RESUMO
BACKGROUND: Human papillomavirus (HPV) has been identified as an etiopathogenetic factor in oropharyngeal squamous cell carcinoma. The HPV E6 and E7 oncogenes are instrumental in promoting proliferation and blocking differentiation leading to tumorigenesis. Although surgical intervention can remove such tumors, the potential for an etiologic field effect with recurrent disease is real. A downstream effector of E7 oncoprotein, enhancer of zeste homolog 2 (EZH2), is known to promote proliferation and to pose a block in differentiation and in turn, could lead to HPV-induced malignant transformation. However, the EZH2 pathway is amenable to low toxicity therapies designed to promote differentiation to a more benign state and prevent recurrent disease by inhibiting the incorporation of HPV into the genome. This is the first study using clinical specimens to demonstrate EZH2 protein expression in oropharyngeal carcinoma (OPC). METHODS: The study included eight patients with oropharyngeal carcinoma, confirmed p16INK4a- positive by immunohistochemistry (IHC). The tissue expression of E6/E7 messenger RNA (mRNA) was measured by RNAscope® in-situ hybridization technology. Expression of EZH2, Ki-67, and mitotic indices were assessed by morphoproteomic analysis. Biomedical analytics expanded the results with data from Ingenuity Pathway Analysis (IPA) and KEGG databases to construct a molecular network pathway for further insights. RESULTS: Expression of E6 and E7 oncogenes in p16INK4a- positive oropharyngeal carcinoma was confirmed. EZH2 and its correlates, including elevated proliferation index (Ki-67) and mitotic progression were also present. Biomedical analytics validated the relationship between HPV- E6 and E7 and the expression of the EZH2 pathway. CONCLUSION: There is morphoproteomic and mRNA evidence of the association of p16INK4a-HPV infection with the E6 and E7 oncogenes and the expression of EZH2, Ki-67 and mitotic progression in oropharyngeal carcinoma. The molecular network biology was confirmed by biomedical analytics as consistent with published literature. This is significant because the biology lends itself to targeted therapeutic options using metformin, curcumin, celecoxib and sulforaphane as therapeutic strategies to prevent progression or recurrence of disease.
Assuntos
Regulação Neoplásica da Expressão Gênica , Terapia de Alvo Molecular/métodos , Proteínas Oncogênicas Virais/genética , Neoplasias Orofaríngeas/virologia , Proteínas E7 de Papillomavirus/genética , Proteínas Repressoras/genética , Idoso , Biópsia por Agulha , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ/métodos , Masculino , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/patologia , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Prognóstico , Proteômica , RNA Mensageiro/metabolismo , Estudos de Amostragem , Resultado do Tratamento , Infecções Tumorais por Vírus/tratamento farmacológico , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/patologiaRESUMO
BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy that exhibits clinically aggressive features and is associated with a poor prognosis. The incidence of MCC seems to be increasing for reasons unknown, and is estimated to be 0.32/100,000 in the United States. METHODS: This article will review the current literature and National Comprehensive Cancer Network practice guidelines in the treatment of MCC. RESULTS: Resection of MCC with negative margins remains the mainstay of therapy. Positive nodal disease should be treated with neck dissection and adjuvant radiotherapy. High-risk patients should undergo adjuvant radiotherapy, which improves oncologic outcomes. The role of chemotherapy is less clear and is currently reserved for advanced-stage MCC and palliative therapy. CONCLUSION: The pathogenesis of MCC has recently been impacted with the discovery of the Merkel cell polyomavirus (MCPyV). Research to establish targeted and immunologic therapeutic options are ongoing.
