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1.
Eur Rev Med Pharmacol Sci ; 27(19): 8985-8992, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37843310

RESUMO

OBJECTIVE: The aim of the study was to investigate the safety and antiviral efficacy of a Chinese multiherb extract-based tincture (GWK) on a population of patients with high-risk human papilloma (hrHPV) infections and hrHPV-caused cervical low-grade squamous intraepithelial lesions (LSILs). PATIENTS AND METHODS: Patients with persistent hrHPV infection were enrolled in Group A, including A1 subjects, who received the intervention, and A2 subjects, who received the control. Patients with hrHPV infection causing cervical LSIL were enrolled in Group B, which included B1 subjects, who received the intervention, and B2 subjects, who served as the control. For Groups A1 and B1, hrHPV was tested at 3 months (M3) and 6 months (M6) after the intervention. The side effects were also analyzed. RESULTS: At baseline (D0), a total of 99 patients were enrolled in Group A, with 50 subjects in Group A1 and 49 subjects in Group A2. A total of 91 patients were enrolled in Group B, with 45 subjects in Group B1 and 46 subjects in Group B2. There was no significant difference in the characteristics, including average age, age stratification, and HPV genotype. At M6, both Group A1 and Group B1 had a higher hrHPV clearance rate than the control group (A1/A2: 80.0% vs. 20.4%; B1/B2: 64.4% vs. 15.2%, p<0.001). At M6, the effective rates of Group A1 and Group B1 were 84% (42/50) and 68.9% (31/45), respectively. The side effect rates of Groups A1 and B1 were 11.5% (6/52) and 11.1% (5/45), respectively. Most adverse reactions involved local discomfort, including vulvar erythema, vulvar itch, increased vaginal discharge, cervical bleeding, and mild pain in the lower abdomen. Univariate logistic regression analysis showed that the intervention had an OR of 12 (95% CI 4.431-32.50) for clearing persistent HPV infection (p<0.001). For cervical LSIL, the intervention had an OR of 10.1 for clearing persistent HPV infection (95% CI 3.68-27.7) (p<0.001). CONCLUSIONS: The results of this study suggest that the Chinese multiherb extract-based tincture GWK is safe and well tolerated. Furthermore, this preliminary study showed that this Chinese multiherb extract-based tincture is helpful for promoting HPV clearance in cases of persistent HPV and HPV-induced LSIL.


Assuntos
Medicamentos de Ervas Chinesas , Infecções por Papillomavirus , Feminino , Humanos , China , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , População do Leste Asiático , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/virologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Extratos Vegetais/uso terapêutico , Estudos Prospectivos , Displasia do Colo do Útero/tratamento farmacológico , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
2.
JAMA Netw Open ; 4(8): e2121893, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34424304

RESUMO

Importance: Rates of human papillomavirus (HPV) infection have decreased since the introduction of HPV vaccines in populations with high vaccine uptake. Data are limited for adolescent and young adult populations in US metropolitan centers. Objective: To determine HPV infection rates in adolescent girls and young women aged 13 to 21 years in New York City following HPV vaccination. Design, Setting, and Participants: This cohort study of type-specific cervical HPV detection was conducted at a large adolescent-specific integrated health center in New York City between October 2007 and September 2019. Participants included an open cohort of adolescent girls and young adult women who received the HPV vaccine (Gardasil; Merck & Co) over a 12-year period following HPV vaccination introduction. Data analysis was concluded September 2019. Exposures: Calendar date and time since receipt of first vaccine dose. Main Outcomes and Measures: Temporal associations in age-adjusted postvaccine HPV rates. Results: A total of 1453 participants, with a mean (SD) age at baseline of 18.2 (1.4) years, were included in the cohort (African American with no Hispanic ethnicity, 515 [35.4%] participants; African American with Hispanic ethnicity, 218 [15.0%] participants; Hispanic with no reported race, 637 [43.8%] participants). Approximately half (694 [47.8%] participants) were vaccinated prior to coitarche. Age-adjusted detection rates for quadrivalent vaccine types (HPV-6, HPV-11, HPV-16, and HPV-18) and related types (HPV-31, and HPV-45) decreased year over year, with the largest effect sizes observed among individuals who had been vaccinated before coitarche (adjusted odds ratio [aOR], 0.81; 95% CI, 0.67-0.98). By contrast, detection was higher year over year for nonvaccine high-risk cervical HPV types (aOR, 1.08; 95% CI, 1.04-1.13) and anal HPV types (aOR, 1.11; 95% CI, 1.05-1.17). The largest effect sizes were observed with nonvaccine types HPV-56 and HPV-68. Conclusions and Relevance: Whereas lower detection rates of vaccine-related HPV types were observed since introduction of vaccines in female youth in New York City, rates of some nonvaccine high-risk HPV types were higher. Continued monitoring of high-risk HPV prevalence is warranted.


