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1

Cervical Cancer  

Cancer.gov

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

2

Cervical Cancer  

MedlinePLUS

... for cervical cancer are related to sexual practices. Sexually transmitted infections (STIs) may make your cells more likely to ... had many sexual partners Being infected with a sexually transmitted infection (STI) or having had a sex partner who ...

3

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

ClinicalTrials.gov

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

2014-05-12

4

ADXS11-001 High Dose HPV+ Cervical Cancer  

ClinicalTrials.gov

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

2014-06-16

5

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

ClinicalTrials.gov

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

2014-06-10

6

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

ClinicalTrials.gov

Cervical Adenocarcinoma; Cervical Adenosquamous Cell 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

2013-12-12

7

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

ClinicalTrials.gov

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

2014-06-18

8

Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer  

ClinicalTrials.gov

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

2014-03-07

9

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

ClinicalTrials.gov

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

2014-03-07

10

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

PubMed Central

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

WANG, LI; GUO, HUIJIE; LIN, CAIYU; YANG, LIUQI; WANG, XIUJIE

2014-01-01

11

High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer  

PubMed Central

High aldehyde dehydrogenase (ALDH) activity characterizes a subpopulation of cells with cancer stem cell (CSC) properties in several malignancies. To clarify whether ALDH can be used as a marker of cervical cancer stem cells (CCSCs), ALDHhigh and ALDHlow cells were sorted from 4 cervical cancer cell lines and 5 primary tumor xenografts and examined for CSC characteristics. Here, we demonstrate that cervical cancer cells with high ALDH activity fulfill the functional criteria for CSCs: (1) ALDHhigh cells, unlike ALDHlow cells, are highly tumorigenic in vivo; (2) ALDHhigh cells can give rise to both ALDHhigh and ALDHlow cells in vitro and in vivo, thereby establishing a cellular hierarchy; and (3) ALDHhigh cells have enhanced self-renewal and differentiation potentials. Additionally, ALDHhigh cervical cancer cells are more resistant to cisplatin treatment than ALDHlow cells. Finally, expression of the stem cell self-renewal-associated transcription factors OCT4, NANOG, KLF4 and BMI1 is elevated in ALDHhigh cervical cancer cells. Taken together, our data indicated that high ALDH activity may represent both a functional marker for CCSCs and a target for novel cervical cancer therapies.

Liu, Shu-Yan; Zheng, Peng-Sheng

2013-01-01

12

Cervical Cancer Prevention  

MedlinePLUS

... risk factors increase the risk of cervical cancer: HPV Infection The most common cause of cervical cancer ... may decrease the risk of cervical cancer: Preventing HPV infection HPV may be prevented by the following: ...

13

A specific miRNA signature promotes radioresistance of human cervical cancer cells  

PubMed Central

Background The mechanisms responsible for cervical cancer radioresistance are still largely unexplored. The present study aimed to identify miRNAs associated with radioresistance of cervical cancer cells. Methods The radioresistant cervical cancer cell variants were established by repeated selection with irradiation. The miRNA profiles of radioresistant cells and their corresponding controls were analyzed and compared using microarray. Differentially expressed miRNAs were confirmed by quantitative real-time PCR. Cervical cancer cells were transfected with miRNA-specific mimics or inhibitors. Radiosensitivity of cervical cancer cells were determined using colony-forming assay. Results Among the differentially expressed miRNAs, 20 miRNAs showed the similar pattern of alteration (14 miRNAs were overexpressed whilst 6 were suppressed) in all three radioresistant cervical cancer cell variants compared to their controls. A miRNA signature consisting of 4 miRNAs (miR-630, miR-1246, miR-1290 and miR-3138) exhibited more than 5 folds of increase in radioresistant cells. Subsequent analysis revealed that these four miRNAs could be up-regulated in cervical cancer cells by radiation treatment in both time-dependent and dose-dependent manners. Ectopic expression of each of these 4 miRNAs can dramatically increase the survival fraction of irradiated cervical cancer cells. Moreover, inhibition of miR-630, one miRNA of the specific signature, could reverse radioresistance of cervical cancer cells. Conclusions The present study indicated that miRNA is involved in radioresistance of human cervical cancer cells and that a specific miRNA signature consisting of miR-630, miR-1246, miR-1290 and miR-3138 could promote radioresistance of cervical cancer cells.

2013-01-01

14

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

PubMed Central

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

2013-01-01

15

Ubiquitin B in Cervical Cancer: Critical for the Maintenance of Cancer Stem-Like Cell Characters  

PubMed Central

Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate. Ubiquitin, which is a small, highly conserved protein expressed in all eukaryotic cells, can be covalently linked to certain target proteins to mark them for degradation by the ubiquitin-proteasome system. Previous studies highlight the essential role of Ubiquitin B (UbB) and UbB-dependent proteasomal protein degradation in histone deacetylase inhibitor (HDACi) -induced tumor selectivity. We hypothesized that UbB plays a critical role in the function of cervical cancer stem cells. We measured endogenous UbB levels in mammospheres in vitro by real-time PCR and Western blotting. The function of UbB in cancer stem-like cells was assessed after knockdown of UbB expression in prolonged Trichostatin A-selected HeLa cells (HeLa/TSA) by measuring in vitro cell proliferation, cell apoptosis, invasion, and chemotherapy resistance as well as by measuring in vivo growth in an orthotopic model of cervical cancer. We also assessed the cancer stem cell frequency, tumorsphere formation, and in vivo growth of human cervical cancer xenografts after UbB silencing. We found that HeLa/TSA were resistant to chemotherapy, highly expressed the UbB gene and the stem cell markers Sox2, Oct4 and Nanog. These cells also displayed induced differentiation abilities, including enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Furthermore, an elevated expression of UbB was shown in the tumor samples of chemotherapy patients. Silencing of UbB inhibited tumorsphere formation, lowered the expression of stem cell markers and decreased cervical xenograft growth. Our results demonstrate that UbB was significantly increased in prolonged Trichostatin A-selected HeLa cells and it played a key role in the maintenance of cervical cancer stem-like cells.

Wang, Yingying; Ji, Teng; Sun, Shujuan; Mo, Qingqing; Chen, Pingbo; Fang, Yong; Liu, Jia; Wang, Beibei; Zhou, Jianfeng; Ma, Ding; Wu, Peng

2013-01-01

16

AAC-11 overexpression induces invasion and protects cervical cancer cells from apoptosis.  

PubMed

To identify the genes involved in cervical carcinogenesis, we applied the mRNA differential display (DD) method to analyze normal cervical tissue, cervical cancer, metastatic lymph node, and cervical cancer cell line. We cloned a 491-bp cDNA fragment, CC231, which was present in metastatic tissue and cervical cancer cell line, but absent in normal cervical and cervical cancer tissues. The 491 bp cDNA fragment has 98% homology to the previously published sequence, AAC-11 (antiapoptosis clone 11). The levels of AAC-11 mRNA expressions in nine normal cervical and nine primary cervical cancer tissues were low. Its expression was higher in three metastatic tissues and five cervical cancer cell lines (HeLa, CaSki, SiHa, CUMC-3, and CUMC-6). Invasion of matrigel and adhesion to laminin by AAC-11 transfected CUMC-6 cells were increased by approximately 2-fold and 4-fold, respectively. Northern blot analysis showed that matrix metalloproteinase (MMP)-2 and membrane type 1 MMP (MT1-MMP) genes were found to be expressed in high levels in AAC-11-transfected cancer cells. But MMP-2 and MT1-MMP were not expressed in cells transfected with vector alone or wild-type cells. AAC-11-transfected cells expressed an elevated level of MMP-2 protein as assessed by immunoblotting. On the contrary, tissue inhibitor of MMP (TIMP-2) expression was detectable in cells transfected with vector alone or wild-type cells, respectively. Its expression was undetectable in AAC-11 transfected cells. In cervical cancer cells transfected with AAC-11, the expression of beta-catenin was up-regulated. These suggest that overexpressions of MMP-2 and MT1-MMP, loss of TIMP-2 expression, and up-regulation of beta-catenin by AAC-11 transfection may contribute to the development of cervical cancer invasion. AAC-11 gene transfection increased cervical cancer cell colonization. The effect of AAC-11 on cultured cervical cancer cells was associated with antiapoptotic process. Approximately 50% of the AAC-11 transfected cells in serum-free medium died after 2 weeks, compared to 1 week for vector alone or wild-type cells. These results suggest that AAC-11 may serve as a candidate metastasis-related and apoptosis-inhibiting gene in human cervical cancer. PMID:10780674

Kim, J W; Cho, H S; Kim, J H; Hur, S Y; Kim, T E; Lee, J M; Kim, I K; Namkoong, S E

2000-04-01

17

Cervical Cancer Cells with Positive Sox2 Expression Exhibit the Properties of Cancer Stem Cells  

PubMed Central

Background Although Sox2 expression has been found in several types of cancer, it has not yet been used to identify or isolate CSCs in somatic carcinoma. Methods SiHa and C33A cells stably transfected with a plasmid containing human Sox2 transcriptional elements driving the enhanced green fluorescent protein (EGFP) reporter were sorted into the Sox2-positive and the Sox2-negative populations by FACS, and Sox2 expression was detected by western blot and immunohistochemistry. The differentiation, self-renewal and tumor formation abilities, as well as the expression of the stemness and the EMT related genes of the Sox2-positive and the Sox2-negative cervical cancer cells were characterized in vitro and in vivo. Results A pSox2/EGFP system was used to separate the Sox2-positive and the Sox2-negative cells from cervical cancer cell lines, SiHa and C33A cells. Compared with the Sox2-negative cells, the Sox2-positive SiHa and C33A cells exhibited greater capacities for self-renewal, differentiation and tumor formation. Furthermore, Sox2-positive SiHa and C33A cells expressed higher levels of stemness-related genes, such as Sox2/Bmi-1/Oct4/ALDH1, and EMT-related genes, such as vimentin/snail/?-catenin. Taken together, all these results indicated that cells expressing endogenous Sox2 are CSCs in cervical carcinomas. Conclusion This study is the first to establish a functional link between endogenous Sox2 expression and CSCs in cervical carcinomas. Additionally, this study demonstrated that it is feasible to develop a tool to isolate CSCs from somatic tumors based on the expression of the endogenous nuclear protein Sox2 instead of cell surface markers.

Xu, Rui; Liu, Jun-Tian; Zheng, Peng-Sheng

2014-01-01

18

Retention of cell adhesion and growth capability in human cervical cancer cells deprived of cell anchorage.  

PubMed

Cell adhesion is linked to various regulatory processes of growth as well as apoptotic cell death in normal and transformed epithelial cells. We investigated changes of cellular responses to the deprivation of cell anchorage associated with immortalization or malignant transformation. Normal human ectocervical keratinocytes (NCE cells) deprived of cell anchorage become susceptible to apoptosis, and in parallel they lose their adhesion to the culture substratum. The loss of cell adhesion is not directly due to apoptosis. NCE16 cells, an immortalized but not malignantly transformed subline of NCE, underwent apoptosis and lost cell adhesion in suspension, as the NCE cells did. By contrast, apoptosis was not inducible in human cervical cancer-derived C33A cells in suspension. Of other cell lines derived from human cervical cancer, SiHa cells showed a weak apoptotic response and Caski cells were highly sensitive to apoptosis in the absence of cell anchorage. Unlike NCE or NCE16 cells, all these cancer cells retained cell adhesion as well as growth capability in suspension cultures. These results indicate that retention of cell adhesion and growth capability in the absence of cell anchorage is more closely associated with cancer cell lines than resistance to apoptosis upon the deprivation of cell anchorage. PMID:10543259

Kikuchi, K; Yasumoto, S

1999-08-01

19

ICSN - Cervical Cancer  

Cancer.gov

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

20

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

PubMed Central

Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer.

ZHAO, BING; HU, MENGCAI

2013-01-01

21

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

ClinicalTrials.gov

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

2014-05-30

22

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

PubMed

Human papillomavirus (HPV) infection is considered to be a primary hit that causes cervical cancer. However, infection with this agent, although needed, is not sufficient for a cancer to develop. Additional cellular changes are required to complement the action of HPV, but the precise nature of these changes is not clear. Here, we studied the function of the Hedgehog (Hh) signaling pathway in cervical cancer. The Hh pathway can have a role in a number of cancers, including those of liver, lung and digestive tract. We found that components of the Hh pathway are expressed in several cervical cancer cell lines, indicating that there could exists an autocrine Hh signaling loop in these cells. Inhibition of Hh signaling reduces proliferation and survival of the cervical cancer cells and induces their apoptosis as seen by the up-regulation of the pro-apoptotic protein cleaved caspase 3. Our results indicate that Hh signaling is not induced directly by HPV-encoded proteins but rather that Hh-activating mutations are selected in cells initially immortalized by HPV. Sonic Hedgehog (Shh) ligand induces proliferation and promotes migration of the cervical cancer cells studied. Together, these results indicate pro-survival and protective roles of an activated Hh signaling pathway in cervical cancer-derived cells, and suggest that inhibition of this pathway may be a therapeutic option in fighting cervical cancer. PMID:22820185

Samarzija, Ivana; Beard, Peter

2012-08-17

23

Tumor-associated lymphatic endothelial cell promotes invasion of cervical cancer cells.  

PubMed

The most common way for cervical cancer to spread is through the lymphatic system. Tumor-associated lymphatic endothelial cell (TLEC) has been considered to play a crucial role in metastasis of certain cancers. The aim of this study was to isolate TLEC from human cervical cancers and explore its involvement in metastasis-associated behaviors in vitro. Lymphatic vessels in 62 cervix tissue specimens ranging from cervical intraepithelial neoplasia (CIN) to advanced invasive cancer were detected using immunochemical staining with D2-40 antibody. Relation of lymphatic vessel density (LVD) to clinicopathological characters was analyzed. Primary TLECs were isolated by LYVE-1 immuno-magnetic beads from cervical cancer tissues and verified through expression of LEC markers Prox-1 and D2-40, and then cultured in vitro. Invasiveness and viability of cells were assessed by transwell assay and typan blue exclusion, respectively. Our results showed that higher LVD was significantly associated with advanced FIGO stage, pelvic lymphatic nodal metastasis (LNM), and poorer cell differentiation. TLECs were successfully primarily isolated and cultured in vitro. Supernatant of TLEC enhanced invasiveness of Hela cell, but did not significantly affect cell viability. In conclusion, TLECs might actively promote lymphatic metastasis of cervical cancer. Further studies are needed to demonstrate the underlying mechanisms. PMID:23566114

Cai, Liqiong; Yang, Shouhua; Ding, Hui; Cai, Jing; Wang, Zehua

2013-04-01

24

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

SciTech Connect

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

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

2012-08-17

25

Development of a new method for cervical cancer cells determination using light scattering spectrum  

NASA Astrophysics Data System (ADS)

Conventional methods for cervical cancer screening usually employ microscopic observations that may require fluorescence labeling of the cells, which could be time-consuming and expensive. Development of a novel method for cervical cancer cells determination in a rapid, label-free manner may significantly improve the cervical cancer screening technique. Here two-dimensional (2D) light scattering patterns are obtained from yeast cells on a CMOS chip, where laser light is used to excite single cells via fiber-coupling under a microscope. Good agreements between the experimental and Mie theory simulation results convey that 2D light scattering patterns from cervical cancer cells may be obtained upon the apparatus developed here. Mie theory simulations on simplified normal and cancerous cervical cells show that side scattering spectrum may be used for cervical cancer cells screening. Future experiments further convincing the 2D light scattering method proposed here may bring up a powerful technique that has profound applications in cervical cancer cell determination.

Yang, Yan; Jia, Rongfeng; Sun, Qiyong; Song, Kun; Kong, Beihua; Su, Xuantao

26

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

PubMed Central

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

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

2012-01-01

27

Biomarkers in Cervical Cancer  

PubMed Central

Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus (HPV) is the single most important etiological agent in cervical cancer, contributing to neoplastic progression through the action of viral oncoproteins, mainly E6 and E7. Cervical screening programs using Pap smear testing have dramatically improved cervical cancer incidence and reduced deaths, but cervical cancer still remains a global health burden. The biomarker discovery for accurate detection and diagnosis of cervical carcinoma and its malignant precursors (collectively referred to as high-grade cervical disease) represents one of the current challenges in clinical medicine and cytopathology.

Yim, Eun-Kyoung; Park, Jong-Sup

2006-01-01

28

Sine oculis homeobox homolog 1 promotes DNA replication and cell proliferation in cervical cancer.  

PubMed

Malignant proliferation is the fundamental trait of tumor cells. The initiation of DNA replication represents a key process for cell proliferation, and has a marked impact on tumorigenesis and progression. Here we report that Sine oculis homeobox homolog 1 (SIX1) functions as a master regulator in DNA replication of cervical cancer cells. The expression of SIX1 was induced by the E7 oncoprotein of human papillomaviruses in cervical intraepithelial neoplasia and cervical cancer. The increase of SIX1 expression resulted in the upregulation of multiple genes related to the initiation of DNA replication, including the genes coding for the proteins in minichromosome maintenance complex (MCM2, MCM3, MCM6), DNA polymerase ?-primase complex (POLA1, PRIM1, PRIM2), clamp loader (RFC3, RFC4, RFC5), DNA polymerase ? complex (POLD3) and DNA polymerase ? complex (POLE2). In line with this, the increase of SIX1 expression enhanced DNA synthesis, accelerated G1 to S phase progression, and promoted the proliferation of cervical cancer cells and the growth of cervical cancer. Consistently, knockdown of SIX1 could hamper DNA synthesis, slow down G1 to S phase progression, and suppress tumor cell proliferation and tumor growth. Importantly, SIX1 could more efficiently promote anchorage-independent cell growth. These results suggest that the increase of SIX1 expression could promote tumorigenesis, progression and invasive growth of cervical cancer by promoting DNA replication, and that targeting SIX1 may have significant therapeutic value in cervical cancer treatment. PMID:24970368

Liu, Dan; Zhang, Xiao-Xue; Xi, Bi-Xin; Wan, Dong-Yi; Li, Li; Zhou, Jin; Wang, Wei; Ma, Ding; Wang, Hui; Gao, Qing-Lei

2014-09-01

29

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

PubMed Central

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

BRONIARCZYK, JUSTYNA K.; WAROWICKA, ALICJA; KWASNIEWSKA, ANNA; WOHUN-CHOLEWA, MARIA; KWASNIEWSKI, WOJCIECH; GOZDZICKA-JOZEFIAK, ANNA

2014-01-01

30

Prostitution, Condom Use, and Invasive Squamous Cell Cervical Cancer in Thailand  

Microsoft Academic Search

Cervical cancer is probably caused by a sexually transmitted agent. A case-control study was conducted in three hospitals in Thailand to investigate further the role of male sexual behavior, particularly regarding sexual contacts with prostitutes, in the development of this disease. Data were obtained from interviews with 225 manned women with invasive squamous cell cervical carcinoma and 791 hospitalized controls,

David B. Thomas; Roberta M. Ray; Tieng Pardthaisong; Supawat Chutivongse; Supom Koetsawang; Suporn Silpisornkosol; Pramuan Virutamasen; William M. Christopherson; Joseph L. Melnick; Olav Meirik; Timothy M. M. Farley; Gustave Riotton

31

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

PubMed

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

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

2013-05-01

32

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

ClinicalTrials.gov

Anemia; Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Drug/Agent Toxicity by Tissue/Organ; Radiation Toxicity; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

2014-02-12

33

Serum squamous cell carcinoma antigen and CYFRA 21-1 in cervical cancer treatment  

Microsoft Academic Search

Purpose: To analyze whether serum squamous cell carcinoma (SCC) antigen and cytokeratin-19 fragments (CYFRA) levels can assist in selecting patients with locally advanced cervical cancer who will benefit from combined treatment or additive surgery.Methods and Materials: Of 114 patients with cervical cancer Stage IB–IV, the first 39 patients received radiotherapy, the following 75 patients received identical radiotherapy plus concomitant chemotherapy

Elisabeth Pras; Pax H. B Willemse; Alof A Canrinus; Henk W. A de Bruijn; Wim J Sluiter; Klaske A ten Hoor; Jan G Aalders; Ben G Szabo; Elisabeth G. E de Vries

2002-01-01

34

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 ... statement. To learn more, visit the Task Force Web site. USPSTF Recommendation Grades ... Happens During Screening Tests Screening for Cervical Cancer Get Tested for Cervical ...

35

ICSN - Cervical Cancer  

Cancer.gov

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

36

Cervical Cancer Screening Programs  

Cancer.gov

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

37

Cervical Cancer Screening Programs  

Cancer.gov

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

38

Cervical Cancer Participation Rates  

Cancer.gov

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

39

Cervical Cancer Other Characteristics  

Cancer.gov

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

40

Cervical Cancer Other Characteristics  

Cancer.gov

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

41

Cervical Cancer  

MedlinePLUS

... a biopsy. By getting regular Pap tests and pelvic exams you can find and treat any problems before they turn into cancer. Treatment may include surgery, radiation therapy, ... including some that can cause cancer. NIH: National Cancer Institute

42

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

PubMed

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

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

2013-02-01

43

Crosstalk with cancer-associated fibroblasts increases the growth and radiation survival of cervical cancer cells.  

PubMed

Crosstalk between cancer cells and the surrounding cancer associated fibroblasts (CAFs) plays an illusive role in cancer radiotherapy. This study investigated the effect of cancer cell-cancer associated fibroblasts crosstalk on the proliferation and survival of irradiated cervical cancer cells. A pretreatment with conditioned medium from a mixed culture of CAF and HeLa cells (mixCAF) had a stronger effect on enhancing the proliferation and survival of irradiated HeLa cells compared to pretreatment with CAF conditioned medium alone. In addition, pretreatment with a mixed culture of CAF and HeLa cells conditioned medium reduced the levels of two major radiation-induced genes, GADD45 and BTG2, and phosphorylation of p38. Profiling of the growth and survival factors in the conditioned medium revealed PDGF and VEGF, and IGF2, EGF, FGF-4, IGFBPs and GM-CSF to be specifically secreted from HeLa cells and CAFs, respectively. This study demonstrated radiation protective effects of CAF-cancer cell crosstalk, and identified multiple growth factors and radiation response genes that might be involved in these effects. PMID:24785588

Chu, Tang-Yuan; Yang, June-Ting; Huang, Tien-Hung; Liu, Hwan-Wun

2014-05-01

44

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

SciTech Connect

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

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

2013-11-01

45

Clinical significance of the stem cell gene Oct-4 in cervical cancer.  

PubMed

This study aims to investigate the association between the expression of Oct-4 and the biological behavior or prognosis of cervical cancer. Serum-free suspension culture technology was used to select a suspension of microspheres that can stabilize clones. The tumorigenicity of the microsphere suspension was analyzed in NOD/SCID mice. Microarray analysis was used to detect the specific expression of genes in the microsphere suspension. The expression of Oct-4 was detected by immunohistochemistry, and the correlation between Oct-4 expression and clinical pathological prognostic indicators was analyzed in cervical cancer. The expression of the following genes was significantly different between the experimental and control groups: stem cell differentiation (CD44 and Oct-4), markers cell cycle regulators (APC), cell cycle regulators (MYC), and self-renewal markers (MYST2, NEUROG2, and SOX1). The expression of Oct-4 was significantly higher in cervical cancer tissues than in adjacent normal tissues and was significantly related to differentiation, clinical stage, and lymph node metastasis. The 5-year survival rate of patients with Oct-4-positive expression was lower than that of patients with Oct-4-negative expression (36.7 vs. 67.7 %, respectively; P?=?0.001). Cox regression analysis revealed that clinical stage, lymph node metastasis, and Oct-4 were independent prognostic factors in cervical cancer (P?=?0.031, 0.012, and 0.001, respectively). Our results showed that Oct-4 was highly expressed in cervical cancer stem cells; Oct-4 expression was associated with biological behavior and was an independent prognostic factor in cervical cancer. Therefore, it may represent a potential target for cervical cancer treatment. PMID:24532469

Yang, Yanyan; Wang, Yimin; Yin, Chunxia; Li, Xiuying

2014-06-01

46

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

ClinicalTrials.gov

Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Chemotherapeutic Agent Toxicity; Cognitive/Functional Effects; Psychosocial Effects of Cancer and Its Treatment; Radiation Toxicity; Sexuality and Reproductive Issues; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

2014-06-25

47

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

PubMed

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

Roy, Madhumita; Mukherjee, Sutapa

2014-01-01

48

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

PubMed Central

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

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

2013-01-01

49

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

PubMed Central

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

Crescencio, Maria Elena; Rodriguez, Emma; Paez, Araceli; Masso, Felipe A.; Montano, Luis F.; Lopez-Marure, Rebeca

2009-01-01

50

Spaceflight alters the gene expression profile of cervical cancer cells  

PubMed Central

Our previous study revealed that spaceflight induced biological changes in human cervical carcinoma Caski cells. Here, we report that 48A9 cells, which were subcloned from Caski cells, experienced significant growth suppression and exhibited low tumorigenic ability after spaceflight. To further understand the potential mechanism at the transcriptional level, we compared gene expression between 48A9 cells and ground control Caski cells with suppression subtractive hybridization (SSH) and reverse Northern blotting methods, and analyzed the relative gene network and molecular functions with the Ingenuity Pathways Analysis (IPA) program. We found 5 genes, SUB1, SGEF, MALAT-1, MYL6, and MT-CO2, to be up-regulated and identified 3 new cDNAs, termed B4, B5, and C4, in 48A9 cells. In addition, we also identified the two most significant gene networks to indicate the function of these genes using the IPA program. To our knowledge, our results show for the first time that spaceflight can reduce the growth of tumor cells, and we also provide a new model for oncogenesis study.

Zhang, Zhi-Jie; Tong, Yong-Qing; Wang, Jia-Jia; Yang, Cheng; Zhou, Guo-Hua; Li, Yue-Hui; Xie, Ping-Li; Hu, Jin-Yue; Li, Guan-Cheng

2011-01-01

51

Ectonucleotidase expression profile and activity in human cervical cancer cell lines.  

PubMed

Cervical cancer is the third most frequent cancer in women worldwide. Adenine nucleotide signaling is modulated by the ectonucleotidases that act in sequence, forming an enzymatic cascade. Considering the relationship between the purinergic signaling and cancer, we studied the E-NTPDases, ecto-5'-nucleotidase, and E-NPPs in human cervical cancer cell lines and keratinocytes. We evaluated the expression profiles of these enzymes using RT-PCR and quantitative real-time PCR analysis. The activities of these enzymes were examined using ATP, ADP, AMP, and p-nitrophenyl-5'-thymidine monophosphate (p-Nph-5'-TMP) as substrate, in a colorimetric assay. The extracellular adenine nucleotide hydrolysis was estimated by HPLC analysis. The hydrolysis of all substrates exhibited a linear pattern and these activities were cation-dependent. An interesting difference in the degradation rate was observed between cervical cancer cell lines SiHa, HeLa, and C33A and normal imortalized keratinocytes, HaCaT cells. The mRNA of ecto-5'-nucleotidase, E-NTPDases 5 and 6 were detectable in all cell lines, and the dominant gene expressed was the Entpd 5 enzyme, in SiHa cell line (HPV16 positive). In accordance with this result, a higher hydrolysis activity for UDP and GDP nucleotides was observed in the supernatant of the SiHa cells. Both normal and cancer cells presented activity and mRNAs of members of the NPP family. Considering that these enzymes exert an important catalytic activity, controlling purinergic nucleotide concentrations in tumors, the presence of ectonucleotidases in cervical cancer cells can be important to regulate the levels of extracellular adenine nucleotides, limiting their effects. PMID:24697693

Beckenkamp, Aline; Santana, Danielle Bertodo; Bruno, Alessandra Nejar; Calil, Luciane Noal; Casali, Emerson André; Paccez, Juliano Domiraci; Zerbini, Luiz F; Lenz, Guido; Wink, Márcia R; Buffon, Andréia

2014-04-01

52

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

ClinicalTrials.gov

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

2014-06-30

53

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

PubMed Central

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

2014-01-01

54

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

Microsoft Academic Search

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

Marlene F Shehata

2005-01-01

55

The p53 R72P polymorphism does not influence cervical cancer development in a Portuguese population: a study in exfoliated cervical cells.  

PubMed

The interaction between the E6 protein of the high-risk human papillomaviruses (HPVs) with p53 seems to be crucial in cervical carcinogenesis. The presence of Arg/Arg genotype at codon 72 of TP53 gene was characterized as a risk factor in development of cervical cancer. However, the role of this polymorphism remains controversial and some authors suggested that the origin of DNA (blood or exfoliated cervical cells) might influence these results. This study analyzed the effect of the p53 codon 72 polymorphism (R72P) in exfoliated cervical cells of women from the northern region of Portugal using two methodologies: allele-specific polymerase chain reaction and real-time polymerase chain reaction. We studied 700 cervical exfoliated cells which showed: 334 cases from women without cervical cancer or cervical lesion (N), 114 low-grade squamous intraepithelial lesions (LSIL), 107 high-grade squamous intraepithelial lesions (HSIL), 20 invasive cervical cancers (ICC) and 125 atypical squamous cells of unknown significance (ASCUS). No statistically significant differences between cases and controls were found, regarding the influence of the R72P polymorphism with cytological classification, high risk-HPV infection and HPV16 presence (P = 0.336, P = 0.945, and P = 0.964, respectively). Also, the influence of this polymorphism in the median age of onset for LSIL, HSIL, and ICC was not statistically significant (P = 0.674, P = 0.810, and P = 0.928, respectively). Therefore, the hypothesis that women with Arg/Arg genotype have an increased risk of developing cervical cancer failed to be proven in this study. Moreover, our study reveals that results using exfoliated cervical cells are reliable as compared with studies on blood. PMID:18205229

Oliveira, S; Sousa, H; Santos, A M; Pinto, D; Pinto-Correia, A L; Fontoura, D; Moutinho, J; Medeiros, R

2008-03-01

56

Smoking and Cervical Cancer  

PubMed Central

Cervical cancer (CC) is the third most common cancer in women worldwide; however, CC is a preventable disease, and much effort should be done to prevent it. Persistence of high-risk HPV infection is the strongest epidemiologic risk factor for CC, however it is not sufficient for development of the disease it cofactors should be present. In 2004; IARC listed cervical cancer among those causally related to smoking. Smoking interferes with incidence and prevalence of HPV infection and is associated with cervical intraepithelial neoplasia and invasive CC. Multiple factors seem to intervene on cervical carcinogenesis related with tobacco, especially by direct local carcinogenic effect and local immunosuppression. Smoking addition is also closely related with other confounding factors, like unfavorable psychosocial events, systemic immunity, contraception, and nutrition, which got difficult epidemiologic evaluation of smoking role on cervical carcinogenesis. Smoking habits should be taken in account in clinical practice and in research concerning CC.

Fonseca-Moutinho, Jose Alberto

2011-01-01

57

Defective antioxidant systems in cervical cancer.  

PubMed

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

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

2013-08-01

58

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

PubMed Central

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

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

2014-01-01

59

Oncogenic mutations in cervical cancer: genomic differences between adenocarcinomas and squamous cell carcinomas of the cervix  

PubMed Central

Background Cervical cancer is the second leading cause of cancer deaths among women worldwide. We sought to describe the most common oncogenic mutations in cervical cancers, and to explore genomic differences between the two most common histological subtypes: adenocarcinoma and squamous cell carcinoma. Methods A high-throughput genotyping platform, termed Oncomap, was used to interrogate 80 cervical tumors for 1250 known mutations in 139 cancer genes. Samples were analyzed using a mass spectrometry-based genotyping platform (Sequenom), and validated with an orthogonal chemistry. EGFR mutations were further validated by massively parallel sequencing (Illumina). Human papilloma virus (HPV) genotyping was also performed. Results Validated mutations were detected in 60.0% (48/80) of tumors examined. The highest mutation rates were PIK3CA (31.3%), KRAS (8.8%), and EGFR (3.8%). PIK3CA mutation rates were not significantly different in adenocarcinoma and squamous cell carcinomas (25.0% vs. 37.5%, respectively, p=0.33). In contrast, KRAS mutations were identified only in adenocarcinoma (17.5% vs. 0%, p=0.01), and a novel EGFR mutation was detected only in squamous cell carcinomas (0% vs. 7.5%, p=0.24). There were no associations between HPV-16 or HPV-18 and somatic mutations or overall survival. In adjusted analyses, PIK3CA mutations were associated with shorter survival—67.1 vs. 90.3 months (HR=9.1, 95% CI 2.8–29.5, p<0.001). Conclusions Cervical cancers harbor high rates of potentially targetable oncogenic mutations. In addition, cervical squamous cell carcinoma and adenocarcinoma have distinct molecular profiles, suggesting that clinical outcomes may be improved with the use of more tailored treatment strategies, including PI3-kinase and MEK inhibitors.

Wright, Alexi A.; Howitt, Brooke E.; Myers, Andrea P; Dahlberg, Suzanne E.; Palescandolo, Emanuele; Hummelen, Paul Van; MacConaill, Laura E; Shoni, Melina; Wagle, Nikhil; Jones, Robert T.; Quick, Charles M.; Laury, Anna; Katz, Ingrid T.; Hahn, William C.; Matulonis, Ursula A.; Hirsch, Michelle S.