Assuntos
Carcinoma de Célula de Merkel/patologia , Poliomavírus das Células de Merkel , Infecções por Polyomavirus/patologia , Neoplasias Cutâneas/patologia , Infecções Tumorais por Vírus/patologia , Antineoplásicos/uso terapêutico , Carcinoma de Célula de Merkel/terapia , Carcinoma de Célula de Merkel/virologia , Guias como Assunto , Humanos , Estadiamento de Neoplasias , Infecções por Polyomavirus/terapia , Infecções por Polyomavirus/virologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/virologia , Infecções Tumorais por Vírus/terapia , Infecções Tumorais por Vírus/virologiaRESUMO
Therapy for BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is limited after hematopoietic stem cell transplantation (HSCT). We examined whether choreito, a formula from Japanese traditional Kampo medicine, is effective for treating BKV-HC. Among children who underwent allogeneic HSCT between October 2006 and March 2014, 14 were diagnosed with BKV-HC (median, 36 days; range, 14 to 330 days) after HSCT, and 6 consecutive children received pharmaceutical-grade choreito extract granules. The hematuria grade before treatment was significantly higher in the choreito group than in the nonchoreito group (P = .018). The duration from therapy to complete resolution was significantly shorter in the choreito group (median, 9 days; range, 4 to 17 days) than in the nonchoreito group (median, 17 days; range, 15 to 66 days; P = .037). In 11 children with macroscopic hematuria, the duration from treatment to resolution of macroscopic hematuria was significantly shorter in the choreito group than in the nonchoreito group (median, 2 days versus 11 days; P = .0043). The BKV load in urine was significantly decreased 1 month after choreito administration. No adverse effects related to choreito administration were observed. Choreito may be a safe and considerably promising therapy for the hemostasis of BKV-HC after HSCT.
Assuntos
Antivirais/uso terapêutico , Cistite/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Hematúria/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Viremia/tratamento farmacológico , Adolescente , Vírus BK/efeitos dos fármacos , Vírus BK/imunologia , Criança , Cistite/imunologia , Cistite/patologia , Cistite/virologia , DNA Viral/antagonistas & inibidores , DNA Viral/urina , Feminino , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/virologia , Hematúria/imunologia , Hematúria/patologia , Hematúria/virologia , Humanos , Japão , Masculino , Medicina Tradicional do Leste Asiático , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/virologia , Carga Viral/efeitos dos fármacos , Viremia/imunologia , Viremia/patologia , Viremia/virologiaRESUMO
BACKGROUND: To date, the outcomes of transplant tourism have not been reported extensively. In addition, data about the accuracy of urine cytology for the detection and the role of the BK virus (BKV) in the carcinogenesis of urothelial carcinoma (UC) after renal transplantation are lacking. METHODS: Three hundred seven patients who received deceased donor kidney transplants between January 2003 and December 2009 were retrospectively studied. The clinical parameters and outcomes between the domestic and tourist groups were compared. We also investigated the risk factors and role of BKV in the carcinogenesis of de novo UC by quantitative real-time polymerase chain reaction. RESULTS: The subjects in the tourist group were older at transplantation and had a shorter dialysis time before transplantation. There were significantly higher incidence rates of BKV viruria, Pneumocystis jiroveci pneumonia, and malignancy in the tourist group. Graft and patient survival were superior in the domestic group. A total of 43 cancers were identified, and the most common type of malignancy was UC (23 patients, 53.5%). The tourist group had a significantly higher incidence of tumors. The sensitivity and specificity of urine cytology for detecting UC were 73.9% and 94.7%, respectively. Independent predictors of UC included female sex, use of Chinese herbal medicine, and transplant tourism. Only two patients (8.7%) with UC had detectable BKV. CONCLUSIONS: Transplant tourism was a risk factor for infection and de novo malignancy. Urothelial carcinoma was the most common malignancy after kidney transplantation. Regular screening for the early detection of UC by urine cytology or periodic sonographic surveys is mandatory, especially for those at high risk.
Assuntos
Carcinoma/epidemiologia , Transplante de Rim/efeitos adversos , Turismo Médico , Infecções por Polyomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Neoplasias Urológicas/epidemiologia , Urotélio/patologia , Adulto , Vírus BK/genética , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/virologia , DNA Viral/sangue , DNA Viral/urina , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Estimativa de Kaplan-Meier , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/mortalidade , Infecções por Polyomavirus/patologia , Infecções por Polyomavirus/virologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Taiwan/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Infecções Tumorais por Vírus/mortalidade , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/virologia , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Neoplasias Urológicas/virologia , Urotélio/virologiaRESUMO
Non-human primates have assumed an important role in preclinical safety assessment studies, particularly in the evaluation of biopharmaceutical and immunomodulatory therapies. Naturally occurring simian retrovirus infections may adversely affect the suitability of primates for use in such studies. Various species of non-human primates are the natural hosts for six exogenous retroviruses, representing five genera within the family Retroviridae. Retroviruses establish persistent infections with a broad spectrum of pathogenic potential, ranging from nonpathogenic to highly pathogenic, depending on the variety of the host, virus, and environmental factors. In the context of immunotoxicology, in which the research objective is to specifically evaluate the effect of drugs or biologics on the immune system, the immune modulatory effects of simian retroviruses, which may be subtle or profound, may introduce significant confounding into the studies of immunotoxic effects utilizing non-human primates. Latent or subclinical retrovirus infections are common and research-related procedures may lead to virus reactivation or overt disease. Adverse effects of undetected retrovirus infections on preclinical research include the loss of experimental subjects (and potentially of statistical power) due to increased morbidity and mortality, virus-induced clinical abnormalities, histologic lesions, alteration of physiologic parameters and biologic responses, and interference with in vitro assays and/or cytolytic destruction of primary cell cultures. The aim of this review is to provide an overview of the key biological, clinical, and pathological features of several important simian retroviruses, with emphasis on viruses infecting macaques and other primate species commonly used in preclinical research, and a discussion of the implications of these infections for immunotoxicology and other preclinical research in primates. Adequate pre-study retrovirus screening is essential to exclude retrovirus-infected primates from research protocols.
