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1. Sharma A, Rajappa M, Saxena A, Sharma M: Telomerase activity as a tumor marker in Indian women with cervical intraepithelial neoplasia and cervical cancer. Mol Diagn Ther; 2007;11(3):193-201
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  • [Title] Telomerase activity as a tumor marker in Indian women with cervical intraepithelial neoplasia and cervical cancer.
  • BACKGROUND AND OBJECTIVES: Cervical cancer is the most common cancer in Indian women and is a leading cause of death in women worldwide.
  • Cervical cancer develops from pre-neoplastic cervical intraepithelial neoplasia (CIN).
  • This study was conducted to evaluate telomerase activity as a tumor marker for the detection of cancer in patients with CIN and cervical cancer.
  • METHODS: Telomerase activity was detected using the PCR-based telomeric repeat amplification protocol (TRAP) assay in cervical tissues collected by routine punch biopsy from the uterine cervix of patients with suspected cervical cancer.
  • A total of 125 patients (including 50 patients with CIN and 75 patients with cervical cancer [including nine patients with adeno-squamous disease]) and 22 control subjects were studied.
  • The sensitivity and specificity for detecting CIN and cervical cancer were calculated.
  • RESULTS: Patients with grade I, II, and III CIN showed 17%, 33%, and 57% positivity for telomerase, respectively.
  • In patients with cervical cancer, those at early clinical stages (Ia-IIb) showed 68% positivity and those at later clinical stages showed 92% positivity for telomerase activity.
  • In the present study, telomerase positivity correlated significantly with the detection of HR HPV-16 and -18 (p < 0.001).
  • As a diagnostic test, none of the described analyses combined a sensitivity of > or =90% with a specificity of > or =90%, except in patients with advanced cancer when telomerase activity was used as a diagnostic test.
  • CONCLUSION: Our findings suggest that telomerase activation is a relatively early event in cervical carcinogenesis and correlates with the grade of cervical lesion, HR-HPV status (16 and 18 subtypes), and clinical staging.
  • Hence, these associations suggest it as a possible target for detection of cervical cancer.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / enzymology. Human papillomavirus 16 / metabolism. Human papillomavirus 18 / metabolism. Papillomavirus Infections / complications. Telomerase / metabolism. Uterine Cervical Neoplasms / enzymology

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  • (PMID = 17570741.001).
  • [ISSN] 1177-1062
  • [Journal-full-title] Molecular diagnosis & therapy
  • [ISO-abbreviation] Mol Diagn Ther
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] New Zealand
  • [Chemical-registry-number] EC 2.7.7.49 / Telomerase
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2. Ruan YH, Wei WL, Zhang HX, Liang ZN, Liu BY, Chen Y: [Comparison and analysis of expression of c-myc and p16 in cervical carcinoma]. Ai Zheng; 2003 Jun;22(6):602-6
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  • [Title] [Comparison and analysis of expression of c-myc and p16 in cervical carcinoma].
  • It is still unclear whether abnormal expression of c-myc and p16 cooperate in the occurrence and progression of cervical carcinoma, and whether there exists a connection between the expression of two genes and the chemotherapy response of cervical carcinoma.
  • This study was designed to investigate the correlation between the expression of c-myc and p16 and their roles in the genesis and development of the uterine cervical carcinoma and chemotherapy response.
  • METHODS: Using in situ hybridization, 37 cases of cervical carcinoma (including 11 cases after chemotherapy), 21 cases of precancerous lesion and 5 cases of normal cervix were observed for c-myc and p16 mRNA with dig-labeled probes.
  • RESULTS: The positive expression rates of p16 in normal cervix,CIN (cervical intraepithelial neoplasia) and cervical carcinoma were 100%, 71.4%, and 21.6%, respectively (P=0.0001), whereas the expression rates of c-myc were 0%, 42.9%, and 75.7% (P=0.0011), respectively.
  • The expression of positive signals of c-myc increased with the increase of malignant degree, and the positive signals in CIN III were also higher than that in CIN II and CIN I.
  • The expression rates of c-myc were decreased in cervical carcinoma after chemotherapy.
  • Expression of p16 and c-myc showed no significant difference between effectual and ineffectual chemotherapy groups.
  • CONCLUSION: Both over expression of c-myc and descended expression of p16 may play an important role in the genesis and development of uterine cervical carcinoma.
  • The increased expression of c-myc in different grade CIN suggests that carcinogenesis of cervix be progressive.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / genetics. Genes, myc. Uterine Cervical Neoplasms / genetics
  • [MeSH-minor] Female. Genes, p16. Humans. Neoplasm Staging. RNA, Messenger / analysis