2014-01-01

60

Cervical Cancer Stage IVA  

MedlinePLUS

... Home About My Pictures Browse Search Quick Search Image Details Cervical Cancer Stage IVA View/Download: Small: ... Added: 4/23/2012 Reuse Restrictions: Yes - This image is copyright protected. Any use of this image ...

61

Cervical Cancer Stage IVB  

MedlinePLUS

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62

Cervical Cancer Stage IIIB  

MedlinePLUS

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63

Cervical Cancer Stage IB  

MedlinePLUS

... Home About My Pictures Browse Search Quick Search Image Details Cervical Cancer Stage IB View/Download: Small: ... Added: 4/23/2012 Reuse Restrictions: Yes - This image is copyright protected. Any use of this image ...

64

Cervical Cancer Stage IIIA  

MedlinePLUS

... Home About My Pictures Browse Search Quick Search Image Details Cervical Cancer Stage IIIA View/Download: Small: ... Added: 4/23/2012 Reuse Restrictions: Yes - This image is copyright protected. Any use of this image ...

65

Cervical Cancer Stage IA  

MedlinePLUS

... Home About My Pictures Browse Search Quick Search Image Details Cervical Cancer Stage IA View/Download: Small: ... Added: 4/23/2012 Reuse Restrictions: Yes - This image is copyright protected. Any use of this image ...

66

Cervical Cancer (PDQ): Screening  

MedlinePLUS

... often in black women than in white women. Human papillomavirus (HPV) infection is the major risk factor ... Although most women with cervical cancer have the human papillomavirus (HPV) infection , not all women with an ...

67

Cervical Cancer Screening  

MedlinePLUS

... often in black women than in white women. Human papillomavirus (HPV) infection is the major risk factor ... Although most women with cervical cancer have the human papillomavirus (HPV) infection , not all women with an ...

68

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

PubMed

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

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

2014-03-01

69

Antiproliferative action of Xylopia aethiopica fruit extract on human cervical cancer cells.  

PubMed

The anticancer potential of Xylopia aethiopica fruit extract (XAFE), and the mechanism of cell death it elicits, was investigated in various cell lines. Treatment with XAFE led to a dose-dependent growth inhibition in most cell lines, with selective cytotoxicity towards cancer cells and particularly the human cervical cancer cell line C-33A. In this study, apoptosis was confirmed by nuclear fragmentation and sub-G(0)/G(1) phase accumulation. The cell cycle was arrested at the G(2)/M phase with a decreased G(0)/G(1) population. A semi-quantitative gene expression study revealed dose-dependent up-regulation of p53 and p21 genes, and an increase in the Bax/Bcl-2 ratio. These results indicate that XAFE could be a potential therapeutic agent against cancer since it inhibits cell proliferation, and induces apoptosis and cell cycle arrest in C-33A cells. PMID:21698670

Adaramoye, Oluwatosin A; Sarkar, Jayanta; Singh, Neetu; Meena, Sanjeev; Changkija, Bendangla; Yadav, Prem P; Kanojiya, Sanjeev; Sinha, Sudhir

2011-10-01

70

Comparison of DNA hypermethylation patterns in different types of uterine cancer: cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma.  

PubMed

The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite-modification technique and methylation-specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms. PMID:16331610

Kang, Sokbom; Kim, Jae Weon; Kang, Gyeong Hoon; Lee, Sun; Park, Noh Hyun; Song, Yong Sang; Park, Sang Yoon; Kang, Soon Beom; Lee, Hyo Pyo

2006-05-01

71

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

PubMed

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

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

2014-07-01

72

Stressing the Ubiquitin-Proteasome System without 20S Proteolytic Inhibition Selectively Kills Cervical Cancer Cells  

PubMed Central

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

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

2011-01-01

73

Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion by targeting focal adhesion pathways in cervical squamous cell carcinoma  

PubMed Central

Cervical cancer is one of the most common cancers in women. More than 275,100 women die from cervical cancer each year. Cervical squamous cell carcinoma (cervical SCC), one of the most frequent types of cervical cancers, is associated with high-risk human papilloma virus (HPV), although HPV infection alone may not be enough to induce malignant transformation. MicroRNAs (miRNAs), a class of small non-coding RNAs, regulate protein-coding gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. A growing body of evidence suggests that miRNAs contribute to cervical SCC progression, development and metastasis. miRNA expression signatures in SCC (hypopharyngeal SCC and esophageal SCC) revealed that miR-218 expression was significantly reduced in cancer tissues compared with adjacent non-cancerous epithelium, suggesting that miR-218 is a candidate tumor suppressor. The aim of this study was to investigate the functional significance of miR-218 in cervical SCC and to identify novel miR-218-mediated cancer pathways in cervical SCC. Restoration of miR-218 significantly inhibited cancer cell migration and invasion in both HPV-positive and HPV-negative cervical SCC cell lines. These data indicated that miR-218 acts as a tumor suppressor in cervical SCC. Our in silico analysis showed that miR-218 appeared to be an important modulator of tumor cell processes through suppression of many targets, particularly those involved in focal adhesion signaling pathways. Gene expression data indicated that LAMB3, a laminin protein known to influence cell differentiation, migration, adhesion, proliferation and survival, was upregulated in cervical SCC clinical specimens, and silencing studies demonstrated that LAMB3 functioned as an oncogene in cervical SCC. The identification of novel tumor-suppressive miR-218-mediated molecular pathways has provided new insights into cervical SCC oncogenesis and metastasis.

YAMAMOTO, NORIKO; KINOSHITA, TAKASHI; NOHATA, NIJIRO; ITESAKO, TOSHIHIKO; YOSHINO, HIROFUMI; ENOKIDA, HIDEKI; NAKAGAWA, MASAYUKI; SHOZU, MAKIO; SEKI, NAOHIKO

2013-01-01

74

Cervical cancer - screening and prevention  

MedlinePLUS

... Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin . 2012;62(3):147- ...

75

Combination of cetuximab with chemoradiation, trastuzumab or MAPK inhibitors: mechanisms of sensitisation of cervical cancer cells  

Microsoft Academic Search

Background:Cervical cancer (CC) annually kills 288 000 women worldwide. Unfortunately, responses to chemoradiation are partial and are of short duration. As anti-EGFR monoclonal antibodies sensitise tumours, we investigated cetuximab's toxicity plus chemoradiation on CC cells, which express different EGFR levels.Methods:EGFR, HER2, AKT and MAPK expression and phosphorylation status were determined by western blotting. Cytotoxicity was assessed by MTT or clonogenic

D D Meira; V H de Almeida; J S Mororó; I Nóbrega; L Bardella; R L A Silva; R M Albano; C G Ferreira

2009-01-01

76

Inactivation of lysyl oxidase by ?-aminopropionitrile inhibits hypoxia-induced invasion and migration of cervical cancer cells.  

PubMed

Tumor invasion and migration are major causes of mortality in patients with cervical carcinoma. Tumors under hypoxic conditions are more invasive and have a higher metastasic activity. Lysyl oxidase (LOX) is a hypoxia-responsive gene. LOX has been shown to be essential for hypoxia-induced metastasis in breast cancer. However, the direct impact of LOX on cervical cancer cell motility remains poorly understood. Our study revealed that LOX expression at protein and catalytic levels is upregulated in cervical cancer cells upon exposure to hypoxia. Hypoxia induced mesenchymal-like morphological changes in HeLa and SiHa cells which were accompanied by upregulation of ?-SMA and vimentin, two mesenchymal markers, and downregulation of E-cadherin, an epithelial marker, indicating the epithelial-mesenchymal transition (EMT) of cervical cancer cells occurred under hypoxic conditions. Treatment of tumor cells with ?-aminopropionitrile (BAPN), an active site inhibitor of LOX, blocked the hypoxia-induced EMT morphological and marker protein changes, and inhibited invasion and migration capacities of cervical carcinoma cells in vitro. Collectively, these findings suggest LOX enhances hypoxia-induced invasion and migration in cervical cancer cells mediated by the EMT which can be inhibited by BAPN. PMID:23165370

Yang, Xiaoxiao; Li, Shifeng; Li, Wande; Chen, Jingkao; Xiao, Xiao; Wang, Youqiong; Yan, Guangmei; Chen, Lijun

2013-02-01

77

Seminal plasma induces angiogenic chemokine expression in cervical cancer cells and regulates vascular function.  

PubMed

Cervical cancer is one of the leading gynecological malignancies in women. We have recently shown that seminal plasma (SP) can regulate the inflammatory cyclooxygenase-prostaglandin pathway and enhance the growth of cervical epithelial tumours in vivo by promoting cellular proliferation and alteration of vascular function. This study investigated the molecular mechanism whereby SP regulates vascular function using an in vitro model system of HeLa cervical adenocarcinoma cells and human umbilical vein endothelial cells (HUVECs). We found that SP rapidly enhanced the expression of the angiogenic chemokines, interleukin (IL)-8 and growth regulated oncogene alpha (GRO) in HeLa cells in a time-dependent manner. We investigated the molecular mechanism of SP-mediated regulation of IL-8 and GRO using a panel of chemical inhibitors of cell signalling. We found that treatment of HeLa cells with SP elevated expression of IL-8 and GRO by transactivation of the epidermal growth factor receptor, activation of extracellular signal-regulated kinase and induction of cyclooxygenase enzymes and nuclear factor kappa B. We investigated the impact of IL-8 and GRO, released from HeLa cells after treatment with SP, on vascular function using a co-culture model system of conditioned medium (CM) from HeLa cells, treated with or without SP, and HUVECs. We found that CM from HeLa cells induced the arrangement of endothelial cells into a network of tube-like structures via the CXCR2 receptor on HUVECs. Taken together our data outline a molecular mechanism whereby SP can alter vascular function in cervical cancers via the pro-angiogenic chemokines, IL-8 and GRO. PMID:22732298

Sales, Kurt J; Sutherland, Jason R; Jabbour, Henry N; Katz, Arieh A

2012-10-01

78

Univariate and multivariate methods for chemical mapping of cervical cancer cells  

NASA Astrophysics Data System (ADS)

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

Duraipandian, Shiyamala; Zheng, Wei; Huang, Zhiwei

2012-02-01

79

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

PubMed Central

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

2014-01-01

80

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

PubMed

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

Singh, Mayank; Singh, Neeta

2011-01-01

81

Nogo-B promotes the epithelial-mesenchymal transition in HeLa cervical cancer cells via Fibulin-5.  

PubMed

Cervical cancer is a common malignancy in women worldwide, and the occurrence of invasion and metastasis is the major cause for most cancer-related deaths. Epithelial-mesenchymal transition (EMT) has been implicated in the metastasis of primary tumors and provides molecular mechanisms for cervical cancer metastasis. We previously reported that Nogo-B mediates cell motility by binding Fibulin-5. Herein, we show that the increased expression of Nogo-B is correlated with the degree of cervical cancer metastasis. In HeLa cervical cancer cells, overexpression of Nogo-B induces the EMT and promotes cell migration and invasion, while inhibiting cell adhesion. Furthermore, we found that Nogo-B accumulates and co-localizes with Fibulin-5 in pseudopods, and the downstream effects of overexpression of Nogo-B on cell motility could be partially abolished by RNA interference against Fibulin-5. These results suggest that Nogo-B functions as an inducer of cervical cancer metastasis and that this effect is mediated, at least in part, through Fibulin-5. PMID:23042479

Xiao, Wei; Zhou, Shumin; Xu, Hua; Li, Heng; He, Guoqing; Liu, Yingle; Qi, Yipeng

2013-01-01

82

EGCG suppresses Fused Toes Homolog protein through p53 in cervical cancer cells.  

PubMed

The anticarcinogenic actions of epigallocatechin-3-gallate (EGCG), one of the main ingredients of green tea, against various cancer types including cervical cancer are well documented. Studies pertaining to the exact molecular mechanism by which EGCG induces cancer cell growth inhibition needs to be investigated extensively. In the present study, we observed a stupendous dose dependent reduction in the protein expression of Fused Toes Homolog (FTS) after treatment with EGCG at 1, 10, 25 and 50 ?M. Further, we were interested in finding out whether the decrease in the protein expression of FTS was due to decreased mRNA synthesis. Real time reverse transcriptase polymerase chain reaction results revealed a similar dose dependent reduction in the FTS mRNA after EGCG treatment. Chromatin immunoprecipitation analysis revealed the interaction between p53 and the promoter region of FTS. A dose dependent increase in this interaction was evidenced at 25 and 50 ?M EGCG treatment. p53 silencing increased the expression of FTS and also decreased the reduction in the levels of FTS expression after EGCG treatment. The decrease in the levels of FTS was more significant at 25 and 50 ?M and is associated with reduced physical interaction of FTS with Akt, phosphorylation of Akt and survival of HeLa cells. Collectively, these results conclude that EGCG induced anti-proliferative action in the cervical cancer cell involves reduced mRNA expression of FTS through p53. PMID:24065519

Muthusami, Sridhar; Prabakaran, D S; An, Zhengzhe; Yu, Jae-Ran; Park, Woo-Yoon

2013-10-01

83

Early cervical cancer  

Microsoft Academic Search

Opinion statement  Early cervical cancer includes a broad range of disease, from clinically undetectable microinvasive cancer to large, bulky\\u000a tumors that replace the entire cervix. Further subgrouping of this category is therefore necessary to define the optimal treatment\\u000a approach for individual cases. The International Federation of Gynecology and Obstetrics (FIGO) staging system stratifies\\u000a stage I tumors into two broad categories, stage

Karen H. Lu; Thomas W. Burke

2000-01-01

84

Cervical Cancer HPV Vaccine Use  

Cancer.gov

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

85

Sanguinarine inhibits growth of human cervical cancer cells through the induction of apoptosis.  

PubMed

Sanguinarine, a natural benzophenanthridine alkaloid, has been shown to possess anticancer activity in vitro and in vivo. In the present study, we demonstrated that sanguinarine caused a dose-dependent inhibition of growth in HeLa and SiHa human cervical cancer cells, i.e., 2.43 µmol/l (IC50) in HeLa cells and 3.07 µmol/l in SiHa cells. Cell cycle analysis revealed that sanguinarine significantly increased the sub-G1 population, from 1.7 to 59.7% in HeLa cells and from 1.7 to 41.7% in SiHa cells. Sanguinarine caused a dose-dependent decrease in Bcl-2 and NF-?B protein expression and a significant increase in Bax protein expression. Our findings indicate that sanguinarine as an effective anticancer drug candidate inhibits the growth of cervical cancer cells through the induction of apoptosis. PMID:22965493

Xu, Jia-Ying; Meng, Qing-Hui; Chong, Yu; Jiao, Yang; Zhao, Lin; Rosen, Eliot M; Fan, Saijun

2012-12-01

86

Identification of a cancer stem cell-like side population in the HeLa human cervical carcinoma cell line  

PubMed Central

The present study aimed to identify the stem cell characteristics of side population (SP) cells sorted from the widely-used HeLa human cervical carcinoma cell line. The SP cells were sorted from the HeLa cell line using fluorescence-activating cell sorting (FACS). Stem cell characteristics of the SP cells, including proliferation, self-renewal, differentiation and the ability to form xenografts, were investigated in vitro and in vivo. The SP cells demonstrated strong tumorigenesis following in vivo transplantation into five to six-week-old female Balb/c mice. The SP cells were observed to be more resistant to chemotherapy and radiotherapy compared with non-side population (NSP) cells. A higher expression of CD133 was observed in the SP cells compared with the NSP cells following FACS. The results demonstrated that the SP cells from the HeLa human cervical carcinoma cell line exhibit stem cell characteristics in vitro and also have a strong ability to form tumors in vivo. The cell surface marker CD133 may serve as a potential molecular marker for the identification of cervical cancer stem cells (CSCs).

WANG, KEFANG; ZENG, JIANFANG; LUO, LIJING; YANG, JIAXIN; CHEN, JIE; LI, BIN; SHEN, KENG

2013-01-01

87

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

PubMed

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

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

2005-05-01

88

Low-dose radiation-induced epithelial-mesenchymal transition through NF-?B in cervical cancer cells.  

PubMed

Cervical cancer is the leading cause of death from cancer among women. Radiotherapy for cervical cancer is an effective treatment method; however, the response to radiotherapy varies among patients. Epithelial-mesenchymal transition (EMT) is a morphogenesis process involved in embryonic and organismal development. During tumour progression, EMT may enhance cancer cell invasion, promoting tumour metastasis. We hypothesised that EMT was involved in the enhanced invasiveness of cervical cancer cells after low-dose radiation and aimed to elucidate the underlying mechanism of this process in low-dose radiation of cervical cancer. The irradiated cells (FIR cells) were derived from the parental cells (N cells) with a cumulative dose of 75 Gy. After resting and reorganisation, the effect of low-dose radiation on the FIR cells was analysed. The expression of E-cadherin, N-cadherin and p65 was detected by real-time qPCR and western blotting in parental cancer cells and irradiated cancer cells. Motility was detected using the migration/invasion assay. After silencing of NF-?B p65 expression using siRNA against p65, the expression of E-cadherin and N-cadherin was examined by real?time qPCR and western blotting. We found that low-dose radiation induced morphological changes of cells. The expression of epithelial markers was downregulated and mesenchymal markers were induced in irradiated cells, both of which are characteristics of EMT. Additionally, in irradiated cells, migration and invasion were enhanced and the expression of p65 was increased. To investigate whether p65 was involved in EMT, we silenced the expression of p65 in irradiated cells using siRNA and found that the features of EMT were suppressed. In summary, p65-regulated EMT induced by low-dose irradiation of cervical cancer cell lines promoted the invasiveness and metastasis of cervical cancer cells. The reversal of EMT may be a new therapeutic target for improving the effectiveness of radiotherapy for cervical cancer. PMID:23483258

Yan, Shi; Wang, Yu; Yang, Qifeng; Li, Xiaoyan; Kong, Xiaoli; Zhang, Ning; Yuan, Cunzhong; Yang, Ning; Kong, Beihua

2013-05-01

89

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

PubMed Central

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

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

2009-01-01

90

Treatment Options by Stage (Cervical Cancer)  

MedlinePLUS

... used for cervical cancer: Carcinoma in Situ (Stage 0) In carcinoma in situ (stage 0) , abnormal cells ... Treatment Options by Stage Carcinoma in Situ (Stage 0) Treatment of carcinoma in situ (stage 0) may ...

91

DEK overexpression in uterine cervical cancers.  

PubMed

The purpose of the present paper was to investigate the significance of DEK protein expression in uterine cervical lesions and its relationship with HPV infection status. DEK protein expression was studied in 253 cervical lesions, including 30 non-neoplastic cervix with or without squamous metaplasia, 64 cervical intra-epithelial neoplasias (CIN; CIN-1, n = 28; CIN-2, n = 17; CIN-3, n = 19), 102 squamous cell carcinomas (SCC), 51 adenocarcinomas, and six adenosquamous cell carcinomas (adenoSCC) on immunohistochemistry. For comparison, HPV-positive and -negative cervical cancer cell lines were also included. The HPV screening was performed using TaKaRa polymerase chain reaction. On immunohistochemistry DEK was found to be negative in all 30 non-neoplastic cervical epithelia, but it was positive in 96.1% of SCC (98/102), 92.2% of adenocarcinomas (47/51), 100% of adenoSCC (6/6), 85.7% of CIN-1 (24/28), 94.1% of CIN-2 (16/17), and 89.5% of CIN-3 (17/19). There was no significant difference between HPV-positive and -negative cervical lesions. Also, strongly positive staining was observed in all aforementioned cervical cancer cell lines regardless of HPV infection, according to immunocytochemistry. In summary, DEK plays an important role in the carcinogenesis of cervical cancers, and can be helpful for early diagnosis, and is a potential therapeutic target. PMID:18477217

Wu, Qunying; Li, Zhuhu; Lin, Hai; Han, Longzhe; Liu, Shuangping; Lin, Zhenhua

2008-06-01

92

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

PubMed Central

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

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

2014-01-01

93

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

SciTech Connect

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

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

2011-02-01

94

Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D.  

PubMed

Corticotropin-releasing factor (CRF), a coordinator of the body's responses to stress, is found in various cancer tissues and cell lines. However, the exact abilities of CRF to manipulate natural killer (NK) cells during immune response have not been studied. NKG2D is an activating receptor that is expressed on most NK and CD8+ T cells. MHC class I-related chain A (MICA) and UL16-binding protein (ULBP) 1, 2 and 3 are well-known ligands for NKG2D. In the present study, we reported our findings regarding the role of CRF in cervical cancer cell survival. Human cervical cancer cell line, HeLa cells, had significantly higher intracellular expression of UL16-binding protein 2 (ULBP2) following CRF treatment but had only slightly increased surface expression of ULBP2. Notably, MMPi (pan-metalloproteases inhibitor) blocked the release of ULBP2 molecules from the surface of HeLa cells. Furthermore, incubating NK cells with culture supernatants from CRF-treated HeLa cells, which contained soluble NKG2D ligand, reduced NK cell activity by decreasing surface expression of NKG2D. Collectively, downregulation of NKG2D by CRF-induced soluble NKG2D ligand provides a potential mechanism by which cervical cancer cells escape NKG2D-mediated attack under stress conditions. PMID:24841552

Song, Hyunkeun; Park, Hyunjin; Park, Gabin; Kim, Yeong Seok; Lee, Hyun-Kyung; Jin, Dong-Hoon; Kang, Hyung-Sik; Cho, Dae-Ho; Hur, Daeyoung

2014-07-01

95

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

PubMed Central

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 ?g/ml which resolved to fraction F4 (Petroleum Ether: Ethyl Acetate:: 50:50) and showed IC50 at 91 ?g/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.

2012-01-01

96

Early Invasive Cervical Cancer  

PubMed Central

Purpose To compare MRI, CT, clinical exam and histopathological analysis for predicting lymph node involvement in women with cervical carcinoma, verified by lymphadenectomy. Methods A 25-center ACRIN/GOG study enrolled 208 patients with biopsy-proven invasive cervical cancer for MRI and CT prior to attempted curative radical hysterectomy. Each imaging study was interpreted prospectively by one onsite radiologist, and retrospectively by 4 independent offsite radiologists, all blinded to surgical, histopathological and other imaging findings. Likelihood of parametrial and uterine body involvement was rated on a 5-point scale. Tumor size measurements were attempted in 3 axes. Association with histologic lymph node involvement, scored as absent, pelvic only and common iliac or paraaortic, was evaluated using Cochran-Mantel Haenszel statistics, univariate and multivariate logistic regression, generalized estimating equations, accuracy statistics and ROC analysis. Results Lymphatic metastases were found in 34% of women; 13% had common iliac nodal metastases, and 9% had paraortic nodal metastases. Based on the retrospective multi-observer re-reads, average AUC for predicting histologic lymph node involvement between MRI and CT for tumor size were higher for MRI versus CT, although formal statistic comparisons could not be conducted. Multivariate analysis showed improved model fit incorporating predictors from MRI, but not CT, over and above the initial clinical and biopsy predictors, although the increase in discriminatory ability was not statistically significant. Conclusion MRI findings may help predict the presence of histologic lymph node involvement in women with early invasive cervical carcinoma, thus providing important prognostic information.

Mitchell, Donald G; Snyder, Bradley; Coakley, Fergus; Reinhold, Caroline; Thomas, Gillian; Amendola, Marco A.; Schwartz, Lawrence H; Woodward, Paula; Pannu, Harpreet; Atri, Mostafa; Hricak, Hedvig

2008-01-01

97

DNA vaccines for cervical cancer  

PubMed Central

Human papillomavirus (HPV), particularly type 16, has been associated with more than 99% of cervical cancers. There are two HPV oncogenic proteins, E6 and E7, which play a major role in the induction and maintenance of cellular transformation. Thus, immunotherapy targeting these proteins may be employed for the control of HPV-associated cervical lesions. Although the commercially available preventive HPV vaccines are highly efficient in preventing new HPV infection, they do not have therapeutic effects against established HPV infection or HPV-associated lesions. Since T cell-mediated immunity is important for treating established HPV infections and HPV-associated lesions, therapeutic HPV vaccine should aim at generating potent E6 and E7-specific T cell-mediated immune responses. DNA vaccines have now developed into a promising approach for antigen-specific T cell-mediated immunotherapy to combat infection and cancer. Because dendritic cells are the most potent professional antigen-presenting cells, and are highly effective in priming antigen-specific T cells, several DNA vaccines have employed innovative strategies to modify the properties of dendritic cells (DCs) for the enhancement of the DNA vaccine potency. These studies have revealed impressive pre-clinical data that has led to several ongoing HPV DNA vaccine clinical trials.

Huang, Chien-Fu; Monie, Archana; Weng, Wei-Hung; Wu, TC

2010-01-01

98

MicroRNA-26a inhibits cell proliferation and invasion of cervical cancer cells by targeting protein tyrosine phosphatase type IVA 1.  

PubMed

The downregulation of microRNA?26a (miR?26a) has been reported in numerous types of cancer, but its detailed functional role in cervical cancer is not yet clear. In the present study, the expression of miR?26a in human cervical cancer was confirmed and its contribution to cervical cancer progression was investigated. The expression of miR?26a was determined by reverse transcription quantitative polymerase chain reaction in human cervical tissues and cell lines. Cell growth and invasion were detected by cell counting kit?8, colony?forming assays and transwell assays following restoration of miR?26a expression. Protein tyrosine phosphatase type IVA 1 (PRL?1) was further validated as a target of miR?26a by a functional luciferase assay and western blot analysis. In addition, the overexpression of miR?26a in tumor formation in SCID mice was investigated in vivo, and the association between miR?26a and PRL?1 was assayed by Pearson's correlation coefficient. First, it was identified that miR?26a was significantly downregulated in cervical cancer compared with the paired adjacent tissues. Forced expression of miR?26a suppressed cell proliferation and invasion in vitro and inhibited the growth of tumor xenografts in vivo. PRL?1 was determined as a novel target for miR?26a and knockdown of PRL?1 partially phenocopied the effect of miR?26a restoration. In addition, PRL?1 expression was inversely correlated with miR?26a expression in cervical cancer tissues. In conclusion, the results demonstrated the role of miR?26a in cervical cancer pathogenesis and suggest it may be used as a potential novel therapeutic strategy for cervical cancer. PMID:24939702

Dong, Jing; Sui, Long; Wang, Qing; Chen, Mingjun; Sun, Hong

2014-09-01

99

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

PubMed

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. PMID:21463610

Zhao, Gang; Chen, Jiawei; Deng, Yanqiu; Gao, Feng; Zhu, Jiwei; Feng, Zhenzhong; Lv, Xiuhong; Zhao, Zheng

2011-04-29

100

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

PubMed

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

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

2014-01-15

101

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

PubMed

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 ?-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 ?-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

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

2014-08-01

102

Short hairpin RNA targeting Twist1 suppresses cell proliferation and improves chemosensitivity to cisplatin in HeLa human cervical cancer cells  

PubMed Central

Development of multidrug resistance (MDR) remains a major hurdle to successful cancer chemotherapy and MDR1/P-gp overexpression is believed to be mainly responsible for MDR of tumor cells. Twist1, which is a highly conserved transcription factor that belongs to the family of basic helix-loop-helix proteins, has been shown to be a major regulator of the epithelial-mesenchymal transition (EMT), and therefore promotes carcinoma metastasis. Recently, a novel function of Twist1 was reported to confer radioresistance or chemoresistance in cervical cancer. However, mechanisms of such efficacy are not completely elucidated. In the present study, we firstly analyzed the relationship between Twist1 and MDR1/P-gp expression in human cervical cancer specimens and demonstrated a positive correlation between Twist1 and MDR1/P-gp expression in the same patient. Additionally, we provide the first evidence that silencing of Twist1 by RNAi downregulated MDR1/P-gp expression in HeLa cervical cancer cells, suppressed the cell proliferation, inhibited Rhodamine123 efflux activity of cells and sensitized cells to cisplatin treatment. Collectively, these findings suggest that Twist1-mediated modulation of MDR1/P-gp expression plays an important role in sensitization of cervical cancer cells to cisplatin, and also indicate a novel therapeutic strategy to overcome drug resistance through inactivation of Twist1 expression in cervical cancer.

ZHU, KEXIU; CHEN, LIHONG; HAN, XIAOBING; WANG, JIA; WANG, JUE

2012-01-01

103

Decursin and decursinol angelate from Angelica gigas Nakai induce apoptosis via induction of TRAIL expression on cervical cancer cells  

Microsoft Academic Search

Aim of the studyThe root of Angelica gigas Nakai (Korean “Dang-Gui”) has been used to treat female afflictions and anemia in traditional oriental herbal medicine since ancient times in Korea. The objective of this study is to identify the anti-cancer mechanism induced by A. gigas extract including decursin and decursinol angelate in human cervical cancer cells for scientific evidence regarding

Nam-Hui Yim; Ju Hye Lee; Won-Kyung Cho; Min Chul Yang; Dong Hoon Kwak; Jin Yeul Ma

104

Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines.  

PubMed

Honey is reported to contain various compounds such as phenols, vitamins and antioxidants. The present study investigates the anticancer potential of Tualang honey (Agromas) (TH) in human breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cell lines; as well as in the normal breast epithelial cell line, MCF-10A. The cells were treated with increasing doses of TH (1-10%) for up to 72 h. Increase in lactate dehydrogenase (LDH) leakage from the cell membranes indicates that TH is cytotoxic to all three cancer cells with effective concentrations (EC(50)) of 2.4-2.8%. TH is however, not cytotoxic to the MCF-10A cells. Reactivity with annexin V fluorescence antibody and propidium iodide as analysed by flow cytometry and fluorescence microscopy shows that apoptosis occurred in these cancer cells. TH also reduced the mitochondrial membrane potential (??(m)) in the cancer cell lines after 24h of treatment. The activation of caspase-3/7 and -9 was observed in all TH-treated cancer cells indicating the involvement of mitochondrial apoptotic pathway. This study shows that TH has significant anticancer activity against human breast and cervical cancer cell lines. PMID:21167897

Fauzi, Agustine Nengsih; Norazmi, Mohd Nor; Yaacob, Nik Soriani

2011-04-01

105

Multifactorial Etiology of Cervical Cancer: A Hypothesis  

PubMed Central

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

Haverkos, Harry W.

2005-01-01

106

Inhibition of cervical cancer cell growth through activation of upstream kinases of AMP-activated protein kinase.  

PubMed

AMP-activated protein kinase (AMPK) is a critical energy-balancing sensor in the regulation of cellular metabolism in response to external stimuli. Emerging evidence has suggested that AMPK is a potential therapeutic target for human cancers. AICAR, one of the pharmacological AMPK activators, has been widely used to suppress cancer cell growth through activation of LKB1, an upstream kinase of AMPK. However, frequent mutations and deletions of LKB1 found in some cancer cells limit the application of AICAR as an efficient therapeutic drug. Here we show that an alternative pharmacological AMPK activator, A23187, was able to inhibit cervical cancer cell growth through activation of Ca(2+)/calmodulin-dependent protein kinase kinase beta, another upstream kinase of AMPK. Using cervical cancer cell models, we found that HeLa (LKB1-deficient cell) responded less to the anti-proliferative effect exerted by AICAR treatment (p < 0.001) compared with CaSki and C41 (LKB1-expressing cells). Conversely, the anti-proliferative effect was increased significantly in HeLa but not in CaSki and C41 cells under treatment by A23187 (p < 0.001). Moreover, co-treatment of AICAR and A23187 was able to further enhance the inhibitory effect on cell growth of Hela, CaSki and C41 cells. Notably, both AICAR and A23187 exerted the anti-proliferative effect on cervical cancer cells by suppressing AMPK/mTOR signalling activity. These data suggest that A23187 could be an alternative potential therapeutic drug used for anti-proliferation in LKB1-deficient cancer cells. PMID:19407487

Yu, Sandy Yee Man; Chan, David Wai; Liu, Vincent Wing Sun; Ngan, Hextan Yuen Sheung

2009-01-01

107

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

PubMed Central

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.

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

108

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

PubMed

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

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

2013-12-01

109

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

ClinicalTrials.gov

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

2014-04-21

110

Inhibition of the nuclear transporter, Kpn?1, results in prolonged mitotic arrest and activation of the intrinsic apoptotic pathway in cervical cancer cells.  

PubMed

The karyopherin ? proteins are involved in nuclear-cytoplasmic trafficking and are crucial for protein and RNA subcellular localization. We previously showed that Kpn?1, a nuclear importin protein, is overexpressed in cervical cancer and is critical for cervical cancer cell survival and proliferation, whereas non-cancer cells are less dependent on its expression. This study aimed to identify the mechanisms by which inhibition of Kpn?1 results in cervical cancer cell death. We show that the inhibition of Kpn?1 results in the induction of apoptosis and a prolonged mitotic arrest, accompanied by distinct mitotic defects in cervical cancer cells but not non-cancer cells. In cervical cancer cells, Kpn?1 downregulation results in sustained degradation of the antiapoptotic protein, Mcl-1, and elevated Noxa expression, as well as mitochondrial membrane permeabilization resulting in the release of cytochrome C and activation of associated caspases. Although p53 becomes stabilized in Kpn?1 knockdown cervical cancer cells, apoptosis occurs in a p53-independent manner. These results demonstrate that blocking Kpn?1 has potential as an anticancer therapeutic approach. PMID:24398670

Angus, Liselotte; van der Watt, Pauline J; Leaner, Virna D

2014-05-01

111

Establishment and characterization of a human-papillomavirus negative, p53-mutation negative human cervical cancer cell line.  