Assuntos
Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Imunização/estatística & dados numéricos , Papillomaviridae/efeitos dos fármacos , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Eficácia de Vacinas/estatística & dados numéricos , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Incidência , Cidade de Nova Iorque/epidemiologia , Fatores de Risco , Adulto Jovem
3.
JAMA Netw Open ; 2(11): e1914729, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31693128

RESUMO

Importance: In the United States, more than 50% of cervical cancers are diagnosed in underscreened women. Cervical cancer screening guidelines now include primary human papillomavirus (HPV) testing as a recommended strategy. Home-based HPV self-sampling is a viable option for increasing screening compliance and effectiveness; however, US data are needed to inform health care system implementation. Objective: To evaluate effectiveness of mailed HPV self-sampling kits vs usual care reminders for in-clinic screening to increase detection and treatment of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and uptake of cervical cancer screening. Design, Setting, and Participants: Randomized clinical trial conducted in Kaiser Permanente Washington, a US integrated health care delivery system. Women aged 30 to 64 years with health plan enrollment for 3 years and 5 months or more, a primary care clinician, no Papanicolaou test within 3 years and 5 months, and no hysterectomy were identified through electronic medical records and enrolled from February 25, 2014, to August 29, 2016, with follow-up through February 26, 2018. Interventions: The control group received usual care (annual patient reminders and ad hoc outreach from primary care clinics). The intervention group received usual care plus a mailed HPV self-sampling kit. Main Outcomes and Measures: Two primary outcomes were (1) CIN2+ detection within 6 months of screening and (2) treatment within 6 months of CIN2+ detection. Screening uptake within 6 months of randomization was a secondary outcome. Results: A total of 19 851 women (mean [SD] age, 50.1 [9.5] years) were included, with 9960 randomized to the intervention group and 9891 randomized to the control group. All women randomized were included in analysis. In the intervention group, 12 participants with CIN2+ were detected compared with 8 in the control group (relative risk, 1.49; 95% CI, 0.61-3.64) and 12 cases were treated vs 7 in the control group (relative risk, 1.70; 95% CI, 0.67-4.32). Screening uptake was higher in the intervention group (2618 participants [26.3%] vs 1719 participants [17.4%]; relative risk, 1.51; 95% CI, 1.43-1.60). Conclusions and Relevance: Mailing HPV kits to underscreened women increased screening uptake compared with usual care alone, with no significant differences in precancer detection or treatment. Results support the feasibility of mailing HPV kits to women who are overdue for screening as an outreach strategy to increase screening uptake in US health care systems. Efforts to increase kit uptake and follow-up of positive results are warranted to maximize detection and treatment of CIN2+. Trial Registration: ClinicalTrials.gov identifier: NCT02005510.


Assuntos
Infecções por Papillomavirus/diagnóstico , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Serviços Postais/métodos , Kit de Reagentes para Diagnóstico/normas , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Detecção Precoce de Câncer , Feminino , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Serviços Postais/normas , Serviços Postais/estatística & dados numéricos , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Cooperação e Adesão ao Tratamento/psicologia , Cooperação e Adesão ao Tratamento/estatística & dados numéricos
4.
Photochem Photobiol Sci ; 18(11): 2565-2612, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31397467

