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1. 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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  • [Title] Role of human papillomavirus DNA testing in management of women with atypical squamous cells of undetermined significance.
  • 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


2. Stanley M: Chapter 17: Genital human papillomavirus infections--current and prospective therapies. J Natl Cancer Inst Monogr; 2003;(31):117-24
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  • [Title] Chapter 17: Genital human papillomavirus infections--current and prospective therapies.
  • Many therapies are available for the treatment of human papillomavirus (HPV)-associated disease, particularly external genital warts.
  • However, at present, these therapies aim to remove the lesion rather than specifically target HPV infection.
  • When disease and infection are local, as in cervical intraepithelial neoplasia (CIN), excisional therapies removing lesion and transformation-susceptible cells are highly effective.
  • However, when infection is regional, as is usually the case for the anogenital warts, vulval intraepithelial neoplasia (VIN), anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia, and vaginal intraepithelial neoplasia, then current treatments are generally inadequate, with high recurrence rates.
  • Future therapies will be directly or indirectly antiviral, targeting HPV protein functions or enhancing the ability of the immune system to resolve infection or inducing apoptosis indirectly in HPV-infected cells.
  • In the short to the medium term, immunotherapies for low-grade disease are the most likely to be in the clinic.
  • Vaccines designed to target high-grade intraepithelial disease, even when used in combination with immunomodulators, are unlikely to effect lesion clearance in more than a fraction of the cases.
  • However, they may have a role as adjunct therapy after cervical conization to prevent the recurrence of CIN or HPV reinfection.
  • They certainly appear to have a role in multifocal disease, such as VIN and AIN, where partial clearance may be effected and lesion size reduced enough for effective ablative or excisional therapy.
  • [MeSH-major] Adjuvants, Immunologic / therapeutic use. Anticarcinogenic Agents / therapeutic use. Antiviral Agents / therapeutic use. Papillomaviridae. Papillomavirus Infections / therapy. Tumor Virus Infections / therapy. Uterine Cervical Neoplasms / prevention & control. Uterine Cervical Neoplasms / virology
  • [MeSH-minor] Anus Neoplasms / prevention & control. Anus Neoplasms / virology. Cancer Vaccines / therapeutic use. Cervical Intraepithelial Neoplasia / prevention & control. Cervical Intraepithelial Neoplasia / virology. Clinical Trials as Topic. Combined Modality Therapy. Conization. DNA, Viral / isolation & purification. Female. Humans. Indoles / therapeutic use. Male. Photochemotherapy. Precancerous Conditions / therapy. Precancerous Conditions / virology. Retinoids / therapeutic use. Sexually Transmitted Diseases, Viral / therapy. Viral Vaccines / therapeutic use


3. van Hamont D, Bekkers RL, Massuger LF, Melchers WJ: Detection, management, and follow-up of pre-malignant cervical lesions and the role for human papillomavirus. Rev Med Virol; 2008 Mar-Apr;18(2):117-32
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  • [Title] Detection, management, and follow-up of pre-malignant cervical lesions and the role for human papillomavirus.
  • Cervical cytological pathology is common.
  • Prevention of cervical cancer by detecting the disease process at an early and pre-malignant stage is practised globally either through population-based screening programmes (PSP) or through non-organised ones.
  • High-grade cervical intraepithelial neoplasia (CIN) detected by cervical cytological screening is extensively visualised by colposcopy and successively treated by, for instance, large loop electro-surgical excision of the transformation zone.
  • Persistent infections with certain high-risk human papillomavirus (hr-HPV) genotypes play an essential role in cervical cancer carcinogenesis by mechanisms discussed in this review.
  • HPV assessment, either DNA detection or HPV genotyping, could enhance the current cervical cancer screening programmes.
  • Furthermore, primary prevention of cervical cancer through the introduction of HPV vaccines looks promising although the current vaccines merely protect against two hr-HPV genotypes, leaving a niche for at least 11 other hr-HPV's.
  • Cervical screening in the post-vaccination era cannot be abolished but could be altered, as discussed in this review.
  • [MeSH-major] Papillomaviridae / classification. Papillomaviridae / isolation & purification. Papillomavirus Infections / diagnosis. Papillomavirus Infections / drug therapy. Precancerous Conditions / diagnosis. Precancerous Conditions / drug therapy
  • [MeSH-minor] Cervical Intraepithelial Neoplasia / diagnosis. Cervical Intraepithelial Neoplasia / drug therapy. Cervical Intraepithelial Neoplasia / virology. DNA, Viral / analysis. Electrosurgery. Female. Humans. Papillomavirus Vaccines. Uterine Cervical Neoplasms / diagnosis. Uterine Cervical Neoplasms / drug therapy. Uterine Cervical Neoplasms / virology. Vaginal Smears