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  • (PMID = 12948409.001).
  • [Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer
  • [ISO-abbreviation] Ai Zheng
  • [Language] chi
  • [Publication-type] Comparative Study; English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 0 / RNA, Messenger
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3. Russomano F, Reis A, Camargo MJ, Grinsztejn B, Tristão MA: Recurrence of cervical intraepithelial neoplasia grades 2 or 3 in HIV-infected women treated by large loop excision of the transformation zone (LLETZ). Sao Paulo Med J; 2008 Jan 2;126(1):17-22
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  • [Title] Recurrence of cervical intraepithelial neoplasia grades 2 or 3 in HIV-infected women treated by large loop excision of the transformation zone (LLETZ).
  • CONTEXT AND OBJECTIVE: Women infected by HIV are more likely to have cervical cancer and its precursors.
  • Treatment of the precursor lesions can prevent this neoplasia.
  • The aim of this study was to assess the likelihood of recurrent cervical intraepithelial neoplasia grades 2 or 3 (CIN 2-3) in HIV-infected women, compared with HIV-negative women, all treated by large loop excision of the transformation zone (LLETZ).
  • METHOD: 55 HIV-positive and 212 HIV-negative women were followed up after LLETZ for CIN 2-3 (range: 6-133 months).
  • RESULTS: The incidence of recurrent CIN 2-3 was 30.06/10,000 woman-months in the HIV-positive group and 4.88/10,000 woman-months in the HIV-negative group (relative risk, RR = 6.16; 95% confidence interval, CI: 2.07-18.34).
  • We were unable to demonstrate other prognostic factors relating to CIN recurrence, but the use of highly active antiretroviral therapy (HAART) may decrease the risk of this occurrence among HIV patients.
  • CONCLUSION: After LLETZ there is a higher risk of recurrence of CIN 2-3 among HIV-positive women than among HIV-negative women.
  • This higher risk was not influenced by margin status or grade of cervical disease treated.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / surgery. HIV Infections / complications. Neoplasm Recurrence, Local / prevention & control. Uterine Cervical Neoplasms / surgery
  • [MeSH-minor] Adolescent. Adult. Antiretroviral Therapy, Highly Active. Brazil / epidemiology. CD4 Lymphocyte Count. Cohort Studies. Colposcopy / methods. Female. Follow-Up Studies. HIV Seropositivity / complications. HIV Seropositivity / drug therapy. HIV Seropositivity / virology. Humans. Middle Aged. Recurrence. Risk Factors. Time Factors. Young Adult


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4. van der Burg SH, Kwappenberg KM, O'Neill T, Brandt RM, Melief CJ, Hickling JK, Offringa R: Pre-clinical safety and efficacy of TA-CIN, a recombinant HPV16 L2E6E7 fusion protein vaccine, in homologous and heterologous prime-boost regimens. Vaccine; 2001 Jun 14;19(27):3652-60
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  • [Title] Pre-clinical safety and efficacy of TA-CIN, a recombinant HPV16 L2E6E7 fusion protein vaccine, in homologous and heterologous prime-boost regimens.
  • Human papillomavirus (HPV) E6 and E7 oncoproteins are attractive targets for T-cell-based immunotherapy of cervical intraepithelial neoplasia (CIN) and cancer.
  • A newly designed vaccine, comprising the HPV16 L2, E6 and E7 as a single fusion protein (TA-CIN), was shown to elicit HPV16-specific CTL, T-helper cells and antibodies in a pre-clinical mouse model.
  • CTL immunity was optimally induced when TA-CIN was employed in heterologous prime-boost regimens in combination with TA-HPV, a clinical grade vaccinia-based vaccine.
  • These data provide a scientific basis for the use of TA-CIN, alone or in combination with TA-HPV in future human trials.
  • [MeSH-major] Cancer Vaccines / toxicity. Capsid / toxicity. Capsid Proteins. Oncogene Proteins, Viral / toxicity. Papillomaviridae / immunology. Recombinant Fusion Proteins / toxicity
  • [MeSH-minor] Animals. Antigens, Neoplasm / administration & dosage. Antigens, Neoplasm / immunology. Antigens, Neoplasm / therapeutic use. Antigens, Neoplasm / toxicity. Antigens, Viral / administration & dosage. Antigens, Viral / immunology. Antigens, Viral / therapeutic use. Antigens, Viral / toxicity. Cell Line. Cell Line, Transformed. Cervical Intraepithelial Neoplasia / prevention & control. Cervical Intraepithelial Neoplasia / therapy. Cervical Intraepithelial Neoplasia / virology. Drug Evaluation, Preclinical. Immunotherapy. Mice. Mice, Inbred C57BL. Papillomavirus E7 Proteins. Vaccines, Acellular / administration & dosage. Vaccines, Acellular / immunology. Vaccines, Acellular / therapeutic use. Vaccines, Acellular / toxicity