RESUMO

Photodynamic therapy (PDT) is a well-established treatment option in the treatment of certain cancerous and pre-cancerous lesions. Though best-known for its application in tumor therapy, historically the photodynamic effect was first demonstrated against bacteria at the beginning of the 20th century. Today, in light of spreading antibiotic resistance and the rise of new infections, this photodynamic inactivation (PDI) of microbes, such as bacteria, fungi, and viruses, is gaining considerable attention. This review focuses on the PDI of viruses as an alternative treatment in antiviral therapy, but also as a means of viral decontamination, covering mainly the literature of the last decade. The PDI of viruses shares the general action mechanism of photodynamic applications: the irradiation of a dye with light and the subsequent generation of reactive oxygen species (ROS) which are the effective phototoxic agents damaging virus targets by reacting with viral nucleic acids, lipids and proteins. Interestingly, a light-independent antiviral activity has also been found for some of these dyes. This review covers the compound classes employed in the PDI of viruses and their various areas of use. In the medical area, currently two fields stand out in which the PDI of viruses has found broader application: the purification of blood products and the treatment of human papilloma virus manifestations. However, the PDI of viruses has also found interest in such diverse areas as water and surface decontamination, and biosafety.


Assuntos
Luz , Fotoquimioterapia/tendências , Viroses/terapia , Vírus/efeitos da radiação , Humanos , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/efeitos da radiação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Viroses/tratamento farmacológico , Viroses/metabolismo , Vírus/efeitos dos fármacos , Vírus/metabolismo
5.
Int J Med Mushrooms ; 21(3): 225-235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002607

RESUMO

A review of scientific information about the potential role of medicinal mushrooms in the prevention and treatment of gynecological cancers, human immunodeficiency virus, and human papillomavirus infections is reported here. The results of in vivo and in vitro experiments on 16 different species of Basidiomycetes and three Ascomycetes, which possess chemopreventive potential and are effective in clinical application in combination with chemotherapy, are also discussed. Medicinal mushroom extracts confirm an evident efficacy on the reduction of tumor cell proliferation and side effects in patients with gynecological tumors who are undergoing chemotherapy treatments. This review, the first on the use of medicinal mushrooms in the prevention and treatment of gynecological cancers, aims to highlight the remarkable potential of mushrooms in integrated oncology.


Assuntos
Agaricales/química , Produtos Biológicos/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/prevenção & controle , Animais , Antioxidantes/uso terapêutico , Ascomicetos/química , Basidiomycota/química , Produtos Biológicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios Clínicos como Assunto , Feminino , HIV/efeitos dos fármacos , Humanos , Camundongos , Papillomaviridae/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias Vaginais/tratamento farmacológico , Neoplasias Vaginais/prevenção & controle
6.
PLoS One ; 14(1): e0211235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30682126

RESUMO

Due to the extreme tissue and species restriction of the papillomaviruses (PVs), there is a great need for animal models that accurately mimic PV infection in humans for testing therapeutic strategies against human papillomaviruses (HPVs). In this study, we present data that demonstrate that in terms of gene expression during initial viral DNA amplification, Macaca fascicularis PV (MfPV) types 5 and 8 appear to be similar to mucosal oncogenic HPVs, while MfPV1 (isolated from skin) resembles most high-risk cutaneous beta HPVs (HPV5). Similarities were also observed in replication properties during the initial amplification phase of the MfPV genomes. We demonstrate that high-risk mucosal HPV-specific inhibitors target the transient replication of the MfPV8 genomes, which indicates that similar pathways are used by the high-risk HPVs and MfPVs during their genome replication. Taking all into account, we propose that Macaca fascicularis may serve as a highly relevant model for preclinical tests designed to evaluate therapeutic strategies against HPV-associated lesions.