Assuntos
Haplorrinos/virologia , Sistema Imunitário/efeitos dos fármacos , Doenças dos Macacos/virologia , Infecções por Retroviridae/veterinária , Retrovirus dos Símios/patogenicidade , Infecções Tumorais por Vírus/veterinária , Xenobióticos/toxicidade , Animais , Animais de Laboratório , Avaliação Pré-Clínica de Medicamentos , Sistema Imunitário/fisiologia , Sistema Imunitário/virologia , Doenças dos Macacos/patologia , Infecções por Retroviridae/patologia , Infecções por Retroviridae/transmissão , Retrovirus dos Símios/isolamento & purificação , Retrovirus dos Símios/fisiologia , Testes de Toxicidade , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/transmissão , Xenobióticos/classificaçãoRESUMO
Friend murine leukemia virus (FMuLv) is an acutely oncogenic retrovirus, and its infection leads to erythroblastosis and leukemia in mice. This infection model is used in the search for new antiviral agents. In the present study, the authors have evaluated the potential of an extract of Phyllanthus amarus against FMuLv-induced erythroleukemia in BALB/c mice. Injection of newborn mice with FMuLv resulted in leukemia and animals died due to splenomegaly. Oral administration of P.amarus was found to enhance the life span of leukemia-harboring animals and decrease the incidence of anemia. The authors also performed a series of hematological, biochemical, histopathological, and gene expression analyses to evaluate the effect of P.amarus administration on erythroleukemia initiation and progression. The data obtained indicate that P.amarus administration could significantly decrease the progression of erythroleukemia. Treatment with P.amarus induced the expression of p53 and p45NFE2 and decreased the expression of Bcl-2 in the spleen of infected mice. Histopathological evaluations of the spleen demonstrated that administration of P.amarus decreased the infiltration of leukemic cells into the sinusoidal space when compared with the vehicle treated group. P.amarus is known to inhibit chemically induced neoplasm in different rodent models.The current results indicate that P.amarus has the ability to suppress virally induced cancers as well.
Assuntos
Vírus da Leucemia Murina de Friend , Leucemia Eritroblástica Aguda/tratamento farmacológico , Leucemia Experimental/tratamento farmacológico , Phyllanthus/química , Extratos Vegetais/uso terapêutico , Infecções por Retroviridae/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Anemia/sangue , Anemia/tratamento farmacológico , Animais , Contagem de Células Sanguíneas , Peso Corporal/efeitos dos fármacos , Transformação Celular Viral/efeitos dos fármacos , Progressão da Doença , Expressão Gênica/genética , Hemoglobinas/análise , Hemoglobinas/metabolismo , Leucemia Eritroblástica Aguda/sangue , Leucemia Eritroblástica Aguda/patologia , Leucemia Experimental/sangue , Leucemia Experimental/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Subunidade p45 do Fator de Transcrição NF-E2/genética , Tamanho do Órgão/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Infecções por Retroviridae/sangue , Infecções por Retroviridae/patologia , Infecções por Retroviridae/virologia , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Análise de Sobrevida , Proteína Supressora de Tumor p53/genética , Infecções Tumorais por Vírus/sangue , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/virologia , Ácido Úrico/sangueRESUMO
BACKGROUND: Recurrent respiratory papillomatosis is caused by the human papillomavirus types (HPV) 6 and 11. It affects both children and adults. In a small number of cases, the disease can be very aggressive causing significant morbidity and possibly death. Surgical therapy is the primary treatment but in patients with aggressive disease, adjunctive therapy is initiated. The majority of these adjuncts center on immunomodulation, disruption of molecular signaling cascades or interruption of viral replication to help decrease the severity of the disease. Recently, a preventative vaccine has become available but data on its effectiveness will be at least a decade away. In the mean time, researchers are examining other vaccination strategies in the fight against HPV disease. OBJECTIVE: We will review the following pharmacotherapies used in the adjunct treatment of RRP: interferon, acyclovir, ribivirin, cidofovir, COX-2 inhibitors, retinoids, anti-reflux medications, zinc, indole-3-carbinol, therapeutic/preventative vaccines. METHODS: This is a review paper. Utilizing Medline and Pubmed from 1966 to present, the key words as well as the above listed adjunct treatments were searched for relevant papers. CONCLUSION: The evidence supporting each of these adjuncts varies with a majority having only case reports or cases-series to support their use. However, there is hope on the horizon with regard to the HPV vaccine and its potential to prevent future transmission of this disease.
