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Sample records for cell cervical cancer

  1. Cervical cancer

    MedlinePlus

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

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

    ClinicalTrials.gov

    2016-03-14

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

  3. 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

  4. 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

  5. ADXS11-001 High Dose HPV+ Cervical Cancer

    ClinicalTrials.gov

    2016-04-13

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

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

    PubMed Central

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

    2013-01-01

    Cervical cancer can be treated by surgical resection, chemotherapy, and/or radiation. Titanium biomaterials have been suggested as a tool to help in the local delivery of chemotherapeutic agents and/or radiation to cervical cancer sites. However, current titanium medical devices used for treating cervical cancer do not by themselves possess any anticancer properties; such devices act as carriers for pharmaceutical agents or radiation sources and may even allow for the growth of cancer cells. Based on studies, which have demonstrated decreased lung, breast, and bone cancer cell functions on nanostructured compared to nanosmooth polymers, the objective of the present in vitro study was to modify titanium to possess nanotubular surface features and determine cervical cancer cell adhesion after 4 hours. Here, titanium was anodized to possess nanotubular surface features. Results demonstrated the ability to decrease cervical cancer cell adhesion by about a half on nanotubular compared to currently used nanosmooth titanium (without the use of chemotherapeutics or radiation), opening up numerous possibilities for the use of nanotubular titanium in local drug delivery or radiation treatment of cervical cancer. PMID:23493522

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  8. Cervical Cancer

    MedlinePlus

    f AQ FREQUENTLY ASKED QUESTIONS FAQ163 GYNECOLOGIC PROBLEMS Cervical Cancer • What is cancer of the cervix? • How long does it take for cervical cancer to develop? • What is the main cause of ...

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

    ClinicalTrials.gov

    2016-05-02

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

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

    ClinicalTrials.gov

    2014-12-23

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

  11. Cervical Cancer

    MedlinePlus

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

  12. 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

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

    PubMed Central

    2012-01-01

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

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

    ClinicalTrials.gov

    2014-12-29

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

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

    ClinicalTrials.gov

    2016-03-16

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

  16. Tc17 Cells in Patients with Uterine Cervical Cancer

    PubMed Central

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

    2014-01-01

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

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

    ClinicalTrials.gov

    2016-04-28

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

  18. Cervical Cancer

    MedlinePlus

    ... even if it spreads to other body parts later. When cancer starts in the cervix, it is called cervical cancer. The cervix is the lower, narrow end of the uterus. The cervix connects the vagina ( ...

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

    PubMed

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

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

    PubMed Central

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

    2016-01-01

    Objectives To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. Design Nationwide population based cohort study. Setting Cancer and population registries in Sweden. Participants 3 054 328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2 899 968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. Main outcome measures Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. Results The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment within six months, much less than after HSIL (86%). Among women with histology assessment within six months, the incidence rate of cervical cancer after AGC was significantly higher than that after HSIL for up to 6.5 years. Conclusions AGC found at cervical screening is associated with a high and persistent risk of cervical cancer for up to 15 years, particularly for cervical adenocarcinoma and women with AGC at age 30-39. Compared with the reduction in risk of cancer seen after HSIL management, management of AGC seems to have been suboptimal in preventing cervical cancer. Research to optimise management is needed, and a more aggressive assessment strategy is warranted. PMID:26869597

  2. Cervical Cancer

    MedlinePlus

    ... Risk factors for cervical cancer Starting to have sex early (before age 18) Having had many sexual partners Being infected with a sexually transmitted infection (STI) or having had a sex partner who has an STI Smoking Diagnosis & Tests ...

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

    ClinicalTrials.gov

    2014-12-29

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

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

    ClinicalTrials.gov

    2016-02-19

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

  5. Cervical cancer.

    PubMed

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

    2013-03-01

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

  6. 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.

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

    PubMed Central

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

    2016-01-01

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

  8. Cervical Cancer Screening

    MedlinePlus

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

  9. Immunotherapy for Cervical Cancer

    Cancer.gov

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

  10. Cervical Cancer Stage IVA

    MedlinePlus

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

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

    ClinicalTrials.gov

    2016-03-25

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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Smoking and Cervical Cancer

    MedlinePlus

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

  18. 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 ...

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-03-01

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

  2. The effect of Lactobacillus casei extract on cervical cancer cell lines

    PubMed Central

    Kim, Soo-Nyung; Lee, Won Moo; Park, Kyoung Sik; Kim, Jong Bin; Han, Dae Jong

    2015-01-01

    Aim of the study Lactobacillus casei (L. casei) has been shown to inhibit the proliferation of several types of cancer in vivo, but its effect on cervical cells has not been reported. We incubated cells of the human cervical cell lines Caski and HeLa with extracts of L. casei and investigated its effects on the growth of the cells and possible synergy with anticancer drugs. Material and methods Cell-free extracts of L. casei were prepared and purified. Cultures of Caski and HeLa cells adhering to tissue culture plates were treated with L. casei extract. The effects of L. casei extract on the growth of cancer cells and its possible synergy with anti-cancer drugs in cervical cancer cell lines were investigated. The cells were treated with L. casei extract alone, anti-cancer drugs alone [doxorubicin, paclitaxel, 5-fluorouracil (5-FU), and cisplatin], or L. casei extract plus anti-cancer drugs. Results L. casei extract had no significant effect on the growth rate of the two cell lines. Anti-cancer drugs alone induced growth inhibition, but there was no synergistic effect of L. casei extract on growth inhibition. Conclusions L. casei extract does not have a potent effect on the viability of cervical cancer cells in vitro. In addition, L. casei extract has no synergistic effect on the inhibition of growth of cancer cells in the presence of anti-cancer drugs. PMID:26557779

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

    PubMed

    Broniarczyk, Justyna K; Warowicka, Alicja; Kwaśniewska, Anna; Wohuń-Cholewa, Maria; Kwaśniewski, Wojciech; Goździcka-Józefiak, Anna

    2014-05-01

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

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

    PubMed

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

    2016-03-01

    We have recently reported that CYB5D2 plays a role in suppression of cervical cancer tumorigenesis, "CYB5D2 displays tumor suppression activities towards cervical cancer" [1]. We provide the accompany data here describing the effects of CYB5D2 overexpression and addition of recombinant CYB5D2 on HeLa cell cycle distribution. Furthermore, we will present the conditions used to specifically determine CYB5D2 expression in primary cervical and cervical cancer tissues using immunohistochemistry (IHC) and the patient cohort involved in assessing the CYB5D2 protein levels in primary cervical and cervical cancer tissues. PMID:26937452

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  6. Cervical Cancer

    MedlinePlus

    ... Role in Cancer Research Intramural Research Extramural Research Bioinformatics and Cancer NCI-Designated Cancer Centers Frederick National ... Role in Cancer Research Intramural Research Extramural Research Bioinformatics and Cancer NCI-Designated Cancer Centers Frederick National ...

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

    ClinicalTrials.gov

    2016-01-11

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

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

    PubMed Central

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

    2016-01-01

    We have recently reported that CYB5D2 plays a role in suppression of cervical cancer tumorigenesis, “CYB5D2 displays tumor suppression activities towards cervical cancer” [1]. We provide the accompany data here describing the effects of CYB5D2 overexpression and addition of recombinant CYB5D2 on HeLa cell cycle distribution. Furthermore, we will present the conditions used to specifically determine CYB5D2 expression in primary cervical and cervical cancer tissues using immunohistochemistry (IHC) and the patient cohort involved in assessing the CYB5D2 protein levels in primary cervical and cervical cancer tissues. PMID:26937452

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

    PubMed

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

    2015-01-01

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

  10. 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

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

    PubMed Central

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

    2015-01-01

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

  12. 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.

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

    ClinicalTrials.gov

    2016-02-09

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    ClinicalTrials.gov

    2016-03-17

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

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

    PubMed

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

    2013-09-11

    Gold nanoparticles (GNPs) that can release nitric oxide (NO) on visible-light irradiation were prepared using 2-mercapto-5-nitro benzimidazole (MNBI) as stabilizer. These nanoparticles meet overall prerequisites for biomedical applications like small sizes, water solubility, and stability. It was found that even a very low dosage of MNBI-stabilized GNPs exhibit appreciable tumor cell mortality against cervical cancer cell lines, demonstrating the role of NO in killing cancer cells. PMID:23952053

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

    PubMed Central

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

    2015-01-01

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

  19. 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

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

    PubMed Central

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

    2015-01-01

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

  1. 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.

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

    PubMed

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

    2016-05-01

    The clinical management of cervical cancer remains a challenge and the development of new treatment strategies merits attention. However, the discovery and development of novel compounds can be a long and labourious process. Drug repositioning may circumvent this process and facilitate the rapid translation of hypothesis-driven science into the clinics. In this work, we show that a FDA-approved antibiotic, doxycycline, effectively targets human papillomavirus (HPV) positive and negative cervical cancer cells in vitro and in vivo. Doxycycline significantly inhibits proliferation of a panel of cervical cancer cell lines. It also induces apoptosis of cervical cancer cells in a time- and dose-dependent manner. In addition, the apoptosis induced by doxycycline is through caspase-dependent pathway. Mechanism studies demonstrate that doxycycline affects oxygen consumption rate, glycolysis, and reduces ATP levels in cervical cancer cells. In HeLa xenograft mouse model, doxycycline significantly inhibits growth of tumour. Our in vitro and in vivo data clearly demonstrate the inhibitory effects of doxycycline on the growth and survival of cervical cancer cells. Our work provides the evidence that doxycycline can be repurposed for the treatment of cervical cancer and targeting energy metabolism may represent a potential therapeutic strategy for cervical cancer. PMID:26913972

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2009-01-01

    Statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have anti-tumoral effects on multiple cancer types; however, little is known about their effect on cervical cancer. We evaluated the effect on proliferation, cell cycle, oxidative stress and cell death of three statins on CaSki, HeLa (HPV+) and ViBo (HPV−) cervical cancer cell lines. Cell proliferation was assayed by crystal violet staining, cell cycle by flow cytometry and cell death by annexin-V staining. Reactive oxygen species (ROS) production was evaluated by the oxidation of 2,7-dichlorofluorescein diacetate and nitrite concentration (an indirect measure of nitric oxide (NO) production), by the Griess reaction. Inhibition of cell proliferation by atorvastatin, fluvastatin and simvastatin was dose-dependent. ViBo cells were the most responsive. Statins did not affect the cell cycle, instead they induced cell death. The antiproliferative effect in ViBo cells was completely inhibited with mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) treatments. In contrast, cell proliferation of CaSki and HeLa cells was partially (33%) rescued with these intermediates. The three statins increased ROS and nitrite production, mainly in the ViBo cell line. These results suggest that statins exert anti-tumoral effects on cervical cancer through inhibition of cell proliferation and induction of cell death and oxidative stress. Statins could be an aid in the treatment of cervical cancer, especially in HPV− tumors. PMID:23675166

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

    PubMed Central

    Thacker, Pooja Chandrakant; Karunagaran, Devarajan

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. 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

  8. 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

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

    SciTech Connect

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

    2015-02-27

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

  10. 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

  11. 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

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

    PubMed

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

    2016-05-01

    Prolonged accumulation of misfolded or unfolded proteins caused by cellular stress, including oxidative stress, induces endoplasmic reticulum stress, which then activates an unfolded protein response (UPR). ER stress is usually maintained at higher levels in cancer cells as compared to normal cells due to altered metabolism in cancer. Here, we investigated whether curcumin is ER stress-mediated apoptosis in cervical cancer cells, and ROS increased by curcumin are involved in the process as an upstream contributor. Curcumin inhibited proliferation of cervical cancer cells (C33A, CaSki, HeLa, and ME180) and induced apoptotic cell death. Curcumin activated ER-resident UPR sensors, such as PERK, IRE-1α, and ATF6, and their downstream-signaling proteins in cervical cancer cells, but not in normal epithelial cells and peripheral blood mononuclear cells (PBMCs). CHOP, a key factor involved in ER stress-mediated apoptosis, was also activated by curcumin. CHOP decreased the ratio of anti-apoptotic protein Bcl-2 to pro-apoptotic protein Bax expression, and subsequently increased the apoptotic population of cervical cancer cells. Furthermore, curcumin elevated levels of intracellular reactive oxygen species (ROS) in cervical cancer cells, but not in normal epithelial cells. Scavenging ROS resulted in inhibition of ER stress and partially restored cell viability in curcumin-treated cancer cells. Collectively, these observations show that curcumin promotes ER stress-mediated apoptosis in cervical cancer cells through increase of cell type-specific ROS generation. Therefore, modulation of these differential responses to curcumin between normal and cervical cancer cells could be an effective therapeutic strategy without adverse effects on normal cells. © 2015 Wiley Periodicals, Inc. PMID:25980682

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

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

    PubMed

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

    2005-06-01

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

  15. 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 ...

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

    ClinicalTrials.gov

    2016-05-19

    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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-06-01

    Extracellular ATP is known to permeabilize certain cell types to polyatomic cations like YO-PRO1. Here, we report that extracellularly applied ATP stimulated rapid uptake and accumulation of an otherwise weakly membrane permeable fluorescent DNA-binding cytotoxin, Hoechst 33258, into cervical cancer cells. While ATP stimulated Hoechst 33258 uptake in 20-70% of cells from seven cervical cancer cell lines, it stimulated uptake in less than 8% of cervical epithelial cells obtained from the normal transformation zone and ectocervix tissue of 11 patients. ATP-evoked Hoechst 33258 uptake was independent of ionotropic P2X receptors, but dependent on activation of P2Y receptors. Thus, we show here that cervical cancer cells can be selectively induced to take up and accumulate an ionic cytotoxin by exposure to extracellular ATP. PMID:25937122

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

    PubMed Central

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

    2016-01-01

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

  20. 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

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

    SciTech Connect

    Mack, Hildegard I.D.; Munger, Karl

    2013-11-15

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

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

    NASA Astrophysics Data System (ADS)

    Duraipandian, Shiyamala; Zheng, Wei; Huang, Zhiwei

    2012-01-01

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

  3. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

    Carboplatin (CRB) possesses superior anticancer effect in cervical cancer cells with lower incidence of side effects compared to that of cisplatin. However, CRB suffers from severe side effects due to undesirable tissue distributions which contribute to the low therapeutic efficacy. Here, we report a unique folic acid-conjugated chitosan-coated poly(D-L-lactideco-glycolide) (PLGA) nanoparticles (FPCC) prepared for the selective delivery of carboplatin to the cervical cancer cells. The particles were nanosized and spherical shaped with size less than <200nm. The presence of protective chitosan layer controlled the overall release rate of CRB from chitosan-coated PLGA nanoparticles (PCC) and FPCC. FPCC displayed a higher cellular uptake capacity in HeLa cells than compared to non-targeted nanoparticles. Selective uptake of FPCC was due to an interaction of folic acid (FA) with the folate receptors alpha (FRs-?) which is overexpressed on the HeLa and promoted active targeting. These results indicated that FPCC had a specific affinity for the cancerous, HeLa cells owing to ligand-receptor (FA-FR-?) recognition. Consistently, FPCC showed superior cytotoxic effect than any other formulations. The IC50 (concentration of the drug required to kill 50% of the cells) value of FPCC was 0.65?g/ml while it was 1.08, 1.56, and 2.35?g/ml for PCC, PLGA NP, and free CRB, respectively. Consistent with the cytotoxicity assay, FPCC induced higher fraction of early as well as late apoptosis cells. Especially, FPCC induced nearly 45% of early apoptosis cells and more than 35% in late apoptosis. Therefore, we propose that folate-conjugated nanoparticles might have potential applications in cervical cancer therapy. PMID:26608536

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

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

    SciTech Connect

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

    2015-04-17

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

  8. Overexpression of SPARC correlates with poor prognosis in patients with cervical carcinoma and regulates cancer cell epithelial-mesenchymal transition

    PubMed Central

    SHI, DEHUAN; JIANG, KAN; FU, YING; FANG, RUI; LIU, XI; CHEN, JIE

    2016-01-01

    Secreted protein acidic and rich in cysteine (SPARC) is associated with the progression of numerous types of cancer. However, the role of SPARC in the progression of cervical cancer has not yet been adequately elucidated. In the current study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were employed to evaluate the mRNA and protein expression of SPARC in normal cervical tissue, cervical intraepithelial neoplasia (CIN) and cervical cancer. In addition, three epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and vimentin) were detected by immunohistochemistry in the same specimens, and an enzyme-linked immunosorbent assay was conducted to detect the serum levels of SPARC in patients with cervical neoplasia. In highly invasive subclones of human cervical carcinoma cells, HeLa-1 and SiHa-1, lentiviral transfections were performed and RT-qPCR and western blot were used to investigate the effects of downregulated EGF-containing fibulin-like extracellular matrix protein 1 on the expression of E-cadherin, N-cadherin and vimentin. The results revealed that, in cervical carcinoma tissue, SPARC expression was significantly upregulated in a manner that positively correlated with N-cadherin and vimentin expression, and negatively correlated with E-cadherin expression. SPARC overexpression and high serum levels were significantly associated with the progression of cervical cancer and adverse prognosis of cervical cancer patients. Downregulation of SPARC can markedly reduce the expression of N-cadherin and vimentin and increase the expression of E-cadherin. Thus, overexpression of SPARC is significantly associated with poor prognostic clinicopathological characteristics in cervical carcinoma, and may be important in EMT. The results of the current study suggest that SPARC may be a potential therapeutic option for individuals diagnosed with cervical carcinoma. PMID:27123099

  9. DNA Methylation-Independent Reversion of Gemcitabine Resistance by Hydralazine in Cervical Cancer Cells

    PubMed Central

    Candelaria, Myrna; de la Cruz-Hernandez, Erick; Taja-Chayeb, Lucia; Perez-Cardenas, Enrique; Trejo-Becerril, Catalina; Gonzalez-Fierro, Aurora; Chavez-Blanco, Alma; Soto-Reyes, Ernesto; Dominguez, Guadalupe; Trujillo, Jaenai E.; Diaz-Chavez, Jose; Duenas-Gonzalez, Alfonso

    2012-01-01

    Background Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervical cancer cells. Methodology/Principal Findings The cervical cancer cell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR) which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity. Conclusions/Significance Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervical cancer cells via inhibition of G9A histone methyltransferase. PMID:22427797

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

    PubMed

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

    2013-01-01

    Cervical cancer is the second most common cause of cancer in women and has a high mortality rate. Cisplatin, an antitumor agent, is generally used for its treatment. However, the administration of cisplatin is associated with side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown to have anti-cancer properties. In this study, we used Noni, cisplatin, and the two in combination to study their cytotoxic and apoptosis-inducing effects in cervical cancer HeLa and SiHa cell lines. We demonstrate here, that Noni/Cisplatin by themselves and their combination were able to induce apoptosis in both these cell lines. Cisplatin showed slightly higher cell killing as compared to Noni and their combination showed additive effects. The observed apoptosis appeared to be mediated particularly through the up-regulation of p53 and pro-apoptotic Bax proteins, as well as down- regulation of the anti-apoptotic Bcl-2, Bcl-XL proteins and survivin. Augmentation in the activity of caspase-9 and -3 was also observed, suggesting the involvement of the intrinsic mitochondrial pathway of apoptosis for both Noni and Cisplatin in HeLa and SiHa cell lines. PMID:23534730

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

    PubMed

    Mthembu, Nonkululeko N; Motadi, Lesetja Raymond

    2014-09-01

    Cervical cancer, a gynaecological malignant disorder, is a common cause of death in females in Sub-Saharan Africa, striking nearly half a million of lives each year worldwide. Currently, more than 50 % of all modern drugs in clinical use are of natural products, many of which have an ability to control cancer cells (Madhuri and Pandey, Curr Sci 96:779-783, 2009; Richter, Traditional medicines and traditional healers in South Africa, 2003). In South Africa, plants used to treat cancer are rare even though majority of our population continue to put their trust in traditional medicine. In this study we aimed to screen Agave palmeri (AG) and Tulbaghia violacea (TV) for potential role in inducing cell death in cervical cancer cell lines HeLa and ME-180, and in normal human fibroblast cell line KMST-6 cell lines. To achieve this, AG and TV crude extracts were utilized to screen for apoptosis induction, inhibition of cell proliferation followed by elucidation of the role of Bax, Bcl-2, p53, Rb, RBBP and Mdm2 genes in cervical cancer. In brief, plant leaves and roots were collected, crushed and methanolic extracts obtained. Different concentrations of the stock extracts were used to treat cancer cells and measure cell death using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and flow cytometry. Western blot was applied to measure gene expression at protein level using RBBP6, p53, Mdm2, Rb, Bax, Bcl-2 and β-actin mouse monoclonal primary antibodies (IgG) and goat anti mouse coupled with horseradish peroxidase secondary antibody from Santa Cruz Biotechnology and real time-PCR was used for mRNA expression level. Plant extracts of AG and TV were time (24 h) and dose (50, 100, 150 μg/ml) dependent in their induction of cell death with an IC50 ~ 150 μg/ml. A further mixed respond by several genes was observed following treatment with the two plant extracts where RBBP6 was seen to be spliced in cancer cells while Bax was induced and Bcl-2 was inhibited with the levels of p53 remaining the same. The two plant extracts do induce cell death, in a p53 independent manner. PMID:24993114

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

    PubMed Central

    2014-01-01

    Objective Cervical cancer is the third most common type of cancer in women worldwide and radiotherapy remains its predominant therapeutic treatment. Artesunate (ART), a derivative of artemisinin, has shown radiosensitization effect in previous studies. However, such effects of ART have not yet been revealed for cervical cancer cells. Methods The effect of ART on radiosensitivity of human cervical cancer cell lines HeLa and SiHa was assessed using the clonogenic assay. Cell cycle progression and apoptosis alterations were analyzed by flow cytometry. For in vivo study, HeLa or SiHa cells were inoculated into nude mice to establish tumors. Tissues from xenografts were obtained to detect the changes of microvessel density, apoptosis and cell cycle distribution. Microarray was used to analyze differentially expressed genes. Results ART increased the radiosensitivity of HeLa cells (SER = 1.43, P < 0.001) but not of SiHa cells. Apoptosis and the G2-M phase transition induced by X-ray irradiation (IR) were enhanced by ART via increased Cyclin B1 expression in HeLa cells. Tumor growth of xenografts from HeLa but not SiHa cells was significantly inhibited by irradiation combined with ART (tumor volume reduction of 72.34% in IR + ART group vs. 41.22% in IR group in HeLa cells and 48.79% in IR + ART group vs. 44.03% in IR alone group in SiHa cells). Compared with the irradiated group, cell apoptosis was increased and the G2/M cell cycle arrest was enhanced in the group receiving irradiation combined with ART. Furthermore, compared with radiation alone, X-ray irradiation plus ART affected the expression of 203 genes that function in multiple pathways including RNA transport, the spliceosome, RNA degradation and p53 signaling. Conclusion ART potently abrogates the G2 checkpoint control in HeLa cells. ART can induce radiosensitivity of HeLa cells in vitro and in vivo. PMID:24666614

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

    SciTech Connect

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

    2005-05-01

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

  14. Primary small cell cancer of cervical trachea: a case report and literature review

    PubMed Central

    Qiu, Jun; Lin, Wei; Zhou, Min-Li; Zhou, Shui-Hong; Wang, Qin-Ying; Bao, Yang-Yang