Assuntos
Antivirais/uso terapêutico , Macaca fascicularis/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/tratamento farmacológico , Animais , Antivirais/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Regulação Viral da Expressão Gênica , Humanos , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/genética , Infecções por Papillomavirus/veterinária , Infecções por Papillomavirus/virologia , Proteínas Virais/genética , Replicação Viral/efeitos dos fármacos
8.
Drug Des Devel Ther ; 11: 575-583, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28424535

RESUMO

PURPOSE: This paper reports the results of a clinical study that tested the effect of systemic treatment with the botanical product Gene-Eden-VIR/Novirin on the clearance rate (also called time to clearance) of the human papillomavirus (HPV). The study compared the clearance rate in treated and untreated individuals suffering from a symptomatic HPV infection. The data on the untreated individuals were obtained by reverse engineering of the Kaplan-Meier figures in five published papers. MATERIALS AND METHODS: The study included 59 treated participants. All participants were suffering from a symptomatic HPV infection prior to the commencement of treatment. The treatment was one to four capsules of Gene-Eden-VIR/Novirin per day. The duration of treatment was 2-12 months. The study included five groups of external controls with diverse characteristics. RESULTS: The mean time to clearance in Gene-Eden-VIR/Novirin-treated individuals was 5.1 months or 151.5 days (95% CI: 4.2-5.9 months or 95% CI: 125.7-177.3 days, respectively). The median time to clearance was 3.5 months. The mean time to clearance in the five untreated groups ranged from 6.9 to 20.0 months (P<0.0001 for the difference between treatment group and each untreated group). Also, 100% of the participants in the treatment group were HPV free at the end of 12 months vs 53%, 52%, 65%, 20%, and 77% in the untreated control groups. The treated participants reported no adverse experiences. CONCLUSION: This clinical study has two major contributions. First, it showed that systemic treatment with the natural Gene-Eden-VIR/Novirin decreased the time to HPV clearance, increased the percentage of HPV-free individuals, and caused no adverse experiences in individuals suffering from a symptomatic HPV infection. Since there are no other systemic treatments for symptomatic HPV infections, this study presents highly valuable information on the clinical effects of the first treatment in this category. Second, the study presents a new method for conducting clinical studies that addresses one of the major deficiencies associated with the practice of the randomized controlled trial method.


Assuntos
Antivirais/farmacologia , Papillomaviridae/efeitos dos fármacos , Infecções por Papillomavirus/tratamento farmacológico , Extratos Vegetais/farmacologia , Quercetina/farmacologia , Selênio/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Adulto Jovem
9.
Pol Merkur Lekarski ; 42(249): 110-115, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28333902

RESUMO

Reporting of clinical trials results for Proteflazid® in the drug formulation suppositories and vaginal swabs soaked in the solution of the drug to the local immunity of the female reproductive tract. AIM: The aim of study was to examine the state of local immunity in the reproductive tract of women with sexually transmitted diseases caused by human papillomavirus, herpes viruses (Type 1, 2) and mixed infection (herpes viruses + chlamydia). MATERIALS AND METHODS: The trials involved 216 women with viral sexually transmitted diseases: Cervical Dysplasia associated with papillomavirus infection (HPV) (Group 1); Herpes genitalis type 1 (HSV- 1) and type 2 (HSV-1) (Group 2); mixed infection - HSV-1, HSV-2 and chlamydia (Group 3). RESULTS: Treatment results have confirmed that Proteflazid® contributes to sustainable performance improvement of basic factors of local immunity - sIgA, lysozyme and complement component C3 in the cervical mucus for all three groups of women. CONCLUSIONS: Proteflazid® enhances level of local immunity markers (sIgA, lysozyme, C3 complement component) and improves their ratios. Also it intensifies anticontagious activity of mucosal protection and female reproductive system as whole, during treatment diseases caused by human papillomavirus, herpesvirus and mixed urogenital infections (herpesvirus and chlamydia).


Assuntos
Infecções por Chlamydia/tratamento farmacológico , Coinfecção/tratamento farmacológico , Infecções por Herpesviridae/tratamento farmacológico , Sistema Imunitário/efeitos dos fármacos , Infecções por Papillomavirus/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Infecções Sexualmente Transmissíveis/tratamento farmacológico , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Doenças Urogenitais Femininas/tratamento farmacológico , Doenças Urogenitais Femininas/microbiologia , Doenças Urogenitais Femininas/virologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Humanos , Papillomaviridae/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Medicinais , Poaceae , Infecções Sexualmente Transmissíveis/microbiologia , Infecções Sexualmente Transmissíveis/virologia , Resultado do Tratamento
10.
Curr Top Med Chem ; 15(2): 120-35, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25496269