Assuntos
Antivirais/uso terapêutico , Neoplasias Laríngeas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Papiloma/tratamento farmacológico , Infecções por Papillomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Adulto , Quimioterapia Adjuvante , Criança , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Papiloma/patologia , Papiloma/cirurgia , Papillomaviridae/isolamento & purificação , Papillomaviridae/fisiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/cirurgia , Infecções Tumorais por Vírus/patologiaRESUMO
BACKGROUND: Epstein-Barr virus (EBV) has been shown to be associated with gastric cancer. However, inconsistent findings have been reported regarding the distribution of EBV infected cells (in normal gastric epithelium vs. intestinal metaplastic cells vs. in neoplastic cells) and the characteristics of EBV-associated gastric cancer. Lymph node positive EBV-associated gastric cancer has not been systematically studied. The aims of this study were to evaluate EBV-associated gastric cancer, to assess the distribution of EBV infected cells including all positive lymph nodes, and to define the characteristics of EBV-associated gastric cancer. DESIGN: The study included primary gastric cancer patients who underwent surgical resection with no preoperative treatment at M.D. Anderson Cancer Center between 1987 and 2006. Formalin-fixed paraffin-embedded tissue from these resection specimens were assessed for EBV by in situ hybridization, the gold standard for EBV detection in tissue. EBV status was analyzed along with clinicopathologic parameters including age, gender, tumor type, lymph node status, and pathologic stage of the tumor. RESULTS: Among 235 patients, 12 had intranuclear expression of EBV. EBV staining was seen only in tumor cells and no detectable EBV was observed in normal gastric mucosa, intestinal metaplasia or stromal cells. Eight of 12 patients with EBV-associated gastric cancer had regional lymph node metastasis. Of note, metastatic tumor cells in all of the involved lymph nodes of these 8 cases contained EBV. The epidemiologic data showed 11 of the 12 patients with EBV-associated gastric cancer were men, ranging in age from 54 to 78 years (mean age, 60 years; median age, 62.1 years). The age distribution for non-EBV associated gastric cancer patients ranged from 21 to 93 years (mean age, 67 years; median age, 66.4 years). CONCLUSION: Our study demonstrated that EBV is present exclusively in gastric cancer cells. The detection of EBV in tumor cells in all of the lymph nodes involved with metastatic gastric carcinoma suggests simultaneous replication of EBV and tumor cells. The predominantly male gender and relatively younger age observed for the EBV-infected gastric cancer cases suggest an association between this disease and other factors, such as life style.
Assuntos
Adenocarcinoma/virologia , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Gástricas/virologia , Infecções Tumorais por Vírus/patologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Vírus Epstein-Barr/virologia , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Mucosa Gástrica/virologia , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , RNA Viral/biossíntese , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Infecções Tumorais por Vírus/virologia , Estados Unidos , Proteínas da Matriz Viral/biossíntese , Adulto JovemRESUMO
Evidence for interactive effects of chromium and selenium on the appearance of mammary tumors was obtained by exposing female virgin C3H mice infected with the murine mammary tumorvirus (MMTV) to subtoxic levels of Cr [as Cr(III) nitrate] and Se (as sodium selenite) in the supply water. Cr counteracted the inhibitory effect of Se on tumor development in a dose-dependent manner, shortened the tumor latency period, and accelerated tumor growth rates. Exposure to Cr also altered the levels of Se in the liver and kidneys of the mice, indicating that Cr interacts with Se and affects its organ distribution. Chromium must be added to the list of Se-antagonistic elements that weaken or abolish the antitumorigenic effects of Se. These findings are relevant to human cancer as previous studies revealed the age-corrected mortalities from breast and other major forms of cancer in different countries to be inversely correlated with the dietary Se intakes, and directly correlated with the estimated intakes of Cr and of other Se-antagonistic elements. The presence of these elements in foods must be taken into account when estimating the optimal dose of supplemental Se for cancer risk reduction.