    2015-01-01

    Primary small cell carcinoma of trachea is even more uncommon and only a few cases have been reported. Our search revealed only 90 cases in the English-language literatures. Case report: we report a case of cervical tracheal small cell cancer. A 67-year-old male presented with over 2-month history of cough and dyspnea. CT and MRI revealed a 1.0 cm × 2.5 cm intraluminal, irregular soft tissue mass in the upper trachea, approximately 2.5 cm below the glottis. A bronchoscopic examination disclosed a large tumor in the cervical trachea and the lesion occupied more than 60% of the tracheal lumen. Cytological examination suggested some poorly differentiated carcinoma cells. The patient received concurrent chemoradiotherapyand did not perform surgery. One week after CCR, the patient occurred difficulty in breath and tracheal stent was implanted. The symptom was improved markedly. Four days after implant of tracheal stent, the patient presented irritable cough and hemoptysis. The amount of bleeding was about 300 ml. The hemorrhage stopped by treatment of vasoconstrictor and fresh plasma. However, two days later, hemoptysis was continuing even if treatment of vasoconstrictor and fresh plasma. The patient and relatives waived the further therapies. The patient died of massive hemoptysis one week out of hospital. Conclusions: The tracheal small cell cancer is rare. The optimal treatment is unclear. In general, the strategy is introduced concurrent chemoradiotherapy following as small cell lung cancer. In cervical trachea, we suggest that surgical resection should be performed followed by postoperative adjuvant therapy. PMID:26261658

  15. Screening for Cervical Cancer

    MedlinePlus

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

  16. Inhibition of papillomavirus protein function in cervical cancer cells by intrabody targeting.

    PubMed

    Griffin, Heather; Elston, Robert; Jackson, Deborah; Ansell, Keith; Coleman, Michael; Winter, Greg; Doorbar, John

    2006-01-20

    Papillomaviruses (HPVs) are a major cause of human disease, and are responsible for approximately half a million cases of cervical cancer each year. HPVs also cause genital warts, and are the most common sexually transmitted disease in many countries. Despite their importance, there are currently no specific antivirals that are active against HPVs. Papillomavirus protein function is mediated largely by protein-protein interactions, which are difficult to inhibit using conventional approaches. To circumvent these problems, we have prepared an scFv library, and have used this to isolate high-affinity binding molecules that may stearically hinder the association of E6 with p53 and prevent E6-mediated p53 degradation in cervical cancer cells. One of the molecules isolated from the library (GTE6-1), had an affinity for 16E6 of 60nM, and bound within the first zinc finger of the protein. GTE6-1 was able to associate with non-denatured E6 following expression in mammalian cells and could inhibit E6-mediated p53 degradation in in vitro assays. E6-mediated p53 degradation is essential for the continuous growth of cervical cancer cells caused by HPV16. To examine the potential of GTE6-1 as an inhibitor of E6 function in such cells, the molecule was expressed in scFv, diabody and triabody formats in a number of cell lines that are driven to proliferate by the HPV16 oncogenes E6 and E7, including the cervical cancer cell line SiHa. In contrast to small E6-binding peptides containing the ELLG E6-binding motif, GTE6-1 expression lead to changes in nuclear structure, the appearance of apoptosis markers, and an elevation in the levels of p53. No effects were seen with a control scFv molecule, or when GTE6-1 was expressed in cells that are driven to proliferate by simian virus 40 (SV40) T-antigen. Given the accessibility of HPV-associated lesions to topical therapy, our results suggest that large interfering molecules such as intrabodies may be useful inhibitors of viral protein-protein interactions and be particularly appropriate for the treatment of HPV-associated disease. PMID:16324714

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

    PubMed

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

    2015-04-20

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

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

    PubMed Central

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

    2015-01-01

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

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

    MedlinePlus

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

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

    PubMed Central

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

    2016-01-01

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

  1. 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.

  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. Association of cervical cancer with the presence of CD4+ regulatory T cells specific for human papillomavirus antigens.

    PubMed

    van der Burg, Sjoerd H; Piersma, Sytse J; de Jong, Annemieke; van der Hulst, Jeanette M; Kwappenberg, Kitty M C; van den Hende, Muriel; Welters, Marij J P; Van Rood, Jon J; Fleuren, Gert Jan; Melief, Cornelis J M; Kenter, Gemma G; Offringa, Rienk

    2007-07-17

    Because of their important role in the maintenance of self-tolerance, CD4(+) regulatory T cells prevent autoimmune diseases but also curtail the efficacy of T cell immune responses against cancers. We now show that this suppressive action of CD4(+) regulatory T cells is not limited to cancers displaying tumor-associated self antigens, such as melanomas, but also extends to human papillomavirus (HPV)-positive cervical cancers that express foreign tumor antigens. HPV-specific CD4(+) T cells isolated from lymph node biopsies of cervical cancer patients were found to suppress proliferation and cytokine (IFN-gamma, IL-2) production by responder T cells. The capacity of HPV-specific CD4(+) T cells to exert this suppressive effect depended on their activation by cognate HPV antigen and on close-range interactions with responder T cells. HPV-specific CD4(+) regulatory T cells were also retrieved from cervical cancer biopsies, suggesting that they interfere with the anti-tumor immune response at both the induction and effector levels. Our findings offer a plausible explanation for the observed failure of the tumor-specific immune response in patients with cervical carcinoma. PMID:17615234

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

    PubMed Central

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

    2012-01-01

    This study investigated the cytotoxicity of 55 species of plants. Each plant was rated as medicinal, or nonmedicinal based on the existing literature. About 79% of the medicinal plants showed some cytotoxicity, while 75% of the nonmedicinal plants showed bioactivity. It appears that Asteraceae, Labiatae, Pinaceae, and Chenopodiaceae were particularly active against human cervical cancer cells. Based on the literature, only three of the 55 plants have been significantly investigated for cytotoxicity. It is clear that there is much toxicological work yet to be done with both medicinal and nonmedicinal plants. PMID:22500074

  6. 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.

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

    PubMed

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

    2015-01-01

    Many of the anti-cancer agents currently used have an origin in natural sources including plants. Aloe vera is one such plant being studied extensively for its diverse health benefits, including cancer prevention. In this study, the cytotoxic potential of Aloe vera crude extract (ACE) alone or in combination with cisplatin in human breast (MCF-7) and cervical (HeLa) cancer cells was studied by cell viability assay, nuclear morphological examination and cell cycle analysis. Effects were correlated with modulation of expression of genes involved in cell cycle regulation, apoptosis and drug metabolism by RT-PCR. Exposure of cells to ACE resulted in considerable loss of cell viability in a dose- and time-dependent fashion, which was found to be mediated by through the apoptotic pathway as evidenced by changes in the nuclear morphology and the distribution of cells in the different phases of the cell cycle. Interestingly, ACE did not have any significant cytotoxicity towards normal cells, thus placing it in the category of safe chemopreventive agent. Further, the effects were correlated with the downregulation of cyclin D1, CYP 1A1, CYP 1A2 and increased expression of bax and p21 in MCF-7 and HeLa cells. In addition, low dose combination of ACE and cisplatin showed a combination index less than 1, indicating synergistic growth inhibition compared to the agents applied individually. In conclusion, these results signify that Aloe vera may be an effective anti-neoplastic agent to inhibit cancer cell growth and increase the therapeutic efficacy of conventional drugs like cispolatin. Thus promoting the development of plant-derived therapeutic agents appears warranted for novel cancer treatment strategies. PMID:25854386

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Cervical Cancer Rates by Race and Ethnicity

    MedlinePlus

    ... The rate of women getting cervical cancer or dying from cervical cancer varies by race and ethnicity. ... Ethnicity From 1999–2012, the rate of women dying from cervical cancer has varied, depending on their ...

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

    PubMed

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

    2014-11-01

    Gold nanoparticles have been functionalized by non-ionic surfactants (polysorbates) used in pharmaceutical formulations. This results in the formation of more well-dispersed gold nanoparticles (GNPs) than the GNPs formed in neat water. The synthesized GNPs show good temporal stability. The synthesis conditions are mild and environmentally benign. The GNPs can bind to ct-DNA and displace bound dye molecules. The DNA-binding assay is significant as it preliminarily indicated that DNA-GNP conjugates can be formed. Such conjugates are extremely promising for applications in nanobiotechnology. The GNPs can also stain the human cervical cancer (HeLa) cells over a wide concentration range while remaining non-cytotoxic, thus providing a non invasive cell staining method. This result is very promising as we observe staining of HeLa cells at very low GNP concentrations (1 μM) while the cell viability is retained even at 10-fold higher GNP concentrations. PMID:25116948

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

    PubMed

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

    2005-07-27

    Methods were devised for the isolation of large amounts of pure alpha-chaconine and alpha-solanine from Dejima potatoes and for the extraction and analysis of total glycoalkaloids from five fresh potato varieties (Dejima, Jowon, Sumi, Toya, and Vora Valley). These compounds were then evaluated in experiments using a tetrazolium microculture (MTT) assay to assess the anticarcinogenic effects of (a) the isolated pure glycoalkaloids separately, (b) artificial mixtures of the two glycoalkaloids, and (c) the total glycoalkaloids isolated from each of the five potato varieties. All samples tested reduced the numbers of the following human cell lines: cervical (HeLa), liver (HepG2), lymphoma (U937), stomach (AGS and KATO III) cancer cells and normal liver (Chang) cells. The results show that (a) the effects of the glycoalkaloids were concentration dependent in the range of 0.1-10 mug/mL (0.117-11.7 nmol/mL); (b) alpha-chaconine was more active than was alpha-solanine; (c) some mixtures exhibited synergistic effects, whereas other produced additive ones; (d) the different cancer cells varied in their susceptibilities to destruction; and (e) the destruction of normal liver cells was generally lower than that of cancer liver cells. The decreases in cell populations were also observed visually by reversed-phase microscopy. The results complement related observations on the anticarcinogenic potential of food ingredients. PMID:16029012

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

    PubMed Central

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

    2014-01-01

    Background PI3K/AKT pathway alterations are associated with incomplete response to chemoradiation in human cervical cancer. This study was performed to test for mutations in the PI3K pathway and to evaluate the effects of AKT inhibitors on glucose uptake and cell viability. Experimental Design Mutational analysis of DNA from 140 pretreatment tumor biopsies and 8 human cervical cancer cell lines was performed. C33A cells (PIK3CAR88Q and PTENR233*) were treated with increasing concentrations of two allosteric AKT inhibitors (SC-66 and MK-2206) with or without the glucose analogue 2-deoxyglucose (2-DG). Cell viability and activation status of the AKT/mTOR pathway were determined in response to the treatment. Glucose uptake was evaluated by incubation with 18F-fluorodeoxyglucose (FDG). Cell migration was assessed by scratch assay. Results Activating PIK3CA (E545K, E542K) and inactivating PTEN (R233*) mutations were identified in human cervical cancer. SC-66 effectively inhibited AKT, mTOR and mTOR substrates in C33A cells. SC-66 inhibited glucose uptake via reduced delivery of Glut1 and Glut4 to the cell membrane. SC-66 (1 µg/ml-56%) and MK-2206 (30 µM-49%) treatment decreased cell viability through a non-apoptotic mechanism. Decreases in cell viability were enhanced when AKT inhibitors were combined with 2-DG. The scratch assay showed a substantial reduction in cell migration upon SC-66 treatment. Conclusions The mutational spectrum of the PI3K/AKT pathway in cervical cancer is complex. AKT inhibitors effectively block mTORC1/2, decrease glucose uptake, glycolysis, and decrease cell viability in vitro. These results suggest that AKT inhibitors may improve response to chemoradiation in cervical cancer. PMID:24705275

  14. 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 μM concentration of curcumin was used. Curcumin was not genotoxic to HeLa cells. Because argyrophilic nucleolar protein (AgNOR protein) expression is elevated in malignant cells compared to normal cells reflecting the rapidity of cancer cell proliferation, we evaluated curcumin-associated changes in size (area) and number of silver deposits. We showed curcumin-induced decrease in AgNOR protein pools, which may be mediated by global DNA hypermethylation observed after low concentration curcumin treatment. In summary, we have shown for the first time that curcumin at low micromolar range may be effective against HeLa cells, which may have implications for curcumin-based treatment of cervical cancer in humans. PMID:25308441

  15. Suppression of forkhead box Q1 by microRNA-506 represses the proliferation and epithelial-mesenchymal transition of cervical cancer cells.

    PubMed

    Zhang, Mingting; Xu, Qingli; Yan, Shufen; Li, Zhigang; Yan, Wei; Jia, Xiaojing

    2016-05-01

    MicroRNAs (miRNAs) play a pivotal role in cancer progression and development, representing novel therapeutic tools for cancer therapy. Forkhead box Q1 (FOXQ1) functions as an oncogene in various cancer types. However, the functional significance of FOXQ1 in cervical cancer remains unknown. In this study, we investigated the biological function of FOXQ1 in cervical cancer and tested whether or not FOXQ1 can be targeted and regulated by specific miRNAs. We found that FOXQ1 was highly expressed in cervical cancer cell lines. Knockdown of FOXQ1 by small interfering RNA (siRNA) significantly suppressed the proliferation and epithelial-mesenchymal transition (EMT) of cervical cancer cells. FOXQ1 was predicted as a target gene of microRNA-506 (miR-506), and this prediction was validated by dual-luciferase reporter assay. Quantitative real-time PCR and western blot analyses demonstrated that mRNA and protein expression was negatively regulated by miR-506. The expression of miR-506 was downregulated in cervical cancer tissues, and miR-506 expression was inversely correlated with FOXQ1 expression in cervical cancer. The overexpression of miR-506 dramatically suppressed the proliferation and EMT of cervical cancer cells that mimicked the suppression of FOXO1 siRNA. Furthermore, the restoration of FOXQ1 expression significantly reversed the inhibitory effect of miR-506. Overall, our study demonstrated that miR-506 inhibited the proliferation and EMT of cervical cancer cells by targeting FOXQ1 and provided evidence that the miR-506/FOXQ1 axis plays an important role in the pathogenesis of cervical cancer, representing potential molecular targets for the development of anticancer agents for cervical cancer treatment. PMID:26935526

  16. Differential expression of IGF-I and insulin receptor isoforms in HPV positive and negative human cervical cancer cell lines.

    PubMed

    Serrano, M-L; Sánchez-Gómez, M; Bravo, M-M; Yakar, S; LeRoith, D

    2008-10-01

    Human papillomavirus (HPV) is the main risk factor for cervical cancer; however, some carcinomas occur in the absence of the virus. IGF-IR and an isoform of the insulin receptor, IR-A, play important roles in cancer. In this study we assessed the role of the IGF/insulin receptors in cervical cancer cell lines with different HPV status, SiHa (HPV positive), and C33a (HPV negative). Different patterns of receptor expression were found; while SiHa expressed IGF-IR, IR-A and IR-B, and IR/IGF-IR hybrid receptors, C33a cells expressed the IR-A only. Tyrosine phosphorylation of these receptors in response to their corresponding ligands correlated with the expression level of these receptors in the cell lines. Activation of PI3-K and MAPK pathways was revealed in both cell lines, however, no effects on proliferation, migration, or invasion were observed. Here we show that cervical cancer cell lines--positive and negative for HPV--differ in the type of insulin and IGF-1 receptors expressed. Additional studies are needed for characterization of the role of IR-A in cervical carcinogenesis. PMID:18711691

  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. 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

  19. 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 PPARγ 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

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

    PubMed Central

    2012-01-01

    Background Bryophyllum pinnata (B. pinnata) is a common medicinal plant used in traditional medicine of India and of other countries for curing various infections, bowel diseases, healing wounds and other ailments. However, its anticancer properties are poorly defined. In view of broad spectrum therapeutic potential of B. pinnata we designed a study to examine anti-cancer and anti-Human Papillomavirus (HPV) activities in its leaf extracts and tried to isolate its active principle. Methods A chloroform extract derived from a bulk of botanically well-characterized pulverized B. pinnata leaves was separated using column chromatography with step- gradient of petroleum ether and ethyl acetate. Fractions were characterized for phyto-chemical compounds by TLC, HPTLC and NMR and Biological activity of the fractions were examined by MTT-based cell viability assay, Electrophoretic Mobility Shift Assay, Northern blotting and assay of apoptosis related proteins by immunoblotting in human cervical cancer cells. Results Results showed presence of growth inhibitory activity in the crude leaf extracts with IC50 at 552 μg/ml which resolved to fraction F4 (Petroleum Ether: Ethyl Acetate:: 50:50) and showed IC50 at 91 μg/ml. Investigations of anti-viral activity of the extract and its fraction revealed a specific anti-HPV activity on cervical cancer cells as evidenced by downregulation of constitutively active AP1 specific DNA binding activity and suppression of oncogenic c-Fos and c-Jun expression which was accompanied by inhibition of HPV18 transcription. In addition to inhibiting growth, fraction F4 strongly induced apoptosis as evidenced by an increased expression of the pro-apoptotic protein Bax, suppression of the anti-apoptotic molecules Bcl-2, and activation of caspase-3 and cleavage of PARP-1. Phytochemical analysis of fraction F4 by HPTLC and NMR indicated presence of activity that resembled Bryophyllin A. Conclusions Our study therefore demonstrates presence of anticancer and anti-HPV an activity in B. pinnata leaves that can be further exploited as a potential anticancer, anti-HPV therapeutic for treatment of HPV infection and cervical cancer. PMID:22405256

  1. The effects of Micro-429 on inhibition of cervical cancer cells through targeting ZEB1 and CRKL.

    PubMed

    Wang, Yan; Dong, Xue; Hu, Bin; Wang, Xiao-Jing; Wang, Qian; Wang, Wu-Liang

    2016-05-01

    MicroRNA-429 (miR-429) has been suggested to inhibit epithelial-mesenchymal transition (EMT), mainly due to targeting of ZEB1 and ZEB2, which are repressors of the cell to cell contact protein, E-cadherin. In this study, we indicated that regulation of miR-429 in cervical cancer cells modulates cell migration, elongation, as well as transforming growth factor β (TGF-β)-induced stress fiber formation through regulating the cytoskeleton reorganization which is likely independent of the zinc finger E-box binding homeobox (ZEB)/E-cadherin axis. ZEB1 and Crk-like adapter protein (CRKL), as novel targets of miR-429 and direct regulators of the actin cytoskeleton were identified. Remarkably, expression levels of ZEB1 and CRKL were inversely associated with the level of miR-429 in cervical cancer cell lines. In addition, individual knockdown and over-expression of these targeting genes phenocopied the roles of miR-429 over-expression and inhibition on cell elongation, migration, stress fiber formation, and invasion. Targeting of ZEB1 by miR-429 led to a decreased expression and transcriptional activity of CRB3, regulated by interference with the translocation of the CRB3. This finally led to decreasing of the expression of Crumbs 3 (CRB3), which is needed for the formation of stress fiber and contractility. Therefore, miR-429 affects cervical cancer by modulating some EMT-related processes. And in this study, evidences were provided to support a role for miR-429 as a novel target suppressing invasion and migration of human cervical cancer cells through modulation of its targeting genes ZEB1 and CRKL. Taken together, our data indicate that miR-429 plays a pivotal role in cervical cancer progression, which is a potential therapeutic target for patients. PMID:27133071

  2. 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

  3. 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

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

    SciTech Connect

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

    2015-07-01

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

  5. MicroRNA-18a enhances the radiosensitivity of cervical cancer cells by promoting radiation-induced apoptosis.

    PubMed

    Liu, Sha; Pan, Xiaofen; Yang, Qin; Wen, Lu; Jiang, Yao; Zhao, Yingchao; Li, Guiling

    2015-06-01

    Evidence has demonstrated that microRNAs (miRNAs) are important in the regulation of cellular radiosensitivity of various types of human cancer. The aim of this study was to examine the role of miR-18a in regulating the radiosensitivity of cervical cancer, in order to understand the underlying mechanism and to assess the potential of miR-18a as a biomarker for predicting radiosensitivity. The expression of miR-18a was investigated in 48 cervical cancer patients. The results revealed that miR-18a expression was significantly higher in radiosensitive patients than in radioresistant patients by RT-qPCR (P<0.05). Transient transfection experiments showed that miR-18a was upregulated by the miR-18a mimic and downregulated by the miR-18a inhibitor in the SiHa and HeLa cells. Without irradiation treatment, a similar growth was observed in the cells with or without transfection of miR-18a. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Hoechst staining assays showed that miR-18a had no effect on the proliferation and apoptosis of cervical cancer cells after transfection. However, the upregulation of miR-18a suppressed the level of ataxia-telangiectasia mutated and attenuated DNA double-strand break repair after irradiation, which re-sensitized the cervical cancer cells to radiotherapy by promoting apoptosis. Taken together, these results demonstrated that miR-18a is a potential molecule predictor of radiosensitivity in cervical cancer patients and played an important role in the response to radiotherapy. PMID:25963391

  6. 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

  7. Combination of aloe-emodin with radiation enhances radiation effects and improves differentiation in human cervical cancer cells.

    PubMed

    Luo, Jinghua; Yuan, Yong; Chang, Pengyu; Li, Dawei; Liu, Zhiqiang; Qu, Yaqin

    2014-08-01

    The aim of the present study was to investigate the effects of aloe-emodin (AE) on the radiosensitivity and differentiation of HeLa human cervical cancer cells. Cell proliferation was assessed in the HeLa cervical cancer cell line by a methylthiazolyldiphenyl-tetrazolium bromide assay. Radiosensitivity was determined by a colony‑forming assay. Flow cytometry was used for analysis of cell cycle distribution and apoptosis. The expression of γ-H2AX and cyclin B was assessed by western blotting. Alkaline phosphatase (ALP) activity was measured by an ALP activity kit. It was demonstrated that AE inhibited the proliferation of HeLa cells in a concentration- and time-dependent manner, induced G2/M and S phase cell cycle arrest and enhanced the radiosensitivity of HeLa cells. The combination of AE and radiation induced apoptosis, upregulated cyclin B and γ-H2AX expression and further improved ALP activity compared with treatment with AE or radiation alone. AE enhanced the radiosensitivity of HeLa human cervical cancer cells in vitro, inhibited the proliferation of HeLa cells, induced G2/M phase cell cycle arrest and, in combination with radiation, induced the apoptosis and improved the differentiation of HeLa cells. PMID:24920336

  8. 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 < preneoplasia < 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

  9. 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.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. Curcumin Nanoformulation for Cervical Cancer Treatment.