RESUMO

Causative connections between infections and cancer are ascertained for several types of viruses, bacteria, and parasites. The mechanisms of cancer induction in chronically infected inflamed tissues strongly implicate oxygen- and nitrogen-centered reactive species, and an impairment of redox-sensitive molecular pathways involved in the tumorigenic transformation, tumor growth, altered immune defense, and in the mechanisms of tumor cell death and survival. Here, we briefly reviewed mechanistic data on carcinogenesis and tumor progression of three major infection-associated tumors, human papillomavirus-induced cervical cancer, hepatitis B virus-positive hepatocarcinoma, and Helicobacter pylori-positive gastric cancer. Notwithstanding the contradictory results of clinical studies on cancer chemoprevention with long-term, high dosage antioxidant vitamin/micronutrient supplementation, natural and synthetic agents with proven capacity to affect redox-dependent molecular pathways still hold the promise for preventing/delaying carcinogenesis initiation, as well as the overt malignancy evolution from dysplastic/ aplastic stages. Novel directions for a targeted antioxidant-based approach to the reduction of persistent infection-driven cancer risk stems from the current knowledge of critical factors in the host-microbe interaction leading to oncogenesis. An emerging role of redox active substances in the chemotherapy of tumors relies on their stimulating effects towards TRAIL-related apoptosis and the induction of intracellular oxidative stress.


Assuntos
Antioxidantes/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Antioxidantes/uso terapêutico , Feminino , Helicobacter pylori/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/virologia , Papillomaviridae/efeitos dos fármacos , Neoplasias Gástricas/virologia , Neoplasias do Colo do Útero/virologia
11.
Antiviral Res ; 108: 88-93, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24909570

RESUMO

Commercial vaccines against human papillomavirus (HPV) have low uptake due to parental autonomy, dosing regimen, cost, and cold chain storage requirements. Carrageenan (CG)-based formulations prevent HPV infection in vitro and in vivo but data are needed on the durability of anti-HPV activity and the effect of seminal plasma (SP). The Population Council's PC-515 gel and the lubricant Divine 9 were tested for their physicochemical properties and anti-HPV activity against HPV16, 18, and 45 pseudoviruses (PsVs). Anti-PsV activity was estimated using the luciferase assay in HeLa cells and the HPV PsV luciferase mouse model. Formulations were applied intravaginally either 2h pre/2h post (-2h/+2h) or 24h pre (-24h) relative to challenge with HPV16 or 45 PsV in PBS or SP/PBS. Both formulations showed broad-spectrum anti-HPV activity in vitro (IC50: 1-20ng/ml), significantly decreasing HPV PsV infection in the mouse model (-2h/+2h, p<0.0001). PC-515 protected better than Divine 9 in the -24h dosing regimen (p<0.0001) and comparable to Divine 9 in the -2h/+2h regimen (p=0.9841). PC-515 retained full activity in the murine model when PsV solutions contained human SP. The durable, potential broad-spectrum anti-HPV activity of CG formulations in the presence of SP supports their further development to prevent HPV acquisition.


Assuntos
Carragenina/farmacologia , Carragenina/uso terapêutico , Quimioprevenção/métodos , Papillomaviridae/efeitos dos fármacos , Infecções por Papillomavirus/prevenção & controle , Administração Intravaginal , Animais , Modelos Animais de Doenças , Genes Reporter , Células HeLa , Humanos , Concentração Inibidora 50 , Luciferases/análise , Luciferases/genética , Camundongos , Testes de Sensibilidade Microbiana , Profilaxia Pós-Exposição/métodos , Profilaxia Pré-Exposição/métodos , Sêmen/metabolismo , Resultado do Tratamento
12.
Asian Pac J Cancer Prev ; 14(10): 5753-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24289574