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  • (PMID = 11395199.001).
  • [ISSN] 0264-410X
  • [Journal-full-title] Vaccine
  • [ISO-abbreviation] Vaccine
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / Antigens, Viral; 0 / Cancer Vaccines; 0 / Capsid Proteins; 0 / L2 protein, Human papillomavirus type 16; 0 / Oncogene Proteins, Viral; 0 / Papillomavirus E7 Proteins; 0 / Recombinant Fusion Proteins; 0 / Vaccines, Acellular; 0 / oncogene protein E7, Human papillomavirus type 16
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5. Piura B, Rabinovich A, Huleihel M: [Matrix metalloproteinases and their tissue inhibitors in malignancies of the female genital tract]. Harefuah; 2003 Nov;142(11):786-91, 804
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  • [Title] [Matrix metalloproteinases and their tissue inhibitors in malignancies of the female genital tract].
  • Their proteolytic activity depends on their binding to metal Zinc and is controlled by tissue inhibitors of MMP (TIMPs).
  • Since MMPs may serve as markers of tumor behavior and as predictors of survival and since synthetic inhibitors of MMP may have a place in the treatment of cancer, researching MMPs and their tissue inhibitors in malignant diseases has attracted growing attention.
  • Studies on MMPs and their tissue inhibitors in malignancies of the female genital tract have shown the following:.
  • 1) In ovarian carcinoma and cervical carcinoma, over-expression of MMP-2 and MMP-9 is associated with invasiveness, metastatic spread and poor prognosis;.
  • 3) In cervical intra-epithelial neoplasia (CIN), measuring MMP-2 can assist in identifying high-risk for progression CIN I and CIN II; 4).
  • It is speculated that using synthetic drugs that inhibit MMPs in combination with conventional chemotherapy may contribute to the improvement of treatment results in cancer patients.
  • [MeSH-major] Genital Neoplasms, Female / enzymology. Genital Neoplasms, Female / pathology. Matrix Metalloproteinases / metabolism. Tissue Inhibitor of Metalloproteinases / metabolism

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  • (PMID = 14631913.001).
  • [ISSN] 0017-7768
  • [Journal-full-title] Harefuah
  • [ISO-abbreviation] Harefuah
  • [Language] heb
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Israel
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Tissue Inhibitor of Metalloproteinases; EC 3.4.24.- / Matrix Metalloproteinases
  • [Number-of-references] 32
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6. Kiatpongsan S, Niruthisard S, Mutirangura A, Trivijitsilp P, Vasuratna A, Chaithongwongwatthana S, Lertkhachonsuk R: Role of human papillomavirus DNA testing in management of women with atypical squamous cells of undetermined significance. Int J Gynecol Cancer; 2006 Jan-Feb;16(1):262-5
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  • To find the sensitivity, specificity, and positive and negative predictive values of the high-risk group human papillomavirus (HPV) DNA testing as a triage tool to detect high-grade squamous intraepithelial lesions (HSILs, ie, cervical intraepithelial neoplasia [CIN] 2 or worse) in women with a cytologic smear showing atypical squamous cells of undetermined significance (ASC-US).
  • Cervical cell samplings were done by cervical cytobrush technique and tested for high-risk group HPV with the Hybrid Capture 2 (HC2) test.
  • Then cervicographs were taken before colposcopic-directed cervical biopsies were done.
  • Of the 90 ASC-US cases enrolled, the pathologic results were normal in 30.0%, squamous metaplasia in 16.7%, CIN 1 in 37.8%, CIN 2 in 1.1%, CIN 3 in 11.1%, and microinvasive cervical carcinoma in 3.3%.
  • The prevalence of HSILs and the prevalence of high-risk HPV detection were 15.6% and 38.9%, respectively.
  • Using pathologic results from cervical biopsy as the gold standard, the HC2 has the sensitivity, specificity, and positive and negative predictive values of 85.7%, 69.7%, 34.3%, and 96.4%, respectively, to detect HSILs.
  • High-risk group HPV detection can be used as an additional triage test to detect HSILs in women having ASC-US with high sensitivity and negative predictive value.
  • [MeSH-major] Carcinoma, Squamous Cell / virology. Cervical Intraepithelial Neoplasia / virology. DNA, Viral / analysis. Papillomaviridae / isolation & purification. Uterine Cervical Neoplasms / virology
  • [MeSH-minor] Adolescent. Adult. Biopsy, Needle. Cohort Studies. DNA Probes, HPV. Female. Humans. Immunohistochemistry. Middle Aged. Papillomavirus Infections / diagnosis. Papillomavirus Infections / drug therapy. Risk Assessment. Sensitivity and Specificity. Thailand. Triage


7. Giraudo E, Inoue M, Hanahan D: An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest; 2004 Sep;114(5):623-33
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  • [Title] An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis.
  • A mouse model involving the human papillomavirus type-16 oncogenes develops cervical cancers by lesional stages analogous to those in humans.
  • In this study the angiogenic phenotype was characterized, revealing intense angiogenesis in high-grade cervical intraepithelial neoplasias (CIN-3) and carcinomas.
  • ZA therapy increased neoplastic epithelial and endothelial cell apoptosis without affecting hyperproliferation, indicating that ZA was not antimitotic.
  • Given its track record in clinical use with limited toxicity, ZA holds promise as an "unconventional" MMP-9 inhibitor for antiangiogenic therapy of cervical cancer and potentially for additional cancers and other diseases where MMP-9 expression by infiltrating macrophages is evident.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / blood supply. Diphosphonates / pharmacology. Imidazoles / pharmacology. Macrophages / drug effects. Matrix Metalloproteinase Inhibitors. Neovascularization, Pathologic / drug therapy. Uterine Cervical Neoplasms / blood supply
  • [MeSH-minor] Angiogenesis Inhibitors / pharmacology. Animals. Cell Movement / drug effects. Enzyme Activation / drug effects. Female. Humans. Macrophage Activation / drug effects. Matrix Metalloproteinase 9 / metabolism. Mice. Mice, Transgenic. Vascular Endothelial Growth Factors / metabolism