    PubMed

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

    2016-01-01

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

  15. Curcumin Nanoformulation for Cervical Cancer Treatment

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-03-23

    The metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a member of the long non-coding RNA (lncRNA) family, has been reported to be highly enriched in many kinds of cancers and to be a metastasis marker and a prognostic factor. In this study, we found that MALAT1 expression levels were significantly increased in cervical cancer (CC) cells and tissues. The down-regulation of MALAT1 by shRNA in CC cells inhibited the invasion and metastasis in vitro and in vivo. Microarray analysis showed that the knockdown of MALAT1 up-regulated the epithelial markers E-cadherin and ZO-1, and down-regulated the mesenchymal markers β-catenin and Vimentin. This regulation was further confirmed by subsequent observation from RT-PCR, western blot, and immunofluorescence results. Meanwhile, the transcription factor snail, which functions to modulate epithelial-mesenchymal transition (EMT), was also down-regulated at both transcript and protein levels by MALAT1 down-regulation. In addition, we found that MALAT1 expression levels were positively related to HPV infection in cervical epithelial tissues by microarray analysis. Taken together, these results suggest that MALAT1 functions to promote cervical cancer invasion and metastasis via induction of EMT, and it may be a target for the prevention and therapy of cervical cancers. PMID:26798987

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

    PubMed

    Liu, Chun-Tao; Xin, Ying; Tong, Chun-Yan; Li, Bing; Bao, Hong-Li; Zhang, Cai-Yun; Wang, Xue-Hui

    2016-06-01

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

  18. Cigarette smoking and invasive cervical cancer

    SciTech Connect

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

    1986-06-20

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

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

    PubMed Central

    2012-01-01

    Background Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Methods Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. Results CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). Conclusions We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, SiHa, Ca Ski and C-4 I) and found that they express characteristic markers of stem cell, EMT and radioresistance. The fact that CICs demonstrated a higher degree of resistance to radiation than differentiated cells suggests that specific detection and targeting of CICs could be highly valuable for the therapy of tumors from the uterine cervix. PMID:22284662

  20. 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

  1. Calcium efflux from the endoplasmic reticulum regulates cisplatin-induced apoptosis in human cervical cancer HeLa cells

    PubMed Central

    SHEN, LUYAN; WEN, NAIYAN; XIA, MEIHUI; ZHANG, YU; LIU, WEIMIN; XU, YE; SUN, LIANKUN

    2016-01-01

    The function of calcium efflux from the endoplasmic reticulum (ER) in cisplatin-induced apoptosis is not fully understood in cancer cells. The present study used western blot analysis, flow cytometry, immunofluorescence and 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay to investigate calcium signaling in human cervical cancer cells exposed to cisplatin. In the present study, treatment with cisplatin increased free Ca2+ levels in the cytoplasm and mitochondria of human cervical cancer HeLa cells, which further triggers the mitochondria-mediated and ER stress-associated apoptosis pathways. Notably, blocking calcium signaling using the calcium chelating agent bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid acetoxymethyl ester inhibited cisplatin-induced apoptosis via downregulation of the calcium-dependent proteases, the calpains, and innate apoptosis proteins, such as caspsae-3, caspase-4 and C/EBP homologous protein (CHOP). In addition, use of the inositol triphosphate receptor inhibitor, 2-aminoethyl diphenylborinate, to inhibit calcium efflux from the ER resulted in similar effects. This data indicated that calcium efflux from the ER plays a significant role in cisplatin-induced apoptosis in human cervical cancer HeLa cells, which provides further mechanistic insights into the tumor cell-killing effect of cisplatin and potential therapeutic strategies to improve cisplatin chemotherapy. PMID:27073489

  2. 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.

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

    PubMed Central

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

    2014-01-01

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

  4. 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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. 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, ERα 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 ERα 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    The p21-activated kinase 3 (PAK3) and the serum and glucocorticoid-induced kinase 2 (SGK2) have been previously proposed as essential kinases for human papillomavirus positive (HPV+) cervical cancer cell survival. This was established using a shRNA knockdown approach. To validate PAK3 and SGK2 as potential targets for HPV+ cervical cancer therapy, the relationship between shRNA-induced phenotypes in HPV+ cervical cancer cells and PAK3 or SGK2 knockdown was carefully examined. We observed that the phenotypes of HPV+ cervical cancer cells induced by various PAK3 and SGK2 shRNAs could not be rescued by complement expression of respective cDNA constructs. A knockdown-deficient PAK3 shRNA with a single mismatch was sufficient to inhibit HeLa cell growth to a similar extent as wild-type PAK3 shRNA. The HPV+ cervical cancer cells were also susceptible to several non-human target shRNAs. The discrepancy between PAK3 and SGK2 shRNA-induced apoptosis and gene expression knockdown, as well as cell death stimulation, suggested that these shRNAs killed HeLa cells through different pathways that may not be target-specific. These data demonstrated that HPV+ cervical cancer cell death was not associated with RNAi-induced PAK3 and SGK2 knockdown but likely through off-target effects. PMID:25615606

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

    PubMed Central

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

    2012-01-01

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

  11. 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

  12. Drugs Approved for Cervical Cancer

    Cancer.gov

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

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

    MedlinePlus

    ... for cervical cancer? What should you ask your doctor about cervical cancer? It is important for you ... and Staging Treating Cervical Cancer Talking With Your Doctor After Treatment What`s New in Cervical Cancer Research? ...

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

    PubMed Central

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

    2016-01-01

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

  15. Mesenchymal stromal cells derived from cervical cancer tumors induce TGF-β1 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-β1 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-β1 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-β1 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-β to the CeCa/CeCa-MSCs coculture strongly inhibited the expression and production of IL-10 by CeCa cells. Anti-TGF-β as well as anti-IL-10 also abolished HLA-I downregulation, and reversed the inhibition of CTL cytotoxicity. These results provide evidence that TGF-β1 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

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

    PubMed

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

    2015-12-15

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

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

    PubMed Central

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

    2015-01-01

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

  18. 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

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

    PubMed Central

    Smotkin, D; Wettstein, F O

    1986-01-01

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

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

    PubMed

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

    2011-10-01

    The colony-forming ability of cervical cancer is affected by many factors. Oct4, an important transcription factor, is highly expressed in several tumors and promotes the colony-forming ability of cancer cells. Thus, it is considered a potential target for the treatment of cancer. However, we know little about the expression level of Oct4 and its epigenetic regulatory mechanism in cervical cancer cells. In this study, we are the first to observe that human papillomavirus (HPV)-positive cervical cancer cell lines (HeLa, Caski) have a stronger colony-forming ability than HPV-negative cervical cancer cell lines (C-33A). Moreover, the expression level of Oct4 in both HeLa and Caski cells was also higher than that in C-33A cells. We then confirmed that there was a negative correlation between the expression of Oct4 and DNMT3A in these three types of cervical cancer cells, whereas DNA methyltransferase 1 and 3B had no differences among the cell lines. However, after DNA methylation in both key regulatory regions of the Oct4 gene and the genomic levels were analyzed, we found that DNA methyltransferase 3A could neither regulate the expression of Oct4 nor affect the whole level of genomic DNA methylation. These results suggest three points: (1) Oct4 might be treated as a new target for the treatment of cervical cancer, (2) we could not inhibit the expression of Oct4 by DNA demethylation, and (3) HPV virus might initiate cervical carcinogenesis by upregulation of Oct4 expression. PMID:21674242

  1. 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

  2. HPV vaccination and cervical cancer.

    PubMed

    Szarewski, Anne

    2012-12-01

    Cervical cancer is the third most common cancer in women worldwide and often affects women under 40 years with young families. Vaccination against the human papillomavirus (HPV) is a major advance, since it offers primary prevention against the infectious agent that is the main cause of the disease. Two prophylactic vaccines have shown great promise in clinical trials. One of these (Gardasil(®)) contains all four HPV types, offering protection against genital warts (types 6 and 11) as well as cervical cancer (types 16 and 18). The other (Cervarix(®)) contains types 16 and 18, targeting cervical cancer alone, but also has a degree of cross-protection against types 31 and 45, which could significantly increase the level of protection. Adolescent girls remain the primary target of vaccination programmes, but the issues of vaccinating boys and older women are increasingly debated. PMID:22890794

  3. 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.

  4. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

    Merz, B.

    1988-11-18

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

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

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

    PubMed

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

    2015-01-01

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

  9. 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

  10. 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

  11. 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.

  12. Cervical cancer screening in Serbia.

    PubMed

    Kesić, Vesna; Jovićević-Bekić, Ana; Vujnović, Melita

    2007-04-01

    Cervical cancer is the second most common female malignancy in Serbia, after breast cancer, with 1089 new registered cases and an age-standardized incidence rate of 27.2 per 100,000 women in 2002. It is the fourth leading cause of cancer death with 452 deaths and an age-standardized death rate of 7.2 per 100,000 women. Compared with other European countries, the incidence of cervical cancer in Central Serbia is the highest. Regional differences in incidence are pronounced in Serbia with the lowest age-standardized incidence rate (16.6 per 100,000 women) registered in the Macvanski region and the highest in eastern Serbia and the region of Belgrade where the rates are double at 32.5-38.1 per 100,000 women. Cervical cancer prevention in Serbia has relied on opportunistic screening that is characterized by high coverage in younger and low coverage in middle-aged and older women. Screening of selected groups of women employed in large companies is performed annually by many regional hospitals but this approach has little effect on morbidity and mortality. Recently, the Ministry of Health nominated an Expert Group to develop and implement a national cervical cancer screening program. A number of pilot projects have been undertaken with the results used for development of a national programme for cervical cancer screening. This is expected to be finalized in 2007, and launched over a 3-years period in order to cover all women aged 25-64 in entire Serbia. PMID:17598502

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

    PubMed Central

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

    2005-01-01

    The FAS receptor–ligand system plays a key role in regulating apoptotic cell death, and corruption of this signaling pathway has been shown to participate in tumor-immune escape and carcinogenesis. We have recently demonstrated (Sun, T., X. Miao, X. Zhang, W. Tan, P. Xiong, and D. Lin. 2004. J. Natl. Cancer Inst. 96:1030–1036; Zhang, X., X. Miao, T. Sun, W. Tan, S. Qu, P. Xiong, Y. Zhou, and D. Lin. 2005. J. Med. Genet. 42:479–484) that functional polymorphisms in FAS and FAS ligand (FASL) are associated with susceptibility to lung cancer and esophageal cancer; however, the mechanisms underlying this association have not been elucidated. We show that the FAS –1377G, FAS –670A, and FASL –844T variants are expressed more highly on ex vivo–stimulated T cells than the FAS –1377A, FAS –670G, and FASL –844C variants. Moreover, activation-induced cell death (AICD) of T cells carrying the FASL –844C allele was increased. We also found a threefold increased risk of cervical cancer among subjects with the FASL –844CC genotype compared with those with the –844TT genotype in a case-control study in Chinese women. Together, these observations suggest that genetic polymorphisms in the FAS–FASL pathway confer host susceptibility to cervical cancers, which might be caused by immune escape of tumor cells because of enhanced AICD of tumor-specific T cells. PMID:16186185

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

    PubMed Central

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

    2016-01-01

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

  15. 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian

    MedlinePlus

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-01-01

    High-risk human papillomaviruses (HR-HPVs) are consistently associated with human cervical cancer Additionally, the early oncoproteins of HPVs E5, E6 and E7 are known to contribute to tumor progression. The role of E5 is still nebulous. In this study, we aimed to explore the mechanism of E5 action during the human cervical carcinogenesis process. We created four cell models overexpressing HPV16 or HPV18 E5 (HPV16/18 E5) and investigated their ability to proliferate, along with their metastatic characteristics such as migration and invasion. The expression of HPV16/18 E5 protein in various cell lines was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, we compared the levels of phosphorylated paxillin as well as E-cadherin in cell models and controls by western blot analysis. Finally, we assessed the tumor growth rate of human cervical cancer cells overexpressing HPV16/18 E5 in vivo. We discovered that the expression of HPV16/18 E5 consistently increased the malignant potential of various human cervical cancer cells compared with the primary counterparts. We demonstrated the involvement of HPV16/18 E5 in proliferation, migration, invasion and regulation of the actin cytoskeleton in human cervical cancer cells. In particular we discovered that HPV16/18 E5 overexpression in human cervical cancer cells correlated with higher levels of paxillin proteins phosphorylated on tyrosine residues and with the downregulation of E-cadherin. Importantly, injection of HPV16/18 E5-overexpressing human cervical cancer cells into mice increased both HPV-and non-HPV-derived tumor growth. Collectively, our data indicate that HPV16/18 E5 influences progression of the human cervical cancer malignant phenotype. This study provides new insights into HPV16/18 E5 as a possible agent that may have an impact on the therapeutic strategies targeting human cervical cancer. PMID:23128977

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  20. Molecular imaging in cervical cancer.

    PubMed

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

    2016-06-01

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

  1. 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

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

    PubMed Central

    Baharara, Javad; Amini, Elaheh; Namvar, Farideh

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-02-01

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

  5. 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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2014-11-15

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

  8. 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

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

    PubMed

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

    2015-06-15

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

  10. Anal cancer and cervical cancer screening: key differences.

    PubMed

    Darragh, Teresa M; Winkler, Barbara

    2011-02-25

    Cervical cancer and anal cancer share many similarities including causation by oncogenic human papillomaviruses; however, significant differences exist in their epidemiology, risk factors, biologic behavior, management, and treatment. Although rare, the incidence of anal cancer is alarmingly high and continues to increase in high-risk populations, particularly men who have sex with men regardless of their human immunodeficiency virus (HIV) status. There are no national screening guidelines for anal cancer. Using the success of cervical cancer screening as a model, anal cancer screening approaches apply anal cytology, high-resolution anoscopy, and directed biopsy to guide treatment and management strategies. Although much has been learned about the natural history and epidemiology of anal intraepithelial neoplasia (AIN), the rate of progression of high-grade anal intraepithelial neoplasia (HGAIN) to invasive squamous cell carcinomas is not known. The impact of screening and treatment of HGAIN on morbidity and mortality from anal cancer are also unknown. Because the incidence of HGAIN and anal squamous cell carcinoma continue to increase, it is imperative to find pathways for effective screening, early detection, and therapeutic intervention. This article provides an overview of anal cancer screening while highlighting its differences from cervical cancer screening and the remaining obstacles and controversies to implementation of a successful anal cancer screening program. PMID:21319310

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

    PubMed Central

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

    2013-01-01

    Background In Greenland, the incidence of cervical cancer caused by human papillomavirus (HPV) is 25 per 100,000 women; 2.5 times the Danish rate. In Greenland, the disease is most frequent among women aged 30–40. Systematic screening can identify women with cervical cell changes, which if untreated may cause cervical cancer. In 2007, less than 40% of eligible women in Greenland participated in screening. Objective To examine Greenlandic women's perception of disease, their understanding of the connection between HPV and cervical cancer, and the knowledge that they deem necessary to decide whether to participate in cervical cancer screening. Study design The methods used to perform this research were 2 focus-group interviews with 5 Danish-speaking women and 2 individual interviews with Greenlandic-speaking women. The analysis involved a phenomenological-hermeneutic approach with 3 levels of analysis: naive reading, structural analysis and critical interpretation. Results These revealed that women were unprepared for screening results showing cervical cell changes, since they had no symptoms. When diagnosed, participants believed that they had early-stage cancer, leading to feelings of vulnerability and an increased need to care for themselves. Later on, an understanding of HPV as the basis for diagnosis and the realization that disease might not be accompanied by symptoms developed. The outcome for participants was a life experience, which they used to encourage others to participate in screening and to suggest ways that information about screening and HPV might reach a wider Greenlandic population. Conclusion Women living through the process of cervical disease, treatment and follow-up develop knowledge about HPV, cervical cell changes, cervical disease and their connection, which, if used to inform cervical screening programmes, will improve the quality of information about HPV, cervical cancer and screening participation. This includes that verbal and written information given at the point of screening and diagnosis needs to be complemented by visual imagery. PMID:23984277

  12. 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.

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

    PubMed Central

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

    2015-01-01

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

  14. B4GALT3 up-regulation by miR-27a contributes to the oncogenic activity in human cervical cancer cells.

    PubMed

    Sun, Yanrui; Yang, Xi; Liu, Min; Tang, Hua

    2016-06-01

    β-1,4-Galactosyltransferase III (B4GALT3) is an enzyme responsible for the generation of poly-N-acetyllactosamine and is involved in tumorigenesis. However, B4GALT3-dysregulation and its role in cervical cancer cells are unknown. Herein, we found that B4GALT3 was upregulated in cervical cancer tissues compared to adjacent non-tumor tissues. B4GALT3-overexpression promoted, whereas B4GALT3-knockdown suppressed the cellular migration, invasion and EMT of HeLa and C33A cervical cancer cells. To explore the mechanism of dysregulation, B4GALT3 was predicted to be a target of miR-27a. EGFP and pGL3-promoter reporter assay showed miR-27a binds to B4GALT3 3'UTR region but enhanced its expression. RT-qPCR showed miR-27a was also upregulated and presented positive correlation with B4GALT3-expression in cervical cancer tissues. miR-27a-overexpression promoted, but blocking-miR-27a repressed these malignancies in HeLa and C33A cells. Furthermore, shR-B4GALT3 counteracted the promotion of malignancies induced by miR-27a, suggesting miR-27a upregulates B4GALT3 to enhance tumorigenic activities. In addition, we found that B4GALT3 significantly enhances β1-integrin stability, thus mediating promotion of B4GALT3 on malignancy in cervical cancer cells. Altogether, our findings evidenced that B4GALT3 upregulated by miR-27a contributes to the tumorigenic activities by β1-integrin pathway and might provide potential biomarkers for cervical cancer. PMID:26987623

  15. Cervical Cancer, Version 2.2015.

    PubMed

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

    2015-04-01

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

  16. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-01-01

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

  19. Prevent Cervical Cancer

    MedlinePlus

    ... Are the Symptoms? What Should I Know About Screening? How Is Ovarian Cancer Treated? Information for Health Care Providers Statistics Rates by Race and Ethnicity Rates by State Trends Related Links ... I Know About Screening? How Is Uterine Cancer Treated? Statistics Rates by ...

  20. CDC's Cervical Cancer Study

    MedlinePlus

    ... Using Science to Prevent Cancer World Cancer Day Web Buttons and Banners Twitter Health E-Cards About Us Leaders Lisa C. Richardson Frances Babcock Vicki Benard Djenaba A. Joseph Jacqueline W. Miller Thomas B. Richards Mona Saraiya Judith Lee Smith Sherri L. Stewart Mary C. White Debra Younginer ...

  1. Cervical cancer: A comprehensive approach towards extermination.

    PubMed

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

    2016-05-01

    Human Papilloma Virus (HPV) is one of the most common sexually transmitted pathogen, globally. Oncogenic types of HPV are the causative agents of many neoplastic diseases, including cervical cancer, which ranks as the most common cancer affecting females in developing countries. HPV infection of the cervical epithelium and the subsequent integration of viral DNA into the host genome are the major risk factors for cervical cancer. The scientific discovery of HPV as the causal agent of cervical cancer has led to the development of HPV-based diagnostic tools. Prophylactic vaccines, based on the oncogenic HPV type virus-like particles have been introduced in several developed countries as a preliminary preventive approach. Nevertheless, it remains a continuous threat to women in developing countries, where the prophylactic vaccines are unaffordable and organized screening programmes are lacking. This warrants implementation of prevention strategies that will reduce cervical cancer-related mortality. In this review, we have discussed molecular pathogenesis of HPV infection and the risk factors associated with it. The diagnosis, treatment and prevention strategies of HPV-related cervical cancer have also been discussed. Key messages HPV-related cervical cancer: risk factors, diagnosis and prevention strategies. HPV pathogenesis, diagnosis, and prevention strategies of cervical cancer. Risk factors, diagnosis and prevention strategies of HPV-related cervical cancer. PMID:26911282

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

    PubMed

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

    2016-03-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. Fundamental Differences in Cell Cycle Deregulation in Human Papillomavirus–Positive and Human Papillomavirus–Negative Head/Neck and Cervical Cancers

    PubMed Central

    Pyeon, Dohun; Newton, Michael A.; Lambert, Paul F.; den Boon, Johan A.; Sengupta, Srikumar; Marsit, Carmen J.; Woodworth, Craig D.; Connor, Joseph P.; Haugen, Thomas H.; Smith, Elaine M.; Kelsey, Karl T.; Turek, Lubomir P.; Ahlquist, Paul

    2010-01-01

    Human papillomaviruses (HPV) are associated with nearly all cervical cancers, 20% to 30% of head and neck cancers (HNC), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, cervical cancers, and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV+ HNCs and cervical cancers differed in their patterns of gene expression yet shared many changes compared with HPV− HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV+ HNCs and cervical cancers were found to be up-regulated in their expression of a distinct and larger subset of cell cycle genes than that observed in HPV− HNC. Moreover, HPV+ cancers overexpressed testis-specific genes that are normally expressed only in meiotic cells. Many, although not all, of the hallmark differences between HPV+ HNC and HPV− HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testis-specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV+ and HPV− cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV+ cancers. PMID:17510386

  5. Stages of Cervical Cancer

    MedlinePlus

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

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

    PubMed

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

    2016-02-01

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

  7. Necrotic Effect versus Apoptotic Nature of Camptothecin in Human Cervical Cancer Cells

    PubMed Central

    Zare-Mirakabadi, Abbas; Sarzaeem, Ali; Moradhaseli, Saeed; Sayad, Aida; Negahdary, Masoud

    2012-01-01

    Background Functional defects in mitochondria are involved in the induction of cell death in cancer cells. The process of programmed cell death may occur through the mechanisms of apoptosis. Several potential lead molecules such as Camptothecin (CPT) and its analogues have been isolated from plants with anticancer effect. The aim of the present study was to understand the necrotic effect versus apoptotic nature of CPT in HeLa cancer cells. Methods The anti-proliferative activity of CPT was estimated through 3-(4, 5- Dimethyl Thiazol-2-yl)-2, 5-diphenyl Tetrazolium bromide (MTT) assay and DNA fragmentation analysis using gel electrophoresis. Lactate Dehydrogenase (LDH) activity and cell morphology were assessed under control and CPT exposed conditions to evaluate the necrotic effect of CPT. Results The results showed that CPT inhibited the proliferation of HeLa cells in a dose-dependent manner with an Inhibitory Concentration 50% (IC50) of 0.08±0.012 µg/ml. However the significant (p<0.05) increase happens in LDH activity at concentrations 1×10-1µg/ml and above. Morphological changes showed that CPT in low concentrations induced an apoptotic mechanism of cell death, such as cell shrinkage and characteristic rounding of dying cells, while at high concentrations showed necrosis changes. The characteristic DNA ladder formation of CPT-treated cells in agarose gel electrophoresis confirmed the results obtained by light microscopy and LDH assay. Conclusion Camptothecin as an anticancer drug may have anti-proliferative effect on HeLa cancer cells in low concentrations, through its nature of induction of apoptosis. The border line between necrotic effect and apoptotic nature of CPT in HeLa cancer cells has been found to be at concentration of 1×10-1 µg/ml. PMID:25628829

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

    PubMed

    2010-08-01

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

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

    PubMed Central

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

    2014-01-01

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

  10. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

  12. 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

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

    PubMed

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

    2016-03-01

    Bis(indolyl)methane appended biaryls were designed, synthesized and evaluated in human cervical cancer cell lines (HeLa) for their anticancer activities and compared against normal rat cardiac myoblasts (H9C2) cells. Compounds 1-12 were synthesized, with variations in one of the phenyl unit, in a single step by condensation of biaryl-2-carbaldehydes with indole in the presence of para-toluenesulfonic acid. Compound 1 exhibited a GI50 value of 11.000.707?M and the derivatives, compounds 4 and 11 showed a GI50 value of 8.330.416?M and 9.130.177?M respectively in HeLa cells and was found to be non-toxic to H9C2 cells up to 20?M. Furthermore, compounds 1, 4 and 11 induced caspase dependent cellular apoptosis in a concentration-dependent manner, reduced mitochondrial membrane potential, inhibited the cell migration and downregulated the production of MMP-2 and MMP-9 in HeLa cells. PMID:26807764

  14. Proliferation inhibition and apoptosis enhancement of human cervical cancer cells by ultrasound-targeted microbubble destruction delivered double suicide genes.