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  • (PMID = 18001004.001).
  • [ISSN] 1052-9276
  • [Journal-full-title] Reviews in medical virology
  • [ISO-abbreviation] Rev. Med. Virol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / DNA, Viral; 0 / Papillomavirus Vaccines
  • [Number-of-references] 125
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4. Bulten J, de Wilde PC, Boonstra H, Gemmink JH, Hanselaar AG: Proliferation in "atypical" atrophic pap smears. Gynecol Oncol; 2000 Nov;79(2):225-9
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  • OBJECTIVE: Atrophic cervical epithelium of postmenopausal women may mimic high-grade cervical intraepithelial neoplasia (CIN2-3) in Papanicolaou-stained cervical smears (Pap smears).
  • The aim of this study was to determine whether measurement of proliferative activity in Pap smears of postmenopausal patients that were difficult to interpret is a reliable test for differentiating between cervical atrophy and high-grade CIN.
  • METHODS: Pap smears obtained before and after estrogen treatment of 30 postmenopausal women with an atypical Pap smear were restained with the monoclonal antibody MIB1 to visualize proliferating cells.
  • The proliferative activity index (PAI) was subsequently measured in order to explore the feasibility of a recently proposed PAI-based diagnostic decision tree to reduce the number of estrogen courses and follow-up Pap smears in postmenopausal women.
  • RESULTS: The PAI-based test to discriminate between cervical atrophy and high-grade CIN resulted in 100 and 96% correct diagnoses in women with high-grade CIN and cervical atrophy, respectively.
  • Only 2 of the 30 women would have needed a repeated Pap smear after estrogen treatment for definite diagnosis if the PAI-based diagnostic decision had been used.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / pathology. Cervix Uteri / pathology. Uterine Cervical Neoplasms / pathology
  • [MeSH-minor] Antibodies, Monoclonal. Atrophy / drug therapy. Atrophy / pathology. Cell Division / drug effects. Decision Trees. Diagnosis, Differential. Epithelium / drug effects. Epithelium / pathology. Estriol / therapeutic use. Female. Humans. Immunohistochemistry. Ki-67 Antigen / immunology. Postmenopause / physiology. Retrospective Studies

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  • [Copyright] Copyright 2000 Academic Press.
  • (PMID = 11063649.001).
  • [ISSN] 0090-8258
  • [Journal-full-title] Gynecologic oncology
  • [ISO-abbreviation] Gynecol. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Ki-67 Antigen; FB33469R8E / Estriol
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5. Sewaki T: [Generation of mucosal vaccine utilizing lactobacillus display system]. Yakugaku Zasshi; 2009 Nov;129(11):1327-32
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  • We have developed novel surface display system based on PgsA gene, which isolated from Bacillus subtilis chungkookjang.
  • HPV oncogene, E7, is a reliable target protein since E7 is expressed in the CIN lesion.
  • There is no therapeutic vaccine utilizing oral administration and there is no clinical trial which addresses cervical mucosal cellular immune responses to the vaccine.
  • Our recent progress is production of a mucosal vaccine to treat cervical intraepithelial neoplasia (CIN) that has potential of cervical cancer.
  • The vaccine is expected to help the vast number of women suffering from high grade CIN.
  • Lac-E7 is a candidate for new therapeutic vaccine for cervical intraepithelial neoplasia.
  • [MeSH-major] Cancer Vaccines. Drug Design. Genetic Engineering / methods. Lactobacillus. Papillomavirus Vaccines
  • [MeSH-minor] Antigen Presentation. Cervical Intraepithelial Neoplasia / therapy. Cervical Intraepithelial Neoplasia / virology. Female. Humans. Oncogene Proteins, Viral. Papillomavirus E7 Proteins