RESUMO

Curcumin and curcumin containing polyherbal preparations have demonstrated anti-microbial and anti- viral properties in pre-clinical studies. Till date no therapeutic intervention has been proved to be effective and safe in clearing established cervical human papillomavirus (HPV) infection. The present study evaluated the efficacy of Basant polyherbal vaginal cream (containing extracts of curcumin, reetha, amla and aloe vera) and of curcumin vaginal capsules to eliminate HPV infection from cervix. Women were screened by Pap smear and HPV DNA test by PCR. HPV positive women without high grade cervical neoplasias (N=287) were randomized to four intervention arms to be treated with vaginal Basant cream, vaginal placebo cream, curcumin vaginal capsules and placebo vaginal capsules respectively. All subjects were instructed to use one application of the assigned formulation daily for 30 consecutive days except during menstruation and recalled within seven days of the last application for repeat HPV test, cytology and colposcopy. HPV clearance rate in Basant arm (87.7%) was significantly higher than the combined placebo arms (73.3%). Curcumin caused higher rate of clearance (81.3%) than placebo though the difference was not statistically significant. Vaginal irritation and itching, mostly mild to moderate, was significantly higher after Basant application. No serious adverse events were noted.


Assuntos
Curcumina/uso terapêutico , Papillomaviridae/efeitos dos fármacos , Infecções por Papillomavirus/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Cremes, Espumas e Géis Vaginais/uso terapêutico , Adulto , Colo do Útero/efeitos dos fármacos , Colo do Útero/virologia , Feminino , Humanos , Teste de Papanicolaou/métodos , Infecções por Papillomavirus/virologia , Plantas Medicinais , Esfregaço Vaginal/métodos
13.
Nutr Cancer ; 65 Suppl 1: 88-97, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23682787

RESUMO

Plant products of Phyllanthus emblica Linn. are traditionally consumed for its immense nutritive and medicinal values. However, the molecular mechanism(s) by which it exerts it effects is less understood. In this study, we investigated mechanism of action of P. emblica fruit extract (PE) by studying its effect on activator protein-1 (AP-1) activity and human papillomavirus (HPV) transcription that are essential for tumorigenicity of cervical cancer cells. PE resulted in a dose-and time-dependent inhibition of DNA binding activity of constitutively active AP-1 in both HPV16-positive (SiHa) and HPV18-positive (HeLa) cervical cancer cells. PE-induced AP-1 inhibition was found mediated through downregulation of constituent AP-1 proteins, c-Jun, JunB, JunD, and c-Fos; however, the kinetics of their inhibition varied in both the cell types. Inhibition of AP-1 by PE was accompanied by suppression of viral transcription that resulted in growth inhibition of cervical cancer cells. Growth inhibitory activity of PE was primarily manifested through induction of apoptotic cell death. These results suggest that P. emblica exhibits its anticancer activities through inhibition of AP-1 and targets transcription of viral oncogenes responsible for development and progression of cervical cancer thus indicating its possible utility for treatment of HPV-induced cervical cancers.


Assuntos
Antineoplásicos/farmacologia , Papillomaviridae/efeitos dos fármacos , Phyllanthus emblica/química , Extratos Vegetais/farmacologia , Fator de Transcrição AP-1/metabolismo , Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteínas de Ligação a DNA , Relação Dose-Resposta a Droga , Regulação para Baixo , Feminino , Frutas/química , Células HeLa , Humanos , Papillomaviridae/genética , Fitoterapia , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Fator de Transcrição AP-1/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia
14.
BMC Complement Altern Med ; 12: 15, 2012 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-22405256