    PubMed

    Hao, Yi; Guo, Li; Abudula, Abulizi; Saidoula, Wuliyati; Guo, Xia

    2014-01-01

    Successful gene therapy requires safe and efficient gene vectors and gene delivery methods. This study is to investigate the effects of double suicide genes on the proliferation and apoptosis of HeLa cells by using the ultrasound-targeted microbubble destruction (UTMD). A lentiviral vector with the KDR promoter was constructed, packaged, and delivered into HeLa cells by UTMD. The results showed that the encapsulation efficiency was 90.6 ± 3.1% and the drug-loading efficiency was 29.2 ± 0.9% assessed by reversed-phase high performance liquid chromatography (RP-HPLC). Cell proliferation was determined by MTT assay and apoptosis was detected by flow cytometry. The proliferation rates of HeLa cells were significantly inhibited when treated with dual-gene lentiviral vectors or lentiviral vector-loaded microbubbles plus UTMD (P < 0.05). Moreover, the inhibiting effects were enhanced along with the increased ultrasonic intensities and declined at 24 h post-irradiation. Additionally, in comparison with the control group, the apoptotic rates of HeLa cells were significantly elevated in the lentiviral vector group and the lentiviral vector microbubble groups (P < 0.05). The apoptotic rates were also elevated as the ultrasonic irradiation intensities were increased (P < 0.05). The results suggest that dual-gene lentiviral vector-loaded microbubbles inhibit proliferation and enhance apoptosis of cervical cancer cells. PMID:25664039

  15. 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

  16. 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

  17. Cervical cancer screening in Luxembourg.

    PubMed

    Scheiden, R; Knolle, U; Wagener, C; Wehenkel, A M; Capesius, C

    2000-11-01

    In 1962, a programme for early detection of cervical cancer was established at the national level. The programme is based on the collaboration of different groups of doctors and not on a system of sending out invitations to every woman. This programme was re-adapted twice according to the needs for assuring quality in a system of mainly liberal medicine. At present the programme is 'institutionalised' and is carried out according to the criteria defined in 1990. This includes a centralisation of the smear readings and handing out the material needed to take the smears. The contribution of the doctors is regulated by a system of bonuses given by the government and a reimbursement by the Health Fund. The annual cervical smear is free of charge for every woman. The participation of the women targeted by the programme (>15 years old) has increased by approximately 50% every decade from the early 1970s increasing from 10950 in 1972 to 70441 in 1999. Between 1980 and 1999, the number of women at risk taking part in the programme increased from 10.80 to 38.92%. The number of all the doctors taking smear samples increased from 68 to 105 and the number of gynaecologists increased from 19 (ratio Gyn/GP (gynaecologists/General Practitioners) of 28%) to 52 (ratio Gyn/GP of 50%). The mortality rate has decreased continuously from 6. 1/100000 in 1990 to 0.9/100000 in 1997. In conclusion, to be successful, a cervical cancer screening programme should be flexible enough to allow short-term adaptations to unexpected local situations and needs a highly motivated team of the different participants involved in the regional and national health policy. PMID:11072212

  18. Proliferation of cells and expression of RARs, RXRs and HPV viral E6 and E7 proteins in cervical cancer cell lines after treatment with ATRA.

    PubMed

    Myga-Nowak, Magdalena; Pacholska-Bogalska, Joanna; Kwaśniewski, Wojciech; Kwaśniewska, Anna; Goździcka-Józefiak, Anna

    2011-01-01

    All-trans retinoic acid (ATRA) is considered to be a potential chemotherapeutic drug due to its capability to regulate cell growth and differentiation. The effects of ATRA on the proliferation of cells and gene regulation are mediated by retinoid receptors (RAR and RXR), which belong to the nuclear receptor superfamily of ligand- inducible transcription factors. ATRA can act either as a growth inhibitor or growth promoter, according to the functional state of retinoic receptors. Thus, we have established the effect of ATRA on the proliferation of cervical cancer cells line HeLa and CaSki and expression of retinoids receptors as well as the viral HPV oncogenic proteins E6 and E7. ATRA had no effect on proliferation CaSki cells, but it stimulated the growth of HeLa cells, which depended on the incubation time and the concentration of ATRA in cell culture. The overexpression of RAR alpha in HeLa cells after the administration of 10(-7) mM ATRA was also observed 72 hours, and the decrease of CaSki by 60-90%. In the study of cervical cancer cell lines, the very low levels of other endogenous RAR and RXR receptors were observed. ATRA does not repress the expression of two viral oncoproteins E6 and E7 HPV16/18, which play a key role in carcinogenesis of the cervix. Our results support the suggestions that the cell response to vitamin A, and other retinoids in the diet, may depend on cell type, and that the cancer cells are differentially resistant to retinoids. Thus, despite the important biological functions of retinoids, the effects of retinoids in a supplementation in supra-physiological doses as well as their physiological action are difficult to define. PMID:21736279

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

    PubMed

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

    2012-01-01

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

  20. 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

  1. Role of Activating Transcription Factor 3 on TAp73 Stability and Apoptosis in Paclitaxel-Treated Cervical Cancer Cells

    PubMed Central

    Oh, Yeo Kyoung; Lee, Hyun Jung; Jeong, Mi-Hee; Rhee, Marie; Mo, Ji-Won; Song, Eun Hyeon; Lim, Joong-Yeon; Choi, Kyung-Hee; Jo, Inho; Park, Sang Ick; Gao, Bin; Kwon, Yongil; Kim, Won-Ho

    2013-01-01

    Taxol (paclitaxel) is a potent anticancer drug that has been found to be effective against several tumor types, including cervical cancer. However, the exact mechanism underlying the antitumor effects of paclitaxel is poorly understood. Here, paclitaxel induced the apoptosis of cervical cancer HeLa cells and correlated with the enhanced activation of caspase-3 and TAp73, which was strongly inhibited by TAp73β small interfering RNA (siRNA). In wild-type activating transcription factor 3 (ATF3)–overexpressed cells, paclitaxel enhanced apoptosis through increased α and β isoform expression of TAp73; however, these events were attenuated in cells containing inactive COOH-terminal–deleted ATF3 [ATF3(ΔC)] or ATF3 siRNA. In contrast, paclitaxel-induced ATF3 expression did not change in TAp73β -overexpressed or TAp73β siRNA–cotransfected cells. Furthermore, paclitaxel-induced ATF3 translocated into the nucleus where TAp73β is expressed, but not in ATF3 (ΔC) or TAp73β siRNA–transfected cells. As confirmed by the GST pull-down assay, ATF3 bound to the DNA-binding domain of p73, resulting in the activation of p21 or Bax transcription, a downstream target of p73. Overexpression of ATF3 prolonged the half-life of TAp73β by inhibiting its ubiquitination and thereby enhancing its transactivation and proapoptotic activities. Additionally, ATF3 induced by paclitaxel potentiated the stability of TAp73β, not its transcriptional level. Chromatin immunoprecipitation analyses show that TAp73β and ATF3 are recruited directly to the p21 and Bax promoter. Collectively, these results reveal that overexpression of ATF3 potentiates paclitaxel-induced apoptosis of HeLa cells, at least in part, by enhancing TAp73β's stability and its transcriptional activity. The investigation shows that ATF3 may function as a tumor-inhibiting factor through direct regulatory effects on TAp73β, suggesting a functional link between ATF3 and TAp73β. PMID:18644986

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

    PubMed Central

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

    2012-01-01

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

  3. Accuracy of registration of invasive cervical cancer.

    PubMed Central

    Husted, J. A.; Anderson, T. W.; Gallagher, R.

    1983-01-01

    The quality of the data recorded by the British Columbia Cancer Registry for 521 new cases of invasive cervical cancer was evaluated. The registry's pathological diagnosis in all new registrations of invasive cervical cancer diagnosed in British Columbia between 1977 and 1979 was compared with a best estimate of the true diagnosis, which was determined from the results of the provincial cervical cytology screening program and the clinical charts at the Cancer Control Agency of British Columbia. The registry's data overestimated the true incidence of invasive cervical cancer by approximately 55%, since 184 (35%) of the cases were incorrectly registered. Of the 184, 141 (77%) were cases of preinvasive cervical cancer, 26 (14%) did not meet the criteria for a true case (i.e., they were not newly diagnosed in British Columbia between 1977 and 1979) and 17 (9%) were cases of invasive cancer of another primary site. In addition, 28 cases of invasive cervical cancer diagnosed in the province during the study period had not been reported to the registry. Thus, both over-reporting and under-reporting occurred. There is a need for constant evaluation of registry data if cancer registries are to fulfil their potential contribution to cancer control programs and research. PMID:6652593

  4. [Knockdown of angiopoietin-like protein 4 inhibits proliferation and promotes apoptosis in cervical cancer SiHa cells].

    PubMed

    Nie, Dan; Liu, Ling; Xia, Jiyi; Wang, Chunyan; Zhan, Ping; Mao, Xiguang

    2016-04-01

    Objective To investigate the effect of lentivirus-mediated shRNA silencing of angiopoietin-like protein 4 (ANGPTL4) on the proliferation and apoptosis of cervical cancer SiHa cells. Methods The ANGPTL4 lentiviral vectors were used to transfect SiHa cells. Real-time quantitative PCR (qRT-PCR) and Western blotting were respectively used to detect ANGPTL4 expression at mRNA and protein levels. The proliferation ability of SiHa cells after transfection was assessed by MTT assay and colony formation assay. The cell cycle was examined by flow cytometry. The annexin V-phycoerythrin/7-aminoactinomycin D (annexin V-PE/7-AAD) staining combined with flow cytometry was used to examine the effect of ANGPTL4 silence on the apoptosis of SiHa cells. Results After the ANGPTL4 lentiviral vectors were transfected into SiHa cells, qRT-PCR and Western blotting showed that the expression of ANGPTL4 mRNA and protein were significantly inhibited in LV3-ANGPTL4 group. The MTT assay showed that the proliferation ability of SiHa cells in LV3-ANGPTL4 group was also inhibited. Colony formation assay revealed that the colony number in LV3-ANGPTL4 group was reduced. The cells in G0/G1 phase and the apoptosis rate increased in LV3-ANGPTL4 group. Conclusion The lentivirus-mediated ANGPTL4 shRNA can inhibit the proliferation, induce the cell cycle arrest in G0/G1 phase, and promote the apoptosis in SiHa cells. PMID:27053616

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

    PubMed Central

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

    2016-01-01

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

  6. Breast and Cervical Cancer Screening

    PubMed Central

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

    2010-01-01

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

  7. 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

  8. How will HPV vaccines affect cervical cancer?

    PubMed Central

    Roden, Richard; Wu, T.-C.

    2011-01-01

    Cancer of the uterine cervix is the second largest cause of cancer deaths in women, and its toll is greatest in populations that lack screening programmes to detect precursor lesions. Persistent infection with ‘high risk’ genotypes of human papillomavirus (HPV) is necessary, although not sufficient, to cause cervical carcinoma. Therefore, HPV vaccination provides an opportunity to profoundly affect cervical cancer incidence worldwide. A recently licensed HPV subunit vaccine protects women from a high proportion of precursor lesions of cervical carcinoma and most genital warts. Here we examine the ramifications and remaining questions that surround preventive HPV vaccines. PMID:16990853

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

    PubMed Central

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

    2015-01-01

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

  10. Cervical Cancer Awareness and Screening in Botswana

    PubMed Central

    Mingo, Alicea M.; Panozzo, Catherine A.; DiAngi, Yumi Taylor; Smith, Jennifer S.; Steenhoff, Andrew P.; Ramogola-Masire, Doreen; Brewer, Noel T.

    2012-01-01

    Objective Cervical cancer remains a leading cause of death in many developing countries due to limited screening by Papanicolaou (Pap) smear. We sought to better understand women’s beliefs about cervical cancer and screening in Botswana, a middle income African country with high rates of cervical cancer. Methods We interviewed 289 women attending general medicine or human immunodeficiency virus (HIV) clinics, where Pap testing was available, in Gaborone, Botswana in January 2009. Results About three-quarters (72%) of respondents reported having ever had a Pap smear. HIV-positive women were more likely to have had a Pap smear than HIV-negative women (80% vs. 64%, OR=1.97, 95% CI: 1.10, 3.55). Screening was also more common among women who were older, had higher incomes, or had heard of cervical cancer. Almost all participants reported a desire to have a Pap smear. Reasons included to determine cervical health (56%), to improve overall health (33%), and to obtain early treatment (34%). About half (54%) of respondents said they did not know what causes cervical cancer, and almost none attributed the disease to HPV infection. Conclusion Study findings can inform interventions that seek to increase cervical cancer awareness and uptake of screening as it becomes more widely available. PMID:22367370

  11. 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

  12. Somatic LKB1 mutations promote cervical cancer progression.

    PubMed

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

    2009-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  14. Laparoscopic fertility sparing management of cervical cancer.

    PubMed

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

    2014-04-01

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

  15. Epidemiology of cervical cancer in Colombia

    PubMed Central

    Muñoz, Nubia

    2012-01-01

    Worldwide, cervical cancer is the third most common cancer in women, and the first or second most common in developing countries. Cervical cancer remains in Colombia the first cause of cancer mortality and the second cause of cancer incidence among women, despite the existence of screening programs during the last 3 decades. Bucaramanga, Manizales and Cali reported rates around 20 per 100,000and Pasto 27 per 100,000. The Cali cancer registry has reported a progressive decrease in the age standardized incidence and mortality rates of cervical cancer over the past 40 years. Reasons for the decline in incidence and mortality of cervical cancer are multiple and probably include: improvement in socio-economic conditions, decrease in parity rates and some effect of screening programs. Human papilloma Virus is the main cause of cervical cancer, HPV natural history studies have now revealed that HPVs are the commonest of the sexually transmitted infections in most populations. Most HPV exposures result in spontaneous clearance without clinical manifestations and only a small fraction of the infected persons, known as chronic or persistent carriers, will retain the virus and progress to precancerous and cancer. HPV 16 and 18 account for 70% of cervical cancer and the 8 most common types. (HPV 16, 18, 45, 33, 31, 52, 58 and 35) account for about 90% of cervical cancer. Case-control studies also allowed the identification of the following cofactors that acting together with HPV increase the risk of progression from HPV persistent infection to cervical cancer: tobacco, high parity, long term use of oral contraceptives and past infections with herpes simplex type 2 and Chlamydia trachomatis. The demonstration that infection with certain types of human papillomavirus (HPV) is not only the main cause but also a necessary cause of cervical cancer has led to great advances in the prevention of this disease on two fronts: (i) Primary prevention by the use of prophylactic HPV vaccines; and (ii) secondary prevention by increasing the accuracy of cervical cancer screening. PMID:24893303

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

    ClinicalTrials.gov

    2012-06-08

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

  17. 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

  18. Cervical cancer: screening and therapeutic perspectives.

    PubMed

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

    2008-01-01

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

  19. NIH Research Leads to Cervical Cancer Vaccine

    MedlinePlus

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

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

    SciTech Connect

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

    2015-04-10

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

  1. Nuclear factor-κB-dependent microRNA-130a upregulation promotes cervical cancer cell growth by targeting phosphatase and tensin homolog.

    PubMed

    Feng, Yeqian; Zhou, Shenghua; Li, Guiyuan; Hu, Chunhong; Zou, Wen; Zhang, Haixia; Sun, Lili

    2016-05-15

    Nuclear factor-κB (NF-κB) may activate a series of gene transcription control cellular signaling pathways whose products are components in a wide range of biological processes. MicroRNAs, a group of non-coding endogenous ones, may regulate gene expression and plays specific roles in tumorigenesis. Using human cervical cancer cell lines, we explored whether NF-κB regulates the expression of microRNA-130a (miR-130a) through binding elements in the miR-130a promoter region. We found that miR-130a accelerates cervical cancer cell proliferation by targeting the phosphatase and tensin homolog on chromosome 10 (PTEN). Further, NF-κB activates both HeLa and CaSki cell growth by upregulating miR-130a. In addition, by targeting PTEN 3' untranslated region, miR-130a might increase cell growth and initiate protein kinase B (AKT) pathway activation. Lastly, PTEN protein was upregulated in response to NF-κB overexpression and downregulated in response to NF-κB inhibition. Compared to total AKT protein level, p-AKT was downregulated by NF-κB overexpression while upregulated by NF-κB inhibition, indicating PTEN pathway activated and affected by NF-κB. Taken together, our findings shed new light on the NF-κB/miR-130a/PTEN pathway in cervical cancer and add new insight regarding the carcinogenesis of cervical cancer. PMID:27040383

  2. Second Primary Cancer after Diagnosis and Treatment of Cervical Cancer

    PubMed Central

    Lim, Myong Cheol; Won, Young-Joo; Lim, Jiwon; Kim, Yeon-Joo; Seo, Sang Soo; Kang, Sokbom; Lee, Eun Sook; Oh, Jae Hwan; Kim, Joo-Young; Park, Sang-Yoon

    2016-01-01

    Purpose This study was conducted to investigate the incidence and survival outcomes of second primary cancers after the diagnosis of cervical cancer. Materials and Methods Data from the Korea Central Cancer Registry between 1993 and 2010 were reviewed and analyzed. Standardized incidence ratios (SIRs) of second primary cancers among women with cervical cancer were analyzed. Kaplan-Meier survival curves were constructed for cervical cancer patients with or without a second primary cancer. Results Among 72,805 women with cervical cancer, 2,678 (3.68%) developed a second primary cancer within a mean follow-up period of 7.34 years. The overall SIR for a second cancer was 1.08 (95% confidence interval, 1.04 to 1.12). The most frequent sites of second primary cancers were the vagina, bone and joints, vulva, anus, bladder, lung and bronchus, corpus uteri, and esophagus. However, the incidence rates of four second primary cancers (breast, rectum, liver, and brain) were decreased. The 5-year and 10-year overall survival rates were 78.3% and 72.7% in all women with cervical cancer, and for women with a second primary cancer, these rates were 83.2% and 65.5% from the onset of cervical cancer and 54.9% and 46.7% from the onset of the second primary cancer, respectively. Conclusion The incidence rates of second primary cancers were increased in women with cervical cancer compared to the general population, with the exception of four decreasing cancers. The 10-year overall survival rates were decreased in cervical cancer patients with a second primary cancer. PMID:26194366

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-12-01

    Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether this could reduce drug toxicity and improve the efficacy of ATO in treating human papillomavirus (HPV)-associated cancers. HeLa, C33a, and human keratinocytes were exposed to 5 μm of ATO in both free and liposomal forms for 48 h. The stability of the prepared samples was tested using inductively coupled plasma optical emission spectrometer (ICP-OES) to measure the intracellular arsenic concentrations after treatment. Fluorescent double-immunocytochemical staining was carried out to evaluate the protein expression levels of HPV-E6 oncogene and caspase-3. Cell apoptosis was analysed by flow cytometry. Results showed that liposomal ATO was more effective than free ATO in reducing protein levels of HPV-E6 and inducing cell apoptosis in HeLa cells. Moreover, lower toxicity was observed when liposomal-delivered ATO was used. This could be explained by lower intracellular concentrations of arsenic. The slowly accumulated intracellular ATO through liposomal delivery might act as a reservoir which releases ATO gradually to maintain its anti-HPV effects. To conclude, liposome-delivered ATO could protect cells from the direct toxic effects induced by higher concentrations of intracellular ATO. Different pathways may be involved in this process, depending on local architecture of the tissues and HPV status. PMID:26887578

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  7. 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

  8. Roles of plant extracts and constituents in cervical cancer therapy.

    PubMed

    Kma, Lakhan

    2013-01-01

    Cervical cancer is a major health problem worldwide and is the most frequent cause of cancer in women in India. Early detection and affordable drugs with clinical efficacy have to go hand-in-hand in order to comprehensibly address this serious health challenge. Plant-based drugs with potent anticancer effects should add to the efforts to find a cheap drug with limited clinical side effects. Keeping this very purpose in mind, an attempt has been made in this review to explore the potential of plant extracts or constituents known to exhibit antitumorigenic activity or exert cytotoxic effect in human cervical carcinoma cells. Alkaloids such as those isolated from C. vincetoxicum and T. Tanakae, naucleaorals A and B, isolated from the roots of N. orientalis, (6aR)-normecambroline, isolated from the bark of N. dealbata appear promising in different human cervical carcinoma cells with the IC50 of 4.0-8 μg/mL. However, other compounds such as rhinacanthone and neolignans isolated from different plants are not far behind and kill cervical cancer cells at a very low concentrations. Among plant extracts or its constituents that enhance the effect of known anticancer drugs, noni, derived from the plant M. citrifolia perhaps is the best candidate. The cytotoxic potency and apoptotic index of cisplatin was found to significantly enhanced in combination with noni in different human cervical carcinoma cells and it therefore holds significance as promising herbal-based anticancer agent. However, efficacy needs to be further investigated in various cervical cell lines and more importantly, in in vivo cervical cancer models for possible use as an alternative and safe anticancer drug. PMID:23886123

  9. DNA methylation changes in cervical cancers.

    PubMed

    Lu, Qiang; Ma, Dehua; Zhao, Shuping

    2012-01-01

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

  10. Cervical cancer in India and HPV vaccination.

    PubMed

    Kaarthigeyan, K

    2012-01-01

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

  11. Molecular biology of human papillomavirus infection and cervical cancer.

    PubMed

    Doorbar, John

    2006-05-01

    HPVs (human papillomaviruses) infect epithelial cells and cause a variety of lesions ranging from common warts/verrucas to cervical neoplasia and cancer. Over 100 different HPV types have been identified so far, with a subset of these being classified as high risk. High-risk HPV DNA is found in almost all cervical cancers (>99.7%), with HPV16 being the most prevalent type in both low-grade disease and cervical neoplasia. Productive infection by high-risk HPV types is manifest as cervical flat warts or condyloma that shed infectious virions from their surface. Viral genomes are maintained as episomes in the basal layer, with viral gene expression being tightly controlled as the infected cells move towards the epithelial surface. The pattern of viral gene expression in low-grade cervical lesions resembles that seen in productive warts caused by other HPV types. High-grade neoplasia represents an abortive infection in which viral gene expression becomes deregulated, and the normal life cycle of the virus cannot be completed. Most cervical cancers arise within the cervical transformation zone at the squamous/columnar junction, and it has been suggested that this is a site where productive infection may be inefficiently supported. The high-risk E6 and E7 proteins drive cell proliferation through their association with PDZ domain proteins and Rb (retinoblastoma), and contribute to neoplastic progression, whereas E6-mediated p53 degradation prevents the normal repair of chance mutations in the cellular genome. Cancers usually arise in individuals who fail to resolve their infection and who retain oncogene expression for years or decades. In most individuals, immune regression eventually leads to clearance of the virus, or to its maintenance in a latent or asymptomatic state in the basal cells. PMID:16597322

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

    PubMed Central

    2014-01-01

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

  13. 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.