PubMed

A human cervical cancer cell line, CX, was established from a patient with squamous cell carcinoma of the uterine cervix. The CX cells were epithelial in morphology with relatively large vesicular nuclei, and prominent nucleoli. Cytoplasmic organelles were generally sparse but tonofilaments were relatively abundant. The cells grew as a compact sheet with close membrane approximation interconnected by desmosome-like junctions. CX cells contained cytokeratin, but not vimentin. Elevated levels of squamous cell carcinoma antigen and carcinoembryonic antigen were detected in the cell supernatants. Population doubling time was estimated to be about 20 h. CX cells were not able to grow in soft agar and not tumorigenic in nude mice. Chromosome analysis revealed that CX cells were heterogeneous and mainly had a female diploid karyotype. Unlike cervical cancer cell lines published previously, CX cells were demonstrated to be human papillomavirus-negative, p53 mutation-negative. Based on the distinct characteristics, CX cell line may prove to be a useful tool for the study of human cervical carcinogenesis. PMID:8603367

Chou, C Y; Chen, Y H; Tzeng, C C; Cheng, Y C; Chang, C F; Chen, T M

1996-04-19

112

Sine oculis homeobox homolog 1 promotes ?5?1-mediated invasive migration and metastasis of cervical cancer cells.  

PubMed

Sine oculis homeobox homolog 1 (SIX1) has been supposed to be correlated with the metastasis and poor prognosis of several malignancies. However, the effect of SIX1 on the metastatic phenotype of tumor cells and the underlying mechanisms were still unclear to date. Here we report that SIX1 can promote ?5?1-mediated metastatic capability of cervical cancer cells. SIX1 promoted the expression of ?5?1 integrin to enhance the adhesion capacity of tumor cells in vitro and tumor cell arrest in circulation in vivo. Moreover, higher expression of SIX1 in tumor cells resulted in the increased production of active MMP-2 and MMP-9, up-regulation of anti-apoptotic genes (BCL-XL and BCL2) and down-regulation of pro-apoptotic genes (BIM and BAX), thus promoting the invasive migration and anoikis-resistance of tumor cells. Importantly, blocking ?5?1 abrogated the regulatory effect of SIX1 on the expression of these genes, and also abolished the promotional effect of SIX1 on invasive capability of tumor cells. Furthermore, knock-down of ?5 could abolish the promoting effect of SIX1 on the development of metastatic lesions in both experimental and spontaneous metastasis model. Therefore, by up-regulating ?5?1 expression, SIX1 not only promoted the adhesion capacity, but also augmented ECM-?5?1-mediated regulation of gene expression to enhance the metastatic potential of cervical cancer cells. These results suggest that SIX1/?5?1 might be considered as valuable marker for metastatic potential of cervical cancer cells, or a therapeutic target in cervical cancer treatment. PMID:24613848

Liu, Dan; Zhang, Xiao-Xue; Wan, Dong-Yi; Xi, Bi-Xin; Ma, Ding; Wang, Hui; Gao, Qing-Lei

2014-04-01

113

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

PubMed

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

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

2013-02-01

114

Downregulation of p16(ink4a) inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells.  

PubMed

Studies have suggested that p16(ink4a) may be a surrogate biomarker for the diagnosis of cervical cancer; however, the function of p16(ink4a) in human cervical cancer cells remains largely unknown. Therefore, in this study, we aimed to investigate the role of p16(ink4a) in human cervical cancer cells. Immunocytochemistry was used to examine invasive squamous cell carcinoma and its precancerous lesions. p16(ink4a)-siRNA was transfected into SiHa and HeLa cells to deplete its expression. The cellular levels of p16(ink4a) mRNA and protein were detected by qRT-PCR and western blot analysis. Proliferation rates were assessed by methyl thiazolyl tetrazolium (MTT) and plate colony formation assays. Cellular migration and invasion ability were assessed by a wound healing assay and Transwell assay. Cellular apoptosis and the cell cycle were measured by flow cytometry. The protein levels of retinoblastoma (Rb), phosphorylated Rb (phospho-Rb), cyclin D1 and caspase-3 were determined by western blot analysis. The results revealed that p16(ink4a) was overexpressed in the cervical cancer and precancerous lesions (P<0.05). The downregulation of p16(ink4a) in the SiHa and HeLa cells inhibited their proliferation, migration and invasion. In the SiHa cells, p16(ink4a)-siRNA also induced G1 cell cycle arrest and apoptosis. Western blot analysis revealed that the downregulation of p16(ink4a) in the SiHa cells markedly induced caspase-3 activation and decreased cyclin D1 expression. These data suggest that the overexpression of p16(ink4a) appears to be useful in monitoring cervical precancerous lesions, which supports that the hypothesis that p16(ink4a) is a surrogate biomarker for the diagnosis of cervical cancer. The therapeutic targeting of overexpressed p16(ink4a) in the p16(ink4a)-cyclin-Rb pathway may be a useful strategy in the treatment of cervical cancer. PMID:24714974

Zhang, Chu-Yue; Bao, Wei; Wang, Li-Hua

2014-06-01

115

Radiation Sensitivity, H2AX Phosphorylation, and Kinetics of Repair of DNA Strand Breaks in Irradiated Cervical Cancer Cell Lines  

Microsoft Academic Search

Six human cervical cancer cell lines (five human papillomavirus (HPV) positive, one HPV negative) for induction and rejoining of DNA strand breaks and for kinetics of formation and loss of serine 139 phosphorylated histone H2AX (H2AX). X-rays induced the same level of DNA breakage for all cell lines. By 8 hours after 20 Gy, <2% of the initial single-strand breaks

Judit P. Banath; Susan H. MacPhail; Peggy L. Olive

2004-01-01

116

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

SciTech Connect

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

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

2010-07-15

117

Morphological changes of ricin toxin-induced apoptosis in human cervical cancer cells.  

PubMed

The morphological changes of ricin-induced apoptosis in a human cervical cancer cell line were studied. To shed light on the mechanism of action of ricin toxin (RT) at the cellular level, we examined cell growth, apoptosis, changes of mitochondrial membrane potential (MMP) and cytochrome C translocation in HeLa cells by exposing these cells to RT for indicated times. The effect of RT on cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), inner salt; MTS assay and apoptosis were measured using flow cytometry, fluorescence microscopy and electron microscopy. Changes in MMP were monitored using flow cytometry. Western blot analysis was used to evaluate the release of mitochondrial cytochrome C. RT noticeably inhibited the proliferation of HeLa cells, and the half maximal inhibitory concentration dose was about 100 ng/ml. HeLa cells treated with RT showed typical characteristics of apoptosis rather than necrosis, including phosphatidylserine exposed from the inner to the outer leaflet of the plasma membrane, abnormal cell morphology, chromatin condensation and nuclear fragmentation. In contrast, during the process of cellular apoptosis, the messenger RNA (mRNA) and protein expression of cytochrome C in treated and untreated Hela cells were not significantly changed (data not shown). However, when cells were treated with RT, the massive translocation of cytochrome C to the nucleus was evident. Our results indicate that RT-induced HeLa cell apoptosis, especially for cytochrome C translocation, may play an important role in apoptosis induced by RT. PMID:21937530

Liao, Peng; Liu, Wensen; Li, Hongyang; Gao, Hongwei; Wang, Haiying; Li, Nan; Xu, Na; Li, Jiping; Wan, Jiayu; Liu, Linna; Sun, Yucheng

2012-06-01

118

Tertiary prevention of cervical cancer.  

PubMed

Human pappilomavirus (HPV) has been recognized as the most common sexually transmitted disease in the world and over 100 different HPV types have been identified. Persistent HPV infection has been closely linked to the development of invasive cervical cancer. Although surgical and ablative therapies have been the mainstay of treatment, vaccination against the main oncogenic type of HPV is a reasonable preventive strategy for HPV-induced cervical cancer. PMID:24633405

Divine, Laura M; Huh, Warner K

2014-06-01

119

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

PubMed Central

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

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

2014-01-01

120

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? ...

121

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

PubMed Central

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

YAMAMOTO, NORIKO; KINOSHITA, TAKASHI; NOHATA, NIJIRO; YOSHINO, HIROFUMI; ITESAKO, TOSHIHIKO; FUJIMURA, LISA; MITSUHASHI, AKIRA; USUI, HIROKAZU; ENOKIDA, HIDEKI; NAKAGAWA, MASAYUKI; SHOZU, MAKIO; SEKI, NAOHIKO

2013-01-01

122

Cervical cancer: a developmental perspective.  

PubMed

Cervical cancer is a disease that affects women worldwide. In some countries it is the leading cause of death among women. Although the incidence of cervical cancer has decreased with the advent of the Papanicolaou smear, it remains a problem in adult women. Cervical dysplasia most often affects women in their 20s; carcinoma in situ affects women 30 to 39 years of age; and invasive carcinoma affects women older than 40 years. These age groups fall into the final three of Erickson's eight stages of ego development. However, taking a developmental approach in planning nursing interventions for women with cervical cancer has its drawbacks. Much of developmental theory research has been conducted on nonrepresentative samples, with women being underrepresented. A template for exploring patient problems from a life stage (developmental) perspective has been developed within the context of three different nursing diagnoses (sexual dysfunction, spiritual distress, and alteration in family processes). PMID:8892133

Klemm, P R; Guarnieri, C

1996-09-01

123

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

PubMed

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

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

2005-10-01

124

The overexpression of MCPH1 inhibits cell growth through regulating cell cycle-related proteins and activating cytochrome c-caspase 3 signaling in cervical cancer.  

PubMed

MCPH1, initially identified as an hTERT repressor, has recently been implicated in mediating DNA damage response and maintaining chromosome integrity. This study is to investigate its potential role in the onset of cervical cancer. In the study, decreased expression of MCPH1 was observed in 19 of 31 cases (61.3 %) at mRNA level and 44 of 63 cases (69.8 %) at protein level of cervical tumor tissues compared with the paired nontumor tissues. Reduced MCPH1 protein expression was significantly associated with high-tumor grade (1 vs. 3 P = 0.013; 2 vs. 3 P = 0.047). In addition to inhibit SiHa cell migration and invasion, the overexpression of MCPH1 inhibited cervical cancer cells growth through inducing S phase arrest and mitochondrial apoptosis. Further analysis demonstrated cyclinA2/CDK2, CDC25C-cyclinB/CDC2, and p53/p21 pathways were involved in the MCPH1 overexpression-induced S phase arrest. Moreover, the overexpression of MCPH1 activated mitochondrial apoptosis through regulating several apoptosis-related proteins such as p53, Bcl-2, Bax, cytochrome c, caspase-3, and PARP-1. Our findings indicate that downregulated MCPH1 correlates with tumor progression in cervical cancer, and MCPH1 has an important role in regulating cell growth through regulating the cell cycle and apoptosis. Thus, it may be a crucial tumor suppressor gene and a novel candidate therapeutic target for cervical cancer. PMID:24633962

Mai, Li; Yi, Faping; Gou, Xiaoyan; Zhang, Ji; Wang, Changdong; Liu, Geli; Bu, Youquan; Yuan, Chengfu; Deng, Linman; Song, Fangzhou

2014-07-01

125

Secondary prevention of cervical cancer part 1: screening for cervical cancer and its precursors.  

PubMed

Discussion of screening for cervical cancer and it precursors, management of abnormal cervical cancer screening test, and evidence-based management of women with cervical intraepithelial neoplasia. PMID:24785416

Boisen, Michelle; Diedrich, Justin T; Lonky, Neal M; Guido, Richard

2014-06-01

126

Conditionally replicating E1B-deleted adenovirus driven by the squamous cell carcinoma antigen 2 promoter for uterine cervical cancer therapy.  

PubMed

Cervical cancer is the second most common type of malignant tumor among women worldwide. When the disease is confined locally, it can be controlled with surgical resection and radiotherapy. However, patients with recurrent or metastatic disease often have a poor prognosis. Measurement of serum levels of squamous cell carcinoma (SCC) antigens has been widely used as serological markers for SCC of uterine cervix. Recently, it has been demonstrated that cervical cancer patients with elevated squamous cell carcinoma antigen-2 (SCCA2) expression in tumor cells carry a poor prognosis. Here, by using a luciferase reporter assay, we show that SCCA2 promoter was active in SCCA2-producing human cervical cancer cell lines, including Cx, Cxwj, SiHa and HeLa cells, but relatively quiescent in normal cervical epithelial cells. We then developed a conditionally replicating adenovirus, designated Ad-KFH, under the transcriptional control of the SCCA2 promoter. This E1B-55 kDa-deleted oncolytic adenovirus replicated specifically in and lysed SCCA2-producing cervical cancer cells. Furthermore, in a peritoneal metastatic tumor model, Ad-KFH retarded Cxwj tumor growth in NOD/severe combined immunodeficient mice and prolonged survival of tumor-bearing mice, especially when combined with cisplatin. These results suggest that Ad-KFH may provide a new strategy of gene therapy for advanced or recurrent uterine cervical cancer. PMID:18497852

Hsu, K-F; Wu, C-L; Huang, S-C; Hsieh, J-L; Huang, Y-S; Chen, Y-F; Shen, M-R; Chung, W-J; Chou, C-Y; Shiau, A-L

2008-08-01

127

HeLa Human Cervical Cancer Cell Migration Is Inhibited by Treatment with Dibutyryl-cAMP.  

PubMed

Cyclic AMP (cAMP) activates both protein kinase A (PKA) and guanine-nucleotide exchange factor exchange protein directly activated by CAMP (EPAC)-mediated Ras-related Protein(1) (RAP(1)) GTPase that regulates various cellular functions including cell migration. Herein, we investigated whether cAMP-mediated PKA and EPAC1/RAP1 pathways differentially control HeLa cervical cancer cell migration. Although HeLa cell migration was reduced by dibutyryl-cAMP, we observed an increase in cAMP/PKA, cAMP/EPAC1/RAP1-GTPase, and RAC1-GTPase. HeLa cell migration and RAC1-GTPase were increased by treatment with 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cAMP analogue to activate EPAC-specific signaling pathways. When HeLa cells were treated with H-89, a PKA inhibitor, cell migration was enhanced but RAC1-GTPase was inhibited. In addition, cell migration induced by dibutyryl-cAMP was reversed but the activity of Rac1-GTPase was inhibited by H-89 treatment. Taken together, these data demonstrate that cAMP/PKA and cAMP/EPAC1/RAP1-GTPase might inversely control cervical cancer cell migration, although both signaling pathways may up-regulate RAC1-GTPase. It also suggests that cAMP-mediated cancer cell migration was independent of RAC1-GTPase activation. PMID:24982353

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

2014-07-01

128

What's New in Cervical Cancer Research and Treatment?  

MedlinePLUS

... the effect of certain growth factors on cancer cells. In studies of patients with advanced cervical cancer, it helped them live longer. Bevacizumab (Avastin ® ) is a targeted therapy drug that helps block the formation of new ...

129

Cervical cancer screening at crossroads.  

PubMed

Cervical screening has been one of the most successful public health prevention programmes. For 50 years, cytology formed the basis for screening, and detected cervical intraepithelial lesions (CIN) were treated surgically to prevent progression to cancer. In a high-risk country as Denmark, screening decreased the incidence of cervical cancer from 34 to 11 per 100 000, age-standardized rate (World Standard Population). Screening is, however, also expensive; Denmark (population: 5.6 million) undertakes close to half a million tests per year, and has 6-8 CIN-treated women for each prevented cancer case. The discovery of human papillomavirus (HPV) as the cause of cervical cancer dramatically changed perspectives for disease control. Screening with HPV testing was launched around 1990, and preventive HPV vaccination was licensed in 2006. Long-term randomized controlled trials (RCT) demonstrated that HPV testing provides better protection against cervical cancer than cytology, but it requires extra repeated testing. HPV vaccination RCTs, furthermore, have proved that HPV vaccination protects against vaccine-type high-grade CIN in women vaccinated prior to sexual activity, but less so in women vaccinated later. The challenge now is therefore to find an algorithm for screening of a heterogeneous population including non-vaccinated women; women vaccinated prior to start of sexual activity; and women vaccinated later. PMID:25046198

Lynge, Elsebeth; Rygaard, Carsten; Baillet, Miguel Vazquez-Prada; Dugué, Pierre-Antoine; Sander, Bente Braad; Bonde, Jesper; Rebolj, Matejka

2014-08-01

130

Jordanian women's attitudes towards cervical screening and cervical cancer.  

PubMed

This paper looks at Jordanian women's attitudes towards cervical screening and cervical cancer. The sample consisted of 600 women attending gynaecology clinics at King Hussein Medical Centre, Amman, Jordan. Seventy-five per cent of women had never had a smear before; however, the majority agreed that it is important; 34.5% of women did not know the significance of a positive cervical smear; 77% of women were not aware of causes of cervical cancer. Finally, when asked who would they like to take their cervical smear test, a clear preference was stated for a female doctor or a female nurse. These findings provide a useful background for developing strategies to increase the uptake of cervical smears among Jordanian women. It also emphasises the need to educate and promote awareness of women to risk factors for cervical cancer and to the need for screening programmes. PMID:12521469

Maaita, M; Barakat, M

2002-07-01

131

Isoliquiritigenin induces caspase-dependent apoptosis via downregulation of HPV16 E6 expression in cervical cancer Ca Ski cells.  

PubMed

Flavonoids have antitumoral properties and may be attractive candidates as anticancer therapy. Isoliquiritigenin which is a constituent of licorice (Glycyrrhiza inflata), a plant commonly used in traditional Uyghur medicine in Xinjiang, China, was studied for antiproliferative and apoptotic activity in human cervical cancer cells, Ca Ski, SiHa, HeLa, and C-33A. Its molecular mechanism of action was specifically examined in Ca Ski cells. Isoliquiritigenin decreased cell viability, induced cell accumulation in G2/M and morphological and biochemical features of apoptosis in the four cancer cell lines. In Ca Ski cells, isoliquiritigenin led to a downregulation of HPV16 E6 expression associated with an increase of p53 and p21 levels, enhanced expression of Bax and decreased expression of Bcl-2 and Bid proform triggering dissipation of the mitochondrial membrane potential, released cytochrome c to the cytosol followed by activation of caspase cascade with cleavage of caspase-9, caspase-3, and PARP. Caspase-8 was also cleaved. Moreover treatment with a pan-caspase inhibitor prevented apoptosis. As Ca Ski cells are representative of carcinoma naturally occurring in the cervix, our results suggest a potential benefit of isoliquiritigenin for cervical cancer prevention and treatment. PMID:24214831

Hirchaud, Fabienne; Hermetet, François; Ablise, Mourboul; Fauconnet, Sylvie; Vuitton, Dominique A; Prétet, Jean-Luc; Mougin, Christiane

2013-11-01

132

Demethylation restores SN38 sensitivity in cells with acquired resistance to SN38 derived from human cervical squamous cancer cells.  

PubMed

Using seven monoclonal SN38-resistant subclones established from ME180 human cervical squamous cell carcinoma cells, we examined the demethylation effects of 5-aza-2'-deoxycytidine (5-aza-CdR) on the SN38-sensitivity of the cells as well as the expression of death-associated protein kinase (DAPK) in the SN38-resistant cells. The DAPK expression levels were evaluated among parent ME180 cells, SN38-resistant ME180 cells and cisplatin-resistant ME180 cells by methylation-specific DAPK-PCR, quantitative RT-PCR and western blot analysis. The SN38-resistant cells co-treated with SN38 and 5-aza-CdR strongly exhibited enhanced SN38-sensitivities resembling those found in the parent cells. In the SN38-resistant subclones, no relationships were found between the restored SN38 sensitivity and hypermethylation of the DAPK promoter, DAPK mRNA expression, DAPK protein expression and induction of DAPK protein after 5-aza-CdR treatment, unlike the strong suppression of 5-aza-CdR-induced DAPK protein expression in the cisplatin-resistant subclones. These findings indicate that reversibly methylated molecules, but not DAPK, may regulate SN38 resistance, and that demethylating agents can be strong sensitizing anticancer chemotherapeutic drugs for SN38-resistant cancers. PMID:22246465

Tanaka, Tetsuji; Bai, Tao; Toujima, Saori; Utsunomiya, Tomoko; Matsuoka, Toshihide; Kobayashi, Aya; Yamamoto, Madoka; Sasaki, Noriyuki; Tanizaki, Yuko; Utsunomiya, Hirotoshi; Tanaka, Junko; Yukawa, Kazunori

2012-04-01

133

Demethylation restores SN38 sensitivity in cells with acquired resistance to SN38 derived from human cervical squamous cancer cells  

PubMed Central

Using seven monoclonal SN38-resistant subclones established from ME180 human cervical squamous cell carcinoma cells, we examined the demethylation effects of 5-aza-2?-deoxycytidine (5-aza-CdR) on the SN38-sensitivity of the cells as well as the expression of death-associated protein kinase (DAPK) in the SN38-resistant cells. The DAPK expression levels were evaluated among parent ME180 cells, SN38-resistant ME180 cells and cisplatin-resistant ME180 cells by methylation-specific DAPK-PCR, quantitative RT-PCR and western blot analysis. The SN38-resistant cells co-treated with SN38 and 5-aza-CdR strongly exhibited enhanced SN38-sensitivities resembling those found in the parent cells. In the SN38-resistant subclones, no relationships were found between the restored SN38 sensitivity and hypermethylation of the DAPK promoter, DAPK mRNA expression, DAPK protein expression and induction of DAPK protein after 5-aza-CdR treatment, unlike the strong suppression of 5-aza-CdR-induced DAPK protein expression in the cisplatin-resistant subclones. These findings indicate that reversibly methylated molecules, but not DAPK, may regulate SN38 resistance, and that demethylating agents can be strong sensitizing anticancer chemotherapeutic drugs for SN38-resistant cancers.

TANAKA, TETSUJI; BAI, TAO; TOUJIMA, SAORI; UTSUNOMIYA, TOMOKO; MATSUOKA, TOSHIHIDE; KOBAYASHI, AYA; YAMAMOTO, MADOKA; SASAKI, NORIYUKI; TANIZAKI, YUKO; UTSUNOMIYA, HIROTOSHI; TANAKA, JUNKO; YUKAWA, KAZUNORI

2012-01-01

134

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

PubMed

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

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

2014-06-01

135

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

PubMed Central

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

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

136

Cervical Cancer and Pregnancy  

MedlinePLUS

... the baby is born, treatment most likely a hysterectomy ? is recommended. If the cancer is at a ... Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects Cancer Facts & Statistics News About Cancer Expert Voices ...

137

Valproic acid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis.  

PubMed

Valproic acid (VPA) as a histone deacetylase (HDAC) inhibitor has an anticancer effect. In the present study, we evaluated the effects of VPA on the growth and death of HeLa cervical cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH). Dose- and time-dependent growth inhibition was observed in HeLa cells with an IC50 of approximately 10 mM at 24 h. DNA flow cytometric analysis indicated that 10 mM VPA induced a G2/M phase arrest of the cell cycle. This agent also induced apoptosis, which was accompanied by the cleavage of PARP, the activation of caspase-3, -8 and -9, and the loss of mitochondrial membrane potential (MMP; ??m). All the tested caspase inhibitors significantly prevented HeLa apoptotic cell death induced by VPA, whereas TNF-? intensified the apoptotic cell death. With respect to ROS and GSH levels, VPA increased ROS levels and induced GSH depletion. However, N-acetyl cysteine (NAC; an antioxidant) and L-buthionine sulfoximine (BSO; a GSH synthesis inhibitor) did not significantly affect cell death in VPA-treated HeLa cells. In conclusion, VPA inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis and the growth inhibition is independent of ROS and GSH level changes. PMID:24064712

Han, Bo Ram; You, Bo Ra; Park, Woo Hyun

2013-12-01

138

OCT4 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b/BAK1 pathway  

PubMed Central

Octamer-binding transcription factor 4 (OCT4) is a key regulatory gene that maintains the pluripotency and self-renewal properties of embryonic stem cells. Although there is emerging evidence that it can function as oncogene in several cancers, the role in mediating cervical cancer remains unexplored. Here we found that OCT4 protein expression showed a pattern of gradual increase from normal cervix to cervical carcinoma in situ and then to invasive cervical cancer. Overexpression of OCT4 in two types of cervical cancer cells promotes the carcinogenesis, and inhibits cancer cell apoptosis. OCT4 induces upregulation of miR-125b through directly binding to the promoter of miR-125b-1 confirmed by chromatin immunoprecipitation analysis. MiRNA-125b overexpression suppressed apoptosis and expression of BAK1 protein. In contrast, miR-125b sponge impaired the anti-apoptotic effect of OCT4, along with the upregulated expression of BAK1. Significantly, Luciferase assay showed that the activity of the wild-type BAK1 3?-untranslated region reporter was suppressed and this suppression was diminished when the miR-125b response element was mutated or deleted. In addition, we observed negative correlation between levels of BAK1 and OCT4, and positive between OCT4 and miR-125b in primary cervical cancers. These findings suggest an undescribed regulatory pathway in cervical cancer, by which OCT4 directly induces expression of miR-125b, which inhibits its direct target BAK1, leading to suppression of cervical cancer cell apoptosis.

Wang, Y-D; Cai, N; Wu, X-L; Cao, H-Z; Xie, L-L; Zheng, P-S

2013-01-01

139

Apoptotic effect of methanol extract of Picrasma quassioides by regulating specificity protein 1 in human cervical cancer cells.  

PubMed

In the present study, we examined the effects of methanol extracts of Picrasma quassioides (MEPQ) on apoptosis in human cervical cancer cells. The results showed that MEPQ decreased the viability and induced caspase-dependent apoptosis in HEp-2 cells. MEPQ decreased specificity protein 1 (Sp1) in HEp-2 cells, whereas Sp1 mRNA was not changed. We found that MEPQ reduced Sp1 protein through proteasome-dependent protein degradation, but not the inhibition of protein synthesis. Also, MEPQ increased the expressions of Bad and truncated Bid (t-Bid) but did not alter other Bcl-2 family members. The knock-down of Sp1 by both Sp1 interfering RNA and Mithramycin A, Sp1 specific inhibitor clearly increased Bad and t-Bid expression to decrease cell viability and induce apoptosis. In addition, MEPQ inhibited cell viability and induced apoptotic cell death through the modulation of Sp1 in KB cells. These results suggest that MEPQ may be a potential anticancer agent for human cervical cancer. PMID:24037733

Lee, Hang-Eun; Choi, Eun-Sun; Shin, Ji-Ae; Kim, Lee-Han; Cho, Nam-Pyo; Cho, Sung-Dae

2014-04-01

140

Knock-down of NDRG2 sensitizes cervical cancer Hela cells to cisplatin through suppressing Bcl-2 expression  

PubMed Central

Background NDRG2, a member of N-Myc downstream regulated gene family, plays some roles in cellular stress, cell differentiation and tumor suppression. We have found that NDRG2 expression in cervical cancer Hela cells increases significantly upon stimulation with cisplatin, the most popular chemotherapeutic agent currently used for the treatment of advanced cervical cancer. This interesting phenomenon drove us to evaluate the role of NDRG2 in chemosensitivity of Hela cells. Methods In the present study, RNA interference was employed to down-regulate NDRG2 expression in Hela cells. RT-PCR and Western blot were used to detect expression of NDRG2, Bcl-2 and Bax in cancer cells. Real-time PCR was applied to detect miR-15b and miR-16 expression levels. Drug sensitivity was determined with MTT assay. Cell cloning efficiency was evaluated by Colony-forming assay. Apoptotic cells were detected with annexin V staining and flow cytometry. Results In vitro drug sensitivity assay revealed that suppression of NDRG2 could sensitize Hela cells to cisplatin. Down-regulation of NDRG2 didn’t influence the colony-forming ability but promoted cisplatin-induced apoptosis of Hela cells. Inhibition of NDRG2 in Hela cells was accompanied by decreased Bcl-2 protein level. However, Bcl-2 mRNA level was not changed in Hela cells with down-regulation of NDRG2. Further study indicated that miR-15b and miR-16, two microRNAs targetting Bcl-2, were significantly up-regulated in NDRG2-suppressed Hela cells. Conclusions These data suggested that down-regulation of NDRG2 could enhance sensitivity of Hela cells to cisplatin through inhibiting Bcl-2 protein expression, which might be mediated by up-regulating miR-15b and miR-16.

2012-01-01

141

Chemopreventive effect of tolfenamic acid on KB human cervical cancer cells and tumor xenograft by downregulating specificity protein 1.  

PubMed

Earlier studies have shown that tolfenamic acid (Tol) exhibits anticancer activity in several cancer models by inhibiting tumor growth and angiogenesis. However, the chemopreventive effect of Tol on a cervical cancer model and the underlying mechanism of action are unknown. In this study, Tol was found to inhibit cell proliferation by inducing apoptosis without affecting cyclo-oxygenase 2 expression, but ampiroxicam did not. Tol decreases the specificity protein 1 (Sp1) mRNA and its promoter activity in KB cervical cancer cells, and the downregulation of Sp1 protein by affecting several proteins that contain GC-rich sites on their promoters. Studies using small interference RNA and an Sp1-specific inhibitor (mithramycin A) confirmed that the decrease in Sp1 by Tol affects survivin and p27. Tol also inhibited tumor growth and Sp1 protein in athymic nude mice xenografts. These results show that Tol could be a potent anticervical cancer drug that acts by regulating Sp1 protein and its downstream pathways. PMID:21131823

Shim, Jung-Hyun; Shin, Ji-Ae; Jung, Ji-Youn; Choi, Kyeong-Hee; Choi, Eun-Sun; Cho, Nam-Pyo; Kong, Gu; Ryu, Mi Heon; Chae, Jung-Ii; Cho, Sung-Dae

2011-03-01

142

How Is Cervical Cancer Staged?  

MedlinePLUS

... of the cervix. This stage is also called carcinoma in situ (CIS) which is part of cervical intraepithelial neoplasia ... Stage IVB (any T, any N, M1): The cancer has spread to distant organs beyond the pelvic area, such as the lungs or liver. Last Medical Review: 04/11/2013 ...

143

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

NASA Astrophysics Data System (ADS)

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

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

2013-06-01

144

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

PubMed Central

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.

2013-01-01

145

Leea indica Ethyl Acetate Fraction Induces Growth-Inhibitory Effect in Various Cancer Cell Lines and Apoptosis in Ca Ski Human Cervical Epidermoid Carcinoma Cells  

PubMed Central

The anticancer potential of Leea indica, a Chinese medicinal plant was investigated for the first time. The crude ethanol extract and fractions (ethyl acetate, hexane, and water) of Leea indica were evaluated their cytotoxicity on various cell lines (Ca Ski, MCF 7, MDA-MB-435, KB, HEP G2, WRL 68, and Vero) by MTT assay. Leea indica ethyl acetate fraction (LIEAF) was found showing the greatest cytotoxic effect against Ca Ski cervical cancer cells. Typical apoptotic morphological changes such as DNA fragmentation and chromatin condensation were observed in LIEAF-treated cells. Early signs of apoptosis such as externalization of phosphatidylserine and disruption of mitochondrial membrane potential indicated apoptosis induction. This was further substantiated by dose- and time-dependent accumulation of sub-G1 cells, depletion of intracellular glutathione, and activation of caspase-3. In conclusion, these results suggested that LIEAF inhibited cervical cancer cells growth by inducing apoptosis and could be developed as potential anticancer drugs.

Yau Hsiung, Wong; Abdul Kadir, Habsah

2011-01-01

146

Leea indica Ethyl Acetate Fraction Induces Growth-Inhibitory Effect in Various Cancer Cell Lines and Apoptosis in Ca Ski Human Cervical Epidermoid Carcinoma Cells.  

PubMed

The anticancer potential of Leea indica, a Chinese medicinal plant was investigated for the first time. The crude ethanol extract and fractions (ethyl acetate, hexane, and water) of Leea indica were evaluated their cytotoxicity on various cell lines (Ca Ski, MCF 7, MDA-MB-435, KB, HEP G2, WRL 68, and Vero) by MTT assay. Leea indica ethyl acetate fraction (LIEAF) was found showing the greatest cytotoxic effect against Ca Ski cervical cancer cells. Typical apoptotic morphological changes such as DNA fragmentation and chromatin condensation were observed in LIEAF-treated cells. Early signs of apoptosis such as externalization of phosphatidylserine and disruption of mitochondrial membrane potential indicated apoptosis induction. This was further substantiated by dose- and time-dependent accumulation of sub-G(1) cells, depletion of intracellular glutathione, and activation of caspase-3. In conclusion, these results suggested that LIEAF inhibited cervical cancer cells growth by inducing apoptosis and could be developed as potential anticancer drugs. PMID:21423690

Yau Hsiung, Wong; Abdul Kadir, Habsah

2011-01-01

147

Cervical Cancer Incidence and Mortality Rates  

Cancer.gov

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

148

IL-2 enhances cervical cancer cells proliferation and JAK3/STAT5 phosphorylation at low doses, while at high doses IL-2 has opposite effects.  