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  • (PMID = 19881204.001).
  • [ISSN] 0031-6903
  • [Journal-full-title] Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
  • [ISO-abbreviation] Yakugaku Zasshi
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Cancer Vaccines; 0 / Oncogene Proteins, Viral; 0 / Papillomavirus E7 Proteins; 0 / Papillomavirus Vaccines; 0 / oncogene protein E7, Human papillomavirus type 16
  • [Number-of-references] 29
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6. Trimble C, Lin CT, Hung CF, Pai S, Juang J, He L, Gillison M, Pardoll D, Wu L, Wu TC: Comparison of the CD8+ T cell responses and antitumor effects generated by DNA vaccine administered through gene gun, biojector, and syringe. Vaccine; 2003 Sep 8;21(25-26):4036-42
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  • We have previously linked Mycobacterium tuberculosis heat shock protein 70 (HSP70) to human papillomavirus type 16 (HPV-16) E7 in the context of a DNA vaccine.
  • The success of our strategy has led to two phases I/II clinical trial proposals in patients with HPV-16 associated high-grade squamous intraepithelial lesion (HSIL) of the cervix and in patients with advanced HPV-associated head and neck squamous cell carcinoma (HNSCC).
  • [MeSH-minor] Animals. Antibody Specificity. Biolistics. Cytokines / biosynthesis. Female. Flow Cytometry. HSP70 Heat-Shock Proteins / immunology. Injections, Intramuscular. Interferon-gamma / biosynthesis. Mice. Mice, Inbred C57BL. Papilloma / drug therapy. Papilloma / pathology. Papilloma / prevention & control. Papillomaviridae / immunology. Plasmids / genetics. Vaccines, DNA / administration & dosage. Vaccines, DNA / immunology

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  • (PMID = 12922140.001).
  • [ISSN] 0264-410X
  • [Journal-full-title] Vaccine
  • [ISO-abbreviation] Vaccine
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Cancer Vaccines; 0 / Cytokines; 0 / HSP70 Heat-Shock Proteins; 0 / Vaccines, DNA; 82115-62-6 / Interferon-gamma
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7. 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.
  • High-risk (HR) HPV-16 and -18 status was determined in all the study groups, including controls.
  • 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).
  • 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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8. Feng W, Duan X, Liu J, Xiao J, Brown RE: Morphoproteomic evidence of constitutively activated and overexpressed mTOR pathway in cervical squamous carcinoma and high grade squamous intraepithelial lesions. Int J Clin Exp Pathol; 2009;2(3):249-60
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  • [Title] Morphoproteomic evidence of constitutively activated and overexpressed mTOR pathway in cervical squamous carcinoma and high grade squamous intraepithelial lesions.
  • Human papilloma virus (HPV) infection of the uterine cervix is linked to the pathogenesis of cervical cancer.
  • Preclinical in vitro and in vivo studies using HPV-containing human cervical carcinoma cell lines have shown that the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, erlotinib, can induce growth delay of xenografts.
  • Activation of Akt and mTOR are also observed in cervical squamous cell carcinoma and, the expression of phosphorylated mTOR was reported to serve as a marker to predict response to chemotherapy and survival of cervical cancer patients.
  • Therefore, we investigated: a) the expression level of EGFR in cervical squamous cell carcinoma (SCC) and high-grade squamous intraepithelial lesions (HSIL) versus non-neoplastic cervical squamous epithelium;.
  • b) the state of activation of the mTOR pathway in these same tissues; and c) any impact of these signal transduction molecules on cell cycle.
  • Formalin-fixed paraffin-embedded tissue microarray blocks containing 20 samples each of normal cervix, HSIL and invasive SCC, derived from a total of 60 cases of cervical biopsies and cervical conizations were examined.
  • We found that plasmalemmal EGFR expression was limited to the basal/parabasal cells (2-3+, EI = 67) in normal cervical epithelium (NL), but was diffusely positive in all HSIL (EI = 237) and SCC (EI 226).
  • The pattern of cytoplasmic p-mTOR and nuclear p-p70S6K expression was similar to that of EGFR; all showed a significantly increased EI in HSIL/SCC versus NL (p<0.02).
  • Nuclear translocation of p-mTOR was observed in all SCC lesions (EI = 202) and was significantly increased versus both HSIL (EI = 89) and NL (EI = 54) with p<0.015 and p<0.0001, respectively.
  • Concomitant increases in MI and proportion of nuclear Ki-67 and Skp2 expression were noted in HSIL and SCC.
  • In conclusion, morphoproteomic analysis reveals constitutive activation and overexpression of the mTOR pathway in HSIL and SCC as evidenced by: increased nuclear translocation of pmTOR and p-p70S6K, phosphorylated at putative sites of activation, Ser2448 and Thr389, respectively; correlative overexpression of the upstream signal transducer, EGFR, and increases in cell cycle correlates, Skp2 and mitotic indices.
  • These results suggest that the mTOR pathway plays a key role in cervical carcinogenesis and targeted therapies may be developed for SCC as well as its precursor lesion, HSIL.