  14. Emerging therapeutic agents for cervical cancer.

    PubMed

    Cornelio, Daniela B; Roesler, Rafael; Schwartsmann, Gilberto

    2009-11-01

    Cervical cancer is the second most frequent malignancy affecting women worldwide. The highest incidences occur in the developing world, where, in most countries, cervical cancer is the leading cause of cancer mortality in women. Although surgery and chemoradiotherapy can cure 80-95% of women with early stage cancer and 60% of locoregionally advanced cancer, the recurrent and metastatic disease remains a major cause of cancer death. The current cytotoxic treatment options for advanced and metastatic cancer demonstrate modest results, with response rates of maximum 30% and overall survival of less than 10 months. Given this limited degree of success with conventional therapies, interest has increased in other therapeutic alternatives. In this way, targeted agents are emerging as potential candidates for improving survival in cervical cancer patients. In this review we highlight the main current therapeutic strategies for cervical cancer and summarize the most relevant patents from the latest five years. Special attention was given to patents with potential applications in the clinical practice. PMID:19522698

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

    Although fully treatable in the early stages, once cervical cancer has metastasized, patient outcome is poor. The main objective of this study was to examine the effect of dietary supplementation with a nutrient mixture (NM) containing lysine, ascorbic acid, proline, green tea extract and other micronutrients on HeLa cell xenografts in nude female mice. Tumor growth was measured and immunohistochemical staining was evaluated for the following cancer markers: Ki67 (proliferation); matrix metalloproteinase (MMP)-2 and -9 (invasion/metastasis); vascular endothelial growth factor (VEGF) (angiogenesis); terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and B-cell lymphoma 2 (Bcl-2) (apoptosis); cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) (inflammation); and glutathione S-transferase π (GSTπ) (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 GSTπ all showed a lower intensity and frequency of staining in the NM group compared with that in the control group. In conclusion, NM supplementation strongly inhibited tumor growth and cancer markers in female nude mice injected with HeLa xenografts. PMID:25574189

  17. Cervical cancer screening in India: strategies revisited.

    PubMed

    Juneja, A; Sehgal, A; Sharma, S; Pandey, A

    2007-01-01

    With the change in the life styles and demographic profiles of developing countries, noncommunicable diseases are emerging to be important health problems that demand appropriate control program before they assume epidemic proportion. One of these is the problem of cancer. In India, cervical cancer is a significant problem in terms of incidence, mortality and morbidity. Cervical cancer is a disease that can be prevented through both primary prevention and early detection using screening techniques. Several screening modalities are now available for early detection of cervical cancer and its precursor lesions. They all differ with regard to their test characteristics, feasibility and economic considerations. This communication reviews different aspects of these screening modalities and provides different options considering mass application. PMID:17197739

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

    PubMed

    Cai, Liqiong; Wang, Zehua; Liu, Denghua

    2016-05-01

    Cervical cancer is one of the most common female malignancies in the world, and chemotherapeutic drug resistance is a major obstacle to cancer therapy. Enhancer of zeste homolog 2 (EZH2) is an enzymatic subunit of polycomb repressive complex 2 (PRC2) and catalyzes the repressive histone H3 lysine 27 trimethylation (H3K27me3). However, the role of EZH2 on the chemotherapy drug resistance in cervical cancers remains unclear. In the present study, the cervical carcinoma specimens and paired normal tissue specimens were obtained and the expression of EZH2 was detected by western blotting. The results showed that high levels of EZH2 were detected in cervical carcinoma tissues, compared with paired control tissues (**p < 0.01). Next, three pairs of shRNA specific to EZH2 were designed and used to interfere with endogenous EZH2 expression. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays following treatment with various concentrations of cisplatin in HeLa and HeLa/DDP cells. The MTT assay results showed that knockdown of EZH2 in HeLa/DDP cells caused a 2.29- or 1.83-fold decrease in the cisplatin IC50 values (for shRNA1-EZH2, 34.88 vs. 15.21 μg/mL; p < 0.01; for shRNA3-EZH2, 34.88 vs. 19.09 μg/mL; p < 0.01). The EZH2 activity was also suppressed by 3-deazaneplanocin A (DZNep), EZH2 inhibitor, and the results demonstrated that, meanwhile, DZNep potently inhibited cell viability of HeLa/DDP cells, partly by suppression the levels of EZH2 and H3K27me3, but not H3K27me2, which was detected by western blotting analysis. Moreover, cell migration assay results showed that knockdown of EZH2 decreased cell metastasis of cervical cancer cells. Furthermore, cell cycle was detected by fluorescence-activated cell sorting (FACS) assay and the results demonstrated that interference with EZH2 expression increased the percentage of cells at G0/G1 phase and the HeLa/DDP cells were blocked at G0/G1 phase. Interestingly, western blotting results revealed that higher expression of EZH2 was related with lower level of Dicer in HeLa/DDP cells. Finally, in vivo tumorigenicity experiments results demonstrated that interference with endogenous EZH2 by shRNA specific to EZH2 or inhibition EZH2 by DZNep could significantly increase antitumor effects in nude mice. Thus, inhibiting the levels of endogenous EZH2 effectively reversed the cisplatin resistance and increased the cisplatin sensitivity in cisplatin-resistant HeLa/DDP cells. EZH2 might be a potential target for treating chemotherapeutic drug-resistant cervical cancers. PMID:26631032

  19. What Are the Key Statistics about Cervical Cancer?

    MedlinePlus

    ... women who have been getting regular tests to screen for cervical cancer before they were 65. See the section, " Can ... Detection for more information about tests used to screen for cervical cancer. In the United States, Hispanic women are most ...

  20. Inactive Women May Face Higher Risk for Cervical Cancer

    MedlinePlus

    ... html Inactive Women May Face Higher Risk for Cervical Cancer But study found just 30 minutes of exercise ... who are sedentary appear more likely to develop cervical cancer, but just 30 minutes of exercise each week ...

  1. 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

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

    PubMed Central

    2010-01-01

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

  3. 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

  4. 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

  5. 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

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

    PubMed

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

    2012-04-15

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

  7. Lineage-specific silencing of human IL-10 gene expression by promoter methylation in cervical cancer cells.

    PubMed

    Szalmás, Anita; Bánáti, Ferenc; Koroknai, Anita; László, Brigitta; Fehér, Eniko; Salamon, Dániel; Gergely, Lajos; Minárovits, János; Kónya, József

    2008-05-01

    Epigenetic analysis was performed to demonstrate that the normal and neoplastic epithelial cells do not serve as the source of the locally elevated IL-10 production during cervical carcinogenesis. Bisulfite sequencing was used to correlate promoter CpG methylation with the transcription of the gene. Lack of IL-10 transcription in HeLa, SiHa, Caski, HT-3, C33-A, HaCaT cell lines and in primary human keratinocytes correlated consistently with the methylated state of the proximal CpG residues, particularly with the two most proximal CpGs at positions -185 and -110. These two sites were also highly methylated in normal and malignant cervical cells directly isolated from patient material. On the other hand, IL-10 producing peripheral blood mononuclear cells had unmethylated CpG residues in the proximal promoter associated with acetylated H3 and H4 histones as determined by chromatin immunoprecipitation. In HeLa carrying epigenetically silenced endogeneous IL-10 promoter, the transfected non-CpG methylated 1 kb and 0.6 kb proximal promoter fragments could drive reporter gene expression, which was reversed by cassette methylation of these promoter fragments. In conclusion, the CpG methylation pattern of the proximal promoter is implicated as a major determinant of transcriptional silencing of human IL-10 expression in cells of cervical epithelial origin. PMID:18378443

  8. Antigen-specific immunotherapy of cervical and ovarian cancer

    PubMed Central

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

    2009-01-01

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

  9. 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

  10. New molecular targets against cervical cancer

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Di, Jiangli; Rutherford, Shannon; Chu, Cordia

    2015-01-01

    Cervical cancer continues to be a serious public health problem in the developing world, including China. Because of its large population with geographical and socioeconomic inequities, China has a high burden of cervical cancer and important disparities among different regions. In this review, we first present an overview of the cervical cancer incidence and mortality over time, and focus on diversity and disparity in access to care for various subpopulations across geographical regions and socioeconomic strata in China. Then, we describe population-based cervical cancer screening in China, and in particular implementation of the National Cervical Cancer Screening Program in Rural Areas (NACCSPRA) and the challenges that this program faces. These include low screening coverage, shortage of qualified health care personnel and limited funds. To improve prevention of cervical cancer and obtain better cancer outcomes, the Chinese government needs to urgently consider the following key factors: reducing disparities in health care access, collecting accurate and broadly representative data in cancer registries, expanding target population size and increasing allocation of government funding for training of personnel, improving health education for women, enhancing quality control of screening services and improving a system to increase follow up for women with positive results. PMID:26625735

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2015-07-01

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

  15. Angiogenesis and antiangiogenic agents in cervical cancer

    PubMed Central

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

    2014-01-01

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

  16. [Chromosomal instability in carcinogenesis of cervical cancer.

    PubMed

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

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

    PubMed

    Pariente, Roberto; Pariente, Jos A; Rodrguez, Ana B; Espino, Javier

    2016-01-01

    Melatonin has antitumor activity via several mechanisms including its antiproliferative and pro-apoptotic effects as well as its potent antioxidant actions, although recent evidence has indicated that melatonin may perform pro-oxidant actions in tumor cells. Therefore, melatonin may be useful in the treatment of tumors in association with chemotherapy drugs. This study was intended to evaluate the invitro effect of melatonin on the cytotoxic and pro-apoptotic actions of various chemotherapeutic agents in cervical cancer HeLa cells. Herein, we found that both melatonin and three of the chemotherapeutic drugs tested, namely cisplatin (CIS), 5-fluorouracil (5-FU), and doxorubicin, induced a decrease in HeLa cell viability. Furthermore, melatonin significantly increased the cytotoxic effect of such chemotherapeutic agents. Consistently, costimulation of HeLa cells with any chemotherapeutic agent in the presence of melatonin further increased caspase-3 activation, particularly in CIS- and 5-FU-challenged cells. Likewise, concomitant treatments with melatonin and CIS significantly enhanced the ratio of cells entering mitochondrial apoptosis due to reactive oxygen species (ROS) overproduction, substantially augmented the population of apoptotic cells, and markedly enlarged DNA fragmentation compared to the treatments with CIS alone. Nonetheless, melatonin only displayed moderate chemosensitizing effects in 5-FU-stimulated HeLa cells, as suggested by slight increments in the percentage of cells stimulated for ROS production and in the proportion of early apoptotic cells compared to the treatments with 5-FU alone. In summary, our findings provided evidence that invitro melatonin strongly enhances CIS-induced cytotoxicity and apoptosis in HeLa cells and, hence, the indoleamine could be potentially applied to cervical cancer treatment as a powerful synergistic agent. PMID:26462739

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

    PubMed Central

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

    2011-01-01

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

  20. Neem leaf glycoprotein overcomes indoleamine 2,3 dioxygenase mediated tolerance in dendritic cells by attenuating hyperactive regulatory T cells in cervical cancer stage IIIB patients.

    PubMed

    Roy, Soumyabrata; Barik, Subhasis; Banerjee, Saptak; Bhuniya, Avishek; Pal, Smarajit; Basu, Parthasarathi; Biswas, Jaydip; Goswami, Shyamal; Chakraborty, Tathagata; Bose, Anamika; Baral, Rathindranath

    2013-08-01

    Tolerogenic dendritic cells (DCs) are a subset of DCs characterized by abundant indoleamine 2,3 dioxygenase (IDO) expressions. IDO may be co-operatively induced in DCs by regulatory T (Tregs) cells and various DC maturation agents. Tregs are markedly amplified in the physiological system of cancer patients, inducing over tolerance in DCs that leads to the hyper accumulation of immunosuppressive IDO in tumor microenvironment, thereby, hampering anti-tumor immunity. Consequently, a major focus of current immunotherapeutic strategies in cancer is to minimize IDO, which is possible by reducing Tregs and using various IDO inhibitors. Neem leaf glycoprotein (NLGP), a natural and nontoxic immunomodulator, demonstrated several unique immunoregulatory activities. Noteworthy activities of NLGP are to mature DCs and to inhibit Tregs. As Tregs are inducer of IDO in DCs and hyperactive Tregs is a hallmark of cancer, we anticipated that NLGP might abrogate IDO induction in DCs by inhibiting Tregs. Evidences are presented here that in a co-culture of DCs and Tregs isolated from cervical cancer stage IIIB (CaCx-IIIB) patients, NLGP does inhibit IDO induction in DCs by curtailing the over expression of Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) on Tregs and concomitantly induces optimal DC maturation. In contrast, in the presence of LPS as maturation agent the DCs displays a tolerogenic profile. This finding suggests the reduction of tolerogenecity of DCs in CaCx-IIIB patients by reducing the IDO pool using NLGP. Accordingly, this study sheds more light on the diverse immunomodulatory repertoire of NLGP. PMID:23628394

  1. Cervical cancer: Can it be prevented?

    PubMed Central

    Aggarwal, Pakhee

    2014-01-01

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

  2. Cervical cancer: Can it be prevented?

    PubMed

    Aggarwal, Pakhee

    2014-10-10

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

  3. 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

  4. 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

  5. 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…

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

    PubMed Central

    Das, Soumen; Chatterjee, Jyotirmoy

    2015-01-01

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

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

    PubMed Central

    Cesur, Özlem; Nicol, Clare; Groves, Helen; Mankouri, Jamel; Blair, George Eric; Stonehouse, Nicola J.

    2015-01-01

    Human papillomavirus (HPV) is the most common viral infection of the reproductive tract, affecting both men and women. High-risk oncogenic types are responsible for almost 90% of anogenital and oropharyngeal cancers including cervical cancer. Some of the HPV “early” genes, particularly E6 and E7, are known to act as oncogenes that promote tumour growth and malignant transformation. Most notably, HPV-16 E7 interacts with the tumour suppressor protein pRb, promoting its degradation, leading to cell cycle dysregulation in infected cells. We have previously shown that an RNA aptamer (termed A2) selectively binds to HPV16 E7 and is able to induce apoptosis in HPV16-transformed cervical carcinoma cell lines (SiHa) through reduction of E7 levels. In this study, we investigated the effects of the A2 aptamer on E7 localisation in order to define its effects on E7 activity. We demonstrate for the first time that E7 localised to the plasma membrane. In addition, we show that A2 enhanced E7 localisation in the ER and that the A2-mediated reduction of E7 was not associated with proteasomal degradation. These data suggest that A2 perturbs normal E7 trafficking through promoting E7 ER retention. PMID:26131956

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    2010-01-01

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

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

    PubMed

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

    2015-01-01

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

  11. 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

  12. 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

  13. 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

  14. HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes.

    PubMed

    Alvarado-Ruiz, Liliana; Martinez-Silva, Maria Guadalupe; Torres-Reyes, Luis Alberto; Pina-Sanchez, Patricia; Ortiz-Lazareno, Pablo; Bravo-Cuellar, Alejandro; Aguilar-Lemarroy, Adriana; Jave-Suarez, Luis Felipe

    2016-01-01

    HOX transcription factors are evolutionarily conserved in many different species and are involved in important cellular processes such as morphogenesis, differentiation, and proliferation. They have also recently been implicated in carcinogenesis, but their precise role in cancer, especially in cervical cancer (CC), remains unclear. In this work, using microarray assays followed by the quantitative polymerase chain reaction (qPCR), we found that the expression of 25 HOX genes was downregulated in CC derived cell lines compared with nontumorigenic keratinocytes. In particular, the expression of HOXA9 was observed as down-modulated in CCderived cell lines. The expression of HOXA9 has not been previously reported in CC, or in normal keratinocytes of the cervix. We found that normal CC from women without cervical lesions express HOXA9; in contrast, CC cell lines and samples of biopsies from women with CC showed significantly diminished HOXA9 expression. Furthermore, we found that methylation at the first exon of HOXA9 could play an important role in modulating the expression of this gene. Exogenous restoration of HOXA9 expression in CC cell lines decreased cell proliferation and migration, and induced an epithelial-like phenotype. Interestingly, the silencing of human papilloma virus (HPV) E6 and E7 oncogenes induced expression of HOXA9. In conclusion, controlling HOXA9 expression appears to be a necessary step during CC development. Further studies are needed to delineate the role of HOXA9 during malignant progression and to afford more insights into the relationship between downmodulation of HOXA9 and viral HPV oncoprotein expression during cercical cancer development. PMID:27039722

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

    PubMed

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

    2015-02-01

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

  16. Problems of cervical cancer screening programmes

    PubMed Central

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

    1988-01-01

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

  17. 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.

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

    PubMed

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

    2016-03-15

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

  19. Reduced BCL2 and CCND1 mRNA expression in human cervical cancer HeLa cells treated with a combination of everolimus and paclitaxel

    PubMed Central

    Alp, Ebru; Onen, H. Ilke; Menevse, Sevda

    2016-01-01

    Aim of the study Cervical cancer is the second most common malignancy in women worldwide. Everolimus displays direct effects on growth and proliferation of cancer cells via inhibition of mammalian target of rapamycin (mTOR) protein, which is known to be associated with drug resistance. In this study, we aimed to investigate the effects of everolimus, gemcitabine, and paclitaxel in terms of cell viability and mRNA expression levels of GRP78, CCND1, CASP2, and BCL2 genes. Material and methods HeLa cells were treated with different doses of everolimus, gemcitabine, and paclitaxel. Cell viability was assessed using MTT assay, and obtained dose response curves were used for the calculations of inhibitory concentration (IC) values. At the end of the treatment times with selected doses, RNA isolation and cDNA synthesis were performed. Finally, GRP78, CCND1, CASP2, and BCL2 genes mRNA expression levels were analysed using quantitative PCR. Results The IC50 value of everolimus was 0.9 µM for 24-hour treatment. Moreover, the IC50 value of gemcitabine and paclitaxel was found to be around 18.1 µM and 7.08 µM, respectively. Everolimus, gemcitabine, and paclitaxel treatments alone did not change the GRP78, CCND1, BCL2 and CASP2 mRNA expression levels significantly. However, combined treatment of everolimus and paclitaxel significantly reduced BCL2 and CCND1 mRNA expression (p < 0.05). In contrast, this combination did not change GRP78 and CASP2 mRNA expression levels (p > 0.05). Conclusions Down-regulation of CCND1 and BCL2 expression may be an important mechanism by which everolimus increases the therapeutic window of paclitaxel in cervical cancers. PMID:27095936

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  2. Computer aided decision support system for cervical cancer classification

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

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

    PubMed Central

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

    2015-01-01

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

  4. 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.

  5. Epidemiology of cervical cancer in Latin America.

    PubMed

    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

  6. Chemoradiotherapy for cervical cancer in 2010.

    PubMed

    Klopp, Ann H; Eifel, Patricia J

    2011-02-01

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

  7. Review on risk factors of cervical cancer.

    PubMed

    Chou, P

    1991-08-01

    This article reviews risk factors of cervical cancer which have been studied in the following aspects: (1) sociodemographic factors including educational level, urbanizational level, socioeconomic status, race and marriage; (2) sexual activity including age at first marriage, age at first coitus, multiple marriage, multiple sexual partners, broken marriage, unstable sex relationship, syphilis/gonorrhea history, coital frequency, multiple pregnancies and age at menarche; (3) factors related to husband including circumcision, sperm, smegma, previous wife with cervical cancer and occupations entailed mobility of husband and periods away from home; (4) psychosocial factors including stressful emotional status, deprived economic background and discontent home situation; (5) virus including herpes simplex type 2 and papilloma virus; (6) other factors including smoking, barrier and oral contraceptives. PMID:1654190

  8. 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

  9. Screening for cervical cancer in Poland.

    PubMed

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

    1993-01-01

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

  10. Cervical cancer screening: evidence behind the guidelines.

    PubMed

    Lees, Brittany F; Erickson, Britt K; Huh, Warner K

    2016-04-01

    Cervical cancer screening involves a complex process of cytology, human papillomavirus (HPV) testing, colposcopy, and a multitude of algorithms for the identification of preinvasive disease and prevention of invasive disease. High-risk HPV is a prerequisite for the development of almost all types of cervical cancer; therefore, a test for high-risk HPV has become an integral part of new screening strategies. Major changes to screening guidelines in the last decade include initiation of screening at age 21 years, conservative management of young women with abnormal cytology, extended screening intervals for women age ≥30 years, and cessation of screening in low-risk women at age 65 years. This review will focus on the evidence that has led to the current evidence-based guidelines. Evidence regarding primary HPV testing as well as postvaccine-based screening strategies will also be reviewed. PMID:26519782

  11. MicroRNA-200b inhibits epithelial-mesenchymal transition and migration of cervical cancer cells by directly targeting RhoE.

    PubMed

    Cheng, Yan-Xiang; Chen, Gan-Tao; Chen, Chuang; Zhang, Qi-Fan; Pan, Feng; Hu, Min; Li, Bing-Shu

    2016-04-01

    Previous studies have identified microRNA-200b (miR-200b) as a powerful regulator of epithelial-mesenchymal transition (EMT) via the control of gene expression. EMT is a critical event that is associated with the initiation of malignant tumor metastasis. A lack of E-cadherin expression and overexpression of vimentin are hallmarks of EMT. It is well‑known that RhoE, which is associated with regulation of the actin cytoskeleton and migration via alterations in cell motility, regulates the expression of E-cadherin, matrix metalloproteinase-9 (MMP-9) and vimentin. However, it remains to be elucidated whether miR‑200b may alter the molecular behavior of RhoE. The present study aimed to determine whether miR‑200b was able to regulate the EMT of cervical cancer, in order to control metastasis. In addition, the correlation between miR‑200b and RhoE, E‑cadherin and vimentin expression was investigated. Notably, miR‑200b was shown to inhibit the function of RhoE and suppress the EMT of cervical cancer. Furthermore, HeLa cells were transfected with miR‑200b mimics or inhibitors, and the protein expression levels of E‑cadherin, MMP‑9, vimentin and RhoE were subsequently detected. A Transwell assay was also conducted, in order to observe the metastatic ability of the HeLa cells. In addition, a luciferase reporter assay was performed using luciferase reporter vectors containing the full length 3'‑untranslated region (UTR) of RhoE; miR‑200b was able to significantly suppress relative luciferase activity by targeting the 3'‑UTR of RhoE. These results suggested that miR‑200b may markedly inhibit metastatic potential by regulating cell EMT and inhibiting RhoE; therefore, miR-200b may be considered an effective target for the treatment of patients with highly metastatic cervical cancer. PMID:26935796

  12. Aortitis during intraarterial chemotherapy for cervical cancer.

    PubMed

    Tanaka, Hirohiko; Kondo, Eiji; Kawato, Hiroaki; Kikukawa, Toyo; Toyoda, Nagayasu

    2002-02-01

    A 76-year-old woman with stage IIb cervical cancer with a bulky tumor experienced aortitis during continuous intraarterial cisplatin-based chemotherapy. The chemotherapy was administered through a catheter tip placed in the aorta abdominalis, utilizing an external infusion pump. During the third course of chemotherapy, she complained of left-sided lower back pain and moderate fever was observed. Elevated white blood cell count (WBC) and C-reactive protein (CRP) level were noted, and an abdominal X-ray and urgent computed tomography (CT) were performed. The catheter tip was displaced against the arterial blood flow. At this level of the aortic wall, soft tissue density surrounded the aorta completely. Aortitis caused by the intraarterial chemotherapy, was strongly suspected. It was thought that the maldistribution of drugs and changes in the drug flow occurred due to the vertebral height movement of the catheter tip against the aortic blood flow, and there, flow to the vasa vasorum may have occurred. Chemical vasculitis of the vasa vasorum due to the anticancer drugs was strongly suspected as a contributing factor of the aortitis. Because of the long-term use of an intraarterial catheter, the maldistribution of drugs and changes in the drug flow occurred physically and biologically during the course of the chemotherapy. We recommend occasional monitoring of the location of the catheter tip and a repeat evaluation with contrast medium in regard to flow to the vasa vasorum. PMID:11942052

