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1. Liu DS, Krebs CE, Liu SJ: Proliferation of human breast cancer cells and anti-cancer action of doxorubicin and vinblastine are independent of PKC-alpha. J Cell Biochem; 2007 May 15;101(2):517-28
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  • Protein kinase C (PKC) has been considered for a potential target of anticancer chemotherapy.
  • However, the role of PKC-alpha in human breast cancer cell proliferation and anticancer chemotherapy remains unclear.
  • Exposure for 24 h to doxorubicin (DOX) and vinblastine (VIN) caused a concentration-dependent reduction in proliferation of MCF-7 cells.
  • However, these two anticancer drugs altered cellular morphology and growth pattern in distinct manners.
  • Phorbol 12,13-dibutyrate (PDBu, 100 nM), which enhanced activities of PKC-alpha, increased cancer cell proliferation and attenuated VIN (1 microM)-induced cytotoxicity.
  • Phorbol myristate acetate (PMA, 100 nM) that completely depleted PKC-alpha also enhanced cancer cell proliferation and attenuated VIN-induced cytotoxicity.
  • Three potent PKC inhibitors, staurosporine (10 nM), chelerythrine (5 microM) and bisindolylmaleimide-I (100 nM), had no significant effect on MCF-7 cell proliferation; staurosporine and chelerythrine, but not bisindolylmaleimide-I, attenuated VIN-induced cytotoxicity.
  • Moreover, neither phorbol esters nor PKC inhibitors had an effect on cytotoxic effects of DOX (1 microM) on MCF-7 cell proliferation.
  • Thus, these data suggest that MCF-7 cell proliferation or the anti-cancer action of DOX and VIN on breast cancer cells is independent of PKC-alpha.
  • [MeSH-major] Antineoplastic Agents / metabolism. Breast Neoplasms / metabolism. Cell Proliferation. Doxorubicin / metabolism. Protein Kinase C-alpha / metabolism. Vinblastine / metabolism
  • [MeSH-minor] Carcinogens / metabolism. Cell Line, Tumor. Cell Shape. Enzyme Activation. Enzyme Inhibitors / metabolism. Female. Humans. Phorbol 12,13-Dibutyrate / metabolism. Staurosporine / metabolism

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  • (PMID = 17171646.001).
  • [ISSN] 0730-2312
  • [Journal-full-title] Journal of cellular biochemistry
  • [ISO-abbreviation] J. Cell. Biochem.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Carcinogens; 0 / Enzyme Inhibitors; 37558-16-0 / Phorbol 12,13-Dibutyrate; 5V9KLZ54CY / Vinblastine; 80168379AG / Doxorubicin; EC 2.7.11.13 / Protein Kinase C-alpha; H88EPA0A3N / Staurosporine
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2. Olejek A, Rembielak-Stawecka B, Kozak-Darmas I, Biniszkiewicz T, SieroĊ„ A: [Photodynamic diagnosis and therapy in gynecology--current knowledge]. Ginekol Pol; 2004 Mar;75(3):228-34
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  • [Title] [Photodynamic diagnosis and therapy in gynecology--current knowledge].
  • [Transliterated title] Diagnostyka i terapia fotodynamiczna w ginekologii--aktualny stan wiedzy.
  • Photodynamic diagnosis (PDD) is a new method based on the detection of different forms of fluorescence of tissues after previous administration of photosensitizers.
  • The photosensitizer is gathered in the pathological tissue at much higher concentration than in the healthy tissue, thus the fluorescence differs.
  • Localizing wrong fluorescence allows precise choosing of the spot to collect tissue for histopathological or cytological study.
  • Photodynamic therapy (PDT) is a technique in which tissue is irradiated with light after the use of a photosensitizing drug that produces singlet oxygen, which has a cytotoxic effect.
  • The authors describe new trends in photodynamic diagnosis and treatment of some vulvar epithelial diseases (VIN, lichen sclerosus, condylomata acuminata) and cervical intraepithelial neoplasia.