RESUMO

BACKGROUND: Bryophyllum pinnata (B. pinnata) is a common medicinal plant used in traditional medicine of India and of other countries for curing various infections, bowel diseases, healing wounds and other ailments. However, its anticancer properties are poorly defined. In view of broad spectrum therapeutic potential of B. pinnata we designed a study to examine anti-cancer and anti-Human Papillomavirus (HPV) activities in its leaf extracts and tried to isolate its active principle. METHODS: A chloroform extract derived from a bulk of botanically well-characterized pulverized B. pinnata leaves was separated using column chromatography with step- gradient of petroleum ether and ethyl acetate. Fractions were characterized for phyto-chemical compounds by TLC, HPTLC and NMR and Biological activity of the fractions were examined by MTT-based cell viability assay, Electrophoretic Mobility Shift Assay, Northern blotting and assay of apoptosis related proteins by immunoblotting in human cervical cancer cells. RESULTS: Results showed presence of growth inhibitory activity in the crude leaf extracts with IC50 at 552 µg/ml which resolved to fraction F4 (Petroleum Ether: Ethyl Acetate:: 50:50) and showed IC50 at 91 µg/ml. Investigations of anti-viral activity of the extract and its fraction revealed a specific anti-HPV activity on cervical cancer cells as evidenced by downregulation of constitutively active AP1 specific DNA binding activity and suppression of oncogenic c-Fos and c-Jun expression which was accompanied by inhibition of HPV18 transcription. In addition to inhibiting growth, fraction F4 strongly induced apoptosis as evidenced by an increased expression of the pro-apoptotic protein Bax, suppression of the anti-apoptotic molecules Bcl-2, and activation of caspase-3 and cleavage of PARP-1. Phytochemical analysis of fraction F4 by HPTLC and NMR indicated presence of activity that resembled Bryophyllin A. CONCLUSIONS: Our study therefore demonstrates presence of anticancer and anti-HPV an activity in B. pinnata leaves that can be further exploited as a potential anticancer, anti-HPV therapeutic for treatment of HPV infection and cervical cancer.


Assuntos
Bufanolídeos/uso terapêutico , Kalanchoe/química , Papillomaviridae/efeitos dos fármacos , Infecções por Papillomavirus/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Apoptose/efeitos dos fármacos , Bufanolídeos/isolamento & purificação , Bufanolídeos/farmacologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Feminino , Humanos , Concentração Inibidora 50 , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Extratos Vegetais/farmacologia , Folhas de Planta , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Fator de Transcrição AP-1 , Neoplasias do Colo do Útero/metabolismo , Proteína X Associada a bcl-2/metabolismo
15.
Antiviral Res ; 91(2): 161-6, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21669231

RESUMO

Non-surgical, antiviral treatment options are desirable for HPV-related lesions within the genitourinary and upper digestive tract. We compared the toxicity of three zinc finger-ejecting (ZFE) compounds (4,4-dithiodimorpholine, azodicarbonamide, and diamide) to the HIV protease inhibitor lopinavir using HPV-positive SiHa, CaSki, HeLa, ME180, and HPV-negative C33A cervical carcinoma cell lines as well as primary human foreskin keratinocytes (PHFKs). Colorimetric growth assays revealed selective toxicity when treated with lopinavir. All carcinoma cell lines, except CaSki, were sensitive to 20 µM lopinavir whereas primary PHFKs were highly resistant. In contrast, 4,4-dithiodimorpholine was uniformly toxic to all cells tested while azodicarbonamide and diamide showed no effect at all. It is concluded that lopinavir may be an attractive candidate to treat pre-cancerous and cancerous HPV-positive lesions.


Assuntos
Antivirais/farmacologia , Compostos Azo/farmacologia , Diamida/farmacologia , Morfolinas/farmacologia , Papillomaviridae/efeitos dos fármacos , Pirimidinonas/farmacologia , Linhagem Celular Tumoral , Feminino , Inibidores da Protease de HIV/farmacologia , Humanos , Queratinócitos , Dose Letal Mediana , Lopinavir , Testes de Sensibilidade Microbiana , Infecções por Papillomavirus/tratamento farmacológico
18.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 25(5): 392-6, 2005 May.
Artigo em Chinês | MEDLINE | ID: mdl-15957827

