; Willemse, Pax H.B.; Mourits, Marian J.E. . E-mail: m.j.e.mourits@og.umcg.nl

    2006-11-01

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

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

    PubMed

    Breitenecker, G

    2009-12-01

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

  5. Therapeutic Vaccines Against Human Papillomavirus and Cervical Cancer

    PubMed Central

    Cid-Arregui, Angel

    2009-01-01

    Cervical cancer and its precursor intra-epithelial lesions are linked to infection by a subset of so-called “highrisk” human papillomavirus types, which are estimated to infect nearly four hundred million women worldwide. Two prophylactic vaccines have been commercialized recently targeting HPV16 and 18, the most prevalent viral types found in cervical cancer, which operate through induction of capsid-specific neutralizing antibodies. However, in patients with persistent infection these vaccines have not been found to protect against progression to neoplasia. Attempts are being made to develop therapeutic vaccines targeting nonstructural early viral proteins. Among these, E6 and E7 are the preferred targets, since they are essential for induction and maintenance of the malignant phenotype and are constitutively expressed by the transformed epithelial cells. Here are reviewed the most relevant potential vaccines based on HPV early antigens that have shown efficacy in preclinical models and that are being tested in clinical studies, which should determine their therapeutic capacity for eradicating HPV-induced premalignant and malignant lesions and cure cervical cancer. PMID:19915722

  6. Image-based brachytherapy for cervical cancer

    PubMed Central

    Vargo, John A; Beriwal, Sushil

    2014-01-01

    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

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

    Cancer.gov

    This study is examining the decision-making processes employed by older women for breast, cervical, and colorectal cancer screening. Research includes identifying decisionmaking preferences, actual involvement in cancer screening decisions, decisional conflict, and the influence of these on planning and obtaining breast, cervical, and colorectal screening.

  8. Social Construction of Cervical Cancer Screening among Panamanian Women

    ERIC Educational Resources Information Center

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

    2012-01-01

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

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

    PubMed

    Fan, Zhongyi; Cui, Hanzhi; Xu, Xiaojie; Lin, Zhi; Zhang, Xuelin; Kang, Lei; Han, Baiyu; Meng, Jing; Yan, Zhifeng; Yan, Xiang; Jiao, Shunchang

    2015-09-22

    MiR-125a has been characterized as a tumor suppressor in several cancers. However, the role of miR-125a in cervical cancer is unknown. In this study, we found the expression of miR-125a was downregulated in cervical cancer patients, and negatively correlated with the tumor size, FIGO stage, and preoperative metastasis. Kaplan-Meier analysis showed that miR-125a expression predicted favorable outcome for cervical cancer patients. Dual luciferase assays identified the STAT3 gene as a novel direct target of miR-125a. Functional studies showed that miR-125a overexpression significantly suppressed the growth, invasion and epithelial-mesenchymal transition (EMT) of cervical cancer cells both in vitro and in vivo via decreasing STAT3 expression. Moreover, miR-125a conferred to G2/M cell cycle arrest, accompanied by inhibition of several G2/M checkpoint proteins. Mechanistically, inactivation of miR-125a during cervical carcinogenesis was caused by HPV suppression of p53 expression. Clinically, STAT3, the expression of which, predicted poorer outcome, was inversely correlated with miR-125a in cervical cancer. These data highlight the importance of miR-125a in the cell proliferation and progression of cervical cancer, and indicate that miR-125a may be a useful therapeutic target for cervical cancer. PMID:26389681

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

    PubMed Central

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

    2015-01-01

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

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

    Cancer.gov

    Twitter Multimedia Home About Key Initiatives Funding Resources Tools Cancer Control & Population Sciences Home Behavioral Research Program Home Process of Care Research Branch Key Initiatives Behavioral Studies Regarding HPV and Cervical Cancer Enhanced

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

    Cancer.gov

    Twitter Multimedia Home About Key Initiatives Funding Resources Tools Cancer Control & Population Sciences Home Behavioral Research Program Home Process of Care Research Branch Process of Care Research Branch (PCRB) Key Initiatives HPV and Cervical Cancer

  13. DCCPS: BRP: PCRB: Key Initiatives: HPV and Cervical Cancer

    Cancer.gov

    Twitter Multimedia Home About Key Initiatives Funding Resources Tools Cancer Control & Population Sciences Home Behavioral Research Program Home Process of Care Research Branch Process of Care Research Branch (PCRB) Key Initiatives HPV and Cervical Cancer HPV

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

    PubMed Central

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

    2009-01-01

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

  15. The role of human cervical cancer oncogene in cancer progression

    PubMed Central

    Li, Xin-Yu; Wang, Xin

    2015-01-01

    Human cervical cancer oncogene (HCCR) was identified by differential display RT-PCR by screened abnormally expressed genes in cervical human cancers. The overexpressed gene is not only identified in cervical tissues, but also in various human cancers as leukemia/lymphoma, breast, stomach, colon, liver, kidney and ovarian cancer. For its special sensitivities and specificities in human breast cancer and hepatocellular carcinoma, it is expected to be a new biomarker to replace or combine with the existing biomarkers in the diagnose. The HCCR manifests as a negative regulator of the p53 tumor suppressor gene, and its expression is regulated by the PI3K/Akt signaling pathway, modulated by TCF/?-catenin, it also participates in induction of the c-kit proto-oncogene, in activation of PKC and telomerase activities, but the accurate biochemical mechanisms of how HCCR contributes to the malignancies is still unknown. The aim of this review is to summarize the roles of HCCR in cancer progression and the molecular mechanisms involved. PMID:26309489

  16. The role of human cervical cancer oncogene in cancer progression.

    PubMed

    Li, Xin-Yu; Wang, Xin

    2015-01-01

    Human cervical cancer oncogene (HCCR) was identified by differential display RT-PCR by screened abnormally expressed genes in cervical human cancers. The overexpressed gene is not only identified in cervical tissues, but also in various human cancers as leukemia/lymphoma, breast, stomach, colon, liver, kidney and ovarian cancer. For its special sensitivities and specificities in human breast cancer and hepatocellular carcinoma, it is expected to be a new biomarker to replace or combine with the existing biomarkers in the diagnose. The HCCR manifests as a negative regulator of the p53 tumor suppressor gene, and its expression is regulated by the PI3K/Akt signaling pathway, modulated by TCF/?-catenin, it also participates in induction of the c-kit proto-oncogene, in activation of PKC and telomerase activities, but the accurate biochemical mechanisms of how HCCR contributes to the malignancies is still unknown. The aim of this review is to summarize the roles of HCCR in cancer progression and the molecular mechanisms involved. PMID:26309489

  17. Human papillomavirus type 16 E7 oncoprotein upregulates the retinoic acid receptor-beta expression in cervical cancer cell lines and K14E7 transgenic mice.

    PubMed

    Gutiérrez, Jorge; García-Villa, Enrique; Ocadiz-Delgado, Rodolfo; Cortés-Malagón, Enoc M; Vázquez, Juan; Roman-Rosales, Alejandra; Alvarez-Rios, Elizabeth; Celik, Haydar; Romano, Marta C; Üren, Aykut; Lambert, Paul F; Gariglio, Patricio

    2015-10-01

    Persistent infection with high-risk human papillomaviruses is the main etiological factor in cervical cancer (CC). The human papillomavirus type 16 (HPV16) E7 oncoprotein alters several cellular processes, regulating the expression of many genes in order to avoid cell cycle control. Retinoic acid receptor beta (RARB) blocks cell growth, inducing differentiation and apoptosis. This tumor suppressor gene is gradually silenced in late passages of foreskin keratinocytes immortalized with HPV16 and in various tumors, including CC, mainly by epigenetic modifications. We investigated the effect of E7 oncoprotein on RARB gene expression. We found that HPV16 E7 increases RARB mRNA and RAR-beta protein expression both in vitro and in the cervix of young K14E7 transgenic mice. In E7-expressing cells, RARB overexpression is further increased in the presence of the tumor suppressor p53 (TP53) R273C mutant. This effect does not change when either C33-A or E7-expressing C33-A cell line is treated with Trichostatin A, suggesting that E7 enhances RARB expression independently of histone deacetylases inhibition. These findings indicate that RARB overexpression is part of the early molecular events induced by the E7 oncoprotein. PMID:26173416

  18. TBLR1 is a novel prognostic marker and promotes epithelial–mesenchymal transition in cervical cancer

    PubMed Central

    Wang, J; Ou, J; Guo, Y; Dai, T; Li, X; Liu, J; Xia, M; Liu, L; He, M

    2014-01-01

    Background: Invasion and metastasis remain a critical issue in cervical cancer. However, the underlying mechanism of it in cervical cancer remains unclear. The newly discovered protein, TBLR1, plays a crucial role in regulating various key cellular functions. Methods: In this study, western blot, real-time RT–PCR, immunohistochemical staining, 3D morphogenesis Matrigel culture, wound healing and Boyden chamber invasion assays, xenografted tumour model, luciferase assays, and chromatin immunoprecipitation assays were used. Results: The expression of TBLR1 in cervical cancer cell lines and tissues was significantly upregulated at both the RNA and protein levels compared with that in normal cervical cells. Statistical analysis suggested that TBLR1 as an independent prognostic factor was significantly correlated with the clinical stage, survival time and recurrence. Moreover, overexpression of TBLR1 in Hela and Siha cell lines promoted invasion in vitro and in vivo with the increases of the mesenchymal factors vimentin and fibronectin and decreases of the epithelial marker ?-catenin. In contrast, RNAi-mediated knockdown of TBLR1 inhibited epithelial–mesenchymal transition in vitro and in vivo. Further study indicated that this might be mediated via the NF-?B and Wnt/?-Catenin signalling pathway, and involve regulation of Snail and Twist. Conclusions: The TBLR1 protein may be a prognostic marker in cervical cancer and play an important role in the invasion and metastasis of human cervical cancer. PMID:24874481

  19. Relationship between hWAPL polymorphisms and cervical cancer susceptibility

    PubMed Central

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

    2015-01-01

    Purpose: To analyze the correlation of the polymorphisms of human wing-apart like (hWAPL) gene (rs7083506 and rs11202058) with the susceptibility to cervical cancer. Besides, the relationship of haplotypes between the polymorphisms with cervical cancer susceptibility was analyzed. Methods: Taqman probe genotyping method was adopted to detect the genotype distribution of hWAPL rs7083506 and rs11202058 polymorphisms in 117 cervical cancer patients and 128 healthy controls. Linkage disequilibrium and haplotypes were analyzed by Haploview software. ?2 test was utilized to analyze the differences of genotype, allele and haplotype frequencies between the case and control groups. Results: Correlation analysis of hWAPL rs7083506 and rs11202058 polymorphisms with cervical cancer susceptibility was based on the five genetic models. TT genotype of rs7083506 increased the susceptibility of cervical cancer in TT vs. CC model and TT vs. CT+TT model (OR=2.249, 95% CI=1.018-4.970; OR=2.287, 95% CI=1.069-4.896). For rs11202058, the A allele increased the cervical cancer susceptibility (A vs. G, OR=1.502, 95% CI=1.005-2.245). No significant correlation was observed between rs11202058 genotypes and cervical cancer susceptibility. We performed the haplotype analysis between the two polymorphisms, and found that T-A haplotype significantly correlated with cervical cancer, the susceptibility of cervical cancer increased to 1.78 times. Conclusions: Rs7083506 and rs11202058 polymorphisms of hWAPL and their haplotype T-A were associated with cervical cancer. PMID:26722608

  20. Health Beliefs Associated with Cervical Cancer Screening Among Vietnamese Americans

    PubMed Central

    Gao, Wanzhen; Fang, Carolyn Y.; Tan, Yin; Feng, Ziding; Ge, Shaokui; Nguyen, Joseph An

    2013-01-01

    Abstract Background Vietnamese American women represent one of the ethnic subgroups at great risk for cervical cancer in the United States. The underutilization of cervical cancer screening and the vulnerability of Vietnamese American women to cervical cancer may be compounded by their health beliefs. Objective The objective of this study was to explore the associations between factors of the Health Belief Model (HBM) and cervical cancer screening among Vietnamese American women. Methods Vietnamese American women (n=1,450) were enrolled into the randomized controlled trial (RCT) study who were recruited from 30 Vietnamese community-based organizations located in Pennsylvania and New Jersey. Participants completed baseline assessments of demographic and acculturation variables, health care access factors, and constructs of the HBM, as well as health behaviors in either English or Vietnamese. Results The rate of those who had ever undergone cervical cancer screening was 53% (769/1450) among the participants. After adjusting for sociodemographic variables, the significant associated factors from HBM included: believing themselves at risk and more likely than average women to get cervical cancer; believing that cervical cancer changes life; believing a Pap test is important for staying healthy, not understanding what is done during a Pap test, being scared to know having cervical cancer; taking a Pap test is embarrassing; not being available by doctors at convenient times; having too much time for a test; believing no need for a Pap test when feeling well; and being confident in getting a test. Conclusion Understanding how health beliefs may be associated with cervical cancer screening among underserved Vietnamese American women is essential for identifying the subgroup of women who are most at risk for cervical cancer and would benefit from intervention programs to increase screening rates. PMID:23428284

  1. Practice Bulletin No. 157: Cervical Cancer Screening and Prevention.

    PubMed

    2016-01-01

    The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.3 per 100,000 women in 2011 (). The American Cancer Society (ACS) estimated that there would be 12,900 new cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases of the disease and 265,672 resultant deaths each year (). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed ().New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the results. In addition, there are different risk-benefit considerations for women at different ages, as reflected in age-specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer screening (), as did the U.S. Preventive Services Task Force (USPSTF) (). Subsequently, in 2015, ASCCP and the Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA) (). The purpose of this document is to provide a review of the best available evidence regarding the prevention and early detection of cervical cancer. PMID:26695583

  2. Practice Bulletin No. 157 Summary: Cervical Cancer Screening and Prevention.

    PubMed

    2016-01-01

    The incidence of cervical cancer in the United States has decreased more than 50% in the past 30 years because of widespread screening. In 1975, the rate was 14.8 per 100,000 women. By 2011, it decreased to 6.7 per 100,000 women. Mortality from the disease has undergone a similar decrease from 5.55 per 100,000 women in 1975 to 2.3 per 100,000 women in 2011 (1). The American Cancer Society (ACS) estimated that there would be 12,900 new cases of cervical cancer in the United States in 2015, with 4,100 deaths from the disease (2). Cervical cancer is much more common worldwide, particularly in countries without screening programs, with an estimated 527,624 new cases of the disease and 265,672 resultant deaths each year (3). When cervical cancer screening programs have been introduced into communities, marked reductions in cervical cancer incidence have followed (4, 5).New technologies for cervical cancer screening continue to evolve, as do recommendations for managing the results. In addition, there are different risk-benefit considerations for women at different ages, as reflected in age-specific screening recommendations. In 2011, the ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their joint guidelines for cervical cancer screening (6), as did the U.S. Preventive Services Task Force (USPSTF) (7). Subsequently, in 2015, ASCCP and the Society of Gynecologic Oncology (SGO) issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening for cervical cancer that was approved in 2014 by the U.S. Food and Drug Administration (FDA) (8). The purpose of this document is to provide a review of the best available evidence regarding the prevention and early detection of cervical cancer. PMID:26695578

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

    PubMed

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

    2013-01-01

    Cervical cancer is the leading cause of cancer mortality in India, accounting for 17% of all cancer deaths among women aged 30 to 69 years. At current incidence rates, the annual burden of new cases in India is projected to increase to 225,000 by 2025, but there are few large-scale, organized cervical cancer prevention programs in the country. We conducted a review of the cervical cancer prevention research literature and programmatic experiences in India to summarize the current state of knowledge and practices and recommend research priorities to address the gap in services. We found that research and programs in India have demonstrated the feasibility and acceptability of cervical cancer prevention efforts and that screening strategies requiring minimal additional human resources and laboratory infrastructure can reduce morbidity and mortality. However, additional evidence generated through implementation science research is needed to ensure that cervical cancer prevention efforts have the desired impact and are cost-effective. Specifically, implementation science research is needed to understand individual- and community-level barriers to screening and diagnostic and treatment services; to improve health care worker performance; to strengthen links among screening, diagnosis, and treatment; and to determine optimal program design, outcomes, and costs. With a quarter of the global burden of cervical cancer in India, there is no better time than now to translate research findings to practice. Implementation science can help ensure that investments in cervical cancer prevention and control result in the greatest impact. PMID:24217555

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

    PubMed

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

    2015-03-01

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

  5. 75 FR 7282 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-18

    ... SERVICES Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control... Force guidelines for breast and cervical cancer screening; Impact of the revised clinical screening recommendations for both breast and cervical cancer on the National Breast and Cervical Cancer Early...

  6. 76 FR 30723 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-26

    ... SERVICES Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control..., and the Director, CDC, regarding the early detection and control of breast and cervical cancer. The... cervical cancer screening; updates on the National Breast and Cervical Cancer Early Detection...

  7. Detection of Human Papillomavirus in Chronic Cervicitis, Cervical Adenocarcinoma, Intraepithelial Neoplasia and Squamus Cell Carcinoma

    PubMed Central

    Mirzaie-Kashani, Elahe; Bouzari, Majid; Talebi, Ardeshir; Arbabzadeh-Zavareh, Farahnaz

    2014-01-01

    Background: Cervical cancer is the second most common cancer in women worldwide. Recent studies show that human papillomavirus (HPV) DNA is present in all cervical carcinomas and in some cervicitis cases, with some geographical variation in viral subtypes. Therefore determination of the presence of HPV in the general population of each region can help reveal the role of these viruses in tumors. Objectives: This study aimed to estimate the frequency of infection with HPV in cervicitis, cervical adenocarcinoma, intraepithelial neoplasia and squamus cell carcinoma samples from the Isfahan Province, Iran. Patients and Methods: One hundred and twenty two formalin fixed paraffin embedded tissue samples of crevicitis cases and different cervix tumors including cervical intraepithelial neoplasia (CIN) (I, II, III), squamus cell carcinoma (SCC) and adenocarcinoma were collected from histopathological files of Al-Zahra Hospital in Isfahan. Data about histopathological changes were collected by reexamination of the hematoxylin and eosin stained sections. DNA was extracted and subjected to Nested PCR using consensus primers, MY09/MY11 and GP5+/GP6+, designed for amplification of a conserved region of the genome coding for L1 protein. Results: In total 74.5% of the tested samples were positive for HPV. Amongst the tested tumors 8 out of 20 (40%) of CIN (I, II, III), 5 out of 21 (23.8%) of adenocarcinoma cases and 78 out of 79 chronic cervicitis cases were positive for HPV. Conclusions: The rate of different carcinomas and also the rate of HPV infection in each case were lower than other reports from different countries. This could be correlated with the social behavior of women in the area, where they mostly have only one partner throughout their life, and also the rate of smoking behavior of women in the studied population. On the other hand the rate of HPV infection in chronic cervicitis cases was much higher than cases reported by previous studies. This necessitates more attention to the role of human papillomaviruses in the their induction in the studied area. PMID:25147721

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-10-13

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

  10. 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

    2014-12-23

    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

  11. HPV testing as a screen for cervical cancer.

    PubMed

    Goodman, Annekathryn

    2015-01-01

    Human papillomavirus (HPV) has been identified as a necessary factor in the development of pre-invasive and invasive cancers of the lower genital tract, of which cervical cancer is the most prevalent. A molecular understanding of malignant transformation and epidemiologic information has led to the development of many strategies for detection and early intervention. Newer tests for oncogenic subtypes of HPV have made it possible to predict the risk of future development of cervical cancer. This review summarizes the current understanding of HPV related disease and examines the role of HPV testing as a screening tool for cervical cancer. It summarizes the data from prospective and randomized controlled trials on HPV screening from Europe and North America and includes smaller studies from low and middle income countries where cervical cancer is the most common cancer in women. PMID:26126623

  12. Vaccines against human papilloma virus and cervical cancer: an overview.

    PubMed

    Sharma, Savita

    2008-07-01

    The paradigm of preventing human papilloma virus (HPV) infection through currently approved vaccines, namely, Gardasil, manufactured by Merck and Co., Inc. (Whitehouse Station, NJ) and Cervarix, manufactured by GlaxoSmithKline (GSK, Philadelphia) holds tremendous promise for the developing countries in decreasing the burden of HPV infection and its sequelae, such as cervical cancer, genital warts and anogenital cancers. Effective screening programs that have reduced the burden of this killer disease in the developed countries are still lacking in India, despite the high incidence of cervical cancer and the implementation of the National Cancer Control Programme since 1975. The recent breakthrough in the global war against cervical cancer will provide new insight for meeting the future challenge of the prevention of cervical cancer in India. PMID:19876472

  13. Update on prevention and screening of cervical cancer

    PubMed Central

    McGraw, Shaniqua L; Ferrante, Jeanne M

    2014-01-01

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

  14. [Management of Cervical Cancer Stage I B during Pregnancy].

    PubMed

    Suzuki, Kazuhiro; Shinbo, Akiko; Hando, Mioko; Hiromura, Katsuhiko; Mizuno, Kimio

    2015-09-01

    Management and treatment of stage I B1 cervical cancer during pregnancy depends on the estimated gestational age and personal desires. We report 4 cases of stage I B1 cervical cancer during pregnancy that were treated differently. Case 1: A 29- year-old woman, primipara, visited our hospital at 7 weeks' gestation. She was diagnosed with a stage I B1 cervical cancer by using conization at 12 weeks' gestation. She strongly desired childbirth and therefore was treated at 29 weeks' gestation with a simultaneous cesarean section and radical surgery. Case 2: A 26-year-old woman, para 1, was diagnosed with stage I B1 cervical cancer at 23 weeks' gestation. She was treated at 28 weeks' gestation with a simultaneous cesarean section and radical surgery. Case 3: A 36-year-old woman, para 7, at 18 weeks' gestation, visited our hospital because of a stage I A cervical cancer. She chose to undergo abortion and radical surgery, which were performed simultaneously at 21 weeks' gestation. After the surgery, she was diagnosed with a stage I B1 cervical cancer pathologically. Case 4: A 33-year-old woman, para 2, was diagnosed with a stage I B2 cervical cancer at 30 weeks' gestation and was treated with a simultaneous cesarean section and radical surgery at 31 weeks' gestation. PMID:26469174

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Marván, Ma Luisa; Ehrenzweig, Yamilet; Catillo-López, Rosa Lilia

    2016-01-01

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

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

    PubMed

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

    2015-10-01

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

  18. Changing paradigms in the systemic treatment of advanced cervical cancer.

    PubMed

    Pfaendler, Krista S; Tewari, Krishnansu S

    2016-01-01

    Despite availability of primary and secondary prevention measures, cervical cancer persists as one of the most common cancers among women around the world. Although early-stage disease can be cured with radical and even fertility-sparing surgery, patients with metastatic and recurrent cervical cancer have poor prognosis with historically limited treatment options and incurable disease. Significant advances in cervical cancer treatment have emerged as the result of clinical trials that have sought to determine the best therapy to prolong overall and progression-free survival. Most recently, trials that have involved angiogenesis blockade in addition to standard chemotherapy have demonstrated improved overall and progression-free survival. This review serves to highlight pivotal trials in chemotherapy development for advanced, metastatic, and recurrent cervical cancer that includes the paradigm-shifting work that demonstrates increased overall survival with angiogenesis blockade. PMID:26212178

  19. [Epidemiological overview of uterine cervical cancer].

    PubMed

    Hernández-Hernández, Dulce M; Apresa-García, Teresa; Patlán-Pérez, Rosa Ma

    2015-01-01

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

  20. Enhancement of Cisplatin Sensitivity in Human Cervical Cancer: Epigallocatechin-3-Gallate

    PubMed Central

    Kilic, Ulkan; Sahin, Kazim; Tuzcu, Mehmet; Basak, Nazli; Orhan, Cemal; Elibol-Can, Birsen; Kilic, Ertugrul; Sahin, Fikrettin; Kucuk, Omer

    2015-01-01

    Cisplatin is one of the effective chemotherapeutics in the treatment of several types of cancers. However, in addition to the efforts against to its toxicity, the amelioration of cisplatin sensitivity is an important point in treatment of cervical cancer. To do so, additional substances such as epigallocatechin gallate (EGCG), a polyphenol in green tea, have been used in combination with chemotherapeutics. We aimed to investigate the possible molecular pathways to potentiate cervical cancer cell (HeLa) growth inhibition by combination therapy of cisplatin and EGCG. HeLa cells were treated with EGCG (25??M), cisplatin (250?nM), and their combination for 24?h. Cell viability was determined by MTS Assay. We analyzed the expressions of NF-?B p65, COX-2, Nrf2, HO-1, p-mTOR, p-p70S6K1, p-4E-BP1, and p-Akt by Western blot analysis. Herein, we have demonstrated that EGCG works synergistic with cisplatin in inhibiting growth of cervical cancer cells. EGCG improved efficacy of cisplatin treatment in HeLa cells by regulating NF?B p65, COX-2, p-Akt, and p-mTOR pathways, whereas it increased the expression levels of Nrf2/HO-1 in combined therapy. Our observations revealed that EGCG increases the sensitization of cisplatin to cervical cancer cells by inhibiting cell survival and inducing apoptosis. PMID:25988128

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

    Cancer.gov

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

  2. Anthocyanins from Vitis coignetiae Pulliat Inhibit Cancer Invasion and Epithelial-Mesenchymal Transition, but These Effects Can Be Attenuated by Tumor Necrosis Factor in Human Uterine Cervical Cancer HeLa Cells

    PubMed Central

    Lu, Jing Nan; Lee, Won Sup; Yun, Jeong Won; Kim, Min Jeong; Kim, Hye Jung; Kim, Dong Chul; Jeong, Jae-Hoon; Kim, Gon-Sup; Ryu, Chung Ho; Shin, Sung Chul

    2013-01-01

    Recently we have demonstrated that anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) have anticancer effects. Here, we investigate the effects of AIMs on cell proliferation and invasion as well as epithelial-mesenchymal transition (EMT) which have been linked to cancer metastasis in human uterine cervical cancer HeLa cells. AIMs inhibited the invasion of HeLa cells in a dose-dependent manner. AIMs inhibited MMP-9 expression in a dose-dependent manner. AIMs inhibited the motility of HeLa cells in a wound healing test. AIMs still suppressed NF-?B activation induced by TNF. AIMs also inhibited EMT in HeLa cells. AIMs suppressed vimentin, N-cadherin, and ?-catenin expression and induced E-cadherin. AIMs also suppressed expression of ?-catenin and Snail, which was regulated by GSK-3. These effects of AIMs were also limited in the HeLa cells treated with TNF. In conclusion, this study indicates that AIMs have anticancer effects by suppressing NF-?B-regulated genes and EMT, which relates to suppression of I?B? phosphorylation and GSK-3 activity, respectively. However, the effects of AIMs were attenuated in the TNF-high condition. PMID:23864892

  3. MicroRNA-218 increases cellular sensitivity to Rapamycin via targeting Rictor in cervical cancer.

    PubMed

    Li, Jing; Li, Xiaocui; Wang, Jingpu; Wang, Yuan; Qiu, Haifeng

    2015-07-01

    We previously reported that microRNA-218 was frequently lost in cervical cancer and restoration of microRNA-218 increased cellular radio-sensitivity via inhibiting. Herein, we aim to investigate the effects of microRNA-218 on cellular response to mTOR inhibition. The expression of microRNA-218 and Rictor were measured by Taqman PCR and real time PCR in a panel of 15 cervical cancer tissues. MicroRNA-218 was stably overexpressed in four cervical cancer cell lines and a series of in vitro and in vivo experiments were performed to investigate cellular sensitivity to Rapamycin. In primary cultured cervical cancer cells, the expression of microRNA-218 was negatively correlated with the mRNA level of Rictor, which predicted cellular sensitivity to Rapamycin (p = 0.002, R(2)  = 0.6810). In vitro, overexpression of microRNA-218 significantly reduced the level of Rictor and enhanced the growth-inhibition, cell cycle arrest, and apoptosis induced by Rapamycin. In vivo, overexpression of microRNA-218 further enhanced the suppressive effects of Rapamycin on tumor growth. In conclusion, we demonstrated that microRNA-218 could re-sensitize cervical cancer to Rapamycin through targeting Rictor. Moreover, patients with loss of microRNA-218 presented notable resistance to Rapamycin, indicating that microRNA-218 might be a valid marker for patients-stratification in future clinical trials. PMID:25908215

  4. 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.

