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1. 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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  • [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


2. 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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3. Cazorla E, Urgal A, Córdoba J, Boldó A, Marín M, Sánchez Gutiérrez M, Molina JM, Llixiona J: [Immunomodulatory treatment with beta-interferon in patients with cervical intraepithelial neoplasia and human papillomavirus infection: long-term follow-up]. Rev Esp Quimioter; 2005 Mar;18(1):26-31
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  • [Title] [Immunomodulatory treatment with beta-interferon in patients with cervical intraepithelial neoplasia and human papillomavirus infection: long-term follow-up].
  • [Transliterated title] Tratamiento inmunomodulador con interferón beta en pacientes con neoplasia cervical intraepitelial e infección por virus del papiloma humano. Seguimiento a largo plazo.
  • The aim of this study was to evaluate the long-term efficacy of beta-interferon treatment in the management of cervical intraepithelial neoplasia associated with human papillomavirus (HPV) infection in a selected group of patients.
  • Thirty-nine patients who had histologically proven cervical intraepithelial neoplasia I or II with concurrent HPV infection were administered 27,000,000 IU of intramuscular beta-interferon.
  • An initial complete response rate of 75% was obtained, with a recurrence rate of 25%, cervical intraepithelial neoplasia with late manifestation was of higher grade.
  • Treatment interruption due to side-effects was not necessary.
  • While immunomodulatory treatment with beta-interferon has good long-term results in cervical intraepithelial neoplasia I/II treatment, wider randomized studies are required to obtain conclusive results.
  • [MeSH-major] Adjuvants, Immunologic / therapeutic use. Cervical Intraepithelial Neoplasia / complications. Cervical Intraepithelial Neoplasia / drug therapy. Interferon-beta / therapeutic use. Papillomavirus Infections / complications. Papillomavirus Infections / drug therapy. Uterine Cervical Diseases / complications. Uterine Cervical Diseases / drug therapy. Uterine Cervical Neoplasms / complications. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Female. Follow-Up Studies. Humans. Middle Aged. Time Factors

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  • (PMID = 15915229.001).
  • [ISSN] 0214-3429
  • [Journal-full-title] Revista española de quimioterapia : publicación oficial de la Sociedad Española de Quimioterapia
  • [ISO-abbreviation] Rev Esp Quimioter
  • [Language] spa
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Spain
  • [Chemical-registry-number] 0 / Adjuvants, Immunologic; 77238-31-4 / Interferon-beta
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4. 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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5. Sikorski M, Zrubek H: Long-term follow-up of patients treated with recombinant human interferon gamma for cervical intraepithelial neoplasia. Int J Gynaecol Obstet; 2003 Aug;82(2):179-85
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Long-term follow-up of patients treated with recombinant human interferon gamma for cervical intraepithelial neoplasia.
  • OBJECTIVES: The immediate results of interferon gamma (IFN-gamma) treatment in the management of cervical intraepithelial neoplasia (CIN) have been described.
  • However, little is known of the long-term results of this conservative treatment and we aimed to assess them.
  • METHODS: We conducted a 5-year follow-up of 13 women with either complete response to intracervical administration of 6,000,000 IU of IFN-gamma (remission from human papilloma virus-induced CIN occurred in nine cases) or partial response (a lower grade of CIN and/or HPV clearance was achieved in four cases).
  • We found three cases of relapse of stage 1 CIN (CIN I), for a recurrence rate of 33.3%, and three cases of complete remission in four subjects with initial diagnosis of partial response.
  • This allowed us to assess the overall lesion-free rate at 53% for the entire group of patients who had CIN I and CIN II treated with IFN-gamma.
  • CONCLUSIONS: Immunomodulation therapy with IFN-gamma has a high long-term efficacy; however, it is inferior to that of surgery.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Cervical Intraepithelial Neoplasia / drug therapy. Interferon-gamma / therapeutic use. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Colposcopes. Female. Follow-Up Studies. Humans. Middle Aged. Papanicolaou Test. Recombinant Proteins. Treatment Outcome. Vaginal Smears