8. Karp CL, Moore JK, Rosa RH Jr: Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon alpha-2b. Ophthalmology; 2001 Jun;108(6):1093-8
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  • [Title] Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon alpha-2b.
  • OBJECTIVE: To evaluate the role of topical interferon alfa-2b (IFNalpha2b) in the treatment of conjunctival and corneal intraepithelial neoplasia (CIN).
  • PARTICIPANTS: Five patients with histologically proven CIN or recurrences of proven CIN were studied prospectively.
  • INTERVENTION: After histologic confirmation, patients were given topical recombinant IFNalpha2b (INTRON A, Schering Plough, Kenilworth, NJ) 1 million IU/ml four times a day.
  • RESULTS: All patients had complete resolution of the CIN lesion on IFNalpha2b.
  • The mean time to clinical resolution was 11.6 weeks (range, 4-22 weeks).
  • One patient had a clinical recurrence of his corneal CIN 1 year after tumor resolution.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Carcinoma in Situ / drug therapy. Conjunctival Neoplasms / drug therapy. Corneal Diseases / drug therapy. Interferon-alpha / therapeutic use
  • [MeSH-minor] Administration, Topical. Adult. Aged. Eye Neoplasms / drug therapy. Eye Neoplasms / pathology. Female. Humans. Male. Middle Aged. Neoplasm Recurrence, Local. Ophthalmic Solutions. Recombinant Proteins. Treatment Outcome

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  • (PMID = 11382635.001).
  • [ISSN] 0161-6420
  • [Journal-full-title] Ophthalmology
  • [ISO-abbreviation] Ophthalmology
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Ophthalmic Solutions; 0 / Recombinant Proteins; 99210-65-8 / interferon alfa-2b
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9. Balasubramani L, Orbell S, Hagger M, Brown V, Tidy J: Do women with high-grade cervical intraepithelial neoplasia prefer a see and treat option in colposcopy? BJOG; 2007 Jan;114(1):39-45
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  • [Title] Do women with high-grade cervical intraepithelial neoplasia prefer a see and treat option in colposcopy?
  • OBJECTIVE: To compare women's experiences of either see and treat (ST) or defer and treat (DT) at first visit to colposcopy following abnormal cytology.
  • SAMPLE: A total of 272 women with high-grade cervical intraepithelial neoplasia (CIN) referred to colposcopy.
  • METHODS: A total of 136 women receiving ST and a matched sample of women receiving DT (N = 136) were sent a postal questionnaire 7 days after first appointment at colposcopy to assess evaluations of their experience, psychological distress and relief.
  • RESULTS: Women undergoing ST were significantly less anxious and more relieved than those undergoing DT.
  • [MeSH-major] Anxiety / etiology. Cervical Intraepithelial Neoplasia / psychology. Colposcopy / psychology. Patient Satisfaction. Uterine Cervical Neoplasms / psychology


10. Palomba M, Melis GB: Oral use of interferon therapy in cervical human papillomavirus infection. Clin Ter; 2000;151(1 Suppl 1):59-61
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  • [Title] Oral use of interferon therapy in cervical human papillomavirus infection.
  • The efficacy and the optimal dose of systemic alpha-interferon treatment of genital human papillomavirus infection is now under discussion because of high cost, low compliance and systemic toxicity of this drug.
  • Recent studies seem to suggest that natural alpha-interferon may also have antiviral efficacy in humans after oral administration of low doses of the drug.
  • Low doses (150U tid for 8 weeks) of the drug were administered to 12 patients with mild cervical dysplasia and human papillomavirus infection.
  • A significantly higher proportion of Interferon treated subjects showed a colposcopic and histological regression of the lesion after months of treatment in comparison with 9 placebo treated patients (75% vs 30%) without major side effects.
  • These results seem to justify wider evaluations of this approach to Interferon treatment characterized by lower costs and fewer side effects in comparison with traditional systemic high dose treatment of alpha Interferon.
  • [MeSH-major] Antiviral Agents / administration & dosage. Interferon-alpha / administration & dosage. Papillomaviridae. Papillomavirus Infections / drug therapy. Tumor Virus Infections / drug therapy. Uterine Cervical Neoplasms / drug therapy