  5. 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

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

    2015-01-01

    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

  6. Staging of cervical cancer with soft computing.

    PubMed

    Mitra, P; Mitra, S; Pal, S K

    2000-07-01

    This paper describes a way of designing a hybrid decision support system in soft computing paradigm for detecting the different stages of cervical cancer. Hybridization includes the evolution of knowledge-based subnetwork modules with genetic algorithms (GA's) using rough set theory and the Interactive Dichotomizer 3 (ID3) algorithm. Crude subnetworks obtained via rough set theory and the ID3 algorithm are evolved using GA's. The evolution uses a restricted mutation operator which utilizes the knowledge of the modular structure, already generated, for faster convergence. The GA tunes the network weights and structure simultaneously. The aforesaid integration enhances the performance in terms of classification score, network size and training time, as compared to the conventional multilayer perceptron. This methodology also helps in imposing a structure on the weights, which results in a network more suitable for extraction of logical rules and human interpretation of the inferencing procedure. PMID:10916265

  7. A review of cervical cancer research in malaysia.

    PubMed

    Zaridah, S

    2014-08-01

    Despite cervical cancer being potentially preventable, it is the second most common cancer among women in Malaysia. One hundred and five articles related to Cervical Cancer were found in a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. Fifty seven articles were selected and reviewed for the articles' clinical relevance and future research implications. This article reviews the various aspects of cervical cancer in Malaysia, mainly persistent infection of high risk human papillomavirus (HPV), primary prevention (HPV vaccination), screening method (Pap smear issues), and the attitude and knowledge of various groups of Malaysian women that contributed to the failure to reduce the incidence and mortality of cervical cancer. Most of the studies focused on prevention, Pap smear issues, HPV DNA testing, HPV vaccination and various recommendations for prevention of cervical cancer. Secondary prevention by screening is still an important aspect because even with HPV vaccination, screening still plays an important role as vaccination does not cover all high risk HPVs. There is a need to seriously consider a properly organised screening programme, taking into consideration what we already know about the attitude and knowledge of Malaysian women, economic factors and psychosocial issues of the screening method. There is also a large gap in clinical studies on the outcome, management and survival of cervical cancer patients in Malaysia. PMID:25417949

  8. Cervical cancer screening: what's new and what's coming?

    PubMed

    Jin, Xian Wen; Lipold, Laura; McKenzie, Margaret; Sikon, Andrea

    2013-03-01

    In their 2012 guidelines for cervical cancer screening, several organizations call for less-frequent but more-effective screening that incorporates testing for human papillomavirus (HPV). We review these recommendations and the possible future direction of screening. PMID:23456465

  9. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  12. 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

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

    Cancer.gov

    Conducted in India, this study is evaluating the effectiveness of a well-planned health education breast and cervical cancer program in regions where there are limited resources. By using trained primary health workers to conduct low-cost screening methods, such as a clinical breast examination or visual inspection of the cervix painted with 4% acetic acid, the study hopes to reduce the incidence of cervical cancer and mortality.

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

    Cancer.gov

    This randomized controlled trial will evaluate the effectiveness of an outreach intervention in increasing Pap testing among never screened Vietnamese women, as well as examine the effectiveness of the intervention in improving knowledge about cervical cancer and Pap test and assess the cost-effectiveness of the intervention. 250 Vietnamese women between age 20 and 79, with no prior cervical cancer screening, will be individually randomized to either intervention or control group.

  15. Cervical cancer worry and screening among appalachian women.

    PubMed

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

    2015-04-01

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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2016-01-01

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

  18. Transcription factor KLF4 regulates microRNA-544 that targets YWHAZ in cervical cancer.

    PubMed

    Mao, Langyong; Zhang, Yan; Deng, Xiaolong; Mo, Wenjuan; Yu, Yao; Lu, Hong

    2015-01-01

    The deregulation of microRNAs has been demonstrated in various tumor processes. Here, we report that microRNA-544 (miR-544) is decreased in cervical cancer tissues compared with normal cervical tissues. To identify the mechanisms involved in miR-544 deregulation, we studied the regulation of miR-544 expression at the transcriptional level. We first identified the transcriptional start site of miR-544 by 5' rapid amplification of cDNA ends and subsequently determined the miR-544 promoter. We discovered that the transcription factor Krueppel-like factor 4 (KLF4) is involved in the transcriptional regulation of miR-544 through interaction with the miR-544 promoter. In addition, we found that miR-544 directly targets the YWHAZ oncogene and functions as a tumor suppressor in cervical cancer cells. miR-544 is involved in cell cycle regulation and suppresses cervical cancer cell proliferation, colony formation, migration and invasion in a manner associated with YWHAZ downregulation. In summary, our findings demonstrate that KLF4 upregulates miR-544 transcription by activating the miR-544 promoter and that miR-544 functions as a tumor suppressor by targeting YWHAZ. Therefore, miR-544 may be a potential novel therapeutic target and prognostic marker for cervical cancer. PMID:26269755

  19. Transcription factor KLF4 regulates microRNA-544 that targets YWHAZ in cervical cancer

    PubMed Central

    Mao, Langyong; Zhang, Yan; Deng, Xiaolong; Mo, Wenjuan; Yu, Yao; Lu, Hong

    2015-01-01

    The deregulation of microRNAs has been demonstrated in various tumor processes. Here, we report that microRNA-544 (miR-544) is decreased in cervical cancer tissues compared with normal cervical tissues. To identify the mechanisms involved in miR-544 deregulation, we studied the regulation of miR-544 expression at the transcriptional level. We first identified the transcriptional start site of miR-544 by 5’ rapid amplification of cDNA ends and subsequently determined the miR-544 promoter. We discovered that the transcription factor Krueppel-like factor 4 (KLF4) is involved in the transcriptional regulation of miR-544 through interaction with the miR-544 promoter. In addition, we found that miR-544 directly targets the YWHAZ oncogene and functions as a tumor suppressor in cervical cancer cells. miR-544 is involved in cell cycle regulation and suppresses cervical cancer cell proliferation, colony formation, migration and invasion in a manner associated with YWHAZ downregulation. In summary, our findings demonstrate that KLF4 upregulates miR-544 transcription by activating the miR-544 promoter and that miR-544 functions as a tumor suppressor by targeting YWHAZ. Therefore, miR-544 may be a potential novel therapeutic target and prognostic marker for cervical cancer. PMID:26269755

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

    Cancer.gov

    The purpose of this study is to understand the molecular changes linked to HIV-associated invasive cervical cancer (ICC) and its precursor, cervical intraepithelial neoplasia grade 3 (CIN 3). A key goal of the study is to create low-cost assays that identify molecular changes marking the development of ICC and CIN-3. Cost effective assays for detection of cervical cancer are needed in developing areas, where HIV is endemic and resources are limited. Current tests are costly and insensitive, which results in over-treatment.

  1. Application of PDT for Uterine Cervical Cancer

    PubMed Central

    Kawasaki, K.; Suehiro, Y.; Kunugi, T.; Umayahara, K.; Akiya, T.; Iwabuchi, H.; Sakunaga, H.; Sakamoto, M.; Sugishita, T.; Tenjin, Y.

    1999-01-01

    We have been performing PDT using Excimer Dye Laser (EDL) or YAG-OPO laser, a type of low power laser, both of which have a considerably higher degree of tissue penetration even when compared to PDT using Argon Dye Laser (ADL). PDT is a relatively simple procedure without any bleeding and does not require anesthesia since it causes no pain. PDT is performed 48 h after intravenous injection of 1.5–2.0 mg/kg of PHE (Photofrin®). Precise spot irradiation is possible using a colposcope with an optical laser path. We also use a cervical probe which enables photoirradiation of the entire cervical canal. We have performed PDT on 131 cases (95 CIS, 31 dysplasia, 1 vulval dysplasia (VIN), 3 squamous cell carcinoma, microinvasion, and 1 CIS + endocervical adenocarcinoma, microinvasion). Of these cases, 127 became CR (96.9%). The first CR case was 10 years ago and no recurrence has been observed yet. PDT is extremely effective to preserve fertility. Except for sensitive reactions to sunlight, there are no noticeable side effects or difficulties related to pregnancy or delivery. We expect that in the near future PDT will be performed using diode lasers and without hospitalization due to new photosensitizers which have shorter retention times. PMID:18493501

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Objectives Most non-screen-detected cervical cancers are advanced stage. We assess the potential for cytology to expedite diagnosis when used outside of routine call and recall screening for cervical cancer. Methods Two cohorts of women with cytology that did not appear to have been taken as part of routine screening, nested within a census of cervical cytology, in England between April 2007 and March 2010 were studied: 93,322 women aged 40–69 at first cytology, and 14,668 women aged ?70. The diagnostic performance of high grade cervical squamous intraepithelial lesion (HSIL) or worse cytology was estimated. We also estimated case-fatality from stage distribution in women aged ?66 with and without cytology in the year prior to diagnosis. Results There were 259 cancers diagnosed in women aged 40–69 at first cytology, and 78 in women aged ?70. The sensitivity of cytology ? HSIL for cancer was 89% and 83% respectively, and the number of women needed to test to identify one cancer was 404 (95% confidence interval [CI]: 355–462) and 226 (95% CI: 177–292) respectively. Women aged ?66 with cytology within a year of diagnosis had earlier stage cancers than those without, corresponding to a 17–22% reduction in case fatality. Conclusions Cervical cytology is an excellent identifier of cancer among women tested outside routine screening call and recall. Its use as a triage tool, for instance in women with vague gynaecological symptoms, could facilitate earlier stage diagnosis and reduce cervical cancer mortality. PMID:26346038

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

    PubMed

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

    2015-10-01

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

  5. Down-regulation of the expression of CCAAT/enhancer binding protein ? gene in cervical squamous cell carcinoma

    PubMed Central

    2014-01-01

    Background Cervical carcinoma is the second most common cancer and is an important cause of death in women worldwide. CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that regulate cellular differentiation and proliferation in a variety of tissues. However, the role of C/EBP? gene in cervical cancer is still not clear. Methods We investigated the expression of C/EBP? gene in cervical squamous cell carcinoma. C/EBP? mRNA level was measured by real-time quantitative RT-PCR in cervical cancer tissues and their adjacent normal tissues. C/EBP? protein level was measured by immunohistochemistry. Methylation in the promoter of C/EBP? gene was detected by MALDI TOF MassARRAY. We transfected HeLa cells with C/EBP? expression vector. C/EBP? expression in HeLa cells was examined and HeLa cell proliferation was measured by MTT assay and HeLa cells migration was analyzed by matrigel-coated transwell migration assays. Results There were significant difference in C/EBP? protein expression between chronic cervicitis and cervical carcinoma (P?cervical cancer tissues than in normal cervical tissues (P?cervical cancer than in normal cervical tissues (P?cells inhibited cell proliferation and decreased cell migration. Conclusions Our results indicate that reduced C/EBP? gene expression may play a role in the development of cervical squamous cell carcinoma. PMID:24913332

  6. Epidemiology of cervical cancer with special focus on India

    PubMed Central

    Sreedevi, Aswathy; Javed, Reshma; Dinesh, Avani

    2015-01-01

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

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

    ERIC Educational Resources Information Center

    Ehrhardt, Jeanie

    2007-01-01

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

  8. EGFR Promoter Methylation, EGFR Mutation, and HPV Infection in Chinese Cervical Squamous Cell Carcinoma.

    PubMed

    Zhang, Wei; Jiang, Yinghao; Yu, Qingmiao; Qiang, Shaoying; Liang, Ping; Gao, Yane; Zhao, Xingye; Liu, Wenchao; Zhang, Ju

    2015-10-01

    Therapy strategy toward epidermal growth factor receptor (EGFR) inhibition in cervical cancer has been ongoing. EGFR promoter methylation status and EGFR tyrosine kinase inhibitor-sensitive mutations in cervical cancer may be significant for clinical outcome prediction using anti-EGFR treatment. In this study, EGFR tyrosine kinase inhibitor-sensitive mutations, EGFR exons 18, 19, and 21 mutations, were detected by sequencing in a total of 293 Chinese cervical squamous cell carcinoma tissue samples. EGFR promoter methylation status was detected by an EGFR asymmetric PCR and hybridization-fluorescence polarization assay and sequencing in 293 Chinese cervical squamous cell carcinoma tissue samples. High-risk human papillomavirus (HPV) genotypes in 293 Chinese cervical squamous cell carcinoma tissue samples were detected by an asymmetric GP5+/6+ PCR and hybridization-fluorescence polarization assay. No EGFR exons 18, 19, and 21 mutations were detected, EGFR promoter methylation status was identified in 98 samples, and HPV 16 infection was the first frequent HPV genotype. The methylated EGFR promoter was identified most frequently in cervical squamous cell carcinoma samples with HPV 16 infection (53.4%). Statistical significant difference of EGFR promoter methylation prevalence was found between HPV 16 and other HPV genotypes (P<0.01). This study suggested that there was no EGFR tyrosine kinase inhibitor-sensitive mutation in EGFR exons 18, 19, and 21 in Chinese cervical squamous cell carcinoma tissue samples. EGFR promoter methylation was common and it might be associated with HPV 16 infection in Chinese cervical squamous cell carcinoma. The results provided a novel understanding and an applicable pharmacogenomic tool for individualized management of cervical cancer patients. PMID:25789535

  9. Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck

    ClinicalTrials.gov

    2015-12-08

    Carcinoma, Squamous Cell of Head and Neck; HPV Positive Oropharyngeal Squamous Cell Carcinoma; Hypopharyngeal Cancer; Early Invasive Cervical Squamous Cell Carcinoma; Carcinoma of Larynx; Cancer of Nasopharynx

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

    SciTech Connect

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

    2009-10-23

    MicroRNAs are involved in cancer-related processes. The microRNA-21(miR-21) has been identified as the only miRNA over-expressed in a wide variety of cancers, including cervical cancer. However, the function of miR-21 is unknown in cervical carcinomas. In this study, we found that the inhibition of miR-21 in HeLa cervical cancer cells caused profound suppression of cell proliferation, and up-regulated the expression of the tumor suppressor gene PDCD4. We also provide direct evidence that PDCD4-3'UTR is a functional target of miR-21 and that the 18 bp putative target site can function as the sole regulatory element in HeLa cells. These results suggest that miR-21 may play an oncogenic role in the cellular processes of cervical cancer and may serve as a target for effective therapies.

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

    Cancer.gov

    The progression of human papillomavirus (HPV) infection to cervical neoplasia is likely influenced by the immune response. Toll-like receptors (TLRs) induce secretion of cytokines and activation of T cells that may play an important role in cervical immunity to HPV infection.

  12. Women's lay knowledge of cervical cancer/cervical screening: accounting for non-attendance at cervical screening clinics.

    PubMed

    Neilson, A; Jones, R K

    1998-09-01

    An assessment of women's knowledge of cervical screening and cervical cancer was considered important as up to 92% of those dying from this form of cancer had never been tested. What were the reasons which determined their non-attendance? Issues to be addressed were reactions to invitation, women's knowledge of screening, and the possible factors which they envisaged as being associated with cervical cancer. Other issues to be considered were practical problems associated with attendance, and preference for the sex and professional status of the health professionals involved; 187 women in a general practitioner practice in Lothian, Scotland were targeted by questionnaire. As with other studies in this field 50% of those contacted were ineligible for a variety of reasons. Seventy-two women completed the questionnaire, providing a mix of qualitative and quantitative data. Although the majority of women felt the invitation to attend screening was clear and easy to understand, there was a lack of knowledge with regard to both the screening itself and the possible causes of cervical cancer. The main 'causes' were seen as higher sexual activity among those aged under 37 and smoking and a virus by those over 37. The majority of women showed preference for a female professional to take the smear. Practical problems of time and venue were not considered insurmountable. The main reasons cited for non-compliance were the fear and dislike of the test itself. PMID:9756225

  13. Lactobacillus Decelerates Cervical Epithelial Cell Cycle Progression

    PubMed Central

    Vielfort, Katarina; Weyler, Linda; Söderholm, Niklas; Engelbrecht, Mattias; Löfmark, Sonja; Aro, Helena

    2013-01-01

    We investigated cell cycle progression in epithelial cervical ME-180 cells during colonization of three different Lactobacillus species utilizing live cell microscopy, bromodeoxyuridine incorporation assays, and flow cytometry. The colonization of these ME-180 cells by L. rhamnosus and L. reuteri, originating from human gastric epithelia and saliva, respectively, was shown to reduce cell cycle progression and to cause host cells to accumulate in the G1 phase of the cell cycle. The G1 phase accumulation in L. rhamnosus-colonized cells was accompanied by the up-regulation and nuclear accumulation of p21. By contrast, the vaginal isolate L. crispatus did not affect cell cycle progression. Furthermore, both the supernatants from the lactic acid-producing L. rhamnosus colonies and lactic acid added to cell culture media were able to reduce the proliferation of ME-180 cells. In this study, we reveal the diversity of the Lactobacillus species to affect host cell cycle progression and demonstrate that L. rhamnosus and L. reuteri exert anti-proliferative effects on human cervical carcinoma cells. PMID:23675492

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

    PubMed Central

    Ntekim, Atara; Campbell, Oladapo; Rothenbacher, Dietrich

    2015-01-01

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

  15. Improving compliance with cervical cancer screening guidelines

    PubMed Central

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

    2015-01-01

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

  16. Nominated texture based cervical cancer classification.

    PubMed

    Mariarputham, Edwin Jayasingh; Stephen, Allwin

    2015-01-01

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

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

    Cancer.gov

    This project seeks to reduce the disproportionately high cervical cancer rates among middle age and older Appalachian women with low rates of Pap testing. It is utilizing a community participatory, tailored, faith-based intervention entitled "Faith Moves Mountains." A multidisciplinary team of social scientists, community leaders, physicians, and cancer control experts are evaluating the efficacy of the intervention using a grouprandomized experimental design.

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  20. Tanshinone IIA inhibits viral oncogene expression leading to apoptosis and inhibition of cervical cancer.

    PubMed

    Munagala, Radha; Aqil, Farrukh; Jeyabalan, Jeyaprakash; Gupta, Ramesh C

    2015-01-28

    Human papilloma virus (HPV) is the well-established etiological factor of cervical cancer. E6 and E7 oncoproteins expressed by HPV are known to inactivate tumor suppressor proteins p53 and pRb, respectively. Tanshinone IIA (Tan IIA) is a diterpenoid naphthoquinone found in the traditional Chinese medicine Danshen (Salvia sp.). Tan IIA has been shown to possess anti-tumor activity against several cancer types. In this study we show that Tan IIA potently inhibited proliferation of the human cervical cancer CaSki, SiHa, HeLa and C33a cells. Mechanistically in HPV positive CaSki cells, Tan IIA was found to (i) downregulate expression of HPV E6 and E7 genes and modulate associated proteins E6AP and E2F1, (ii) cause S phase cell cycle arrest, (iii) induce accumulation of p53 and alter expression of p53-dependent targets, (iv) modulate pRb and related proteins, and (v) cause p53-mediated apoptosis by moderating Bcl2, Bax, caspase-3, and PARP cleavage expressions. In vivo, Tan IIA resulted in over 66% reduction in tumor volume of cervical cancer xenograft in athymic nude mice. Tan IIA treated tumor tissues had lower expression of proliferation marker PCNA and changes in apoptosis targets were in agreement with in vitro studies, further confirming reduced proliferation and involvement of multiple targets behind anti-cancer effects. This is the first demonstration of Tan IIA to possess significant anti-viral activity by repressing HPV oncogenes leading to inhibition of cervical cancer. Together, our data suggest that Tan IIA can be exploited as a potent therapeutic agent for the prevention and treatment of cervical and other HPV-related cancers. PMID:25304375

  1. Multistep Model of Cervical Cancer: Participation of miRNAs and Coding Genes

    PubMed Central

    López, Angelica Judith Granados; López, Jesús Adrián

    2014-01-01

    Aberrant miRNA expression is well recognized as an important step in the development of cancer. Close to 70 microRNAs (miRNAs) have been implicated in cervical cancer up to now, nevertheless it is unknown if aberrant miRNA expression causes the onset of cervical cancer. One of the best ways to address this issue is through a multistep model of carcinogenesis. In the progression of cervical cancer there are three well-established steps to reach cancer that we used in the model proposed here. The first step of the model comprises the gene changes that occur in normal cells to be transformed into immortal cells (CIN 1), the second comprises immortal cell changes to tumorigenic cells (CIN 2), the third step includes cell changes to increase tumorigenic capacity (CIN 3), and the final step covers tumorigenic changes to carcinogenic cells. Altered miRNAs and their target genes are located in each one of the four steps of the multistep model of carcinogenesis. miRNA expression has shown discrepancies in different works; therefore, in this model we include miRNAs recording similar results in at least two studies. The present model is a useful insight into studying potential prognostic, diagnostic, and therapeutic miRNAs. PMID:25192291

  2. Molecular transitions from papillomavirus infection to cervical precancer and cancer: Role of stromal estrogen receptor signaling.

    PubMed

    den Boon, Johan A; Pyeon, Dohun; Wang, Sophia S; Horswill, Mark; Schiffman, Mark; Sherman, Mark; Zuna, Rosemary E; Wang, Zhishi; Hewitt, Stephen M; Pearson, Rachel; Schott, Meghan; Chung, Lisa; He, Qiuling; Lambert, Paul; Walker, Joan; Newton, Michael A; Wentzensen, Nicolas; Ahlquist, Paul

    2015-06-23

    To study the multistep process of cervical cancer development, we analyzed 128 frozen cervical samples spanning normalcy, increasingly severe cervical intraepithelial neoplasia (CIN1- CIN3), and cervical cancer (CxCa) from multiple perspectives, revealing a cascade of progressive changes. Compared with normal tissue, expression of many DNA replication/repair and cell proliferation genes was increased in CIN1/CIN2 lesions and further sustained in CIN3, consistent with high-risk human papillomavirus (HPV)-induced tumor suppressor inactivation. The CIN3-to-CxCa transition showed metabolic shifts, including decreased expression of mitochondrial electron transport complex components and ribosomal protein genes. Significantly, despite clinical, epidemiological, and animal model results linking estrogen and estrogen receptor alpha (ER?) to CxCa, ER? expression declined >15-fold from normalcy to cancer, showing the strongest inverse correlation of any gene with the increasing expression of p16, a marker for HPV-linked cancers. This drop in ER? in CIN and tumor cells was confirmed at the protein level. However, ER? expression in stromal cells continued throughout CxCa development. Our further studies localized stromal ER? to FSP1+, CD34+, SMA- precursor fibrocytes adjacent to normal and precancerous CIN epithelium, and FSP1-, CD34-, SMA+ activated fibroblasts in CxCas. Moreover, rank correlations with ER? mRNA identified IL-8, CXCL12, CXCL14, their receptors, and other angiogenesis and immune cell infiltration and inflammatory factors as candidates for ER?-induced stroma-tumor signaling pathways. The results indicate that estrogen signaling in cervical cancer has dramatic differences from ER?+ breast cancers, and imply that estrogen signaling increasingly proceeds indirectly through ER? in tumor-associated stromal fibroblasts. PMID:26056290

  3. Molecular transitions from papillomavirus infection to cervical precancer and cancer: Role of stromal estrogen receptor signaling

    PubMed Central

    den Boon, Johan A.; Pyeon, Dohun; Wang, Sophia S.; Horswill, Mark; Schiffman, Mark; Sherman, Mark; Zuna, Rosemary E.; Wang, Zhishi; Hewitt, Stephen M.; Pearson, Rachel; Schott, Meghan; Chung, Lisa; He, Qiuling; Lambert, Paul; Walker, Joan; Newton, Michael A.; Wentzensen, Nicolas; Ahlquist, Paul

    2015-01-01

    To study the multistep process of cervical cancer development, we analyzed 128 frozen cervical samples spanning normalcy, increasingly severe cervical intraepithelial neoplasia (CIN1– CIN3), and cervical cancer (CxCa) from multiple perspectives, revealing a cascade of progressive changes. Compared with normal tissue, expression of many DNA replication/repair and cell proliferation genes was increased in CIN1/CIN2 lesions and further sustained in CIN3, consistent with high-risk human papillomavirus (HPV)-induced tumor suppressor inactivation. The CIN3-to-CxCa transition showed metabolic shifts, including decreased expression of mitochondrial electron transport complex components and ribosomal protein genes. Significantly, despite clinical, epidemiological, and animal model results linking estrogen and estrogen receptor alpha (ER?) to CxCa, ER? expression declined >15-fold from normalcy to cancer, showing the strongest inverse correlation of any gene with the increasing expression of p16, a marker for HPV-linked cancers. This drop in ER? in CIN and tumor cells was confirmed at the protein level. However, ER? expression in stromal cells continued throughout CxCa development. Our further studies localized stromal ER? to FSP1+, CD34+, SMA? precursor fibrocytes adjacent to normal and precancerous CIN epithelium, and FSP1?, CD34?, SMA+ activated fibroblasts in CxCas. Moreover, rank correlations with ER? mRNA identified IL-8, CXCL12, CXCL14, their receptors, and other angiogenesis and immune cell infiltration and inflammatory factors as candidates for ER?-induced stroma–tumor signaling pathways. The results indicate that estrogen signaling in cervical cancer has dramatic differences from ER?+ breast cancers, and imply that estrogen signaling increasingly proceeds indirectly through ER? in tumor-associated stromal fibroblasts. PMID:26056290

  4. CERVICAL CANCER CONTROL RESEARCH IN VIETNAMESE AMERICAN COMMUNITIES

    PubMed Central

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

    2009-01-01

    Census data show that the US Vietnamese population now exceeds 1,250,000. Cervical cancer among Vietnamese American women has been identified as an important health disparity. Available data indicate the cervical cancer disparity may be due to low Pap testing rates rather than variations in HPV infection rates and/or types. The cervical cancer incidence rates among Vietnamese and non-Latina white women in California during 2000–2002 were 14.0 and 7.3 per 100,000, respectively. Only 70% of Vietnamese women who participated in the 2003 California Health Interview Survey reported a recent Pap smear, compared to 84% of non-Latina white women. Higher levels of cervical cancer screening participation among Vietnamese women are strongly associated with current/previous marriage, having a usual source of care/doctor, and previous physician recommendation. Vietnamese language media campaigns and lay health worker intervention programs have been effective in increasing Pap smear use in Vietnamese American communities. Cervical cancer control programs for Vietnamese women should address knowledge deficits; enable women who are without a usual source of care to find a primary care doctor; and improve patient-provider communication by encouraging health care providers to recommend Pap testing, as well as by empowering women to ask for testing. PMID:18990732

  5. 77 FR 66469 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-05

    ... SERVICES Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control... of the aforementioned committee: Name: Breast and Cervical Cancer Early Detection and Control..., regarding the early detection and control of breast and cervical cancer. The committee makes...