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  • (PMID = 12873779.001).
  • [ISSN] 0020-7292
  • [Journal-full-title] International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics
  • [ISO-abbreviation] Int J Gynaecol Obstet
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Recombinant Proteins; 82115-62-6 / Interferon-gamma
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6. Corona Gutierrez CM, Tinoco A, Navarro T, Contreras ML, Cortes RR, Calzado P, Reyes L, Posternak R, Morosoli G, Verde ML, Rosales R: Therapeutic vaccination with MVA E2 can eliminate precancerous lesions (CIN 1, CIN 2, and CIN 3) associated with infection by oncogenic human papillomavirus. Hum Gene Ther; 2004 May;15(5):421-31
International Agency for Research on Cancer - Screening Group. diagnostics - Planning and Implementing Cervical Cancer Prevention and Control Programs: A Manual for Managers .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Therapeutic vaccination with MVA E2 can eliminate precancerous lesions (CIN 1, CIN 2, and CIN 3) associated with infection by oncogenic human papillomavirus.
  • Human papillomavirus (HPV) infection is associated with cervical cancer.
  • Cervical cancer is a serious problem in developing countries because it is usually not detected at an early stage.
  • In a phase I/II clinical trial, we evaluated the potential use of the MVA E2 recombinant vaccinia virus to treat cervical intraepithelial neoplasia CIN 1, CIN 2, and CIN 3 lesions associated with human papillomavirus (HPV) infection.
  • Seventy-eight women with CIN 1-, CIN 2-, and CIN 3-grade lesions were treated with either an MVA E2 recombinant virus vaccine or with cryosurgery.
  • The type of immune response after MVA E2 injection was determined by measuring antibody titers against MVA E2 virus and the E2 protein, and by the presence of cytotoxic activity against cancer cells bearing papillomavirus DNA.
  • Thirty-four of 36 patients showed complete elimination of precancerous lesions after treatment with the MVA E2 vaccine.
  • In two patients, precancerous lesions were reduced from grade CIN 3 to CIN 1.
  • Three other patients presented isolated koilocytes after treatment with MVA E2.
  • Colposcopy revealed no lesions in 85% of patients, and only small aceto-white spots were detected in 15% of patients after treatment with MVA E2.
  • All patients developed antibodies against the MVA E2 vaccine, and vaccination generated a specific cytotoxic response against HPV-transformed cells.
  • Furthermore, 50% of patients showed no evidence of papillomavirus after treatment with MVA E2, while the remaining 50% showed persistence of HPV DNA, but at approximately only 10% of the original viral load.
  • Cryosurgery eliminated the lesions of CIN 1 in all patients, but patients so treated did not develop cytotoxic activity against cancer cells.
  • These results show that therapeutic vaccination with MVA E2 vaccine is an excellent prospective means for stimulating the immune system and causing the regression of precancerous CIN 1, CIN 2, and CIN 3 lesions when the vaccine is given locally.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / drug therapy. Uterine Cervical Neoplasms / prevention & control. Vaccines, DNA / therapeutic use. Vaccinia virus / immunology
  • [MeSH-minor] Adult. Cell Transformation, Viral. Colposcopy. Cytotoxicity Tests, Immunologic. Enzyme-Linked Immunosorbent Assay. Female. Humans. Middle Aged. Papillomaviridae / immunology. Papillomavirus Infections / blood. Patient Selection. Treatment Outcome. Viral Load

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  • (PMID = 15144573.001).
  • [ISSN] 1043-0342
  • [Journal-full-title] Human gene therapy
  • [ISO-abbreviation] Hum. Gene Ther.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Vaccines, DNA
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7. Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY: Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res; 2001 Jul-Aug;21(4B):2895-900
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  • 1) recently resected urinary bladder cancer;.
  • 3) uterine cervical intraepithelial neoplasm (CIN);.
  • If no toxicity > or = grade II was noted in at least 3 successive patients, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day.
  • There was no treatment-related toxicity up to 8,000 mg/day.
  • Beyond 8,000 mg/day, the bulky volume of the drug was unacceptable to the patients.
  • One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia proceeded to develop frank malignancies in spite of curcumin treatment.
  • In contrast, histologic improvement of precancerous lesions was seen in 1 out of 2 patients with recently resected bladder cancer, 2 out of 7 patients of oral leucoplakia, 1 out of 6 patients of intestinal metaplasia of the stomach, I out of 4 patients with CIN and 2 out of 6 patients with Bowen's disease.
  • Our results also suggest a biologic effect of curcumin in the chemoprevention of cancer.
  • [MeSH-major] Anticarcinogenic Agents / therapeutic use. Bowen's Disease / drug therapy. Carcinoma, Transitional Cell / drug therapy. Cervical Intraepithelial Neoplasia / drug therapy. Curcumin / therapeutic use. Leukoplakia, Oral / drug therapy. Precancerous Conditions / drug therapy. Skin Neoplasms / drug therapy. Stomach / pathology. Stomach Neoplasms / prevention & control. Urinary Bladder Neoplasms / drug therapy. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Aged. Arsenicals / adverse effects. Dose-Response Relationship, Drug. Female. Humans. Male. Metaplasia. Middle Aged. Neoplasm Recurrence, Local / prevention & control. Prospective Studies. Risk. Treatment Outcome


8. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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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  • (PMID = 11723421.001).
  • [ISSN] 0026-4784
  • [Journal-full-title] Minerva ginecologica
  • [ISO-abbreviation] Minerva Ginecol
  • [Language] ita
  • [Publication-type] Comparative Study; English Abstract; Journal Article; Multicenter Study
  • [Publication-country] Italy
  • [Chemical-registry-number] 9008-11-1 / Interferons
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9. 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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  • [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


10. 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
International Agency for Research on Cancer - Screening Group. diagnostics - A practical manual on visual screening for cervical neoplasia .

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

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  • (PMID = 16445642.001).
  • [ISSN] 1048-891X
  • [Journal-full-title] International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
  • [ISO-abbreviation] Int. J. Gynecol. Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA Probes, HPV; 0 / DNA, Viral
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11. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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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12. Caprara L, Monari F, De Bianchi PS, Amadori A, Bondi A: [ASCUS in screening]. Pathologica; 2001 Dec;93(6):645-50
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • The significance and use of the cytological diagnosis "atypical squamous cells of undetermined significance" (ASCUS) remain a major problem in cervical cancer screening.
  • The prevalence of diagnoses of low-grade squamous intraepithelial lesions (LG-SIL) decreased progressively with age while that of high-grade SIL was slightly higher between 30 and 39 years.
  • The observed peak reflects the prevalence of (1) cytological changes closely associated with perimenopausal age and at least compatible with the ASCUS diagnosis, and (2) cytological abnormalities induced by hormone replacement therapy.
  • [MeSH-major] Cervix Uteri / pathology. Mass Screening. Papanicolaou Test. Vaginal Smears
  • [MeSH-minor] Adult. Aged. Carcinoma, Squamous Cell / diagnosis. Carcinoma, Squamous Cell / pathology. Cervical Intraepithelial Neoplasia / diagnosis. Cervical Intraepithelial Neoplasia / pathology. Epithelial Cells / drug effects. Epithelial Cells / ultrastructure. Estrogens / pharmacology. False Positive Reactions. Female. Hormone Replacement Therapy. Humans. Italy. Menopause. Middle Aged. Neoplastic Stem Cells / ultrastructure. Progesterone / pharmacology. Uterine Cervical Neoplasms / diagnosis. Uterine Cervical Neoplasms / pathology


13. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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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14. Ou KY, Chen YC, Hsu SC, Tsai EM: Topical vaginal oestrogen cream used for treatment of burn injury of vaginal mucosa after misapplication of 100% acetic acid in a perimenopausal woman: a case report. Aust N Z J Obstet Gynaecol; 2007 Aug;47(4):345-6
Hazardous Substances Data Bank. ACETIC ACID .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Topical vaginal oestrogen cream used for treatment of burn injury of vaginal mucosa after misapplication of 100% acetic acid in a perimenopausal woman: a case report.
  • BACKGROUND: Three to five per cent acetic acid is commonly used in the field of gynaecology for colposcopic examinations of the cervix.
  • CASE: A perimenopausal woman was treated with acetic acid for abnormal Pap smear report (cervical intraepithelial neoplasia 1).
  • [MeSH-major] Acetic Acid / adverse effects. Burns, Chemical / drug therapy. Estradiol Congeners / administration & dosage. Indicators and Reagents / adverse effects. Medication Errors