PubMed

The IL-2R signaling is critical for normal lymphocyte proliferation. However, the role of the IL-2 signaling in cervical cancer is not yet fully understood. We show that in IL-2R-expressing cervical cancer cells, JAK1 molecules are not phosphorylated. At low doses of IL-2, the constitutive phosphorylation of JAK3 and STAT5 increases in the tumor cells and decreases in lymphocytes, whereas the opposite occurs at high doses of IL-2. Using AG-490, the activation of JAK3 and the proliferation of cervical cancer cells were inhibited. We describe differences in the response of molecules downstream the IL-2R in lymphocytes and tumor cells. PMID:24548303

Valle-Mendiola, Arturo; Weiss-Steider, Benny; Rocha-Zavaleta, Leticia; Soto-Cruz, Isabel

2014-05-01

149

Epidermal growth factor-stimulated human cervical cancer cell growth is associated with EGFR and cyclin D1 activation, independent of COX-2 expression levels.  

PubMed

Cervical cancer constitutes the second most common cancer in women. It is evident from earlier studies that epidermal growth factor (EGF) is a mitogen, in that it mimics the function of estrogen by mediating cross-talk with other oncoproteins. Although epidermal growth factor receptor (EGFR) is highly expressed in breast and ovarian tumor tissues, its regulation by the exogenous source of its ligand EGF in human papillomavirus (HPV)-associated cervical cancer remains unclear. In this study, we addressed the question of whether EGF is required for the proliferation of HPV-positive cervical cancer cells and what mechanisms are involved. To determine this, we conducted a series of studies using HPV-positive human cervical cancer cells, CaSki and HeLa, and stimulated the cells with EGF. Our findings suggest that 6 h of stimulation with 10 ng/ml of EGF is sufficient to induce cell cycle progression associated with a significant increase in DNA synthesis, EGFR, COX-2 and cyclin D1 levels. Consistently, cellular localization and Western blot analysis for p-EGFR (Try-1045) protein showed an increase after EGF stimulation. Using siRNA gene knockdown assays we have shown that cyclin D1 siRNA has a significant negative effect on EGFR and inhibit cell growth independent of COX-2 levels. In summary, our findings reveal that an exogenous EGF stimulation may enhance HPV-related cervical cancer cell proliferation by activating EGFR and cyclin D1 that is independent of COX-2 levels, suggesting that the inhibitors of EGFR and cyclin D1 may be effective against cervical cancer cell proliferation. PMID:21946890

Narayanan, Rajkishen; Kim, Hye Na; Narayanan, Narayanan K; Nargi, Dominick; Narayanan, Bhagavathi

2012-01-01

150

Robotic Surgery for Cervical Cancer  

PubMed Central

The development of robotic technology has facilitated the application of minimally invasive techniques for the treatment and evaluation of patients with early, advanced, and recurrent cervical cancer. The application of robotic technology for selected patients with cervical cancer and the data available in the literature are addressed in the present review paper. The robotic radical hysterectomy technique developed at the Mayo Clinic Arizona is presented with data comparing 27 patients who underwent the robotic procedure with 2 matched groups of patients treated by laparoscopic (N = 31), and laparotomic radical hysterectomy (N = 35). A few other studies confirmed the feasibility and safety of robotic radical hysterectomy and comparisons to either to the laparoscopic or open approach were discussed. Based on data from the literature, minimally invasive techniques including laparoscopy and robotics are preferable to laparotomy for patients requiring radical hysterectomy, with some advantages noted for robotics over laparoscopy. A prospective randomised trial is currently being perfomred under the auspices of the American Association of Gyneoclogic Laparoscopists comparing minimally invasive radical hysterectomy (laparoscopy or robotics) with laparotomy. For early cervical cancer radical parametrectomy and fertility preserving trachelectomy have been performed using robotic technology and been shown to be feasible, safe, and easier to perform when compared to the laparoscopic approach. Similar benefits have been noted in the treatment of advanced and recurrent cervical cancer where complex procedures such as extraperitoneal paraortic lymphadenectomy and pelvic exenteration have been required. Conclusion: Robotic technology better facilitates the surgical approach as compared to laparoscopy for technically challenging operations performed to treat primary, early or advanced, and recurrent cervical cancer. Although patient advantages are similar or slightly improved with robotics, there are multiple advantages for surgeons.

Zanagnolo, Vanna L.

2008-01-01

151

Robotic surgery for cervical cancer.  

PubMed

The development of robotic technology has facilitated the application of minimally invasive techniques for the treatment and evaluation of patients with early, advanced, and recurrent cervical cancer. The application of robotic technology for selected patients with cervical cancer and the data available in the literature are addressed in the present review paper. The robotic radical hysterectomy technique developed at the Mayo Clinic Arizona is presented with data comparing 27 patients who underwent the robotic procedure with 2 matched groups of patients treated by laparoscopic (N = 31), and laparotomic radical hysterectomy (N = 35). A few other studies confirmed the feasibility and safety of robotic radical hysterectomy and comparisons to either to the laparoscopic or open approach were discussed. Based on data from the literature, minimally invasive techniques including laparoscopy and robotics are preferable to laparotomy for patients requiring radical hysterectomy, with some advantages noted for robotics over laparoscopy. A prospective randomised trial is currently being performed under the auspices of the American Association of Gyneoclogic Laparoscopists comparing minimally invasive radical hysterectomy (laparoscopy or robotics) with laparotomy. For early cervical cancer radical parametrectomy and fertility preserving trachelectomy have been performed using robotic technology and been shown to be feasible, safe, and easier to perform when compared to the laparoscopic approach. Similar benefits have been noted in the treatment of advanced and recurrent cervical cancer where complex procedures such as extraperitoneal paraortic lymphadenectomy and pelvic exenteration have been required. Conclusion: Robotic technology better facilitates the surgical approach as compared to laparoscopy for technically challenging operations performed to treat primary, early or advanced, and recurrent cervical cancer. Although patient advantages are similar or slightly improved with robotics, there are multiple advantages for surgeons. PMID:19108008

Magrina, Javier F; Zanagnolo, Vanna L

2008-12-31

152

[Cervical cancer prevention: an update].  

PubMed

It has been seen an increase of the cervical cancer and of intraepithelial cancer in the last years. The most important risk factors for cervical cancer are sexual conduct, early of sexual relationships, number of partners, cigarettes, oral anticonceptive, pregnancy, immunosuppression, sexually transmitted illness. And an important role of the Human Papilloma Virus. The HPV has been classified in 3 groups; low risk, the most frequents are 11 and 6, middle risk, tipe 31, 33 and 35, and high risk, 16 and 18, that have frequent association with cervical cancer and with high grade intraepithelial lesions. The cervicovaginal citology is still the most accurate diagnosis method to detect SIL or CIN and invasive cancer in early stages, it is discussed the periodicity and group of women to whom the method must point. There are different options depending if it is a SIL of low or high grade or and cancer. With the possibility of doing follow up or treatment, such as. LLETZ, Laser, Criotraphy, cone and interferon for the preneoplastic lesions. The achievement of a vaccine for HPV could have a significant impact on these pathology. PMID:16972742

Irico, G; Escobar, H; Marinelli, B

2005-01-01

153

Cervical cancer in the Netherlands 1989-1998: Decrease of squamous cell carcinoma in older women, increase of adenocarcinoma in younger women.  

PubMed

Cervical cancer is a preventable disease, occurring in relatively young women. In the Netherlands, population-based cervical screening aims at women aged 30-60 years. We performed a population-based study of the incidence of invasive cervical cancer in the Netherlands to evaluate trends, with emphasis on age at time of diagnosis. Histologic diagnosis was retrieved from the Netherlands Cancer Registry for all women residing in the Netherlands with invasive cervical cancer between January 1, 1989, and December 31, 1998. In this 10-year period, the incidence rate of squamous cell carcinoma decreased significantly from 7.1/100,000 to 6.1/100,000 (p < 0.001), with the greatest decrease in women aged 60-74 (-5.5%). While the overall incidence rate of adenocarcinoma remained stable, it increased in women aged 15-29 (+15.8%) and in women aged 30-44 (+2.5%), though the number of cases was small. For squamous cell carcinoma, the incidence of stage II at diagnosis decreased most (-2.7%). There was no change in stage at diagnosis for adenocarcinoma. Most cases of cervical cancer, 60.5%, were detected between ages 30 and 60 years, i.e., the Dutch screening age interval. Cervical cancer in women below age 30 contributed 5.0% to the total incidence, with 3.0% occurring between ages 27 and 29. Thus, screening for cervical cancer in the Netherlands is associated with a decrease in the incidence of squamous cell carcinoma and adenocarcinoma incidence appears to be increasing in younger women. PMID:15515017

Bulk, Saskia; Visser, Otto; Rozendaal, Lawrence; Verheijen, René H M; Meijer, Chris J L M

2005-03-01

154

Enhancement of radiation response in human cervical cancer cells in vitro and in vivo by arsenic trioxide (As 2O 3)  

Microsoft Academic Search

Arsenic trioxide (As2O3) inhibits cell growth and induces apoptosis in certain types of cancer cells including acute promyelocytic leukemia, prostate and ovarian carcinomas, but its effect on response of tumor cells to ionizing radiation has never been explored before. Here we demonstrate that As2O3 can sensitize human cervical cancer cells to ionizing radiation both in vitro and in vivo. As2O3

Yong-Jin Chun; In-Chul Park; Myung-Jin Park; Sang-Hyeok Woo; Seok-Il Hong; Hee Yong Chung; Tae-Hwan Kim; Yun-Sil Lee; Chang-Hun Rhee; Su-Jae Lee

2002-01-01

155

Knockdown of astrocyte elevated gene-1 (AEG-1) in cervical cancer cells decreases their invasiveness, epithelial to mesenchymal transition, and chemoresistance.  

PubMed

During cancer development, epithelial-mesenchymal transition (EMT) facilitates tumor dissemination and metastatic spread, which is characterized by morphologic changes from epithelial cells to fibroblast-like cells, disassembly of intercellular junction, and increased cell motility. Overexpression of astrocyte elevated gene-1(AEG-1) in various cancer cell lines and cancers has been found to be associated with aggressive tumor behavior. We found that AEG-1 expression was elevated in low differentiation cervical cancer specimens from patients. However, little is known about the AEG-1's precise role in invasion and metastasis. Here we demonstrate that downregulation of AEG-1 by RNAi significantly decreased the invasion and migration of cervical cancer cells, suggesting that AEG-1 overexpression may enhance cancer cell motility by inducing EMT. Downregulation of AEG-1 also led to reduced expression of mesenchymal marker vimentin and the transcription factor Snail but upregulation of epithelial marker E-cadherin in HeLa cells. In addition, knockdown of AEG-1 decreased colony forming units and increased sensitivity to cancer drugs in vitro. Taken together, our results suggest that knockdown of AEG-1 could decrease EMT and chemoresistance in cervical cancer cells and attenuate their aggressive behavior. PMID:24675891

Liu, Xiangwen; Wang, Degui; Liu, Huiling; Feng, Ying; Zhu, Tianyuan; Zhang, Lang; Zhu, Bingdong; Zhang, Ying

2014-06-01

156

Therapeutic Mechanisms of Treatment in Cervical and Vaginal Cancer  

PubMed Central

Cervical and vaginal cancers remain serious health problems. Worldwide, more than 530,000 women annually are diagnosed with these diseases, with most new incident cases occurring in nations with limited health resources and underdeveloped screening programs. For women whose disease is too bulky or widespread for surgery, radiochemotherapy should be looked upon as the standard of care. Randomized clinical trials have indicated that radiochemotherapy strategies that disrupt the repair of damaged DNA are key to the management of advanced stage cervical and vaginal cancers. Here, from a viewpoint of cancer cell molecular biology, treatments for advanced stage cervical and vaginal cancers are discussed.

Kunos, Charles A

2012-01-01

157

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

PubMed Central

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

Hounsgaard, Lise; Augustussen, Mikaela; M?ller, Helle; Bradley, Stephen K.; M?ller, Suzanne

2013-01-01

158

Secondary prevention of cervical cancer part 2: initial management of abnormal cervical cancer screening test.  

PubMed

Cervical cancer screening has become more complex with the addition of HPV testing to pap testing. This chapter covers evidence based national recommendations for managing abnormal cervical cancer screening tests. PMID:24785417

Guido, Richard

2014-06-01

159

Cervical cancer: combined modality therapy.  

PubMed

Prospective, randomized studies conducted over the past 10 years have changed the management of patients with advanced cervical cancer. The reviewed studies evaluated the use of surgery, irradiation, and chemotherapy in patients with various stages of cervical carcinoma in the absence and presence of high-risk factors for recurrence. A study by the Radiation Therapy Oncology Group (RTOG) compared pelvic with pelvic plus prophylactic para-aortic irradiation in patients with stages IB (> 4 cm), IIA, and IIB cervical cancer. The 10-year survival advantage was 11% for patients treated with prophylactic para-aortic irradiation. A follow-up study compared pelvic plus prophylactic para-aortic irradiation and brachytherapy with pelvic irradiation, brachytherapy, and chemotherapy with cisplatin and 5-FU in patients with IB-to IVA-stage cervical cancer. Overall and disease-free survivals were significantly improved in patients receiving chemotherapy. In patients with a prevalence of stage IIB and III, the Gynecologic Oncology Group (GOG) demonstrated that treatment with hydroxyurea alone was inferior to cisplatin or cisplatin, 5-FU, and hydroxy-urea in patients treated concurrently with pelvic irradiation and brachytherapy, and the GOG adopted irradiation and weekly cisplatin as standard therapy. Further GOG studies suggest that irradiation and weekly cisplatin chemotherapy without hysterectomy is the optimal treatment for patients with stage IB cervical cancer. High-risk factors for recurrence include tumor size, depth of tumor invasion, lymphovascular space involvement, and lymph node involvement. Prospective, randomized studies conducted by the GOG evaluated the effectiveness of various treatments in patients with high-risk factors. In one study that did not use chemotherapy, the recurrence-free interval was about 10% better for stage IB patients receiving postoperative irradiation after radical hysterectomy and pelvic lymphadenectomy compared with those who received no further therapy. Patients with Stages IB and IIA disease who, following radical hysterectomy and lymph node dissection, are identified as having positive pelvic lymph nodes and positive parametrial involvement, are at higher risk for recurrence and death than the high-risk group described above. An intergroup study conducted by the GOG, RTOG, and Southwest Oncology Group compared postoperative pelvic irradiation alone with postoperative pelvic irradiation plus concurrent chemotherapy in this group of patients. Overall and progression-free survivals were superior for patients receiving chemotherapy, and their greatest survival occurred in patients who received 3 or 4 chemotherapy cycles compared with 1 or 2 cycles or no chemotherapy. These findings are summarized with respect to their implications fortreatment of patients with advanced cervical cancer. PMID:11504285

Grigsby, P W

2001-01-01

160

Comparison of outcomes between squamous cell carcinoma and adenocarcinoma in patients with surgically treated stage I-II cervical cancer  

PubMed Central

To improve our understanding of cervical adenocarcinoma (AD) and evaluate the clinical and pathological variables affecting its prognosis, we retrospectively reviewed the medical records of 455 patients with cervical cancer [International Federation of Gynecology and Obstetrics stage I/II; 91 cases with AD and 364 with squamous cell carcinoma (SCC)] who underwent surgery at our hospital between January, 1995 and August, 2012 and compared the characteristics and prognoses between AD and SCC cases, including age, clinical stage, histological type, lymph node metastasis, lymphovascular space invasion (LVSI), cervical stromal invasion, parametrial invasion, vaginal invasion, corpus invasion, ovarian metastasis and tumor diameter. We used Cox regression analysis to determine independent prognostic factors. AD was found to have a significantly poorer prognosis in all the patients (P=0.001), stage I patients (P=0.001) and stage IB patients (P<0.05). The prognosis did not differ in patients who did not require postoperative treatment; however, patients who received postoperative treatment exhibited a significantly poorer prognosis (P<0.05). Patients with AD who received postoperative irradiation alone had a significantly poorer prognosis (P<0.05). The multivariate analysis identified LVSI (P=0.008), stromal invasion (P=0.024) and ovarian metastasis (P=0.032) as independent predictors of shorter survival. AD was associated with a worse prognosis compared to SCC in patients with stage IB disease, particularly in those who required postoperative treatment. Such patients may benefit from individualized postoperative treatments that differ from those applied for SCC.

YAMAUCHI, MAKOTO; FUKUDA, TAKESHI; WADA, TAKUMA; KAWANISHI, MASARU; IMAI, KENJI; HASHIGUCHI, YASUNORI; ICHIMURA, TOMOYUKI; YASUI, TOMOYO; SUMI, TOSHIYUKI

2014-01-01

161

Knockdown of hTERT by siRNA inhibits cervical cancer cell growth in vitro and in vivo.  

PubMed

Human telomerase reverse transcriptase (hTERT) is the catalytic component of telomerase that facilitates tumor cell invasion and proliferation. It has been reported that telomerase and hTERT are significantly upregulated in majority of cancers including cervical cancer, thus, downregulation of hTERT is a promising target in malignant tumor treatment. We established a short interfering RNA (siRNA) targeting hTERT, and transfected it into HeLa cells (a cervical cancer cell line) to investi-gate the effect of cell proliferation, apoptosis, migration and invasion in cervical cancer cells. The results showed that siRNA targeting hTERT could effectively knock down hTERT expression, remarkably suppress telomerase activity, cell proliferation, migration and invasion, and induced cell apoptosis of cervical cancers cells in vitro. In addition, we evaluated whether siRNA targeting hTERT affects tumor growth in nude mice, and found that it dramatically inhibited tumorigenesis and growth of mice injected with siRNA targeting hTERT. Furthermore, we also found that knockdown of hTERT was able to significantly suppress constitutive phosphorylation of Akt, PI3K, which might imply that reduction of hTERT inhibited tumor growth via the PI3K/Akt signaling pathway to some extent. These results suggest that the suppression of hTERT expression by siRNA inhibits cervical cancer cell growth in vitro and in vivo, and may provide a novel target for anticancer gene therapy. PMID:24920549

Shi, Ying-Ai; Zhao, Qiang; Zhang, Li-Hong; Du, Wei; Wang, Xue-Yao; He, Xu; Wu, Shan; Li, Yu-Lin

2014-09-01

162

What Are the Key Statistics about Cervical Cancer?  

MedlinePLUS

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

163

Cervical Cancer: Screening and Therapeutic Perspectives  

Microsoft Academic Search

Cervical cancer is a major cause of mortality and premature death among women in their most productive years in low- and medium-resourced countries in Asia, Africa and Latin America, despite the fact that it is an eminently preventable cancer. While cytology screening programmes have resulted in a substantial reduction of cervical cancer mortality in developed countries, they have been shown

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

2008-01-01

164

Genetic susceptibility of cervical cancer  

PubMed Central

Epidemiological and laboratory-based studies have identified infection with one of 15 high-risk human papillomavirus (HPV) types as a necessary but not sufficient cause of cervical cancer. The prevalence of genital HPV infections is high in young women, but most of the infections regress without interventions. Host genetic variations in genes involved in immune response pathways may be related to HPV clearance, and HPV E6/E7 oncoproteins interacting or downstream genes, both coding and non-coding, may contribute to the outcome of high risk HPV infection and cervical cancer. Of specific interest for this review has been the selection of genetic variants in genes involved in the above-referred pathways with a summary of their applications in association studies. Because the supportive and opposing data have been reported in different populations, well-designed international collaborative studies need to be conducted to define the consistency of the associations, paving the way to better define the patients at high risk of developing cervical cancer.

Chen, Xiaojun; Jiang, Jie; Shen, Hongbing; Hu, Zhibin

2011-01-01

165

Different effects of adenylyl cyclase activators and phosphodiesterases inhibitors on cervical cancer (HeLa) and breast cancer (MCF-7) cells proliferation.  

PubMed

Abstract Breast and cervical cancers are the most common cancers in Iran and worldwide. Hormonal stimulation of cyclic adenosine mono phosphate (cAMP) and the cAMP-dependent protein kinase PKA regulates cell growth by different mechanism. cAMP can stimulate cell growth in many cell types while inhibiting cell growth in others. In some cell lines have been shown that the proliferation of tumor cells is reduced by increasing cAMP in cells. In this study, we evaluate growth arrest of selective PDE3 and non-selective PDE inhibitors, which lead to increase level of cAMP in cervical (HeLa) and breast cancer (MCF7) cell lines have been studied. Cells were incubated with different concentrations of selective, non-selective PDE inhibitors, beta adrenergic receptor agonist and direct stimulator of adenylyl cyclase. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). Result showed that selective PDE inhibitors decreased cell viability in HeLa and MCF-7 cells as a time-dependent manner. Non-selective inhibitor and beta-adrenergic receptor agonist also decrease cell viability but they are less powerful than selective PDE3 inhibitors. Forskolin had no effect in viability of cells. Analysis of DNA fragmentation by flow cytometry showed apoptosis involved in selective PDE3 inhibitors induced toxicity in HeLa cell. Thus, the growth inhibitory effects of selective PDE3 inhibitors are more effective than non-selective inhibitor. Further studies are needed to investigate the mechanism of action is on the field. PMID:24593874

Mahdian, Davood; Shafiee-Nick, Reza; Mousavi, Seyed Hadi

2014-05-01

166

Cervical Cancer (PDQ): Treatment  

MedlinePLUS

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

167

CDC's Cervical Cancer Study  

MedlinePLUS

... Miller Thomas B. Richards Mona Saraiya Judith Lee Smith Sherri L. Stewart Mary C. White National Programs ... Related Links Help for the Uninsured News Resources Web Features Podcasts More Cancer Healthbeat Podcasts Health-e- ...

168

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

ClinicalTrials.gov

Lymphedema; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Vulvar Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Vulvar Cancer; Stage II Endometrial Carcinoma; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVB Vulvar Cancer

2014-03-07

169

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

PubMed Central

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

Villegas-Ruiz, Vanessa; Juarez-Mendez, Sergio; Perez-Gonzalez, Oscar A; Arreola, Hugo; Paniagua-Garcia, Lucero; Parra-Melquiadez, Miriam; Peralta-Rodriguez, Raul; Lopez-Romero, Ricardo; Monroy-Garcia, Alberto; Mantilla-Morales, Alejandra; Gomez-Gutierrez, Guillermo; Roman-Bassaure, Edgar; Salcedo, Mauricio

2014-01-01

170

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

PubMed Central

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.

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

171

A novel radioresistant mechanism of galectin-1 mediated by H-Ras-dependent pathways in cervical cancer cells  

PubMed Central

Galectin-1 is a lectin recognized by galactoside-containing glycoproteins, and is involved in cancer progression and metastasis. The role of galectin-1 in radiosensitivity has not previously been investigated. Therefore, this study tests whether galectin-1 is involved in the radiosensitivity mediated by the H-Ras signaling pathway using cervical carcinoma cell lines. A knockdown of galectin-1 expression in HeLa cells decreased clonogenic survival following irradiation. The clonogenic survival increased in both HeLa and C33A cells with galectin-1 overexpression. The overexpression or knockdown of galectin-1 did not alter radiosensitivity, whereas H-Ras was silenced in both cell lines. Whereas K-Ras was knocked down, galectin-1 restored the radiosensitivity in HeLa cells and C33A cells. The knockdown of galectin-1 increased the high-dose radiation-induced cell death of HeLa cells transfected by constitutively active H-Ras. The knockdown of galectin-1 inhibited the radiation-induced phosphorylation of Raf-1 and ERK in HeLa cells. Overexpression of galectin-1 enhanced the phosphorylation of Raf-1 and ERK in C33A cells following irradiation. Galectin-1 decreased the DNA damage detected using comet assay and ?-H2AX in both cells following irradiation. These findings suggest that galectin-1 mediates radioresistance through the H-Ras-dependent pathway involved in DNA damage repair.

Huang, E-Y; Chen, Y-F; Chen, Y-M; Lin, I-H; Wang, C-C; Su, W-H; Chuang, P-C; Yang, K-D

2012-01-01

172

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

Microsoft Academic Search

BACKGROUND: Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but

Trinidad Garcia-Iglesias; Alicia del Toro-Arreola; Benibelks Albarran-Somoza; Susana del Toro-Arreola; Pedro E Sanchez-Hernandez; Maria Guadalupe Ramirez-Dueñas; Luz Ma Adriana Balderas-Peña; Alejandro Bravo-Cuellar; Pablo C Ortiz-Lazareno; Adrian Daneri-Navarro

2009-01-01

173

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

PubMed Central

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

Lindstrom, A.K.; Hellberg, D.

2014-01-01

174

Medical Interventions: Vaccine to Prevent Cervical Cancer  

Cancer.gov

As recently as the 1940s, cervical cancer was a major cause of death among women of childbearing age in the U.S. but widespread introduction of the Pap test in the 1950s helped reduce cervical cancer incidence and mortality in this country by more than 70 percent.

175

Study finds genomic differences in types of cervical cancer  

Cancer.gov

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

176

EGF-induced expression of Fused Toes Homolog (FTS) facilitates epithelial-mesenchymal transition and promotes cell migration in ME180 cervical cancer cells.  

PubMed

The role of Fused Toes Homolog (FTS) in epidermal growth factor (EGF) induced epithelial-mesenchymal transition (EMT) in cervical cancer cells was studied. EGF treatment induced the change of EMT markers and increased cell migration. EGF treatment also increased phosphorylated EGFR and ERK and nuclear level of ATF-2. The binding of ATF-2 to the promoter region of FTS was evidenced after EGF treatment. Pretreatment with PD98059 and gefitinib prevented EGF-induced FTS expression. FTS silencing reduced EMT and cell migration by EGF treatment. These results demonstrate a novel function for FTS in EGF-mediated EMT process. PMID:24971934

Muthusami, Sridhar; Prabakaran, D S; Yu, Jae-Ran; Park, Woo-Yoon

2014-09-01

177

Caffeic acid phenethyl ester induces E2F-1-mediated growth inhibition and cell-cycle arrest in human cervical cancer cells.  

PubMed

Caffeic acid phenyl ester (CAPE) has been identified as an active component of propolis, a substance that confers diverse activities in cells of various origins. However, the molecular basis of CAPE-mediated cellular activity remains to be clarified. Here, we show that CAPE preferentially induced S- and G2 /M-phase cell-cycle arrests and initiated apoptosis in human cervical cancer lines. The effect was found to be associated with increased expression of E2F-1, as there is no CAPE-mediated induction of E2F-1 in the pre-cancerous cervical Z172 cells. CAPE also up-regulated the E2F-1 target genes cyclin A, cyclin E and apoptotic protease activating of factor 1 (Apaf-1) but down-regulated cyclin B and induced myeloid leukemia cell differentiation protein (Mcl-1). These results suggest the involvement of E2F-1 in CAPE-mediated growth inhibition and cell-cycle arrest. Transient transfection studies with luciferase reporters revealed that CAPE altered the transcriptional activity of the apaf-1 and mcl-1 promoters. Further studies using chromatin immunoprecipitation assays demonstrated that E2F-1 binding to the apaf-1 and cyclin B promoters was increased and decreased, respectively, in CAPE-treated cells. Furthermore, E2F-1 silencing abolished CAPE-mediated effects on cell-cycle arrest, apoptosis and related gene expression. Taken together, these results indicate a crucial role for E2F-1 in CAPE-mediated cellular activities in cervical cancer cells. PMID:23497083

Hsu, Tzu-Hui; Chu, Chin-Chen; Hung, Mei-Whey; Lee, Hwei-Jen; Hsu, Hsien-Jun; Chang, Tsu-Chung

2013-06-01

178

Prognostic Significance of Peritumoral Lymphatic Vessel Density and Vascular Endothelial Growth Factor Receptor 3 in Invasive Squamous Cell Cervical Cancer  

PubMed Central

Cervical cancer is known to metastasize primarily by the lymphatic system. Dissemination through lymphatic vessels represents an early step in regional tumor progression, and the presence of lymphatic metastasis is associated with a poor prognosis. In patients who have undergone a radical hysterectomy, lymphovascular space invasion (LVSI), assessed on hematoxylin and eosin-stained slides, is a major factor for adjuvant therapy in patients with cervical cancer. With the advent of a lymphatic endothelial cell-specific marker, such as D2-40, it is now possible to distinguish between blood and lymphatic space invasion (LSI). In this study, the utility of D2-40 was assessed for the detection of lymphatic vessel density (LVD) and identification of LSI. The expressions of vascular endothelial growth factor receptor-3 (VEGFR-3), VEGF-C, tyrosine receptor kinase-2, and angiopoietin-1 were assessed by immunohistochemical methods on 50 patients with squamous cell carcinoma of the cervix. Clinicopathologic characteristics, including pelvic lymph node metastasis, were correlated with the above histochemical findings. We found that lymphangiogenesis, measured by an increase in peritumoral LVD, was significantly associated with positive lymph node status (P < .005). VEGFR-3 expression was significantly associated with LVD (P < .05). D2-40 staining verified LSI (P = .03) and surpassed that of hematoxylin and eosin-identified LVSI (P = .54). In conclusion, lymphangiogenic markers, specifically LVD quantified by D2-40 and VEGFR-3, are independently associated with LSI and lymph node metastasis in patients with early squamous cell carcinoma of the cervix treated with radical hysterectomy and pelvic lymphadenectomy.

Botting, Shaleen K; Fouad, Hala; Elwell, Kyler; Rampy, Bill A; Salama, Salama A; Freeman, Daniel H; Diaz-Arrastia, Concepcion R

2010-01-01

179

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

PubMed Central

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

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

2014-01-01

180

Estrogen and ER?: Culprits in Cervical Cancer?  

PubMed Central

Estrogen and its receptors are implicated in the promotion and prevention of various cancers. While the uterine cervix is highly responsive to estrogen, the role of estrogen in cervical cancer, which is strongly associated with human papillomavirus (HPV) infections, is poorly understood. Recent studies in HPV transgenic mouse models provide evidence that estrogen and its nuclear receptor promote cervical cancer in combination with HPV oncogenes. While epidemiological studies further support this hypothesis, there is little experimental data assessing the hormonal responsiveness of human cervical cancers. If these cancers are dependent upon estrogen, then drugs targeting estrogen and its receptors may be effective in treating and/or preventing cervical cancer, the second leading cause of death by cancer amongst women worldwide.

Chung, Sang-Hyuk; Franceschi, Silvia; Lambert, Paul F.

2010-01-01

181

The transcervical extended mediastinal lymphadenectomy versus cervical mediastinoscopy in non-small cell lung cancer staging  

Microsoft Academic Search

Objective: To compare the diagnostic yield of the transcervical extended mediastinal lymphadenectomy (TEMLA) and the cervical mediastinoscopy (CM) in detecting metastatic mediastinal lymph nodes in NSCLC patients. Methods: Prospective, randomized, single-blind clinical study. Results: There were 41 NSCLC patients enrolled in the study; 21 were randomized to the TEMLA group and 20 to the cervical mediastinoscopy group. The TEMLA revealed

Jaros?aw Ku?d?a?; Marcin Zieli?ski; Boles?aw Papla; Andrzej Urbanik; Wadim Wojciechowski; Maciej Narski; Artur Szlubowski; ?ukasz Hauer

2007-01-01

182

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

PubMed

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

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

2010-11-01

183

The Japanese guideline for cervical cancer screening.  

PubMed

Cervical cancer is the 11th leading cause of death from cancer for females in Japan. In 2005, there were 2486 deaths from cervical cancer, accounting for 1.8% of the total number of cancer deaths in Japan. Cervical cancer screening using conventional cytology has been conducted worldwide. The guideline for cervical cancer screening was developed based on the established method. The efficacies of conventional and liquid-based cytology, human papillomavirus testing alone and two combination methods were evaluated. On the basis of the balance of the benefits and harms, recommendations for population-based and opportunistic screening were formulated. Five methods of cervical cancer screening were evaluated. On the basis of the analytic framework involving key questions, 3450 articles published from January 1985 to October 2007 were selected using MEDLINE and other methods. After the systematic literature review, 66 articles were confirmed. The results of 33 studies were consistent, and the evidence was sufficient to evaluate the effect of conventional cytology screening. The accuracy of liquid-based cytology was almost equal to that of conventional cytology. Although human papillomavirus testing and combination methods showed high sensitivity, no study has evaluated the reduction in mortality from cervical cancer. Except for the possibility of overdiagnosis, no serious adverse effects of cervical cancer screening were found. Cervical cancer screening using conventional and liquid-based cytology is recommended for population-based and opportunistic screening due to sufficient evidence. Cervical cancer screening using either human papillomavirus testing alone or two combination methods is not recommended for population-based screening due to insufficient evidence. PMID:20436034

Hamashima, Chisato; Aoki, Daisuke; Miyagi, Etsuko; Saito, Eiko; Nakayama, Tomio; Sagawa, Motoyasu; Saito, Hiroshi; Sobue, Tomotaka

2010-06-01

184

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

NASA Astrophysics Data System (ADS)

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

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

2013-07-01

185

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

SciTech Connect

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

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

2013-07-18

186

Involvement of autophagy in cervical, endometrial and ovarian cancer.  