  6. 77 FR 66469 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-05

    ... HUMAN SERVICES Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and... meeting of the aforementioned committee: Name: Breast and Cervical Cancer Early Detection and Control..., regarding the early detection and control of breast and cervical cancer. The committee makes...

  7. College Students' Knowledge of the Connection between HPV and Cervical Cancer.

    ERIC Educational Resources Information Center

    Applegate, Trent E.; Jones, Iesha K.

    2002-01-01

    Investigated college students' knowledge of the relationship between human papillomavirus (HPV) and cervical cancer. Few students knew what HPV was. Most of the females who had been screened knew that a Pap smear could detect HPV and cervical cancer. Over half of the students did not realize the link between HPV and cervical cancer. Students…

  8. Cervical Cancer Screening Interventions for U.S. Latinas: A Systematic Review

    ERIC Educational Resources Information Center

    Corcoran, Jacqueline; Dattalo, Patrick; Crowley, Meghan

    2012-01-01

    The high cervical cancer mortality rate among Latinas compared with other ethnic groups in the United States is of major concern. Latina women are almost twice as likely to die from cervical cancer as non-Hispanic white women. To improve Latina cervical cancer screening rates, interventions have been developed and tested. This systematic review…

  9. Impact of Cervical Cancer Screening Guidelines on Screening for Chlamydia.

    PubMed

    Ursu, Allison; Sen, Ananda; Ruffin, Mack

    2015-01-01

    The highest prevalence of chlamydia infection in the United States is among people aged 15 to 24 years. We assessed the impact of not doing routine cervical cancer screening on the rates of chlamydia screening in women aged 15 to 21 years. We classified visits to family medicine ambulatory clinics according to their timing relative to the 2009 guideline change that led to more restrictive cervical cancer screening. Women had higher odds of being screened for chlamydia before vs after the guideline change (odds ratio = 13.97; 95% CI, 9.17-21.29; P <.001). Chlamydia and cervical cancer screening need to be uncoupled and new screening opportunities should be identified. PMID:26195682

  10. Prevention and early detection of cervical cancer in the UK.

    PubMed

    Foran, Claire; Brennan, Arthur

    This literature review explores the prevention and early detection of cervical cancer in the UK. Current findings indicate that there is a risk for women under the age of 25 years, who may develop cervical cancer. There appears to be a gap in UK policy that may overlook these women, who are beneath the age for initial screening but exceed the age for vaccination. Despite the inextricable link between sexual activity and cervical cancer, cervical screening and sexual health promotion still appear to be disjointed, and the role of a sexually transmitted infection leading to the development of cervical cancer has not been emphasised enough in public health messages. Further training should be provided and its impact monitored, designed to address this anomaly in health promotion. There are many barriers to health promotion including, those of a societal, cultural and religious nature. Additional research is required to ascertain the types of educational and awareness interventions that would be most effective in promoting and encouraging positive sexual behaviours among young people, and to explore how these might be successfully implemented. PMID:26018178

  11. Prevalence and risk factors for cervical cancer and pre-cancerous lesions in Rwanda

    PubMed Central

    Makuza, Jean Damascène; Nsanzimana, Sabin; Muhimpundu, Marie Aimee; Pace, Lydia Eleanor; Ntaganira, Joseph; Riedel, David James

    2015-01-01

    Introduction Cervical cancer prevalence in Rwanda has not been well-described. Visual inspection with acetic acid or Lugol solution has been shown to be effective for cervical cancer screening in low resource settings. The aim of the study is to understand the prevalence and risk factors for cervical cancer and pre- cancerous lesions among Rwandan women between 30 and 50 old undergoing screening. Methods This cross-sectional analytical study was done in 3 districts of Rwanda from October 2010 to June 2013. Women aged 30 to 50 years screened for cervical cancer by trained doctors, nurses and midwives. Prevalence of pre-cancerous and cancerous cervical lesions was determined. Bivariate and multivariate logistic regressions were used to assess risk factors associated with cervical cancer. Results The prevalence of pre-cancer and invasive cervical cancer was 5.9% (95% CI 4.5, 7.5) and 1.7% (95% CI 0.9, 2.5), respectively. Risk factors associated with cervical cancer in multivariate analysis included initiation of sexual activity at less than 20 years (OR=1.75; 95% CI=(1.01, 3.03); being unmarried (single, divorced and widowed) (OR=3.29; 95% CI=( 1.26, 8.60)); Older age of participants (OR= 0.52; 95% CI= (0.28, 0.97)), older age at the first pregnancy (OR=2.10; 95% CI=(1.20, 3.67) and higher number of children born (OR=0.42; 95%CI =(0.23, 0.76)) were protective. Conclusion Cervical cancer continues to be a public health problem in Rwanda, but screening using VIA is practical and feasible even in rural settings. PMID:26664527

  12. Metabolic components and recurrence in early-stage cervical cancer.

    PubMed

    Ahn, Hee Kyung; Shin, Jin Woo; Ahn, Hong Yup; Park, Chan-Yong; Lee, Nak Woo; Lee, Jae Kwan; Hwang, In Cheol

    2015-03-01

    Epidemiological evidence suggests that the metabolic syndrome (MetS) is associated with increased risk of cervical cancer. However, research on the impact of MetS on prognosis in cervical cancer is lacking. This study investigated the association between MetS and recurrence-free survival (RFS) in patients with early-stage cervical cancer. This is a retrospective study of patients diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) stage I-II cervical cancer in three tertiary hospitals during 2006-2009. Cox proportional hazards model was used to estimate the association between MetS or MetS components and RFS. We were able to evaluate MetS status in 84 patients out of 127. Forty patients had MetS. RFS was not significantly different according to MetS status; however, there was no further event of recurrence in non-MetS group after 2 years from primary surgical treatment. Hypertriglyceridemia (HR 3.67, 95% CI 1.18-11.43) and impaired fasting glucose (HR 4.30, 95% CI 1.23-15.03) were independent risk factors for shorter RFS, after adjustment for age, lymph node involvement, tumor involvement of resection margin, parametrial invasion, FIGO stage at diagnosis, and adjuvant treatment. Hypertriglyceridemia and impaired fasting glucose were associated with higher risk of recurrence in patients with early-stage cervical cancer. Prospective validation in large populations and further studies on the impact of MetS treatment in patients with cervical cancer are warranted. PMID:25398694

  13. COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer.

    PubMed

    Gao, Shujun; Fang, Lekun; Phan, Liem Minh; Qdaisat, Aiham; Yeung, Sai-Ching J; Lee, Mong-Hong

    2015-09-29

    Cervical cancer is one of the leading causes of cancer death in women. Human papillomaviruses (HPVs) are the major cause in almost 99.7% of cervical cancer. E6 oncoprotein of HPV and E6-associated protein (E6AP) are critical in causing p53 degradation and malignancy. Understanding the E6AP regulation is critical to develop treating strategy for cervical cancer patients. The COP9 signalosome subunit 6 (CSN6) is involved in ubiquitin-mediated protein degradation. We found that both CSN6 and E6AP are overexpressed in cervical cancer. We characterized that CSN6 associated with E6AP and stabilized E6AP expression by reducing E6AP poly-ubiquitination, thereby regulating p53 activity in cell proliferation and apoptosis. Mechanistic studies revealed that CSN6-E6AP axis can be regulated by EGF/Akt signaling. Furthermore, inhibition of CSN6-E6AP axis hinders cervical cancer growth in mice. Taken together, our results indicate that CSN6 is a positive regulator of E6AP and is important for cervical cancer development. PMID:26318036

  14. Rotating-shield brachytherapy for cervical cancer

    NASA Astrophysics Data System (ADS)

    Yang, Wenjun; Kim, Yusung; Wu, Xiaodong; Song, Qi; Liu, Yunlong; Bhatia, Sudershan K.; Sun, Wenqing; Flynn, Ryan T.

    2013-06-01

    In this treatment planning study, the potential benefits of a rotating shield brachytherapy (RSBT) technique based on a partially-shielded electronic brachytherapy source were assessed for treating cervical cancer. Conventional intracavitary brachytherapy (ICBT), intracavitary plus supplementary interstitial (IS+ICBT), and RSBT treatment plans for azimuthal emission angles of 180° (RSBT-180) and 45° (RSBT-45) were generated for five patients. For each patient, high-risk clinical target volume (HR-CTV) equivalent dose in 2 Gy fractions (EQD2) (?/? = 10 Gy) was escalated until bladder, rectum, or sigmoid colon tolerance EQD2 values were reached. External beam radiotherapy dose (1.8 Gy × 25) was accounted for, and brachytherapy was assumed to have been delivered in 5 fractions. IS+ICBT provided a greater HR-CTV D90 (minimum EQD2 to the hottest 90%) than ICBT. D90 was greater for RSBT-45 than IS+ICBT for all five patients, and greater for RSBT-180 than IS+ICBT for two patients. When the RSBT-45/180 plan with the lowest HR-CTV D90 that was greater than the D90 the ICBT or IS+ICBT plan was selected, the average (range) of D90 increases for RSBT over ICBT and IS+ICBT were 16.2 (6.3-27.2)and 8.5 (0.03-20.16) Gy, respectively. The average (range) treatment time increase per fraction of RSBT was 34.56 (3.68-70.41) min over ICBT and 34.59 (3.57-70.13) min over IS+ICBT. RSBT can increase D90 over ICBT and IS+ICBT without compromising organ-at-risk sparing. The D90 and treatment time improvements from RSBT depend on the patient and shield emission angle.

  15. Patterns of known and novel small RNAs in human cervical cancer.

    PubMed

    Lui, Weng-Onn; Pourmand, Nader; Patterson, Bruce K; Fire, Andrew

    2007-07-01

    Recent studies suggest that knowledge of differential expression of microRNAs (miRNA) in cancer may have substantial diagnostic and prognostic value. Here, we use a direct sequencing method to characterize the profiles of miRNAs and other small RNA segments for six human cervical carcinoma cell lines and five normal cervical samples. Of 166 miRNAs expressed in normal cervix and cancer cell lines, we observed significant expression variation of six miRNAs between the two groups. To further show the biological relevance of our findings, we examined the expression level of two significantly varying miRNAs in a panel of 29 matched pairs of human cervical cancer and normal cervical samples. Reduced expression of miR-143 and increased expression of miR-21 were reproducibly displayed in cancer samples, suggesting the potential value of these miRNAs as tumor markers. In addition to the known miRNAs, we found a number of novel miRNAs and an additional set of small RNAs that do not meet miRNA criteria. PMID:17616659

  16. Cervical cancer with human papilloma virus and Epstein Barr virus positive.

    PubMed

    Prayitno, Adi

    2006-01-01

    The Early-7 (E7) protein of HPV binds to the underphosphorelated form of the tumor suppressor protein--pRb and displaces the E2F transcription factor that is normally bound by pRb. The latent membrane protein-1 (LMP-1) of EBV prevents apoptosis of B cells by up regulating the expression of bcl-2, and it activates growth promoting pathway that are normally triggered by T cell-derivate signal. The aims of this study to know that in cervical cancer stay HPV and EBV. DNA was isolated from nineteen sample cervical cancer tissues frozen section. Diagnose related with HPV and EBV was made by Polymerase Chains Reaction (PCR). The result of this experiment showed that from 19 samples diagnosed as cervical cancer, 17 samples are positive HPV and 13 samples had HPV and EBV positive. The conclusion of this experiment is 89% of cervical cancers are infected with HPV and 68% also infected with HPV and EBV. PMID:16686948

  17. Cervical cancer with Human Papilloma Virus and Epstein Barr Virus positive

    PubMed Central

    Prayitno, Adi

    2006-01-01

    The Early-7 (E7) protein of HPV binds to the underphosphorelated form of the tumor suppressor protein – pRb and displaces the E2F transcription factor that is normally bound by pRb. The latent membrane protein-1 (LMP-1) of EBV prevents apoptosis of B cells by up regulating the expression of bcl-2, and it activates growth promoting pathway that are normally triggered by T cell – derivate signal. The aims of this study to know that in cervical cancer stay HPV and EBV. DNA was isolated from nineteen sample cervical cancer tissues frozen section. Diagnose related with HPV and EBV was made by Polymerase Chains Reaction (PCR). The result of this experiment showed that from 19 samples diagnosed as cervical cancer, 17 samples are positive HPV and 13 samples had HPV and EBV positive. The conclusion of this experiment is 89% of cervical cancers are infected with HPV and 68% also infected with HPV and EBV. PMID:16686948

  18. A Gompertzian model with random effects to cervical cancer growth

    SciTech Connect

    Mazlan, Mazma Syahidatul Ayuni; Rosli, Norhayati

    2015-05-15

    In this paper, a Gompertzian model with random effects is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via maximum likehood estimation. We apply 4-stage Runge-Kutta (SRK4) for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of the cervical cancer growth. Low values of root mean-square error (RMSE) of Gompertzian model with random effect indicate good fits.

  19. Gompertzian stochastic model with delay effect to cervical cancer growth

    SciTech Connect

    Mazlan, Mazma Syahidatul Ayuni binti; Rosli, Norhayati binti; Bahar, Arifah

    2015-02-03

    In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits.

  20. A Gompertzian model with random effects to cervical cancer growth

    NASA Astrophysics Data System (ADS)

    Mazlan, Mazma Syahidatul Ayuni; Rosli, Norhayati

    2015-05-01

    In this paper, a Gompertzian model with random effects is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via maximum likehood estimation. We apply 4-stage Runge-Kutta (SRK4) for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of the cervical cancer growth. Low values of root mean-square error (RMSE) of Gompertzian model with random effect indicate good fits.

  1. Gompertzian stochastic model with delay effect to cervical cancer growth

    NASA Astrophysics Data System (ADS)

    Mazlan, Mazma Syahidatul Ayuni binti; Rosli, Norhayati binti; Bahar, Arifah

    2015-02-01

    In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits.

  2. Immune responses against human papillomavirus (HPV) infection and evasion of host defense in cervical cancer.

    PubMed

    Sasagawa, Toshiyuki; Takagi, Hiroaki; Makinoda, Satoru

    2012-12-01

    Human papillomavirus (HPV) is the most important etiological factor for cervical cancer. A recent study demonstrated that more than 20 HPV types were thought to be oncogenic for uterine cervical cancer. Notably, more than one-half of women show cervical HPV infections soon after their sexual debut, and about 90 % of such infections are cleared within 3 years. Immunity against HPV might be important for elimination of the virus. The innate immune responses involving macrophages, natural killer cells, and natural killer T cells may play a role in the first line of defense against HPV infection. In the second line of defense, adaptive immunity via cytotoxic T lymphocytes (CTLs) targeting HPV16 E2 and E6 proteins appears to eliminate cells infected with HPV16. However, HPV can evade host immune responses. First, HPV does not kill host cells during viral replication and therefore neither presents viral antigen nor induces inflammation. HPV16 E6 and E7 proteins downregulate the expression of type-1 interferons (IFNs) in host cells. The lack of co-stimulatory signals by inflammatory cytokines including IFNs during antigen recognition may induce immune tolerance rather than the appropriate responses. Moreover, HPV16 E5 protein downregulates the expression of HLA-class 1, and it facilitates evasion of CTL attack. These mechanisms of immune evasion may eventually support the establishment of persistent HPV infection, leading to the induction of cervical cancer. Considering such immunological events, prophylactic HPV16 and 18 vaccine appears to be the best way to prevent cervical cancer in women who are immunized in adolescence. PMID:23117294

  3. 11-Keto-boswellic acid derived amides and monodesmosidic saponins induce apoptosis in breast and cervical cancers cells.

    PubMed

    Csuk, René; Barthel-Niesen, Anja; Barthel, Alexander; Schäfer, Renate; Al-Harrasi, Ahmed

    2015-07-15

    Beta-boswellic acids are considered the main bioactive components of frankincense. Their potential to act as cytotoxic agents, as well as that of their derivatives remained unexploited so far. In this study we were able to prepare derivatives of 11-keto-?-boswellic acid (KBA) that showed lower IC50 values as determined by a sulphorhodamine B (SRB) assay using several different human tumour cell lines. Monodesmosidic saponins of KBA are as cytotoxic as 3-acetyl-KBA. The presence of a free hydroxyl group at position C-3 seems to lower cytotoxicity while the presence of an amide function at C-24 improves cytotoxicity. The most active compound of this series gave IC50 values as low as 4.5 ?M. Cell death proceeded mainly via apoptosis. PMID:26073487

  4. Efficacy of screening for cervical cancer: a review.

    PubMed Central

    Guzick, D S

    1978-01-01

    Cytologic screening for cervical cancer currently enjoys wide acceptance, but there remains controversy in the literature concerning its efficacy in prolonging life. On the basis of a literature review, several conclusions are reached: 1) Cervical screening can identify women who are at greater-than-average risk of developing invasive cervical cancer by detecting asymptomatic lesions that would frequently progress to invasion if left untreated; 2) Therapy based on confirmed positive smears can reduce the incidence and mortality rates of invasive cervical cancer, as shown by declining rates in many centers that had constant or increasing rates before screening began, lower rates for geographic areas and occupational groups having less screening, and lower rates among screened women than unscreened women; and 3) Attempts to estimate the amount of life prolongation attributable to cervical screening have not yet yielded reliable figures, because of difficulties with the models or data used. However, in view of the available evidence, it is suggested that incomplete data should not prevent a vigorous continuation of screening where it is already extensive, and an escalation where it is not. PMID:626255

  5. GSK3? mediates the carcinogenic effect of HPV16 in cervical cancer

    PubMed Central

    Ma, Cuiling; Zeng, Chenglong; Jin, Liang; Yang, Yang; Li, Pengfei; Chen, Liangfeng; Wang, Jian

    2015-01-01

    Cervical cancer is one of the most prevalent and fatal cancers among women and infection of the human papillomavirus (HPV) is the most important risk factor. This study investigated how HPV16 regulated GSK3? expression and function to promote cervical cancers. The expression of GSK3? was analyzed by quantitative PCR and western blot. The proliferation, invasion, and clonogenic survival of cells with different E6/E7 levels were measured by MTT, transwell invasion assays, and soft agar colony-forming assays, respectively. The levels of GSK3? were correlated with the copy numbers and expression levels of HPV16 E6/E7 genes. HPV16 E6/E7 genes regulated GSK3? transcription through an element located in the promoter 85 and 250 base pairs upstream of the transcription start site. The abilities of cell proliferation, invasion, and clonogenic survival were increased in C33A cells by ectopic HPV16 E6/E7 and decreased in CaSki cells by knocking down HPV16 E6/E7 levels. Meanwhile, LiCl increased GSK3? transcript levels and the proliferation of CaSki cells in a HPV16-dependent manner. These data indicated that GSK3? may participated in HPV16 mediated deregulation of wnt/?-catenin and other signaling pathways promoting the progression and invasion of cervical cancers. PMID:26560046

  6. Promoter region methylation and loss of protein expression of PTEN and significance in cervical cancer

    PubMed Central

    QI, QIUFENG; LING, YANG; ZHU, MING; ZHOU, LINYAN; WAN, MEIZHEN; BAO, YANQING; LIU, YONGPING

    2014-01-01

    The genetic basis underlying cervical tumorigenesis and progression are largely unknown. Phosphatase and tensin homologue (PTEN) is a tumor suppressor gene, and genetic changes of PTEN occurs in various types of cancer suggesting that the inactivation of PTEN may play an important role in the pathogenesis of a variety of human malignancies. In the present study, 102 cervical cancer specimens were examined for the expression of the PTEN gene and promoter methylation using methylation-specific-polymerase chain reaction and immunohistochemistry. The PTEN gene mutation was also assessed using PCR single-strand conformational polymorphism. We examined the correlation between PTEN expression and its associated methylation status and the clinical characteristics of cervical cancer. The results showed that there was one case of an A to G point mutation on exon 9 of the PTEN gene in the cervical cancer tissues. This mutation caused the change of aspartic acid to glycine, and the rate of mutation was 1%. The PTEN gene methylation rate of cervical cancer was 62% (63/102) and the rate was associated with the International Federation of Gynecology and Obstetrics stage, cell differentiation, tumor size and lymph node metastasis (P<0.05). The positive rate of PTEN expression was 49% (50/102) in cervical carcinoma and the PTEN expression between stage I–II and III–IV [60 (27/45) vs. 40% (23/57)] was statistically significant (P<0.01). The PTEN gene expression between the metastasis and no lymph node metastasis groups [26 (10/38) vs. 63% (40/64)] was significantly different (P<0.01). The PTEN gene promoter methylation and its protein expression had a significant correlation (P=0.042). These results suggest that hypermethylation can inactivate the transcription of PTEN and reduce its protein expression. Downregulated PTEN expression is involved in the pathogenesis, invasion and metastasis of cervical cancer, possibly by regulating the balance between apoptosis and proliferation. Therefore, the PTEN expression may be a good marker for the prognosis of cervical cancer. PMID:25054006

  7. Cervical Cancer Cell Supernatants Induce a Phenotypic Switch from U937-Derived Macrophage-Activated M1 State into M2-Like Suppressor Phenotype with Change in Toll-Like Receptor Profile

    PubMed Central

    Sánchez-Reyes, Karina; Bravo-Cuellar, Alejandro; Hernández-Flores, Georgina; Lerma-Díaz, José Manuel; Jave-Suárez, Luis Felipe; Gómez-Lomelí, Paulina; de Celis, Ruth; Aguilar-Lemarroy, Adriana; Domínguez-Rodríguez, Jorge Ramiro; Ortiz-Lazareno, Pablo Cesar

    2014-01-01

    Cervical cancer (CC) is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV) is the main risk factor for developing CC. Macrophages are important immune effector cells; they can be differentiated into two phenotypes, identified as M1 (classically activated) and M2 (alternatively activated). Macrophage polarization exerts profound effects on the Toll-like receptor (TLR) profile. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shift of M1 macrophage toward M2 macrophage in U937-derived macrophages. Results. The results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinflammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. These cells increased CD163 and IL-10 expression. The expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells. Conclusions. Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages. PMID:25309919

  8. Methylation of Cervical Neoplastic Cells Infected With Human Papillomavirus 16

    PubMed Central

    Ki, Eun Young; Lee, Keun Ho; Hur, Soo Young; Rhee, Jee Eun; Kee, Mee Kyung; Kang, Chung; Park, Jong Sup

    2016-01-01

    Objective This study was conducted to evaluate the role of methylation of adenylate cyclase activating peptide 1 (ADCYAP1), paired box gene 1 (PAX1), cell adhesion molecule 1 (CADM1), and T-lymphocyte maturation–associated protein (MAL) during carcinogenesis. Methods We evaluated the methylation of 4 genes by using the cervical carcinoma cell lines (CaSki, SiHa, HeLa, and C33A) and cervical neoplastic cells from 56 subjects with human papillomavirus 16 (HPV16)–infected low-grade squamous intraepithelial lesions (LSILs), 50 subjects with HPV16-infected high-grade squamous intraepithelial lesions (HSILs), and 24 subjects with HPV16-infected invasive cervical cancer who attended Seoul St. Mary’s Hospital. Methylation of the 4 genes was evaluated using quantitative bisulfate pyrosequencing. Results The ADCYAP1 promoter was hypermethylated in the 4 cell lines (CaSki, 97.40 ± 1.39; SiHa, 82.04 ± 17.02; HeLa, 96.14 ± 2.08; and C33A, 78 ± 10.18). PAX1 and CADM1 were hypermethylated in the HPV16/18-infected cell lines CaSki (PAX1, 91.18 ± 9.91; CADM1, 93.5 ± 7.33), SiHa (PAX1, 96.14 ± 2.08; CADM1, 93.15 ± 8.81), and HeLa (PAX1, 82.04 ± 17.02; CADM1, 92.43 ± 9.95). MAL was hypermethylated in the CaSki cell line (96.04 ± 4.74). Among human cervical neoplastic cells, the methylation indices of ADCYAP1 were 7.8 (95% confidence interval [95% CI], 7.0–8.6) in subjects with LSILs and 39.8 (95% CI, 29.0–54.7) in those with cervical cancer (P < 0.001); for PAX1, 7.2 (95% CI, 6.1–8.5) and 37.8 (95% CI, 27.1–52.7), respectively; for CADM1, 3.5 (95% CI, 3.0–4.0) and 17.7 (95% CI, 10.8–29.1), respectively; for MAL, 2.7 (95% CI, 2.5–3.0) and 13.0 (95% CI, 7.6–22.0), respectively (P < 0.001 for each). Immunohistochemical staining results were positive in the cytoplasm of subjects with low methylation of the 4 gene promoters; however, they were negative in the cytoplasm of those with hypermethylation of the 4 gene promoters. Conclusions The results of this study suggest that the methylation of ADCYAP1, PAX1, CADM1, and MAL may be highly associated with the development of cervical cancer, and that gene expression can be suppressed by gene promoter hypermethylation. PMID:26552048

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

    Cancer.gov

    The overall goal of this study is to determine the association between serum biomarkers of oxidant load and cervical carcinogenesis among women from the Ludwig-McGill Cohort Study. The Ludgwig-McGill Cohort Study is a large prospective study which collected multiple measurements of relevant risk factors (e.g., smoking, presence of cervical inflammatory cells, dietary and circulatory concentrations of antioxidant nutrients) and endpoints (e.g., type-specific HPV persistence, viral load, and development of SIL).

  10. Immunologic treatments for precancerous lesions and uterine cervical cancer

    PubMed Central

    2014-01-01

    Development of HPV-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. In this way, HPV-related tumors usually present MHC class I down-regulation, impaired antigen-processing ability, avoidance of T-cell mediated killing, increased immunosuppression due to Treg infiltration and secrete immunosuppressive cytokines. Thus, these are the main obstacles that immunotherapy has to face in the treatment of HPV-related pathologies where a number of different strategies have been developed to overcome them including new adjuvants. Although antigen-specific immunotherapy induced by therapeutic HPV vaccines was proved extremely efficacious in pre-clinical models, its progression through clinical trials suffered poor responses in the initial trials. Later attempts seem to have been more promising, particularly against the well-defined precursors of cervical, anal or vulvar cancer, where the local immunosuppressive milieu is less active. This review focuses on the advances made in these fields, highlighting several new technologies (such as mRNA vaccine, plant-derived vaccine). The most promising immunotherapies used in clinical trials are also summarized, along with integrated strategies, particularly promising in controlling tumor metastasis and in eliminating cancer cells altogether. After the early promising clinical results, the development of therapeutic HPV vaccines need to be implemented and applied to the users in order to eradicate HPV-associated malignancies, eradicating existing perception (after the effectiveness of commercial preventive vaccines) that we have already solved the problem. PMID:24667138

  11. Perceived risk of cervical cancer among low-income women

    PubMed Central

    Asiedu, Gladys B.; Breitkopf, Carmen Radecki; Breitkopf, Daniel M.

    2015-01-01

    Background Risk perception is an important predictor of cancer prevention behaviors. We examined perceived risk of cervical cancer among an ethnically diverse population of women of lower socioeconomic status. Materials and Methods Females attending a women's health clinic were recruited for a study addressing cervical cancer prevention. Survey questions evaluated lifetime perceived risk of cervical cancer (0% to 100%), beliefs about the accuracy of the Pap test, and estimated incidence of abnormal Pap test results. Risk estimates for oneself were followed with an item seeking a brief, qualitative explanation of the risk estimate. Results Surveys were completed by 338 women. The mean (M ±SD) age of respondents was 29.9 ±8.6 years. Women self-identified as Hispanic/Latina (32%, n=107), White (34%, n=116), and African American (34%, n=115). Estimated perceived lifetime risk of getting cervical cancer ranged from 0% to 100% (M=59.2 ±29.5). Risk estimates were associated with perceived prevalence of abnormal results, r=0.24, p<0.001, and perceptions regarding the accuracy of the Pap test, r=0.13, p<0.05. On average, women estimated that nearly half of all women have ever had an abnormal result (49.2 ± 26.9; n=335; range 0%-100%), with African-American women estimating a higher percentage compared to Hispanic/Latina and White women. Women who themselves experienced an abnormal Pap test result reported higher proportions of other women experiencing an abnormal result, t(333) = ?3.67, p<0.01. Conclusions This study advances our understanding of misperception of risk and how women qualitatively view their risk of cervical cancer. The findings underscore areas for practitioners to enhance patient education efforts. PMID:24633172

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

    Cancer.gov

    This study will explore human papillomavirus (HPV) infection in a large, representative sample of high-risk women in Costa Rica who have been enrolled and followed for approximately 7 years with regard to developing cervical cancer. This unique cohort is derived from an admixed population and provides a natural genetic heterogeneity of viral genomes.