  • They describe photodynamic method in their own studies: diagnosis and treatment of lichen sclerosus and diagnosis of uterine cervix cancer.
  • [MeSH-major] Diagnostic Techniques, Obstetrical and Gynecological. Photochemotherapy. Photosensitizing Agents / therapeutic use. Vulvar Diseases / diagnosis. Vulvar Diseases / drug therapy
  • [MeSH-minor] Cervical Intraepithelial Neoplasia / diagnosis. Cervical Intraepithelial Neoplasia / drug therapy. Condylomata Acuminata / diagnosis. Condylomata Acuminata / drug therapy. Female. Humans. Lichen Sclerosus et Atrophicus / diagnosis. Lichen Sclerosus et Atrophicus / drug therapy. Precancerous Conditions / diagnosis. Precancerous Conditions / drug therapy. Tumor Virus Infections / diagnosis. Tumor Virus Infections / drug therapy. Vulvar Neoplasms / diagnosis

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  • (PMID = 15181882.001).
  • [ISSN] 0017-0011
  • [Journal-full-title] Ginekologia polska
  • [ISO-abbreviation] Ginekol. Pol.
  • [Language] pol
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Poland
  • [Chemical-registry-number] 0 / Photosensitizing Agents
  • [Number-of-references] 30
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3. Davis G, Wentworth J, Richard J: Self-administered topical imiquimod treatment of vulvar intraepithelial neoplasia. A report of four cases. J Reprod Med; 2000 Aug;45(8):619-23
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  • [Title] Self-administered topical imiquimod treatment of vulvar intraepithelial neoplasia. A report of four cases.
  • BACKGROUND: Vulvar intraepithelial neoplasia (VIN) generally can be classified into viral and nonviral etiologies.
  • The histopathologic diagnosis is often separable into basaloid and warty types.
  • A large percentage of VIN lesions have been shown to harbor human papillomavirus (HPV), principally type 16.
  • Imiquimod, an immune response modifier, has been shown to be safe and effective for the treatment of external and perianal genital warts caused by HPV.
  • CASES: Four cases occurred of clinical and histopathologically diagnosed viral VIN 3.
  • An imiquimod treatment protocol, previously used in a study of this drug for the treatment of external genital warts, was followed.
  • Imiquimod 5% cream was patient applied three times per week until all lesions cleared, for a maximum of 16 weeks.
  • CONCLUSION: Imiquimod may be an effective treatment modality for viral VIN 3 in the future.
  • [MeSH-major] Adjuvants, Immunologic / administration & dosage. Aminoquinolines / administration & dosage. Carcinoma in Situ / drug therapy. Tumor Virus Infections / drug therapy. Vulvar Neoplasms / drug therapy
  • [MeSH-minor] Administration, Cutaneous. Adult. Condylomata Acuminata / drug therapy. Condylomata Acuminata / virology. Drug Administration Schedule. Female. Humans. Middle Aged. Neoplasm Recurrence, Local / drug therapy. Neoplasm Recurrence, Local / virology. Ointments. Papillomaviridae / isolation & purification. Self Administration

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  • (PMID = 10986679.001).
  • [ISSN] 0024-7758
  • [Journal-full-title] The Journal of reproductive medicine
  • [ISO-abbreviation] J Reprod Med
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Adjuvants, Immunologic; 0 / Aminoquinolines; 0 / Ointments; 99011-02-6 / imiquimod
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4. Zawislak A, Donnelly RF, McCluggage WG, Price JH, McClelland HR, Woolfson AD, Dobbs S, Maxwell P, McCarron PA: Clinical and immunohistochemical assessment of vulval intraepithelial neoplasia following photodynamic therapy using a novel bioadhesive patch-type system loaded with 5-aminolevulinic acid. Photodiagnosis Photodyn Ther; 2009 Mar;6(1):28-40
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  • [Title] Clinical and immunohistochemical assessment of vulval intraepithelial neoplasia following photodynamic therapy using a novel bioadhesive patch-type system loaded with 5-aminolevulinic acid.