Assuntos
Anticarcinógenos/antagonistas & inibidores , Cromo/farmacologia , Neoplasias Mamárias Experimentais/prevenção & controle , Vírus do Tumor Mamário do Camundongo , Selênio/antagonistas & inibidores , Animais , Anticarcinógenos/metabolismo , Anticarcinógenos/farmacologia , Cromo/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Humanos , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos C3H , Infecções por Retroviridae/metabolismo , Infecções por Retroviridae/patologia , Selênio/metabolismo , Selênio/farmacologia , Fatores de Tempo , Infecções Tumorais por Vírus/metabolismo , Infecções Tumorais por Vírus/patologiaRESUMO
The authors established a protocol for the use of 5-fluorouracil (5FU) adjuvant in lasertherapy for clinical and subclinical HPV infection in immunosuppressed patients, persistent lesions and as reinforcement treatment in cases of poor progress. Sixty-four patients were evaluated, of whom 26 were immunosuppressed, 34 presented persistent lesions and four received intravaginal reinforcement treatment with 2.5 g 5% 5FU every two weeks, or biweekly vulvar reinforcement after lasertherapy. On average, five 5FU courses were used, but in the immunossuppressed patients its use was maintained indefinitely. The rate of complete response was 66%, but the immunossuppressed patients showed less response (46.2%) when compared with the persistent lesion/reinforcement treatment group (78.9%). The responses were positive in the two groups when compared to that with no response. We deem the use of low-dose 5FU an excellent alternative in cases of difficult HPV progress, presenting a low cost and minimal side-effects.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Fluoruracila/administração & dosagem , Hospedeiro Imunocomprometido , Papillomaviridae , Infecções por Papillomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Neoplasias Vulvares/tratamento farmacológico , Administração Intravaginal , Adolescente , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Terapia a Laser , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/cirurgia , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/cirurgia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgiaRESUMO
A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG) has been known to possess antiproliferative properties. In this study, we investigated the anticancer effects of EGCG in human papillomavirus (HPV)-16 associated cervical cancer cell line, CaSki cells. The growth inhibitory mechanism(s) and regulation of gene expression by EGCG were also evaluated. EGCG showed growth inhibitory effects in CaSki cells in a dose-dependent fashion, with an inhibitory dose (ID)(50) of approximately 35 microM. When CaSki cells were further tested for EGCG-induced apoptosis, apoptotic cells were significantly observed after 24 h at 100 microM EGCG. In contrast, an insignificant induction of apoptotic cells was observed at 35 microM EGCG. However, cell cycles at the G1 phase were arrested at 35 microM EGCG, suggesting that cell cycle arrests might precede apoptosis. When CaSki cells were tested for their gene expression using 384 cDNA microarray, an alteration in the gene expression was observed by EGCG treatment. EGCG downregulated the expression of 16 genes over time more than twofold. In contrast, EGCG upregulated the expression of four genes more than twofold, suggesting a possible gene regulatory role of EGCG. This data supports that EGCG can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest as well as regulation of gene expression in vitro. Furthermore, in vivo antitumor effects of EGCG were also observed. Thus, EGCG likely provides an additional option for a new and potential drug approach for cervical cancer patients.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma/tratamento farmacológico , Catequina/análogos & derivados , Catequina/farmacologia , Fase G1/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Camellia sinensis/química , Testes de Carcinogenicidade , Carcinoma/genética , Carcinoma/patologia , Carcinoma/virologia , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Análise de Sequência com Séries de Oligonucleotídeos , Papillomaviridae , Células Tumorais Cultivadas , Infecções Tumorais por Vírus/tratamento farmacológico , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