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

    PubMed Central

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

    2007-01-01

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

  14. Human papillomavirus screening and cervical cancer prevention.

    PubMed

    Sasieni, P D

    2000-01-01

    Infection with one of several types of human papillomavirus (HPV) appears to be a necessary first step in the development of invasive cervical cancer. We cannot currently treat HPV infections; thus, the role of HPV testing is to identify women with precancerous lesions that can be removed and, in so doing, prevent progression to invasive carcinoma. Although HPV testing may help to identify women at risk of cervical cancer who might be missed by other screening tests, it is inherently nonspecific at identifying those who would otherwise develop cervical cancer. In order to avoid overtreatment of women with minor lesions with little potential for progression, HPV testing needs to be repeated or combined with Pap smears. Protocols for HPV screening have yet to be properly evaluated. Here we consider several possible applications of HPV testing in the prevention of cervical cancer. The most immediate role is as a secondary test in women with minor cytological abnormalities. Appropriate use of HPV testing as a primary screening tool depends on the setting. In a developed country without an organized screening program, HPV testing might be used in addition to Pap smears in women age 35 and over to increase sensitivity. Within an organized screening program, HPV testing might be used in combination with Pap testing, but with extended screening intervals so as to obtain the maximum advantage to women without unduly increasing costs. Where resources are strictly limited, an attractive option would be to perform visual inspection of the cervix after application of dilute acetic acid using a low threshold for referral, and to test for HPV only on those with abnormal looking lesions. PMID:10935355

  15. The polycomb group protein enhancer of zeste 2 is a novel therapeutic target for cervical cancer.

    PubMed

    Ding, Muyang; Zhang, Hang; Li, Zhen; Wang, Cuili; Chen, Jasmine; Shi, Liyun; Xu, Dakang; Gao, Yane

    2015-05-01

    Enhancer of zeste 2 (EZH2), a polycomb histone methyltransferase, is overexpressed in various cancers, including cervical cancer. Gene expression analysis revealed that increased expression of EZH2 is associated with cervical cancer progression, particularly the progression to invasive squamous cell carcinoma. Enhancer of zeste 2 is known to trimethylate lysine 27 on histone H3, leading to gene silencing that contributes to the progression of tumours into a more aggressive form of cancer. However, the specific molecular mechanisms by which EZH2 contributes to the development of cervical cancer remain largely unknown. Recently, an EZH2 inhibitor was reported to selectively inhibit trimethylated lysine 27 on histone H3 and to reactivate silenced genes in cancer cells. In this study, we found that GSK343 (a specific inhibitor of EZH2 methyltransferase) induces phenotypic reprogramming of cancer cells from mesenchymal to epithelial cells, reducing proliferation and cell motility and blocking the invasion of cervical cancer cell lines both in vitro and in vivo. Treatment with the EZH2 inhibitor led to increased levels of the epithelial marker E-cadherin and decreased levels of mesenchymal markers such as N-cadherin and vimentin. The observed reprogramming is associated with restrained cervical cancer progression and provides direct evidence in support of EZH2 as a therapeutic target. PMID:25739318

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

    PubMed

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

    2014-02-01

    Exploring novel chemotherapeutic agents is a great challenge in cancer medicine. To that end, 2-substituted benzimidazole copper(II) complex, [Cu(BMA)Cl2]·(CH3OH) (1) [BMA = N,N'-bis(benzimidazol-2-yl-methyl)amine], was synthesized and its cytotoxicity was characterized. The interaction between complex 1 and calf thymus DNA was detected by spectroscopy methods. The binding constant (K b = 1.24 × 10(4 )M(-1)) and the apparent binding constant (K app = 6.67 × 10(6 )M(-1)) of 1 indicated its moderate DNA affinity. Complex 1 induced single strand breaks of pUC19 plasmid DNA in the presence of H2O2 through an oxidative pathway. Cytotoxicity studies proved that complex 1 could inhibit the proliferation of human cervical carcinoma cell line HeLa in both time- and dose-dependent manners. The results of nuclei staining by Hoechst 33342 and alkaline single-cell gel electrophoresis proved that complex 1 caused cellular DNA damage in HeLa cells. Furthermore, treatment of HeLa cells with 1 resulted in S-phase arrest, loss of mitochondrial potential, and up-regulation of caspase-3 and -9 in HeLa cells, suggesting that complex 1 was capable of inducing apoptosis in cancer cells through the intrinsic mitochondrial pathway. PMID:24368745

  17. Opting Out of Cervical Cancer Screening

    PubMed Central

    Cooper, Crystale Purvis; Saraiya, Mona

    2015-01-01

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

  18. Cervical cancer screening in England.

    PubMed

    Patnick, J

    2000-11-01

    Cervical screening in England is provided free of charge by the National Health Service to all women aged 20-64 years. Computerised call and recall was introduced in 1988 and women receive an invitation every 3-5 years. Smears are taken by the local family doctor, by his/her nurse or at community clinics. Approximately 85% of English women have had a smear in the last 5 years. Quality assurance programmes have recently been established for laboratories and colposcopy clinics and lessons have been learned from previous failures of the service. The incidence has fallen from 16 per 100000 in 1986 to 9.3 per 100000 in 1997. Mortality is currently falling by 7% per year. PMID:11072205

  19. High plasma concentration of beta-D-glucan after administration of sizofiran for cervical cancer

    PubMed Central

    Tokuyasu, Hirokazu; Takeda, Kenichi; Kawasaki, Yuji; Sakaguchi, Yasuto; Isowa, Noritaka; Shimizu, Eiji; Ueda, Yasuto

    2010-01-01

    A 69-year-old woman with a history of cervical cancer was admitted to our hospital for further investigation of abnormal shadows on her chest roentgenogram. Histologic examination of transbronchial lung biopsy specimens revealed epithelioid cell granuloma, and Mycobacterium intracellulare was detected in the bronchial lavage fluid. The plasma level of (1→3)-beta-d-glucan was very high, and this elevated level was attributed to administration of sizofiran for treatment of cervical cancer 18 years previously. Therefore, in patients with cervical cancer, it is important to confirm whether or not sizofiran has been administered before measuring (1→3)-beta-d-glucan levels. PMID:21042427

  20. Fisetin Inhibits Migration and Invasion of Human Cervical Cancer Cells by Down-Regulating Urokinase Plasminogen Activator Expression through Suppressing the p38 MAPK-Dependent NF-κB Signaling Pathway

    PubMed Central

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

    2013-01-01

    Fisetin (3,3’,4’,7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion. PMID:23940799

  1. 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

  2. Diagnosis of cervical cancer cell taken from scanning electron and atomic force microscope images of the same patients using discrete wavelet entropy energy and Jensen Shannon, Hellinger, Triangle Measure classifier.

    PubMed

    Aytac Korkmaz, Sevcan

    2016-05-01

    The aim of this article is to provide early detection of cervical cancer by using both Atomic Force Microscope (AFM) and Scanning Electron Microscope (SEM) images of same patient. When the studies in the literature are examined, it is seen that the AFM and SEM images of the same patient are not used together for early diagnosis of cervical cancer. AFM and SEM images can be limited when using only one of them for the early detection of cervical cancer. Therefore, multi-modality solutions which give more accuracy results than single solutions have been realized in this paper. Optimum feature space has been obtained by Discrete Wavelet Entropy Energy (DWEE) applying to the 3×180 AFM and SEM images. Then, optimum features of these images are classified with Jensen Shannon, Hellinger, and Triangle Measure (JHT) Classifier for early diagnosis of cervical cancer. However, between classifiers which are Jensen Shannon, Hellinger, and triangle distance have been validated the measures via relationships. Afterwards, accuracy diagnosis of normal, benign, and malign cervical cancer cell was found by combining mean success rates of Jensen Shannon, Hellinger, and Triangle Measure which are connected with each other. Averages of accuracy diagnosis for AFM and SEM images by averaging the results obtained from these 3 classifiers are found as 98.29% and 97.10%, respectively. It has been observed that AFM images for early diagnosis of cervical cancer have higher performance than SEM images. Also in this article, surface roughness of malign AFM images in the result of the analysis made for the AFM images, according to the normal and benign AFM images is observed as larger, If the volume of particles has found as smaller. PMID:26921605

  3. Diagnosis of cervical cancer cell taken from scanning electron and atomic force microscope images of the same patients using discrete wavelet entropy energy and Jensen Shannon, Hellinger, Triangle Measure classifier

    NASA Astrophysics Data System (ADS)

    Aytac Korkmaz, Sevcan

    2016-05-01

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

  4. General Information about Cervical Cancer

    MedlinePlus

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

  5. Treatment Option Overview (Cervical Cancer)

    MedlinePlus

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

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

    PubMed

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

    2003-01-01

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

  7. 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.

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

    PubMed Central

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

    2015-01-01

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

  9. [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

  10. Human Papillomavirus Testing in the Prevention of Cervical Cancer

    PubMed Central

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

    2011-01-01

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

  11. 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

  12. 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.

  13. Viola plant cyclotide vigno 5 induces mitochondria-mediated apoptosis via cytochrome C release and caspases activation in cervical cancer cells.

    PubMed

    Esmaeili, Mohammad Ali; Abagheri-Mahabadi, Nazanin; Hashempour, Hossein; Farhadpour, Mohsen; Gruber, Christian W; Ghassempour, Alireza

    2016-03-01

    Cyclotides describe a unique cyclic peptide family that displays a broad range of biological activities including uterotonic, anti-bacteria, anti-cancer and anti-HIV. The vigno cyclotides consist of vigno 1-10 were reported recently from Viola ignobilis. In the present study, we examined the effects of vigno 5, a natural cyclopeptide from V. ignobilis, on cervical cancer cells and the underlying mechanisms. We found that vigno 5-treated Hela cells were killed off by apoptosis in a dose-dependent manner within 24h, and were characterized by the appearance of nuclear shrinkage, cleavage of poly (ADP-ribose) polymerase (PARP) and DNA fragmentation. The mitochondrial pathway of apoptosis revealed that cytochrome C is released from mitochondria to cytosol, associated with the activation of caspase-9 and -3, and the cleavage of poly (ADP-ribose) polymerase (PARP). Overall, the results indicate that vigno 5 induces apoptosis in part via the mitochondrial pathway, which is associated with a release of cytochrome C and elevated activity of caspase-9 and -3 in Hela cells. PMID:26751970

  14. 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.

  15. Elevated expression of flotillin-1 is associated with lymph node metastasis and poor prognosis in early-stage cervical cancer

    PubMed Central

    Li, Zheng; Yang, Yang; Gao, Yang; Wu, Xiaoliu; Yang, Xielan; Zhu, Yingjie; Yang, Hongying; Wu, Lin; Yang, Chengang; Song, Libing

    2016-01-01

    Accumulating evidence has revealed that the expression of the lipid raft protein flotillin-1 is elevated in various human cancers, but the role flotillin-1 plays in the carcinogenesis of cervical cancer remains unclear. The expression profile of flotillin-1 was assayed using real-time PCR, western blotting, and immunohistochemical (IHC) staining in cervical cancer cell lines and cancer tissues with paired adjacent noncancerous cervical tissues. The expression of flotillin-1 protein was detected by IHC staining in a large cohort of 308 paraffin-embedded cervical cancer tissues. Ectopic expression and the short hairpin RNA interference approach were employed to determine the role of flotillin-1 in cervical cancer cell metastasis and the possible mechanism involved. Flotillin-1 expression protein and mRNA were significantly upregulated in cervical cancer cell lines and cancer tissues; elevated expression of flotillin-1 protein in early-stage cervical cancer was significantly associated with pelvic lymph node metastasis (P < 0.001), and was an independent predictive factor of poor overall survival. Moreover, flotillin-1 up- and downregulation remarkably affected cervical cancer cell motility and invasion, respectively, through epithelial-mesenchymal transition (EMT) regulated by the Wnt/β-catenin and nuclear factor-κB (NF-κB) pathways. Our results suggest that flotillin-1 facilitates cervical cancer cell metastasis through Wnt/β-catenin and NF-κB pathway-regulated EMT and that the flotillin-1 expression profile serves not only as novel predictor of pelvic lymph node metastasis, but also as neoteric risk factor for patients with early-stage cervical cancer. PMID:27073721

  16. 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

  17. 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…

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

    PubMed Central

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

    2011-01-01

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

  19. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  2. Modeling Cervical Cancer Prevention in Developed Countries

    PubMed Central

    Kim, Jane J.; Brisson, Marc; Edmunds, W. John; Goldie, Sue J.

    2009-01-01

    Cytology-based screening has reduced cervical cancer mortality in countries able to implement, sustain and financially support organized programs that achieve broad coverage. These ongoing secondary prevention efforts considerably complicate the question of whether vaccination against Human Papillomavirus (HPV) types -16 and 18 should be introduced. Policy questions focus primarily on the target ages of vaccination, appropriate ages for a temporary “catch-up” program, possible revisions in screening policies to optimize synergies with vaccination, including the increased used of HPV DNA testing, and the inclusion of boys in the vaccination program. Decision-analytic models are increasingly being developed to simulate disease burden and interventions in different settings in order to evaluate the benefits and cost-effectiveness of primary and secondary interventions for informed decision-making. This article is a focused review on existing mathematical models that have been used to evaluate HPV vaccination in the context of developed countries with existing screening programs. Despite variations in model assumptions and uncertainty in existing data, pre-adolescent vaccination of girls is consistently found to be attractive in the context of current screening practices, provided there is complete and lifelong vaccine protection and widespread vaccination coverage. Questions related to catch-up vaccination programs, potential benefits of other non-cervical cancer outcomes and inclusion of boys are subject to far more uncertainty, and results from these analyses have reached conflicting conclusions. Most analyses find that some catch-up vaccination is warranted but becomes increasingly unattractive as the catch-up age is extended, and vaccination of boys is unlikely to be cost-effective if reasonable levels of coverage are achieved in girls or coverage among girls can be improved. The objective of the review is to highlight points of consensus and qualitative themes, to discuss the areas of divergent findings, and to provide insight into critical decisions related to cervical cancer prevention. PMID:18847560

  3. Why women still die from cervical cancer.

    PubMed

    Masood, S

    1997-01-01

    Cervicovaginal cytology, known as Pap smear, is the most effective screening test in medical oncology. Introduced by Dr. George Papanicolaou in 1940, the Pap smear is now being recognized as a major contributor to the remarkable decrease in cervical cancer morbidity and mortality among women throughout the world. However, there are still significant numbers of women who lose their lives to cervical cancer every day. To overcome this major problem, first, we must search for the reasons for these lost lives and then take appropriate measures to resolve the existing issues. There is now substantial evidence that emphasizes the importance of an effective screening program. This program must integrate education and accessibility to health care for all women regardless of age, race, ethnic background and socioeconomic status. The public, the media, the government and health care providers must also become acutely aware of the inherent difficulties involved in providing a high-quality Pap smear. Compounded by medicolegal pressures and reimbursement issues, the Pap smear has become one of the more difficult tests to perform. Current reimbursement mechanisms are not appropriate for the cost of providing the service and cannot guarantee the resources necessary for a high-quality Pap smear. Congress should consider mandating direct billing to the patient for the service, so that cervicovaginal cytology could be reimbursed on a level commensurate with the requirements of providing quality service. A concerted effort should also be made to enhance the level of public knowledge about the issues surrounding Pap smear. This could be achieved by fostering the idea of designating a "Cervical Cancer Awareness Month," and by encouraging the spirit of community networking. PMID:9379163

  4. Thymoquinone-loaded nanostructured lipid carrier exhibited cytotoxicity towards breast cancer cell lines (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa).

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. Mitochondrial DNA variation analysis in cervical cancer.

    PubMed

    Kabekkodu, Shama Prasada; Bhat, Samatha; Mascarenhas, Roshan; Mallya, Sandeep; Bhat, Manoj; Pandey, Deeksha; Kushtagi, Pralhad; Thangaraj, Kumarasamy; Gopinath, P M; Satyamoorthy, Kapaettu

    2014-05-01

    This study was undertaken to investigate the mitochondrial DNA (mtDNA) variation in non-malignant and malignant cervical tissue samples. We have identified 229 and 739 variations non-malignant and malignant tissues respectively distributed over 321 locations in the D-loop (50 in non-malignant and 166 in malignant; 216 variations), coding region (139 in non-malignant and 455 in malignant; 594 variations) tRNA and rRNA genes (39 in non-malignant and 119 in malignant; 158 variations). Besides, 77 novel and 34 various other disease associated variations were identified in non-malignant and malignant samples. A total of 236 tumor specific variations in 201 locations representing 30.1% in D-loop, 59.3% in coding regions and 10.6% in RNA genes were also identified. Our study shows that D loop (in 67 locations) is highly altered followed by ND5 (35 locations) region. Moreover, mtDNA alterations were significantly higher in malignant samples by two tailed Fisher's exact test (P≤0.05) with decreased mtDNA copy numbers. Bioinformatic analysis of 59 non-synonymous changes predicted several variations as damaging leading to decreased stability of the proteins. Taken together, mtDNA is highly altered in cervical cancer and functional studies are needed to be investigated to understand the consequence of these variations in cervical carcinogenesis and their potential application as biomarkers. PMID:23851045

  7. Targeting angiogenesis in advanced cervical cancer.

    PubMed

    Eskander, Ramez N; Tewari, Krishnansu S

    2014-11-01

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

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

    PubMed

    Scarinci, Isabel C; Garcia, Francisco A R; Kobetz, Erin; Partridge, Edward E; Brandt, Heather M; Bell, Maria C; Dignan, Mark; Ma, Grace X; Daye, Jane L; Castle, Philip E

    2010-06-01

    Cervical cancer is the second most common female tumor worldwide, and its incidence is disproportionately high (>80%) in the developing world. In the United States, in which Papanicolaou (Pap) tests have reduced the annual incidence to approximately 11,000 cervical cancers, >60% of cases are reported to occur in medically underserved populations as part of a complex of diseases linked to poverty, race/ethnicity, and/or health disparities. Because carcinogenic human papillomavirus (HPV) infections cause virtually all cervical cancer, 2 new approaches for cervical cancer prevention have emerged: 1) HPV vaccination to prevent infections in younger women (aged < or =18 years) and 2) carcinogenic HPV detection in older women (aged > or =30 years). Together, HPV vaccination and testing, if used in an age-appropriate manner, have the potential to transform cervical cancer prevention, particularly among underserved populations. Nevertheless, significant barriers of access, acceptability, and adoption to any cervical cancer prevention strategy remain. Without understanding and addressing these obstacles, these promising new tools for cervical cancer prevention may be futile. In the current study, the delivery of cervical cancer prevention strategies to these US populations that experience a high cervical cancer burden (African-American women in South Carolina, Alabama, and Mississippi; Haitian immigrant women in Miami; Hispanic women in the US-Mexico Border; Sioux/Native American women in the Northern Plains; white women in the Appalachia; and Vietnamese-American women in Pennsylvania and New Jersey) is reviewed. The goal was to inform future research and outreach efforts to reduce the burden of cervical cancer in underserved populations. PMID:20310056

  9. Relationship between hWAPL polymorphisms and cervical cancer susceptibility

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Madsen, Emily; Porterfield, Deborah; Varghese, Beena

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-06-01

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

  13. 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

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

    NASA Astrophysics Data System (ADS)

    Li, Wei; Yu, K. N.; Bao, Lingzhi; Shen, Jie; Cheng, Cheng; Han, Wei

    2016-01-01

    Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. However, the mechanism underlying its biological effects remains unclear. In this study, we investigated the inhibitory effect of NTP on the invasion of HeLa cells, and explored the possible mechanism. Our results showed that NTP exposure for 20 or 40 s significantly suppressed the migration and invasion of HeLa cells on the basis of matrigel invasion assay and wound healing assay, respectively. Moreover, NTP reduced the activity and protein expression of the matrix metalloproteinase (MMP)-9 enzyme. Western blot analysis indicated that NTP exposure effectively decreased phosphorylation level of both ERK1/2 and JNK, but not p38 MAPK. Furthermore, treatment with MAPK signal pathway inhibitors or NTP all exhibited significant depression of HeLa cells migration and MMP-9 expression. The result showed that NTP synergistically suppressed migration and MMP-9 expression in the presence of ERK1/2 inhibitor and JNK inhibitor, but not p38 MAPK inhibitor. Taken together, these findings suggested that NTP exposure inhibited the migration and invasion of HeLa cells via down-regulating MMP-9 expression in ERK1/2 and JNK signaling pathways dependent manner. These findings provide hints to the potential clinical research and therapy of NTP on cervical cancer metastasis.

  15. 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

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

    PubMed Central

    Li, Wei; Yu, K. N.; Bao, Lingzhi; Shen, Jie; Cheng, Cheng; Han, Wei

    2016-01-01

    Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. However, the mechanism underlying its biological effects remains unclear. In this study, we investigated the inhibitory effect of NTP on the invasion of HeLa cells, and explored the possible mechanism. Our results showed that NTP exposure for 20 or 40 s significantly suppressed the migration and invasion of HeLa cells on the basis of matrigel invasion assay and wound healing assay, respectively. Moreover, NTP reduced the activity and protein expression of the matrix metalloproteinase (MMP)-9 enzyme. Western blot analysis indicated that NTP exposure effectively decreased phosphorylation level of both ERK1/2 and JNK, but not p38 MAPK. Furthermore, treatment with MAPK signal pathway inhibitors or NTP all exhibited significant depression of HeLa cells migration and MMP-9 expression. The result showed that NTP synergistically suppressed migration and MMP-9 expression in the presence of ERK1/2 inhibitor and JNK inhibitor, but not p38 MAPK inhibitor. Taken together, these findings suggested that NTP exposure inhibited the migration and invasion of HeLa cells via down-regulating MMP-9 expression in ERK1/2 and JNK signaling pathways dependent manner. These findings provide hints to the potential clinical research and therapy of NTP on cervical cancer metastasis. PMID:26818472

  17. Second cancers following radiotherapy for cervical cancer

    SciTech Connect

    Kleinerman, R.A.; Curtis, R.E.; Boice, J.D. Jr.; Flannery, J.T.; Fraumeni, J.F. Jr.

    1982-11-01

    Incidence of second primary cancers was evaluated in 7,127 women with invasive cancer of the cervix uteri, diagnosed between 1935 and 1978, and followed up to 38 years (average, 8.9 yr) in Connecticut. Among 5,997 women treated with radiation, 449 developed second primary cancers compared with 313 expected (relative risk . 1.4) on the basis of rates from the Connecticut Tumor Registry. Excess incidence was noticeable 15 years or more after radiotherapy and attributed mostly to cancers of sites in or near the radiation field, especially the bladder, kidneys, rectum, corpus uteri, and ovaries. No excess was found for these sites among the 1,130 nonirradiated women. The ratio of observed to expected cancers for these sites did not vary appreciably by age at irradiation. The data suggested that high-dose pelvic irradiation was associated with increase in cancers of the bladder, kidneys, rectum, ovaries, corpus uteri, and non-Hodgkin's lymphoma but, apparently, not leukemia, Hodgkin's disease, breast cancer, or colon cancer.