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

    Cancer.gov

    This study examines human papillomavirus (HPV) infection and reactivation among older women (born between 1945 and 1964) and the persistence and progression of this infection to cervical cancer. Specifically, investigators propose to assemble a prospective cohort of 1500 racially and socioeconomically diverse women for HPV infection and squamous intraepithelial lesions (SIL).

  14. Treatment Extends Survival for Women with Cervical Cancer

    Cancer.gov

    Patients with locally advanced cervical cancer who received gemcitabine (Gemzar®) both as part of initial treatment and as part of therapy following primary treatment had improved survival compared with patients whose treatment did not include gemcitabine, according to findings presented at the 2009 ASCO meeting in Orlando.

  15. Cervical Cancer: A Review of the Psychosocial Factors Following Treatment.

    ERIC Educational Resources Information Center

    Gilliland, Kevin Clark

    Cervical cancer is a diagnosis that has a profound psychosocial impact, constituting a physical and emotional crisis for patients as well as family. In general, research indicates that the choice of treatment and the stage of the disease are instrumental in determining the psychosocial adjustment. Disruptions are likely to occur in self-esteem,…

  16. Acceptability of Cervical Cancer Screening in Rural Mozambique

    ERIC Educational Resources Information Center

    Audet, Carolyn M.; Matos, Carla Silva; Blevins, Meridith; Cardoso, Aventina; Moon, Troy D.; Sidat, Mohsin

    2012-01-01

    In Zambezia province, Mozambique, cervical cancer (CC) screening was introduced to rural communities in 2010. Our study sought to determine whether women would accept screening via pelvic examination and visual inspection with acetic acid (VIA) at two clinical sites near the onset of a new CC screening program. A cross-sectional descriptive study…

  17. [New guidelines in regard to cervical cancer screening].

    PubMed

    Vargas-Hernández, Víctor Manuel; Acosta-Altamirano, Gustavo; Moreno-Eutimio, Mario Adán; Vargas-Aguilar, Víctor Manuel

    2014-01-01

    Cancer screening programs have been successful in reducing the incidence and mortality due to cervical cancer. For more than a decade, the human papillomavirus test has been recommended as part of these programs, however, Pap tests is not currently recommended for women 65 years of age who participated adequately in screening programs, continuing with these screening programs is not needed. Screening programs will be different in special populations at greatest risk where tests are frequently needed or use of alternative methods. PMID:25167359

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

    Cancer.gov

    Human papillomavirus (HPV) causes invasive cervical cancer in women and also causes penile cancer in men. Because men transmit HPV to their female partners, reducing HPV infection in men could be an important next step HPV prevention strategy that benefits both men and women. By decreasing the viral load of HPV infection in men this could reduce male-to-female HPV transmission, and thus ultimately reduce HPV prevalence and associated neoplasia in women.

  19. Pennogenyl Saponins from Paris quadrifolia L. Induce Extrinsic and Intrinsic Pathway of Apoptosis in Human Cervical Cancer HeLa Cells

    PubMed Central

    Stefanowicz-Hajduk, Justyna; Bartoszewski, Rafal; Bartoszewska, Sylwia; Kochan, Kinga; Adamska, Anna; Kosi?ski, Igor; Ochocka, J. Renata

    2015-01-01

    Pennogenyl saponins are the active compounds of large number of plant species and consequently many polyherbal formulations. Hence, great interest has been shown in their characterization and in the investigation of their pharmacological and biological properties, especially anticancer. This present study reports on the evaluation of cytotoxic effects and explanation of the molecular mechanisms of action of the two pennogenyl saponins (PS 1 and PS 2) isolated from Paris quadrifolia L. rhizomes on human cervical adenocarcinoma cell line HeLa. To determine the viability of the cells treated with the compounds we used real-time cell proliferation analysis and found that the pennogenyl saponins PS 1 and PS 2 strongly inhibited the tumor cells growth with IC50 values of 1.11 ± 0.04 ?g/ml and 0.87 ± 0.05 ?g/ml, respectively. The flow cytometry analysis indicated that the two compounds induced apoptosis in a dose-dependent manner and decreased mitochondrial membrane potential in HeLa cells in the early stage of apoptosis. Quantitative PCR and Western Blot analysis showed that the two saponins significantly increased mRNA expression of FADD and BID as well as induced caspase-8 via increased of procaspase-8 processing in the treated cells. The results of this study suggest that both the extrinsic death receptor and intrinsic mitochondrial pathways are involved in the programmed cell death. PMID:26295969

  20. Using the Theory of Planned Behavior to Understand Cervical Cancer Screening Among Latinas.

    PubMed

    Roncancio, Angelica M; Ward, Kristy K; Sanchez, Ingrid A; Cano, Miguel A; Byrd, Theresa L; Vernon, Sally W; Fernandez-Esquer, Maria Eugenia; Fernandez, Maria E

    2015-10-01

    To reduce the high incidence of cervical cancer among Latinas in the United States it is important to understand factors that predict screening behavior. The aim of this study was to test the utility of theory of planned behavior in predicting cervical cancer screening among a group of Latinas. A sample of Latinas (N = 614) completed a baseline survey about Pap test attitudes subjective norms, perceived behavioral control, and intention to be screened for cervical cancer. At 6 months postbaseline, cervical cancer screening behavior was assessed. Structural equation modeling was used to test the theory. Model fit statistics indicated good model fit: ?(2)(48) = 54.32, p = .246; comparative fit index = .992; root mean square error of approximation = .015; weighted root mean square residual = .687. Subjective norms (p = .005) and perceived behavioral control (p < .0001) were positively associated with intention to be screened for cervical cancer, and the intention to be screened predicted actual cervical cancer screening (p < .0001). The proportion of variance (R(2)) in intention accounted for by the predictors was .276 and the R(2) in cervical cancer screening accounted for was .130. This study provides support for the use of the theory of planned behavior in predicting cervical cancer screening among Latinas. This knowledge can be used to inform the development of a theory of planned behavior-based intervention to increase cervical cancer screening among Latinas and reduce the high incidence of cervical cancer in this group of women. PMID:25712240

  1. Merkel cell polyomavirus and human papillomavirus infections in cervical disease in Iranian women.

    PubMed

    Salehi-Vaziri, Mostafa; Sadeghi, Farzin; Alamsi-Hashiani, Amir; Haeri, Hayedeh; Monavari, Seyed Hamidreza; Keyvani, Hossein

    2015-05-01

    Human papillomavirus (HPV) infection is a necessary cause of cervical neoplasia. Concomitant infection with other infectious agents has been demonstrated to be a cofactor for HPV-related cervical carcinogenesis. The present investigation aimed to determine the prevalence of HPV and Merkel cell polyomavirus (MCPyV) infections and to evaluate the role of MCPyV as a co-factor for HPV-related cervical carcinogenesis in Iranian women. From 2011 to 2013, a total of 112 cervical samples were examined. Forty-five samples (40.2 %) were positive for HPV. MCPyV was found in 37 samples (33 %). Both HPV and MCPyV were present in 14 samples (12.5 %). MCPyV was seen in 30 % of squamous cell carcinomas, 37.5 % of adenocarcinomas, and 16.7 % of undifferentiated carcinomas. The MCPyV large T antigen (LT-Ag) DNA load was determined as the viral copy number per cell. The median MCPyV LT-Ag copy number in positive women was 0.049 × 10(-3) per cell (range 0.0006 × 10(-3)-4.558 × 10(-3) copies per cell). In comparison with other types of cervical cancer, the MCPyV LT-Ag load was higher in adenocarcinomas (0.1024 × 10(-3) copies per cell). A logistic regression model adjusted to HPV positivity and age revealed no statistically significant association between MCPyV infection and cervical cancer (OR, 1.12; 95 % CI, 0.07-16.83). More studies should be conducted to clarify the role of MCPyV in cervical carcinogenesis. PMID:25721299

  2. Multi-test cervical cancer diagnosis with missing data estimation

    NASA Astrophysics Data System (ADS)

    Xu, Tao; Huang, Xiaolei; Kim, Edward; Long, L. Rodney; Antani, Sameer

    2015-03-01

    Cervical cancer is a leading most common type of cancer for women worldwide. Existing screening programs for cervical cancer suffer from low sensitivity. Using images of the cervix (cervigrams) as an aid in detecting pre-cancerous changes to the cervix has good potential to improve sensitivity and help reduce the number of cervical cancer cases. In this paper, we present a method that utilizes multi-modality information extracted from multiple tests of a patient's visit to classify the patient visit to be either low-risk or high-risk. Our algorithm integrates image features and text features to make a diagnosis. We also present two strategies to estimate the missing values in text features: Image Classifier Supervised Mean Imputation (ICSMI) and Image Classifier Supervised Linear Interpolation (ICSLI). We evaluate our method on a large medical dataset and compare it with several alternative approaches. The results show that the proposed method with ICSLI strategy achieves the best result of 83.03% specificity and 76.36% sensitivity. When higher specificity is desired, our method can achieve 90% specificity with 62.12% sensitivity.

  3. The Prognostic Value of TRAIL and its Death Receptors in Cervical Cancer

    SciTech Connect

    Maduro, John H. Noordhuis, Maartje G.; Hoor, Klaske A. ten; Pras, Elisabeth; Arts, Henriette J.G.; Eijsink, Jasper J.H.; Hollema, Harry; Mom, Constantijne H.; Jong, Steven de; Vries, Elisabeth G.E. de; Bock, Geertruida H. de; Zee, Ate G.J. van der

    2009-09-01

    Purpose: Preclinical data indicate a synergistic effect on apoptosis between irradiation and recombinant human (rh) tumor necrosis factor-related apoptosis inducing ligand (TRAIL), making the TRAIL death receptors (DR) interesting drug targets. The aim of our study was to analyze the expression of DR4, DR5, and TRAIL in cervical cancer and to determine their predictive and prognostic value. Methods and Materials: Tissue microarrays were constructed from tumors of 645 cervical cancer patients treated with surgery and/or (chemo-)radiation between 1980 and 2004. DR4, DR5, and TRAIL expression in the tumor was studied by immunohistochemistry and correlated to clinicopathological variables, response to radiotherapy, and disease-specific survival. Results: Cytoplasmatic DR4, DR5, and TRAIL immunostaining were observed in cervical tumors from 99%, 88%, and 81% of the patients, respectively. In patients treated primarily with radiotherapy, TRAIL-positive tumors less frequently obtained a pathological complete response than TRAIL-negative tumors (66.3% vs. 79.0 %; in multivariate analysis: odds ratio: 2.09, p {<=}0.05). DR4, DR5, and TRAIL expression were not prognostic for disease-specific survival. Conclusions: Immunostaining for DR4, DR5, and TRAIL is frequently observed in the cytoplasm of tumor cells in cervical cancer patients. Absence of TRAIL expression was associated with a higher pathological complete response rate to radiotherapy. DR4, DR5, or TRAIL were not prognostic for disease-specific survival.

  4. From Human Papillomavirus (HPV) Detection to Cervical Cancer Prevention in Clinical Practice

    PubMed Central

    Lee, Sin Hang; Vigliotti, Jessica S.; Vigliotti, Veronica S.; Jones, William

    2014-01-01

    The newly gained knowledge of the viral etiology in cervical carcinogenesis has prompted industrial interests in developing virology-based tools for cervical cancer prevention. Due to the long incubation period from viral infection to developing an invasive cancer, a process whose outcome is influenced by numerous life-style and genetic factors, the true efficacy of the genotype-specific human papillomavirus (HPV) vaccines in cervical cancer prevention cannot be determined for another 30 years. Most HPV DNA test kits designed to replace the traditional Papanicolaou (Pap) smears for precancer detection lack the analytical sensitivity and specificity to comprehensively detect all potentially carcinogenic HPVs and to perform reliable genotyping. The authors implemented the classic nested PCR and Sanger DNA-sequencing technology for routine HPV testing. The results showed a true negative HPV PCR invariably indicates the absence of precancerous cells in the cytology samples. However, 80.5% of single positive HPV-16 tests and 97.3% of single positive HPV-18 tests were associated with a negative or a largely self-reversible Pap cytology. Routine sensitive and reliable HPV type-specific or perhaps even variant-specific methods are needed to address the issues of persistence of HPV infection if a virology-based primary cervical screen is used to replace the Pap cytology screening paradigm. PMID:25279452

  5. Predictors of cervical cancer being at an advanced stage at diagnosis in Sudan

    PubMed Central

    Ibrahim, Ahmed; Rasch, Vibeke; Pukkala, Eero; Aro, Arja R

    2011-01-01

    Background Cervical cancer is the second most common cancer among women in Sudan, with more than two-thirds of all women with invasive cervical cancer being diagnosed at an advanced stage (stages III and IV). The lack of a screening program for cervical cancer in Sudan may contribute to the late presentation of this cancer, but other factors potentially associated with advanced stages of cervical cancer at diagnosis are unknown. The purpose of this research was to investigate the relationship between age, marital status, ethnicity, health insurance coverage, residence in an urban vs a rural setting, and stage (at diagnosis) of cervical cancer in Sudan. Methods This was a cross sectional study of 197 women diagnosed with different stages of cervical cancer. Data was obtained from the cancer registry unit at the Radiation and Isotopes Centre in Khartoum for all women diagnosed with cervical cancer in 2007. Results There was an association between older age and advanced stage (at diagnosis) of cervical cancer (odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.01–1.05). Being of African ethnicity was associated with 76% increased odds (OR: 1.76, 95% CI: 1.01–3.05), living in a rural area was associated with 13% increased odds (OR: 1.13, 95% CI: 1.78–5.50), and being uninsured was associated with an almost eight-fold increase in odds (OR: 7.7, 95% CI: 3.76–15.38). Marital status and education level were not associated with an advanced stage of cervical cancer at diagnosis. Conclusion Women with cervical cancer who are elderly, not covered by health insurance, of African ethnicity, and living in a rural area are more likely to be diagnosed at an advanced stage of cervical cancer in Sudan. These women should be targeted for cervical cancer screening and a health education program, and encouraged to have health insurance. PMID:22140326

  6. Screening for cervical cancer: new alternatives and research.

    PubMed

    Lörincz, Attila T

    2003-01-01

    Evidence for the clinical utility of human papillomavirus (HPV) DNA testing has increased over the years and has now become very convincing. Some specific uses of HPV detection are a) triage of women with cytological determinations of atypical squamous cells of undetermined significance (ASC-US) and related management strategies, b) as a marker for test of cure post-treatment, and c) most importantly, as an adjunct to cytology in routine cervical disease screening programs. There are many studies that support each of these applications and include 8 studies on ASC-US triage, 10 on test of cure and 13 on adjunctive or stand-alone HPV screening. The most notable investigation of ASC-US triage was ALTS, a randomized controlled trial of 3,488 women. With respect to routine HPV screening the combined studies included 77,000 women, providing as a histological endpoint more than 1,000 cases of high-grade cervical intraepithelial neoplasia (CIN) or cancer. Testing methods were either the Hybrid Capture 2 (HC2) test or the polymerase chain reaction (PCR) test. HPV testing of women with ASC-US cytology had on average a higher sensitivity (90%) and specificity (70%) than repeating the cytological test (sensitivity 75%, specificity 60%) and was also more sensitive than colposcopy for follow-up. As an adjunct to the Papanicolaou (Pap) cytology test in routine screening, HPV DNA testing was a more sensitive indicator for prevalent high-grade CIN than either conventional or liquid cytology. A combination of HPV DNA and Papanicolaou testing had almost 100% sensitivity and negative predictive value. The specificity of the combined tests was slightly lower than the specificity of the Papanicolaou test. One "double-negative" HPV DNA and Papanicolaou test indicated a higher prognostic assurance against risk of future CIN 3 than three subsequent negative conventional Papanicolaou tests and may safely allow three-year or longer screening intervals for such low-risk women. It appears that HPV DNA testing is on the way to becoming a common testing strategy in cervical cancer prevention programs. Research continues into approaches for improving the performance and cost-effectiveness of HPV detection methods. Hybrid Capture 3 will offer improved HPV typing capabilities and the Rapid Capture machine allows for robot-assisted HPV DNA testing, permitting greater test throughput. PCR test improvements are expected to contribute to the growth of flexible accurate and cost-effective HPV DNA tests. It is likely that improved diagnostic technology along with HPV genotyping and quantitation may provide more value in future. A particularly promising approach is to combine HPV DNA testing with expression levels of other markers such as proliferative or cell cycle regulatory proteins to subdivide HPV-positive women into those who are at greater risk of cancer and those who can be safely followed by screening at longer intervals. This paper is available too at: http://www.insp.mx/salud/index.html. PMID:14746031

  7. CD24 expression as a marker for predicting clinical outcome and invasive activity in uterine cervical cancer.

    PubMed

    Tanaka, Tomohito; Terai, Yoshito; Kogata, Yuhei; Ashihara, Keisuke; Maeda, Kazuya; Fujiwara, Satoe; Yoo, Saha; Tanaka, Yoshimichi; Tsunetoh, Satoshi; Sasaki, Hiroshi; Kanemura, Masanori; Tanabe, Akiko; Ohmichi, Masahide

    2015-11-01

    CD24, a small heavily glycosylated mucin-like glycosyl-phosphatidylinositol-anchored cell surface protein, plays an important role in the carcinogenesis of various human malignancies. However, its function in cervical cancer remains unclear. The aim of the present study was to evaluate the expression of CD24 clinicopathologically and to analyze its functional behavior biologically in cervical cancer. A total of 117 uterine cervical cancer tumors were immunohistochemically analyzed using a CD24 monoclonal antibody on paraffin blocks. We also examined whether CD24 enhanced the invasive activity or the Akt, ERK, NF-?B and MMP activity in a uterine cervical cancer cell line (CaSki) by a western blot analysis. The patients with enhanced CD24 expression had a higher rate of advanced clinical stage (50 vs. 16.5%, p<0.01), lymph node metastasis (34.6 vs. 14.3%) and lymphovascular involvement (65.4 vs. 20.4%, p=0.01), and a poor overall and disease-free survival (5-year survival rate: 62 vs. 86%, p=0.03). CD24 overexpression in CaSki cells resulted in activation of Cell Signaling proteins, including Akt, ERK, NF-?B and MMP-9. An invasion assay showed that CD24 overexpression in CaSki cells led to increased invasion ability. The CD24 overexpression also increased mRNA expression of Slug but not Snail. Moreover, the CD24 overexpression also decreased expression of E-cadherin and increased N-cadherin protein levels. Increased expression of CD24 may be associated with tumor progression and prognosis in patients with uterine cervical cancer. CD24 expression may therefore be used not only as a prognostic marker in uterine cervical cancer, but also as a target for the development of new therapeutic approaches. PMID:26351781

  8. Scripted Sexual Health Informational Intervention in Improving Sexual Function in Patients With Gynecologic Cancer

    ClinicalTrials.gov

    2015-09-17

    Anxiety Disorder; Cervical Cancer; Endometrial Cancer; Female Reproductive Cancer; Gestational Trophoblastic Tumor; Ovarian Epithelial Cancer; Ovarian Germ Cell Tumor; Sexual Dysfunction; Uterine Sarcoma; Vaginal Cancer; Vulvar Cancer

  9. The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines

    SciTech Connect

    Scheffner, M.; Muenger, K.; Byrne, J.C.; Howley, P.M. )

    1991-07-01

    Human cervical carcinoma cell lines that were either positive or negative for human papillomavirus (HPV) DNA sequences were analyzed for evidence of mutation of the p53 and retinoblastoma genes. Each of five HPV-positive cervical cancer cell lines expressed normal pRB and low levels of wild-type p53 proteins, which are presumed to be altered in function as a consequence of association with HPV E7 and E6 oncoproteins, respectively. In contrast, mutations were identified in the p53 and RB genes expressed in the C-33A and HT-3 cervical cancer cell lines, which lack HPV DNA sequences. Mutations in the p53 genes mapped to codon 273 and codon 245 in the C33-A and HT-3 cell lines, respectively, located in the highly conserved regions of p53, where mutations appear in a variety of human cancers. Mutations in RB occurred at splice junctions, resulting in in-frame deletions, affecting exons 13 and 20 in the HT-3 and C-33A cell lines, respectively. These mutations resulted in aberrant proteins that were not phosphorylated and were unable to complex with the adenovirus E1A oncoprotein. These results support the hypothesis that the inactivation of the normal functions of the tumor-suppressor proteins pRB and p53 are important steps in human cervical carcinogenesis, either by mutation or from complex formation with the HPV E6 and E7 oncoproteins.

  10. Placenta growth factor promotes migration through regulating epithelial-mesenchymal transition-related protein expression in cervical cancer

    PubMed Central

    Huang, Wei; Zhu, Shuli; Liu, Qiang; Li, Chanyu; Li, Li

    2014-01-01

    Epithelial-mesenchymal transition (EMT) plays an important role in cancer invasion and metastasis by enabling cancer cells to depart from the primary tumor, invade surrounding tissue and disseminate to distant organs. The existence and function of EMT in cervical cancer is poorly understood. Placental growth factor (PLGF) has been shown to associate with EMT in various cancers. However, whether PLGF is involved in EMT in cervical cancer remains unclear. Thus the present study examined the relationship between PLGF expression and EMT-related proteins in 110 cervical lesions samples. We detected that PLGF was expressed in 61.8% cervical lesion sections. In addition, PLGF expression is positively correlated with low expression level of E-cadherin and high expression level of vimentin. Serum samples and cervical lavage samples were collected from patients with pre-invasive and invasive lesion of uterine cervix or normal control group, the PLGF levels were determined by enzyme-linked immunosorbent assay (ELISA). We found that a significantly high level of PLGF could be detected both in serum and vaginal lavage compared with normal women group, and there is no significant difference between serum and lavage in PLGF level. In addition, whatever in lavage or in serum, the PLGF level in stage I and II was significantly higher than it in CINIII or cancer in situ. However, there is no significant difference between the stage I and stage II; we also found that exogenous PLGF promotes molecular changes of epithelial-mesenchymal transition (EMT) in siha cells. In addition, application of a specific EKR1/2 inhibitor could reverse the effects of PLGF. These findings suggested that PLGF could regulate the expression of EMT-related proteins and promote migration of siha cells through ERK/MAPK signaling pathway. Therapies that targets PLGF/Flt-1/ERK/MAPK signaling pathway may be beneficial in treatment of cervical cancer. PMID:25674215

  11. Picosecond pulsed electric fields induce apoptosis in a cervical cancer xenograft

    PubMed Central

    JIA, JIA; XIONG, ZHENG-AI; QIN, QIN; YAO, CHEN-GUO; ZHAO, XIAO-ZHEN

    2015-01-01

    The aim of the present study was to evaluate the efficacy of picosecond pulsed electric fields (psPEF) on a cervical cancer xenograft. Human cervical cancer xenografts were established in nude mice by transplantation of HeLa cells, and the tumors were then treated with psPEF. The histological changes were observed by hematoxylin-eosin staining and transmission electron microscopy. The rate of tumor cell apoptosis was determined using a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay. The mitochondrial transmembrane potential of the tumor cells was detected by laser scanning confocal microscopy, and the activity of caspase-3, -8, -9 and -12 was determined. The inhibitory rate seven days post-psPEF treatment was also calculated. The results showed that exposure to psPEF led to an increased rate of apoptosis, collapse of mitochondrial transmembrane potential, and activation of caspases. The inhibitory rate was 9.11% at day 7. The results of the present study indicate that psPEF may induce apoptosis in a cervical cancer xenograft through the endoplasmic reticulum stress and caspase-dependent signaling pathways. PMID:25405328

  12. HPV16 E6 Controls the Gap Junction Protein Cx43 in Cervical Tumour Cells.

    PubMed

    Sun, Peng; Dong, Li; MacDonald, Alasdair I; Akbari, Shahrzad; Edward, Michael; Hodgins, Malcolm B; Johnstone, Scott R; Graham, Sheila V

    2015-01-01

    Human papillomavirus type 16 (HPV16) causes a range of cancers including cervical and head and neck cancers. HPV E6 oncoprotein binds the cell polarity regulator hDlg (human homologue of Drosophila Discs Large). Previously we showed in vitro, and now in vivo, that hDlg also binds Connexin 43 (Cx43), a major component of gap junctions that mediate intercellular transfer of small molecules. In HPV16-positive non-tumour cervical epithelial cells (W12G) Cx43 localised to the plasma membrane, while in W12T tumour cells derived from these, it relocated with hDlg into the cytoplasm. We now provide evidence that E6 regulates this cytoplasmic pool of Cx43. E6 siRNA depletion in W12T cells resulted in restoration of Cx43 and hDlg trafficking to the cell membrane. In C33a HPV-negative cervical tumour cells expressing HPV16 or 18 E6, Cx43 was located primarily in the cytoplasm, but mutation of the 18E6 C-terminal hDlg binding motif resulted in redistribution of Cx43 to the membrane. The data indicate for the first time that increased cytoplasmic E6 levels associated with malignant progression alter Cx43 trafficking and recycling to the membrane and the E6/hDlg interaction may be involved. This suggests a novel E6-associated mechanism for changes in Cx43 trafficking in cervical tumour cells. PMID:26445057

  13. HPV16 E6 Controls the Gap Junction Protein Cx43 in Cervical Tumour Cells

    PubMed Central

    Sun, Peng; Dong, Li; MacDonald, Alasdair I.; Akbari, Shahrzad; Edward, Michael; Hodgins, Malcolm B.; Johnstone, Scott R.; Graham, Sheila V.