OBJECTIVE: Cervical intraepithelial neoplasia (CIN), a common condition among HIV-infected women, has been linked to HIV load and immune status. Highly active antiretroviral therapy (HAART) improves immunologic and virologic status. This study was undertaken to determine the relationship between HAART use and CIN. DESIGN: Cohort study. The Women's Interagency HIV Study (WIHS) in five cities in the USA (Bronx/Manhattan, New York; Brooklyn, New York; Chicago, Illinois; Los Angeles, California; San Francisco Bay area, California; Washington, District of Columbia). METHODS: HIV-infected women were followed every 6 months with Papanicolaou smears and cervicovaginal lavage for human papillomavirus (HPV) DNA testing. To characterize exposures that changed over time and to capture the dynamic nature of cytologic changes, Papanicolaou smear findings from each participant's consecutive visits were defined as a pair. We determined the proportion of all pairs that exhibited either regression or progression, according to HAART exposure, HPV results and Papanicolaou smear status. As participants could contribute multiple pairs, inferences were based on robust methods to adjust for correlated observations. RESULTS: Women with persistent HPV infection were more likely to have progression of their lesions. After adjustment for CD4 cell count and Papanicolaou smear status, women on HAART were 40% (95% confidence interval, 4-81%) more likely to demonstrate regression and less likely (odds ratio, 0.68; 95% confidence interval, 0.52-0.88) to demonstrate progression CONCLUSIONS: HAART altered the course of HPV disease in HIV-infected women, reducing progression and increasing regression. As HPV disease is a common sex-specific manifestation of HIV disease this effect of HAART would be a major additional benefit from this modality of therapy.
Assuntos
Terapia Antirretroviral de Alta Atividade , Colo do Útero/patologia , Infecções por HIV/complicações , Infecções por Papillomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Displasia do Colo do Útero/tratamento farmacológico , Adolescente , Contagem de Linfócito CD4 , Colo do Útero/citologia , Colo do Útero/virologia , Estudos de Coortes , DNA Viral/análise , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Teste de Papanicolaou , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Resultado do Tratamento , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/virologia , Esfregaço Vaginal , Displasia do Colo do Útero/complicações , Displasia do Colo do Útero/patologiaAssuntos
Ética Médica , Infecções por Papillomavirus/diagnóstico , Infecções Tumorais por Vírus/patologia , Doenças do Colo do Útero/virologia , Esfregaço Vaginal/métodos , Erros de Diagnóstico , Feminino , Humanos , Consentimento Livre e Esclarecido , Programas Nacionais de Saúde/normas , Papillomaviridae/isolamento & purificação , Projetos Piloto , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Pesquisa/normas , Infecções Tumorais por Vírus/diagnóstico , Reino Unido , Doenças do Colo do Útero/diagnósticoRESUMO
Cervix carcinoma is an important health problem world-wide, being the second most common cancer among women, ranking first in many developing countries. A number of important epidemiological risk factors have been identified as contributing to the development of CIN and invasive cervix carcinoma. Of key importance is infection with human papillomavirus (HPV), which is the primary risk factor. There are evolving primary and secondary preventive strategies that could further reduce the burden from cervical carcinoma. The possible primary preventive strategies include risk reduction, diet or dietary supplements, HPV vaccines, and other chemopreventive agents. The possible advances in secondary preventive strategies include new technologies for Pap smears, HPV typing triage, and other adjuvant screening procedures. The impact of these strategies will depend upon evidence to support their use along with the characteristics of the population and environment in which they are used.
Assuntos
Anticarcinógenos/uso terapêutico , Antioxidantes/uso terapêutico , Carcinoma de Células Escamosas/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Vitaminas/uso terapêutico , Ácido Ascórbico/uso terapêutico , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , Ensaios Clínicos como Assunto , Colposcopia/métodos , Dieta , Feminino , Ácido Fólico/uso terapêutico , Humanos , Processamento de Imagem Assistida por Computador , Programas de Rastreamento/métodos , Necessidades Nutricionais , Teste de Papanicolaou , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Fotoquimioterapia , Fatores de Risco , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/patologia , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/etiologia , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/instrumentação , Esfregaço Vaginal/métodos , Vacinas Virais , Vitamina E/uso terapêutico , beta Caroteno/uso terapêuticoRESUMO
The outcome of referral to colposcopy of 240 women who had persistently inadequate smears was investigated. Of 232 women who attended colposcopy, 214 (92.2%) had a normal outcome, 12 (5.2%) had low grade abnormalities, and six (2.6%) had high grade abnormalities. This group of women therefore has a negligibly increased risk of harbouring cervical neoplasia. Although not directly comparable, women with a history of previous abnormal cytology did not have a higher risk than those without such a history. Unnecessary colposcopy could have been avoided in the majority of cases if a good quality repeat smear had been taken. Improved smear taker training could decrease the number of referrals. A hospital cytology clinic is proposed as a cost-effective alternative to colposcopy at the first attendance.