PubMed

Autophagy is an intracellular molecular pathway that maintains cellular homeostasis. A role for autophagy in the development as well as in the treatment of gynecologic malignancies, while still under-investigated, is receiving increased interest. Depending on concomitant factors, autophagy can either promote or suppress development of cervical, endometrial and ovarian cancer. Moreover, these cancer cells can utilize autophagy to promote its resistance to chemotherapeutic agents or, conversely, autophagy can enhance the efficacy of cytotoxic agents by promoting autophagic cell death. In this review the key autophagy-related mechanisms in development and treatment of cervical, endometrial and ovarian cancer are elucidated and evaluated. PMID:24122662

Orfanelli, T; Jeong, J M; Doulaveris, G; Holcomb, K; Witkin, S S

2014-08-01

187

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

PubMed

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

Silva, Jani; Cerqueira, Fátima; Medeiros, Rui

2014-04-01

188

Long Noncoding RNA-EBIC Promotes Tumor Cell Invasion by Binding to EZH2 and Repressing E-Cadherin in Cervical Cancer  

PubMed Central

In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to play key roles in tumorgenesis. However, the contributions of lncRNAs to cervical cancer (CC) remain largely unknown. In this study, differentially expressed lncRNAs and mRNAs in cervical cancer and paired peritumoral tissues were detected by transcriptome microarray analysis. We found 708 probe sets of lncRNAs increased and 836 probe sets decreased in CC tissues, while 1288 mRNA differential probe sets increased and 901 mRNA probe sets decreased. The results were validated by quantitative real-time polymerase chain reaction (qPCR). Then, we found a specific differentially expressed lncRNA can physically bind to enhancer of zeste homolog2 (EZH2) by using RNA immunoprecipitation. We termed it as EZH2-binding lncRNA in cervical cancer [lncRNA-EBIC]. Wound healing assays and Matrigel invasion assays were used to determine the function of this lncRNA by silencing it. We observed that the migration and invasion of cervical cancer cells in vitro were inhibited upon suppression of lncRNA-EBIC by siRNA. We also found that the association between lncRNA-EBIC and EZH2 was required for the repression of E-cadherin, which was a key molecular in the metastasis of cervical cancer. Conclusion These results demonstrated that lncRNA-EBIC was an oncogenic lncRNA, which could promote tumor cell invasion in CC by binding to EZH2 and inhibiting E-cadherin expression.

Zhao, Qian; Zhang, Qing; Xu, Chen; Wang, Shao-bing; Jin, Zhi-jun; Sun, Shu-han; Wang, Fang; Li, Wen

2014-01-01

189

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

PubMed Central

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

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

2012-01-01

190

Classification Cervical Cancer Using Histology Images  

Microsoft Academic Search

This papers reports on methodologies and outcome of a study aiming at developing robust tool to evaluate and classify histology images of cervical cancer. Using the histology images acquired from the pathology laboratories in an Indonesian hospital, this study aims to classify cervical biopsy images based on four well known discriminatory features a) the ratio of nuclei to cytoplasm b)

Rahmadwati; G. Naghdy; M. Ross; C. Todd; E. Norachmawati

2010-01-01

191

Cervical Cancer Rates by Race and Ethnicity  

MedlinePLUS

... of getting cervical cancer, followed by Hispanic, white, American Indian/Alaska Native, and Asian/Pacific Islander women. Cervical ... from race categories (white, black, Asian/Pacific Islander, American Indian/Alaska Native). Death Rates by Race/Ethnicity From ...

192

Somatic LKB1 Mutations Promote Cervical Cancer Progression  

PubMed Central

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.

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

193

Laparoscopic Fertility Sparing Management of Cervical Cancer  

PubMed Central

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

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

2014-01-01

194

Laparoscopic fertility sparing management of cervical cancer.  

PubMed

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

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

2014-04-01

195

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

ClinicalTrials.gov

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

2012-06-08

196

Epidemiology of cervical cancer in Colombia  

PubMed Central

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

Munoz, Nubia

2012-01-01

197

Cathepsin B may be a potential biomarker in cervical cancer.  

PubMed

Cathepsin B is a protease which is able to digest extracellular matrix. It is currently unknown whether cathepsin B plays a role in cervical cancer development and progression. With Q-PCR and Western blotting, we observed cathepsin B expression in cervical cancer cell line Hela cells. After the gene was silenced in HeLa cells with SiRNA, we confirmed that cathepsin B expressions at both mRNA and protein levels were significantly reduced. At the same time, cell proliferation, migration and invasion of the HeLa cells were significantly decreased compared to control cells. In addition, a significant regression of tumor growth in nude mice which received the siRNA targeted cathepsin B HeLa cells was observed. We further studied the expression of cathepsin B in a series of 169 clinical samples, including 56 invasive cervical squamous carcinoma, 85 CINs and 28 normal cervical tissues. It was found that cathepsin B expression in invasive carcinomas was significantly higher than that in the CINs and normal tissues (P<0.01). In addition, cathepsin B expression in the invasive carcinomas was positively correlated to tumor invasion depth and lymphatic metastasis. Our results indicate that cathepsin B may be a potential biomarker for further strategical clinical studies in cervical cancer. PMID:22127599

Wu, D; Wang, H; Li, Z; Wang, L; Zheng, F; Jiang, J; Gao, Y; Zhong, H; Huang, Y; Suo, Z

2012-01-01

198

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

PubMed Central

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

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

2013-01-01

199

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

PubMed

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

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

2013-01-01

200

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

PubMed

Cervical cancer is an issue of foremost importance globally, specifically affecting the developing nations. Significant advances have taken place with regard to diagnosis of cervical cancer, especially with screening. Appropriate screening measures can thus reduce the incidence of cervical cancer. The most desirable screening technique should be less invasive, easy to perform, cost-effective and cover a wide range of diagnostic icons. Manual liquid based cytology (MLBC) can be considered as one of the suitable technique for screening with the above-mentioned benefits. The aim of the current study was to compare two cervical screening techniques on the basis of different morphological parameters and staining parameters by using modified acetic acid Pap staining to see the possibility of reducing time economy involved in conventional Pap staining (CPS). The study was conducted on a total 88 cases and all were analyzed with both MLBC and CPS. Forty eight cases that were regarded as satisfactory on the basis of Bethesda system by both methods were further recruited for investigation. Their morphological parameters and staining quality were compared and scored according to a scoring system defined in the study. Quality indices was calculated for both staining procedures and smear techniques. PMID:24568528

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

2014-01-01

201

Chemoradiotherapy for Cervical Cancer in 2010  

Microsoft Academic Search

The introduction of concurrent chemotherapy and radiotherapy for the definitive treatment of cervical cancer constituted a\\u000a major advance in the management of cervical cancer, resulting in a significant improvement in local control, progression-free\\u000a survival, and overall survival. Since the publication of the results of seminal trials demonstrating the benefits of platinum-based\\u000a chemotherapy, investigations of new cytotoxic and targeting agents have

Ann H. Klopp; Patricia J. Eifel

2011-01-01

202

Expression of Mir21 and Mir143 in Cervical Specimens Ranging from Histologically Normal through to Invasive Cervical Cancer  

Microsoft Academic Search

BackgroundMicroRNA expression is severely disrupted in carcinogenesis, however limited evidence is available validating results from cell-line models in human clinical cancer specimens. MicroRNA-21 (mir-21) and microRNA-143 (mir-143) have previously been identified as significantly deregulated in a range of cancers including cervical cancer. Our goal was to investigate the expression patterns of several well-studied microRNA species in cervical samples and compare

Georgios Deftereos; Simon R. Corrie; Qinghua Feng; Janice Morihara; Joshua Stern; Stephen E. Hawes; Nancy B. Kiviat

2011-01-01

203

Selenium activates p53 and p38 pathways and induces caspase-independent cell death in cervical cancer cells.  

PubMed

The mechanisms of sodium selenite-induced cell death in cervical carcinoma cells were studied during 24 h of exposure in the HeLa Hep-2 cell line. Selenite at the employed concentrations of 5 and 50 micromol/L produced time- and dose-dependent suppression of DNA synthesis and induced DNA damage which resulted in phosphorylation of histone H2A.X. These effects were influenced by pretreatment of cells with the SOD/catalase mimetic MnTMPyP or glutathione-depleting buthionine sulfoximine, suggesting the significant role of selenite-generated oxidative stress. Following the DNA damage, selenite activated p53-dependent pathway as evidenced by the appearance of phosphorylated p53 and accumulation of p21 in the treated cells. Concomitantly, selenite activated p38 pathway but its effect on JNK was very weak. p53- and p38-dependent signaling led to the accumulation of Bax protein, which was preventable by specific inhibitors of p38 (SB 203580) and p53 (Pifithrin-alpha). Mitochondria in selenite-treated cells changed their dynamics (shape and localization) and released AIF and Smac/Diablo, which initiated caspase-independent apoptosis as confirmed by the caspase-3 activity assay and the low effect of caspase inhibitors z-DEVD-fmk and z-VAD-fmk on cell death. We conclude that selenite induces caspase-independent apoptosis in cervical carcinoma cells mostly by oxidative stress-mediated activation of p53 and p38 pathways, but other selenite-mediated effects, in particular mitochondria-specific ones, are also involved. PMID:17610029

Rudolf, E; Rudolf, K; Cervinka, M

2008-04-01

204

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

PubMed Central

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

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

2013-01-01

205

Related Resources for Cervical Cancer Screening  

Cancer.gov

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

206

Surgical staging of cervical cancer.  

PubMed

Noninvasive radiologic methods to detect paraaortic lymph node metastases are reliable when combined with FNA of enlarged lymph nodes. However, the sensitivity is low, and undetected microscopic metastases leads to treatment failure. These patients with paraaortic lymph node metastasis are not treated with extended-field radiation, and they all die within 3 years. The CT scanning is probably the best diagnostic method to evaluate cervical cancer, because it can assess the primary tumor, the urinary tract, gastrointestinal tract, liver parenchyma, and retroperitoneum. It also permits the guidance of FNA and the arrangement of radiation ports. Surgical staging provides the direct assessment of the peritoneal cavity and the retroperitoneal spaces. Metastatic tumor, including enlarged lymph nodes, can be resected, but this is of dubious benefit. The operative morbidity is acceptable, with fewer intestinal complications when the extraperitoneal approach is used, and long-term morbidity is minimal when appropriate paraaortic radiation doses are employed (less than 5,000 cGy). Surgical staging has provided data on the frequency of paraaortic lymph node metastasis by stage of cervical cancer, and thus, treatment strategies can be better developed. Extended-field radiation results in 5-year survival rates of 20-25% in patients with microscopic paraaortic lymph node metastasis, patients who would not survive without the treatment. However, surgical staging has produced only a modest boost in survival rates, because of the high rate of pelvic and systemic failure. When extended-field radiation is used prophylactically or in patients with probable lymph node metastasis seen on radiographic studies, survival rates are similar to patients irradiated after surgical staging finds paraaortic lymph node disease. As our ability to predict, and detect nonsurgically, positive paraaortic node disease improves, extended radiation (or other adjuvant therapy) could be used more frequently without operation in patients who are at high risk for metastatic disease. In a study by Haie et al, prophylactic paraaortic radiation was given to patients at high risk for paraaortic metastasis. In patients with a high probability of local disease control, paraaortic radiation significantly reduced the incidence of paraaortic and distant metastases. Patients with known paraaortic lymph node metastases frequently have occult systemic metastases. In these same patients, pelvic failure is also common. Thus, until effective systemic therapies emerge, a marked improvement in survival is unlikely in patients who have paraaortic lymph node metastasis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2289352

Heaps, J M; Berek, J S

1990-12-01

207

Vaccines Against Human Papillomavirus and Cervical Cancer: Promises and Challenges  

Microsoft Academic Search

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

Ali Mahdavi; Bradley J. Monk

208

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

PubMed

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

Chen, H; Duan, J; Zuo, F

2014-01-01

209

TPX2 regulates tumor growth in human cervical carcinoma cells.  

PubMed

The targeting protein for the Xenopus kinesin?like protein 2 (TPX2), a microtubule-associated protein, has been utilized as a tool to evaluate, more precisely, the proliferative behavior of tumor cells. The abnormal expression of TPX2 in a variety of malignant tumor types has been reported, however less is known about its role in cervical cancer. In the present study, the association between TPX2 expression and the biological behavior of cervical cancer, was investigated. Immunohistochemistry and RT-PCR were used to detect the expression of TPX2 in cervical cancer tissues. The inhibitory effect of TPX2-siRNA on the growth of SiHa human cervical carcinoma cells was studied in vitro. TPX2 expression was identified as significantly higher in cervical carcinoma compared with the control, normal cervical tissues. TPX2 siRNA transfected into SiHa cells induced apoptosis and inhibited cell proliferation and invasion. Similar results were obtained by in vivo transplantation, as TPX2 siRNA transfection significantly reduced tumor growth of the xenograft in nude mice. The results demonstrated that TPX2 is important in the regulation of tumor growth in cervical cancer and therefore may be a potential therapeutic target as a novel treatment strategy. PMID:24718984

Jiang, Peiyue; Shen, Kexin; Wang, Xuerui; Song, Haiqin; Yue, Ying; Liu, Tongjun

2014-06-01

210

Nature of cervical cancer and other HPV - associated cancers.  

PubMed

Papillomaviruses are small DNA viruses that infect and multiply in cutaneous or mucosal epithelial tissue. Human papillomavirus (HPV) 16 and 18 cause more than 99% of cervical carcinomas. Simultaneous presence of HPV is found in cervical intraepithelial neoplasia, vaginal intraepithelial neoplasia, vaginal and anal cancer. Invasive vulvar squamous cell carcinoma in younger women under the age of 50 are also associated with HPV. Most of the penile lesions are subclinical and the high prevalence of high-risk HPV suggests that they constitute a reservoir for high-risk HPV. Bowens disease and Buschke-Lowenstein tumors are associated with particular low- and high-risk HPV types. The potential role of HPV infection in the carcinogenic steps of breast, prostate, colorectal and lung cancers should be further tested. HPV-DNA might be transported from the original site of infection to the breast tissue by the bloodstream, and therefore is possibly involved in the carcinogenesis of breast neoplasia in some patients. HPV-DNA is detected in 40-70% of head and neck squamous cell carcinomas and in only 1% in normal epithelial cells. In this paper we propose the hypothesis that many epithelial normal cells are susceptible to HPV infection, which are the most sexually transmitted viruses. Experimental and epidemiological data imply a causative role for HPVs and they appear to be the second most important risk factor for cancer development in humans, exceeded only by tobacco usage. PMID:19810128

Georgieva, St; Iordanov, V; Sergieva, S

2009-01-01

211

HPV-related cervical disease and oropharyngeal cancer.  

PubMed

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

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

2014-08-01

212

[Immunohistochemical studies on a new antigens associated with squamous cell cancer in oncogenesis of uterine cervical cancer].  

PubMed

We examined the localization of squamous cell cancer associated antigens (SCCAA) in dysplasia, cancer in situ (CIS) and microinvasive SCC of the uterine cervix, since detection of SCCAA in these subjects is highly effective for early diagnosis. Anti-squamous cell cancer associated antibody (Anti SCCAAb IgG) was prepared by immunizing rabbits with specific components at around PI 6.1 that were originally purified from SCC of maxillary sinus. In this study, the following results were obtained by the immunoperoxidase method. (1) Eleven out of 15(73%) cases of dysplasia, 20 out of 26(77%) cases of CIS, 21 out of 24(88%) cases of Stage I, 13 out of 14(93%) cases of Stage II and 9 out of 10(90%) cases of Stage III-IV in the clinical stages of SCC showed positive staining, while controls of unrelated SCC were almost negative. (2) The SCCAA positive ratio was 2 out of 2 cases of small cell nonkeratinized type, 86% in large cell nonkeratinized type and 94% in Keratinized type of SCC. (3) The SCCAA was demonstrated on all the layers of stratified squamous epithelium in a lesion of CIS and some layers migrated to adjacent nonneoplastic lesion with lateral invasion in middle layer. These results suggest that the demonstration of SCCAA may be useful in diagnosing the malignant transformation of squamous epithelium in the early stage of SCC. PMID:1997617

Uchimura, M; Kenjo, T; Kuroshima, Y; Fujii, A; Yamauchi, S

1991-01-01

213

Fatal invasive cervical cancer secondary to untreated cervical dysplasia: a case report  

PubMed Central

Introduction Well-documented cases of untreated cervical intra-epithelial dysplasia resulting in fatal progression of invasive cervical cancer are scarce because of a long pre-invasive state, the availability of cervical cytology screening programs, and the efficacy of the treatment of both pre-invasive and early-stage invasive lesions. Case presentation We present a well-documented case of a 29-year-old Caucasian woman who was found, through routine conventional cervical cytology screening, to have pathologic Papanicolaou (Pap) grade III D lesions (squamous cell abnormalities). She subsequently died as a result of human papillomavirus type 18-associated cervical cancer after she refused all recommended curative therapeutic procedures over a period of 13 years. Conclusion This case clearly demonstrates a caveat against the promotion and use of complementary alternative medicine as pseudo-immunologic approaches outside evidence-based medicine paths. It also demonstrates the impact of the individualized demands in diagnosis, treatment and palliative care of patients with advanced cancer express their will to refuse evidence-based treatment recommendations.

2011-01-01

214

Toe metastasis: A rare pattern of cervical cancer spread.  

PubMed

•Toe metastasis is a rare pattern of cervical cancer spread.•Enlarged erythematous toe is an important sign suggesting bone metastasis.•Toe metastasis represents a grave prognostic indicator of cervical cancer. PMID:24567886

Ciccone, Marcia A; Conturie, Charlotte L; Lee, Cassie M; Matsuo, Koji

2014-04-01

215

U.S. Cervical Cancer Rates Higher Than Thought  

MedlinePLUS

... Related MedlinePlus Pages African American Health Cervical Cancer Seniors' Health MONDAY, May 12, 2014 (HealthDay News) -- A new ... Health News on: African American Health Cervical Cancer Seniors' Health Recent Health News Page last updated on 13 ...

216

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

Cancer.gov

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

217

The neem limonoids azadirachtin and nimbolide induce cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells.  

PubMed

Limonoids from the neem tree (Azadirachta indica) have attracted considerable research attention in recent years owing to their potent antioxidant and anti-proliferative effects. The present study was designed to investigate the cellular and molecular mechanisms by which azadirachtin and nimbolide exert cytotoxic effects in the human cervical cancer (HeLa) cell line. Both azadirachtin and nimbolide significantly suppressed the viability of HeLa cells in a dose-dependent manner by inducing cell cycle arrest at G0/G1 phase accompanied by p53-dependent p21 accumulation and down-regulation of the cell cycle regulatory proteins cyclin B, cyclin D1 and PCNA. Characteristic changes in nuclear morphology, presence of a subdiploid peak and annexin-V staining pointed to apoptosis as the mode of cell death. Increased generation of reactive oxygen species with decline in the mitochondrial transmembrane potential and release of cytochrome c confirmed that the neem limonoids transduced the apoptotic signal via the mitochondrial pathway. Altered expression of the Bcl-2 family of proteins, inhibition of NF-kappaB activation and over-expression of caspases and survivin provide compelling evidence that azadirachtin and nimbolide induce a shift of balance toward a pro-apoptotic phenotype. Antioxidants such as azadirachtin and nimbolide that can simultaneously arrest the cell cycle and target multiple molecules involved in mitochondrial apoptosis offer immense potential as anti-cancer therapeutic drugs. PMID:20429769

Priyadarsini, R Vidya; Murugan, R Senthil; Sripriya, P; Karunagaran, D; Nagini, S

2010-06-01

218

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

PubMed Central

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

Wong, Yau Hsiung; Abdul Kadir, Habsah

2012-01-01

219

Expression and effects of high-mobility group box 1 in cervical cancer.  

PubMed

We investigated the significance of high- mobility group box1 (HMGB1) and T-cell-mediated immunity and prognostic value in cervical cancer. HMGB1, forkhead/winged helix transcription factor p3 (Foxp3), IL-2, and IL-10 protein expression was analyzed in 100 cervical tissue samples including cervical cancer, cervical intraepithelial neoplasia (CIN), and healthy control samples using immunohistochemistry. Serum squamous cell carcinoma antigen (SCC-Ag) was immunoradiometrically measured in 32 serum samples from 37 cases of squamous cervical cancer. HMGB1 and SCC-Ag were then correlated to clinicopathological characteristics. HMGB1 expression tends to increase as cervical cancer progresses and it was found to be significantly correlated to FIGO stage and lymph node metastasis. These findings suggest that HMGB1 may be a useful prognostic indicator of cervical carcinoma. In addition, there were significant positive relationships between HMGB1 and FOXP3 or IL-10 expression (both p < 0.05). In contrast, HMGB1 and IL-2 expression was negatively correlated (p < 0.05). HMGB1 expression may activate Tregs or facilitate Th2 polarization to promote immune evasion of cervical cancer. Elevated HMGB1 protein in cervical carcinoma samples was associated with a high recurrence of HPV infection in univariate analysis (p < 0.05). HMGB1 expression and levels of SCC-Ag were directly correlated in SCC (p < 0.05). Thus, HMGB1 may be a useful biomarker for patient prognosis and cervical cancer prediction and treatment. PMID:24837834

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

2014-01-01

220

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

PubMed Central

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

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

2014-01-01

221

Overview of microarray analysis of gene expression and its applications to cervical cancer investigation.  

PubMed

Cervical cancer is one of the leading female cancers in Taiwan and ranks as the fifth cause of cancer death in the female population. Human papillomavirus has been established as the causative agent for cervical neoplasia and cervical cancer. However, the tumor biology involved in the prognoses of different cell types in early cancers and tumor responses to radiation in advanced cancers remain largely unknown. The introduction of microarray technologies in the 1990s has provided genome-wide strategies for searching tens of thousands of genes simultaneously. In this review, we first summarize the two types of microarrays: oligonucleotides microarray and cDNA microarray. Then, we review the studies of functional genomics in cervical cancer. Gene expression studies that involved cervical cancer cell lines, cervical cells of cancer versus normal ectocervix, cancer tissues of different histology, radioresistant versus radiosensitive patients, and the combinatorial gene expression associated with chromosomal amplifications are discussed. In particular, CEACAM5 , TACSTD1 , S100P , and MSLN have shown to be upregulated in adenocarcinoma, and increased expression levels of CEACAM5 and TACSTD1 were significantly correlated with poorer patient outcomes. On the other hand, 35 genes, including apoptotic genes (e.g. BIK , TEGT , SSI-3 ), hypoxia-inducible genes (e.g. HIF1A , CA12 ), and tumor cell invasion and metastasis genes (e.g. CTSL , CTSB , PLAU , CD44 ), have been noted to echo the hypothesis that increased tumor hypoxia leads to radiation resistance in cervical cancer during radiation. PMID:18182341

Chao, Angel; Wang, Tzu-Hao; Lai, Chyong-Huey

2007-12-01

222

Combination of proteasome and HDAC inhibitors for therapy of uterine cervical cancer  

PubMed Central

PURPOSE Cervical cancer cells are addicted to the expression of Human Papillomavirus (HPV) oncoproteins E6 and E7. The oncogencity of E6 is mediated in part by targeting p53 and PDZ-family tumor suppressor proteins for rapid proteasomal degradation, whereas E7 oncoprotein acts in part by co-opting histone deacetylases (HDAC)1/2. Here, we examine the hypothesis that inhibition of proteasome function and HDAC activity would synergistically and specifically trigger cervical cancer cell death by the interruption of E6 and E7 signaling. EXPERIMENTAL DESIGN The sensitivity and molecular responses of keratinocytes and HPV-positive and negative cervical cancer cells and xenografts to combinations of proteasome and HDAC inhibitors were tested. The expression of HDAC1/2 in situ was examined in cervical cancer, its precursors and normal epithelium. RESULTS Cervical cancer cell lines exhibit greater sensitivity to proteasome inhibitors than HPV-negative cervical cancers or primary human keratinocytes. Treatment of cervical cancer cells with Bortezomib elevated the level of p53 but not hDlg, hScribble or hMAGI. Immunohistochemical analysis revealed elevated HDAC1/2 expression in CIN and cervical carcinoma versus normal cervical epithelium. The combination of Bortezomib and HDAC inhibitors Trichostatin A (TSA) or Vorinostat show synergistic killing of HPV-positive, but not HPV-negative, cervical cancer cell lines. Similarly, treatment of HeLa xenografts with the combination of Bortezomib and TSA retarded tumor growth significantly more effectively than either agent alone. CONCLUSIONS A combination of proteasome and HDAC inhibitors, including Bortezomib and Vorinostat respectively, warrants exploration for the treatment of cervical cancer.

Lin, Zhenhua; Bazzaro, Martina; Wang, Mei-Cheng; Chan, Kwun C; Peng, Shiwen; Roden, Richard BS

2008-01-01

223

Antigen-specific immunotherapy of cervical and ovarian cancer.  

PubMed

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 causes cervical cancer. Furthermore, cervical cancer patients frequently mount both humoral and T-cell immune responses to the HPV E6 and E7 oncoproteins, whose expression is required for the transformed phenotype. Numerous vaccine studies target these viral TAAs, including recent trials that may enhance clearance of pre-malignant disease. By contrast, little is known about the etiology of epithelial ovarian cancer. Although it is clear that p53 mutation or loss is a critical early event in the development of epithelial ovarian cancer, no precursor lesion has been described for the most common serous histotype, and even the location of its origin is debated. These issues have complicated the selection of appropriate ovarian TAAs and the design of vaccines. Here we focus on mesothelin as a promising ovarian TAA, because it is overexpressed and immunogenic at high frequency in patients, is displayed on the cell surface, and potentially contributes to ovarian cancer biology. PMID:18363994

Hung, Chien-Fu; Wu, T C; Monie, Archana; Roden, Richard

2008-04-01

224

Antigen-specific immunotherapy of cervical and ovarian cancer  

PubMed Central

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

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

2009-01-01

225

Risks of Cervical Cancer Screening  

MedlinePLUS

... black women than in white women. Human papillomavirus (HPV) infection is the major risk factor for cervical ... disease. After certain positive Pap test results, an HPV test may be done. An HPV test is ...

226

Comparison of As2O3 and As4O6 in the Detection of SiHa Cervical Cancer Cell Growth Inhibition Pathway  

PubMed Central

Purpose An arsenical compound, As2O3, has been reported to be effective for treating acute leukemia and inducing apoptosis in many different tumor cells. In this study, the ability of As4O6 to suppress cell growth and induce gene expression patterns was tested using a cDNA microarray in HPV16 immortalized cervical carcinoma cells, SiHa cells, along with As2O3. Materials and Methods A novel arsenical compound, As4O6, was designed and its ability to induce cell growth inhibition as well as gene expression profiles along with As2O3 in HPV16 infected SiHa cervical cancer cells was compared. Both As2O3 and As4O6 induced apoptosis in SiHa cells, as determined by DNA ladder formation. To further compare the gene expression profiles between these two drugs, a 384 cDNA microarray system was employed. Also, the gene expression profiles were classified into the Gene Ontology (GO) to investigate apoptosis-related cellular processes. Results As4O6 was more effective i suppressing the growth of SiHa cells in vitro compared to As2O3. In the case of treatment with As2O3, 41 genes were up- or down-regulated at least 2 fold compared to non-treatment. However, 65 genes were up- or down-regulated by As4O6 treatment. In particular, 27 genes were commonly regulated by both arsenic compounds. Also, the GO analysis indicated that down-regulation of cell-regulatory functions, such as cell cycle, protein kinase activity and DNA repair, induced anti-tumor effect. Conclusion These data support that As4O6 could be more effective than As2O3 in inhibiting the growth of HPV16 infected cervical cancer cells. This appears to be mediated through a unique, but overlapping regulatory mechanism(s), suggesting that the regulated genes and cellular processes could be further used as a new potential drug approach for treating cervical cancer in clinical settings.

Kim, Yong Wook; Bae, Su Mi; Lee, Keun Ho; Lee, Joon Mo; Namkoong, Sung Eun; Lee, Insu P.; Kim, Chong Kook; Seo, Jeong-Sun; Sin, Jeong-Im; Kim, Yong-Wan

2004-01-01

227

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

PubMed

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

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

2012-04-15

228

The Cytotoxicity Mechanism of 6-Shogaol-Treated HeLa Human Cervical Cancer Cells Revealed by Label-Free Shotgun Proteomics and Bioinformatics Analysis  

PubMed Central

Cervical cancer is one of the most common cancers among women in the world. 6-Shogaol is a natural compound isolated from the rhizome of ginger (Zingiber officinale). In this paper, we demonstrated that 6-shogaol induced apoptosis and G2/M phase arrest in human cervical cancer HeLa cells. Endoplasmic reticulum stress and mitochondrial pathway were involved in 6-shogaol-mediated apoptosis. Proteomic analysis based on label-free strategy by liquid chromatography chip quadrupole time-of-flight mass spectrometry was subsequently proposed to identify, in a non-target-biased manner, the molecular changes in cellular proteins in response to 6-shogaol treatment. A total of 287 proteins were differentially expressed in response to 24 h treatment with 15 ?M 6-shogaol in HeLa cells. Significantly changed proteins were subjected to functional pathway analysis by multiple analyzing software. Ingenuity pathway analysis (IPA) suggested that 14-3-3 signaling is a predominant canonical pathway involved in networks which may be significantly associated with the process of apoptosis and G2/M cell cycle arrest induced by 6-shogaol. In conclusion, this work developed an unbiased protein analysis strategy by shotgun proteomics and bioinformatics analysis. Data observed provide a comprehensive analysis of the 6-shogaol-treated HeLa cell proteome and reveal protein alterations that are associated with its anticancer mechanism.

Liu, Qun; Peng, Yong-Bo; Qi, Lian-Wen; Cheng, Xiao-Lan; Xu, Xiao-Jun; Liu, Le-Le; Liu, E-Hu; Li, Ping

2012-01-01

229

International study identifies the origins of cervical cancer  

Cancer.gov

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

230

Screening for cervical cancer by direct inspection  

Microsoft Academic Search

OBJECTIVE--To assess the efficacy of visual screening for cervical cancer in the maternal and child health setting. DESIGN--Clinical and cytological screening. SETTING--Maternal and child health centres, Delhi. SUBJECTS--44,970 women attending the centres from May 1988 to March 1991. RESULTS--238 cancers in early stages (0-IIa) were detected cytologically and proved through biopsy. Prevalence of cancer in women defined as high risk

V. Singh; A. Sehgal; U. K. Luthra

1992-01-01

231

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

PubMed

Inonotus obliquus is a medicinal mushroom that has been used as an effective agent to treat various diseases such as diabetes, tuberculosis and cancer. Inotodiol, an included triterpenoid shows significant anti-tumor effect. However, the mechanisms have not been well documented. In this study, we aimed to explore the effect of inotodiol on proliferation and apoptosis in human cervical cancer HeLa cells and investigated the underlying molecular mechanisms. HeLa cells were treated with different concentrations of inotodiol. The MTT assay was used to evaluate cell proliferating ability, flow cytometry (FCM) was employed for cell cycle analysis and cell apoptosis, while expression of cyclinE, p27, bcl-2 and bax was detected by immunocytochemistry. Proliferation of HeLa cells was inhibited by inotodiolin a dose-dependent manner at 24h (r=0.9999, p<0.01). A sub-G1 peak (apoptotic cells) of HeLa cells was detected after treatment and the apoptosis rate with the concentration and longer incubation time (r=1.0, p<0.01), while the percentage of cells in S phase and G2/M phase decreased significantly. Immunocytochemistry assay showed that the expression of cyclin E and bcl-2 in the treated cells significantly decreased, while the expression of p27 and bax obviously increased, compared with the control group (p<0.05). The results of our research indicate that inotodiol isolated from Inonotus obliquus inhibited the proliferation of HeLa cells and induced apoptosis in vitro. The mechanisms may be related to promoting apoptosis through increasing the expression of bax and cutting bcl-2 and affecting the cell cycle by down-regulation the expression of cyclin E and up-regulation of p27. The results further indicate the potential value of inotodiol for treatment of human cervical cancer. PMID:24815470

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

2014-01-01

232

Claudin 1 expression characterizes human uterine cervical reserve cells.  

PubMed

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

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

2013-12-01

233

The role of MALAT1 correlates with HPV in cervical cancer  

PubMed Central

Cervical cancer, the second most common type of cancer in women worldwide, is responsible for >275,100 mortalities each year and is associated with high-risk human papilloma virus (HR-HPV). HPVs have two important oncogenes, E6 and E7, which have crucial roles in malignant transformation in cervical cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA originally identified in non-small cell lung cancer. Previous studies have revealed that MALAT1 is expressed in numerous tissue types, and is significant in maintaining the normal function of the body. However, it also appeared to be notably upregulated in numerous carcinoma types compared with adjacent non-cancerous tissues. In the present study, it was identified that MALAT1 expression was upregulated in cervical cancer cell lines compared with normal cervical squamous cell samples. Further study into the effect of MALAT1 on cellular phenotype revealed that MALAT1 was able to promote cell migration and proliferation. Of note, it was revealed that the expression of MALAT1 was decreased with the knockdown of HPV16 E6/E7 in CaSki cells. Furthermore, the investigations in clinical samples also revealed that MALAT1 was expressed in HPV-positive cervical squamous cells, but not in HPV-negative normal cervical squamous cells. These results indicate that HPV correlates with MALAT1 deregulation in cervical cancer.