    2015-01-01

    Human papillomavirus type 16 (HPV16) causes a range of cancers including cervical and head and neck cancers. HPV E6 oncoprotein binds the cell polarity regulator hDlg (human homologue of Drosophila Discs Large). Previously we showed in vitro, and now in vivo, that hDlg also binds Connexin 43 (Cx43), a major component of gap junctions that mediate intercellular transfer of small molecules. In HPV16-positive non-tumour cervical epithelial cells (W12G) Cx43 localised to the plasma membrane, while in W12T tumour cells derived from these, it relocated with hDlg into the cytoplasm. We now provide evidence that E6 regulates this cytoplasmic pool of Cx43. E6 siRNA depletion in W12T cells resulted in restoration of Cx43 and hDlg trafficking to the cell membrane. In C33a HPV-negative cervical tumour cells expressing HPV16 or 18 E6, Cx43 was located primarily in the cytoplasm, but mutation of the 18E6 C-terminal hDlg binding motif resulted in redistribution of Cx43 to the membrane. The data indicate for the first time that increased cytoplasmic E6 levels associated with malignant progression alter Cx43 trafficking and recycling to the membrane and the E6/hDlg interaction may be involved. This suggests a novel E6-associated mechanism for changes in Cx43 trafficking in cervical tumour cells. PMID:26445057

  14. Intelligent screening systems for cervical cancer.

    PubMed

    Jusman, Yessi; Ng, Siew Cheok; Abu Osman, Noor Azuan

    2014-01-01

    Advent of medical image digitalization leads to image processing and computer-aided diagnosis systems in numerous clinical applications. These technologies could be used to automatically diagnose patient or serve as second opinion to pathologists. This paper briefly reviews cervical screening techniques, advantages, and disadvantages. The digital data of the screening techniques are used as data for the computer screening system as replaced in the expert analysis. Four stages of the computer system are enhancement, features extraction, feature selection, and classification reviewed in detail. The computer system based on cytology data and electromagnetic spectra data achieved better accuracy than other data. PMID:24955419

  15. Intelligent Screening Systems for Cervical Cancer

    PubMed Central

    Ng, Siew Cheok; Abu Osman, Noor Azuan

    2014-01-01

    Advent of medical image digitalization leads to image processing and computer-aided diagnosis systems in numerous clinical applications. These technologies could be used to automatically diagnose patient or serve as second opinion to pathologists. This paper briefly reviews cervical screening techniques, advantages, and disadvantages. The digital data of the screening techniques are used as data for the computer screening system as replaced in the expert analysis. Four stages of the computer system are enhancement, features extraction, feature selection, and classification reviewed in detail. The computer system based on cytology data and electromagnetic spectra data achieved better accuracy than other data. PMID:24955419

  16. Image-Based Brachytherapy for the Treatment of Cervical Cancer.

    PubMed

    Harkenrider, Matthew M; Alite, Fiori; Silva, Scott R; Small, William

    2015-07-15

    Cervical cancer is a disease that requires considerable multidisciplinary coordination of care and labor in order to maximize tumor control and survival while minimizing treatment-related toxicity. As with external beam radiation therapy, the use of advanced imaging and 3-dimensional treatment planning has generated a paradigm shift in the delivery of brachytherapy for the treatment of cervical cancer. The use of image-based brachytherapy, most commonly with magnetic resonance imaging (MRI), requires additional attention and effort by the treating physician to prescribe dose to the proper volume and account for adjacent organs at risk. This represents a dramatic change from the classic Manchester approach of orthogonal radiographic images and prescribing dose to point A. We reviewed the history and currently evolving data and recommendations for the clinical use of image-based brachytherapy with an emphasis on MRI-based brachytherapy. PMID:26104944

  17. A Proof of Concept Imaging System for Automated Cervical Cancer Screening in Peru

    ERIC Educational Resources Information Center

    Raza Garcia, Mabel Karel

    2013-01-01

    Cervical cancer is the second most frequent cancer in women around the world and affects half a million women per year. The World Health Organization (WHO) estimates that 275,000 women die every year, and 80% to 85% of these deaths occur in low-resource countries in Africa and South America. In Peru, cervical cancer has the highest incidence and…

  18. Diagnostic performance of HPV E6/E7, hTERT, and Ki67 mRNA RT-qPCR assays on formalin-fixed paraffin-embedded cervical tissue specimens from women with cervical cancer.

    PubMed

    Wang, Hye-Young; Kim, Geehyuk; Cho, Hyemi; Kim, Sunghyun; Lee, Dongsup; Park, Sunyoung; Park, Kwang Hwa; Lee, Hyeyoung

    2015-06-01

    Human papillomavirus (HPV) is a major cause of cervical cancer, which is the third most common cancer in women. Human telomerase reverse transcriptase (hTERT) and Ki67 are tumor cell markers indicating cancer cell proliferation in cancer patients, and activation of hTERT and Ki67 leads to progressive cervical carcinogenesis. In the present study, we evaluated the CervicGen HPVE6/E7 mRNA RT-qDx assay, which detects 16 HPV high-risk (HR) genotypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68 and 69), and the CervicGen hTERT and Ki67 mRNA RT-qDx assay using 117 formalin-fixed paraffin-embedded (FFPE) cervical cancer tissue samples. The diagnostic validity of the CervicGen HPV RT-qDx assay for detecting histologically proven prevalent squamous cell carcinoma (SCC) was 94% sensitivity, 100% specificity, 77.8% positive predictive value (PPV), and 78.9% negative predictive value (NPV). The most common HPV genotypes detected in FFPE cervical cancer tissue samples were HPV 16 (56%) and HPV 18 (10%). The positivity rate of hTERT and Ki67 mRNA expressions in FFPE cervical cancer tissue samples on RT-qPCR was 65% and 93% respectively. Moreover, the positivity rates were 92% for a combination of HPV E6/E7 and hTERT mRNA expressions, 97% for HPV E6/E7 and Ki67 mRNA expressions, and 99% (99/100) for the combination of HPV E6/E7, hTERT, and Ki67 mRNA expressions. These data showed that SSC FFPE cervical cancer tissue samples correlated more strongly with high Ki67 mRNA expressions than with hTERT mRNA expressions. Notably, hTERT and Ki67 mRNA expression level was increased in high-grade cervical lesions, but was very low in normal samples. Our findings suggest that the combination of HPV E6/E7, hTERT, and Ki67 mRNA expression levels could be used in a complementary manner in diagnosing high-grade cervical lesions. Further studies are required to evaluate these assays as a useful predictive tool for screening low-grade cervical lesions. PMID:25835783

  19. Inhibition of cervical carcinoma cell line proliferation by the introduction of a bovine papillomavirus regulatory gene.

    PubMed Central

    Hwang, E S; Riese, D J; Settleman, J; Nilson, L A; Honig, J; Flynn, S; DiMaio, D

    1993-01-01

    Human papillomavirus (HPV) E6 and E7 oncogenes are expressed in the great majority of human cervical carcinomas, whereas the viral E2 regulatory gene is usually disrupted in these cancers. To investigate the roles of the papillomavirus E2 genes in the development and maintenance of cervical carcinoma, the bovine papillomavirus (BPV) E2 gene was acutely introduced into cervical carcinoma cell lines by infection with high-titer stocks of simian virus 40-based recombinant viruses. Expression of the BPV E2 protein in HeLa, C-4I, and MS751 cells results in specific inhibition of the expression of the resident HPV type 18 (HPV18) E6 and E7 genes and in inhibition of cell growth. HeLa cells, in which HPV gene expression is nearly completely abolished, undergo a dramatic and rapid inhibition of proliferation, which appears to be largely a consequence of a block in progression from the G1 to the S phase of the cell cycle. Loss of HPV18 gene expression in HeLa cells is also accompanied by a marked increase in the level of the cellular p53 tumor suppressor protein, apparently as a consequence of abrogation of HPV18 E6-mediated destabilization of p53. The proliferation of HT-3 cells, a human cervical carcinoma cell line devoid of detectable HPV DNA, is also inhibited by E2 expression, whereas two other epithelial cell lines that do not contain HPV DNA are not inhibited. Thus, a number of cervical carcinoma cell lines are remarkably sensitive to growth inhibition by the E2 protein. Although BPV E2-mediated inhibition of HPV18 E6 and E7 expression may contribute to growth inhibition in some of the cervical carcinoma cell lines, the BPV E2 protein also appears to exert a growth-inhibitory effect that is independent of its effects on HPV gene expression. Images PMID:8389903

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

    PubMed Central

    Stewart Massad, L.; Evans, Charlesnika T.; Weber, Kathleen M.; D'Souza, Gypsyamber; Hessol, Nancy A.; Wright, Rodney L.; Colie, Christine; Strickler, Howard D.; Wilson, Tracey E.

    2015-01-01

    Purpose To describe changes in knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination among women at high risk for cervical cancer in the first five years after introduction of HPV vaccination. Methods In 2007, 2008–9, and 2011, women in a multicenter U.S. cohort study completed 44-item self-report questionnaires assessing knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results across time were assessed for individuals, and three study enrollment cohorts were compared. Knowledge scores were correlated with demographic variables, measures of education and attention, and medical factors. Associations were assessed in multivariable models. Results In all, 974 women completed three serial questionnaires; most were minority, low income, and current or former smokers. The group included 652 (67%) HIV infected and 322 (33%) uninfected. Summary knowledge scores (possible range 0–24) increased from 2007 (12.8, S.D. 5.8) to 2008–9 (13.9, S.D. 5.3, P < 0.001) and to 2011 (14.3, S.D. 5.2, P < 0.0001 vs 2007 and < 0.04 vs 2008–9). Higher knowledge scores at first and follow-up administration of questionnaires, higher income, and higher education level were associated with improved knowledge score at third administration. Women not previously surveyed had scores similar to those of the longitudinal group at baseline. Conclusion Substantial gaps in understanding of HPV and cervical cancer prevention exist despite years of health education. While more effective educational interventions may help, optimal cancer prevention may require opt-out vaccination programs that do not require nuanced understanding. PMID:25870859

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

    Cancer.gov

    A large number of women in the United States who are told that their Papanicolaou (Pap) test was abnormal do not adhere to recommendations for follow-up care. This study, based on the Unified Theory of Behavior, is investigating an intervention designed to improve follow-up rates after notification of an abnormal Pap test. If proven successful, the intervention may significantly increase adherence to follow-up recommendations and consequently decrease the number of women who develop invasive cervical cancer.

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

    Cancer.gov

    This study examines whether Posttraumatic Stress Disorder (PTSD) is a risk factor for decreased cervical cancer surveillance care among women. Behavioral factors such as avoidance are common in PTSD and may increase the likelihood that some women will postpone or avoid preventive gynecological care. This avoidance may be particularly pronounced among women whose PTSD was caused by the leading precipitant in women (i.e., sexual trauma) because invasive exams may trigger traumatic memories of a prior assault.

  3. A review of californium-252 neutron brachytherapy for cervical cancer

    SciTech Connect

    Maruyama, Y.; van Nagell, J.R.; Yoneda, J.; Donaldson, E.S.; Gallion, H.H.; Powell, D.; Kryscio, R.J. )

    1991-09-15

    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 schedules; they were extended to include unfavorable presentations of Stages 1 and 2 because of favorable results in the initial trials. The authors began to treat patients with Stage IB bulky or barrel-shaped tumors and the majority were treated with both radiation and hysterectomy. Actuarial survival was determined for Stage IB disease and was 87% at 5 years and 82% at 10 years. For those tested with preoperative radiation it was 92% at 5 and 87% at 10 years. For Stage 2, it was 62% 5 years and 61% at 10. Survival 5 years after combined radiation and surgical therapy for Stage 2 disease was 68%. For Stage 3, it was 33% at 5 years and 25% at 10. However, 5-year survival using the early neutron implant was 46% versus approximately 19% for delayed Cf-252 or cesium 137. Different schedules and sequences of neutrons and photons greatly altered outcome. Neutron treatment before external photon therapy was better for all stages of disease. Only about 5% of all patients developed complications after neutron therapy. No hematologic or mesenchymal second tumors were observed. Neutron brachytherapy was found to be very effective for producing rapid response and greatly improved local control of bulky, barrel, or advanced cervical cancers. The clinical trial identified and evolved schedules, doses, doses per session, and developed methods different from standard photon therapy but highly effective for local control and cure of cervical cancers of all stages.

  4. Cervical cancer screening coverage in a high-incidence region

    PubMed Central

    Navarro, Cibelli; da Fonseca, Allex Jardim; Sibajev, Alexander; Souza, Camila Iasmim de Andrade; Araújo, Daniela Souza; Teles, Daniele Aparecida de Freitas; de Carvalho, Stéphanie Gomes Lins; Cavalcante, Kyldery Wendell Moura; Rabelo, Wendell Lima

    2015-01-01

    OBJECTIVE To analyze the coverage of a cervical cancer screening program in a city with a high incidence of the disease in addition to the factors associated with non-adherence to the current preventive program. METHODS A cross-sectional study based on household surveys was conducted. The sample was composed of women between 25 and 59 years of age of the city of Boa Vista, RR, Northern Brazil who were covered by the cervical cancer screening program. The cluster sampling method was used. The dependent variable was participation in a women’s health program, defined as undergoing at least one Pap smear in the 36 months prior to the interview; the explanatory variables were extracted from individual data. A generalized linear model was used. RESULTS 603 women were analyzed, with an mean age of 38.2 years (SD = 10.2). Five hundred and seventeen women underwent the screening test, and the prevalence of adherence in the last three years was up to 85.7% (95%CI 82.5;88.5). A high per capita household income and recent medical consultation were associated with the lower rate of not being tested in multivariate analysis. Disease ignorance, causes, and prevention methods were correlated with chances of non-adherence to the screening system; 20.0% of the women were reported to have undergone opportunistic and non-routine screening. CONCLUSIONS The informed level of coverage is high, exceeding the level recommended for the control of cervical cancer. The preventive program appears to be opportunistic in nature, particularly for the most vulnerable women (with low income and little information on the disease). Studies on the diagnostic quality of cervicovaginal cytology and therapeutic schedules for positive cases are necessary for understanding the barriers to the control of cervical cancer. PMID:25741655

  5. Current Advances in the Application of Raman Spectroscopy for Molecular Diagnosis of Cervical Cancer

    PubMed Central

    Ramos, Inês Raquel Martins; Malkin, Alison; Lyng, Fiona Mary

    2015-01-01

    Raman spectroscopy provides a unique biochemical fingerprint capable of identifying and characterizing the structure of molecules, cells, and tissues. In cervical cancer, it is acknowledged as a promising biochemical tool due to its ability to detect premalignancy and early malignancy stages. This review summarizes the key research in the area and the evidence compiled is very encouraging for ongoing and further research. In addition to the diagnostic potential, promising results for HPV detection and monitoring treatment response suggest more than just a diagnosis prospective. A greater body of evidence is however necessary before Raman spectroscopy is fully validated for clinical use and larger comprehensive studies are required to fully establish the role of Raman spectroscopy in the molecular diagnostics of cervical cancer. PMID:26180802

  6. Lung cancer - small cell

    MedlinePLUS

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  7. Endometrial and cervical cancer: incidence and mortality among women in the Lodz region

    PubMed Central

    Le?niczak, Beata; Krasomski, Grzegorz; Oszukowski, Przemys?aw; Wo?niak, Piotr

    2015-01-01

    Introduction By the early 21st century the most common cancer of female genitals in Poland was cervical cancer. Now endometrial cancer ranks first. The aim of this study was to analyse the incidence and mortality of endometrial and cervical cancer among women in the Lodz region. Material and methods Data on the incidence and mortality of endometrial and cervical cancer among inhabitants of the Lodz region were obtained from the National Cancer Registry and Bulletin of Cancer Cases in the Lodz region. The analysis covered ten consecutive years beginning in 2001. Results The number of new cases reported in 2010 exceeded that observed in 2001 by 181. The standardized incidence rate of endometrial cancer increased by 6.3, while the standardized incidence rate of cervical cancer decreased by 1.4. Conclusions In the years 2001-2010, the incidence of endometrial cancer increased by 88.3% and that of cervical cancer decreased by 6.5% among inhabitants of the Lodz region. In the years 2001-2010, mortality of endometrial cancer increased by 24.5% and that of cervical cancer decreased by 12.6%. In 2010, the highest crude incidence rates in the Lodz region of both endometrial and cervical cancer at 39.1 were recorded in the district town of Piotrków. PMID:26528109

  8. BANF1 is downregulated by IRF1-regulated microRNA-203 in cervical cancer.

    PubMed

    Mao, Langyong; Zhang, Yan; Mo, Wenjuan; Yu, Yao; Lu, Hong

    2015-01-01

    MicroRNAs (miRNAs) play important roles in various biological processes and are closely associated with the development of cancer. In fact, aberrant expression of miRNAs has been implicated in numerous cancers. In cervical cancer, miR-203 levels are decreased, although the cause of this aberrant expression remains unclear. In this study, we investigate the molecular mechanisms regulating miR-203 gene transcription. We identify the miR-203 transcription start site by 5' rapid amplification of cDNA ends and subsequently identify the miR-203 promoter region. Promoter analysis revealed that IRF1, a transcription factor, regulates miR-203 transcription by binding to the miR-203 promoter. We also demonstrate that miR-203 targets the 3' untranslated region of BANF1, thus downregulating its expression, whereas miR-203 expression is driven by IRF1. MiR-203 is involved in cell cycle regulation and overexpression of miR-203 suppresses cervical cancer cell proliferation, colony formation, migration and invasion. The inhibitory effect of miR-203 on the cancer cells is partially mediated by downregulating its target, BANF1, since knockdown of BANF1 also suppresses colony formation, migration and invasion. PMID:25658920

  9. BANF1 Is Downregulated by IRF1-Regulated MicroRNA-203 in Cervical Cancer

    PubMed Central

    Mao, Langyong; Zhang, Yan; Mo, Wenjuan; Yu, Yao; Lu, Hong

    2015-01-01

    MicroRNAs (miRNAs) play important roles in various biological processes and are closely associated with the development of cancer. In fact, aberrant expression of miRNAs has been implicated in numerous cancers. In cervical cancer, miR-203 levels are decreased, although the cause of this aberrant expression remains unclear. In this study, we investigate the molecular mechanisms regulating miR-203 gene transcription. We identify the miR-203 transcription start site by 5’ rapid amplification of cDNA ends and subsequently identify the miR-203 promoter region. Promoter analysis revealed that IRF1, a transcription factor, regulates miR-203 transcription by binding to the miR-203 promoter. We also demonstrate that miR-203 targets the 3’ untranslated region of BANF1, thus downregulating its expression, whereas miR-203 expression is driven by IRF1. MiR-203 is involved in cell cycle regulation and overexpression of miR-203 suppresses cervical cancer cell proliferation, colony formation, migration and invasion. The inhibitory effect of miR-203 on the cancer cells is partially mediated by downregulating its target, BANF1, since knockdown of BANF1 also suppresses colony formation, migration and invasion. PMID:25658920

  10. Clinical update of the AS04-adjuvanted human papillomavirus-16/18 cervical cancer vaccine, Cervarix.

    PubMed

    Schwarz, Tino F

    2009-11-01

    Persistent infection with human papillomavirus (HPV) is a necessary cause of cervical cancer, resulting annually in 274,000 deaths worldwide. Two prophylactic HPV vaccines are licensed in >100 countries, and immunization programs in young, adolescent girls have been widely implemented. HPV-16/18 AS04-adjuvanted vaccine (Cervarix; GlaxoSmithKline Biologicals, Rixensart, Belgium) has demonstrated type-specific protection against the five most frequent cancer-causing types (16, 18, 31, 33, and 45) that are responsible for 82% of invasive cervical cancers globally. Cervarix has demonstrated efficacy against HPV-45, which is the third most common HPV type in cervical cancer and adenocarcinoma. Final results of a large phase 3 trial recently showed Cervarix substantially reduced the overall burden of cervical precancerous lesions (cervical intraepithelial neoplasia 2+) by 70.2% in an HPV-naïve population approximating young girls prior to sexual debut, the target of most current vaccination programs. Protection offered by Cervarix against nonvaccine types (mainly 31, 33, and 45) might potentially allow for 11%-16% additional protection against cervical cancers, compared to a vaccine only offering protection against HPV-16/18. Another recent study directly compared the antibody response of Cervarix to that of quadrivalent HPV-6/11/16/18 vaccine (Gardasil; Merck, Whitehouse Station, NJ, USA). Cervarix induced significantly superior neutralizing antibody levels as compared with Gardasil for HPV-16 and HPV-18 in all age groups studied. This may translate into more women having detectable (neutralizing) antibodies in cervicovaginal secretions for HPV-16 and HPV-18 after vaccination with Cervarix when compared with Gardasil. Cervarix induced significantly higher frequencies of antigen-specific memory B-cells and T-cells in responders for HPV-16 and HPV-18 as compared with Gardasil. Cervarix continues to show sustained high levels of total and neutralizing antibodies for HPV-16 and HPV-18, 7.3 years after vaccination. This is associated with high efficacy and no breakthrough cases in the HPV-naïve population, and is the longest duration follow-up for safety, immunogenicity, and efficacy for any licensed HPV vaccine to date. PMID:20024678

  11. Personalized peptide vaccination for cervical cancer patients who have received prior platinum-based chemotherapy

    PubMed Central

    Kawano, Kouichiro; Tsuda, Naotake; Waki, Kayoko; Matsueda, Satoko; Hata, Yoshiro; Ushijima, Kimio; Itoh, Kyogo; Yamada, Akira; Kamura, Toshiharu

    2015-01-01

    A feasibility study was performed to evaluate the immunological efficacy and safety of a personalized peptide vaccine (PPV) for cervical cancer patients who have received platinum-based chemotherapy. A total of 24 patients with standard chemotherapy-resistant cervical cancer, including 18 recurrent cases, were enrolled in this study and received a maximum of 4 peptides based on HLA-A types and IgG levels to the vaccine candidate peptides in pre-vaccination plasma. The parental protein expression of most of the vaccine peptides was confirmed in the cervical cancer tissues. No vaccine-related systemic grade 3 or 4 adverse events were observed in any patients. Due to disease progression, 2 patients failed to complete the first cycle of vaccinations (sixth vaccination). Cytotoxic T-lymphocyte (CTL) or IgG responses specific for the peptides used for vaccination were augmented in half of cases after the first cycle. The median overall survival was 8.3 months. The clinical responses of the evaluable 18 cases consisted of 1 case with a partial response and 17 cases with disease progression; the remaining 6 cases were not evaluable. Performance status, injection site skin reaction and circulating PD-1+CD4+ T-cells were significantly prognostic of overall survival, and multivariate analysis also indicated that the performance status and circulating PD-1+CD4+ T-cells were prognostic. Because of the safety and immunological efficacy of PPV and the possible prolongation of overall survival, further clinical trials of PPV at a larger scale in advanced or recurrent cervical cancer patients who have received prior platinum-based chemotherapy are recommended. PMID:26122553

  12. Experiences and unmet needs of women undergoing Pap smear cervical cancer screening: impact on uptake of cervical cancer screening in south eastern Nigeria.

    PubMed

    Chigbu, Chibuike O; Onyebuchi, Azubuike K; Egbuji, Chuma C; Ezugwu, Eusebus C

    2015-03-01

    The burden of cervical cancer is on the increase in sub-Saharan Africa mainly due to inadequate provision and utilisation of cervical cancer prevention services. Several evidence-based strategies have been deployed to improve cervical cancer screening uptake without much success. However, patients' experiences and satisfaction with service provision has not been adequately studied. Inefficiencies in service delivery and less fulfilling experiences by women who attend cervical cancer screening could have considerable impact in future voluntary uptake of cervical cancer screening. Six hundred and eighty women who underwent Pap smear screening in three health care facilities in two states in south eastern Nigeria were interviewed to evaluate their satisfaction, willingness to undertake future voluntary screening, unmet needs and correlation between satisfaction level and willingness to undergo future screening. Satisfaction with Pap smear screening correlated positively with willingness to undertake future voluntary screening (Pearson's correlation coefficient?=?0.78, P?=?0.001). The mean satisfaction score was significantly higher among participants handled by nurses than those handled by the physicians (3.16?±?0.94 vs 2.52?±?0.77, P?=?0.001). 'Scrapping discomfort' of the spatula was reported as the most dissatisfying aspect of Pap smear experience. The need for less invasive screening procedures was the most unmet need. It was concluded that improving the Pap smear screening experience of women and providing less invasive methods of cervical cancer screening with immediate results could improve uptake of cervical cancer screening in south eastern Nigeria. PMID:24980966

  13. Development of a community cancer education program: the Forsyth County, NC cervical cancer prevention project.

    PubMed

    Michielutte, R; Dignan, M B; Wells, H B; Young, L D; Jackson, D S; Sharp, P C

    1989-01-01

    The authors outline the development and implementation of a public health education program for cervical cancer screening among black women in Forsyth County, NC. The educational program includes distributing electronic and printed information media messages, a program of direct education for women, and providing information on current issues in cervical screening to primary-care physicians. Program development was based on social marketing principles, the PRECEDE model, and the communication-behavior change (CBC) model. Since a true experimental design was not feasible, program evaluation is based on several complementary quasi-experimental designs. Analysis of baseline data indicate that the county where the intervention is taking place, and the control county, are similar with respect to both demographic characteristics and the current level of screening activity. Preliminary results indicate that the program has been successful in raising women's level of awareness of cervical cancer and cervical screening. PMID:2511586

  14. [Investigation of Chlamydia trachomatis seropositivity in patients with cervical cancer].

    PubMed

    Onel, Mustafa; Küçücük, Seden; Töre, Gökhan; A?açfidan, Ali

    2013-10-01

    Chlamydia trachomatis is the most frequent bacterial pathogen causing sexually transmitted diseases worldwide. Many studies emphasize that chlamydial infections may play role as a cofactor in cervical cancers caused by high risk human papillomavirus types. The aim of this study was to investigate the presence of antibodies specific for C.trachomatis in patients with cervical cancer in order to detect the frequency of chlamydial infections. A total of 77 patients diagnosed as cervical cancer who have undergone surgery and on treatment at Oncology Institute of Istanbul Faculty of Medicine were included in the study, together with 20 healthy women as the control group. Serum samples obtained from patient and control groups were investigated by a commercial microimmunofluorescence kit (Orgenium Laboratories, Finland) for the detection of C.trachomatis IgG, IgA and IgM antibodies. All of the control subjects (mean age: 30.25 ± 6.4 years) were found seronegative, however the seropositivity rate detected in patients with cervical cancer was 9.1% (7/77). Serological data were interpreted as previous infections in four patients with single IgG positivity (titers: 1/16 in three and 1/32 in one patient), acute infections in two patients with IgG + IgM positivity (titers: IgG 1/64 and IgM 1/64 for both patients), and chronic infection in one patient with IgG + IgA positivity (titers: IgG 1/128 and IgA 1/20). The mean age of seven seropositive patients was 53.88 ± 12.1 years, and three of them had antibodies against FGK, three against BDE and one against CHIJ serogroups of C.trachomatis. None of the cases had the history of sexually transmitted disease. No statistically significance was found between patient and control groups regarding C.trachomatis IgG, IgA and IgM seropositivity (for IgG; p= 0.339, for IgA; p= 1.000, for IgM; p= 1.000). However, it was thought that the statistical evaluations may not be conclusive due to the small number of study groups. In conclusion further studies with large numbers of cases are needed to understand the role of chlamydia infections in the development of cervical cancer. PMID:24237439

  15. Exploring the barriers to health care and psychosocial challenges in cervical cancer management in Kenya

    PubMed Central

    Ngutu, Mariah; Nyamongo, Isaac K

    2015-01-01

    Cervical cancer is the most frequent cancer among women aged between 15 years and 44 years in Kenya, resulting in an estimated 4,802 women being diagnosed with cervical cancer and 2,451 dying from the disease annually. It is often detected at its advanced invasive stages, resulting in a protracted illness upon diagnosis. This qualitative study looked at the illness trajectories of women living with cervical cancer enrolled for follow-up care at Kenyatta National Hospital cancer treatment center and the Nairobi Hospice, both in Nairobi county, Kenya. Using the qualitative phenomenological approach, data were collected through 18 in-depth interviews with women living with cervical cancer between April and July 2011. In-depth interviews with their caregivers, key informant interviews with health care workers, and participant observation field notes were used to provide additional qualitative data. These data were analyzed based on grounded theory’s inductive approach. Two key themes on which the data analysis was then anchored were identified, namely, psychosocial challenges of cervical cancer and structural barriers to quality health care. Findings indicated a prolonged illness trajectory with psychosocial challenges, fueled by structural barriers that women were faced with after a cervical cancer diagnosis. To address issues relevant to the increasing numbers of women with cervical cancer, research studies need to include larger samples of these women. Also important are studies that allow in-depth understanding of the experiences of women living with cervical cancer. PMID:26346001

  16. 76 FR 55915 - Request for Nominations of Candidates to Serve on the Breast and Cervical Cancer Early Detection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ...for Nominations of Candidates to Serve on the Breast and Cervical Cancer Early Detection and Control Advisory Committee...the CDC on the early detection and control of breast and cervical cancer. The role of the BCCEDCAC is to provide...