  18. Venereal factors in human cervical cancer: evidence from marital clusters.

    PubMed

    Kessler, I I

    1977-04-01

    All Caucasian women in a large Eastern city who developed pathologically confirmed cervical cancer between 1950 and 1969 are being prospectively followed in an epidemiological test of the venereal hypothesis of cervical carcinogenesis. We are attempting to identify all men who were married to these probands at any time prior to the date of their cancer diagnosis. The ultimate objective is the identification of all the other wives of the proband husbands in order that their risk of cervical cancer be assessed. A random sample of control wives similar to the other wives in age, race, date and place of marriage as well as prior marital status is also being followed. To date, a total of 1,087 other wives and 659 control wives has been fully traced. Cervical cancer or carcinoma in situ was detected in 29 (2.7%) of the other wives and in seven (1.1%) of the control wives. A total of 14.0% of the other wives had either cervical cancer or a cervical cytological specimen which was other than normal. The corresponding statistic for the control wives was 8.0%. These differences in the prevalence of cervical cancer and of non-normal cervical cytology are statistically significant. In the course of this investigation so far, we have identified 29 "marital clusters" of cervical cancer in which two women married to the same man have all developed cervical neoplasms. The observed number of 29 clusters may be compared with an expected number of 11.6. This investigation, as yet incomplete, offers confirmatory evidence of the possible role of venereal factors in the pathogenesis of human cervical neoplasia. While the genital herpesvirus is the likeliest candidate, other venereal elements might also be involved. PMID:192439

  19. Neoadjuvant chemotherapy in cervical cancer in pregnancy.

    PubMed

    Ilancheran, Arunachalam

    2016-05-01

    Cervical cancer is the most common gynecological cancer encountered in pregnancy. The standard treatment of early cervical cancer is usually surgical removal of the cervix (in selected cases) or, more commonly, the uterus. However, when cervical cancer develops during pregnancy, definitive surgical treatment often needs to be postponed until the fetus reaches maturity. Neoadjuvant chemotherapy (NACT) is an innovative approach in the management of these patients. It helps in controlling the disease and delaying delivery. The paper presents a literature review of the history of NACT, as well as practice points and agenda for further research. PMID:26536815

  20. The Expression of Toll-like Receptor 8 and Its Relationship with VEGF and Bcl-2 in Cervical Cancer

    PubMed Central

    Zhang, Yun; Yang, Heng; Barnie, Prince Amoah; Yang, Peifang; Su, Zhaoliang; Chen, Jianguo; Jiao, Zhijun; Lu, Liwei; Wang, Shengjun; Xu, Huaxi

    2014-01-01

    BACKGROUND: Cervical cancer is one of the most common cancers in women worldwide, often associated with the infection of human papillomavirus (HPV). Toll-like receptor 8 (TLR8), a pattern recognition receptor, is involved in viral nucleic acid sensing. Recently TLR8 has been shown to be expressed in cancer cells, and it has been suggested that it may help cancer cell growth and tumor development. The objective of this study is to investigate the expression of TLR8 expression and its relationship with Bcl-2 and VEGF in cervical cancer cells. METHODOLOGY/PRINCIPAL: The mRNA expression levels of Bcl-2, VEGF and TLR-7,-8,-9 in newly diagnosed cervical cancer patients were detected by quantitative real-time PCR (qRT- PCR). Epifluorescence microscope was used to determine the presence of TLR8 protein in Hela cells. The cell cycle and apoptosis were analyzed by flow cytometer, and the cell proliferation was measured by MTT assay. Our data showed the increased mRNA levels of TLR8 in human cervical cancer samples as well as in HeLa cells, a cell line derived from a human cervical cancer. In addition, there was a positive correlation between the expression levels of TLR8 and Bcl-2 and VEGF in cervical cancer patients. When Hela cells were treated with TLR8 agonist CL075, the percentage of cells in G2/M +S was remarkably increased, accompanied by increased COX-2, BCL-2 and VEGF mRNA levels. CONCLUSIONS/SIGNIFICANCE: The mRNA expression level of TLR8 in the patients with cervical cancer and Hela cells were up-regulated, it consistent with the increased expression of VEGF and Bcl-2. The results suggest that TLR8 may be an interesting therapeutic target in cervical cancer. PMID:24782650

  1. Advanced Composite of Large Cell Neuroendocrine Carcinoma and Squamous Cell Carcinoma: A Case Report of Uterine Cervical Cancer in a Virgin Woman

    PubMed Central

    Kou, Iemasa; Date, Kenjiro; Nakayama, Hirofumi

    2013-01-01

    Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is very rare and aggressive. The prognosis is very poor despite multimodal treatment. We report a virgin woman with FIGO stage 4b LCNEC of uterine cervix coexisting with squamous cell carcinoma. An early thirties virgin woman presented with 2-month history of abdominal pain. A chest X-ray showed multiple lung metastatic tumors. A vaginal smear showed malignant cells, and a biopsy specimen had features of LCNEC. The tumor showed trabecular patterns. Tumor cells possessed a moderate amount of cytoplasm, prominent nucleoli, and large nuclei. The tumor cells are stained positive for synaptophysin, chromogranin A, and neuron specific enolase (NSE). The invasive tumor cells in connection with cervical squamous epithelium were focally positive for 34bE12. We made a diagnosis of composite LCNEC and nonkeratinizing squamous cell carcinoma. High-risk HPV test was negative with hybridized captured method 2. PMID:24062959

  2. 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

  3. 75 FR 7282 - Breast and Cervical Cancer Early Detection and Control Advisory Committee (BCCEDCAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-18

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

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

    PubMed

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

    2011-01-01

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

  5. Nucleolin as activator of human papillomavirus type 18 oncogene transcription in cervical cancer.

    PubMed

    Grinstein, Edgar; Wernet, Peter; Snijders, Peter J F; Rösl, Frank; Weinert, Inge; Jia, Wentao; Kraft, Regine; Schewe, Christiane; Schwabe, Michael; Hauptmann, Steffen; Dietel, Manfred; Meijer, Chris J L M; Royer, Hans-Dieter

    2002-10-21

    High risk human papillomaviruses (HPVs) are central to the development of cervical cancer and the deregulated expression of high risk HPV oncogenes is a critical event in this process. Here, we find that the cell protein nucleolin binds in a sequence-specific manner to the HPV18 enhancer. The DNA binding activity of nucleolin is primarily S phase specific, much like the transcription of the E6 and E7 oncoproteins of HPV18 in cervical cancer cells. Antisense inactivation of nucleolin blocks E6 and E7 oncogene transcription and selectively decreases HPV18(+) cervical cancer cell growth. Furthermore, nucleolin controls the chromatin structure of the HPV18 enhancer. In contrast, HPV16 oncogene transcription and proliferation rates of HPV16(+) SiHa cervical cancer cells are independent of nucleolin activity. Moreover, nucleolin expression is altered in HPV18(+) precancerous and cancerous tissue from the cervix uteri. Whereas nucleolin was homogeneously distributed in the nuclei of normal epithelial cells, it showed a speckled nuclear phenotype in HPV18(+) carcinomas. Thus, the host cell protein nucleolin is directly linked to HPV18-induced cervical carcinogenesis. PMID:12391018

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

    PubMed Central

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

    2015-01-01

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

  7. Dual Regulation of Cell Death and Cell Survival upon Induction of Cellular Stress by Isopimara-7,15-Dien-19-Oic Acid in Cervical Cancer, HeLa Cells In vitro

    PubMed Central

    Abu, Nadiah; Yeap, Swee K.; Pauzi, Ahmad Z. Mat; Akhtar, M. Nadeem; Zamberi, Nur R.; Ismail, Jamil; Zareen, Seema; Alitheen, Noorjahan B.

    2016-01-01

    The Fritillaria imperialis is an ornamental flower that can be found in various parts of the world including Iraq, Afghanistan, Pakistan, and the Himalayas. The use of this plant as traditional remedy is widely known. This study aims to unveil the anti-cancer potentials of Isopimara-7,15-Dien-19-Oic Acid, extracted from the bulbs of F. imperialis in cervical cancer cell line, HeLa cells. Flow cytometry analysis of cell death, gene expression analysis via cDNA microarray and protein array were performed. Based on the results, Isopimara-7,15-Dien-19-Oic acid simultaneously induced cell death and promoted cell survival. The execution of apoptosis was apparent based on the flow cytometry results and regulation of both pro and anti-apoptotic genes. Additionally, the regulation of anti-oxidant genes were up-regulated especially thioredoxin, glutathione and superoxide dismutase- related genes. Moreover, the treatment also induced the activation of pro-survival heat shock proteins. Collectively, Isopimara-7,15-Dien-19-Oic Acid managed to induce cellular stress in HeLa cells and activate several anti- and pro survival pathways. PMID:27065873

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

    PubMed

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

    2010-10-01

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

  9. Anti-proliferative effect of RCE-4 from Reineckia carnea on human cervical cancer HeLa cells by inhibiting the PI3K/Akt/mTOR signaling pathway and NF-κB activation.

    PubMed

    Bai, Caihong; Yang, Xiaojiao; Zou, Kun; He, Haibo; Wang, Junzhi; Qin, Huilin; Yu, Xiaoqin; Liu, Chengxiong; Zheng, Juyan; Cheng, Fan; Chen, Jianfeng

    2016-06-01

    Cervical cancer is the second leading cause of cancer deaths in women worldwide. In recent years, the studies find that inflammation is a critical component of tumor progression, and the ideal therapeutic methods should be aimed at the inflammation reaction triggers. (1β,3β,5β,25S)-spirostan-1,3-diol1-[α-L-rhamnopyranosyl-(1 → 2)-β-D-xylopyranoside] (RCE-4) was the main active composition of Reineckia carnea (Andr.) Kunth. It significantly induced apoptosis in cervical cancer Caski cells through the mitochondrial pathway in our previous studies; however, its underlying mechanism remains poorly understood. This study aimed to further evaluate the effect of RCE-4 on human cervical cancer HeLa cells. Based on this observation, we investigated the anti-cervical cancer effect of RCE-4 by modulating phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway, nuclear factor-kappa B (NF-κB) activation, and inflammation-related key factors in HeLa cells. The results indicated that the HeLa cell was the most sensitive with an IC50 of 7.01 μM; RCE-4 significantly promoted the release of cellular lactate dehydrogenase (LDH); increased DNA fragmentation and apoptosis; reduced PI3K, Akt, mTOR, and NF-κBp65 phosphorylation levels; increased the Bax and cleaved poly (ADP-ribose) polymerase (PARP) protein levels; suppressed Bcl-2 protein expression; elevated the Bax/Bcl-2 expression ratio; and decreased the interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) mRNA expressions in HeLa cells in a concentration-dependent manner. These findings suggest that RCE-4 exerted beneficially anti-cervical cancer effect on HeLa cells, mainly inhibiting PI3K/Akt/mTOR signaling pathway phosphorylation and NF-κB activation, promoting HeLa cell apoptosis. Graphical abstract Anti-tumor effect of RCE-4 on HeLa cells. PMID:26935715

  10. 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

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

    PubMed Central

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

    2015-01-01

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

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

    ClinicalTrials.gov

    2016-02-09

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

  13. Cervical cancer pathogenesis is associated with one-carbon metabolism.

    PubMed

    Pathak, Sujata; Bhatla, Neerja; Singh, Neeta

    2012-10-01

    Cervical cancer is the most common cancer among women in India and a leading cause of death in these women. Most cases of cervical cancer are associated with human papillomavirus (HPV) infection of the high-risk type. It has been reported that aberrant DNA methylation can be associated with HPV infection and cervical cancer, and folate is directly involved in DNA methylation via one-carbon metabolism. We aimed to study the importance of one-carbon metabolism in the progression of cervical carcinogenesis by examining serum levels of vitamin B(12) (cobalamin), homocysteine, and folate and DNA methylation of tumor suppressor genes CDH1, HIC1, and Retinoic acid receptor beta (RARβ) amid these women ranging from normal to squamous intraepithelial neoplastic lesions (SIL) to cervical cancer. Blood and tissue samples were collected from normal (n = 35), SILs (n = 27), and cervical cancer patients (n = 38) in the age group of 26-70 years. Measurement of serum vitamin B(12), folate, and homocysteine were done using kits (Immulite). Promoter methylation was examined using methylation-specific PCR. The frequency of promoter hypermethylation for all the three tumor suppressor genes CDH1, HIC1, and RARβ showed an increasing trend from normal to dysplastic to invasive cervical cancer (p < 0.05). We observed that lower folate and vitamin B(12) status were associated with HPV infection. Taken together, our findings suggest a role of folate and vitamin B(12) in modulating the risk of cervical cancer and HPV infection. CDH1, HIC1, and RARβ genes can be used as potential biomarkers of cervical cancer risk assessment. PMID:22729741

  14. 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

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

    PubMed Central

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

    2015-01-01

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

  16. [Uterine cervical cancer screening in Japan: today and future].

    PubMed

    Matsuura, Yusuke; Kawagoe, Toshinori; Toki, Naoyuki; Hachisuga, Toru; Kashimura, Masamichi

    2009-06-01

    Despite the proven effectiveness of cytological uterine cervical cancer screening, the consultation rate for cancer screening in Japan is markedly low in comparison with other developed countries. Although the mortality of this cancer has been steadily decreasing, it has been on the rise in the recent several years. It is evident that human papillomavirus (HPV) is involved in the occurrence of uterine cervical cancer, and, because of changes in sexual awareness and the diversification of sexual behavior, the increase in the incidence of uterine cervical cancer, especially among young adults, has become a major social problem. There is a false negative rate of about 10% in cytological uterine cervical cancer screening, seen mostly in cervical adenocarcinoma cases. As there is a limit to the effectiveness of cancer screening by cytology alone, there is a movement in Japan to increase the accuracy of cytological screening by using liquid-based cytology (LBC) and adopting HPV testing. There are various problems in cytological cancer screening, but the national and local governments, medical institutions, companies, and educational institutions must have an accurate understanding of the current situation and take an assertive approach in order to decrease the mortality rate of uterine cervical cancer. PMID:19530563

  17. Increasing Efforts to Reduce Cervical Cancer through State-Level Comprehensive Cancer Control Planning.

    PubMed

    Meyerson, Beth E; Zimet, Gregory D; Multani, Gurprit S; Levell, Caleb; Lawrence, Carrie A; Smith, Jennifer S

    2015-07-01

    Reducing cervical cancer disparities in the United States requires intentional focus on structural barriers such as systems and policy that impact access to human papillomavirus (HPV) vaccination, cervical cancer screening, and treatment. Such changes are difficult and often politicized. State comprehensive cancer control (CCC) plans are vehicles that, if designed well, can help build collective focus on structural changes. Study objectives were to identify the prioritization of cervical cancer in state CCC plans, the conceptualization of HPV within these plans, and the focus of plans on structural changes to reduce cervical cancer disparities. Data were gathered by systematic content analysis of CCC plans from 50 states and the District of Columbia from February-June 2014 for evidence of cervical cancer prioritization, conceptualization of HPV, and focus on structural barriers to cervical cancer vaccination, screening or treatment. Findings indicate that prioritization of cervical cancer within state CCC plans may not be a strong indicator of state efforts to reduce screening and treatment disparities. While a majority of plans reflected scientific evidence that HPV causes cervical and other cancers, they did not focus on structural elements impacting access to evidence-based interventions. Opportunities exist to improve state CCC plans by increasing their focus on structural interventions that impact cervical cancer prevention, detection, and treatment, particularly for the 41% of plans ending in 2015 and the 31% ending between 2016 and 2020. Future studies should focus on the use of policy tools in state CCC plans and their application to cervical cancer prevention and treatment. PMID:25943743

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

    PubMed Central

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

    2015-01-01

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

  19. [Prevention and screening of cervical cancer].

    PubMed

    Rakotomahenina, Hajanirina; Garrigue, Isabelle; Marty, Marion; Brun, Jean-Luc

    2014-06-01

    Cervical cancer may be prevented by human papillomavirus (HPV) vaccination and the treatment of intraepithelial lesions diagnosed using cervical pap smears. HPV vaccines are effective for the prevention of CIN2/3 related to HPV 16, 18 and some other oncogenic HPV subtypes in HPV-naïve women. They are very well tolerated and to date, no increase in the incidence of auto-immune diseases has been reported. HPV vaccines primarily target girls aged 11-14 years old and catch-up programs include girls aged 15-19 years old. Vaccination coverage is below 40% in France, which is insufficient to induce herd immunity. Screening via pap smears is performed every three years in women between 25 and 65 years old, after two normal annual smears. However, screening is an individualised decision and is only performed in 57% of women. Abnormal smears require subsequent diagnostic investigations. Apart from high grade intra-epithelial lesions which generally require treatment, these abnormalities may be observed as they often undergo spontaneous regression due to viral clearance. PMID:25090760

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

    PubMed

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

    2013-10-01

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

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

    PubMed

    Powers, Hilary J

    2005-12-01

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

  2. 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

  3. Induction of Apoptosis by Green Synthesized Gold Nanoparticles Through Activation of Caspase-3 and 9 in Human Cervical Cancer Cells

    PubMed Central

    Baharara, Javad; Ramezani, Tayebe; Divsalar, Adeleh; Mousavi, Marzieh; Seyedarabi, Arefeh

    2016-01-01

    Background: Gold Nanoparticles (GNPs) are used in imaging and molecular diagnostic applications. As the development of a novel approach in the green synthesis of metal nanoparticles is of great importance and a necessity, a simple and safe method for the synthesis of GNPs using plant extracts of Zataria multiflora leaves was applied in this study and the results on GNPs’ anticancer activity against HeLa cells were reported. Methods: The GNPs were characterized by UV-visible spectroscopy, FTIR, TEM, DLS and Zeta-potential measurements. In addition, the cellular up-take of nanoparticles was investigated using Dark Field Microscopy (DFM). Induction of apoptosis by high dose of GNPs in HeLa cells was assessed by MTT assay, Acridin orange, DAPI staining, Annexin V/PI double-labeling flow cytometry and caspase activity assay. Results: UV-visible spectroscopy results showed a surface plasmon resonance band for GNPs at 530 nm. FTIR results demonstrated an interaction between plant extract and nanoparticles. TEM images revealed different shapes for GNPs and DLS results indicated that the GNPs range in size from 10 to 42 nm. The Zeta potential values of the synthesized GNPs were between 30 to 50 Mev, indicating the formation of stable particles. As evidenced by MTT assay, GNPs inhibit proliferation of HeLa cells in dose-dependent GNPs and cytotoxicity of GNPs in Bone Marrow Mesenchymal Stem Cell (BMSCs) was lower than cancerous cells. At nontoxic concentrations, the cellular up-take of the nanoparticles took place. Acridin orange and DAPI staining showed morphological changes in the cell’s nucleus due to apoptosis. Finally, caspase activity assay demonstrated HeLa cell’s apoptosis through caspase activation. Conclusion: The results showed that GNPs have the ability to induce apoptosis in HeLa cells. PMID:27141266

  4. 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 μM) 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

  5. Cervical cancer in Indigenous women: The case of Australia.

    PubMed

    Shannon, Geordan D; Franco, Oscar H; Powles, John; Leng, Yue; Pashayan, Nora

    2011-11-01

    Globally, health inequities between Indigenous and non-Indigenous populations exist. The disparity in health outcomes between Indigenous and non-Indigenous Australians is exemplified by cervical cancer. Current evidence suggests that Indigenous women have higher age standardised incidence and mortality than non-Indigenous women when adjusted for stage at diagnosis and co-morbidities; however, there is little information pertaining to national estimates of cervical cancer in Indigenous women. In this paper we review available evidence on the difference in occurrence and case fatality of cervical cancer among Indigenous and non-Indigenous Australian women. The Australian Bureau of Statistics, Australian Institute of Health and Welfare, and State- or Territory-based Cancer Registries were utilised to collect surveillance data. To corroborate existing data, further available journal literature was identified through Medline and Embase. All papers selected for review were cross-referenced to identify further relevant studies. The most recent national estimate of age-standardised cervical cancer incidence rate was 16.9 and 7.1 per 100,000 women-years in Indigenous and non-Indigenous women respectively (incidence ratio 2.4). The Indigenous age-standardised mortality rate was 9.9 per 100,000 women years (95% CI 7.1-13.3), over 5 times the non-Indigenous rate. Cervical cancer incidence, in both Indigenous and non-Indigenous women, has decreased since 1991. Despite the decline, age-standardised incidence among Indigenous women is still higher than non-Indigenous women. The pattern of cervical cancer incidence and survival corroborates the health inequities that exist in Australia. Indigenous women are more likely than non-Indigenous women to develop cervical cancer and are less likely to survive it. Similar patterns exist in Indigenous populations worldwide, such as New Zealander Maoris and Canadian Aboriginals, suggesting that high rates of cervical cancer incidence and mortality may be a symptom of social and economic inequity. PMID:21889857

  6. 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

  7. Survival analysis of cervical cancer using stratified Cox regression

    NASA Astrophysics Data System (ADS)

    Purnami, S. W.; Inayati, K. D.; Sari, N. W. Wulan; Chosuvivatwong, V.; Sriplung, H.

    2016-04-01

    Cervical cancer is one of the mostly widely cancer cause of the women death in the world including Indonesia. Most cervical cancer patients come to the hospital already in an advanced stadium. As a result, the treatment of cervical cancer becomes more difficult and even can increase the death's risk. One of parameter that can be used to assess successfully of treatment is the probability of survival. This study raises the issue of cervical cancer survival patients at Dr. Soetomo Hospital using stratified Cox regression based on six factors such as age, stadium, treatment initiation, companion disease, complication, and anemia. Stratified Cox model is used because there is one independent variable that does not satisfy the proportional hazards assumption that is stadium. The results of the stratified Cox model show that the complication variable is significant factor which influent survival probability of cervical cancer patient. The obtained hazard ratio is 7.35. It means that cervical cancer patient who has complication is at risk of dying 7.35 times greater than patient who did not has complication. While the adjusted survival curves showed that stadium IV had the lowest probability of survival.

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

    PubMed Central

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

    2016-01-01

    Objective In this study, we investigated whether regular use of aspirin or acetaminophen was associated with risk of cervical cancer in women treated at an American cancer hospital. Methods This case-control study included 328 patients with cervical cancer and 1,312 controls matched on age and decade enrolled. Controls were women suspected of having but not ultimately diagnosed with a neoplasm. Analgesic use was defined as regular (at least once per week for ≥6 months), frequent (≥7 tablets/week), very long term (≥11 years), or frequent, long term (≥7 tablets per week for ≥5 years). Results Compared to nonusers, frequent aspirin use was associated with decreased odds of cervical cancer (odds ratio, 0.53; 95%confidence interval, 0.29–0.97). A slightly larger association was observed with frequent, long-term use of aspirin (odds ratio, 0.46; 95% confidence interval, 0.22–0.95). Acetaminophen use was not associated with the risk of cervical cancer. Conclusions Our findings suggest that frequent and frequent, long-term use of aspirin is associated with decreased odds of cervical cancer. To our knowledge, this is the first US-based study examining these associations. Given the widespread use of nonsteroidal anti-inflammatory drugs and acetaminophen worldwide, further investigations of the possible role of analgesics in cervical cancer, using a larger sample size with better-defined dosing regimens, are warranted. PMID:25856123

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

    PubMed

    Flores, Bertha E; Acton, Gayle J

    2013-11-01

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

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

    PubMed

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

    2016-01-01

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

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

    MedlinePlus

    ... injecting indocyanine green (ICG) dye into the cervix. HPV vaccines Vaccines have been developed to prevent infection with some of the HPV types associated with cervical cancer. Currently available vaccines ...

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

    Cancer.gov

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-09-01

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

  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. Cervical cancer detection based on serum sample Raman spectroscopy.