JIANG, YAN; LI, YUEHUI; FANG, SHUJUAN; JIANG, BINYUAN; QIN, CHANGFEI; XIE, PINGLI; ZHOU, GUOHUA; LI, GUANCHENG

2014-01-01

234

Cervical cancer screening service utilisation in UK.  

PubMed

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

Labeit, Alexander; Peinemann, Frank; Kedir, Abbi

2013-01-01

235

Cervical Cancer Screening Service Utilisation in UK  

PubMed Central

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

Labeit, Alexander; Peinemann, Frank; Kedir, Abbi

2013-01-01

236

CD146 is a potential marker for the diagnosis of malignancy in cervical and endometrial cancer  

PubMed Central

Cluster of differentiation 146 (CD146) is an endothelial cell adhesion molecule which is overexpressed in various types of malignant cancer, including ovarian cancer. However, whether CD146 is overexpressed in another two types of gynecological cancer, cervical cancer and endometrial cancer, remains unclear. In the present study, we showed that CD146 expression levels were higher in cells from cervical cancer and endometrial cancer compared with their corresponding normal tissues, using anti-CD146 mouse antibody AA4 (mAb AA4) and that mAb AA4 exhibited a high performance for specificity, sensitivity and positive predictive value in the detection of these two types of cancer. CD146 expression was positively and significantly correlated with the pathological subtype of cervical cancer and with the histological grade and depth of myometrial invasion in endometrial cancer. In addition, we confirmed that CD146 is present in the majority of blood vessels in cervical and endometrial cancer, suggesting that CD146 may be actively implicated in the metastasis of cervical and endometrial cancer via the vascular system. Thus, this study provides insights for further development of CD146 mAb in the detection of gynecological malignant cancer types and implies that a combined treatment strategy of anti-CD146 immunotherapy with other traditional chemo- or radiotherapy treatments may be a promising approach against cervical and endometrial cancer.

ZHANG, HAOFENG; ZHANG, JUN; WANG, ZHAOQING; LU, DI; FENG, JING; YANG, DONGLING; CHEN, XIUQIN; YAN, XIYUN

2013-01-01

237

Cervical Squamous Cell Carcinoma  

MedlinePLUS

... and about 20 percent are over age 65. Precursor lesions may be found at any age once ... in situ: A condition that may precede cancer (precursor) and may progress to invasive carcinoma. Carcinomain-situ ...

238

A unified sample preparation protocol for proteomic and genomic profiling of cervical swabs to identify biomarkers for cervical cancer screening  

PubMed Central

Cervical cancer screening is ideally suited for the development of biomarkers due to the ease of tissue acquisition and the well-established histological transitions. Furthermore, cell and biologic fluid obtained from cervix samples undergo specific molecular changes that can be profiled. However, the ideal manner and techniques for preparing cervical samples remains to be determined. To address this critical issue a patient screening protein and nucleic acid collection protocol was established. RNAlater was used to collect the samples followed by proteomic methods to identify proteins that were differentially expressed in normal cervical epithelial versus cervical cancer cells. Three hundred ninety spots were identified via two-dimensional difference gel electrophoresis (2-D DIGE) that were expressed at either higher or lower levels (>3-fold) in cervical cancer samples. These proteomic results were compared to genes in a cDNA microarray analysis of microdissected neoplastic cervical specimens to identify overlapping patterns of expression. The most frequent pathways represented by the combined dataset were: cell cycle: G2/M DNA damage checkpoint regulation; aryl hydrocarbon receptor signaling; p53 signaling; cell cycle: G1/S checkpoint regulation; and the endoplasmic reticulum stress pathway. HNRPA2B1 was identified as a biomarker candidate with increased expression in cancer compared to normal cervix and validated by Western blot.

Rader, Janet S.; Malone, James P; Gross, Julia; Gilmore, Petra; Brooks, Rebecca A.; Nguyen, Loan; Crimmins, Dan L.; Feng, Sheng; Wright, Jason D.; Taylor, Nicolas; Zighelboim, Israel; Funk, Margo C; Huettner, Phyllis C.; Ladenson, Jack H.; Gius, David; Townsend, R. Reid

2011-01-01

239

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

PubMed Central

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.

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

2011-01-01

240

NIH Research Leads to Cervical Cancer Vaccine  

MedlinePLUS

Skip Navigation Bar Home Current Issue Past Issues Sexually Transmitted Diseases NIH Research Leads to Cervical Cancer Vaccine Past ... Find Out More For more information on individual sexually transmitted infections, visit www.medlineplus.gov , www3.niaid.nih.gov ...

241

Cervical Cancer Screening and Perceived Information Needs  

ERIC Educational Resources Information Center

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…

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

2005-01-01

242

Neem leaf glycoprotein partially rectifies suppressed dendritic cell functions and associated T cell efficacy in patients with stage IIIB cervical cancer.  

PubMed

Myeloid-derived dendritic cells (DCs) generated from monocytes obtained from stage IIIB cervical cancer (CaCx IIIB) patients show dysfunctional maturation; thus, antitumor T cell functions are dysregulated. In an objective to optimize these dysregulated immune functions, the present study is focused on the ability of neem leaf glycoprotein (NLGP), a nontoxic preparation of the neem leaf, to induce optimum maturation of dendritic cells from CaCx IIIB patients. In vitro NLGP treatment of immature DCs (iDCs) obtained from CaCx IIIB patients results in upregulated expression of various cell surface markers (CD40, CD83, CD80, CD86, and HLA-ABC), which indicates DC maturation. Consequently, NLGP-matured DCs displayed balanced cytokine secretions, with type 1 bias and noteworthy functional properties. These DCs displayed substantial T cell allostimulatory capacity and promoted the generation of cytotoxic T lymphocytes (CTLs). Although NLGP-matured DCs derived from CaCx monocytes are generally subdued compared to those with a healthy monocyte origin, considerable revival of the suppressed DC-based immune functions is noted in vitro at a fairly advanced stage of CaCx, and thus, further exploration of ex vivo and in vivo DC-based vaccines is proposed. Moreover, the DC maturating efficacy of NLGP might be much more effective in the earlier stages of CaCx, where the extent of immune dysregulation is less and, thus, the scope of further investigation may be explored. PMID:21307275

Roy, Soumyabrata; Goswami, Shyamal; Bose, Anamika; Chakraborty, Krishnendu; Pal, Smarajit; Haldar, Atanu; Basu, Parthasarathi; Biswas, Jaydip; Baral, Rathindranath

2011-04-01

243

Neem Leaf Glycoprotein Partially Rectifies Suppressed Dendritic Cell Functions and Associated T Cell Efficacy in Patients with Stage IIIB Cervical Cancer ?  

PubMed Central

Myeloid-derived dendritic cells (DCs) generated from monocytes obtained from stage IIIB cervical cancer (CaCx IIIB) patients show dysfunctional maturation; thus, antitumor T cell functions are dysregulated. In an objective to optimize these dysregulated immune functions, the present study is focused on the ability of neem leaf glycoprotein (NLGP), a nontoxic preparation of the neem leaf, to induce optimum maturation of dendritic cells from CaCx IIIB patients. In vitro NLGP treatment of immature DCs (iDCs) obtained from CaCx IIIB patients results in upregulated expression of various cell surface markers (CD40, CD83, CD80, CD86, and HLA-ABC), which indicates DC maturation. Consequently, NLGP-matured DCs displayed balanced cytokine secretions, with type 1 bias and noteworthy functional properties. These DCs displayed substantial T cell allostimulatory capacity and promoted the generation of cytotoxic T lymphocytes (CTLs). Although NLGP-matured DCs derived from CaCx monocytes are generally subdued compared to those with a healthy monocyte origin, considerable revival of the suppressed DC-based immune functions is noted in vitro at a fairly advanced stage of CaCx, and thus, further exploration of ex vivo and in vivo DC-based vaccines is proposed. Moreover, the DC maturating efficacy of NLGP might be much more effective in the earlier stages of CaCx, where the extent of immune dysregulation is less and, thus, the scope of further investigation may be explored.

Roy, Soumyabrata; Goswami, Shyamal; Bose, Anamika; Chakraborty, Krishnendu; Pal, Smarajit; Haldar, Atanu; Basu, Parthasarathi; Biswas, Jaydip; Baral, Rathindranath

2011-01-01

244

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

245

Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selective tumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells.  

PubMed

The aim of the present study was to investigate the therapeutic efficacy of genetically engineered stem cells (GESTECs) expressing bacterial cytosine deaminase (CD) and/or human interferon-beta (IFN-?) gene against HeLa cervical cancer and the migration factors of the GESTECs toward the cancer cells. Anticancer effect of GESTECs was examined in a co-culture with HeLa cells using MTT assay to measure cell viability. A transwell migration assay was performed so as to assess the migration capability of the stem cells to cervical cancer cells. Next, several chemoattractant ligands and their receptors related to a selective migration of the stem cells toward HeLa cells were determined by real-time PCR. The cell viability of HeLa cells was decreased in response to 5-fluorocytosine (5-FC), a prodrug, indicating that 5-fluorouracil (5-FU), a toxic metabolite, was converted from 5-FC by CD gene and it caused the cell death in a co-culture system. When IFN-? was additionally expressed with CD gene by these GESTECs, the anticancer activity was significantly increased. In the migration assay, the GESTECs selectively migrated to HeLa cervical cancer cells. As results of real-time PCR, chemoattractant ligands such as MCP-1, SCF, and VEGF were expressed in HeLa cells, and several receptors such as uPAR, VEGFR2, and c-kit were produced by the GESTECs. These GESTECs transduced with CD gene and IFN-? may provide a potential of a novel gene therapy for anticervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs. PMID:24008363

Kim, Hye-Sun; Yi, Bo-Rim; Hwang, Kyung-A; Kim, Seung U; Choi, Kyung-Chul

2013-10-01

246

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

PubMed

Although cervical cancer is preventable with early detection, it remains the second most common malignancy among women. An understanding of how proteins change in their expression during a particular diseased state such as cervical cancer will contribute to an understanding of how the disease develops and progresses. Potentially, it may also lead to the ability to predict the occurrence of the disease. With this in mind, we aimed to identify differentially expressed proteins in the plasma of cervical cancer patients. Plasma from control, cervical intraepithelial neoplasia (CIN) grade 3 and squamous cell carcinoma (SCC) stage IV subjects was resolved by two-dimensional gel electrophoresis and the resulting proteome profiles compared. Differentially expressed protein spots were then identified by mass spectrometry. Eighteen proteins were found to be differentially expressed in the plasma of CIN 3 and SCC stage IV samples when compared with that of controls. Competitive ELISA further validated the expression of cytokeratin 19 and tetranectin. Functional analyses of these differentially expressed proteins will provide further insight into their potential role(s) in cervical cancer-specific monitoring and therapeutics. PMID:20093745

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

2009-12-01

247

High expression of octamer transcription factor 1 in cervical cancer  

PubMed Central

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

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

2014-01-01

248

Cervical cancer: issues of sexuality and fertility.  

PubMed

Cervical cancer rates have fallen in the United States; regardless, the disease remains a significant concern for women, especially those who are premenopausal. The management of cervical cancer is dependent on stage of disease at diagnosis, and specific needs emerge for patients both during and following treatment. Over the past decade, the focus has been to maintain adequate tumor control while reducing long-term negative consequences. However, problems with sexuality and fertility persist for women treated for cervical cancer despite these advances. Sexual dysfunction following treatment for gynecologic cancer has been well documented in the literature, and recent studies demonstrate the success of brief psychosexual interventions. Treatment of sexual difficulties in cancer patients can be achieved through the provision of information, support, and symptom management, ideally as part of a sexual health program. Resources are not always available to develop such a program. However, medical professionals can identify individuals and organizations with expertise in treating sexual and fertility concerns, which can be provided to their patients, making help with these problems more accessible as needs arise. PMID:14569851

Carter, Jeanne; Auchincloss, Sarah; Sonoda, Yukio; Krychman, Michael

2003-09-01

249

Optical coherence tomography in diagnosing cervical cancer  

NASA Astrophysics Data System (ADS)

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

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

2000-05-01

250

[Papillomavirus and cervical cancer in Chile].  

PubMed

Molecular, clinical and epidemiological studies have established beyond doubt that human papiloma viruses (HPV) cause cervical cancer. The virus is also associated with genital warts and other less common cancers in oropharynx, vulva, vagina and penis. Worldwide, VPH genotypes 16 and 18 are the most common high risk genotypes, detected in near 70% of women with cervical cancer. The discovery of a cause-effect relationship between several carcinogenic microorganisms and cancer open avenues for new diagnostic, treatment and prevention strategies. In this issue of Revista Médica de Chile, two papers on HPV are presented. Guzman and colleagues demonstrate that HPV can be detected in 66% to 77% of healthy male adolescents bypolymerase chain reaction and that positivity depends on the site of the penis that is sampled. These results support the role of male to female transmission of high risk HPVs in Chile and should lead to even more active educational campaigns. The second paper provides recommendations for HPV vaccine use in Chile, generated by the Immunization Advisory Committee of the Chilean Infectious Disease Society. To issue these recommendations, the Committee analyzes the epidemiological information available on HPV infection and cervical cancer in Chile, vaccine safety and effectiveness data, and describes cost-effectiveness studies. Taking into account that universal vaccination is controversial, the Committee favors vaccine use in Chile and it's incorporation into a national program. However, there is an indication that the country requires the implementation of an integrated surveillance approach including cross matching of data obtained from HPV genotype surveillance, monitoring of vaccination coverage, and surveillance of cervical cancer. The final decision of universal vaccine use in Chile should be based on a through analysis of information.ev Mid Chile PMID:19301766

O'Ryan, Miguel; Valenzuela, María Teresa

2008-11-01

251

CD83 Polymorphisms and Cervical Cancer Risk  

PubMed Central

Objectives Studies have suggested that polymorphisms in genes involved in immune recognition and antigen presentation are associated with cervical cancer risk. We sought to replicate a recent study which reported an association between specific SNPs on CD83 and cervical cancer and to further explore whether effects varied by age, clinical stage (in situ versus invasive), and histology (squamous carcinomas versus adenocarcinomas). Methods We evaluated the association between SNPs on CD83 and cervical cancer in a multicenter case-control study of cervical cancer conducted in the Eastern United States (263 cases, 307 controls), focusing on the five SNPs (RS9296925, RS853360, RS9230, RS9370729, RS750749) previously found to be associated with cervical cancer. We also pooled data from the Eastern U.S. (263 cases) with those from the original report (377 cases) to assess the effects of CD83 on the age at diagnosis, disease stage, and histology. Risk estimates (ORs) and 95% confidence intervals were estimated using logistic regression; trend tests were performed under an additive model. Results Consistent with the original report, carriers of the CT or CC genotypes for one of the five CD83 SNPs evaluated (rs750749) demonstrated a 30% and 50% reduction in disease risk, relative to carriers of the more common TT genotype (p-trend = 0.02). Two additional SNPs also resulted in consistent findings (rs9296925: p-trend = 0.07 and rs9370729: p-trend = 0.08), although the effects observed did not reach statistical significance at the 0.05 level. Pooled evaluation of cases from the two aforementioned studies suggested differences in the distribution of susceptibility alleles by histology; adenocarcinoma cases were more likely to be carriers of the susceptibility alleles for SNP rs9370729 (p-trend = 0.02) and SNP rs750749 (p-trend = 0.09). No differences were observed in the age or stage of diagnosis of carriers for CD83 susceptibility alleles relative to non-carriers. Conclusions We confirm an association between CD83 polymorphisms and cervical cancer and suggest the possibility that CD83-disease associations might be heterogenous by tumor histology.

Yu, Kelly J.; Rader, Janet S.; Borecki, Ingrid; Zhang, Zhengyan; Hildesheim, Allan

2009-01-01

252

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

PubMed Central

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

Jones, Guy; Razdan, Dolly; Cracchiolo, Bernadette; Houck, Karen; Sharer, Leroy

2009-01-01

253

Oxidant\\/anti-oxidant dynamics in patients with advanced cervical cancer: correlation with treatment response  

Microsoft Academic Search

Cervical cancer is the most common cancer in Indian women. Oxidative stress is potentially harmful to cells and ROS are involved\\u000a in multistage carcinogenesis, in initiation and promotion. The aim was to study the alterations in the circulating pro-\\/anti-oxidants\\u000a in advanced cervical cancer patients, before and after neoadjuvant chemoradiation and to assess the relevance of the variation\\u000a in the levels

Alpana Sharma; Medha Rajappa; Abhigyan Satyam; Manoj Sharma

2010-01-01

254

The Influence of Mast Cell Mediators on Migration of SW756 Cervical Carcinoma Cells  

Microsoft Academic Search

The role of mast cell mediators on cervical cancer cell migration was assessed using an in vitro assay of scratch wound healing onto monolayers of HPV18-positive cervical carcinoma cells (SW756). Migration of SW756 cells was accelerated by co-culture with the mast cell line LAD2. This effect was inhibited by the H1R antagonist pyrilamine and the cannabinoid agonists 2-arachidonylglycerol (2AG) and

M. Isolde Rudolph; Yadira Boza; Roger Yefi; Sandra Luza; Edilia Andrews; Alicia Penissi; Pablo Garrido; I. Gina Rojas

2008-01-01

255

Surface protein expression and messenger RNA-splicing analysis of CD44 in uterine cervical cancer and normal cervical epithelium.  

PubMed

Variant CD44 has recently been shown to serve as a metastasis marker in human breast cancer. Certain variant epitopes on primary tumors predict poor survival probabilities for the patients. In this study, immunohistochemical analysis of 16 uterine cervical carcinomas showed strong expression of several CD44 variant epitopes in all samples. In normal cervical epithelia from 5 patients, expression of these epitopes was restricted to particular cell layers, with expression being strong in basal and spinal cells but absent in superficial cells. Fifteen of 16 cancer samples were stained strongly with an antibody which recognizes one particular CD44 epitope that is encoded by both variant exons v7 and v8. This epitope was not detectable in normal cervical epithelium. CD44-mRNA splicing analysis showed qualitative and quantitative differences between malignant and normal tissues with a much more complex splice pattern and high expression of a large CD44 isoform containing variant exons v3 to v10 (including the v7/v8 transition epitope) in about one-half of the cancer samples. Interestingly, patients with lymph node metastases were in this group only. These differences in CD44 epitope expression and mRNA splicing in cervical carcinoma reveal dynamic changes in CD44 expression during carcinogenesis. Such changes could provide metastatic cells with a selective advantage during the carcinogenic process. Furthermore, the v7/v8 epitope may be suitable for screening early stages of cervical cancer. PMID:7516819

Dall, P; Heider, K H; Hekele, A; von Minckwitz, G; Kaufmann, M; Ponta, H; Herrlich, P

1994-07-01

256

Post-irradiation cytology of cervical cancer patients.  

PubMed

The accuracy of cervicovaginal cytology following radiotherapy for cervical cancer is compromised by the anatomical and tissue changes resulting from irradiation. Collection of representative samples may be more difficult, and benign radiation changes, post-irradiation dysplasia, and the frequent occurrence of repair cells and active stromal cells in post-irradiation smears may cause diagnostic problems. Nevertheless, cytology is a valuable tool for the detection of locally recurrent cervical cancer. It is simple and economical to perform at the time of clinical follow-up examination, and may detect occult tumour recurrence. Awareness of the cellular changes resulting from irradiation, and the varied composition of post-irradiation smears may lead to more accurate interpretation of the cytological findings. PMID:1511122

Shield, P W; Daunter, B; Wright, R G

1992-01-01

257

IMP3, a new biomarker to predict progression of cervical intraepithelial neoplasia into invasive cancer.  

PubMed

The expression of IMP3, an oncofetal protein, has been strongly associated with aggressive cancers. In this study, we investigated whether IMP3 can serve as a biomarker to predict invasive squamous cell carcinoma (SCC) in patients with cervical intraepithelial neoplasia (CIN) II and III. A total of 1249 patients with no dysplasia, CINs, or invasive SCC were studied for IMP3 expression. The 710 patients with CIN II and III in their cervical biopsies were further evaluated for invasive cancer-free survival analysis. The role of IMP3 in the regulation of cell proliferation and migration of HeLa cervical cancer cells was examined by modification of IMP3 expression with small interference RNA. Compared with CIN I or cervical tissues without dysplasia, IMP3 expression was significantly increased not only in invasive SCC but also most importantly in a subset of CIN III cases with concurrent invasive SCC. Importantly, invasive cancer was found only in patients with IMP3-positive CIN II and III, whereas no invasive cancer was detected in patients with IMP3-negative CIN II and III in their follow-up resections (P<0.0001). Reduction of IMP3 expression in cervical cancer cells significantly reduced cell migration without altering cell proliferation. IMP3 plays a critical role in the development of invasive SCC from cervical dysplasia. IMP3 can be used at the time of initial diagnosis of CIN to identify a group of patients with an increased chance of developing invasive cancer. PMID:21997684

Lu, Di; Yang, Xiaofang; Jiang, Naomi Y; Woda, Bruce A; Liu, Qin; Dresser, Karen; Mercurio, Arthur M; Rock, Kenneth L; Jiang, Zhong

2011-11-01

258

Review on risk factors of cervical cancer.  

PubMed

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

Chou, P

1991-08-01

259

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

Federal Register 2010, 2011, 2012, 2013

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

2012-11-05

260

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

Federal Register 2010, 2011, 2012, 2013

...Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and...regarding the early detection and control of breast and cervical cancer. The committee makes...Preventive Services Task Force guidelines for breast and cervical cancer screening;...

2010-02-18

261

Diffusion-weighted MRI in cervical cancer  

Microsoft Academic Search

The purpose was to investigate the potential value of apparent diffusion coefficient (ADC) measurement with MRI in the assessment\\u000a of cervix cancer. Diffusion-weighted MRI was performed in 47 patients with cervical carcinoma undergoing chemoradiation therapy\\u000a and 26 normal controls on a 1.5-T system with a b-value of 600 s\\/mm2. FIGO stage, tumor volume, nodal status, interstitial fluid pressure (IFP) and oxygen

Patrick Z. McVeigh; Aejaz M. Syed; Michael Milosevic; Anthony Fyles; Masoom A. Haider

2008-01-01

262

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

PubMed Central

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

Dominguez Hernandez, Karem R.; Aguilar Lasserre, Alberto A.; Posada Gomez, Ruben; Palet Guzman, Jose A.; Gonzalez Sanchez, Blanca E.

2013-01-01

263

Candidate biomarkers for cervical cancer treatment: Potential for clinical practice (Review)  

PubMed Central

Cervical cancer ranks high among the causes of female cancer mortalities and is an important disease in developing and developed countries. Current diagnosis of cervical cancer depends on colposcopy, pathological diagnosis and preoperative diagnosis using methods, including magnetic resonance imaging and computed tomography. Advanced cervical cancer has a poor prognosis. The tumor marker squamous cell carcinoma is conventionally used for screening, but recent studies have revealed the mechanisms of carcinogenesis and the factors associated with a poor prognosis in cervical cancer. These include epigenetic biomarkers, with the methylation level of the checkpoint with forkhead and ring finger gene being potentially useful for predicting the malignancy of cervical cancer and sensitivity to treatment with paclitaxel. The extent of methylation of the Werner DNA helicase gene is also useful for determining sensitivity to an anticancer agent, CPT-11. In addition to epigenetic changes, the expression levels of hypoxia-inducible factor 1? subunit, epidermal growth factor receptor and cyclooxygenase-2 have been reported as possible biomarkers in cervical cancer. Novel prognostic factors, including angiogenic factors, fragile histidine triad, thymidylate synthase, glucose-related protein 58 and mucin antigens, have also been described, and hemoglobin and platelets may also be significant prognostic biomarkers. Utilization of these biomarkers may facilitate personalized treatment and improved outcomes in cervical cancer.

IIDA, MIHO; BANNO, KOUJI; YANOKURA, MEGUMI; NAKAMURA, KANAKO; ADACHI, MASATAKA; NOGAMI, YUYA; UMENE, KIYOKO; MASUDA, KENTA; KISU, IORI; IWATA, TAKASHI; TANAKA, KYOKO; AOKI, DAISUKE

2014-01-01

264

Application of human papillomavirus in screening for cervical cancer and precancerous lesions.  

PubMed

Cervical cancer is a commonly-encountered malignant tumor in women. Cervical screening is particularly important due to early symptoms being deficient in specificity. The main purpose of the study is to assess the application value of cervical thinprep cytologic test (TCT) and human papillomavirus (HPV) detection in screening for cervical cancer and precancerous lesions. In the study, cervical TCT and HPV detection were simultaneously performed on 12,500 patients selected in a gynecological clinic. Three hundred patients with positive results demonstrated by cervical TCT and/or HPV detection underwent cervical tissue biopsy under colposcopy, and pathological results were considered as the gold standard. The results revealed that 200 out of 12,500 patients were abnormal by TCT, in which 30 cases pertained to equivocal atypical squamous cells (ASCUS), 80 cases to low squamous intraepithelial lesion (LSIL), 70 cases to high squamous intraepithelial lesion (HSIL) and 20 cases to squamous cell carcinoma (SCC). With increasing pathological grade of cervical biopsy, however, TCT positive rates did not rise. Two hundred and eighty out of 12,500 patients were detected as positive for HPV infection, in which 50 cases were chronic cervicitis and squamous metaplasia, 70 cases cervical intraepithelial neoplasia (CIN) I, 60 cases CIN II, 70 cases CIN III and 30 cases invasive cervical carcinoma. Two hundred and thirty patients with high-risk HPV infection were detected. With increase in pathological grade, the positive rate of high-risk HPV also rose. The detection rates of HPV detection to CIN III and invasive cervical carcinoma as well as the total detection rate of lesions were significantly higher than that of TCT. Hence, HPV detection is a better method for screening of cervical cancer at present. PMID:23803065

Wang, Jin-Liang; Yang, Yi-Zhuo; Dong, Wei-Wei; Sun, Jing; Tao, Hai-Tao; Li, Rui-Xin; Hu, Yi

2013-01-01

265

Cervical Screening a Study on the Prevalence of the Risk-factors for Developing Cervical Cancer Among Young Women  

Microsoft Academic Search

This study had three aims: to determine the prevalence of the risk-factors for contracting HPV (the Human Papillomavirus) and developing cervical cancer among young women; to establish if there are any links between the presence of these risk-factors, attendance for cervical screening and abnormal cervical screening results; and to ascertain the key barriers to the prevention of cervical cancer. The

Jennifer Cann

2008-01-01

266

Epigenetics and cervical cancer: from pathogenesis to therapy.  

PubMed

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

Fang, Jinchuan; Zhang, Hai; Jin, Sufang

2014-06-01

267

miR-375 is upregulated in acquired paclitaxel resistance in cervical cancer  

PubMed Central

Background: Chemo-resistance is one of the key causal factors in cancer death and emerging evidences suggest that microRNAs (miRNAs) have critical roles in the regulation of chemo-sensitivity in cancers. Cervical cancer is one of the most common malignancies in women and insensitive to chemotherapy clinically. Methods: The differentially expressed miRNAs in cervical squamous cell carcinoma tissues were screened by using a microarray platform (?Paraflo Sanger miRBase release 13.0). The expression of miR-375 was determined by stem-loop RT–PCR using 23 clinical cervical cancer samples and 2 cervical cancer cell lines. We exogenously upregulated miR-375 expression in SiHa and Caski cells using a pre-miRNA lentiviral vector transfection and observed its impact on paclitaxel sensitivity using MTS. The cells that stably overexpressed miR-375 were subcutaneously injected into mice to determine tumour growth and chemo-sensitivity in vivo. Results: Twenty-one differentially expressed miRNAs were found by miRNA microarray between pro- and post-paclitaxel cervical cancer tissues. Of those, miR-375 showed consistent high expression levels across paclitaxel-treated cervical cells and tissues. Paclitaxel induced upregulated miR-375 expression in a clear dose-dependent manner. Forced overexpression of miR-375 in cervical cancer cells decreased paclitaxel sensitivity in vitro and in vivo. Conclusion: Collectively, our results suggest that miR-375 might be a therapeutic target in paclitaxel-resistant cervical cancer.

Shen, Y; Wang, P; Li, Y; Ye, F; Wang, F; Wan, X; Cheng, X; Lu, W; Xie, X

2013-01-01

268

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

PubMed

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

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

2014-02-01

269

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

PubMed Central

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

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

2013-01-01

270

Breast and Cervical Cancer Legislation  

MedlinePLUS

... Provider Near You About the Program The NBCCEDP Conceptual Framework Social Ecological Model Screening Program Data Screening Program Summaries Training Breast Cancer Self-Study Modules Workplans Introduction Case Study Goals Measures of Success Objectives Activities Data Time Frame ...

271

Expression of vascular endothelial growth factor (VEGF) and its mRNA in uterine cervical cancers  

PubMed Central

To know the potential of growth, invasion and metastasis of uterine cervical cancer associated with neovascularization, localization of vascular endothelial growth factor (VEGF) and microvessel density in tumours were determined by immunohistochemical staining, the levels of VEGF subtypes were determined by Western blot analysis and by a sandwich enzyme immunoassay, and the levels of VEGF subtype mRNAs were determined by reverse transcription polymerase chain reaction (RT-PCR) – Southern blot analysis in uterine cervical cancers. The relation between VEGF subtype expressions and microvessel density, histological types and clinical stages of uterine cervical cancers was analysed. The expression of VEGF was seen dominantly in the cancer cells, and correlated with microvessel density in uterine cervical cancers. Among the four subtypes of VEGF, the populations of VEGF165 and VEGF121 were dominant in normal uterine cervices and uterine cervical cancers. The levels of VEGF and VEGF165 and VEGF121 mRNAs were remarkably higher in some stage II and III/IV adenocarcinomas of the cervix than in other cases, including normal cervices. Therefore, the elevation of VEGF165 and VEGF121 might contribute to the relatively late advancing via angiogenic activity in some adenocarcinomas of the cervix. © 1999 Cancer Research Campaign

Fujimoto, J; Sakaguchi, H; Hirose, R; Ichigo, S; Tamaya, T

1999-01-01

272

Interferon-? Induced microRNA-129-5p Down-Regulates HPV-18 E6 and E7 Viral Gene Expression by Targeting SP1 in Cervical Cancer Cells  

PubMed Central

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

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

2013-01-01

273

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

PubMed Central

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

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

2014-01-01

274

Human Papillomavirus Testing in the Prevention of Cervical Cancer  

PubMed Central

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

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

2011-01-01

275

Characterization of LMX-1A as a metastasis suppressor in cervical cancer.  

PubMed

DNA methylation is important in cancer development and is a promising biomarker for cancer detection. An epigenomic approach used in our previous work showed that LMX-1A is methylation-silenced in cervical cancer. LMX-1A, a LIM-homeobox gene, is known to participate in developmental events; however, there are at present no data on the role of LMX-1A in cancers. In this study, we characterized the function of this transcription factor by examining cell lines, animal models and human cervical neoplastic tissues, and found that over-expression of LMX-1A does not affect cell proliferation or the cell cycle of cervical cancer cell lines but significantly inhibits colony formation and invasion in vitro. Analysis of changes in epithelial-mesenchymal transition (EMT) markers, such as CDH1, CDH2, VIMENTIN, SNAIL, SLUG and TWIST, revealed involvement of the EMT in LMX-1A-mediated cancer invasion; this result was validated in a stable transfectant over-expressing LMX-1A with RNA interference. Xenograft studies using immunocompromised mice confirmed the suppressor effects of LMX-1A on tumour formation and distant metastasis in cervical cancer cell lines. LMX-1A immunohistochemical staining of tissue arrays containing the full spectrum of cervical neoplasms, including normal cervix, low-grade cervical intra-epithelial neoplasia (CIN), high-grade CIN, locally invasive and distant metastatic cancers, demonstrated the critical role of LMX-1A in invasion and metastasis. Furthermore, we found by analysing TGFbeta-BMP signalling that BMP4 and BMP6 are down-regulated by LMX-1A. The results of this study suggest that LMX-1A suppresses cancer invasion and metastasis in cervical cancer through an incomplete EMT. PMID:19644956

Liu, Chin-Yu; Chao, Tai-Kuang; Su, Po-Hsuan; Lee, Hsin-Yi; Shih, Yu-Lueng; Su, Her-Young; Chu, Tang-Yuan; Yu, Mu-Hsien; Lin, Ya-Wen; Lai, Hung-Cheng

2009-10-01

276

Near-Infrared Micro-Raman Spectroscopy for in Vitro Detection of Cervical Cancer  

PubMed Central

Near-infrared Raman spectroscopy is a powerful analytical tool for detecting critical differences in biological samples with minimum interference in the Raman spectra from the native fluorescence of the samples. The technique is often suggested as a potential screening tool for cancer. In this article we report in vitro Raman spectra of squamous cells in normal and cancerous cervical human tissue from seven patients, which have good signal-to-noise ratio and which were found to be reproducible. These preliminary results show that several Raman features in these spectra could be used to distinguish cancerous cervical squamous cells from normal cervical squamous cells. In general, the Raman spectra of cervical cancer cells show intensity differences compared to those of normal squamous cell spectra. For example, several well-defined Raman peaks of collagen in the 775 to 975 cm ?1 region are observed in the case of normal squamous cells, but these are below the detection limit of normal Raman spectroscopy in the spectra of invasive cervical cancer cells. In the high frequency 2800 to 3100 cm ?1 region, it is found that the peak area under the CH stretching band is lower by a factor of approximately six in the spectra of cervical cancer cells as compared with that of the normal cells. The Raman chemical maps of regions of cancer and normal cells in the cervical epithelium made from the spectral features in the 775 to 975 cm ?1 and 2800 to 3100 cm ?1 regions are also found to show good correlation with each other.