  • BACKGROUND: The work in this study appraised photodynamic treatment (PDT) as a treatment method for vulval intraepithelial neoplasia (VIN) using a novel bioadhesive patch to deliver aminolevulinic acid.
  • An analysis of changes in expression of apoptotic and cell cycle proteins (p53, p21, Mdm2, Blc-2, Bax, Ki-67) in response to PDT was evaluated.
  • METHODS: PDT was performed using non-laser light, either as a one or two-cycle treatment, with clinical and pathological assessment following after 6 weeks.
  • Twenty-three patients with 25 VIN lesions underwent 49 cycles of PDT.
  • Patches were designed to conform to uneven vulval skin and contained 38 mg cm(-2) aminolevulinic acid.
  • Assessment was carried out at 6 weeks post-treatment.
  • Patient-based treatment assessment, along with clinical and pathological changes, were monitored.
  • Changes in expression of cell cycle and apoptotic-related proteins suggested involvement of apoptotic pathways.
  • CONCLUSION: Treatment of VIN lesions using a novel bioadhesive patch induced changes in cell cycle and apoptotic proteins in response to PDT with possible utilisation of apoptotic pathways.
  • The efficacy of PDT in treating VIN could be improved by a better understanding of these apoptotic mechanisms, the influence of factors, such as HPV status, and of the need for effective pain management.
  • [MeSH-major] Aminolevulinic Acid / administration & dosage. Cervical Intraepithelial Neoplasia / drug therapy. Drug Carriers / chemistry. Vulvar Neoplasms / drug therapy
  • [MeSH-minor] Administration, Topical. Adult. Aged. Female. Humans. Middle Aged. Photosensitizing Agents / administration & dosage. Tissue Adhesives / chemistry. Treatment Outcome

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  • (PMID = 19447369.001).
  • [ISSN] 1873-1597
  • [Journal-full-title] Photodiagnosis and photodynamic therapy
  • [ISO-abbreviation] Photodiagnosis Photodyn Ther
  • [Language] eng
  • [Publication-type] Controlled Clinical Trial; Journal Article
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Drug Carriers; 0 / Photosensitizing Agents; 0 / Tissue Adhesives; 88755TAZ87 / Aminolevulinic Acid
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5. Wendling J, Saiag P, Berville-Levy S, Bourgault-Villada I, Clerici T, Moyal-Barracco M: Treatment of undifferentiated vulvar intraepithelial neoplasia with 5% imiquimod cream: a prospective study of 12 cases. Arch Dermatol; 2004 Oct;140(10):1220-4
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  • [Title] Treatment of undifferentiated vulvar intraepithelial neoplasia with 5% imiquimod cream: a prospective study of 12 cases.
  • OBJECTIVE: To assess the efficacy of 5% imiquimod cream on undifferentiated vulvar intraepithelial neoplasia (VIN), a disease caused by high-risk human papillomavirus.
  • SETTING: University hospital vulvar clinic.
  • Patients Twelve consecutive patients treated with 5% imiquimod cream for undifferentiated VIN between March 1, 1999, and May 31, 2001.
  • INTERVENTION: Self-application of 5% imiquimod cream, initially 3 times a week, then adjusted according to tolerance, for up to 7 months according to clinical response.
  • MAIN OUTCOME MEASURES: Therapeutic response, clinically assessed by successive photographs and histologically confirmed for complete responders, was scored as complete, partial (> or =50% decrease in lesion size), or failure.
  • Mean duration of treatment was 3.6 months (37.3 applications), 5.0 months (50.7 applications), and 3.4 months (25.2 applications) for complete responders, partial responders, and failures, respectively.