Assuntos
Colposcopia/estatística & dados numéricos , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal , Colposcopia/economia , Análise Custo-Benefício , Feminino , Humanos , Auditoria Médica , Programas Nacionais de Saúde/economia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Prevalência , Encaminhamento e Consulta , Estudos Retrospectivos , Risco , Manejo de Espécimes , Resultado do Tratamento , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/patologia , Reino Unido/epidemiologia , Displasia do Colo do Útero/economia , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/economia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Cervicite Uterina/diagnóstico , Cervicite Uterina/epidemiologia , Cervicite Uterina/patologia , Esfregaço Vaginal/economiaRESUMO
The aim of this audit was to determine if inadequate cervical smears are associated with significant cervical pathology. Case records for 52 women with three consecutive inadequate smears referred for colposcopy to the Leicester Royal Infirmary (LRI) were retrieved. Sixteen women underwent large loop excision of the transformation zone (LLETZ) and cervical intraepithelial neoplasia (CIN) was identified in six cases. There were no cases of inadequate smears initiating the diagnosis in 100 consecutive women with invasive cervical cancer. Inadequate smears are associated with high rates of treatment for a low yield of CIN. To reduce morbidity associated with colposcopy it may be acceptable to repeat an inadequate smear after 6 months rather than arranging immediate recall.
Assuntos
Colposcopia/estatística & dados numéricos , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal , Adulto , Idoso , Idoso de 80 Anos ou mais , Administração de Caso , Feminino , Humanos , Programas de Rastreamento , Auditoria Médica , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Prevalência , Encaminhamento e Consulta , Estudos Retrospectivos , Risco , Manejo de Espécimes , Resultado do Tratamento , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/patologia , Reino Unido/epidemiologia , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Cervicite Uterina/diagnóstico , Cervicite Uterina/epidemiologia , Cervicite Uterina/patologiaRESUMO
AIMS: To describe and illustrate a novel and highly sensitive peroxidase-based immunohistochemical detection system which employs mutually attractive, mirror image complementary antibodies (MICA). METHODS AND RESULTS: To demonstrate the sensitivity of the MICA system alongside the avidin-biotin complex (ABC) method, we selected a range of mouse monoclonal and rabbit polyclonal primary antibodies against antigens that are generally regarded as relatively difficult or impossible to detect on formalin-fixed, paraffin-embedded lymphoid tissue. Compared with the ABC method, the MICA immunodetection method enabled us to dilute primary antibodies up to 200-fold with equivalent or superior immunostaining results and, usually, considerably shortened primary antibody incubation times. CONCLUSIONS: We have described and illustrated a novel immunohistochemical detection system and demonstrated greatly increased sensitivity over the commonly used ABC system. An additional advantage of the MICA system is that it is avidin-free and so avoids non-specific staining due to endogenous tissue biotin.