    PubMed

    González-Solís, José Luis; Martínez-Espinosa, Juan Carlos; Torres-González, Luis Adolfo; Aguilar-Lemarroy, Adriana; Jave-Suárez, Luis Felipe; Palomares-Anda, Pascual

    2014-05-01

    The use of Raman spectroscopy to analyze the biochemical composition of serum samples and hence distinguish between normal and cervical cancer serum samples was investigated. The serum samples were obtained from 19 patients who were clinically diagnosed with cervical cancer, 3 precancer, and 20 healthy volunteer controls. The imprint was put under an Olympus microscope, and around points were chosen for Raman measurement.All spectra were collected at a Horiba Jobin-Yvon LabRAM HR800 Raman Spectrometer with a laser of 830-nm wavelength and 17-mW power irradiation. Raw spectra were processed by carrying out baseline correction, smoothing, and normalization to remove noise, florescence, and shot noise and then analyzed using principal component analysis (PCA). The control serum spectrum showed the presence of higher amounts of carotenoids indicated by peaks at 1,002, 1,160, and 1,523 cm(-1)and intense peaks associated with protein components at 754, 853, 938, 1,002, 1,300-1,345, 1,447, 1,523, 1,550, 1,620, and 1,654 cm(-1). The Raman bands assigned to glutathione (446, 828, and 1,404 cm(-1)) and tryptophan (509, 1,208, 1,556, 1,603, and 1,620 cm(-1)) in cervical cancer were higher than those of control samples, suggesting that their presence may also play a role in cervical cancer. Furthermore, weak bands in the control samples attributed to tryptophan (545, 760, and 1,174 cm(-1)) and amide III (1,234-1,290 cm(-1)) seem to disappear and decrease in the cervical cancer samples, respectively. It is shown that the serum samples from patients with cervical cancer and from the control group can be discriminated with high sensitivity and specificity when the multivariate statistical methods of PCA is applied to Raman spectra. PCA allowed us to define the wavelength differences between the spectral bands of the control and cervical cancer groups by confirming that the main molecular differences among the control and cervical cancer samples were glutathione, tryptophan, β carotene, and amide III. The preliminary results suggest that Raman spectroscopy could be a highly effective technique with a strong potential of support for current techniques as Papanicolaou smear by reducing the number of these tests; nevertheless, with the construction of a data library integrated with a large number of cervical cancer and control Raman spectra obtained from a wide range of healthy and cervical cancer population, Raman-PCA technique could be converted into a new technique for noninvasive real-time diagnosis of cervical cancer from serum samples. PMID:24197519

  16. Identification of DNA methylation of SOX9 in cervical cancer using methylated-CpG island recovery assay.

    PubMed

    Wu, Jian-Hong; Liang, Xue-Ai; Wu, Yu-Mei; Li, Feng-Shuang; Dai, Yin-Mei

    2013-01-01

    The aim of the present study was to identify novel methylation markers for cervical cancer screening and to test the clinical application of the most promising biomarker in cervical scrapings. Methylated-CpG island recovery assay-based microarray analysis was carried out on a discovery set consisting of cervical cancer tissue and normal cervical tissue to identify significantly hypermethylated genes. Five hundred and four CpG islands, corresponding to 378 genes, were differentially methylated between cervical cancer tissue and normal cervical tissue. Among them, 30 genes were significantly hypermethylated. Of the 30 genes, SOX9, PKLR and DLX4 were selected for further validation by direct bisulfite sequencing. The SOX9 gene revealed complete methylation in the cervical cancer tissue and complete non-methylation in the normal control tissue. A TaqMan-based real-time PCR assay was performed to detect the methylation levels of the SOX9 gene in 156 cervical scrapings, including 48 normal cervical scrapings, 30 scrapings with cervical intraepithelial neoplasia 1 (CIN1), 30 scrapings with CIN2-3 and 48 scrapings with squamous cell carcinoma (SCC). The methylation levels (methylation score) of the SOX9 gene increased significantly with the severity of cervical squamous lesions. The area under the receiver operating characteristic (ROC) curve (AUC) revealed that the methylation score of the SOX9 gene could be used to segregate SCC/CIN2-3 from CIN1/normal (AUC, 0.961; p=0.000). At the optimal cut-off value, a sensitivity of 92.3% and a specificity of 89.7% were obtained. In conclusion, SOX9 methylation is frequently involved in cervical carcinogenesis, and may provide a valuable molecular biomarker for early detection of cervical cancer. PMID:23064448

  17. 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

  18. Cervical Cancer Worry and Screening Among Appalachian Women

    PubMed Central

    Schoenberg, Nancy; Wilson, Tomorrow D.; Atkins, Elvonna; Dickinson, Stephanie; Paskett, Electra

    2015-01-01

    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

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

    PubMed Central

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

    2015-01-01

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

  20. Survival rates of cervical cancer patients in Malaysia.

    PubMed

    Muhamad, Nor Asiah; Kamaluddin, Muhammad Amir; Adon, Mohd Yusoff; Noh, Mohamed Asyraf; Bakhtiar, Mohammed Faizal; Ibrahim Tamim, Nor Saleha; Mahmud, Siti Haniza; Aris, Tahir

    2015-01-01

    Cervical cancer is the most common malignant cancer of the female reproductive organs worldwide. Currently, cervical cancer can be prevented by vaccination and detected at an early stage via various screening methods. Malaysia, as a developing country faces a heavy disease burden of cervical cancer as it is the second most common cancer among Malaysian women. This population based study was carried out to fulfil the primary aim of determining the survival rates of Malaysian women with cervical cancer and associated factors. Data were obtained from two different sources namely, the Malaysian National Cancer Registry (MNCR) and National Health Informatics Centre (NHIC) from 1st January 2000 to 31st December 2005. Kaplan Meier analyses were conducted to identify the overall survival rates and median survival time. Differences in survival among different ethnic and age group were compared using the log-rank test. A total of 5,859 patients were included. The median survival time for cervical cancer in this study was 65.8 months and the 5-year survival rate was 71.1%. The overall observed survival rates at 1, 3 and 5 years were 94.1%, 79.3% and 71.1% respectively. The log-rank test finding also showed that there were significant differences in the 5-year survival rate among different ethnic groups. Malays had the lowest survival rate of 59.2% followed by Indians (69.5%) and Chinese (73.8%). The overall 5-year survival rate among patients with cervical cancer in Malaysia is relatively good. Age and ethnic groups remain as significant determining factors for cervical cancer survival rate. PMID:25854407

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

    PubMed

    Lee, Jongwon; Carvallo, Mauricio

    2014-10-01

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

  2. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-07-01

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

  6. 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

  7. 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

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

    PubMed

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

    2015-01-01

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

  9. Msi1 promotes tumor growth and cell proliferation by targeting cell cycle checkpoint proteins p21, p27 and p53 in cervical carcinomas

    PubMed Central

    Liu, Xian; Yang, Wen-Ting; Zheng, Peng-Sheng

    2014-01-01

    Musashi RNA-binding protein1 (Msi1), a member of the RNA-binding protein family, has been reported to be a diagnostic marker and potential therapeutic target in some cancers, its function in cervical cancer remains unknown. In this study, we found Msi1 was highly expressed in cervical cancer tissues, and over-expressing Msi1 in cervical cancer cells enhanced tumor formation and cell proliferation and accelerated cells into the S phase. Whereas, down-regulating Msi1 by shRNA in cervical cancer cells inhibited tumor formation and cell proliferation and slowed cell into the S phase, suggesting that Msi1 might act as cell cycle regulator. Immunohistochemistry assay showed the negative correlation between Msi1 and p21, p27 and p53, suggesting that Msi1 might regulate these cycle regulators in cervical cancer. Moreover, the expression of the p21, p27 and p53 proteins were down-regulated in Msi1 overexpressing cervical cancer cells and up-regulated in shMsi1 cervical cancer cells. Luciferase assays and RNA-protein binding assays confirmed that Msi1 could bind to the mRNA 3′UTRs of p21, p27 and p53 and suppress the translation of these proteins. Our findings provide new evidence that Msi1 might promote cell proliferation by accelerating the cell cycle by directly targeting p21, p27 and p53. PMID:25362645

  10. Serum one-carbon metabolites and risk of cervical cancer.

    PubMed

    Pathak, Sujata; Bajpai, Deepti; Banerjee, Ayan; Bhatla, Neerja; Jain, Sunesh Kumar; Jayaram, Hiremagular N; Singh, Neeta

    2014-01-01

    Most cases of cervical cancer are associated with human papilloma virus (HPV) infection of high risk types. In folate deficiency, heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) interferes with HPV16 viral capsid protein synthesis. We aimed to study the importance of 1-carbon metabolism in cervical carcinogenesis by examining serum vitamin B12 (cobalamin), homocysteine, folate levels, and the RNA and protein expression of HPV16 L1, L2, E6, E7, and to correlate them with hnRNP-E1 expression and HPV infection in normals, squamous intraepithelial lesions (SILs), and cervical cancer subjects. Serum cobalamin, folate, and homocysteine were estimated using kits, RNA by real time PCR and proteins by Western blotting. We observed that lower folate and vitamin B12 levels were associated with HPV infection. hnRNP-E1 progressively decreased from normals (100%) to SILs (75%) to cervical cancer (52.6%). The findings show that HPV16 E6 and E7 are overexpresed whereas HPV16 L1 and L2 are downregulated at mRNA and protein levels in cervical cancer as compared to normals and SILs. The results indicate that perhaps the reduced expression of hnRNP-E1 might be involved with the cervical cancer pathogenesis, with folate playing a role in the natural history of HPV infection. PMID:24848140

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

    PubMed Central

    Zhou, Hang; Xiang, Qunying; Hu, Ting; Zhang, Qinghua; Chen, Zhilan; Ma, Ding; Feng, Ling

    2013-01-01

    Purpose Cervical cancer screening is an effective method for reducing the incidence and mortality of cervical cancer, but the screening attendance rate in developing countries is far from satisfactory, especially in rural areas. Wufeng is a region of high cervical cancer incidence in China. This study aimed to investigate the issues that concern cervical cancer and screening and the factors that affect women’s willingness to undergo cervical cancer screening in the Wufeng area. Participants and Methods A cross-sectional survey of women was conducted to determine their knowledge about cervical cancer and screening, demographic characteristics and the barriers to screening. Results Women who were willing to undergo screenings had higher knowledge levels. “Anxious feeling once the disease was diagnosed” (47.6%), “No symptoms/discomfort” (34.1%) and “Do not know the benefits of cervical cancer screening” (13.4%) were the top three reasons for refusing cervical cancer screening. Women who were younger than 45 years old or who had lower incomes, positive family histories of cancer, secondary or higher levels of education, higher levels of knowledge and fewer barriers to screening were more willing to participate in cervical cancer screenings than women without these characteristics. Conclusion Efforts are needed to increase women’s knowledge about cervical cancer, especially the screening methods, and to improve their perceptions of the screening process for early detection to reduce cervical cancer incidence and mortality rates. PMID:23843976

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

    PubMed

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

    2010-06-01

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

  13. Multihelix rotating shield brachytherapy for cervical cancer

    SciTech Connect

    Dadkhah, Hossein; Kim, Yusung; Flynn, Ryan T.; Wu, Xiaodong

    2015-11-15

    Purpose: To present a novel brachytherapy technique, called multihelix rotating shield brachytherapy (H-RSBT), for the precise angular and linear positioning of a partial shield in a curved applicator. H-RSBT mechanically enables the dose delivery using only linear translational motion of the radiation source/shield combination. The previously proposed approach of serial rotating shield brachytherapy (S-RSBT), in which the partial shield is rotated to several angular positions at each source dwell position [W. Yang et al., “Rotating-shield brachytherapy for cervical cancer,” Phys. Med. Biol. 58, 3931–3941 (2013)], is mechanically challenging to implement in a curved applicator, and H-RSBT is proposed as a feasible solution. Methods: A Henschke-type applicator, designed for an electronic brachytherapy source (Xoft Axxent™) and a 0.5 mm thick tungsten partial shield with 180° or 45° azimuthal emission angles and 116° asymmetric zenith angle, is proposed. The interior wall of the applicator contains six evenly spaced helical keyways that rigidly define the emission direction of the partial radiation shield as a function of depth in the applicator. The shield contains three uniformly distributed protruding keys on its exterior wall and is attached to the source such that it rotates freely, thus longitudinal translational motion of the source is transferred to rotational motion of the shield. S-RSBT and H-RSBT treatment plans with 180° and 45° azimuthal emission angles were generated for five cervical cancer patients with a diverse range of high-risk target volume (HR-CTV) shapes and applicator positions. For each patient, the total number of emission angles was held nearly constant for S-RSBT and H-RSBT by using dwell positions separated by 5 and 1.7 mm, respectively, and emission directions separated by 22.5° and 60°, respectively. Treatment delivery time and tumor coverage (D{sub 90} of HR-CTV) were the two metrics used as the basis for evaluation and comparison. For all the generated treatment plans, the D{sub 90} of the HR-CTV in units of equivalent dose in 2 Gy fractions (EQD2) was escalated until the D{sub 2cc} (minimum dose to hottest 2 cm{sup 3}) tolerance of either the bladder (90 Gy{sub 3}), rectum (75 Gy{sub 3}), or sigmoid colon (75 Gy{sub 3}) was reached. Results: Treatment time changed for H-RSBT versus S-RSBT by −7.62% to 1.17% with an average change of −2.8%, thus H-RSBT treatments times tended to be shorter than for S-RSBT. The HR-CTV D{sub 90} also changed by −2.7% to 2.38% with an average of −0.65%. Conclusions: H-RSBT is a mechanically feasible delivery technique for use in the curved applicators needed for cervical cancer brachytherapy. S-RSBT and H-RSBT were clinically equivalent for all patients considered, with the H-RSBT technique tending to require less time for delivery.

  14. 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

  15. Disparities in cervical and breast cancer mortality in Brazil

    PubMed Central

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

    2014-01-01

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

  16. Disparities in cervical and breast cancer mortality in Brazil.

    PubMed

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

    2014-06-01

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

  17. Priority Setting for Improvement of Cervical Cancer Prevention in Iran

    PubMed Central

    Majidi, Azam; Ghiasvand, Reza; Hadji, Maryam; Nahvijou, Azin; Mousavi, Azam-Sadat; Pakgohar, Minoo; Khodakarami, Nahid; Abedini, Mehrandokht; Amouzegar Hashemi, Farnaz; Rahnamaye Farzami, Marjan; Shahsiah, Reza; Sajedinejhad, Sima; Mohagheghi, Mohammad Ali; Nadali, Fatemeh; Rashidian, Arash; Weiderpass, Elisabete; Mogensen, Ole; Zendehdel, Kazem

    2016-01-01

    Background: Cervical cancer is the fourth most common cancer among women worldwide. Organized cervical screening and vaccination against human papilloma virus (HPV) have been successful interventions for prevention of invasive cervical cancer (ICC). Because of cultural and religious considerations, ICC has low incidence in Iran and many other Muslim countries. There is no organized cervical screening in these countries. Therefore, ICC is usually diagnosed in advanced stages with poor prognosis in these countries. We performed a priority setting exercise and suggested priorities for prevention of ICC in this setting. Methods: We invited experts and researchers to a workshop and asked them to list important suggestions for ICC prevention in Iran. After merging similar items and removing the duplicates, we asked the experts to rank the list of suggested items. We used a strategy grid and Go-zone analysis to determine final list of priorities for ICC prevention in Iran. Results: From 26 final items suggested as priorities for prevention of ICC, the most important priorities were developing national guidelines for cervical screening and quality control protocol for patient follow-up and management of precancerous lesions. In addition, we emphasized considering insurance coverage for cervical screening, public awareness, and research priorities, and establishment of a cervical screening registry. Conclusion: A comprehensive approach and implementation of organized cervical screening program is necessary for prevention of ICC in Iran and other low incidence Muslim countries. Because of high cost for vaccination and low incidence of cervical cancer, we do not recommend HPV vaccination for the time being in Iran.

  18. 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,

  19. [Epidemiologic factors in cervical cancer--investigation on 306 pairs of partners. Jiangxi Co-operative Group of Cervical Cancer].

    PubMed

    1986-11-01

    To investigate the epidemiologic factors in Jingan and Tonggu counties, high incidence areas of cervical cancer, the 306 patient-control pairs were studied in 1980. These patients with various stages of cervical cancer were pathologically diagnosed in mass screening. The controls were healthy women of the same tribe and occupation, living in the same village as the patients. The age difference between the patients and the controls were not over 2-3 years. The ratio of the patients to the controls was 1:1. 36 doubtful factors were investigated by direct inquiry with uniform tables. After statistical analysis, it was found that sexual activity, smegma and cervical erosion are the high risk factors in causing cervical cancer. These three factors coexist, the relative risk was 11.2. It suggests that these factors have a comprehensive effect in causing cervical cancer. In view of the above, we suggested a preliminary plan for preventing and blocking of the development of cervical cancer and experiments in Jingan county are being carried out. PMID:3582114

  20. Risk Factors for Cervical Cancer in Criminal Justice Settings

    PubMed Central

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

    2011-01-01

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

  1. Chemotherapy and molecular targeting therapy for recurrent cervical cancer

    PubMed Central

    Tsuda, Naotake; Watari, Hidemichi; Ushijima, Kimio

    2016-01-01

    For patients with primary stage ⅣB, persistent, or recurrent cervical cancer, chemotherapy remains the standard treatment, although it is neither curative nor associated with long-term disease control. In this review, we summarized the history of treatment of recurrent cervical cancer, and the current recommendation for chemotherapy and molecular targeted therapy. Eligible articles were identified by a search of the MEDLINE bibliographical database for the period up to November 30, 2014. The search strategy included the following any or all of the keywords: “uterine cervical cancer”, “chemotherapy”, and “targeted therapies”. Since cisplatin every 21 days was considered as the historical standard treatment for recurrent cervical cancer, subsequent trials have evaluated and demonstrated activity for other agents including paclitaxel, gemcitabine, topotecan and vinorelbine among others. Accordingly, promising agents were incorporated into phase Ⅲ trials. To examine the best agent to combine with cisplatin, several landmark phase Ⅲ clinical trials were conducted by Gynecologic Oncology Group (GOG) and Japan Clinical Oncology Group (JCOG). Through, GOG204 and JCOG0505, paclitaxel/cisplatin (TP) and paclitaxel/carboplatin (TC) are now considered to be the recommended therapies for recurrent cervical cancer patients. However, the prognosis of patients who are already resistant to chemotherapy, are very poor. Therefore new therapeutic strategies are urgently required. Molecular targeted therapy will be the most hopeful candidate of these strategies. From the results of GOG240, bevacizumab combined with TP reached its primary endpoint of improving overall survival (OS). Although, the prognosis for recurrent cervical cancer patients is still poor, the results of GOG240 shed light on the usefulness of molecular target agents to chemotherapy in cancer patients. Recurrent cervical cancer is generally considered incurable and current chemotherapy regiments offer only modest gains in OS, particularly for patients with multiple poor prognostic factors. Therefore, it is crucial to consider not only the survival benefit, but also the minimization of treatment toxicity, and maximization of quality of life (QOL). PMID:27199523

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

    PubMed

    Van Kerrebroeck, Helena; Makar, Amin

    2016-03-01

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

  3. Current imaging strategies for the evaluation of uterine cervical cancer

    PubMed Central

    Bourgioti, Charis; Chatoupis, Konstantinos; Moulopoulos, Lia Angela

    2016-01-01

    Uterine cervical cancer still remains an important socioeconomic issue because it largely affects women of reproductive age. Prognosis is highly depended on extent of the disease at diagnosis and, therefore, accurate staging is crucial for optimal management. Cervical cancer is clinically staged, according to International Federation of Gynecology and Obstetrics guidelines, but, currently, there is increased use of cross sectional imaging modalities [computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT)] for the study of important prognostic factors like tumor size, parametrial invasion, endocervical extension, pelvic side wall or adjacent/distal organs involvement and lymph node status. Imaging indications also include cervical cancer follow-up, evaluation of tumor response to treatment and selection of suitable candidates for less radical surgeries like radical trachelectomy for fertility preservation. The preferred imaging method for local cervical cancer evaluation is MRI; CT is equally effective for evaluation of extrauterine spread of the disease. PET-CT shows high diagnostic performance for the detection of tumor relapse and metastatic lymph nodes. The aim of this review is to familiarize radiologists with the MRI appearance of cervical carcinoma and to discuss the indications of cross sectional imaging during the course of the disease in patients with cervical carcinoma. PMID:27158421

  4. HPV-beyond cervical cancer (online resource center).

    PubMed

    Alexander, Kenneth A; Giuliano, Anna R

    2012-07-01

    The human papillomavirus (HPV) causes more than 99% of all cervical cancers (see Am J Med Resource Center: http://supplements.amjmed.com/2011/HPV/). Exposure to HPV infections occurs in a high proportion of the overall population; however, 2 safe and effective vaccines, HPV2 and HPV4, are approved for the prevention of HPV-16 and HPV-18 infection, the most common causes of cervical cancer. Additionally, HPV4 prevents HPV-6 and HPV-11-related genital warts. While prevention of cervical cancer in women has been the initial aim of vaccination programs, it has now become apparent that HPV causes other types of cancer as well, including vulvar and vaginal cancers in women, penile cancer in men, and anal cancer in both sexes. Furthermore, these viruses have been implicated in head and neck cancers in both men and women as well. It is estimated that HPV-related cancers occur in 10,000 American males annually, suggesting that limiting vaccination programs to females may be underserving a significant proportion of the population. The efficacy of the 2 available vaccines against oncogenic HPV is more than 90% for both cervical and anal intraepithelial neoplasia. For those receiving the HPV4 vaccine, efficacy against genital warts is nearly 90%. Adverse effects are few and include episodes of syncope in the period immediately following vaccination. Benefits of vaccinating males include reduction in disease burden in men and enhanced herd immunity to reduce disease burden in women. PMID:22727241

  5. Advances in diagnosis and treatment of metastatic cervical cancer.

    PubMed

    Li, Haoran; Wu, Xiaohua; Cheng, Xi

    2016-07-01

    Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases. PMID:27171673

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

    PubMed

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

    2009-12-01

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

  7. miR-375 Mediated Acquired Chemo-Resistance in Cervical Cancer by Facilitating EMT

    PubMed Central

    Shen, Yuanming; Zhou, Jiansong; Li, Yang; Ye, Feng; Wan, Xiaoyun; Lu, Weiguo; Xie, Xing; Cheng, Xiaodong

    2014-01-01

    Acquired chemo-resistance is one of the key causal factors in cancer death. Emerging evidences suggest that miRNA and epithelial–mesenchymal transition play critical roles in the chemo-resistance in cancers. Here, we showed the association of paclitaxel-resistance with miR-375 over-expression and epithelial–mesenchymal transition inducement in cervical cancer. Using different cervical cancer cell models, we found that paclitaxel transiently induced up-regulation of miR-375 expression, proliferation inhibition, transition from epithelial to mesenchymal phenotype, and consequently impaired paclitaxel sensitivity. Forced over-expression of miR-375 may suppress Ecadherin expression by a directly targeting pathway, which led to paclitaxel resistance. Contrarily, re-expression of Ecadherin partly reversed epithelial–mesenchymal transition phenotype and miR-375 induced paclitaxel-resistance. Our findings suggest that paclitaxel-induced miR-375 over-expression facilitates epithelial–mesenchymal transition process via directly targeting Ecadherin, proliferation inhibition, and consequently results in chemo-resistance in cervical cancer cells. A reversion of miR-375 or Ecadherin expression may be a novel therapeutic approach for overcoming chemo-resistance in cervical cancer. PMID:25330011

  8. Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study

    PubMed Central

    Bahena-Román, Margarita; Téllez-Sosa, Juan; Martínez-Barnetche, Jesús; Cortina-Ceballos, Bernardo; López-Estrada, Guillermina; Delgado-Romero, Karina; Burguete-García, Ana I.; Cantú, David; García-Carrancá, Alejandro; Madrid-Marina, Vicente

    2016-01-01

    Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When β-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006) and the largest distance compared to NCL-HPV negative ones (p<0.00001). The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings. PMID:27115350

  9. 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…

  10. 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; Buchwal