9. 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


10. Snuderl M, Kolman OK, Chen YB, Hsu JJ, Ackerman AM, Dal Cin P, Ferry JA, Harris NL, Hasserjian RP, Zukerberg LR, Abramson JS, Hochberg EP, Lee H, Lee AI, Toomey CE, Sohani AR: B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma. Am J Surg Pathol; 2010 Mar;34(3):327-40
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  • The clinical and pathologic spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined.
  • Six patients had a history of grade 1 to 2 follicular lymphoma; review of the prior biopsy specimens in 2 of 5 cases revealed blastoid morphology.
  • Nineteen patients were treated with combination chemotherapy, of whom 18 received rituximab and 14 received CNS-directed therapy.
  • DHL is a high-grade B-cell neoplasm with a poor prognosis, resistance to multiagent chemotherapy, and clinical and pathologic features distinct from other high-grade B-cell neoplasms.
  • The aggressive clinical behavior and combination of genetic abnormalities seen in these cases may warrant categorization as a separate entity in future classifications and call for novel therapeutic approaches.
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Antineoplastic Combined Chemotherapy Protocols. Child. Drug Resistance, Neoplasm. Female. Humans. Immunophenotyping. In Situ Hybridization, Fluorescence. Kaplan-Meier Estimate. Karyotyping. Male. Middle Aged. Neoplasm Staging. Polymerase Chain Reaction. Predictive Value of Tests. Proportional Hazards Models. Retrospective Studies. Risk Assessment. Terminology as Topic. Time Factors. Treatment Outcome. World Health Organization. Young Adult

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  • (PMID = 20118770.001).
  • [ISSN] 1532-0979
  • [Journal-full-title] The American journal of surgical pathology
  • [ISO-abbreviation] Am. J. Surg. Pathol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / R37 CA076404; United States / NIGMS NIH HHS / GM / T32 GM074897; United States / NIGMS NIH HHS / GM / T32 GM074897-07
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / MYC protein, human; 0 / Proto-Oncogene Proteins c-bcl-2; 0 / Proto-Oncogene Proteins c-myc
  • [Other-IDs] NLM/ NIHMS305320; NLM/ PMC3152212
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11. 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


12. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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

  • MedlinePlus Health Information. consumer health - Cervical Cancer.
  • International Agency for Research on Cancer - Screening Group. diagnostics - Histopathology and cytopathology of the uterine cervix - digital atlas .
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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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13. Ayas S, Karateke A, Aköz I, Kir G, Yenidede I: Primary serous carcinoma of the fallopian tube with synchronous cervical epidermoid carcinoma in situ: a case report. Eur J Gynaecol Oncol; 2007;28(6):501-2
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Primary serous carcinoma of the fallopian tube with synchronous cervical epidermoid carcinoma in situ: a case report.
  • In this report we present a rare case of primary carcinoma of the fallopian tube with synchronous cervical high-grade squamous intraepithelial lesion (HSIL).
  • A 39-year-old women was admitted to our hospital for routine gynecological examination and underwent surgery because of the finding of HSIL on a routine papanicolaou smear.
  • The histological diagnosis on cervical biopsy and conization material were of cervical intraepithelial neoplasia III (CIN III).
  • Postoperatively the patient received six cycles of adjuvant chemotherapy (carboplatin and paclitaxel) and is still under routine control.
  • [MeSH-major] Carcinoma, Squamous Cell / diagnosis. Fallopian Tube Neoplasms / diagnosis. Uterine Cervical Neoplasms / diagnosis


14. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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






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