KAMEMOTO, LORI E.; MISRA, ANUPAM K.; SHARMA, SHIV K.; GOODMAN, MARC T.; LUK, HUGH; DYKES, AVA C.; ACOSTA, TAYRO

2010-01-01

277

Telomerase Activity and Expression of Telomerase RNA Component and Telomerase Catalytic Subunit Gene in Cervical Cancer  

Microsoft Academic Search

Telomerase, a ribonucleoprotein complex that in- cludes the telomerase RNA component (hTR) and the telomerase catalytic subunit gene (hTERT) product, has been shown to be activated in the majority of cancer tissues and immortalized cells. To study telom- erase activation during the progression of cervical cancer, the expression of hTR and hTERT RNAs in tissues of various stages of cervical

Kenji Nakano; Elizabeth Watney; James K. McDougall

1998-01-01

278

Burden of cervical cancer in Europe: estimates for 2004  

Microsoft Academic Search

The European Council recommends that organised cervical cancer screening be offered in all member states. In order to evaluate the impact of existing and new prevention methods, regularly updated information on the burden of cervical cancer is needed. The best estimates of mortality and incidence rates were applied to the 2004 projected population of 40 European countries using methods developed

M. Arbyn; A. O. Raifu; P. Autier; J. Ferlay

2007-01-01

279

Social Construction of Cervical Cancer Screening among Panamanian Women  

ERIC Educational Resources Information Center

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

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

2012-01-01

280

Posttherapy Surveillance of Women with Cervical Cancer: An Outcomes Analysis  

Microsoft Academic Search

Objective. The aim of this study was to develop a surveillance program that optimizes clinical outcome following primary treatment of women with cervical cancer.Methods. The records of 1096 patients with FIGO stage IB cervical cancer treated from 1983 to 1993 were retrospectively reviewed. Recurrence was analyzed by site, presence or absence of symptoms, method of detection, and survival. Univariate and

Diane Bodurka-Bevers; Mitchell Morris; Patricia J. Eifel; Charles Levenback; Michael W. Bevers; Kristin R. Lucas; J. Taylor Wharton

2000-01-01

281

Incidence and mortality of cervical cancer in Latin America  

Microsoft Academic Search

Cervical cancer incidence and mortality estimates for 2000 are presented for the 21 Latin American countries, using estimates from the statistical package GLOBOCAN 2000. Additional data on time-trends are also presented, using the WHO mortality database. By the year 2000, some 76 000 cervical cancer and almost 30 000 deaths were estimated for the whole region, which represent 16% and

Silvina Arrossi; Rengaswamy Sankaranarayanan; Donald Maxwell Parkin

2003-01-01

282

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

PubMed Central

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.

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

2009-01-01

283

DNA vaccines for cervical cancer: from bench to bedside  

PubMed Central

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.

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

2011-01-01

284

Mitochondrial DNA variation analysis in cervical cancer.  

PubMed

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

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

285

Histone deacetylase inhibitor BML-210 induces growth inhibition and apoptosis and regulates HDAC and DAPC complex expression levels in cervical cancer cells.  

PubMed

Histone deacetylase inhibitors (HDACIs) represent a new class of targeted anti-cancer agents and different other diseases, like muscular disorders. A number of studies have shown that extracellular signal-activated kinases can target chromatin-modifying complexes directly and regulate their function. The molecular connection between the dystrophin-associated protein complex (DAPC) and chromatin has been described, by showing that NO signaling regulates histone deacetylase (HDAC) activity and influences gene expression in different cell types. In present study, we investigated HDACs changes in HeLa cells undergoing growth inhibition and apoptosis, caused by HDACI BML-210 and retinoic acid (ATRA). Cell cycle analysis indicated that HeLa cell treatment with 20 and 30 ?M concentration of BML-210 increased the proportion of cells in G0/G1 phase, and caused accumulation in subG1, indicating that the cells are undergoing apoptosis. We determined down-regulation of HDAC 1-5 and 7 after treatment with BML-210. Also, we demonstrated expression of different isoforms of alpha-dystrobrevin (?-DB) and other components of DAPC such as syntrophin, dystrophin, beta-dystrobrevin (?-DB) and NOS in HeLa cells after treatments. We determined changes in protein expression level of dystrophin, NOS1, ?- and ?-DB and in subcellular localization of ?-DB after treatments with BML-210 and ATRA. In conclusion, these results suggest that HDACI BML-210 can inhibit cell growth and induce apoptosis in cervical cancer cells, what correlates with down-regulation of HDAC class I and II and changes in the DAPC expression levels. This can be important for identifying target proteins in DAPC signaling to HDACs, as a target of pharmacological intervention for treatment of muscular dystrophies and other diseases. PMID:23007576

Borutinskaite, Veronika V; Magnusson, Karl-Eric; Navakauskiene, Ruta

2012-12-01

286

Synaptonemal Complex Protein 3 Is a Prognostic Marker in Cervical Cancer  

PubMed Central

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

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

2014-01-01

287

HPV-based Tests for Cervical Cancer Screening and Management of Cervical Disease  

PubMed Central

Current cervical cancer screening programs are changing due to the development of tests that detect the presence of human papillomavirus (HPV), the cause of cervical cancer. These tests are more sensitive than cytology-based methods for detecting cervical precancer and a negative test offers long-term assurance that cervical cancer will not develop and therefore longer screening intervals can be achieved. In screening programs, HPV-based tests have been approved to triage women with equivocal cytology results and as a primary testing method in conjunction with cytology. HPV-based tests also have a role in determining risk of recurrence after treatment for cervical precancer as well as in surveillance for vaccine-related changes in HPV genotype prevalence.

Luhn, Patricia; Wentzensen, Nicolas

2013-01-01

288

Less Radical Surgery for Patient With Early-Stage Cervical Cancer  

PubMed Central

Introduction Surgery in cervical cancer should be used with intention of cure. Radical abdominal trachelectomy is a feasible operation for selected patients with stage I?-1? cervical cancer which fertility can be preserved. Case Report A 30-years-old woman with squamous cell cervical cancer stage (1 A II) diagnosed at September 2011 expressed a wish for fertility-sparing treatment. Radical abdominal hysterectomy and pelvic and para-aortic lymphadenectomy were performed which showed no evidence of lymphatic metastasis. Subsequently, at last follow-up (5 months post-surgery), good oncologic outcomes were found after this procedure. This was the first case of fertility-sparing radical trachelectomy procedures performed at our institution. Conclusions Trachelectomy represents a valuable conservative surgical approach for early stage invasive cervical cancer.

Yousefi, Zohreh; Kazemianfar, Zahra; Kadghodayan, Sima; Hasanzade, Malieheh; Kalantari, Mahmoudreza; Mottaghi, Mansoureh

2013-01-01

289

Cervical cancer prevention: new tools and old barriers.  

PubMed

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

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

290

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

PubMed

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

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

2014-06-01

291

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

PubMed

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

Kessler, I I

1977-04-01

292

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

PubMed

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

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

2014-07-01

293

The Interplay Between Secondhand Cigarette Smoke, Genetics, and Cervical Cancer: A Review of the Literature  

Microsoft Academic Search

Research has suggested a link between smoking and cervical cancer; however, little data are available on secondhand smoke (SHS) exposure and cervical cancer risk. This article reviews the literature on the links among smoking, SHS exposure and cervical cancer. The review was based on a search of electronic databases. The research reviewed clearly showed that smoking increases cervical cancer risk

Natalie Pate Capps; Ayasha Stewart; Cindy Burns

2009-01-01

294

Detection of human papillomavirus DNA in breast cancer of patients with cervical cancer history  

Microsoft Academic Search

Background: Recent studies have revealed a possible role for the human papillomavirus (HPV) in the pathogenesis of breast cancer. In this study, patients having both a history of invasive cervical cancer and breast cancer as second primary cancer were selected for enrolment in a study of breast carcinomas for the presence of HPV. Methods: Paraffin-embedded tissue from cervical cancer, pelvic

Andreas Widschwendter; Thomas Brunhuber; Annemarie Wiedemair; Elisabeth Mueller-Holzner; Christian Marth

2004-01-01

295

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

PubMed Central

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

Austin, R. Marshall; Zhao, Chengquan

2014-01-01

296

Adaptive management of cervical cancer radiotherapy.  

PubMed

Since the breakthrough 10 years ago with concomitant radio-chemotherapy, substantial progress in the treatment of locally advanced cervical cancer has been lacking. Radiotherapy continues to be the cornerstone in the treatment of this disease and now shows much potential for progress, as image guidance of both external beam radiation therapy and brachytherapy, linked with strong tools for treatment planning and dose delivery, is becoming available. With these new techniques, it again seems possible to improve the therapeutic ratio as we begin to understand how the treatment for each patient can be individualized, not only in terms of volume (3-dimensional), but also during treatment (4-dimensional), as the tumor regresses and the topography of the target and organs at risk change significantly. New promising data with increased loco-regional control and decreased morbidity compared with the past are appearing. At the dawn of this new era, it is the aim of the present article to give an overview of the use of image-guided adaptive radiotherapy in the multimodal management of locally advanced cervical cancer. PMID:20219550

Tanderup, Kari; Georg, Dietmar; Pötter, Richard; Kirisits, Christian; Grau, Cai; Lindegaard, Jacob C

2010-04-01

297

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

PubMed Central

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.

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

2014-01-01

298

CpG Methylation of Human Papillomavirus Type 16 DNA in Cervical Cancer Cell Lines and in Clinical Specimens: Genomic Hypomethylation Correlates with Carcinogenic Progression  

Microsoft Academic Search

Infection with genital human papillomaviruses (HPVs) is the primary cause of cervical cancer. The infection is widespread, and little is known about the secondary factors associated with progression from subclinical infection to invasive carcinoma. Here we report that HPV genomes are efficiently targeted in vivo by CpG methylation, a well-known mechanism of transcriptional repression. Indeed, it has been shown previously

Vinay Badal; Linda S. H. Chuang; Eileen Hwee-Hong Tan; Sushma Badal; Luisa L. Villa; Cosette M. Wheeler; Benjamin F. L. Li; Hans-Ulrich Bernard

2003-01-01

299

Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study  

PubMed Central

Background: Infection with human papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN). Variability in host immunogenetic background is important in determining the overall cellular immune response to HPV infections. Objective: To determine whether the HLA-DQ or HLA-DR genes, or others in their vicinity, are associated with cervical cancer. Methods: Markers covering the entire HLA region were genotyped in a large sample of CIN and cervical cancer patients and in controls (311 CIN, 695 cervical cancer, 115 family controls, and 586 unrelated controls). Results: Two markers were associated with susceptibility to cervical neoplasia, G511525 and MICA. G511525, close to the region containing the HLA-DQ and HLA-DR genes, was most strongly associated, showing a decrease in frequency of allele 221 from 6.7% to 3.3% in patients with squamous cell cancer (SCC). An association was found for MICA (allele 184) with SCC (odds ratio (OR) = 1.31 (95% confidence interval, 1.13 to 1.53); homozygotes, OR = 1.48 (1.06 to 2.06)). No associations were observed with adenocarcinoma or CIN. Conclusions: There is an association of the region containing the HLA-DQ and HLA-DR genes with the risk of developing squamous cell carcinoma. An increased risk was observed for carriers of allele 184 at the MICA locus, in particular for homozygotes, suggesting a recessive effect.

Zoodsma, M; Nolte, I; Schipper, M; Oosterom, E; van der Steege, G; de Vries, E G E; te Meerman, G J; van der Zee, A G J

2005-01-01

300

Postmodern cancer: the role of human immunodeficiency virus in uterine cervical cancer  

PubMed Central

The association between cervical cancer and human papillomavirus (HPV) is well known, but its association with human immunodeficiency virus (HIV) is controversial. Coinfection with HPV and HIV is to be expected and recent epidemiological data from Africa show that cervical cancer is the most common AIDS defining neoplasm in women. Unlike other AIDS defining neoplasms, the occurrence of cervical cancer is not dependent on immune compromise. HIV alters the natural history of HPV infection, with decreased regression rates and more rapid progression to high grade and invasive lesions, which are refractory to treatment, requiring more stringent intervention and monitoring. The more aggressive behaviour is mirrored by a different molecular pathway. HIV associated cervical cancers are thought to progress through the microsatellite instability pathway, whereas HIV negative ones progress through loss of heterozygosity. Interaction is probably via viral proteins, with HIV proteins enhancing effectiveness of HPV proteins, and perhaps contributing to cell cycle disruption. Dysregulation of the cellular and humoral arms of the local and systemic immune systems may ensure disease progression. Furthermore, HPV infection may predispose to HIV infection and facilitate its progression.

Clarke, B; Chetty, R

2002-01-01

301

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

PubMed Central

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.

Kou, Iemasa; Date, Kenjiro; Nakayama, Hirofumi

2013-01-01

302

2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors.  

PubMed

A group of 47 experts representing 23 professional societies, national and international health organizations, and federal agencies met in Bethesda, MD, September 14-15, 2012, to revise the 2006 American Society for Colposcopy and Cervical Pathology Consensus Guidelines. The group's goal was to provide revised evidence-based consensus guidelines for managing women with abnormal cervical cancer screening tests, cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS) following adoption of cervical cancer screening guidelines incorporating longer screening intervals and co-testing. In addition to literature review, data from almost 1.4 million women in the Kaiser Permanente Northern California Medical Care Plan provided evidence on risk after abnormal tests. Where data were available, guidelines prescribed similar management for women with similar risks for CIN 3, AIS, and cancer. Most prior guidelines were reaffirmed. Examples of updates include: Human papillomavirus-negative atypical squamous cells of undetermined significance results are followed with co-testing at 3 years before return to routine screening and are not sufficient for exiting women from screening at age 65 years; women aged 21-24 years need less invasive management, especially for minor abnormalities; postcolposcopy management strategies incorporate co-testing; endocervical sampling reported as CIN 1 should be managed as CIN 1; unsatisfactory cytology should be repeated in most circumstances, even when HPV results from co-testing are known, while most cases of negative cytology with absent or insufficient endocervical cells or transformation zone component can be managed without intensive follow-up. PMID:23635684

Massad, L Stewart; Einstein, Mark H; Huh, Warner K; Katki, Hormuzd A; Kinney, Walter K; Schiffman, Mark; Solomon, Diane; Wentzensen, Nicolas; Lawson, Herschel W

2013-04-01

303

2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors.  

PubMed

A group of 47 experts representing 23 professional societies, national and international health organizations, and federal agencies met in Bethesda, MD, September 14-15, 2012, to revise the 2006 American Society for Colposcopy and Cervical Pathology Consensus Guidelines. The group's goal was to provide revised evidence-based consensus guidelines for managing women with abnormal cervical cancer screening tests, cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS) following adoption of cervical cancer screening guidelines incorporating longer screening intervals and co-testing. In addition to literature review, data from almost 1.4 million women in the Kaiser Permanente Northern California Medical Care Plan provided evidence on risk after abnormal tests. Where data were available, guidelines prescribed similar management for women with similar risks for CIN 3, AIS, and cancer. Most prior guidelines were reaffirmed. Examples of updates include: Human papillomavirus-negative atypical squamous cells of undetermined significance results are followed with co-testing at 3 years before return to routine screening and are not sufficient for exiting women from screening at age 65 years; women aged 21-24 years need less invasive management, especially for minor abnormalities; postcolposcopy management strategies incorporate co-testing; endocervical sampling reported as CIN 1 should be managed as CIN 1; unsatisfactory cytology should be repeated in most circumstances, even when HPV results from co-testing are known, while most cases of negative cytology with absent or insufficient endocervical cells or transformation zone component can be managed without intensive follow-up. PMID:23519301

Massad, L Stewart; Einstein, Mark H; Huh, Warner K; Katki, Hormuzd A; Kinney, Walter K; Schiffman, Mark; Solomon, Diane; Wentzensen, Nicolas; Lawson, Herschel W

2013-04-01

304

Update on the treatment of advanced cervical cancer.  

PubMed

In this review we discuss the most important issues concerning the treatment of advanced cervical cancer. Advances in the treatment of cervical cancer are made slowly, but recently the data from five important randomised studies gave rise to an important change in the standard treatment of this disease. For the new standard in advanced cervical cancer, it is clear that chemotherapy should be added to the radiation regimen for an optimal treatment. However, firm conclusions to which drugs or regimens cannot be drawn at this moment. PMID:12270781

Witteveen, P O; Verhaar, M J; Jürgenliemk-Schulz, I M; van Eijkeren, M A

2002-09-01

305

Primary Strategies for HPV Infection and Cervical Cancer Prevention.  

PubMed

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

Harper, Diane M; Demars, Leslie R

2014-06-01

306

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

PubMed

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

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

2014-03-01

307

Magnetic resonance imaging of endometrial and cervical cancer.  

PubMed

In this article we review the current and developing roles of magnetic resonance imaging (MRI) in endometrial and cervical cancer. In endometrial cancer, the purpose of MRI is to stage the primary tumor and in particular to identify myometrial and cervical invasion and extra-uterine disease, thereby informing preoperative surgical planning. MRI is also used to safely select young patients suitable for fertility-preserving medical management. In cervical cancer, MRI has an established role in local staging and in assessing proximal extension of tumors in young women for feasibility of fertility-preserving surgery. It is used to plan radiotherapy for primary tumors in cervical cancer and particularly for conformal radiotherapy to deliver optimal doses to the tumor sites, while limiting unwanted exposure of bowel and other pelvic organs. In both cancers, MRI is used for diagnosing nodal disease, surveillance, detection of recurrence, and evaluation of complications secondary to treatment. PMID:18837902

Sahdev, Anju; Reznek, Rodney H

2008-09-01

308

Preventive and Therapeutic Vaccines against Human Papillomaviruses Associated Cervical Cancers  

PubMed Central

Cervical cancer is, globally known to be, one of the most common cancers among women especially in developing countries. More than 90% of cervical cancers are associated with high-risk human papillomaviruses (HPVs) particularly HPV types 16 and 18. Two major strategies have been developed for prevention and treatment of cervical cancer and other HPV-associated malignancies; the first one is based on HPV virus-like particles (VLPs) containing HPV structural proteins. VLP based vaccines can induce genotype specific virus neutralizing antibodies for preventing HPV infections. The other strategy is based on HPV early genes especially E6 and E7 for eliminating the established HPV infections; therefore they are classified as HPV therapeutic vaccines. This article reviews the preventive and therapeutic vaccines against HPV infections and cervical cancer.

Nayereh, Khadem Ghaebi; Khadem, Ghaeb

2012-01-01

309

Pathways of cervical cancer screening among Chinese women  

PubMed Central

Background The purpose of this community-based study was to develop a structural equation model for factors contributing to cervical cancer screening among Chinese American women. Methods A cross-sectional design included a sample of 573 Chinese American women aged 18 years and older. The initial step involved use of confirmatory factor analysis, that included the following variables: access to and satisfaction with health care, and enabling and predisposing cultural and health beliefs. Structural equation model analyses were conducted on factors related to cervical cancer screening. Results Age, marital status, employment, household income, and having health insurance, but not educational level, were significantly related to cervical screening status. Predisposing and enabling factors were positively associated with cervical cancer screening. The cultural factor was significantly related to the enabling factor or the satisfaction with health care factor. Conclusion This model highlights the significance of sociocultural factors in relation to cervical cancer screening. These factors were significant, with cultural, predisposing, enabling, and health belief factors and access to and satisfaction with health care reinforcing the need to assist Chinese American women with poor English fluency in translation and awareness of the importance of cervical cancer screening. Community organizations may play a role in assisting Chinese American women, which could enhance cervical cancer screening rates.

Ma, Grace X; Wang, Min Qi; Ma, Xiang S; Shive, Steven E; Tan, Yin; Toubbeh, Jamil I

2013-01-01

310

Virus Isolation and Identification in Cervical Cancer Patients.  

National Technical Information Service (NTIS)

7 strains of viruses were isolated from cervical specimens of cervical cancer patients. The viral isolates were herpes simplex viruses according to the morphologic, biologic as well as serologic characteristics. 5 of the 7 strains were typed and 3 were he...

J. Xiang J. Feng P. Huang W. Chen J. Wu

1982-01-01

311

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

PubMed Central

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

2010-01-01

312

Cervical Cancer Prevention: More than Just a Pap in a Diverse Urban Community  

Microsoft Academic Search

Cervical cytologic screening and early management of abnormal pap smears played an important role in reducing invasive cervical cancer incidence and mortality over the past decades. Despite widely available cost effective screening for cervical cancer in the United States, women in lower socioeconomic groups and minorities continue to suffer from a higher incidence and mortality from cervical cancer and national

Josephine R Fowler; Raja Sayegh

2005-01-01

313

Helical Tomotherapy in Cervical Cancer Patients  

Microsoft Academic Search

\\u000a Abstract\\u000a \\u000a \\u000a Purpose:\\u000a   To evaluate the acute toxicity of simultaneous integrated boost (SIB) technique for dose escalation with helical tomotherapy\\u000a (HT) in patients with locally advanced cervical cancer.\\u000a \\u000a \\u000a \\u000a \\u000a \\u000a Patients and Methods:\\u000a   20 patients (FIGO IB1 pN1-IIIB) underwent primary chemoradiation. Prior to chemoradiation, a laparoscopic\\u000a pelvic and para-aortic lymphadenectomy was performed. A boost region was defined using titanium clips during staging for

Simone Marnitz; Carmen Stromberger; Michael Kawgan-Kagan; Waldemar Wlodarczyk; Ulrich Jahn; Achim Schneider; Uwe Ulrich; Volker Budach; Christhardt Köhler

2010-01-01

314

Distribution of HPV Genotypes and Involvement of Risk Factors in Cervical Lesions and Invasive Cervical Cancer: A Study in an Indian Population  

PubMed Central

Human papilloma virus (HPV) is considered as the main sexually transmitted etiological agent for the cause and progression of preneoplastic cervical lesions to cervical cancer. This study is discussing the prevalence of HPV and its genotypes in cervical lesions and invasive cervical cancer tissues and their association with various risk factors in women from Varanasi and its adjoining areas in India. A total of 122 cervical biopsy samples were collected from SS Hospital and Indian Railways Cancer Institute and Research Centre, Varanasi and were screened for HPV infection by PCR using primers from L1 consensus region of the viral genome. HPV positive samples were genotyped by type-specific PCR and sequencing. The association of different risk factors with HPV infection in various grades of cervical lesion was evaluated by chi-square test. A total of 10 different HPV genotypes were observed in women with cervicitis, CIN, invasive squamous cell cervical carcinoma and adenocarcinoma. Increased frequency of HPV infection with increasing lesion grade (p=0.002) was observed. HPV16 being the predominant type was found significantly associated with severity of the disease (p=0.03). Various socio- demographic factors other than HPV including high parity (p<0.0001), rural residential area (p<0.0001), elder age (p<0.0001), low socio-economic status (p<0.0001) and women in postmenopausal group (p<0.0001) were also observed to be associated with cervical cancer.These findings show HPV as a direct cause of cervical cancer suggesting urgent need of screening programs and HPV vaccination in women with low socio-economic status and those residing in rural areas.

Srivastava, Shikha; Shahi, U P; Dibya, Arti; Gupta, Sadhana; Roy, Jagat K

2014-01-01

315

Epidemiology, prevention and treatment of cervical cancer in the Philippines  

PubMed Central

Cervical cancer remains to be one of the leading malignancies among Filipino women. High-risk human papillomavirus (HPV) types, such as 16 and 18, are consistently identified in Filipino women with cervical cancer. Factors identified to increase the likelihood of HPV infection and subsequent development of cervical cancer include young age at first intercourse, low socioeconomic status, high parity, smoking, use of oral contraception and risky sexual behaviors. Cancer screening programs presently available in the Philippines include Pap smears, single visit approach utilizing visual inspection with acetic acid followed by cryotherapy, as well as colposcopy. However, the uptake of screening remains low and is further compounded by the lack of basic knowledge women have regarding screening as an opportunity for prevention of cervical cancer. Prophylactic HPV vaccination of both quadrivalent and bivalent vaccines has already been approved in the Philippines and is gaining popularity among the Filipinos. However, there has been no national or government vaccination policy implemented as of yet. The standard of treatment of cervical cancer is radiotherapy concurrent with chemotherapy. Current researches are directed towards improving availability of both preventive and curative measures of cervical cancer management.

Dy Echo, Ana Victoria V.

2009-01-01

316

Synergistic Anti-Tumor Effects of Combination of Photodynamic Therapy and Arsenic Compound in Cervical Cancer Cells: In Vivo and In Vitro Studies  

PubMed Central

The effects of As4O6 as adjuvant on photodynamic therapy (PDT) were studied. As4O6 is considered to have anticancer activity via several biological actions, such as free radical production and inhibition of VEGF expression. PDT or As4O6 significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P<0.05) by MTT assay. The anti-proliferative effect of the combination treatment was significantly higher than in TC-1 cells treated with either photodynamic therapy or As4O6 alone (62.4 and 52.5% decrease compared to vehicle-only treated TC-1 cells, respectively, P<0.05). In addition, cell proliferation in combination of photodynamic therapy and As4O6 treatment significantly decreased by 77.4% (P<0.05). Cell survival pathway (Naip1, Tert and Aip1) and p53-dependent pathway (Bax, p21Cip1, Fas, Gadd45, IGFBP-3 and Mdm-2) were markedly increased by combination treatment of photodynamic therapy and As4O6. In addition, the immune response in the NEAT pathway (Ly-12, CD178 and IL-2) was also modulated after combination treatment, suggesting improved antitumor effects by controlling unwanted growth-stimulatory pathways. The combination effect apparently reflected concordance with in vitro data, in restricting tumor growth in vivo and in relation to some common signaling pathways to those observed in vitro. These findings suggest the benefit of combinatory treatment with photodynamic therapy and As4O6 for inhibition of cervical cancer cell growth.

Kim, Yong-Wan; Bae, Su Mi; Battogtokh, Gantumur; Bang, Hyo Joo; Ahn, Woong Shick

2012-01-01

317

Cervical Cancer Vaccine Doesn't Boost Clot Risk  

MedlinePLUS

... on this page, please enable JavaScript. Cervical Cancer Vaccine Doesn't Boost Clot Risk: Study Analysis included ... 2014 (HealthDay News) -- Concerns that the human papillomavirus vaccine may increase the risk of serious blood clots ...

318

Breast and Cervical Cancer Prevention and Treatment Act of 2000  

MedlinePLUS

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

319

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

Cancer.gov

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

320

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

PubMed

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

Flores, Bertha E; Acton, Gayle J

2013-11-01

321

Cervical cancer detection based on serum sample Raman spectroscopy.  

PubMed

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, andnormalization 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, ? 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

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

322

Recent advances in optical imaging for cervical cancer detection  

Microsoft Academic Search

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

Irene M. Orfanoudaki; Dimitra Kappou; Stavros Sifakis

323

The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-?B inhibition.  

PubMed

With increasing use of plant-derived cancer chemotherapeutic agents, exploring the antiproliferative effects of phytochemicals has gained increasing momentum for anticancer drug design. The dietary phytochemical quercetin, modulates several signal transduction pathways associated with cell proliferation and apoptosis. The present study was undertaken to examine the effect of quercetin on cell viability, and to determine the molecular mechanism of quercetin-induced cell death by investigating the expression of Bcl-2 family proteins (Bcl-2, Bcl-xL, Mcl1, Bax, Bad, p-Bad), cytochrome C, Apaf-1, caspases, and survivin as well as the cell cycle regulatory proteins (p53, p21, cyclin D1), and NF-?B family members (p50, p65, I?B, p-I?B-?, IKK? and ubiquitin ligase) in human cervical cancer (HeLa) cells. The results demonstrate that quercetin suppressed the viability of HeLa cells in a dose-dependent manner by inducing G2/M phase cell cycle arrest and mitochondrial apoptosis through a p53-dependent mechanism. This involved characteristic changes in nuclear morphology, phosphatidylserine externalization, mitochondrial membrane depolarization, modulation of cell cycle regulatory proteins and NF-?B family members, upregulation of proapoptotic Bcl-2 family proteins, cytochrome C, Apaf-1 and caspases, and downregulation of antiapoptotic Bcl-2 proteins and survivin. Quercetin that exerts opposing effects on different signaling networks to inhibit cancer progression is a classic candidate for anticancer drug design. PMID:20858478

Vidya Priyadarsini, R; Senthil Murugan, R; Maitreyi, S; Ramalingam, K; Karunagaran, D; Nagini, S

2010-12-15

324

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

PubMed Central

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

2014-01-01

325

Objective Diagnosis of Cervical Cancer by Tissue Protein Profile Analysis  

NASA Astrophysics Data System (ADS)

Protein profiles of homogenized normal cervical tissue samples from hysterectomy subjects and cancerous cervical tissues from biopsy samples collected from patients with different stages of cervical cancer were recorded using High Performance Liquid Chromatography coupled with Laser Induced Fluorescence (HPLC-LIF). The Protein profiles were subjected to Principle Component Analysis to derive statistically significant parameters. Diagnosis of sample types were carried out by matching three parameters--scores of factors, squared residuals, and Mahalanobis Distance. ROC and Youden's Index curves for calibration standards were used for objective estimation of the optimum threshold for decision making and performance.

Patil, Ajeetkumar; Bhat, Sujatha; Rai, Lavanya; Kartha, V. B.; Chidangil, Santhosh

2011-07-01

326

Thermochemoradiotherapy using superselective intra-arterial infusionfor N3 cervical lymph node metastases of tongue cancer.  

PubMed

A case of squamous cell carcinoma of the tongue with advanced N3 cervical lymph node metastases in an 80-year-old female is reported. The patient was treated with a combination of radiotherapy (2 Gy/day, total 60 Gy), superselective intra-arterial chemotherapy via a superficial temporal artery and a femoral artery (docetaxel, total 124 mg; cisplatin, total 135 mg), and four sessions of hyperthermia for cervical lymph node metastases. The tumor responded well to therapy, and 18-fluorodeoxyglucose uptake in both primary and neck lesions disappeared on positron emission tomography-computed tomography. The patient has shown no clinical or radiological evidence of local recurrence or distant metastases 6 years after the end of treatment. Advanced oral cancer patients with N3 cervical lymph node metastases are particularly difficult to treat and have a poor prognosis. This method of thermochemoradiotherapy seems a promising modality for patients with N3 cervical lymph node metastases of oral cancer. PMID:24518725

Hiroaki, Nishiguchi; Kenji, Mitsudo; Noriyuki, Yamamoto; Iwai, Tohnai

2013-01-01

327

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

Cancer.gov

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

328

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

Cancer.gov

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

329

Plasma-free amino acid profiling of cervical cancer and cervical intraepithelial neoplasia patients and its application for early detection.  

PubMed

In this study, plasma-free amino acid profiles were used to investigate pre-cancerous cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) metabolic signatures in plasma. Additionally, the diagnostic potential of these profiles was assessed, as well as their ability to provide novel insight into CSCC metabolism and systemic effects. Plasma samples from CIN patients (n = 26), CSCC patients (n = 22), and a control healthy group (n = 35) were analyzed by high-performance liquid chromatography, and their spectral profiles were subjected to the t test for statistical significance. Potential metabolic biomarkers were identified using database comparisons that examine the significance of metabolites. Compared with healthy controls, patients with CIN and CSCC demonstrated lower levels of plasma amino acids; plasma levels of arginine and threonine were increased in CIN patients but were decreased in cervical cancer patients. Additionally, the levels of a larger group of amino acids (aspartate, glutamate, asparagine, serine, glycine, histidine, taurine, tyrosine, valine, methionine, lysine, isoleucine, leucine, and phenylalanine) were gradually reduced from CIN to invasive cancer. These findings suggest that plasma-free amino acid profiling has great potential for improving cancer screening and diagnosis and for understanding disease pathogenesis. Plasma-free amino acid profiles may have the potential be used to determine cancer diagnoses in the early stage from a single blood sample and may enhance our understanding of its mechanisms. PMID:24068431

Hasim, Ayshamgul; Aili, Aixingzi; Maimaiti, Aminigul; Mamtimin, Batur; Abudula, Abulizi; Upur, Halmurat

2013-10-01

330

The role of ATM and 53BP1 as predictive markers in cervical cancer.  