  17. 77 FR 60703 - Breast and Cervical Cancer Early Detection and Control Advisory Committee: Notice of Charter Renewal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-04

    ...SERVICES Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control Advisory Committee...L. 92-463) of October 6, 1972, that the Breast and Cervical Cancer Early Detection and Control Advisory...

  18. 76 FR 55915 - Request for Nominations of Candidates to Serve on the Breast and Cervical Cancer Early Detection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC) The Centers for... the early detection and control of breast and cervical cancer. The role of the BCCEDCAC is to...

  19. Awareness of cervical cancer prevention among mothers of adolescent daughters in Korea: qualitative research

    PubMed Central

    Kim, Hae Won; Kim, Duck Hee

    2015-01-01

    Objectives Korean adolescent girls are unprepared for cervical cancer prevention due to the lack of a mandatory policy regarding human papilloma virus (HPV) vaccination and school health education regarding cervical cancer. The aim of this study was to determine how aware mothers are about cervical cancer prevention in their adolescent daughters, with a view to developing strategies for expanding primary cervical cancer prevention for adolescent girls through the mothers’ involvement. Design A qualitative design was employed. Nine mothers with adolescent daughters participated in this study and were interviewed using open-ended questions. The themes were extracted by content analysis. Setting A general living area in Seoul, South Korea. Participants The snowball method was used to select mothers. Results Five themes emerged. In general, the mothers’ awareness of cervical cancer was not clear, and they exhibited a lack of awareness of the importance of having a regular Papanicolaou screening test. The mothers recognised that they were role models for their daughters, and realised and accepted the necessity of educating their daughters regarding cervical cancer; however, they perceived barriers related to the prevention of cervical cancer in their daughters. The mothers recommended enforcing sex education in schools and the provision of financial support for HPV vaccination. Conclusions The mothers’ awareness and preparedness with respect to the prevention of cervical cancer in their adolescent daughters were low and inadequate. Mothers should be informed and motivated to play a role in the education of their daughters regarding cervical cancer prevention. Strategies for disseminating information regarding early cervical cancer prevention for adolescent girls are recommended by communicating with both the girls and their mothers and providing them with education regarding cervical cancer prevention. PMID:25976761

  20. Epigenetics of cervical cancer. An overview and therapeutic perspectives

    PubMed Central

    Dueñas-González, Alfonso; Lizano, Marcela; Candelaria, Myrna; Cetina, Lucely; Arce, Claudia; Cervera, Eduardo

    2005-01-01

    Cervical cancer remains one of the greatest killers of women worldwide. It is difficult to foresee a dramatic increase in cure rate even with the most optimal combination of cytotoxic drugs, surgery, and radiation; therefore, testing of molecular targeted therapies against this malignancy is highly desirable. A number of epigenetic alterations occur during all stages of cervical carcinogenesis in both human papillomavirus and host cellular genomes, which include global DNA hypomethylation, hypermetylation of key tumor suppressor genes, and histone modifications. The reversible nature of epigenetic changes constitutes a target for transcriptional therapies, namely DNA methylation and histone deacetylase inhibitors. To date, studies in patients with cervical cancer have demonstrated the feasibility of reactivating the expression of hypermethylated and silenced tumor suppressor genes as well as the hyperacetylating and inhibitory effect upon histone deacetylase activity in tumor tissues after treatment with demethylating and histone deacetylase inhibitors. In addition, detection of epigenetic changes in cytological smears, serum DNA, and peripheral blood are of potential interest for development of novel biomolecular markers for early detection, prediction of response, and prognosis. PMID:16248899

  1. Seminal plasma induces the expression of IL-1? in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway

    PubMed Central

    2014-01-01

    Background Cervical cancer is a chronic inflammatory disease of multifactorial etiology usually presenting in sexually active women. Exposure of neoplastic cervical epithelial cells to seminal plasma (SP) has been shown to promote the growth of cancer cells in vitro and tumors in vivo by inducing the expression of inflammatory mediators including pro-inflammatory cytokines. IL-1? is a pleotropic pro-inflammatory cytokine induced in several human cancers and has been associated with virulent tumor phenotype and poorer prognosis. Here we investigated the expression of IL-1? in cervical cancer, the role of SP in the regulation of IL-1? in neoplastic cervical epithelial cells and the molecular mechanism underlying this regulation. Methods and results Real-time quantitative RT-PCR confirmed the elevated expression of IL-1? mRNA in cervical squamous cell carcinoma and adenocarcinoma tissue explants, compared with normal cervix. Using immunohistochemistry, IL-1? was localized to the neoplastically transformed squamous, columnar and glandular epithelium in all cases of squamous cell carcinoma and adenocarcinomas explants studied. We found that SP induced the expression of IL-? in both normal and neoplastic cervical tissue explants. Employing HeLa (adenocarcinoma) cell line as a model system we identified PGE2 and EGF as possible ligands responsible for SP-mediated induction of IL-1? in these neoplastic cells. In addition, we showed that SP activates EP2/EGFR/PI3kinase-Akt signaling to induce IL-1? mRNA and protein expression. Furthermore, we demonstrate that in normal cervical tissue explants the induction of IL-1? by SP is via the activation of EP2/EGFR/PI3 kinase-Akt signaling. Conclusion SP-mediated induction of IL-1? in normal and neoplastic cervical epithelial cells suggests that SP may promote cervical inflammation as well as progression of cervical cancer in sexually active women. PMID:25237386

  2. Factors Associated with the Uptake of Cervical Cancer Screening Among Women in Portland, Jamaica

    PubMed Central

    Ncube, Butho; Bey, Amita; Knight, Jeremy; Bessler, Patricia; Jolly, Pauline E.

    2015-01-01

    Background: Cervical cancer is the second most common cancer among women worldwide and is the leading cause of deaths in developing countries. Despite the strong evidence that cervical cancer screening results in decreased mortality from this disease, the uptake for cervical screening among Jamaican women remains low. Aims: This study was carried out to identify factors associated with Jamaican women's decisions to screen for cervical cancer. Materials and Methods: Cross-sectional descriptive study of 403 women aged 19 years and older from Portland, Jamaica. An interviewer-administered questionnaire assessed the women's cervical cancer screening history, as well as their knowledge, attitudes, and practices regarding the disease and screening. Results: Of the 403 women interviewed, 66% had a Papanicolaou (Pap) smear and only 16% had a Pap test within the past year. Significant predicators of uptake of screening were being married, age, parity, discussing cancer with health provider, perception of consequences of not having a Pap smear, and knowing a person with cervical cancer. Women who did not know where to go for a Pap smear were 85% less likely to have been screened (prevalence odds ratio (POR): 0.15, 95% confidence interval (CI): 0.04, 0.52). Conclusions: This study showed suboptimal uptake of cervical cancer screening among Jamaican women. Multipronged approaches are needed to address barriers to screening, as well as identify and support conditions that encourage women's use of reproductive health services, thereby reducing incidence and mortality rates from cervical cancer. PMID:25839002

  3. Profile of bevacizumab and its potential in the treatment of cervical cancer

    PubMed Central

    Fisher, Christine M; Schefter, Tracey E

    2015-01-01

    Blocking angiogenesis is an effective antitumor strategy proven in many disease sites. Anti-angiogenic therapies are fulfilling the promise of improved outcomes in cervical cancer as demonstrated in several recent trials. With its overall survival improvement in metastatic or recurrent cervical cancer, a frame shift in the management of these patients has occurred. The US Food and Drug Administration approval of bevacizumab in advanced cervical cancer has led to national guidelines, including the US National Comprehensive Cancer Network guidelines for cervical cancer, including systemic regimens containing bevacizumab as first line combination therapy. Future trials will build on this anti-angiogenesis backbone via targeting additional novel pathways and potentially leading to further improved outcomes in cervical cancer. PMID:26640382

  4. Squamous cell skin cancer

    MedlinePLUS

    ... cell; NMSC - squamous cell; Squamous cell skin cancer; Squamous cell carcinoma of the skin ... squamous cell cancer is called Bowen disease (or squamous cell carcinoma in situ). This type does not spread to ...

  5. Gallic acid induces apoptosis in human cervical epithelial cells containing human papillomavirus type 16 episomes.

    PubMed

    Shi, Lin; Lei, Yanjun; Srivastava, Ranjana; Qin, Weihua; Chen, Jason J

    2016-01-01

    The high-risk human papillomaviruses (HPV) that infect the anogenital tract are strongly associated with the development of cervical carcinoma, which is the second most common cancer in women worldwide. Therapeutic drugs specifically targeting HPV are not available. Polyphenolic compounds have gained considerable attention because of their cytotoxic effects against a variety of cancers and certain viruses. In this study, we examined the effects of several polyphenols on cellular proliferation and death of the human cervical cancer cells and human cervical epithelial cells containing stable HPV type 16 episomes (HPVep). Our results show that three polyphenols inhibited proliferation of HeLa cells dose-dependently. Furthermore, one of the examined polyphenols, gallic acid (GA), also inhibited the proliferation of HPVep cells and exhibited significant specificity towards HPV-positive cells. The anti-proliferative effect of GA on HPVep and HeLa cells was associated with apoptosis and upregulation of p53. These results suggest that GA can be a potential candidate for the development of anti-HPV agents. J. Med. Virol. 88:127-134, 2016. © 2015 Wiley Periodicals, Inc. PMID:26059022

  6. Interventions for encouraging sexual behaviours intended to prevent cervical cancer

    PubMed Central

    Shepherd, Jonathan P; Frampton, Geoff K; Harris, Petra

    2014-01-01

    Background Human papillomavirus (HPV) is the key risk factor for cervical cancer. Continuing high rates of HPV and other sexually transmitted infections (STIs) in young people demonstrate the need for effective behavioural interventions. Objectives To assess the effectiveness of behavioural interventions for young women to encourage safer sexual behaviours to prevent transmission of STIs (including HPV) and cervical cancer. Search methods Systematic literature searches were performed on the following databases: Cochrane Central Register of Controlled Trials (CENTRAL Issue 4, 2009) Cochrane Gynaecological Cancer Review Group (CGCRG) Specialised Register, MEDLINE, EMBASE, CINAHL, PsychINFO, Social Science Citation Index and Trials Register of Promoting Health Interventions (TRoPHI) up to the end of 2009. All references were screened for inclusion against selection criteria. Selection criteria Randomised controlled trials (RCTs) of behavioural interventions for young women up to the age of 25 years that included, amongst other things, information provision about the transmission and prevention of STIs. Trials had to measure behavioural outcomes (e.g. condom use) and/or biological outcomes (e.g. incidence of STIs, cervical cancer). Data collection and analysis A narrative synthesis was conducted. Meta-analysis was not considered appropriate due to heterogeneity between the interventions and trial populations. Main results A total of 5271 references were screened and of these 23 RCTs met the inclusion criteria. Most were conducted in the USA and in health-care clinics (e.g. family planning). The majority of interventions provided information about STIs and taught safer sex skills (e.g. communication), occasionally supplemented with provision of resources (e.g. free sexual health services). They were heterogeneous in duration, contact time, provider, behavioural aims and outcomes. A variety of STIs were addressed including HIV and chlamydia. None of the trials explicitly mentioned HPV or cervical cancer prevention. Statistically significant effects for behavioural outcomes (e.g. increasing condom use) were common, though not universal and varied according to the type of outcome. There were no statistically significant effects of abstaining from or reducing sexual activity. There were few statistically significant effects on biological (STI) outcomes. Considerable uncertainty exists in the risk of bias due to incomplete or ambiguous reporting. Authors’ conclusions Behavioural interventions for young women which aim to promote sexual behaviours protective of STI transmission can be effective, primarily at encouraging condom use. Future evaluations should include a greater focus on HPV and its link to cervical cancer, with long-term follow-up to assess impact on behaviour change, rates of HPV infection and progression to cervical cancer. Studies should use an RCT design where possible with integral process evaluation and cost-effectiveness analysis where appropriate. Given the predominance of USA studies in this systematic review evaluations conducted in other countries would be particularly useful. PMID:21491379

  7. Training in the prevention of cervical cancer: advantages of e-learning

    PubMed Central

    Company, Assumpta; Montserrat, Mireia; Bosch, Francesc X; de Sanjosé, Silvia

    2015-01-01

    Cervical cancer remains the second most common cancer for women worldwide and is the cancer priority in most low- and middle-income countries (LMIC). The development of vaccines against the human papilloma virus (HPV) and the impact of technology both for the detection of HPV and cervical cancer represent milestones and new opportunities in prevention. New internet-based technologies are generating mass access to training programmes. This article presents the methodology for developing an online training programme for the prevention of cervical cancer as well as the results obtained during the four year period wherein the same programme was delivered in Latin America. PMID:26557878

  8. Training in the prevention of cervical cancer: advantages of e-learning.

    PubMed

    Company, Assumpta; Montserrat, Mireia; Bosch, Francesc X; de Sanjosé, Silvia

    2015-01-01

    Cervical cancer remains the second most common cancer for women worldwide and is the cancer priority in most low- and middle-income countries (LMIC). The development of vaccines against the human papilloma virus (HPV) and the impact of technology both for the detection of HPV and cervical cancer represent milestones and new opportunities in prevention. New internet-based technologies are generating mass access to training programmes. This article presents the methodology for developing an online training programme for the prevention of cervical cancer as well as the results obtained during the four year period wherein the same programme was delivered in Latin America. PMID:26557878

  9. Using Intervention Mapping as a Participatory Strategy: Development of a Cervical Cancer Screening Intervention for Hispanic Women

    ERIC Educational Resources Information Center

    Byrd, Theresa L.; Wilson, Katherine M.; Smith, Judith Lee; Heckert, Andrea; Orians, Carlyn E.; Vernon, Sally W.; Fernandez-Esquer, Maria E.; Fernandez, Maria E.

    2012-01-01

    Cervical cancer is preventable with treatment of precancerous lesions and treatable at early stages. Hispanics have higher rates of cervical cancer and lower rates of screening. "Ayndando a las Mujeres con Informaccion, Guia, y Amor para su Salud" (AMIGAS) is an intervention to increase cervical cancer screening in U.S. women of Mexican origin.…

  10. NCI-supported research at ASCO highlights advances in cervical cancer screening and treatment

    Cancer.gov

    3 NCI-funded trials were featured as plenaries at the 2013 ASCO Annual Meeting: •Visual inspection with acetic acid reduced cervical cancer mortality •Adding bevacizumab to treatment of recurrent cervical cancer showed survival benefit •No survival benefit for use of bevacizumab in patients with newly diagnosed glioblastoma

  11. BREAST AND CERVICAL CANCER EARLY DETECTION PROGRAM OR MINIMUM DATA ELEMENTS (MDE)

    EPA Science Inventory

    To help improve access to early detection screening for breast and cervical cancers for underserved women, Congress passed the Breast and Cervical Cancer Mortality Prevention Act of 1990, which created the Centers for Disease Control and Prevention's (CDC) National Breast and Cer...

  12. Using the Theory of Planned Behavior to Understand Cervical Cancer Screening among Latinas

    ERIC Educational Resources Information Center

    Roncancio, Angelica M.; Ward, Kristy K.; Sanchez, Ingrid A.; Cano, Miguel A.; Byrd, Theresa L.; Vernon, Sally W.; Fernandez-Esquer, Maria Eugenia; Fernandez, Maria E.

    2015-01-01

    To reduce the high incidence of cervical cancer among Latinas in the United States it is important to understand factors that predict screening behavior. The aim of this study was to test the utility of theory of planned behavior in predicting cervical cancer screening among a group of Latinas. A sample of Latinas (N = 614) completed a baseline…

  13. Actual versus Perceived Risk of Cervical Cancer among College Women Smokers

    ERIC Educational Resources Information Center

    Saules, Karen K.; Vannest, Neo O.; Mehringer, Ann M.; Pomerleau, Cynthia S.; Lee, Keleigh; Opipari, Anthony W.; Midgley, A. Rees; Kleinsmith, Lewis J.; Sen, Ananda; Snedecor, Sandy M.

    2007-01-01

    Cervical cancer is a well-established smoking-related illness, but many at-risk women are unaware of this link. Objective: The authors designed this study to (1) investigate the relationship of smoking behavior with the history of abnormal Pap test results, sexual history, and perceived risk of cervical cancer and (2) determine whether…

  14. Cervical and Breast Cancer-Screening Knowledge of Women with Developmental Disabilities

    ERIC Educational Resources Information Center

    Parish, Susan L.; Swaine, Jamie G.; Luken, Karen; Rose, Roderick A.; Dababnah, Sarah

    2012-01-01

    Women with developmental disabilities are significantly less likely than women without disabilities to receive cervical and breast cancer screening according to clinical guidelines. The reasons for this gap are not understood. The present study examined the extent of women's knowledge about cervical and breast cancer screening, with the intention…

  15. Grantee Spotlight: Dr. Kolawole Okuyemi - Improving Cervical Cancer Screening Attitudes of African Immigrants and Refugees

    Cancer.gov

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

  16. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    SciTech Connect

    Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; Yale Comprehensive Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028 ; DiMaio, Daniel; Department of Therapeutic Radiology, Yale School of Medicine, P.O. Box 208040, New Haven, CT 06520-8040; Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, P.O. Box 208024; Yale Comprehensive Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028

    2012-01-05

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.

  17. Perception of Human Papillomavirus Infection, Cervical Cancer and HPV Vaccination in North Indian Population

    PubMed Central

    Hussain, Showket; Nasare, Vilas; Kumari, Malasha; Sharma, Shashi; Khan, Mohammad Aijaz; Das, Bhudev C.; Bharadwaj, Mausumi

    2014-01-01

    Background Human Papillomavirus (HPV) -associated cervical cancer is the second-most common cancer in women worldwide but it is the most frequent gynaecological cancer and cancer associated death in India women. The objective of this study was to assess knowledge about cervical cancer, HPV, HPV vaccine, HPV vaccine acceptance among school and undergraduates students and their parent’s perception about acceptance of HPV vaccine in Northern part of India (Delhi and NCR regions). Materials and Methods A qualitative questionnaire based survey among 2500 urban/rural students aged 12–22 years was conducted. Results Overall, a low frequency (15%) of HPV and cervical cancer awareness was observed in students and their parents. However, the awareness was much higher in females belonging to urban setup compared to boys with a perception that HPV causes cervical cancer in women only. Additionally, only (13%) participants who were aware of cervical cancer and HPV) were willing to accept HPV vaccination. Apparently, parents of female students were two times more willing to accept HPV vaccination for their ward than male students (p<0.001; OR 95%CI?=?2.09 (1.58–2.76). Conclusion Cervical cancer and HPV awareness among school, undergraduate students and also to their parents was found to be very low in this part of India. The level of awareness and education appears to be insignificant determinants in rural compared to urban setup. Better health education will be needed to maximize public awareness for cervical cancer prevention. PMID:25386964

  18. Dosimetrically Triggered Adaptive Intensity Modulated Radiation Therapy for Cervical Cancer

    SciTech Connect

    Lim, Karen; Stewart, James; Kelly, Valerie; Xie, Jason; Brock, Kristy K.; Moseley, Joanne; Cho, Young-Bin; Fyles, Anthony; Lundin, Anna; Rehbinder, Henrik; Löf, Johan; Jaffray, David A.; Milosevic, Michael

    2014-09-01

    Purpose: The widespread use of intensity modulated radiation therapy (IMRT) for cervical cancer has been limited by internal target and normal tissue motion. Such motion increases the risk of underdosing the target, especially as planning margins are reduced in an effort to reduce toxicity. This study explored 2 adaptive strategies to mitigate this risk and proposes a new, automated method that minimizes replanning workload. Methods and Materials: Thirty patients with cervical cancer participated in a prospective clinical study and underwent pretreatment and weekly magnetic resonance (MR) scans over a 5-week course of daily external beam radiation therapy. Target volumes and organs at risk (OARs) were contoured on each of the scans. Deformable image registration was used to model the accumulated dose (the real dose delivered to the target and OARs) for 2 adaptive replanning scenarios that assumed a very small PTV margin of only 3 mm to account for setup and internal interfractional motion: (1) a preprogrammed, anatomy-driven midtreatment replan (A-IMRT); and (2) a dosimetry-triggered replan driven by target dose accumulation over time (D-IMRT). Results: Across all 30 patients, clinically relevant target dose thresholds failed for 8 patients (27%) if 3-mm margins were used without replanning. A-IMRT failed in only 3 patients and also yielded an additional small reduction in OAR doses at the cost of 30 replans. D-IMRT assured adequate target coverage in all patients, with only 23 replans in 16 patients. Conclusions: A novel, dosimetry-triggered adaptive IMRT strategy for patients with cervical cancer can minimize the risk of target underdosing in the setting of very small margins and substantial interfractional motion while minimizing programmatic workload and cost.

  19. Multiple Biopsies and Detection of Cervical Cancer Precursors at Colposcopy

    PubMed Central

    Wentzensen, Nicolas; Walker, Joan L.; Gold, Michael A.; Smith, Katie M.; Zuna, Rosemary E.; Mathews, Cara; Dunn, S. Terence; Zhang, Roy; Moxley, Katherine; Bishop, Erin; Tenney, Meaghan; Nugent, Elizabeth; Graubard, Barry I.; Wacholder, Sholom; Schiffman, Mark

    2015-01-01

    Purpose Women with abnormal cervical cancer screening results are referred to colposcopy and biopsy for diagnosis of cervical cancer precursors (high-grade squamous intraepithelial lesions [HSILs]). Colposcopy with a single biopsy can miss identification of HSILs. No systematic study has quantified the improved detection of HSIL by taking multiple lesion-directed biopsies. Methods The Biopsy Study was an observational study of 690 women referred to colposcopy after abnormal cervical cancer screening results. Up to four directed biopsies were taken from distinct acetowhite lesions and ranked by colposcopic impression. A nondirected biopsy of a normal-appearing area was added if fewer than four directed biopsies were taken. HSIL identified by any biopsy was the reference standard of disease used to evaluate the incremental yield and sensitivity of multiple biopsies. Results In the overall population, sensitivities for detecting HSIL increased from 60.6% (95% CI, 54.8% to 66.6%) from a single biopsy to 85.6% (95% CI, 80.3% to 90.2%) after two biopsies and to 95.6% (95% CI, 91.3% to 99.2%) after three biopsies. A significant increase in sensitivity of multiple biopsies was observed in all subgroups. The highest increase in yield of HSIL was observed for women with a high-grade colposcopic impression, HSIL cytology, and human papillomavirus (HPV) type 16 positivity. Only 2% of all HSILs diagnosed in the participants were detected by biopsies of normal-appearing transformation zone. Conclusion Collection of additional lesion-directed biopsies during colposcopy increased detection of histologic HSIL, regardless of patient characteristics. Taking additional biopsies when multiple lesions are present should become the standard practice of colposcopic biopsy. PMID:25422481

  20. 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian

    MedlinePLUS

    ... country this year from cancers of the female reproductive system. To avoid these cancers, it's important to understand ... deaths than any other cancer of the female reproductive system and is the leading cause of death from ...

  1. Human Papillomavirus: Current and Future RNAi Therapeutic Strategies for Cervical Cancer.

    PubMed

    Jung, Hun Soon; Rajasekaran, Nirmal; Ju, Woong; Shin, Young Kee

    2015-01-01

    Human papillomaviruses (HPVs) are small DNA viruses; some oncogenic ones can cause different types of cancer, in particular cervical cancer. HPV-associated carcinogenesis provides a classical model system for RNA interference (RNAi) based cancer therapies, because the viral oncogenes E6 and E7 that cause cervical cancer are expressed only in cancerous cells. Previous studies on the development of therapeutic RNAi facilitated the advancement of therapeutic siRNAs and demonstrated its versatility by siRNA-mediated depletion of single or multiple cellular/viral targets. Sequence-specific gene silencing using RNAi shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, siRNA-based targeting requires further validation of its efficacy in vitro and in vivo, for its potential off-target effects, and of the design of conventional therapies to be used in combination with siRNAs and their drug delivery vehicles. In this review we discuss what is currently known about HPV-associated carcinogenesis and the potential for combining siRNA with other treatment strategies for the development of future therapies. Finally, we present our assessment of the most promising path to the development of RNAi therapeutic strategies for clinical settings. PMID:26239469

  2. Human Papillomavirus: Current and Future RNAi Therapeutic Strategies for Cervical Cancer

    PubMed Central

    Jung, Hun Soon; Rajasekaran, Nirmal; Ju, Woong; Shin, Young Kee

    2015-01-01

    Human papillomaviruses (HPVs) are small DNA viruses; some oncogenic ones can cause different types of cancer, in particular cervical cancer. HPV-associated carcinogenesis provides a classical model system for RNA interference (RNAi) based cancer therapies, because the viral oncogenes E6 and E7 that cause cervical cancer are expressed only in cancerous cells. Previous studies on the development of therapeutic RNAi facilitated the advancement of therapeutic siRNAs and demonstrated its versatility by siRNA-mediated depletion of single or multiple cellular/viral targets. Sequence-specific gene silencing using RNAi shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, siRNA-based targeting requires further validation of its efficacy in vitro and in vivo, for its potential off-target effects, and of the design of conventional therapies to be used in combination with siRNAs and their drug delivery vehicles. In this review we discuss what is currently known about HPV-associated carcinogenesis and the potential for combining siRNA with other treatment strategies for the development of future therapies. Finally, we present our assessment of the most promising path to the development of RNAi therapeutic strategies for clinical settings. PMID:26239469

  3. Development of disulfiram-loaded vaginal rings for the localised treatment of cervical cancer.

    PubMed

    Boyd, Peter; Major, Ian; Wang, Weiguang; McConville, Christopher

    2014-11-01

    Cervical cancer is the third most prevalent cancer in women and disproportionately affects those in low resource settings due to limited programs for screening and prevention. In the developed world treatment for the disease in the non-metastasised state usually takes the form of surgical intervention and/or radiotherapy. In the developing world such techniques are less widely available. This paper describes the development of an intravaginal ring for the localised delivery of a chemotherapeutic drug to the cervix that has the potential to reduce the need for surgical intervention and will also provide a novel anti-cancer therapy for women in low resource settings. Disulfiram has demonstrated antineoplastic action against prostate, breast and lung cancer. Both PEVA and silicone elastomer were investigated for suitability as materials in the manufacture of DSF eluting intravaginal rings. DSF inhibited the curing process of the silicone elastomer, therefore PEVA was chosen as the material to manufacture the DSF-loaded vaginal rings. The vaginal rings had an excellent content uniformity while the DSF remained stable throughout the manufacturing process. Furthermore, the rings provided diffusion controlled release of DSF at levels well in excess of the IC50 value for the HeLa cervical cancer cell line. PMID:25128854

  4. Aurora A Is Critical for Survival in HPV-Transformed Cervical Cancer.

    PubMed

    Gabrielli, Brian; Bokhari, Fawzi; Ranall, Max V; Oo, Zay Yar; Stevenson, Alexander J; Wang, Weili; Murrell, Melanie; Shaikh, Mushfiq; Fallaha, Sora; Clarke, Daniel; Kelly, Madison; Sedelies, Karin; Christensen, Melinda; McKee, Sara; Leggatt, Graham; Leo, Paul; Skalamera, Dubravka; Soyer, H Peter; Gonda, Thomas J; McMillan, Nigel A J

    2015-12-01

    Human papillomavirus (HPV) is the causative agent in cervical cancer. HPV oncogenes are major drivers of the transformed phenotype, and the cancers remain addicted to these oncogenes. A screen of the human kinome has identified inhibition of Aurora kinase A (AURKA) as being synthetically lethal on the background of HPV E7 expression. The investigational AURKA inhibitor MLN8237/Alisertib selectively promoted apoptosis in the HPV cancers. The apoptosis was driven by an extended mitotic delay in the Alisertib-treated HPV E7-expressing cells. This had the effect of reducing Mcl-1 levels, which is destabilized in mitosis, and increasing BIM levels, normally destabilized by Aurora A in mitosis. Overexpression of Mcl-1 reduced sensitivity to the drug. The level of HPV E7 expression influenced the extent of Alisertib-induced mitotic delay and Mcl-1 reduction. Xenograft experiments with three cervical cancer cell lines showed Alisertib inhibited growth of HPV and non-HPV xenografts during treatment. Growth of non-HPV tumors was delayed, but in two separate HPV cancer cell lines, regression with no resumption of growth was detected, even at 50 days after treatment. A transgenic model of premalignant disease driven solely by HPV E7 also demonstrated sensitivity to drug treatment. Here, we show for the first time that targeting of the Aurora A kinase in mice using drugs such as Alisertib results in a curative sterilizing therapy that may be useful in treating HPV-driven cancers. Mol Cancer Ther; 14(12); 2753-61. ©2015 AACR. PMID:26516156

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

    Cancer.gov

    The Center for Population Health and Health Disparities at Ohio State University and the University of Michigan study is focused on understanding why high rates of cervical cancer incidence and mortality are observed in Appalachia Ohio. The multidisciplinary group of investigators are using community-based participatory research within the framework of the Social Determinants of Health model in three inter-related projects. An observational study is being used to investigate multi-level (social, environmental, behavioral, and biological) correlates of "risk-appropriate" Pap smear utilization.