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  • (PMID = 10876967.001).
  • [ISSN] 0009-9074
  • [Journal-full-title] La Clinica terapeutica
  • [ISO-abbreviation] Clin Ter
  • [Language] eng; ita
  • [Publication-type] Clinical Trial; Controlled Clinical Trial; Journal Article
  • [Publication-country] ITALY
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / Interferon-alpha
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11. Zou C, Vlastos AT, Yang L, Wang J, Nishioka K, Follen M: Effects of difluoromethylornithine on growth inhibition and apoptosis in human cervical epithelial and cancerous cell lines. Gynecol Oncol; 2002 May;85(2):266-73
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  • [Title] Effects of difluoromethylornithine on growth inhibition and apoptosis in human cervical epithelial and cancerous cell lines.
  • OBJECTIVE: Difluoromethylornithine(DFMO), an irreversible inhibitor of ornithine decarboxylase and an angiogenesis inhibitor, has been used in phase I cervical intraepithelial neoplasia (CIN) trials, producing a 50% regression of CIN 3 lesions.
  • METHODS: Four immortalized cervical epithelial cell lines, serving as in vitro models of precancerous CIN lesions, and nine cervical carcinoma cell lines were studied.
  • DFMO's growth inhibitory effect was tested in monolayer culture and in semisolid medium, and concentrations required for a 50% growth inhibition (IC(50)) with a 5-day treatment were determined.
  • RESULTS: DFMO inhibited growth of immortalized cervical epithelial cell lines and cervical cancer cell lines in monolayer culture and in semisolid medium.
  • The immortalized cervical epithelial cell lines were more sensitive than the cervical cancer cell lines to DFMO's growth inhibitory effect.
  • Concentrations required for 50% growth inhibition after a 5-day treatment ranged from 100 microM to >5 mM for cervical carcinoma cell lines and from 100 microM to 1 mM for immortalized cervical epithelial cell lines.
  • CONCLUSION: DFMO inhibits the growth of cervical precancerous and cancerous cells in vitro in a dose-dependent and time-dependent manner, partially through inducing apoptosis.
  • [MeSH-major] Anticarcinogenic Agents / pharmacology. Apoptosis / drug effects. Eflornithine / pharmacology. Uterine Cervical Neoplasms / prevention & control
  • [MeSH-minor] Cell Division / drug effects. Cervical Intraepithelial Neoplasia / drug therapy. Cervical Intraepithelial Neoplasia / pathology. Female. Growth Inhibitors / pharmacology. Humans. Neoplastic Stem Cells / drug effects. Neoplastic Stem Cells / pathology. Tumor Cells, Cultured


12. Kaufmann AM, Nieland JD, Jochmus I, Baur S, Friese K, Gabelsberger J, Gieseking F, Gissmann L, Glasschröder B, Grubert T, Hillemanns P, Höpfl R, Ikenberg H, Schwarz J, Karrasch M, Knoll A, Küppers V, Lechmann M, Lelle RJ, Meissner H, Müller RT, Pawlita M, Petry KU, Pilch H, Walek E, Schneider A: Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3). Int J Cancer; 2007 Dec 15;121(12):2794-800
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3).
  • Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer.
  • Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential.
  • We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans.
  • A randomized, double blind, placebo-controlled clinical trial has been conducted in 39 HPV16 mono-infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3).
  • Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced.
  • A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients.
  • [MeSH-major] Cancer Vaccines / therapeutic use. Cervical Intraepithelial Neoplasia / drug therapy. Cervical Intraepithelial Neoplasia / virology. Human papillomavirus 16 / immunology. Oncogene Proteins, Fusion / therapeutic use. Oncogene Proteins, Viral / therapeutic use. Papillomavirus Vaccines / therapeutic use. Uterine Cervical Neoplasms / drug therapy. Uterine Cervical Neoplasms / virology
  • [MeSH-minor] Adult. Aged. DNA, Viral / drug effects. DNA, Viral / isolation & purification. Double-Blind Method. Drug Administration Schedule. Female. Humans. Middle Aged. Papillomavirus Infections / complications. Papillomavirus Infections / drug therapy. Papillomavirus Infections / immunology. Time Factors. Treatment Outcome. Tumor Virus Infections / complications. Tumor Virus Infections / drug therapy. Tumor Virus Infections / immunology


13. TOMBOLA Group: Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial. BMJ; 2009 Jul 28;339:b2548
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  • [Title] Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial.
  • OBJECTIVES: To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy.
  • DESIGN: Multicentre individually randomised controlled trial, nested within the NHS cervical screening programmes.
  • PARTICIPANTS: 1983 women, aged 20-59, with cytology showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002.
  • INTERVENTIONS: Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment (by large loop excision) if these showed cervical intraepithelial neoplasia grade II or III or worse.
  • MAIN OUTCOME MEASURES: Clinical end points: cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years.
  • RESULTS: 879 women (44%) had a normal transformation zone at colposcopy and had no further procedures at that time.
  • Of women randomised to biopsy and recall, 157 (16%) required a second clinic visit for treatment.
  • Specimens from almost 60% (n=296) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia (31%; n=156) or showed cervical intraepithelial neoplasia grade I (28%; n=140).
  • The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22% (n=216) in the biopsy and recall arm and 23% (n=228) in the immediate large loop excision arm.
  • There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse (adjusted relative for risk large loop excision v biopsy 1.04, 95% confidence interval 0.86 to 1.25) or grade III or worse (1.03, 0.79 to 1.34).
  • A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm, but time of detection did not differ significantly between arms.
  • CONCLUSION: A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy.