  • Follow-up after treatment was 5 to 18, 14 to 32, and 2 to 28 months, respectively, with 1 partial responder lost to long-term follow-up.
  • No patient developed invasive carcinoma.
  • All but 2 patients experienced vulvar discomfort, resulting in treatment withdrawal for 3.
  • CONCLUSIONS: Imiquimod cream could be a therapeutic option for undifferentiated VIN.
  • Although poorly tolerated, this self-applied treatment could spare patients, either totally or partially, the classic painful and sometimes mutilating treatments of VIN.
  • [MeSH-major] Aminoquinolines / therapeutic use. Antineoplastic Agents / therapeutic use. Vulvar Neoplasms / drug therapy
  • [MeSH-minor] Administration, Cutaneous. Adult. Female. Humans. Middle Aged. Papillomaviridae. Precancerous Conditions / drug therapy. Precancerous Conditions / pathology. Precancerous Conditions / virology. Prospective Studies. Treatment Outcome

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  • (PMID = 15492184.001).
  • [ISSN] 0003-987X
  • [Journal-full-title] Archives of dermatology
  • [ISO-abbreviation] Arch Dermatol
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoquinolines; 0 / Antineoplastic Agents; 99011-02-6 / imiquimod
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6. Winters U, Daayana S, Lear JT, Tomlinson AE, Elkord E, Stern PL, Kitchener HC: Clinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia. Clin Cancer Res; 2008 Aug 15;14(16):5292-9
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  • [Title] Clinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia.
  • PURPOSE: High-risk human papillomavirus (HPV)-associated vulval intraepithelial neoplasia (VIN) is difficult to treat by excision or ablation because of high recurrence rates.
  • Small studies of photodynamic therapy (PDT) and imiquimod treatments have shown some success and function at least in part through stimulation of local immune responses.
  • Indeed, there is evidence that immunosuppressed individuals have higher rates of VIN, suggesting immune control is relevant.
  • EXPERIMENTAL DESIGN: In the study, 20 women with high-grade VIN were treated with topical imiquimod and the PDT sequentially.
  • Vulval biopsy and blood were taken pretreatment and, after imiquimod and PDT, with follow up for 1 year.
  • RESULTS: The treatment was well-tolerated.
  • The nonresponders showed a significantly higher level of T regulatory cells in the lesions after imiquimod treatment.
  • CONCLUSIONS: The response rates are clinically relevant, and the treatment regimen was feasible for the majority.
  • Initial nonresponders to imiquimod seem to be relatively refractory, and this may derive from their unfavorable local immune environment, in particular, the increased proportions of T regulatory cells, possibly the limiting action and/or development of any HPV T-cell immunity.
  • The potential benefit of this treatment is its ability to treat multifocal disease.
  • [MeSH-major] Aminoquinolines / administration & dosage. Antineoplastic Agents / administration & dosage. Carcinoma in Situ / drug therapy. Photochemotherapy. Vulvar Neoplasms / drug therapy
  • [MeSH-minor] Administration, Topical. Adult. Antigens, CD / metabolism. Combined Modality Therapy. Female. Fluorescent Antibody Technique. Humans. Immunohistochemistry. Lymphocytes, Tumor-Infiltrating / drug effects. Lymphocytes, Tumor-Infiltrating / immunology. Middle Aged. T-Lymphocytes, Regulatory

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  • (PMID = 18698049.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Grant] United Kingdom / Cancer Research UK / /
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Aminoquinolines; 0 / Antigens, CD; 0 / Antineoplastic Agents; 99011-02-6 / imiquimod
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7. Bifulco G, Mandato VD, Piccoli R, Giampaolino P, Mignogna C, Mignogna MD, Costagliola L, Nappi C: Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus. BMC Cancer; 2010;10:324
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  • [Title] Early invasive vulvar squamous cell carcinoma arising in a woman with vulvar pemphigus vulgaris and systemic lupus erythematosus.