PubMed

Treatment of advanced-stage cervical cancers with (chemo)radiation causes cytotoxicity through induction of high levels of DNA damage. Tumour cells respond to DNA damage by activation of the 'DNA damage response' (DDR), which induces DNA repair and may counteract chemoradiation efficacy. Here, we investigated DDR components as potential therapeutic targets and verified the predictive and prognostic value of DDR activation in patients with cervical cancer treated with (chemo)radiation. In a panel of cervical cancer cell lines, inactivation of ataxia telangiectasia mutated (ATM) or its substrate p53-binding protein-1 (53BP1) clearly gave rise to cell cycle defects in response to irradiation. Concordantly, clonogenic survival analysis revealed that ATM inhibition, but not 53BP1 depletion, strongly radiosensitised cervical cancer cells. In contrast, ATM inhibition did not radiosensitise non-transformed epithelial cells or non-transformed BJ fibroblasts. Interestingly, high levels of active ATM prior to irradiation were related with increased radioresistance. To test whether active ATM in tumours prior to treatment also resulted in resistance to therapy, immunohistochemistry was performed on tumour material of patients with advanced-stage cervical cancer (n = 375) treated with (chemo)radiation. High levels of phosphorylated (p-)ATM [p = 0.006, hazard ratio (HR) = 1.817] were related to poor locoregional disease-free survival. Furthermore, high levels of p-ATM predicted shorter disease-specific survival (p = 0.038, HR = 1.418). The presence of phosphorylated 53BP1 was associated with p-ATM (p = 0.001, odds ratio = 2.206) but was not related to any clinicopathological features or survival. In conclusion, both our in vitro and patient-related findings indicate a protective role for ATM in response to (chemo)radiation in cervical cancer and point at ATM inhibition as a possible means to improve the efficacy of (chemo)radiation. PMID:22323184

Roossink, Frank; Wieringa, Hylke W; Noordhuis, Maartje G; ten Hoor, Klaske A; Kok, Mirjam; Slagter-Menkema, Lorian; Hollema, Harry; de Bock, Geertruida H; Pras, Elisabeth; de Vries, Elisabeth G E; de Jong, Steven; van der Zee, Ate G J; Schuuring, Ed; Wisman, G Bea A; van Vugt, Marcel A T M

2012-11-01

331

The role of ATM and 53BP1 as predictive markers in cervical cancer  

PubMed Central

Treatment of advanced-stage cervical cancers with (chemo)radiation causes cytotoxicity through induction of high levels of DNA damage. Tumour cells respond to DNA damage by activation of the ‘DNA damage response’ (DDR), which induces DNA repair and may counteract chemoradiation efficacy. Here, we investigated DDR components as potential therapeutic targets and verified the predictive and prognostic value of DDR activation in patients with cervical cancer treated with (chemo)radiation. In a panel of cervical cancer cell lines, inactivation of ataxia telangiectasia mutated (ATM) or its substrate p53-binding protein-1 (53BP1) clearly gave rise to cell cycle defects in response to irradiation. Concordantly, clonogenic survival analysis revealed that ATM inhibition, but not 53BP1 depletion, strongly radiosensitised cervical cancer cells. In contrast, ATM inhibition did not radiosensitise non-transformed epithelial cells or non-transformed BJ fibroblasts. Interestingly, high levels of active ATM prior to irradiation were related with increased radioresistance. To test whether active ATM in tumours prior to treatment also resulted in resistance to therapy, immunohistochemistry was performed on tumour material of patients with advanced-stage cervical cancer (n = 375) treated with (chemo)radiation. High levels of phosphorylated (p-)ATM [p = 0.006, hazard ratio (HR) = 1.817] were related to poor locoregional disease-free survival. Furthermore, high levels of p-ATM predicted shorter disease-specific survival (p = 0.038, HR = 1.418). The presence of phosphorylated 53BP1 was associated with p-ATM (p = 0.001, odds ratio = 2.206) but was not related to any clinicopathological features or survival. In conclusion, both our in vitro and patient-related findings indicate a protective role for ATM in response to (chemo)radiation in cervical cancer and point at ATM inhibition as a possible means to improve the efficacy of (chemo)radiation.

Roossink, Frank; Wieringa, Hylke W; Noordhuis, Maartje G; ten Hoor, Klaske A; Kok, Mirjam; Slagter-Menkema, Lorian; Hollema, Harry; de Bock, Geertruida H; Pras, Elisabeth; de Vries, Elisabeth GE; de Jong, Steven; van der Zee, Ate GJ; Schuuring, Ed; Wisman, G Bea A; van Vugt, Marcel ATM

2012-01-01

332

Outcome of treatment of human HeLa cervical cancer cells with roscovitine strongly depends on the dosage and cell cycle status prior to the treatment.  

PubMed

Exposure of asynchronously growing human HeLa cervical carcinoma cells to roscovitine (ROSC), a selective cyclin-dependent kinases (CDKs) inhibitor, arrests their progression at the transition between G(2)/M and/or induces apoptosis. The outcome depends on the ROSC concentration. At higher dose ROSC represses HPV-encoded E7 oncoprotein and initiates caspase-dependent apoptosis. Inhibition of the site-specific phosphorylation of survivin and Bad, occurring at high-dose ROSC treatment, precedes the onset of apoptosis and seems to be a prerequisite for cell death. Considering the fact that in HeLa cells the G(1)/S restriction checkpoint is abolished by E7, we addressed the question whether the inhibition of CDKs by pharmacological inhibitors in synchronized cells would be able to block the cell-cycle in G(1) phase. For this purpose, we attempted to synchronize cells by serum withdrawal or by blocking of the mitotic apparatus using nocodazole. Unlike human MCF-7 cells, HeLa cells do not undergo G(1) block after serum starvation, but respond with a slight increase of the ratio of G(1) population. Exposure of G(1)-enriched HeLa cells to ROSC after re-feeding does not block their cell-cycle progression at G(1)-phase, but increases the ratio of S- and G(2)-phase, thereby mimicking the effect on asynchronously growing cells. A quite different impact is observed after treatment of HeLa cells released from mitotic block. ROSC prevents their cell cycle progression and cells transiently accumulate in G(1)-phase. These results show that inhibition of CDKs by ROSC in cells lacking the G(1)/S restriction checkpoint has different outcomes depending on the cell-cycle status prior to the onset of treatment. PMID:19180585

Wesierska-Gadek, Józefa; Borza, Andreea; Walzi, Eva; Krystof, Vladimir; Maurer, Margarita; Komina, Oxana; Wandl, Stefanie

2009-04-01

333

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

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.

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

2013-01-01

334

Serum one-carbon metabolites and risk of cervical cancer.  

PubMed

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

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

2014-07-01

335

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

PubMed

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

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

2010-06-01

336

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

ClinicalTrials.gov

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

2014-02-26

337

MHC class I chain-related gene A (MICA) polymorphism and the different histological types of cervical cancer.  

PubMed

Cervical cancer has been one of the most important gynecologic cancer in Taiwan with incidence of 24/100,000 and mortality of 8.7/100,000 annually. About 70-80% are squamous cell carcinoma; the remainder are composed of various types of adenocarcinoma, adenosquamous carcinoma and undifferentiated carcinoma. The Major Histocompatibility Complex (MHC) class I chain-related gene A (MICA) is expressed by keratinocytes and epithelial cells and interacts with gamma-delta T cells. Although MICA was not associated with cervical cancer in the study of Northern Sweden, there are no further studies about the association of MICA polymorphism and the different histological types of cervical cancer. We analyzed the MICA polymorphism in 110 cervical cancer cases (88 squamous cell carcinoma, 12 adenocarcinoma and 10 adenosquamous carcinoma) and 82 randomly selected unrelated controls from 1994 to 2000 in the Mackay Memorial Hospital, Taipei, Taiwan. DNA was extracted part from leukocytes of peripheral blood, part from tumor tissue and 5 polymorphic microsatellite alleles (A4,A5,A5.1,A6,A9) of MICA were identified by a polymerase chain reaction-based (PCR) technique using ABI Prism 377-18 DNA sequencer (Applied Biosystems, Foster City, CA, USA). The phenotypes, alleles and genotypes of MICA gene were calculated. There was no association with cervical cancer patients and non-cervical cancer patients (p=0.337, 0.356 and 0.414). After dividing the cervical cancer patients into 3 major histological types (squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma), the result was still the same (p=0.598, 0.172 and 0.617) in our study. We found no association between MICA gene polymorphism and cervical cancer in Taiwan. Different histological types of cervical cancer also have no significant correlation with MICA gene polymorphism. It demonstrates that polymorphism of MICA gene bears no relation to cervical cancer and the different histological types of cervical cancer in Taiwan. We need further studies for identifying the factors causing the differentiation of cancer cells of the uterine cervix. PMID:16151576

Chen, J R; Lee, Y J; Chen, T; Wang, K L; Dang, C W; Chang, S C; Liu, H F; Yang, Y C

2005-01-01

338

Treatment options in recurrent cervical cancer (Review).  

PubMed

The management of recurrent cervical cancer depends mainly on previous treatment and on the site and extent of recurrence. Concurrent cisplatin-based chemo-radiation is the treatment of choice for patients with pelvic failure after radical hysterectomy alone. However, the safe delivery of high doses of radiotherapy is much more difficult in this clinical setting compared with primary radiotherapy. Pelvic exenteration usually represents the only therapeutic approach with curative intent for women with central pelvic relapse who have previously received irradiation. In a recent series, the 5-year overall survival and operative mortality after pelvic exenteration ranged from 21 to 61% and from 1 to 10%, respectively. Free surgical margins, negative lymph nodes, small tumour size and long disease-free interval were associated with a more favourable prognosis. Currently, pelvic reconstructive procedures (continent urinary conduit, low colorectal anastomosis, vaginal reconstruction with myocutaneous flaps) are strongly recommended after exenteration. Concurrent cisplatin-based chemo-radiation is the treatment of choice for isolated para-aortic lymph node failure, with satisfactory chances of a cure in asymptomatic patients. Chemotherapy is administered with palliative intent to women with distant or loco-regional recurrences not amenable by surgery or radiotherapy. Cisplatin is the most widely used drug, with a response rate of 17-38% and a median overall survival of 6.1-7.1 months. Cisplatin-based combination chemotherapy achieves higher response rates (22-68%) when compared with single-agent cisplatin, but median overall survival is usually less than one year. In a recent Gynecologic Oncology Group (GOG) trial the combination topotecan + cisplatin obtained a significantly longer overall survival than single-agent cisplatin in patients with metastatic or recurrent or persistent cervical cancer. A subsequent GOG study showed a trend in terms of longer overall survival and better quality of life for the doublet cisplatin + paclitaxel vs. the doublets cisplatin + topotecan, cisplatin + vinorelbine, and cisplatin + gemcitabine. Molecularly targeted therapy may represent a novel therapeutic tool, but its use alone or in combination with chemotherapy is still investigational. PMID:22966247

Gadducci, Angiolo; Tana, Roberta; Cosio, Stefania; Cionini, Luca

2010-01-01

339

Treatment options in recurrent cervical cancer (Review)  

PubMed Central

The management of recurrent cervical cancer depends mainly on previous treatment and on the site and extent of recurrence. Concurrent cisplatin-based chemo-radiation is the treatment of choice for patients with pelvic failure after radical hysterectomy alone. However, the safe delivery of high doses of radiotherapy is much more difficult in this clinical setting compared with primary radiotherapy. Pelvic exenteration usually represents the only therapeutic approach with curative intent for women with central pelvic relapse who have previously received irradiation. In a recent series, the 5-year overall survival and operative mortality after pelvic exenteration ranged from 21 to 61% and from 1 to 10%, respectively. Free surgical margins, negative lymph nodes, small tumour size and long disease-free interval were associated with a more favourable prognosis. Currently, pelvic reconstructive procedures (continent urinary conduit, low colorectal anastomosis, vaginal reconstruction with myocutaneous flaps) are strongly recommended after exenteration. Concurrent cisplatin-based chemo-radiation is the treatment of choice for isolated para-aortic lymph node failure, with satisfactory chances of a cure in asymptomatic patients. Chemotherapy is administered with palliative intent to women with distant or loco-regional recurrences not amenable by surgery or radiotherapy. Cisplatin is the most widely used drug, with a response rate of 17–38% and a median overall survival of 6.1–7.1 months. Cisplatin-based combination chemotherapy achieves higher response rates (22–68%) when compared with single-agent cisplatin, but median overall survival is usually less than one year. In a recent Gynecologic Oncology Group (GOG) trial the combination topotecan + cisplatin obtained a significantly longer overall survival than single-agent cisplatin in patients with metastatic or recurrent or persistent cervical cancer. A subsequent GOG study showed a trend in terms of longer overall survival and better quality of life for the doublet cisplatin + paclitaxel vs. the doublets cisplatin + topotecan, cisplatin + vinorelbine, and cisplatin + gemcitabine. Molecularly targeted therapy may represent a novel therapeutic tool, but its use alone or in combination with chemotherapy is still investigational.

GADDUCCI, ANGIOLO; TANA, ROBERTA; COSIO, STEFANIA; CIONINI, LUCA

2010-01-01

340

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

ERIC Educational Resources Information Center

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

Ehrhardt, Jeanie

2007-01-01

341

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

PubMed

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

1986-11-01

342

Risk Factors for Cervical Cancer in Criminal Justice Settings  

PubMed Central

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.

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

2011-01-01

343

Uterine cervical malignant granular cell tumor.  

PubMed

Malignant granular cell tumor is relatively uncommon, constituting only 1-2% of all granular cell tumors. It is a rare and unusual tumor, especially in non-typical sites, such as the uterine cervix, and grows more rapidly than benign granular cell tumor. It can be treated with surgical excision, but recurrence is possible and prognosis can be poor. A malignant granular cell tumor in the uterine cervix of a 37-year-old woman was incidentally diagnosed. The patient has a history of irregular vaginal bleeding. Uterine cervical biopsy under colposcope revealed a malignant granular cell tumor. After isophosphamide, etoposide, and cisplatin neoadjuvant chemotherapy, surgery was performed on the lesion, which approximately involved half the depth of cervical stroma. Computed tomography examination showed no local recurrence or distant metastasis during the 26-month follow-up period. PMID:22414028

Guo, Na; Peng, Zhilan; Yang, Kaixuan; Lou, Jiangyan

2012-06-01

344

HPV-beyond cervical cancer (online resource center).  

PubMed

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

Alexander, Kenneth A; Giuliano, Anna R

2012-07-01

345

The emerging use of IMRT for treatment of cervical cancer.  

PubMed

Radiation therapy plays an important role in both the definitive and adjuvant treatment of patients with cervical cancer. However, although radiation therapy is effective in controlling tumor growth, associated acute and chronic adverse effects are well known. Intensity-modulated radiation therapy (IMRT) is increasingly being used to treat cervical cancer and has the potential to improve the therapeutic ratio because of its ability to escalate dose to cancer targets while sparing adjacent healthy tissue. Multiple dosimetric studies were initially performed, establishing the conceptual feasibility of IMRT in patients with cervical cancer. Subsequent early reported series of patients treated with IMRT showed dosimetric and clinical benefits, with reduction in acute gastrointestinal and hematologic toxicity compared with historic controls, particularly in the posthysterectomy setting. Consensus is evolving regarding the use of IMRT in treating cervical cancer, particularly in the posthysterectomy setting, and for dose escalation to para-aortic nodes and bulky sidewall disease. Target delineation in the context of internal organ motion and tumor shrinkage during a course of fractionated external-beam radiotherapy remains an area of active investigation. IMRT in treating cervical cancer in the setting of an intact uterus remains in its nascent stage and should be used judiciously only within clinical trials. Although not a routine substitute for brachytherapy, it may be considered as a boost for highly selected patients who are not brachytherapy candidates. PMID:21147905

Loiselle, Christopher; Koh, Wui-Jin

2010-12-01

346

Artesunate exerts an anti-immunosuppressive effect on cervical cancer by inhibiting PGE2 production and Foxp3 expression.  

PubMed

Artesunate (ART), derived from a common traditional Chinese medicine, has beeen used an antimalarial for several years. In this study, the effect and mechanism of ART on anti-human cervical cancer cells was examined. The level of prostaglandin E2 (PGE2 ) and the population of CD4+CD25+Foxp3 regulatory T cells (Treg) in peripheral blood were detected by flow cytometry. In vivo antitumor activity was investigated in mice with cervical cancer by the subcutaneous injection of various concentrations of ART. The concentrations of PGE2 in the supernatants of CaSki cells were measured using an ELISA kit. Cyclooxygenase-2 (COX-2) and Foxp3 expression were determined using quantitative polymerase chain reaction (qPCR) and western blot analysis. The effect of ART on the viability of CaSki and Hela cells was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. It was identified that the level of PGE2 and the population of CD4+CD25+Foxp3 Treg cells in the peripheral blood were significantly higher in cervical cancer patients and mice with cervical cancer. ART was capable of inhibiting orthotopic tumor growth, which correlated with a decrease in the level of PGE2 and the percentage of Treg cells in mice with cervical cancer. Furthermore, ART decreased COX-2 expression and the production of PGE2 in CaSki and Hela cells. Notably, the supernatants of CaSki cells treated with ART lowered the expression of Foxp3 in Jurkat T cells, which was capable of being reversed by exogenous PGE2 . Our data revealed that ART may elicit an anti-tumor effect against cervical cancer by inhibition of PGE2 production in CaSki and Hela cells, which resulted in the decrease of Foxp3 expression in T cells. Therefore, ART may be an effective drug for immunotherapy of cervical cancer. PMID:24446394

Zhang, Li-Xin; Liu, Zhi-Neng; Ye, Jun; Sha, Min; Qian, Hua; Bu, Xin-Hua; Luan, Zheng-Yun; Xu, Xin-Lan; Huang, Ai-Hua; Yuan, Dong-Lan; Wu, Yi-Qun; Wang, Xiao-Xiang; Wang, Jia; Huang, Jun-Xing; Ye, Li-Hua

2014-05-01

347

[Clinical significance of lymph node micrometastases in cervical cancer].  

PubMed

In most cancers of epithelial origin, metastases to the lymph nodes constitute the most important prognostic factor and are predictive of the results of the surgical and adjuvant therapies. Data on the lymph node status allows to design an appropriate treatment plan. Despite advances in gynecologic oncology the importance of lymph node micrometastases in cervical cancer especially in nonsentinel lymph nodes which are detected by ultrastaging, has not been fully elucidated. The purpose of the article is to familiarize the reader with the state of current knowledge on cervical cancer micrometastases. The authors attempt to answer the question about the benefits of lymph node assessment in the search for micrometastases in cervical cancer as well as to address emerging doubts. PMID:24191518

Sniadecki, Marcin; Sawicki, Sambor; Wojtylak, Szymon; Liro, Marcin; Wydra, Dariusz

2013-09-01

348

Expression of platelet derived growth factor family members and the potential role of imatinib mesylate for cervical cancer  

PubMed Central

Background Despite significant achievements in the treatment of cervical cancer, it is still a deadly disease; hence newer therapeutical modalities are needed. Preliminary investigations suggest that platelet-derived growth factor (PDGF) might have a role in the development of cervical cancer, therefore it is important to determine whether this growth factor pathway is functional and its targeting with imatinib mesylate leads to growth inhibition of cervical cancer cells. Results PDGF receptors (PDGFR) and their ligands are frequently expressed in cervical cancer and the majority exhibited a combination of family members co-expression. A number of intronic and exonic variations but no known mutations in the coding sequence of the PDGFR? gene were found in cancer cell lines and primary tumors. Growth assays demonstrated that PDGFBB induces growth stimulation that can be blocked by imatinib and that this tyrosine kinase inhibitor on its own inhibits cell growth. These effects were associated with the phosphorylation status of the receptor. Conclusion The PDGFR system may have a role in the pathogenesis of cervical cancer as their members are frequently expressed in this tumor and cervical cancer lines are growth inhibited by the PDGFR antagonist imatinib.

Taja-Chayeb, Lucia; Chavez-Blanco, Alma; Martinez-Tlahuel, Jorge; Gonzalez-Fierro, Aurora; Candelaria, Myrna; Chanona-Vilchis, Jose; Robles, Elizabeth; Duenas-Gonzalez, Alfonso

2006-01-01

349

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

PubMed Central

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

2014-01-01

350

Physical Activity and Cervical Cancer Testing among American Indian Women  

ERIC Educational Resources Information Center

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…

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

2012-01-01

351

Variations in survival for invasive cervical cancer among European women, 1978–89  

Microsoft Academic Search

Objectives: To analyze cervical cancer survival trends in 10 European countries using models that estimate the proportion of cured patients (having the same life expectancy as the general population) and the survival of fatal cases (who die from cervical cancer).

Gemma Gatta; Riccardo Capocaccia; Timo Hakulinen; Milena Sant; Arduino Verdecchia; Gianni De Angelis; Andrea Micheli; Franco Berrino

1999-01-01

352

FDA Appoves First Human Papillomavirus Test for Primary Cervical Cancer Screening  

MedlinePLUS

... Español FDA approves first human papillomavirus test for primary cervical cancer screening The U.S. Food and Drug ... the safety and effectiveness when used as a primary screening tool for cervical cancer.” The FDA first ...

353

Cervical Cancer in Manitoba: evaluating risk, Pap test utilization, and access  

Cancer.gov

Kathleen Decker Alain Demers Daniel Chateau Marion Harrison Cervical Cancer in Manitoba: evaluating risk, Pap test utilization, and access CancerCare Manitoba Foundation Operating Grant (#763096106) Objectives • Compare the risk of invasive cervical

354

Cervical cancer control research in Vietnamese American communities.  

PubMed

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

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

2008-11-01

355

Improving cervical cancer screening rates in an urban HIV clinic.  

PubMed

Human immunodeficiency virus (HIV)-infected women are at increased risk of invasive cervical cancer; however, screening rates remain low. The objectives of this study were to analyze a quality improvement intervention to increase cervical cancer screening rates in an urban academic HIV clinic and to identify factors associated with inadequate screening. Barriers to screening were identified by a multidisciplinary quality improvement committee at the Washington University Infectious Diseases clinic. Several strategies were developed to address these barriers. The years pre- and post-implementation were analyzed to examine the clinical impact of the intervention. A total of 422 women were seen in both the pre-implementation and post-implementation periods. In the pre-implementation period, 222 women (53%) underwent cervical cancer screening in the form of Papanicolaou (Pap) testing. In the post-implementation period, 318 women (75.3%) underwent cervical cancer screening (p < 0.01). Factors associated with lack of screening included fewer visits attended (pre: 4.2 ± 1.5; post: 3.4 ± 1.4; p < 0.01). A multidisciplinary quality improvement intervention was successful in overcoming barriers and increasing cervical cancer screening rates in an urban academic HIV clinic. PMID:24625234

Cross, Sara L; Suharwardy, Sanaa H; Bodavula, Phani; Schechtman, Kenneth; Overton, E Turner; Onen, Nur F; Lane, Michael A

2014-09-01

356

Potent in vitro Antitumor Activity of Symplocos racemosa against Leukaemia and Cervical Cancer  

Microsoft Academic Search

Objective: Assessment of anti-tumor activity of Symplocos racemosa Roxb. (Symplococaceae) plant extracts. Methods: Plant bark was procured, identified and verified. Chloroform, butanol and ethyl acetate extracts were prepared and their cytotoxic activity determined using the XTT salt based cytotoxicity assay in 96- micro plate format against one leukaemia and one cervical cancer cell line. Cyclophosphamide was used as positive control.

Bhuvan P. Raval; Maulik P. Suthar; Rakesh K. Patel

2009-01-01

357

Ceramide induces early and late apoptosis in human papilloma virus+ cervical cancer cells by inhibiting reactive oxygen species decay, diminishing the intracellular concentration of glutathione and increasing nuclear factor-kappaB translocation.  

PubMed

Ceramide is regarded as an important cellular signal for the induction of cell death. We have previously shown that ceramide induces the death of cervical tumor cells without biochemical and morphological markers of apoptosis. The mechanisms by which ceramide induces cell death are not understood, therefore we evaluated the effect of C6-ceramide, a synthetic cell-permeable analog of endogenous ceramides, in signaling pathways involved in the oxidative stress of three cervical human papilloma virus cancer cell lines. Reactive oxygen species production was determined by fluorescent 2,7-dichlorofluorescein, nitrite concentration by the Griess reaction (as an indirect measure of nitric oxide production), mitochondrial membrane potential by staining with Rh123, reduced-glutathione concentration by high-pressure liquid chromatography, nuclear factor-kappaB translocation by electrophoretic mobility shift assay, inhibitory protein of nuclear factor-kappaB expression by Western blot and cell death by a poly-caspases fluorochrome-labeled inhibitors of caspases apoptosis assay. C6-ceramide induced early and late apoptosis, which was associated with an increase in reactive oxygen species and nitric oxide production, a loss in mitochondrial membrane potential, an increase in nuclear factor-kappaB translocation, and a decrease in reduced glutathione concentration. C6-ceramide did not modify the expression of inhibitory protein of nuclear factor-kappaB and its antiproliferative effect was not abrogated by Bay 11-7082, an inhibitory protein of nuclear factor-kappaB kinase inhibitor. Our results suggest that oxidative stress might participate in the ceramide-induced damage to human papilloma virus cervical cancer cells. PMID:17159601

Gutiérrez, Gisela; Mendoza, Criselda; Montaño, Luis F; López-Marure, Rebeca

2007-02-01

358

Cancer Stem Cells: Lung Cancer  

Microsoft Academic Search

Lung cancer is today the most common cause of cancer death worldwide with a mortality rate exceeding that of colon, cervical, breast, and prostate cancers combined. The estimated global burden for 2002 is 1.35 million new cases diagnosed (incidence) and 1.18 million deaths (mortality) ( 1 ) . The causal link between smoking and lung cancer is well established. The

Jaclyn Y. Hung

359

Validation of the European Organization for Research and Treatment of Cancer cervical cancer module for Chinese patients with cervical cancer  

PubMed Central

Purpose The aim of our study was to assess, for the first time, the validity, reliability, and acceptability of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ) cervical cancer module (CX24) in Chinese cervical cancer patients. Patients and methods One hundred fifteen outpatients with cervical cancer in the First Affiliated Hospital of Xinxiang Medical University from May 2013 to July 2013 were included in this study. All participants self-administered the EORTC QLQ-CX24 and the core questionnaire (EORTC QLQ-C30), and the Karnofsky Performance Scale was performed to evaluate scores. Data were analyzed with Cronbach’s ? coefficient, Pearson correlation test, multitrait scaling analysis, and Mann–Whitney U test. Results Scale reliability was confirmed by Cronbach’s ? coefficients for internal consistency, which ranged from 0.71 to 0.82. Convergent and discriminant validity were confirmed by multitrait scaling analysis, which revealed three (3.4%) scaling errors for symptom experience scales and zero (0%) for body image as well as sexual/vaginal functioning scales. Higher missing value rate occurred in sexuality-related items. The clinical validity of the Chinese version of the EORTC QLQ-CX24 was demonstrated by the ability to discriminate among patients in different International Federation of Gynecology and Obstetrics stages. Conclusion The EORTC QLQ-CX24 was proved to be a reliable and valid instrument with which to measure the quality of life in cervical cancer patients in the People’s Republic of China.

Hua, Cai-Hong; Guo, Hui-Min; Guan, Xin-Lei; Kong, Fan-Jing; Hou, Rui-Jie; Zhang, Xue-Ying; Li, Shao-Ru

2013-01-01

360

Lactobacillus Decelerates Cervical Epithelial Cell Cycle Progression  

PubMed Central

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

Vielfort, Katarina; Weyler, Linda; Soderholm, Niklas; Engelbrecht, Mattias; Lofmark, Sonja; Aro, Helena

2013-01-01

361

Vibrational spectroscopy for cervical cancer pathology, from biochemical analysis to diagnostic tool  

Microsoft Academic Search

Cervical cancer is the second most common cancer in women worldwide with 80% of cases arising in the developing world. The mortality associated with cervical cancer can be reduced if this disease is detected at the early stages of development or at the pre-malignant state (cervical intraepithelial neoplasia, CIN). The aim of this study was to investigate the potential of

F. M. Lyng; E. Ó Faoláin; J. Conroy; A. D. Meade; P. Knief; B. Duffy; M. B. Hunter; J. M. Byrne; P. Kelehan; H. J. Byrne

2007-01-01

362

Long-term follow-up after cervical cancer treatment and subsequent successful surrogate pregnancy  

Microsoft Academic Search

Preservation of fertility is a major concern for premenopausal women after diagnosis of cervical cancer. Successful surrogate pregnancy after treatment for cervical cancer has very rarely been reported. In the present report, a case of successful surrogate pregnancy after radical hysterectomy, lymphadenectomy and ovarian transposition for cervical cancer, followed by radiation therapy, is presented. After stimulation of the transposed ovaries

T Agorastos; M Zafrakas; M Mastrominas

2009-01-01

363

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

Federal Register 2010, 2011, 2012, 2013

...Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and...regarding the early detection and control of breast and cervical cancer. The committee makes...of Healthcare Reform and its impact for breast and cervical cancer screening;...

2011-05-26

364

Usefulness of sentinel lymph node detection in early stages of cervical cancer  

Microsoft Academic Search

Purpose: Sentinel lymph node (SLN) mapping in combination with surgical biopsy is an emerging tech- nique for use in the early stages of cervical cancer. The purpose of this study was to evaluate the technique in a series of 40 consecutive women with early stage cervical cancer. Methods: Forty patients with early stage cervical cancer (FIGO stage IA2 (2), IB1

I. Roca; A. P. Caresia; A. Gil-Moreno; P. Pifarre; S. Aguade-Bruix; J. Castell-Conesa; J. M. Martínez-Palones; J. Xercavins

2005-01-01

365

Effective screening programmes for cervical cancer in low- and middle-income developing countries  

Microsoft Academic Search

Cervical cancer is an important public health problem among adult women in developing countries in South and Central America, sub-Saharan Africa, and south and south-east Asia. Frequently repeated cytology screening programmes — either organized or opportunistic — have led to a large decline in cervical cancer incidence and mortality in developed countries. In contrast, cervical cancer remains largely uncontrolled in

Rengaswamy Sankaranarayanan; Atul Madhukar Budukh; Rajamanickam Rajkumar

2001-01-01

366

HIV serostatus and tumor differentiation among patients with cervical cancer at Bugando Medical Centre  

PubMed Central

Background Evidence for the association between Human immunodeficiency virus infection and cervical cancer has been contrasting, with some studies reporting increased risk of cervical cancer among HIV positive women while others report no association. Similar evidence from Tanzania is scarce as HIV seroprevalence among cervical cancer patients has not been rigorously evaluated. The purpose of this study was to determine the association between HIV and tumor differentiation among patients with cervical cancer at Bugando Medical Centre and Teaching Hospital in Mwanza, North-Western Tanzania. Methods This was a descriptive analytical study involving suspected cervical cancer patients seen at the gynaecology outpatient clinic and in the gynaecological ward from November 2010 to March 2011. Results A total of 91 suspected cervical cancer patients were seen during the study period and 74 patients were histologically confirmed with cervical cancer. The mean age of those confirmed of cervical cancer was 50.5?±?12.5?years. Most patients (39 of the total 74–52.7%) were in early disease stages (stages IA-IIA). HIV infection was diagnosed in 22 (29.7%) patients. On average, HIV positive women with early cervical cancer disease had significantly more CD4+ cells than those with advanced disease (385.8?±?170.4 95% CI 354.8-516.7 and 266.2?±?87.5, 95% CI 213.3-319.0 respectively p?=?0.042). In a binary logistic regression model, factors associated with HIV seropositivity were ever use of hormonal contraception (OR 5.79 95% CI 1.99-16.83 p?=?0.001), aged over 50?years (OR 0.09 95% CI 0.02-0.36 p?=?0.001), previous history of STI (OR 3.43 95% CI 1.10-10.80 p?=?0.035) and multiple sexual partners OR 5.56 95% CI 1.18-26.25 p?=?0.030). Of these factors, only ever use of hormonal contraception was associated with tumor cell differentiation (OR 0.16 95% CI 0.06-0.49 p?=?0.001). HIV seropositivity was weakly associated with tumor cell differentiation in an unadjusted analysis (OR 0.21 95% CI 0.04-1.02 p?=?0.053), but strong evidence for the association was found after adjusting for ever use of hormonal contraception with approximately six times more likelihood of HIV infection among women with poorly differentiated tumor cells compared to those with moderately and well differentiated cells (OR 5.62 95% CI 1.76-17.94 p?=?0.004). Conclusion Results from this study setting suggest that HIV is common among cervical cancer patients and that HIV seropositivity may be associated with poor tumour differentiation. Larger studies in this and similar settings with high HIV prevalence and high burden of cervical cancer are required to document this relationship.

2012-01-01

367

CoExpression of HSV2 and Chlamydia trachomatis in HPV-Positive Cervical Cancer and Cervical Intraepithelial Neoplasia Lesions Is Associated with Aberrations in Key Intracellular Pathways  

Microsoft Academic Search

Objective: Oncogenic human papillomaviruses (HPVs) are the etiological agents of cervical cancer. Different cofactors might be needed for maligna