Assuntos
Anticorpos Monoclonais/imunologia , Antígenos de Neoplasias/análise , Técnicas Imunoenzimáticas/métodos , Animais , Antígenos Virais/análise , Células Dendríticas/química , Células Dendríticas/patologia , Infecções por Herpesviridae/patologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Linfoma Folicular/química , Linfoma Folicular/patologia , Linfoma Anaplásico de Células Grandes/química , Linfoma Anaplásico de Células Grandes/patologia , Linfoma não Hodgkin/química , Linfoma não Hodgkin/patologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/virologia , Camundongos , Tonsila Palatina/química , Tonsila Palatina/patologia , Complicações Pós-Operatórias , Coelhos , Sensibilidade e Especificidade , Infecções Tumorais por Vírus/patologiaRESUMO
Our aim was to establish an effective non-surgical treatment for cervical intraepithelial neoplasia (CIN) through inactivation of human papillomavirus (HPV), the major etiological agent for this disease. We show that vidarabine, a DNA polymerase inhibitor, suppressed growth and HPV gene expression in human cervical keratinocytes immortalized by HPV or in cervical cancer cell lines. Expression of HPV-16 E6 and E7 proteins in normal cervical keratinocytes sensitized cells to apoptosis in the presence of podophyllin or vidarabine. We applied vidarabine ointment and/or podophyllin to cervical epithelium in 28 cases of CIN I-II to evaluate the therapeutic effectiveness of these agents. Co-application of vidarabine and podophyllin in six treatments caused regression of lesions cytologically and histologically, and disappearance of HPV-16 or -18 DNA in 17 of 21 (81%) women. Our results suggest that the combination of vidarabine and podophyllin therapy is an effective non-surgical treatment for HPV-positive CIN.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Antivirais/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/tratamento farmacológico , Podofilina/uso terapêutico , Infecções Tumorais por Vírus/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Vidarabina/uso terapêutico , Adulto , Idoso , Apoptose , Carcinoma in Situ/patologia , Carcinoma in Situ/virologia , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/virologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Células Tumorais Cultivadas , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
Research from the past several years has definitively shown intermediate and high risk-type human papillomavirus (HPV) infection to play a significant role in cervical carcinogenesis. Persistent compared with intermittent infection appears to confer an elevated risk, and cofactors may be necessary to allow the virus to progress to cervical cancer. We explored the association between circulating concentrations of the antioxidant nutrients (alpha- and beta-carotene, lutein, lycopene, beta-cryptoxanthin, alpha-tocopherol, gamma-tocopherol, and ascorbate) and persistent HPV infection among 123 low-income Hispanic women who were all nonsmokers and were not currently using vitamin and mineral supplements. In addition, the association between these nutrients and grade of cervical pathology, independent of HPV status, was assessed. Intermediate and high risk-type HPV infection was assessed by the Digene Hybrid Capture System at two time points, 3 months apart. At the second interview, cytology, colposcopy, and a fasting blood draw were conducted. Mean concentrations of serum and plasma antioxidant nutrients were calculated within categories of HPV status (two times HPV negative, one time HPV positive, and two times HPV positive) and colposcopy. Adjusted mean concentrations of serum beta-carotene, beta-cryptoxanthin, lutein, and alpha- and gamma-tocopherol were on average 24% (P < 0.05) lower among women two times HPV positive compared with either two times HPV negative or one time HPV positive. Independent of HPV status, alpha-tocopherol was significantly inversely associated with grade of cervical dysplasia (normal, 21.57 microM; cervical intraepithelial neoplasia III, 17.27 microM). The results obtained in this study need to be confirmed in larger cohort studies with a longer follow-up period.
Assuntos
Antioxidantes/metabolismo , Papillomaviridae , Infecções por Papillomavirus/sangue , Infecções Tumorais por Vírus/sangue , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/virologia , Adulto , Ácido Ascórbico/sangue , Biomarcadores/sangue , Carotenoides/sangue , Doença Crônica , Feminino , Hispânico ou Latino , Humanos , Funções Verossimilhança , Modelos Logísticos , Luteína/sangue , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/etnologia , Infecções por Papillomavirus/patologia , Fatores de Risco , Infecções Tumorais por Vírus/etnologia , Infecções Tumorais por Vírus/patologia , Neoplasias do Colo do Útero/etnologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Vitamina E/sangue , Displasia do Colo do Útero/sangue , Displasia do Colo do Útero/etnologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
BACKGROUND: Oral psoralen with UV-A (PUVA) photochemotherapy is known to cause cutaneous malignancies and has been associated with cutaneous immunosuppression. Human papillomavirus infection has also been associated with cutaneous malignancies and with immunosuppressed individuals. We therefore sought evidence of human papillomavirus infection in a patient with a long history of PUVA therapy and multiple cutaneous malignancies. OBSERVATIONS: During a 15-year period, an otherwise healthy patient with psoriasis who had undergone a 10-year course of PUVA photochemotherapy developed 13 squamous cell carcinomas, eight lesions diagnosed as "squamous cell carcinoma vs keratoacanthoma," 14 other keratoacanthomas, six basal cell carcinomas, one melanoma in situ, and 18 other keratinocytic dysplasias. Twenty-two of the 30 lesions tested for human papillomavirus DNA by polymerase chain reaction were positive for type 16/18, including six of the seven basal or squamous cell carcinomas tested. CONCLUSION: We hypothesize that PUVA therapy-induced immunosuppression may play an important role in PUVA-related carcinogenesis by affecting the extent and pathogenicity of human papillomavirus infection.