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  • (PMID = 17627694.001).
  • [ISSN] 0004-8666
  • [Journal-full-title] The Australian & New Zealand journal of obstetrics & gynaecology
  • [ISO-abbreviation] Aust N Z J Obstet Gynaecol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Estradiol Congeners; 0 / Indicators and Reagents; 0 / Vaginal Creams, Foams, and Jellies; Q40Q9N063P / Acetic Acid
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15. Luxton JC, Nath R, Derias N, Herbert A, Shepherd PS: Human papillomavirus type 16-specific T cell responses and their association with recurrence of cervical disease following treatment. J Gen Virol; 2003 May;84(Pt 5):1063-70
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Human papillomavirus type 16-specific T cell responses and their association with recurrence of cervical disease following treatment.
  • Human papillomavirus type 16 (HPV-16) L1- and E7-specific T cell responses were measured in 58 women with abnormal cervical cytology in a prospective study.
  • On recruitment, patients responded most frequently and with the highest numbers of responding cells to the L1 region aa 311-345 and this response was significantly associated with the presence of cervical disease (P=0.041).
  • Responses to the L1 peptide aa 281-295 were significantly higher in patients with CIN III than in those with HPV/CIN I or CIN II lesions (P=0.027).
  • The E7 region aa 70-98 was the most immunogenic in patients with squamous intraepithelial lesions of the cervix (SIL) but the responses detected were not significantly higher than in patients without SIL.
  • Following treatment, the T cell response profiles of patient groups did not change significantly.
  • Recurrence of disease was associated with T cell responses to the E7 region aa 70-98 at the patient's first clinic visit (P=0.017).
  • [MeSH-major] Capsid Proteins. Cervical Intraepithelial Neoplasia / physiopathology. Papillomaviridae / immunology. T-Lymphocytes / immunology. Uterine Cervical Diseases / drug therapy. Uterine Cervical Diseases / physiopathology. Uterine Cervical Neoplasms / physiopathology

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  • (PMID = 12692269.001).
  • [ISSN] 0022-1317
  • [Journal-full-title] The Journal of general virology
  • [ISO-abbreviation] J. Gen. Virol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Capsid Proteins; 0 / L1 protein, Human papillomavirus type 16; 0 / Oncogene Proteins, Viral; 0 / Papillomavirus E7 Proteins; 0 / Peptides; 0 / oncogene protein E7, Human papillomavirus type 16
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16. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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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17. 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
International Agency for Research on Cancer - Screening Group. diagnostics - Histopathology and cytopathology of the uterine cervix - digital atlas .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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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18. Snoeck R, Noel JC, Muller C, De Clercq E, Bossens M: Cidofovir, a new approach for the treatment of cervix intraepithelial neoplasia grade III (CIN III). J Med Virol; 2000 Feb;60(2):205-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Cidofovir, a new approach for the treatment of cervix intraepithelial neoplasia grade III (CIN III).
  • Cervix intraepithelial neoplasia grade III (CIN III) is an intraepithelial proliferative process with different levels of severity depending on both the extension of the proliferation in the epithelium and the presence of cellular atypia.
  • The results of a preliminary study are described on the local application of cidofovir, an acyclic nucleoside phosphonate derivative with broad-spectrum anti-DNA virus activity for the treatment of CIN III.
  • Cidofovir 1% in gel was applied three times, every other day, on the cervix of each of 15 women with biopsy proven CIN III.
  • Within 1 month after the start of treatment, the cervix was removed surgically.
  • In 7 of the 15 patients the histology showed a complete response, whereas 5 patients had a partial response characterized by the persistence of CIN II-III lesions, 1 patient had a dysplasia of lower grade (CIN I), and 2 patients did not show differences in the histology.
  • Cidofovir 1% gel was able to inhibit partially or completely cervical dysplasia lesions after only three applications (every other day).
  • This effect was specific and tissue other than the dysplastic epithelium was not affected by the treatment.
  • [MeSH-major] Antiviral Agents / therapeutic use. Cervical Intraepithelial Neoplasia / drug therapy. Cytosine / analogs & derivatives. Organophosphonates. Organophosphorus Compounds / therapeutic use. Papillomavirus Infections / drug therapy. Tumor Virus Infections / drug therapy. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Biopsy. Cervix Uteri / pathology. Cervix Uteri / surgery. Cervix Uteri / virology. Conization. Female. Humans. Immunohistochemistry. Middle Aged. Papillomaviridae / drug effects. Papillomaviridae / isolation & purification. Polymerase Chain Reaction