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

    Cancer.gov

    This five-year study focuses on the primary and secondary prevention of cervical cancer among Latina immigrants by testing the efficacy of a theory-based, culturally relevant intervention using a group randomized controlled trial. The intervention combines elements of the sociologic approach (which takes into account cultural beliefs, attitudes, and behaviors) and cognitive-behavioral strategies delivered by lay health educators. The Social Construction Model provides the overall conceptual framework. The PEN-3 and Health Belief Model guides intervention development and implementation.

  7. Cervical dysplasia

    MedlinePLUS

    ... intraepithelial neoplasia (CIN); Precancerous changes of the cervix; Cervical cancer - dysplasia ... Some strains of HPV are known to cause cervical cancer. An HPV DNA test can identify the high- ...

  8. Chromosomal radiosensitivity of human immunodeficiency virus positive/negative cervical cancer patients in South Africa

    PubMed Central

    HERD, OLIVIA; FRANCIES, FLAVIA; KOTZEN, JEFFREY; SMITH, TRUDY; NXUMALO, ZWIDE; MULLER, XANTHENE; SLABBERT, JACOBUS; VRAL, ANNE; BAEYENS, ANS

    2016-01-01

    Cervical cancer is the second most common cancer amongst South African women and is the leading cause of cancer-associated mortality in this region. Several international studies on radiation-induced DNA damage in lymphocytes of cervical cancer patients have remained inconclusive. Despite the high incidence of cervical cancer in South Africa, and the extensive use of radiotherapy to treat it, the chromosomal radiosensitivity of South African cervical cancer patients has not been studied to date. Since a high number of these patients are human immunodeficiency virus (HIV)-positive, the effect of HIV infection on chromosomal radiosensitivity was also investigated. Blood samples from 35 cervical cancer patients (20 HIV-negative and 15 HIV-positive) and 20 healthy controls were exposed to X-rays at doses of 6 MV of 2 and 4 Gy in vitro. Chromosomal radiosensitivity was assessed using the micronucleus (MN) assay. MN scores were obtained using the Metafer 4 platform, an automated microscopic system. Three scoring methods of the MNScore module of Metafer were applied and compared. Cervical cancer patients had higher MN values than healthy controls, with HIV-positive patients having the highest MN values. Differences between groups were significant when using a scoring method that corrects for false positive and false negative MN. The present study suggested increased chromosomal radiosensitivity in HIV-positive South African cervical cancer patients. PMID:26549042

  9. A Comprehensive Review of Dysregulated miRNAs Involved in Cervical Cancer

    PubMed Central

    Sharma, Garima; Dua, Pradeep; Agarwal, Subhash Mohan

    2014-01-01

    MicroRNAs(miRNAs) have become the center of interest in oncology. In recent years, various studies have demonstrated that miRNAs regulate gene expression by influencing important regulatory genes and thus are responsible for causing cervical cancer. Cervical cancer being the third most diagnosed cancer among the females worldwide, is the fourth leading cause of cancer related mortality. Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests, combined with traditional Pap test screening have greatly reduced cervical cancer. Yet, thousands of women continue to be diagnosed with and die of this preventable disease annually. This has necessitated the scientists to ponder over ways of evolving new methods and chalk out novel treatment protocols/strategies. As miRNA deregulation plays a key role in malignant transformation of cervical cancer along with its targets that can be exploited for both prognostic and therapeutic strategies, we have collected and reviewed the role of miRNA in cervical cancer. A systematic search was performed using PubMed for articles that report aberrant expression of miRNA in cervical cancer. The present review provides comprehensive information for 246 differentially expressed miRNAs gathered from 51 published articles that have been implicated in cervical cancer progression. Of these, more than 40 miRNAs have been reported in the literature in several instances signifying their role in the regulation of cancer. We also identified 40 experimentally validated targets, studied the cause of miRNAs dysregulation along with its mechanism and role in different stages of cervical cancer. We also identified and analysed miRNA clusters and their expression pattern in cervical cancer. This review is expected to further enhance our understanding in this field and serve as a valuable reference resource. PMID:25132800

  10. Lymphangiogenesis in cervical cancer evaluated by expression of the VEGF-C gene in clinical stage IB-IIIB

    PubMed Central

    Franc, Magdalena; Kachel-Flis, Agata; Michalski, Bogdan; Fila-Dani?ow, Anna; Mazurek, Urszula; Michalska, Anna; Kuczerawy, Ilona; Skrzypulec-Plinta, Violetta

    2015-01-01

    Introduction The aim of the present study was to evaluate the profile of VEGF-C gene expression in particular stages of cervical cancer (IB-IIIB) and to estimate the correlation between VEGF-C mRNA quantity profile and clinical stage. Material and methods Material for molecular analysis consisted of cervical cancer tissue specimens collected from 38 women (10, 15, 13 cases were classified as IB, IIB and IIIB, respectively). The control group was composed of normal cervical tissues collected from 10 women who underwent hysterectomy for non-oncological reasons. The number of VEGF-C mRNA copies in particular groups was estimated by the reverse transcription quantitative polymerase chain reaction (RT-qPCR) method. Results In the control group the average number of mRNA copies was 134 ± 36 (median: 106), in a group with stage IB it was 16 077 ± 7090 (median: 580), for stage IIB – 35 019 ± 8945 (median: 40 870). The highest number of mRNA VEGF-C copies was derived in a group of patients with cervical cancer of stage IIIB. The average quantity was 56 155 ± 12 470, whereas median 55 981. A statistically significantly higher level of VEGF-C gene expression was disclosed in cervical cancer specimens with stage IIB and IIIB than in the control group. In stage IIIB, the VEGF-C gene expression was significantly higher than in specimens derived from individuals in stage IB. Conclusions In squamous cell carcinoma of the uterine cervix of stage IB-IIIB genes involved in lymphangiogenesis, especially VEGF-C, are expressed, which expression increases as the clinical stage of cervical cancer is higher. PMID:26327898

  11. Bridging Links between Long Noncoding RNA HOTAIR and HPV Oncoprotein E7 in Cervical Cancer Pathogenesis

    PubMed Central

    Sharma, Sweta; Mandal, Paramita; Sadhukhan, Tamal; Roy Chowdhury, Rahul; Ranjan Mondal, Nidhu; Chakravarty, Biman; Chatterjee, Tanmay; Roy, Sudipta; Sengupta, Sharmila

    2015-01-01

    Human Papillomavirus (HPV) type 16 oncoprotein E7 plays a major role in cervical carcinogenesis by interacting with and functionally inactivating various host regulatory molecules. Long noncoding RNA (lncRNA) HOTAIR is one such regulator that recruits chromatin remodelling complex PRC2, creating gene silencing H3K27?me3 marks. Hence, we hypothesized that HOTAIR could be a potential target of E7, in HPV16 related cervical cancers (CaCx). We identified significant linear trend of progressive HOTAIR down-regulation through HPV negative controls, HPV16 positive non-malignants and CaCx samples. Majority of CaCx cases portrayed HOTAIR down-regulation in comparison to HPV negative controls, with corresponding up-regulation of HOTAIR target, HOXD10, and enrichment of cancer related pathways. However, a small subset had significantly higher HOTAIR expression, concomitant with high E7 expression and enrichment of metastatic pathways. Expression of HOTAIR and PRC2-complex members (EZH2 and SUZ12), showed significant positive correlation with E7 expression in CaCx cases and E7 transfected C33A cell line, suggestive of interplay between E7 and HOTAIR. Functional inactivation of HOTAIR by direct interaction with E7 could also be predicted by in silico analysis and confirmed by RNA-Immunoprecipitation. Our study depicts one of the causal mechanisms of cervical carcinogenesis by HPV16 E7, through modulation of HOTAIR expression and function. PMID:26152361

  12. Platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer

    PubMed Central

    Kuji, Shiho; Tanaka, Aki; Takahashi, Nobutaka; Abe, Masakazu; Hirashima, Yasuyuki

    2015-01-01

    Objective The concept of platinum sensitivity and cross-resistance among platinum agents are widely known in the management of recurrent ovarian cancer. The aim of this study was to evaluate two hypotheses regarding the validity of the concept of platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer. Methods In this retrospective study, the clinical data of patients with recurrent cervical cancer, who had a history of receiving cisplatin based chemotherapy (including concurrent chemoradiotherapy [CCRT] with cisplatin) and who received second-line chemotherapy at the time of recurrence between April 2004 and July 2012 were reviewed. Results In total, 49 patients-34 squamous cell carcinomas (69.4%) and 15 non-squamous cell carcinomas (30.6%)-were enrolled. The median age was 53 years (range, 26 to 79 years). Univariate and multivariate analysis showed that a platinum free interval (PFI) of 12 months has a strong relationship with the response rate to second-line chemotherapy. Upon multivariate analysis of survival after second-line platinum-based chemotherapy, a PFI of 12 months significantly influenced both progression-free survival (hazard ratio [HR], 0.349; 95% confidence interval [CI], 0.140 to 0.871; p=0.024) and overall survival (HR, 0.322; 95% CI, 0.123 to 0.842; p=0.021). In patients with a PFI of less than 6 months, the difference of progression-free survival between patients with re-administration of cisplatin (3.0 months) and administration of cisplatin analogue (7.2 months) as second-line chemotherapy was statistically significant (p=0.049, log-rank test). Conclusion The concept of platinum sensitivity could be applied to recurrent cervical cancer and there is a possibility of noncross-resistance of cisplatin analogue with cisplatin. PMID:26197856

  13. Breast and Cervical Cancer Screening: Exploring Perceptions and Barriers with Hmong Women and Men in Oregon

    PubMed Central

    Kue, Jennifer; Zukoski, Ann; Keon, Karen Levy; Thorburn, Sheryl

    2013-01-01

    BACKGROUND Hmong women are reported to have very low rates of breast and cervical cancer screening compared to other Asian and White women in the U.S. Reasons for low cancer screening rates among this population are not well understood. METHODS This qualitative study (n=83) explored Hmong women and men’s perceptions of breast and cervical cancer and cancer screening, women’s experiences with breast and cervical cancer screening, and health care system barriers to screening. RESULTS Hmong women and men perceived breast cancer to be more severe than other types of cancers. Participants believed that breast cancer is curable if detected early. Cervical cancer was not well understood and was of greater concern than breast cancer because of its location within the body and its consequences for reproduction. In general, few participants had personal experiences with breast and/or cervical cancer. Overall, women and men had positive things to say about screenings for breast and cervical cancer, expressing that screenings offered a “proof of illness.” The majority of women did not report any concerns with the exams themselves, although some discussed embarrassment, pain, and discomfort. Barriers to screening included lack of health insurance, making co-payments, language, and issues related to scheduling appointments. Barriers differed for younger and older women. CONCLUSION Results of this study provide new insight into perceptions, experiences, and barriers to breast and cervical cancer screening among Hmong women and men. These findings have implications for developing culturally appropriate interventions to increase breast and cervical cancer screening in this population. PMID:23477387

  14. Cytogenetic characterization of three cell lines derived from primary cervical tumors of different histologic grade

    SciTech Connect

    Hann, E.; Beauregard, L.; Mikumo, R.

    1994-09-01

    Braum et al.(1993) established three cell lines from keratinizing and nonkeratinizing cervical carcinomas. These cell lines were subsequently analyzed for growth properties and the physical state of the human papillomavirus type 16 genome. TC140, derived from a keratinizing cervical tumor, contains human papillomavirus type 16 in the episomal state. TC-146A and TC-146B, derived from a nonkeratinizing large-cell cervical carcinoma, contain human papillomavirus type 16 in the integrated state. The goal of the present study was to cytogenetically characterize these cell lines, developed from cervical carcinoma with a defined histopathology, in order to shed additional light on the biological basis of the histological and clinical heterogeneity of cervical cancers. Information on solid tumors has been limited because they are often difficult to culture and the karyotypes on the available metaphases are often complex with unidentifiable markers. The chromosomes of these three cell lines were characterized in the present study using GTG-banding. For cell line 140, the most striking chromosomal abnormalities noted were the presence of an i(5p) or i(12p) marker, an isochromosome 8q marker and multiple copies of chromosome 9. For cell line 146A, the most notable chromosomal abnormalities noted were the presence of a marker chromosome 7 with additional materials present on the long arms, an isochomosome of the long arms of chromosome 8 and a question of chromosome 19 markers. For cell line 146B, the most notable chromosomal abnormalities were found to be a deleted X chromosome, a marker chromosome 7 with additional material on the long arm, an isochromosome 8q marker, and isochromosome 16q marker and one or more copies of an isochromosome 17q marker. Fluorescent in situ hybridization experiments performed using select probes further corroborate the results of the above-mentioned conventional cytogenetic studies.

  15. Cervical Cancer in Botswana: Current State and Future Steps for Screening and Treatment Programs

    PubMed Central

    Grover, Surbhi; Raesima, Mmakgomo; Bvochora-Nsingo, Memory; Chiyapo, Sebathu P.; Balang, Dawn; Tapela, Neo; Balogun, Onyinye; Kayembe, Mukendi K. A.; Russell, Anthony H.; Monare, Barati; Tanyala, Senate; Bhat, Jailakshmi; Thipe, Kealeboga; Nchunga, Metlha; Mayisela, Susan; Kizito, Balladiah; Ho-Foster, Ari; Gaolebale, Babe Eunice; Gaolebale, Ponatshego A.; Efstathiou, Jason A.; Dryden-Peterson, Scott; Zetola, Nicola; Hahn, Stephen M.; Robertson, Erle S.; Lin, Lilie L.; Morroni, Chelsea; Ramogola-Masire, Doreen

    2015-01-01

    Botswana has a high burden of cervical cancer due to a limited screening program and high HIV prevalence. About 60% of the cervical cancer patients are HIV positive; most present with advanced cervical disease. Through initiatives by the Botswana Ministry of Health and various strategic partnerships, strides have been made in treatment of pre-invasive and invasive cancer. The See and Treat program for cervical cancer is expanding throughout the country. Starting in 2015, school-going girls will be vaccinated against HPV. In regards to treatment of invasive cancer, a multidisciplinary clinic has been initiated at the main oncology hospital to streamline care. However, challenges remain such as delays in treatment, lack of trained human personnel, limited follow-up care, and little patient education. Despite improvements in the care of pre-invasive and invasive cervical cancer patients, for declines in cervical cancer-related morbidity and mortality to be achieved, Botswana needs to continue to invest in decreasing the burden of disease and improving patient outcomes of patients with cervical cancer. PMID:26579491

  16. Increasing cervical cancer screening for a multiethnic population of women in South Texas.

    PubMed

    Fornos, Laura B; Urbansky, Kathleen A; Villarreal, Roberto

    2014-03-01

    Cervical cancer is a preventable disease. Precancers can be identified and treated through cervical screenings. The HPV vaccine prevents precancers from becoming cancers. The aim of the A Su Salud Cervical Cancer Prevention Program was to apply well-understood health promotion techniques and increase the rate of cervical cancer screening among a high-risk, multiethnic, low-income population in South Texas. Qualitative research was used to identify uptake barriers and tailor media messaging. Using existing resources, we applied evidence-based strategies in novel ways that changed personal behaviors, leading to cancer screening, risk reduction, and early detection. We created a database to track a cohort of 32,807 women and measured cervical cancer screenings over 3 years. Our analysis revealed an increase in cervical cancer screenings after use of highly targeted automated telephone reminders and media dissemination on multiple platforms. Those women at low risk for cervical cancer obtained the highest proportion of Pap tests. This innovative, theory-based program increased overall Pap tests up to 9% among women enrolled in a safety net hospital financial assistance plan. This study fills a gap in research on Pap test compliance in uninsured, mostly Hispanic women by building on cultural strengths and tailored messaging. PMID:24170274

  17. Cervical Cancer Screening: Defining the Need for Research

    PubMed Central

    Simoes, E.; Brucker, S.; Beckmann, M. W.; Ortmann, O.; Albring, C.; Wallwiener, D.

    2013-01-01

    With the development of a National Cancer Plan published in 2012, Germany has followed the recommendations of the WHO and the EU. The first area of action listed in Germany?s National Cancer Plan is improving the early detection of cancer. Both citizens and medical specialists are encouraged to take responsibility themselves and contribute to the efforts being made to meet the challenge of cancer. Screening for cervical cancer has long been an integral part of the German Directive for the Early Detection of Cancer and now – following the recommendations given in the European Guideline – an organised screening approach shall be developed to maximise the benefits and minimise the risks through a partial reorganisation of existing structures. Before this can be rolled out nationwide, it will be necessary to check the feasibility and suitability of new contents and organisational structures. The Federal Joint Committee which is largely responsible for the process according to the draft law on the implementation of the National Cancer Plan has emphasised the importance of evidence-based medicine and of collaboration between the autonomous governing bodies within the healthcare system to obtain viable results. For medical specialists, the follow-on question is which areas will need more research in future. New process steps need to be developed and verified to see whether they offer evidence which will support defined approaches or whether such evidence needs to be newly compiled, e.g. by testing invitation procedures for screening in trial schemes. The experience gained during the implementation of the existing directive on early detection of cancer should be integrated into the new process. Research initiated by specialists could encourage the development of a new version of the Directive for the Early Detection of Cancer suitable for the Germany?s healthcare system.

  18. Bee venom induced cell cycle arrest and apoptosis in human cervical epidermoid carcinoma Ca Ski cells.

    PubMed

    Ip, Siu-Wan; Wei, Hsiu-Chuan; Lin, Jing-Pin; Kuo, Hsiu-Maan; Liu, Kuo-Ching; Hsu, Shu-Chun; Yang, Jai-Sing; Mei-Dueyang; Chiu, Tsan-Hung; Han, Sang-Mi; Chung, Jing-Gung

    2008-01-01

    Although it has been previously reported that bee venom (BV) can induce apoptosis in many cancer cell lines, there is no information on the effect of BV on human cervical cancer cells and its molecular mechanisms of action are not fully elucidated. In this study, the possible mechanisms of apoptosis by which BV acts on human cervical cancer Ca Ski cells were investigated. BV induced morphological changes and decreased the percentage of viable Ca Ski cells in a dose- and time-dependent manner. Flow cytometric analysis demonstrated that BV induced the production of reactive oxygen species, increased the level of cytoplasmic Ca2+, reduced mitochondrial membrane potential which led to cytochrome c release, and promoted the activation of caspase-3 which then led to apoptosis. BV also induced an increase in the levels of Fas, p53, p21 and Bax, but a decrease in the level of Bcl-2. The activities of both caspase-8 and caspase-9 were enhanced by BV, promoting caspase-3 activation, leading to DNA fragmentation. Based on the DNA fragmentation and DAPI staining, BV-induced apoptosis was mitochondrial-dependent and caspase-dependent. BV also promoted the expression of AIF and Endo G in the Ca Ski cells. Both AIF and Endo G proteins were released from the mitochondria, and then induced apoptosis which was not through activation of caspase. In conclusion, our data demonstrated that BV-induced apoptosis occurs via a Fas receptor pathway involving mitochondrial-dependent pathways and is closely related to the level of cytoplasmic Ca2+ in Ca Ski cells. PMID:18507026

  19. New paradigms in cervical cancer prevention: opportunities and risks

    PubMed Central

    Ronco, Guglielmo; Giorgi Rossi, Paolo

    2008-01-01

    Testing for the DNA of high-risk types of papilloma virus (HPV) is more sensitive than cytology in detecting pre-cancerous lesions. One of the main advantages will be the possibility of applying prolonged screening intervals. However adequate screening protocols (age of start and stop, screening intervals, management of HPV positive women) need to be applied in order to avoid over-referral to colposcopy and over-treatment and to maintain sustainable costs. Further follow-up of running trials and research on molecular markers will better define these parameters. The new situation will require organised screening programmes with rigorous protocols and monitoring. This will be even more needed when women vaccinated for HPV 16 and 18 will be screened. Research on how to best screen vaccinated women is a priority. This paper proposes an overview of the plausible impact of new technologies in cervical cancer screening in the near future and in the vaccinated cohorts. PMID:19091066

  20. Screening for Cervical Cancer Using Automated Analysis of PAP-Smears

    PubMed Central

    Malm, Patrik

    2014-01-01

    Cervical cancer is one of the most deadly and common forms of cancer among women if no action is taken to prevent it, yet it is preventable through a simple screening test, the so-called PAP-smear. This is the most effective cancer prevention measure developed so far. But the visual examination of the smears is time consuming and expensive and there have been numerous attempts at automating the analysis ever since the test was introduced more than 60 years ago. The first commercial systems for automated analysis of the cell samples appeared around the turn of the millennium but they have had limited impact on the screening costs. In this paper we examine the key issues that need to be addressed when an automated analysis system is developed and discuss how these challenges have been met over the years. The lessons learned may be useful in the efforts to create a cost-effective screening system that could make affordable screening for cervical cancer available for all women globally, thus preventing most of the quarter million annual unnecessary deaths still caused by this disease. PMID:24772188

  1. Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

    PubMed Central

    SONG, DAN; LI, HONG; LI, HAIBO; DAI, JIANRONG

    2015-01-01

    Human papillomavirus (HPV) is widely known as a cause of cervical intraepithelial neoplasia (CIN) and cervical cancer. The mechanisms involved have been studied by numerous studies. The integration of the virus genome into the host cells results in the abnormal regulation of cell cycle control. HPV can also induce immune evasion of the infected cells, which enable the virus to be undetectable for long periods of time. The induction of immunotolerance of the host's immune system by the persistent infection of HPV is one of the most important mechanisms for cervical lesions. The present review elaborates on the roles of several types of immune cells, such as macrophages and natural killer cells, which are classified as innate immune cells, and dendritic cells (DCs), cluster of differentiation (CD)4+/CD8+ T cells and regulatory T cells, which are classified as adaptive immune cells. HPV infection could effect the differentiation of these immune cells in a unique way, resulting in the host's immune tolerance to the infection. The immune system modifications induced by HPV infection include tumor-associated macrophage differentiation, a compromised cellular immune response, an abnormal imbalance between type 1 T-helper cells (Th1) and Th2 cells, regulatory T cell infiltration, and downregulated DC activation and maturation. To date, numerous types of preventative vaccines have been created to slow down carcinogenesis. Immune response activation-based therapeutic vaccine is becoming more and more attractive for the treatment of HPV-associated diseases.

  2. Negative HPV test result is better predictor of low cervical cancer risk than negative Pap test

    Cancer.gov

    Based on a study that included more than 1 million women, DCEG investigators and colleagues have determined that a negative test for human papillomavirus (HPV) infection compared to a negative Pap test provides greater safety, or assurance, against future risk of cervical cancer. That is, women who test negative on the HPV test have an extremely low risk of developing cervical cancer. The findings appeared online July 18, 2014, in the Journal of the National Cancer Institute.

  3. An Updated Natural History Model of Cervical Cancer: Derivation of Model Parameters

    PubMed Central

    Campos, Nicole G.; Burger, Emily A.; Sy, Stephen; Sharma, Monisha; Schiffman, Mark; Rodriguez, Ana Cecilia; Hildesheim, Allan; Herrero, Rolando; Kim, Jane J.