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  • (PMID = 19638647.001).
  • [ISSN] 1756-1833
  • [Journal-full-title] BMJ (Clinical research ed.)
  • [ISO-abbreviation] BMJ
  • [Language] ENG
  • [Databank-accession-numbers] ISRCTN/ ISRCTN34841617
  • [Grant] United Kingdom / Medical Research Council / / G9700808
  • [Publication-type] Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC2718084
  • [Investigator] Cruickshank M; Murray G; Parkin D; Smart L; Walker E; Waugh N; Avis M; Chilvers C; Fielding K; Hammond R; Jenkins D; Johnson J; Neal K; Russell I; Seth R; Whynes D; Duncan I; Robertson A; Little J; Sharp L; Russell I; Walker L; Anthony B; Bell S; Bowie A; Brown K; Brown J; Chew K; Cochran C; Cotton S; Dean J; Dunn K; Edwards J; Evans D; Fenty J; Finlayson A; Gallagher M; Gray N; Heddle M; Innes A; Jobson D; Keillor M; MacGregor J; Mackenzie S; Mackie A; McPherson G; Okorocha I; Reilly M; Rodgers J; Thornton A; Yeats R; Alexander L; Buchanan L; Henderson S; Iterbeke T; Lucas S; Manderson G; Nicol S; Reid G; Robinson C; Sandilands T; Adrian M; Al-Sahab A; Bentley E; Brook H; Bushby C; Cannon R; Cooper B; Dowell R; Dunderdale M; Gabrawi; Guo L; Heideman L; Jones S; Lawson S; Philips Z; Platt C; Prabhakaran S; Rippin J; Thompson R; Williams E; Woolley C; Boroujerdi M; Cotton S; Harrild K; Norrie J; Day N; Marteau T; Parmar M; Patnick J; Woodman C; Altman D; Moss S; Wells M; Sharp L; Cruickshank M; Little J; Cotton S; Harrild K; Cochran C; Duncan I; Gray N; Hammond R; Smart L; Thornton A; Waugh N; Woolley C
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14. Hougardy BM, Reesink-Peters N, van den Heuvel FA, ten Hoor KA, Hollema H, de Vries EG, de Jong S, van der Zee AG: A robust ex vivo model for evaluation of induction of apoptosis by rhTRAIL in combination with proteasome inhibitor MG132 in human premalignant cervical explants. Int J Cancer; 2008 Sep 15;123(6):1457-65
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  • [Title] A robust ex vivo model for evaluation of induction of apoptosis by rhTRAIL in combination with proteasome inhibitor MG132 in human premalignant cervical explants.
  • Development of medical therapies for high-grade cervical intraepithelial neoplasia (CIN II/III) is hampered by the lack of CIN II/III cell lines.
  • Proteasome inhibition by MG132 sensitized cervical cancer cell lines to recombinant human (rh)TRAIL.
  • In our study, we aimed to develop an ex vivo model for CIN II/III and to investigate the apoptosis-inducing effect of rhTRAIL and/or MG132 in cervical explants from CIN II/III patients.
  • A short-term ex vivo culture system was optimized for cervical biopsies, in which explants from normal cervix and CIN II/III lesions were exposed to either rhTRAIL (1 microg/ml), MG132 (5 microM) or the combination and compared to untreated explants for apoptosis induction.
  • Normal cervix (n = 90) and CIN II/III (n = 24) explants could be reproducibly put in culture and kept viable for up to 7 days using a transwell membrane system.
  • CIN II/III explants (n = 5) were highly sensitive to rhTRAIL plus MG132 (mean % apoptosis: 91 +/- 5) compared to normal cervix (n = 10) treated with rhTRAIL plus MG132 (mean % apoptosis: 24 +/- 10, p < 0.0001), while monotherapy with either rhTRAIL, MG132 or medium resulted in a mean % apoptosis <10 in both CIN II/III and normal cervix.
  • Our ex vivo model system allows preclinical evaluation of (topical) medical therapies for CIN II/III.
  • A strong synergistic apoptosis-inducing effect of the combination of rhTRAIL and MG132, especially in CIN II/III lesions indicates that rhTRAIL combined with proteasome inhibitors deserves exploration as medical treatment for CIN II/III.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / pharmacology. Apoptosis / drug effects. Cervical Intraepithelial Neoplasia / drug therapy. Leupeptins / pharmacology. TNF-Related Apoptosis-Inducing Ligand / pharmacology. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Cell Culture Techniques / methods. Cells, Cultured. Female. Humans. Immunohistochemistry. Precancerous Conditions / drug therapy. Precancerous Conditions / pathology. Recombinant Proteins / pharmacology