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  • [Copyright] Copyright 2000 Wiley-Liss, Inc.
  • (PMID = 10596022.001).
  • [ISSN] 0146-6615
  • [Journal-full-title] Journal of medical virology
  • [ISO-abbreviation] J. Med. Virol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / Organophosphonates; 0 / Organophosphorus Compounds; 8J337D1HZY / Cytosine; JIL713Q00N / cidofovir
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19. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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

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  • (PMID = 19697616.001).
  • [ISSN] 0392-2936
  • [Journal-full-title] European journal of gynaecological oncology
  • [ISO-abbreviation] Eur. J. Gynaecol. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Receptors, Glucocorticoid
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20. Sikorski M, Bobek M, Zrubek H, Marcinkiewicz J: Dynamics of selected MHC class I and II molecule expression in the course of HPV positive CIN treatment with the use of human recombinant IFN-gamma. Acta Obstet Gynecol Scand; 2004 Mar;83(3):299-307
International Agency for Research on Cancer - Screening Group. diagnostics - A practical manual on visual screening for cervical neoplasia .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Dynamics of selected MHC class I and II molecule expression in the course of HPV positive CIN treatment with the use of human recombinant IFN-gamma.
  • BACKGROUND: Studies consistently reveal downregulation of major histocompatibility complex (MHC)-I molecules or/and selective loss of individual MHC-I alleles and upregulation of MHC-II molecules in the areas of cervical intraepithelial neoplasia (CIN) and in cervical cancers.
  • In vitro studies demonstrated the interferon-gamma (IFN-gamma) potential of MHC class I and II molecule upregulation followed by increased cytolytic response against some cervical cancer cell lines.
  • AIM OF THE STUDY: In vivo assessment of the correlation between regression/persistence state of CIN and the IFN-gamma-induced changes in both class of selected MHC molecule expression.
  • METHODS: Seventeen subjects with CIN I/CIN II associated with high-risk HPV infection underwent uniform IFN-gamma treatment (four intracervical injections over 2-day interval for a total dose of 6,000,000 IU).
  • Immunohistochemical staining has been performed within cervical punch biopsy specimens with the use of monoclonal antibody reacting with HLA-DR, HLA-HC and HLA-Bw4, and the mean proportion of given molecules expressing keratinocytes was counted before, immediately after and 2 months after IFN-gamma treatment RESULTS: The analysis revealed a rapid and significant increase of the HLA-Bw4 proportion in response to IFN-gamma, persistent in the group of complete responders (with CIN clearance).
  • No significant changes in the proportion of HLA-HC 10 positive cells in response to IFN-gamma administration was demonstrated, nor a significant increase in HLA-DR positivity; however, the transient trend towards increasing the proportion of HLA-DR immediately after treatment completion was observed.
  • CONCLUSIONS: Upregulation of selected MHC class I allele expression, but not necessary MHC class II or heavy chain fragments of MHC-I, induced by IFN-gamma correlates with the resolution of cervical intraepithelial lesions and high-risk HPV DNA clearance in vivo.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / drug therapy. Histocompatibility Antigens Class I / analysis. Histocompatibility Antigens Class II / analysis. Interferon-gamma / administration & dosage. Papillomavirus Infections / diagnosis. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adult. Biomarkers, Tumor / blood. Biopsy, Needle. DNA, Viral / analysis. Dose-Response Relationship, Drug. Drug Administration Schedule. Female. Follow-Up Studies. Humans. Immunohistochemistry. Injections, Intralesional. Middle Aged. Neoplasm Staging. Papillomaviridae / isolation & purification. Probability. Prospective Studies. Recombinant Proteins. Statistics, Nonparametric. Treatment Outcome