RESUMO

OBJECTIVE: To investigate the clinical efficacy of compound periploca liquid (CPL) in treating condyloma acuminatum (CA), and to explore its mechanisms at molecular level. METHODS: Eighty-one patients with CA were randomly divided into three groups, 30 patients in Group A were treated with CPL, 21 in Group B were treated with periploca syrup and 30 in Group C were treated with Youtuoxin (YXG). The clinical efficacy and adverse reaction occurred in the three groups was evaluated respectively. Besides, change of human papilloma virus (HPV) DNA in two patients with CA was determined by polymerase chain reaction (PCR) in vitro after being treated with CPL and periploca, the monarchic drug of CPL. RESULTS: The cure rate obtained in group A, B, and C was 56.67%, 42.86% and 63.33% respectively, the total effective rate in them was 83.33%, 71.43% and 86.67% respectively, the difference of therapeutic efficacy was insignificant among the three groups. But the adverse reaction occurrence in them (6.67%, 4.76% and 86.67%) was significantly different (P < 0.01). The recurrent rate in them was 14.29%, 12.5% and 47.1% respectively. PCR showed negative expression of HPV in the two samples of CA of same concentration after the verrucous homogenate suspension being treated with CPL or periploca syrup of different concentration, while it was positive after the suspension was treated with the group of normal saline without any drug. CONCLUSION: The therapeutic efficacies of CPL, periploca syrup and Youtuoxin are not significantly different, but the former two have advantages of less adverse effects and lower recurrent rate. And they are possibly having germicidal action on HPV-DNA in CA tissue in vitro.


Assuntos
Condiloma Acuminado/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Papillomaviridae/efeitos dos fármacos , Periploca/química , Fitoterapia , Administração Tópica , Adulto , DNA Viral/análise , DNA Viral/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Doenças dos Genitais Femininos/tratamento farmacológico , Doenças dos Genitais Femininos/virologia , Doenças dos Genitais Masculinos/tratamento farmacológico , Doenças dos Genitais Masculinos/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/tratamento farmacológico , Reação em Cadeia da Polimerase
19.
Anticancer Res ; 24(2B): 807-9, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15161031

RESUMO

Earlier we found that SiHa cervical squamous carcinoma cells that harbor HPV type 16 respond to ATRA treatment in a dose-dependent manner: high-dose (10(-5)-10(-4) M) but not low-dose (10(-7)-10(-6) M) ATRA induced growth arrest. Growth of HPV-infected cells is highly dependent on the expression of the viral E6/E7 proteins. Thus, targeting expression of the viral E6/E7 genes might influence growth properties of HPV-infected cells. Here, we demonstrated that high-dose ATRA inhibited expression of HPV16 E7 through suppression of the HPV16 promoter (p97) activity. Gelshift assay (EMSA) revealed that binding of the AP-1 transcription factor to an oligonucleotide originated from the HPV type 16 promoter was diminished after high-dose, but not low-dose ATRA treatment. This suggests that high-dose ATRA suppresses HPV 16 promoter activity, at least in part, via a decreased AP-1 binding. Our data might be useful in treatment of cervical dysplasias and/or carcinomas.


Assuntos
Proteínas Oncogênicas Virais/genética , Papillomaviridae/efeitos dos fármacos , Tretinoína/farmacologia , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/virologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Humanos , Proteínas Oncogênicas Virais/antagonistas & inibidores , Proteínas Oncogênicas Virais/biossíntese , Papillomaviridae/genética , Proteínas E7 de Papillomavirus , Regiões Promotoras Genéticas/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Neoplasias do Colo do Útero/virologia
20.
Zhong Yao Cai ; 27(9): 665-7, 2004 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-15704588

RESUMO

OBJECTIVE: To screen anti-HPV effective fraction from Asarum heterotropoides. METHODS: Asarum heterotropoides was extracted with systematic solvents (petroleum benzine, ether, ethyl acetate, n-butanol, ethanol and distilled water) accordingly. The Polymerase Chain Reaction (FQ-PCR) was applied in the vitro pharmacodynamics for the extracts from Asarum heterotropoides. The amplification of HPV-DNA in the lesions of the isolated Condyloma acuminatum. RESULTS: After the water extracts of Asarum heterotropoides was used for HPV-DNA, the PCR amplification showed negative, with the minimum effective concentration 0.4 g/ml. But the other solvents extracts from Asarum heterotropoides appeared positive. CONCLUSION: The water extracts from Asarum heterotropoides are effective on anti-Human papillomavirus.


Assuntos
Antivirais/farmacologia , Asarum/química , Medicamentos de Ervas Chinesas/farmacologia , Papillomaviridae/efeitos dos fármacos , Plantas Medicinais/química , Condiloma Acuminado/virologia , DNA Viral/efeitos dos fármacos , DNA Viral/isolamento & purificação , Humanos , Reação em Cadeia da Polimerase/métodos
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