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  • [Copyright] Copyright 2008 Wiley-Liss, Inc.
  • (PMID = 18567003.001).
  • [ISSN] 1097-0215
  • [Journal-full-title] International journal of cancer
  • [ISO-abbreviation] Int. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Leupeptins; 0 / Recombinant Proteins; 0 / TNF-Related Apoptosis-Inducing Ligand; 0 / TNFSF10 protein, human; 133407-82-6 / benzyloxycarbonylleucyl-leucyl-leucine aldehyde
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15. Barnett AA, Haller JC, Cairnduff F, Lane G, Brown SB, Roberts DJ: A randomised, double-blind, placebo-controlled trial of photodynamic therapy using 5-aminolaevulinic acid for the treatment of cervical intraepithelial neoplasia. Int J Cancer; 2003 Mar 1;103(6):829-32
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  • [Title] A randomised, double-blind, placebo-controlled trial of photodynamic therapy using 5-aminolaevulinic acid for the treatment of cervical intraepithelial neoplasia.
  • Photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (ALA) has been used to treat histologically confirmed cervical intraepithelial neoplasia (CIN-I and -I/II) in a randomised, double-blind, placebo-controlled protocol.
  • Fluorescence microscopy revealed that topical application of 3% ALA in Intrasite Gel to the cervix for 3 hr resulted in the accumulation of protoporphyrin IX in the cervical epithelium.
  • Treatment of CIN with ALA-PDT was well tolerated, with only 3/12 patients in the PDT arm (0/13 in the placebo arm) reporting any discomfort during illumination.
  • Histologic examination of the treated tissue following loop excision 3 months post-PDT indicated that 33% of patients had no evidence of CIN, 42% had no change in the grade of their disease, whilst 25% exhibited an apparent progression of disease.
  • There was no significant difference in response between the groups receiving ALA-PDT and those receiving placebo treatment.
  • [MeSH-major] Aminolevulinic Acid / therapeutic use. Cervical Intraepithelial Neoplasia / drug therapy. Photochemotherapy. Photosensitizing Agents / therapeutic use. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Administration, Topical. Adult. Cervix Uteri / drug effects. Colposcopy. Double-Blind Method. Female. Humans. Image Processing, Computer-Assisted. Microscopy, Fluorescence. Protoporphyrins / metabolism

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  • [Copyright] Copyright 2002 Wiley-Liss, Inc.
  • (PMID = 12516106.001).
  • [ISSN] 0020-7136
  • [Journal-full-title] International journal of cancer
  • [ISO-abbreviation] Int. J. Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Photosensitizing Agents; 0 / Protoporphyrins; 553-12-8 / protoporphyrin IX; 88755TAZ87 / Aminolevulinic Acid
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16. Buxant F, Bucella D, Anaf V, Simon P, Noël JC: Glucocorticoid receptor expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix. Eur J Gynaecol Oncol; 2009;30(3):259-62
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  • [Title] Glucocorticoid receptor expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix.
  • OBJECTIVES: Glucocorticoids (GCs) are used in cancer treatment to cause programmed cell death in transformed cells of the hematopoietic system and to lessen side-effects as nausea, vomiting, edema formation and allergies to specific chemotherapeutic agents.
  • GCs act also as cofactor with human papillomaviruses in the etiology of cervical cancer.
  • Moreover, recently GCs were described as inhibitors of some chemotherapy or radiation-induced apoptosis.
  • METHODS: To clarify the issue, we tested by immunohistochemistry the expression status of GR in normal cervix epithelium (n = 30), in low-grade cervical intraepithelial neoplasia (LSIL) (n = 30), in high-grade cervical intraepithelial neoplasia (HSIL) (n = 30) and in invasive squamous cell carcinoma (ISCC) (n = 30).
  • CONCLUSION: Because GCs could play a positive role in the progression of cancer, our demonstration of GR persistence in cervix cancer cells raises concern about the widespread combined use of GCs with antineoplastic drugs or agents in the clinical management of cervix cancer in women.
  • [MeSH-major] Carcinoma, Squamous Cell / metabolism. Cervical Intraepithelial Neoplasia / metabolism. Receptors, Glucocorticoid / metabolism. Uterine Cervical Neoplasms / metabolism


17. Soergel P, Wang X, Stepp H, Hertel H, Hillemanns P: Photodynamic therapy of cervical intraepithelial neoplasia with hexaminolevulinate. Lasers Surg Med; 2008 Nov;40(9):611-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Photodynamic therapy of cervical intraepithelial neoplasia with hexaminolevulinate.
  • BACKGROUND AND OBJECTIVE: CIN is a disease of women in their reproductive years, and treatment includes excisional techniques with increased risk of preterm deliveries.
  • Photodynamic therapy (PDT) using topical precursor of photoactive porphyrins may be a non-invasive alternative with minimal side effects.
  • This study assessed the feasibility and response rate of PDT with hexaminolevulinate (HAL) in cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection.
  • STUDY DESIGN/MATERIALS AND METHODS: Twenty four patients with a CIN 2 or 3 or a persistent CIN 1 and a positive high-risk HPV-DNA test were included.
  • Each patient had gynaecologic examination including cervical cytology, HPV DNA testing, colposcopy and biopsy.
  • Ten milliliters of HAL-thermogel (10 mM) were topically applied to the cervix for 3-5 hours, followed by 1,000 seconds of illumination of both ecto- and endocervical canal with red coherent light (wave length 633 nm) using a PDT laser and a special light catheter.
  • RESULTS: Seven, 10, and 7 patients had a CIN 1, 2, or 3, respectively.
  • Treatment could be accomplished in all cases and no severe side effects were encountered.
  • Fifteen out of the 24 patients had a complete response (15/24 = 63%) and a HPV remission 6 months after 1-3 treatments.
  • The remission rates were 71%, 50%, and 71% for CIN 1, 2 and 3.
  • CONCLUSION: HAL PDT seems to be a non-invasive, repeatable procedure for CIN and cervical HPV infection with minimal side effects which can be easily performed on outpatient basis.
  • [MeSH-major] Aminolevulinic Acid / analogs & derivatives. Cervical Intraepithelial Neoplasia / drug therapy. Photochemotherapy. Photosensitizing Agents / therapeutic use. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Feasibility Studies. Female. Humans. Papillomavirus Infections / drug therapy. Papillomavirus Infections / pathology. Treatment Outcome. Young Adult