  • Here, we report the first case of a woman affected with SLE presenting with early invasive squamous cell carcinoma (SCC) arising from Pemphigus Vulgaris of the vulva.
  • CASE PRESENTATION: A 27-year-old Caucasian woman was admitted to our Gynaecology Unit for bleeding vegetant lesions of the vulva.
  • Biopsy showed concomitant PV and vulvar intraepithelial neoplasia (VIN) grade 3.
  • One month later a new biopsy revealed progression from VIN 3 to early SCC.
  • Despite chemotherapy, no remission of disease was observed.
  • She died six months after diagnosis CONCLUSION: Our case underlines PV as another chronic inflammatory disease of the lower genital tract predisposing to VIN-SCC.
  • [MeSH-major] Carcinoma in Situ / etiology. Carcinoma, Squamous Cell / etiology. Lupus Erythematosus, Systemic / complications. Pemphigus / complications. Vulvar Diseases / complications. Vulvar Neoplasms / etiology
  • [MeSH-minor] Adult. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Biopsy. Disease Progression. Fatal Outcome. Female. Humans. Neoplasm Invasiveness. Neoplasm Staging. Time Factors


8. Fehr MK, Hornung R, Schwarz VA, Simeon R, Haller U, Wyss P: Photodynamic therapy of vulvar intraepithelial neoplasia III using topically applied 5-aminolevulinic acid. Gynecol Oncol; 2001 Jan;80(1):62-6
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  • [Title] Photodynamic therapy of vulvar intraepithelial neoplasia III using topically applied 5-aminolevulinic acid.
  • OBJECTIVES: The aim of this study was twofold: first, to determine the feasibility of photodynamic therapy (PDT) of vulvar intraepithelial neoplasia III (VIN III) using topically applied 5-aminolevulinic acid (ALA) for photosensitization, and second, to compare PDT results with those of laser evaporation and local excision.
  • METHODS: Fifteen patients with VIN III had 10 g of 10% ALA gel applied to the entire vulva.
  • Two to three hours after drug application the vulva was irradiated with 120 J/cm(2) laser light at a wavelength of 635 nm.
  • The procedure was performed without anesthesia in most patients.
  • Thirty patients with VIN III treated by laser evaporation and 27 patients treated by surgical excision served as controls.
  • RESULTS: Eight weeks following PDT, 11 of 15 patients were free of VIN III as determined by biopsy.
  • Excellent tissue preservation was achieved and no ulcers or scarring occurred.
  • Twelve months after treatment, analysis of disease-free survival revealed no statistically significant difference between patients treated with PDT and patients treated with conventional treatment modalities (P = 0.67) but the power of this analysis is low.
  • CONCLUSION: While PDT of VIN III seems to show efficacy similar to that of conventional treatment modalities it offers unique advantages: healing time is short, preservation of normal vulvar appearance is excellent, and PDT may be performed without anesthesia.
  • Hence, PDT of VIN III deserves further investigation.
  • [MeSH-major] Aminolevulinic Acid / administration & dosage. Carcinoma in Situ / drug therapy. Photochemotherapy. Photosensitizing Agents / administration & dosage. Vulvar Neoplasms / drug therapy
  • [MeSH-minor] Administration, Topical. Adult. Disease-Free Survival. Feasibility Studies. Female. Gels. Humans. Laser Therapy. Middle Aged. Multivariate Analysis

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  • [Copyright] Copyright 2001 Academic Press.
  • [CommentIn] Gynecol Oncol. 2002 Jan;84(1):187-9 [11749005.001]
  • (PMID = 11136571.001).
  • [ISSN] 0090-8258
  • [Journal-full-title] Gynecologic oncology
  • [ISO-abbreviation] Gynecol. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] UNITED STATES
  • [Chemical-registry-number] 0 / Gels; 0 / Photosensitizing Agents; 88755TAZ87 / Aminolevulinic Acid
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