    2014-01-01

    Mathematical models of cervical cancer have been widely used to evaluate the comparative effectiveness and cost-effectiveness of preventive strategies. Major advances in the understanding of cervical carcinogenesis motivate the creation of a new disease paradigm in such models. To keep pace with the most recent evidence, we updated a previously developed microsimulation model of human papillomavirus (HPV) infection and cervical cancer to reflect 1) a shift towards health states based on HPV rather than poorly reproducible histological diagnoses and 2) HPV clearance and progression to precancer as a function of infection duration and genotype, as derived from the control arm of the Costa Rica Vaccine Trial (2004–2010). The model was calibrated leveraging empirical data from the New Mexico Surveillance, Epidemiology, and End Results Registry (1980–1999) and a state-of-the-art cervical cancer screening registry in New Mexico (2007–2009). The calibrated model had good correspondence with data on genotype- and age-specific HPV prevalence, genotype frequency in precancer and cancer, and age-specific cancer incidence. We present this model in response to a call for new natural history models of cervical cancer intended for decision analysis and economic evaluation at a time when global cervical cancer prevention policy continues to evolve and evidence of the long-term health effects of cervical interventions remains critical. PMID:25081182

  4. Invasive Cervical Cancer and Antidepressants: A Nationwide Population-Based Study.

    PubMed

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

    2015-10-01

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

  5. An updated natural history model of cervical cancer: derivation of model parameters.

    PubMed

    Campos, Nicole G; Burger, Emily A; Sy, Stephen; Sharma, Monisha; Schiffman, Mark; Rodriguez, Ana Cecilia; Hildesheim, Allan; Herrero, Rolando; Kim, Jane J

    2014-09-01

    Mathematical models of cervical cancer have been widely used to evaluate the comparative effectiveness and cost-effectiveness of preventive strategies. Major advances in the understanding of cervical carcinogenesis motivate the creation of a new disease paradigm in such models. To keep pace with the most recent evidence, we updated a previously developed microsimulation model of human papillomavirus (HPV) infection and cervical cancer to reflect 1) a shift towards health states based on HPV rather than poorly reproducible histological diagnoses and 2) HPV clearance and progression to precancer as a function of infection duration and genotype, as derived from the control arm of the Costa Rica Vaccine Trial (2004-2010). The model was calibrated leveraging empirical data from the New Mexico Surveillance, Epidemiology, and End Results Registry (1980-1999) and a state-of-the-art cervical cancer screening registry in New Mexico (2007-2009). The calibrated model had good correspondence with data on genotype- and age-specific HPV prevalence, genotype frequency in precancer and cancer, and age-specific cancer incidence. We present this model in response to a call for new natural history models of cervical cancer intended for decision analysis and economic evaluation at a time when global cervical cancer prevention policy continues to evolve and evidence of the long-term health effects of cervical interventions remains critical. PMID:25081182

  6. Resistance of cervical adenocarcinoma cells (HeLa) to venom from the scorpion Centruroides limpidus limpidus

    PubMed Central

    2013-01-01

    Background The venom of Centruroides limpidus limpidus (Cll) is a mixture of pharmacologically active principles. The most important of these are toxic proteins that interact both selectively and specifically with different cellular targets such as ion channels. Recently, anticancer properties of the venom from other scorpion species have been described. Studies in vitro have shown that scorpion venom induces cell death, inhibits proliferation and triggers the apoptotic pathway in different cancer cell lines. Herein, after treating human cervical adenocarcinoma (HeLa) cells with Cll crude venom, their cytotoxic activity and apoptosis induction were assessed. Results Cll crude venom induced cell death in normal macrophages in a dose-dependent manner. However, through viability assays, HeLa cells showed high survival rates after exposure to Cll venom. Also, Cll venom did not induce apoptosis after performing ethidium bromide/acridine orange assays, nor was there any evidence of chromatin condensation or DNA fragmentation. Conclusions Crude Cll venom exposure was not detrimental to HeLa cell cultures. This may be partially attributable to the absence of specific HeLa cell membrane targets for molecules present in the venom of Centruroides limpidus limpidus. Although these results might discourage additional studies exploring the potential of Cll venom to treat human papilloma cervical cancer, further research is required to explore positive effects of crude Cll venom on other cancer cell lines. PMID:24004568

  7. Prognostic Significance of p16 Expression in Advanced Cervical Cancer Treated With Definitive Radiotherapy

    SciTech Connect

    Schwarz, Julie K.; Lewis, James S.; Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO ; Pfeifer, John; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO ; Huettner, Phyllis; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO ; Grigsby, Perry; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO; Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO

    2012-09-01

    Purpose: The purpose of this study was to evaluate the prognostic significance of p16 immunohistochemistry (IHC) in patients with advanced cervical cancer treated with radiation therapy. Materials and Methods: This was a retrospective study of 126 patients with International Federation of Gynecology and Obstetrics Stages Ib1-IVb cervical cancer treated with radiation. Concurrent cisplatin chemotherapy was given to 108 patients. A tissue microarray (TMA) was constructed from the paraffin-embedded diagnostic biopsy specimens. Immunoperoxidase staining was performed on the TMA and a p16 monoclonal antibody was utilized. IHC p16 extent was evaluated and scored in quartiles: 0 = no staining, 1 = 1-25% of cells staining, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100%. Results: The p16 IHC score was 4 in 115 cases, 3 in 1, 2 in 3 and 0 in 7. There was no relationship between p16 score and tumor histology. Patients with p16-negative tumors were older (mean age at diagnosis 65 vs. 52 years for p16-positive tumors; p = 0.01). The 5-year cause-specific survivals were 33% for p16-negative cases (score = 0) compared with 63% for p16-positive cases (scores 1, 2, 3 or 4; p = 0.07). The 5-year recurrence-free survivals were 34% for those who were p16-negative vs. 57% for those who were p16-positive (p = 0.09). In addition, patients with p16-positive tumors (score > 0) were more likely to be complete metabolic responders as assessed by the 3-month posttherapy 18 [F]-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomograph compared with patients with p16-negative tumors (p = 0.03). Conclusion: p16 expression is predictive of improved survival outcome after chemoradiation therapy for advanced-stage invasive cervical carcinoma. Further testing will be needed to evaluate p16-negative cervical tumors.

  8. Factors Mediating the Relationship Between Intimate Partner Violence and Cervical Cancer Among Thai Women.

    PubMed

    Thananowan, Nanthana; Vongsirimas, Nopporn

    2016-02-01

    Previous research suggests that intimate partner violence (IPV), particularly physical or sexual violence, was associated with cervical cancer. However, there is less work examining the mechanism of the relationship between IPV and cervical cancer. The purpose of this cross-sectional study was to examine psychosocial factors (e.g., stress, social support, self-esteem, and depressive symptoms) as mediators of the relationship between IPV and cervical cancer among 532 Thai women with gynecological problems. About 21.1% of participants reported any type of IPV (e.g., physical, sexual, or emotional violence) in the past year and 22.2% had cervical cancer. IPV was significantly positively associated with stress, depressive symptoms, and cervical cancer but negatively correlated with social support and self-esteem. Results from structural equation modeling indicated that not only did IPV exhibit significantly direct effects on social support, stress, and depressive symptoms, and indirect effects on self-esteem, but it also had a significant, positive, total effect on cervical cancer. IPV exhibited the significant indirect effect on cervical cancer through social support, self-esteem, stress, and depressive symptoms. The model fitted very well to the empirical data and explained 9% of variance. The findings affirmed that those psychosocial factors were mediators of the relationship between IPV and cervical cancer. Health care protocols for abused women should include screening for and treatment of IPV-related psychosocial factors. Interventions that provide social support and protect self-esteem should reduce stress and depressive symptoms among abused women, thereby reducing the risk of cervical cancer. PMID:25381266

  9. Long-Term Survival and Risk of Second Cancers After Radiotherapy for Cervical Cancer

    SciTech Connect

    Ohno, Tatsuya; Kato, Shingo; Sato, Shinichiro; Fukuhisa, Kenjiro; Nakano, Takashi; Tsujii, Hirohiko; Arai, Tatsuo

    2007-11-01

    Purpose: To evaluate the risk of second cancers after cervical cancer treated with radiotherapy for Asian populations. Methods and Materials: We reviewed 2,167 patients with cervical cancer undergoing radiotherapy between 1961 and 1986. Intracavitary brachytherapy was performed with high-dose rate source (82%) or low-dose rate source (12%). Relative risk (RR), absolute excess risk (AR), and cumulative risk of second cancer were calculated using the Japanese disease expectancy table. For 1,031 patients, the impact of smoking habit on the increasing risk of second cancer was also evaluated. Results: The total number of person-years of follow-up was 25,771, with 60 patients being lost to follow-up. Among the 2,167 patients, 1,063 (49%) survived more than 10 years. Second cancers were observed in 210 patients, representing a significant 1.2-fold risk (95% confidence interval [CI], 1.1-1.4) of developing second cancer compared with the general population, 1.6% excess risk per person per decade of follow-up, and elevating cumulative risk up to 23.8% (95% CI, 20.3-27.3) at 30 years after radiotherapy. The RR of second cancer was 1.6-fold for patients with the smoking habit and 1.4-fold for those without. Conclusions: Small but significant increased risk of second cancer was observed among Japanese women with cervical cancer mainly treated with high-dose rate brachytherapy. Considering the fact that about half of the patients survived more than 10 years, the benefit of radiotherapy outweighs the risk of developing second cancer.

  10. Radiation Dose and Subsequent Risk for Stomach Cancer in Long-term Survivors of Cervical Cancer

    SciTech Connect

    Kleinerman, Ruth A.; Smith, Susan A.; Holowaty, Eric; Hall, Per; Pukkala, Eero; Vaalavirta, Leila; Stovall, Marilyn; Weathers, Rita; Gilbert, Ethel; Aleman, Berthe M.P.; Kaijser, Magnus; Andersson, Michael; Storm, Hans; Joensuu, Heikki; Lynch, Charles F.; and others

    2013-08-01

    Purpose: To assess the dose–response relationship for stomach cancer after radiation therapy for cervical cancer. Methods and Materials: We conducted a nested, matched case–control study of 201 cases and 378 controls among 53,547 5-year survivors of cervical cancer diagnosed from 1943 to 1995, from 5 international, population-based cancer registries. We estimated individual radiation doses to the site of the stomach cancer for all cases and to corresponding sites for the matched controls (overall mean stomach tumor dose, 2.56 Gy, range 0.03-46.1 and after parallel opposed pelvic fields, 1.63 Gy, range 0.12-6.3). Results: More than 90% of women received radiation therapy, mostly with external beam therapy in combination with brachytherapy. Stomach cancer risk was nonsignificantly increased (odds ratio 1.27-2.28) for women receiving between 0.5 and 4.9 Gy to the stomach cancer site and significantly increased at doses ?5 Gy (odds ratio 4.20, 95% confidence interval 1.41-13.4, P{sub trend}=.047) compared with nonirradiated women. A highly significant radiation dose–response relationship was evident when analyses were restricted to the 131 cases (251 controls) whose stomach cancer was located in the middle and lower portions of the stomach (P{sub trend}=.003), whereas there was no indication of increasing risk with increasing dose for 30 cases (57 controls) whose cancer was located in the upper stomach (P{sub trend}=.23). Conclusions: Our findings show for the first time a significant linear dose–response relationship for risk of stomach cancer in long-term survivors of cervical cancer.

  11. Molecular mechanism of curcumin induced cytotoxicity in human cervical carcinoma cells.

    PubMed

    Singh, Mayank; Singh, Neeta

    2009-05-01

    Cervical cancer is the most common cancer in Indian females and is associated with infection with high risk Human papillomaviruses (HPVs). Curcumin (Diferuloyl methane), a chemopreventive agent, is a natural compound extracted from Curcuma longa that allows suppression of carcinogenesis. The objective of this study was to identify the molecular mechanism of curcumin induced apoptosis in HPV positive cervical cancer HeLa, SiHa and Ca Ski cells. Curcumin causes distinct inhibition of human telomerase reverse transcriptase (hTERT) the catalytic core of telomerase thereby reducing proliferation of cancer cells. Curcumin mediated apoptosis in these cells appears to be due to upregulation of proapoptotic Bax, AIF, release of cytochrome c and down regulation of antiapoptotic Bcl-2, Bcl-XL in HeLa and SiHa. This was accompanied by an increase in caspase-3 and -9 activity, suggesting the role of mitochondria in curcumin mediated apoptotic cell death. Curcumin acts as an anti-inflammatory and anti-proliferative agent by causing down regulation of COX-2, iNOS and cyclin D1 in all the three cell lines but to different extent. PMID:19191010

  12. Feasibility of Utilizing Ethnic Beauty Salons for Cervical Cancer Screening Education.

    PubMed

    Lee, Jongwon; Carvallo, Mauricio; Lee, Eunice

    2015-11-01

    The purpose of this study was to assess the feasibility of using ethnic beauty salons to reach out to Vietnamese and Korean American women for cervical cancer screening education. Participants (N = 62) were conveniently recruited from ethnic beauty salons located in Albuquerque, New Mexico. Two feasibility questionnaires were separately administered to cosmetologists and their customers. Findings support the view that ethnic beauty salons can be used as a gateway to reach out to these populations, and cosmetologists have the potential to operate as community lay health workers to deliver cervical cancer screening education aimed at reducing disparities in cervical cancer and screening to their ethnic customers. PMID:24698810

  13. Risk messages about HPV, cervical cancer, and the HPV vaccine gardasil in North American news magazines.

    PubMed

    Abdelmutti, Nazek; Hoffman-Goetz, Laurie

    2010-09-01

    The human papillomavirus (HPV) vaccine (Gardasil) is a significant advancement in reducing women's risk for cervical cancer. Public opinion of the vaccine can be influenced by the mass media. We used content analysis to assess the discussion of risks, fear-inducing messages about HPV, cervical cancer, and the HPV vaccine in four high circulating North American news magazines from January 2006 to December 2007. Risk messages about HPV and cervical cancer focused on threatening illness or injury. Reporting on the HPV vaccine emphasized it being poorly understood by science. News magazine articles on the HPV vaccine and cervical cancer included fear-inducing messages. Cancer educators need to be aware of media reporting in order to alleviate fears that the public may experience about the HPV vaccine. PMID:20232189

  14. CIP2A cooperates with H-Ras to promote epithelial-mesenchymal transition in cervical-cancer progression.

    PubMed

    Wu, Yi; Gu, Ting-Ting; Zheng, Peng-Sheng

    2015-01-28

    The oncoprotein Cancerous Inhibitor of PP2A (CIP2A) has been reported to interact with Protein phosphatase 2 (PP2A) to stabilize c-Myc and prevent its degradation, and high expression levels of CIP2A have been proved to be related to poor clinical outcomes in multiple cancers. Here, we not only proved that the expression of CIP2A is positively correlated with lymph-node metastasis and cervical-cancer progression, but also revealed a close correlation between the protein's expression and the expression levels of two core epithelial-to-mesenchymal transition (EMT) markers, Vimentin and Snail. In addition, we manipulated CIP2A expression to regulate EMT conversion and employed a pull-down assay, mass-spectrometric (MS) peptide sequencing, as well as bilateral co-immunoprecipitation to identify potentially interacting proteins in cervical-cancer cells. In this study, we proposed and successfully proved, for the first time, that CIP2A physically associates with H-Ras, which leads to the activation of the MEK/ERK signaling pathway and promotes EMT and cervical-cancer progression. Based on our observations and prior findings that CIP2A participates in c-Myc regulation, we conjecture that CIP2A may be a potentially promising molecular target for the adoptive therapy of human cancer. PMID:25458953

  15. Cumulative gene and chromosome alterations associated with in-vitro neoplastic transformation of human cervical cells.

    PubMed

    Popescu, N; Zimonjic, D; Simpson, S; Dipaolo, J

    1995-08-01

    The development of cancer is a multistep process requiring cumulative genetic alterations. An in vit ro model utilizing human cervical cells and papillomaviruses (HPV) that mimics human cervical cancer has been developed. Chromosome and gene alterations associated with distinctive stages of neoplastic transformation were demonstrated with an exocervical cell line obtained after sequential transfection with recombinant HPV-16 DNA and v-Ha-ras oncogene. Acquisition of immortality after HPV-16 transfection was associated with aneuploidy, structural changes of chromosomes 8, 10, 17, 19, 20, and 21, as well as proto-oncogene alterations. HPV-16 DNA was localized to two sites on chromosome 21, with one site at 21q22.2-22.3 near the ets-2 proto-oncogene. Ets-2 as well as c-myc gene mRNA levels were elevated in HPV immortal cells compared to primary nontransfected exocervical strains. Although the HPV-immortalized cells had several features characteristic of malignant cells, they lacked tumorigenic potential. Tumorigenicity occurred after transfection with v-Ha-ras oncogene, which was found stably integrated on chromosome 12 at the telomeric band q24.3. The tumorigenic line had additional clonal chromosomal abnormalities; consisting of multiple deletions involving regions of chromosomes 1p/q, 3p, 9q, loss of one copy of chromosome 11, and a complex rearrangement of chromosomes 8 and 13 as shown by in situ suppression hybridization with whole chromosome probes. Loss of tumor suppressor genes on deleted regions may have contributed to the acquisition of tumorigenicity. The genetic changes observed in these cells parallel those found in cervical carcinomas, demonstrating the validity of the in vitro model for studying the multistep progression resulting in cervical carcinoma. PMID:21552837

  16. The role of mTOR during cisplatin treatment in an in vitro and ex vivo model of cervical cancer.

    PubMed

    Leisching, G R; Loos, B; Botha, M H; Engelbrecht, A-M

    2015-09-01

    Cisplatin is used as a cytotoxic agent for the management of cervical cancer. However, the severity of the side-effects limits the use of this drug, particularly at high doses. Resistance to cisplatin is often attributed to a disruption in the normal apoptotic response via aberrant activation of pathways such as the mTOR pathway. Here we assess the role of mTOR and its effect on cell death sensitization and autophagy in response to a low concentration of cisplatin in cervical cancer cells. Additionally we measured the expression profile of mTOR in normal, low- and high-grade squamous intraepithelial (LSIL and HSIL) lesions and cancerous tissue. An in vitro model of cervical cancer was established using HeLa and CaSki cells. mTOR protein expression as well as autophagy-related proteins were evaluated through Western blotting. Inhibition of mTOR was achieved with the use of rapamycin and RNA silencing. A low concentration of cisplatin administered as a single agent induces autophagy, but not apoptosis. Cisplatin cytotoxicity was greatly enhanced in cancer cells when mTOR had been inhibited prior to cisplatin treatment which was likely due to autophagy being increased above cisplatin-induced levels, thereby inducing apoptosis. Cervical tissue samples revealed an increase in mTOR protein expression in LSIL and carcinoma tissue which suggests a change in autophagy control. Our data suggest that utilising a lower dose of cisplatin combined with mTOR inhibition is a viable treatment option and addresses the challenge of cisplatin dose-dependent toxicity, however future studies are required to confirm this in a clinical setting. PMID:26201060

  17. Multiple Adaptive Neuro-Fuzzy Inference System with Automatic Features Extraction Algorithm for Cervical Cancer Recognition

    PubMed Central

    Subhi Al-batah, Mohammad; Mat Isa, Nor Ashidi; Klaib, Mohammad Fadel; Al-Betar, Mohammed Azmi

    2014-01-01

    To date, cancer of uterine cervix is still a leading cause of cancer-related deaths in women worldwide. The current methods (i.e., Pap smear and liquid-based cytology (LBC)) to screen for cervical cancer are time-consuming and dependent on the skill of the cytopathologist and thus are rather subjective. Therefore, this paper presents an intelligent computer vision system to assist pathologists in overcoming these problems and, consequently, produce more accurate results. The developed system consists of two stages. In the first stage, the automatic features extraction (AFE) algorithm is performed. In the second stage, a neuro-fuzzy model called multiple adaptive neuro-fuzzy inference system (MANFIS) is proposed for recognition process. The MANFIS contains a set of ANFIS models which are arranged in parallel combination to produce a model with multi-input-multioutput structure. The system is capable of classifying cervical cell image into three groups, namely, normal, low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). The experimental results prove the capability of the AFE algorithm to be as effective as the manual extraction by human experts, while the proposed MANFIS produces a good classification performance with 94.2% accuracy. PMID:24707316

  18. The Role of High-Risk Human Papilloma Virus Testing in the Surveillance of Cervical Cancer After Treatment.

    PubMed

    Yu, Miao Crystal; Austin, R Marshall; Lin, Jeff; Beck, Tiffany; Beriwal, Sushil; Comerci, John T; Edwards, Robert P; Sukumvanich, Paniti; Kelley, Joseph; Olawaiye, Alexander B

    2015-11-01

    Context .- Cervical cancer affects 12?000 women in the United States annually. However, despite its prevalence, there remains no good methodology to detect its recurrence. Objective .- To identify the role of cervicovaginal high-risk human papilloma virus (hr-HPV) testing in predicting cervical cancer recurrence. Design .- This is a retrospective study of patients who underwent hr-HPV testing as part of their routine surveillance for cervical cancer. Standard statistical analyses, including ?(2) test and multivariable logistic regression, were performed with IBM SPSS 19.0. Results .- A total of 133 patients were identified, of whom 107 (80%) had squamous cell carcinoma. Ninety patients (68%) had bulky disease and were treated primarily with chemoradiation and brachytherapy. Of patients whose disease recurred, 5 patients (42%) had tested positive for hr-HPV during their surveillance period, compared to 13 patients (11%) for whom disease did not recur (relative risk: 3.88, P = .002). On multivariate logistic regression, hr-HPV status remained significantly predictive of disease recurrence (odds ratio: 12.3, P = .02, 95% confidence interval: 1.5-99.6). Using 2 × 2 table analysis, we found that while cervicovaginal cytology has limited specificity (5.7%) in predicting recurrence, the combination of cytology with hr-HPV testing increases the specificity of testing to 89.3%. Conclusions .- Persistence of hr-HPV is a risk factor for disease recurrence. High-risk-HPV testing is not routinely used during surveillance for cervical cancer, but this study suggests that large, prospective trials investigating the role of hr-HPV testing in cervical cancer surveillance are needed. PMID:26516940

  19. Electron transfer-based combination therapy of cisplatin with tetramethyl-p-phenylenediamine for ovarian, cervical, and lung cancers

    PubMed Central

    Luo, Ting; Yu, Jianqing; Nguyen, Jenny; Wang, Chun-Rong; Bristow, Robert G.; Jaffray, David A.; Zhou, Xiao Zhen; Lu, Kun Ping; Lu, Qing-Bin

    2012-01-01

    The platinum-based chemotherapy is the standard treatment for several types of cancer. However, cancer cells often become refractory with time and most patients with serious cancers die of drug resistance. Recently, we have discovered a unique dissociative electron-transfer mechanism of action of cisplatin, the first and most widely used platinum-based anticancer drug. Here, we show that the combination of cisplatin with an exemplary biological electron donor, N,N,N?,N?-tetramethyl-p-phenylenediamine (TMPD), may overcome the resistance of cancer cells to cisplatin. Our steady-state absorption and fluorescence spectroscopic measurements confirm the effective dissociative electron-transfer reaction between TMPD and cisplatin. More significantly, we found that the combination of 100 ?M TMPD with cisplatin enhances double-strand breaks of plasmid DNA by a factor of approximately 3.5 and dramatically reduces the viability of cisplatin-sensitive human cervical (HeLa) cancer cells and highly cisplatin-resistant human ovarian (NIH:OVCAR-3) and lung (A549) cancer cells. Furthermore, this combination enhances apoptosis and DNA fragmentation by factors of 2–5 compared with cisplatin alone. These results demonstrate that this combination treatment not only results in a strong synergetic effect, but also makes resistant cancer cells sensitive to cisplatin. Because cisplatin is the cornerstone agent for the treatment of a variety of human cancers (including testicular, ovarian, cervical, bladder, head/neck, and lung cancers), our results show both the potential to improve platinum-based chemotherapy of various human cancers and the promise of femtomedicine as an emerging frontier in advancing cancer therapy. PMID:22685209

  20. A novel MLL5 isoform that is essential to activate E6 and E7 transcription in HPV16/18-associated cervical cancers.

    PubMed

    Yew, Chow Wenn; Lee, Pei; Chan, Wai Keong; Lim, Vania Kai Jun; Tay, Sun Kuie; Tan, Theresa M C; Deng, Lih-Wen

    2011-11-01

    Human papillomavirus (HPV) is the primary cause of human cervical cancer. The viral proteins E6 and E7 are essential to transform noncancerous epithelial cells into cancerous carcinomas by targeting key tumor suppressors p53 and retinoblastoma (Rb) proteins, respectively, but the cellular factors involved in E6 and E7 transcription themselves are incompletely understood. In this study, we defined a novel isoform of the mixed lineage leukemia 5 gene (MLL5?) as a specific and critical regulator of E6 and E7 transcription in cervical carcinoma cells. MLL5? is present in HPV16/18-positive cells including human primary cervical carcinoma specimens. Interaction of MLL5? with the AP-1-binding site at the distal region of the HPV18 long control region led to activation of E6/E7 transcription. Conversely, RNA interference-mediated knockdown of MLL5? downregulated both E6 and E7 expression. MLL5? downregulation was sufficient to restore p53 protein levels and reduce Rb phosphorylation, thereby reactivating apoptosis and cell-cycle checkpoints. By defining this novel MLL5? isoform and its specific critical role in activating E6/E7 gene transcription in HPV16/18-induced cervical cancers, our work highlights the potential of MLL5? as a biomarker and new therapeutic target in primary HPV-induced cervical cancers. PMID:21908553

  1. Cervical cancer screening and treatment of cervical intraepithelial neoplasia in female sex workers using “screen and treat” approach

    PubMed Central

    Joshi, Smita; Kulkarni, Vinay; Darak, Trupti; Mahajan, Uma; Srivastava, Yogesh; Gupta, Sanjay; Krishnan, Sumitra; Mandolkar, Mahesh; Bharti, Alok Chandra

    2015-01-01

    Objective Female sex workers (FSWs) are at an increased risk of human immunodeficiency virus (HIV) as well as human papillomavirus (HPV) infections and thus have an increased risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. We evaluated the feasibility of “screen and treat approach” for cervical cancer prevention and the performance of different screening tests among FSWs. Methods Women were screened using cytology, VIA (visual inspection with acetic acid), and VILI (visual inspection with Lugol’s iodine) and underwent colposcopy, biopsy, and immediate treatment using cold coagulation, if indicated, at the same visit. Results We screened 300 FSWs of whom 200 (66.67%) were HIV uninfected and 100 (33.34%) were HIV infected. The overall prevalence of CIN 2–3 lesions was 4.7%. But all women with CIN 2–3 lesions were HIV infected, and thus the prevalence of CIN 2–3 lesions in HIV-infected FSWs was 14/100 (14%, 95% confidence interval: 7.2–20.8). All of them screened positive by all three screening tests. Cold coagulation was well tolerated, with no appreciable side effects. Conclusion Cervical cancer prevention by “screen and treat” approach using VIA, followed by ablative treatment, in this high-risk group of women is feasible and can be implemented through various targeted intervention programs. PMID:25999765

  2. GLTSCR2 is an upstream negative regulator of nucleophosmin in cervical cancer

    PubMed Central

    Kim, Jee-Youn; Cho, Young-Eun; An, Yong-Min; Kim, Sang-Hoon; Lee, Yong-Gwan; Park, Jae-Hoon; Lee, Sun

    2015-01-01

    Nucleophosmin (NPM)/B23, a multifunctional nucleolar phosphoprotein, plays an important role in ribosome biogenesis, cell cycle regulation, apoptosis and cancer pathogenesis. The role of NPM in cells is determined by several factors, including total expression level, oligomerization or phosphorylation status, and subcellular localization. In the nucleolus, NPM participates in rRNA maturation to enhance ribosomal biogenesis. Consistent with this finding, NPM expression is increased in rapidly proliferating cells and many types of human cancers. In response to ribosomal stress, NPM is redistributed to the nucleoplasm, where it inactivates mouse double minute 2 homologue to stabilize p53 and inhibit cell cycle progression. These observations indicate that nucleolus-nucleoplasmic mobilization of NPM is one of the key molecular mechanisms that determine the role of NPM within the cell. However, the regulatory molecule(s) that control(s) NPM stability and subcellular localization, crucial to the pluripotency of intercellular NPM, remain(s) unidentified. In this study, we showed that nucleolar protein GLTSCR2/Pict-1 induced nucleoplasmic translocation and enhanced the degradation of NPM via the proteasomal polyubiquitination pathway. In addition, we showed that GLTSCR2 expression decreased the transforming activity of cells mediated by NPM and that the expression of NPM is reciprocally related to that of GLTSCR2 in cervical cancer tissue. In this study, we demonstrated that GLTSCR2 is an upstream negative regulator of NPM. PMID:25818168

  3. Hormone profiles in women treated for cervical cancer

    SciTech Connect

    Eby, N.L.

    1986-01-01

    Some investigators believe that the protective effect of radiotherapy is hormonally mediated. To determine whether ovarian radiation affects serum hormone levels differently from surgical removal of the ovaries, serum estradiol, estrone, testosterone and androstenedione were evaluated by radioimmunoassay in 320 women (203 irradiated and 117 nonirradiated) from six US clinics participating in a large international cohort study of women treated for cervical cancer since the 1960's. Overall, estradiol levels were similar for both treatment groups, while estrone, testosterone and androstenedione levels were somewhat lower in irradiated women than in nonirradiated women after adjustment for year of birth. Notably, among women in both groups whose treatment included bilateral oophorectomy, irradiated women consistently had lower levels of androstenedione, testosterone and estrone but similar levels of estradiol.

  4. Beyond angiogenesis blockade: targeted therapy for advanced cervical cancer

    PubMed Central

    Eskander, Ramez N.

    2014-01-01

    The global burden of advanced stage cervical cancer remains significant, particular in resource poor countries where effective screening programs are absent. Unfortunately, a proportion of patients will be diagnosed with advanced stage disease, and may suffer from persistent or recurrent disease despite treatment with combination chemotherapy and radiation. Patients with recurrent disease have a poor salvage rate, with an expected 5-year survival of less than 10%. Recently, significant gains have been made in the antiangiogenic arena; nonetheless the need to develop effective alternate targeted strategies is implicit. As such, a review of molecular targeted therapy in the treatment of this disease is warranted. In an era of biologics, combined therapy with cytotoxic drugs and molecular targeted agents, represents an exciting arena yet to be fully explored. PMID:2504543