18. Sikorski M, Bieda T, Bobek M, Zrubek H: Dynamics of cervical langerhans cell counts in the course of HPV-positive CIN treatment with the use of human recombinant interferon gamma. Eur J Gynaecol Oncol; 2005;26(3):294-8
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  • [Title] Dynamics of cervical langerhans cell counts in the course of HPV-positive CIN treatment with the use of human recombinant interferon gamma.
  • OBJECTIVES: Langerhans cells play a pivotal role as professional antigens presenting cells in cervical epithelium, thus changes in their density or/and function may profoundly influence the proper activation of the afferent arm of immune response in cases of HPV-related intraepithelial lesions.
  • AIM OF THE STUDY: Assessment of intraepithelial Langerhans cell count changes in CIN I/CIN II after human recombinant interferon gamma (IFNgamma) application and correlation with clinical outcome.
  • MATERIAL & METHODS: The present study is a part of prospective trial on IFNgamma application in the treatment of CIN I/CINII associated with high-risk HPV infection.
  • Seventeen subjects underwent uniform IFNgamma treatment (four intracervical injections in a two-day interval for a total dose of 6,000,000 IU).
  • Langerhans cells were stained within cervical punch biopsy specimens with the use of polyclonal anti-S-100 antibody according to the three-step indirect peroxidase protocol, and their mean count calculated for the following groups: before IFNgamma treatment launching, immediately after completion of the treatment, and after two months of follow-up.
  • RESULTS: The analysis revealed a rapid and significant increase in Lagerhans' cell count immediately after treatment completion (21.17/mm2 and 25.94/mm2, respectively, at p = 0.019) which further increased in the group of complete response (in 9 subjects; 32.22/mm2).
  • CONCLUSION: Our data strongly support the observation from static studies suggesting that regression of HPV-related cervical lesions is associated with increased density of epithelial Langerhans cells.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Cervical Intraepithelial Neoplasia / drug therapy. Interferon-gamma / administration & dosage. Langerhans Cells / immunology. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Antiviral Agents / administration & dosage. Cell Count. Cervix Uteri / drug effects. Cervix Uteri / immunology. Female. Humans. Injections, Intralesional. Middle Aged. Papillomaviridae. Papillomavirus Infections / drug therapy. Papillomavirus Infections / immunology. Recombinant Proteins. Remission Induction. Treatment Outcome

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  • (PMID = 15991530.001).
  • [ISSN] 0392-2936
  • [Journal-full-title] European journal of gynaecological oncology
  • [ISO-abbreviation] Eur. J. Gynaecol. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Antiviral Agents; 0 / Recombinant Proteins; 82115-62-6 / Interferon-gamma
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19. Di Roma E, Parlavecchio E, Vettraino G, Corosu R: [CIN: multicentric study of therapeutic strategies]. Minerva Ginecol; 2001 Dec;53(6):379-2
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  • [Title] [CIN: multicentric study of therapeutic strategies].
  • [Transliterated title] CIN: studio multicentrico sulle strategie terapeutiche.
  • BACKGROUND: Cervical Intraepithelial Neoplasia (CIN) is a dysplastic lesion that precedes cervical cancer.
  • The diagnosis is made by colposcopic, cytologic and bioptic exams.
  • Therapy may be physical, pharmacological or surgical.
  • Our aim was to evaluate their therapeutic strategies for CIN and cervical condylomata.
  • We referred to SIGO 1999 guidelines for CIN therapy and to European guidelines for cervical condylomata therapy.
  • RESULTS: The centers used drugs more for HPV infections (57%) than for dysplasia (33%).
  • Drug therapy was used more in the past (66.67%).
  • Actually they prefer treating CIN I with electrocoagulation diathermy (DTC), CIN II with loop electrosurgical excision procedures (LEEP) or Laser, CIN III with cold knife conization or LEEP, cervical condylomata with laser or DTC.
  • CONCLUSIONS: The results show that the centers prefer physical therapy.
  • Therapeutic strategies comply with SIGO 1999 guidelines for therapy of CIN and with European guidelines for cervical condylomata partially.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / therapy. Uterine Cervical Neoplasms / therapy
  • [MeSH-minor] Conization. Electrocoagulation. Electrosurgery. Female. Humans. Hysterectomy. Interferons / therapeutic use. Interviews as Topic. Italy. Laser Therapy. Practice Guidelines as Topic. Surveys and Questionnaires






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