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  • (PMID = 14995928.001).
  • [ISSN] 0001-6349
  • [Journal-full-title] Acta obstetricia et gynecologica Scandinavica
  • [ISO-abbreviation] Acta Obstet Gynecol Scand
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / DNA, Viral; 0 / Histocompatibility Antigens Class I; 0 / Histocompatibility Antigens Class II; 0 / Recombinant Proteins; 82115-62-6 / Interferon-gamma
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21. Hefler L, Grimm C, Tempfer C, Reinthaller A: Treatment with vaginal progesterone in women with low-grade cervical dysplasia: a phase II trial. Anticancer Res; 2010 Apr;30(4):1257-61
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Treatment with vaginal progesterone in women with low-grade cervical dysplasia: a phase II trial.
  • BACKGROUND: The development of low-grade cervical dysplasia (CIN I) has been linked to a decrease of apoptosis and Langerhans cell (LC) count in the cervical epithelium and to an increase in the expression of various adhesion molecules.
  • We hypothesized that vaginal progesterone would increase the regression rate in women with CIN I.
  • MATERIALS AND METHODS: A non-randomized, open phase II trial with vaginal progesterone as treatment of CIN I was performed.
  • The control group consisted of 96 consecutive women with CIN I treated prior and after the study period.
  • RESULTS: The mean (standard deviation) age of women in the treatment and control groups was 32.0 (7.6) and 32.6 (8.5) years, respectively.
  • A total of 30% and 38.3% of CIN I regressed in the treatment and control group, respectively.
  • In a multivariate model, a higher number of children, a higher lifetime number of sexual partners, a lower age at first intercourse, non-use of condoms as contraception, current smoking, and treatment with vaginal progesterone were associated with a higher probability of having persistent or progressive CIN.
  • Current smoking and treatment with vaginal progesterone were associated with a higher probability of undergoing LLETZ.
  • CONCLUSION: Treatment with vaginal progesterone is associated with a lower rate of disease regression and a higher rate of surgical interventions in women with CIN I.
  • We suggest that vaginal progesterone treatment should not be applied in women with known dysplasia.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / drug therapy. Progesterone / administration & dosage. Progestins / administration & dosage. Uterine Cervical Neoplasms / drug therapy

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  • (PMID = 20530437.001).
  • [ISSN] 1791-7530
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase II; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Progestins; 0 / Suppositories; 4G7DS2Q64Y / Progesterone
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22. 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
Hazardous Substances Data Bank. Eflornithine .

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


23. 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

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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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24. Khanna N, Dalby R, Tan M, Arnold S, Stern J, Frazer N: Phase I/II clinical safety studies of terameprocol vaginal ointment. Gynecol Oncol; 2007 Dec;107(3):554-62
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • This trial was designed to define the maximum tolerated dose (MTD), dose-limiting toxicity and determine the pharmacokinetic profiles of intravaginal terameprocol in women with HPV-linked cervical squamous intraepithelial neoplasia.
  • METHODS: An open label, dose escalation Phase I/II clinical trial enrolled women with biopsy confirmed CIN 1, 2 or 3.
  • Terameprocol (45 or 90 mg) was physician-administered directly to the cervix uteri in 3 once weekly applications.
  • The pharmacokinetics after administration were examined on Day 1 of dosing.
  • Patients underwent colposcopic examinations, HPV testing, biomarker assessments, cytology and cervical punch biopsy.
  • There were no serious adverse events (SAEs) and possible treatment-related Adverse Events (AEs) reported were mild and self-limiting.
  • CONCLUSIONS: Terameprocol in 1% and 2% vaginal ointment use in Phase I/II trials with women with HPV-linked cervical intraepithelial neoplasia has an excellent safety profile, no SAEs reported and mild, self-limiting treatment-related AEs.
  • These data support the continued evaluation of terameprocol in in vitro and animal efficacy models followed by definitive human Phase II clinical trials in CIN.
  • [MeSH-major] Cervical Intraepithelial Neoplasia / drug therapy. Masoprocol / analogs & derivatives. Uterine Cervical Neoplasms / drug therapy
  • [MeSH-minor] Adolescent. Adult. Biomarkers, Tumor / biosynthesis. CDC2-CDC28 Kinases / biosynthesis. Dose-Response Relationship, Drug. Female. Humans. Immunohistochemistry. Inhibitor of Apoptosis Proteins. Microtubule-Associated Proteins / biosynthesis. Neoplasm Proteins / biosynthesis. Neoplasm Staging. Ointments. Papillomaviridae / classification. Papillomavirus Infections / complications. Papillomavirus Infections / virology

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  • (PMID = 17905420.001).
  • [ISSN] 1095-6859
  • [Journal-full-title] Gynecologic oncology
  • [ISO-abbreviation] Gynecol. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / BIRC5 protein, human; 0 / Biomarkers, Tumor; 0 / Inhibitor of Apoptosis Proteins; 0 / Microtubule-Associated Proteins; 0 / Neoplasm Proteins; 0 / Ointments; 53YET703F2 / terameprocol; 7BO8G1BYQU / Masoprocol; EC 2.7.11.22 / CDC2-CDC28 Kinases
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